https://oncopaedia.net/w/api.php?action=feedcontributions&feedformat=atom&user=Alex 2026-04-07T17:41:50Z User contributions MediaWiki 1.32.0 https://oncopaedia.net/w/index.php?title=Home&diff=337 2020-11-29T18:41:46Z

<p>Alex: </p> <hr /> <div>{{seo|pagetitle=Home|meta_keywords=oncopedia,oncopaedia,cancer}}<br /> <br /> ==Oncopaedia is an online collaborative learning resource for use by oncology professionals ''everywhere''.==<br /> Our aim is to create '''one of the web's finest medical educational platforms''' '''to''' '''enhance the care of cancer patients worldwide'''. With your help, we hope to compile articles on every known cancer type, and we encourage all users to contribute anonymised case examples to each cancer article.<br /> <br /> You can very easily begin editing this website yourself! You don't need to even sign up, but we recommend that you do so we can give you proper credit! You need only provide a username, an email (which you must verify), and a unique password. You can create (or update) articles immediately (subject to a moderation queue if you are new to prevent abuse), and, although our interface is still in development, you can also contribute case data to articles of your choice.<br /> <br /> The oncology case information you can contribute includes (but is not limited to):<br /> <br /> *'''Contoured CT or MRI images''' of the tumour in question, with or without treatment planning beams and dose distributions.<br /> *'''Histopathology slides''' demonstrating the textbook microscopic appearance of that tumour subtype on biopsy.<br /> *'''Immunohistochemical stain images''' showing which are used to positively and negatively discriminate tumour tissue.<br /> *'''Pictures of the gross macroscopic appearance''' of the example cancer, with (if possible) video media showing its successful removal during surgery.<br /> *'''Textbook radiological imaging''' of the cancer in situ, which we would encourage you to submit to [https://radiopaedia.org Radiopaedia.org] (with whom we have no affiliation!) as well.<br /> *'''Genetic information''' from the types of tumour, and mutation signature of the tumour (if available).<br /> *'''The latest medical treatment guidelines''' from your country of practice, to compare with oncology practice globally.<br /> *'''Links to on-going clinical trials''' that are testing novel therapies and/or optimising drugs regimens for treating that specific cancer.<br /> <br /> This website is primarily for use by medical professionals; however, the information contained within these articles is accessible to—and undoubtedly will be used by—cancer patients and their families. We aim to keep access to our website permanently free in the spirit of the [https://lifeinthefastlane.com/foam #FOAMed] movement.<br /> <br /> __NOEDITSECTION__</div>

Alex https://oncopaedia.net/w/index.php?title=Articles:Bone_metastases&diff=336 2020-08-14T16:56:48Z

<p>Alex: </p> <hr /> <div>Metastases within bone can cause extreme and debilitating pain. Bone metastases are far more common than primary bone cancer, and many different cancer types can spread to the bone. The most common types of cancer which spread to bone are:<br /> <br /> *Breast<br /> *Prostate<br /> *Lung<br /> *Kidney<br /> *Thyroid<br /> <br /> Cancer can theoretically metastasize to any bone in the body, but in reality there is a predilection for certain sites. The most common sites are the vertebrae, ribs, pelvis, sternum, and the skull.<br /> <br /> ==Classification==<br /> A bone is a rigid organ, but it is far from physiologically static. To maintain bone strength, there is continuous breakdown and simultaneous reformation of bone, two processes which must finely balance for good bone health.<br /> <br /> '''Osteoblastic''' (or '''sclerotic''') metastases are characterised by the deposition of new bone. These are present most commonly in prostate cancer, but also occur in carcinoid, small cell lung cancer, medulloblastoma, and Hodgkin lymphoma. The molecular crosstalk between tumour and bone cells involves osteoblast-generating proteins such as Transforming Growth Factor, Bone Morphogenic Proteins (BMPs), and Endothelin-1&lt;ref&gt;https://pubmed.ncbi.nlm.nih.gov/12085970/&lt;/ref&gt;.<br /> <br /> '''Osteolytic''' (or '''lytic''') metastases are characterised by the destruction and breakdown of normal bone. These often occur when breast cancer spreads to bone, which is primarily mediated by osteoclasts (bone cells that breaks down bone tissue) and is not a direct effect of metastasized tumour cells&lt;ref&gt;https://pubmed.ncbi.nlm.nih.gov/8086233/&lt;/ref&gt;. Other tumour types with osteolytic metastases include multiple myeloma, non-small cell lung cancer, thyroid cancer, non-Hodgkin lymphoma, and Langerhans' cell histiocytosis. Osteolytic metastases are more common than osteoblastic metastases.<br /> <br /> '''Mixed''' metastases are characterised by the presence of both osteolytic and osteoblastic lesions together in the same area of bone. These metastases are usually present in metastatic gastrointestinal and squamous cancers, as well as in secondary breast cancer. Although breast cancer gives rise to predominantly lytic lesions, around 15–20% of women have sclerotic or both types of lesions&lt;ref&gt;https://pubmed.ncbi.nlm.nih.gov/11346860/&lt;/ref&gt;.<br /> <br /> ==Diagnosis==<br /> <br /> ===Signs and symptoms===<br /> Bone metastases cause major morbidity, and high clinical suspicion should be kept for any patient with cancer that presents with:<br /> <br /> *Severe pain (poorly localised, worse at night)<br /> *Impaired mobility<br /> *[[Pathological fracture|Bone fracture]]<br /> *Bone marrow aplasia<br /> *Symptoms of (metastatic) [[Metastatic spinal cord compression|spinal cord compression]] (MSCC)<br /> *Symptoms in keeping with [[hypercalcaemia]]:<br /> **Constipation<br /> **Fatigue<br /> **Polyuria/polydipsia<br /> **Acute kidney injury (AKI)<br /> **Cardiac arrhythmia<br /> <br /> ===Bloods===<br /> When a patient with cancer presents with any of the signs or symptoms above, basic screening in the form of simple blood testing must be undertaken and complemented with appropriate imaging tests:<br /> <br /> *Full evaluation of bone turnover and potential hypercalcaemia:<br /> **Serum calcium<br /> **Serum phosphate<br /> **25-Hydroxyvitamin D<br /> **Thyroid-stimulating hormone (TSH)<br /> **Parathyroid hormone (PTH)<br /> **Serum creatinine<br /> **Alkaline phosphatase (ALP)<br /> *Full blood count (myelosuppression, anaemia)<br /> *Serum protein electrophoresis (SPEP; myeloma screen)<br /> *Tumour markers (such as PSA in prostate cancer)<br /> <br /> ===Imaging===<br /> Radiological tests are an essential component of diagnosing bony metastases. One or more imaging modalities may be required to confirm suspected cancerous spread to bone.<br /> <br /> '''Plain radiographs''' (X-ray scans) are quick, cost-effective, and widely-available, and should be the initial diagnostic test of choice when investigating bone pain. They are highly specific but lack sensitivity (44-50%) because early-stage metastatic lesions, particularly those up to 1 cm, may be more difficult to visualise. More than 50% of the trabecular bone must be involved before the lesion will be apparent on film and, due to the poor contrast of trabecular bone, lesions within the medulla are often less evident than those within cortical bone&lt;ref&gt;https://pubmed.ncbi.nlm.nih.gov/9025785/&lt;/ref&gt;. As outlined above, sclerotic metastases will appear more radiopaque than the surrounding bone, whereas lytic metastases will appear more radiolucent.<br /> <br /> '''Bone scintigraphy''' (bone scans) on the other hand is highly sensitive but with low specificity. Data from Technetium-99m ('''&lt;sup&gt;99m&lt;/sup&gt;Tc''') scintigraphy have shown false-negative rates as low as 11 to 38% (good sensitivity), with false-positive rates as high as 40% (poor specificity). It thus provides a non-specific osteoblastic indication of bone status, be it inflammatory, traumatic, or neoplastic in origin. Scintigraphy is still more specific and sensitive than either plain radiography or computed tomography, whilst magnetic resonance imaging is more efficacious in assessing vertebral metastases&lt;ref&gt;https://pubmed.ncbi.nlm.nih.gov/2028061/&lt;/ref&gt;.<br /> <br /> '''Computed tomography''' (CT scans) has a high sensitivity, ranging from 71 to 100%, for the detection of metastatic bone lesions&lt;ref&gt;https://pubmed.ncbi.nlm.nih.gov/9362427/&lt;/ref&gt;. Because of the excellent soft tissue resolution of the images produced by CT, it is a particularly helpful modality to distinguish lytic and sclerotic metastases and to visualise their precise location(s) for biopsy.<br /> <br /> '''Magnetic resonance imaging''' (MRI scans) is useful in assessing bone marrow infiltration by tumour deposits, and is required (whole spine) for the proper diagnosis of [[Metastatic spinal cord compression|MSCC]]. It has similarly high specificity (73 to 100%) and sensitivity (82 to 100%) in screening for bone metastases&lt;ref&gt;https://pubmed.ncbi.nlm.nih.gov/10964746/&lt;/ref&gt;.<br /> <br /> '''Positron emission tomography''' (PET scans) detects tumour indirectly by measuring metabolic activity in the form of fluorodeoxyglucose ('''&lt;sup&gt;18&lt;/sup&gt;F''') tissue uptake. As such, its use is not limited to visualising only bony metastases, as &lt;sup&gt;18&lt;/sup&gt;F PET will reveal non-bony metastatic spread also&lt;ref&gt;https://pubmed.ncbi.nlm.nih.gov/8638000/&lt;/ref&gt;. The accuracy of PET is highly dependent on the primary tumour site from which imaged metastases originate. As a modality it is superior to scintigraphy in the screening of bony metastases from breast (specificity 94%, sensitivity 95%)&lt;ref&gt;https://pubmed.ncbi.nlm.nih.gov/12073051/&lt;/ref&gt; and lung (specificity 99%, sensitivity 92%)&lt;ref&gt;https://pubmed.ncbi.nlm.nih.gov/10478250/&lt;/ref&gt; malignancies, but has lower sensitivity in detecting the comparatively slower-growing bone metastases of prostate and renal cancers&lt;ref&gt;https://pubmed.ncbi.nlm.nih.gov/10520701/&lt;/ref&gt;. <br /> <br /> ===Biopsy===<br /> Sometimes it is necessary to diagnose metastases histologically, by removing cells or tissue from the bone lesion(s) directly. Usually this is in the form of a needle or surgical biopsy, and may be indicated if a primary cancer is not known. If the patient has a known primary cancer, then often imaging alone will suffice for the diagnosis of metastatic bone disease.<br /> <br /> ==Treatment==<br /> There are a variety of therapeutic interventions available to patients presenting with bone metastases, but consideration must be given to several patient-specific and tumour-dependent parameters, which include&lt;ref&gt;https://pubmed.ncbi.nlm.nih.gov/11738947/&lt;/ref&gt; (but are not limited to):<br /> <br /> *Lesion site(s) (localised or widespread)<br /> *Presence of extraskeletal metastasis<br /> *Tumour type and features (like receptors)<br /> *Prior treatment history (and response)<br /> *Clinical symptoms<br /> *Performance status<br /> <br /> ===Radiotherapy===<br /> Radiation therapy can provide excellent pain relief and is the treatment of choice for localised metastatic bone pain. However, the analgesic mechanisms of therapeutic skeletal irradiation are poorly understood. Onset of pain relief is usually quick, with a majority of patients experiencing benefit within one to two weeks. Patients who have little reduction in pain by six weeks are unlikely to demonstrate significant overall benefit&lt;ref&gt;https://pubmed.ncbi.nlm.nih.gov/24782453/&lt;/ref&gt;. Other than localised bone pain, additional indications for radiotherapy include [[Metastatic spinal cord compression|MSCC]] and bones at high risk for [[pathological fracture]]&lt;ref&gt;https://pubmed.ncbi.nlm.nih.gov/15978828/&lt;/ref&gt;. Two of the three main divisions of radiation therapy—the third being (sealed source) [[brachytherapy]]—can be used to treat bone metastases: systemic (unsealed source) [[radionuclide therapy]] and [[external beam radiotherapy]] (EBRT). <br /> <br /> '''Local-field [[External beam radiotherapy|EBRT]]''' is the standard choice of radiation therapy for treating bone metastases, as it focally targets the bone lesion and can achieve rates of substantial pain relief of up to 80 to 90%&lt;ref&gt;https://pubmed.ncbi.nlm.nih.gov/6178497/&lt;/ref&gt;. Randomised controlled trials (RCTs) from the 1990s have shown that a single fraction of 8 gray (Gy) is as effective as fractionated doses of 20 Gy&lt;ref&gt;https://pubmed.ncbi.nlm.nih.gov/9681885/&lt;/ref&gt;, 24 Gy&lt;ref&gt;https://pubmed.ncbi.nlm.nih.gov/10577695/&lt;/ref&gt;, and 30 Gy&lt;ref&gt;https://pubmed.ncbi.nlm.nih.gov/10577696/&lt;/ref&gt;. <br /> <br /> '''Wide-field''' (or '''hemibody''') '''[[External beam radiotherapy|EBRT]]''' is useful for widespread metastatic skeletal disease, though was more commonly used for multifocal pain when other effective therapies (chemo- and radionuclide) were not available. There are no RCTs comparing analgesic effect with and without wide-field radiotherapy. However, in terms of quasi-randomised and low-quality RCTs, there is data to suggest that use of fractionation is no more effective than single fraction treatment&lt;ref&gt;https://pubmed.ncbi.nlm.nih.gov/8823257/&lt;/ref&gt;, that increasing doses beyond 8 Gy does not improve overall pain responses&lt;ref&gt;https://pubmed.ncbi.nlm.nih.gov/11395246/&lt;/ref&gt;, and adding wide-field to local-field radiotherapy, whilst significantly halting disease progression (lesion size: P = 0.03; lesion number: P = 0.01), increases grade 3 to 4 haematological toxicity&lt;ref&gt;https://pubmed.ncbi.nlm.nih.gov/1374061/&lt;/ref&gt;. It is possible to classify wide-field treatments into three body regions, each with recommended single-fraction dose limits. Upper treatments (from skull or C1 to L2–L3) should be limited to 6 Gy, whereas mid-body (from L1 to upper third of femur) and lower (from L3–L4 to above knee) treatments should be limited to 8 Gy&lt;ref&gt;https://pubmed.ncbi.nlm.nih.gov/6178497/&lt;/ref&gt;. Any treatments must be delivered with fields shaped to minimise irradiation of organs at risk, such as lung, liver, kidney and bowel. <br /> <br /> '''[[Stereotactic radiotherapy|Stereotactic]] [[External beam radiotherapy|EBRT]]''' is a promising treatment option which delivers higher doses of radiation to tumours in shorter periods in time. When used for extracranial cancers it is interchangeably termed Stereotactic Body Radiation Therapy ('''[[Stereotactic radiotherapy|SBRT]]''') or Stereotactic Ablative Radiotherapy ('''[[Stereotactic radiotherapy|SABR]]'''), the latter of which is appealingly onomatopoeic. When this technique is used for treating malignancy within the brain or some other part of the head, it is termed Stereotactic RadioSurgery ('''[[Stereotactic radiotherapy|SRS]]'''). SBRT/SABR can be used both for primary cancers (lung, liver, prostate, renal) and secondary metastases (bone/spine, lung, liver). There are a number of advantages of stereotactic radiotherapy, the most obvious of which is the potential completion of treatment within a single day, rather than over a number of weeks. The other major benefit is that it obviates the need to irradiate large portions of bone, which lowers the risk of further functional marrow depletion in a patient cohort already at risk of poor marrow reserve. Preserving skeletal marrow function can permit continuous chemotherapy in these patients. The primary limitations of SBRT/SABR are that it is more expensive to deliver than conventional EBRT and that there is a paucity of RCT data comparing its use to standard EBRT management&lt;ref&gt;https://pubmed.ncbi.nlm.nih.gov/18619121/&lt;/ref&gt;. However, a recent single-centre phase II trial appeared to show that SBRT/SABR provides superior pain relief to conventional multifraction radiotherapy, with no observed difference in adverse events or other aspects of quality of life&lt;ref&gt;https://pubmed.ncbi.nlm.nih.gov/31021390/&lt;/ref&gt;. <br /> <br /> '''[[Radionuclide therapy]]''' (or '''radioisotope therapy''') is the systemic administration of radionuclides (also known as radioisotopes) as unsealed radioactive sources that selectively deliver radiation to tumours or target organs. They are taken up predominantly at sites of bone formation, and are therefore most likely best effective for the palliation of osteoblastic (sclerotic) metastases. Common radionuclides approved for the treatment of painful bone metastases include phosphorus-32 ('''&lt;sup&gt;32&lt;/sup&gt;P'''; ''β''-decay), strontium-89 ('''&lt;sup&gt;89&lt;/sup&gt;Sr'''; ''β''-decay), samarium-153 ('''&lt;sup&gt;153&lt;/sup&gt;Sm'''; ''β''- and ''γ''-decay), and rhenium-186 ('''&lt;sup&gt;186&lt;/sup&gt;Re'''; ''β''- and ''γ''-decay). The added advantage of gamma ray emission during decay is that it permits nuclear imaging monitoring of radionuclide biodistribution during therapy. These radionuclides target bone through various mechanisms. &lt;sup&gt;32&lt;/sup&gt;P passes through inorganic phosphate pathways, whereas &lt;sup&gt;89&lt;/sup&gt;Sr is a calcium mimetic and is taken up as a direct analogue of this earth metal. The final two agents are targeted to bone via chelation to phosphonate compounds: &lt;sup&gt;153&lt;/sup&gt;Sm is paired to ethylenediaminetetramethylenephosphonate (EDTMP) and &lt;sup&gt;186&lt;/sup&gt;Re to 1,1-hydroxyethylidene diphosphonate (HEDP). Common toxicities from treatment include myelosuppression and a transient pain flare, the latter of which usually heralds a favourable response. A more recently developed radionuclide, radium-223 (&lt;sup&gt;'''223'''&lt;/sup&gt;'''Ra'''; ''α''-, ''β''-, and ''γ''-decay) is a calcium mimetic which emits over 95% of decay energy in the form of alpha radiation&lt;ref&gt;https://pubmed.ncbi.nlm.nih.gov/17062709/&lt;/ref&gt;. Owing to their comparatively large size the emitted alpha particles have a more limited depth of penetration into surrounding tissues (around 2–10 cells), thereby producing a more potently localised cytotoxic effect. Despite their symptomatic benefits in refractory, widespread bone metastases, neither &lt;sup&gt;89&lt;/sup&gt;Sr nor &lt;sup&gt;153&lt;/sup&gt;Sm have been shown to improve overall survival in interventional trials; however, &lt;sup&gt;223&lt;/sup&gt;Ra use in metastatic castration-resistant prostate cancer patients in the ALSYMPCA (ALpharadin in SYMptomatic Prostate CAncer) trial was shown to significantly prolong overall survival&lt;ref&gt;https://pubmed.ncbi.nlm.nih.gov/23863050/&lt;/ref&gt;. <br /> <br /> ===Bisphosphonates===<br /> Analogues of the natural bone demineralisation inhibitor pyrophosphate, bisphosphonates are useful in the treatment of poorly localised bone pain and in previously irradiated bone lesions. They bind with high affinity to exposed bone mineral where they are internalised by osteoclasts, within which they disrupt the processes of bone resorption and can induce apoptosis. Data have shown that bisphosphonates may have direct pro-apoptotic effects on nearby metastatic cancer cells also&lt;ref&gt;https://pubmed.ncbi.nlm.nih.gov/9362432/&lt;/ref&gt;. In halting the mobilisation of calcium and phosphate from bone, bisphosphonate use (together with rehydration) is now standard of care for malignancy-induced hypercalcaemia&lt;ref&gt;https://pubmed.ncbi.nlm.nih.gov/9025784/&lt;/ref&gt;. The analgesic effect of these agents is independent of underlying tumour characteristics, with osteolytic and osteoblastic lesions responding similarly&lt;ref&gt;https://pubmed.ncbi.nlm.nih.gov/9496390/&lt;/ref&gt;. Many patients tolerate bisphosphonates without major concern, but common side-effects include flu-like myalgic symptoms, diarrhoea, nausea and reflux. It is exceedingly rare but one must be aware of the risk of developing osteonecrosis of the jaw. These medications undergo renal excretion and as such should be avoided in tumour-induced hypercalcaemia or metastatic bone disease if serum creatinine is greater than 400 μmol/L or 265 μmol/L, respectively. Bisphosphonates are divided into three generations of drug: first-generation (tiludronate, clodronate, etidronate), second-generation (ibandronate, alendronate, paimdronate), and third-generation (zoledronate, risedronate). One of the newest agents, zoledronate is 100-times more effective than second-generation pamidronate&lt;ref&gt;https://pubmed.ncbi.nlm.nih.gov/12558465/&lt;/ref&gt;. Whilst receiving bisphosphonate therapy, patients should take protective vitamin D and calcium supplements.<br /> <br /> ===Denosumab===<br /> Denosumab is a monoclonal antibody which binds to and inhibits the action of the RANK receptor ligand (RANKL). RANK is located on the surface of osteoclast progenitor cells and its activation stimulates their development into mature osteoclasts. Therefore denosumab, administered as a subcutaneous injection of 120 mg every four weeks, can help prevent bone destruction and fracture in patients with bone metastases. The antibody is cleared from the body by the reticuloendothelial system and can therefore be used in patients with poor renal function, in whom bisphosphonate use would be contraindicated&lt;ref&gt;https://pubmed.ncbi.nlm.nih.gov/21145999/&lt;/ref&gt;. Additionally, data have shown that denosumab use causes greater suppression of osteolytic markers than bisphosphonate use in metastatic patients with breast&lt;ref&gt;https://pubmed.ncbi.nlm.nih.gov/21060033/&lt;/ref&gt; or prostate&lt;ref&gt;https://pubmed.ncbi.nlm.nih.gov/21353695/&lt;/ref&gt; cancer. However its effectiveness in comparison to bisphosphonates for patients with lung cancer or multiple myeloma is similar for the prevention of skeletal-related events (SRE), and indeed patients with multiple myeloma showed worse overall survival when treated with denosumab instead of zoledronate&lt;ref&gt;https://pubmed.ncbi.nlm.nih.gov/21343556/&lt;/ref&gt;. <br /> <br /> ===Systemic anticancer therapies===<br /> [[Systemic anticancer therapy]] (SACT) refers to all drugs administered systemically with direct anticancer activity. This includes all conventional cytotoxic chemotherapies, all small molecule or antibody treatments, and all types of immunotherapy. Hormonal agents are not included within this categorisation. SACT may be considered for bone metastases if a primary tumour is known or subsequently confirmed. The specific therapy used will be the same therapy as typically used for the culprit primary cancer, though the precise dose and schedule will vary. SACT is sometimes used concurrently with other treatments such as bisphosphonates or radiotherapy. Side-effects will be treatment-specific.<br /> <br /> ===Hormone therapies===<br /> <br /> <br /> Hormone therapy is an indirect antitumour treatment which blocks the action of endogenous hormones or reduces their production within the body. Certain hormone-sensitive malignancies, particularly those of the prostate and breast, will often grow in response to specific hormones (androgens and oestrogens, respectively). Secondary metastases stemming from these primary tumours will, by extension, respond to hormone levels too. Androgen-responsive prostate cancer may be treated with drugs which lower androgen levels, such as gonadotrophin-releasing hormone (GnRH) receptor antagonists (peptides: '-''relix''&lt;nowiki/&gt;'; small-molecules: '-''golix''&lt;nowiki/&gt;'), GnRH receptor agonists ('-''relin''&lt;nowiki/&gt;'), and CYP17A1 inhibitors (such as abiraterone). Alternatively, androgen receptor blockers, such as bicalutamide or flutamide, can be effective. Oestrogen-responsive breast cancer may be treated with drugs which lower oestrogen levels, such as type I (exemestane) and type II (anastrozole, letrozole) aromatase inhibitors. Alternatively, selective oestrogen receptor modulators (SERMs), such as tamoxifen, can be effective. These modulators have mixed oestrogenic and antioestrogenic activity, which differs according to receptive tissue. Usefully in breast cancer, it is antioestrogenic in the breast; however, in the uterus and liver it is oestrogenic.<br /> ===Interventional radiology===<br /> The role of the interventional radiologist is ever-expanding. In the treatment of metastatic cancer there are procedures which are shared with or done solely by these interventionists. Two important treatments offered by the specialty for bone metastases are ablation and cementoplasty.<br /> <br /> '''Ablation''' is a medical term for when a procedural probe is introduced to an area of tissue (in this case tumour) and, using physical energy (heat or cold) or chemicals, cellular necrosis with subsequent scarring is achieved. It is useful for bony lesions if only there are one or two lesions to be targeted. The most common types of ablation are [[radiofrequency ablation]] (RFA), where an electric current passes through and heats a needle within the lesion, and cryoablation, where a cold probe within the lesion freezes and destroys cancer cells. Both are effective analgesic therapies; however, unlike in RFA, the ablation edge in cryoablation can be readily visualised with CT monitoring (as low-attenuation) and does not produce increased pain in the periprocedural period&lt;ref&gt;https://pubmed.ncbi.nlm.nih.gov/21785102/&lt;/ref&gt;. Complications rates for each procedure are low, but localised infection and enduring neuropathic pain have been reported. <br /> <br /> '''Cementoplasty''' is a generic term for a group of medical procedures whereby acrylic bone cement, commonly polymethylmethacrylate (PMMA), is injected percutaneously into bone lesions for analgesic effect and/or stabilisation. It is commonly performed under sedation with local anaesthesia, and the cement is mixed with a radiopaque agent to allow visualisation with multi-plane fluoroscopy during injection&lt;ref&gt;https://pubmed.ncbi.nlm.nih.gov/21629403/&lt;/ref&gt;. Depending on where cementoplasty is used, it may be termed differently:<br /> <br /> *Osteoplasty (generic term, injection into non-axial bone lesions)<br /> *Vertebroplasty (injection into a vertebral lesion)<br /> *Kyphoplasty (mostly for vertebral fractures, this is vertebroplasty with use of intravertebral balloon inflation beforehand to restore vertebral height)<br /> *Sacroplasty (injection into a sacral lesion)<br /> <br /> ===Surgery===<br /> Surgery is not considered to be amongst the conventional treatments for bony metastases. It is indicated for fractures of the hip and of long bones, and if there is need for vertebral surgery in [[Metastatic spinal cord compression|MSCC]]. Sometimes if bone involvement leads to fracture causing peripheral nerve impingement or compression, surgery may also be necessary.<br /> <br /> ==Living with bone metastases==<br /> It is important to grasp that, in many instances, patients live with their bone metastases as a chronic (non-curable) condition. Adjustments will often need to be made to permit a continued good quality of life.<br /> <br /> '''Pain''' is very common with metastatic bony disease, and many treatments can be given to alleviate this pain. If pain is difficult to manage then input from pain and palliative care specialists (doctors and nurses) can be enormously helpful. Some patients find complementary therapies, such as massage and acupuncture, to be of benefit to their symptoms.<br /> <br /> '''Mobility''' can be severely impacted by skeletal metastasis. Depending on the location, burden, and extent of the bone disease, the risk of fracture can be high. Input from occupational therapists and physiotherapists can enhance the safety of patients and their environments, and minimise the risks of falling and fracture.<br /> <br /> '''Survival''' is an understandably common topic of discussion, particularly in the context of advanced metastatic cancer. The factors affecting survival with bone metastases are multifarious and as such any attempt at predicting exact survival is impracticable. However, there is some scope for estimation. The survival of patients who develop bone metastases from prostate or breast cancer is often measured in years, whereas the survival of patients with bone metastases from lung cancer is often measured in months.&lt;references /&gt;</div>

Alex https://oncopaedia.net/w/index.php?title=Articles:Bone_metastases&diff=335 2020-08-14T13:52:31Z

<p>Alex: </p> <hr /> <div>Metastases within bone can cause extreme and debilitating pain. Bone metastases are far more common than primary bone cancer, and many different cancer types can spread to the bone. The most common types of cancer which spread to bone are:<br /> <br /> *Breast<br /> *Prostate<br /> *Lung<br /> *Kidney<br /> *Thyroid<br /> <br /> Cancer can theoretically metastasize to any bone in the body, but in reality there is a predilection for certain sites. The most common sites are the vertebrae, ribs, pelvis, sternum, and the skull.<br /> <br /> ==Classification==<br /> A bone is a rigid organ, but it is far from physiologically static. To maintain bone strength, there is continuous breakdown and simultaneous reformation of bone, two processes which must finely balance for good bone health.<br /> <br /> '''Osteoblastic''' (or '''sclerotic''') metastases are characterised by the deposition of new bone. These are present most commonly in prostate cancer, but also occur in carcinoid, small cell lung cancer, medulloblastoma, and Hodgkin lymphoma. The molecular crosstalk between tumour and bone cells involves osteoblast-generating proteins such as Transforming Growth Factor, Bone Morphogenic Proteins (BMPs), and Endothelin-1&lt;ref&gt;https://pubmed.ncbi.nlm.nih.gov/12085970/&lt;/ref&gt;.<br /> <br /> '''Osteolytic''' (or '''lytic''') metastases are characterised by the destruction and breakdown of normal bone. These often occur when breast cancer spreads to bone, which is primarily mediated by osteoclasts (bone cells that breaks down bone tissue) and is not a direct effect of metastasized tumour cells&lt;ref&gt;https://pubmed.ncbi.nlm.nih.gov/8086233/&lt;/ref&gt;. Other tumour types with osteolytic metastases include multiple myeloma, non-small cell lung cancer, thyroid cancer, non-Hodgkin lymphoma, and Langerhans' cell histiocytosis. Osteolytic metastases are more common than osteoblastic metastases.<br /> <br /> '''Mixed''' metastases are characterised by the presence of both osteolytic and osteoblastic lesions together in the same area of bone. These metastases are usually present in metastatic gastrointestinal and squamous cancers, as well as in secondary breast cancer. Although breast cancer gives rise to predominantly lytic lesions, around 15–20% of women have sclerotic or both types of lesions&lt;ref&gt;https://pubmed.ncbi.nlm.nih.gov/11346860/&lt;/ref&gt;.<br /> <br /> ==Diagnosis==<br /> <br /> ===Signs and symptoms===<br /> Bone metastases cause major morbidity, and high clinical suspicion should be kept for any patient with cancer that presents with:<br /> <br /> *Severe pain (poorly localised, worse at night)<br /> *Impaired mobility<br /> *[[Pathological fracture|Bone fracture]]<br /> *Bone marrow aplasia<br /> *Symptoms of (metastatic) [[Metastatic spinal cord compression|spinal cord compression]] (MSCC)<br /> *Symptoms in keeping with [[hypercalcaemia]]:<br /> **Constipation<br /> **Fatigue<br /> **Polyuria/polydipsia<br /> **Acute kidney injury (AKI)<br /> **Cardiac arrhythmia<br /> <br /> ===Bloods===<br /> When a patient with cancer presents with any of the signs or symptoms above, basic screening in the form of simple blood testing must be undertaken and complemented with appropriate imaging tests:<br /> <br /> *Full evaluation of bone turnover and potential hypercalcaemia:<br /> **Serum calcium<br /> **Serum phosphate<br /> **25-Hydroxyvitamin D<br /> **Thyroid-stimulating hormone (TSH)<br /> **Parathyroid hormone (PTH)<br /> **Serum creatinine<br /> **Alkaline phosphatase (ALP)<br /> *Full blood count (myelosuppression, anaemia)<br /> *Serum protein electrophoresis (SPEP; myeloma screen)<br /> *Tumour markers (such as PSA in prostate cancer)<br /> <br /> ===Imaging===<br /> Radiological tests are an essential component of diagnosing bony metastases. One or more imaging modalities may be required to confirm suspected cancerous spread to bone.<br /> <br /> '''Plain radiographs''' (X-ray scans) are quick, cost-effective, and widely-available, and should be the initial diagnostic test of choice when investigating bone pain. They are highly specific but lack sensitivity (44-50%) because early-stage metastatic lesions, particularly those up to 1 cm, may be more difficult to visualise. More than 50% of the trabecular bone must be involved before the lesion will be apparent on film and, due to the poor contrast of trabecular bone, lesions within the medulla are often less evident than those within cortical bone&lt;ref&gt;https://pubmed.ncbi.nlm.nih.gov/9025785/&lt;/ref&gt;. As outlined above, sclerotic metastases will appear more radiopaque than the surrounding bone, whereas lytic metastases will appear more radiolucent.<br /> <br /> '''Bone scintigraphy''' (bone scans) on the other hand is highly sensitive but with low specificity. Data from Technetium-99m ('''&lt;sup&gt;99m&lt;/sup&gt;Tc''') scintigraphy have shown false-negative rates as low as 11 to 38% (good sensitivity), with false-positive rates as high as 40% (poor specificity). It thus provides a non-specific osteoblastic indication of bone status, be it inflammatory, traumatic, or neoplastic in origin. Scintigraphy is still more specific and sensitive than either plain radiography or computed tomography, whilst magnetic resonance imaging is more efficacious in assessing vertebral metastases&lt;ref&gt;https://pubmed.ncbi.nlm.nih.gov/2028061/&lt;/ref&gt;.<br /> <br /> '''Computed tomography''' (CT scans) has a high sensitivity, ranging from 71 to 100%, for the detection of metastatic bone lesions&lt;ref&gt;https://pubmed.ncbi.nlm.nih.gov/9362427/&lt;/ref&gt;. Because of the excellent soft tissue resolution of the images produced by CT, it is a particularly helpful modality to distinguish lytic and sclerotic metastases and to visualise their precise location(s) for biopsy.<br /> <br /> '''Magnetic resonance imaging''' (MRI scans) is useful in assessing bone marrow infiltration by tumour deposits, and is required (whole spine) for the proper diagnosis of [[Metastatic spinal cord compression|MSCC]]. It has similarly high specificity (73 to 100%) and sensitivity (82 to 100%) in screening for bone metastases&lt;ref&gt;https://pubmed.ncbi.nlm.nih.gov/10964746/&lt;/ref&gt;.<br /> <br /> '''Positron emission tomography''' (PET scans) detects tumour indirectly by measuring metabolic activity in the form of fluorodeoxyglucose ('''&lt;sup&gt;18&lt;/sup&gt;F''') tissue uptake. As such, its use is not limited to visualising only bony metastases, as &lt;sup&gt;18&lt;/sup&gt;F PET will reveal non-bony metastatic spread also&lt;ref&gt;https://pubmed.ncbi.nlm.nih.gov/8638000/&lt;/ref&gt;. The accuracy of PET is highly dependent on the primary tumour site from which imaged metastases originate. As a modality it is superior to scintigraphy in the screening of bony metastases from breast (specificity 94%, sensitivity 95%)&lt;ref&gt;https://pubmed.ncbi.nlm.nih.gov/12073051/&lt;/ref&gt; and lung (specificity 99%, sensitivity 92%)&lt;ref&gt;https://pubmed.ncbi.nlm.nih.gov/10478250/&lt;/ref&gt; malignancies, but has lower sensitivity in detecting the comparatively slower-growing bone metastases of prostate and renal cancers&lt;ref&gt;https://pubmed.ncbi.nlm.nih.gov/10520701/&lt;/ref&gt;. <br /> <br /> ===Biopsy===<br /> Sometimes it is necessary to diagnose metastases histologically, by removing cells or tissue from the bone lesion(s) directly. Usually this is in the form of a needle or surgical biopsy, and may be indicated if a primary cancer is not known. If the patient has a known primary cancer, then often imaging alone will suffice for the diagnosis of metastatic bone disease.<br /> <br /> ==Treatment==<br /> There are a variety of therapeutic interventions available to patients presenting with bone metastases, but consideration must be given to several patient-specific and tumour-dependent parameters, which include&lt;ref&gt;https://pubmed.ncbi.nlm.nih.gov/11738947/&lt;/ref&gt; (but are not limited to):<br /> <br /> *Lesion site(s) (localised or widespread)<br /> *Presence of extraskeletal metastasis<br /> *Tumour type and features (like receptors)<br /> *Prior treatment history (and response)<br /> *Clinical symptoms<br /> *Performance status<br /> <br /> ===Radiotherapy===<br /> Radiation therapy can provide excellent pain relief and is the treatment of choice for localised metastatic bone pain. However, the analgesic mechanisms of therapeutic skeletal irradiation are poorly understood. Onset of pain relief is usually quick, with a majority of patients experiencing benefit within one to two weeks. Patients who have little reduction in pain by six weeks are unlikely to demonstrate significant overall benefit&lt;ref&gt;https://pubmed.ncbi.nlm.nih.gov/24782453/&lt;/ref&gt;. Other than localised bone pain, additional indications for radiotherapy include [[Metastatic spinal cord compression|MSCC]] and bones at high risk for [[pathological fracture]]&lt;ref&gt;https://pubmed.ncbi.nlm.nih.gov/15978828/&lt;/ref&gt;. Two of the three main divisions of radiation therapy—the third being (sealed source) [[brachytherapy]]—can be used to treat bone metastases: systemic (unsealed source) [[radionuclide therapy]] and [[external beam radiotherapy]] (EBRT). <br /> <br /> '''Local-field [[External beam radiotherapy|EBRT]]''' is the standard choice of radiation therapy for treating bone metastases, as it focally targets the bone lesion and can achieve rates of substantial pain relief of up to 80 to 90%&lt;ref&gt;https://pubmed.ncbi.nlm.nih.gov/6178497/&lt;/ref&gt;. Randomised controlled trials (RCTs) from the 1990s have shown that a single fraction of 8 gray (Gy) is as effective as fractionated doses of 20 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9681885&lt;/ref&gt;, 24 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10577695&lt;/ref&gt;, and 30 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10577696&lt;/ref&gt;. <br /> <br /> '''Wide-field''' (or '''hemibody''') '''[[External beam radiotherapy|EBRT]]''' is useful for widespread metastatic skeletal disease, though was more commonly used for multifocal pain when other effective therapies (chemo- and radionuclide) were not available. There are no RCTs comparing analgesic effect with and without wide-field radiotherapy. However, in terms of quasi-randomised and low-quality RCTs, there is data to suggest that use of fractionation is no more effective than single fraction treatment&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8823257&lt;/ref&gt;, that increasing doses beyond 8 Gy does not improve overall pain responses&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11395246&lt;/ref&gt;, and adding wide-field to local-field radiotherapy, whilst significantly halting disease progression (lesion size: P = 0.03; lesion number: P = 0.01), increases grade 3 to 4 haematological toxicity&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/1374061&lt;/ref&gt;. It is possible to classify wide-field treatments into three body regions, each with recommended single-fraction dose limits. Upper treatments (from skull or C1 to L2–L3) should be limited to 6 Gy, whereas mid-body (from L1 to upper third of femur) and lower (from L3–L4 to above knee) treatments should be limited to 8 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/6178497/&lt;/ref&gt;. Any treatments must be delivered with fields shaped to minimise irradiation of organs at risk, such as lung, liver, kidney and bowel. <br /> <br /> '''[[Stereotactic radiotherapy|Stereotactic]] [[External beam radiotherapy|EBRT]]''' is a promising treatment option which delivers higher doses of radiation to tumours in shorter periods in time. When used for extracranial cancers it is interchangeably termed Stereotactic Body Radiation Therapy ('''[[Stereotactic radiotherapy|SBRT]]''') or Stereotactic Ablative Radiotherapy ('''[[Stereotactic radiotherapy|SABR]]'''), the latter of which is appealingly onomatopoeic. When this technique is used for treating malignancy within the brain or some other part of the head, it is termed Stereotactic RadioSurgery ('''[[Stereotactic radiotherapy|SRS]]'''). SBRT/SABR can be used both for primary cancers (lung, liver, prostate, renal) and secondary metastases (bone/spine, lung, liver). There are a number of advantages of stereotactic radiotherapy, the most obvious of which is the potential completion of treatment within a single day, rather than over a number of weeks. The other major benefit is that it obviates the need to irradiate large portions of bone, which lowers the risk of further functional marrow depletion in a patient cohort already at risk of poor marrow reserve. Preserving skeletal marrow function can permit continuous chemotherapy in these patients. The primary limitations of SBRT/SABR are that it is more expensive to deliver than conventional EBRT and that there is a paucity of RCT data comparing its use to standard EBRT management&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/18619121/&lt;/ref&gt;. However, a recent single-centre phase II trial appeared to show that SBRT/SABR provides superior pain relief to conventional multifraction radiotherapy, with no observed difference in adverse events or other aspects of quality of life&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/31021390&lt;/ref&gt;. <br /> <br /> '''[[Radionuclide therapy]]''' (or '''radioisotope therapy''') is the systemic administration of radionuclides (also known as radioisotopes) as unsealed radioactive sources that selectively deliver radiation to tumours or target organs. They are taken up predominantly at sites of bone formation, and are therefore most likely best effective for the palliation of osteoblastic (sclerotic) metastases. Common radionuclides approved for the treatment of painful bone metastases include phosphorus-32 ('''&lt;sup&gt;32&lt;/sup&gt;P'''; ''β''-decay), strontium-89 ('''&lt;sup&gt;89&lt;/sup&gt;Sr'''; ''β''-decay), samarium-153 ('''&lt;sup&gt;153&lt;/sup&gt;Sm'''; ''β''- and ''γ''-decay), and rhenium-186 ('''&lt;sup&gt;186&lt;/sup&gt;Re'''; ''β''- and ''γ''-decay). The added advantage of gamma ray emission during decay is that it permits nuclear imaging monitoring of radionuclide biodistribution during therapy. These radionuclides target bone through various mechanisms. &lt;sup&gt;32&lt;/sup&gt;P passes through inorganic phosphate pathways, whereas &lt;sup&gt;89&lt;/sup&gt;Sr is a calcium mimetic and is taken up as a direct analogue of this earth metal. The final two agents are targeted to bone via chelation to phosphonate compounds: &lt;sup&gt;153&lt;/sup&gt;Sm is paired to ethylenediaminetetramethylenephosphonate (EDTMP) and &lt;sup&gt;186&lt;/sup&gt;Re to 1,1-hydroxyethylidene diphosphonate (HEDP). Common toxicities from treatment include myelosuppression and a transient pain flare, the latter of which usually heralds a favourable response. A more recently developed radionuclide, radium-223 (&lt;sup&gt;'''223'''&lt;/sup&gt;'''Ra'''; ''α''-, ''β''-, and ''γ''-decay) is a calcium mimetic which emits over 95% of decay energy in the form of alpha radiation&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/17062709&lt;/ref&gt;. Owing to their comparatively large size the emitted alpha particles have a more limited depth of penetration into surrounding tissues (around 2–10 cells), thereby producing a more potently localised cytotoxic effect. Despite their symptomatic benefits in refractory, widespread bone metastases, neither &lt;sup&gt;89&lt;/sup&gt;Sr nor &lt;sup&gt;153&lt;/sup&gt;Sm have been shown to improve overall survival in interventional trials; however, &lt;sup&gt;223&lt;/sup&gt;Ra use in metastatic castration-resistant prostate cancer patients in the ALSYMPCA (ALpharadin in SYMptomatic Prostate CAncer) trial was shown to significantly prolong overall survival&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/23863050/&lt;/ref&gt;. <br /> <br /> ===Bisphosphonates===<br /> Analogues of the natural bone demineralisation inhibitor pyrophosphate, bisphosphonates are useful in the treatment of poorly localised bone pain and in previously irradiated bone lesions. They bind with high affinity to exposed bone mineral where they are internalised by osteoclasts, within which they disrupt the processes of bone resorption and can induce apoptosis. Data have shown that bisphosphonates may have direct pro-apoptotic effects on nearby metastatic cancer cells also&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9362432/&lt;/ref&gt;. In halting the mobilisation of calcium and phosphate from bone, bisphosphonate use (together with rehydration) is now standard of care for malignancy-induced hypercalcaemia&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9025784/&lt;/ref&gt;. The analgesic effect of these agents is independent of underlying tumour characteristics, with osteolytic and osteoblastic lesions responding similarly&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9496390&lt;/ref&gt;. Many patients tolerate bisphosphonates without major concern, but common side-effects include flu-like myalgic symptoms, diarrhoea, nausea and reflux. It is exceedingly rare but one must be aware of the risk of developing osteonecrosis of the jaw. These medications undergo renal excretion and as such should be avoided in tumour-induced hypercalcaemia or metastatic bone disease if serum creatinine is greater than 400 μmol/L or 265 μmol/L, respectively. Bisphosphonates are divided into three generations of drug: first-generation (tiludronate, clodronate, etidronate), second-generation (ibandronate, alendronate, paimdronate), and third-generation (zoledronate, risedronate). One of the newest agents, zoledronate is 100-times more effective than second-generation pamidronate&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12558465/&lt;/ref&gt;. Whilst receiving bisphosphonate therapy, patients should take protective vitamin D and calcium supplements.<br /> <br /> ===Denosumab===<br /> Denosumab is a monoclonal antibody which binds to and inhibits the action of the RANK receptor ligand (RANKL). RANK is located on the surface of osteoclast progenitor cells and its activation stimulates their development into mature osteoclasts. Therefore denosumab, administered as a subcutaneous injection of 120 mg every four weeks, can help prevent bone destruction and fracture in patients with bone metastases. The antibody is cleared from the body by the reticuloendothelial system and can therefore be used in patients with poor renal function, in whom bisphosphonate use would be contraindicated&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/21145999/&lt;/ref&gt;. Additionally, data have shown that denosumab use causes greater suppression of osteolytic markers than bisphosphonate use in metastatic patients with breast&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/21060033/&lt;/ref&gt; or prostate&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/21353695/&lt;/ref&gt; cancer. However its effectiveness in comparison to bisphosphonates for patients with lung cancer or multiple myeloma is similar for the prevention of skeletal-related events (SRE), and indeed patients with multiple myeloma showed worse overall survival when treated with denosumab instead of zoledronate&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/21343556/&lt;/ref&gt;. <br /> <br /> ===Systemic anticancer therapies===<br /> [[Systemic anticancer therapy]] (SACT) refers to all drugs administered systemically with direct anticancer activity. This includes all conventional cytotoxic chemotherapies, all small molecule or antibody treatments, and all types of immunotherapy. Hormonal agents are not included within this categorisation. SACT may be considered for bone metastases if a primary tumour is known or subsequently confirmed. The specific therapy used will be the same therapy as typically used for the culprit primary cancer, though the precise dose and schedule will vary. SACT is sometimes used concurrently with other treatments such as bisphosphonates or radiotherapy. Side-effects will be treatment-specific.<br /> <br /> ===Hormone therapies===<br /> <br /> <br /> Hormone therapy is an indirect antitumour treatment which blocks the action of endogenous hormones or reduces their production within the body. Certain hormone-sensitive malignancies, particularly those of the prostate and breast, will often grow in response to specific hormones (androgens and oestrogens, respectively). Secondary metastases stemming from these primary tumours will, by extension, respond to hormone levels too. Androgen-responsive prostate cancer may be treated with drugs which lower androgen levels, such as gonadotrophin-releasing hormone (GnRH) receptor antagonists (peptides: '-''relix''&lt;nowiki/&gt;'; small-molecules: '-''golix''&lt;nowiki/&gt;'), GnRH receptor agonists ('-''relin''&lt;nowiki/&gt;'), and CYP17A1 inhibitors (such as abiraterone). Alternatively, androgen receptor blockers, such as bicalutamide or flutamide, can be effective. Oestrogen-responsive breast cancer may be treated with drugs which lower oestrogen levels, such as type I (exemestane) and type II (anastrozole, letrozole) aromatase inhibitors. Alternatively, selective oestrogen receptor modulators (SERMs), such as tamoxifen, can be effective. These modulators have mixed oestrogenic and antioestrogenic activity, which differs according to receptive tissue. Usefully in breast cancer, it is antioestrogenic in the breast; however, in the uterus and liver it is oestrogenic.<br /> ===Interventional radiology===<br /> The role of the interventional radiologist is ever-expanding. In the treatment of metastatic cancer there are procedures which are shared with or done solely by these interventionists. Two important treatments offered by the specialty for bone metastases are ablation and cementoplasty.<br /> <br /> '''Ablation''' is a medical term for when a procedural probe is introduced to an area of tissue (in this case tumour) and, using physical energy (heat or cold) or chemicals, cellular necrosis with subsequent scarring is achieved. It is useful for bony lesions if only there are one or two lesions to be targeted. The most common types of ablation are [[radiofrequency ablation]] (RFA), where an electric current passes through and heats a needle within the lesion, and cryoablation, where a cold probe within the lesion freezes and destroys cancer cells. Both are effective analgesic therapies; however, unlike in RFA, the ablation edge in cryoablation can be readily visualised with CT monitoring (as low-attenuation) and does not produce increased pain in the periprocedural period&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/21785102/&lt;/ref&gt;. Complications rates for each procedure are low, but localised infection and enduring neuropathic pain have been reported. <br /> <br /> '''Cementoplasty''' is a generic term for a group of medical procedures whereby acrylic bone cement, commonly polymethylmethacrylate (PMMA), is injected percutaneously into bone lesions for analgesic effect and/or stabilisation. It is commonly performed under sedation with local anaesthesia, and the cement is mixed with a radiopaque agent to allow visualisation with multi-plane fluoroscopy during injection&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/21629403&lt;/ref&gt;. Depending on where cementoplasty is used, it may be termed differently:<br /> <br /> *Osteoplasty (generic term, injection into non-axial bone lesions)<br /> *Vertebroplasty (injection into a vertebral lesion)<br /> *Kyphoplasty (mostly for vertebral fractures, this is vertebroplasty with use of intravertebral balloon inflation beforehand to restore vertebral height)<br /> *Sacroplasty (injection into a sacral lesion)<br /> <br /> ===Surgery===<br /> Surgery is not considered to be amongst the conventional treatments for bony metastases. It is indicated for fractures of the hip and of long bones, and if there is need for vertebral surgery in [[Metastatic spinal cord compression|MSCC]]. Sometimes if bone involvement leads to fracture causing peripheral nerve impingement or compression, surgery may also be necessary.<br /> <br /> ==Living with bone metastases==<br /> It is important to grasp that, in many instances, patients live with their bone metastases as a chronic (non-curable) condition. Adjustments will often need to be made to permit a continued good quality of life.<br /> <br /> '''Pain''' is very common with metastatic bony disease, and many treatments can be given to alleviate this pain. If pain is difficult to manage then input from pain and palliative care specialists (doctors and nurses) can be enormously helpful. Some patients find complementary therapies, such as massage and acupuncture, to be of benefit to their symptoms.<br /> <br /> '''Mobility''' can be severely impacted by skeletal metastasis. Depending on the location, burden, and extent of the bone disease, the risk of fracture can be high. Input from occupational therapists and physiotherapists can enhance the safety of patients and their environments, and minimise the risks of falling and fracture.<br /> <br /> '''Survival''' is an understandably common topic of discussion, particularly in the context of advanced metastatic cancer. The factors affecting survival with bone metastases are multifarious and as such any attempt at predicting exact survival is impracticable. However, there is some scope for estimation. The survival of patients who develop bone metastases from prostate or breast cancer is often measured in years, whereas the survival of patients with bone metastases from lung cancer is often measured in months.&lt;references /&gt;</div>

Alex https://oncopaedia.net/w/index.php?title=Articles:Steroid-induced_psychosis&diff=334 2020-08-14T12:25:58Z

<p>Alex: </p> <hr /> <div>Psychosis following administration of exogenous steroidal medication is a well-known but uncommon phenomenon. It is a dose-dependent disorder more often occurring after systemic steroid treatment, although there are reports of psychotic episodes following local steroid injections. In most instances the psychosis resolves without treatment, and is often of low severity and a short duration&lt;ref&gt;https://pubmed.ncbi.nlm.nih.gov/31656440/&lt;/ref&gt;. The diagnosis of steroid-induced psychosis hinges on exclusion, with a number of criteria needing to be met:<br /> <br /> *Psychosis (hallucination or delusion) must follow steroid administration<br /> *The episode is not better explained by a preexisting psychotic disorder<br /> *The episode does not occur concurrently with patient delirium<br /> *The episode must cause significant clinical distress or impairment<br /> <br /> It is therefore crucial to investigate and exclude potential differentials such as non-steroidal (potentially) psychosis-inducing medication, illicit drug use, intoxication by other licit means, electrolyte imbalance, any contributory infections, recent hypo- or hyper-glycaemia, intracranial pathology, or known psychiatric illness.<br /> &lt;references /&gt;</div>

Alex https://oncopaedia.net/w/index.php?title=User:Alex&diff=333 2020-04-30T14:22:47Z

<p>Alex: </p> <hr /> <div>Hello! My name's Alex and I am the founding editor of '''Oncopaedia'''. I'm a doctor working at Mount Vernon Cancer Centre in London.<br /> <br /> This site was built by my good friend (and now colleague!) [[User:Souradip|Souradip]] in May 2019, and he is responsible for keeping the site running. The designing and planning for Oncopaedia has been almost a year in the making, so I am very excited that the website has now finally launched!<br /> <br /> Please—create an account and start editing! This cancer wiki is only as good as ''you'' make it.<br /> <br /> For more about me, feel free to visit my [https://munster.me personal website] or follow my [https://twitter.com/DrMunster Twitter account].</div>

Alex https://oncopaedia.net/w/index.php?title=Articles:Oncological_emergencies&diff=332 2020-04-24T15:08:26Z

<p>Alex: </p> <hr /> <div>Acute emergencies in oncology are a group of conditions caused by complications of cancer or its treatment, that are life-threatening or irreversibly disabling if clinical management is delayed. As a consequence of our ability to treat increasingly larger numbers of patients effectively, the knowledge to recognise and respond swiftly to such presentations has never been more important.<br /> <br /> These emergencies may be encountered at any stage in the pathway of a patient's journey through cancer. This may be at presentation, during the course of treatment, or later in the disease process. Below reviews the most frequently encountered oncological emergencies. It may sound obvious, but it is worth bearing in mind that unrelated acute medical or surgical conditions may occur in patients with malignant disease. Generally, the management will be the same as that of a patient without known cancer.<br /> <br /> The emergencies are grouped according to the causative system of origin.<br /> <br /> ==Cardiovascular emergencies==<br /> <br /> *Superior vena cava obstruction<br /> *Cardiac tamponade (malignant pericardial effusion)<br /> *Venous thromboembolism<br /> *Extravasation injury<br /> *Complications of central venous devices&lt;ref&gt;https://oncologypro.esmo.org/Education-Library/Handbooks/Oncological-Emergencies&lt;/ref&gt;<br /> *Hypertensive crises<br /> <br /> ==Respiratory emergencies==<br /> <br /> *Acute large airway obstruction<br /> *Pulmonary haemorrhage<br /> *Respiratory failure<br /> *Intractable hiccups<br /> *Radiation pneumonitis<br /> *Pleural effusion (malignant)<br /> <br /> ==Metabolic emergencies==<br /> <br /> *Tumour lysis syndrome<br /> *[[Hypercalcaemia]]<br /> *Syndrome of inappropriate antidiuretic hormone secretion (SIADH)<br /> *Hypomagnesaemia<br /> *Hypoglycaemia<br /> <br /> ==Endocrine emergencies==<br /> <br /> *Thyroid dysfunction<br /> *Adrenal insufficiency<br /> <br /> ==Renal &amp; Urological emergencies==<br /> <br /> *Obstructive uropathy<br /> *Urate nephropathy (from TLS)<br /> *Haemorrhagic cystitis&lt;ref&gt;https://www.cancernetwork.com/articles/oncologic-emergencies&lt;/ref&gt;<br /> *Nephritis<br /> <br /> ==Gastrointestinal emergencies==<br /> <br /> *Bowel obstruction<br /> *Bowel perforation<br /> *Gastrointestinal haemorrhage<br /> *Nausea and vomiting (uncontrolled)<br /> *Mucositis (uncontrolled)<br /> *Diarrhoea (uncontrolled)<br /> *Biliary obstruction<br /> *Oesophageal obstruction<br /> *Abdominal ascites (malignant)<br /> *Neutropaenic enterocolitis<br /> *Transaminitis<br /> *Colitis<br /> <br /> ==Neurological emergencies==<br /> <br /> *Spinal cord compression<br /> *Cauda equina syndrome<br /> *Raised intracranial pressure<br /> *Seizures (fits)<br /> *Leptomeningeal disease<br /> <br /> ==Haematological emergencies==<br /> <br /> *Leukostasis<br /> *Hyperviscosity<br /> *Disseminated intravascular coagulation<br /> *Thrombocytopaenia<br /> *Febrile neutropaenia (neutropaenic sepsis)<br /> <br /> ==Ophthalmological emergencies==<br /> <br /> *[[Articles:Ocular and orbital metastases|Ocular and orbital metastases]]<br /> <br /> ==Musculoskeletal emergencies==<br /> <br /> *[[Articles:Bone metastases|Metastatic bone pain]]<br /> *[[Articles:Bone metastases|Pathological fractures]]<br /> <br /> ==Gynaecological emergencies==<br /> <br /> *[[Articles:Gynaecological haemorrhage|Gynaecological haemorrhage]]<br /> <br /> ==Dermatological emergencies==<br /> <br /> *[[Acute skin reactions]]<br /> <br /> ==Psychiatric emergencies==<br /> <br /> *[[Articles:Steroid-induced psychosis|Steroid-induced psychosis]]&lt;br /&gt;<br /> &lt;references /&gt;</div>

Alex https://oncopaedia.net/w/index.php?title=Articles:Steroid-induced_psychosis&diff=331 2020-04-24T15:06:01Z

<p>Alex: Page creation</p> <hr /> <div>Psychosis following administration of exogenous steroidal medication is a well-known but uncommon phenomenon. It is a dose-dependent disorder more often occurring after systemic steroid treatment, although there are reports of psychotic episodes following local steroid injections. In most instances the psychosis resolves without treatment, and is often of low severity and a short duration&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/31656440&lt;/ref&gt;. The diagnosis of steroid-induced psychosis hinges on exclusion, with a number of criteria needing to be met:<br /> <br /> * Psychosis (hallucination or delusion) must follow steroid administration<br /> * The episode is not better explained by a preexisting psychotic disorder<br /> * The episode does not occur concurrently with patient delirium<br /> * The episode must cause significant clinical distress or impairment<br /> <br /> It is therefore crucial to investigate and exclude potential differentials such as non-steroidal (potentially) psychosis-inducing medication, illicit drug use, intoxication by other licit means, electrolyte imbalance, any contributory infections, recent hypo- or hyper-glycaemia, intracranial pathology, or known psychiatric illness.</div>

Alex https://oncopaedia.net/w/index.php?title=Articles:Oncological_emergencies&diff=330 2020-04-24T14:09:29Z

<p>Alex: /* Musculoskeletal emergencies */</p> <hr /> <div>Acute emergencies in oncology are a group of conditions caused by complications of cancer or its treatment, that are life-threatening or irreversibly disabling if clinical management is delayed. As a consequence of our ability to treat increasingly larger numbers of patients effectively, the knowledge to recognise and respond swiftly to such presentations has never been more important.<br /> <br /> These emergencies may be encountered at any stage in the pathway of a patient's journey through cancer. This may be at presentation, during the course of treatment, or later in the disease process. Below reviews the most frequently encountered oncological emergencies. It may sound obvious, but it is worth bearing in mind that unrelated acute medical or surgical conditions may occur in patients with malignant disease. Generally, the management will be the same as that of a patient without known cancer.<br /> <br /> The emergencies are grouped according to the causative system of origin.<br /> <br /> ==Cardiovascular emergencies==<br /> <br /> *Superior vena cava obstruction<br /> *Cardiac tamponade (malignant pericardial effusion)<br /> *Venous thromboembolism<br /> *Extravasation injury<br /> *Complications of central venous devices&lt;ref&gt;https://oncologypro.esmo.org/Education-Library/Handbooks/Oncological-Emergencies&lt;/ref&gt;<br /> *Hypertensive crises<br /> <br /> ==Respiratory emergencies==<br /> <br /> *Acute large airway obstruction<br /> *Pulmonary haemorrhage<br /> *Respiratory failure<br /> *Intractable hiccups<br /> *Radiation pneumonitis<br /> *Pleural effusion (malignant)<br /> <br /> ==Metabolic emergencies==<br /> <br /> *Tumour lysis syndrome<br /> *[[Hypercalcaemia]]<br /> *Syndrome of inappropriate antidiuretic hormone secretion (SIADH)<br /> *Hypomagnesaemia<br /> *Hypoglycaemia<br /> <br /> ==Endocrine emergencies==<br /> <br /> *Thyroid dysfunction<br /> *Adrenal insufficiency<br /> <br /> ==Renal &amp; Urological emergencies==<br /> <br /> *Obstructive uropathy<br /> *Urate nephropathy (from TLS)<br /> *Haemorrhagic cystitis&lt;ref&gt;https://www.cancernetwork.com/articles/oncologic-emergencies&lt;/ref&gt;<br /> *Nephritis<br /> <br /> ==Gastrointestinal emergencies==<br /> <br /> *Bowel obstruction<br /> *Bowel perforation<br /> *Gastrointestinal haemorrhage<br /> *Nausea and vomiting (uncontrolled)<br /> *Mucositis (uncontrolled)<br /> *Diarrhoea (uncontrolled)<br /> *Biliary obstruction<br /> *Oesophageal obstruction<br /> *Abdominal ascites (malignant)<br /> *Neutropaenic enterocolitis<br /> *Transaminitis<br /> *Colitis<br /> <br /> ==Neurological emergencies==<br /> <br /> *Spinal cord compression<br /> *Cauda equina syndrome<br /> *Raised intracranial pressure<br /> *Seizures (fits)<br /> *Leptomeningeal disease<br /> <br /> ==Haematological emergencies==<br /> <br /> *Leukostasis<br /> *Hyperviscosity<br /> *Disseminated intravascular coagulation<br /> *Thrombocytopaenia<br /> *Febrile neutropaenia (neutropaenic sepsis)<br /> <br /> ==Ophthalmological emergencies==<br /> <br /> *[[Articles:Ocular and orbital metastases|Ocular and orbital metastases]]<br /> <br /> ==Musculoskeletal emergencies==<br /> <br /> *[[Articles:Bone metastases|Metastatic bone pain]]<br /> *[[Articles:Bone metastases|Pathological fractures]]<br /> <br /> ==Gynaecological emergencies==<br /> <br /> *[[Articles:Gynaecological haemorrhage|Gynaecological haemorrhage]]<br /> <br /> ==Dermatological emergencies==<br /> <br /> *[[Acute skin reactions]]<br /> <br /> ==Psychiatric emergencies==<br /> <br /> *[[Steroid-induced psychosis]]&lt;br /&gt;<br /> &lt;references /&gt;</div>

Alex https://oncopaedia.net/w/index.php?title=Articles:Bone_metastases&diff=329 2020-04-24T13:37:34Z

<p>Alex: </p> <hr /> <div>Metastases within bone can cause extreme and debilitating pain. Bone metastases are far more common than primary bone cancer, and many different cancer types can spread to the bone. The most common types of cancer which spread to bone are:<br /> <br /> *Breast<br /> *Prostate<br /> *Lung<br /> *Kidney<br /> *Thyroid<br /> <br /> Cancer can theoretically metastasize to any bone in the body, but in reality there is a predilection for certain sites. The most common sites are the vertebrae, ribs, pelvis, sternum, and the skull.<br /> <br /> ==Classification==<br /> A bone is a rigid organ, but it is far from physiologically static. To maintain bone strength, there is continuous breakdown and simultaneous reformation of bone, two processes which must finely balance for good bone health.<br /> <br /> '''Osteoblastic''' (or '''sclerotic''') metastases are characterised by the deposition of new bone. These are present most commonly in prostate cancer, but also occur in carcinoid, small cell lung cancer, medulloblastoma, and Hodgkin lymphoma. The molecular crosstalk between tumour and bone cells involves osteoblast-generating proteins such as Transforming Growth Factor, Bone Morphogenic Proteins (BMPs), and Endothelin-1&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12085970&lt;/ref&gt;.<br /> <br /> '''Osteolytic''' (or '''lytic''') metastases are characterised by the destruction and breakdown of normal bone. These often occur when breast cancer spreads to bone, which is primarily mediated by osteoclasts (bone cells that breaks down bone tissue) and is not a direct effect of metastasized tumour cells&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8086233/&lt;/ref&gt;. Other tumour types with osteolytic metastases include multiple myeloma, non-small cell lung cancer, thyroid cancer, non-Hodgkin lymphoma, and Langerhans' cell histiocytosis. Osteolytic metastases are more common than osteoblastic metastases.<br /> <br /> '''Mixed''' metastases are characterised by the presence of both osteolytic and osteoblastic lesions together in the same area of bone. These metastases are usually present in metastatic gastrointestinal and squamous cancers, as well as in secondary breast cancer. Although breast cancer gives rise to predominantly lytic lesions, around 15–20% of women have sclerotic or both types of lesions&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11346860/&lt;/ref&gt;.<br /> <br /> ==Diagnosis==<br /> <br /> ===Signs and symptoms===<br /> Bone metastases cause major morbidity, and high clinical suspicion should be kept for any patient with cancer that presents with:<br /> <br /> *Severe pain (poorly localised, worse at night)<br /> *Impaired mobility<br /> *[[Pathological fracture|Bone fracture]]<br /> *Bone marrow aplasia<br /> *Symptoms of (metastatic) [[Metastatic spinal cord compression|spinal cord compression]] (MSCC)<br /> *Symptoms in keeping with [[hypercalcaemia]]:<br /> **Constipation<br /> **Fatigue<br /> **Polyuria/polydipsia<br /> **Acute kidney injury (AKI)<br /> **Cardiac arrhythmia<br /> <br /> ===Bloods===<br /> When a patient with cancer presents with any of the signs or symptoms above, basic screening in the form of simple blood testing must be undertaken and complemented with appropriate imaging tests:<br /> <br /> *Full evaluation of bone turnover and potential hypercalcaemia:<br /> **Serum calcium<br /> **Serum phosphate<br /> **25-Hydroxyvitamin D<br /> **Thyroid-stimulating hormone (TSH)<br /> **Parathyroid hormone (PTH)<br /> **Serum creatinine<br /> **Alkaline phosphatase (ALP)<br /> *Full blood count (myelosuppression, anaemia)<br /> *Serum protein electrophoresis (SPEP; myeloma screen)<br /> *Tumour markers (such as PSA in prostate cancer)<br /> <br /> ===Imaging===<br /> Radiological tests are an essential component of diagnosing bony metastases. One or more imaging modalities may be required to confirm suspected cancerous spread to bone.<br /> <br /> '''Plain radiographs''' (X-ray scans) are quick, cost-effective, and widely-available, and should be the initial diagnostic test of choice when investigating bone pain. They are highly specific but lack sensitivity (44-50%) because early-stage metastatic lesions, particularly those up to 1 cm, may be more difficult to visualise. More than 50% of the trabecular bone must be involved before the lesion will be apparent on film and, due to the poor contrast of trabecular bone, lesions within the medulla are often less evident than those within cortical bone&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9025785/&lt;/ref&gt;. As outlined above, sclerotic metastases will appear more radiopaque than the surrounding bone, whereas lytic metastases will appear more radiolucent.<br /> <br /> '''Bone scintigraphy''' (bone scans) on the other hand is highly sensitive but with low specificity. Data from Technetium-99m ('''&lt;sup&gt;99m&lt;/sup&gt;Tc''') scintigraphy have shown false-negative rates as low as 11 to 38% (good sensitivity), with false-positive rates as high as 40% (poor specificity). It thus provides a non-specific osteoblastic indication of bone status, be it inflammatory, traumatic, or neoplastic in origin. Scintigraphy is still more specific and sensitive than either plain radiography or computed tomography, whilst magnetic resonance imaging is more efficacious in assessing vertebral metastases&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/2028061/&lt;/ref&gt;.<br /> <br /> '''Computed tomography''' (CT scans) has a high sensitivity, ranging from 71 to 100%, for the detection of metastatic bone lesions&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9362427/&lt;/ref&gt;. Because of the excellent soft tissue resolution of the images produced by CT, it is a particularly helpful modality to distinguish lytic and sclerotic metastases and to visualise their precise location(s) for biopsy.<br /> <br /> '''Magnetic resonance imaging''' (MRI scans) is useful in assessing bone marrow infiltration by tumour deposits, and is required (whole spine) for the proper diagnosis of [[Metastatic spinal cord compression|MSCC]]. It has similarly high specificity (73 to 100%) and sensitivity (82 to 100%) in screening for bone metastases&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10964746/&lt;/ref&gt;.<br /> <br /> '''Positron emission tomography''' (PET scans) detects tumour indirectly by measuring metabolic activity in the form of fluorodeoxyglucose ('''&lt;sup&gt;18&lt;/sup&gt;F''') tissue uptake. As such, its use is not limited to visualising only bony metastases, as &lt;sup&gt;18&lt;/sup&gt;F PET will reveal non-bony metastatic spread also&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8638000/&lt;/ref&gt;. The accuracy of PET is highly dependent on the primary tumour site from which imaged metastases originate. As a modality it is superior to scintigraphy in the screening of bony metastases from breast (specificity 94%, sensitivity 95%)&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12073051/&lt;/ref&gt; and lung (specificity 99%, sensitivity 92%)&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10478250/&lt;/ref&gt; malignancies, but has lower sensitivity in detecting the comparatively slower-growing bone metastases of prostate and renal cancers&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10520701/&lt;/ref&gt;. <br /> <br /> ===Biopsy===<br /> Sometimes it is necessary to diagnose metastases histologically, by removing cells or tissue from the bone lesion(s) directly. Usually this is in the form of a needle or surgical biopsy, and may be indicated if a primary cancer is not known. If the patient has a known primary cancer, then often imaging alone will suffice for the diagnosis of metastatic bone disease.<br /> <br /> ==Treatment==<br /> There are a variety of therapeutic interventions available to patients presenting with bone metastases, but consideration must be given to several patient-specific and tumour-dependent parameters, which include&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11738947/&lt;/ref&gt; (but are not limited to):<br /> <br /> *Lesion site(s) (localised or widespread)<br /> *Presence of extraskeletal metastasis<br /> *Tumour type and features (like receptors)<br /> *Prior treatment history (and response)<br /> *Clinical symptoms<br /> *Performance status<br /> <br /> ===Radiotherapy===<br /> Radiation therapy can provide excellent pain relief and is the treatment of choice for localised metastatic bone pain. However, the analgesic mechanisms of therapeutic skeletal irradiation are poorly understood. Onset of pain relief is usually quick, with a majority of patients experiencing benefit within one to two weeks. Patients who have little reduction in pain by six weeks are unlikely to demonstrate significant overall benefit&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/24782453/&lt;/ref&gt;. Other than localised bone pain, additional indications for radiotherapy include [[Metastatic spinal cord compression|MSCC]] and bones at high risk for [[pathological fracture]]&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/15978828/&lt;/ref&gt;. Two of the three main divisions of radiation therapy—the third being (sealed source) [[brachytherapy]]—can be used to treat bone metastases: systemic (unsealed source) [[radionuclide therapy]] and [[external beam radiotherapy]] (EBRT). <br /> <br /> '''Local-field [[External beam radiotherapy|EBRT]]''' is the standard choice of radiation therapy for treating bone metastases, as it focally targets the bone lesion and can achieve rates of substantial pain relief of up to 80 to 90%&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/6178497/&lt;/ref&gt;. Randomised controlled trials (RCTs) from the 1990s have shown that a single fraction of 8 gray (Gy) is as effective as fractionated doses of 20 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9681885&lt;/ref&gt;, 24 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10577695&lt;/ref&gt;, and 30 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10577696&lt;/ref&gt;. <br /> <br /> '''Wide-field''' (or '''hemibody''') '''[[External beam radiotherapy|EBRT]]''' is useful for widespread metastatic skeletal disease, though was more commonly used for multifocal pain when other effective therapies (chemo- and radionuclide) were not available. There are no RCTs comparing analgesic effect with and without wide-field radiotherapy. However, in terms of quasi-randomised and low-quality RCTs, there is data to suggest that use of fractionation is no more effective than single fraction treatment&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8823257&lt;/ref&gt;, that increasing doses beyond 8 Gy does not improve overall pain responses&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11395246&lt;/ref&gt;, and adding wide-field to local-field radiotherapy, whilst significantly halting disease progression (lesion size: P = 0.03; lesion number: P = 0.01), increases grade 3 to 4 haematological toxicity&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/1374061&lt;/ref&gt;. It is possible to classify wide-field treatments into three body regions, each with recommended single-fraction dose limits. Upper treatments (from skull or C1 to L2–L3) should be limited to 6 Gy, whereas mid-body (from L1 to upper third of femur) and lower (from L3–L4 to above knee) treatments should be limited to 8 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/6178497/&lt;/ref&gt;. Any treatments must be delivered with fields shaped to minimise irradiation of organs at risk, such as lung, liver, kidney and bowel. <br /> <br /> '''[[Stereotactic radiotherapy|Stereotactic]] [[External beam radiotherapy|EBRT]]''' is a promising treatment option which delivers higher doses of radiation to tumours in shorter periods in time. When used for extracranial cancers it is interchangeably termed Stereotactic Body Radiation Therapy ('''[[Stereotactic radiotherapy|SBRT]]''') or Stereotactic Ablative Radiotherapy ('''[[Stereotactic radiotherapy|SABR]]'''), the latter of which is appealingly onomatopoeic. When this technique is used for treating malignancy within the brain or some other part of the head, it is termed Stereotactic RadioSurgery ('''[[Stereotactic radiotherapy|SRS]]'''). SBRT/SABR can be used both for primary cancers (lung, liver, prostate, renal) and secondary metastases (bone/spine, lung, liver). There are a number of advantages of stereotactic radiotherapy, the most obvious of which is the potential completion of treatment within a single day, rather than over a number of weeks. The other major benefit is that it obviates the need to irradiate large portions of bone, which lowers the risk of further functional marrow depletion in a patient cohort already at risk of poor marrow reserve. Preserving skeletal marrow function can permit continuous chemotherapy in these patients. The primary limitations of SBRT/SABR are that it is more expensive to deliver than conventional EBRT and that there is a paucity of RCT data comparing its use to standard EBRT management&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/18619121/&lt;/ref&gt;. However, a recent single-centre phase II trial appeared to show that SBRT/SABR provides superior pain relief to conventional multifraction radiotherapy, with no observed difference in adverse events or other aspects of quality of life&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/31021390&lt;/ref&gt;. <br /> <br /> '''[[Radionuclide therapy]]''' (or '''radioisotope therapy''') is the systemic administration of radionuclides (also known as radioisotopes) as unsealed radioactive sources that selectively deliver radiation to tumours or target organs. They are taken up predominantly at sites of bone formation, and are therefore most likely best effective for the palliation of osteoblastic (sclerotic) metastases. Common radionuclides approved for the treatment of painful bone metastases include phosphorus-32 ('''&lt;sup&gt;32&lt;/sup&gt;P'''; ''β''-decay), strontium-89 ('''&lt;sup&gt;89&lt;/sup&gt;Sr'''; ''β''-decay), samarium-153 ('''&lt;sup&gt;153&lt;/sup&gt;Sm'''; ''β''- and ''γ''-decay), and rhenium-186 ('''&lt;sup&gt;186&lt;/sup&gt;Re'''; ''β''- and ''γ''-decay). The added advantage of gamma ray emission during decay is that it permits nuclear imaging monitoring of radionuclide biodistribution during therapy. These radionuclides target bone through various mechanisms. &lt;sup&gt;32&lt;/sup&gt;P passes through inorganic phosphate pathways, whereas &lt;sup&gt;89&lt;/sup&gt;Sr is a calcium mimetic and is taken up as a direct analogue of this earth metal. The final two agents are targeted to bone via chelation to phosphonate compounds: &lt;sup&gt;153&lt;/sup&gt;Sm is paired to ethylenediaminetetramethylenephosphonate (EDTMP) and &lt;sup&gt;186&lt;/sup&gt;Re to 1,1-hydroxyethylidene diphosphonate (HEDP). Common toxicities from treatment include myelosuppression and a transient pain flare, the latter of which usually heralds a favourable response. A more recently developed radionuclide, radium-223 (&lt;sup&gt;'''223'''&lt;/sup&gt;'''Ra'''; ''α''-, ''β''-, and ''γ''-decay) is a calcium mimetic which emits over 95% of decay energy in the form of alpha radiation&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/17062709&lt;/ref&gt;. Owing to their comparatively large size the emitted alpha particles have a more limited depth of penetration into surrounding tissues (around 2–10 cells), thereby producing a more potently localised cytotoxic effect. Despite their symptomatic benefits in refractory, widespread bone metastases, neither &lt;sup&gt;89&lt;/sup&gt;Sr nor &lt;sup&gt;153&lt;/sup&gt;Sm have been shown to improve overall survival in interventional trials; however, &lt;sup&gt;223&lt;/sup&gt;Ra use in metastatic castration-resistant prostate cancer patients in the ALSYMPCA (ALpharadin in SYMptomatic Prostate CAncer) trial was shown to significantly prolong overall survival&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/23863050/&lt;/ref&gt;. <br /> <br /> ===Bisphosphonates===<br /> Analogues of the natural bone demineralisation inhibitor pyrophosphate, bisphosphonates are useful in the treatment of poorly localised bone pain and in previously irradiated bone lesions. They bind with high affinity to exposed bone mineral where they are internalised by osteoclasts, within which they disrupt the processes of bone resorption and can induce apoptosis. Data have shown that bisphosphonates may have direct pro-apoptotic effects on nearby metastatic cancer cells also&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9362432/&lt;/ref&gt;. In halting the mobilisation of calcium and phosphate from bone, bisphosphonate use (together with rehydration) is now standard of care for malignancy-induced hypercalcaemia&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9025784/&lt;/ref&gt;. The analgesic effect of these agents is independent of underlying tumour characteristics, with osteolytic and osteoblastic lesions responding similarly&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9496390&lt;/ref&gt;. Many patients tolerate bisphosphonates without major concern, but common side-effects include flu-like myalgic symptoms, diarrhoea, nausea and reflux. It is exceedingly rare but one must be aware of the risk of developing osteonecrosis of the jaw. These medications undergo renal excretion and as such should be avoided in tumour-induced hypercalcaemia or metastatic bone disease if serum creatinine is greater than 400 μmol/L or 265 μmol/L, respectively. Bisphosphonates are divided into three generations of drug: first-generation (tiludronate, clodronate, etidronate), second-generation (ibandronate, alendronate, paimdronate), and third-generation (zoledronate, risedronate). One of the newest agents, zoledronate is 100-times more effective than second-generation pamidronate&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12558465/&lt;/ref&gt;. Whilst receiving bisphosphonate therapy, patients should take protective vitamin D and calcium supplements.<br /> <br /> ===Denosumab===<br /> Denosumab is a monoclonal antibody which binds to and inhibits the action of the RANK receptor ligand (RANKL). RANK is located on the surface of osteoclast progenitor cells and its activation stimulates their development into mature osteoclasts. Therefore denosumab, administered as a subcutaneous injection of 120 mg every four weeks, can help prevent bone destruction and fracture in patients with bone metastases. The antibody is cleared from the body by the reticuloendothelial system and can therefore be used in patients with poor renal function, in whom bisphosphonate use would be contraindicated&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/21145999/&lt;/ref&gt;. Additionally, data have shown that denosumab use causes greater suppression of osteolytic markers than bisphosphonate use in metastatic patients with breast&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/21060033/&lt;/ref&gt; or prostate&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/21353695/&lt;/ref&gt; cancer. However its effectiveness in comparison to bisphosphonates for patients with lung cancer or multiple myeloma is similar for the prevention of skeletal-related events (SRE), and indeed patients with multiple myeloma showed worse overall survival when treated with denosumab instead of zoledronate&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/21343556/&lt;/ref&gt;. <br /> <br /> ===Systemic anticancer therapies===<br /> [[Systemic anticancer therapy]] (SACT) refers to all drugs administered systemically with direct anticancer activity. This includes all conventional cytotoxic chemotherapies, all small molecule or antibody treatments, and all types of immunotherapy. Hormonal agents are not included within this categorisation. SACT may be considered for bone metastases if a primary tumour is known or subsequently confirmed. The specific therapy used will be the same therapy as typically used for the culprit primary cancer, though the precise dose and schedule will vary. SACT is sometimes used concurrently with other treatments such as bisphosphonates or radiotherapy. Side-effects will be treatment-specific.<br /> <br /> ===Hormone therapies===<br /> <br /> <br /> Hormone therapy is an indirect antitumour treatment which blocks the action of endogenous hormones or reduces their production within the body. Certain hormone-sensitive malignancies, particularly those of the prostate and breast, will often grow in response to specific hormones (androgens and oestrogens, respectively). Secondary metastases stemming from these primary tumours will, by extension, respond to hormone levels too. Androgen-responsive prostate cancer may be treated with drugs which lower androgen levels, such as gonadotrophin-releasing hormone (GnRH) receptor antagonists (peptides: '-''relix''&lt;nowiki/&gt;'; small-molecules: '-''golix''&lt;nowiki/&gt;'), GnRH receptor agonists ('-''relin''&lt;nowiki/&gt;'), and CYP17A1 inhibitors (such as abiraterone). Alternatively, androgen receptor blockers, such as bicalutamide or flutamide, can be effective. Oestrogen-responsive breast cancer may be treated with drugs which lower oestrogen levels, such as type I (exemestane) and type II (anastrozole, letrozole) aromatase inhibitors. Alternatively, selective oestrogen receptor modulators (SERMs), such as tamoxifen, can be effective. These modulators have mixed oestrogenic and antioestrogenic activity, which differs according to receptive tissue. Usefully in breast cancer, it is antioestrogenic in the breast; however, in the uterus and liver it is oestrogenic.<br /> ===Interventional radiology===<br /> The role of the interventional radiologist is ever-expanding. In the treatment of metastatic cancer there are procedures which are shared with or done solely by these interventionists. Two important treatments offered by the specialty for bone metastases are ablation and cementoplasty.<br /> <br /> '''Ablation''' is a medical term for when a procedural probe is introduced to an area of tissue (in this case tumour) and, using physical energy (heat or cold) or chemicals, cellular necrosis with subsequent scarring is achieved. It is useful for bony lesions if only there are one or two lesions to be targeted. The most common types of ablation are [[radiofrequency ablation]] (RFA), where an electric current passes through and heats a needle within the lesion, and cryoablation, where a cold probe within the lesion freezes and destroys cancer cells. Both are effective analgesic therapies; however, unlike in RFA, the ablation edge in cryoablation can be readily visualised with CT monitoring (as low-attenuation) and does not produce increased pain in the periprocedural period&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/21785102/&lt;/ref&gt;. Complications rates for each procedure are low, but localised infection and enduring neuropathic pain have been reported. <br /> <br /> '''Cementoplasty''' is a generic term for a group of medical procedures whereby acrylic bone cement, commonly polymethylmethacrylate (PMMA), is injected percutaneously into bone lesions for analgesic effect and/or stabilisation. It is commonly performed under sedation with local anaesthesia, and the cement is mixed with a radiopaque agent to allow visualisation with multi-plane fluoroscopy during injection&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/21629403&lt;/ref&gt;. Depending on where cementoplasty is used, it may be termed differently:<br /> <br /> *Osteoplasty (generic term, injection into non-axial bone lesions)<br /> *Vertebroplasty (injection into a vertebral lesion)<br /> *Kyphoplasty (mostly for vertebral fractures, this is vertebroplasty with use of intravertebral balloon inflation beforehand to restore vertebral height)<br /> *Sacroplasty (injection into a sacral lesion)<br /> <br /> ===Surgery===<br /> Surgery is not considered to be amongst the conventional treatments for bony metastases. It is indicated for fractures of the hip and of long bones, and if there is need for vertebral surgery in [[Metastatic spinal cord compression|MSCC]]. Sometimes if bone involvement leads to fracture causing peripheral nerve impingement or compression, surgery may also be necessary.<br /> <br /> ==Living with bone metastases==<br /> It is important to grasp that, in many instances, patients live with their bone metastases as a chronic (non-curable) condition. Adjustments will often need to be made to permit a continued good quality of life.<br /> <br /> '''Pain''' is very common with metastatic bony disease, and many treatments can be given to alleviate this pain. If pain is difficult to manage then input from pain and palliative care specialists (doctors and nurses) can be enormously helpful. Some patients find complementary therapies, such as massage and acupuncture, to be of benefit to their symptoms.<br /> <br /> '''Mobility''' can be severely impacted by skeletal metastasis. Depending on the location, burden, and extent of the bone disease, the risk of fracture can be high. Input from occupational therapists and physiotherapists can enhance the safety of patients and their environments, and minimise the risks of falling and fracture.<br /> <br /> '''Survival''' is an understandably common topic of discussion, particularly in the context of advanced metastatic cancer. The factors affecting survival with bone metastases are multifarious and as such any attempt at predicting exact survival is impracticable. However, there is some scope for estimation. The survival of patients who develop bone metastases from prostate or breast cancer is often measured in years, whereas the survival of patients with bone metastases from lung cancer is often measured in months.&lt;references /&gt;</div>

Alex https://oncopaedia.net/w/index.php?title=Articles:Bone_metastases&diff=328 2020-04-24T07:47:29Z

<p>Alex: </p> <hr /> <div>Metastases within bone can cause extreme and debilitating pain. Bone metastases are far more common than primary bone cancer, and many different cancer types can spread to the bone. The most common types of cancer which spread to bone are:<br /> <br /> *Breast<br /> *Prostate<br /> *Lung<br /> *Kidney<br /> *Thyroid<br /> <br /> Cancer can theoretically metastasize to any bone in the body, but in reality there is a predilection for certain sites. The most common sites are the vertebrae, ribs, pelvis, sternum, and the skull.<br /> <br /> ==Classification==<br /> A bone is a rigid organ, but it is far from physiologically static. To maintain bone strength, there is continuous breakdown and simultaneous reformation of bone, two processes which must finely balance for good bone health.<br /> <br /> '''Osteoblastic''' (or '''sclerotic''') metastases are characterised by the deposition of new bone. These are present most commonly in prostate cancer, but also occur in carcinoid, small cell lung cancer, medulloblastoma, and Hodgkin lymphoma. The molecular crosstalk between tumour and bone cells involves osteoblast-generating proteins such as Transforming Growth Factor, Bone Morphogenic Proteins (BMPs), and Endothelin-1&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12085970&lt;/ref&gt;.<br /> <br /> '''Osteolytic''' (or '''lytic''') metastases are characterised by the destruction and breakdown of normal bone. These often occur when breast cancer spreads to bone, which is primarily mediated by osteoclasts (bone cells that breaks down bone tissue) and is not a direct effect of metastasized tumour cells&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8086233/&lt;/ref&gt;. Other tumour types with osteolytic metastases include multiple myeloma, non-small cell lung cancer, thyroid cancer, non-Hodgkin lymphoma, and Langerhans' cell histiocytosis. Osteolytic metastases are more common than osteoblastic metastases.<br /> <br /> '''Mixed''' metastases are characterised by the presence of both osteolytic and osteoblastic lesions together in the same area of bone. These metastases are usually present in metastatic gastrointestinal and squamous cancers, as well as in secondary breast cancer. Although breast cancer gives rise to predominantly lytic lesions, around 15–20% of women have sclerotic or both types of lesions&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11346860/&lt;/ref&gt;.<br /> <br /> ==Diagnosis==<br /> <br /> ===Signs and symptoms===<br /> Bone metastases cause major morbidity, and high clinical suspicion should be kept for any patient with cancer that presents with:<br /> <br /> *Severe pain (poorly localised, worse at night)<br /> *Impaired mobility<br /> *[[Pathological fracture|Bone fracture]]<br /> *Bone marrow aplasia<br /> *Symptoms of (metastatic) [[Metastatic spinal cord compression|spinal cord compression]] (MSCC)<br /> *Symptoms in keeping with [[hypercalcaemia]]:<br /> **Constipation<br /> **Fatigue<br /> **Polyuria/polydipsia<br /> **Acute kidney injury (AKI)<br /> **Cardiac arrhythmia<br /> <br /> ===Bloods===<br /> When a patient with cancer presents with any of the signs or symptoms above, basic screening in the form of simple blood testing must be undertaken and complemented with appropriate imaging tests:<br /> <br /> *Full evaluation of bone turnover and potential hypercalcaemia:<br /> **Serum calcium<br /> **Serum phosphate<br /> **25-Hydroxyvitamin D<br /> **Thyroid-stimulating hormone (TSH)<br /> **Parathyroid hormone (PTH)<br /> **Serum creatinine<br /> **Alkaline phosphatase (ALP)<br /> *Full blood count (myelosuppression, anaemia)<br /> *Serum protein electrophoresis (SPEP; myeloma screen)<br /> *Tumour markers (such as PSA in prostate cancer)<br /> <br /> ===Imaging===<br /> Radiological tests are an essential component of diagnosing bony metastases. One or more imaging modalities may be required to confirm suspected cancerous spread to bone.<br /> <br /> '''Plain radiographs''' (X-ray scans) are quick, cost-effective, and widely-available, and should be the initial diagnostic test of choice when investigating bone pain. They are highly specific but lack sensitivity (44-50%) because early-stage metastatic lesions, particularly those up to 1 cm, may be more difficult to visualise. More than 50% of the trabecular bone must be involved before the lesion will be apparent on film and, due to the poor contrast of trabecular bone, lesions within the medulla are often less evident than those within cortical bone&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9025785/&lt;/ref&gt;. As outlined above, sclerotic metastases will appear more radiopaque than the surrounding bone, whereas lytic metastases will appear more radiolucent.<br /> <br /> '''Bone scintigraphy''' (bone scans) on the other hand is highly sensitive but with low specificity. Data from Technetium-99m ('''&lt;sup&gt;99m&lt;/sup&gt;Tc''') scintigraphy have shown false-negative rates as low as 11 to 38% (good sensitivity), with false-positive rates as high as 40% (poor specificity). It thus provides a non-specific osteoblastic indication of bone status, be it inflammatory, traumatic, or neoplastic in origin. Scintigraphy is still more specific and sensitive than either plain radiography or computed tomography, whilst magnetic resonance imaging is more efficacious in assessing vertebral metastases&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/2028061/&lt;/ref&gt;.<br /> <br /> '''Computed tomography''' (CT scans) has a high sensitivity, ranging from 71 to 100%, for the detection of metastatic bone lesions&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9362427/&lt;/ref&gt;. Because of the excellent soft tissue resolution of the images produced by CT, it is a particularly helpful modality to distinguish lytic and sclerotic metastases and to visualise their precise location(s) for biopsy.<br /> <br /> '''Magnetic resonance imaging''' (MRI scans) is useful in assessing bone marrow infiltration by tumour deposits, and is required (whole spine) for the proper diagnosis of [[Metastatic spinal cord compression|MSCC]]. It has similarly high specificity (73 to 100%) and sensitivity (82 to 100%) in screening for bone metastases&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10964746/&lt;/ref&gt;.<br /> <br /> '''Positron emission tomography''' (PET scans) detects tumour indirectly by measuring metabolic activity in the form of fluorodeoxyglucose ('''&lt;sup&gt;18&lt;/sup&gt;F''') tissue uptake. As such, its use is not limited to visualising only bony metastases, as &lt;sup&gt;18&lt;/sup&gt;F PET will reveal non-bony metastatic spread also&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8638000/&lt;/ref&gt;. The accuracy of PET is highly dependent on the primary tumour site from which imaged metastases originate. As a modality it is superior to scintigraphy in the screening of bony metastases from breast (specificity 94%, sensitivity 95%)&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12073051/&lt;/ref&gt; and lung (specificity 99%, sensitivity 92%)&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10478250/&lt;/ref&gt; malignancies, but has lower sensitivity in detecting the comparatively slower-growing bone metastases of prostate and renal cancers&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10520701/&lt;/ref&gt;. <br /> <br /> ===Biopsy===<br /> Sometimes it is necessary to diagnose metastases histologically, by removing cells or tissue from the bone lesion(s) directly. Usually this is in the form of a needle or surgical biopsy, and may be indicated if a primary cancer is not known. If the patient has a known primary cancer, then often imaging alone will suffice for the diagnosis of metastatic bone disease.<br /> <br /> ==Treatment==<br /> There are a variety of therapeutic interventions available to patients presenting with bone metastases, but consideration must be given to several patient-specific and tumour-dependent parameters, which include&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11738947/&lt;/ref&gt; (but are not limited to):<br /> <br /> *Lesion site(s) (localised or widespread)<br /> *Presence of extraskeletal metastasis<br /> *Tumour type and features (like receptors)<br /> *Prior treatment history (and response)<br /> *Clinical symptoms<br /> *Performance status<br /> <br /> ===Radiotherapy===<br /> Radiation therapy can provide excellent pain relief and is the treatment of choice for localised metastatic bone pain. However, the analgesic mechanisms of therapeutic skeletal irradiation are poorly understood. Onset of pain relief is usually quick, with a majority of patients experiencing benefit within one to two weeks. Patients who have little reduction in pain by six weeks are unlikely to demonstrate significant overall benefit&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/24782453/&lt;/ref&gt;. Other than localised bone pain, additional indications for radiotherapy include [[Metastatic spinal cord compression|MSCC]] and bones at high risk for [[pathological fracture]]&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/15978828/&lt;/ref&gt;. Two of the three main divisions of radiation therapy—the third being (sealed source) [[brachytherapy]]—can be used to treat bone metastases: systemic (unsealed source) [[radionuclide therapy]] and [[external beam radiotherapy]] (EBRT). <br /> <br /> '''Local-field [[External beam radiotherapy|EBRT]]''' is the standard choice of radiation therapy for treating bone metastases, as it focally targets the bone lesion and can achieve rates of substantial pain relief of up to 80 to 90%&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/6178497/&lt;/ref&gt;. Randomised controlled trials (RCTs) from the 1990s have shown that a single fraction of 8 gray (Gy) is as effective as fractionated doses of 20 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9681885&lt;/ref&gt;, 24 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10577695&lt;/ref&gt;, and 30 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10577696&lt;/ref&gt;. <br /> <br /> '''Wide-field''' (or '''hemibody''') '''[[External beam radiotherapy|EBRT]]''' is useful for widespread metastatic skeletal disease, though was more commonly used for multifocal pain when other effective therapies (chemo- and radionuclide) were not available. There are no RCTs comparing analgesic effect with and without wide-field radiotherapy. However, in terms of quasi-randomised and low-quality RCTs, there is data to suggest that use of fractionation is no more effective than single fraction treatment&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8823257&lt;/ref&gt;, that increasing doses beyond 8 Gy does not improve overall pain responses&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11395246&lt;/ref&gt;, and adding wide-field to local-field radiotherapy, whilst significantly halting disease progression (lesion size: P = 0.03; lesion number: P = 0.01), increases grade 3 to 4 haematological toxicity&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/1374061&lt;/ref&gt;. It is possible to classify wide-field treatments into three body regions, each with recommended single-fraction dose limits. Upper treatments (from skull or C1 to L2–L3) should be limited to 6 Gy, whereas mid-body (from L1 to upper third of femur) and lower (from L3–L4 to above knee) treatments should be limited to 8 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/6178497/&lt;/ref&gt;. Any treatments must be delivered with fields shaped to minimise irradiation of organs at risk, such as lung, liver, kidney and bowel. <br /> <br /> '''[[Stereotactic radiotherapy|Stereotactic]] [[External beam radiotherapy|EBRT]]''' is a promising treatment option which delivers higher doses of radiation to tumours in shorter periods in time. When used for extracranial cancers it is interchangeably termed Stereotactic Body Radiation Therapy ('''[[Stereotactic radiotherapy|SBRT]]''') or Stereotactic Ablative Radiotherapy ('''[[Stereotactic radiotherapy|SABR]]'''), the latter of which is appealingly onomatopoeic. When this technique is used for treating malignancy within the brain or some other part of the head, it is termed Stereotactic RadioSurgery ('''[[Stereotactic radiotherapy|SRS]]'''). SBRT/SABR can be used both for primary cancers (lung, liver, prostate, renal) and secondary metastases (bone/spine, lung, liver). There are a number of advantages of stereotactic radiotherapy, the most obvious of which is the potential completion of treatment within a single day, rather than over a number of weeks. The other major benefit is that it obviates the need to irradiate large portions of bone, which lowers the risk of further functional marrow depletion in a patient cohort already at risk of poor marrow reserve. Preserving skeletal marrow function can permit continuous chemotherapy in these patients. The primary limitations of SBRT/SABR are that it is more expensive to deliver than conventional EBRT and that there is a paucity of RCT data comparing its use to standard EBRT management&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/18619121/&lt;/ref&gt;. However, a recent single-centre phase II trial appeared to show that SBRT/SABR provides superior pain relief to conventional multifraction radiotherapy, with no observed difference in adverse events or other aspects of quality of life&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/31021390&lt;/ref&gt;. <br /> <br /> '''[[Radionuclide therapy]]''' (or '''radioisotope therapy''') is the systemic administration of radionuclides (also known as radioisotopes) as unsealed radioactive sources that selectively deliver radiation to tumours or target organs. They are taken up predominantly at sites of bone formation, and are therefore most likely best effective for the palliation of osteoblastic (sclerotic) metastases. Common radionuclides approved for the treatment of painful bone metastases include phosphorus-32 ('''&lt;sup&gt;32&lt;/sup&gt;P'''; ''β''-decay), strontium-89 ('''&lt;sup&gt;89&lt;/sup&gt;Sr'''; ''β''-decay), samarium-153 ('''&lt;sup&gt;153&lt;/sup&gt;Sm'''; ''β''- and ''γ''-decay), and rhenium-186 ('''&lt;sup&gt;186&lt;/sup&gt;Re'''; ''β''- and ''γ''-decay). The added advantage of gamma ray emission during decay is that it permits nuclear imaging monitoring of radionuclide biodistribution during therapy. These radionuclides target bone through various mechanisms. &lt;sup&gt;32&lt;/sup&gt;P passes through inorganic phosphate pathways, whereas &lt;sup&gt;89&lt;/sup&gt;Sr is a calcium mimetic and is taken up as a direct analogue of this earth metal. The final two agents are targeted to bone via chelation to phosphonate compounds: &lt;sup&gt;153&lt;/sup&gt;Sm is paired to ethylenediaminetetramethylenephosphonate (EDTMP) and &lt;sup&gt;186&lt;/sup&gt;Re to 1,1-hydroxyethylidene diphosphonate (HEDP). Common toxicities from treatment include myelosuppression and a transient pain flare, the latter of which usually heralds a favourable response. A more recently developed radionuclide, radium-223 (&lt;sup&gt;'''223'''&lt;/sup&gt;'''Ra'''; ''α''-, ''β''-, and ''γ''-decay) is a calcium mimetic which emits over 95% of decay energy in the form of alpha radiation&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/17062709&lt;/ref&gt;. Owing to their comparatively large size the emitted alpha particles have a more limited depth of penetration into surrounding tissues (around 2–10 cells), thereby producing a more potently localised cytotoxic effect. Despite their symptomatic benefits in refractory, widespread bone metastases, neither &lt;sup&gt;89&lt;/sup&gt;Sr nor &lt;sup&gt;153&lt;/sup&gt;Sm have been shown to improve overall survival in interventional trials; however, &lt;sup&gt;223&lt;/sup&gt;Ra use in metastatic castration-resistant prostate cancer patients in the ALSYMPCA (ALpharadin in SYMptomatic Prostate CAncer) trial was shown to significantly prolong overall survival&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/23863050/&lt;/ref&gt;. <br /> <br /> ===Bisphosphonates===<br /> Analogues of the natural bone demineralisation inhibitor pyrophosphate, bisphosphonates are useful in the treatment of poorly localised bone pain and in previously irradiated bone lesions. They bind with high affinity to exposed bone mineral where they are internalised by osteoclasts, within which they disrupt the processes of bone resorption and can induce apoptosis. Data have shown that bisphosphonates may have direct pro-apoptotic effects on nearby metastatic cancer cells also&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9362432/&lt;/ref&gt;. In halting the mobilisation of calcium and phosphate from bone, bisphosphonate use (together with rehydration) is now standard of care for malignancy-induced hypercalcaemia&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9025784/&lt;/ref&gt;. The analgesic effect of these agents is independent of underlying tumour characteristics, with osteolytic and osteoblastic lesions responding similarly&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9496390&lt;/ref&gt;. Many patients tolerate bisphosphonates without major concern, but common side-effects include flu-like myalgic symptoms, diarrhoea, nausea and reflux. It is exceedingly rare but one must be aware of the risk of developing osteonecrosis of the jaw. These medications undergo renal excretion and as such should be avoided in tumour-induced hypercalcaemia or metastatic bone disease if serum creatinine is greater than 400 μmol/L or 265 μmol/L, respectively. Bisphosphonates are divided into three generations of drug: first-generation (tiludronate, clodronate, etidronate), second-generation (ibandronate, alendronate, paimdronate), and third-generation (zoledronate, risedronate). One of the newest agents, zoledronate is 100-times more effective than second-generation pamidronate&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12558465/&lt;/ref&gt;. Whilst receiving bisphosphonate therapy, patients should take protective vitamin D and calcium supplements.<br /> <br /> ===Denosumab===<br /> Denosumab is a monoclonal antibody which binds to and inhibits the action of the RANK receptor ligand (RANKL). RANK is located on the surface of osteoclast progenitor cells and its activation stimulates their development into mature osteoclasts. Therefore denosumab, administered as a subcutaneous injection of 120 mg every four weeks, can help prevent bone destruction and fracture in patients with bone metastases. The antibody is cleared from the body by the reticuloendothelial system and can therefore be used in patients with poor renal function, in whom bisphosphonate use would be contraindicated&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/21145999/&lt;/ref&gt;. Additionally, data have shown that denosumab use causes greater suppression of osteolytic markers than bisphosphonate use in metastatic patients with breast&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/21060033/&lt;/ref&gt; or prostate&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/21353695/&lt;/ref&gt; cancer. However its effectiveness in comparison to bisphosphonates for patients with lung cancer or multiple myeloma is similar for the prevention of skeletal-related events (SRE), and indeed patients with multiple myeloma showed worse overall survival when treated with denosumab instead of zoledronate&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/21343556/&lt;/ref&gt;. <br /> <br /> ===Systemic anticancer therapies===<br /> [[Systemic anticancer therapy]] (SACT) refers to all drugs administered systemically with direct anticancer activity. This includes all conventional cytotoxic chemotherapies, all small molecule or antibody treatments, and all types of immunotherapy. Hormonal agents are not included within this categorisation. SACT may be considered for bone metastases if a primary tumour is known or subsequently confirmed. The specific therapy used will be the same therapy as typically used for the culprit primary cancer, though the precise dose and schedule will vary. SACT is sometimes used concurrently with other treatments such as bisphosphonates or radiotherapy. Side-effects will be treatment-specific.<br /> <br /> ===Hormone therapies===<br /> <br /> <br /> Hormone therapy is an indirect antitumour treatment which blocks the action of endogenous hormones or reduces their production within the body. Certain hormone-sensitive malignancies, particularly those of the prostate and breast, will often grow in response to specific hormones (androgens and oestrogens, respectively). Secondary metastases stemming from these primary tumours will, by extension, respond to hormone levels too. Androgen-responsive prostate cancer may be treated with drugs which lower androgen levels, such as gonadotrophin-releasing hormone (GnRH) receptor antagonists (peptides: '-''relix''&lt;nowiki/&gt;'; small-molecules: '-''golix''&lt;nowiki/&gt;'), GnRH receptor agonists ('-''relin''&lt;nowiki/&gt;'), and CYP17A1 inhibitors (such as abiraterone). Alternatively, androgen receptor blockers, such as bicalutamide or flutamide, can be effective. Oestrogen-responsive breast cancer may be treated with drugs which lower oestrogen levels, such as type I (exemestane) and type II (anastrozole, letrozole) aromatase inhibitors. Alternatively, selective oestrogen receptor modulators (SERMs), such as tamoxifen, can be effective. These modulators have mixed oestrogenic and antioestrogenic activity, which differs according to receptive tissue. Usefully in breast cancer, it is antioestrogenic in the breast; however, in the uterus and liver it is oestrogenic.<br /> ===Interventional radiology===<br /> The role of the interventional radiologist is ever-expanding. In the treatment of metastatic cancer there are procedures which are shared with or done solely by these interventionists. Two important treatments offered by the specialty for bone metastases are ablation and cementoplasty.<br /> <br /> '''Ablation''' is a medical term for when a procedural probe is introduced to an area of tissue (in this case tumour) and, using physical energy (heat or cold) or chemicals, cellular necrosis with subsequent scarring is achieved. It is useful for bony lesions if only there are one or two lesions to be targeted. The most common types of ablation are [[radiofrequency ablation]] (RFA), where an electric current passes through and heats a needle within the lesion, and cryoablation, where a cold probe within the lesion freezes and destroys cancer cells. Both are effective analgesic therapies; however, unlike in RFA, the ablation edge in cryoablation can be readily visualised with CT monitoring (as low-attenuation) and does not produce increased pain in the periprocedural period&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/21785102/&lt;/ref&gt;. Complications rates for each procedure are low, but localised infection and enduring neuropathic pain have been reported. <br /> <br /> '''Cementoplasty''' is a generic term for a group of medical procedures whereby acrylic bone cement, commonly polymethylmethacrylate (PMMA), is injected percutaneously into bone lesions for analgesic effect and/or stabilisation. It is commonly performed under sedation with local anaesthesia, and the cement is mixed with a radiopaque agent to allow visualisation with multi-plane fluoroscopy during injection&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/21629403&lt;/ref&gt;. Depending on where cementoplasty is used, it may be termed differently:<br /> <br /> *Osteoplasty (generic term, injection into non-axial bone lesions)<br /> *Vertebroplasty (injection into a vertebral lesion)<br /> *Kyphoplasty (mostly for vertebral fractures, this is vertebroplasty with use of intravertebral balloon inflation beforehand to restore vertebral height)<br /> *Sacroplasty (injection into a sacral lesion)<br /> <br /> ===Surgery===<br /> Surgery is not considered to be amongst the conventional treatments for bony metastases. It is indicated for fractures of the hip and of long bones, and if there is need for vertebral surgery in [[Metastatic spinal cord compression|MSCC]]. Sometimes if bone involvement leads to fracture causing peripheral nerve impingement or compression, surgery may also be necessary.<br /> <br /> ==Living with bone metastases==<br /> Pain, mobility and safety, survival&lt;references /&gt;</div>

Alex https://oncopaedia.net/w/index.php?title=Articles:Bone_metastases&diff=327 2020-04-24T07:42:32Z

<p>Alex: </p> <hr /> <div>Metastases within bone can cause extreme and debilitating pain. Bone metastases are far more common than primary bone cancer, and many different cancer types can spread to the bone. The most common types of cancer which spread to bone are:<br /> <br /> *Breast<br /> *Prostate<br /> *Lung<br /> *Kidney<br /> *Thyroid<br /> <br /> Cancer can theoretically metastasize to any bone in the body, but in reality there is a predilection for certain sites. The most common sites are the vertebrae, ribs, pelvis, sternum, and the skull.<br /> <br /> ==Classification==<br /> A bone is a rigid organ, but it is far from physiologically static. To maintain bone strength, there is continuous breakdown and simultaneous reformation of bone, two processes which must finely balance for good bone health.<br /> <br /> '''Osteoblastic''' (or '''sclerotic''') metastases are characterised by the deposition of new bone. These are present most commonly in prostate cancer, but also occur in carcinoid, small cell lung cancer, medulloblastoma, and Hodgkin lymphoma. The molecular crosstalk between tumour and bone cells involves osteoblast-generating proteins such as Transforming Growth Factor, Bone Morphogenic Proteins (BMPs), and Endothelin-1&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12085970&lt;/ref&gt;.<br /> <br /> '''Osteolytic''' (or '''lytic''') metastases are characterised by the destruction and breakdown of normal bone. These often occur when breast cancer spreads to bone, which is primarily mediated by osteoclasts (bone cells that breaks down bone tissue) and is not a direct effect of metastasized tumour cells&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8086233/&lt;/ref&gt;. Other tumour types with osteolytic metastases include multiple myeloma, non-small cell lung cancer, thyroid cancer, non-Hodgkin lymphoma, and Langerhans' cell histiocytosis. Osteolytic metastases are more common than osteoblastic metastases.<br /> <br /> '''Mixed''' metastases are characterised by the presence of both osteolytic and osteoblastic lesions together in the same area of bone. These metastases are usually present in metastatic gastrointestinal and squamous cancers, as well as in secondary breast cancer. Although breast cancer gives rise to predominantly lytic lesions, around 15–20% of women have sclerotic or both types of lesions&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11346860/&lt;/ref&gt;.<br /> <br /> ==Diagnosis==<br /> <br /> ===Signs and symptoms===<br /> Bone metastases cause major morbidity, and high clinical suspicion should be kept for any patient with cancer that presents with:<br /> <br /> *Severe pain (poorly localised, worse at night)<br /> *Impaired mobility<br /> *[[Pathological fracture|Bone fracture]]<br /> *Bone marrow aplasia<br /> *Symptoms of (metastatic) [[Metastatic spinal cord compression|spinal cord compression]] (MSCC)<br /> *Symptoms in keeping with [[hypercalcaemia]]:<br /> **Constipation<br /> **Fatigue<br /> **Polyuria/polydipsia<br /> **Acute kidney injury (AKI)<br /> **Cardiac arrhythmia<br /> <br /> ===Bloods===<br /> When a patient with cancer presents with any of the signs or symptoms above, basic screening in the form of simple blood testing must be undertaken and complemented with appropriate imaging tests:<br /> <br /> *Full evaluation of bone turnover and potential hypercalcaemia:<br /> **Serum calcium<br /> **Serum phosphate<br /> **25-Hydroxyvitamin D<br /> **Thyroid-stimulating hormone (TSH)<br /> **Parathyroid hormone (PTH)<br /> **Serum creatinine<br /> **Alkaline phosphatase (ALP)<br /> *Full blood count (myelosuppression, anaemia)<br /> *Serum protein electrophoresis (SPEP; myeloma screen)<br /> *Tumour markers (such as PSA in prostate cancer)<br /> <br /> ===Imaging===<br /> Radiological tests are an essential component of diagnosing bony metastases. One or more imaging modalities may be required to confirm suspected cancerous spread to bone.<br /> <br /> '''Plain radiographs''' (X-ray scans) are quick, cost-effective, and widely-available, and should be the initial diagnostic test of choice when investigating bone pain. They are highly specific but lack sensitivity (44-50%) because early-stage metastatic lesions, particularly those up to 1 cm, may be more difficult to visualise. More than 50% of the trabecular bone must be involved before the lesion will be apparent on film and, due to the poor contrast of trabecular bone, lesions within the medulla are often less evident than those within cortical bone&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9025785/&lt;/ref&gt;. As outlined above, sclerotic metastases will appear more radiopaque than the surrounding bone, whereas lytic metastases will appear more radiolucent.<br /> <br /> '''Bone scintigraphy''' (bone scans) on the other hand is highly sensitive but with low specificity. Data from Technetium-99m ('''&lt;sup&gt;99m&lt;/sup&gt;Tc''') scintigraphy have shown false-negative rates as low as 11 to 38% (good sensitivity), with false-positive rates as high as 40% (poor specificity). It thus provides a non-specific osteoblastic indication of bone status, be it inflammatory, traumatic, or neoplastic in origin. Scintigraphy is still more specific and sensitive than either plain radiography or computed tomography, whilst magnetic resonance imaging is more efficacious in assessing vertebral metastases&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/2028061/&lt;/ref&gt;.<br /> <br /> '''Computed tomography''' (CT scans) has a high sensitivity, ranging from 71 to 100%, for the detection of metastatic bone lesions&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9362427/&lt;/ref&gt;. Because of the excellent soft tissue resolution of the images produced by CT, it is a particularly helpful modality to distinguish lytic and sclerotic metastases and to visualise their precise location(s) for biopsy.<br /> <br /> '''Magnetic resonance imaging''' (MRI scans) is useful in assessing bone marrow infiltration by tumour deposits, and is required (whole spine) for the proper diagnosis of [[Metastatic spinal cord compression|MSCC]]. It has similarly high specificity (73 to 100%) and sensitivity (82 to 100%) in screening for bone metastases&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10964746/&lt;/ref&gt;.<br /> <br /> '''Positron emission tomography''' (PET scans) detects tumour indirectly by measuring metabolic activity in the form of fluorodeoxyglucose ('''&lt;sup&gt;18&lt;/sup&gt;F''') tissue uptake. As such, its use is not limited to visualising only bony metastases, as &lt;sup&gt;18&lt;/sup&gt;F PET will reveal non-bony metastatic spread also&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8638000/&lt;/ref&gt;. The accuracy of PET is highly dependent on the primary tumour site from which imaged metastases originate. As a modality it is superior to scintigraphy in the screening of bony metastases from breast (specificity 94%, sensitivity 95%)&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12073051/&lt;/ref&gt; and lung (specificity 99%, sensitivity 92%)&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10478250/&lt;/ref&gt; malignancies, but has lower sensitivity in detecting the comparatively slower-growing bone metastases of prostate and renal cancers&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10520701/&lt;/ref&gt;. <br /> <br /> ===Biopsy===<br /> Sometimes it is necessary to diagnose metastases histologically, by removing cells or tissue from the bone lesion(s) directly. Usually this is in the form of a needle or surgical biopsy, and may be indicated if a primary cancer is not known. If the patient has a known primary cancer, then often imaging alone will suffice for the diagnosis of metastatic bone disease.<br /> <br /> ==Treatment==<br /> There are a variety of therapeutic interventions available to patients presenting with bone metastases, but consideration must be given to several patient-specific and tumour-dependent parameters, which include&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11738947/&lt;/ref&gt; (but are not limited to):<br /> <br /> *Lesion site(s) (localised or widespread)<br /> *Presence of extraskeletal metastasis<br /> *Tumour type and features (like receptors)<br /> *Prior treatment history (and response)<br /> *Clinical symptoms<br /> *Performance status<br /> <br /> ===Radiotherapy===<br /> Radiation therapy can provide excellent pain relief and is the treatment of choice for localised metastatic bone pain. However, the analgesic mechanisms of therapeutic skeletal irradiation are poorly understood. Onset of pain relief is usually quick, with a majority of patients experiencing benefit within one to two weeks. Patients who have little reduction in pain by six weeks are unlikely to demonstrate significant overall benefit&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/24782453/&lt;/ref&gt;. Other than localised bone pain, additional indications for radiotherapy include [[Metastatic spinal cord compression|MSCC]] and bones at high risk for [[pathological fracture]]&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/15978828/&lt;/ref&gt;. Two of the three main divisions of radiation therapy—the third being (sealed source) [[brachytherapy]]—can be used to treat bone metastases: systemic (unsealed source) [[radionuclide therapy]] and [[external beam radiotherapy]] (EBRT). <br /> <br /> '''Local-field [[External beam radiotherapy|EBRT]]''' is the standard choice of radiation therapy for treating bone metastases, as it focally targets the bone lesion and can achieve rates of substantial pain relief of up to 80 to 90%&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/6178497/&lt;/ref&gt;. Randomised controlled trials (RCTs) from the 1990s have shown that a single fraction of 8 gray (Gy) is as effective as fractionated doses of 20 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9681885&lt;/ref&gt;, 24 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10577695&lt;/ref&gt;, and 30 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10577696&lt;/ref&gt;. <br /> <br /> '''Wide-field''' (or '''hemibody''') '''[[External beam radiotherapy|EBRT]]''' is useful for widespread metastatic skeletal disease, though was more commonly used for multifocal pain when other effective therapies (chemo- and radionuclide) were not available. There are no RCTs comparing analgesic effect with and without wide-field radiotherapy. However, in terms of quasi-randomised and low-quality RCTs, there is data to suggest that use of fractionation is no more effective than single fraction treatment&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8823257&lt;/ref&gt;, that increasing doses beyond 8 Gy does not improve overall pain responses&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11395246&lt;/ref&gt;, and adding wide-field to local-field radiotherapy, whilst significantly halting disease progression (lesion size: P = 0.03; lesion number: P = 0.01), increases grade 3 to 4 haematological toxicity&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/1374061&lt;/ref&gt;. It is possible to classify wide-field treatments into three body regions, each with recommended single-fraction dose limits. Upper treatments (from skull or C1 to L2–L3) should be limited to 6 Gy, whereas mid-body (from L1 to upper third of femur) and lower (from L3–L4 to above knee) treatments should be limited to 8 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/6178497/&lt;/ref&gt;. Any treatments must be delivered with fields shaped to minimise irradiation of organs at risk, such as lung, liver, kidney and bowel. <br /> <br /> '''[[Stereotactic radiotherapy|Stereotactic]] [[External beam radiotherapy|EBRT]]''' is a promising treatment option which delivers higher doses of radiation to tumours in shorter periods in time. When used for extracranial cancers it is interchangeably termed Stereotactic Body Radiation Therapy ('''[[Stereotactic radiotherapy|SBRT]]''') or Stereotactic Ablative Radiotherapy ('''[[Stereotactic radiotherapy|SABR]]'''), the latter of which is appealingly onomatopoeic. When this technique is used for treating malignancy within the brain or some other part of the head, it is termed Stereotactic RadioSurgery ('''[[Stereotactic radiotherapy|SRS]]'''). SBRT/SABR can be used both for primary cancers (lung, liver, prostate, renal) and secondary metastases (bone/spine, lung, liver). There are a number of advantages of stereotactic radiotherapy, the most obvious of which is the potential completion of treatment within a single day, rather than over a number of weeks. The other major benefit is that it obviates the need to irradiate large portions of bone, which lowers the risk of further functional marrow depletion in a patient cohort already at risk of poor marrow reserve. Preserving skeletal marrow function can permit continuous chemotherapy in these patients. The primary limitations of SBRT/SABR are that it is more expensive to deliver than conventional EBRT and that there is a paucity of RCT data comparing its use to standard EBRT management&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/18619121/&lt;/ref&gt;. However, a recent single-centre phase II trial appeared to show that SBRT/SABR provides superior pain relief to conventional multifraction radiotherapy, with no observed difference in adverse events or other aspects of quality of life&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/31021390&lt;/ref&gt;. <br /> <br /> '''[[Radionuclide therapy]]''' (or '''radioisotope therapy''') is the systemic administration of radionuclides (also known as radioisotopes) as unsealed radioactive sources that selectively deliver radiation to tumours or target organs. They are taken up predominantly at sites of bone formation, and are therefore most likely best effective for the palliation of osteoblastic (sclerotic) metastases. Common radionuclides approved for the treatment of painful bone metastases include phosphorus-32 ('''&lt;sup&gt;32&lt;/sup&gt;P'''; ''β''-decay), strontium-89 ('''&lt;sup&gt;89&lt;/sup&gt;Sr'''; ''β''-decay), samarium-153 ('''&lt;sup&gt;153&lt;/sup&gt;Sm'''; ''β''- and ''γ''-decay), and rhenium-186 ('''&lt;sup&gt;186&lt;/sup&gt;Re'''; ''β''- and ''γ''-decay). The added advantage of gamma ray emission during decay is that it permits nuclear imaging monitoring of radionuclide biodistribution during therapy. These radionuclides target bone through various mechanisms. &lt;sup&gt;32&lt;/sup&gt;P passes through inorganic phosphate pathways, whereas &lt;sup&gt;89&lt;/sup&gt;Sr is a calcium mimetic and is taken up as a direct analogue of this earth metal. The final two agents are targeted to bone via chelation to phosphonate compounds: &lt;sup&gt;153&lt;/sup&gt;Sm is paired to ethylenediaminetetramethylenephosphonate (EDTMP) and &lt;sup&gt;186&lt;/sup&gt;Re to 1,1-hydroxyethylidene diphosphonate (HEDP). Common toxicities from treatment include myelosuppression and a transient pain flare, the latter of which usually heralds a favourable response. A more recently developed radionuclide, radium-223 (&lt;sup&gt;'''223'''&lt;/sup&gt;'''Ra'''; ''α''-, ''β''-, and ''γ''-decay) is a calcium mimetic which emits over 95% of decay energy in the form of alpha radiation&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/17062709&lt;/ref&gt;. Owing to their comparatively large size the emitted alpha particles have a more limited depth of penetration into surrounding tissues (around 2–10 cells), thereby producing a more potently localised cytotoxic effect. Despite their symptomatic benefits in refractory, widespread bone metastases, neither &lt;sup&gt;89&lt;/sup&gt;Sr nor &lt;sup&gt;153&lt;/sup&gt;Sm have been shown to improve overall survival in interventional trials; however, &lt;sup&gt;223&lt;/sup&gt;Ra use in metastatic castration-resistant prostate cancer patients in the ALSYMPCA (ALpharadin in SYMptomatic Prostate CAncer) trial was shown to significantly prolong overall survival&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/23863050/&lt;/ref&gt;. <br /> <br /> ===Bisphosphonates===<br /> Analogues of the natural bone demineralisation inhibitor pyrophosphate, bisphosphonates are useful in the treatment of poorly localised bone pain and in previously irradiated bone lesions. They bind with high affinity to exposed bone mineral where they are internalised by osteoclasts, within which they disrupt the processes of bone resorption and can induce apoptosis. Data have shown that bisphosphonates may have direct pro-apoptotic effects on nearby metastatic cancer cells also&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9362432/&lt;/ref&gt;. In halting the mobilisation of calcium and phosphate from bone, bisphosphonate use (together with rehydration) is now standard of care for malignancy-induced hypercalcaemia&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9025784/&lt;/ref&gt;. The analgesic effect of these agents is independent of underlying tumour characteristics, with osteolytic and osteoblastic lesions responding similarly&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9496390&lt;/ref&gt;. Many patients tolerate bisphosphonates without major concern, but common side-effects include flu-like myalgic symptoms, diarrhoea, nausea and reflux. It is exceedingly rare but one must be aware of the risk of developing osteonecrosis of the jaw. These medications undergo renal excretion and as such should be avoided in tumour-induced hypercalcaemia or metastatic bone disease if serum creatinine is greater than 400 μmol/L or 265 μmol/L, respectively. Bisphosphonates are divided into three generations of drug: first-generation (tiludronate, clodronate, etidronate), second-generation (ibandronate, alendronate, paimdronate), and third-generation (zoledronate, risedronate). One of the newest agents, zoledronate is 100-times more effective than second-generation pamidronate&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12558465/&lt;/ref&gt;. Whilst receiving bisphosphonate therapy, patients should take protective vitamin D and calcium supplements.<br /> <br /> ===Denosumab===<br /> Denosumab is a monoclonal antibody which binds to and inhibits the action of the RANK receptor ligand (RANKL). RANK is located on the surface of osteoclast progenitor cells and its activation stimulates their development into mature osteoclasts. Therefore denosumab, administered as a subcutaneous injection of 120 mg every four weeks, can help prevent bone destruction and fracture in patients with bone metastases. The antibody is cleared from the body by the reticuloendothelial system and can therefore be used in patients with poor renal function, in whom bisphosphonate use would be contraindicated&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/21145999/&lt;/ref&gt;. Additionally, data have shown that denosumab use causes greater suppression of osteolytic markers than bisphosphonate use in metastatic patients with breast&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/21060033/&lt;/ref&gt; or prostate&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/21353695/&lt;/ref&gt; cancer. However its effectiveness in comparison to bisphosphonates for patients with lung cancer or multiple myeloma is similar for the prevention of skeletal-related events (SRE), and indeed patients with multiple myeloma showed worse overall survival when treated with denosumab instead of zoledronate&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/21343556/&lt;/ref&gt;. <br /> <br /> ===Systemic anticancer therapies===<br /> [[Systemic anticancer therapy]] (SACT) refers to all drugs administered systemically with direct anticancer activity. This includes all conventional cytotoxic chemotherapies, all small molecule or antibody treatments, and all types of immunotherapy. Hormonal agents are not included within this categorisation. SACT may be considered for bone metastases if a primary tumour is known or subsequently confirmed. The specific therapy used will be the same therapy as typically used for the culprit primary cancer, though the precise dose and schedule will vary. SACT is sometimes used concurrently with other treatments such as bisphosphonates or radiotherapy. Side-effects will be treatment-specific.<br /> <br /> ===Hormone therapies===<br /> <br /> <br /> Hormone therapy is an indirect antitumour treatment which blocks the action of endogenous hormones or reduces their production within the body. Certain hormone-sensitive malignancies, particularly those of the prostate and breast, will often grow in response to specific hormones (androgens and oestrogens, respectively). Secondary metastases stemming from these primary tumours will, by extension, respond to hormone levels too. Androgen-responsive prostate cancer may be treated with drugs which lower androgen levels, such as gonadotrophin-releasing hormone (GnRH) receptor antagonists (peptides: '-''relix''&lt;nowiki/&gt;'; small-molecules: '-''golix''&lt;nowiki/&gt;'), GnRH receptor agonists ('-''relin''&lt;nowiki/&gt;'), and CYP17A1 inhibitors (such as abiraterone). Alternatively, androgen receptor blockers, such as bicalutamide or flutamide, can be effective. Oestrogen-responsive breast cancer may be treated with drugs which lower oestrogen levels, such as type I (exemestane) and type II (anastrozole, letrozole) aromatase inhibitors. Alternatively, selective oestrogen receptor modulators (SERMs), such as tamoxifen, can be effective. These modulators have mixed oestrogenic and antioestrogenic activity, which differs according to receptive tissue. Usefully in breast cancer, it is antioestrogenic in the breast; however, in the uterus and liver it is oestrogenic.<br /> ===Interventional radiology===<br /> The role of the interventional radiologist is ever-expanding. In the treatment of metastatic cancer there are procedures which are shared with or done solely by these interventionists. Two important treatments offered by the specialty for bone metastases are ablation and cementoplasty.<br /> <br /> '''Ablation''' is a medical term for when a procedural probe is introduced to an area of tissue (in this case tumour) and, using physical energy (heat or cold) or chemicals, cellular necrosis with subsequent scarring is achieved. It is useful for bony lesions if only there are one or two lesions to be targeted. The most common types of ablation are [[radiofrequency ablation]] (RFA), where an electric current passes through and heats a needle within the lesion, and cryoablation, where a cold probe within the lesion freezes and destroys cancer cells. Both are effective analgesic therapies; however, unlike in RFA, the ablation edge in cryoablation can be readily visualised with CT monitoring (as low-attenuation) and does not produce increased pain in the periprocedural period&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/21785102/&lt;/ref&gt;. Complications rates for each procedure are low, but localised infection and enduring neuropathic pain have been reported. <br /> <br /> '''Cementoplasty''' is a generic term for a group of medical procedures whereby acrylic bone cement, commonly polymethylmethacrylate (PMMA), is injected percutaneously into bone lesions for analgesic effect and/or stabilisation. It is commonly performed under sedation with local anaesthesia, and the cement is mixed with a radiopaque agent to allow visualisation with multi-plane fluoroscopy during injection&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/21629403&lt;/ref&gt;. Depending on where cementoplasty is used, it may be termed differently:<br /> <br /> * Osteoplasty (generic term, into non-axial bones)<br /> * Vertebroplasty (into an affected vertebra)<br /> * Kyphoplasty (mostly for vertebral fractures, this is vertebroplasty with use of balloon inflation beforehand to restore vertebral height)<br /> * Sacroplasty (into a sacral lesion)<br /> <br /> ===Surgery===<br /> Surgery is not considered to be amongst the conventional treatments for bony metastases. It is indicated for fractures of the hip and of long bones, and if there is need for vertebral surgery in [[Metastatic spinal cord compression|MSCC]]. Sometimes if bone involvement leads to fracture causing peripheral nerve impingement or compression, surgery may also be necessary.<br /> <br /> ==Living with bone metastases==<br /> Pain, mobility and safety, survival&lt;references /&gt;</div>

Alex https://oncopaedia.net/w/index.php?title=Articles:Bone_metastases&diff=326 2020-04-23T14:04:50Z

<p>Alex: </p> <hr /> <div>Metastases within bone can cause extreme and debilitating pain. Bone metastases are far more common than primary bone cancer, and many different cancer types can spread to the bone. The most common types of cancer which spread to bone are:<br /> <br /> *Breast<br /> *Prostate<br /> *Lung<br /> *Kidney<br /> *Thyroid<br /> <br /> Cancer can theoretically metastasize to any bone in the body, but in reality there is a predilection for certain sites. The most common sites are the vertebrae, ribs, pelvis, sternum, and the skull.<br /> <br /> ==Classification==<br /> A bone is a rigid organ, but it is far from physiologically static. To maintain bone strength, there is continuous breakdown and simultaneous reformation of bone, two processes which must finely balance for good bone health.<br /> <br /> '''Osteoblastic''' (or '''sclerotic''') metastases are characterised by the deposition of new bone. These are present most commonly in prostate cancer, but also occur in carcinoid, small cell lung cancer, medulloblastoma, and Hodgkin lymphoma. The molecular crosstalk between tumour and bone cells involves osteoblast-generating proteins such as Transforming Growth Factor, Bone Morphogenic Proteins (BMPs), and Endothelin-1&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12085970&lt;/ref&gt;.<br /> <br /> '''Osteolytic''' (or '''lytic''') metastases are characterised by the destruction and breakdown of normal bone. These often occur when breast cancer spreads to bone, which is primarily mediated by osteoclasts (bone cells that breaks down bone tissue) and is not a direct effect of metastasized tumour cells&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8086233/&lt;/ref&gt;. Other tumour types with osteolytic metastases include multiple myeloma, non-small cell lung cancer, thyroid cancer, non-Hodgkin lymphoma, and Langerhans' cell histiocytosis. Osteolytic metastases are more common than osteoblastic metastases.<br /> <br /> '''Mixed''' metastases are characterised by the presence of both osteolytic and osteoblastic lesions together in the same area of bone. These metastases are usually present in metastatic gastrointestinal and squamous cancers, as well as in secondary breast cancer. Although breast cancer gives rise to predominantly lytic lesions, around 15–20% of women have sclerotic or both types of lesions&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11346860/&lt;/ref&gt;.<br /> <br /> ==Diagnosis==<br /> <br /> ===Signs and symptoms===<br /> Bone metastases cause major morbidity, and high clinical suspicion should be kept for any patient with cancer that presents with:<br /> <br /> *Severe pain (poorly localised, worse at night)<br /> *Impaired mobility<br /> *[[Pathological fracture|Bone fracture]]<br /> *Bone marrow aplasia<br /> *Symptoms of (metastatic) [[Metastatic spinal cord compression|spinal cord compression]] (MSCC)<br /> *Symptoms in keeping with [[hypercalcaemia]]:<br /> **Constipation<br /> **Fatigue<br /> **Polyuria/polydipsia<br /> **Acute kidney injury (AKI)<br /> **Cardiac arrhythmia<br /> <br /> ===Bloods===<br /> When a patient with cancer presents with any of the signs or symptoms above, basic screening in the form of simple blood testing must be undertaken and complemented with appropriate imaging tests:<br /> <br /> *Full evaluation of bone turnover and potential hypercalcaemia:<br /> **Serum calcium<br /> **Serum phosphate<br /> **25-Hydroxyvitamin D<br /> **Thyroid-stimulating hormone (TSH)<br /> **Parathyroid hormone (PTH)<br /> **Serum creatinine<br /> **Alkaline phosphatase (ALP)<br /> *Full blood count (myelosuppression, anaemia)<br /> *Serum protein electrophoresis (SPEP; myeloma screen)<br /> *Tumour markers (such as PSA in prostate cancer)<br /> <br /> ===Imaging===<br /> Radiological tests are an essential component of diagnosing bony metastases. One or more imaging modalities may be required to confirm suspected cancerous spread to bone.<br /> <br /> '''Plain radiographs''' (X-ray scans) are quick, cost-effective, and widely-available, and should be the initial diagnostic test of choice when investigating bone pain. They are highly specific but lack sensitivity (44-50%) because early-stage metastatic lesions, particularly those up to 1 cm, may be more difficult to visualise. More than 50% of the trabecular bone must be involved before the lesion will be apparent on film and, due to the poor contrast of trabecular bone, lesions within the medulla are often less evident than those within cortical bone&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9025785/&lt;/ref&gt;. As outlined above, sclerotic metastases will appear more radiopaque than the surrounding bone, whereas lytic metastases will appear more radiolucent.<br /> <br /> '''Bone scintigraphy''' (bone scans) on the other hand is highly sensitive but with low specificity. Data from Technetium-99m ('''&lt;sup&gt;99m&lt;/sup&gt;Tc''') scintigraphy have shown false-negative rates as low as 11 to 38% (good sensitivity), with false-positive rates as high as 40% (poor specificity). It thus provides a non-specific osteoblastic indication of bone status, be it inflammatory, traumatic, or neoplastic in origin. Scintigraphy is still more specific and sensitive than either plain radiography or computed tomography, whilst magnetic resonance imaging is more efficacious in assessing vertebral metastases&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/2028061/&lt;/ref&gt;.<br /> <br /> '''Computed tomography''' (CT scans) has a high sensitivity, ranging from 71 to 100%, for the detection of metastatic bone lesions&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9362427/&lt;/ref&gt;. Because of the excellent soft tissue resolution of the images produced by CT, it is a particularly helpful modality to distinguish lytic and sclerotic metastases and to visualise their precise location(s) for biopsy.<br /> <br /> '''Magnetic resonance imaging''' (MRI scans) is useful in assessing bone marrow infiltration by tumour deposits, and is required (whole spine) for the proper diagnosis of [[Metastatic spinal cord compression|MSCC]]. It has similarly high specificity (73 to 100%) and sensitivity (82 to 100%) in screening for bone metastases&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10964746/&lt;/ref&gt;.<br /> <br /> '''Positron emission tomography''' (PET scans) detects tumour indirectly by measuring metabolic activity in the form of fluorodeoxyglucose ('''&lt;sup&gt;18&lt;/sup&gt;F''') tissue uptake. As such, its use is not limited to visualising only bony metastases, as &lt;sup&gt;18&lt;/sup&gt;F PET will reveal non-bony metastatic spread also&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8638000/&lt;/ref&gt;. The accuracy of PET is highly dependent on the primary tumour site from which imaged metastases originate. As a modality it is superior to scintigraphy in the screening of bony metastases from breast (specificity 94%, sensitivity 95%)&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12073051/&lt;/ref&gt; and lung (specificity 99%, sensitivity 92%)&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10478250/&lt;/ref&gt; malignancies, but has lower sensitivity in detecting the comparatively slower-growing bone metastases of prostate and renal cancers&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10520701/&lt;/ref&gt;. <br /> <br /> ===Biopsy===<br /> Sometimes it is necessary to diagnose metastases histologically, by removing cells or tissue from the bone lesion(s) directly. Usually this is in the form of a needle or surgical biopsy, and may be indicated if a primary cancer is not known. If the patient has a known primary cancer, then often imaging alone will suffice for the diagnosis of metastatic bone disease.<br /> <br /> ==Treatment==<br /> There are a variety of therapeutic interventions available to patients presenting with bone metastases, but consideration must be given to several patient-specific and tumour-dependent parameters, which include&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11738947/&lt;/ref&gt; (but are not limited to):<br /> <br /> *Lesion site(s) (localised or widespread)<br /> *Presence of extraskeletal metastasis<br /> *Tumour type and features (like receptors)<br /> *Prior treatment history (and response)<br /> *Clinical symptoms<br /> *Performance status<br /> <br /> ===Radiotherapy===<br /> Radiation therapy can provide excellent pain relief and is the treatment of choice for localised metastatic bone pain. However, the analgesic mechanisms of therapeutic skeletal irradiation are poorly understood. Onset of pain relief is usually quick, with a majority of patients experiencing benefit within one to two weeks. Patients who have little reduction in pain by six weeks are unlikely to demonstrate significant overall benefit&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/24782453/&lt;/ref&gt;. Other than localised bone pain, additional indications for radiotherapy include [[Metastatic spinal cord compression|MSCC]] and bones at high risk for [[pathological fracture]]&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/15978828/&lt;/ref&gt;. Two of the three main divisions of radiation therapy—the third being (sealed source) [[brachytherapy]]—can be used to treat bone metastases: systemic (unsealed source) [[radionuclide therapy]] and [[external beam radiotherapy]] (EBRT). <br /> <br /> '''Local-field [[External beam radiotherapy|EBRT]]''' is the standard choice of radiation therapy for treating bone metastases, as it focally targets the bone lesion and can achieve rates of substantial pain relief of up to 80 to 90%&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/6178497/&lt;/ref&gt;. Randomised controlled trials (RCTs) from the 1990s have shown that a single fraction of 8 gray (Gy) is as effective as fractionated doses of 20 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9681885&lt;/ref&gt;, 24 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10577695&lt;/ref&gt;, and 30 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10577696&lt;/ref&gt;. <br /> <br /> '''Wide-field''' (or '''hemibody''') '''[[External beam radiotherapy|EBRT]]''' is useful for widespread metastatic skeletal disease, though was more commonly used for multifocal pain when other effective therapies (chemo- and radionuclide) were not available. There are no RCTs comparing analgesic effect with and without wide-field radiotherapy. However, in terms of quasi-randomised and low-quality RCTs, there is data to suggest that use of fractionation is no more effective than single fraction treatment&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8823257&lt;/ref&gt;, that increasing doses beyond 8 Gy does not improve overall pain responses&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11395246&lt;/ref&gt;, and adding wide-field to local-field radiotherapy, whilst significantly halting disease progression (lesion size: P = 0.03; lesion number: P = 0.01), increases grade 3 to 4 haematological toxicity&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/1374061&lt;/ref&gt;. It is possible to classify wide-field treatments into three body regions, each with recommended single-fraction dose limits. Upper treatments (from skull or C1 to L2–L3) should be limited to 6 Gy, whereas mid-body (from L1 to upper third of femur) and lower (from L3–L4 to above knee) treatments should be limited to 8 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/6178497/&lt;/ref&gt;. Any treatments must be delivered with fields shaped to minimise irradiation of organs at risk, such as lung, liver, kidney and bowel. <br /> <br /> '''[[Stereotactic radiotherapy|Stereotactic]] [[External beam radiotherapy|EBRT]]''' is a promising treatment option which delivers higher doses of radiation to tumours in shorter periods in time. When used for extracranial cancers it is interchangeably termed Stereotactic Body Radiation Therapy ('''[[Stereotactic radiotherapy|SBRT]]''') or Stereotactic Ablative Radiotherapy ('''[[Stereotactic radiotherapy|SABR]]'''), the latter of which is appealingly onomatopoeic. When this technique is used for treating malignancy within the brain or some other part of the head, it is termed Stereotactic RadioSurgery ('''[[Stereotactic radiotherapy|SRS]]'''). SBRT/SABR can be used both for primary cancers (lung, liver, prostate, renal) and secondary metastases (bone/spine, lung, liver). There are a number of advantages of stereotactic radiotherapy, the most obvious of which is the potential completion of treatment within a single day, rather than over a number of weeks. The other major benefit is that it obviates the need to irradiate large portions of bone, which lowers the risk of further functional marrow depletion in a patient cohort already at risk of poor marrow reserve. Preserving skeletal marrow function can permit continuous chemotherapy in these patients. The primary limitations of SBRT/SABR are that it is more expensive to deliver than conventional EBRT and that there is a paucity of RCT data comparing its use to standard EBRT management&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/18619121/&lt;/ref&gt;. However, a recent single-centre phase II trial appeared to show that SBRT/SABR provides superior pain relief to conventional multifraction radiotherapy, with no observed difference in adverse events or other aspects of quality of life&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/31021390&lt;/ref&gt;. <br /> <br /> '''[[Radionuclide therapy]]''' (or '''radioisotope therapy''') is the systemic administration of radionuclides (also known as radioisotopes) as unsealed radioactive sources that selectively deliver radiation to tumours or target organs. They are taken up predominantly at sites of bone formation, and are therefore most likely best effective for the palliation of osteoblastic (sclerotic) metastases. Common radionuclides approved for the treatment of painful bone metastases include phosphorus-32 ('''&lt;sup&gt;32&lt;/sup&gt;P'''; ''β''-decay), strontium-89 ('''&lt;sup&gt;89&lt;/sup&gt;Sr'''; ''β''-decay), samarium-153 ('''&lt;sup&gt;153&lt;/sup&gt;Sm'''; ''β''- and ''γ''-decay), and rhenium-186 ('''&lt;sup&gt;186&lt;/sup&gt;Re'''; ''β''- and ''γ''-decay). The added advantage of gamma ray emission during decay is that it permits nuclear imaging monitoring of radionuclide biodistribution during therapy. These radionuclides target bone through various mechanisms. &lt;sup&gt;32&lt;/sup&gt;P passes through inorganic phosphate pathways, whereas &lt;sup&gt;89&lt;/sup&gt;Sr is a calcium mimetic and is taken up as a direct analogue of this earth metal. The final two agents are targeted to bone via chelation to phosphonate compounds: &lt;sup&gt;153&lt;/sup&gt;Sm is paired to ethylenediaminetetramethylenephosphonate (EDTMP) and &lt;sup&gt;186&lt;/sup&gt;Re to 1,1-hydroxyethylidene diphosphonate (HEDP). Common toxicities from treatment include myelosuppression and a transient pain flare, the latter of which usually heralds a favourable response. A more recently developed radionuclide, radium-223 (&lt;sup&gt;'''223'''&lt;/sup&gt;'''Ra'''; ''α''-, ''β''-, and ''γ''-decay) is a calcium mimetic which emits over 95% of decay energy in the form of alpha radiation&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/17062709&lt;/ref&gt;. Owing to their comparatively large size the emitted alpha particles have a more limited depth of penetration into surrounding tissues (around 2–10 cells), thereby producing a more potently localised cytotoxic effect. Despite their symptomatic benefits in refractory, widespread bone metastases, neither &lt;sup&gt;89&lt;/sup&gt;Sr nor &lt;sup&gt;153&lt;/sup&gt;Sm have been shown to improve overall survival in interventional trials; however, &lt;sup&gt;223&lt;/sup&gt;Ra use in metastatic castration-resistant prostate cancer patients in the ALSYMPCA (ALpharadin in SYMptomatic Prostate CAncer) trial was shown to significantly prolong overall survival&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/23863050/&lt;/ref&gt;. <br /> <br /> ===Bisphosphonates===<br /> Analogues of the natural bone demineralisation inhibitor pyrophosphate, bisphosphonates are useful in the treatment of poorly localised bone pain and in previously irradiated bone lesions. They bind with high affinity to exposed bone mineral where they are internalised by osteoclasts, within which they disrupt the processes of bone resorption and can induce apoptosis. Data have shown that bisphosphonates may have direct pro-apoptotic effects on nearby metastatic cancer cells also&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9362432/&lt;/ref&gt;. In halting the mobilisation of calcium and phosphate from bone, bisphosphonate use (together with rehydration) is now standard of care for malignancy-induced hypercalcaemia&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9025784/&lt;/ref&gt;. The analgesic effect of these agents is independent of underlying tumour characteristics, with osteolytic and osteoblastic lesions responding similarly&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9496390&lt;/ref&gt;. Many patients tolerate bisphosphonates without major concern, but common side-effects include flu-like myalgic symptoms, diarrhoea, nausea and reflux. It is exceedingly rare but one must be aware of the risk of developing osteonecrosis of the jaw. These medications undergo renal excretion and as such should be avoided in tumour-induced hypercalcaemia or metastatic bone disease if serum creatinine is greater than 400 μmol/L or 265 μmol/L, respectively. Bisphosphonates are divided into three generations of drug: first-generation (tiludronate, clodronate, etidronate), second-generation (ibandronate, alendronate, paimdronate), and third-generation (zoledronate, risedronate). One of the newest agents, zoledronate is 100-times more effective than second-generation pamidronate&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12558465/&lt;/ref&gt;. Whilst receiving bisphosphonate therapy, patients should take protective vitamin D and calcium supplements.<br /> <br /> ===Denosumab===<br /> Denosumab is a monoclonal antibody which binds to and inhibits the action of the RANK receptor ligand (RANKL). RANK is located on the surface of osteoclast progenitor cells and its activation stimulates their development into mature osteoclasts. Therefore denosumab, administered as a subcutaneous injection of 120 mg every four weeks, can help prevent bone destruction and fracture in patients with bone metastases. The antibody is cleared from the body by the reticuloendothelial system and can therefore be used in patients with poor renal function, in whom bisphosphonate use would be contraindicated&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/21145999/&lt;/ref&gt;. Additionally, data have shown that denosumab use causes greater suppression of osteolytic markers than bisphosphonate use in metastatic patients with breast&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/21060033/&lt;/ref&gt; or prostate&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/21353695/&lt;/ref&gt; cancer. However its effectiveness in comparison to bisphosphonates for patients with lung cancer or multiple myeloma is similar for the prevention of skeletal-related events (SRE), and indeed patients with multiple myeloma showed worse overall survival when treated with denosumab instead of zoledronate&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/21343556/&lt;/ref&gt;. <br /> <br /> ===Systemic anticancer therapies===<br /> [[Systemic anticancer therapy]] (SACT) refers to all drugs administered systemically with direct anticancer activity. This includes all conventional cytotoxic chemotherapies, all small molecule or antibody treatments, and all types of immunotherapy. Hormonal agents are not included within this categorisation. SACT may be considered for bone metastases if a primary tumour is known or subsequently confirmed. The specific therapy used will be the same therapy as typically used for the culprit primary cancer, though the precise dose and schedule will vary. SACT is sometimes used concurrently with other treatments such as bisphosphonates or radiotherapy. Side-effects will be treatment-specific.<br /> <br /> ===Hormone therapies===<br /> <br /> <br /> Hormone therapy is an indirect antitumour treatment which blocks the action of endogenous hormones or reduces their production within the body. Certain hormone-sensitive malignancies, particularly those of the prostate and breast, will often grow in response to specific hormones (androgens and oestrogens, respectively). Secondary metastases stemming from these primary tumours will, by extension, respond to hormone levels too. Androgen-responsive prostate cancer may be treated with drugs which lower androgen levels, such as gonadotrophin-releasing hormone (GnRH) receptor antagonists (peptides: '-''relix''&lt;nowiki/&gt;'; small-molecules: '-''golix''&lt;nowiki/&gt;'), GnRH receptor agonists ('-''relin''&lt;nowiki/&gt;'), and CYP17A1 inhibitors (such as abiraterone). Alternatively, androgen receptor blockers, such as bicalutamide or flutamide, can be effective. Oestrogen-responsive breast cancer may be treated with drugs which lower oestrogen levels, such as type I (exemestane) and type II (anastrozole, letrozole) aromatase inhibitors. Alternatively, selective oestrogen receptor modulators (SERMs), such as tamoxifen, can be effective. These modulators have mixed oestrogenic and antioestrogenic activity, which differs according to receptive tissue. Usefully in breast cancer, it is antioestrogenic in the breast; however, in the uterus and liver it is oestrogenic.<br /> ===Interventional radiology===<br /> The role of the interventional radiologist is ever-expanding. In the treatment of metastatic cancer there are procedures which are shared with or done solely by these interventionists. Two important treatments offered by the specialty for bone metastases are ablation and cementoplasty.<br /> <br /> '''Ablation''' is a medical term for when a procedural probe is introduced to an area of tissue (in this case tumour) and, using physical energy (heat or cold) or chemicals, cellular necrosis with subsequent scarring is achieved. It is useful for bony lesions if only there are one or two lesions to be targeted. The most common types of ablation are [[radiofrequency ablation]] (RFA), where an electric current passes through and heats a needle within the lesion, and cryoablation, where a cold probe within the lesion freezes and destroys cancer cells. Both are effective analgesic therapies; however, unlike in RFA, the ablation edge in cryoablation can be readily visualised with CT monitoring (as low-attenuation) and does not produce increased pain in the periprocedural period&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/21785102/&lt;/ref&gt;. Complications rates for each procedure are low, but localised infection and enduring neuropathic pain have been reported. <br /> <br /> percutaneous cementoplasty (bone cement)<br /> <br /> ===Surgery===<br /> Surgery is not considered to be amongst the conventional treatments for bony metastases. It is indicated for fractures of the hip and of long bones, and if there is need for vertebral surgery in [[Metastatic spinal cord compression|MSCC]]. Sometimes if bone involvement leads to fracture causing peripheral nerve impingement or compression, surgery may also be necessary.<br /> <br /> ==Living with bone metastases==<br /> Pain, mobility and safety, survival&lt;references /&gt;</div>

Alex https://oncopaedia.net/w/index.php?title=Articles:Bone_metastases&diff=325 2020-04-23T14:01:47Z

<p>Alex: </p> <hr /> <div>Metastases within bone can cause extreme and debilitating pain. Bone metastases are far more common than primary bone cancer, and many different cancer types can spread to the bone. The most common types of cancer which spread to bone are:<br /> <br /> *Breast<br /> *Prostate<br /> *Lung<br /> *Kidney<br /> *Thyroid<br /> <br /> Cancer can theoretically metastasize to any bone in the body, but in reality there is a predilection for certain sites. The most common sites are the vertebrae, ribs, pelvis, sternum, and the skull.<br /> <br /> ==Classification==<br /> A bone is a rigid organ, but it is far from physiologically static. To maintain bone strength, there is continuous breakdown and simultaneous reformation of bone, two processes which must finely balance for good bone health.<br /> <br /> '''Osteoblastic''' (or '''sclerotic''') metastases are characterised by the deposition of new bone. These are present most commonly in prostate cancer, but also occur in carcinoid, small cell lung cancer, medulloblastoma, and Hodgkin lymphoma. The molecular crosstalk between tumour and bone cells involves osteoblast-generating proteins such as Transforming Growth Factor, Bone Morphogenic Proteins (BMPs), and Endothelin-1&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12085970&lt;/ref&gt;.<br /> <br /> '''Osteolytic''' (or '''lytic''') metastases are characterised by the destruction and breakdown of normal bone. These often occur when breast cancer spreads to bone, which is primarily mediated by osteoclasts (bone cells that breaks down bone tissue) and is not a direct effect of metastasized tumour cells&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8086233/&lt;/ref&gt;. Other tumour types with osteolytic metastases include multiple myeloma, non-small cell lung cancer, thyroid cancer, non-Hodgkin lymphoma, and Langerhans' cell histiocytosis. Osteolytic metastases are more common than osteoblastic metastases.<br /> <br /> '''Mixed''' metastases are characterised by the presence of both osteolytic and osteoblastic lesions together in the same area of bone. These metastases are usually present in metastatic gastrointestinal and squamous cancers, as well as in secondary breast cancer. Although breast cancer gives rise to predominantly lytic lesions, around 15–20% of women have sclerotic or both types of lesions&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11346860/&lt;/ref&gt;.<br /> <br /> ==Diagnosis==<br /> <br /> ===Signs and symptoms===<br /> Bone metastases cause major morbidity, and high clinical suspicion should be kept for any patient with cancer that presents with:<br /> <br /> *Severe pain (poorly localised, worse at night)<br /> *Impaired mobility<br /> *[[Pathological fracture|Bone fracture]]<br /> *Bone marrow aplasia<br /> *Symptoms of (metastatic) [[Metastatic spinal cord compression|spinal cord compression]] (MSCC)<br /> *Symptoms in keeping with [[hypercalcaemia]]:<br /> **Constipation<br /> **Fatigue<br /> **Polyuria/polydipsia<br /> **Acute kidney injury (AKI)<br /> **Cardiac arrhythmia<br /> <br /> ===Bloods===<br /> When a patient with cancer presents with any of the signs or symptoms above, basic screening in the form of simple blood testing must be undertaken and complemented with appropriate imaging tests:<br /> <br /> *Full evaluation of bone turnover and potential hypercalcaemia:<br /> **Serum calcium<br /> **Serum phosphate<br /> **25-Hydroxyvitamin D<br /> **Thyroid-stimulating hormone (TSH)<br /> **Parathyroid hormone (PTH)<br /> **Serum creatinine<br /> **Alkaline phosphatase (ALP)<br /> *Full blood count (myelosuppression, anaemia)<br /> *Serum protein electrophoresis (SPEP; myeloma screen)<br /> *Tumour markers (such as PSA in prostate cancer)<br /> <br /> ===Imaging===<br /> Radiological tests are an essential component of diagnosing bony metastases. One or more imaging modalities may be required to confirm suspected cancerous spread to bone.<br /> <br /> '''Plain radiographs''' (X-ray scans) are quick, cost-effective, and widely-available, and should be the initial diagnostic test of choice when investigating bone pain. They are highly specific but lack sensitivity (44-50%) because early-stage metastatic lesions, particularly those up to 1 cm, may be more difficult to visualise. More than 50% of the trabecular bone must be involved before the lesion will be apparent on film and, due to the poor contrast of trabecular bone, lesions within the medulla are often less evident than those within cortical bone&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9025785/&lt;/ref&gt;. As outlined above, sclerotic metastases will appear more radiopaque than the surrounding bone, whereas lytic metastases will appear more radiolucent.<br /> <br /> '''Bone scintigraphy''' (bone scans) on the other hand is highly sensitive but with low specificity. Data from Technetium-99m ('''&lt;sup&gt;99m&lt;/sup&gt;Tc''') scintigraphy have shown false-negative rates as low as 11 to 38% (good sensitivity), with false-positive rates as high as 40% (poor specificity). It thus provides a non-specific osteoblastic indication of bone status, be it inflammatory, traumatic, or neoplastic in origin. Scintigraphy is still more specific and sensitive than either plain radiography or computed tomography, whilst magnetic resonance imaging is more efficacious in assessing vertebral metastases&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/2028061/&lt;/ref&gt;.<br /> <br /> '''Computed tomography''' (CT scans) has a high sensitivity, ranging from 71 to 100%, for the detection of metastatic bone lesions&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9362427/&lt;/ref&gt;. Because of the excellent soft tissue resolution of the images produced by CT, it is a particularly helpful modality to distinguish lytic and sclerotic metastases and to visualise their precise location(s) for biopsy.<br /> <br /> '''Magnetic resonance imaging''' (MRI scans) is useful in assessing bone marrow infiltration by tumour deposits, and is required (whole spine) for the proper diagnosis of [[Metastatic spinal cord compression|MSCC]]. It has similarly high specificity (73 to 100%) and sensitivity (82 to 100%) in screening for bone metastases&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10964746/&lt;/ref&gt;.<br /> <br /> '''Positron emission tomography''' (PET scans) detects tumour indirectly by measuring metabolic activity in the form of fluorodeoxyglucose ('''&lt;sup&gt;18&lt;/sup&gt;F''') tissue uptake. As such, its use is not limited to visualising only bony metastases, as &lt;sup&gt;18&lt;/sup&gt;F PET will reveal non-bony metastatic spread also&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8638000/&lt;/ref&gt;. The accuracy of PET is highly dependent on the primary tumour site from which imaged metastases originate. As a modality it is superior to scintigraphy in the screening of bony metastases from breast (specificity 94%, sensitivity 95%)&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12073051/&lt;/ref&gt; and lung (specificity 99%, sensitivity 92%)&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10478250/&lt;/ref&gt; malignancies, but has lower sensitivity in detecting the comparatively slower-growing bone metastases of prostate and renal cancers&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10520701/&lt;/ref&gt;. <br /> <br /> ===Biopsy===<br /> Sometimes it is necessary to diagnose metastases histologically, by removing cells or tissue from the bone lesion(s) directly. Usually this is in the form of a needle or surgical biopsy, and may be indicated if a primary cancer is not known. If the patient has a known primary cancer, then often imaging alone will suffice for the diagnosis of metastatic bone disease.<br /> <br /> ==Treatment==<br /> There are a variety of therapeutic interventions available to patients presenting with bone metastases, but consideration must be given to several patient-specific and tumour-dependent parameters, which include&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11738947/&lt;/ref&gt; (but are not limited to):<br /> <br /> *Lesion site(s) (localised or widespread)<br /> *Presence of extraskeletal metastasis<br /> *Tumour type and features (like receptors)<br /> *Prior treatment history (and response)<br /> *Clinical symptoms<br /> *Performance status<br /> <br /> ===Radiotherapy===<br /> Radiation therapy can provide excellent pain relief and is the treatment of choice for localised metastatic bone pain. However, the analgesic mechanisms of therapeutic skeletal irradiation are poorly understood. Onset of pain relief is usually quick, with a majority of patients experiencing benefit within one to two weeks. Patients who have little reduction in pain by six weeks are unlikely to demonstrate significant overall benefit&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/24782453/&lt;/ref&gt;. Other than localised bone pain, additional indications for radiotherapy include [[Metastatic spinal cord compression|MSCC]] and bones at high risk for [[pathological fracture]]&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/15978828/&lt;/ref&gt;. Two of the three main divisions of radiation therapy—the third being (sealed source) [[brachytherapy]]—can be used to treat bone metastases: systemic (unsealed source) [[radionuclide therapy]] and [[external beam radiotherapy]] (EBRT). <br /> <br /> '''Local-field [[External beam radiotherapy|EBRT]]''' is the standard choice of radiation therapy for treating bone metastases, as it focally targets the bone lesion and can achieve rates of substantial pain relief of up to 80 to 90%&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/6178497/&lt;/ref&gt;. Randomised controlled trials (RCTs) from the 1990s have shown that a single fraction of 8 gray (Gy) is as effective as fractionated doses of 20 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9681885&lt;/ref&gt;, 24 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10577695&lt;/ref&gt;, and 30 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10577696&lt;/ref&gt;. <br /> <br /> '''Wide-field''' (or '''hemibody''') '''[[External beam radiotherapy|EBRT]]''' is useful for widespread metastatic skeletal disease, though was more commonly used for multifocal pain when other effective therapies (chemo- and radionuclide) were not available. There are no RCTs comparing analgesic effect with and without wide-field radiotherapy. However, in terms of quasi-randomised and low-quality RCTs, there is data to suggest that use of fractionation is no more effective than single fraction treatment&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8823257&lt;/ref&gt;, that increasing doses beyond 8 Gy does not improve overall pain responses&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11395246&lt;/ref&gt;, and adding wide-field to local-field radiotherapy, whilst significantly halting disease progression (lesion size: P = 0.03; lesion number: P = 0.01), increases grade 3 to 4 haematological toxicity&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/1374061&lt;/ref&gt;. It is possible to classify wide-field treatments into three body regions, each with recommended single-fraction dose limits. Upper treatments (from skull or C1 to L2–L3) should be limited to 6 Gy, whereas mid-body (from L1 to upper third of femur) and lower (from L3–L4 to above knee) treatments should be limited to 8 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/6178497/&lt;/ref&gt;. Any treatments must be delivered with fields shaped to minimise irradiation of organs at risk, such as lung, liver, kidney and bowel. <br /> <br /> '''[[Stereotactic radiotherapy|Stereotactic]] [[External beam radiotherapy|EBRT]]''' is a promising treatment option which delivers higher doses of radiation to tumours in shorter periods in time. When used for extracranial cancers it is interchangeably termed Stereotactic Body Radiation Therapy ('''[[Stereotactic radiotherapy|SBRT]]''') or Stereotactic Ablative Radiotherapy ('''[[Stereotactic radiotherapy|SABR]]'''), the latter of which is appealingly onomatopoeic. When this technique is used for treating malignancy within the brain or some other part of the head, it is termed Stereotactic RadioSurgery ('''[[Stereotactic radiotherapy|SRS]]'''). SBRT/SABR can be used both for primary cancers (lung, liver, prostate, renal) and secondary metastases (bone/spine, lung, liver). There are a number of advantages of stereotactic radiotherapy, the most obvious of which is the potential completion of treatment within a single day, rather than over a number of weeks. The other major benefit is that it obviates the need to irradiate large portions of bone, which lowers the risk of further functional marrow depletion in a patient cohort already at risk of poor marrow reserve. Preserving skeletal marrow function can permit continuous chemotherapy in these patients. The primary limitations of SBRT/SABR are that it is more expensive to deliver than conventional EBRT and that there is a paucity of RCT data comparing its use to standard EBRT management&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/18619121/&lt;/ref&gt;. However, a recent single-centre phase II trial appeared to show that SBRT/SABR provides superior pain relief to conventional multifraction radiotherapy, with no observed difference in adverse events or other aspects of quality of life&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/31021390&lt;/ref&gt;. <br /> <br /> '''[[Radionuclide therapy]]''' (or '''radioisotope therapy''') is the systemic administration of radionuclides (also known as radioisotopes) as unsealed radioactive sources that selectively deliver radiation to tumours or target organs. They are taken up predominantly at sites of bone formation, and are therefore most likely best effective for the palliation of osteoblastic (sclerotic) metastases. Common radionuclides approved for the treatment of painful bone metastases include phosphorus-32 ('''&lt;sup&gt;32&lt;/sup&gt;P'''; ''β''-decay), strontium-89 ('''&lt;sup&gt;89&lt;/sup&gt;Sr'''; ''β''-decay), samarium-153 ('''&lt;sup&gt;153&lt;/sup&gt;Sm'''; ''β''- and ''γ''-decay), and rhenium-186 ('''&lt;sup&gt;186&lt;/sup&gt;Re'''; ''β''- and ''γ''-decay). The added advantage of gamma ray emission during decay is that it permits nuclear imaging monitoring of radionuclide biodistribution during therapy. These radionuclides target bone through various mechanisms. &lt;sup&gt;32&lt;/sup&gt;P passes through inorganic phosphate pathways, whereas &lt;sup&gt;89&lt;/sup&gt;Sr is a calcium mimetic and is taken up as a direct analogue of this earth metal. The final two agents are targeted to bone via chelation to phosphonate compounds: &lt;sup&gt;153&lt;/sup&gt;Sm is paired to ethylenediaminetetramethylenephosphonate (EDTMP) and &lt;sup&gt;186&lt;/sup&gt;Re to 1,1-hydroxyethylidene diphosphonate (HEDP). Common toxicities from treatment include myelosuppression and a transient pain flare, the latter of which usually heralds a favourable response. A more recently developed radionuclide, radium-223 (&lt;sup&gt;'''223'''&lt;/sup&gt;'''Ra'''; ''α''-, ''β''-, and ''γ''-decay) is a calcium mimetic which emits over 95% of decay energy in the form of alpha radiation&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/17062709&lt;/ref&gt;. Owing to their comparatively large size the emitted alpha particles have a more limited depth of penetration into surrounding tissues (around 2–10 cells), thereby producing a more potently localised cytotoxic effect. Despite their symptomatic benefits in refractory, widespread bone metastases, neither &lt;sup&gt;89&lt;/sup&gt;Sr nor &lt;sup&gt;153&lt;/sup&gt;Sm have been shown to improve overall survival in interventional trials; however, &lt;sup&gt;223&lt;/sup&gt;Ra use in metastatic castration-resistant prostate cancer patients in the ALSYMPCA (ALpharadin in SYMptomatic Prostate CAncer) trial was shown to significantly prolong overall survival&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/23863050/&lt;/ref&gt;. <br /> <br /> ===Bisphosphonates===<br /> Analogues of the natural bone demineralisation inhibitor pyrophosphate, bisphosphonates are useful in the treatment of poorly localised bone pain and in previously irradiated bone lesions. They bind with high affinity to exposed bone mineral where they are internalised by osteoclasts, within which they disrupt the processes of bone resorption and can induce apoptosis. Data have shown that bisphosphonates may have direct pro-apoptotic effects on nearby metastatic cancer cells also&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9362432/&lt;/ref&gt;. In halting the mobilisation of calcium and phosphate from bone, bisphosphonate use (together with rehydration) is now standard of care for malignancy-induced hypercalcaemia&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9025784/&lt;/ref&gt;. The analgesic effect of these agents is independent of underlying tumour characteristics, with osteolytic and osteoblastic lesions responding similarly&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9496390&lt;/ref&gt;. Many patients tolerate bisphosphonates without major concern, but common side-effects include flu-like myalgic symptoms, diarrhoea, nausea and reflux. It is exceedingly rare but one must be aware of the risk of developing osteonecrosis of the jaw. These medications undergo renal excretion and as such should be avoided in tumour-induced hypercalcaemia or metastatic bone disease if serum creatinine is greater than 400 μmol/L or 265 μmol/L, respectively. Bisphosphonates are divided into three generations of drug: first-generation (tiludronate, clodronate, etidronate), second-generation (ibandronate, alendronate, paimdronate), and third-generation (zoledronate, risedronate). One of the newest agents, zoledronate is 100-times more effective than second-generation pamidronate&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12558465/&lt;/ref&gt;. Whilst receiving bisphosphonate therapy, patients should take protective vitamin D and calcium supplements.<br /> <br /> ===Denosumab===<br /> Denosumab is a monoclonal antibody which binds to and inhibits the action of the RANK receptor ligand (RANKL). RANK is located on the surface of osteoclast progenitor cells and its activation stimulates their development into mature osteoclasts. Therefore denosumab, administered as a subcutaneous injection of 120 mg every four weeks, can help prevent bone destruction and fracture in patients with bone metastases. The antibody is cleared from the body by the reticuloendothelial system and can therefore be used in patients with poor renal function, in whom bisphosphonate use would be contraindicated&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/21145999/&lt;/ref&gt;. Additionally, data have shown that denosumab use causes greater suppression of osteolytic markers than bisphosphonate use in metastatic patients with breast&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/21060033/&lt;/ref&gt; or prostate&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/21353695/&lt;/ref&gt; cancer. However its effectiveness in comparison to bisphosphonates for patients with lung cancer or multiple myeloma is similar for the prevention of skeletal-related events (SRE), and indeed patients with multiple myeloma showed worse overall survival when treated with denosumab instead of zoledronate&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/21343556/&lt;/ref&gt;. <br /> <br /> ===Systemic anticancer therapies===<br /> [[Systemic anticancer therapy]] (SACT) refers to all drugs administered systemically with direct anticancer activity. This includes all conventional cytotoxic chemotherapies, all small molecule or antibody treatments, and all types of immunotherapy. Hormonal agents are not included within this categorisation. SACT may be considered for bone metastases if a primary tumour is known or subsequently confirmed. The specific therapy used will be the same therapy as typically used for the culprit primary cancer, though the precise dose and schedule will vary. SACT is sometimes used concurrently with other treatments such as bisphosphonates or radiotherapy. Side-effects will be treatment-specific.<br /> <br /> ===Hormone therapies===<br /> <br /> <br /> Hormone therapy is an indirect antitumour treatment which blocks the action of endogenous hormones or reduces their production within the body. Certain hormone-sensitive malignancies, particularly those of the prostate and breast, will often grow in response to specific hormones (androgens and oestrogens, respectively). Secondary metastases stemming from these primary tumours will, by extension, respond to hormone levels too. Androgen-responsive prostate cancer may be treated with drugs which lower androgen levels, such as gonadotrophin-releasing hormone (GnRH) receptor antagonists (peptides: '-''relix''&lt;nowiki/&gt;'; small-molecules: '-''golix''&lt;nowiki/&gt;'), GnRH receptor agonists ('-''relin''&lt;nowiki/&gt;'), and CYP17A1 inhibitors (such as abiraterone). Alternatively, androgen receptor blockers, such as bicalutamide or flutamide, can be effective. Oestrogen-responsive breast cancer may be treated with drugs which lower oestrogen levels, such as type I (exemestane) and type II (anastrozole, letrozole) aromatase inhibitors. Alternatively, selective oestrogen receptor modulators (SERMs), such as tamoxifen, can be effective. These modulators have mixed oestrogenic and antioestrogenic activity, which differs according to receptive tissue. Usefully in breast cancer, it is antioestrogenic in the breast; however, in the uterus and liver it is oestrogenic.<br /> ===Interventional radiology===<br /> The role of the interventional radiologist is ever-expanding. In the treatment of cancer there are procedures which are shared with or even done solely by these interventionists. Two important treatments offered the specialty for bone metastases are ablation and cementoplasty.<br /> <br /> '''Ablation''' is a medical term for when a procedural probe is introduced to an area of tissue (in this case tumour) and, using physical energy (heat or cold) or chemicals, cellular necrosis with subsequent scarring is achieved. It is useful for bony lesions if only there are one or two lesions to be targeted. The most common types of ablation are [[radiofrequency ablation]] (RFA), where an electric current passes through and heats a needle within the lesion, and cryoablation, where a cold probe within the lesion freezes and destroys cancer cells. Both are effective analgesic therapies; however, unlike in RFA, the ablation edge in cryoablation can be readily visualised with CT monitoring (as low-attenuation) and does not produce increased pain in the periprocedural period&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/21785102/&lt;/ref&gt;. Complications rates for each procedure are low, but localised infection and enduring neuropathic pain have been reported. <br /> <br /> percutaneous cementoplasty (bone cement)<br /> <br /> ===Surgery===<br /> Surgery is not considered to be amongst the conventional treatments for bony metastases. It is indicated for fractures of the hip and of long bones, and if there is need for vertebral surgery in [[Metastatic spinal cord compression|MSCC]]. Sometimes if bone involvement leads to fracture causing peripheral nerve impingement or compression, surgery may also be necessary.<br /> <br /> ==Living with bone metastases==<br /> Pain, mobility and safety, survival&lt;references /&gt;</div>

Alex https://oncopaedia.net/w/index.php?title=Articles:Bone_metastases&diff=324 2020-04-23T10:56:05Z

<p>Alex: </p> <hr /> <div>Metastases within bone can cause extreme and debilitating pain. Bone metastases are far more common than primary bone cancer, and many different cancer types can spread to the bone. The most common types of cancer which spread to bone are:<br /> <br /> *Breast<br /> *Prostate<br /> *Lung<br /> *Kidney<br /> *Thyroid<br /> <br /> Cancer can theoretically metastasize to any bone in the body, but in reality there is a predilection for certain sites. The most common sites are the vertebrae, ribs, pelvis, sternum, and the skull.<br /> <br /> ==Classification==<br /> A bone is a rigid organ, but it is far from physiologically static. To maintain bone strength, there is continuous breakdown and simultaneous reformation of bone, two processes which must finely balance for good bone health.<br /> <br /> '''Osteoblastic''' (or '''sclerotic''') metastases are characterised by the deposition of new bone. These are present most commonly in prostate cancer, but also occur in carcinoid, small cell lung cancer, medulloblastoma, and Hodgkin lymphoma. The molecular crosstalk between tumour and bone cells involves osteoblast-generating proteins such as Transforming Growth Factor, Bone Morphogenic Proteins (BMPs), and Endothelin-1&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12085970&lt;/ref&gt;.<br /> <br /> '''Osteolytic''' (or '''lytic''') metastases are characterised by the destruction and breakdown of normal bone. These often occur when breast cancer spreads to bone, which is primarily mediated by osteoclasts (bone cells that breaks down bone tissue) and is not a direct effect of metastasized tumour cells&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8086233/&lt;/ref&gt;. Other tumour types with osteolytic metastases include multiple myeloma, non-small cell lung cancer, thyroid cancer, non-Hodgkin lymphoma, and Langerhans' cell histiocytosis. Osteolytic metastases are more common than osteoblastic metastases.<br /> <br /> '''Mixed''' metastases are characterised by the presence of both osteolytic and osteoblastic lesions together in the same area of bone. These metastases are usually present in metastatic gastrointestinal and squamous cancers, as well as in secondary breast cancer. Although breast cancer gives rise to predominantly lytic lesions, around 15–20% of women have sclerotic or both types of lesions&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11346860/&lt;/ref&gt;.<br /> <br /> ==Diagnosis==<br /> <br /> ===Signs and symptoms===<br /> Bone metastases cause major morbidity, and high clinical suspicion should be kept for any patient with cancer that presents with:<br /> <br /> *Severe pain (poorly localised, worse at night)<br /> *Impaired mobility<br /> *[[Pathological fracture|Bone fracture]]<br /> *Bone marrow aplasia<br /> *Symptoms of (metastatic) [[Metastatic spinal cord compression|spinal cord compression]] (MSCC)<br /> *Symptoms in keeping with [[hypercalcaemia]]:<br /> **Constipation<br /> **Fatigue<br /> **Polyuria/polydipsia<br /> **Acute kidney injury (AKI)<br /> **Cardiac arrhythmia<br /> <br /> ===Bloods===<br /> When a patient with cancer presents with any of the signs or symptoms above, basic screening in the form of simple blood testing must be undertaken and complemented with appropriate imaging tests:<br /> <br /> *Full evaluation of bone turnover and potential hypercalcaemia:<br /> **Serum calcium<br /> **Serum phosphate<br /> **25-Hydroxyvitamin D<br /> **Thyroid-stimulating hormone (TSH)<br /> **Parathyroid hormone (PTH)<br /> **Serum creatinine<br /> **Alkaline phosphatase (ALP)<br /> *Full blood count (myelosuppression, anaemia)<br /> *Serum protein electrophoresis (SPEP; myeloma screen)<br /> *Tumour markers (such as PSA in prostate cancer)<br /> <br /> ===Imaging===<br /> Radiological tests are an essential component of diagnosing bony metastases. One or more imaging modalities may be required to confirm suspected cancerous spread to bone.<br /> <br /> '''Plain radiographs''' (X-ray scans) are quick, cost-effective, and widely-available, and should be the initial diagnostic test of choice when investigating bone pain. They are highly specific but lack sensitivity (44-50%) because early-stage metastatic lesions, particularly those up to 1 cm, may be more difficult to visualise. More than 50% of the trabecular bone must be involved before the lesion will be apparent on film and, due to the poor contrast of trabecular bone, lesions within the medulla are often less evident than those within cortical bone&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9025785/&lt;/ref&gt;. As outlined above, sclerotic metastases will appear more radiopaque than the surrounding bone, whereas lytic metastases will appear more radiolucent.<br /> <br /> '''Bone scintigraphy''' (bone scans) on the other hand is highly sensitive but with low specificity. Data from Technetium-99m ('''&lt;sup&gt;99m&lt;/sup&gt;Tc''') scintigraphy have shown false-negative rates as low as 11 to 38% (good sensitivity), with false-positive rates as high as 40% (poor specificity). It thus provides a non-specific osteoblastic indication of bone status, be it inflammatory, traumatic, or neoplastic in origin. Scintigraphy is still more specific and sensitive than either plain radiography or computed tomography, whilst magnetic resonance imaging is more efficacious in assessing vertebral metastases&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/2028061/&lt;/ref&gt;.<br /> <br /> '''Computed tomography''' (CT scans) has a high sensitivity, ranging from 71 to 100%, for the detection of metastatic bone lesions&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9362427/&lt;/ref&gt;. Because of the excellent soft tissue resolution of the images produced by CT, it is a particularly helpful modality to distinguish lytic and sclerotic metastases and to visualise their precise location(s) for biopsy.<br /> <br /> '''Magnetic resonance imaging''' (MRI scans) is useful in assessing bone marrow infiltration by tumour deposits, and is required (whole spine) for the proper diagnosis of [[Metastatic spinal cord compression|MSCC]]. It has similarly high specificity (73 to 100%) and sensitivity (82 to 100%) in screening for bone metastases&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10964746/&lt;/ref&gt;.<br /> <br /> '''Positron emission tomography''' (PET scans) detects tumour indirectly by measuring metabolic activity in the form of fluorodeoxyglucose ('''&lt;sup&gt;18&lt;/sup&gt;F''') tissue uptake. As such, its use is not limited to visualising only bony metastases, as &lt;sup&gt;18&lt;/sup&gt;F PET will reveal non-bony metastatic spread also&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8638000/&lt;/ref&gt;. The accuracy of PET is highly dependent on the primary tumour site from which imaged metastases originate. As a modality it is superior to scintigraphy in the screening of bony metastases from breast (specificity 94%, sensitivity 95%)&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12073051/&lt;/ref&gt; and lung (specificity 99%, sensitivity 92%)&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10478250/&lt;/ref&gt; malignancies, but has lower sensitivity in detecting the comparatively slower-growing bone metastases of prostate and renal cancers&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10520701/&lt;/ref&gt;. <br /> <br /> ===Biopsy===<br /> Sometimes it is necessary to diagnose metastases histologically, by removing cells or tissue from the bone lesion(s) directly. Usually this is in the form of a needle or surgical biopsy, and may be indicated if a primary cancer is not known. If the patient has a known primary cancer, then often imaging alone will suffice for the diagnosis of metastatic bone disease.<br /> <br /> ==Treatment==<br /> There are a variety of therapeutic interventions available to patients presenting with bone metastases, but consideration must be given to several patient-specific and tumour-dependent parameters, which include&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11738947/&lt;/ref&gt; (but are not limited to):<br /> <br /> *Lesion site(s) (localised or widespread)<br /> *Presence of extraskeletal metastasis<br /> *Tumour type and features (like receptors)<br /> *Prior treatment history (and response)<br /> *Clinical symptoms<br /> *Performance status<br /> <br /> ===Radiotherapy===<br /> Radiation therapy can provide excellent pain relief and is the treatment of choice for localised metastatic bone pain. However, the analgesic mechanisms of therapeutic skeletal irradiation are poorly understood. Onset of pain relief is usually quick, with a majority of patients experiencing benefit within one to two weeks. Patients who have little reduction in pain by six weeks are unlikely to demonstrate significant overall benefit&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/24782453/&lt;/ref&gt;. Other than localised bone pain, additional indications for radiotherapy include [[Metastatic spinal cord compression|MSCC]] and bones at high risk for [[pathological fracture]]&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/15978828/&lt;/ref&gt;. Two of the three main divisions of radiation therapy—the third being (sealed source) [[brachytherapy]]—can be used to treat bone metastases: systemic (unsealed source) [[radionuclide therapy]] and [[external beam radiotherapy]] (EBRT). <br /> <br /> '''Local-field [[External beam radiotherapy|EBRT]]''' is the standard choice of radiation therapy for treating bone metastases, as it focally targets the bone lesion and can achieve rates of substantial pain relief of up to 80 to 90%&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/6178497/&lt;/ref&gt;. Randomised controlled trials (RCTs) from the 1990s have shown that a single fraction of 8 gray (Gy) is as effective as fractionated doses of 20 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9681885&lt;/ref&gt;, 24 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10577695&lt;/ref&gt;, and 30 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10577696&lt;/ref&gt;. <br /> <br /> '''Wide-field''' (or '''hemibody''') '''[[External beam radiotherapy|EBRT]]''' is useful for widespread metastatic skeletal disease, though was more commonly used for multifocal pain when other effective therapies (chemo- and radionuclide) were not available. There are no RCTs comparing analgesic effect with and without wide-field radiotherapy. However, in terms of quasi-randomised and low-quality RCTs, there is data to suggest that use of fractionation is no more effective than single fraction treatment&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8823257&lt;/ref&gt;, that increasing doses beyond 8 Gy does not improve overall pain responses&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11395246&lt;/ref&gt;, and adding wide-field to local-field radiotherapy, whilst significantly halting disease progression (lesion size: P = 0.03; lesion number: P = 0.01), increases grade 3 to 4 haematological toxicity&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/1374061&lt;/ref&gt;. It is possible to classify wide-field treatments into three body regions, each with recommended single-fraction dose limits. Upper treatments (from skull or C1 to L2–L3) should be limited to 6 Gy, whereas mid-body (from L1 to upper third of femur) and lower (from L3–L4 to above knee) treatments should be limited to 8 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/6178497/&lt;/ref&gt;. Any treatments must be delivered with fields shaped to minimise irradiation of organs at risk, such as lung, liver, kidney and bowel. <br /> <br /> '''[[Stereotactic radiotherapy|Stereotactic]] [[External beam radiotherapy|EBRT]]''' is a promising treatment option which delivers higher doses of radiation to tumours in shorter periods in time. When used for extracranial cancers it is interchangeably termed Stereotactic Body Radiation Therapy ('''[[Stereotactic radiotherapy|SBRT]]''') or Stereotactic Ablative Radiotherapy ('''[[Stereotactic radiotherapy|SABR]]'''), the latter of which is appealingly onomatopoeic. When this technique is used for treating malignancy within the brain or some other part of the head, it is termed Stereotactic RadioSurgery ('''[[Stereotactic radiotherapy|SRS]]'''). SBRT/SABR can be used both for primary cancers (lung, liver, prostate, renal) and secondary metastases (bone/spine, lung, liver). There are a number of advantages of stereotactic radiotherapy, the most obvious of which is the potential completion of treatment within a single day, rather than over a number of weeks. The other major benefit is that it obviates the need to irradiate large portions of bone, which lowers the risk of further functional marrow depletion in a patient cohort already at risk of poor marrow reserve. Preserving skeletal marrow function can permit continuous chemotherapy in these patients. The primary limitations of SBRT/SABR are that it is more expensive to deliver than conventional EBRT and that there is a paucity of RCT data comparing its use to standard EBRT management&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/18619121/&lt;/ref&gt;. However, a recent single-centre phase II trial appeared to show that SBRT/SABR provides superior pain relief to conventional multifraction radiotherapy, with no observed difference in adverse events or other aspects of quality of life&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/31021390&lt;/ref&gt;. <br /> <br /> '''[[Radionuclide therapy]]''' (or '''radioisotope therapy''') is the systemic administration of radionuclides (also known as radioisotopes) as unsealed radioactive sources that selectively deliver radiation to tumours or target organs. They are taken up predominantly at sites of bone formation, and are therefore most likely best effective for the palliation of osteoblastic (sclerotic) metastases. Common radionuclides approved for the treatment of painful bone metastases include phosphorus-32 ('''&lt;sup&gt;32&lt;/sup&gt;P'''; ''β''-decay), strontium-89 ('''&lt;sup&gt;89&lt;/sup&gt;Sr'''; ''β''-decay), samarium-153 ('''&lt;sup&gt;153&lt;/sup&gt;Sm'''; ''β''- and ''γ''-decay), and rhenium-186 ('''&lt;sup&gt;186&lt;/sup&gt;Re'''; ''β''- and ''γ''-decay). The added advantage of gamma ray emission during decay is that it permits nuclear imaging monitoring of radionuclide biodistribution during therapy. These radionuclides target bone through various mechanisms. &lt;sup&gt;32&lt;/sup&gt;P passes through inorganic phosphate pathways, whereas &lt;sup&gt;89&lt;/sup&gt;Sr is a calcium mimetic and is taken up as a direct analogue of this earth metal. The final two agents are targeted to bone via chelation to phosphonate compounds: &lt;sup&gt;153&lt;/sup&gt;Sm is paired to ethylenediaminetetramethylenephosphonate (EDTMP) and &lt;sup&gt;186&lt;/sup&gt;Re to 1,1-hydroxyethylidene diphosphonate (HEDP). Common toxicities from treatment include myelosuppression and a transient pain flare, the latter of which usually heralds a favourable response. A more recently developed radionuclide, radium-223 (&lt;sup&gt;'''223'''&lt;/sup&gt;'''Ra'''; ''α''-, ''β''-, and ''γ''-decay) is a calcium mimetic which emits over 95% of decay energy in the form of alpha radiation&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/17062709&lt;/ref&gt;. Owing to their comparatively large size the emitted alpha particles have a more limited depth of penetration into surrounding tissues (around 2–10 cells), thereby producing a more potently localised cytotoxic effect. Despite their symptomatic benefits in refractory, widespread bone metastases, neither &lt;sup&gt;89&lt;/sup&gt;Sr nor &lt;sup&gt;153&lt;/sup&gt;Sm have been shown to improve overall survival in interventional trials; however, &lt;sup&gt;223&lt;/sup&gt;Ra use in metastatic castration-resistant prostate cancer patients in the ALSYMPCA (ALpharadin in SYMptomatic Prostate CAncer) trial was shown to significantly prolong overall survival&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/23863050/&lt;/ref&gt;. <br /> <br /> ===Bisphosphonates===<br /> Analogues of the natural bone demineralisation inhibitor pyrophosphate, bisphosphonates are useful in the treatment of poorly localised bone pain and in previously irradiated bone lesions. They bind with high affinity to exposed bone mineral where they are internalised by osteoclasts, within which they disrupt the processes of bone resorption and can induce apoptosis. Data have shown that bisphosphonates may have direct pro-apoptotic effects on nearby metastatic cancer cells also&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9362432/&lt;/ref&gt;. In halting the mobilisation of calcium and phosphate from bone, bisphosphonate use (together with rehydration) is now standard of care for malignancy-induced hypercalcaemia&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9025784/&lt;/ref&gt;. The analgesic effect of these agents is independent of underlying tumour characteristics, with osteolytic and osteoblastic lesions responding similarly&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9496390&lt;/ref&gt;. Many patients tolerate bisphosphonates without major concern, but common side-effects include flu-like myalgic symptoms, diarrhoea, nausea and reflux. It is exceedingly rare but one must be aware of the risk of developing osteonecrosis of the jaw. These medications undergo renal excretion and as such should be avoided in tumour-induced hypercalcaemia or metastatic bone disease if serum creatinine is greater than 400 μmol/L or 265 μmol/L, respectively. Bisphosphonates are divided into three generations of drug: first-generation (tiludronate, clodronate, etidronate), second-generation (ibandronate, alendronate, paimdronate), and third-generation (zoledronate, risedronate). One of the newest agents, zoledronate is 100-times more effective than second-generation pamidronate&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12558465/&lt;/ref&gt;. Whilst receiving bisphosphonate therapy, patients should take protective vitamin D and calcium supplements.<br /> <br /> ===Denosumab===<br /> Denosumab is a monoclonal antibody which binds to and inhibits the action of the RANK receptor ligand (RANKL). RANK is located on the surface of osteoclast progenitor cells and its activation stimulates their development into mature osteoclasts. Therefore denosumab, administered as a subcutaneous injection of 120 mg every four weeks, can help prevent bone destruction and fracture in patients with bone metastases. The antibody is cleared from the body by the reticuloendothelial system and can therefore be used in patients with poor renal function, in whom bisphosphonate use would be contraindicated&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/21145999/&lt;/ref&gt;. Additionally, data have shown that denosumab use causes greater suppression of osteolytic markers than bisphosphonate use in metastatic patients with breast&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/21060033/&lt;/ref&gt; or prostate&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/21353695/&lt;/ref&gt; cancer. However its effectiveness in comparison to bisphosphonates for patients with lung cancer or multiple myeloma is similar for the prevention of skeletal-related events (SRE), and indeed patients with multiple myeloma showed worse overall survival when treated with denosumab instead of zoledronate&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/21343556/&lt;/ref&gt;. <br /> <br /> ===Systemic anticancer therapies===<br /> [[Systemic anticancer therapy]] (SACT) refers to all drugs administered systemically with direct anticancer activity. This includes all conventional cytotoxic chemotherapies, all small molecule or antibody treatments, and all types of immunotherapy. Hormonal agents are not included within this categorisation. SACT may be considered for bone metastases if a primary tumour is known or subsequently confirmed. The specific therapy used will be the same therapy as typically used for the culprit primary cancer, though the precise dose and schedule will vary. SACT is sometimes used concurrently with other treatments such as bisphosphonates or radiotherapy. Side-effects will be treatment-specific.<br /> <br /> ===Hormone therapies===<br /> <br /> <br /> Hormone therapy is an indirect antitumour treatment which blocks the action of endogenous hormones or reduces their production within the body. Certain hormone-sensitive malignancies, particularly those of the prostate and breast, will often grow in response to specific hormones (androgens and oestrogens, respectively). Secondary metastases stemming from these primary tumours will, by extension, respond to hormone levels too. Androgen-responsive prostate cancer may be treated with drugs which lower androgen levels, such as gonadotrophin-releasing hormone (GnRH) receptor antagonists (peptides: '-''relix''&lt;nowiki/&gt;'; small-molecules: '-''golix''&lt;nowiki/&gt;'), GnRH receptor agonists ('-''relin''&lt;nowiki/&gt;'), and CYP17A1 inhibitors (such as abiraterone). Alternatively, androgen receptor blockers, such as bicalutamide or flutamide, can be effective. Oestrogen-responsive breast cancer may be treated with drugs which lower oestrogen levels, such as type I (exemestane) and type II (anastrozole, letrozole) aromatase inhibitors. Alternatively, selective oestrogen receptor modulators (SERMs), such as tamoxifen, can be effective. These modulators have mixed oestrogenic and antioestrogenic activity, which differs according to receptive tissue. Usefully in breast cancer, it is antioestrogenic in the breast; however, in the uterus and liver it is oestrogenic.<br /> ===Interventional radiology===<br /> The role of the interventional radiologist is ever-expanding. In the treatment of cancer there are procedures which are shared with or even done solely by these interventionists. Two important treatments offered the specialty for bone metastases are ablation and cementoplasty.<br /> <br /> '''Ablation''' is a generic medical term for when a procedural probe is introduced to an area of tissue (in this case tumour) and, using physical energy (heat or cold) or chemicals, cellular necrosis with subsequent scarring is achieved. It is useful for bony lesions if only <br /> <br /> Ablation (inc. RFA), percutaneous cementoplasty (bone cement)<br /> <br /> ===Surgery===<br /> Surgery is not considered to be amongst the conventional treatments for bony metastases. It is indicated for fractures of the hip and of long bones, and if there is need for vertebral surgery in [[Metastatic spinal cord compression|MSCC]]. Sometimes if bone involvement leads to fracture causing peripheral nerve impingement or compression, surgery may also be necessary.<br /> <br /> ==Living with bone metastases==<br /> Pain, mobility and safety, survival&lt;references /&gt;</div>

Alex https://oncopaedia.net/w/index.php?title=Home&diff=323 2020-04-22T19:54:05Z

<p>Alex: </p> <hr /> <div>{{seo|pagetitle=Home|meta_keywords=oncopedia,oncopaedia,cancer}}<br /> <br /> ==Oncopaedia is an online collaborative learning resource for use by oncology professionals ''everywhere''.==<br /> Our aim is to create '''one of the web's finest medical educational platforms''' '''to''' '''enhance the care of cancer patients worldwide'''. With your help, we hope to compile articles on every known cancer type, and we encourage all users to contribute anonymised case examples to each cancer article.<br /> <br /> You can very easily begin editing this website yourself! You don't need to even sign up, but we recommend that you do so we can give you proper credit! You need only provide a username, an email (which you must verify), and a unique password. You can create (or update) articles immediately (subject to a moderation queue if you are new to prevent abuse), and, although our interface is still in development, you can also contribute case data to articles of your choice.<br /> <br /> The oncology case information you can contribute includes (but is not limited to):<br /> <br /> *'''Contoured CT or MRI images''' of the tumour in question, with or without treatment planning beams and dose distributions.<br /> *'''Histopathology slides''' demonstrating the textbook microscopic appearance of that tumour subtype on biopsy.<br /> *'''Immunohistochemical stain images''' showing which are used to positively and negatively discriminate tumour tissue.<br /> *'''Pictures of the gross macroscopic appearance''' of the example cancer, with (if possible) video media showing its successful removal during surgery.<br /> *'''Textbook radiological imaging''' of the cancer in situ, which we would encourage you to submit to Radiopaedia.org (with whom we have no affiliation!) as well.<br /> *'''Genetic information''' from the types of tumour, and mutation signature of the tumour (if available).<br /> *'''The latest medical treatment guidelines''' from your country of practice, to compare with oncology practice globally.<br /> *'''Links to on-going clinical trials''' that are testing novel therapies and/or optimising drugs regimens for treating that specific cancer.<br /> <br /> This website is primarily for use by medical professionals; however, the information contained within these articles is accessible to—and undoubtedly will be used by—cancer patients and their families. We aim to keep access to our website permanently free in the spirit of the [https://lifeinthefastlane.com/foam #FOAMed] movement.<br /> <br /> __NOEDITSECTION__</div>

Alex https://oncopaedia.net/w/index.php?title=Articles:Bone_metastases&diff=315 2020-04-22T15:08:16Z

<p>Alex: </p> <hr /> <div>Metastases within bone can cause extreme and debilitating pain. Bone metastases are far more common than primary bone cancer, and many different cancer types can spread to the bone. The most common types of cancer which spread to bone are:<br /> <br /> *Breast<br /> *Prostate<br /> *Lung<br /> *Kidney<br /> *Thyroid<br /> <br /> Cancer can theoretically metastasize to any bone in the body, but in reality there is a predilection for certain sites. The most common sites are the vertebrae, ribs, pelvis, sternum, and the skull.<br /> <br /> ==Classification==<br /> A bone is a rigid organ, but it is far from physiologically static. To maintain bone strength, there is continuous breakdown and simultaneous reformation of bone, two processes which must finely balance for good bone health.<br /> <br /> '''Osteoblastic''' (or '''sclerotic''') metastases are characterised by the deposition of new bone. These are present most commonly in prostate cancer, but also occur in carcinoid, small cell lung cancer, medulloblastoma, and Hodgkin lymphoma. The molecular crosstalk between tumour and bone cells involves osteoblast-generating proteins such as Transforming Growth Factor, Bone Morphogenic Proteins (BMPs), and Endothelin-1&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12085970&lt;/ref&gt;.<br /> <br /> '''Osteolytic''' (or '''lytic''') metastases are characterised by the destruction and breakdown of normal bone. These often occur when breast cancer spreads to bone, which is primarily mediated by osteoclasts (bone cells that breaks down bone tissue) and is not a direct effect of metastasized tumour cells&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8086233/&lt;/ref&gt;. Other tumour types with osteolytic metastases include multiple myeloma, non-small cell lung cancer, thyroid cancer, non-Hodgkin lymphoma, and Langerhans' cell histiocytosis. Osteolytic metastases are more common than osteoblastic metastases.<br /> <br /> '''Mixed''' metastases are characterised by the presence of both osteolytic and osteoblastic lesions together in the same area of bone. These metastases are usually present in metastatic gastrointestinal and squamous cancers, as well as in secondary breast cancer. Although breast cancer gives rise to predominantly lytic lesions, around 15–20% of women have sclerotic or both types of lesions&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11346860/&lt;/ref&gt;.<br /> <br /> ==Diagnosis==<br /> <br /> ===Signs and symptoms===<br /> Bone metastases cause major morbidity, and high clinical suspicion should be kept for any patient with cancer that presents with:<br /> <br /> *Severe pain (poorly localised, worse at night)<br /> *Impaired mobility<br /> *[[Pathological fracture|Bone fracture]]<br /> *Bone marrow aplasia<br /> *Symptoms of (metastatic) [[Metastatic spinal cord compression|spinal cord compression]] (MSCC)<br /> *Symptoms in keeping with [[hypercalcaemia]]:<br /> **Constipation<br /> **Fatigue<br /> **Polyuria/polydipsia<br /> **Acute kidney injury (AKI)<br /> **Cardiac arrhythmia<br /> <br /> ===Bloods===<br /> When a patient with cancer presents with any of the signs or symptoms above, basic screening in the form of simple blood testing must be undertaken and complemented with appropriate imaging tests:<br /> <br /> *Full evaluation of bone turnover and potential hypercalcaemia:<br /> **Serum calcium<br /> **Serum phosphate<br /> **25-Hydroxyvitamin D<br /> **Thyroid-stimulating hormone (TSH)<br /> **Parathyroid hormone (PTH)<br /> **Serum creatinine<br /> **Alkaline phosphatase (ALP)<br /> *Full blood count (myelosuppression, anaemia)<br /> *Serum protein electrophoresis (SPEP; myeloma screen)<br /> *Tumour markers (such as PSA in prostate cancer)<br /> <br /> ===Imaging===<br /> Radiological tests are an essential component of diagnosing bony metastases. One or more imaging modalities may be required to confirm suspected cancerous spread to bone.<br /> <br /> '''Plain radiographs''' (X-ray scans) are quick, cost-effective, and widely-available, and should be the initial diagnostic test of choice when investigating bone pain. They are highly specific but lack sensitivity (44-50%) because early-stage metastatic lesions, particularly those up to 1 cm, may be more difficult to visualise. More than 50% of the trabecular bone must be involved before the lesion will be apparent on film and, due to the poor contrast of trabecular bone, lesions within the medulla are often less evident than those within cortical bone&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9025785/&lt;/ref&gt;. As outlined above, sclerotic metastases will appear more radiopaque than the surrounding bone, whereas lytic metastases will appear more radiolucent.<br /> <br /> '''Bone scintigraphy''' (bone scans) on the other hand is highly sensitive but with low specificity. Data from Technetium-99m ('''&lt;sup&gt;99m&lt;/sup&gt;Tc''') scintigraphy have shown false-negative rates as low as 11 to 38% (good sensitivity), with false-positive rates as high as 40% (poor specificity). It thus provides a non-specific osteoblastic indication of bone status, be it inflammatory, traumatic, or neoplastic in origin. Scintigraphy is still more specific and sensitive than either plain radiography or computed tomography, whilst magnetic resonance imaging is more efficacious in assessing vertebral metastases&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/2028061/&lt;/ref&gt;.<br /> <br /> '''Computed tomography''' (CT scans) has a high sensitivity, ranging from 71 to 100%, for the detection of metastatic bone lesions&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9362427/&lt;/ref&gt;. Because of the excellent soft tissue resolution of the images produced by CT, it is a particularly helpful modality to distinguish lytic and sclerotic metastases and to visualise their precise location(s) for biopsy.<br /> <br /> '''Magnetic resonance imaging''' (MRI scans) is useful in assessing bone marrow infiltration by tumour deposits, and is required (whole spine) for the proper diagnosis of [[Metastatic spinal cord compression|MSCC]]. It has similarly high specificity (73 to 100%) and sensitivity (82 to 100%) in screening for bone metastases&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10964746/&lt;/ref&gt;.<br /> <br /> '''Positron emission tomography''' (PET scans) detects tumour indirectly by measuring metabolic activity in the form of fluorodeoxyglucose ('''&lt;sup&gt;18&lt;/sup&gt;F''') tissue uptake. As such, its use is not limited to visualising only bony metastases, as &lt;sup&gt;18&lt;/sup&gt;F PET will reveal non-bony metastatic spread also&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8638000/&lt;/ref&gt;. The accuracy of PET is highly dependent on the primary tumour site from which imaged metastases originate. As a modality it is superior to scintigraphy in the screening of bony metastases from breast (specificity 94%, sensitivity 95%)&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12073051/&lt;/ref&gt; and lung (specificity 99%, sensitivity 92%)&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10478250/&lt;/ref&gt; malignancies, but has lower sensitivity in detecting the comparatively slower-growing bone metastases of prostate and renal cancers&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10520701/&lt;/ref&gt;. <br /> <br /> ===Biopsy===<br /> Sometimes it is necessary to diagnose metastases histologically, by removing cells or tissue from the bone lesion(s) directly. Usually this is in the form of a needle or surgical biopsy, and may be indicated if a primary cancer is not known. If the patient has a known primary cancer, then often imaging alone will suffice for the diagnosis of metastatic bone disease.<br /> <br /> ==Treatment==<br /> There are a variety of therapeutic interventions available to patients presenting with bone metastases, but consideration must be given to several patient-specific and tumour-dependent parameters, which include&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11738947/&lt;/ref&gt; (but are not limited to):<br /> <br /> *Lesion site(s) (localised or widespread)<br /> *Presence of extraskeletal metastasis<br /> *Tumour type and features (like receptors)<br /> *Prior treatment history (and response)<br /> *Clinical symptoms<br /> *Performance status<br /> <br /> ===Radiotherapy===<br /> Radiation therapy can provide excellent pain relief and is the treatment of choice for localised metastatic bone pain. However, the analgesic mechanisms of therapeutic skeletal irradiation are poorly understood. Onset of pain relief is usually quick, with a majority of patients experiencing benefit within one to two weeks. Patients who have little reduction in pain by six weeks are unlikely to demonstrate significant overall benefit&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/24782453/&lt;/ref&gt;. Other than localised bone pain, additional indications for radiotherapy include [[Metastatic spinal cord compression|MSCC]] and bones at high risk for [[pathological fracture]]&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/15978828/&lt;/ref&gt;. Two of the three main divisions of radiation therapy—the third being (sealed source) [[brachytherapy]]—can be used to treat bone metastases: systemic (unsealed source) [[radionuclide therapy]] and [[external beam radiotherapy]] (EBRT). <br /> <br /> '''Local-field [[External beam radiotherapy|EBRT]]''' is the standard choice of radiation therapy for treating bone metastases, as it focally targets the bone lesion and can achieve rates of substantial pain relief of up to 80 to 90%&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/6178497/&lt;/ref&gt;. Randomised controlled trials (RCTs) from the 1990s have shown that a single fraction of 8 gray (Gy) is as effective as fractionated doses of 20 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9681885&lt;/ref&gt;, 24 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10577695&lt;/ref&gt;, and 30 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10577696&lt;/ref&gt;. <br /> <br /> '''Wide-field''' (or '''hemibody''') '''[[External beam radiotherapy|EBRT]]''' is useful for widespread metastatic skeletal disease, though was more commonly used for multifocal pain when other effective therapies (chemo- and radionuclide) were not available. There are no RCTs comparing analgesic effect with and without wide-field radiotherapy. However, in terms of quasi-randomised and low-quality RCTs, there is data to suggest that use of fractionation is no more effective than single fraction treatment&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8823257&lt;/ref&gt;, that increasing doses beyond 8 Gy does not improve overall pain responses&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11395246&lt;/ref&gt;, and adding wide-field to local-field radiotherapy, whilst significantly halting disease progression (lesion size: P = 0.03; lesion number: P = 0.01), increases grade 3 to 4 haematological toxicity&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/1374061&lt;/ref&gt;. It is possible to classify wide-field treatments into three body regions, each with recommended single-fraction dose limits. Upper treatments (from skull or C1 to L2–L3) should be limited to 6 Gy, whereas mid-body (from L1 to upper third of femur) and lower (from L3–L4 to above knee) treatments should be limited to 8 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/6178497/&lt;/ref&gt;. Any treatments must be delivered with fields shaped to minimise irradiation of organs at risk, such as lung, liver, kidney and bowel. <br /> <br /> '''[[Stereotactic radiotherapy|Stereotactic]] [[External beam radiotherapy|EBRT]]''' is a promising treatment option which delivers higher doses of radiation to tumours in shorter periods in time. When used for extracranial cancers it is interchangeably termed Stereotactic Body Radiation Therapy ('''[[Stereotactic radiotherapy|SBRT]]''') or Stereotactic Ablative Radiotherapy ('''[[Stereotactic radiotherapy|SABR]]'''), the latter of which is appealingly onomatopoeic. When this technique is used for treating malignancy within the brain or some other part of the head, it is termed Stereotactic RadioSurgery ('''[[Stereotactic radiotherapy|SRS]]'''). SBRT/SABR can be used both for primary cancers (lung, liver, prostate, renal) and secondary metastases (bone/spine, lung, liver). There are a number of advantages of stereotactic radiotherapy, the most obvious of which is the potential completion of treatment within a single day, rather than over a number of weeks. The other major benefit is that it obviates the need to irradiate large portions of bone, which lowers the risk of further functional marrow depletion in a patient cohort already at risk of poor marrow reserve. Preserving skeletal marrow function can permit continuous chemotherapy in these patients. The primary limitations of SBRT/SABR are that it is more expensive to deliver than conventional EBRT and that there is a paucity of RCT data comparing its use to standard EBRT management&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/18619121/&lt;/ref&gt;. However, a recent single-centre phase II trial appeared to show that SBRT/SABR provides superior pain relief to conventional multifraction radiotherapy, with no observed difference in adverse events or other aspects of quality of life&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/31021390&lt;/ref&gt;. <br /> <br /> '''[[Radionuclide therapy]]''' (or '''radioisotope therapy''') is the systemic administration of radionuclides (also known as radioisotopes) as unsealed radioactive sources that selectively deliver radiation to tumours or target organs. They are taken up predominantly at sites of bone formation, and are therefore most likely best effective for the palliation of osteoblastic (sclerotic) metastases. Common radionuclides approved for the treatment of painful bone metastases include phosphorus-32 ('''&lt;sup&gt;32&lt;/sup&gt;P'''; ''β''-decay), strontium-89 ('''&lt;sup&gt;89&lt;/sup&gt;Sr'''; ''β''-decay), samarium-153 ('''&lt;sup&gt;153&lt;/sup&gt;Sm'''; ''β''- and ''γ''-decay), and rhenium-186 ('''&lt;sup&gt;186&lt;/sup&gt;Re'''; ''β''- and ''γ''-decay). The added advantage of gamma ray emission during decay is that it permits nuclear imaging monitoring of radionuclide biodistribution during therapy. These radionuclides target bone through various mechanisms. &lt;sup&gt;32&lt;/sup&gt;P passes through inorganic phosphate pathways, whereas &lt;sup&gt;89&lt;/sup&gt;Sr is a calcium mimetic and is taken up as a direct analogue of this earth metal. The final two agents are targeted to bone via chelation to phosphonate compounds: &lt;sup&gt;153&lt;/sup&gt;Sm is paired to ethylenediaminetetramethylenephosphonate (EDTMP) and &lt;sup&gt;186&lt;/sup&gt;Re to 1,1-hydroxyethylidene diphosphonate (HEDP). Common toxicities from treatment include myelosuppression and a transient pain flare, the latter of which usually heralds a favourable response. A more recently developed radionuclide, radium-223 (&lt;sup&gt;'''223'''&lt;/sup&gt;'''Ra'''; ''α''-, ''β''-, and ''γ''-decay) is a calcium mimetic which emits over 95% of decay energy in the form of alpha radiation&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/17062709&lt;/ref&gt;. Owing to their comparatively large size the emitted alpha particles have a more limited depth of penetration into surrounding tissues (around 2–10 cells), thereby producing a more potently localised cytotoxic effect. Despite their symptomatic benefits in refractory, widespread bone metastases, neither &lt;sup&gt;89&lt;/sup&gt;Sr nor &lt;sup&gt;153&lt;/sup&gt;Sm have been shown to improve overall survival in interventional trials; however, &lt;sup&gt;223&lt;/sup&gt;Ra use in metastatic castration-resistant prostate cancer patients in the ALSYMPCA (ALpharadin in SYMptomatic Prostate CAncer) trial was shown to significantly prolong overall survival&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/23863050/&lt;/ref&gt;. <br /> <br /> ===Bisphosphonates===<br /> Analogues of the natural bone demineralisation inhibitor pyrophosphate, bisphosphonates are useful in the treatment of poorly localised bone pain and in previously irradiated bone lesions. They bind with high affinity to exposed bone mineral where they are internalised by osteoclasts, within which they disrupt the processes of bone resorption and can induce apoptosis. Data have shown that bisphosphonates may have direct pro-apoptotic effects on nearby metastatic cancer cells also&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9362432/&lt;/ref&gt;. In halting the mobilisation of calcium and phosphate from bone, bisphosphonate use (together with rehydration) is now standard of care for malignancy-induced hypercalcaemia&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9025784/&lt;/ref&gt;. The analgesic effect of these agents is independent of underlying tumour characteristics, with osteolytic and osteoblastic lesions responding similarly&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9496390&lt;/ref&gt;. Many patients tolerate bisphosphonates without major concern, but common side-effects include flu-like myalgic symptoms, diarrhoea, nausea and reflux. It is exceedingly rare but one must be aware of the risk of developing osteonecrosis of the jaw. These medications undergo renal excretion and as such should be avoided in tumour-induced hypercalcaemia or metastatic bone disease if serum creatinine is greater than 400 μmol/L or 265 μmol/L, respectively. Bisphosphonates are divided into three generations of drug: first-generation (tiludronate, clodronate, etidronate), second-generation (ibandronate, alendronate, paimdronate), and third-generation (zoledronate, risedronate). One of the newest agents, zoledronate is 100-times more effective than second-generation pamidronate&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12558465/&lt;/ref&gt;. Whilst receiving bisphosphonate therapy, patients should take protective vitamin D and calcium supplements.<br /> <br /> ===Denosumab===<br /> Denosumab is a monoclonal antibody which binds to and inhibits the action of the RANK receptor ligand (RANKL). RANK is located on the surface of osteoclast progenitor cells and its activation stimulates their development into mature osteoclasts. Therefore denosumab, administered as a subcutaneous injection of 120 mg every four weeks, can help prevent bone destruction and fracture in patients with bone metastases. The antibody is cleared from the body by the reticuloendothelial system and can therefore be used in patients with poor renal function, in whom bisphosphonate use would be contraindicated&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/21145999/&lt;/ref&gt;. Additionally, data have shown that denosumab use causes greater suppression of osteolytic markers than bisphosphonate use in metastatic patients with breast&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/21060033/&lt;/ref&gt; or prostate&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/21353695/&lt;/ref&gt; cancer. However its effectiveness in comparison to bisphosphonates for patients with lung cancer or multiple myeloma is similar for the prevention of skeletal-related events (SRE), and indeed patients with multiple myeloma showed worse overall survival when treated with denosumab instead of zoledronate&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/21343556/&lt;/ref&gt;. <br /> <br /> ===Systemic anticancer therapies===<br /> [[Systemic anticancer therapy]] (SACT) refers to all drugs administered systemically with direct anticancer activity. This includes all conventional cytotoxic chemotherapies, all small molecule or antibody treatments, and all types of immunotherapy. Hormonal agents are not included within this categorisation. SACT may be considered for bone metastases if a primary tumour is known or subsequently confirmed. The specific therapy used will be the same therapy as typically used for the culprit primary cancer, though the precise dose and schedule will vary. SACT is sometimes used concurrently with other treatments such as bisphosphonates or radiotherapy. Side-effects will be treatment-specific.<br /> <br /> ===Hormone therapies===<br /> <br /> <br /> Hormone therapy is an indirect antitumour treatment which blocks the action of endogenous hormones or reduces their production within the body. Certain hormone-sensitive malignancies, particularly those of the prostate and breast, will often grow in response to specific hormones (androgens and oestrogens, respectively). Secondary metastases stemming from these primary tumours will, by extension, respond to hormone levels too. Androgen-responsive prostate cancer may be treated with drugs which lower androgen levels, such as gonadotrophin-releasing hormone (GnRH) receptor antagonists (peptides: '-''relix''&lt;nowiki/&gt;'; small-molecules: '-''golix''&lt;nowiki/&gt;'), GnRH receptor agonists ('-''relin''&lt;nowiki/&gt;'), and CYP17A1 inhibitors (such as abiraterone). Alternatively, androgen receptor blockers, such as bicalutamide or flutamide, can be effective. Oestrogen-responsive breast cancer may be treated with drugs which lower oestrogen levels, such as type I (exemestane) and type II (anastrozole, letrozole) aromatase inhibitors. Alternatively, selective oestrogen receptor modulators (SERMs), such as tamoxifen, can be effective. These modulators have mixed oestrogenic and antioestrogenic activity, which differs according to receptive tissue. Usefully in breast cancer, it is antioestrogenic in the breast; however, in the uterus and liver it is oestrogenic.<br /> ===Interventional radiology===<br /> Ablation (inc. RFA), percutaneous cementoplasty (bone cement)<br /> <br /> ===Surgery===<br /> Surgery is not considered to be amongst the conventional treatments for bony metastases. It is indicated for fractures of the hip and of long bones, and if there is need for vertebral surgery in [[Metastatic spinal cord compression|MSCC]]. Sometimes if bone involvement leads to fracture causing peripheral nerve impingement or compression, surgery may also be necessary.<br /> <br /> ==Living with bone metastases==<br /> Pain, mobility and safety, survival&lt;references /&gt;</div>

Alex https://oncopaedia.net/w/index.php?title=Articles:Bone_metastases&diff=314 2020-04-22T14:49:13Z

<p>Alex: </p> <hr /> <div>Metastases within bone can cause extreme and debilitating pain. Bone metastases are far more common than primary bone cancer, and many different cancer types can spread to the bone. The most common types of cancer which spread to bone are:<br /> <br /> *Breast<br /> *Prostate<br /> *Lung<br /> *Kidney<br /> *Thyroid<br /> <br /> Cancer can theoretically metastasize to any bone in the body, but in reality there is a predilection for certain sites. The most common sites are the vertebrae, ribs, pelvis, sternum, and the skull.<br /> <br /> ==Classification==<br /> A bone is a rigid organ, but it is far from physiologically static. To maintain bone strength, there is continuous breakdown and simultaneous reformation of bone, two processes which must finely balance for good bone health.<br /> <br /> '''Osteoblastic''' (or '''sclerotic''') metastases are characterised by the deposition of new bone. These are present most commonly in prostate cancer, but also occur in carcinoid, small cell lung cancer, medulloblastoma, and Hodgkin lymphoma. The molecular crosstalk between tumour and bone cells involves osteoblast-generating proteins such as Transforming Growth Factor, Bone Morphogenic Proteins (BMPs), and Endothelin-1&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12085970&lt;/ref&gt;.<br /> <br /> '''Osteolytic''' (or '''lytic''') metastases are characterised by the destruction and breakdown of normal bone. These often occur when breast cancer spreads to bone, which is primarily mediated by osteoclasts (bone cells that breaks down bone tissue) and is not a direct effect of metastasized tumour cells&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8086233/&lt;/ref&gt;. Other tumour types with osteolytic metastases include multiple myeloma, non-small cell lung cancer, thyroid cancer, non-Hodgkin lymphoma, and Langerhans' cell histiocytosis. Osteolytic metastases are more common than osteoblastic metastases.<br /> <br /> '''Mixed''' metastases are characterised by the presence of both osteolytic and osteoblastic lesions together in the same area of bone. These metastases are usually present in metastatic gastrointestinal and squamous cancers, as well as in secondary breast cancer. Although breast cancer gives rise to predominantly lytic lesions, around 15–20% of women have sclerotic or both types of lesions&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11346860/&lt;/ref&gt;.<br /> <br /> ==Diagnosis==<br /> <br /> ===Signs and symptoms===<br /> Bone metastases cause major morbidity, and high clinical suspicion should be kept for any patient with cancer that presents with:<br /> <br /> *Severe pain (poorly localised, worse at night)<br /> *Impaired mobility<br /> *[[Pathological fracture|Bone fracture]]<br /> *Bone marrow aplasia<br /> *Symptoms of (metastatic) [[Metastatic spinal cord compression|spinal cord compression]] (MSCC)<br /> *Symptoms in keeping with [[hypercalcaemia]]:<br /> **Constipation<br /> **Fatigue<br /> **Polyuria/polydipsia<br /> **Acute kidney injury (AKI)<br /> **Cardiac arrhythmia<br /> <br /> ===Bloods===<br /> When a patient with cancer presents with any of the signs or symptoms above, basic screening in the form of simple blood testing must be undertaken and complemented with appropriate imaging tests:<br /> <br /> *Full evaluation of bone turnover and potential hypercalcaemia:<br /> **Serum calcium<br /> **Serum phosphate<br /> **25-Hydroxyvitamin D<br /> **Thyroid-stimulating hormone (TSH)<br /> **Parathyroid hormone (PTH)<br /> **Serum creatinine<br /> **Alkaline phosphatase (ALP)<br /> *Full blood count (myelosuppression, anaemia)<br /> *Serum protein electrophoresis (SPEP; myeloma screen)<br /> *Tumour markers (such as PSA in prostate cancer)<br /> <br /> ===Imaging===<br /> Radiological tests are an essential component of diagnosing bony metastases. One or more imaging modalities may be required to confirm suspected cancerous spread to bone.<br /> <br /> '''Plain radiographs''' (X-ray scans) are quick, cost-effective, and widely-available, and should be the initial diagnostic test of choice when investigating bone pain. They are highly specific but lack sensitivity (44-50%) because early-stage metastatic lesions, particularly those up to 1 cm, may be more difficult to visualise. More than 50% of the trabecular bone must be involved before the lesion will be apparent on film and, due to the poor contrast of trabecular bone, lesions within the medulla are often less evident than those within cortical bone&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9025785/&lt;/ref&gt;. As outlined above, sclerotic metastases will appear more radiopaque than the surrounding bone, whereas lytic metastases will appear more radiolucent.<br /> <br /> '''Bone scintigraphy''' (bone scans) on the other hand is highly sensitive but with low specificity. Data from Technetium-99m ('''&lt;sup&gt;99m&lt;/sup&gt;Tc''') scintigraphy have shown false-negative rates as low as 11 to 38% (good sensitivity), with false-positive rates as high as 40% (poor specificity). It thus provides a non-specific osteoblastic indication of bone status, be it inflammatory, traumatic, or neoplastic in origin. Scintigraphy is still more specific and sensitive than either plain radiography or computed tomography, whilst magnetic resonance imaging is more efficacious in assessing vertebral metastases&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/2028061/&lt;/ref&gt;.<br /> <br /> '''Computed tomography''' (CT scans) has a high sensitivity, ranging from 71 to 100%, for the detection of metastatic bone lesions&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9362427/&lt;/ref&gt;. Because of the excellent soft tissue resolution of the images produced by CT, it is a particularly helpful modality to distinguish lytic and sclerotic metastases and to visualise their precise location(s) for biopsy.<br /> <br /> '''Magnetic resonance imaging''' (MRI scans) is useful in assessing bone marrow infiltration by tumour deposits, and is required (whole spine) for the proper diagnosis of [[Metastatic spinal cord compression|MSCC]]. It has similarly high specificity (73 to 100%) and sensitivity (82 to 100%) in screening for bone metastases&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10964746/&lt;/ref&gt;.<br /> <br /> '''Positron emission tomography''' (PET scans) detects tumour indirectly by measuring metabolic activity in the form of fluorodeoxyglucose ('''&lt;sup&gt;18&lt;/sup&gt;F''') tissue uptake. As such, its use is not limited to visualising only bony metastases, as &lt;sup&gt;18&lt;/sup&gt;F PET will reveal non-bony metastatic spread also&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8638000/&lt;/ref&gt;. The accuracy of PET is highly dependent on the primary tumour site from which imaged metastases originate. As a modality it is superior to scintigraphy in the screening of bony metastases from breast (specificity 94%, sensitivity 95%)&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12073051/&lt;/ref&gt; and lung (specificity 99%, sensitivity 92%)&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10478250/&lt;/ref&gt; malignancies, but has lower sensitivity in detecting the comparatively slower-growing bone metastases of prostate and renal cancers&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10520701/&lt;/ref&gt;. <br /> <br /> ===Biopsy===<br /> Sometimes it is necessary to diagnose metastases histologically, by removing cells or tissue from the bone lesion(s) directly. Usually this is in the form of a needle or surgical biopsy, and may be indicated if a primary cancer is not known. If the patient has a known primary cancer, then often imaging alone will suffice for the diagnosis of metastatic bone disease.<br /> <br /> ==Treatment==<br /> There are a variety of therapeutic interventions available to patients presenting with bone metastases, but consideration must be given to several patient-specific and tumour-dependent parameters, which include&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11738947/&lt;/ref&gt; (but are not limited to):<br /> <br /> *Lesion site(s) (localised or widespread)<br /> *Presence of extraskeletal metastasis<br /> *Tumour type and features (like receptors)<br /> *Prior treatment history (and response)<br /> *Clinical symptoms<br /> *Performance status<br /> <br /> ===Radiotherapy===<br /> Radiation therapy can provide excellent pain relief and is the treatment of choice for localised metastatic bone pain. However, the analgesic mechanisms of therapeutic skeletal irradiation are poorly understood. Onset of pain relief is usually quick, with a majority of patients experiencing benefit within one to two weeks. Patients who have little reduction in pain by six weeks are unlikely to demonstrate significant overall benefit&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/24782453/&lt;/ref&gt;. Other than localised bone pain, additional indications for radiotherapy include [[Metastatic spinal cord compression|MSCC]] and bones at high risk for [[pathological fracture]]&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/15978828/&lt;/ref&gt;. Two of the three main divisions of radiation therapy—the third being (sealed source) [[brachytherapy]]—can be used to treat bone metastases: systemic (unsealed source) [[radionuclide therapy]] and [[external beam radiotherapy]] (EBRT). <br /> <br /> '''Local-field [[External beam radiotherapy|EBRT]]''' is the standard choice of radiation therapy for treating bone metastases, as it focally targets the bone lesion and can achieve rates of substantial pain relief of up to 80 to 90%&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/6178497/&lt;/ref&gt;. Randomised controlled trials (RCTs) from the 1990s have shown that a single fraction of 8 gray (Gy) is as effective as fractionated doses of 20 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9681885&lt;/ref&gt;, 24 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10577695&lt;/ref&gt;, and 30 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10577696&lt;/ref&gt;. <br /> <br /> '''Wide-field''' (or '''hemibody''') '''[[External beam radiotherapy|EBRT]]''' is useful for widespread metastatic skeletal disease, though was more commonly used for multifocal pain when other effective therapies (chemo- and radionuclide) were not available. There are no RCTs comparing analgesic effect with and without wide-field radiotherapy. However, in terms of quasi-randomised and low-quality RCTs, there is data to suggest that use of fractionation is no more effective than single fraction treatment&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8823257&lt;/ref&gt;, that increasing doses beyond 8 Gy does not improve overall pain responses&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11395246&lt;/ref&gt;, and adding wide-field to local-field radiotherapy, whilst significantly halting disease progression (lesion size: P = 0.03; lesion number: P = 0.01), increases grade 3 to 4 haematological toxicity&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/1374061&lt;/ref&gt;. It is possible to classify wide-field treatments into three body regions, each with recommended single-fraction dose limits. Upper treatments (from skull or C1 to L2–L3) should be limited to 6 Gy, whereas mid-body (from L1 to upper third of femur) and lower (from L3–L4 to above knee) treatments should be limited to 8 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/6178497/&lt;/ref&gt;. Any treatments must be delivered with fields shaped to minimise irradiation of organs at risk, such as lung, liver, kidney and bowel. <br /> <br /> '''[[Stereotactic radiotherapy|Stereotactic]] [[External beam radiotherapy|EBRT]]''' is a promising treatment option which delivers higher doses of radiation to tumours in shorter periods in time. When used for extracranial cancers it is interchangeably termed Stereotactic Body Radiation Therapy ('''[[Stereotactic radiotherapy|SBRT]]''') or Stereotactic Ablative Radiotherapy ('''[[Stereotactic radiotherapy|SABR]]'''), the latter of which is appealingly onomatopoeic. When this technique is used for treating malignancy within the brain or some other part of the head, it is termed Stereotactic RadioSurgery ('''[[Stereotactic radiotherapy|SRS]]'''). SBRT/SABR can be used both for primary cancers (lung, liver, prostate, renal) and secondary metastases (bone/spine, lung, liver). There are a number of advantages of stereotactic radiotherapy, the most obvious of which is the potential completion of treatment within a single day, rather than over a number of weeks. The other major benefit is that it obviates the need to irradiate large portions of bone, which lowers the risk of further functional marrow depletion in a patient cohort already at risk of poor marrow reserve. Preserving skeletal marrow function can permit continuous chemotherapy in these patients. The primary limitations of SBRT/SABR are that it is more expensive to deliver than conventional EBRT and that there is a paucity of RCT data comparing its use to standard EBRT management&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/18619121/&lt;/ref&gt;. However, a recent single-centre phase II trial appeared to show that SBRT/SABR provides superior pain relief to conventional multifraction radiotherapy, with no observed difference in adverse events or other aspects of quality of life&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/31021390&lt;/ref&gt;. <br /> <br /> '''[[Radionuclide therapy]]''' (or '''radioisotope therapy''') is the systemic administration of radionuclides (also known as radioisotopes) as unsealed radioactive sources that selectively deliver radiation to tumours or target organs. They are taken up predominantly at sites of bone formation, and are therefore most likely best effective for the palliation of osteoblastic (sclerotic) metastases. Common radionuclides approved for the treatment of painful bone metastases include phosphorus-32 ('''&lt;sup&gt;32&lt;/sup&gt;P'''; ''β''-decay), strontium-89 ('''&lt;sup&gt;89&lt;/sup&gt;Sr'''; ''β''-decay), samarium-153 ('''&lt;sup&gt;153&lt;/sup&gt;Sm'''; ''β''- and ''γ''-decay), and rhenium-186 ('''&lt;sup&gt;186&lt;/sup&gt;Re'''; ''β''- and ''γ''-decay). The added advantage of gamma ray emission during decay is that it permits nuclear imaging monitoring of radionuclide biodistribution during therapy. These radionuclides target bone through various mechanisms. &lt;sup&gt;32&lt;/sup&gt;P passes through inorganic phosphate pathways, whereas &lt;sup&gt;89&lt;/sup&gt;Sr is a calcium mimetic and is taken up as a direct analogue of this earth metal. The final two agents are targeted to bone via chelation to phosphonate compounds: &lt;sup&gt;153&lt;/sup&gt;Sm is paired to ethylenediaminetetramethylenephosphonate (EDTMP) and &lt;sup&gt;186&lt;/sup&gt;Re to 1,1-hydroxyethylidene diphosphonate (HEDP). Common toxicities from treatment include myelosuppression and a transient pain flare, the latter of which usually heralds a favourable response. A more recently developed radionuclide, radium-223 (&lt;sup&gt;'''223'''&lt;/sup&gt;'''Ra'''; ''α''-, ''β''-, and ''γ''-decay) is a calcium mimetic which emits over 95% of decay energy in the form of alpha radiation&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/17062709&lt;/ref&gt;. Owing to their comparatively large size the emitted alpha particles have a more limited depth of penetration into surrounding tissues (around 2–10 cells), thereby producing a more potently localised cytotoxic effect. Despite their symptomatic benefits in refractory, widespread bone metastases, neither &lt;sup&gt;89&lt;/sup&gt;Sr nor &lt;sup&gt;153&lt;/sup&gt;Sm have been shown to improve overall survival in interventional trials; however, &lt;sup&gt;223&lt;/sup&gt;Ra use in metastatic castration-resistant prostate cancer patients in the ALSYMPCA (ALpharadin in SYMptomatic Prostate CAncer) trial was shown to significantly prolong overall survival&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/23863050/&lt;/ref&gt;. <br /> <br /> ===Bisphosphonates===<br /> Analogues of the natural bone demineralisation inhibitor pyrophosphate, bisphosphonates are useful in the treatment of poorly localised bone pain and in previously irradiated bone lesions. They bind with high affinity to exposed bone mineral where they are internalised by osteoclasts, within which they disrupt the processes of bone resorption and can induce apoptosis. Data have shown that bisphosphonates may have direct pro-apoptotic effects on nearby metastatic cancer cells also&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9362432/&lt;/ref&gt;. In halting the mobilisation of calcium and phosphate from bone, bisphosphonate use (together with rehydration) is now standard of care for malignancy-induced hypercalcaemia&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9025784/&lt;/ref&gt;. The analgesic effect of these agents is independent of underlying tumour characteristics, with osteolytic and osteoblastic lesions responding similarly&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9496390&lt;/ref&gt;. Many patients tolerate bisphosphonates without major concern, but common side-effects include flu-like myalgic symptoms, diarrhoea, nausea and reflux. It is exceedingly rare but one must be aware of the risk of developing osteonecrosis of the jaw. These medications undergo renal excretion and as such should be avoided in tumour-induced hypercalcaemia or metastatic bone disease if serum creatinine is greater than 400 μmol/L or 265 μmol/L, respectively. Bisphosphonates are divided into three generations of drug: first-generation (tiludronate, clodronate, etidronate), second-generation (ibandronate, alendronate, paimdronate), and third-generation (zoledronate, risedronate). One of the newest agents, zoledronate is 100-times more effective than second-generation pamidronate&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12558465/&lt;/ref&gt;. Whilst receiving bisphosphonate therapy, patients should take protective vitamin D and calcium supplements.<br /> <br /> ===Denosumab===<br /> Denosumab is a monoclonal antibody which binds to and inhibits the action of the RANK receptor ligand (RANKL). RANK is located on the surface of osteoclast progenitor cells and its activation stimulates their development into mature osteoclasts. Therefore denosumab, administered as a subcutaneous injection of 120 mg every four weeks, can help prevent bone destruction and fracture in patients with bone metastases. The antibody is cleared from the body by the reticuloendothelial system and can therefore be used in patients with poor renal function, in whom bisphosphonate use would be contraindicated&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/21145999/&lt;/ref&gt;. Additionally, data have shown that denosumab use causes greater suppression of osteolytic markers than bisphosphonate use in metastatic patients with breast&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/21060033/&lt;/ref&gt; or prostate&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/21353695/&lt;/ref&gt; cancer. However its effectiveness in comparison to bisphosphonates for patients with lung cancer or multiple myeloma is similar for the prevention of skeletal-related events (SRE), and indeed patients with multiple myeloma showed worse overall survival when treated with denosumab instead of zoledronate&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/21343556/&lt;/ref&gt;. <br /> <br /> ===Systemic anticancer therapies===<br /> [[Systemic anticancer therapy]] (SACT) refers to all drugs administered systemically with direct anticancer activity. This includes all conventional cytotoxic chemotherapies, all small molecule or antibody treatments, and all types of immunotherapy. Hormonal agents are not included within this categorisation. SACT may be considered for bone metastases if a primary tumour is known or subsequently confirmed. The specific therapy used will be the same therapy as typically used for the culprit primary cancer, though the precise dose and schedule will vary. SACT is sometimes used concurrently with other treatments such as bisphosphonates or radiotherapy. Side-effects will be treatment-specific.<br /> <br /> ===Hormone therapies===<br /> <br /> <br /> Hormone therapy is an indirect antitumour treatment which blocks the action of endogenous hormones or reduces their production within the body. Certain hormone-sensitive malignancies, particularly those of the prostate and breast, will often grow in response to specific hormones (androgens and oestrogens, respectively). Secondary metastases stemming from these primary tumours will, by extension, respond to hormone levels too. Androgen-responsive prostate cancer may be treated with drugs which lower androgen levels, such as gonadotrophin-releasing hormone (GnRH) receptor antagonists (peptides: '-''relix''&lt;nowiki/&gt;'; small-molecules: '-''golix''&lt;nowiki/&gt;'), GnRH receptor agonists ('-''relin''&lt;nowiki/&gt;'), and CYP17A1 inhibitors (such as abiraterone). Alternatively, androgen receptor blockers, such as bicalutamide or flutamide, can be effective. Oestrogen-responsive breast cancer may be treated with drugs which lower oestrogen levels, such as type I (exemestane) and type II (anastrozole, letrozole) aromatase inhibitors. Alternatively, selective oestrogen receptor modulators (SERMs), such as tamoxifen, can be effective. These modulators have mixed oestrogenic and antioestrogenic activity, which differs according to receptive tissue. Usefully in breast cancer, it is antioestrogenic in the breast; however, in the uterus and liver it is oestrogenic.<br /> ===Interventional radiology===<br /> Ablation (inc. RFA), percutaneous cementoplasty (bone cement)<br /> <br /> ===Surgery===<br /> -<br /> <br /> ==Living with bone metastases==<br /> Pain, mobility and safety, survival&lt;references /&gt;</div>

Alex https://oncopaedia.net/w/index.php?title=Articles:Bone_metastases&diff=313 2020-04-22T14:43:21Z

<p>Alex: </p> <hr /> <div>Metastases within bone can cause extreme and debilitating pain. Bone metastases are far more common than primary bone cancer, and many different cancer types can spread to the bone. The most common types of cancer which spread to bone are:<br /> <br /> *Breast<br /> *Prostate<br /> *Lung<br /> *Kidney<br /> *Thyroid<br /> <br /> Cancer can theoretically metastasize to any bone in the body, but in reality there is a predilection for certain sites. The most common sites are the vertebrae, ribs, pelvis, sternum, and the skull.<br /> <br /> ==Classification==<br /> A bone is a rigid organ, but it is far from physiologically static. To maintain bone strength, there is continuous breakdown and simultaneous reformation of bone, two processes which must finely balance for good bone health.<br /> <br /> '''Osteoblastic''' (or '''sclerotic''') metastases are characterised by the deposition of new bone. These are present most commonly in prostate cancer, but also occur in carcinoid, small cell lung cancer, medulloblastoma, and Hodgkin lymphoma. The molecular crosstalk between tumour and bone cells involves osteoblast-generating proteins such as Transforming Growth Factor, Bone Morphogenic Proteins (BMPs), and Endothelin-1&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12085970&lt;/ref&gt;.<br /> <br /> '''Osteolytic''' (or '''lytic''') metastases are characterised by the destruction and breakdown of normal bone. These often occur when breast cancer spreads to bone, which is primarily mediated by osteoclasts (bone cells that breaks down bone tissue) and is not a direct effect of metastasized tumour cells&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8086233/&lt;/ref&gt;. Other tumour types with osteolytic metastases include multiple myeloma, non-small cell lung cancer, thyroid cancer, non-Hodgkin lymphoma, and Langerhans' cell histiocytosis. Osteolytic metastases are more common than osteoblastic metastases.<br /> <br /> '''Mixed''' metastases are characterised by the presence of both osteolytic and osteoblastic lesions together in the same area of bone. These metastases are usually present in metastatic gastrointestinal and squamous cancers, as well as in secondary breast cancer. Although breast cancer gives rise to predominantly lytic lesions, around 15–20% of women have sclerotic or both types of lesions&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11346860/&lt;/ref&gt;.<br /> <br /> ==Diagnosis==<br /> <br /> ===Signs and symptoms===<br /> Bone metastases cause major morbidity, and high clinical suspicion should be kept for any patient with cancer that presents with:<br /> <br /> *Severe pain (poorly localised, worse at night)<br /> *Impaired mobility<br /> *[[Pathological fracture|Bone fracture]]<br /> *Bone marrow aplasia<br /> *Symptoms of (metastatic) [[Metastatic spinal cord compression|spinal cord compression]] (MSCC)<br /> *Symptoms in keeping with [[hypercalcaemia]]:<br /> **Constipation<br /> **Fatigue<br /> **Polyuria/polydipsia<br /> **Acute kidney injury (AKI)<br /> **Cardiac arrhythmia<br /> <br /> ===Bloods===<br /> When a patient with cancer presents with any of the signs or symptoms above, basic screening in the form of simple blood testing must be undertaken and complemented with appropriate imaging tests:<br /> <br /> *Full evaluation of bone turnover and potential hypercalcaemia:<br /> **Serum calcium<br /> **Serum phosphate<br /> **25-Hydroxyvitamin D<br /> **Thyroid-stimulating hormone (TSH)<br /> **Parathyroid hormone (PTH)<br /> **Serum creatinine<br /> **Alkaline phosphatase (ALP)<br /> *Full blood count (myelosuppression, anaemia)<br /> *Serum protein electrophoresis (SPEP; myeloma screen)<br /> *Tumour markers (such as PSA in prostate cancer)<br /> <br /> ===Imaging===<br /> Radiological tests are an essential component of diagnosing bony metastases. One or more imaging modalities may be required to confirm suspected cancerous spread to bone.<br /> <br /> '''Plain radiographs''' (X-ray scans) are quick, cost-effective, and widely-available, and should be the initial diagnostic test of choice when investigating bone pain. They are highly specific but lack sensitivity (44-50%) because early-stage metastatic lesions, particularly those up to 1 cm, may be more difficult to visualise. More than 50% of the trabecular bone must be involved before the lesion will be apparent on film and, due to the poor contrast of trabecular bone, lesions within the medulla are often less evident than those within cortical bone&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9025785/&lt;/ref&gt;. As outlined above, sclerotic metastases will appear more radiopaque than the surrounding bone, whereas lytic metastases will appear more radiolucent.<br /> <br /> '''Bone scintigraphy''' (bone scans) on the other hand is highly sensitive but with low specificity. Data from Technetium-99m ('''&lt;sup&gt;99m&lt;/sup&gt;Tc''') scintigraphy have shown false-negative rates as low as 11 to 38% (good sensitivity), with false-positive rates as high as 40% (poor specificity). It thus provides a non-specific osteoblastic indication of bone status, be it inflammatory, traumatic, or neoplastic in origin. Scintigraphy is still more specific and sensitive than either plain radiography or computed tomography, whilst magnetic resonance imaging is more efficacious in assessing vertebral metastases&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/2028061/&lt;/ref&gt;.<br /> <br /> '''Computed tomography''' (CT scans) has a high sensitivity, ranging from 71 to 100%, for the detection of metastatic bone lesions&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9362427/&lt;/ref&gt;. Because of the excellent soft tissue resolution of the images produced by CT, it is a particularly helpful modality to distinguish lytic and sclerotic metastases and to visualise their precise location(s) for biopsy.<br /> <br /> '''Magnetic resonance imaging''' (MRI scans) is useful in assessing bone marrow infiltration by tumour deposits, and is required (whole spine) for the proper diagnosis of [[Metastatic spinal cord compression|MSCC]]. It has similarly high specificity (73 to 100%) and sensitivity (82 to 100%) in screening for bone metastases&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10964746/&lt;/ref&gt;.<br /> <br /> '''Positron emission tomography''' (PET scans) detects tumour indirectly by measuring metabolic activity in the form of fluorodeoxyglucose ('''&lt;sup&gt;18&lt;/sup&gt;F''') tissue uptake. As such, its use is not limited to visualising only bony metastases, as &lt;sup&gt;18&lt;/sup&gt;F PET will reveal non-bony metastatic spread also&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8638000/&lt;/ref&gt;. The accuracy of PET is highly dependent on the primary tumour site from which imaged metastases originate. As a modality it is superior to scintigraphy in the screening of bony metastases from breast (specificity 94%, sensitivity 95%)&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12073051/&lt;/ref&gt; and lung (specificity 99%, sensitivity 92%)&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10478250/&lt;/ref&gt; malignancies, but has lower sensitivity in detecting the comparatively slower-growing bone metastases of prostate and renal cancers&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10520701/&lt;/ref&gt;. <br /> <br /> ===Biopsy===<br /> Sometimes it is necessary to diagnose metastases histologically, by removing cells or tissue from the bone lesion(s) directly. Usually this is in the form of a needle or surgical biopsy, and may be indicated if a primary cancer is not known. If the patient has a known primary cancer, then often imaging alone will suffice for the diagnosis of metastatic bone disease.<br /> <br /> ==Treatment==<br /> There are a variety of therapeutic interventions available to patients presenting with bone metastases, but consideration must be given to several patient-specific and tumour-dependent parameters, which include&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11738947/&lt;/ref&gt; (but are not limited to):<br /> <br /> *Lesion site(s) (localised or widespread)<br /> *Presence of extraskeletal metastasis<br /> *Tumour type and features (like receptors)<br /> *Prior treatment history (and response)<br /> *Clinical symptoms<br /> *Performance status<br /> <br /> ===Radiotherapy===<br /> Radiation therapy can provide excellent pain relief and is the treatment of choice for localised metastatic bone pain. However, the analgesic mechanisms of therapeutic skeletal irradiation are poorly understood. Onset of pain relief is usually quick, with a majority of patients experiencing benefit within one to two weeks. Patients who have little reduction in pain by six weeks are unlikely to demonstrate significant overall benefit&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/24782453/&lt;/ref&gt;. Other than localised bone pain, additional indications for radiotherapy include [[Metastatic spinal cord compression|MSCC]] and bones at high risk for [[pathological fracture]]&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/15978828/&lt;/ref&gt;. Two of the three main divisions of radiation therapy—the third being (sealed source) [[brachytherapy]]—can be used to treat bone metastases: systemic (unsealed source) [[radionuclide therapy]] and [[external beam radiotherapy]] (EBRT). <br /> <br /> '''Local-field [[External beam radiotherapy|EBRT]]''' is the standard choice of radiation therapy for treating bone metastases, as it focally targets the bone lesion and can achieve rates of substantial pain relief of up to 80 to 90%&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/6178497/&lt;/ref&gt;. Randomised controlled trials (RCTs) from the 1990s have shown that a single fraction of 8 gray (Gy) is as effective as fractionated doses of 20 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9681885&lt;/ref&gt;, 24 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10577695&lt;/ref&gt;, and 30 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10577696&lt;/ref&gt;. <br /> <br /> '''Wide-field''' (or '''hemibody''') '''[[External beam radiotherapy|EBRT]]''' is useful for widespread metastatic skeletal disease, though was more commonly used for multifocal pain when other effective therapies (chemo- and radionuclide) were not available. There are no RCTs comparing analgesic effect with and without wide-field radiotherapy. However, in terms of quasi-randomised and low-quality RCTs, there is data to suggest that use of fractionation is no more effective than single fraction treatment&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8823257&lt;/ref&gt;, that increasing doses beyond 8 Gy does not improve overall pain responses&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11395246&lt;/ref&gt;, and adding wide-field to local-field radiotherapy, whilst significantly halting disease progression (lesion size: P = 0.03; lesion number: P = 0.01), increases grade 3 to 4 haematological toxicity&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/1374061&lt;/ref&gt;. It is possible to classify wide-field treatments into three body regions, each with recommended single-fraction dose limits. Upper treatments (from skull or C1 to L2–L3) should be limited to 6 Gy, whereas mid-body (from L1 to upper third of femur) and lower (from L3–L4 to above knee) treatments should be limited to 8 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/6178497/&lt;/ref&gt;. Any treatments must be delivered with fields shaped to minimise irradiation of organs at risk, such as lung, liver, kidney and bowel. <br /> <br /> '''[[Stereotactic radiotherapy|Stereotactic]] [[External beam radiotherapy|EBRT]]''' is a promising treatment option which delivers higher doses of radiation to tumours in shorter periods in time. When used for extracranial cancers it is interchangeably termed Stereotactic Body Radiation Therapy ('''[[Stereotactic radiotherapy|SBRT]]''') or Stereotactic Ablative Radiotherapy ('''[[Stereotactic radiotherapy|SABR]]'''), the latter of which is appealingly onomatopoeic. When this technique is used for treating malignancy within the brain or some other part of the head, it is termed Stereotactic RadioSurgery ('''[[Stereotactic radiotherapy|SRS]]'''). SBRT/SABR can be used both for primary cancers (lung, liver, prostate, renal) and secondary metastases (bone/spine, lung, liver). There are a number of advantages of stereotactic radiotherapy, the most obvious of which is the potential completion of treatment within a single day, rather than over a number of weeks. The other major benefit is that it obviates the need to irradiate large portions of bone, which lowers the risk of further functional marrow depletion in a patient cohort already at risk of poor marrow reserve. Preserving skeletal marrow function can permit continuous chemotherapy in these patients. The primary limitations of SBRT/SABR are that it is more expensive to deliver than conventional EBRT and that there is a paucity of RCT data comparing its use to standard EBRT management&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/18619121/&lt;/ref&gt;. However, a recent single-centre phase II trial appeared to show that SBRT/SABR provides superior pain relief to conventional multifraction radiotherapy, with no observed difference in adverse events or other aspects of quality of life&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/31021390&lt;/ref&gt;. <br /> <br /> '''[[Radionuclide therapy]]''' (or '''radioisotope therapy''') is the systemic administration of radionuclides (also known as radioisotopes) as unsealed radioactive sources that selectively deliver radiation to tumours or target organs. They are taken up predominantly at sites of bone formation, and are therefore most likely best effective for the palliation of osteoblastic (sclerotic) metastases. Common radionuclides approved for the treatment of painful bone metastases include phosphorus-32 ('''&lt;sup&gt;32&lt;/sup&gt;P'''; ''β''-decay), strontium-89 ('''&lt;sup&gt;89&lt;/sup&gt;Sr'''; ''β''-decay), samarium-153 ('''&lt;sup&gt;153&lt;/sup&gt;Sm'''; ''β''- and ''γ''-decay), and rhenium-186 ('''&lt;sup&gt;186&lt;/sup&gt;Re'''; ''β''- and ''γ''-decay). The added advantage of gamma ray emission during decay is that it permits nuclear imaging monitoring of radionuclide biodistribution during therapy. These radionuclides target bone through various mechanisms. &lt;sup&gt;32&lt;/sup&gt;P passes through inorganic phosphate pathways, whereas &lt;sup&gt;89&lt;/sup&gt;Sr is a calcium mimetic and is taken up as a direct analogue of this earth metal. The final two agents are targeted to bone via chelation to phosphonate compounds: &lt;sup&gt;153&lt;/sup&gt;Sm is paired to ethylenediaminetetramethylenephosphonate (EDTMP) and &lt;sup&gt;186&lt;/sup&gt;Re to 1,1-hydroxyethylidene diphosphonate (HEDP). Common toxicities from treatment include myelosuppression and a transient pain flare, the latter of which usually heralds a favourable response. A more recently developed radionuclide, radium-223 (&lt;sup&gt;'''223'''&lt;/sup&gt;'''Ra'''; ''α''-, ''β''-, and ''γ''-decay) is a calcium mimetic which emits over 95% of decay energy in the form of alpha radiation&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/17062709&lt;/ref&gt;. Owing to their comparatively large size the emitted alpha particles have a more limited depth of penetration into surrounding tissues (around 2–10 cells), thereby producing a more potently localised cytotoxic effect. Despite their symptomatic benefits in refractory, widespread bone metastases, neither &lt;sup&gt;89&lt;/sup&gt;Sr nor &lt;sup&gt;153&lt;/sup&gt;Sm have been shown to improve overall survival in interventional trials; however, &lt;sup&gt;223&lt;/sup&gt;Ra use in metastatic castration-resistant prostate cancer patients in the ALSYMPCA (ALpharadin in SYMptomatic Prostate CAncer) trial was shown to significantly prolong overall survival&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/23863050/&lt;/ref&gt;. <br /> <br /> ===Bisphosphonates===<br /> Analogues of the natural bone demineralisation inhibitor pyrophosphate, bisphosphonates are useful in the treatment of poorly localised bone pain and in previously irradiated bone lesions. They bind with high affinity to exposed bone mineral where they are internalised by osteoclasts, within which they disrupt the processes of bone resorption and can induce apoptosis. Data have shown that bisphosphonates may have direct pro-apoptotic effects on nearby metastatic cancer cells also&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9362432/&lt;/ref&gt;. In halting the mobilisation of calcium and phosphate from bone, bisphosphonate use (together with rehydration) is now standard of care for malignancy-induced hypercalcaemia&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9025784/&lt;/ref&gt;. The analgesic effect of these agents is independent of underlying tumour characteristics, with osteolytic and osteoblastic lesions responding similarly&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9496390&lt;/ref&gt;. Many patients tolerate bisphosphonates without major concern, but common side-effects include flu-like myalgic symptoms, diarrhoea, nausea and reflux. It is exceedingly rare but one must be aware of the risk of developing osteonecrosis of the jaw. These medications undergo renal excretion and as such should be avoided in tumour-induced hypercalcaemia or metastatic bone disease if serum creatinine is greater than 400 μmol/L or 265 μmol/L, respectively. Bisphosphonates are divided into three generations of drug: first-generation (tiludronate, clodronate, etidronate), second-generation (ibandronate, alendronate, paimdronate), and third-generation (zoledronate, risedronate). One of the newest agents, zoledronate is 100-times more effective than second-generation pamidronate&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12558465/&lt;/ref&gt;. Whilst receiving bisphosphonate therapy, patients should take protective vitamin D and calcium supplements.<br /> <br /> ===Denosumab===<br /> Denosumab is a monoclonal antibody which binds to and inhibits the action of the RANK receptor ligand (RANKL). RANK is located on the surface of osteoclast progenitor cells and its activation stimulates their development into mature osteoclasts. Therefore denosumab, administered as a subcutaneous injection of 120 mg every four weeks, can help prevent bone destruction and fracture in patients with bone metastases. The antibody is cleared from the body by the reticuloendothelial system and can therefore be used in patients with poor renal function, in whom bisphosphonate use would be contraindicated&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/21145999/&lt;/ref&gt;. Additionally, data have shown that denosumab use causes greater suppression of osteolytic markers than bisphosphonate use in metastatic patients with breast&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/21060033/&lt;/ref&gt; or prostate&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/21353695/&lt;/ref&gt; cancer. However its effectiveness in comparison to bisphosphonates for patients with lung cancer or multiple myeloma is similar for the prevention of skeletal-related events (SRE), and indeed patients with multiple myeloma showed worse overall survival when treated with denosumab instead of zoledronate&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/21343556/&lt;/ref&gt;. <br /> <br /> ===Systemic anticancer therapies===<br /> [[Systemic anticancer therapy]] (SACT) refers to all drugs administered systemically with direct anticancer activity. This includes all conventional cytotoxic chemotherapies, all small molecule or antibody treatments, and all types of immunotherapy. Hormonal agents are not included within this categorisation. SACT may be considered for bone metastases if a primary tumour is known or subsequently confirmed. The specific therapy used will be the same therapy as typically used for the culprit primary cancer, though the precise dose and schedule will vary. SACT is sometimes used concurrently with other treatments such as bisphosphonates or radiotherapy. Side-effects will be treatment-specific.<br /> <br /> ===Hormone therapies===<br /> Hormone therapy is an indirect antitumour treatment which blocks the action of endogenous hormones or reduces their production within the body. Certain hormone-sensitive malignancies, particularly those of the prostate and breast, will often grow in response to specific hormones (androgens and oestrogens, respectively). Secondary metastases stemming from these primary tumours will, by extension, respond to hormone levels too. Androgen-responsive prostate cancer may be treated with drugs which lower androgen levels, such as gonadotrophin-releasing hormone (GnRH) receptor antagonists (peptides: '-''relix''&lt;nowiki/&gt;'; small-molecules: '-''golix''&lt;nowiki/&gt;'), GnRH receptor agonists ('-''relin''&lt;nowiki/&gt;'), and CYP17A1 inhibitors (such as abiraterone). Alternatively, androgen receptor blockers, such as bicalutamide or flutamide, can be effective. Oestrogen-responsive breast cancer may be treated with drugs which lower oestrogen levels, such as type I (exemestane) and type II (anastrozole, letrozole) aromatase inhibitors. Alternatively, selective oestrogen receptor modulators (SERMs), such as tamoxifen, can be effective. These modulators have mixed oestrogenic and antioestrogenic activity, which differs according to receptive tissue. Usefully in breast cancer, it is antioestrogenic in the breast; however, in the uterus and liver it is oestrogenic.<br /> <br /> <br /> ===Interventional radiology===<br /> Ablation (inc. RFA), percutaneous cementoplasty (bone cement)<br /> <br /> ===Surgery===<br /> -<br /> <br /> ==Living with bone metastases==<br /> Pain, mobility and safety, survival&lt;references /&gt;</div>

Alex https://oncopaedia.net/w/index.php?title=Articles:Bone_metastases&diff=312 2020-04-22T13:56:27Z

<p>Alex: </p> <hr /> <div>Metastases within bone can cause extreme and debilitating pain. Bone metastases are far more common than primary bone cancer, and many different cancer types can spread to the bone. The most common types of cancer which spread to bone are:<br /> <br /> *Breast<br /> *Prostate<br /> *Lung<br /> *Kidney<br /> *Thyroid<br /> <br /> Cancer can theoretically metastasize to any bone in the body, but in reality there is a predilection for certain sites. The most common sites are the vertebrae, ribs, pelvis, sternum, and the skull.<br /> <br /> ==Classification==<br /> A bone is a rigid organ, but it is far from physiologically static. To maintain bone strength, there is continuous breakdown and simultaneous reformation of bone, two processes which must finely balance for good bone health.<br /> <br /> '''Osteoblastic''' (or '''sclerotic''') metastases are characterised by the deposition of new bone. These are present most commonly in prostate cancer, but also occur in carcinoid, small cell lung cancer, medulloblastoma, and Hodgkin lymphoma. The molecular crosstalk between tumour and bone cells involves osteoblast-generating proteins such as Transforming Growth Factor, Bone Morphogenic Proteins (BMPs), and Endothelin-1&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12085970&lt;/ref&gt;.<br /> <br /> '''Osteolytic''' (or '''lytic''') metastases are characterised by the destruction and breakdown of normal bone. These often occur when breast cancer spreads to bone, which is primarily mediated by osteoclasts (bone cells that breaks down bone tissue) and is not a direct effect of metastasized tumour cells&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8086233/&lt;/ref&gt;. Other tumour types with osteolytic metastases include multiple myeloma, non-small cell lung cancer, thyroid cancer, non-Hodgkin lymphoma, and Langerhans' cell histiocytosis. Osteolytic metastases are more common than osteoblastic metastases.<br /> <br /> '''Mixed''' metastases are characterised by the presence of both osteolytic and osteoblastic lesions together in the same area of bone. These metastases are usually present in metastatic gastrointestinal and squamous cancers, as well as in secondary breast cancer. Although breast cancer gives rise to predominantly lytic lesions, around 15–20% of women have sclerotic or both types of lesions&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11346860/&lt;/ref&gt;.<br /> <br /> ==Diagnosis==<br /> <br /> ===Signs and symptoms===<br /> Bone metastases cause major morbidity, and high clinical suspicion should be kept for any patient with cancer that presents with:<br /> <br /> *Severe pain (poorly localised, worse at night)<br /> *Impaired mobility<br /> *[[Pathological fracture|Bone fracture]]<br /> *Bone marrow aplasia<br /> *Symptoms of (metastatic) [[Metastatic spinal cord compression|spinal cord compression]] (MSCC)<br /> *Symptoms in keeping with [[hypercalcaemia]]:<br /> **Constipation<br /> **Fatigue<br /> **Polyuria/polydipsia<br /> **Acute kidney injury (AKI)<br /> **Cardiac arrhythmia<br /> <br /> ===Bloods===<br /> When a patient with cancer presents with any of the signs or symptoms above, basic screening in the form of simple blood testing must be undertaken and complemented with appropriate imaging tests:<br /> <br /> *Full evaluation of bone turnover and potential hypercalcaemia:<br /> **Serum calcium<br /> **Serum phosphate<br /> **25-Hydroxyvitamin D<br /> **Thyroid-stimulating hormone (TSH)<br /> **Parathyroid hormone (PTH)<br /> **Serum creatinine<br /> **Alkaline phosphatase (ALP)<br /> *Full blood count (myelosuppression, anaemia)<br /> *Serum protein electrophoresis (SPEP; myeloma screen)<br /> *Tumour markers (such as PSA in prostate cancer)<br /> <br /> ===Imaging===<br /> Radiological tests are an essential component of diagnosing bony metastases. One or more imaging modalities may be required to confirm suspected cancerous spread to bone.<br /> <br /> '''Plain radiographs''' (X-ray scans) are quick, cost-effective, and widely-available, and should be the initial diagnostic test of choice when investigating bone pain. They are highly specific but lack sensitivity (44-50%) because early-stage metastatic lesions, particularly those up to 1 cm, may be more difficult to visualise. More than 50% of the trabecular bone must be involved before the lesion will be apparent on film and, due to the poor contrast of trabecular bone, lesions within the medulla are often less evident than those within cortical bone&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9025785/&lt;/ref&gt;. As outlined above, sclerotic metastases will appear more radiopaque than the surrounding bone, whereas lytic metastases will appear more radiolucent.<br /> <br /> '''Bone scintigraphy''' (bone scans) on the other hand is highly sensitive but with low specificity. Data from Technetium-99m ('''&lt;sup&gt;99m&lt;/sup&gt;Tc''') scintigraphy have shown false-negative rates as low as 11 to 38% (good sensitivity), with false-positive rates as high as 40% (poor specificity). It thus provides a non-specific osteoblastic indication of bone status, be it inflammatory, traumatic, or neoplastic in origin. Scintigraphy is still more specific and sensitive than either plain radiography or computed tomography, whilst magnetic resonance imaging is more efficacious in assessing vertebral metastases&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/2028061/&lt;/ref&gt;.<br /> <br /> '''Computed tomography''' (CT scans) has a high sensitivity, ranging from 71 to 100%, for the detection of metastatic bone lesions&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9362427/&lt;/ref&gt;. Because of the excellent soft tissue resolution of the images produced by CT, it is a particularly helpful modality to distinguish lytic and sclerotic metastases and to visualise their precise location(s) for biopsy.<br /> <br /> '''Magnetic resonance imaging''' (MRI scans) is useful in assessing bone marrow infiltration by tumour deposits, and is required (whole spine) for the proper diagnosis of [[Metastatic spinal cord compression|MSCC]]. It has similarly high specificity (73 to 100%) and sensitivity (82 to 100%) in screening for bone metastases&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10964746/&lt;/ref&gt;.<br /> <br /> '''Positron emission tomography''' (PET scans) detects tumour indirectly by measuring metabolic activity in the form of fluorodeoxyglucose ('''&lt;sup&gt;18&lt;/sup&gt;F''') tissue uptake. As such, its use is not limited to visualising only bony metastases, as &lt;sup&gt;18&lt;/sup&gt;F PET will reveal non-bony metastatic spread also&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8638000/&lt;/ref&gt;. The accuracy of PET is highly dependent on the primary tumour site from which imaged metastases originate. As a modality it is superior to scintigraphy in the screening of bony metastases from breast (specificity 94%, sensitivity 95%)&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12073051/&lt;/ref&gt; and lung (specificity 99%, sensitivity 92%)&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10478250/&lt;/ref&gt; malignancies, but has lower sensitivity in detecting the comparatively slower-growing bone metastases of prostate and renal cancers&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10520701/&lt;/ref&gt;. <br /> <br /> ===Biopsy===<br /> Sometimes it is necessary to diagnose metastases histologically, by removing cells or tissue from the bone lesion(s) directly. Usually this is in the form of a needle or surgical biopsy, and may be indicated if a primary cancer is not known. If the patient has a known primary cancer, then often imaging alone will suffice for the diagnosis of metastatic bone disease.<br /> <br /> ==Treatment==<br /> There are a variety of therapeutic interventions available to patients presenting with bone metastases, but consideration must be given to several patient-specific and tumour-dependent parameters, which include&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11738947/&lt;/ref&gt; (but are not limited to):<br /> <br /> *Lesion site(s) (localised or widespread)<br /> *Presence of extraskeletal metastasis<br /> *Tumour type and features (like receptors)<br /> *Prior treatment history (and response)<br /> *Clinical symptoms<br /> *Performance status<br /> <br /> ===Radiotherapy===<br /> Radiation therapy can provide excellent pain relief and is the treatment of choice for localised metastatic bone pain. However, the analgesic mechanisms of therapeutic skeletal irradiation are poorly understood. Onset of pain relief is usually quick, with a majority of patients experiencing benefit within one to two weeks. Patients who have little reduction in pain by six weeks are unlikely to demonstrate significant overall benefit&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/24782453/&lt;/ref&gt;. Other than localised bone pain, additional indications for radiotherapy include [[Metastatic spinal cord compression|MSCC]] and bones at high risk for [[pathological fracture]]&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/15978828/&lt;/ref&gt;. Two of the three main divisions of radiation therapy—the third being (sealed source) [[brachytherapy]]—can be used to treat bone metastases: systemic (unsealed source) [[radionuclide therapy]] and [[external beam radiotherapy]] (EBRT). <br /> <br /> '''Local-field [[External beam radiotherapy|EBRT]]''' is the standard choice of radiation therapy for treating bone metastases, as it focally targets the bone lesion and can achieve rates of substantial pain relief of up to 80 to 90%&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/6178497/&lt;/ref&gt;. Randomised controlled trials (RCTs) from the 1990s have shown that a single fraction of 8 gray (Gy) is as effective as fractionated doses of 20 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9681885&lt;/ref&gt;, 24 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10577695&lt;/ref&gt;, and 30 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10577696&lt;/ref&gt;. <br /> <br /> '''Wide-field''' (or '''hemibody''') '''[[External beam radiotherapy|EBRT]]''' is useful for widespread metastatic skeletal disease, though was more commonly used for multifocal pain when other effective therapies (chemo- and radionuclide) were not available. There are no RCTs comparing analgesic effect with and without wide-field radiotherapy. However, in terms of quasi-randomised and low-quality RCTs, there is data to suggest that use of fractionation is no more effective than single fraction treatment&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8823257&lt;/ref&gt;, that increasing doses beyond 8 Gy does not improve overall pain responses&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11395246&lt;/ref&gt;, and adding wide-field to local-field radiotherapy, whilst significantly halting disease progression (lesion size: P = 0.03; lesion number: P = 0.01), increases grade 3 to 4 haematological toxicity&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/1374061&lt;/ref&gt;. It is possible to classify wide-field treatments into three body regions, each with recommended single-fraction dose limits. Upper treatments (from skull or C1 to L2–L3) should be limited to 6 Gy, whereas mid-body (from L1 to upper third of femur) and lower (from L3–L4 to above knee) treatments should be limited to 8 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/6178497/&lt;/ref&gt;. Any treatments must be delivered with fields shaped to minimise irradiation of organs at risk, such as lung, liver, kidney and bowel. <br /> <br /> '''[[Stereotactic radiotherapy|Stereotactic]] [[External beam radiotherapy|EBRT]]''' is a promising treatment option which delivers higher doses of radiation to tumours in shorter periods in time. When used for extracranial cancers it is interchangeably termed Stereotactic Body Radiation Therapy ('''[[Stereotactic radiotherapy|SBRT]]''') or Stereotactic Ablative Radiotherapy ('''[[Stereotactic radiotherapy|SABR]]'''), the latter of which is appealingly onomatopoeic. When this technique is used for treating malignancy within the brain or some other part of the head, it is termed Stereotactic RadioSurgery ('''[[Stereotactic radiotherapy|SRS]]'''). SBRT/SABR can be used both for primary cancers (lung, liver, prostate, renal) and secondary metastases (bone/spine, lung, liver). There are a number of advantages of stereotactic radiotherapy, the most obvious of which is the potential completion of treatment within a single day, rather than over a number of weeks. The other major benefit is that it obviates the need to irradiate large portions of bone, which lowers the risk of further functional marrow depletion in a patient cohort already at risk of poor marrow reserve. Preserving skeletal marrow function can permit continuous chemotherapy in these patients. The primary limitations of SBRT/SABR are that it is more expensive to deliver than conventional EBRT and that there is a paucity of RCT data comparing its use to standard EBRT management&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/18619121/&lt;/ref&gt;. However, a recent single-centre phase II trial appeared to show that SBRT/SABR provides superior pain relief to conventional multifraction radiotherapy, with no observed difference in adverse events or other aspects of quality of life&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/31021390&lt;/ref&gt;. <br /> <br /> '''[[Radionuclide therapy]]''' (or '''radioisotope therapy''') is the systemic administration of radionuclides (also known as radioisotopes) as unsealed radioactive sources that selectively deliver radiation to tumours or target organs. They are taken up predominantly at sites of bone formation, and are therefore most likely best effective for the palliation of osteoblastic (sclerotic) metastases. Common radionuclides approved for the treatment of painful bone metastases include phosphorus-32 ('''&lt;sup&gt;32&lt;/sup&gt;P'''; ''β''-decay), strontium-89 ('''&lt;sup&gt;89&lt;/sup&gt;Sr'''; ''β''-decay), samarium-153 ('''&lt;sup&gt;153&lt;/sup&gt;Sm'''; ''β''- and ''γ''-decay), and rhenium-186 ('''&lt;sup&gt;186&lt;/sup&gt;Re'''; ''β''- and ''γ''-decay). The added advantage of gamma ray emission during decay is that it permits nuclear imaging monitoring of radionuclide biodistribution during therapy. These radionuclides target bone through various mechanisms. &lt;sup&gt;32&lt;/sup&gt;P passes through inorganic phosphate pathways, whereas &lt;sup&gt;89&lt;/sup&gt;Sr is a calcium mimetic and is taken up as a direct analogue of this earth metal. The final two agents are targeted to bone via chelation to phosphonate compounds: &lt;sup&gt;153&lt;/sup&gt;Sm is paired to ethylenediaminetetramethylenephosphonate (EDTMP) and &lt;sup&gt;186&lt;/sup&gt;Re to 1,1-hydroxyethylidene diphosphonate (HEDP). Common toxicities from treatment include myelosuppression and a transient pain flare, the latter of which usually heralds a favourable response. A more recently developed radionuclide, radium-223 (&lt;sup&gt;'''223'''&lt;/sup&gt;'''Ra'''; ''α''-, ''β''-, and ''γ''-decay) is a calcium mimetic which emits over 95% of decay energy in the form of alpha radiation&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/17062709&lt;/ref&gt;. Owing to their comparatively large size the emitted alpha particles have a more limited depth of penetration into surrounding tissues (around 2–10 cells), thereby producing a more potently localised cytotoxic effect. Despite their symptomatic benefits in refractory, widespread bone metastases, neither &lt;sup&gt;89&lt;/sup&gt;Sr nor &lt;sup&gt;153&lt;/sup&gt;Sm have been shown to improve overall survival in interventional trials; however, &lt;sup&gt;223&lt;/sup&gt;Ra use in metastatic castration-resistant prostate cancer patients in the ALSYMPCA (ALpharadin in SYMptomatic Prostate CAncer) trial was shown to significantly prolong overall survival&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/23863050/&lt;/ref&gt;. <br /> <br /> ===Bisphosphonates===<br /> Analogues of the natural bone demineralisation inhibitor pyrophosphate, bisphosphonates are useful in the treatment of poorly localised bone pain and in previously irradiated bone lesions. They bind with high affinity to exposed bone mineral where they are internalised by osteoclasts, within which they disrupt the processes of bone resorption and can induce apoptosis. Data have shown that bisphosphonates may have direct pro-apoptotic effects on nearby metastatic cancer cells also&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9362432/&lt;/ref&gt;. In halting the mobilisation of calcium and phosphate from bone, bisphosphonate use (together with rehydration) is now standard of care for malignancy-induced hypercalcaemia&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9025784/&lt;/ref&gt;. The analgesic effect of these agents is independent of underlying tumour characteristics, with osteolytic and osteoblastic lesions responding similarly&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9496390&lt;/ref&gt;. Many patients tolerate bisphosphonates without major concern, but common side-effects include flu-like myalgic symptoms, diarrhoea, nausea and reflux. It is exceedingly rare but one must be aware of the risk of developing osteonecrosis of the jaw. These medications undergo renal excretion and as such should be avoided in tumour-induced hypercalcaemia or metastatic bone disease if serum creatinine is greater than 400 μmol/L or 265 μmol/L, respectively. Bisphosphonates are divided into three generations of drug: first-generation (tiludronate, clodronate, etidronate), second-generation (ibandronate, alendronate, paimdronate), and third-generation (zoledronate, risedronate). One of the newest agents, zoledronate is 100-times more effective than second-generation pamidronate&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12558465/&lt;/ref&gt;. Whilst receiving bisphosphonate therapy, patients should take protective vitamin D and calcium supplements.<br /> <br /> ===Denosumab===<br /> Denosumab is a monoclonal antibody which binds to and inhibits the action of the RANK receptor ligand (RANKL). RANK is located on the surface of osteoclast progenitor cells and its activation stimulates their development into mature osteoclasts. Therefore denosumab, administered as a subcutaneous injection of 120 mg every four weeks, can help prevent bone destruction and fracture in patients with bone metastases. The antibody is cleared from the body by the reticuloendothelial system and can therefore be used in patients with poor renal function, in whom bisphosphonate use would be contraindicated&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/21145999/&lt;/ref&gt;. Additionally, data have shown that denosumab use causes greater suppression of osteolytic markers than bisphosphonate use in metastatic patients with breast&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/21060033/&lt;/ref&gt; or prostate&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/21353695/&lt;/ref&gt; cancer. However its effectiveness in comparison to bisphosphonates for patients with lung cancer or multiple myeloma is similar for the prevention of skeletal-related events (SRE), and indeed patients with multiple myeloma showed worse overall survival when treated with denosumab instead of zoledronate&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/21343556/&lt;/ref&gt;. <br /> <br /> ===Systemic anticancer therapies===<br /> [[Systemic anticancer therapy]] (SACT) refers to all drugs administered systemically with direct anticancer activity. This includes all conventional cytotoxic chemotherapies, all small molecule or antibody treatments, and all types of immunotherapy. Hormonal agents are not included within this categorisation. SACT may be considered for bone metastases if a primary tumour is known or subsequently confirmed. The specific therapy used will be the same therapy as typically used for the culprit primary cancer, though the precise dose and schedule will vary. SACT is sometimes used concurrently with other treatments such as bisphosphonates or radiotherapy. Side-effects will be treatment-specific.<br /> <br /> ===Hormone therapies===<br /> Hormone therapy is an indirect antitumour treatment which blocks the action of endogenous hormones or reduces their production within the body. Certain hormone-sensitive malignancies, particularly those of the prostate and breast, will often grow in response to specific hormones (androgens and oestrogens, respectively). Secondary metastases stemming from these primary tumours will, by extension, respond to hormone levels too. Androgen-responsive prostate cancer may be treated with drugs which lower androgen levels, such as gonadotrophin-releasing hormone (GnRH) receptor antagonists (peptides: '-''relix''&lt;nowiki/&gt;'; small-molecules: '-''golix''&lt;nowiki/&gt;'), GnRH receptor agonists ('-''relin''&lt;nowiki/&gt;'), and CYP17A1 inhibitors (such as abiraterone). Alternatively, androgen receptor blockers, such as bicalutamide or flutamide, can be effective.<br /> <br /> ===Interventional radiology===<br /> Ablation (inc. RFA), percutaneous cementoplasty (bone cement)<br /> <br /> ===Surgery===<br /> -<br /> <br /> ==Living with bone metastases==<br /> Pain, mobility and safety, survival&lt;references /&gt;</div>

Alex https://oncopaedia.net/w/index.php?title=Articles:Bone_metastases&diff=311 2020-04-22T11:16:12Z

<p>Alex: </p> <hr /> <div>Metastases within bone can cause extreme and debilitating pain. Bone metastases are far more common than primary bone cancer, and many different cancer types can spread to the bone. The most common types of cancer which spread to bone are:<br /> <br /> *Breast<br /> *Prostate<br /> *Lung<br /> *Kidney<br /> *Thyroid<br /> <br /> Cancer can theoretically metastasize to any bone in the body, but in reality there is a predilection for certain sites. The most common sites are the vertebrae, ribs, pelvis, sternum, and the skull.<br /> <br /> ==Classification==<br /> A bone is a rigid organ, but it is far from physiologically static. To maintain bone strength, there is continuous breakdown and simultaneous reformation of bone, two processes which must finely balance for good bone health.<br /> <br /> '''Osteoblastic''' (or '''sclerotic''') metastases are characterised by the deposition of new bone. These are present most commonly in prostate cancer, but also occur in carcinoid, small cell lung cancer, medulloblastoma, and Hodgkin lymphoma. The molecular crosstalk between tumour and bone cells involves osteoblast-generating proteins such as Transforming Growth Factor, Bone Morphogenic Proteins (BMPs), and Endothelin-1&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12085970&lt;/ref&gt;.<br /> <br /> '''Osteolytic''' (or '''lytic''') metastases are characterised by the destruction and breakdown of normal bone. These often occur when breast cancer spreads to bone, which is primarily mediated by osteoclasts (bone cells that breaks down bone tissue) and is not a direct effect of metastasized tumour cells&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8086233/&lt;/ref&gt;. Other tumour types with osteolytic metastases include multiple myeloma, non-small cell lung cancer, thyroid cancer, non-Hodgkin lymphoma, and Langerhans' cell histiocytosis. Osteolytic metastases are more common than osteoblastic metastases.<br /> <br /> '''Mixed''' metastases are characterised by the presence of both osteolytic and osteoblastic lesions together in the same area of bone. These metastases are usually present in metastatic gastrointestinal and squamous cancers, as well as in secondary breast cancer. Although breast cancer gives rise to predominantly lytic lesions, around 15–20% of women have sclerotic or both types of lesions&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11346860/&lt;/ref&gt;.<br /> <br /> ==Diagnosis==<br /> <br /> ===Signs and symptoms===<br /> Bone metastases cause major morbidity, and high clinical suspicion should be kept for any patient with cancer that presents with:<br /> <br /> *Severe pain (poorly localised, worse at night)<br /> *Impaired mobility<br /> *[[Pathological fracture|Bone fracture]]<br /> *Bone marrow aplasia<br /> *Symptoms of (metastatic) [[Metastatic spinal cord compression|spinal cord compression]] (MSCC)<br /> *Symptoms in keeping with [[hypercalcaemia]]:<br /> **Constipation<br /> **Fatigue<br /> **Polyuria/polydipsia<br /> **Acute kidney injury (AKI)<br /> **Cardiac arrhythmia<br /> <br /> ===Bloods===<br /> When a patient with cancer presents with any of the signs or symptoms above, basic screening in the form of simple blood testing must be undertaken and complemented with appropriate imaging tests:<br /> <br /> *Full evaluation of bone turnover and potential hypercalcaemia:<br /> **Serum calcium<br /> **Serum phosphate<br /> **25-Hydroxyvitamin D<br /> **Thyroid-stimulating hormone (TSH)<br /> **Parathyroid hormone (PTH)<br /> **Serum creatinine<br /> **Alkaline phosphatase (ALP)<br /> *Full blood count (myelosuppression, anaemia)<br /> *Serum protein electrophoresis (SPEP; myeloma screen)<br /> *Tumour markers (such as PSA in prostate cancer)<br /> <br /> ===Imaging===<br /> Radiological tests are an essential component of diagnosing bony metastases. One or more imaging modalities may be required to confirm suspected cancerous spread to bone.<br /> <br /> '''Plain radiographs''' (X-ray scans) are quick, cost-effective, and widely-available, and should be the initial diagnostic test of choice when investigating bone pain. They are highly specific but lack sensitivity (44-50%) because early-stage metastatic lesions, particularly those up to 1 cm, may be more difficult to visualise. More than 50% of the trabecular bone must be involved before the lesion will be apparent on film and, due to the poor contrast of trabecular bone, lesions within the medulla are often less evident than those within cortical bone&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9025785/&lt;/ref&gt;. As outlined above, sclerotic metastases will appear more radiopaque than the surrounding bone, whereas lytic metastases will appear more radiolucent.<br /> <br /> '''Bone scintigraphy''' (bone scans) on the other hand is highly sensitive but with low specificity. Data from Technetium-99m ('''&lt;sup&gt;99m&lt;/sup&gt;Tc''') scintigraphy have shown false-negative rates as low as 11 to 38% (good sensitivity), with false-positive rates as high as 40% (poor specificity). It thus provides a non-specific osteoblastic indication of bone status, be it inflammatory, traumatic, or neoplastic in origin. Scintigraphy is still more specific and sensitive than either plain radiography or computed tomography, whilst magnetic resonance imaging is more efficacious in assessing vertebral metastases&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/2028061/&lt;/ref&gt;.<br /> <br /> '''Computed tomography''' (CT scans) has a high sensitivity, ranging from 71 to 100%, for the detection of metastatic bone lesions&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9362427/&lt;/ref&gt;. Because of the excellent soft tissue resolution of the images produced by CT, it is a particularly helpful modality to distinguish lytic and sclerotic metastases and to visualise their precise location(s) for biopsy.<br /> <br /> '''Magnetic resonance imaging''' (MRI scans) is useful in assessing bone marrow infiltration by tumour deposits, and is required (whole spine) for the proper diagnosis of [[Metastatic spinal cord compression|MSCC]]. It has similarly high specificity (73 to 100%) and sensitivity (82 to 100%) in screening for bone metastases&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10964746/&lt;/ref&gt;.<br /> <br /> '''Positron emission tomography''' (PET scans) detects tumour indirectly by measuring metabolic activity in the form of fluorodeoxyglucose ('''&lt;sup&gt;18&lt;/sup&gt;F''') tissue uptake. As such, its use is not limited to visualising only bony metastases, as &lt;sup&gt;18&lt;/sup&gt;F PET will reveal non-bony metastatic spread also&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8638000/&lt;/ref&gt;. The accuracy of PET is highly dependent on the primary tumour site from which imaged metastases originate. As a modality it is superior to scintigraphy in the screening of bony metastases from breast (specificity 94%, sensitivity 95%)&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12073051/&lt;/ref&gt; and lung (specificity 99%, sensitivity 92%)&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10478250/&lt;/ref&gt; malignancies, but has lower sensitivity in detecting the comparatively slower-growing bone metastases of prostate and renal cancers&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10520701/&lt;/ref&gt;. <br /> <br /> ===Biopsy===<br /> Sometimes it is necessary to diagnose metastases histologically, by removing cells or tissue from the bone lesion(s) directly. Usually this is in the form of a needle or surgical biopsy, and may be indicated if a primary cancer is not known. If the patient has a known primary cancer, then often imaging alone will suffice for the diagnosis of metastatic bone disease.<br /> <br /> ==Treatment==<br /> There are a variety of therapeutic interventions available to patients presenting with bone metastases, but consideration must be given to several patient-specific and tumour-dependent parameters, which include&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11738947/&lt;/ref&gt; (but are not limited to):<br /> <br /> *Lesion site(s) (localised or widespread)<br /> *Presence of extraskeletal metastasis<br /> *Tumour type and features (like receptors)<br /> *Prior treatment history (and response)<br /> *Clinical symptoms<br /> *Performance status<br /> <br /> ===Radiotherapy===<br /> Radiation therapy can provide excellent pain relief and is the treatment of choice for localised metastatic bone pain. However, the analgesic mechanisms of therapeutic skeletal irradiation are poorly understood. Onset of pain relief is usually quick, with a majority of patients experiencing benefit within one to two weeks. Patients who have little reduction in pain by six weeks are unlikely to demonstrate significant overall benefit&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/24782453/&lt;/ref&gt;. Other than localised bone pain, additional indications for radiotherapy include [[Metastatic spinal cord compression|MSCC]] and bones at high risk for [[pathological fracture]]&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/15978828/&lt;/ref&gt;. Two of the three main divisions of radiation therapy—the third being (sealed source) [[brachytherapy]]—can be used to treat bone metastases: systemic (unsealed source) [[radionuclide therapy]] and [[external beam radiotherapy]] (EBRT). <br /> <br /> '''Local-field [[External beam radiotherapy|EBRT]]''' is the standard choice of radiation therapy for treating bone metastases, as it focally targets the bone lesion and can achieve rates of substantial pain relief of up to 80 to 90%&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/6178497/&lt;/ref&gt;. Randomised controlled trials (RCTs) from the 1990s have shown that a single fraction of 8 gray (Gy) is as effective as fractionated doses of 20 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9681885&lt;/ref&gt;, 24 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10577695&lt;/ref&gt;, and 30 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10577696&lt;/ref&gt;. <br /> <br /> '''Wide-field''' (or '''hemibody''') '''[[External beam radiotherapy|EBRT]]''' is useful for widespread metastatic skeletal disease, though was more commonly used for multifocal pain when other effective therapies (chemo- and radionuclide) were not available. There are no RCTs comparing analgesic effect with and without wide-field radiotherapy. However, in terms of quasi-randomised and low-quality RCTs, there is data to suggest that use of fractionation is no more effective than single fraction treatment&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8823257&lt;/ref&gt;, that increasing doses beyond 8 Gy does not improve overall pain responses&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11395246&lt;/ref&gt;, and adding wide-field to local-field radiotherapy, whilst significantly halting disease progression (lesion size: P = 0.03; lesion number: P = 0.01), increases grade 3 to 4 haematological toxicity&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/1374061&lt;/ref&gt;. It is possible to classify wide-field treatments into three body regions, each with recommended single-fraction dose limits. Upper treatments (from skull or C1 to L2–L3) should be limited to 6 Gy, whereas mid-body (from L1 to upper third of femur) and lower (from L3–L4 to above knee) treatments should be limited to 8 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/6178497/&lt;/ref&gt;. Any treatments must be delivered with fields shaped to minimise irradiation of organs at risk, such as lung, liver, kidney and bowel. <br /> <br /> '''[[Stereotactic radiotherapy|Stereotactic]] [[External beam radiotherapy|EBRT]]''' is a promising treatment option which delivers higher doses of radiation to tumours in shorter periods in time. When used for extracranial cancers it is interchangeably termed Stereotactic Body Radiation Therapy ('''[[Stereotactic radiotherapy|SBRT]]''') or Stereotactic Ablative Radiotherapy ('''[[Stereotactic radiotherapy|SABR]]'''), the latter of which is appealingly onomatopoeic. When this technique is used for treating malignancy within the brain or some other part of the head, it is termed Stereotactic RadioSurgery ('''[[Stereotactic radiotherapy|SRS]]'''). SBRT/SABR can be used both for primary cancers (lung, liver, prostate, renal) and secondary metastases (bone/spine, lung, liver). There are a number of advantages of stereotactic radiotherapy, the most obvious of which is the potential completion of treatment within a single day, rather than over a number of weeks. The other major benefit is that it obviates the need to irradiate large portions of bone, which lowers the risk of further functional marrow depletion in a patient cohort already at risk of poor marrow reserve. Preserving skeletal marrow function can permit continuous chemotherapy in these patients. The primary limitations of SBRT/SABR are that it is more expensive to deliver than conventional EBRT and that there is a paucity of RCT data comparing its use to standard EBRT management&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/18619121/&lt;/ref&gt;. However, a recent single-centre phase II trial appeared to show that SBRT/SABR provides superior pain relief to conventional multifraction radiotherapy, with no observed difference in adverse events or other aspects of quality of life&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/31021390&lt;/ref&gt;. <br /> <br /> '''[[Radionuclide therapy]]''' (or '''radioisotope therapy''') is the systemic administration of radionuclides (also known as radioisotopes) as unsealed radioactive sources that selectively deliver radiation to tumours or target organs. They are taken up predominantly at sites of bone formation, and are therefore most likely best effective for the palliation of osteoblastic (sclerotic) metastases. Common radionuclides approved for the treatment of painful bone metastases include phosphorus-32 ('''&lt;sup&gt;32&lt;/sup&gt;P'''; ''β''-decay), strontium-89 ('''&lt;sup&gt;89&lt;/sup&gt;Sr'''; ''β''-decay), samarium-153 ('''&lt;sup&gt;153&lt;/sup&gt;Sm'''; ''β''- and ''γ''-decay), and rhenium-186 ('''&lt;sup&gt;186&lt;/sup&gt;Re'''; ''β''- and ''γ''-decay). The added advantage of gamma ray emission during decay is that it permits nuclear imaging monitoring of radionuclide biodistribution during therapy. These radionuclides target bone through various mechanisms. &lt;sup&gt;32&lt;/sup&gt;P passes through inorganic phosphate pathways, whereas &lt;sup&gt;89&lt;/sup&gt;Sr is a calcium mimetic and is taken up as a direct analogue of this earth metal. The final two agents are targeted to bone via chelation to phosphonate compounds: &lt;sup&gt;153&lt;/sup&gt;Sm is paired to ethylenediaminetetramethylenephosphonate (EDTMP) and &lt;sup&gt;186&lt;/sup&gt;Re to 1,1-hydroxyethylidene diphosphonate (HEDP). Common toxicities from treatment include myelosuppression and a transient pain flare, the latter of which usually heralds a favourable response. A more recently developed radionuclide, radium-223 (&lt;sup&gt;'''223'''&lt;/sup&gt;'''Ra'''; ''α''-, ''β''-, and ''γ''-decay) is a calcium mimetic which emits over 95% of decay energy in the form of alpha radiation&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/17062709&lt;/ref&gt;. Owing to their comparatively large size the emitted alpha particles have a more limited depth of penetration into surrounding tissues (around 2–10 cells), thereby producing a more potently localised cytotoxic effect. Despite their symptomatic benefits in refractory, widespread bone metastases, neither &lt;sup&gt;89&lt;/sup&gt;Sr nor &lt;sup&gt;153&lt;/sup&gt;Sm have been shown to improve overall survival in interventional trials; however, &lt;sup&gt;223&lt;/sup&gt;Ra use in metastatic castration-resistant prostate cancer patients in the ALSYMPCA (ALpharadin in SYMptomatic Prostate CAncer) trial was shown to significantly prolong overall survival&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/23863050/&lt;/ref&gt;. <br /> <br /> ===Bisphosphonates===<br /> Analogues of the natural bone demineralisation inhibitor pyrophosphate, bisphosphonates are useful in the treatment of poorly localised bone pain and in previously irradiated bone lesions. They bind with high affinity to exposed bone mineral where they are internalised by osteoclasts, within which they disrupt the processes of bone resorption and can induce apoptosis. Data have shown that bisphosphonates may have direct pro-apoptotic effects on nearby metastatic cancer cells also&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9362432/&lt;/ref&gt;. In halting the mobilisation of calcium and phosphate from bone, bisphosphonate use (together with rehydration) is now standard of care for malignancy-induced hypercalcaemia&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9025784/&lt;/ref&gt;. The analgesic effect of these agents is independent of underlying tumour characteristics, with osteolytic and osteoblastic lesions responding similarly&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9496390&lt;/ref&gt;. Many patients tolerate bisphosphonates without major concern, but common side-effects include flu-like myalgic symptoms, diarrhoea, nausea and reflux. It is exceedingly rare but one must be aware of the risk of developing osteonecrosis of the jaw. These medications undergo renal excretion and as such should be avoided in tumour-induced hypercalcaemia or metastatic bone disease if serum creatinine is greater than 400 μmol/L or 265 μmol/L, respectively. Bisphosphonates are divided into three generations of drug: first-generation (tiludronate, clodronate, etidronate), second-generation (ibandronate, alendronate, paimdronate), and third-generation (zoledronate, risedronate). One of the newest agents, zoledronate is 100-times more effective than second-generation pamidronate&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12558465/&lt;/ref&gt;. Whilst receiving bisphosphonate therapy, patients should take protective vitamin D and calcium supplements.<br /> <br /> ===Denosumab===<br /> Denosumab is a monoclonal antibody which binds to and inhibits the action of the RANK receptor ligand (RANKL). RANK is located on the surface of osteoclast progenitor cells and its activation stimulates their development into mature osteoclasts. Therefore denosumab, administered as a subcutaneous injection of 120 mg every four weeks, can help prevent bone destruction and fracture in patients with bone metastases. The antibody is cleared from the body by the reticuloendothelial system and can therefore be used in patients with poor renal function, in whom bisphosphonate use would be contraindicated&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/21145999/&lt;/ref&gt;. Additionally, data have shown that denosumab use causes greater suppression of osteolytic markers than bisphosphonate use in metastatic patients with breast&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/21060033/&lt;/ref&gt; or prostate&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/21353695/&lt;/ref&gt; cancer. However its effectiveness in comparison to bisphosphonates for patients with lung cancer or multiple myeloma is similar for the prevention of skeletal-related events (SRE), and indeed patients with multiple myeloma showed worse overall survival when treated with denosumab instead of zoledronate&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/21343556/&lt;/ref&gt;. <br /> <br /> ===Systemic anticancer therapies===<br /> [[Systemic anticancer therapy]] (SACT) refers to all drugs administered systemically with direct anticancer activity. This includes all conventional cytotoxic chemotherapies, all small molecule or antibody treatments, and all types of immunotherapy. Hormonal agents are not included within this categorisation. SACT may be considered for bone metastases if a primary tumour is known or subsequently confirmed. The specific therapy used will be the same therapy as typically used for the culprit primary cancer, though the precise dose and schedule will vary. SACT is sometimes used concurrently with other treatments such as bisphosphonates or radiotherapy. Side-effects will be treatment-specific.<br /> <br /> ===Hormone therapies===<br /> Hormone therapy is an indirect antitumour treatment which blocks the action of endogenous hormones or reduces their production within the body. Certain hormone-sensitive malignancies, particularly those of the prostate and breast, will grow in response to specific hormones. Secondary metastases stemming from these primary tumours will, by extension, respond to hormone levels too.<br /> <br /> ===Interventional radiology===<br /> Ablation (inc. RFA), percutaneous cementoplasty (bone cement)<br /> <br /> ===Surgery===<br /> -<br /> <br /> ==Living with bone metastases==<br /> Pain, mobility and safety, survival&lt;references /&gt;</div>

Alex https://oncopaedia.net/w/index.php?title=Articles:Bone_metastases&diff=310 2020-04-22T10:26:45Z

<p>Alex: </p> <hr /> <div>Metastases within bone can cause extreme and debilitating pain. Bone metastases are far more common than primary bone cancer, and many different cancer types can spread to the bone. The most common types of cancer which spread to bone are:<br /> <br /> *Breast<br /> *Prostate<br /> *Lung<br /> *Kidney<br /> *Thyroid<br /> <br /> Cancer can theoretically metastasize to any bone in the body, but in reality there is a predilection for certain sites. The most common sites are the vertebrae, ribs, pelvis, sternum, and the skull.<br /> <br /> ==Classification==<br /> A bone is a rigid organ, but it is far from physiologically static. To maintain bone strength, there is continuous breakdown and simultaneous reformation of bone, two processes which must finely balance for good bone health.<br /> <br /> '''Osteoblastic''' (or '''sclerotic''') metastases are characterised by the deposition of new bone. These are present most commonly in prostate cancer, but also occur in carcinoid, small cell lung cancer, medulloblastoma, and Hodgkin lymphoma. The molecular crosstalk between tumour and bone cells involves osteoblast-generating proteins such as Transforming Growth Factor, Bone Morphogenic Proteins (BMPs), and Endothelin-1&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12085970&lt;/ref&gt;.<br /> <br /> '''Osteolytic''' (or '''lytic''') metastases are characterised by the destruction and breakdown of normal bone. These often occur when breast cancer spreads to bone, which is primarily mediated by osteoclasts (bone cells that breaks down bone tissue) and is not a direct effect of metastasized tumour cells&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8086233/&lt;/ref&gt;. Other tumour types with osteolytic metastases include multiple myeloma, non-small cell lung cancer, thyroid cancer, non-Hodgkin lymphoma, and Langerhans' cell histiocytosis. Osteolytic metastases are more common than osteoblastic metastases.<br /> <br /> '''Mixed''' metastases are characterised by the presence of both osteolytic and osteoblastic lesions together in the same area of bone. These metastases are usually present in metastatic gastrointestinal and squamous cancers, as well as in secondary breast cancer. Although breast cancer gives rise to predominantly lytic lesions, around 15–20% of women have sclerotic or both types of lesions&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11346860/&lt;/ref&gt;.<br /> <br /> ==Diagnosis==<br /> <br /> ===Signs and symptoms===<br /> Bone metastases cause major morbidity, and high clinical suspicion should be kept for any patient with cancer that presents with:<br /> <br /> *Severe pain (poorly localised, worse at night)<br /> *Impaired mobility<br /> *[[Pathological fracture|Bone fracture]]<br /> *Bone marrow aplasia<br /> *Symptoms of (metastatic) [[Metastatic spinal cord compression|spinal cord compression]] (MSCC)<br /> *Symptoms in keeping with [[hypercalcaemia]]:<br /> **Constipation<br /> **Fatigue<br /> **Polyuria/polydipsia<br /> **Acute kidney injury (AKI)<br /> **Cardiac arrhythmia<br /> <br /> ===Bloods===<br /> When a patient with cancer presents with any of the signs or symptoms above, basic screening in the form of simple blood testing must be undertaken and complemented with appropriate imaging tests:<br /> <br /> *Full evaluation of bone turnover and potential hypercalcaemia:<br /> **Serum calcium<br /> **Serum phosphate<br /> **25-Hydroxyvitamin D<br /> **Thyroid-stimulating hormone (TSH)<br /> **Parathyroid hormone (PTH)<br /> **Serum creatinine<br /> **Alkaline phosphatase (ALP)<br /> *Full blood count (myelosuppression, anaemia)<br /> *Serum protein electrophoresis (SPEP; myeloma screen)<br /> *Tumour markers (such as PSA in prostate cancer)<br /> <br /> ===Imaging===<br /> Radiological tests are an essential component of diagnosing bony metastases. One or more imaging modalities may be required to confirm suspected cancerous spread to bone.<br /> <br /> '''Plain radiographs''' (X-ray scans) are quick, cost-effective, and widely-available, and should be the initial diagnostic test of choice when investigating bone pain. They are highly specific but lack sensitivity (44-50%) because early-stage metastatic lesions, particularly those up to 1 cm, may be more difficult to visualise. More than 50% of the trabecular bone must be involved before the lesion will be apparent on film and, due to the poor contrast of trabecular bone, lesions within the medulla are often less evident than those within cortical bone&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9025785/&lt;/ref&gt;. As outlined above, sclerotic metastases will appear more radiopaque than the surrounding bone, whereas lytic metastases will appear more radiolucent.<br /> <br /> '''Bone scintigraphy''' (bone scans) on the other hand is highly sensitive but with low specificity. Data from Technetium-99m ('''&lt;sup&gt;99m&lt;/sup&gt;Tc''') scintigraphy have shown false-negative rates as low as 11 to 38% (good sensitivity), with false-positive rates as high as 40% (poor specificity). It thus provides a non-specific osteoblastic indication of bone status, be it inflammatory, traumatic, or neoplastic in origin. Scintigraphy is still more specific and sensitive than either plain radiography or computed tomography, whilst magnetic resonance imaging is more efficacious in assessing vertebral metastases&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/2028061/&lt;/ref&gt;.<br /> <br /> '''Computed tomography''' (CT scans) has a high sensitivity, ranging from 71 to 100%, for the detection of metastatic bone lesions&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9362427/&lt;/ref&gt;. Because of the excellent soft tissue resolution of the images produced by CT, it is a particularly helpful modality to distinguish lytic and sclerotic metastases and to visualise their precise location(s) for biopsy.<br /> <br /> '''Magnetic resonance imaging''' (MRI scans) is useful in assessing bone marrow infiltration by tumour deposits, and is required (whole spine) for the proper diagnosis of [[Metastatic spinal cord compression|MSCC]]. It has similarly high specificity (73 to 100%) and sensitivity (82 to 100%) in screening for bone metastases&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10964746/&lt;/ref&gt;.<br /> <br /> '''Positron emission tomography''' (PET scans) detects tumour indirectly by measuring metabolic activity in the form of fluorodeoxyglucose ('''&lt;sup&gt;18&lt;/sup&gt;F''') tissue uptake. As such, its use is not limited to visualising only bony metastases, as &lt;sup&gt;18&lt;/sup&gt;F PET will reveal non-bony metastatic spread also&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8638000/&lt;/ref&gt;. The accuracy of PET is highly dependent on the primary tumour site from which imaged metastases originate. As a modality it is superior to scintigraphy in the screening of bony metastases from breast (specificity 94%, sensitivity 95%)&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12073051/&lt;/ref&gt; and lung (specificity 99%, sensitivity 92%)&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10478250/&lt;/ref&gt; malignancies, but has lower sensitivity in detecting the comparatively slower-growing bone metastases of prostate and renal cancers&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10520701/&lt;/ref&gt;. <br /> <br /> ===Biopsy===<br /> Sometimes it is necessary to diagnose metastases histologically, by removing cells or tissue from the bone lesion(s) directly. Usually this is in the form of a needle or surgical biopsy, and may be indicated if a primary cancer is not known. If the patient has a known primary cancer, then often imaging alone will suffice for the diagnosis of metastatic bone disease.<br /> <br /> ==Treatment==<br /> There are a variety of therapeutic interventions available to patients presenting with bone metastases, but consideration must be given to several patient-specific and tumour-dependent parameters, which include&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11738947/&lt;/ref&gt; (but are not limited to):<br /> <br /> *Lesion site(s) (localised or widespread)<br /> *Presence of extraskeletal metastasis<br /> *Tumour type and features (like receptors)<br /> *Prior treatment history (and response)<br /> *Clinical symptoms<br /> *Performance status<br /> <br /> ===Radiotherapy===<br /> Radiation therapy can provide excellent pain relief and is the treatment of choice for localised metastatic bone pain. However, the analgesic mechanisms of therapeutic skeletal irradiation are poorly understood. Onset of pain relief is usually quick, with a majority of patients experiencing benefit within one to two weeks. Patients who have little reduction in pain by six weeks are unlikely to demonstrate significant overall benefit&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/24782453/&lt;/ref&gt;. Other than localised bone pain, additional indications for radiotherapy include [[Metastatic spinal cord compression|MSCC]] and bones at high risk for [[pathological fracture]]&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/15978828/&lt;/ref&gt;. Two of the three main divisions of radiation therapy—the third being (sealed source) [[brachytherapy]]—can be used to treat bone metastases: systemic (unsealed source) [[radionuclide therapy]] and [[external beam radiotherapy]] (EBRT). <br /> <br /> '''Local-field [[External beam radiotherapy|EBRT]]''' is the standard choice of radiation therapy for treating bone metastases, as it focally targets the bone lesion and can achieve rates of substantial pain relief of up to 80 to 90%&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/6178497/&lt;/ref&gt;. Randomised controlled trials (RCTs) from the 1990s have shown that a single fraction of 8 gray (Gy) is as effective as fractionated doses of 20 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9681885&lt;/ref&gt;, 24 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10577695&lt;/ref&gt;, and 30 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10577696&lt;/ref&gt;. <br /> <br /> '''Wide-field''' (or '''hemibody''') '''[[External beam radiotherapy|EBRT]]''' is useful for widespread metastatic skeletal disease, though was more commonly used for multifocal pain when other effective therapies (chemo- and radionuclide) were not available. There are no RCTs comparing analgesic effect with and without wide-field radiotherapy. However, in terms of quasi-randomised and low-quality RCTs, there is data to suggest that use of fractionation is no more effective than single fraction treatment&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8823257&lt;/ref&gt;, that increasing doses beyond 8 Gy does not improve overall pain responses&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11395246&lt;/ref&gt;, and adding wide-field to local-field radiotherapy, whilst significantly halting disease progression (lesion size: P = 0.03; lesion number: P = 0.01), increases grade 3 to 4 haematological toxicity&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/1374061&lt;/ref&gt;. It is possible to classify wide-field treatments into three body regions, each with recommended single-fraction dose limits. Upper treatments (from skull or C1 to L2–L3) should be limited to 6 Gy, whereas mid-body (from L1 to upper third of femur) and lower (from L3–L4 to above knee) treatments should be limited to 8 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/6178497/&lt;/ref&gt;. Any treatments must be delivered with fields shaped to minimise irradiation of organs at risk, such as lung, liver, kidney and bowel. <br /> <br /> '''[[Stereotactic radiotherapy|Stereotactic]] [[External beam radiotherapy|EBRT]]''' is a promising treatment option which delivers higher doses of radiation to tumours in shorter periods in time. When used for extracranial cancers it is interchangeably termed Stereotactic Body Radiation Therapy ('''[[Stereotactic radiotherapy|SBRT]]''') or Stereotactic Ablative Radiotherapy ('''[[Stereotactic radiotherapy|SABR]]'''), the latter of which is appealingly onomatopoeic. When this technique is used for treating malignancy within the brain or some other part of the head, it is termed Stereotactic RadioSurgery ('''[[Stereotactic radiotherapy|SRS]]'''). SBRT/SABR can be used both for primary cancers (lung, liver, prostate, renal) and secondary metastases (bone/spine, lung, liver). There are a number of advantages of stereotactic radiotherapy, the most obvious of which is the potential completion of treatment within a single day, rather than over a number of weeks. The other major benefit is that it obviates the need to irradiate large portions of bone, which lowers the risk of further functional marrow depletion in a patient cohort already at risk of poor marrow reserve. Preserving skeletal marrow function can permit continuous chemotherapy in these patients. The primary limitations of SBRT/SABR are that it is more expensive to deliver than conventional EBRT and that there is a paucity of RCT data comparing its use to standard EBRT management&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/18619121/&lt;/ref&gt;. However, a recent single-centre phase II trial appeared to show that SBRT/SABR provides superior pain relief to conventional multifraction radiotherapy, with no observed difference in adverse events or other aspects of quality of life&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/31021390&lt;/ref&gt;. <br /> <br /> '''[[Radionuclide therapy]]''' (or '''radioisotope therapy''') is the systemic administration of radionuclides (also known as radioisotopes) as unsealed radioactive sources that selectively deliver radiation to tumours or target organs. They are taken up predominantly at sites of bone formation, and are therefore most likely best effective for the palliation of osteoblastic (sclerotic) metastases. Common radionuclides approved for the treatment of painful bone metastases include phosphorus-32 ('''&lt;sup&gt;32&lt;/sup&gt;P'''; ''β''-decay), strontium-89 ('''&lt;sup&gt;89&lt;/sup&gt;Sr'''; ''β''-decay), samarium-153 ('''&lt;sup&gt;153&lt;/sup&gt;Sm'''; ''β''- and ''γ''-decay), and rhenium-186 ('''&lt;sup&gt;186&lt;/sup&gt;Re'''; ''β''- and ''γ''-decay). The added advantage of gamma ray emission during decay is that it permits nuclear imaging monitoring of radionuclide biodistribution during therapy. These radionuclides target bone through various mechanisms. &lt;sup&gt;32&lt;/sup&gt;P passes through inorganic phosphate pathways, whereas &lt;sup&gt;89&lt;/sup&gt;Sr is a calcium mimetic and is taken up as a direct analogue of this earth metal. The final two agents are targeted to bone via chelation to phosphonate compounds: &lt;sup&gt;153&lt;/sup&gt;Sm is paired to ethylenediaminetetramethylenephosphonate (EDTMP) and &lt;sup&gt;186&lt;/sup&gt;Re to 1,1-hydroxyethylidene diphosphonate (HEDP). Common toxicities from treatment include myelosuppression and a transient pain flare, the latter of which usually heralds a favourable response. A more recently developed radionuclide, radium-223 (&lt;sup&gt;'''223'''&lt;/sup&gt;'''Ra'''; ''α''-, ''β''-, and ''γ''-decay) is a calcium mimetic which emits over 95% of decay energy in the form of alpha radiation&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/17062709&lt;/ref&gt;. Owing to their comparatively large size the emitted alpha particles have a more limited depth of penetration into surrounding tissues (around 2–10 cells), thereby producing a more potently localised cytotoxic effect. Despite their symptomatic benefits in refractory, widespread bone metastases, neither &lt;sup&gt;89&lt;/sup&gt;Sr nor &lt;sup&gt;153&lt;/sup&gt;Sm have been shown to improve overall survival in interventional trials; however, &lt;sup&gt;223&lt;/sup&gt;Ra use in metastatic castration-resistant prostate cancer patients in the ALSYMPCA (ALpharadin in SYMptomatic Prostate CAncer) trial was shown to significantly prolong overall survival&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/23863050/&lt;/ref&gt;. <br /> <br /> ===Bisphosphonates===<br /> Analogues of the natural bone demineralisation inhibitor pyrophosphate, bisphosphonates are useful in the treatment of poorly localised bone pain and in previously irradiated bone lesions. They bind with high affinity to exposed bone mineral where they are internalised by osteoclasts, within which they disrupt the processes of bone resorption and can induce apoptosis. Data have shown that bisphosphonates may have direct pro-apoptotic effects on nearby metastatic cancer cells also&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9362432/&lt;/ref&gt;. In halting the mobilisation of calcium and phosphate from bone, bisphosphonate use (together with rehydration) is now standard of care for malignancy-induced hypercalcaemia&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9025784/&lt;/ref&gt;. The analgesic effect of these agents is independent of underlying tumour characteristics, with osteolytic and osteoblastic lesions responding similarly&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9496390&lt;/ref&gt;. Many patients tolerate bisphosphonates without major concern, but common side-effects include flu-like myalgic symptoms, diarrhoea, nausea and reflux. It is exceedingly rare but one must be aware of the risk of developing osteonecrosis of the jaw. These medications undergo renal excretion and as such should be avoided in tumour-induced hypercalcaemia or metastatic bone disease if serum creatinine is greater than 400 μmol/L or 265 μmol/L, respectively. Bisphosphonates are divided into three generations of drug: first-generation (tiludronate, clodronate, etidronate), second-generation (ibandronate, alendronate, paimdronate), and third-generation (zoledronate, risedronate). One of the newest agents, zoledronate is 100-times more effective than second-generation pamidronate&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12558465/&lt;/ref&gt;. Whilst receiving bisphosphonate therapy, patients should take protective vitamin D and calcium supplements.<br /> <br /> ===Denosumab===<br /> Denosumab is a monoclonal antibody which binds to and inhibits the action of the RANK receptor ligand (RANKL). RANK is located on the surface of osteoclast progenitor cells and its activation stimulates their development into mature osteoclasts. Therefore denosumab, administered as a subcutaneous injection of 120 mg every four weeks, can help prevent bone destruction and fracture in patients with bone metastases. The antibody is cleared from the body by the reticuloendothelial system and can therefore be used in patients with poor renal function, in whom bisphosphonate use would be contraindicated&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/21145999/&lt;/ref&gt;. Additionally, data have shown that denosumab use causes greater suppression of osteolytic markers than bisphosphonate use in metastatic patients with breast&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/21060033/&lt;/ref&gt; or prostate&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/21353695/&lt;/ref&gt; cancer. However its effectiveness in comparison to bisphosphonates for patients with lung cancer or multiple myeloma is similar for the prevention of skeletal-related events (SRE), and indeed patients with multiple myeloma showed worse overall survival when treated with denosumab instead of zoledronate&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/21343556/&lt;/ref&gt;. <br /> <br /> ===Systemic anticancer therapies===<br /> Systemic anticancer therapy (SACT) refers to all drugs administered systemically with direct anticancer activity. This includes all conventional cytotoxic chemotherapies, all small molecule or antibody treatments, and all types of immunotherapy. Hormonal agents are not included within this categorisation. SACT may be considered for bone metastases if a primary tumour is known or subsequently confirmed. The specific therapy used will be the same therapy as typically used for the culprit primary cancer, though the precise dose and schedule will vary. SACT is sometimes used concurrently with other treatments such as bisphosphonates or radiotherapy. Side-effects will be treatment-specific.<br /> <br /> ===Hormonal therapies===<br /> -<br /> <br /> ===Interventional radiology===<br /> Ablation (inc. RFA), percutaneous cementoplasty (bone cement)<br /> <br /> ===Surgery===<br /> -<br /> <br /> ==Living with bone metastases==<br /> Pain, mobility and safety, survival&lt;references /&gt;</div>

Alex https://oncopaedia.net/w/index.php?title=Articles:Bone_metastases&diff=309 2020-04-22T10:13:12Z

<p>Alex: </p> <hr /> <div>Metastases within bone can cause extreme and debilitating pain. Bone metastases are far more common than primary bone cancer, and many different cancer types can spread to the bone. The most common types of cancer which spread to bone are:<br /> <br /> *Breast<br /> *Prostate<br /> *Lung<br /> *Kidney<br /> *Thyroid<br /> <br /> Cancer can theoretically metastasize to any bone in the body, but in reality there is a predilection for certain sites. The most common sites are the vertebrae, ribs, pelvis, sternum, and the skull.<br /> <br /> ==Classification==<br /> A bone is a rigid organ, but it is far from physiologically static. To maintain bone strength, there is continuous breakdown and simultaneous reformation of bone, two processes which must finely balance for good bone health.<br /> <br /> '''Osteoblastic''' (or '''sclerotic''') metastases are characterised by the deposition of new bone. These are present most commonly in prostate cancer, but also occur in carcinoid, small cell lung cancer, medulloblastoma, and Hodgkin lymphoma. The molecular crosstalk between tumour and bone cells involves osteoblast-generating proteins such as Transforming Growth Factor, Bone Morphogenic Proteins (BMPs), and Endothelin-1&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12085970&lt;/ref&gt;.<br /> <br /> '''Osteolytic''' (or '''lytic''') metastases are characterised by the destruction and breakdown of normal bone. These often occur when breast cancer spreads to bone, which is primarily mediated by osteoclasts (bone cells that breaks down bone tissue) and is not a direct effect of metastasized tumour cells&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8086233/&lt;/ref&gt;. Other tumour types with osteolytic metastases include multiple myeloma, non-small cell lung cancer, thyroid cancer, non-Hodgkin lymphoma, and Langerhans' cell histiocytosis. Osteolytic metastases are more common than osteoblastic metastases.<br /> <br /> '''Mixed''' metastases are characterised by the presence of both osteolytic and osteoblastic lesions together in the same area of bone. These metastases are usually present in metastatic gastrointestinal and squamous cancers, as well as in secondary breast cancer. Although breast cancer gives rise to predominantly lytic lesions, around 15–20% of women have sclerotic or both types of lesions&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11346860/&lt;/ref&gt;.<br /> <br /> ==Diagnosis==<br /> <br /> ===Signs and symptoms===<br /> Bone metastases cause major morbidity, and high clinical suspicion should be kept for any patient with cancer that presents with:<br /> <br /> *Severe pain (poorly localised, worse at night)<br /> *Impaired mobility<br /> *[[Pathological fracture|Bone fracture]]<br /> *Bone marrow aplasia<br /> *Symptoms of (metastatic) [[Metastatic spinal cord compression|spinal cord compression]] (MSCC)<br /> *Symptoms in keeping with [[hypercalcaemia]]:<br /> **Constipation<br /> **Fatigue<br /> **Polyuria/polydipsia<br /> **Acute kidney injury (AKI)<br /> **Cardiac arrhythmia<br /> <br /> ===Bloods===<br /> When a patient with cancer presents with any of the signs or symptoms above, basic screening in the form of simple blood testing must be undertaken and complemented with appropriate imaging tests:<br /> <br /> *Full evaluation of bone turnover and potential hypercalcaemia:<br /> **Serum calcium<br /> **Serum phosphate<br /> **25-Hydroxyvitamin D<br /> **Thyroid-stimulating hormone (TSH)<br /> **Parathyroid hormone (PTH)<br /> **Serum creatinine<br /> **Alkaline phosphatase (ALP)<br /> *Full blood count (myelosuppression, anaemia)<br /> *Serum protein electrophoresis (SPEP; myeloma screen)<br /> *Tumour markers (such as PSA in prostate cancer)<br /> <br /> ===Imaging===<br /> Radiological tests are an essential component of diagnosing bony metastases. One or more imaging modalities may be required to confirm suspected cancerous spread to bone.<br /> <br /> '''Plain radiographs''' (X-ray scans) are quick, cost-effective, and widely-available, and should be the initial diagnostic test of choice when investigating bone pain. They are highly specific but lack sensitivity (44-50%) because early-stage metastatic lesions, particularly those up to 1 cm, may be more difficult to visualise. More than 50% of the trabecular bone must be involved before the lesion will be apparent on film and, due to the poor contrast of trabecular bone, lesions within the medulla are often less evident than those within cortical bone&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9025785/&lt;/ref&gt;. As outlined above, sclerotic metastases will appear more radiopaque than the surrounding bone, whereas lytic metastases will appear more radiolucent.<br /> <br /> '''Bone scintigraphy''' (bone scans) on the other hand is highly sensitive but with low specificity. Data from Technetium-99m ('''&lt;sup&gt;99m&lt;/sup&gt;Tc''') scintigraphy have shown false-negative rates as low as 11 to 38% (good sensitivity), with false-positive rates as high as 40% (poor specificity). It thus provides a non-specific osteoblastic indication of bone status, be it inflammatory, traumatic, or neoplastic in origin. Scintigraphy is still more specific and sensitive than either plain radiography or computed tomography, whilst magnetic resonance imaging is more efficacious in assessing vertebral metastases&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/2028061/&lt;/ref&gt;.<br /> <br /> '''Computed tomography''' (CT scans) has a high sensitivity, ranging from 71 to 100%, for the detection of metastatic bone lesions&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9362427/&lt;/ref&gt;. Because of the excellent soft tissue resolution of the images produced by CT, it is a particularly helpful modality to distinguish lytic and sclerotic metastases and to visualise their precise location(s) for biopsy.<br /> <br /> '''Magnetic resonance imaging''' (MRI scans) is useful in assessing bone marrow infiltration by tumour deposits, and is required (whole spine) for the proper diagnosis of [[Metastatic spinal cord compression|MSCC]]. It has similarly high specificity (73 to 100%) and sensitivity (82 to 100%) in screening for bone metastases&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10964746/&lt;/ref&gt;.<br /> <br /> '''Positron emission tomography''' (PET scans) detects tumour indirectly by measuring metabolic activity in the form of fluorodeoxyglucose ('''&lt;sup&gt;18&lt;/sup&gt;F''') tissue uptake. As such, its use is not limited to visualising only bony metastases, as &lt;sup&gt;18&lt;/sup&gt;F PET will reveal non-bony metastatic spread also&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8638000/&lt;/ref&gt;. The accuracy of PET is highly dependent on the primary tumour site from which imaged metastases originate. As a modality it is superior to scintigraphy in the screening of bony metastases from breast (specificity 94%, sensitivity 95%)&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12073051/&lt;/ref&gt; and lung (specificity 99%, sensitivity 92%)&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10478250/&lt;/ref&gt; malignancies, but has lower sensitivity in detecting the comparatively slower-growing bone metastases of prostate and renal cancers&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10520701/&lt;/ref&gt;. <br /> <br /> ===Biopsy===<br /> Sometimes it is necessary to diagnose metastases histologically, by removing cells or tissue from the bone lesion(s) directly. Usually this is in the form of a needle or surgical biopsy, and may be indicated if a primary cancer is not known. If the patient has a known primary cancer, then often imaging alone will suffice for the diagnosis of metastatic bone disease.<br /> <br /> ==Treatment==<br /> There are a variety of therapeutic interventions available to patients presenting with bone metastases, but consideration must be given to several patient-specific and tumour-dependent parameters, which include&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11738947/&lt;/ref&gt; (but are not limited to):<br /> <br /> *Lesion site(s) (localised or widespread)<br /> *Presence of extraskeletal metastasis<br /> *Tumour type and features (like receptors)<br /> *Prior treatment history (and response)<br /> *Clinical symptoms<br /> *Performance status<br /> <br /> ===Radiotherapy===<br /> Radiation therapy can provide excellent pain relief and is the treatment of choice for localised metastatic bone pain. However, the analgesic mechanisms of therapeutic skeletal irradiation are poorly understood. Onset of pain relief is usually quick, with a majority of patients experiencing benefit within one to two weeks. Patients who have little reduction in pain by six weeks are unlikely to demonstrate significant overall benefit&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/24782453/&lt;/ref&gt;. Other than localised bone pain, additional indications for radiotherapy include [[Metastatic spinal cord compression|MSCC]] and bones at high risk for [[pathological fracture]]&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/15978828/&lt;/ref&gt;. Two of the three main divisions of radiation therapy—the third being (sealed source) [[brachytherapy]]—can be used to treat bone metastases: systemic (unsealed source) [[radionuclide therapy]] and [[external beam radiotherapy]] (EBRT). <br /> <br /> '''Local-field [[External beam radiotherapy|EBRT]]''' is the standard choice of radiation therapy for treating bone metastases, as it focally targets the bone lesion and can achieve rates of substantial pain relief of up to 80 to 90%&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/6178497/&lt;/ref&gt;. Randomised controlled trials (RCTs) from the 1990s have shown that a single fraction of 8 gray (Gy) is as effective as fractionated doses of 20 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9681885&lt;/ref&gt;, 24 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10577695&lt;/ref&gt;, and 30 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10577696&lt;/ref&gt;. <br /> <br /> '''Wide-field''' (or '''hemibody''') '''[[External beam radiotherapy|EBRT]]''' is useful for widespread metastatic skeletal disease, though was more commonly used for multifocal pain when other effective therapies (chemo- and radionuclide) were not available. There are no RCTs comparing analgesic effect with and without wide-field radiotherapy. However, in terms of quasi-randomised and low-quality RCTs, there is data to suggest that use of fractionation is no more effective than single fraction treatment&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8823257&lt;/ref&gt;, that increasing doses beyond 8 Gy does not improve overall pain responses&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11395246&lt;/ref&gt;, and adding wide-field to local-field radiotherapy, whilst significantly halting disease progression (lesion size: P = 0.03; lesion number: P = 0.01), increases grade 3 to 4 haematological toxicity&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/1374061&lt;/ref&gt;. It is possible to classify wide-field treatments into three body regions, each with recommended single-fraction dose limits. Upper treatments (from skull or C1 to L2–L3) should be limited to 6 Gy, whereas mid-body (from L1 to upper third of femur) and lower (from L3–L4 to above knee) treatments should be limited to 8 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/6178497/&lt;/ref&gt;. Any treatments must be delivered with fields shaped to minimise irradiation of organs at risk, such as lung, liver, kidney and bowel. <br /> <br /> '''[[Stereotactic radiotherapy|Stereotactic]] [[External beam radiotherapy|EBRT]]''' is a promising treatment option which delivers higher doses of radiation to tumours in shorter periods in time. When used for extracranial cancers it is interchangeably termed Stereotactic Body Radiation Therapy ('''[[Stereotactic radiotherapy|SBRT]]''') or Stereotactic Ablative Radiotherapy ('''[[Stereotactic radiotherapy|SABR]]'''), the latter of which is appealingly onomatopoeic. When this technique is used for treating malignancy within the brain or some other part of the head, it is termed Stereotactic RadioSurgery ('''[[Stereotactic radiotherapy|SRS]]'''). SBRT/SABR can be used both for primary cancers (lung, liver, prostate, renal) and secondary metastases (bone/spine, lung, liver). There are a number of advantages of stereotactic radiotherapy, the most obvious of which is the potential completion of treatment within a single day, rather than over a number of weeks. The other major benefit is that it obviates the need to irradiate large portions of bone, which lowers the risk of further functional marrow depletion in a patient cohort already at risk of poor marrow reserve. Preserving skeletal marrow function can permit continuous chemotherapy in these patients. The primary limitations of SBRT/SABR are that it is more expensive to deliver than conventional EBRT and that there is a paucity of RCT data comparing its use to standard EBRT management&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/18619121/&lt;/ref&gt;. However, a recent single-centre phase II trial appeared to show that SBRT/SABR provides superior pain relief to conventional multifraction radiotherapy, with no observed difference in adverse events or other aspects of quality of life&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/31021390&lt;/ref&gt;. <br /> <br /> '''[[Radionuclide therapy]]''' (or '''radioisotope therapy''') is the systemic administration of radionuclides (also known as radioisotopes) as unsealed radioactive sources that selectively deliver radiation to tumours or target organs. They are taken up predominantly at sites of bone formation, and are therefore most likely best effective for the palliation of osteoblastic (sclerotic) metastases. Common radionuclides approved for the treatment of painful bone metastases include phosphorus-32 ('''&lt;sup&gt;32&lt;/sup&gt;P'''; ''β''-decay), strontium-89 ('''&lt;sup&gt;89&lt;/sup&gt;Sr'''; ''β''-decay), samarium-153 ('''&lt;sup&gt;153&lt;/sup&gt;Sm'''; ''β''- and ''γ''-decay), and rhenium-186 ('''&lt;sup&gt;186&lt;/sup&gt;Re'''; ''β''- and ''γ''-decay). The added advantage of gamma ray emission during decay is that it permits nuclear imaging monitoring of radionuclide biodistribution during therapy. These radionuclides target bone through various mechanisms. &lt;sup&gt;32&lt;/sup&gt;P passes through inorganic phosphate pathways, whereas &lt;sup&gt;89&lt;/sup&gt;Sr is a calcium mimetic and is taken up as a direct analogue of this earth metal. The final two agents are targeted to bone via chelation to phosphonate compounds: &lt;sup&gt;153&lt;/sup&gt;Sm is paired to ethylenediaminetetramethylenephosphonate (EDTMP) and &lt;sup&gt;186&lt;/sup&gt;Re to 1,1-hydroxyethylidene diphosphonate (HEDP). Common toxicities from treatment include myelosuppression and a transient pain flare, the latter of which usually heralds a favourable response. A more recently developed radionuclide, radium-223 (&lt;sup&gt;'''223'''&lt;/sup&gt;'''Ra'''; ''α''-, ''β''-, and ''γ''-decay) is a calcium mimetic which emits over 95% of decay energy in the form of alpha radiation&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/17062709&lt;/ref&gt;. Owing to their comparatively large size the emitted alpha particles have a more limited depth of penetration into surrounding tissues (around 2–10 cells), thereby producing a more potently localised cytotoxic effect. Despite their symptomatic benefits in refractory, widespread bone metastases, neither &lt;sup&gt;89&lt;/sup&gt;Sr nor &lt;sup&gt;153&lt;/sup&gt;Sm have been shown to improve overall survival in interventional trials; however, &lt;sup&gt;223&lt;/sup&gt;Ra use in metastatic castration-resistant prostate cancer patients in the ALSYMPCA (ALpharadin in SYMptomatic Prostate CAncer) trial was shown to significantly prolong overall survival&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/23863050/&lt;/ref&gt;. <br /> <br /> ===Bisphosphonates===<br /> Analogues of the natural bone demineralisation inhibitor pyrophosphate, bisphosphonates are useful in the treatment of poorly localised bone pain and in previously irradiated bone lesions. They bind with high affinity to exposed bone mineral where they are internalised by osteoclasts, within which they disrupt the processes of bone resorption and can induce apoptosis. Data have shown that bisphosphonates may have direct pro-apoptotic effects on nearby metastatic cancer cells also&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9362432/&lt;/ref&gt;. In halting the mobilisation of calcium and phosphate from bone, bisphosphonate use (together with rehydration) is now standard of care for malignancy-induced hypercalcaemia&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9025784/&lt;/ref&gt;. The analgesic effect of these agents is independent of underlying tumour characteristics, with osteolytic and osteoblastic lesions responding similarly&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9496390&lt;/ref&gt;. Many patients tolerate bisphosphonates without major concern, but common side-effects include flu-like myalgic symptoms, diarrhoea, nausea and reflux. It is exceedingly rare but one must be aware of the risk of developing osteonecrosis of the jaw. These medications undergo renal excretion and as such should be avoided in tumour-induced hypercalcaemia or metastatic bone disease if serum creatinine is greater than 400 μmol/L or 265 μmol/L, respectively. Bisphosphonates are divided into three generations of drug: first-generation (tiludronate, clodronate, etidronate), second-generation (ibandronate, alendronate, paimdronate), and third-generation (zoledronate, risedronate). One of the newest agents, zoledronate is 100-times more effective than second-generation pamidronate&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12558465/&lt;/ref&gt;. Whilst receiving bisphosphonate therapy, patients should take protective vitamin D and calcium supplements.<br /> <br /> ===Denosumab===<br /> Denosumab is a monoclonal antibody which binds to and inhibits the action of the RANK receptor ligand (RANKL). RANK is located on the surface of osteoclast progenitor cells and its activation stimulates their development into mature osteoclasts. Therefore denosumab, administered as a subcutaneous injection of 120 mg every four weeks, can help prevent bone destruction and fracture in patients with bone metastases. The antibody is cleared from the body by the reticuloendothelial system and can therefore be used in patients with poor renal function, in whom bisphosphonate use would be contraindicated&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/21145999/&lt;/ref&gt;. Additionally, data have shown that denosumab use causes greater suppression of osteolytic markers than bisphosphonate use in metastatic patients with breast&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/21060033/&lt;/ref&gt; or prostate&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/21353695/&lt;/ref&gt; cancer. However its effectiveness in comparison to bisphosphonates for patients with lung cancer or multiple myeloma is similar for the prevention of skeletal-related events (SRE), and indeed patients with multiple myeloma showed worse overall survival when treated with denosumab instead of zoledronate&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/21343556/&lt;/ref&gt;. <br /> <br /> ===Systemic anticancer therapies===<br /> Systemic anticancer therapy (SACT) refers to all drugs administered systemically with direct anticancer activity. This includes all conventional cytotoxic chemotherapies, all small molecule or antibody treatments, and all types of immunotherapy. Hormonal agents are not included within this categorisation. SACT may be considered for bone metastases if a primary tumour is known or subsequently confirmed. The specific therapy used will be the same therapy as typically used for the culprit primary cancer, though the precise dose and schedule will vary. SACT is sometimes used concurrently with other treatments such as bisphosphonates or radiotherapy. Side-effects will be treatment-specific.<br /> <br /> ===Hormonal therapies===<br /> -<br /> <br /> ===Surgery &amp; IR===<br /> -<br /> <br /> ===Bone cement===<br /> -<br /> <br /> ==Living with bone metastases==<br /> Pain, mobility and safety, survival&lt;references /&gt;</div>

Alex https://oncopaedia.net/w/index.php?title=Articles:Bone_metastases&diff=308 2020-04-17T15:15:27Z

<p>Alex: </p> <hr /> <div>Metastases within bone can cause extreme and debilitating pain. Bone metastases are far more common than primary bone cancer, and many different cancer types can spread to the bone. The most common types of cancer which spread to bone are:<br /> <br /> *Breast<br /> *Prostate<br /> *Lung<br /> *Kidney<br /> *Thyroid<br /> <br /> Cancer can theoretically metastasize to any bone in the body, but in reality there is a predilection for certain sites. The most common sites are the vertebrae, ribs, pelvis, sternum, and the skull.<br /> <br /> ==Classification==<br /> A bone is a rigid organ, but it is far from physiologically static. To maintain bone strength, there is continuous breakdown and simultaneous reformation of bone, two processes which must finely balance for good bone health.<br /> <br /> '''Osteoblastic''' (or '''sclerotic''') metastases are characterised by the deposition of new bone. These are present most commonly in prostate cancer, but also occur in carcinoid, small cell lung cancer, medulloblastoma, and Hodgkin lymphoma. The molecular crosstalk between tumour and bone cells involves osteoblast-generating proteins such as Transforming Growth Factor, Bone Morphogenic Proteins (BMPs), and Endothelin-1&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12085970&lt;/ref&gt;.<br /> <br /> '''Osteolytic''' (or '''lytic''') metastases are characterised by the destruction and breakdown of normal bone. These often occur when breast cancer spreads to bone, which is primarily mediated by osteoclasts (bone cells that breaks down bone tissue) and is not a direct effect of metastasized tumour cells&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8086233/&lt;/ref&gt;. Other tumour types with osteolytic metastases include multiple myeloma, non-small cell lung cancer, thyroid cancer, non-Hodgkin lymphoma, and Langerhans' cell histiocytosis. Osteolytic metastases are more common than osteoblastic metastases.<br /> <br /> '''Mixed''' metastases are characterised by the presence of both osteolytic and osteoblastic lesions together in the same area of bone. These metastases are usually present in metastatic gastrointestinal and squamous cancers, as well as in secondary breast cancer. Although breast cancer gives rise to predominantly lytic lesions, around 15–20% of women have sclerotic or both types of lesions&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11346860/&lt;/ref&gt;.<br /> <br /> ==Diagnosis==<br /> <br /> ===Signs and symptoms===<br /> Bone metastases cause major morbidity, and high clinical suspicion should be kept for any patient with cancer that presents with:<br /> <br /> *Severe pain (poorly localised, worse at night)<br /> *Impaired mobility<br /> *[[Pathological fracture|Bone fracture]]<br /> *Bone marrow aplasia<br /> *Symptoms of (metastatic) [[Metastatic spinal cord compression|spinal cord compression]] (MSCC)<br /> *Symptoms in keeping with [[hypercalcaemia]]:<br /> **Constipation<br /> **Fatigue<br /> **Polyuria/polydipsia<br /> **Acute kidney injury (AKI)<br /> **Cardiac arrhythmia<br /> <br /> ===Bloods===<br /> When a patient with cancer presents with any of the signs or symptoms above, basic screening in the form of simple blood testing must be undertaken and complemented with appropriate imaging tests:<br /> <br /> *Full evaluation of bone turnover and potential hypercalcaemia:<br /> **Serum calcium<br /> **Serum phosphate<br /> **25-Hydroxyvitamin D<br /> **Thyroid-stimulating hormone (TSH)<br /> **Parathyroid hormone (PTH)<br /> **Serum creatinine<br /> **Alkaline phosphatase (ALP)<br /> *Full blood count (myelosuppression, anaemia)<br /> *Serum protein electrophoresis (SPEP; myeloma screen)<br /> *Tumour markers (such as PSA in prostate cancer)<br /> <br /> ===Imaging===<br /> Radiological tests are an essential component of diagnosing bony metastases. One or more imaging modalities may be required to confirm suspected cancerous spread to bone.<br /> <br /> '''Plain radiographs''' (X-ray scans) are quick, cost-effective, and widely-available, and should be the initial diagnostic test of choice when investigating bone pain. They are highly specific but lack sensitivity (44-50%) because early-stage metastatic lesions, particularly those up to 1 cm, may be more difficult to visualise. More than 50% of the trabecular bone must be involved before the lesion will be apparent on film and, due to the poor contrast of trabecular bone, lesions within the medulla are often less evident than those within cortical bone&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9025785/&lt;/ref&gt;. As outlined above, sclerotic metastases will appear more radiopaque than the surrounding bone, whereas lytic metastases will appear more radiolucent.<br /> <br /> '''Bone scintigraphy''' (bone scans) on the other hand is highly sensitive but with low specificity. Data from Technetium-99m ('''&lt;sup&gt;99m&lt;/sup&gt;Tc''') scintigraphy have shown false-negative rates as low as 11 to 38% (good sensitivity), with false-positive rates as high as 40% (poor specificity). It thus provides a non-specific osteoblastic indication of bone status, be it inflammatory, traumatic, or neoplastic in origin. Scintigraphy is still more specific and sensitive than either plain radiography or computed tomography, whilst magnetic resonance imaging is more efficacious in assessing vertebral metastases&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/2028061/&lt;/ref&gt;.<br /> <br /> '''Computed tomography''' (CT scans) has a high sensitivity, ranging from 71 to 100%, for the detection of metastatic bone lesions&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9362427/&lt;/ref&gt;. Because of the excellent soft tissue resolution of the images produced by CT, it is a particularly helpful modality to distinguish lytic and sclerotic metastases and to visualise their precise location(s) for biopsy.<br /> <br /> '''Magnetic resonance imaging''' (MRI scans) is useful in assessing bone marrow infiltration by tumour deposits, and is required (whole spine) for the proper diagnosis of [[Metastatic spinal cord compression|MSCC]]. It has similarly high specificity (73 to 100%) and sensitivity (82 to 100%) in screening for bone metastases&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10964746/&lt;/ref&gt;.<br /> <br /> '''Positron emission tomography''' (PET scans) detects tumour indirectly by measuring metabolic activity in the form of fluorodeoxyglucose ('''&lt;sup&gt;18&lt;/sup&gt;F''') tissue uptake. As such, its use is not limited to visualising only bony metastases, as &lt;sup&gt;18&lt;/sup&gt;F PET will reveal non-bony metastatic spread also&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8638000/&lt;/ref&gt;. The accuracy of PET is highly dependent on the primary tumour site from which imaged metastases originate. As a modality it is superior to scintigraphy in the screening of bony metastases from breast (specificity 94%, sensitivity 95%)&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12073051/&lt;/ref&gt; and lung (specificity 99%, sensitivity 92%)&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10478250/&lt;/ref&gt; malignancies, but has lower sensitivity in detecting the comparatively slower-growing bone metastases of prostate and renal cancers&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10520701/&lt;/ref&gt;. <br /> <br /> ===Biopsy===<br /> Sometimes it is necessary to diagnose metastases histologically, by removing cells or tissue from the bone lesion(s) directly. Usually this is in the form of a needle or surgical biopsy, and may be indicated if a primary cancer is not known. If the patient has a known primary cancer, then often imaging alone will suffice for the diagnosis of metastatic bone disease.<br /> <br /> ==Treatment==<br /> There are a variety of therapeutic interventions available to patients presenting with bone metastases, but consideration must be given to several patient-specific and tumour-dependent parameters, which include&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11738947/&lt;/ref&gt; (but are not limited to):<br /> <br /> *Lesion site(s) (localised or widespread)<br /> *Presence of extraskeletal metastasis<br /> *Tumour type and features (like receptors)<br /> *Prior treatment history (and response)<br /> *Clinical symptoms<br /> *Performance status<br /> <br /> ===Radiotherapy===<br /> Radiation therapy can provide excellent pain relief and is the treatment of choice for localised metastatic bone pain. However, the analgesic mechanisms of therapeutic skeletal irradiation are poorly understood. Onset of pain relief is usually quick, with a majority of patients experiencing benefit within one to two weeks. Patients who have little reduction in pain by six weeks are unlikely to demonstrate significant overall benefit&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/24782453/&lt;/ref&gt;. Other than localised bone pain, additional indications for radiotherapy include [[Metastatic spinal cord compression|MSCC]] and bones at high risk for [[pathological fracture]]&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/15978828/&lt;/ref&gt;. Two of the three main divisions of radiation therapy—the third being (sealed source) [[brachytherapy]]—can be used to treat bone metastases: systemic (unsealed source) [[radionuclide therapy]] and [[external beam radiotherapy]] (EBRT). <br /> <br /> '''Local-field [[External beam radiotherapy|EBRT]]''' is the standard choice of radiation therapy for treating bone metastases, as it focally targets the bone lesion and can achieve rates of substantial pain relief of up to 80 to 90%&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/6178497/&lt;/ref&gt;. Randomised controlled trials (RCTs) from the 1990s have shown that a single fraction of 8 gray (Gy) is as effective as fractionated doses of 20 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9681885&lt;/ref&gt;, 24 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10577695&lt;/ref&gt;, and 30 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10577696&lt;/ref&gt;. <br /> <br /> '''Wide-field''' (or '''hemibody''') '''[[External beam radiotherapy|EBRT]]''' is useful for widespread metastatic skeletal disease, though was more commonly used for multifocal pain when other effective therapies (chemo- and radionuclide) were not available. There are no RCTs comparing analgesic effect with and without wide-field radiotherapy. However, in terms of quasi-randomised and low-quality RCTs, there is data to suggest that use of fractionation is no more effective than single fraction treatment&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8823257&lt;/ref&gt;, that increasing doses beyond 8 Gy does not improve overall pain responses&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11395246&lt;/ref&gt;, and adding wide-field to local-field radiotherapy, whilst significantly halting disease progression (lesion size: P = 0.03; lesion number: P = 0.01), increases grade 3 to 4 haematological toxicity&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/1374061&lt;/ref&gt;. It is possible to classify wide-field treatments into three body regions, each with recommended single-fraction dose limits. Upper treatments (from skull or C1 to L2–L3) should be limited to 6 Gy, whereas mid-body (from L1 to upper third of femur) and lower (from L3–L4 to above knee) treatments should be limited to 8 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/6178497/&lt;/ref&gt;. Any treatments must be delivered with fields shaped to minimise irradiation of organs at risk, such as lung, liver, kidney and bowel. <br /> <br /> '''[[Stereotactic radiotherapy|Stereotactic]] [[External beam radiotherapy|EBRT]]''' is a promising treatment option which delivers higher doses of radiation to tumours in shorter periods in time. When used for extracranial cancers it is interchangeably termed Stereotactic Body Radiation Therapy ('''[[Stereotactic radiotherapy|SBRT]]''') or Stereotactic Ablative Radiotherapy ('''[[Stereotactic radiotherapy|SABR]]'''), the latter of which is appealingly onomatopoeic. When this technique is used for treating malignancy within the brain or some other part of the head, it is termed Stereotactic RadioSurgery ('''[[Stereotactic radiotherapy|SRS]]'''). SBRT/SABR can be used both for primary cancers (lung, liver, prostate, renal) and secondary metastases (bone/spine, lung, liver). There are a number of advantages of stereotactic radiotherapy, the most obvious of which is the potential completion of treatment within a single day, rather than over a number of weeks. The other major benefit is that it obviates the need to irradiate large portions of bone, which lowers the risk of further functional marrow depletion in a patient cohort already at risk of poor marrow reserve. Preserving skeletal marrow function can permit continuous chemotherapy in these patients. The primary limitations of SBRT/SABR are that it is more expensive to deliver than conventional EBRT and that there is a paucity of RCT data comparing its use to standard EBRT management&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/18619121/&lt;/ref&gt;. However, a recent single-centre phase II trial appeared to show that SBRT/SABR provides superior pain relief to conventional multifraction radiotherapy, with no observed difference in adverse events or other aspects of quality of life&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/31021390&lt;/ref&gt;. <br /> <br /> '''[[Radionuclide therapy]]''' (or '''radioisotope therapy''') is the systemic administration of radionuclides (also known as radioisotopes) as unsealed radioactive sources that selectively deliver radiation to tumours or target organs. They are taken up predominantly at sites of bone formation, and are therefore most likely best effective for the palliation of osteoblastic (sclerotic) metastases. Common radionuclides approved for the treatment of painful bone metastases include phosphorus-32 ('''&lt;sup&gt;32&lt;/sup&gt;P'''; ''β''-decay), strontium-89 ('''&lt;sup&gt;89&lt;/sup&gt;Sr'''; ''β''-decay), samarium-153 ('''&lt;sup&gt;153&lt;/sup&gt;Sm'''; ''β''- and ''γ''-decay), and rhenium-186 ('''&lt;sup&gt;186&lt;/sup&gt;Re'''; ''β''- and ''γ''-decay). The added advantage of gamma ray emission during decay is that it permits nuclear imaging monitoring of radionuclide biodistribution during therapy. These radionuclides target bone through various mechanisms. &lt;sup&gt;32&lt;/sup&gt;P passes through inorganic phosphate pathways, whereas &lt;sup&gt;89&lt;/sup&gt;Sr is a calcium mimetic and is taken up as a direct analogue of this earth metal. The final two agents are targeted to bone via chelation to phosphonate compounds: &lt;sup&gt;153&lt;/sup&gt;Sm is paired to ethylenediaminetetramethylenephosphonate (EDTMP) and &lt;sup&gt;186&lt;/sup&gt;Re to 1,1-hydroxyethylidene diphosphonate (HEDP). Common toxicities from treatment include myelosuppression and a transient pain flare, the latter of which usually heralds a favourable response. A more recently developed radionuclide, radium-223 (&lt;sup&gt;'''223'''&lt;/sup&gt;'''Ra'''; ''α''-, ''β''-, and ''γ''-decay) is a calcium mimetic which emits over 95% of decay energy in the form of alpha radiation&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/17062709&lt;/ref&gt;. Owing to their comparatively large size the emitted alpha particles have a more limited depth of penetration into surrounding tissues (around 2–10 cells), thereby producing a more potently localised cytotoxic effect. Despite their symptomatic benefits in refractory, widespread bone metastases, neither &lt;sup&gt;89&lt;/sup&gt;Sr nor &lt;sup&gt;153&lt;/sup&gt;Sm have been shown to improve overall survival in interventional trials; however, &lt;sup&gt;223&lt;/sup&gt;Ra use in metastatic castration-resistant prostate cancer patients in the ALSYMPCA (ALpharadin in SYMptomatic Prostate CAncer) trial was shown to significantly prolong overall survival&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/23863050/&lt;/ref&gt;. <br /> <br /> ===Bisphosphonates===<br /> Analogues of the natural bone demineralisation inhibitor pyrophosphate, bisphosphonates are useful in the treatment of poorly localised bone pain and in previously irradiated bone lesions. They bind with high affinity to exposed bone mineral where they are internalised by osteoclasts, within which they disrupt the processes of bone resorption and can induce apoptosis. Data have shown that bisphosphonates may have direct pro-apoptotic effects on nearby metastatic cancer cells also&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9362432/&lt;/ref&gt;. In halting the mobilisation of calcium and phosphate from bone, bisphosphonate use (together with rehydration) is now standard of care for malignancy-induced hypercalcaemia&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9025784/&lt;/ref&gt;. The analgesic effect of these agents is independent of underlying tumour characteristics, with osteolytic and osteoblastic lesions responding similarly&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9496390&lt;/ref&gt;. Many patients tolerate bisphosphonates without major concern, but common side-effects include flu-like myalgic symptoms, diarrhoea, nausea and reflux. It is exceedingly rare but one must be aware of the risk of developing osteonecrosis of the jaw. These medications undergo renal excretion and as such should be avoided in tumour-induced hypercalcaemia or metastatic bone disease if serum creatinine is greater than 400 μmol/L or 265 μmol/L, respectively. Bisphosphonates are divided into three generations of drug: first-generation (tiludronate, clodronate, etidronate), second-generation (ibandronate, alendronate, paimdronate), and third-generation (zoledronate, risedronate). One of the newest agents, zoledronate is 100-times more effective than second-generation pamidronate&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12558465/&lt;/ref&gt;. Whilst receiving bisphosphonate therapy, patients should take protective vitamin D and calcium supplements.<br /> <br /> ===Denosumab===<br /> Denosumab is a monoclonal antibody which binds to and inhibits the action of the RANK receptor ligand (RANKL). RANK is located on the surface of osteoclast progenitor cells and its activation stimulates their development into mature osteoclasts. Therefore denosumab, administered as a subcutaneous injection of 120 mg every four weeks, can help prevent bone destruction and fracture in patients with bone metastases. The antibody is cleared from the body by the reticuloendothelial system and can therefore be used in patients with poor renal function, in whom bisphosphonate use would be contraindicated&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/21145999/&lt;/ref&gt;. Additionally, data have shown that denosumab use causes greater suppression of osteolytic markers than bisphosphonate use in metastatic patients with breast&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/21060033/&lt;/ref&gt; or prostate&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/21353695/&lt;/ref&gt; cancer. However its effectiveness in comparison to bisphosphonates for patients with lung cancer or multiple myeloma is similar for the prevention of skeletal-related events (SRE), and indeed patients with multiple myeloma showed worse overall survival when treated with denosumab instead of zoledronate&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/21343556/&lt;/ref&gt;. <br /> <br /> ===Analgesia===<br /> -<br /> <br /> ===Chemotherapy===<br /> -<br /> <br /> ===Hormonal therapies===<br /> -<br /> <br /> ===Surgery &amp; IR===<br /> -<br /> <br /> ===Bone cement===<br /> -<br /> <br /> ==Living with bone metastases==<br /> Pain, mobility and safety, survival&lt;references /&gt;</div>

Alex https://oncopaedia.net/w/index.php?title=Articles:Bone_metastases&diff=307 2020-04-17T15:02:27Z

<p>Alex: </p> <hr /> <div>Metastases within bone can cause extreme and debilitating pain. Bone metastases are far more common than primary bone cancer, and many different cancer types can spread to the bone. The most common types of cancer which spread to bone are:<br /> <br /> *Breast<br /> *Prostate<br /> *Lung<br /> *Kidney<br /> *Thyroid<br /> <br /> Cancer can theoretically metastasize to any bone in the body, but in reality there is a predilection for certain sites. The most common sites are the vertebrae, ribs, pelvis, sternum, and the skull.<br /> <br /> ==Classification==<br /> A bone is a rigid organ, but it is far from physiologically static. To maintain bone strength, there is continuous breakdown and simultaneous reformation of bone, two processes which must finely balance for good bone health.<br /> <br /> '''Osteoblastic''' (or '''sclerotic''') metastases are characterised by the deposition of new bone. These are present most commonly in prostate cancer, but also occur in carcinoid, small cell lung cancer, medulloblastoma, and Hodgkin lymphoma. The molecular crosstalk between tumour and bone cells involves osteoblast-generating proteins such as Transforming Growth Factor, Bone Morphogenic Proteins (BMPs), and Endothelin-1&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12085970&lt;/ref&gt;.<br /> <br /> '''Osteolytic''' (or '''lytic''') metastases are characterised by the destruction and breakdown of normal bone. These often occur when breast cancer spreads to bone, which is primarily mediated by osteoclasts (bone cells that breaks down bone tissue) and is not a direct effect of metastasized tumour cells&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8086233/&lt;/ref&gt;. Other tumour types with osteolytic metastases include multiple myeloma, non-small cell lung cancer, thyroid cancer, non-Hodgkin lymphoma, and Langerhans' cell histiocytosis. Osteolytic metastases are more common than osteoblastic metastases.<br /> <br /> '''Mixed''' metastases are characterised by the presence of both osteolytic and osteoblastic lesions together in the same area of bone. These metastases are usually present in metastatic gastrointestinal and squamous cancers, as well as in secondary breast cancer. Although breast cancer gives rise to predominantly lytic lesions, around 15–20% of women have sclerotic or both types of lesions&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11346860/&lt;/ref&gt;.<br /> <br /> ==Diagnosis==<br /> <br /> ===Signs and symptoms===<br /> Bone metastases cause major morbidity, and high clinical suspicion should be kept for any patient with cancer that presents with:<br /> <br /> *Severe pain (poorly localised, worse at night)<br /> *Impaired mobility<br /> *[[Pathological fracture|Bone fracture]]<br /> *Bone marrow aplasia<br /> *Symptoms of (metastatic) [[Metastatic spinal cord compression|spinal cord compression]] (MSCC)<br /> *Symptoms in keeping with [[hypercalcaemia]]:<br /> **Constipation<br /> **Fatigue<br /> **Polyuria/polydipsia<br /> **Acute kidney injury (AKI)<br /> **Cardiac arrhythmia<br /> <br /> ===Bloods===<br /> When a patient with cancer presents with any of the signs or symptoms above, basic screening in the form of simple blood testing must be undertaken and complemented with appropriate imaging tests:<br /> <br /> *Full evaluation of bone turnover and potential hypercalcaemia:<br /> **Serum calcium<br /> **Serum phosphate<br /> **25-Hydroxyvitamin D<br /> **Thyroid-stimulating hormone (TSH)<br /> **Parathyroid hormone (PTH)<br /> **Serum creatinine<br /> **Alkaline phosphatase (ALP)<br /> *Full blood count (myelosuppression, anaemia)<br /> *Serum protein electrophoresis (SPEP; myeloma screen)<br /> *Tumour markers (such as PSA in prostate cancer)<br /> <br /> ===Imaging===<br /> Radiological tests are an essential component of diagnosing bony metastases. One or more imaging modalities may be required to confirm suspected cancerous spread to bone.<br /> <br /> '''Plain radiographs''' (X-ray scans) are quick, cost-effective, and widely-available, and should be the initial diagnostic test of choice when investigating bone pain. They are highly specific but lack sensitivity (44-50%) because early-stage metastatic lesions, particularly those up to 1 cm, may be more difficult to visualise. More than 50% of the trabecular bone must be involved before the lesion will be apparent on film and, due to the poor contrast of trabecular bone, lesions within the medulla are often less evident than those within cortical bone&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9025785/&lt;/ref&gt;. As outlined above, sclerotic metastases will appear more radiopaque than the surrounding bone, whereas lytic metastases will appear more radiolucent.<br /> <br /> '''Bone scintigraphy''' (bone scans) on the other hand is highly sensitive but with low specificity. Data from Technetium-99m ('''&lt;sup&gt;99m&lt;/sup&gt;Tc''') scintigraphy have shown false-negative rates as low as 11 to 38% (good sensitivity), with false-positive rates as high as 40% (poor specificity). It thus provides a non-specific osteoblastic indication of bone status, be it inflammatory, traumatic, or neoplastic in origin. Scintigraphy is still more specific and sensitive than either plain radiography or computed tomography, whilst magnetic resonance imaging is more efficacious in assessing vertebral metastases&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/2028061/&lt;/ref&gt;.<br /> <br /> '''Computed tomography''' (CT scans) has a high sensitivity, ranging from 71 to 100%, for the detection of metastatic bone lesions&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9362427/&lt;/ref&gt;. Because of the excellent soft tissue resolution of the images produced by CT, it is a particularly helpful modality to distinguish lytic and sclerotic metastases and to visualise their precise location(s) for biopsy.<br /> <br /> '''Magnetic resonance imaging''' (MRI scans) is useful in assessing bone marrow infiltration by tumour deposits, and is required (whole spine) for the proper diagnosis of [[Metastatic spinal cord compression|MSCC]]. It has similarly high specificity (73 to 100%) and sensitivity (82 to 100%) in screening for bone metastases&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10964746/&lt;/ref&gt;.<br /> <br /> '''Positron emission tomography''' (PET scans) detects tumour indirectly by measuring metabolic activity in the form of fluorodeoxyglucose ('''&lt;sup&gt;18&lt;/sup&gt;F''') tissue uptake. As such, its use is not limited to visualising only bony metastases, as &lt;sup&gt;18&lt;/sup&gt;F PET will reveal non-bony metastatic spread also&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8638000/&lt;/ref&gt;. The accuracy of PET is highly dependent on the primary tumour site from which imaged metastases originate. As a modality it is superior to scintigraphy in the screening of bony metastases from breast (specificity 94%, sensitivity 95%)&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12073051/&lt;/ref&gt; and lung (specificity 99%, sensitivity 92%)&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10478250/&lt;/ref&gt; malignancies, but has lower sensitivity in detecting the comparatively slower-growing bone metastases of prostate and renal cancers&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10520701/&lt;/ref&gt;. <br /> <br /> ===Biopsy===<br /> Sometimes it is necessary to diagnose metastases histologically, by removing cells or tissue from the bone lesion(s) directly. Usually this is in the form of a needle or surgical biopsy, and may be indicated if a primary cancer is not known. If the patient has a known primary cancer, then often imaging alone will suffice for the diagnosis of metastatic bone disease.<br /> <br /> ==Treatment==<br /> There are a variety of therapeutic interventions available to patients presenting with bone metastases, but consideration must be given to several patient-specific and tumour-dependent parameters, which include&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11738947/&lt;/ref&gt; (but are not limited to):<br /> <br /> *Lesion site(s) (localised or widespread)<br /> *Presence of extraskeletal metastasis<br /> *Tumour type and features (like receptors)<br /> *Prior treatment history (and response)<br /> *Clinical symptoms<br /> *Performance status<br /> <br /> ===Radiotherapy===<br /> Radiation therapy can provide excellent pain relief and is the treatment of choice for localised metastatic bone pain. However, the analgesic mechanisms of therapeutic skeletal irradiation are poorly understood. Onset of pain relief is usually quick, with a majority of patients experiencing benefit within one to two weeks. Patients who have little reduction in pain by six weeks are unlikely to demonstrate significant overall benefit&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/24782453/&lt;/ref&gt;. Other than localised bone pain, additional indications for radiotherapy include [[Metastatic spinal cord compression|MSCC]] and bones at high risk for [[pathological fracture]]&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/15978828/&lt;/ref&gt;. Two of the three main divisions of radiation therapy—the third being (sealed source) [[brachytherapy]]—can be used to treat bone metastases: systemic (unsealed source) [[radionuclide therapy]] and [[external beam radiotherapy]] (EBRT). <br /> <br /> '''Local-field [[External beam radiotherapy|EBRT]]''' is the standard choice of radiation therapy for treating bone metastases, as it focally targets the bone lesion and can achieve rates of substantial pain relief of up to 80 to 90%&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/6178497/&lt;/ref&gt;. Randomised controlled trials (RCTs) from the 1990s have shown that a single fraction of 8 gray (Gy) is as effective as fractionated doses of 20 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9681885&lt;/ref&gt;, 24 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10577695&lt;/ref&gt;, and 30 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10577696&lt;/ref&gt;. <br /> <br /> '''Wide-field''' (or '''hemibody''') '''[[External beam radiotherapy|EBRT]]''' is useful for widespread metastatic skeletal disease, though was more commonly used for multifocal pain when other effective therapies (chemo- and radionuclide) were not available. There are no RCTs comparing analgesic effect with and without wide-field radiotherapy. However, in terms of quasi-randomised and low-quality RCTs, there is data to suggest that use of fractionation is no more effective than single fraction treatment&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8823257&lt;/ref&gt;, that increasing doses beyond 8 Gy does not improve overall pain responses&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11395246&lt;/ref&gt;, and adding wide-field to local-field radiotherapy, whilst significantly halting disease progression (lesion size: P = 0.03; lesion number: P = 0.01), increases grade 3 to 4 haematological toxicity&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/1374061&lt;/ref&gt;. It is possible to classify wide-field treatments into three body regions, each with recommended single-fraction dose limits. Upper treatments (from skull or C1 to L2–L3) should be limited to 6 Gy, whereas mid-body (from L1 to upper third of femur) and lower (from L3–L4 to above knee) treatments should be limited to 8 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/6178497/&lt;/ref&gt;. Any treatments must be delivered with fields shaped to minimise irradiation of organs at risk, such as lung, liver, kidney and bowel. <br /> <br /> '''[[Stereotactic radiotherapy|Stereotactic]] [[External beam radiotherapy|EBRT]]''' is a promising treatment option which delivers higher doses of radiation to tumours in shorter periods in time. When used for extracranial cancers it is interchangeably termed Stereotactic Body Radiation Therapy ('''[[Stereotactic radiotherapy|SBRT]]''') or Stereotactic Ablative Radiotherapy ('''[[Stereotactic radiotherapy|SABR]]'''), the latter of which is appealingly onomatopoeic. When this technique is used for treating malignancy within the brain or some other part of the head, it is termed Stereotactic RadioSurgery ('''[[Stereotactic radiotherapy|SRS]]'''). SBRT/SABR can be used both for primary cancers (lung, liver, prostate, renal) and secondary metastases (bone/spine, lung, liver). There are a number of advantages of stereotactic radiotherapy, the most obvious of which is the potential completion of treatment within a single day, rather than over a number of weeks. The other major benefit is that it obviates the need to irradiate large portions of bone, which lowers the risk of further functional marrow depletion in a patient cohort already at risk of poor marrow reserve. Preserving skeletal marrow function can permit continuous chemotherapy in these patients. The primary limitations of SBRT/SABR are that it is more expensive to deliver than conventional EBRT and that there is a paucity of RCT data comparing its use to standard EBRT management&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/18619121/&lt;/ref&gt;. However, a recent single-centre phase II trial appeared to show that SBRT/SABR provides superior pain relief to conventional multifraction radiotherapy, with no observed difference in adverse events or other aspects of quality of life&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/31021390&lt;/ref&gt;. <br /> <br /> '''[[Radionuclide therapy]]''' (or '''radioisotope therapy''') is the systemic administration of radionuclides (also known as radioisotopes) as unsealed radioactive sources that selectively deliver radiation to tumours or target organs. They are taken up predominantly at sites of bone formation, and are therefore most likely best effective for the palliation of osteoblastic (sclerotic) metastases. Common radionuclides approved for the treatment of painful bone metastases include phosphorus-32 ('''&lt;sup&gt;32&lt;/sup&gt;P'''; ''β''-decay), strontium-89 ('''&lt;sup&gt;89&lt;/sup&gt;Sr'''; ''β''-decay), samarium-153 ('''&lt;sup&gt;153&lt;/sup&gt;Sm'''; ''β''- and ''γ''-decay), and rhenium-186 ('''&lt;sup&gt;186&lt;/sup&gt;Re'''; ''β''- and ''γ''-decay). The added advantage of gamma ray emission during decay is that it permits nuclear imaging monitoring of radionuclide biodistribution during therapy. These radionuclides target bone through various mechanisms. &lt;sup&gt;32&lt;/sup&gt;P passes through inorganic phosphate pathways, whereas &lt;sup&gt;89&lt;/sup&gt;Sr is a calcium mimetic and is taken up as a direct analogue of this earth metal. The final two agents are targeted to bone via chelation to phosphonate compounds: &lt;sup&gt;153&lt;/sup&gt;Sm is paired to ethylenediaminetetramethylenephosphonate (EDTMP) and &lt;sup&gt;186&lt;/sup&gt;Re to 1,1-hydroxyethylidene diphosphonate (HEDP). Common toxicities from treatment include myelosuppression and a transient pain flare, the latter of which usually heralds a favourable response. A more recently developed radionuclide, radium-223 (&lt;sup&gt;'''223'''&lt;/sup&gt;'''Ra'''; ''α''-, ''β''-, and ''γ''-decay) is a calcium mimetic which emits over 95% of decay energy in the form of alpha radiation&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/17062709&lt;/ref&gt;. Owing to their comparatively large size the emitted alpha particles have a more limited depth of penetration into surrounding tissues (around 2–10 cells), thereby producing a more potently localised cytotoxic effect. Despite their symptomatic benefits in refractory, widespread bone metastases, neither &lt;sup&gt;89&lt;/sup&gt;Sr nor &lt;sup&gt;153&lt;/sup&gt;Sm have been shown to improve overall survival in interventional trials; however, &lt;sup&gt;223&lt;/sup&gt;Ra use in metastatic castration-resistant prostate cancer patients in the ALSYMPCA (ALpharadin in SYMptomatic Prostate CAncer) trial was shown to significantly prolong overall survival&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/23863050/&lt;/ref&gt;. <br /> <br /> ===Bisphosphonates===<br /> Analogues of the natural bone demineralisation inhibitor pyrophosphate, bisphosphonates are useful in the treatment of poorly localised bone pain and in previously irradiated bone lesions. They bind with high affinity to exposed bone mineral where they are internalised by osteoclasts, within which they disrupt the processes of bone resorption and can induce apoptosis. Data have shown that bisphosphonates may have direct pro-apoptotic effects on nearby metastatic cancer cells also&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9362432/&lt;/ref&gt;. In halting the mobilisation of calcium and phosphate from bone, bisphosphonate use (together with rehydration) is now standard of care for malignancy-induced hypercalcaemia&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9025784/&lt;/ref&gt;. The analgesic effect of these agents is independent of underlying tumour characteristics, with osteolytic and osteoblastic lesions responding similarly&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9496390&lt;/ref&gt;. Many patients tolerate bisphosphonates without major concern, but common side-effects include flu-like myalgic symptoms, diarrhoea, nausea and reflux. It is exceedingly rare but one must be aware of the risk of developing osteonecrosis of the jaw. These medications undergo renal excretion and as such should be avoided in tumour-induced hypercalcaemia or metastatic bone disease if serum creatinine is greater than 400 μmol/L or 265 μmol/L, respectively. Bisphosphonates are divided into three generations of drug: first-generation (tiludronate, clodronate, etidronate), second-generation (ibandronate, alendronate, paimdronate), and third-generation (zoledronate, risedronate). One of the newest agents, zoledronate is 100-times more effective than second-generation pamidronate&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12558465/&lt;/ref&gt;. Whilst receiving bisphosphonate therapy, patients should take protective vitamin D and calcium supplements.<br /> <br /> ===Denosumab===<br /> Denosumab is a monoclonal antibody which binds to and inhibits the action of the RANK receptor ligand (RANKL). RANK is located on the surface of osteoclast progenitor cells and its activation stimulates their development into mature osteoclasts. Therefore denosumab, administered as a subcutaneous injection of 120 mg every four weeks, can help prevent bone destruction and fracture in patients with bone metastases. The antibody is cleared from the body by the reticuloendothelial system and can therefore be used in patients with poor renal function, in whom bisphosphonate use would be contraindicated&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/21145999/&lt;/ref&gt;. Additionally, data have shown that denosumab use causes greater suppression of osteolytic markers than bisphosphonate use in metastatic patients with breast&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/21060033/&lt;/ref&gt; or prostate&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/21353695/&lt;/ref&gt; cancer. <br /> <br /> ===Analgesia===<br /> -<br /> <br /> ===Chemotherapy===<br /> -<br /> <br /> ===Hormonal therapies===<br /> -<br /> <br /> ===Surgery &amp; IR===<br /> -<br /> <br /> ===Bone cement===<br /> -<br /> <br /> ==Living with bone metastases==<br /> Pain, mobility and safety, survival&lt;references /&gt;</div>

Alex https://oncopaedia.net/w/index.php?title=Articles:Bone_metastases&diff=306 2020-04-17T11:09:42Z

<p>Alex: </p> <hr /> <div>Metastases within bone can cause extreme and debilitating pain. Bone metastases are far more common than primary bone cancer, and many different cancer types can spread to the bone. The most common types of cancer which spread to bone are:<br /> <br /> *Breast<br /> *Prostate<br /> *Lung<br /> *Kidney<br /> *Thyroid<br /> <br /> Cancer can theoretically metastasize to any bone in the body, but in reality there is a predilection for certain sites. The most common sites are the vertebrae, ribs, pelvis, sternum, and the skull.<br /> <br /> ==Classification==<br /> A bone is a rigid organ, but it is far from physiologically static. To maintain bone strength, there is continuous breakdown and simultaneous reformation of bone, two processes which must finely balance for good bone health.<br /> <br /> '''Osteoblastic''' (or '''sclerotic''') metastases are characterised by the deposition of new bone. These are present most commonly in prostate cancer, but also occur in carcinoid, small cell lung cancer, medulloblastoma, and Hodgkin lymphoma. The molecular crosstalk between tumour and bone cells involves osteoblast-generating proteins such as Transforming Growth Factor, Bone Morphogenic Proteins (BMPs), and Endothelin-1&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12085970&lt;/ref&gt;.<br /> <br /> '''Osteolytic''' (or '''lytic''') metastases are characterised by the destruction and breakdown of normal bone. These often occur when breast cancer spreads to bone, which is primarily mediated by osteoclasts (bone cells that breaks down bone tissue) and is not a direct effect of metastasized tumour cells&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8086233/&lt;/ref&gt;. Other tumour types with osteolytic metastases include multiple myeloma, non-small cell lung cancer, thyroid cancer, non-Hodgkin lymphoma, and Langerhans' cell histiocytosis. Osteolytic metastases are more common than osteoblastic metastases.<br /> <br /> '''Mixed''' metastases are characterised by the presence of both osteolytic and osteoblastic lesions together in the same area of bone. These metastases are usually present in metastatic gastrointestinal and squamous cancers, as well as in secondary breast cancer. Although breast cancer gives rise to predominantly lytic lesions, around 15–20% of women have sclerotic or both types of lesions&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11346860/&lt;/ref&gt;.<br /> <br /> ==Diagnosis==<br /> <br /> ===Signs and symptoms===<br /> Bone metastases cause major morbidity, and high clinical suspicion should be kept for any patient with cancer that presents with:<br /> <br /> *Severe pain (poorly localised, worse at night)<br /> *Impaired mobility<br /> *[[Pathological fracture|Bone fracture]]<br /> *Bone marrow aplasia<br /> *Symptoms of (metastatic) [[Metastatic spinal cord compression|spinal cord compression]] (MSCC)<br /> *Symptoms in keeping with [[hypercalcaemia]]:<br /> **Constipation<br /> **Fatigue<br /> **Polyuria/polydipsia<br /> **Acute kidney injury (AKI)<br /> **Cardiac arrhythmia<br /> <br /> ===Bloods===<br /> When a patient with cancer presents with any of the signs or symptoms above, basic screening in the form of simple blood testing must be undertaken and complemented with appropriate imaging tests:<br /> <br /> *Full evaluation of bone turnover and potential hypercalcaemia:<br /> **Serum calcium<br /> **Serum phosphate<br /> **25-Hydroxyvitamin D<br /> **Thyroid-stimulating hormone (TSH)<br /> **Parathyroid hormone (PTH)<br /> **Serum creatinine<br /> **Alkaline phosphatase (ALP)<br /> *Full blood count (myelosuppression, anaemia)<br /> *Serum protein electrophoresis (SPEP; myeloma screen)<br /> *Tumour markers (such as PSA in prostate cancer)<br /> <br /> ===Imaging===<br /> Radiological tests are an essential component of diagnosing bony metastases. One or more imaging modalities may be required to confirm suspected cancerous spread to bone.<br /> <br /> '''Plain radiographs''' (X-ray scans) are quick, cost-effective, and widely-available, and should be the initial diagnostic test of choice when investigating bone pain. They are highly specific but lack sensitivity (44-50%) because early-stage metastatic lesions, particularly those up to 1 cm, may be more difficult to visualise. More than 50% of the trabecular bone must be involved before the lesion will be apparent on film and, due to the poor contrast of trabecular bone, lesions within the medulla are often less evident than those within cortical bone&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9025785/&lt;/ref&gt;. As outlined above, sclerotic metastases will appear more radiopaque than the surrounding bone, whereas lytic metastases will appear more radiolucent.<br /> <br /> '''Bone scintigraphy''' (bone scans) on the other hand is highly sensitive but with low specificity. Data from Technetium-99m ('''&lt;sup&gt;99m&lt;/sup&gt;Tc''') scintigraphy have shown false-negative rates as low as 11 to 38% (good sensitivity), with false-positive rates as high as 40% (poor specificity). It thus provides a non-specific osteoblastic indication of bone status, be it inflammatory, traumatic, or neoplastic in origin. Scintigraphy is still more specific and sensitive than either plain radiography or computed tomography, whilst magnetic resonance imaging is more efficacious in assessing vertebral metastases&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/2028061/&lt;/ref&gt;.<br /> <br /> '''Computed tomography''' (CT scans) has a high sensitivity, ranging from 71 to 100%, for the detection of metastatic bone lesions&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9362427/&lt;/ref&gt;. Because of the excellent soft tissue resolution of the images produced by CT, it is a particularly helpful modality to distinguish lytic and sclerotic metastases and to visualise their precise location(s) for biopsy.<br /> <br /> '''Magnetic resonance imaging''' (MRI scans) is useful in assessing bone marrow infiltration by tumour deposits, and is required (whole spine) for the proper diagnosis of [[Metastatic spinal cord compression|MSCC]]. It has similarly high specificity (73 to 100%) and sensitivity (82 to 100%) in screening for bone metastases&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10964746/&lt;/ref&gt;.<br /> <br /> '''Positron emission tomography''' (PET scans) detects tumour indirectly by measuring metabolic activity in the form of fluorodeoxyglucose ('''&lt;sup&gt;18&lt;/sup&gt;F''') tissue uptake. As such, its use is not limited to visualising only bony metastases, as &lt;sup&gt;18&lt;/sup&gt;F PET will reveal non-bony metastatic spread also&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8638000/&lt;/ref&gt;. The accuracy of PET is highly dependent on the primary tumour site from which imaged metastases originate. As a modality it is superior to scintigraphy in the screening of bony metastases from breast (specificity 94%, sensitivity 95%)&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12073051/&lt;/ref&gt; and lung (specificity 99%, sensitivity 92%)&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10478250/&lt;/ref&gt; malignancies, but has lower sensitivity in detecting the comparatively slower-growing bone metastases of prostate and renal cancers&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10520701/&lt;/ref&gt;. <br /> <br /> ===Biopsy===<br /> Sometimes it is necessary to diagnose metastases histologically, by removing cells or tissue from the bone lesion(s) directly. Usually this is in the form of a needle or surgical biopsy, and may be indicated if a primary cancer is not known. If the patient has a known primary cancer, then often imaging alone will suffice for the diagnosis of metastatic bone disease.<br /> <br /> ==Treatment==<br /> There are a variety of therapeutic interventions available to patients presenting with bone metastases, but consideration must be given to several patient-specific and tumour-dependent parameters, which include&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11738947/&lt;/ref&gt; (but are not limited to):<br /> <br /> *Lesion site(s) (localised or widespread)<br /> *Presence of extraskeletal metastasis<br /> *Tumour type and features (like receptors)<br /> *Prior treatment history (and response)<br /> *Clinical symptoms<br /> *Performance status<br /> <br /> ===Radiotherapy===<br /> Radiation therapy can provide excellent pain relief and is the treatment of choice for localised metastatic bone pain. However, the analgesic mechanisms of therapeutic skeletal irradiation are poorly understood. Onset of pain relief is usually quick, with a majority of patients experiencing benefit within one to two weeks. Patients who have little reduction in pain by six weeks are unlikely to demonstrate significant overall benefit&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/24782453/&lt;/ref&gt;. Other than localised bone pain, additional indications for radiotherapy include [[Metastatic spinal cord compression|MSCC]] and bones at high risk for [[pathological fracture]]&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/15978828/&lt;/ref&gt;. Two of the three main divisions of radiation therapy—the third being (sealed source) [[brachytherapy]]—can be used to treat bone metastases: systemic (unsealed source) [[radionuclide therapy]] and [[external beam radiotherapy]] (EBRT). <br /> <br /> '''Local-field [[External beam radiotherapy|EBRT]]''' is the standard choice of radiation therapy for treating bone metastases, as it focally targets the bone lesion and can achieve rates of substantial pain relief of up to 80 to 90%&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/6178497/&lt;/ref&gt;. Randomised controlled trials (RCTs) from the 1990s have shown that a single fraction of 8 gray (Gy) is as effective as fractionated doses of 20 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9681885&lt;/ref&gt;, 24 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10577695&lt;/ref&gt;, and 30 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10577696&lt;/ref&gt;. <br /> <br /> '''Wide-field''' (or '''hemibody''') '''[[External beam radiotherapy|EBRT]]''' is useful for widespread metastatic skeletal disease, though was more commonly used for multifocal pain when other effective therapies (chemo- and radionuclide) were not available. There are no RCTs comparing analgesic effect with and without wide-field radiotherapy. However, in terms of quasi-randomised and low-quality RCTs, there is data to suggest that use of fractionation is no more effective than single fraction treatment&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8823257&lt;/ref&gt;, that increasing doses beyond 8 Gy does not improve overall pain responses&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11395246&lt;/ref&gt;, and adding wide-field to local-field radiotherapy, whilst significantly halting disease progression (lesion size: P = 0.03; lesion number: P = 0.01), increases grade 3 to 4 haematological toxicity&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/1374061&lt;/ref&gt;. It is possible to classify wide-field treatments into three body regions, each with recommended single-fraction dose limits. Upper treatments (from skull or C1 to L2–L3) should be limited to 6 Gy, whereas mid-body (from L1 to upper third of femur) and lower (from L3–L4 to above knee) treatments should be limited to 8 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/6178497/&lt;/ref&gt;. Any treatments must be delivered with fields shaped to minimise irradiation of organs at risk, such as lung, liver, kidney and bowel. <br /> <br /> '''[[Stereotactic radiotherapy|Stereotactic]] [[External beam radiotherapy|EBRT]]''' is a promising treatment option which delivers higher doses of radiation to tumours in shorter periods in time. When used for extracranial cancers it is interchangeably termed Stereotactic Body Radiation Therapy ('''[[Stereotactic radiotherapy|SBRT]]''') or Stereotactic Ablative Radiotherapy ('''[[Stereotactic radiotherapy|SABR]]'''), the latter of which is appealingly onomatopoeic. When this technique is used for treating malignancy within the brain or some other part of the head, it is termed Stereotactic RadioSurgery ('''[[Stereotactic radiotherapy|SRS]]'''). SBRT/SABR can be used both for primary cancers (lung, liver, prostate, renal) and secondary metastases (bone/spine, lung, liver). There are a number of advantages of stereotactic radiotherapy, the most obvious of which is the potential completion of treatment within a single day, rather than over a number of weeks. The other major benefit is that it obviates the need to irradiate large portions of bone, which lowers the risk of further functional marrow depletion in a patient cohort already at risk of poor marrow reserve. Preserving skeletal marrow function can permit continuous chemotherapy in these patients. The primary limitations of SBRT/SABR are that it is more expensive to deliver than conventional EBRT and that there is a paucity of RCT data comparing its use to standard EBRT management&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/18619121/&lt;/ref&gt;. However, a recent single-centre phase II trial appeared to show that SBRT/SABR provides superior pain relief to conventional multifraction radiotherapy, with no observed difference in adverse events or other aspects of quality of life&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/31021390&lt;/ref&gt;. <br /> <br /> '''[[Radionuclide therapy]]''' (or '''radioisotope therapy''') is the systemic administration of radionuclides (also known as radioisotopes) as unsealed radioactive sources that selectively deliver radiation to tumours or target organs. They are taken up predominantly at sites of bone formation, and are therefore most likely best effective for the palliation of osteoblastic (sclerotic) metastases. Common radionuclides approved for the treatment of painful bone metastases include phosphorus-32 ('''&lt;sup&gt;32&lt;/sup&gt;P'''; ''β''-decay), strontium-89 ('''&lt;sup&gt;89&lt;/sup&gt;Sr'''; ''β''-decay), samarium-153 ('''&lt;sup&gt;153&lt;/sup&gt;Sm'''; ''β''- and ''γ''-decay), and rhenium-186 ('''&lt;sup&gt;186&lt;/sup&gt;Re'''; ''β''- and ''γ''-decay). The added advantage of gamma ray emission during decay is that it permits nuclear imaging monitoring of radionuclide biodistribution during therapy. These radionuclides target bone through various mechanisms. &lt;sup&gt;32&lt;/sup&gt;P passes through inorganic phosphate pathways, whereas &lt;sup&gt;89&lt;/sup&gt;Sr is a calcium mimetic and is taken up as a direct analogue of this earth metal. The final two agents are targeted to bone via chelation to phosphonate compounds: &lt;sup&gt;153&lt;/sup&gt;Sm is paired to ethylenediaminetetramethylenephosphonate (EDTMP) and &lt;sup&gt;186&lt;/sup&gt;Re to 1,1-hydroxyethylidene diphosphonate (HEDP). Common toxicities from treatment include myelosuppression and a transient pain flare, the latter of which usually heralds a favourable response. A more recently developed radionuclide, radium-223 (&lt;sup&gt;'''223'''&lt;/sup&gt;'''Ra'''; ''α''-, ''β''-, and ''γ''-decay) is a calcium mimetic which emits over 95% of decay energy in the form of alpha radiation&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/17062709&lt;/ref&gt;. Owing to their comparatively large size the emitted alpha particles have a more limited depth of penetration into surrounding tissues (around 2–10 cells), thereby producing a more potently localised cytotoxic effect. Despite their symptomatic benefits in refractory, widespread bone metastases, neither &lt;sup&gt;89&lt;/sup&gt;Sr nor &lt;sup&gt;153&lt;/sup&gt;Sm have been shown to improve overall survival in interventional trials; however, &lt;sup&gt;223&lt;/sup&gt;Ra use in metastatic castration-resistant prostate cancer patients in the ALSYMPCA (ALpharadin in SYMptomatic Prostate CAncer) trial was shown to significantly prolong overall survival&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/23863050/&lt;/ref&gt;. <br /> <br /> ===Bisphosphonates===<br /> Analogues of the natural bone demineralisation inhibitor pyrophosphate, bisphosphonates are useful in the treatment of poorly localised bone pain and in previously irradiated bone lesions. They bind with high affinity to exposed bone mineral where they are internalised by osteoclasts, within which they disrupt the processes of bone resorption and can induce apoptosis. Data have shown that bisphosphonates may have direct pro-apoptotic effects on nearby metastatic cancer cells also&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9362432/&lt;/ref&gt;. In halting the mobilisation of calcium and phosphate from bone, bisphosphonate use (together with rehydration) is now standard of care for malignancy-induced hypercalcaemia&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9025784/&lt;/ref&gt;. The analgesic effect of these agents is independent of underlying tumour characteristics, with osteolytic and osteoblastic lesions responding similarly&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9496390&lt;/ref&gt;. Many patients tolerate bisphosphonates without major concern, but common side-effects include flu-like myalgic symptoms, diarrhoea, nausea and reflux. It is exceedingly rare but one must be aware of the risk of developing osteonecrosis of the jaw. These medications undergo renal excretion and as such should be avoided in tumour-induced hypercalcaemia or metastatic bone disease if serum creatinine is greater than 400 μmol/L or 265 μmol/L, respectively. Bisphosphonates are divided into three generations of drug: first-generation (tiludronate, clodronate, etidronate), second-generation (ibandronate, alendronate, paimdronate), and third-generation (zoledronate, risedronate). One of the newest agents, zoledronate is 100-times more effective than second-generation pamidronate&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12558465/&lt;/ref&gt;. Whilst receiving bisphosphonate therapy, patients should take protective vitamin D and calcium supplements.<br /> <br /> ===Denosumab===<br /> -<br /> <br /> ===Analgesia===<br /> -<br /> <br /> ===Chemotherapy===<br /> -<br /> <br /> ===Hormonal therapies===<br /> -<br /> <br /> ===Surgery &amp; IR===<br /> -<br /> <br /> ===Bone cement===<br /> -<br /> <br /> ==Living with bone metastases==<br /> Pain, mobility and safety, survival&lt;references /&gt;</div>

Alex https://oncopaedia.net/w/index.php?title=Articles:Bone_metastases&diff=305 2020-04-17T11:05:53Z

<p>Alex: </p> <hr /> <div>Metastases within bone can cause extreme and debilitating pain. Bone metastases are far more common than primary bone cancer, and many different cancer types can spread to the bone. The most common types of cancer which spread to bone are:<br /> <br /> *Breast<br /> *Prostate<br /> *Lung<br /> *Kidney<br /> *Thyroid<br /> <br /> Cancer can theoretically metastasize to any bone in the body, but in reality there is a predilection for certain sites. The most common sites are the vertebrae, ribs, pelvis, sternum, and the skull.<br /> <br /> ==Classification==<br /> A bone is a rigid organ, but it is far from physiologically static. To maintain bone strength, there is continuous breakdown and simultaneous reformation of bone, two processes which must finely balance for good bone health.<br /> <br /> '''Osteoblastic''' (or '''sclerotic''') metastases are characterised by the deposition of new bone. These are present most commonly in prostate cancer, but also occur in carcinoid, small cell lung cancer, medulloblastoma, and Hodgkin lymphoma. The molecular crosstalk between tumour and bone cells involves osteoblast-generating proteins such as Transforming Growth Factor, Bone Morphogenic Proteins (BMPs), and Endothelin-1&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12085970&lt;/ref&gt;.<br /> <br /> '''Osteolytic''' (or '''lytic''') metastases are characterised by the destruction and breakdown of normal bone. These often occur when breast cancer spreads to bone, which is primarily mediated by osteoclasts (bone cells that breaks down bone tissue) and is not a direct effect of metastasized tumour cells&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8086233/&lt;/ref&gt;. Other tumour types with osteolytic metastases include multiple myeloma, non-small cell lung cancer, thyroid cancer, non-Hodgkin lymphoma, and Langerhans' cell histiocytosis. Osteolytic metastases are more common than osteoblastic metastases.<br /> <br /> '''Mixed''' metastases are characterised by the presence of both osteolytic and osteoblastic lesions together in the same area of bone. These metastases are usually present in metastatic gastrointestinal and squamous cancers, as well as in secondary breast cancer. Although breast cancer gives rise to predominantly lytic lesions, around 15–20% of women have sclerotic or both types of lesions&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11346860/&lt;/ref&gt;.<br /> <br /> ==Diagnosis==<br /> <br /> ===Signs and symptoms===<br /> Bone metastases cause major morbidity, and high clinical suspicion should be kept for any patient with cancer that presents with:<br /> <br /> *Severe pain (poorly localised, worse at night)<br /> *Impaired mobility<br /> *[[Pathological fracture|Bone fracture]]<br /> *Bone marrow aplasia<br /> *Symptoms of (metastatic) [[Metastatic spinal cord compression|spinal cord compression]] (MSCC)<br /> *Symptoms in keeping with [[hypercalcaemia]]:<br /> **Constipation<br /> **Fatigue<br /> **Polyuria/polydipsia<br /> **Acute kidney injury (AKI)<br /> **Cardiac arrhythmia<br /> <br /> ===Bloods===<br /> When a patient with cancer presents with any of the signs or symptoms above, basic screening in the form of simple blood testing must be undertaken and complemented with appropriate imaging tests:<br /> <br /> *Full evaluation of bone turnover and potential hypercalcaemia:<br /> **Serum calcium<br /> **Serum phosphate<br /> **25-Hydroxyvitamin D<br /> **Thyroid-stimulating hormone (TSH)<br /> **Parathyroid hormone (PTH)<br /> **Serum creatinine<br /> **Alkaline phosphatase (ALP)<br /> *Full blood count (myelosuppression, anaemia)<br /> *Serum protein electrophoresis (SPEP; myeloma screen)<br /> *Tumour markers (such as PSA in prostate cancer)<br /> <br /> ===Imaging===<br /> Radiological tests are an essential component of diagnosing bony metastases. One or more imaging modalities may be required to confirm suspected cancerous spread to bone.<br /> <br /> '''Plain radiographs''' (X-ray scans) are quick, cost-effective, and widely-available, and should be the initial diagnostic test of choice when investigating bone pain. They are highly specific but lack sensitivity (44-50%) because early-stage metastatic lesions, particularly those up to 1 cm, may be more difficult to visualise. More than 50% of the trabecular bone must be involved before the lesion will be apparent on film and, due to the poor contrast of trabecular bone, lesions within the medulla are often less evident than those within cortical bone&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9025785/&lt;/ref&gt;. As outlined above, sclerotic metastases will appear more radiopaque than the surrounding bone, whereas lytic metastases will appear more radiolucent.<br /> <br /> '''Bone scintigraphy''' (bone scans) on the other hand is highly sensitive but with low specificity. Data from Technetium-99m ('''&lt;sup&gt;99m&lt;/sup&gt;Tc''') scintigraphy have shown false-negative rates as low as 11 to 38% (good sensitivity), with false-positive rates as high as 40% (poor specificity). It thus provides a non-specific osteoblastic indication of bone status, be it inflammatory, traumatic, or neoplastic in origin. Scintigraphy is still more specific and sensitive than either plain radiography or computed tomography, whilst magnetic resonance imaging is more efficacious in assessing vertebral metastases&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/2028061/&lt;/ref&gt;.<br /> <br /> '''Computed tomography''' (CT scans) has a high sensitivity, ranging from 71 to 100%, for the detection of metastatic bone lesions&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9362427/&lt;/ref&gt;. Because of the excellent soft tissue resolution of the images produced by CT, it is a particularly helpful modality to distinguish lytic and sclerotic metastases and to visualise their precise location(s) for biopsy.<br /> <br /> '''Magnetic resonance imaging''' (MRI scans) is useful in assessing bone marrow infiltration by tumour deposits, and is required (whole spine) for the proper diagnosis of [[Metastatic spinal cord compression|MSCC]]. It has similarly high specificity (73 to 100%) and sensitivity (82 to 100%) in screening for bone metastases&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10964746/&lt;/ref&gt;.<br /> <br /> '''Positron emission tomography''' (PET scans) detects tumour indirectly by measuring metabolic activity in the form of fluorodeoxyglucose ('''&lt;sup&gt;18&lt;/sup&gt;F''') tissue uptake. As such, its use is not limited to visualising only bony metastases, as &lt;sup&gt;18&lt;/sup&gt;F PET will reveal non-bony metastatic spread also&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8638000/&lt;/ref&gt;. The accuracy of PET is highly dependent on the primary tumour site from which imaged metastases originate. As a modality it is superior to scintigraphy in the screening of bony metastases from breast (specificity 94%, sensitivity 95%)&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12073051/&lt;/ref&gt; and lung (specificity 99%, sensitivity 92%)&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10478250/&lt;/ref&gt; malignancies, but has lower sensitivity in detecting the comparatively slower-growing bone metastases of prostate and renal cancers&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10520701/&lt;/ref&gt;. <br /> <br /> ===Biopsy===<br /> Sometimes it is necessary to diagnose metastases histologically, by removing cells or tissue from the bone lesion(s) directly. Usually this is in the form of a needle or surgical biopsy, and may be indicated if a primary cancer is not known. If the patient has a known primary cancer, then often imaging alone will suffice for the diagnosis of metastatic bone disease.<br /> <br /> ==Treatment==<br /> There are a variety of therapeutic interventions available to patients presenting with bone metastases, but consideration must be given to several patient-specific and tumour-dependent parameters, which include&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11738947/&lt;/ref&gt; (but are not limited to):<br /> <br /> *Lesion site(s) (localised or widespread)<br /> *Presence of extraskeletal metastasis<br /> *Tumour type and features (like receptors)<br /> *Prior treatment history (and response)<br /> *Clinical symptoms<br /> *Performance status<br /> <br /> ===Radiotherapy===<br /> Radiation therapy can provide excellent pain relief and is the treatment of choice for localised metastatic bone pain. However, the analgesic mechanisms of therapeutic skeletal irradiation are poorly understood. Onset of pain relief is usually quick, with a majority of patients experiencing benefit within one to two weeks. Patients who have little reduction in pain by six weeks are unlikely to demonstrate significant overall benefit&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/24782453/&lt;/ref&gt;. Other than localised bone pain, additional indications for radiotherapy include [[Metastatic spinal cord compression|MSCC]] and bones at high risk for [[pathological fracture]]&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/15978828/&lt;/ref&gt;. Two of the three main divisions of radiation therapy—the third being (sealed source) [[brachytherapy]]—can be used to treat bone metastases: systemic (unsealed source) [[radionuclide therapy]] and [[external beam radiotherapy]] (EBRT). <br /> <br /> '''Local-field [[External beam radiotherapy|EBRT]]''' is the standard choice of radiation therapy for treating bone metastases, as it focally targets the bone lesion and can achieve rates of substantial pain relief of up to 80 to 90%&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/6178497/&lt;/ref&gt;. Randomised controlled trials (RCTs) from the 1990s have shown that a single fraction of 8 gray (Gy) is as effective as fractionated doses of 20 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9681885&lt;/ref&gt;, 24 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10577695&lt;/ref&gt;, and 30 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10577696&lt;/ref&gt;. <br /> <br /> '''Wide-field''' (or '''hemibody''') '''[[External beam radiotherapy|EBRT]]''' is useful for widespread metastatic skeletal disease, though was more commonly used for multifocal pain when other effective therapies (chemo- and radionuclide) were not available. There are no RCTs comparing analgesic effect with and without wide-field radiotherapy. However, in terms of quasi-randomised and low-quality RCTs, there is data to suggest that use of fractionation is no more effective than single fraction treatment&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8823257&lt;/ref&gt;, that increasing doses beyond 8 Gy does not improve overall pain responses&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11395246&lt;/ref&gt;, and adding wide-field to local-field radiotherapy, whilst significantly halting disease progression (lesion size: P = 0.03; lesion number: P = 0.01), increases grade 3 to 4 haematological toxicity&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/1374061&lt;/ref&gt;. It is possible to classify wide-field treatments into three body regions, each with recommended single-fraction dose limits. Upper treatments (from skull or C1 to L2–L3) should be limited to 6 Gy, whereas mid-body (from L1 to upper third of femur) and lower (from L3–L4 to above knee) treatments should be limited to 8 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/6178497/&lt;/ref&gt;. Any treatments must be delivered with fields shaped to minimise irradiation of organs at risk, such as lung, liver, kidney and bowel. <br /> <br /> '''[[Stereotactic radiotherapy|Stereotactic]] [[External beam radiotherapy|EBRT]]''' is a promising treatment option which delivers higher doses of radiation to tumours in shorter periods in time. When used for extracranial cancers it is interchangeably termed Stereotactic Body Radiation Therapy ('''[[Stereotactic radiotherapy|SBRT]]''') or Stereotactic Ablative Radiotherapy ('''[[Stereotactic radiotherapy|SABR]]'''), the latter of which is appealingly onomatopoeic. When this technique is used for treating malignancy within the brain or some other part of the head, it is termed Stereotactic RadioSurgery ('''[[Stereotactic radiotherapy|SRS]]'''). SBRT/SABR can be used both for primary cancers (lung, liver, prostate, renal) and secondary metastases (bone/spine, lung, liver). There are a number of advantages of stereotactic radiotherapy, the most obvious of which is the potential completion of treatment within a single day, rather than over a number of weeks. The other major benefit is that it obviates the need to irradiate large portions of bone, which lowers the risk of further functional marrow depletion in a patient cohort already at risk of poor marrow reserve. Preserving skeletal marrow function can permit continuous chemotherapy in these patients. The primary limitations of SBRT/SABR are that it is more expensive to deliver than conventional EBRT and that there is a paucity of RCT data comparing its use to standard EBRT management&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/18619121/&lt;/ref&gt;. However, a recent single-centre phase II trial appeared to show that SBRT/SABR provides superior pain relief to conventional multifraction radiotherapy, with no observed difference in adverse events or other aspects of quality of life&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/31021390&lt;/ref&gt;. <br /> <br /> '''[[Radionuclide therapy]]''' (or '''radioisotope therapy''') is the systemic administration of radionuclides (also known as radioisotopes) as unsealed radioactive sources that selectively deliver radiation to tumours or target organs. They are taken up predominantly at sites of bone formation, and are therefore most likely best effective for the palliation of osteoblastic (sclerotic) metastases. Common radionuclides approved for the treatment of painful bone metastases include phosphorus-32 ('''&lt;sup&gt;32&lt;/sup&gt;P'''; ''β''-decay), strontium-89 ('''&lt;sup&gt;89&lt;/sup&gt;Sr'''; ''β''-decay), samarium-153 ('''&lt;sup&gt;153&lt;/sup&gt;Sm'''; ''β''- and ''γ''-decay), and rhenium-186 ('''&lt;sup&gt;186&lt;/sup&gt;Re'''; ''β''- and ''γ''-decay). The added advantage of gamma ray emission during decay is that it permits nuclear imaging monitoring of radionuclide biodistribution during therapy. These radionuclides target bone through various mechanisms. &lt;sup&gt;32&lt;/sup&gt;P passes through inorganic phosphate pathways, whereas &lt;sup&gt;89&lt;/sup&gt;Sr is a calcium mimetic and is taken up as a direct analogue of this earth metal. The final two agents are targeted to bone via chelation to phosphonate compounds: &lt;sup&gt;153&lt;/sup&gt;Sm is paired to ethylenediaminetetramethylenephosphonate (EDTMP) and &lt;sup&gt;186&lt;/sup&gt;Re to 1,1-hydroxyethylidene diphosphonate (HEDP). Common toxicities from treatment include myelosuppression and a transient pain flare, the latter of which usually heralds a favourable response. A more recently developed radionuclide, radium-223 (&lt;sup&gt;'''223'''&lt;/sup&gt;'''Ra'''; ''α''-, ''β''-, and ''γ''-decay) is a calcium mimetic which emits over 95% of decay energy in the form of alpha radiation&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/17062709&lt;/ref&gt;. Owing to their comparatively large size the emitted alpha particles have a more limited depth of penetration into surrounding tissues (around 2–10 cells), thereby producing a more potently localised cytotoxic effect. Despite their symptomatic benefits in refractory, widespread bone metastases, neither &lt;sup&gt;89&lt;/sup&gt;Sr nor &lt;sup&gt;153&lt;/sup&gt;Sm have been shown to improve overall survival in interventional trials; however, &lt;sup&gt;223&lt;/sup&gt;Ra use in metastatic castration-resistant prostate cancer patients in the ALSYMPCA (ALpharadin in SYMptomatic Prostate CAncer) trial was shown to significantly prolong overall survival&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/23863050/&lt;/ref&gt;. <br /> <br /> ===Bisphosphonates===<br /> Analogues of the natural bone demineralisation inhibitor pyrophosphate, bisphosphonates are useful in the treatment of poorly localised bone pain and in previously irradiated bone lesions. They bind with high affinity to exposed bone mineral where they are internalised by osteoclasts, within which they disrupt the processes of bone resorption and can induce apoptosis. Data have shown that bisphosphonates may have direct pro-apoptotic effects on nearby metastatic cancer cells also&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9362432/&lt;/ref&gt;. In halting the mobilisation of calcium and phosphate from bone, bisphosphonate use (together with rehydration) is now standard of care for malignancy-induced hypercalcaemia&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9025784/&lt;/ref&gt;. The analgesic effect of these agents is independent of underlying tumour characteristics, with osteolytic and osteoblastic lesions responding similarly&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9496390&lt;/ref&gt;. Many patients tolerate bisphosphonates without major concern, but common side-effects include flu-like myalgic symptoms, diarrhoea, nausea and reflux. It is exceedingly rare but one must be aware of the risk of developing osteonecrosis of the jaw. These medications undergo renal excretion and as such should be avoided in tumour-induced hypercalcaemia or metastatic bone disease if serum creatinine is greater than 400 μmol/L or 265 μmol/L, respectively. Bisphosphonates are divided into three generations of drug: first-generation (tiludronate, clodronate, etidronate), second-generation (ibandronate, alendronate, paimdronate), and third-generation (zoledronate, risedronate). One of the newest agents, zoledronate is 100-times more effective than second-generation pamidronate&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12558465/&lt;/ref&gt;. Whilst receiving bisphosphonate therapy, patients should take vitamin D and calcium supplements.<br /> <br /> ===Denosumab===<br /> -<br /> <br /> ===Analgesia===<br /> -<br /> <br /> ===Chemotherapy===<br /> -<br /> <br /> ===Hormonal therapies===<br /> -<br /> <br /> ===Surgery &amp; IR===<br /> -<br /> <br /> ===Bone cement===<br /> -<br /> <br /> ==Living with bone metastases==<br /> Pain, mobility and safety, survival&lt;references /&gt;</div>

Alex https://oncopaedia.net/w/index.php?title=Articles:Bone_metastases&diff=304 2020-04-17T11:01:28Z

<p>Alex: </p> <hr /> <div>Metastases within bone can cause extreme and debilitating pain. Bone metastases are far more common than primary bone cancer, and many different cancer types can spread to the bone. The most common types of cancer which spread to bone are:<br /> <br /> *Breast<br /> *Prostate<br /> *Lung<br /> *Kidney<br /> *Thyroid<br /> <br /> Cancer can theoretically metastasize to any bone in the body, but in reality there is a predilection for certain sites. The most common sites are the vertebrae, ribs, pelvis, sternum, and the skull.<br /> <br /> ==Classification==<br /> A bone is a rigid organ, but it is far from physiologically static. To maintain bone strength, there is continuous breakdown and simultaneous reformation of bone, two processes which must finely balance for good bone health.<br /> <br /> '''Osteoblastic''' (or '''sclerotic''') metastases are characterised by the deposition of new bone. These are present most commonly in prostate cancer, but also occur in carcinoid, small cell lung cancer, medulloblastoma, and Hodgkin lymphoma. The molecular crosstalk between tumour and bone cells involves osteoblast-generating proteins such as Transforming Growth Factor, Bone Morphogenic Proteins (BMPs), and Endothelin-1&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12085970&lt;/ref&gt;.<br /> <br /> '''Osteolytic''' (or '''lytic''') metastases are characterised by the destruction and breakdown of normal bone. These often occur when breast cancer spreads to bone, which is primarily mediated by osteoclasts (bone cells that breaks down bone tissue) and is not a direct effect of metastasized tumour cells&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8086233/&lt;/ref&gt;. Other tumour types with osteolytic metastases include multiple myeloma, non-small cell lung cancer, thyroid cancer, non-Hodgkin lymphoma, and Langerhans' cell histiocytosis. Osteolytic metastases are more common than osteoblastic metastases.<br /> <br /> '''Mixed''' metastases are characterised by the presence of both osteolytic and osteoblastic lesions together in the same area of bone. These metastases are usually present in metastatic gastrointestinal and squamous cancers, as well as in secondary breast cancer. Although breast cancer gives rise to predominantly lytic lesions, around 15–20% of women have sclerotic or both types of lesions&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11346860/&lt;/ref&gt;.<br /> <br /> ==Diagnosis==<br /> <br /> ===Signs and symptoms===<br /> Bone metastases cause major morbidity, and high clinical suspicion should be kept for any patient with cancer that presents with:<br /> <br /> *Severe pain (poorly localised, worse at night)<br /> *Impaired mobility<br /> *[[Pathological fracture|Bone fracture]]<br /> *Bone marrow aplasia<br /> *Symptoms of (metastatic) [[Metastatic spinal cord compression|spinal cord compression]] (MSCC)<br /> *Symptoms in keeping with [[hypercalcaemia]]:<br /> **Constipation<br /> **Fatigue<br /> **Polyuria/polydipsia<br /> **Acute kidney injury (AKI)<br /> **Cardiac arrhythmia<br /> <br /> ===Bloods===<br /> When a patient with cancer presents with any of the signs or symptoms above, basic screening in the form of simple blood testing must be undertaken and complemented with appropriate imaging tests:<br /> <br /> *Full evaluation of bone turnover and potential hypercalcaemia:<br /> **Serum calcium<br /> **Serum phosphate<br /> **25-Hydroxyvitamin D<br /> **Thyroid-stimulating hormone (TSH)<br /> **Parathyroid hormone (PTH)<br /> **Serum creatinine<br /> **Alkaline phosphatase (ALP)<br /> *Full blood count (myelosuppression, anaemia)<br /> *Serum protein electrophoresis (SPEP; myeloma screen)<br /> *Tumour markers (such as PSA in prostate cancer)<br /> <br /> ===Imaging===<br /> Radiological tests are an essential component of diagnosing bony metastases. One or more imaging modalities may be required to confirm suspected cancerous spread to bone.<br /> <br /> '''Plain radiographs''' (X-ray scans) are quick, cost-effective, and widely-available, and should be the initial diagnostic test of choice when investigating bone pain. They are highly specific but lack sensitivity (44-50%) because early-stage metastatic lesions, particularly those up to 1 cm, may be more difficult to visualise. More than 50% of the trabecular bone must be involved before the lesion will be apparent on film and, due to the poor contrast of trabecular bone, lesions within the medulla are often less evident than those within cortical bone&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9025785/&lt;/ref&gt;. As outlined above, sclerotic metastases will appear more radiopaque than the surrounding bone, whereas lytic metastases will appear more radiolucent.<br /> <br /> '''Bone scintigraphy''' (bone scans) on the other hand is highly sensitive but with low specificity. Data from Technetium-99m ('''&lt;sup&gt;99m&lt;/sup&gt;Tc''') scintigraphy have shown false-negative rates as low as 11 to 38% (good sensitivity), with false-positive rates as high as 40% (poor specificity). It thus provides a non-specific osteoblastic indication of bone status, be it inflammatory, traumatic, or neoplastic in origin. Scintigraphy is still more specific and sensitive than either plain radiography or computed tomography, whilst magnetic resonance imaging is more efficacious in assessing vertebral metastases&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/2028061/&lt;/ref&gt;.<br /> <br /> '''Computed tomography''' (CT scans) has a high sensitivity, ranging from 71 to 100%, for the detection of metastatic bone lesions&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9362427/&lt;/ref&gt;. Because of the excellent soft tissue resolution of the images produced by CT, it is a particularly helpful modality to distinguish lytic and sclerotic metastases and to visualise their precise location(s) for biopsy.<br /> <br /> '''Magnetic resonance imaging''' (MRI scans) is useful in assessing bone marrow infiltration by tumour deposits, and is required (whole spine) for the proper diagnosis of [[Metastatic spinal cord compression|MSCC]]. It has similarly high specificity (73 to 100%) and sensitivity (82 to 100%) in screening for bone metastases&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10964746/&lt;/ref&gt;.<br /> <br /> '''Positron emission tomography''' (PET scans) detects tumour indirectly by measuring metabolic activity in the form of fluorodeoxyglucose ('''&lt;sup&gt;18&lt;/sup&gt;F''') tissue uptake. As such, its use is not limited to visualising only bony metastases, as &lt;sup&gt;18&lt;/sup&gt;F PET will reveal non-bony metastatic spread also&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8638000/&lt;/ref&gt;. The accuracy of PET is highly dependent on the primary tumour site from which imaged metastases originate. As a modality it is superior to scintigraphy in the screening of bony metastases from breast (specificity 94%, sensitivity 95%)&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12073051/&lt;/ref&gt; and lung (specificity 99%, sensitivity 92%)&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10478250/&lt;/ref&gt; malignancies, but has lower sensitivity in detecting the comparatively slower-growing bone metastases of prostate and renal cancers&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10520701/&lt;/ref&gt;. <br /> <br /> ===Biopsy===<br /> Sometimes it is necessary to diagnose metastases histologically, by removing cells or tissue from the bone lesion(s) directly. Usually this is in the form of a needle or surgical biopsy, and may be indicated if a primary cancer is not known. If the patient has a known primary cancer, then often imaging alone will suffice for the diagnosis of metastatic bone disease.<br /> <br /> ==Treatment==<br /> There are a variety of therapeutic interventions available to patients presenting with bone metastases, but consideration must be given to several patient-specific and tumour-dependent parameters, which include&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11738947/&lt;/ref&gt; (but are not limited to):<br /> <br /> *Lesion site(s) (localised or widespread)<br /> *Presence of extraskeletal metastasis<br /> *Tumour type and features (like receptors)<br /> *Prior treatment history (and response)<br /> *Clinical symptoms<br /> *Performance status<br /> <br /> ===Radiotherapy===<br /> Radiation therapy can provide excellent pain relief and is the treatment of choice for localised metastatic bone pain. However, the analgesic mechanisms of therapeutic skeletal irradiation are poorly understood. Onset of pain relief is usually quick, with a majority of patients experiencing benefit within one to two weeks. Patients who have little reduction in pain by six weeks are unlikely to demonstrate significant overall benefit&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/24782453/&lt;/ref&gt;. Other than localised bone pain, additional indications for radiotherapy include [[Metastatic spinal cord compression|MSCC]] and bones at high risk for [[pathological fracture]]&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/15978828/&lt;/ref&gt;. Two of the three main divisions of radiation therapy—the third being (sealed source) [[brachytherapy]]—can be used to treat bone metastases: systemic (unsealed source) [[radionuclide therapy]] and [[external beam radiotherapy]] (EBRT). <br /> <br /> '''Local-field [[External beam radiotherapy|EBRT]]''' is the standard choice of radiation therapy for treating bone metastases, as it focally targets the bone lesion and can achieve rates of substantial pain relief of up to 80 to 90%&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/6178497/&lt;/ref&gt;. Randomised controlled trials (RCTs) from the 1990s have shown that a single fraction of 8 gray (Gy) is as effective as fractionated doses of 20 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9681885&lt;/ref&gt;, 24 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10577695&lt;/ref&gt;, and 30 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10577696&lt;/ref&gt;. <br /> <br /> '''Wide-field''' (or '''hemibody''') '''[[External beam radiotherapy|EBRT]]''' is useful for widespread metastatic skeletal disease, though was more commonly used for multifocal pain when other effective therapies (chemo- and radionuclide) were not available. There are no RCTs comparing analgesic effect with and without wide-field radiotherapy. However, in terms of quasi-randomised and low-quality RCTs, there is data to suggest that use of fractionation is no more effective than single fraction treatment&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8823257&lt;/ref&gt;, that increasing doses beyond 8 Gy does not improve overall pain responses&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11395246&lt;/ref&gt;, and adding wide-field to local-field radiotherapy, whilst significantly halting disease progression (lesion size: P = 0.03; lesion number: P = 0.01), increases grade 3 to 4 haematological toxicity&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/1374061&lt;/ref&gt;. It is possible to classify wide-field treatments into three body regions, each with recommended single-fraction dose limits. Upper treatments (from skull or C1 to L2–L3) should be limited to 6 Gy, whereas mid-body (from L1 to upper third of femur) and lower (from L3–L4 to above knee) treatments should be limited to 8 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/6178497/&lt;/ref&gt;. Any treatments must be delivered with fields shaped to minimise irradiation of organs at risk, such as lung, liver, kidney and bowel. <br /> <br /> '''[[Stereotactic radiotherapy|Stereotactic]] [[External beam radiotherapy|EBRT]]''' is a promising treatment option which delivers higher doses of radiation to tumours in shorter periods in time. When used for extracranial cancers it is interchangeably termed Stereotactic Body Radiation Therapy ('''[[Stereotactic radiotherapy|SBRT]]''') or Stereotactic Ablative Radiotherapy ('''[[Stereotactic radiotherapy|SABR]]'''), the latter of which is appealingly onomatopoeic. When this technique is used for treating malignancy within the brain or some other part of the head, it is termed Stereotactic RadioSurgery ('''[[Stereotactic radiotherapy|SRS]]'''). SBRT/SABR can be used both for primary cancers (lung, liver, prostate, renal) and secondary metastases (bone/spine, lung, liver). There are a number of advantages of stereotactic radiotherapy, the most obvious of which is the potential completion of treatment within a single day, rather than over a number of weeks. The other major benefit is that it obviates the need to irradiate large portions of bone, which lowers the risk of further functional marrow depletion in a patient cohort already at risk of poor marrow reserve. Preserving skeletal marrow function can permit continuous chemotherapy in these patients. The primary limitations of SBRT/SABR are that it is more expensive to deliver than conventional EBRT and that there is a paucity of RCT data comparing its use to standard EBRT management&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/18619121/&lt;/ref&gt;. However, a recent single-centre phase II trial appeared to show that SBRT/SABR provides superior pain relief to conventional multifraction radiotherapy, with no observed difference in adverse events or other aspects of quality of life&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/31021390&lt;/ref&gt;. <br /> <br /> '''[[Radionuclide therapy]]''' (or '''radioisotope therapy''') is the systemic administration of radionuclides (also known as radioisotopes) as unsealed radioactive sources that selectively deliver radiation to tumours or target organs. They are taken up predominantly at sites of bone formation, and are therefore most likely best effective for the palliation of osteoblastic (sclerotic) metastases. Common radionuclides approved for the treatment of painful bone metastases include phosphorus-32 ('''&lt;sup&gt;32&lt;/sup&gt;P'''; ''β''-decay), strontium-89 ('''&lt;sup&gt;89&lt;/sup&gt;Sr'''; ''β''-decay), samarium-153 ('''&lt;sup&gt;153&lt;/sup&gt;Sm'''; ''β''- and ''γ''-decay), and rhenium-186 ('''&lt;sup&gt;186&lt;/sup&gt;Re'''; ''β''- and ''γ''-decay). The added advantage of gamma ray emission during decay is that it permits nuclear imaging monitoring of radionuclide biodistribution during therapy. These radionuclides target bone through various mechanisms. &lt;sup&gt;32&lt;/sup&gt;P passes through inorganic phosphate pathways, whereas &lt;sup&gt;89&lt;/sup&gt;Sr is a calcium mimetic and is taken up as a direct analogue of this earth metal. The final two agents are targeted to bone via chelation to phosphonate compounds: &lt;sup&gt;153&lt;/sup&gt;Sm is paired to ethylenediaminetetramethylenephosphonate (EDTMP) and &lt;sup&gt;186&lt;/sup&gt;Re to 1,1-hydroxyethylidene diphosphonate (HEDP). Common toxicities from treatment include myelosuppression and a transient pain flare, the latter of which usually heralds a favourable response. A more recently developed radionuclide, radium-223 (&lt;sup&gt;'''223'''&lt;/sup&gt;'''Ra'''; ''α''-, ''β''-, and ''γ''-decay) is a calcium mimetic which emits over 95% of decay energy in the form of alpha radiation&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/17062709&lt;/ref&gt;. Owing to their comparatively large size the emitted alpha particles have a more limited depth of penetration into surrounding tissues (around 2–10 cells), thereby producing a more potently localised cytotoxic effect. Despite their symptomatic benefits in refractory, widespread bone metastases, neither &lt;sup&gt;89&lt;/sup&gt;Sr nor &lt;sup&gt;153&lt;/sup&gt;Sm have been shown to improve overall survival in interventional trials; however, &lt;sup&gt;223&lt;/sup&gt;Ra use in metastatic castration-resistant prostate cancer patients in the ALSYMPCA (ALpharadin in SYMptomatic Prostate CAncer) trial was shown to significantly prolong overall survival&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/23863050/&lt;/ref&gt;. <br /> <br /> ===Bisphosphonates===<br /> Analogues of the natural bone demineralisation inhibitor pyrophosphate, bisphosphonates are useful in the treatment of poorly localised bone pain and in previously irradiated bone lesions. They bind with high affinity to exposed bone mineral where they are internalised by osteoclasts, within which they disrupt the processes of bone resorption and can induce apoptosis. Data have shown that bisphosphonates may have direct pro-apoptotic effects on nearby metastatic cancer cells also&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9362432/&lt;/ref&gt;. In halting the mobilisation of calcium and phosphate from bone, bisphosphonate use (together with rehydration) is now standard of care for malignancy-induced hypercalcaemia&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9025784/&lt;/ref&gt;. The analgesic effect of these agents is independent of underlying tumour characteristics, with osteolytic and osteoblastic lesions responding similarly&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9496390&lt;/ref&gt;. Many patients tolerate bisphosphonates without major concern, but common side-effects include flu-like myalgic symptoms, diarrhoea, nausea and reflux. It is exceedingly rare but one must be aware of the risk of developing osteonecrosis of the jaw. These medications undergo renal excretion and as such should be avoided in tumour-induced hypercalcaemia or metastatic bone disease if serum creatinine is greater than 400 μmol/L or 265 μmol/L, respectively. Bisphosphonates are divided into three generations of drug: first-generation (tiludronate, clodronate, etidronate), second-generation (ibandronate, alendronate, paimdronate), and third-generation (zoledronate, risedronate). One of the newest bisphosphonate agents, zoledronate is 100-times more effective than second-generation pamidronate&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12558465/&lt;/ref&gt;.<br /> <br /> ===Denosumab===<br /> -<br /> <br /> ===Analgesia===<br /> -<br /> <br /> ===Chemotherapy===<br /> -<br /> <br /> ===Hormonal therapies===<br /> -<br /> <br /> ===Surgery &amp; IR===<br /> -<br /> <br /> ===Bone cement===<br /> -<br /> <br /> ==Living with bone metastases==<br /> Pain, mobility and safety, survival&lt;references /&gt;</div>

Alex https://oncopaedia.net/w/index.php?title=Articles:Bone_metastases&diff=303 2020-04-16T17:30:48Z

<p>Alex: </p> <hr /> <div>Metastases within bone can cause extreme and debilitating pain. Bone metastases are far more common than primary bone cancer, and many different cancer types can spread to the bone. The most common types of cancer which spread to bone are:<br /> <br /> *Breast<br /> *Prostate<br /> *Lung<br /> *Kidney<br /> *Thyroid<br /> <br /> Cancer can theoretically metastasize to any bone in the body, but in reality there is a predilection for certain sites. The most common sites are the vertebrae, ribs, pelvis, sternum, and the skull.<br /> <br /> ==Classification==<br /> A bone is a rigid organ, but it is far from physiologically static. To maintain bone strength, there is continuous breakdown and simultaneous reformation of bone, two processes which must finely balance for good bone health.<br /> <br /> '''Osteoblastic''' (or '''sclerotic''') metastases are characterised by the deposition of new bone. These are present most commonly in prostate cancer, but also occur in carcinoid, small cell lung cancer, medulloblastoma, and Hodgkin lymphoma. The molecular crosstalk between tumour and bone cells involves osteoblast-generating proteins such as Transforming Growth Factor, Bone Morphogenic Proteins (BMPs), and Endothelin-1&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12085970&lt;/ref&gt;.<br /> <br /> '''Osteolytic''' (or '''lytic''') metastases are characterised by the destruction and breakdown of normal bone. These often occur when breast cancer spreads to bone, which is primarily mediated by osteoclasts (bone cells that breaks down bone tissue) and is not a direct effect of metastasized tumour cells&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8086233/&lt;/ref&gt;. Other tumour types with osteolytic metastases include multiple myeloma, non-small cell lung cancer, thyroid cancer, non-Hodgkin lymphoma, and Langerhans' cell histiocytosis. Osteolytic metastases are more common than osteoblastic metastases.<br /> <br /> '''Mixed''' metastases are characterised by the presence of both osteolytic and osteoblastic lesions together in the same area of bone. These metastases are usually present in metastatic gastrointestinal and squamous cancers, as well as in secondary breast cancer. Although breast cancer gives rise to predominantly lytic lesions, around 15–20% of women have sclerotic or both types of lesions&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11346860/&lt;/ref&gt;.<br /> <br /> ==Diagnosis==<br /> <br /> ===Signs and symptoms===<br /> Bone metastases cause major morbidity, and high clinical suspicion should be kept for any patient with cancer that presents with:<br /> <br /> *Severe pain (poorly localised, worse at night)<br /> *Impaired mobility<br /> *[[Pathological fracture|Bone fracture]]<br /> *Bone marrow aplasia<br /> *Symptoms of (metastatic) [[Metastatic spinal cord compression|spinal cord compression]] (MSCC)<br /> *Symptoms in keeping with [[hypercalcaemia]]:<br /> **Constipation<br /> **Fatigue<br /> **Polyuria/polydipsia<br /> **Acute kidney injury (AKI)<br /> **Cardiac arrhythmia<br /> <br /> ===Bloods===<br /> When a patient with cancer presents with any of the signs or symptoms above, basic screening in the form of simple blood testing must be undertaken and complemented with appropriate imaging tests:<br /> <br /> *Full evaluation of bone turnover and potential hypercalcaemia:<br /> **Serum calcium<br /> **Serum phosphate<br /> **25-Hydroxyvitamin D<br /> **Thyroid-stimulating hormone (TSH)<br /> **Parathyroid hormone (PTH)<br /> **Serum creatinine<br /> **Alkaline phosphatase (ALP)<br /> *Full blood count (myelosuppression, anaemia)<br /> *Serum protein electrophoresis (SPEP; myeloma screen)<br /> *Tumour markers (such as PSA in prostate cancer)<br /> <br /> ===Imaging===<br /> Radiological tests are an essential component of diagnosing bony metastases. One or more imaging modalities may be required to confirm suspected cancerous spread to bone.<br /> <br /> '''Plain radiographs''' (X-ray scans) are quick, cost-effective, and widely-available, and should be the initial diagnostic test of choice when investigating bone pain. They are highly specific but lack sensitivity (44-50%) because early-stage metastatic lesions, particularly those up to 1 cm, may be more difficult to visualise. More than 50% of the trabecular bone must be involved before the lesion will be apparent on film and, due to the poor contrast of trabecular bone, lesions within the medulla are often less evident than those within cortical bone&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9025785/&lt;/ref&gt;. As outlined above, sclerotic metastases will appear more radiopaque than the surrounding bone, whereas lytic metastases will appear more radiolucent.<br /> <br /> '''Bone scintigraphy''' (bone scans) on the other hand is highly sensitive but with low specificity. Data from Technetium-99m ('''&lt;sup&gt;99m&lt;/sup&gt;Tc''') scintigraphy have shown false-negative rates as low as 11 to 38% (good sensitivity), with false-positive rates as high as 40% (poor specificity). It thus provides a non-specific osteoblastic indication of bone status, be it inflammatory, traumatic, or neoplastic in origin. Scintigraphy is still more specific and sensitive than either plain radiography or computed tomography, whilst magnetic resonance imaging is more efficacious in assessing vertebral metastases&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/2028061/&lt;/ref&gt;.<br /> <br /> '''Computed tomography''' (CT scans) has a high sensitivity, ranging from 71 to 100%, for the detection of metastatic bone lesions&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9362427/&lt;/ref&gt;. Because of the excellent soft tissue resolution of the images produced by CT, it is a particularly helpful modality to distinguish lytic and sclerotic metastases and to visualise their precise location(s) for biopsy.<br /> <br /> '''Magnetic resonance imaging''' (MRI scans) is useful in assessing bone marrow infiltration by tumour deposits, and is required (whole spine) for the proper diagnosis of [[Metastatic spinal cord compression|MSCC]]. It has similarly high specificity (73 to 100%) and sensitivity (82 to 100%) in screening for bone metastases&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10964746/&lt;/ref&gt;.<br /> <br /> '''Positron emission tomography''' (PET scans) detects tumour indirectly by measuring metabolic activity in the form of fluorodeoxyglucose ('''&lt;sup&gt;18&lt;/sup&gt;F''') tissue uptake. As such, its use is not limited to visualising only bony metastases, as &lt;sup&gt;18&lt;/sup&gt;F PET will reveal non-bony metastatic spread also&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8638000/&lt;/ref&gt;. The accuracy of PET is highly dependent on the primary tumour site from which imaged metastases originate. As a modality it is superior to scintigraphy in the screening of bony metastases from breast (specificity 94%, sensitivity 95%)&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12073051/&lt;/ref&gt; and lung (specificity 99%, sensitivity 92%)&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10478250/&lt;/ref&gt; malignancies, but has lower sensitivity in detecting the comparatively slower-growing bone metastases of prostate and renal cancers&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10520701/&lt;/ref&gt;. <br /> <br /> ===Biopsy===<br /> Sometimes it is necessary to diagnose metastases histologically, by removing cells or tissue from the bone lesion(s) directly. Usually this is in the form of a needle or surgical biopsy, and may be indicated if a primary cancer is not known. If the patient has a known primary cancer, then often imaging alone will suffice for the diagnosis of metastatic bone disease.<br /> <br /> ==Treatment==<br /> There are a variety of therapeutic interventions available to patients presenting with bone metastases, but consideration must be given to several patient-specific and tumour-dependent parameters, which include&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11738947/&lt;/ref&gt; (but are not limited to):<br /> <br /> *Lesion site(s) (localised or widespread)<br /> *Presence of extraskeletal metastasis<br /> *Tumour type and features (like receptors)<br /> *Prior treatment history (and response)<br /> *Clinical symptoms<br /> *Performance status<br /> <br /> ===Radiotherapy===<br /> Radiation therapy can provide excellent pain relief and is the treatment of choice for localised metastatic bone pain. However, the analgesic mechanisms of therapeutic skeletal irradiation are poorly understood. Onset of pain relief is usually quick, with a majority of patients experiencing benefit within one to two weeks. Patients who have little reduction in pain by six weeks are unlikely to demonstrate significant overall benefit&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/24782453/&lt;/ref&gt;. Other than localised bone pain, additional indications for radiotherapy include [[Metastatic spinal cord compression|MSCC]] and bones at high risk for [[pathological fracture]]&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/15978828/&lt;/ref&gt;. Two of the three main divisions of radiation therapy—the third being (sealed source) [[brachytherapy]]—can be used to treat bone metastases: systemic (unsealed source) [[radionuclide therapy]] and [[external beam radiotherapy]] (EBRT). <br /> <br /> '''Local-field [[External beam radiotherapy|EBRT]]''' is the standard choice of radiation therapy for treating bone metastases, as it focally targets the bone lesion and can achieve rates of substantial pain relief of up to 80 to 90%&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/6178497/&lt;/ref&gt;. Randomised controlled trials (RCTs) from the 1990s have shown that a single fraction of 8 gray (Gy) is as effective as fractionated doses of 20 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9681885&lt;/ref&gt;, 24 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10577695&lt;/ref&gt;, and 30 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10577696&lt;/ref&gt;. <br /> <br /> '''Wide-field''' (or '''hemibody''') '''[[External beam radiotherapy|EBRT]]''' is useful for widespread metastatic skeletal disease, though was more commonly used for multifocal pain when other effective therapies (chemo- and radionuclide) were not available. There are no RCTs comparing analgesic effect with and without wide-field radiotherapy. However, in terms of quasi-randomised and low-quality RCTs, there is data to suggest that use of fractionation is no more effective than single fraction treatment&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8823257&lt;/ref&gt;, that increasing doses beyond 8 Gy does not improve overall pain responses&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11395246&lt;/ref&gt;, and adding wide-field to local-field radiotherapy, whilst significantly halting disease progression (lesion size: P = 0.03; lesion number: P = 0.01), increases grade 3 to 4 haematological toxicity&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/1374061&lt;/ref&gt;. It is possible to classify wide-field treatments into three body regions, each with recommended single-fraction dose limits. Upper treatments (from skull or C1 to L2–L3) should be limited to 6 Gy, whereas mid-body (from L1 to upper third of femur) and lower (from L3–L4 to above knee) treatments should be limited to 8 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/6178497/&lt;/ref&gt;. Any treatments must be delivered with fields shaped to minimise irradiation of organs at risk, such as lung, liver, kidney and bowel. <br /> <br /> '''[[Stereotactic radiotherapy|Stereotactic]] [[External beam radiotherapy|EBRT]]''' is a promising treatment option which delivers higher doses of radiation to tumours in shorter periods in time. When used for extracranial cancers it is interchangeably termed Stereotactic Body Radiation Therapy ('''[[Stereotactic radiotherapy|SBRT]]''') or Stereotactic Ablative Radiotherapy ('''[[Stereotactic radiotherapy|SABR]]'''), the latter of which is appealingly onomatopoeic. When this technique is used for treating malignancy within the brain or some other part of the head, it is termed Stereotactic RadioSurgery ('''[[Stereotactic radiotherapy|SRS]]'''). SBRT/SABR can be used both for primary cancers (lung, liver, prostate, renal) and secondary metastases (bone/spine, lung, liver). There are a number of advantages of stereotactic radiotherapy, the most obvious of which is the potential completion of treatment within a single day, rather than over a number of weeks. The other major benefit is that it obviates the need to irradiate large portions of bone, which lowers the risk of further functional marrow depletion in a patient cohort already at risk of poor marrow reserve. Preserving skeletal marrow function can permit continuous chemotherapy in these patients. The primary limitations of SBRT/SABR are that it is more expensive to deliver than conventional EBRT and that there is a paucity of RCT data comparing its use to standard EBRT management&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/18619121/&lt;/ref&gt;. However, a recent single-centre phase II trial appeared to show that SBRT/SABR provides superior pain relief to conventional multifraction radiotherapy, with no observed difference in adverse events or other aspects of quality of life&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/31021390&lt;/ref&gt;. <br /> <br /> '''[[Radionuclide therapy]]''' (or '''radioisotope therapy''') is the systemic administration of radionuclides (also known as radioisotopes) as unsealed radioactive sources that selectively deliver radiation to tumours or target organs. They are taken up predominantly at sites of bone formation, and are therefore most likely best effective for the palliation of osteoblastic (sclerotic) metastases. Common radionuclides approved for the treatment of painful bone metastases include phosphorus-32 ('''&lt;sup&gt;32&lt;/sup&gt;P'''; ''β''-decay), strontium-89 ('''&lt;sup&gt;89&lt;/sup&gt;Sr'''; ''β''-decay), samarium-153 ('''&lt;sup&gt;153&lt;/sup&gt;Sm'''; ''β''- and ''γ''-decay), and rhenium-186 ('''&lt;sup&gt;186&lt;/sup&gt;Re'''; ''β''- and ''γ''-decay). The added advantage of gamma ray emission during decay is that it permits nuclear imaging monitoring of radionuclide biodistribution during therapy. These radionuclides target bone through various mechanisms. &lt;sup&gt;32&lt;/sup&gt;P passes through inorganic phosphate pathways, whereas &lt;sup&gt;89&lt;/sup&gt;Sr is a calcium mimetic and is taken up as a direct analogue of this earth metal. The final two agents are targeted to bone via chelation to phosphonate compounds: &lt;sup&gt;153&lt;/sup&gt;Sm is paired to ethylenediaminetetramethylenephosphonate (EDTMP) and &lt;sup&gt;186&lt;/sup&gt;Re to 1,1-hydroxyethylidene diphosphonate (HEDP). Common toxicities from treatment include myelosuppression and a transient pain flare, the latter of which usually heralds a favourable response. A more recently developed radionuclide, radium-223 (&lt;sup&gt;'''223'''&lt;/sup&gt;'''Ra'''; ''α''-, ''β''-, and ''γ''-decay) is a calcium mimetic which emits over 95% of decay energy in the form of alpha radiation&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/17062709&lt;/ref&gt;. Owing to their comparatively large size the emitted alpha particles have a more limited depth of penetration into surrounding tissues (around 2–10 cells), thereby producing a more potently localised cytotoxic effect. Despite their symptomatic benefits in refractory, widespread bone metastases, neither &lt;sup&gt;89&lt;/sup&gt;Sr nor &lt;sup&gt;153&lt;/sup&gt;Sm have been shown to improve overall survival in interventional trials; however, &lt;sup&gt;223&lt;/sup&gt;Ra use in metastatic castration-resistant prostate cancer patients in the ALSYMPCA (ALpharadin in SYMptomatic Prostate CAncer) trial was shown to significantly prolong overall survival&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/23863050/&lt;/ref&gt;. <br /> <br /> ===Bisphosphonates===<br /> Analogues of the natural bone demineralisation inhibitor pyrophosphate, bisphosphonates are useful in the treatment of poorly localised bone pain and in previously irradiated bone lesions. They bind with high affinity to exposed bone mineral where they are internalised by osteoclasts, within which they disrupt the processes of bone resorption and can induce apoptosis. Data have shown that bisphosphonates may have direct pro-apoptotic effects on nearby metastatic cancer cells also&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9362432/&lt;/ref&gt;. In halting the mobilisation of calcium and phosphate from bone, bisphosphonate use (together with rehydration) is now standard of care for malignancy-induced hypercalcaemia&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9025784/&lt;/ref&gt;. The analgesic effect of these agents is independent of underlying tumour characteristics, with osteolytic and osteoblastic lesions responding similarly&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9496390&lt;/ref&gt;. [side effects], [osteonecrosis of jaw + renal impairment], + [generations + potency + take supplement].<br /> <br /> ===Denosumab===<br /> -<br /> <br /> ===Analgesia===<br /> -<br /> <br /> ===Chemotherapy===<br /> -<br /> <br /> ===Hormonal therapies===<br /> -<br /> <br /> ===Surgery &amp; IR===<br /> -<br /> <br /> ===Bone cement===<br /> -<br /> <br /> ==Living with bone metastases==<br /> Pain, mobility and safety, survival&lt;references /&gt;</div>

Alex https://oncopaedia.net/w/index.php?title=Articles:Oncological_emergencies&diff=302 2020-04-16T17:07:12Z

<p>Alex: </p> <hr /> <div>Acute emergencies in oncology are a group of conditions caused by complications of cancer or its treatment, that are life-threatening or irreversibly disabling if clinical management is delayed. As a consequence of our ability to treat increasingly larger numbers of patients effectively, the knowledge to recognise and respond swiftly to such presentations has never been more important.<br /> <br /> These emergencies may be encountered at any stage in the pathway of a patient's journey through cancer. This may be at presentation, during the course of treatment, or later in the disease process. Below reviews the most frequently encountered oncological emergencies. It may sound obvious, but it is worth bearing in mind that unrelated acute medical or surgical conditions may occur in patients with malignant disease. Generally, the management will be the same as that of a patient without known cancer.<br /> <br /> The emergencies are grouped according to the causative system of origin.<br /> <br /> ==Cardiovascular emergencies==<br /> <br /> *Superior vena cava obstruction<br /> *Cardiac tamponade (malignant pericardial effusion)<br /> *Venous thromboembolism<br /> *Extravasation injury<br /> *Complications of central venous devices&lt;ref&gt;https://oncologypro.esmo.org/Education-Library/Handbooks/Oncological-Emergencies&lt;/ref&gt;<br /> *Hypertensive crises<br /> <br /> ==Respiratory emergencies==<br /> <br /> *Acute large airway obstruction<br /> *Pulmonary haemorrhage<br /> *Respiratory failure<br /> *Intractable hiccups<br /> *Radiation pneumonitis<br /> *Pleural effusion (malignant)<br /> <br /> ==Metabolic emergencies==<br /> <br /> *Tumour lysis syndrome<br /> *[[Hypercalcaemia]]<br /> *Syndrome of inappropriate antidiuretic hormone secretion (SIADH)<br /> *Hypomagnesaemia<br /> *Hypoglycaemia<br /> <br /> ==Endocrine emergencies==<br /> <br /> *Thyroid dysfunction<br /> *Adrenal insufficiency<br /> <br /> ==Renal &amp; Urological emergencies==<br /> <br /> *Obstructive uropathy<br /> *Urate nephropathy (from TLS)<br /> *Haemorrhagic cystitis&lt;ref&gt;https://www.cancernetwork.com/articles/oncologic-emergencies&lt;/ref&gt;<br /> *Nephritis<br /> <br /> ==Gastrointestinal emergencies==<br /> <br /> *Bowel obstruction<br /> *Bowel perforation<br /> *Gastrointestinal haemorrhage<br /> *Nausea and vomiting (uncontrolled)<br /> *Mucositis (uncontrolled)<br /> *Diarrhoea (uncontrolled)<br /> *Biliary obstruction<br /> *Oesophageal obstruction<br /> *Abdominal ascites (malignant)<br /> *Neutropaenic enterocolitis<br /> *Transaminitis<br /> *Colitis<br /> <br /> ==Neurological emergencies==<br /> <br /> *Spinal cord compression<br /> *Cauda equina syndrome<br /> *Raised intracranial pressure<br /> *Seizures (fits)<br /> *Leptomeningeal disease<br /> <br /> ==Haematological emergencies==<br /> <br /> *Leukostasis<br /> *Hyperviscosity<br /> *Disseminated intravascular coagulation<br /> *Thrombocytopaenia<br /> *Febrile neutropaenia (neutropaenic sepsis)<br /> <br /> ==Ophthalmological emergencies==<br /> <br /> *[[Articles:Ocular and orbital metastases|Ocular and orbital metastases]]<br /> <br /> ==Musculoskeletal emergencies==<br /> <br /> *[[Articles:Bone metastases|Metastatic bone pain]]<br /> *[[Pathological fractures]]<br /> <br /> ==Gynaecological emergencies==<br /> <br /> *[[Articles:Gynaecological haemorrhage|Gynaecological haemorrhage]]<br /> <br /> ==Dermatological emergencies==<br /> <br /> *[[Acute skin reactions]]<br /> <br /> ==Psychiatric emergencies==<br /> <br /> *[[Steroid-induced psychosis]]&lt;br /&gt;<br /> &lt;references /&gt;</div>

Alex https://oncopaedia.net/w/index.php?title=Articles:Bone_metastases&diff=301 2020-04-16T17:04:54Z

<p>Alex: </p> <hr /> <div>Metastases within bone can cause extreme and debilitating pain. Bone metastases are far more common than primary bone cancer, and many different cancer types can spread to the bone. The most common types of cancer which spread to bone are:<br /> <br /> *Breast<br /> *Prostate<br /> *Lung<br /> *Kidney<br /> *Thyroid<br /> <br /> Cancer can theoretically metastasize to any bone in the body, but in reality there is a predilection for certain sites. The most common sites are the vertebrae, ribs, pelvis, sternum, and the skull.<br /> <br /> ==Classification==<br /> A bone is a rigid organ, but it is far from physiologically static. To maintain bone strength, there is continuous breakdown and simultaneous reformation of bone, two processes which must finely balance for good bone health.<br /> <br /> '''Osteoblastic''' (or '''sclerotic''') metastases are characterised by the deposition of new bone. These are present most commonly in prostate cancer, but also occur in carcinoid, small cell lung cancer, medulloblastoma, and Hodgkin lymphoma. The molecular crosstalk between tumour and bone cells involves osteoblast-generating proteins such as Transforming Growth Factor, Bone Morphogenic Proteins (BMPs), and Endothelin-1&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12085970&lt;/ref&gt;.<br /> <br /> '''Osteolytic''' (or '''lytic''') metastases are characterised by the destruction and breakdown of normal bone. These often occur when breast cancer spreads to bone, which is primarily mediated by osteoclasts (bone cells that breaks down bone tissue) and is not a direct effect of metastasized tumour cells&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8086233/&lt;/ref&gt;. Other tumour types with osteolytic metastases include multiple myeloma, non-small cell lung cancer, thyroid cancer, non-Hodgkin lymphoma, and Langerhans' cell histiocytosis. Osteolytic metastases are more common than osteoblastic metastases.<br /> <br /> '''Mixed''' metastases are characterised by the presence of both osteolytic and osteoblastic lesions together in the same area of bone. These metastases are usually present in metastatic gastrointestinal and squamous cancers, as well as in secondary breast cancer. Although breast cancer gives rise to predominantly lytic lesions, around 15–20% of women have sclerotic or both types of lesions&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11346860/&lt;/ref&gt;.<br /> <br /> ==Diagnosis==<br /> <br /> ===Signs and symptoms===<br /> Bone metastases cause major morbidity, and high clinical suspicion should be kept for any patient with cancer that presents with:<br /> <br /> *Severe pain (poorly localised, worse at night)<br /> *Impaired mobility<br /> *[[Pathological fracture|Bone fracture]]<br /> *Bone marrow aplasia<br /> *Symptoms of (metastatic) [[Metastatic spinal cord compression|spinal cord compression]] (MSCC)<br /> *Symptoms in keeping with [[hypercalcaemia]]:<br /> **Constipation<br /> **Fatigue<br /> **Polyuria/polydipsia<br /> **Acute kidney injury (AKI)<br /> **Cardiac arrhythmia<br /> <br /> ===Bloods===<br /> When a patient with cancer presents with any of the signs or symptoms above, basic screening in the form of simple blood testing must be undertaken and complemented with appropriate imaging tests:<br /> <br /> *Full evaluation of bone turnover and potential hypercalcaemia:<br /> **Serum calcium<br /> **Serum phosphate<br /> **25-Hydroxyvitamin D<br /> **Thyroid-stimulating hormone (TSH)<br /> **Parathyroid hormone (PTH)<br /> **Serum creatinine<br /> **Alkaline phosphatase (ALP)<br /> *Full blood count (myelosuppression, anaemia)<br /> *Serum protein electrophoresis (SPEP; myeloma screen)<br /> *Tumour markers (such as PSA in prostate cancer)<br /> <br /> ===Imaging===<br /> Radiological tests are an essential component of diagnosing bony metastases. One or more imaging modalities may be required to confirm suspected cancerous spread to bone.<br /> <br /> '''Plain radiographs''' (X-ray scans) are quick, cost-effective, and widely-available, and should be the initial diagnostic test of choice when investigating bone pain. They are highly specific but lack sensitivity (44-50%) because early-stage metastatic lesions, particularly those up to 1 cm, may be more difficult to visualise. More than 50% of the trabecular bone must be involved before the lesion will be apparent on film and, due to the poor contrast of trabecular bone, lesions within the medulla are often less evident than those within cortical bone&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9025785/&lt;/ref&gt;. As outlined above, sclerotic metastases will appear more radiopaque than the surrounding bone, whereas lytic metastases will appear more radiolucent.<br /> <br /> '''Bone scintigraphy''' (bone scans) on the other hand is highly sensitive but with low specificity. Data from Technetium-99m ('''&lt;sup&gt;99m&lt;/sup&gt;Tc''') scintigraphy have shown false-negative rates as low as 11 to 38% (good sensitivity), with false-positive rates as high as 40% (poor specificity). It thus provides a non-specific osteoblastic indication of bone status, be it inflammatory, traumatic, or neoplastic in origin. Scintigraphy is still more specific and sensitive than either plain radiography or computed tomography, whilst magnetic resonance imaging is more efficacious in assessing vertebral metastases&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/2028061/&lt;/ref&gt;.<br /> <br /> '''Computed tomography''' (CT scans) has a high sensitivity, ranging from 71 to 100%, for the detection of metastatic bone lesions&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9362427/&lt;/ref&gt;. Because of the excellent soft tissue resolution of the images produced by CT, it is a particularly helpful modality to distinguish lytic and sclerotic metastases and to visualise their precise location(s) for biopsy.<br /> <br /> '''Magnetic resonance imaging''' (MRI scans) is useful in assessing bone marrow infiltration by tumour deposits, and is required (whole spine) for the proper diagnosis of [[Metastatic spinal cord compression|MSCC]]. It has similarly high specificity (73 to 100%) and sensitivity (82 to 100%) in screening for bone metastases&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10964746/&lt;/ref&gt;.<br /> <br /> '''Positron emission tomography''' (PET scans) detects tumour indirectly by measuring metabolic activity in the form of fluorodeoxyglucose ('''&lt;sup&gt;18&lt;/sup&gt;F''') tissue uptake. As such, its use is not limited to visualising only bony metastases, as &lt;sup&gt;18&lt;/sup&gt;F PET will reveal non-bony metastatic spread also&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8638000/&lt;/ref&gt;. The accuracy of PET is highly dependent on the primary tumour site from which imaged metastases originate. As a modality it is superior to scintigraphy in the screening of bony metastases from breast (specificity 94%, sensitivity 95%)&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12073051/&lt;/ref&gt; and lung (specificity 99%, sensitivity 92%)&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10478250/&lt;/ref&gt; malignancies, but has lower sensitivity in detecting the comparatively slower-growing bone metastases of prostate and renal cancers&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10520701/&lt;/ref&gt;. <br /> <br /> ===Biopsy===<br /> Sometimes it is necessary to diagnose metastases histologically, by removing cells or tissue from the bone lesion(s) directly. Usually this is in the form of a needle or surgical biopsy, and may be indicated if a primary cancer is not known. If the patient has a known primary cancer, then often imaging alone will suffice for the diagnosis of metastatic bone disease.<br /> <br /> ==Treatment==<br /> There are a variety of therapeutic interventions available to patients presenting with bone metastases, but consideration must be given to several patient-specific and tumour-dependent parameters, which include&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11738947/&lt;/ref&gt; (but are not limited to):<br /> <br /> *Lesion site(s) (localised or widespread)<br /> *Presence of extraskeletal metastasis<br /> *Tumour type and features (like receptors)<br /> *Prior treatment history (and response)<br /> *Clinical symptoms<br /> *Performance status<br /> <br /> ===Radiotherapy===<br /> Radiation therapy can provide excellent pain relief and is the treatment of choice for localised metastatic bone pain. However, the analgesic mechanisms of therapeutic skeletal irradiation are poorly understood. Onset of pain relief is usually quick, with a majority of patients experiencing benefit within one to two weeks. Patients who have little reduction in pain by six weeks are unlikely to demonstrate significant overall benefit&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/24782453/&lt;/ref&gt;. Other than localised bone pain, additional indications for radiotherapy include [[Metastatic spinal cord compression|MSCC]] and bones at high risk for [[pathological fracture]]&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/15978828/&lt;/ref&gt;. Two of the three main divisions of radiation therapy—the third being (sealed source) [[brachytherapy]]—can be used to treat bone metastases: systemic (unsealed source) [[radionuclide therapy]] and [[external beam radiotherapy]] (EBRT). <br /> <br /> '''Local-field [[External beam radiotherapy|EBRT]]''' is the standard choice of radiation therapy for treating bone metastases, as it focally targets the bone lesion and can achieve rates of substantial pain relief of up to 80 to 90%&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/6178497/&lt;/ref&gt;. Randomised controlled trials (RCTs) from the 1990s have shown that a single fraction of 8 gray (Gy) is as effective as fractionated doses of 20 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9681885&lt;/ref&gt;, 24 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10577695&lt;/ref&gt;, and 30 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10577696&lt;/ref&gt;. <br /> <br /> '''Wide-field''' (or '''hemibody''') '''[[External beam radiotherapy|EBRT]]''' is useful for widespread metastatic skeletal disease, though was more commonly used for multifocal pain when other effective therapies (chemo- and radionuclide) were not available. There are no RCTs comparing analgesic effect with and without wide-field radiotherapy. However, in terms of quasi-randomised and low-quality RCTs, there is data to suggest that use of fractionation is no more effective than single fraction treatment&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8823257&lt;/ref&gt;, that increasing doses beyond 8 Gy does not improve overall pain responses&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11395246&lt;/ref&gt;, and adding wide-field to local-field radiotherapy, whilst significantly halting disease progression (lesion size: P = 0.03; lesion number: P = 0.01), increases grade 3 to 4 haematological toxicity&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/1374061&lt;/ref&gt;. It is possible to classify wide-field treatments into three body regions, each with recommended single-fraction dose limits. Upper treatments (from skull or C1 to L2–L3) should be limited to 6 Gy, whereas mid-body (from L1 to upper third of femur) and lower (from L3–L4 to above knee) treatments should be limited to 8 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/6178497/&lt;/ref&gt;. Any treatments must be delivered with fields shaped to minimise irradiation of organs at risk, such as lung, liver, kidney and bowel. <br /> <br /> '''[[Stereotactic radiotherapy|Stereotactic]] [[External beam radiotherapy|EBRT]]''' is a promising treatment option which delivers higher doses of radiation to tumours in shorter periods in time. When used for extracranial cancers it is interchangeably termed Stereotactic Body Radiation Therapy ('''[[Stereotactic radiotherapy|SBRT]]''') or Stereotactic Ablative Radiotherapy ('''[[Stereotactic radiotherapy|SABR]]'''), the latter of which is appealingly onomatopoeic. When this technique is used for treating malignancy within the brain or some other part of the head, it is termed Stereotactic RadioSurgery ('''[[Stereotactic radiotherapy|SRS]]'''). SBRT/SABR can be used both for primary cancers (lung, liver, prostate, renal) and secondary metastases (bone/spine, lung, liver). There are a number of advantages of stereotactic radiotherapy, the most obvious of which is the potential completion of treatment within a single day, rather than over a number of weeks. The other major benefit is that it obviates the need to irradiate large portions of bone, which lowers the risk of further functional marrow depletion in a patient cohort already at risk of poor marrow reserve. Preserving skeletal marrow function can permit continuous chemotherapy in these patients. The primary limitations of SBRT/SABR are that it is more expensive to deliver than conventional EBRT and that there is a paucity of RCT data comparing its use to standard EBRT management&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/18619121/&lt;/ref&gt;. However, a recent single-centre phase II trial appeared to show that SBRT/SABR provides superior pain relief to conventional multifraction radiotherapy, with no observed difference in adverse events or other aspects of quality of life&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/31021390&lt;/ref&gt;. <br /> <br /> '''[[Radionuclide therapy]]''' (or '''radioisotope therapy''') is the systemic administration of radionuclides (also known as radioisotopes) as unsealed radioactive sources that selectively deliver radiation to tumours or target organs. They are taken up predominantly at sites of bone formation, and are therefore most likely best effective for the palliation of osteoblastic (sclerotic) metastases. Common radionuclides approved for the treatment of painful bone metastases include phosphorus-32 ('''&lt;sup&gt;32&lt;/sup&gt;P'''; ''β''-decay), strontium-89 ('''&lt;sup&gt;89&lt;/sup&gt;Sr'''; ''β''-decay), samarium-153 ('''&lt;sup&gt;153&lt;/sup&gt;Sm'''; ''β''- and ''γ''-decay), and rhenium-186 ('''&lt;sup&gt;186&lt;/sup&gt;Re'''; ''β''- and ''γ''-decay). The added advantage of gamma ray emission during decay is that it permits nuclear imaging monitoring of radionuclide biodistribution during therapy. These radionuclides target bone through various mechanisms. &lt;sup&gt;32&lt;/sup&gt;P passes through inorganic phosphate pathways, whereas &lt;sup&gt;89&lt;/sup&gt;Sr is a calcium mimetic and is taken up as a direct analogue of this earth metal. The final two agents are targeted to bone via chelation to phosphonate compounds: &lt;sup&gt;153&lt;/sup&gt;Sm is paired to ethylenediaminetetramethylenephosphonate (EDTMP) and &lt;sup&gt;186&lt;/sup&gt;Re to 1,1-hydroxyethylidene diphosphonate (HEDP). Common toxicities from treatment include myelosuppression and a transient pain flare, the latter of which usually heralds a favourable response. A more recently developed radionuclide, radium-223 (&lt;sup&gt;'''223'''&lt;/sup&gt;'''Ra'''; ''α''-, ''β''-, and ''γ''-decay) is a calcium mimetic which emits over 95% of decay energy in the form of alpha radiation&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/17062709&lt;/ref&gt;. Owing to their comparatively large size the emitted alpha particles have a more limited depth of penetration into surrounding tissues (around 2–10 cells), thereby producing a more potently localised cytotoxic effect. Despite their symptomatic benefits in refractory, widespread bone metastases, neither &lt;sup&gt;89&lt;/sup&gt;Sr nor &lt;sup&gt;153&lt;/sup&gt;Sm have been shown to improve overall survival in interventional trials; however, &lt;sup&gt;223&lt;/sup&gt;Ra use in metastatic castration-resistant prostate cancer patients in the ALSYMPCA (ALpharadin in SYMptomatic Prostate CAncer) trial was shown to significantly prolong overall survival&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/23863050/&lt;/ref&gt;. <br /> <br /> ===Bisphosphonates===<br /> Analogues of the natural bone demineralisation inhibitor pyrophosphate, bisphosphonates are useful in the treatment of poorly localised bone pain and in previously irradiated bone lesions. They bind with high affinity to exposed bone mineral where they are internalised by osteoclasts, within which they disrupt the processes of bone resorption and may induce apoptosis. Data have shown that bisphosphonates may have direct pro-apoptotic effects on nearby metastatic cancer cells also&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9362432/&lt;/ref&gt;. In halting the mobilisation of calcium and phosphate from bone, bisphosphonate use is now standard of care for malignancy-induced hypercalcaemia&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9025784/&lt;/ref&gt;.<br /> <br /> ===Denosumab===<br /> -<br /> <br /> ===Analgesia===<br /> -<br /> <br /> ===Chemotherapy===<br /> -<br /> <br /> ===Hormonal therapies===<br /> -<br /> <br /> ===Surgery &amp; IR===<br /> -<br /> <br /> ===Bone cement===<br /> -<br /> <br /> ==Living with bone metastases==<br /> Pain, mobility and safety, survival&lt;references /&gt;</div>

Alex https://oncopaedia.net/w/index.php?title=Articles:Bone_metastases&diff=300 2020-04-15T14:09:02Z

<p>Alex: </p> <hr /> <div>Metastases within bone can cause extreme and debilitating pain. Bone metastases are far more common than primary bone cancer, and many different cancer types can spread to the bone. The most common types of cancer which spread to bone are:<br /> <br /> *Breast<br /> *Prostate<br /> *Lung<br /> *Kidney<br /> *Thyroid<br /> <br /> Cancer can theoretically metastasize to any bone in the body, but in reality there is a predilection for certain sites. The most common sites are the vertebrae, ribs, pelvis, sternum, and the skull.<br /> <br /> ==Classification==<br /> A bone is a rigid organ, but it is far from physiologically static. To maintain bone strength, there is continuous breakdown and simultaneous reformation of bone, two processes which must finely balance for good bone health.<br /> <br /> '''Osteoblastic''' (or '''sclerotic''') metastases are characterised by the deposition of new bone. These are present most commonly in prostate cancer, but also occur in carcinoid, small cell lung cancer, medulloblastoma, and Hodgkin lymphoma. The molecular crosstalk between tumour and bone cells involves osteoblast-generating proteins such as Transforming Growth Factor, Bone Morphogenic Proteins (BMPs), and Endothelin-1&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12085970&lt;/ref&gt;.<br /> <br /> '''Osteolytic''' (or '''lytic''') metastases are characterised by the destruction and breakdown of normal bone. These often occur when breast cancer spreads to bone, which is primarily mediated by osteoclasts (bone cells that breaks down bone tissue) and is not a direct effect of metastasized tumour cells&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8086233/&lt;/ref&gt;. Other tumour types with osteolytic metastases include multiple myeloma, non-small cell lung cancer, thyroid cancer, non-Hodgkin lymphoma, and Langerhans' cell histiocytosis. Osteolytic metastases are more common than osteoblastic metastases.<br /> <br /> '''Mixed''' metastases are characterised by the presence of both osteolytic and osteoblastic lesions together in the same area of bone. These metastases are usually present in metastatic gastrointestinal and squamous cancers, as well as in secondary breast cancer. Although breast cancer gives rise to predominantly lytic lesions, around 15–20% of women have sclerotic or both types of lesions&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11346860/&lt;/ref&gt;.<br /> <br /> ==Diagnosis==<br /> <br /> ===Signs and symptoms===<br /> Bone metastases cause major morbidity, and high clinical suspicion should be kept for any patient with cancer that presents with:<br /> <br /> *Severe pain (poorly localised, worse at night)<br /> *Impaired mobility<br /> *[[Pathological fracture|Bone fracture]]<br /> *Bone marrow aplasia<br /> *Symptoms of (metastatic) [[Metastatic spinal cord compression|spinal cord compression]] (MSCC)<br /> *Symptoms in keeping with [[hypercalcaemia]]:<br /> **Constipation<br /> **Fatigue<br /> **Polyuria/polydipsia<br /> **Acute kidney injury (AKI)<br /> **Cardiac arrhythmia<br /> <br /> ===Bloods===<br /> When a patient with cancer presents with any of the signs or symptoms above, basic screening in the form of simple blood testing must be undertaken and complemented with appropriate imaging tests:<br /> <br /> *Full evaluation of bone turnover and potential hypercalcaemia:<br /> **Serum calcium<br /> **Serum phosphate<br /> **25-Hydroxyvitamin D<br /> **Thyroid-stimulating hormone (TSH)<br /> **Parathyroid hormone (PTH)<br /> **Serum creatinine<br /> **Alkaline phosphatase (ALP)<br /> *Full blood count (myelosuppression, anaemia)<br /> *Serum protein electrophoresis (SPEP; myeloma screen)<br /> *Tumour markers (such as PSA in prostate cancer)<br /> <br /> ===Imaging===<br /> Radiological tests are an essential component of diagnosing bony metastases. One or more imaging modalities may be required to confirm suspected cancerous spread to bone.<br /> <br /> '''Plain radiographs''' (X-ray scans) are quick, cost-effective, and widely-available, and should be the initial diagnostic test of choice when investigating bone pain. They are highly specific but lack sensitivity (44-50%) because early-stage metastatic lesions, particularly those up to 1 cm, may be more difficult to visualise. More than 50% of the trabecular bone must be involved before the lesion will be apparent on film and, due to the poor contrast of trabecular bone, lesions within the medulla are often less evident than those within cortical bone&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9025785/&lt;/ref&gt;. As outlined above, sclerotic metastases will appear more radiopaque than the surrounding bone, whereas lytic metastases will appear more radiolucent.<br /> <br /> '''Bone scintigraphy''' (bone scans) on the other hand is highly sensitive but with low specificity. Data from Technetium-99m ('''&lt;sup&gt;99m&lt;/sup&gt;Tc''') scintigraphy have shown false-negative rates as low as 11 to 38% (good sensitivity), with false-positive rates as high as 40% (poor specificity). It thus provides a non-specific osteoblastic indication of bone status, be it inflammatory, traumatic, or neoplastic in origin. Scintigraphy is still more specific and sensitive than either plain radiography or computed tomography, whilst magnetic resonance imaging is more efficacious in assessing vertebral metastases&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/2028061/&lt;/ref&gt;.<br /> <br /> '''Computed tomography''' (CT scans) has a high sensitivity, ranging from 71 to 100%, for the detection of metastatic bone lesions&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9362427/&lt;/ref&gt;. Because of the excellent soft tissue resolution of the images produced by CT, it is a particularly helpful modality to distinguish lytic and sclerotic metastases and to visualise their precise location(s) for biopsy.<br /> <br /> '''Magnetic resonance imaging''' (MRI scans) is useful in assessing bone marrow infiltration by tumour deposits, and is required (whole spine) for the proper diagnosis of [[Metastatic spinal cord compression|MSCC]]. It has similarly high specificity (73 to 100%) and sensitivity (82 to 100%) in screening for bone metastases&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10964746/&lt;/ref&gt;.<br /> <br /> '''Positron emission tomography''' (PET scans) detects tumour indirectly by measuring metabolic activity in the form of fluorodeoxyglucose ('''&lt;sup&gt;18&lt;/sup&gt;F''') tissue uptake. As such, its use is not limited to visualising only bony metastases, as &lt;sup&gt;18&lt;/sup&gt;F PET will reveal non-bony metastatic spread also&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8638000/&lt;/ref&gt;. The accuracy of PET is highly dependent on the primary tumour site from which imaged metastases originate. As a modality it is superior to scintigraphy in the screening of bony metastases from breast (specificity 94%, sensitivity 95%)&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12073051/&lt;/ref&gt; and lung (specificity 99%, sensitivity 92%)&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10478250/&lt;/ref&gt; malignancies, but has lower sensitivity in detecting the comparatively slower-growing bone metastases of prostate and renal cancers&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10520701/&lt;/ref&gt;. <br /> <br /> ===Biopsy===<br /> Sometimes it is necessary to diagnose metastases histologically, by removing cells or tissue from the bone lesion(s) directly. Usually this is in the form of a needle or surgical biopsy, and may be indicated if a primary cancer is not known. If the patient has a known primary cancer, then often imaging alone will suffice for the diagnosis of metastatic bone disease.<br /> <br /> ==Treatment==<br /> There are a variety of therapeutic interventions available to patients presenting with bone metastases, but consideration must be given to several patient-specific and tumour-dependent parameters, which include&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11738947/&lt;/ref&gt; (but are not limited to):<br /> <br /> *Lesion site(s) (localised or widespread)<br /> *Presence of extraskeletal metastasis<br /> *Tumour type and features (like receptors)<br /> *Prior treatment history (and response)<br /> *Clinical symptoms<br /> *Performance status<br /> <br /> ===Radiotherapy===<br /> Radiation therapy can provide excellent pain relief and is the treatment of choice for localised metastatic bone pain. However, the analgesic mechanisms of therapeutic skeletal irradiation are poorly understood. Onset of pain relief is usually quick, with a majority of patients experiencing benefit within one to two weeks. Patients who have little reduction in pain by six weeks are unlikely to demonstrate significant overall benefit&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/24782453/&lt;/ref&gt;. Other than localised bone pain, additional indications for radiotherapy include [[Metastatic spinal cord compression|MSCC]] and bones at high risk for [[pathological fracture]]&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/15978828/&lt;/ref&gt;. Two of the three main divisions of radiation therapy—the third being (sealed source) [[brachytherapy]]—can be used to treat bone metastases: systemic (unsealed source) [[radionuclide therapy]] and [[external beam radiotherapy]] (EBRT). <br /> <br /> '''Local-field [[External beam radiotherapy|EBRT]]''' is the standard choice of radiation therapy for treating bone metastases, as it focally targets the bone lesion and can achieve rates of substantial pain relief of up to 80 to 90%&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/6178497/&lt;/ref&gt;. Randomised controlled trials (RCTs) from the 1990s have shown that a single fraction of 8 gray (Gy) is as effective as fractionated doses of 20 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9681885&lt;/ref&gt;, 24 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10577695&lt;/ref&gt;, and 30 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10577696&lt;/ref&gt;. <br /> <br /> '''Wide-field''' (or '''hemibody''') '''[[External beam radiotherapy|EBRT]]''' is useful for widespread metastatic skeletal disease, though was more commonly used for multifocal pain when other effective therapies (chemo- and radionuclide) were not available. There are no RCTs comparing analgesic effect with and without wide-field radiotherapy. However, in terms of quasi-randomised and low-quality RCTs, there is data to suggest that use of fractionation is no more effective than single fraction treatment&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8823257&lt;/ref&gt;, that increasing doses beyond 8 Gy does not improve overall pain responses&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11395246&lt;/ref&gt;, and adding wide-field to local-field radiotherapy, whilst significantly halting disease progression (lesion size: P = 0.03; lesion number: P = 0.01), increases grade 3 to 4 haematological toxicity&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/1374061&lt;/ref&gt;. It is possible to classify wide-field treatments into three body regions, each with recommended single-fraction dose limits. Upper treatments (from skull or C1 to L2–L3) should be limited to 6 Gy, whereas mid-body (from L1 to upper third of femur) and lower (from L3–L4 to above knee) treatments should be limited to 8 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/6178497/&lt;/ref&gt;. Any treatments must be delivered with fields shaped to minimise irradiation of organs at risk, such as lung, liver, kidney and bowel. <br /> <br /> '''[[Stereotactic radiotherapy|Stereotactic]] [[External beam radiotherapy|EBRT]]''' is a promising treatment option which delivers higher doses of radiation to tumours in shorter periods in time. When used for extracranial cancers it is interchangeably termed Stereotactic Body Radiation Therapy ('''[[Stereotactic radiotherapy|SBRT]]''') or Stereotactic Ablative Radiotherapy ('''[[Stereotactic radiotherapy|SABR]]'''), the latter of which is appealingly onomatopoeic. When this technique is used for treating malignancy within the brain or some other part of the head, it is termed Stereotactic RadioSurgery ('''[[Stereotactic radiotherapy|SRS]]'''). SBRT/SABR can be used both for primary cancers (lung, liver, prostate, renal) and secondary metastases (bone/spine, lung, liver). There are a number of advantages of stereotactic radiotherapy, the most obvious of which is the potential completion of treatment within a single day, rather than over a number of weeks. The other major benefit is that it obviates the need to irradiate large portions of bone, which lowers the risk of further functional marrow depletion in a patient cohort already at risk of poor marrow reserve. Preserving skeletal marrow function can permit continuous chemotherapy in these patients. The primary limitations of SBRT/SABR are that it is more expensive to deliver than conventional EBRT and that there is a paucity of RCT data comparing its use to standard EBRT management&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/18619121/&lt;/ref&gt;. However, a recent single-centre phase II trial appeared to show that SBRT/SABR provides superior pain relief to conventional multifraction radiotherapy, with no observed difference in adverse events or other aspects of quality of life&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/31021390&lt;/ref&gt;. <br /> <br /> '''[[Radionuclide therapy]]''' (or '''radioisotope therapy''') is the systemic administration of radionuclides (also known as radioisotopes) as unsealed radioactive sources that selectively deliver radiation to tumours or target organs. They are taken up predominantly at sites of bone formation, and are therefore most likely best effective for the palliation of osteoblastic (sclerotic) metastases. Common radionuclides approved for the treatment of painful bone metastases include phosphorus-32 ('''&lt;sup&gt;32&lt;/sup&gt;P'''; ''β''-decay), strontium-89 ('''&lt;sup&gt;89&lt;/sup&gt;Sr'''; ''β''-decay), samarium-153 ('''&lt;sup&gt;153&lt;/sup&gt;Sm'''; ''β''- and ''γ''-decay), and rhenium-186 ('''&lt;sup&gt;186&lt;/sup&gt;Re'''; ''β''- and ''γ''-decay). The added advantage of gamma ray emission during decay is that it permits nuclear imaging monitoring of radionuclide biodistribution during therapy. These radionuclides target bone through various mechanisms. &lt;sup&gt;32&lt;/sup&gt;P passes through inorganic phosphate pathways, whereas &lt;sup&gt;89&lt;/sup&gt;Sr is a calcium mimetic and is taken up as a direct analogue of this earth metal. The final two agents are targeted to bone via chelation to phosphonate compounds: &lt;sup&gt;153&lt;/sup&gt;Sm is paired to ethylenediaminetetramethylenephosphonate (EDTMP) and &lt;sup&gt;186&lt;/sup&gt;Re to 1,1-hydroxyethylidene diphosphonate (HEDP). Common toxicities from treatment include myelosuppression and a transient pain flare, the latter of which usually heralds a favourable response. A more recently developed radionuclide, radium-223 (&lt;sup&gt;'''223'''&lt;/sup&gt;'''Ra'''; ''α''-, ''β''-, and ''γ''-decay) is a calcium mimetic which emits over 95% of decay energy in the form of alpha radiation&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/17062709&lt;/ref&gt;. Owing to their comparatively large size the emitted alpha particles have a more limited depth of penetration into surrounding tissues (around 2–10 cells), thereby producing a more potently localised cytotoxic effect. Despite their symptomatic benefits in refractory, widespread bone metastases, neither &lt;sup&gt;89&lt;/sup&gt;Sr nor &lt;sup&gt;153&lt;/sup&gt;Sm have been shown to improve overall survival in interventional trials; however, &lt;sup&gt;223&lt;/sup&gt;Ra use in metastatic castration-resistant prostate cancer patients in the ALSYMPCA (ALpharadin in SYMptomatic Prostate CAncer) trial was shown to significantly prolong overall survival&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/23863050/&lt;/ref&gt;. <br /> <br /> ===Bisphosphonates===<br /> Poorly localised bone pain/previously irradiated bone lesions<br /> <br /> ===Denosumab===<br /> -<br /> <br /> ===Analgesia===<br /> -<br /> <br /> ===Chemotherapy===<br /> -<br /> <br /> ===Hormonal therapies===<br /> -<br /> <br /> ===Surgery &amp; IR===<br /> -<br /> <br /> ===Bone cement===<br /> -<br /> <br /> ==Living with bone metastases==<br /> Pain, mobility and safety, survival&lt;references /&gt;</div>

Alex https://oncopaedia.net/w/index.php?title=Articles:Bone_metastases&diff=299 2020-04-15T13:36:10Z

<p>Alex: </p> <hr /> <div>Metastases within bone can cause extreme and debilitating pain. Bone metastases are far more common than primary bone cancer, and many different cancer types can spread to the bone. The most common types of cancer which spread to bone are:<br /> <br /> *Breast<br /> *Prostate<br /> *Lung<br /> *Kidney<br /> *Thyroid<br /> <br /> Cancer can theoretically metastasize to any bone in the body, but in reality there is a predilection for certain sites. The most common sites are the vertebrae, ribs, pelvis, sternum, and the skull.<br /> <br /> ==Classification==<br /> A bone is a rigid organ, but it is far from physiologically static. To maintain bone strength, there is continuous breakdown and simultaneous reformation of bone, two processes which must finely balance for good bone health.<br /> <br /> '''Osteoblastic''' (or '''sclerotic''') metastases are characterised by the deposition of new bone. These are present most commonly in prostate cancer, but also occur in carcinoid, small cell lung cancer, medulloblastoma, and Hodgkin lymphoma. The molecular crosstalk between tumour and bone cells involves osteoblast-generating proteins such as Transforming Growth Factor, Bone Morphogenic Proteins (BMPs), and Endothelin-1&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12085970&lt;/ref&gt;.<br /> <br /> '''Osteolytic''' (or '''lytic''') metastases are characterised by the destruction and breakdown of normal bone. These often occur when breast cancer spreads to bone, which is primarily mediated by osteoclasts (bone cells that breaks down bone tissue) and is not a direct effect of metastasized tumour cells&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8086233/&lt;/ref&gt;. Other tumour types with osteolytic metastases include multiple myeloma, non-small cell lung cancer, thyroid cancer, non-Hodgkin lymphoma, and Langerhans' cell histiocytosis. Osteolytic metastases are more common than osteoblastic metastases.<br /> <br /> '''Mixed''' metastases are characterised by the presence of both osteolytic and osteoblastic lesions together in the same area of bone. These metastases are usually present in metastatic gastrointestinal and squamous cancers, as well as in secondary breast cancer. Although breast cancer gives rise to predominantly lytic lesions, around 15–20% of women have sclerotic or both types of lesions&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11346860/&lt;/ref&gt;.<br /> <br /> ==Diagnosis==<br /> <br /> ===Signs and symptoms===<br /> Bone metastases cause major morbidity, and high clinical suspicion should be kept for any patient with cancer that presents with:<br /> <br /> *Severe pain (poorly localised, worse at night)<br /> *Impaired mobility<br /> *[[Pathological fracture|Bone fracture]]<br /> *Bone marrow aplasia<br /> *Symptoms of (metastatic) [[Metastatic spinal cord compression|spinal cord compression]] (MSCC)<br /> *Symptoms in keeping with [[hypercalcaemia]]:<br /> **Constipation<br /> **Fatigue<br /> **Polyuria/polydipsia<br /> **Acute kidney injury (AKI)<br /> **Cardiac arrhythmia<br /> <br /> ===Bloods===<br /> When a patient with cancer presents with any of the signs or symptoms above, basic screening in the form of simple blood testing must be undertaken and complemented with appropriate imaging tests:<br /> <br /> *Full evaluation of bone turnover and potential hypercalcaemia:<br /> **Serum calcium<br /> **Serum phosphate<br /> **25-Hydroxyvitamin D<br /> **Thyroid-stimulating hormone (TSH)<br /> **Parathyroid hormone (PTH)<br /> **Serum creatinine<br /> **Alkaline phosphatase (ALP)<br /> *Full blood count (myelosuppression, anaemia)<br /> *Serum protein electrophoresis (SPEP; myeloma screen)<br /> *Tumour markers (such as PSA in prostate cancer)<br /> <br /> ===Imaging===<br /> Radiological tests are an essential component of diagnosing bony metastases. One or more imaging modalities may be required to confirm suspected cancerous spread to bone.<br /> <br /> '''Plain radiographs''' (X-ray scans) are quick, cost-effective, and widely-available, and should be the initial diagnostic test of choice when investigating bone pain. They are highly specific but lack sensitivity (44-50%) because early-stage metastatic lesions, particularly those up to 1 cm, may be more difficult to visualise. More than 50% of the trabecular bone must be involved before the lesion will be apparent on film and, due to the poor contrast of trabecular bone, lesions within the medulla are often less evident than those within cortical bone&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9025785/&lt;/ref&gt;. As outlined above, sclerotic metastases will appear more radiopaque than the surrounding bone, whereas lytic metastases will appear more radiolucent.<br /> <br /> '''Bone scintigraphy''' (bone scans) on the other hand is highly sensitive but with low specificity. Data from Technetium-99m ('''&lt;sup&gt;99m&lt;/sup&gt;Tc''') scintigraphy have shown false-negative rates as low as 11 to 38% (good sensitivity), with false-positive rates as high as 40% (poor specificity). It thus provides a non-specific osteoblastic indication of bone status, be it inflammatory, traumatic, or neoplastic in origin. Scintigraphy is still more specific and sensitive than either plain radiography or computed tomography, whilst magnetic resonance imaging is more efficacious in assessing vertebral metastases&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/2028061/&lt;/ref&gt;.<br /> <br /> '''Computed tomography''' (CT scans) has a high sensitivity, ranging from 71 to 100%, for the detection of metastatic bone lesions&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9362427/&lt;/ref&gt;. Because of the excellent soft tissue resolution of the images produced by CT, it is a particularly helpful modality to distinguish lytic and sclerotic metastases and to visualise their precise location(s) for biopsy.<br /> <br /> '''Magnetic resonance imaging''' (MRI scans) is useful in assessing bone marrow infiltration by tumour deposits, and is required (whole spine) for the proper diagnosis of [[Metastatic spinal cord compression|MSCC]]. It has similarly high specificity (73 to 100%) and sensitivity (82 to 100%) in screening for bone metastases&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10964746/&lt;/ref&gt;.<br /> <br /> '''Positron emission tomography''' (PET scans) detects tumour indirectly by measuring metabolic activity in the form of fluorodeoxyglucose ('''&lt;sup&gt;18&lt;/sup&gt;F''') tissue uptake. As such, its use is not limited to visualising only bony metastases, as &lt;sup&gt;18&lt;/sup&gt;F PET will reveal non-bony metastatic spread also&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8638000/&lt;/ref&gt;. The accuracy of PET is highly dependent on the primary tumour site from which imaged metastases originate. As a modality it is superior to scintigraphy in the screening of bony metastases from breast (specificity 94%, sensitivity 95%)&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12073051/&lt;/ref&gt; and lung (specificity 99%, sensitivity 92%)&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10478250/&lt;/ref&gt; malignancies, but has lower sensitivity in detecting the comparatively slower-growing bone metastases of prostate and renal cancers&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10520701/&lt;/ref&gt;. <br /> <br /> ===Biopsy===<br /> Sometimes it is necessary to diagnose metastases histologically, by removing cells or tissue from the bone lesion(s) directly. Usually this is in the form of a needle or surgical biopsy, and may be indicated if a primary cancer is not known. If the patient has a known primary cancer, then often imaging alone will suffice for the diagnosis of metastatic bone disease.<br /> <br /> ==Treatment==<br /> There are a variety of therapeutic interventions available to patients presenting with bone metastases, but consideration must be given to several patient-specific and tumour-dependent parameters, which include&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11738947/&lt;/ref&gt; (but are not limited to):<br /> <br /> *Lesion site(s) (localised or widespread)<br /> *Presence of extraskeletal metastasis<br /> *Tumour type and features (like receptors)<br /> *Prior treatment history (and response)<br /> *Clinical symptoms<br /> *Performance status<br /> <br /> ===Radiotherapy===<br /> Radiation therapy can provide excellent pain relief and is the treatment of choice for localised metastatic bone pain. However, the analgesic mechanisms of therapeutic skeletal irradiation are poorly understood. Onset of pain relief is usually quick, with a majority of patients experiencing benefit within one to two weeks. Patients who have little reduction in pain by six weeks are unlikely to demonstrate significant overall benefit&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/24782453/&lt;/ref&gt;. Other than localised bone pain, additional indications for radiotherapy include [[Metastatic spinal cord compression|MSCC]] and bones at high risk for [[pathological fracture]]&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/15978828/&lt;/ref&gt;. Two of the three main divisions of radiation therapy—the third being (sealed source) [[brachytherapy]]—can be used to treat bone metastases: systemic (unsealed source) [[radionuclide therapy]] and [[external beam radiotherapy]] (EBRT). <br /> <br /> '''Local-field [[External beam radiotherapy|EBRT]]''' is the standard choice of radiation therapy for treating bone metastases, as it focally targets the bone lesion and can achieve rates of substantial pain relief of up to 80 to 90%&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/6178497/&lt;/ref&gt;. Randomised controlled trials (RCTs) from the 1990s have shown that a single fraction of 8 gray (Gy) is as effective as fractionated doses of 20 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9681885&lt;/ref&gt;, 24 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10577695&lt;/ref&gt;, and 30 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10577696&lt;/ref&gt;. <br /> <br /> '''Wide-field''' (or '''hemibody''') '''[[External beam radiotherapy|EBRT]]''' is useful for widespread metastatic skeletal disease, though was more commonly used for multifocal pain when other effective therapies (chemo- and radionuclide) were not available. There are no RCTs comparing analgesic effect with and without wide-field radiotherapy. However, in terms of quasi-randomised and low-quality RCTs, there is data to suggest that use of fractionation is no more effective than single fraction treatment&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8823257&lt;/ref&gt;, that increasing doses beyond 8 Gy does not improve overall pain responses&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11395246&lt;/ref&gt;, and adding wide-field to local-field radiotherapy, whilst significantly halting disease progression (lesion size: P = 0.03; lesion number: P = 0.01), increases grade 3 to 4 haematological toxicity&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/1374061&lt;/ref&gt;. [Gy doses from pubmed] + [structures to avoid]. <br /> <br /> '''[[Stereotactic radiotherapy|Stereotactic]] [[External beam radiotherapy|EBRT]]''' is a promising treatment option which delivers higher doses of radiation to tumours in shorter periods in time. When used for extracranial cancers it is interchangeably termed Stereotactic Body Radiation Therapy ('''[[Stereotactic radiotherapy|SBRT]]''') or Stereotactic Ablative Radiotherapy ('''[[Stereotactic radiotherapy|SABR]]'''), the latter of which is appealingly onomatopoeic. When this technique is used for treating malignancy within the brain or some other part of the head, it is termed Stereotactic RadioSurgery ('''[[Stereotactic radiotherapy|SRS]]'''). SBRT/SABR can be used both for primary cancers (lung, liver, prostate, renal) and secondary metastases (bone/spine, lung, liver). There are a number of advantages of stereotactic radiotherapy, the most obvious of which is the potential completion of treatment within a single day, rather than over a number of weeks. The other major benefit is that it obviates the need to irradiate large portions of bone, which lowers the risk of further functional marrow depletion in a patient cohort already at risk of poor marrow reserve. Preserving skeletal marrow function can permit continuous chemotherapy in these patients. The primary limitations of SBRT/SABR are that it is more expensive to deliver than conventional EBRT and that there is a paucity of RCT data comparing its use to standard EBRT management&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/18619121/&lt;/ref&gt;. However, a recent single-centre phase II trial appeared to show that SBRT/SABR provides superior pain relief to conventional multifraction radiotherapy, with no observed difference in adverse events or other aspects of quality of life&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/31021390&lt;/ref&gt;. <br /> <br /> '''[[Radionuclide therapy]]''' (or '''radioisotope therapy''') is the systemic administration of radionuclides (also known as radioisotopes) as unsealed radioactive sources that selectively deliver radiation to tumours or target organs. They are taken up predominantly at sites of bone formation, and are therefore most likely best effective for the palliation of osteoblastic (sclerotic) metastases. Common radionuclides approved for the treatment of painful bone metastases include phosphorus-32 ('''&lt;sup&gt;32&lt;/sup&gt;P'''; ''β''-decay), strontium-89 ('''&lt;sup&gt;89&lt;/sup&gt;Sr'''; ''β''-decay), samarium-153 ('''&lt;sup&gt;153&lt;/sup&gt;Sm'''; ''β''- and ''γ''-decay), and rhenium-186 ('''&lt;sup&gt;186&lt;/sup&gt;Re'''; ''β''- and ''γ''-decay). The added advantage of gamma ray emission during decay is that it permits nuclear imaging monitoring of radionuclide biodistribution during therapy. These radionuclides target bone through various mechanisms. &lt;sup&gt;32&lt;/sup&gt;P passes through inorganic phosphate pathways, whereas &lt;sup&gt;89&lt;/sup&gt;Sr is a calcium mimetic and is taken up as a direct analogue of this earth metal. The final two agents are targeted to bone via chelation to phosphonate compounds: &lt;sup&gt;153&lt;/sup&gt;Sm is paired to ethylenediaminetetramethylenephosphonate (EDTMP) and &lt;sup&gt;186&lt;/sup&gt;Re to 1,1-hydroxyethylidene diphosphonate (HEDP). Common toxicities from treatment include myelosuppression and a transient pain flare, the latter of which usually heralds a favourable response. A more recently developed radionuclide, radium-223 (&lt;sup&gt;'''223'''&lt;/sup&gt;'''Ra'''; ''α''-, ''β''-, and ''γ''-decay) is a calcium mimetic which emits over 95% of decay energy in the form of alpha radiation&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/17062709&lt;/ref&gt;. Owing to their comparatively large size the emitted alpha particles have a more limited depth of penetration into surrounding tissues (around 2–10 cells), thereby producing a more potently localised cytotoxic effect. Despite their symptomatic benefits in refractory, widespread bone metastases, neither &lt;sup&gt;89&lt;/sup&gt;Sr nor &lt;sup&gt;153&lt;/sup&gt;Sm have been shown to improve overall survival in interventional trials; however, &lt;sup&gt;223&lt;/sup&gt;Ra use in metastatic castration-resistant prostate cancer patients in the ALSYMPCA (ALpharadin in SYMptomatic Prostate CAncer) trial was shown to significantly prolong overall survival. <br /> <br /> ===Bisphosphonates===<br /> Poorly localised bone pain/previously irradiated bone lesions<br /> <br /> ===Denosumab===<br /> -<br /> <br /> ===Analgesia===<br /> -<br /> <br /> ===Chemotherapy===<br /> -<br /> <br /> ===Hormonal therapies===<br /> -<br /> <br /> ===Surgery &amp; IR===<br /> -<br /> <br /> ===Bone cement===<br /> -<br /> <br /> ==Living with bone metastases==<br /> Pain, mobility and safety, survival&lt;references /&gt;</div>

Alex https://oncopaedia.net/w/index.php?title=Articles:Bone_metastases&diff=298 2020-04-15T13:07:47Z

<p>Alex: </p> <hr /> <div>Metastases within bone can cause extreme and debilitating pain. Bone metastases are far more common than primary bone cancer, and many different cancer types can spread to the bone. The most common types of cancer which spread to bone are:<br /> <br /> *Breast<br /> *Prostate<br /> *Lung<br /> *Kidney<br /> *Thyroid<br /> <br /> Cancer can theoretically metastasize to any bone in the body, but in reality there is a predilection for certain sites. The most common sites are the vertebrae, ribs, pelvis, sternum, and the skull.<br /> <br /> ==Classification==<br /> A bone is a rigid organ, but it is far from physiologically static. To maintain bone strength, there is continuous breakdown and simultaneous reformation of bone, two processes which must finely balance for good bone health.<br /> <br /> '''Osteoblastic''' (or '''sclerotic''') metastases are characterised by the deposition of new bone. These are present most commonly in prostate cancer, but also occur in carcinoid, small cell lung cancer, medulloblastoma, and Hodgkin lymphoma. The molecular crosstalk between tumour and bone cells involves osteoblast-generating proteins such as Transforming Growth Factor, Bone Morphogenic Proteins (BMPs), and Endothelin-1&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12085970&lt;/ref&gt;.<br /> <br /> '''Osteolytic''' (or '''lytic''') metastases are characterised by the destruction and breakdown of normal bone. These often occur when breast cancer spreads to bone, which is primarily mediated by osteoclasts (bone cells that breaks down bone tissue) and is not a direct effect of metastasized tumour cells&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8086233/&lt;/ref&gt;. Other tumour types with osteolytic metastases include multiple myeloma, non-small cell lung cancer, thyroid cancer, non-Hodgkin lymphoma, and Langerhans' cell histiocytosis. Osteolytic metastases are more common than osteoblastic metastases.<br /> <br /> '''Mixed''' metastases are characterised by the presence of both osteolytic and osteoblastic lesions together in the same area of bone. These metastases are usually present in metastatic gastrointestinal and squamous cancers, as well as in secondary breast cancer. Although breast cancer gives rise to predominantly lytic lesions, around 15–20% of women have sclerotic or both types of lesions&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11346860/&lt;/ref&gt;.<br /> <br /> ==Diagnosis==<br /> <br /> ===Signs and symptoms===<br /> Bone metastases cause major morbidity, and high clinical suspicion should be kept for any patient with cancer that presents with:<br /> <br /> *Severe pain (poorly localised, worse at night)<br /> *Impaired mobility<br /> *[[Pathological fracture|Bone fracture]]<br /> *Bone marrow aplasia<br /> *Symptoms of (metastatic) [[Metastatic spinal cord compression|spinal cord compression]] (MSCC)<br /> *Symptoms in keeping with [[hypercalcaemia]]:<br /> **Constipation<br /> **Fatigue<br /> **Polyuria/polydipsia<br /> **Acute kidney injury (AKI)<br /> **Cardiac arrhythmia<br /> <br /> ===Bloods===<br /> When a patient with cancer presents with any of the signs or symptoms above, basic screening in the form of simple blood testing must be undertaken and complemented with appropriate imaging tests:<br /> <br /> *Full evaluation of bone turnover and potential hypercalcaemia:<br /> **Serum calcium<br /> **Serum phosphate<br /> **25-Hydroxyvitamin D<br /> **Thyroid-stimulating hormone (TSH)<br /> **Parathyroid hormone (PTH)<br /> **Serum creatinine<br /> **Alkaline phosphatase (ALP)<br /> *Full blood count (myelosuppression, anaemia)<br /> *Serum protein electrophoresis (SPEP; myeloma screen)<br /> *Tumour markers (such as PSA in prostate cancer)<br /> <br /> ===Imaging===<br /> Radiological tests are an essential component of diagnosing bony metastases. One or more imaging modalities may be required to confirm suspected cancerous spread to bone.<br /> <br /> '''Plain radiographs''' (X-ray scans) are quick, cost-effective, and widely-available, and should be the initial diagnostic test of choice when investigating bone pain. They are highly specific but lack sensitivity (44-50%) because early-stage metastatic lesions, particularly those up to 1 cm, may be more difficult to visualise. More than 50% of the trabecular bone must be involved before the lesion will be apparent on film and, due to the poor contrast of trabecular bone, lesions within the medulla are often less evident than those within cortical bone&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9025785/&lt;/ref&gt;. As outlined above, sclerotic metastases will appear more radiopaque than the surrounding bone, whereas lytic metastases will appear more radiolucent.<br /> <br /> '''Bone scintigraphy''' (bone scans) on the other hand is highly sensitive but with low specificity. Data from Technetium-99m ('''&lt;sup&gt;99m&lt;/sup&gt;Tc''') scintigraphy have shown false-negative rates as low as 11 to 38% (good sensitivity), with false-positive rates as high as 40% (poor specificity). It thus provides a non-specific osteoblastic indication of bone status, be it inflammatory, traumatic, or neoplastic in origin. Scintigraphy is still more specific and sensitive than either plain radiography or computed tomography, whilst magnetic resonance imaging is more efficacious in assessing vertebral metastases&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/2028061/&lt;/ref&gt;.<br /> <br /> '''Computed tomography''' (CT scans) has a high sensitivity, ranging from 71 to 100%, for the detection of metastatic bone lesions&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9362427/&lt;/ref&gt;. Because of the excellent soft tissue resolution of the images produced by CT, it is a particularly helpful modality to distinguish lytic and sclerotic metastases and to visualise their precise location(s) for biopsy.<br /> <br /> '''Magnetic resonance imaging''' (MRI scans) is useful in assessing bone marrow infiltration by tumour deposits, and is required (whole spine) for the proper diagnosis of [[Metastatic spinal cord compression|MSCC]]. It has similarly high specificity (73 to 100%) and sensitivity (82 to 100%) in screening for bone metastases&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10964746/&lt;/ref&gt;.<br /> <br /> '''Positron emission tomography''' (PET scans) detects tumour indirectly by measuring metabolic activity in the form of fluorodeoxyglucose ('''&lt;sup&gt;18&lt;/sup&gt;F''') tissue uptake. As such, its use is not limited to visualising only bony metastases, as &lt;sup&gt;18&lt;/sup&gt;F PET will reveal non-bony metastatic spread also&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8638000/&lt;/ref&gt;. The accuracy of PET is highly dependent on the primary tumour site from which imaged metastases originate. As a modality it is superior to scintigraphy in the screening of bony metastases from breast (specificity 94%, sensitivity 95%)&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12073051/&lt;/ref&gt; and lung (specificity 99%, sensitivity 92%)&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10478250/&lt;/ref&gt; malignancies, but has lower sensitivity in detecting the comparatively slower-growing bone metastases of prostate and renal cancers&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10520701/&lt;/ref&gt;. <br /> <br /> ===Biopsy===<br /> Sometimes it is necessary to diagnose metastases histologically, by removing cells or tissue from the bone lesion(s) directly. Usually this is in the form of a needle or surgical biopsy, and may be indicated if a primary cancer is not known. If the patient has a known primary cancer, then often imaging alone will suffice for the diagnosis of metastatic bone disease.<br /> <br /> ==Treatment==<br /> There are a variety of therapeutic interventions available to patients presenting with bone metastases, but consideration must be given to several patient-specific and tumour-dependent parameters, which include&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11738947/&lt;/ref&gt; (but are not limited to):<br /> <br /> *Lesion site(s) (localised or widespread)<br /> *Presence of extraskeletal metastasis<br /> *Tumour type and features (like receptors)<br /> *Prior treatment history (and response)<br /> *Clinical symptoms<br /> *Performance status<br /> <br /> ===Radiotherapy===<br /> Radiation therapy can provide excellent pain relief and is the treatment of choice for localised metastatic bone pain. However, the analgesic mechanisms of therapeutic skeletal irradiation are poorly understood. Onset of pain relief is usually quick, with a majority of patients experiencing benefit within one to two weeks. Patients who have little reduction in pain by six weeks are unlikely to demonstrate significant overall benefit&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/24782453/&lt;/ref&gt;. Other than localised bone pain, additional indications for radiotherapy include [[Metastatic spinal cord compression|MSCC]] and bones at high risk for [[pathological fracture]]&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/15978828/&lt;/ref&gt;. Two of the three main divisions of radiation therapy—the third being (sealed source) [[brachytherapy]]—can be used to treat bone metastases: systemic (unsealed source) [[radionuclide therapy]] and [[external beam radiotherapy]] (EBRT). <br /> <br /> '''Local-field [[External beam radiotherapy|EBRT]]''' is the standard choice of radiation therapy for treating bone metastases, as it focally targets the bone lesion and can achieve rates of substantial pain relief of up to 80 to 90%&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/6178497/&lt;/ref&gt;. Randomised controlled trials (RCTs) from the 1990s have shown that a single fraction of 8 gray (Gy) is as effective as fractionated doses of 20 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9681885&lt;/ref&gt;, 24 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10577695&lt;/ref&gt;, and 30 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10577696&lt;/ref&gt;. <br /> <br /> '''Wide-field''' (or '''hemibody''') '''[[External beam radiotherapy|EBRT]]''' is useful for widespread metastatic skeletal disease, though was more commonly used for multifocal pain when other effective therapies (chemo- and radionuclide) were not available. There are no RCTs comparing analgesic effect with and without wide-field radiotherapy. However, in terms of quasi-randomised and low-quality RCTs, there is data to suggest that use of fractionation is no more effective than single fraction treatment&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8823257&lt;/ref&gt;, that increasing doses beyond 8 Gy does not improve overall pain responses&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11395246&lt;/ref&gt;, and adding wide-field to local-field radiotherapy, whilst significantly halting disease progression (lesion size: P = 0.03; lesion number: P = 0.01), increases grade 3 to 4 haematological toxicity&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/1374061&lt;/ref&gt;. [Gy doses from pubmed] + [structures to avoid]. <br /> <br /> '''[[Stereotactic radiotherapy|Stereotactic]] [[External beam radiotherapy|EBRT]]''' is a promising treatment option which delivers higher doses of radiation to tumours in shorter periods in time. When used for extracranial cancers it is interchangeably termed Stereotactic Body Radiation Therapy ('''[[Stereotactic radiotherapy|SBRT]]''') or Stereotactic Ablative Radiotherapy ('''[[Stereotactic radiotherapy|SABR]]'''), the latter of which is appealingly onomatopoeic. When this technique is used for treating malignancy within the brain or some other part of the head, it is termed Stereotactic Radiosurgery ('''[[Stereotactic radiotherapy|SRS]]'''). SBRT/SABR can be used both for primary cancers (lung, liver, prostate, renal) and secondary metastases (bone/spine, lung, liver). There are a number of advantages of stereotactic radiotherapy, the most obvious of which is the potential completion of treatment within a single day, rather than over a number of weeks. The other major benefit is that it obviates the need to irradiate large portions of bone, which lowers the risk of further functional marrow depletion in a patient cohort already at risk of poor marrow reserve. Preserving skeletal marrow function can permit continuous chemotherapy in these patients. The primary limitations of SBRT/SABR are that it is more expensive to deliver than conventional EBRT and that there is a paucity of RCT data comparing its use to standard EBRT management&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/18619121/&lt;/ref&gt;. However, a recent single-centre phase II trial appeared to show that SBRT/SABR provides superior pain relief to conventional multifraction radiotherapy, with no observed difference in adverse events or other aspects of quality of life&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/31021390&lt;/ref&gt;. <br /> <br /> '''[[Radionuclide therapy]]''' (or '''radioisotope therapy''') is the systemic administration of radionuclides (also known as radioisotopes) as unsealed radioactive sources that selectively deliver radiation to tumours or target organs. They are taken up predominantly at sites of bone formation, and are therefore most likely best effective for the palliation of osteoblastic (sclerotic) metastases. Common radionuclides approved for the treatment of painful bone metastases include phosphorus-32 ('''&lt;sup&gt;32&lt;/sup&gt;P'''; ''β''-decay), strontium-89 ('''&lt;sup&gt;89&lt;/sup&gt;Sr'''; ''β''-decay), samarium-153 ('''&lt;sup&gt;153&lt;/sup&gt;Sm'''; ''β''- and ''γ''-decay), and rhenium-186 ('''&lt;sup&gt;186&lt;/sup&gt;Re'''; ''β''- and ''γ''-decay). The added advantage of gamma ray emission during decay is that it permits nuclear imaging monitoring of radionuclide biodistribution during therapy. These radionuclides target bone through various mechanisms. &lt;sup&gt;32&lt;/sup&gt;P passes through inorganic phosphate pathways, whereas &lt;sup&gt;89&lt;/sup&gt;Sr is a calcium mimetic and is taken up as a direct analogue of this earth metal. The final two agents are targeted to bone via chelation to phosphonate compounds: &lt;sup&gt;153&lt;/sup&gt;Sm is paired to ethylenediaminetetramethylenephosphonate (EDTMP) and &lt;sup&gt;186&lt;/sup&gt;Re to 1,1-hydroxyethylidene diphosphonate (HEDP). Common toxicities from treatment include myelosuppression and a transient pain flare, the latter of which usually heralds a favourable response. A more recently developed radionuclide, radium-223 (&lt;sup&gt;'''223'''&lt;/sup&gt;'''Ra'''; ''α''-, ''β''-, and ''γ''-decay) is a calcium mimetic which emits over 95% of decay energy in the form of alpha radiation&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/17062709&lt;/ref&gt;. Owing to their comparatively large size these alpha particles have a more limited depth of penetration into surrounding tissues (around 2–10 cells), thereby producing a more potently localised cytotoxic effect. Despite their symptomatic benefits in refractory, widespread bone metastases, neither &lt;sup&gt;89&lt;/sup&gt;Sr nor &lt;sup&gt;153&lt;/sup&gt;Sm have been shown to improve overall survival in phase III trials; however, [ALSYMPCA] <br /> <br /> ===Bisphosphonates===<br /> Poorly localised bone pain/previously irradiated bone lesions<br /> <br /> ===Denosumab===<br /> -<br /> <br /> ===Analgesia===<br /> -<br /> <br /> ===Chemotherapy===<br /> -<br /> <br /> ===Hormonal therapies===<br /> -<br /> <br /> ===Surgery &amp; IR===<br /> -<br /> <br /> ===Bone cement===<br /> -<br /> <br /> ==Living with bone metastases==<br /> Pain, mobility and safety, survival&lt;references /&gt;</div>

Alex https://oncopaedia.net/w/index.php?title=Articles:Bone_metastases&diff=297 2020-04-15T11:24:18Z

<p>Alex: </p> <hr /> <div>Metastases within bone can cause extreme and debilitating pain. Bone metastases are far more common than primary bone cancer, and many different cancer types can spread to the bone. The most common types of cancer which spread to bone are:<br /> <br /> *Breast<br /> *Prostate<br /> *Lung<br /> *Kidney<br /> *Thyroid<br /> <br /> Cancer can theoretically metastasize to any bone in the body, but in reality there is a predilection for certain sites. The most common sites are the vertebrae, ribs, pelvis, sternum, and the skull.<br /> <br /> ==Classification==<br /> A bone is a rigid organ, but it is far from physiologically static. To maintain bone strength, there is continuous breakdown and simultaneous reformation of bone, two processes which must finely balance for good bone health.<br /> <br /> '''Osteoblastic''' (or '''sclerotic''') metastases are characterised by the deposition of new bone. These are present most commonly in prostate cancer, but also occur in carcinoid, small cell lung cancer, medulloblastoma, and Hodgkin lymphoma. The molecular crosstalk between tumour and bone cells involves osteoblast-generating proteins such as Transforming Growth Factor, Bone Morphogenic Proteins (BMPs), and Endothelin-1&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12085970&lt;/ref&gt;.<br /> <br /> '''Osteolytic''' (or '''lytic''') metastases are characterised by the destruction and breakdown of normal bone. These often occur when breast cancer spreads to bone, which is primarily mediated by osteoclasts (bone cells that breaks down bone tissue) and is not a direct effect of metastasized tumour cells&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8086233/&lt;/ref&gt;. Other tumour types with osteolytic metastases include multiple myeloma, non-small cell lung cancer, thyroid cancer, non-Hodgkin lymphoma, and Langerhans' cell histiocytosis. Osteolytic metastases are more common than osteoblastic metastases.<br /> <br /> '''Mixed''' metastases are characterised by the presence of both osteolytic and osteoblastic lesions together in the same area of bone. These metastases are usually present in metastatic gastrointestinal and squamous cancers, as well as in secondary breast cancer. Although breast cancer gives rise to predominantly lytic lesions, around 15–20% of women have sclerotic or both types of lesions&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11346860/&lt;/ref&gt;.<br /> <br /> ==Diagnosis==<br /> <br /> ===Signs and symptoms===<br /> Bone metastases cause major morbidity, and high clinical suspicion should be kept for any patient with cancer that presents with:<br /> <br /> *Severe pain (poorly localised, worse at night)<br /> *Impaired mobility<br /> *[[Pathological fracture|Bone fracture]]<br /> *Bone marrow aplasia<br /> *Symptoms of (metastatic) [[Metastatic spinal cord compression|spinal cord compression]] (MSCC)<br /> *Symptoms in keeping with [[hypercalcaemia]]:<br /> **Constipation<br /> **Fatigue<br /> **Polyuria/polydipsia<br /> **Acute kidney injury (AKI)<br /> **Cardiac arrhythmia<br /> <br /> ===Bloods===<br /> When a patient with cancer presents with any of the signs or symptoms above, basic screening in the form of simple blood testing must be undertaken and complemented with appropriate imaging tests:<br /> <br /> *Full evaluation of bone turnover and potential hypercalcaemia:<br /> **Serum calcium<br /> **Serum phosphate<br /> **25-Hydroxyvitamin D<br /> **Thyroid-stimulating hormone (TSH)<br /> **Parathyroid hormone (PTH)<br /> **Serum creatinine<br /> **Alkaline phosphatase (ALP)<br /> *Full blood count (myelosuppression, anaemia)<br /> *Serum protein electrophoresis (SPEP; myeloma screen)<br /> *Tumour markers (such as PSA in prostate cancer)<br /> <br /> ===Imaging===<br /> Radiological tests are an essential component of diagnosing bony metastases. One or more imaging modalities may be required to confirm suspected cancerous spread to bone.<br /> <br /> '''Plain radiographs''' (X-ray scans) are quick, cost-effective, and widely-available, and should be the initial diagnostic test of choice when investigating bone pain. They are highly specific but lack sensitivity (44-50%) because early-stage metastatic lesions, particularly those up to 1 cm, may be more difficult to visualise. More than 50% of the trabecular bone must be involved before the lesion will be apparent on film and, due to the poor contrast of trabecular bone, lesions within the medulla are often less evident than those within cortical bone&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9025785/&lt;/ref&gt;. As outlined above, sclerotic metastases will appear more radiopaque than the surrounding bone, whereas lytic metastases will appear more radiolucent.<br /> <br /> '''Bone scintigraphy''' (bone scans) on the other hand is highly sensitive but with low specificity. Data from Technetium-99m ('''&lt;sup&gt;99m&lt;/sup&gt;Tc''') scintigraphy have shown false-negative rates as low as 11 to 38% (good sensitivity), with false-positive rates as high as 40% (poor specificity). It thus provides a non-specific osteoblastic indication of bone status, be it inflammatory, traumatic, or neoplastic in origin. Scintigraphy is still more specific and sensitive than either plain radiography or computed tomography, whilst magnetic resonance imaging is more efficacious in assessing vertebral metastases&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/2028061/&lt;/ref&gt;.<br /> <br /> '''Computed tomography''' (CT scans) has a high sensitivity, ranging from 71 to 100%, for the detection of metastatic bone lesions&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9362427/&lt;/ref&gt;. Because of the excellent soft tissue resolution of the images produced by CT, it is a particularly helpful modality to distinguish lytic and sclerotic metastases and to visualise their precise location(s) for biopsy.<br /> <br /> '''Magnetic resonance imaging''' (MRI scans) is useful in assessing bone marrow infiltration by tumour deposits, and is required (whole spine) for the proper diagnosis of [[Metastatic spinal cord compression|MSCC]]. It has similarly high specificity (73 to 100%) and sensitivity (82 to 100%) in screening for bone metastases&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10964746/&lt;/ref&gt;.<br /> <br /> '''Positron emission tomography''' (PET scans) detects tumour indirectly by measuring metabolic activity in the form of fluorodeoxyglucose ('''&lt;sup&gt;18&lt;/sup&gt;F''') tissue uptake. As such, its use is not limited to visualising only bony metastases, as &lt;sup&gt;18&lt;/sup&gt;F PET will reveal non-bony metastatic spread also&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8638000/&lt;/ref&gt;. The accuracy of PET is highly dependent on the primary tumour site from which imaged metastases originate. As a modality it is superior to scintigraphy in the screening of bony metastases from breast (specificity 94%, sensitivity 95%)&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12073051/&lt;/ref&gt; and lung (specificity 99%, sensitivity 92%)&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10478250/&lt;/ref&gt; malignancies, but has lower sensitivity in detecting the comparatively slower-growing bone metastases of prostate and renal cancers&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10520701/&lt;/ref&gt;. <br /> <br /> ===Biopsy===<br /> Sometimes it is necessary to diagnose metastases histologically, by removing cells or tissue from the bone lesion(s) directly. Usually this is in the form of a needle or surgical biopsy, and may be indicated if a primary cancer is not known. If the patient has a known primary cancer, then often imaging alone will suffice for the diagnosis of metastatic bone disease.<br /> <br /> ==Treatment==<br /> There are a variety of therapeutic interventions available to patients presenting with bone metastases, but consideration must be given to several patient-specific and tumour-dependent parameters, which include&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11738947/&lt;/ref&gt; (but are not limited to):<br /> <br /> *Lesion site(s) (localised or widespread)<br /> *Presence of extraskeletal metastasis<br /> *Tumour type and features (like receptors)<br /> *Prior treatment history (and response)<br /> *Clinical symptoms<br /> *Performance status<br /> <br /> ===Radiotherapy===<br /> Radiation therapy can provide excellent pain relief and is the treatment of choice for localised metastatic bone pain. However, the analgesic mechanisms of therapeutic skeletal irradiation are poorly understood. Onset of pain relief is usually quick, with a majority of patients experiencing benefit within one to two weeks. Patients who have little reduction in pain by six weeks are unlikely to demonstrate significant overall benefit&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/24782453/&lt;/ref&gt;. Other than localised bone pain, additional indications for radiotherapy include [[Metastatic spinal cord compression|MSCC]] and bones at high risk for [[pathological fracture]]&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/15978828/&lt;/ref&gt;. Two of the three main divisions of radiation therapy—the third being (sealed source) [[brachytherapy]]—can be used to treat bone metastases: systemic (unsealed source) [[radionuclide therapy]] and [[external beam radiotherapy]] (EBRT). <br /> <br /> '''Local-field [[External beam radiotherapy|EBRT]]''' is the standard choice of radiation therapy for treating bone metastases, as it focally targets the bone lesion and can achieve rates of substantial pain relief of up to 80 to 90%&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/6178497/&lt;/ref&gt;. Randomised controlled trials (RCTs) from the 1990s have shown that a single fraction of 8 gray (Gy) is as effective as fractionated doses of 20 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9681885&lt;/ref&gt;, 24 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10577695&lt;/ref&gt;, and 30 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10577696&lt;/ref&gt;. <br /> <br /> '''Wide-field''' (or '''hemibody''') '''[[External beam radiotherapy|EBRT]]''' is useful for widespread metastatic skeletal disease, though was more commonly used for multifocal pain when other effective therapies (chemo- and radionuclide) were not available. There are no RCTs comparing analgesic effect with and without wide-field radiotherapy. However, in terms of quasi-randomised and low-quality RCTs, there is data to suggest that use of fractionation is no more effective than single fraction treatment&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8823257&lt;/ref&gt;, that increasing doses beyond 8 Gy does not improve overall pain responses&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11395246&lt;/ref&gt;, and adding wide-field to local-field radiotherapy, whilst significantly halting disease progression (lesion size: P = 0.03; lesion number: P = 0.01), increases grade 3 to 4 haematological toxicity&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/1374061&lt;/ref&gt;. [Gy doses from pubmed] + [structures to avoid]. <br /> <br /> '''[[Stereotactic radiotherapy|Stereotactic]] [[External beam radiotherapy|EBRT]]''' is a promising treatment option which delivers higher doses of radiation to tumours in shorter periods in time. When used for extracranial cancers it is interchangeably termed Stereotactic Body Radiation Therapy ('''[[Stereotactic radiotherapy|SBRT]]''') or Stereotactic Ablative Radiotherapy ('''[[Stereotactic radiotherapy|SABR]]'''), the latter of which is appealingly onomatopoeic. When this technique is used for treating malignancy within the brain or some other part of the head, it is termed Stereotactic Radiosurgery ('''[[Stereotactic radiotherapy|SRS]]'''). SBRT/SABR can be used both for primary cancers (lung, liver, prostate, renal) and secondary metastases (bone/spine, lung, liver). There are a number of advantages of stereotactic radiotherapy, the most obvious of which is the potential completion of treatment within a single day, rather than over a number of weeks. The other major benefit is that it obviates the need to irradiate large portions of bone, which lowers the risk of further functional marrow depletion in a patient cohort already at risk of poor marrow reserve. Preserving skeletal marrow function can permit continuous chemotherapy in these patients. The primary limitations of SBRT/SABR are that it is more expensive to deliver than conventional EBRT and that there is a paucity of RCT data comparing its use to standard EBRT management&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/18619121/&lt;/ref&gt;. However, a recent single-centre phase II trial appeared to show that SBRT/SABR provides superior pain relief to conventional multifraction radiotherapy, with no observed difference in adverse events or other aspects of quality of life&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/31021390&lt;/ref&gt;. <br /> <br /> '''[[Radionuclide therapy]]''' (or '''radioisotope therapy''') is the systemic administration of radionuclides (also known as radioisotopes) as unsealed radioactive sources that selectively deliver radiation to tumours or target organs. They are taken up predominantly at sites of bone formation, and are therefore most likely best effective for the palliation of osteoblastic (sclerotic) metastases. Common radionuclides approved for treatment of painful bone metastases include phosphorus-32 ('''&lt;sup&gt;32&lt;/sup&gt;P'''; ''β''-decay), strontium-89 ('''&lt;sup&gt;89&lt;/sup&gt;Sr'''; ''β''-decay), samarium-153 ('''&lt;sup&gt;153&lt;/sup&gt;Sm'''; ''β''- and ''γ''-decay), and rhenium-186 ('''&lt;sup&gt;186&lt;/sup&gt;Re'''; ''β''- and ''γ''-decay). The added advantage of gamma ray emission during decay is that it permits nuclear imaging monitoring of radionuclide biodistribution during therapy. These radionuclides target bone through various mechanisms. &lt;sup&gt;32&lt;/sup&gt;P passes through inorganic phosphate pathways, whereas &lt;sup&gt;89&lt;/sup&gt;Sr is a calcium mimetic and is taken up as a direct analogue of this earth metal. The final two agents are targeted to bone via chelation to phosphonate compounds: &lt;sup&gt;153&lt;/sup&gt;Sm is paired to ethylenediaminetetramethylenephosphonate (EDTMP) and &lt;sup&gt;186&lt;/sup&gt;Re to 1,1-hydroxyethylidene diphosphonate (HEDP). Common toxicities from treatment include myelosuppression and a transient pain flare, the latter of which usually heralds a favourable response. A more recently developed radionuclide, radium-223 (&lt;sup&gt;'''223'''&lt;/sup&gt;'''Ra'''; ''α''-, ''β''-, and ''γ''-decay) is a calcium mimetic which emits over 95% of decay energy in the form of alpha radiation&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/17062709&lt;/ref&gt;. These alpha particles have a much more limited penetration into surrounding tissues (around 2–10 cells), thereby producing a more potently localised cytotoxic effect. [ALSYMPCA] <br /> <br /> ===Bisphosphonates===<br /> Poorly localised bone pain/previously irradiated bone lesions<br /> <br /> ===Denosumab===<br /> -<br /> <br /> ===Analgesia===<br /> -<br /> <br /> ===Chemotherapy===<br /> -<br /> <br /> ===Hormonal therapies===<br /> -<br /> <br /> ===Surgery &amp; IR===<br /> -<br /> <br /> ===Bone cement===<br /> -<br /> <br /> ==Living with bone metastases==<br /> Pain, mobility and safety, survival&lt;references /&gt;</div>

Alex https://oncopaedia.net/w/index.php?title=Articles:Bone_metastases&diff=296 2020-04-15T10:52:22Z

<p>Alex: </p> <hr /> <div>Metastases within bone can cause extreme and debilitating pain. Bone metastases are far more common than primary bone cancer, and many different cancer types can spread to the bone. The most common types of cancer which spread to bone are:<br /> <br /> *Breast<br /> *Prostate<br /> *Lung<br /> *Kidney<br /> *Thyroid<br /> <br /> Cancer can theoretically metastasize to any bone in the body, but in reality there is a predilection for certain sites. The most common sites are the vertebrae, ribs, pelvis, sternum, and the skull.<br /> <br /> ==Classification==<br /> A bone is a rigid organ, but it is far from physiologically static. To maintain bone strength, there is continuous breakdown and simultaneous reformation of bone, two processes which must finely balance for good bone health.<br /> <br /> '''Osteoblastic''' (or '''sclerotic''') metastases are characterised by the deposition of new bone. These are present most commonly in prostate cancer, but also occur in carcinoid, small cell lung cancer, medulloblastoma, and Hodgkin lymphoma. The molecular crosstalk between tumour and bone cells involves osteoblast-generating proteins such as Transforming Growth Factor, Bone Morphogenic Proteins (BMPs), and Endothelin-1&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12085970&lt;/ref&gt;.<br /> <br /> '''Osteolytic''' (or '''lytic''') metastases are characterised by the destruction and breakdown of normal bone. These often occur when breast cancer spreads to bone, which is primarily mediated by osteoclasts (bone cells that breaks down bone tissue) and is not a direct effect of metastasized tumour cells&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8086233/&lt;/ref&gt;. Other tumour types with osteolytic metastases include multiple myeloma, non-small cell lung cancer, thyroid cancer, non-Hodgkin lymphoma, and Langerhans' cell histiocytosis. Osteolytic metastases are more common than osteoblastic metastases.<br /> <br /> '''Mixed''' metastases are characterised by the presence of both osteolytic and osteoblastic lesions together in the same area of bone. These metastases are usually present in metastatic gastrointestinal and squamous cancers, as well as in secondary breast cancer. Although breast cancer gives rise to predominantly lytic lesions, around 15–20% of women have sclerotic or both types of lesions&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11346860/&lt;/ref&gt;.<br /> <br /> ==Diagnosis==<br /> <br /> ===Signs and symptoms===<br /> Bone metastases cause major morbidity, and high clinical suspicion should be kept for any patient with cancer that presents with:<br /> <br /> *Severe pain (poorly localised, worse at night)<br /> *Impaired mobility<br /> *[[Pathological fracture|Bone fracture]]<br /> *Bone marrow aplasia<br /> *Symptoms of (metastatic) [[Metastatic spinal cord compression|spinal cord compression]] (MSCC)<br /> *Symptoms in keeping with [[hypercalcaemia]]:<br /> **Constipation<br /> **Fatigue<br /> **Polyuria/polydipsia<br /> **Acute kidney injury (AKI)<br /> **Cardiac arrhythmia<br /> <br /> ===Bloods===<br /> When a patient with cancer presents with any of the signs or symptoms above, basic screening in the form of simple blood testing must be undertaken and complemented with appropriate imaging tests:<br /> <br /> *Full evaluation of bone turnover and potential hypercalcaemia:<br /> **Serum calcium<br /> **Serum phosphate<br /> **25-Hydroxyvitamin D<br /> **Thyroid-stimulating hormone (TSH)<br /> **Parathyroid hormone (PTH)<br /> **Serum creatinine<br /> **Alkaline phosphatase (ALP)<br /> *Full blood count (myelosuppression, anaemia)<br /> *Serum protein electrophoresis (SPEP; myeloma screen)<br /> *Tumour markers (such as PSA in prostate cancer)<br /> <br /> ===Imaging===<br /> Radiological tests are an essential component of diagnosing bony metastases. One or more imaging modalities may be required to confirm suspected cancerous spread to bone.<br /> <br /> '''Plain radiographs''' (X-ray scans) are quick, cost-effective, and widely-available, and should be the initial diagnostic test of choice when investigating bone pain. They are highly specific but lack sensitivity (44-50%) because early-stage metastatic lesions, particularly those up to 1 cm, may be more difficult to visualise. More than 50% of the trabecular bone must be involved before the lesion will be apparent on film and, due to the poor contrast of trabecular bone, lesions within the medulla are often less evident than those within cortical bone&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9025785/&lt;/ref&gt;. As outlined above, sclerotic metastases will appear more radiopaque than the surrounding bone, whereas lytic metastases will appear more radiolucent.<br /> <br /> '''Bone scintigraphy''' (bone scans) on the other hand is highly sensitive but with low specificity. Data from Technetium-99m ('''&lt;sup&gt;99m&lt;/sup&gt;Tc''') scintigraphy have shown false-negative rates as low as 11 to 38% (good sensitivity), with false-positive rates as high as 40% (poor specificity). It thus provides a non-specific osteoblastic indication of bone status, be it inflammatory, traumatic, or neoplastic in origin. Scintigraphy is still more specific and sensitive than either plain radiography or computed tomography, whilst magnetic resonance imaging is more efficacious in assessing vertebral metastases&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/2028061/&lt;/ref&gt;.<br /> <br /> '''Computed tomography''' (CT scans) has a high sensitivity, ranging from 71 to 100%, for the detection of metastatic bone lesions&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9362427/&lt;/ref&gt;. Because of the excellent soft tissue resolution of the images produced by CT, it is a particularly helpful modality to distinguish lytic and sclerotic metastases and to visualise their precise location(s) for biopsy.<br /> <br /> '''Magnetic resonance imaging''' (MRI scans) is useful in assessing bone marrow infiltration by tumour deposits, and is required (whole spine) for the proper diagnosis of [[Metastatic spinal cord compression|MSCC]]. It has similarly high specificity (73 to 100%) and sensitivity (82 to 100%) in screening for bone metastases&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10964746/&lt;/ref&gt;.<br /> <br /> '''Positron emission tomography''' (PET scans) detects tumour indirectly by measuring metabolic activity in the form of fluorodeoxyglucose ('''&lt;sup&gt;18&lt;/sup&gt;F''') tissue uptake. As such, its use is not limited to visualising only bony metastases, as &lt;sup&gt;18&lt;/sup&gt;F PET will reveal non-bony metastatic spread also&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8638000/&lt;/ref&gt;. The accuracy of PET is highly dependent on the primary tumour site from which imaged metastases originate. As a modality it is superior to scintigraphy in the screening of bony metastases from breast (specificity 94%, sensitivity 95%)&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12073051/&lt;/ref&gt; and lung (specificity 99%, sensitivity 92%)&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10478250/&lt;/ref&gt; malignancies, but has lower sensitivity in detecting the comparatively slower-growing bone metastases of prostate and renal cancers&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10520701/&lt;/ref&gt;. <br /> <br /> ===Biopsy===<br /> Sometimes it is necessary to diagnose metastases histologically, by removing cells or tissue from the bone lesion(s) directly. Usually this is in the form of a needle or surgical biopsy, and may be indicated if a primary cancer is not known. If the patient has a known primary cancer, then often imaging alone will suffice for the diagnosis of metastatic bone disease.<br /> <br /> ==Treatment==<br /> There are a variety of therapeutic interventions available to patients presenting with bone metastases, but consideration must be given to several patient-specific and tumour-dependent parameters, which include&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11738947/&lt;/ref&gt; (but are not limited to):<br /> <br /> *Lesion site(s) (localised or widespread)<br /> *Presence of extraskeletal metastasis<br /> *Tumour type and features (like receptors)<br /> *Prior treatment history (and response)<br /> *Clinical symptoms<br /> *Performance status<br /> <br /> ===Radiotherapy===<br /> Radiation therapy can provide excellent pain relief and is the treatment of choice for localised metastatic bone pain. However, the analgesic mechanisms of therapeutic skeletal irradiation are poorly understood. Onset of pain relief is usually quick, with a majority of patients experiencing benefit within one to two weeks. Patients who have little reduction in pain by six weeks are unlikely to demonstrate significant overall benefit&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/24782453/&lt;/ref&gt;. Other than localised bone pain, additional indications for radiotherapy include [[Metastatic spinal cord compression|MSCC]] and bones at high risk for [[pathological fracture]]&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/15978828/&lt;/ref&gt;. Two of the three main divisions of radiation therapy—the third being (sealed source) [[brachytherapy]]—can be used to treat bone metastases: systemic (unsealed source) [[radionuclide therapy]] and [[external beam radiotherapy]] (EBRT). <br /> <br /> '''Local-field [[External beam radiotherapy|EBRT]]''' is the standard choice of radiation therapy for treating bone metastases, as it focally targets the bone lesion and can achieve rates of substantial pain relief of up to 80 to 90%&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/6178497/&lt;/ref&gt;. Randomised controlled trials (RCTs) from the 1990s have shown that a single fraction of 8 gray (Gy) is as effective as fractionated doses of 20 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9681885&lt;/ref&gt;, 24 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10577695&lt;/ref&gt;, and 30 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10577696&lt;/ref&gt;. <br /> <br /> '''Wide-field''' (or '''hemibody''') '''[[External beam radiotherapy|EBRT]]''' is useful for widespread metastatic skeletal disease, though was more commonly used for multifocal pain when other effective therapies (chemo- and radionuclide) were not available. There are no RCTs comparing analgesic effect with and without wide-field radiotherapy. However, in terms of quasi-randomised and low-quality RCTs, there is data to suggest that use of fractionation is no more effective than single fraction treatment&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8823257&lt;/ref&gt;, that increasing doses beyond 8 Gy does not improve overall pain responses&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11395246&lt;/ref&gt;, and adding wide-field to local-field radiotherapy, whilst significantly halting disease progression (lesion size: P = 0.03; lesion number: P = 0.01), increases grade 3 to 4 haematological toxicity&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/1374061&lt;/ref&gt;. [Gy doses from pubmed] + [structures to avoid]. <br /> <br /> '''[[Stereotactic radiotherapy|Stereotactic]] [[External beam radiotherapy|EBRT]]''' is a promising treatment option which delivers higher doses of radiation to tumours in shorter periods in time. When used for extracranial cancers it is interchangeably termed Stereotactic Body Radiation Therapy ('''[[Stereotactic radiotherapy|SBRT]]''') or Stereotactic Ablative Radiotherapy ('''[[Stereotactic radiotherapy|SABR]]'''), the latter of which is appealingly onomatopoeic. When this technique is used for treating malignancy within the brain or some other part of the head, it is termed Stereotactic Radiosurgery ('''[[Stereotactic radiotherapy|SRS]]'''). SBRT/SABR can be used both for primary cancers (lung, liver, prostate, renal) and secondary metastases (bone/spine, lung, liver). There are a number of advantages of stereotactic radiotherapy, the most obvious of which is the potential completion of treatment within a single day, rather than over a number of weeks. The other major benefit is that it obviates the need to irradiate large portions of bone, which lowers the risk of further functional marrow depletion in a patient cohort already at risk of poor marrow reserve. Preserving skeletal marrow function can permit continuous chemotherapy in these patients. The primary limitations of SBRT/SABR are that it is more expensive to deliver than conventional EBRT and that there is a paucity of RCT data comparing its use to standard EBRT management&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/18619121/&lt;/ref&gt;. However, a recent single-centre phase II trial appeared to show that SBRT/SABR provides superior pain relief to conventional multifraction radiotherapy, with no observed difference in adverse events or other aspects of quality of life&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/31021390&lt;/ref&gt;. <br /> <br /> '''[[Radionuclide therapy]]''' (or '''radioisotope therapy''') is the systemic administration of radionuclides (also known as radioisotopes) as unsealed radioactive sources that selectively deliver radiation to tumours or target organs. They are taken up selectively at sites of new bone formation, and are therefore most likely best effective for palliation of osteoblastic (sclerotic) metastases. Common radionuclides approved for treatment of painful bone metastases include phosphorus-32 ('''&lt;sup&gt;32&lt;/sup&gt;P'''; ''β''-decay), strontium-89 ('''&lt;sup&gt;89&lt;/sup&gt;Sr'''; ''β''-decay), samarium-153 ('''&lt;sup&gt;153&lt;/sup&gt;Sm'''; ''β''- and ''γ''-decay), and rhenium-186 ('''&lt;sup&gt;186&lt;/sup&gt;Re'''; ''β''- and ''γ''-decay). The added advantage of ''γ''-ray emission during decay is that it permits nuclear imaging monitoring of radionuclide biodistribution during therapy. These radionuclides target bone through various mechanisms. &lt;sup&gt;32&lt;/sup&gt;P passes through inorganic phosphate pathways, whereas &lt;sup&gt;89&lt;/sup&gt;Sr is a calcium mimetic and is taken up as a direct analogue of this earth metal. The final two agents are targeted to bone via chelation to phosphonate compounds: &lt;sup&gt;153&lt;/sup&gt;Sm is paired to ethylenediaminetetramethylenephosphonate (EDTMP) and &lt;sup&gt;186&lt;/sup&gt;Re to 1,1-hydroxyethylidene diphosphonate (HEDP). Common toxicities from treatment include myelosuppression and a transient pain flare, the latter of which usually heralds a favourable response. <br /> <br /> ===Bisphosphonates===<br /> Poorly localised bone pain/previously irradiated bone lesions<br /> <br /> ===Denosumab===<br /> -<br /> <br /> ===Analgesia===<br /> -<br /> <br /> ===Chemotherapy===<br /> -<br /> <br /> ===Hormonal therapies===<br /> -<br /> <br /> ===Surgery &amp; IR===<br /> -<br /> <br /> ===Bone cement===<br /> -<br /> <br /> ==Living with bone metastases==<br /> Pain, mobility and safety, survival&lt;references /&gt;</div>

Alex https://oncopaedia.net/w/index.php?title=Articles:Bone_metastases&diff=295 2020-04-15T10:15:03Z

<p>Alex: </p> <hr /> <div>Metastases within bone can cause extreme and debilitating pain. Bone metastases are far more common than primary bone cancer, and many different cancer types can spread to the bone. The most common types of cancer which spread to bone are:<br /> <br /> *Breast<br /> *Prostate<br /> *Lung<br /> *Kidney<br /> *Thyroid<br /> <br /> Cancer can theoretically metastasize to any bone in the body, but in reality there is a predilection for certain sites. The most common sites are the vertebrae, ribs, pelvis, sternum, and the skull.<br /> <br /> ==Classification==<br /> A bone is a rigid organ, but it is far from physiologically static. To maintain bone strength, there is continuous breakdown and simultaneous reformation of bone, two processes which must finely balance for good bone health.<br /> <br /> '''Osteoblastic''' (or '''sclerotic''') metastases are characterised by the deposition of new bone. These are present most commonly in prostate cancer, but also occur in carcinoid, small cell lung cancer, medulloblastoma, and Hodgkin lymphoma. The molecular crosstalk between tumour and bone cells involves osteoblast-generating proteins such as Transforming Growth Factor, Bone Morphogenic Proteins (BMPs), and Endothelin-1&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12085970&lt;/ref&gt;.<br /> <br /> '''Osteolytic''' (or '''lytic''') metastases are characterised by the destruction and breakdown of normal bone. These often occur when breast cancer spreads to bone, which is primarily mediated by osteoclasts (bone cells that breaks down bone tissue) and is not a direct effect of metastasized tumour cells&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8086233/&lt;/ref&gt;. Other tumour types with osteolytic metastases include multiple myeloma, non-small cell lung cancer, thyroid cancer, non-Hodgkin lymphoma, and Langerhans' cell histiocytosis. Osteolytic metastases are more common than osteoblastic metastases.<br /> <br /> '''Mixed''' metastases are characterised by the presence of both osteolytic and osteoblastic lesions together in the same area of bone. These metastases are usually present in metastatic gastrointestinal and squamous cancers, as well as in secondary breast cancer. Although breast cancer gives rise to predominantly lytic lesions, around 15–20% of women have sclerotic or both types of lesions&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11346860/&lt;/ref&gt;.<br /> <br /> ==Diagnosis==<br /> <br /> ===Signs and symptoms===<br /> Bone metastases cause major morbidity, and high clinical suspicion should be kept for any patient with cancer that presents with:<br /> <br /> *Severe pain (poorly localised, worse at night)<br /> *Impaired mobility<br /> *[[Pathological fracture|Bone fracture]]<br /> *Bone marrow aplasia<br /> *Symptoms of (metastatic) [[Metastatic spinal cord compression|spinal cord compression]] (MSCC)<br /> *Symptoms in keeping with [[hypercalcaemia]]:<br /> **Constipation<br /> **Fatigue<br /> **Polyuria/polydipsia<br /> **Acute kidney injury (AKI)<br /> **Cardiac arrhythmia<br /> <br /> ===Bloods===<br /> When a patient with cancer presents with any of the signs or symptoms above, basic screening in the form of simple blood testing must be undertaken and complemented with appropriate imaging tests:<br /> <br /> *Full evaluation of bone turnover and potential hypercalcaemia:<br /> **Serum calcium<br /> **Serum phosphate<br /> **25-Hydroxyvitamin D<br /> **Thyroid-stimulating hormone (TSH)<br /> **Parathyroid hormone (PTH)<br /> **Serum creatinine<br /> **Alkaline phosphatase (ALP)<br /> *Full blood count (myelosuppression, anaemia)<br /> *Serum protein electrophoresis (SPEP; myeloma screen)<br /> *Tumour markers (such as PSA in prostate cancer)<br /> <br /> ===Imaging===<br /> Radiological tests are an essential component of diagnosing bony metastases. One or more imaging modalities may be required to confirm suspected cancerous spread to bone.<br /> <br /> '''Plain radiographs''' (X-ray scans) are quick, cost-effective, and widely-available, and should be the initial diagnostic test of choice when investigating bone pain. They are highly specific but lack sensitivity (44-50%) because early-stage metastatic lesions, particularly those up to 1 cm, may be more difficult to visualise. More than 50% of the trabecular bone must be involved before the lesion will be apparent on film and, due to the poor contrast of trabecular bone, lesions within the medulla are often less evident than those within cortical bone&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9025785/&lt;/ref&gt;. As outlined above, sclerotic metastases will appear more radiopaque than the surrounding bone, whereas lytic metastases will appear more radiolucent.<br /> <br /> '''Bone scintigraphy''' (bone scans) on the other hand is highly sensitive but with low specificity. Data from Technetium-99m ('''&lt;sup&gt;99m&lt;/sup&gt;Tc''') scintigraphy have shown false-negative rates as low as 11 to 38% (good sensitivity), with false-positive rates as high as 40% (poor specificity). It thus provides a non-specific osteoblastic indication of bone status, be it inflammatory, traumatic, or neoplastic in origin. Scintigraphy is still more specific and sensitive than either plain radiography or computed tomography, whilst magnetic resonance imaging is more efficacious in assessing vertebral metastases&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/2028061/&lt;/ref&gt;.<br /> <br /> '''Computed tomography''' (CT scans) has a high sensitivity, ranging from 71 to 100%, for the detection of metastatic bone lesions&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9362427/&lt;/ref&gt;. Because of the excellent soft tissue resolution of the images produced by CT, it is a particularly helpful modality to distinguish lytic and sclerotic metastases and to visualise their precise location(s) for biopsy.<br /> <br /> '''Magnetic resonance imaging''' (MRI scans) is useful in assessing bone marrow infiltration by tumour deposits, and is required (whole spine) for the proper diagnosis of [[Metastatic spinal cord compression|MSCC]]. It has similarly high specificity (73 to 100%) and sensitivity (82 to 100%) in screening for bone metastases&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10964746/&lt;/ref&gt;.<br /> <br /> '''Positron emission tomography''' (PET scans) detects tumour indirectly by measuring metabolic activity in the form of fluorodeoxyglucose ('''&lt;sup&gt;18&lt;/sup&gt;F''') tissue uptake. As such, its use is not limited to visualising only bony metastases, as &lt;sup&gt;18&lt;/sup&gt;F PET will reveal non-bony metastatic spread also&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8638000/&lt;/ref&gt;. The accuracy of PET is highly dependent on the primary tumour site from which imaged metastases originate. As a modality it is superior to scintigraphy in the screening of bony metastases from breast (specificity 94%, sensitivity 95%)&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12073051/&lt;/ref&gt; and lung (specificity 99%, sensitivity 92%)&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10478250/&lt;/ref&gt; malignancies, but has lower sensitivity in detecting the comparatively slower-growing bone metastases of prostate and renal cancers&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10520701/&lt;/ref&gt;. <br /> <br /> ===Biopsy===<br /> Sometimes it is necessary to diagnose metastases histologically, by removing cells or tissue from the bone lesion(s) directly. Usually this is in the form of a needle or surgical biopsy, and may be indicated if a primary cancer is not known. If the patient has a known primary cancer, then often imaging alone will suffice for the diagnosis of metastatic bone disease.<br /> <br /> ==Treatment==<br /> There are a variety of therapeutic interventions available to patients presenting with bone metastases, but consideration must be given to several patient-specific and tumour-dependent parameters, which include&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11738947/&lt;/ref&gt; (but are not limited to):<br /> <br /> *Lesion site(s) (localised or widespread)<br /> *Presence of extraskeletal metastasis<br /> *Tumour type and features (like receptors)<br /> *Prior treatment history (and response)<br /> *Clinical symptoms<br /> *Performance status<br /> <br /> ===Radiotherapy===<br /> Radiation therapy can provide excellent pain relief and is the treatment of choice for localised metastatic bone pain. However, the analgesic mechanisms of therapeutic skeletal irradiation are poorly understood. Onset of pain relief is usually quick, with a majority of patients experiencing benefit within one to two weeks. Patients who have little reduction in pain by six weeks are unlikely to demonstrate significant overall benefit&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/24782453/&lt;/ref&gt;. Other than localised bone pain, additional indications for radiotherapy include [[Metastatic spinal cord compression|MSCC]] and bones at high risk for [[pathological fracture]]&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/15978828/&lt;/ref&gt;. Two of the three main divisions of radiation therapy—the third being (sealed source) [[brachytherapy]]—can be used to treat bone metastases: systemic (unsealed source) [[radionuclide therapy]] and [[external beam radiotherapy]] (EBRT). <br /> <br /> '''Local-field [[External beam radiotherapy|EBRT]]''' is the standard choice of radiation therapy for treating bone metastases, as it focally targets the bone lesion and can achieve rates of substantial pain relief of up to 80 to 90%&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/6178497/&lt;/ref&gt;. Randomised controlled trials (RCTs) from the 1990s have shown that a single fraction of 8 gray (Gy) is as effective as fractionated doses of 20 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9681885&lt;/ref&gt;, 24 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10577695&lt;/ref&gt;, and 30 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10577696&lt;/ref&gt;. <br /> <br /> '''Wide-field''' (or '''hemibody''') '''[[External beam radiotherapy|EBRT]]''' is useful for widespread metastatic skeletal disease, though was more commonly used for multifocal pain when other effective therapies (chemo- and radionuclide) were not available. There are no RCTs comparing analgesic effect with and without wide-field radiotherapy. However, in terms of quasi-randomised and low-quality RCTs, there is data to suggest that use of fractionation is no more effective than single fraction treatment&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8823257&lt;/ref&gt;, that increasing doses beyond 8 Gy does not improve overall pain responses&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11395246&lt;/ref&gt;, and adding wide-field to local-field radiotherapy, whilst significantly halting disease progression (lesion size: P = 0.03; lesion number: P = 0.01), increases grade 3 to 4 haematological toxicity&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/1374061&lt;/ref&gt;. [Gy doses from pubmed] + [structures to avoid]. <br /> <br /> '''[[Stereotactic radiotherapy|Stereotactic]] [[External beam radiotherapy|EBRT]]''' is a promising treatment option which delivers higher doses of radiation to tumours in shorter periods in time. When used for extracranial cancers it is interchangeably termed Stereotactic Body Radiation Therapy ('''[[Stereotactic radiotherapy|SBRT]]''') or Stereotactic Ablative Radiotherapy ('''[[Stereotactic radiotherapy|SABR]]'''), the latter of which is appealingly onomatopoeic. When this technique is used for treating malignancy within the brain or some other part of the head, it is termed Stereotactic Radiosurgery ('''[[Stereotactic radiotherapy|SRS]]'''). SBRT/SABR can be used both for primary cancers (lung, liver, prostate, renal) and secondary metastases (bone/spine, lung, liver). There are a number of advantages of stereotactic radiotherapy, the most obvious of which is the potential completion of treatment within a single day, rather than over a number of weeks. The other major benefit is that it obviates the need to irradiate large portions of bone, which lowers the risk of further functional marrow depletion in a patient cohort already at risk of poor marrow reserve. Preserving skeletal marrow function can permit continuous chemotherapy in these patients. The primary limitations of SBRT/SABR are that it is more expensive to deliver than conventional EBRT and that there is a paucity of RCT data comparing its use to standard EBRT management&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/18619121/&lt;/ref&gt;. However, a recent single-centre phase II trial appeared to show that SBRT/SABR provides superior pain relief to conventional multifraction radiotherapy, with no observed difference in adverse events or other aspects of quality of life&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/31021390&lt;/ref&gt;. <br /> <br /> '''[[Radionuclide therapy]]''' (or '''radioisotope therapy''') is the systemic administration of radionuclides (also known as radioisotopes) as unsealed radioactive sources that selectively deliver radiation to tumours or target organs. Common radionuclides approved for treatment of painful bone metastases include phosphorus-32 ('''&lt;sup&gt;32&lt;/sup&gt;P'''; ''β''-decay), strontium-89 ('''&lt;sup&gt;89&lt;/sup&gt;Sr'''; ''β''-decay), samarium-153 ('''&lt;sup&gt;153&lt;/sup&gt;Sm'''; ''β''- and ''γ''-decay), and rhenium-186 ('''&lt;sup&gt;186&lt;/sup&gt;Re'''; ''β''- and ''γ''-decay). The added advantage of ''γ''-ray emission during decay is that it permits nuclear imaging monitoring of radionuclide biodistribution during therapy. These radionuclides target bone through various mechanisms. &lt;sup&gt;32&lt;/sup&gt;P passes through inorganic phosphate pathways, whereas &lt;sup&gt;89&lt;/sup&gt;Sr is a calcium mimetic and is taken up as a direct analogue of this earth metal. The final two agents are targeted to bone via chelation to phosphonate compounds: <br /> <br /> ===Bisphosphonates===<br /> Poorly localised bone pain/previously irradiated bone lesions<br /> <br /> ===Denosumab===<br /> -<br /> <br /> ===Analgesia===<br /> -<br /> <br /> ===Chemotherapy===<br /> -<br /> <br /> ===Hormonal therapies===<br /> -<br /> <br /> ===Surgery &amp; IR===<br /> -<br /> <br /> ===Bone cement===<br /> -<br /> <br /> ==Living with bone metastases==<br /> Pain, mobility and safety, survival&lt;references /&gt;</div>

Alex https://oncopaedia.net/w/index.php?title=Articles:Bone_metastases&diff=294 2020-04-15T07:52:39Z

<p>Alex: </p> <hr /> <div>Metastases within bone can cause extreme and debilitating pain. Bone metastases are far more common than primary bone cancer, and many different cancer types can spread to the bone. The most common types of cancer which spread to bone are:<br /> <br /> *Breast<br /> *Prostate<br /> *Lung<br /> *Kidney<br /> *Thyroid<br /> <br /> Cancer can theoretically metastasize to any bone in the body, but in reality there is a predilection for certain sites. The most common sites are the vertebrae, ribs, pelvis, sternum, and the skull.<br /> <br /> ==Classification==<br /> A bone is a rigid organ, but it is far from physiologically static. To maintain bone strength, there is continuous breakdown and simultaneous reformation of bone, two processes which must finely balance for good bone health.<br /> <br /> '''Osteoblastic''' (or '''sclerotic''') metastases are characterised by the deposition of new bone. These are present most commonly in prostate cancer, but also occur in carcinoid, small cell lung cancer, medulloblastoma, and Hodgkin lymphoma. The molecular crosstalk between tumour and bone cells involves osteoblast-generating proteins such as Transforming Growth Factor, Bone Morphogenic Proteins (BMPs), and Endothelin-1&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12085970&lt;/ref&gt;.<br /> <br /> '''Osteolytic''' (or '''lytic''') metastases are characterised by the destruction and breakdown of normal bone. These often occur when breast cancer spreads to bone, which is primarily mediated by osteoclasts (bone cells that breaks down bone tissue) and is not a direct effect of metastasized tumour cells&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8086233/&lt;/ref&gt;. Other tumour types with osteolytic metastases include multiple myeloma, non-small cell lung cancer, thyroid cancer, non-Hodgkin lymphoma, and Langerhans' cell histiocytosis. Osteolytic metastases are more common than osteoblastic metastases.<br /> <br /> '''Mixed''' metastases are characterised by the presence of both osteolytic and osteoblastic lesions together in the same area of bone. These metastases are usually present in metastatic gastrointestinal and squamous cancers, as well as in secondary breast cancer. Although breast cancer gives rise to predominantly lytic lesions, around 15–20% of women have sclerotic or both types of lesions&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11346860/&lt;/ref&gt;.<br /> <br /> ==Diagnosis==<br /> <br /> ===Signs and symptoms===<br /> Bone metastases cause major morbidity, and high clinical suspicion should be kept for any patient with cancer that presents with:<br /> <br /> *Severe pain (poorly localised, worse at night)<br /> *Impaired mobility<br /> *[[Pathological fracture|Bone fracture]]<br /> *Bone marrow aplasia<br /> *Symptoms of (metastatic) [[Metastatic spinal cord compression|spinal cord compression]] (MSCC)<br /> *Symptoms in keeping with [[hypercalcaemia]]:<br /> **Constipation<br /> **Fatigue<br /> **Polyuria/polydipsia<br /> **Acute kidney injury (AKI)<br /> **Cardiac arrhythmia<br /> <br /> ===Bloods===<br /> When a patient with cancer presents with any of the signs or symptoms above, basic screening in the form of simple blood testing must be undertaken and complemented with appropriate imaging tests:<br /> <br /> *Full evaluation of bone turnover and potential hypercalcaemia:<br /> **Serum calcium<br /> **Serum phosphate<br /> **25-Hydroxyvitamin D<br /> **Thyroid-stimulating hormone (TSH)<br /> **Parathyroid hormone (PTH)<br /> **Serum creatinine<br /> **Alkaline phosphatase (ALP)<br /> *Full blood count (myelosuppression, anaemia)<br /> *Serum protein electrophoresis (SPEP; myeloma screen)<br /> *Tumour markers (such as PSA in prostate cancer)<br /> <br /> ===Imaging===<br /> Radiological tests are an essential component of diagnosing bony metastases. One or more imaging modalities may be required to confirm suspected cancerous spread to bone.<br /> <br /> '''Plain radiographs''' (X-ray scans) are quick, cost-effective, and widely-available, and should be the initial diagnostic test of choice when investigating bone pain. They are highly specific but lack sensitivity (44-50%) because early-stage metastatic lesions, particularly those up to 1 cm, may be more difficult to visualise. More than 50% of the trabecular bone must be involved before the lesion will be apparent on film and, due to the poor contrast of trabecular bone, lesions within the medulla are often less evident than those within cortical bone&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9025785/&lt;/ref&gt;. As outlined above, sclerotic metastases will appear more radiopaque than the surrounding bone, whereas lytic metastases will appear more radiolucent.<br /> <br /> '''Bone scintigraphy''' (bone scans) on the other hand is highly sensitive but with low specificity. Data from Technetium-99m (&lt;sup&gt;99m&lt;/sup&gt;Tc) scintigraphy have shown false-negative rates as low as 11 to 38% (good sensitivity), with false-positive rates as high as 40% (poor specificity). It thus provides a non-specific osteoblastic indication of bone status, be it inflammatory, traumatic, or neoplastic in origin. Scintigraphy is still more specific and sensitive than either plain radiography or computed tomography, whilst magnetic resonance imaging is more efficacious in assessing vertebral metastases&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/2028061/&lt;/ref&gt;.<br /> <br /> '''Computed tomography''' (CT scans) has a high sensitivity, ranging from 71 to 100%, for the detection of metastatic bone lesions&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9362427/&lt;/ref&gt;. Because of the excellent soft tissue resolution of the images produced by CT, it is a particularly helpful modality to distinguish lytic and sclerotic metastases and to visualise their precise location(s) for biopsy.<br /> <br /> '''Magnetic resonance imaging''' (MRI scans) is useful in assessing bone marrow infiltration by tumour deposits, and is required (whole spine) for the proper diagnosis of [[Metastatic spinal cord compression|MSCC]]. It has similarly high specificity (73 to 100%) and sensitivity (82 to 100%) in screening for bone metastases&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10964746/&lt;/ref&gt;.<br /> <br /> '''Positron emission tomography''' (PET scans) detects tumour indirectly by measuring metabolic activity in the form of fluorodeoxyglucose (&lt;sup&gt;18&lt;/sup&gt;F) tissue uptake. As such, its use is not limited to visualising only bony metastases, as &lt;sup&gt;18&lt;/sup&gt;F PET will reveal non-bony metastatic spread also&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8638000/&lt;/ref&gt;. The accuracy of PET is highly dependent on the primary tumour site from which imaged metastases originate. As a modality it is superior to scintigraphy in the screening of bony metastases from breast (specificity 94%, sensitivity 95%)&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12073051/&lt;/ref&gt; and lung (specificity 99%, sensitivity 92%)&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10478250/&lt;/ref&gt; malignancies, but has lower sensitivity in detecting the comparatively slower-growing bone metastases of prostate and renal cancers&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10520701/&lt;/ref&gt;. <br /> <br /> ===Biopsy===<br /> Sometimes it is necessary to diagnose metastases histologically, by removing cells or tissue from the bone lesion(s) directly. Usually this is in the form of a needle or surgical biopsy, and may be indicated if a primary cancer is not known. If the patient has a known primary cancer, then often imaging alone will suffice for the diagnosis of metastatic bone disease.<br /> <br /> ==Treatment==<br /> There are a variety of therapeutic interventions available to patients presenting with bone metastases, but consideration must be given to several patient-specific and tumour-dependent parameters, which include&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11738947/&lt;/ref&gt; (but are not limited to):<br /> <br /> *Lesion site(s) (localised or widespread)<br /> *Presence of extraskeletal metastasis<br /> *Tumour type and features (like receptors)<br /> *Prior treatment history (and response)<br /> *Clinical symptoms<br /> *Performance status<br /> <br /> ===Radiotherapy===<br /> Radiation therapy can provide excellent pain relief and is the treatment of choice for localised metastatic bone pain. However, the analgesic mechanisms of therapeutic skeletal irradiation are poorly understood. Onset of pain relief is usually quick, with a majority of patients experiencing benefit within one to two weeks. Patients who have little reduction in pain by six weeks are unlikely to demonstrate significant overall benefit&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/24782453/&lt;/ref&gt;. Other than localised bone pain, additional indications for radiotherapy include [[Metastatic spinal cord compression|MSCC]] and bones at high risk for [[pathological fracture]]&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/15978828/&lt;/ref&gt;. Two of the three main divisions of radiation therapy—the third being (sealed source) [[brachytherapy]]—can be used to treat bone metastases: systemic (unsealed source) [[radionuclide therapy]] and [[external beam radiotherapy]] (EBRT). <br /> <br /> '''Local-field [[External beam radiotherapy|EBRT]]''' is the standard choice of radiation therapy for treating bone metastases, as it focally targets the bone lesion and can achieve rates of substantial pain relief of up to 80 to 90%&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/6178497/&lt;/ref&gt;. Randomised controlled trials (RCTs) from the 1990s have shown that a single fraction of 8 gray (Gy) is as effective as fractionated doses of 20 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9681885&lt;/ref&gt;, 24 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10577695&lt;/ref&gt;, and 30 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10577696&lt;/ref&gt;. <br /> <br /> '''Wide-field''' (or '''hemibody''') '''[[External beam radiotherapy|EBRT]]''' is useful for widespread metastatic skeletal disease, though was more commonly used for multifocal pain when other effective therapies (chemo- and radionuclide) were not available. There are no RCTs comparing analgesic effect with and without wide-field radiotherapy. However, in terms of quasi-randomised and low-quality RCTs, there is data to suggest that use of fractionation is no more effective than single fraction treatment&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8823257&lt;/ref&gt;, that increasing doses beyond 8 Gy does not improve overall pain responses&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11395246&lt;/ref&gt;, and adding wide-field to local-field radiotherapy, whilst significantly halting disease progression (lesion size: P = 0.03; lesion number: P = 0.01), increases grade 3 to 4 haematological toxicity&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/1374061&lt;/ref&gt;. [Gy doses from pubmed] + [structures to avoid]. <br /> <br /> '''[[Stereotactic radiotherapy|Stereotactic]] [[External beam radiotherapy|EBRT]]''' is a promising treatment option which delivers higher doses of radiation to tumours in shorter periods in time. When used for extracranial cancers it is interchangeably termed Stereotactic Body Radiation Therapy ('''[[Stereotactic radiotherapy|SBRT]]''') or Stereotactic Ablative Radiotherapy ('''[[Stereotactic radiotherapy|SABR]]'''), the latter of which is appealingly onomatopoeic. When this technique is used for treating malignancy within the brain or some other part of the head, it is termed Stereotactic Radiosurgery ('''[[Stereotactic radiotherapy|SRS]]'''). SBRT/SABR can be used both for primary cancers (lung, liver, prostate, renal) and secondary metastases (bone/spine, lung, liver). There are a number of advantages of stereotactic radiotherapy, the most obvious of which is the potential completion of treatment within a single day, rather than over a number of weeks. The other major benefit is that it obviates the need to irradiate large portions of bone, which lowers the risk of further functional marrow depletion in a patient cohort already at risk of poor marrow reserve. Preserving skeletal marrow function can permit continuous chemotherapy in these patients. The primary limitations of SBRT/SABR are that it is more expensive to deliver than conventional EBRT and that there is a paucity of RCT data comparing its use to standard EBRT management&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/18619121/&lt;/ref&gt;. However, a recent single-centre phase II trial appeared to show that SBRT/SABR provides superior pain relief to conventional multifraction radiotherapy, with no observed difference in adverse events or other aspects of quality of life&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/31021390&lt;/ref&gt;. <br /> <br /> '''[[Radionuclide therapy]]''' (or '''radioisotope therapy''') is the systemic administration of radionuclides (also known as radioisotopes) as unsealed radioactive sources that selectively deliver radiation to tumours or target organs. Common radionuclides used in the treatment of painful bone metastases include strontium-89 (&lt;sup&gt;89&lt;/sup&gt;Sr; ''β''-decay), samarium-153 (&lt;sup&gt;153&lt;/sup&gt;Sm; ''β''- and ''γ''-decay), and rhenium-186 (&lt;sup&gt;186&lt;/sup&gt;Re; ''β''- and ''γ''-decay). [89Sr is Ca+ mimetic, whereas 153Sm and 186Re are conjugates] + [the advantage of latter two being] that ''γ''-rays emitted during radionuclide decay have sufficient energy for nuclear medicine imaging, and therefore the biodistribution of such radionuclides can be assessed and monitored during therapy. <br /> <br /> ===Bisphosphonates===<br /> Poorly localised bone pain/previously irradiated bone lesions<br /> <br /> ===Denosumab===<br /> -<br /> <br /> ===Analgesia===<br /> -<br /> <br /> ===Chemotherapy===<br /> -<br /> <br /> ===Hormonal therapies===<br /> -<br /> <br /> ===Surgery &amp; IR===<br /> -<br /> <br /> ===Bone cement===<br /> -<br /> <br /> ==Living with bone metastases==<br /> Pain, mobility and safety, survival&lt;references /&gt;</div>

Alex https://oncopaedia.net/w/index.php?title=Articles:Bone_metastases&diff=293 2020-04-14T15:05:48Z

<p>Alex: </p> <hr /> <div>Metastases within bone can cause extreme and debilitating pain. Bone metastases are far more common than primary bone cancer, and many different cancer types can spread to the bone. The most common types of cancer which spread to bone are:<br /> <br /> *Breast<br /> *Prostate<br /> *Lung<br /> *Kidney<br /> *Thyroid<br /> <br /> Cancer can theoretically metastasize to any bone in the body, but in reality there is a predilection for certain sites. The most common sites are the vertebrae, ribs, pelvis, sternum, and the skull.<br /> <br /> ==Classification==<br /> A bone is a rigid organ, but it is far from physiologically static. To maintain bone strength, there is continuous breakdown and simultaneous reformation of bone, two processes which must finely balance for good bone health.<br /> <br /> '''Osteoblastic''' (or '''sclerotic''') metastases are characterised by the deposition of new bone. These are present most commonly in prostate cancer, but also occur in carcinoid, small cell lung cancer, medulloblastoma, and Hodgkin lymphoma. The molecular crosstalk between tumour and bone cells involves osteoblast-generating proteins such as Transforming Growth Factor, Bone Morphogenic Proteins (BMPs), and Endothelin-1&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12085970&lt;/ref&gt;.<br /> <br /> '''Osteolytic''' (or '''lytic''') metastases are characterised by the destruction and breakdown of normal bone. These often occur when breast cancer spreads to bone, which is primarily mediated by osteoclasts (bone cells that breaks down bone tissue) and is not a direct effect of metastasized tumour cells&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8086233/&lt;/ref&gt;. Other tumour types with osteolytic metastases include multiple myeloma, non-small cell lung cancer, thyroid cancer, non-Hodgkin lymphoma, and Langerhans' cell histiocytosis. Osteolytic metastases are more common than osteoblastic metastases.<br /> <br /> '''Mixed''' metastases are characterised by the presence of both osteolytic and osteoblastic lesions together in the same area of bone. These metastases are usually present in metastatic gastrointestinal and squamous cancers, as well as in secondary breast cancer. Although breast cancer gives rise to predominantly lytic lesions, around 15–20% of women have sclerotic or both types of lesions&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11346860/&lt;/ref&gt;.<br /> <br /> ==Diagnosis==<br /> <br /> ===Signs and symptoms===<br /> Bone metastases cause major morbidity, and high clinical suspicion should be kept for any patient with cancer that presents with:<br /> <br /> *Severe pain (poorly localised, worse at night)<br /> *Impaired mobility<br /> *[[Pathological fracture|Bone fracture]]<br /> *Bone marrow aplasia<br /> *Symptoms of (metastatic) [[Metastatic spinal cord compression|spinal cord compression]] (MSCC)<br /> *Symptoms in keeping with [[hypercalcaemia]]:<br /> **Constipation<br /> **Fatigue<br /> **Polyuria/polydipsia<br /> **Acute kidney injury (AKI)<br /> **Cardiac arrhythmia<br /> <br /> ===Bloods===<br /> When a patient with cancer presents with any of the signs or symptoms above, basic screening in the form of simple blood testing must be undertaken and complemented with appropriate imaging tests:<br /> <br /> *Full evaluation of bone turnover and potential hypercalcaemia:<br /> **Serum calcium<br /> **Serum phosphate<br /> **25-Hydroxyvitamin D<br /> **Thyroid-stimulating hormone (TSH)<br /> **Parathyroid hormone (PTH)<br /> **Serum creatinine<br /> **Alkaline phosphatase (ALP)<br /> *Full blood count (myelosuppression, anaemia)<br /> *Serum protein electrophoresis (SPEP; myeloma screen)<br /> *Tumour markers (such as PSA in prostate cancer)<br /> <br /> ===Imaging===<br /> Radiological tests are an essential component of diagnosing bony metastases. One or more imaging modalities may be required to confirm suspected cancerous spread to bone.<br /> <br /> '''Plain radiographs''' (X-ray scans) are quick, cost-effective, and widely-available, and should be the initial diagnostic test of choice when investigating bone pain. They are highly specific but lack sensitivity (44-50%) because early-stage metastatic lesions, particularly those up to 1 cm, may be more difficult to visualise. More than 50% of the trabecular bone must be involved before the lesion will be apparent on film and, due to the poor contrast of trabecular bone, lesions within the medulla are often less evident than those within cortical bone&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9025785/&lt;/ref&gt;. As outlined above, sclerotic metastases will appear more radiopaque than the surrounding bone, whereas lytic metastases will appear more radiolucent.<br /> <br /> '''Bone scintigraphy''' (bone scans) on the other hand is highly sensitive but with low specificity. Data from Technetium-99m (&lt;sup&gt;99m&lt;/sup&gt;Tc) scintigraphy have shown false-negative rates as low as 11 to 38% (good sensitivity), with false-positive rates as high as 40% (poor specificity). It thus provides a non-specific osteoblastic indication of bone status, be it inflammatory, traumatic, or neoplastic in origin. Scintigraphy is still more specific and sensitive than either plain radiography or computed tomography, whilst magnetic resonance imaging is more efficacious in assessing vertebral metastases&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/2028061/&lt;/ref&gt;.<br /> <br /> '''Computed tomography''' (CT scans) has a high sensitivity, ranging from 71 to 100%, for the detection of metastatic bone lesions&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9362427/&lt;/ref&gt;. Because of the excellent soft tissue resolution of the images produced by CT, it is a particularly helpful modality to distinguish lytic and sclerotic metastases and to visualise their precise location(s) for biopsy.<br /> <br /> '''Magnetic resonance imaging''' (MRI scans) is useful in assessing bone marrow infiltration by tumour deposits, and is required (whole spine) for the proper diagnosis of [[Metastatic spinal cord compression|MSCC]]. It has similarly high specificity (73 to 100%) and sensitivity (82 to 100%) in screening for bone metastases&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10964746/&lt;/ref&gt;.<br /> <br /> '''Positron emission tomography''' (PET scans) detects tumour indirectly by measuring metabolic activity in the form of fluorodeoxyglucose (&lt;sup&gt;18&lt;/sup&gt;F) tissue uptake. As such, its use is not limited to visualising only bony metastases, as &lt;sup&gt;18&lt;/sup&gt;F PET will reveal non-bony metastatic spread also&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8638000/&lt;/ref&gt;. The accuracy of PET is highly dependent on the primary tumour site from which imaged metastases originate. As a modality it is superior to scintigraphy in the screening of bony metastases from breast (specificity 94%, sensitivity 95%)&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12073051/&lt;/ref&gt; and lung (specificity 99%, sensitivity 92%)&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10478250/&lt;/ref&gt; malignancies, but has lower sensitivity in detecting the comparatively slower-growing bone metastases of prostate and renal cancers&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10520701/&lt;/ref&gt;. <br /> <br /> ===Biopsy===<br /> Sometimes it is necessary to diagnose metastases histologically, by removing cells or tissue from the bone lesion(s) directly. Usually this is in the form of a needle or surgical biopsy, and may be indicated if a primary cancer is not known. If the patient has a known primary cancer, then often imaging alone will suffice for the diagnosis of metastatic bone disease.<br /> <br /> ==Treatment==<br /> There are a variety of therapeutic interventions available to patients presenting with bone metastases, but consideration must be given to several patient-specific and tumour-dependent parameters, which include&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11738947/&lt;/ref&gt; (but are not limited to):<br /> <br /> *Lesion site(s) (localised or widespread)<br /> *Presence of extraskeletal metastasis<br /> *Tumour type and features (like receptors)<br /> *Prior treatment history (and response)<br /> *Clinical symptoms<br /> *Performance status<br /> <br /> ===Radiotherapy===<br /> Radiation therapy can provide excellent pain relief and is the treatment of choice for localised metastatic bone pain. However, the analgesic mechanisms of therapeutic skeletal irradiation are poorly understood. Onset of pain relief is usually quick, with a majority of patients experiencing benefit within one to two weeks. Patients who have little reduction in pain by six weeks are unlikely to demonstrate significant overall benefit&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/24782453/&lt;/ref&gt;. Other than localised bone pain, additional indications for radiotherapy include [[Metastatic spinal cord compression|MSCC]] and bones at high risk for [[pathological fracture]]&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/15978828/&lt;/ref&gt;. Two of the three main divisions of radiation therapy—the third being (sealed source) [[brachytherapy]]—can be used to treat bone metastases: systemic (unsealed source) [[radionuclide therapy]] and [[external beam radiotherapy]] (EBRT). <br /> <br /> '''Local-field [[External beam radiotherapy|EBRT]]''' is the standard choice of radiation therapy for treating bone metastases, as it focally targets the bone lesion and can achieve rates of substantial pain relief of up to 80 to 90%&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/6178497/&lt;/ref&gt;. Randomised controlled trials (RCTs) from the 1990s have shown that a single fraction of 8 gray (Gy) is as effective as fractionated doses of 20 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9681885&lt;/ref&gt;, 24 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10577695&lt;/ref&gt;, and 30 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10577696&lt;/ref&gt;. <br /> <br /> '''Wide-field''' (or '''hemibody''') '''[[External beam radiotherapy|EBRT]]''' is useful for widespread metastatic skeletal disease, though was more commonly used for multifocal pain when other effective therapies (chemo- and radionuclide) were not available. There are no RCTs comparing analgesic effect with and without wide-field radiotherapy. However, in terms of quasi-randomised and low-quality RCTs, there is data to suggest that use of fractionation is no more effective than single fraction treatment&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8823257&lt;/ref&gt;, that increasing doses beyond 8 Gy does not improve overall pain responses&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11395246&lt;/ref&gt;, and adding wide-field to local-field radiotherapy, whilst significantly halting disease progression (lesion size: P = 0.03; lesion number: P = 0.01), increases grade 3 to 4 haematological toxicity&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/1374061&lt;/ref&gt;. [Gy doses from pubmed] + [structures to avoid]. <br /> <br /> '''[[Stereotactic radiotherapy|Stereotactic]] [[External beam radiotherapy|EBRT]]''' is a promising treatment option which delivers higher doses of radiation to tumours in shorter periods in time. When used for extracranial cancers it is interchangeably termed Stereotactic Body Radiation Therapy ('''[[Stereotactic radiotherapy|SBRT]]''') or Stereotactic Ablative Radiotherapy ('''[[Stereotactic radiotherapy|SABR]]'''), the latter of which is appealingly onomatopoeic. When this technique is used for treating malignancy within the brain or some other part of the head, it is termed Stereotactic Radiosurgery ('''[[Stereotactic radiotherapy|SRS]]'''). SBRT/SABR can be used both for primary cancers (lung, liver, prostate, renal) and secondary metastases (bone/spine, lung, liver). There are a number of advantages of stereotactic radiotherapy, the most obvious of which is the potential completion of treatment within a single day, rather than over a number of weeks. The other major benefit is that it obviates the need to irradiate large portions of bone, which lowers the risk of further functional marrow depletion in a patient cohort already at risk of poor marrow reserve. Preserving skeletal marrow function can permit continuous chemotherapy in these patients. The primary limitations of SBRT/SABR are that it is more expensive to deliver than conventional EBRT and that there is a paucity of RCT data comparing its use to standard EBRT management&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/18619121/&lt;/ref&gt;. However, a recent single-centre phase II trial appeared to show that SBRT/SABR provides superior pain relief to conventional multifraction radiotherapy, with no observed difference in adverse events or other aspects of quality of life&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/31021390&lt;/ref&gt;. <br /> <br /> '''[[Radionuclide therapy]]''' (or '''radioisotope therapy''') is the systemic administration of radionuclides (also known as radioisotopes) as unsealed radioactive sources that selectively deliver radiation to tumours or target organs. Common radionuclides used in the treatment of painful bone metastases include strontium-89 (&lt;sup&gt;89&lt;/sup&gt;Sr; ''β''-decay), <br /> <br /> ===Bisphosphonates===<br /> Poorly localised bone pain/previously irradiated bone lesions<br /> <br /> ===Denosumab===<br /> -<br /> <br /> ===Analgesia===<br /> -<br /> <br /> ===Chemotherapy===<br /> -<br /> <br /> ===Hormonal therapies===<br /> -<br /> <br /> ===Surgery &amp; IR===<br /> -<br /> <br /> ===Bone cement===<br /> -<br /> <br /> ==Living with bone metastases==<br /> Pain, mobility and safety, survival&lt;references /&gt;</div>

Alex https://oncopaedia.net/w/index.php?title=Articles:Bone_metastases&diff=292 2020-04-14T14:15:47Z

<p>Alex: </p> <hr /> <div>Metastases within bone can cause extreme and debilitating pain. Bone metastases are far more common than primary bone cancer, and many different cancer types can spread to the bone. The most common types of cancer which spread to bone are:<br /> <br /> *Breast<br /> *Prostate<br /> *Lung<br /> *Kidney<br /> *Thyroid<br /> <br /> Cancer can theoretically metastasize to any bone in the body, but in reality there is a predilection for certain sites. The most common sites are the vertebrae, ribs, pelvis, sternum, and the skull.<br /> <br /> ==Classification==<br /> A bone is a rigid organ, but it is far from physiologically static. To maintain bone strength, there is continuous breakdown and simultaneous reformation of bone, two processes which must finely balance for good bone health.<br /> <br /> '''Osteoblastic''' (or '''sclerotic''') metastases are characterised by the deposition of new bone. These are present most commonly in prostate cancer, but also occur in carcinoid, small cell lung cancer, medulloblastoma, and Hodgkin lymphoma. The molecular crosstalk between tumour and bone cells involves osteoblast-generating proteins such as Transforming Growth Factor, Bone Morphogenic Proteins (BMPs), and Endothelin-1&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12085970&lt;/ref&gt;.<br /> <br /> '''Osteolytic''' (or '''lytic''') metastases are characterised by the destruction and breakdown of normal bone. These often occur when breast cancer spreads to bone, which is primarily mediated by osteoclasts (bone cells that breaks down bone tissue) and is not a direct effect of metastasized tumour cells&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8086233/&lt;/ref&gt;. Other tumour types with osteolytic metastases include multiple myeloma, non-small cell lung cancer, thyroid cancer, non-Hodgkin lymphoma, and Langerhans' cell histiocytosis. Osteolytic metastases are more common than osteoblastic metastases.<br /> <br /> '''Mixed''' metastases are characterised by the presence of both osteolytic and osteoblastic lesions together in the same area of bone. These metastases are usually present in metastatic gastrointestinal and squamous cancers, as well as in secondary breast cancer. Although breast cancer gives rise to predominantly lytic lesions, around 15–20% of women have sclerotic or both types of lesions&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11346860/&lt;/ref&gt;.<br /> <br /> ==Diagnosis==<br /> <br /> ===Signs and symptoms===<br /> Bone metastases cause major morbidity, and high clinical suspicion should be kept for any patient with cancer that presents with:<br /> <br /> *Severe pain (poorly localised, worse at night)<br /> *Impaired mobility<br /> *[[Pathological fracture|Bone fracture]]<br /> *Bone marrow aplasia<br /> *Symptoms of (metastatic) [[Metastatic spinal cord compression|spinal cord compression]] (MSCC)<br /> *Symptoms in keeping with [[hypercalcaemia]]:<br /> **Constipation<br /> **Fatigue<br /> **Polyuria/polydipsia<br /> **Acute kidney injury (AKI)<br /> **Cardiac arrhythmia<br /> <br /> ===Bloods===<br /> When a patient with cancer presents with any of the signs or symptoms above, basic screening in the form of simple blood testing must be undertaken and complemented with appropriate imaging tests:<br /> <br /> *Full evaluation of bone turnover and potential hypercalcaemia:<br /> **Serum calcium<br /> **Serum phosphate<br /> **25-Hydroxyvitamin D<br /> **Thyroid-stimulating hormone (TSH)<br /> **Parathyroid hormone (PTH)<br /> **Serum creatinine<br /> **Alkaline phosphatase (ALP)<br /> *Full blood count (myelosuppression, anaemia)<br /> *Serum protein electrophoresis (SPEP; myeloma screen)<br /> *Tumour markers (such as PSA in prostate cancer)<br /> <br /> ===Imaging===<br /> Radiological tests are an essential component of diagnosing bony metastases. One or more imaging modalities may be required to confirm suspected cancerous spread to bone.<br /> <br /> '''Plain radiographs''' (X-ray scans) are quick, cost-effective, and widely-available, and should be the initial diagnostic test of choice when investigating bone pain. They are highly specific but lack sensitivity (44-50%) because early-stage metastatic lesions, particularly those up to 1 cm, may be more difficult to visualise. More than 50% of the trabecular bone must be involved before the lesion will be apparent on film and, due to the poor contrast of trabecular bone, lesions within the medulla are often less evident than those within cortical bone&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9025785/&lt;/ref&gt;. As outlined above, sclerotic metastases will appear more radiopaque than the surrounding bone, whereas lytic metastases will appear more radiolucent.<br /> <br /> '''Bone scintigraphy''' (bone scans) on the other hand is highly sensitive but with low specificity. Data from Technetium-99m (&lt;sup&gt;99m&lt;/sup&gt;Tc) scintigraphy have shown false-negative rates as low as 11 to 38% (good sensitivity), with false-positive rates as high as 40% (poor specificity). It thus provides a non-specific osteoblastic indication of bone status, be it inflammatory, traumatic, or neoplastic in origin. Scintigraphy is still more specific and sensitive than either plain radiography or computed tomography, whilst magnetic resonance imaging is more efficacious in assessing vertebral metastases&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/2028061/&lt;/ref&gt;.<br /> <br /> '''Computed tomography''' (CT scans) has a high sensitivity, ranging from 71 to 100%, for the detection of metastatic bone lesions&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9362427/&lt;/ref&gt;. Because of the excellent soft tissue resolution of the images produced by CT, it is a particularly helpful modality to distinguish lytic and sclerotic metastases and to visualise their precise location(s) for biopsy.<br /> <br /> '''Magnetic resonance imaging''' (MRI scans) is useful in assessing bone marrow infiltration by tumour deposits, and is required (whole spine) for the proper diagnosis of [[Metastatic spinal cord compression|MSCC]]. It has similarly high specificity (73 to 100%) and sensitivity (82 to 100%) in screening for bone metastases&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10964746/&lt;/ref&gt;.<br /> <br /> '''Positron emission tomography''' (PET scans) detects tumour indirectly by measuring metabolic activity in the form of fluorodeoxyglucose (&lt;sup&gt;18&lt;/sup&gt;F) tissue uptake. As such, its use is not limited to visualising only bony metastases, as &lt;sup&gt;18&lt;/sup&gt;F PET will reveal non-bony metastatic spread also&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8638000/&lt;/ref&gt;. The accuracy of PET is highly dependent on the primary tumour site from which imaged metastases originate. As a modality it is superior to scintigraphy in the screening of bony metastases from breast (specificity 94%, sensitivity 95%)&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12073051/&lt;/ref&gt; and lung (specificity 99%, sensitivity 92%)&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10478250/&lt;/ref&gt; malignancies, but has lower sensitivity in detecting the comparatively slower-growing bone metastases of prostate and renal cancers&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10520701/&lt;/ref&gt;. <br /> <br /> ===Biopsy===<br /> Sometimes it is necessary to diagnose metastases histologically, by removing cells or tissue from the bone lesion(s) directly. Usually this is in the form of a needle or surgical biopsy, and may be indicated if a primary cancer is not known. If the patient has a known primary cancer, then often imaging alone will suffice for the diagnosis of metastatic bone disease.<br /> <br /> ==Treatment==<br /> There are a variety of therapeutic interventions available to patients presenting with bone metastases, but consideration must be given to several patient-specific and tumour-dependent parameters, which include&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11738947/&lt;/ref&gt; (but are not limited to):<br /> <br /> *Lesion site(s) (localised or widespread)<br /> *Presence of extraskeletal metastasis<br /> *Tumour type and features (like receptors)<br /> *Prior treatment history (and response)<br /> *Clinical symptoms<br /> *Performance status<br /> <br /> ===Radiotherapy===<br /> Radiation therapy can provide excellent pain relief and is the treatment of choice for localised metastatic bone pain. However, the analgesic mechanisms of therapeutic skeletal irradiation are poorly understood. Onset of pain relief is usually quick, with a majority of patients experiencing benefit within one to two weeks. Patients who have little reduction in pain by six weeks are unlikely to demonstrate significant overall benefit&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/24782453/&lt;/ref&gt;. Other than localised bone pain, additional indications for radiotherapy include [[Metastatic spinal cord compression|MSCC]] and bones at high risk for [[pathological fracture]]&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/15978828/&lt;/ref&gt;. Two of the three main divisions of radiation therapy—the third being (sealed source) [[brachytherapy]]—can be used to treat bone metastases: systemic (unsealed source) [[radionuclide therapy]] and [[external beam radiotherapy]] (EBRT). <br /> <br /> '''Local-field [[External beam radiotherapy|EBRT]]''' is the standard choice of radiation therapy for treating bone metastases, as it focally targets the bone lesion and can achieve rates of substantial pain relief of up to 80 to 90%&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/6178497/&lt;/ref&gt;. Randomised controlled trials (RCTs) from the 1990s have shown that a single fraction of 8 gray (Gy) is as effective as fractionated doses of 20 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9681885&lt;/ref&gt;, 24 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10577695&lt;/ref&gt;, and 30 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10577696&lt;/ref&gt;. <br /> <br /> '''Wide-field''' (or '''hemibody''') '''[[External beam radiotherapy|EBRT]]''' is useful for widespread metastatic skeletal disease, though was more commonly used for multifocal pain when other effective therapies (chemo- and radionuclide) were not available. There are no RCTs comparing analgesic effect with and without wide-field radiotherapy. However, in terms of quasi-randomised and low-quality RCTs, there is data to suggest that use of fractionation is no more effective than single fraction treatment&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8823257&lt;/ref&gt;, that increasing doses beyond 8 Gy does not improve overall pain responses&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11395246&lt;/ref&gt;, and adding wide-field to local-field radiotherapy, whilst significantly halting disease progression (lesion size: P = 0.03; lesion number: P = 0.01), increases grade 3 to 4 haematological toxicity&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/1374061&lt;/ref&gt;. [Gy doses from pubmed] + [structures to avoid]. <br /> <br /> '''[[Stereotactic radiotherapy|Stereotactic]] [[External beam radiotherapy|EBRT]]''' is a promising treatment option which delivers higher doses of radiation to tumours in shorter periods in time. When used for extracranial cancers it is interchangeably termed Stereotactic Body Radiation Therapy ('''[[Stereotactic radiotherapy|SBRT]]''') or Stereotactic Ablative Radiotherapy ('''[[Stereotactic radiotherapy|SABR]]'''), the latter of which is appealingly onomatopoeic. When this technique is used for treating malignancy within the brain or some other part of the head, it is termed Stereotactic Radiosurgery ('''[[Stereotactic radiotherapy|SRS]]'''). SBRT/SABR can be used both for primary cancers (lung, liver, prostate, renal) and secondary metastases (bone/spine, lung, liver). There are a number of advantages of stereotactic radiotherapy, the most obvious of which is the potential completion of treatment within a single day, rather than over a number of weeks. The other major benefit is that it obviates the need to irradiate large portions of bone, which lowers the risk of further functional marrow depletion in a patient cohort already at risk of poor marrow reserve. Preserving skeletal marrow function can permit continuous chemotherapy in these patients. The primary limitations of SBRT/SABR are that it is more expensive to deliver than conventional EBRT and that there is a paucity of RCT data comparing its use to standard EBRT management&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/18619121/&lt;/ref&gt;. However, a recent single-centre phase II trial appeared to show that SBRT/SABR provides superior pain relief to conventional multifraction radiotherapy, with no observed difference in adverse events or other aspects of quality of life&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/31021390&lt;/ref&gt;. <br /> <br /> '''[[Radionuclide therapy]]''' (or '''radioisotope therapy''') is <br /> <br /> ===Bisphosphonates===<br /> Poorly localised bone pain/previously irradiated bone lesions<br /> <br /> ===Denosumab===<br /> -<br /> <br /> ===Analgesia===<br /> -<br /> <br /> ===Chemotherapy===<br /> -<br /> <br /> ===Hormonal therapies===<br /> -<br /> <br /> ===Surgery &amp; IR===<br /> -<br /> <br /> ===Bone cement===<br /> -<br /> <br /> ==Living with bone metastases==<br /> Pain, mobility and safety, survival&lt;references /&gt;</div>

Alex https://oncopaedia.net/w/index.php?title=Articles:Bone_metastases&diff=291 2020-04-10T10:14:13Z

<p>Alex: </p> <hr /> <div>Metastases within bone can cause extreme and debilitating pain. Bone metastases are far more common than primary bone cancer, and many different cancer types can spread to the bone. The most common types of cancer which spread to bone are:<br /> <br /> *Breast<br /> *Prostate<br /> *Lung<br /> *Kidney<br /> *Thyroid<br /> <br /> Cancer can theoretically metastasize to any bone in the body, but in reality there is a predilection for certain sites. The most common sites are the vertebrae, ribs, pelvis, sternum, and the skull.<br /> <br /> ==Classification==<br /> A bone is a rigid organ, but it is far from physiologically static. To maintain bone strength, there is continuous breakdown and simultaneous reformation of bone, two processes which must finely balance for good bone health.<br /> <br /> '''Osteoblastic''' (or '''sclerotic''') metastases are characterised by the deposition of new bone. These are present most commonly in prostate cancer, but also occur in carcinoid, small cell lung cancer, medulloblastoma, and Hodgkin lymphoma. The molecular crosstalk between tumour and bone cells involves osteoblast-generating proteins such as Transforming Growth Factor, Bone Morphogenic Proteins (BMPs), and Endothelin-1&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12085970&lt;/ref&gt;.<br /> <br /> '''Osteolytic''' (or '''lytic''') metastases are characterised by the destruction and breakdown of normal bone. These often occur when breast cancer spreads to bone, which is primarily mediated by osteoclasts (bone cells that breaks down bone tissue) and is not a direct effect of metastasized tumour cells&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8086233/&lt;/ref&gt;. Other tumour types with osteolytic metastases include multiple myeloma, non-small cell lung cancer, thyroid cancer, non-Hodgkin lymphoma, and Langerhans' cell histiocytosis. Osteolytic metastases are more common than osteoblastic metastases.<br /> <br /> '''Mixed''' metastases are characterised by the presence of both osteolytic and osteoblastic lesions together in the same area of bone. These metastases are usually present in metastatic gastrointestinal and squamous cancers, as well as in secondary breast cancer. Although breast cancer gives rise to predominantly lytic lesions, around 15–20% of women have sclerotic or both types of lesions&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11346860/&lt;/ref&gt;.<br /> <br /> ==Diagnosis==<br /> <br /> ===Signs and symptoms===<br /> Bone metastases cause major morbidity, and high clinical suspicion should be kept for any patient with cancer that presents with:<br /> <br /> *Severe pain (poorly localised, worse at night)<br /> *Impaired mobility<br /> *[[Pathological fracture|Bone fracture]]<br /> *Bone marrow aplasia<br /> *Symptoms of (metastatic) [[Metastatic spinal cord compression|spinal cord compression]] (MSCC)<br /> *Symptoms in keeping with [[hypercalcaemia]]:<br /> **Constipation<br /> **Fatigue<br /> **Polyuria/polydipsia<br /> **Acute kidney injury (AKI)<br /> **Cardiac arrhythmia<br /> <br /> ===Bloods===<br /> When a patient with cancer presents with any of the signs or symptoms above, basic screening in the form of simple blood testing must be undertaken and complemented with appropriate imaging tests:<br /> <br /> *Full evaluation of bone turnover and potential hypercalcaemia:<br /> **Serum calcium<br /> **Serum phosphate<br /> **25-Hydroxyvitamin D<br /> **Thyroid-stimulating hormone (TSH)<br /> **Parathyroid hormone (PTH)<br /> **Serum creatinine<br /> **Alkaline phosphatase (ALP)<br /> *Full blood count (myelosuppression, anaemia)<br /> *Serum protein electrophoresis (SPEP; myeloma screen)<br /> *Tumour markers (such as PSA in prostate cancer)<br /> <br /> ===Imaging===<br /> Radiological tests are an essential component of diagnosing bony metastases. One or more imaging modalities may be required to confirm suspected cancerous spread to bone.<br /> <br /> '''Plain radiographs''' (X-ray scans) are quick, cost-effective, and widely-available, and should be the initial diagnostic test of choice when investigating bone pain. They are highly specific but lack sensitivity (44-50%) because early-stage metastatic lesions, particularly those up to 1 cm, may be more difficult to visualise. More than 50% of the trabecular bone must be involved before the lesion will be apparent on film and, due to the poor contrast of trabecular bone, lesions within the medulla are often less evident than those within cortical bone&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9025785/&lt;/ref&gt;. As outlined above, sclerotic metastases will appear more radiopaque than the surrounding bone, whereas lytic metastases will appear more radiolucent.<br /> <br /> '''Bone scintigraphy''' (bone scans) on the other hand is highly sensitive but with low specificity. Data from Technetium-99m (&lt;sup&gt;99m&lt;/sup&gt;Tc) scintigraphy have shown false-negative rates as low as 11 to 38% (good sensitivity), with false-positive rates as high as 40% (poor specificity). It thus provides a non-specific osteoblastic indication of bone status, be it inflammatory, traumatic, or neoplastic in origin. Scintigraphy is still more specific and sensitive than either plain radiography or computed tomography, whilst magnetic resonance imaging is more efficacious in assessing vertebral metastases&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/2028061/&lt;/ref&gt;.<br /> <br /> '''Computed tomography''' (CT scans) has a high sensitivity, ranging from 71 to 100%, for the detection of metastatic bone lesions&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9362427/&lt;/ref&gt;. Because of the excellent soft tissue resolution of the images produced by CT, it is a particularly helpful modality to distinguish lytic and sclerotic metastases and to visualise their precise location(s) for biopsy.<br /> <br /> '''Magnetic resonance imaging''' (MRI scans) is useful in assessing bone marrow infiltration by tumour deposits, and is required (whole spine) for the proper diagnosis of [[Metastatic spinal cord compression|MSCC]]. It has similarly high specificity (73 to 100%) and sensitivity (82 to 100%) in screening for bone metastases&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10964746/&lt;/ref&gt;.<br /> <br /> '''Positron emission tomography''' (PET scans) detects tumour indirectly by measuring metabolic activity in the form of fluorodeoxyglucose (&lt;sup&gt;18&lt;/sup&gt;F) tissue uptake. As such, its use is not limited to visualising only bony metastases, as &lt;sup&gt;18&lt;/sup&gt;F PET will reveal non-bony metastatic spread also&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8638000/&lt;/ref&gt;. The accuracy of PET is highly dependent on the primary tumour site from which imaged metastases originate. As a modality it is superior to scintigraphy in the screening of bony metastases from breast (specificity 94%, sensitivity 95%)&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12073051/&lt;/ref&gt; and lung (specificity 99%, sensitivity 92%)&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10478250/&lt;/ref&gt; malignancies, but has lower sensitivity in detecting the comparatively slower-growing bone metastases of prostate and renal cancers&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10520701/&lt;/ref&gt;. <br /> <br /> ===Biopsy===<br /> Sometimes it is necessary to diagnose metastases histologically, by removing cells or tissue from the bone lesion(s) directly. Usually this is in the form of a needle or surgical biopsy, and may be indicated if a primary cancer is not known. If the patient has a known primary cancer, then often imaging alone will suffice for the diagnosis of metastatic bone disease.<br /> <br /> ==Treatment==<br /> There are a variety of therapeutic interventions available to patients presenting with bone metastases, but consideration must be given to several patient-specific and tumour-dependent parameters, which include&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11738947/&lt;/ref&gt; (but are not limited to):<br /> <br /> *Lesion site(s) (localised or widespread)<br /> *Presence of extraskeletal metastasis<br /> *Tumour type and features (like receptors)<br /> *Prior treatment history (and response)<br /> *Clinical symptoms<br /> *Performance status<br /> <br /> ===Radiotherapy===<br /> Radiation therapy can provide excellent pain relief and is the treatment of choice for localised metastatic bone pain. However, the analgesic mechanisms of therapeutic skeletal irradiation are poorly understood. Onset of pain relief is usually quick, with a majority of patients experiencing benefit within one to two weeks. Patients who have little reduction in pain by six weeks are unlikely to demonstrate significant overall benefit&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/24782453/&lt;/ref&gt;. Other than localised bone pain, additional indications for radiotherapy include [[Metastatic spinal cord compression|MSCC]] and bones at high risk for [[pathological fracture]]&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/15978828/&lt;/ref&gt;. Two of the three main divisions of radiation therapy—the third being (sealed source) [[brachytherapy]]—can be used to treat bone metastases: systemic (unsealed source) [[radionuclide therapy]] and [[external beam radiotherapy]] (EBRT). <br /> <br /> '''Local-field [[External beam radiotherapy|EBRT]]''' is the standard choice of radiation therapy for treating bone metastases, as it focally targets the bone lesion and can achieve rates of substantial pain relief of up to 80 to 90%&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/6178497/&lt;/ref&gt;. Randomised controlled trials (RCTs) from the 1990s have shown that a single fraction of 8 gray (Gy) is as effective as fractionated doses of 20 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9681885&lt;/ref&gt;, 24 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10577695&lt;/ref&gt;, and 30 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10577696&lt;/ref&gt;. <br /> <br /> '''Wide-field''' (or '''hemibody''') '''[[External beam radiotherapy|EBRT]]''' is useful for widespread metastatic skeletal disease, though was more commonly used for multifocal pain when other effective therapies (chemo- and radionuclide) were not available. There are no RCTs comparing analgesic effect with and without wide-field radiotherapy. However, in terms of quasi-randomised and low-quality RCTs, there is data to suggest that use of fractionation is no more effective than single fraction treatment&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8823257&lt;/ref&gt;, that increasing doses beyond 8 Gy does not improve overall pain responses&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11395246&lt;/ref&gt;, and adding wide-field to local-field radiotherapy, whilst significantly halting disease progression (lesion size: P = 0.03; lesion number: P = 0.01), increases grade 3 to 4 haematological toxicity&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/1374061&lt;/ref&gt;. [Gy doses from pubmed] + [structures to avoid]. <br /> <br /> '''[[Stereotactic radiotherapy|Stereotactic]] [[External beam radiotherapy|EBRT]]''' is a promising treatment option which delivers higher doses of radiation to tumours in shorter periods in time. When used for extracranial cancers it is interchangeably termed Stereotactic Body Radiation Therapy ('''[[Stereotactic radiotherapy|SBRT]]''') or Stereotactic Ablative Radiotherapy ('''[[Stereotactic radiotherapy|SABR]]'''), the latter of which is appealingly onomatopoeic. When this technique is used for treating malignancy within the brain or some other part of the head, it is termed Stereotactic Radiosurgery ('''[[Stereotactic radiotherapy|SRS]]'''). SBRT/SABR can be used both for primary cancers (lung, liver, prostate, renal) and secondary metastases (bone/spine, lung, liver). <br /> <br /> '''[[Radionuclide therapy]]''' (or '''radioisotope therapy''') is <br /> <br /> ===Bisphosphonates===<br /> Poorly localised bone pain/previously irradiated bone lesions<br /> <br /> ===Denosumab===<br /> -<br /> <br /> ===Analgesia===<br /> -<br /> <br /> ===Chemotherapy===<br /> -<br /> <br /> ===Hormonal therapies===<br /> -<br /> <br /> ===Surgery===<br /> -<br /> <br /> ===Bone cement===<br /> -<br /> <br /> ==Living with bone metastases==<br /> Pain, mobility and safety, survival&lt;references /&gt;</div>

Alex https://oncopaedia.net/w/index.php?title=Articles:Bone_metastases&diff=290 2020-04-10T09:23:54Z

<p>Alex: </p> <hr /> <div>Metastases within bone can cause extreme and debilitating pain. Bone metastases are far more common than primary bone cancer, and many different cancer types can spread to the bone. The most common types of cancer which spread to bone are:<br /> <br /> *Breast<br /> *Prostate<br /> *Lung<br /> *Kidney<br /> *Thyroid<br /> <br /> Cancer can theoretically metastasize to any bone in the body, but in reality there is a predilection for certain sites. The most common sites are the vertebrae, ribs, pelvis, sternum, and the skull.<br /> <br /> ==Classification==<br /> A bone is a rigid organ, but it is far from physiologically static. To maintain bone strength, there is continuous breakdown and simultaneous reformation of bone, two processes which must finely balance for good bone health.<br /> <br /> '''Osteoblastic''' (or '''sclerotic''') metastases are characterised by the deposition of new bone. These are present most commonly in prostate cancer, but also occur in carcinoid, small cell lung cancer, medulloblastoma, and Hodgkin lymphoma. The molecular crosstalk between tumour and bone cells involves osteoblast-generating proteins such as Transforming Growth Factor, Bone Morphogenic Proteins (BMPs), and Endothelin-1&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12085970&lt;/ref&gt;.<br /> <br /> '''Osteolytic''' (or '''lytic''') metastases are characterised by the destruction and breakdown of normal bone. These often occur when breast cancer spreads to bone, which is primarily mediated by osteoclasts (bone cells that breaks down bone tissue) and is not a direct effect of metastasized tumour cells&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8086233/&lt;/ref&gt;. Other tumour types with osteolytic metastases include multiple myeloma, non-small cell lung cancer, thyroid cancer, non-Hodgkin lymphoma, and Langerhans' cell histiocytosis. Osteolytic metastases are more common than osteoblastic metastases.<br /> <br /> '''Mixed''' metastases are characterised by the presence of both osteolytic and osteoblastic lesions together in the same area of bone. These metastases are usually present in metastatic gastrointestinal and squamous cancers, as well as in secondary breast cancer. Although breast cancer gives rise to predominantly lytic lesions, around 15–20% of women have sclerotic or both types of lesions&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11346860/&lt;/ref&gt;.<br /> <br /> ==Diagnosis==<br /> <br /> ===Signs and symptoms===<br /> Bone metastases cause major morbidity, and high clinical suspicion should be kept for any patient with cancer that presents with:<br /> <br /> *Severe pain (poorly localised, worse at night)<br /> *Impaired mobility<br /> *[[Pathological fracture|Bone fracture]]<br /> *Bone marrow aplasia<br /> *Symptoms of (metastatic) [[Metastatic spinal cord compression|spinal cord compression]] (MSCC)<br /> *Symptoms in keeping with [[hypercalcaemia]]:<br /> **Constipation<br /> **Fatigue<br /> **Polyuria/polydipsia<br /> **Acute kidney injury (AKI)<br /> **Cardiac arrhythmia<br /> <br /> ===Bloods===<br /> When a patient with cancer presents with any of the signs or symptoms above, basic screening in the form of simple blood testing must be undertaken and complemented with appropriate imaging tests:<br /> <br /> *Full evaluation of bone turnover and potential hypercalcaemia:<br /> **Serum calcium<br /> **Serum phosphate<br /> **25-Hydroxyvitamin D<br /> **Thyroid-stimulating hormone (TSH)<br /> **Parathyroid hormone (PTH)<br /> **Serum creatinine<br /> **Alkaline phosphatase (ALP)<br /> *Full blood count (myelosuppression, anaemia)<br /> *Serum protein electrophoresis (SPEP; myeloma screen)<br /> *Tumour markers (such as PSA in prostate cancer)<br /> <br /> ===Imaging===<br /> Radiological tests are an essential component of diagnosing bony metastases. One or more imaging modalities may be required to confirm suspected cancerous spread to bone.<br /> <br /> '''Plain radiographs''' (X-ray scans) are quick, cost-effective, and widely-available, and should be the initial diagnostic test of choice when investigating bone pain. They are highly specific but lack sensitivity (44-50%) because early-stage metastatic lesions, particularly those up to 1 cm, may be more difficult to visualise. More than 50% of the trabecular bone must be involved before the lesion will be apparent on film and, due to the poor contrast of trabecular bone, lesions within the medulla are often less evident than those within cortical bone&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9025785/&lt;/ref&gt;. As outlined above, sclerotic metastases will appear more radiopaque than the surrounding bone, whereas lytic metastases will appear more radiolucent.<br /> <br /> '''Bone scintigraphy''' (bone scans) on the other hand is highly sensitive but with low specificity. Data from Technetium-99m (&lt;sup&gt;99m&lt;/sup&gt;Tc) scintigraphy have shown false-negative rates as low as 11 to 38% (good sensitivity), with false-positive rates as high as 40% (poor specificity). It thus provides a non-specific osteoblastic indication of bone status, be it inflammatory, traumatic, or neoplastic in origin. Scintigraphy is still more specific and sensitive than either plain radiography or computed tomography, whilst magnetic resonance imaging is more efficacious in assessing vertebral metastases&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/2028061/&lt;/ref&gt;.<br /> <br /> '''Computed tomography''' (CT scans) has a high sensitivity, ranging from 71 to 100%, for the detection of metastatic bone lesions&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9362427/&lt;/ref&gt;. Because of the excellent soft tissue resolution of the images produced by CT, it is a particularly helpful modality to distinguish lytic and sclerotic metastases and to visualise their precise location(s) for biopsy.<br /> <br /> '''Magnetic resonance imaging''' (MRI scans) is useful in assessing bone marrow infiltration by tumour deposits, and is required (whole spine) for the proper diagnosis of [[Metastatic spinal cord compression|MSCC]]. It has similarly high specificity (73 to 100%) and sensitivity (82 to 100%) in screening for bone metastases&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10964746/&lt;/ref&gt;.<br /> <br /> '''Positron emission tomography''' (PET scans) detects tumour indirectly by measuring metabolic activity in the form of fluorodeoxyglucose (&lt;sup&gt;18&lt;/sup&gt;F) tissue uptake. As such, its use is not limited to visualising only bony metastases, as &lt;sup&gt;18&lt;/sup&gt;F PET will reveal non-bony metastatic spread also&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8638000/&lt;/ref&gt;. The accuracy of PET is highly dependent on the primary tumour site from which imaged metastases originate. As a modality it is superior to scintigraphy in the screening of bony metastases from breast (specificity 94%, sensitivity 95%)&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12073051/&lt;/ref&gt; and lung (specificity 99%, sensitivity 92%)&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10478250/&lt;/ref&gt; malignancies, but has lower sensitivity in detecting the comparatively slower-growing bone metastases of prostate and renal cancers&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10520701/&lt;/ref&gt;. <br /> <br /> ===Biopsy===<br /> Sometimes it is necessary to diagnose metastases histologically, by removing cells or tissue from the bone lesion(s) directly. Usually this is in the form of a needle or surgical biopsy, and may be indicated if a primary cancer is not known. If the patient has a known primary cancer, then often imaging alone will suffice for the diagnosis of metastatic bone disease.<br /> <br /> ==Treatment==<br /> There are a variety of therapeutic interventions available to patients presenting with bone metastases, but consideration must be given to several patient-specific and tumour-dependent parameters, which include&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11738947/&lt;/ref&gt; (but are not limited to):<br /> <br /> *Lesion site(s) (localised or widespread)<br /> *Presence of extraskeletal metastasis<br /> *Tumour type and features (like receptors)<br /> *Prior treatment history (and response)<br /> *Clinical symptoms<br /> *Performance status<br /> <br /> ===Radiotherapy===<br /> Radiation therapy can provide excellent pain relief and is the treatment of choice for localised metastatic bone pain. However, the analgesic mechanisms of therapeutic skeletal irradiation are poorly understood. Onset of pain relief is usually quick, with a majority of patients experiencing benefit within one to two weeks. Patients who have little reduction in pain by six weeks are unlikely to demonstrate significant overall benefit&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/24782453/&lt;/ref&gt;. Other than localised bone pain, additional indications for radiotherapy include [[Metastatic spinal cord compression|MSCC]] and bones at high risk for [[pathological fracture]]&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/15978828/&lt;/ref&gt;. Two of the three main divisions of radiation therapy—the third being (sealed source) [[brachytherapy]]—can be used to treat bone metastases: both local- and wide-field [[external beam radiotherapy]] (EBRT), and systemic (unsealed source) [[radionuclide therapy]]. <br /> <br /> '''Local-field [[External beam radiotherapy|EBRT]]''' is the standard choice of radiation therapy for treating bone metastases, as it focally targets the bone lesion and can achieve rates of substantial pain relief of up to 80 to 90%&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/6178497/&lt;/ref&gt;. Randomised controlled trials (RCTs) from the 1990s have shown that a single fraction of 8 gray (Gy) is as effective as fractionated doses of 20 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9681885&lt;/ref&gt;, 24 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10577695&lt;/ref&gt;, and 30 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10577696&lt;/ref&gt;. <br /> <br /> '''Wide-field''' (or '''hemibody''') '''[[External beam radiotherapy|EBRT]]''' is useful for widespread metastatic skeletal disease, though was more commonly used for multifocal pain when other effective therapies (chemo- and radionuclide) were not available. There are no RCTs comparing analgesic effect with and without wide-field radiotherapy. However, in terms of quasi-randomised and low-quality RCTs, there is data to suggest that use of fractionation is no more effective than single fraction treatment&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8823257&lt;/ref&gt;, that increasing doses beyond 8 Gy does not improve overall pain responses&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11395246&lt;/ref&gt;, and adding wide-field to local-field radiotherapy, whilst significantly halting disease progression (lesion size: P = 0.03; lesion number: P = 0.01), increases grade 3 to 4 haematological toxicity&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/1374061&lt;/ref&gt;. [Gy doses from pubmed] + [structures to avoid]. <br /> <br /> '''[[Radionuclide therapy]]''' (or '''radioisotope therapy''') is <br /> <br /> ===Bisphosphonates===<br /> Poorly localised bone pain/previously irradiated bone lesions<br /> <br /> ===Denosumab===<br /> -<br /> <br /> ===Analgesia===<br /> -<br /> <br /> ===Chemotherapy===<br /> -<br /> <br /> ===Hormonal therapies===<br /> -<br /> <br /> ===Surgery===<br /> -<br /> <br /> ===Bone cement===<br /> -<br /> <br /> ==Living with bone metastases==<br /> Pain, mobility and safety, survival&lt;references /&gt;</div>

Alex https://oncopaedia.net/w/index.php?title=Articles:Bone_metastases&diff=289 2020-04-09T14:26:41Z

<p>Alex: </p> <hr /> <div>Metastases within bone can cause extreme and debilitating pain. Bone metastases are far more common than primary bone cancer, and many different cancer types can spread to the bone. The most common types of cancer which spread to bone are:<br /> <br /> *Breast<br /> *Prostate<br /> *Lung<br /> *Kidney<br /> *Thyroid<br /> <br /> Cancer can theoretically metastasize to any bone in the body, but in reality there is a predilection for certain sites. The most common sites are the vertebrae, ribs, pelvis, sternum, and the skull.<br /> <br /> ==Classification==<br /> A bone is a rigid organ, but it is far from physiologically static. To maintain bone strength, there is continuous breakdown and simultaneous reformation of bone, two processes which must finely balance for good bone health.<br /> <br /> '''Osteoblastic''' (or '''sclerotic''') metastases are characterised by the deposition of new bone. These are present most commonly in prostate cancer, but also occur in carcinoid, small cell lung cancer, medulloblastoma, and Hodgkin lymphoma. The molecular crosstalk between tumour and bone cells involves osteoblast-generating proteins such as Transforming Growth Factor, Bone Morphogenic Proteins (BMPs), and Endothelin-1&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12085970&lt;/ref&gt;.<br /> <br /> '''Osteolytic''' (or '''lytic''') metastases are characterised by the destruction and breakdown of normal bone. These often occur when breast cancer spreads to bone, which is primarily mediated by osteoclasts (bone cells that breaks down bone tissue) and is not a direct effect of metastasized tumour cells&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8086233/&lt;/ref&gt;. Other tumour types with osteolytic metastases include multiple myeloma, non-small cell lung cancer, thyroid cancer, non-Hodgkin lymphoma, and Langerhans' cell histiocytosis. Osteolytic metastases are more common than osteoblastic metastases.<br /> <br /> '''Mixed''' metastases are characterised by the presence of both osteolytic and osteoblastic lesions together in the same area of bone. These metastases are usually present in metastatic gastrointestinal and squamous cancers, as well as in secondary breast cancer. Although breast cancer gives rise to predominantly lytic lesions, around 15–20% of women have sclerotic or both types of lesions&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11346860/&lt;/ref&gt;.<br /> <br /> ==Diagnosis==<br /> <br /> ===Signs and symptoms===<br /> Bone metastases cause major morbidity, and high clinical suspicion should be kept for any patient with cancer that presents with:<br /> <br /> *Severe pain (poorly localised, worse at night)<br /> *Impaired mobility<br /> *[[Pathological fracture|Bone fracture]]<br /> *Bone marrow aplasia<br /> *Symptoms of (metastatic) [[Metastatic spinal cord compression|spinal cord compression]] (MSCC)<br /> *Symptoms in keeping with [[hypercalcaemia]]:<br /> **Constipation<br /> **Fatigue<br /> **Polyuria/polydipsia<br /> **Acute kidney injury (AKI)<br /> **Cardiac arrhythmia<br /> <br /> ===Bloods===<br /> When a patient with cancer presents with any of the signs or symptoms above, basic screening in the form of simple blood testing must be undertaken and complemented with appropriate imaging tests:<br /> <br /> *Full evaluation of bone turnover and potential hypercalcaemia:<br /> **Serum calcium<br /> **Serum phosphate<br /> **25-Hydroxyvitamin D<br /> **Thyroid-stimulating hormone (TSH)<br /> **Parathyroid hormone (PTH)<br /> **Serum creatinine<br /> **Alkaline phosphatase (ALP)<br /> *Full blood count (myelosuppression, anaemia)<br /> *Serum protein electrophoresis (SPEP; myeloma screen)<br /> *Tumour markers (such as PSA in prostate cancer)<br /> <br /> ===Imaging===<br /> Radiological tests are an essential component of diagnosing bony metastases. One or more imaging modalities may be required to confirm suspected cancerous spread to bone.<br /> <br /> '''Plain radiographs''' (X-ray scans) are quick, cost-effective, and widely-available, and should be the initial diagnostic test of choice when investigating bone pain. They are highly specific but lack sensitivity (44-50%) because early-stage metastatic lesions, particularly those up to 1 cm, may be more difficult to visualise. More than 50% of the trabecular bone must be involved before the lesion will be apparent on film and, due to the poor contrast of trabecular bone, lesions within the medulla are often less evident than those within cortical bone&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9025785/&lt;/ref&gt;. As outlined above, sclerotic metastases will appear more radiopaque than the surrounding bone, whereas lytic metastases will appear more radiolucent.<br /> <br /> '''Bone scintigraphy''' (bone scans) on the other hand is highly sensitive but with low specificity. Data from Technetium-99m (&lt;sup&gt;99m&lt;/sup&gt;Tc) scintigraphy have shown false-negative rates as low as 11 to 38% (good sensitivity), with false-positive rates as high as 40% (poor specificity). It thus provides a non-specific osteoblastic indication of bone status, be it inflammatory, traumatic, or neoplastic in origin. Scintigraphy is still more specific and sensitive than either plain radiography or computed tomography, whilst magnetic resonance imaging is more efficacious in assessing vertebral metastases&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/2028061/&lt;/ref&gt;.<br /> <br /> '''Computed tomography''' (CT scans) has a high sensitivity, ranging from 71 to 100%, for the detection of metastatic bone lesions&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9362427/&lt;/ref&gt;. Because of the excellent soft tissue resolution of the images produced by CT, it is a particularly helpful modality to distinguish lytic and sclerotic metastases and to visualise their precise location(s) for biopsy.<br /> <br /> '''Magnetic resonance imaging''' (MRI scans) is useful in assessing bone marrow infiltration by tumour deposits, and is required (whole spine) for the proper diagnosis of [[Metastatic spinal cord compression|MSCC]]. It has similarly high specificity (73 to 100%) and sensitivity (82 to 100%) in screening for bone metastases&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10964746/&lt;/ref&gt;.<br /> <br /> '''Positron emission tomography''' (PET scans) detects tumour indirectly by measuring metabolic activity in the form of fluorodeoxyglucose (&lt;sup&gt;18&lt;/sup&gt;F) tissue uptake. As such, its use is not limited to visualising only bony metastases, as &lt;sup&gt;18&lt;/sup&gt;F PET will reveal non-bony metastatic spread also&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8638000/&lt;/ref&gt;. The accuracy of PET is highly dependent on the primary tumour site from which imaged metastases originate. As a modality it is superior to scintigraphy in the screening of bony metastases from breast (specificity 94%, sensitivity 95%)&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12073051/&lt;/ref&gt; and lung (specificity 99%, sensitivity 92%)&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10478250/&lt;/ref&gt; malignancies, but has lower sensitivity in detecting the comparatively slower-growing bone metastases of prostate and renal cancers&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10520701/&lt;/ref&gt;. <br /> <br /> ===Biopsy===<br /> Sometimes it is necessary to diagnose metastases histologically, by removing cells or tissue from the bone lesion(s) directly. Usually this is in the form of a needle or surgical biopsy, and may be indicated if a primary cancer is not known. If the patient has a known primary cancer, then often imaging alone will suffice for the diagnosis of metastatic bone disease.<br /> <br /> ==Treatment==<br /> There are a variety of therapeutic interventions available to patients presenting with bone metastases, but consideration must be given to several patient-specific and tumour-dependent parameters, which include&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11738947/&lt;/ref&gt; (but are not limited to):<br /> <br /> *Lesion site(s) (localised or widespread)<br /> *Presence of extraskeletal metastasis<br /> *Tumour type and features (like receptors)<br /> *Prior treatment history (and response)<br /> *Clinical symptoms<br /> *Performance status<br /> <br /> ===Radiotherapy===<br /> Radiation therapy can provide excellent pain relief and is the treatment of choice for localised metastatic bone pain. However, the analgesic mechanisms of therapeutic skeletal irradiation are poorly understood. Onset of pain relief is usually quick, with a majority of patients experiencing benefit within one to two weeks. Patients who have little reduction in pain by six weeks are unlikely to demonstrate significant overall benefit&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/24782453/&lt;/ref&gt;. Other than localised bone pain, additional indications for radiotherapy include [[Metastatic spinal cord compression|MSCC]] and bones at high risk for [[pathological fracture]]&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/15978828/&lt;/ref&gt;. Two of the three main divisions of radiation therapy—the third being (sealed source) [[brachytherapy]]—can be used to treat bone metastases: both local- and wide-field [[external beam radiotherapy]] (EBRT), and systemic (unsealed source) [[radionuclide therapy]]. <br /> <br /> '''Local-field [[External beam radiotherapy|EBRT]]''' is the standard choice of radiation therapy for treating bone metastases, as it focally targets the bone lesion and can achieve rates of substantial pain relief of the order of 80 to 90%&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/6178497/&lt;/ref&gt;. Randomised controlled trials (RCTs) from the 1990s have shown that a single fraction of 8 gray (Gy) is as effective as fractionated doses of 20 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9681885&lt;/ref&gt;, 24 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10577695&lt;/ref&gt;, and 30 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10577696&lt;/ref&gt;. <br /> <br /> '''Wide-field''' (or '''hemibody''') '''[[External beam radiotherapy|EBRT]]''' is useful for widespread metastatic skeletal disease, though was more commonly used for multifocal pain when other effective therapies (chemo- and radionuclide) were not available. There are no RCTs comparing analgesic effect with and without wide-field radiotherapy. However, in terms of quasi-randomised and low-quality RCTs, there is data to suggest that use of fractionation is no more effective than single fraction treatment&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8823257&lt;/ref&gt;, that increasing doses about 8 Gy does not improve overall pain responses&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11395246&lt;/ref&gt;, and adding wide-field to local-field radiotherapy, whilst halting disease progression (lesion size: p=0.03; lesion number: p=0.01), significantly increases grade 3–4 haematological toxicity&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/1374061&lt;/ref&gt;. [Gy doses from pubmed] + [structures to avoid]. <br /> <br /> '''[[Radionuclide therapy]]''' (or '''radioisotope therapy''') is <br /> <br /> ===Bisphosphonates===<br /> Poorly localised bone pain/previously irradiated bone lesions<br /> <br /> ===Denosumab===<br /> -<br /> <br /> ===Analgesia===<br /> -<br /> <br /> ===Chemotherapy===<br /> -<br /> <br /> ===Hormonal therapies===<br /> -<br /> <br /> ===Surgery===<br /> -<br /> <br /> ===Bone cement===<br /> -<br /> <br /> ==Living with bone metastases==<br /> Pain, mobility and safety, survival&lt;references /&gt;</div>

Alex https://oncopaedia.net/w/index.php?title=Articles:Bone_metastases&diff=288 2020-04-09T14:21:13Z

<p>Alex: </p> <hr /> <div>Metastases within bone can cause extreme and debilitating pain. Bone metastases are far more common than primary bone cancer, and many different cancer types can spread to the bone. The most common types of cancer which spread to bone are:<br /> <br /> *Breast<br /> *Prostate<br /> *Lung<br /> *Kidney<br /> *Thyroid<br /> <br /> Cancer can theoretically metastasize to any bone in the body, but in reality there is a predilection for certain sites. The most common sites are the vertebrae, ribs, pelvis, sternum, and the skull.<br /> <br /> ==Classification==<br /> A bone is a rigid organ, but it is far from physiologically static. To maintain bone strength, there is continuous breakdown and simultaneous reformation of bone, two processes which must finely balance for good bone health.<br /> <br /> '''Osteoblastic''' (or '''sclerotic''') metastases are characterised by the deposition of new bone. These are present most commonly in prostate cancer, but also occur in carcinoid, small cell lung cancer, medulloblastoma, and Hodgkin lymphoma. The molecular crosstalk between tumour and bone cells involves osteoblast-generating proteins such as Transforming Growth Factor, Bone Morphogenic Proteins (BMPs), and Endothelin-1&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12085970&lt;/ref&gt;.<br /> <br /> '''Osteolytic''' (or '''lytic''') metastases are characterised by the destruction and breakdown of normal bone. These often occur when breast cancer spreads to bone, which is primarily mediated by osteoclasts (bone cells that breaks down bone tissue) and is not a direct effect of metastasized tumour cells&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8086233/&lt;/ref&gt;. Other tumour types with osteolytic metastases include multiple myeloma, non-small cell lung cancer, thyroid cancer, non-Hodgkin lymphoma, and Langerhans' cell histiocytosis. Osteolytic metastases are more common than osteoblastic metastases.<br /> <br /> '''Mixed''' metastases are characterised by the presence of both osteolytic and osteoblastic lesions together in the same area of bone. These metastases are usually present in metastatic gastrointestinal and squamous cancers, as well as in secondary breast cancer. Although breast cancer gives rise to predominantly lytic lesions, around 15–20% of women have sclerotic or both types of lesions&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11346860/&lt;/ref&gt;.<br /> <br /> ==Diagnosis==<br /> <br /> ===Signs and symptoms===<br /> Bone metastases cause major morbidity, and high clinical suspicion should be kept for any patient with cancer that presents with:<br /> <br /> *Severe pain (poorly localised, worse at night)<br /> *Impaired mobility<br /> *[[Pathological fracture|Bone fracture]]<br /> *Bone marrow aplasia<br /> *Symptoms of (metastatic) [[Metastatic spinal cord compression|spinal cord compression]] (MSCC)<br /> *Symptoms in keeping with [[hypercalcaemia]]:<br /> **Constipation<br /> **Fatigue<br /> **Polyuria/polydipsia<br /> **Acute kidney injury (AKI)<br /> **Cardiac arrhythmia<br /> <br /> ===Bloods===<br /> When a patient with cancer presents with any of the signs or symptoms above, basic screening in the form of simple blood testing must be undertaken and complemented with appropriate imaging tests:<br /> <br /> *Full evaluation of bone turnover and potential hypercalcaemia:<br /> **Serum calcium<br /> **Serum phosphate<br /> **25-Hydroxyvitamin D<br /> **Thyroid-stimulating hormone (TSH)<br /> **Parathyroid hormone (PTH)<br /> **Serum creatinine<br /> **Alkaline phosphatase (ALP)<br /> *Full blood count (myelosuppression, anaemia)<br /> *Serum protein electrophoresis (SPEP; myeloma screen)<br /> *Tumour markers (such as PSA in prostate cancer)<br /> <br /> ===Imaging===<br /> Radiological tests are an essential component of diagnosing bony metastases. One or more imaging modalities may be required to confirm suspected cancerous spread to bone.<br /> <br /> '''Plain radiographs''' (X-ray scans) are quick, cost-effective, and widely-available, and should be the initial diagnostic test of choice when investigating bone pain. They are highly specific but lack sensitivity (44-50%) because early-stage metastatic lesions, particularly those up to 1 cm, may be more difficult to visualise. More than 50% of the trabecular bone must be involved before the lesion will be apparent on film and, due to the poor contrast of trabecular bone, lesions within the medulla are often less evident than those within cortical bone&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9025785/&lt;/ref&gt;. As outlined above, sclerotic metastases will appear more radiopaque than the surrounding bone, whereas lytic metastases will appear more radiolucent.<br /> <br /> '''Bone scintigraphy''' (bone scans) on the other hand is highly sensitive but with low specificity. Data from Technetium-99m (&lt;sup&gt;99m&lt;/sup&gt;Tc) scintigraphy have shown false-negative rates as low as 11 to 38% (good sensitivity), with false-positive rates as high as 40% (poor specificity). It thus provides a non-specific osteoblastic indication of bone status, be it inflammatory, traumatic, or neoplastic in origin. Scintigraphy is still more specific and sensitive than either plain radiography or computed tomography, whilst magnetic resonance imaging is more efficacious in assessing vertebral metastases&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/2028061/&lt;/ref&gt;.<br /> <br /> '''Computed tomography''' (CT scans) has a high sensitivity, ranging from 71 to 100%, for the detection of metastatic bone lesions&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9362427/&lt;/ref&gt;. Because of the excellent soft tissue resolution of the images produced by CT, it is a particularly helpful modality to distinguish lytic and sclerotic metastases and to visualise their precise location(s) for biopsy.<br /> <br /> '''Magnetic resonance imaging''' (MRI scans) is useful in assessing bone marrow infiltration by tumour deposits, and is required (whole spine) for the proper diagnosis of [[Metastatic spinal cord compression|MSCC]]. It has similarly high specificity (73 to 100%) and sensitivity (82 to 100%) in screening for bone metastases&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10964746/&lt;/ref&gt;.<br /> <br /> '''Positron emission tomography''' (PET scans) detects tumour indirectly by measuring metabolic activity in the form of fluorodeoxyglucose (&lt;sup&gt;18&lt;/sup&gt;F) tissue uptake. As such, its use is not limited to visualising only bony metastases, as &lt;sup&gt;18&lt;/sup&gt;F PET will reveal non-bony metastatic spread also&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8638000/&lt;/ref&gt;. The accuracy of PET is highly dependent on the primary tumour site from which imaged metastases originate. As a modality it is superior to scintigraphy in the screening of bony metastases from breast (specificity 94%, sensitivity 95%)&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12073051/&lt;/ref&gt; and lung (specificity 99%, sensitivity 92%)&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10478250/&lt;/ref&gt; malignancies, but has lower sensitivity in detecting the comparatively slower-growing bone metastases of prostate and renal cancers&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10520701/&lt;/ref&gt;. <br /> <br /> ===Biopsy===<br /> Sometimes it is necessary to diagnose metastases histologically, by removing cells or tissue from the bone lesion(s) directly. Usually this is in the form of a needle or surgical biopsy, and may be indicated if a primary cancer is not known. If the patient has a known primary cancer, then often imaging alone will suffice for the diagnosis of metastatic bone disease.<br /> <br /> ==Treatment==<br /> There are a variety of therapeutic interventions available to patients presenting with bone metastases, but consideration must be given to several patient-specific and tumour-dependent parameters, which include&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11738947/&lt;/ref&gt; (but are not limited to):<br /> <br /> *Lesion site(s) (localised or widespread)<br /> *Presence of extraskeletal metastasis<br /> *Tumour type and features (like receptors)<br /> *Prior treatment history (and response)<br /> *Clinical symptoms<br /> *Performance status<br /> <br /> ===Radiotherapy===<br /> Radiation therapy can provide excellent pain relief and is the treatment of choice for localised metastatic bone pain. However, the analgesic mechanisms of therapeutic skeletal irradiation are poorly understood. Onset of pain relief is usually quick, with a majority of patients experiencing benefit within one to two weeks. Patients who have little reduction in pain by six weeks are unlikely to demonstrate significant overall benefit&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/24782453/&lt;/ref&gt;. Other than localised bone pain, additional indications for radiotherapy include [[Metastatic spinal cord compression|MSCC]] and bones at high risk for [[pathological fracture]]&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/15978828/&lt;/ref&gt;. Two of the three main divisions of radiation therapy—the third being (sealed source) [[brachytherapy]]—can be used to treat bone metastases: both local- and wide-field [[external beam radiotherapy]] (EBRT), and systemic (unsealed source) [[radionuclide therapy]]. <br /> <br /> '''Local-field [[External beam radiotherapy|EBRT]]''' is the standard choice of radiation therapy for treating bone metastases, as it focally targets the bone lesion and can achieve rates of substantial pain relief of the order of 80 to 90%&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/6178497/&lt;/ref&gt;. Randomised controlled trials (RCTs) from the 1990s have shown that a single fraction of 8 gray (Gy) is as effective as fractionated doses of 20 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9681885&lt;/ref&gt;, 24 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10577695&lt;/ref&gt;, and 30 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10577696&lt;/ref&gt;. <br /> <br /> '''Wide-field''' (or '''hemibody''') '''[[External beam radiotherapy|EBRT]]''' is useful for widespread metastatic skeletal disease, though was more commonly used for multifocal pain when other effective therapies (chemo- and radionuclide) were not available. There are no RCTs comparing analgesic effect with and without wide-field radiotherapy. However, in terms of quasi-randomised and low-quality RCTs, there is data to suggest that use of fractionation is no more effective than single fraction treatment&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8823257&lt;/ref&gt;, that increasing doses about 8 Gy does not improve overall pain responses&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11395246&lt;/ref&gt;, [summary from cancer.org.au] + [Gy doses from pubmed] + [structures to avoid]. <br /> <br /> '''[[Radionuclide therapy]]''' (or '''radioisotope therapy''') is <br /> <br /> ===Bisphosphonates===<br /> Poorly localised bone pain/previously irradiated bone lesions<br /> <br /> ===Denosumab===<br /> -<br /> <br /> ===Analgesia===<br /> -<br /> <br /> ===Chemotherapy===<br /> -<br /> <br /> ===Hormonal therapies===<br /> -<br /> <br /> ===Surgery===<br /> -<br /> <br /> ===Bone cement===<br /> -<br /> <br /> ==Living with bone metastases==<br /> Pain, mobility and safety, survival&lt;references /&gt;</div>

Alex https://oncopaedia.net/w/index.php?title=Articles:Bone_metastases&diff=287 2020-04-09T13:52:38Z

<p>Alex: </p> <hr /> <div>Metastases within bone can cause extreme and debilitating pain. Bone metastases are far more common than primary bone cancer, and many different cancer types can spread to the bone. The most common types of cancer which spread to bone are:<br /> <br /> *Breast<br /> *Prostate<br /> *Lung<br /> *Kidney<br /> *Thyroid<br /> <br /> Cancer can theoretically metastasize to any bone in the body, but in reality there is a predilection for certain sites. The most common sites are the vertebrae, ribs, pelvis, sternum, and the skull.<br /> <br /> ==Classification==<br /> A bone is a rigid organ, but it is far from physiologically static. To maintain bone strength, there is continuous breakdown and simultaneous reformation of bone, two processes which must finely balance for good bone health.<br /> <br /> '''Osteoblastic''' (or '''sclerotic''') metastases are characterised by the deposition of new bone. These are present most commonly in prostate cancer, but also occur in carcinoid, small cell lung cancer, medulloblastoma, and Hodgkin lymphoma. The molecular crosstalk between tumour and bone cells involves osteoblast-generating proteins such as Transforming Growth Factor, Bone Morphogenic Proteins (BMPs), and Endothelin-1&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12085970&lt;/ref&gt;.<br /> <br /> '''Osteolytic''' (or '''lytic''') metastases are characterised by the destruction and breakdown of normal bone. These often occur when breast cancer spreads to bone, which is primarily mediated by osteoclasts (bone cells that breaks down bone tissue) and is not a direct effect of metastasized tumour cells&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8086233/&lt;/ref&gt;. Other tumour types with osteolytic metastases include multiple myeloma, non-small cell lung cancer, thyroid cancer, non-Hodgkin lymphoma, and Langerhans' cell histiocytosis. Osteolytic metastases are more common than osteoblastic metastases.<br /> <br /> '''Mixed''' metastases are characterised by the presence of both osteolytic and osteoblastic lesions together in the same area of bone. These metastases are usually present in metastatic gastrointestinal and squamous cancers, as well as in secondary breast cancer. Although breast cancer gives rise to predominantly lytic lesions, around 15–20% of women have sclerotic or both types of lesions&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11346860/&lt;/ref&gt;.<br /> <br /> ==Diagnosis==<br /> <br /> ===Signs and symptoms===<br /> Bone metastases cause major morbidity, and high clinical suspicion should be kept for any patient with cancer that presents with:<br /> <br /> *Severe pain (poorly localised, worse at night)<br /> *Impaired mobility<br /> *[[Pathological fracture|Bone fracture]]<br /> *Bone marrow aplasia<br /> *Symptoms of (metastatic) [[Metastatic spinal cord compression|spinal cord compression]] (MSCC)<br /> *Symptoms in keeping with [[hypercalcaemia]]:<br /> **Constipation<br /> **Fatigue<br /> **Polyuria/polydipsia<br /> **Acute kidney injury (AKI)<br /> **Cardiac arrhythmia<br /> <br /> ===Bloods===<br /> When a patient with cancer presents with any of the signs or symptoms above, basic screening in the form of simple blood testing must be undertaken and complemented with appropriate imaging tests:<br /> <br /> *Full evaluation of bone turnover and potential hypercalcaemia:<br /> **Serum calcium<br /> **Serum phosphate<br /> **25-Hydroxyvitamin D<br /> **Thyroid-stimulating hormone (TSH)<br /> **Parathyroid hormone (PTH)<br /> **Serum creatinine<br /> **Alkaline phosphatase (ALP)<br /> *Full blood count (myelosuppression, anaemia)<br /> *Serum protein electrophoresis (SPEP; myeloma screen)<br /> *Tumour markers (such as PSA in prostate cancer)<br /> <br /> ===Imaging===<br /> Radiological tests are an essential component of diagnosing bony metastases. One or more imaging modalities may be required to confirm suspected cancerous spread to bone.<br /> <br /> '''Plain radiographs''' (X-ray scans) are quick, cost-effective, and widely-available, and should be the initial diagnostic test of choice when investigating bone pain. They are highly specific but lack sensitivity (44-50%) because early-stage metastatic lesions, particularly those up to 1 cm, may be more difficult to visualise. More than 50% of the trabecular bone must be involved before the lesion will be apparent on film and, due to the poor contrast of trabecular bone, lesions within the medulla are often less evident than those within cortical bone&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9025785/&lt;/ref&gt;. As outlined above, sclerotic metastases will appear more radiopaque than the surrounding bone, whereas lytic metastases will appear more radiolucent.<br /> <br /> '''Bone scintigraphy''' (bone scans) on the other hand is highly sensitive but with low specificity. Data from Technetium-99m (&lt;sup&gt;99m&lt;/sup&gt;Tc) scintigraphy have shown false-negative rates as low as 11 to 38% (good sensitivity), with false-positive rates as high as 40% (poor specificity). It thus provides a non-specific osteoblastic indication of bone status, be it inflammatory, traumatic, or neoplastic in origin. Scintigraphy is still more specific and sensitive than either plain radiography or computed tomography, whilst magnetic resonance imaging is more efficacious in assessing vertebral metastases&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/2028061/&lt;/ref&gt;.<br /> <br /> '''Computed tomography''' (CT scans) has a high sensitivity, ranging from 71 to 100%, for the detection of metastatic bone lesions&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9362427/&lt;/ref&gt;. Because of the excellent soft tissue resolution of the images produced by CT, it is a particularly helpful modality to distinguish lytic and sclerotic metastases and to visualise their precise location(s) for biopsy.<br /> <br /> '''Magnetic resonance imaging''' (MRI scans) is useful in assessing bone marrow infiltration by tumour deposits, and is required (whole spine) for the proper diagnosis of [[Metastatic spinal cord compression|MSCC]]. It has similarly high specificity (73 to 100%) and sensitivity (82 to 100%) in screening for bone metastases&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10964746/&lt;/ref&gt;.<br /> <br /> '''Positron emission tomography''' (PET scans) detects tumour indirectly by measuring metabolic activity in the form of fluorodeoxyglucose (&lt;sup&gt;18&lt;/sup&gt;F) tissue uptake. As such, its use is not limited to visualising only bony metastases, as &lt;sup&gt;18&lt;/sup&gt;F PET will reveal non-bony metastatic spread also&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8638000/&lt;/ref&gt;. The accuracy of PET is highly dependent on the primary tumour site from which imaged metastases originate. As a modality it is superior to scintigraphy in the screening of bony metastases from breast (specificity 94%, sensitivity 95%)&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12073051/&lt;/ref&gt; and lung (specificity 99%, sensitivity 92%)&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10478250/&lt;/ref&gt; malignancies, but has lower sensitivity in detecting the comparatively slower-growing bone metastases of prostate and renal cancers&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10520701/&lt;/ref&gt;. <br /> <br /> ===Biopsy===<br /> Sometimes it is necessary to diagnose metastases histologically, by removing cells or tissue from the bone lesion(s) directly. Usually this is in the form of a needle or surgical biopsy, and may be indicated if a primary cancer is not known. If the patient has a known primary cancer, then often imaging alone will suffice for the diagnosis of metastatic bone disease.<br /> <br /> ==Treatment==<br /> There are a variety of therapeutic interventions available to patients presenting with bone metastases, but consideration must be given to several patient-specific and tumour-dependent parameters, which include&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11738947/&lt;/ref&gt; (but are not limited to):<br /> <br /> *Lesion site(s) (localised or widespread)<br /> *Presence of extraskeletal metastasis<br /> *Tumour type and features (like receptors)<br /> *Prior treatment history (and response)<br /> *Clinical symptoms<br /> *Performance status<br /> <br /> ===Radiotherapy===<br /> Radiation therapy can provide excellent pain relief and is the treatment of choice for localised metastatic bone pain. However, the analgesic mechanisms of therapeutic skeletal irradiation are poorly understood. Onset of pain relief is usually quick, with a majority of patients experiencing benefit within one to two weeks. Patients who have little reduction in pain by six weeks are unlikely to demonstrate significant overall benefit&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/24782453/&lt;/ref&gt;. Other than localised bone pain, additional indications for radiotherapy include [[Metastatic spinal cord compression|MSCC]] and bones at high risk for [[pathological fracture]]&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/15978828/&lt;/ref&gt;. Two of the three main divisions of radiation therapy—the third being (sealed source) [[brachytherapy]]—can be used to treat bone metastases: both local- and wide-field [[external beam radiotherapy]] (EBRT), and systemic (unsealed source) [[radionuclide therapy]]. <br /> <br /> '''Local-field [[External beam radiotherapy|EBRT]]''' is the standard choice of radiation therapy for treating bone metastases, as it focally targets the bone lesion and can achieve rates of substantial pain relief of the order of 80 to 90%&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/6178497/&lt;/ref&gt;. Randomised trials from the 1990s have shown that a single fraction of 8 gray (Gy) is as effective as fractionated doses of 20 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9681885&lt;/ref&gt;, 24 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10577695&lt;/ref&gt;, and 30 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10577696&lt;/ref&gt;. <br /> <br /> '''Wide-field''' (or '''hemibody''') '''[[External beam radiotherapy|EBRT]]''' is useful for widespread metastatic skeletal disease, though was more commonly used for multifocal pain when other effective therapies (chemo- and radionuclide) were not available. [summary from cancer.org.au] + [Gy doses from pubmed] + [structures to avoid]. <br /> <br /> '''[[Radionuclide therapy]]''' (or '''radioisotope therapy''') is <br /> <br /> ===Bisphosphonates===<br /> Poorly localised bone pain/previously irradiated bone lesions<br /> <br /> ===Denosumab===<br /> -<br /> <br /> ===Analgesia===<br /> -<br /> <br /> ===Chemotherapy===<br /> -<br /> <br /> ===Hormonal therapies===<br /> -<br /> <br /> ===Surgery===<br /> -<br /> <br /> ===Bone cement===<br /> -<br /> <br /> ==Living with bone metastases==<br /> Pain, mobility and safety, survival&lt;references /&gt;</div>

Alex https://oncopaedia.net/w/index.php?title=Articles:Bone_metastases&diff=286 2020-04-09T12:15:19Z

<p>Alex: </p> <hr /> <div>Metastases within bone can cause extreme and debilitating pain. Bone metastases are far more common than primary bone cancer, and many different cancer types can spread to the bone. The most common types of cancer which spread to bone are:<br /> <br /> *Breast<br /> *Prostate<br /> *Lung<br /> *Kidney<br /> *Thyroid<br /> <br /> Cancer can theoretically metastasize to any bone in the body, but in reality there is a predilection for certain sites. The most common sites are the vertebrae, ribs, pelvis, sternum, and the skull.<br /> <br /> ==Classification==<br /> A bone is a rigid organ, but it is far from physiologically static. To maintain bone strength, there is continuous breakdown and simultaneous reformation of bone, two processes which must finely balance for good bone health.<br /> <br /> '''Osteoblastic''' (or '''sclerotic''') metastases are characterised by the deposition of new bone. These are present most commonly in prostate cancer, but also occur in carcinoid, small cell lung cancer, medulloblastoma, and Hodgkin lymphoma. The molecular crosstalk between tumour and bone cells involves osteoblast-generating proteins such as Transforming Growth Factor, Bone Morphogenic Proteins (BMPs), and Endothelin-1&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12085970&lt;/ref&gt;.<br /> <br /> '''Osteolytic''' (or '''lytic''') metastases are characterised by the destruction and breakdown of normal bone. These often occur when breast cancer spreads to bone, which is primarily mediated by osteoclasts (bone cells that breaks down bone tissue) and is not a direct effect of metastasized tumour cells&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8086233/&lt;/ref&gt;. Other tumour types with osteolytic metastases include multiple myeloma, non-small cell lung cancer, thyroid cancer, non-Hodgkin lymphoma, and Langerhans' cell histiocytosis. Osteolytic metastases are more common than osteoblastic metastases.<br /> <br /> '''Mixed''' metastases are characterised by the presence of both osteolytic and osteoblastic lesions together in the same area of bone. These metastases are usually present in metastatic gastrointestinal and squamous cancers, as well as in secondary breast cancer. Although breast cancer gives rise to predominantly lytic lesions, around 15–20% of women have sclerotic or both types of lesions&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11346860/&lt;/ref&gt;.<br /> <br /> ==Diagnosis==<br /> <br /> ===Signs and symptoms===<br /> Bone metastases cause major morbidity, and high clinical suspicion should be kept for any patient with cancer that presents with:<br /> <br /> *Severe pain (poorly localised, worse at night)<br /> *Impaired mobility<br /> *[[Pathological fracture|Bone fracture]]<br /> *Bone marrow aplasia<br /> *Symptoms of (metastatic) [[Metastatic spinal cord compression|spinal cord compression]] (MSCC)<br /> *Symptoms in keeping with [[hypercalcaemia]]:<br /> **Constipation<br /> **Fatigue<br /> **Polyuria/polydipsia<br /> **Acute kidney injury (AKI)<br /> **Cardiac arrhythmia<br /> <br /> ===Bloods===<br /> When a patient with cancer presents with any of the signs or symptoms above, basic screening in the form of simple blood testing must be undertaken and complemented with appropriate imaging tests:<br /> <br /> *Full evaluation of bone turnover and potential hypercalcaemia:<br /> **Serum calcium<br /> **Serum phosphate<br /> **25-Hydroxyvitamin D<br /> **Thyroid-stimulating hormone (TSH)<br /> **Parathyroid hormone (PTH)<br /> **Serum creatinine<br /> **Alkaline phosphatase (ALP)<br /> *Full blood count (myelosuppression, anaemia)<br /> *Serum protein electrophoresis (SPEP; myeloma screen)<br /> *Tumour markers (such as PSA in prostate cancer)<br /> <br /> ===Imaging===<br /> Radiological tests are an essential component of diagnosing bony metastases. One or more imaging modalities may be required to confirm suspected cancerous spread to bone.<br /> <br /> '''Plain radiographs''' (X-ray scans) are quick, cost-effective, and widely-available, and should be the initial diagnostic test of choice when investigating bone pain. They are highly specific but lack sensitivity (44-50%) because early-stage metastatic lesions, particularly those up to 1 cm, may be more difficult to visualise. More than 50% of the trabecular bone must be involved before the lesion will be apparent on film and, due to the poor contrast of trabecular bone, lesions within the medulla are often less evident than those within cortical bone&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9025785/&lt;/ref&gt;. As outlined above, sclerotic metastases will appear more radiopaque than the surrounding bone, whereas lytic metastases will appear more radiolucent.<br /> <br /> '''Bone scintigraphy''' (bone scans) on the other hand is highly sensitive but with low specificity. Data from Technetium-99m (&lt;sup&gt;99m&lt;/sup&gt;Tc) scintigraphy have shown false-negative rates as low as 11 to 38% (good sensitivity), with false-positive rates as high as 40% (poor specificity). It thus provides a non-specific osteoblastic indication of bone status, be it inflammatory, traumatic, or neoplastic in origin. Scintigraphy is still more specific and sensitive than either plain radiography or computed tomography, whilst magnetic resonance imaging is more efficacious in assessing vertebral metastases&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/2028061/&lt;/ref&gt;.<br /> <br /> '''Computed tomography''' (CT scans) has a high sensitivity, ranging from 71 to 100%, for the detection of metastatic bone lesions&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9362427/&lt;/ref&gt;. Because of the excellent soft tissue resolution of the images produced by CT, it is a particularly helpful modality to distinguish lytic and sclerotic metastases and to visualise their precise location(s) for biopsy.<br /> <br /> '''Magnetic resonance imaging''' (MRI scans) is useful in assessing bone marrow infiltration by tumour deposits, and is required (whole spine) for the proper diagnosis of [[Metastatic spinal cord compression|MSCC]]. It has similarly high specificity (73 to 100%) and sensitivity (82 to 100%) in screening for bone metastases&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10964746/&lt;/ref&gt;.<br /> <br /> '''Positron emission tomography''' (PET scans) detects tumour indirectly by measuring metabolic activity in the form of fluorodeoxyglucose (&lt;sup&gt;18&lt;/sup&gt;F) tissue uptake. As such, its use is not limited to visualising only bony metastases, as &lt;sup&gt;18&lt;/sup&gt;F PET will reveal non-bony metastatic spread also&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8638000/&lt;/ref&gt;. The accuracy of PET is highly dependent on the primary tumour site from which imaged metastases originate. As a modality it is superior to scintigraphy in the screening of bony metastases from breast (specificity 94%, sensitivity 95%)&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12073051/&lt;/ref&gt; and lung (specificity 99%, sensitivity 92%)&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10478250/&lt;/ref&gt; malignancies, but has lower sensitivity in detecting the comparatively slower-growing bone metastases of prostate and renal cancers&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10520701/&lt;/ref&gt;. <br /> <br /> ===Biopsy===<br /> Sometimes it is necessary to diagnose metastases histologically, by removing cells or tissue from the bone lesion(s) directly. Usually this is in the form of a needle or surgical biopsy, and may be indicated if a primary cancer is not known. If the patient has a known primary cancer, then often imaging alone will suffice for the diagnosis of metastatic bone disease.<br /> <br /> ==Treatment==<br /> There are a variety of therapeutic interventions available to patients presenting with bone metastases, but consideration must be given to several patient-specific and tumour-dependent parameters, which include&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11738947/&lt;/ref&gt; (but are not limited to):<br /> <br /> *Lesion site(s) (localised or widespread)<br /> *Presence of extraskeletal metastasis<br /> *Tumour type and features (like receptors)<br /> *Prior treatment history (and response)<br /> *Clinical symptoms<br /> *Performance status<br /> <br /> ===Radiotherapy===<br /> Radiation therapy can provide excellent pain relief and is the treatment of choice for localised metastatic bone pain. However, the analgesic mechanisms of therapeutic skeletal irradiation are poorly understood. Onset of pain relief is usually quick, with a majority of patients experiencing benefit within one to two weeks. Patients who have little reduction in pain by six weeks are unlikely to demonstrate significant overall benefit&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/24782453/&lt;/ref&gt;. Other than localised bone pain, additional indications for radiotherapy include [[Metastatic spinal cord compression|MSCC]] and bones at high risk for [[pathological fracture]]&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/15978828/&lt;/ref&gt;. Two of the three main divisions of radiation therapy—the third being (sealed source) [[brachytherapy]]—can be used to treat bone metastases: both local- and wide-field [[external beam radiotherapy]] (EBRT), and systemic (unsealed source) [[radionuclide therapy]]. <br /> <br /> '''Local-field [[External beam radiotherapy|EBRT]]''' is the standard choice of radiation therapy for treating bone metastases, as it focally targets the bone lesion and can achieve rates of substantial pain relief of the order of 80 to 90%&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/6178497/&lt;/ref&gt;. Randomised trials from the 1990s have shown that a single fraction of 8 gray (Gy) is as effective as fractionated doses of 20 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9681885&lt;/ref&gt;, 24 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10577695&lt;/ref&gt;, and 30 Gy&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10577696&lt;/ref&gt;. <br /> <br /> '''Wide-field [[External beam radiotherapy|EBRT]]''' is <br /> <br /> '''[[Radionuclide therapy]]''' (or '''radioisotope therapy''') is <br /> <br /> ===Bisphosphonates===<br /> Poorly localised bone pain/previously irradiated bone lesions<br /> <br /> ===Denosumab===<br /> -<br /> <br /> ===Analgesia===<br /> -<br /> <br /> ===Chemotherapy===<br /> -<br /> <br /> ===Hormonal therapies===<br /> -<br /> <br /> ===Surgery===<br /> -<br /> <br /> ===Bone cement===<br /> -<br /> <br /> ==Living with bone metastases==<br /> Pain, mobility and safety, survival&lt;references /&gt;</div>

Alex https://oncopaedia.net/w/index.php?title=Articles:Bone_metastases&diff=285 2020-04-09T10:41:16Z

<p>Alex: </p> <hr /> <div>Metastases within bone can cause extreme and debilitating pain. Bone metastases are far more common than primary bone cancer, and many different cancer types can spread to the bone. The most common types of cancer which spread to bone are:<br /> <br /> *Breast<br /> *Prostate<br /> *Lung<br /> *Kidney<br /> *Thyroid<br /> <br /> Cancer can theoretically metastasize to any bone in the body, but in reality there is a predilection for certain sites. The most common sites are the vertebrae, ribs, pelvis, sternum, and the skull.<br /> <br /> ==Classification==<br /> A bone is a rigid organ, but it is far from physiologically static. To maintain bone strength, there is continuous breakdown and simultaneous reformation of bone, two processes which must finely balance for good bone health.<br /> <br /> '''Osteoblastic''' (or '''sclerotic''') metastases are characterised by the deposition of new bone. These are present most commonly in prostate cancer, but also occur in carcinoid, small cell lung cancer, medulloblastoma, and Hodgkin lymphoma. The molecular crosstalk between tumour and bone cells involves osteoblast-generating proteins such as Transforming Growth Factor, Bone Morphogenic Proteins (BMPs), and Endothelin-1&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12085970&lt;/ref&gt;.<br /> <br /> '''Osteolytic''' (or '''lytic''') metastases are characterised by the destruction and breakdown of normal bone. These often occur when breast cancer spreads to bone, which is primarily mediated by osteoclasts (bone cells that breaks down bone tissue) and is not a direct effect of metastasized tumour cells&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8086233/&lt;/ref&gt;. Other tumour types with osteolytic metastases include multiple myeloma, non-small cell lung cancer, thyroid cancer, non-Hodgkin lymphoma, and Langerhans' cell histiocytosis. Osteolytic metastases are more common than osteoblastic metastases.<br /> <br /> '''Mixed''' metastases are characterised by the presence of both osteolytic and osteoblastic lesions together in the same area of bone. These metastases are usually present in metastatic gastrointestinal and squamous cancers, as well as in secondary breast cancer. Although breast cancer gives rise to predominantly lytic lesions, around 15–20% of women have sclerotic or both types of lesions&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11346860/&lt;/ref&gt;.<br /> <br /> ==Diagnosis==<br /> <br /> ===Signs and symptoms===<br /> Bone metastases cause major morbidity, and high clinical suspicion should be kept for any patient with cancer that presents with:<br /> <br /> *Severe pain (poorly localised, worse at night)<br /> *Impaired mobility<br /> *[[Pathological fracture|Bone fracture]]<br /> *Bone marrow aplasia<br /> *Symptoms of (metastatic) [[Metastatic spinal cord compression|spinal cord compression]] (MSCC)<br /> *Symptoms in keeping with [[hypercalcaemia]]:<br /> **Constipation<br /> **Fatigue<br /> **Polyuria/polydipsia<br /> **Acute kidney injury (AKI)<br /> **Cardiac arrhythmia<br /> <br /> ===Bloods===<br /> When a patient with cancer presents with any of the signs or symptoms above, basic screening in the form of simple blood testing must be undertaken and complemented with appropriate imaging tests:<br /> <br /> *Full evaluation of bone turnover and potential hypercalcaemia:<br /> **Serum calcium<br /> **Serum phosphate<br /> **25-Hydroxyvitamin D<br /> **Thyroid-stimulating hormone (TSH)<br /> **Parathyroid hormone (PTH)<br /> **Serum creatinine<br /> **Alkaline phosphatase (ALP)<br /> *Full blood count (myelosuppression, anaemia)<br /> *Serum protein electrophoresis (SPEP; myeloma screen)<br /> *Tumour markers (such as PSA in prostate cancer)<br /> <br /> ===Imaging===<br /> Radiological tests are an essential component of diagnosing bony metastases. One or more imaging modalities may be required to confirm suspected cancerous spread to bone.<br /> <br /> '''Plain radiographs''' (X-ray scans) are quick, cost-effective, and widely-available, and should be the initial diagnostic test of choice when investigating bone pain. They are highly specific but lack sensitivity (44-50%) because early-stage metastatic lesions, particularly those up to 1 cm, may be more difficult to visualise. More than 50% of the trabecular bone must be involved before the lesion will be apparent on film and, due to the poor contrast of trabecular bone, lesions within the medulla are often less evident than those within cortical bone&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9025785/&lt;/ref&gt;. As outlined above, sclerotic metastases will appear more radiopaque than the surrounding bone, whereas lytic metastases will appear more radiolucent.<br /> <br /> '''Bone scintigraphy''' (bone scans) on the other hand is highly sensitive but with low specificity. Data from Technetium-99m (&lt;sup&gt;99m&lt;/sup&gt;Tc) scintigraphy have shown false-negative rates as low as 11 to 38% (good sensitivity), with false-positive rates as high as 40% (poor specificity). It thus provides a non-specific osteoblastic indication of bone status, be it inflammatory, traumatic, or neoplastic in origin. Scintigraphy is still more specific and sensitive than either plain radiography or computed tomography, whilst magnetic resonance imaging is more efficacious in assessing vertebral metastases&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/2028061/&lt;/ref&gt;.<br /> <br /> '''Computed tomography''' (CT scans) has a high sensitivity, ranging from 71 to 100%, for the detection of metastatic bone lesions&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9362427/&lt;/ref&gt;. Because of the excellent soft tissue resolution of the images produced by CT, it is a particularly helpful modality to distinguish lytic and sclerotic metastases and to visualise their precise location(s) for biopsy.<br /> <br /> '''Magnetic resonance imaging''' (MRI scans) is useful in assessing bone marrow infiltration by tumour deposits, and is required (whole spine) for the proper diagnosis of [[Metastatic spinal cord compression|MSCC]]. It has similarly high specificity (73 to 100%) and sensitivity (82 to 100%) in screening for bone metastases&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10964746/&lt;/ref&gt;.<br /> <br /> '''Positron emission tomography''' (PET scans) detects tumour indirectly by measuring metabolic activity in the form of fluorodeoxyglucose (&lt;sup&gt;18&lt;/sup&gt;F) tissue uptake. As such, its use is not limited to visualising only bony metastases, as &lt;sup&gt;18&lt;/sup&gt;F PET will reveal non-bony metastatic spread also&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8638000/&lt;/ref&gt;. The accuracy of PET is highly dependent on the primary tumour site from which imaged metastases originate. As a modality it is superior to scintigraphy in the screening of bony metastases from breast (specificity 94%, sensitivity 95%)&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12073051/&lt;/ref&gt; and lung (specificity 99%, sensitivity 92%)&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10478250/&lt;/ref&gt; malignancies, but has lower sensitivity in detecting the comparatively slower-growing bone metastases of prostate and renal cancers&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10520701/&lt;/ref&gt;. <br /> <br /> ===Biopsy===<br /> Sometimes it is necessary to diagnose metastases histologically, by removing cells or tissue from the bone lesion(s) directly. Usually this is in the form of a needle or surgical biopsy, and may be indicated if a primary cancer is not known. If the patient has a known primary cancer, then often imaging alone will suffice for the diagnosis of metastatic bone disease.<br /> <br /> ==Treatment==<br /> There are a variety of therapeutic interventions available to patients presenting with bone metastases, but consideration must be given to several patient-specific and tumour-dependent parameters, which include&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11738947/&lt;/ref&gt; (but are not limited to):<br /> <br /> *Lesion site(s) (localised or widespread)<br /> *Presence of extraskeletal metastasis<br /> *Tumour type and features (like receptors)<br /> *Prior treatment history (and response)<br /> *Clinical symptoms<br /> *Performance status<br /> <br /> ===Radiotherapy===<br /> Radiation therapy can provide excellent pain relief and is the treatment of choice for localised metastatic bone pain. However, the analgesic mechanisms of therapeutic skeletal irradiation are poorly understood. Onset of pain relief is usually quick, with a majority of patients experiencing benefit within one to two weeks. Patients who have little reduction in pain by six weeks are unlikely to demonstrate significant overall benefit&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/24782453/&lt;/ref&gt;. Other than localised bone pain, additional indications for radiotherapy include [[Metastatic spinal cord compression|MSCC]] and bones at high risk for [[pathological fracture]]&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/15978828/&lt;/ref&gt;. Two of the three main divisions of radiation therapy—the third being (sealed source) [[brachytherapy]]—can be used to treat bone metastases: both local- and wide-field [[external beam radiotherapy]] (EBRT), and systemic (unsealed source) [[radionuclide therapy]]. <br /> <br /> '''Local-field [[External beam radiotherapy|EBRT]]''' is <br /> <br /> '''Wide-field [[External beam radiotherapy|EBRT]]''' is <br /> <br /> '''[[Radionuclide therapy]]''' (or '''radioisotope therapy''') is <br /> <br /> ===Bisphosphonates===<br /> Poorly localised bone pain/previously irradiated bone lesions<br /> <br /> ===Denosumab===<br /> -<br /> <br /> ===Analgesia===<br /> -<br /> <br /> ===Chemotherapy===<br /> -<br /> <br /> ===Hormonal therapies===<br /> -<br /> <br /> ===Surgery===<br /> -<br /> <br /> ===Bone cement===<br /> -<br /> <br /> ==Living with bone metastases==<br /> Pain, mobility and safety, survival&lt;references /&gt;</div>

Alex https://oncopaedia.net/w/index.php?title=Articles:Bone_metastases&diff=284 2020-04-08T18:28:25Z

<p>Alex: </p> <hr /> <div>Metastases within bone can cause extreme and debilitating pain. Bone metastases are far more common than primary bone cancer, and many different cancer types can spread to the bone. The most common types of cancer which spread to bone are:<br /> <br /> *Breast<br /> *Prostate<br /> *Lung<br /> *Kidney<br /> *Thyroid<br /> <br /> Cancer can theoretically metastasize to any bone in the body, but in reality there is a predilection for certain sites. The most common sites are the vertebrae, ribs, pelvis, sternum, and the skull.<br /> <br /> ==Classification==<br /> A bone is a rigid organ, but it is far from physiologically static. To maintain bone strength, there is continuous breakdown and simultaneous reformation of bone, two processes which must finely balance for good bone health.<br /> <br /> '''Osteoblastic''' (or '''sclerotic''') metastases are characterised by the deposition of new bone. These are present most commonly in prostate cancer, but also occur in carcinoid, small cell lung cancer, medulloblastoma, and Hodgkin lymphoma. The molecular crosstalk between tumour and bone cells involves osteoblast-generating proteins such as Transforming Growth Factor, Bone Morphogenic Proteins (BMPs), and Endothelin-1&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12085970&lt;/ref&gt;.<br /> <br /> '''Osteolytic''' (or '''lytic''') metastases are characterised by the destruction and breakdown of normal bone. These often occur when breast cancer spreads to bone, which is primarily mediated by osteoclasts (bone cells that breaks down bone tissue) and is not a direct effect of metastasized tumour cells&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8086233/&lt;/ref&gt;. Other tumour types with osteolytic metastases include multiple myeloma, non-small cell lung cancer, thyroid cancer, non-Hodgkin lymphoma, and Langerhans' cell histiocytosis. Osteolytic metastases are more common than osteoblastic metastases.<br /> <br /> '''Mixed''' metastases are characterised by the presence of both osteolytic and osteoblastic lesions together in the same area of bone. These metastases are usually present in metastatic gastrointestinal and squamous cancers, as well as in secondary breast cancer. Although breast cancer gives rise to predominantly lytic lesions, around 15–20% of women have sclerotic or both types of lesions&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11346860/&lt;/ref&gt;.<br /> <br /> ==Diagnosis==<br /> <br /> ===Signs and symptoms===<br /> Bone metastases cause major morbidity, and high clinical suspicion should be kept for any patient with cancer that presents with:<br /> <br /> *Severe pain (poorly localised, worse at night)<br /> *Impaired mobility<br /> *[[Pathological fracture|Bone fracture]]<br /> *Bone marrow aplasia<br /> *Symptoms of (metastatic) [[Metastatic spinal cord compression|spinal cord compression]] (MSCC)<br /> *Symptoms in keeping with [[hypercalcaemia]]:<br /> **Constipation<br /> **Fatigue<br /> **Polyuria/polydipsia<br /> **Acute kidney injury (AKI)<br /> **Cardiac arrhythmia<br /> <br /> ===Bloods===<br /> When a patient with cancer presents with any of the signs or symptoms above, basic screening in the form of simple blood testing must be undertaken and complemented with appropriate imaging tests:<br /> <br /> *Full evaluation of bone turnover and potential hypercalcaemia:<br /> **Serum calcium<br /> **Serum phosphate<br /> **25-Hydroxyvitamin D<br /> **Thyroid-stimulating hormone (TSH)<br /> **Parathyroid hormone (PTH)<br /> **Serum creatinine<br /> **Alkaline phosphatase (ALP)<br /> *Full blood count (myelosuppression, anaemia)<br /> *Serum protein electrophoresis (SPEP; myeloma screen)<br /> *Tumour markers (such as PSA in prostate cancer)<br /> <br /> ===Imaging===<br /> Radiological tests are an essential component of diagnosing bony metastases. One or more imaging modalities may be required to confirm suspected cancerous spread to bone.<br /> <br /> '''Plain radiographs''' (X-ray scans) are quick, cost-effective, and widely-available, and should be the initial diagnostic test of choice when investigating bone pain. They are highly specific but lack sensitivity (44-50%) because early-stage metastatic lesions, particularly those up to 1 cm, may be more difficult to visualise. More than 50% of the trabecular bone must be involved before the lesion will be apparent on film and, due to the poor contrast of trabecular bone, lesions within the medulla are often less evident than those within cortical bone&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9025785/&lt;/ref&gt;. As outlined above, sclerotic metastases will appear more radiopaque than the surrounding bone, whereas lytic metastases will appear more radiolucent.<br /> <br /> '''Bone scintigraphy''' (bone scans) on the other hand is highly sensitive but with low specificity. Data from Technetium-99m (&lt;sup&gt;99m&lt;/sup&gt;Tc) scintigraphy have shown false-negative rates as low as 11 to 38% (good sensitivity), with false-positive rates as high as 40% (poor specificity). It thus provides a non-specific osteoblastic indication of bone status, be it inflammatory, traumatic, or neoplastic in origin. Scintigraphy is still more specific and sensitive than either plain radiography or computed tomography, whilst magnetic resonance imaging is more efficacious in assessing vertebral metastases&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/2028061/&lt;/ref&gt;.<br /> <br /> '''Computed tomography''' (CT scans) has a high sensitivity, ranging from 71 to 100%, for the detection of metastatic bone lesions&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9362427/&lt;/ref&gt;. Because of the excellent soft tissue resolution of the images produced by CT, it is a particularly helpful modality to distinguish lytic and sclerotic metastases and to visualise their precise location(s) for biopsy.<br /> <br /> '''Magnetic resonance imaging''' (MRI scans) is useful in assessing bone marrow infiltration by tumour deposits, and is required (whole spine) for the proper diagnosis of [[Metastatic spinal cord compression|MSCC]]. It has similarly high specificity (73 to 100%) and sensitivity (82 to 100%) in screening for bone metastases&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10964746/&lt;/ref&gt;.<br /> <br /> '''Positron emission tomography''' (PET scans) detects tumour indirectly by measuring metabolic activity in the form of fluorodeoxyglucose (&lt;sup&gt;18&lt;/sup&gt;F) tissue uptake. As such, its use is not limited to visualising only bony metastases, as &lt;sup&gt;18&lt;/sup&gt;F PET will reveal non-bony metastatic spread also&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8638000/&lt;/ref&gt;. The accuracy of PET is highly dependent on the primary tumour site from which imaged metastases originate. As a modality it is superior to scintigraphy in the screening of bony metastases from breast (specificity 94%, sensitivity 95%)&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12073051/&lt;/ref&gt; and lung (specificity 99%, sensitivity 92%)&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10478250/&lt;/ref&gt; malignancies, but has lower sensitivity in detecting the comparatively slower-growing bone metastases of prostate and renal cancers&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10520701/&lt;/ref&gt;. <br /> <br /> ===Biopsy===<br /> Sometimes it is necessary to diagnose metastases histologically, by removing cells or tissue from the bone lesion(s) directly. Usually this is in the form of a needle or surgical biopsy, and may be indicated if a primary cancer is not known. If the patient has a known primary cancer, then often imaging alone will suffice for the diagnosis of metastatic bone disease.<br /> <br /> ==Treatment==<br /> There are a variety of therapeutic interventions available to patients presenting with bone metastases, but consideration must be given to several patient-specific and tumour-dependent parameters, which include&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11738947/&lt;/ref&gt; (but are not limited to):<br /> <br /> *Lesion site(s) (localised or widespread)<br /> *Presence of extraskeletal metastasis<br /> *Tumour type and features (like receptors)<br /> *Prior treatment history (and response)<br /> *Clinical symptoms<br /> *Performance status<br /> <br /> ===Radiotherapy===<br /> Radiation therapy can provide excellent pain relief and is the treatment of choice for localised metastatic bone pain. However, the analgesic mechanisms of therapeutic skeletal irradiation are poorly understood. Onset of pain relief is usually quick, with a majority of patients experiencing benefit within one to two weeks. Patients who have little reduction in pain by six weeks are unlikely to demonstrate significant overall benefit&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/24782453/&lt;/ref&gt;. Other than localised bone pain, additional indications for radiotherapy include [[Metastatic spinal cord compression|MSCC]] and bones at high risk for [[pathological fracture]]&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/15978828/&lt;/ref&gt;. Two of the three main divisions of radiation therapy—the third being (sealed source) [[brachytherapy]]—can be used to treat bone metastases: both local- and wide-field [[external beam radiotherapy]] (EBRT) and systemic (unsealed source) [[radionuclide therapy]]. <br /> <br /> '''Local-field [[External beam radiotherapy|EBRT]]''' is <br /> <br /> '''Wide-field [[External beam radiotherapy|EBRT]]''' is <br /> <br /> '''[[Radionuclide therapy]]''' (or '''radioisotope therapy''') is <br /> <br /> ===Bisphosphonates===<br /> Poorly localised bone pain/previously irradiated bone lesions<br /> <br /> ===Denosumab===<br /> -<br /> <br /> ===Analgesia===<br /> -<br /> <br /> ===Chemotherapy===<br /> -<br /> <br /> ===Hormonal therapies===<br /> -<br /> <br /> ===Surgery===<br /> -<br /> <br /> ===Bone cement===<br /> -<br /> <br /> ==Living with bone metastases==<br /> Pain, mobility and safety, survival&lt;references /&gt;</div>

Alex https://oncopaedia.net/w/index.php?title=Articles:Bone_metastases&diff=283 2020-04-08T18:20:25Z

<p>Alex: </p> <hr /> <div>Metastases within bone can cause extreme and debilitating pain. Bone metastases are far more common than primary bone cancer, and many different cancer types can spread to the bone. The most common types of cancer which spread to bone are:<br /> <br /> *Breast<br /> *Prostate<br /> *Lung<br /> *Kidney<br /> *Thyroid<br /> <br /> Cancer can theoretically metastasize to any bone in the body, but in reality there is a predilection for certain sites. The most common sites are the vertebrae, ribs, pelvis, sternum, and the skull.<br /> <br /> ==Classification==<br /> A bone is a rigid organ, but it is far from physiologically static. To maintain bone strength, there is continuous breakdown and simultaneous reformation of bone, two processes which must finely balance for good bone health.<br /> <br /> '''Osteoblastic''' (or '''sclerotic''') metastases are characterised by the deposition of new bone. These are present most commonly in prostate cancer, but also occur in carcinoid, small cell lung cancer, medulloblastoma, and Hodgkin lymphoma. The molecular crosstalk between tumour and bone cells involves osteoblast-generating proteins such as Transforming Growth Factor, Bone Morphogenic Proteins (BMPs), and Endothelin-1&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12085970&lt;/ref&gt;.<br /> <br /> '''Osteolytic''' (or '''lytic''') metastases are characterised by the destruction and breakdown of normal bone. These often occur when breast cancer spreads to bone, which is primarily mediated by osteoclasts (bone cells that breaks down bone tissue) and is not a direct effect of metastasized tumour cells&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8086233/&lt;/ref&gt;. Other tumour types with osteolytic metastases include multiple myeloma, non-small cell lung cancer, thyroid cancer, non-Hodgkin lymphoma, and Langerhans' cell histiocytosis. Osteolytic metastases are more common than osteoblastic metastases.<br /> <br /> '''Mixed''' metastases are characterised by the presence of both osteolytic and osteoblastic lesions together in the same area of bone. These metastases are usually present in metastatic gastrointestinal and squamous cancers, as well as in secondary breast cancer. Although breast cancer gives rise to predominantly lytic lesions, around 15–20% of women have sclerotic or both types of lesions&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11346860/&lt;/ref&gt;.<br /> <br /> ==Diagnosis==<br /> <br /> ===Signs and symptoms===<br /> Bone metastases cause major morbidity, and high clinical suspicion should be kept for any patient with cancer that presents with:<br /> <br /> *Severe pain (poorly localised, worse at night)<br /> *Impaired mobility<br /> *[[Pathological fracture|Bone fracture]]<br /> *Bone marrow aplasia<br /> *Symptoms of (metastatic) [[Metastatic spinal cord compression|spinal cord compression]] (MSCC)<br /> *Symptoms in keeping with [[hypercalcaemia]]:<br /> **Constipation<br /> **Fatigue<br /> **Polyuria/polydipsia<br /> **Acute kidney injury (AKI)<br /> **Cardiac arrhythmia<br /> <br /> ===Bloods===<br /> When a patient with cancer presents with any of the signs or symptoms above, basic screening in the form of simple blood testing must be undertaken and complemented with appropriate imaging tests:<br /> <br /> *Full evaluation of bone turnover and potential hypercalcaemia:<br /> **Serum calcium<br /> **Serum phosphate<br /> **25-Hydroxyvitamin D<br /> **Thyroid-stimulating hormone (TSH)<br /> **Parathyroid hormone (PTH)<br /> **Serum creatinine<br /> **Alkaline phosphatase (ALP)<br /> *Full blood count (myelosuppression, anaemia)<br /> *Serum protein electrophoresis (SPEP; myeloma screen)<br /> *Tumour markers (such as PSA in prostate cancer)<br /> <br /> ===Imaging===<br /> Radiological tests are an essential component of diagnosing bony metastases. One or more imaging modalities may be required to confirm suspected cancerous spread to bone.<br /> <br /> '''Plain radiographs''' (X-ray scans) are quick, cost-effective, and widely-available, and should be the initial diagnostic test of choice when investigating bone pain. They are highly specific but lack sensitivity (44-50%) because early-stage metastatic lesions, particularly those up to 1 cm, may be more difficult to visualise. More than 50% of the trabecular bone must be involved before the lesion will be apparent on film and, due to the poor contrast of trabecular bone, lesions within the medulla are often less evident than those within cortical bone&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9025785/&lt;/ref&gt;. As outlined above, sclerotic metastases will appear more radiopaque than the surrounding bone, whereas lytic metastases will appear more radiolucent.<br /> <br /> '''Bone scintigraphy''' (bone scans) on the other hand is highly sensitive but with low specificity. Data from Technetium-99m (&lt;sup&gt;99m&lt;/sup&gt;Tc) scintigraphy have shown false-negative rates as low as 11 to 38% (good sensitivity), with false-positive rates as high as 40% (poor specificity). It thus provides a non-specific osteoblastic indication of bone status, be it inflammatory, traumatic, or neoplastic in origin. Scintigraphy is still more specific and sensitive than either plain radiography or computed tomography, whilst magnetic resonance imaging is more efficacious in assessing vertebral metastases&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/2028061/&lt;/ref&gt;.<br /> <br /> '''Computed tomography''' (CT scans) has a high sensitivity, ranging from 71 to 100%, for the detection of metastatic bone lesions&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9362427/&lt;/ref&gt;. Because of the excellent soft tissue resolution of the images produced by CT, it is a particularly helpful modality to distinguish lytic and sclerotic metastases and to visualise their precise location(s) for biopsy.<br /> <br /> '''Magnetic resonance imaging''' (MRI scans) is useful in assessing bone marrow infiltration by tumour deposits, and is required (whole spine) for the proper diagnosis of [[Metastatic spinal cord compression|MSCC]]. It has similarly high specificity (73 to 100%) and sensitivity (82 to 100%) in screening for bone metastases&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10964746/&lt;/ref&gt;.<br /> <br /> '''Positron emission tomography''' (PET scans) detects tumour indirectly by measuring metabolic activity in the form of fluorodeoxyglucose (&lt;sup&gt;18&lt;/sup&gt;F) tissue uptake. As such, its use is not limited to visualising only bony metastases, as &lt;sup&gt;18&lt;/sup&gt;F PET will reveal non-bony metastatic spread also&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8638000/&lt;/ref&gt;. The accuracy of PET is highly dependent on the primary tumour site from which imaged metastases originate. As a modality it is superior to scintigraphy in the screening of bony metastases from breast (specificity 94%, sensitivity 95%)&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12073051/&lt;/ref&gt; and lung (specificity 99%, sensitivity 92%)&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10478250/&lt;/ref&gt; malignancies, but has lower sensitivity in detecting the comparatively slower-growing bone metastases of prostate and renal cancers&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10520701/&lt;/ref&gt;. <br /> <br /> ===Biopsy===<br /> Sometimes it is necessary to diagnose metastases histologically, by removing cells or tissue from the bone lesion(s) directly. Usually this is in the form of a needle or surgical biopsy, and may be indicated if a primary cancer is not known. If the patient has a known primary cancer, then often imaging alone will suffice for the diagnosis of metastatic bone disease.<br /> <br /> ==Treatment==<br /> There are a variety of therapeutic interventions available to patients presenting with bone metastases, but consideration must be given to several patient-specific and tumour-dependent parameters, which include&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11738947/&lt;/ref&gt; (but are not limited to):<br /> <br /> *Lesion site(s) (localised or widespread)<br /> *Presence of extraskeletal metastasis<br /> *Tumour type and features (like receptors)<br /> *Prior treatment history (and response)<br /> *Clinical symptoms<br /> *Performance status<br /> <br /> ===Radiotherapy===<br /> Radiation therapy can provide excellent pain relief and is the treatment of choice for localised metastatic bone pain. However, the analgesic mechanisms of therapeutic radiation are poorly understood. Onset of pain relief is usually quick, with a majority of patients experiencing benefit within one to two weeks. Patients who have little reduction in pain by six weeks are unlikely to demonstrate significant overall benefit&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/24782453/&lt;/ref&gt;. Other than localised bone pain, additional indications for radiotherapy include [[Metastatic spinal cord compression|MSCC]] and bones at high risk for [[pathological fracture]]&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/15978828/&lt;/ref&gt;. Two of the three main divisions of radiation therapy—the third being (sealed source) [[brachytherapy]]—can be used to treat bone metastases: both local- and wide-field [[external beam radiotherapy]] (EBRT) and systemic (unsealed source) [[radionuclide therapy]]. <br /> <br /> '''Local-field [[External beam radiotherapy|EBRT]]''' is <br /> <br /> '''Wide-field [[External beam radiotherapy|EBRT]]''' is <br /> <br /> '''[[Radionuclide therapy]]''' (or '''radioisotope therapy''') is <br /> <br /> ===Bisphosphonates===<br /> Poorly localised bone pain/previously irradiated bone lesions<br /> <br /> ===Denosumab===<br /> -<br /> <br /> ===Analgesia===<br /> -<br /> <br /> ===Chemotherapy===<br /> -<br /> <br /> ===Hormonal therapies===<br /> -<br /> <br /> ===Surgery===<br /> -<br /> <br /> ===Bone cement===<br /> -<br /> <br /> ==Living with bone metastases==<br /> Pain, mobility and safety, survival&lt;references /&gt;</div>

Alex https://oncopaedia.net/w/index.php?title=Articles:Bone_metastases&diff=282 2020-04-07T14:50:53Z

<p>Alex: </p> <hr /> <div>Metastases within bone can cause extreme and debilitating pain. Bone metastases are far more common than primary bone cancer, and many different cancer types can spread to the bone. The most common types of cancer which spread to bone are:<br /> <br /> *Breast<br /> *Prostate<br /> *Lung<br /> *Kidney<br /> *Thyroid<br /> <br /> Cancer can theoretically metastasize to any bone in the body, but in reality there is a predilection for certain sites. The most common sites are the vertebrae, ribs, pelvis, sternum, and the skull.<br /> <br /> ==Classification==<br /> A bone is a rigid organ, but it is far from physiologically static. To maintain bone strength, there is continuous breakdown and simultaneous reformation of bone, two processes which must finely balance for good bone health.<br /> <br /> '''Osteoblastic''' (or '''sclerotic''') metastases are characterised by the deposition of new bone. These are present most commonly in prostate cancer, but also occur in carcinoid, small cell lung cancer, medulloblastoma, and Hodgkin lymphoma. The molecular crosstalk between tumour and bone cells involves osteoblast-generating proteins such as Transforming Growth Factor, Bone Morphogenic Proteins (BMPs), and Endothelin-1&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12085970&lt;/ref&gt;.<br /> <br /> '''Osteolytic''' (or '''lytic''') metastases are characterised by the destruction and breakdown of normal bone. These often occur when breast cancer spreads to bone, which is primarily mediated by osteoclasts (bone cells that breaks down bone tissue) and is not a direct effect of metastasized tumour cells&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8086233/&lt;/ref&gt;. Other tumour types with osteolytic metastases include multiple myeloma, non-small cell lung cancer, thyroid cancer, non-Hodgkin lymphoma, and Langerhans' cell histiocytosis. Osteolytic metastases are more common than osteoblastic metastases.<br /> <br /> '''Mixed''' metastases are characterised by the presence of both osteolytic and osteoblastic lesions together in the same area of bone. These metastases are usually present in metastatic gastrointestinal and squamous cancers, as well as in secondary breast cancer. Although breast cancer gives rise to predominantly lytic lesions, around 15–20% of women have sclerotic or both types of lesions&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11346860/&lt;/ref&gt;.<br /> <br /> ==Diagnosis==<br /> <br /> ===Signs and symptoms===<br /> Bone metastases cause major morbidity, and high clinical suspicion should be kept for any patient with cancer that presents with:<br /> <br /> *Severe pain (poorly localised, worse at night)<br /> *Impaired mobility<br /> *[[Pathological fracture|Bone fracture]]<br /> *Bone marrow aplasia<br /> *Symptoms of (metastatic) [[Metastatic spinal cord compression|spinal cord compression]] (MSCC)<br /> *Symptoms in keeping with [[hypercalcaemia]]:<br /> **Constipation<br /> **Fatigue<br /> **Polyuria/polydipsia<br /> **Acute kidney injury (AKI)<br /> **Cardiac arrhythmia<br /> <br /> ===Bloods===<br /> When a patient with cancer presents with any of the signs or symptoms above, basic screening in the form of simple blood testing must be undertaken&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/24782453/&lt;/ref&gt; and complemented with appropriate imaging tests&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/15978828/&lt;/ref&gt;:<br /> <br /> *Full evaluation of bone turnover and potential hypercalcaemia:<br /> **Serum calcium<br /> **Serum phosphate<br /> **25-Hydroxyvitamin D<br /> **Thyroid-stimulating hormone (TSH)<br /> **Parathyroid hormone (PTH)<br /> **Serum creatinine<br /> **Alkaline phosphatase (ALP)<br /> *Full blood count (myelosuppression, anaemia)<br /> *Serum protein electrophoresis (SPEP; myeloma screen)<br /> *Tumour markers (such as PSA in prostate cancer)<br /> <br /> ===Imaging===<br /> Radiological tests are an essential component of diagnosing bony metastases. One or more imaging modalities may be required to confirm suspected cancerous spread to bone.<br /> <br /> '''Plain radiographs''' (X-ray scans) are quick, cost-effective, and widely-available, and should be the initial diagnostic test of choice when investigating bone pain. They are highly specific but lack sensitivity (44-50%) because early-stage metastatic lesions, particularly those up to 1 cm, may be more difficult to visualise. More than 50% of the trabecular bone must be involved before the lesion will be apparent on film and, due to the poor contrast of trabecular bone, lesions within the medulla are often less evident than those within cortical bone&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9025785/&lt;/ref&gt;. As outlined above, sclerotic metastases will appear more radiopaque than the surrounding bone, whereas lytic metastases will appear more radiolucent.<br /> <br /> '''Bone scintigraphy''' (bone scans) on the other hand is highly sensitive but with low specificity. Data from Technetium-99m (&lt;sup&gt;99m&lt;/sup&gt;Tc) scintigraphy have shown false-negative rates as low as 11 to 38% (good sensitivity), with false-positive rates as high as 40% (poor specificity). It thus provides a non-specific osteoblastic indication of bone status, be it inflammatory, traumatic, or neoplastic in origin. Scintigraphy is still more specific and sensitive than either plain radiography or computed tomography, whilst magnetic resonance imaging is more efficacious in assessing vertebral metastases&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/2028061/&lt;/ref&gt;.<br /> <br /> '''Computed tomography''' (CT scans) has a high sensitivity, ranging from 71 to 100%, for the detection of metastatic bone lesions&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9362427/&lt;/ref&gt;. Because of the excellent soft tissue resolution of the images produced by CT, it is a particularly helpful modality to distinguish lytic and sclerotic metastases and to visualise their precise location(s) for biopsy.<br /> <br /> '''Magnetic resonance imaging''' (MRI scans) is useful in assessing bone marrow infiltration by tumour deposits, and is required (whole spine) for the proper diagnosis of [[Metastatic spinal cord compression|MSCC]]. It has similarly high specificity (73 to 100%) and sensitivity (82 to 100%) in screening for bone metastases&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10964746/&lt;/ref&gt;.<br /> <br /> '''Positron emission tomography''' (PET scans) detects tumour indirectly by measuring metabolic activity in the form of fluorodeoxyglucose (&lt;sup&gt;18&lt;/sup&gt;F) tissue uptake. As such, its use is not limited to visualising only bony metastases, as &lt;sup&gt;18&lt;/sup&gt;F PET will reveal non-bony metastatic spread also&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8638000/&lt;/ref&gt;. The accuracy of PET is highly dependent on the primary tumour site from which imaged metastases originate. As a modality it is superior to scintigraphy in the screening of bony metastases from breast (specificity 94%, sensitivity 95%)&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12073051/&lt;/ref&gt; and lung (specificity 99%, sensitivity 92%)&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10478250/&lt;/ref&gt; malignancies, but has lower sensitivity in detecting the comparatively slower-growing bone metastases of prostate and renal cancers&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10520701/&lt;/ref&gt;. <br /> <br /> ===Biopsy===<br /> Sometimes it is necessary to diagnose metastases histologically, by removing cells or tissue from the bone lesion(s) directly. Usually this is in the form of a needle or surgical biopsy, and may be indicated if a primary cancer is not known. If the patient has a known primary cancer, then often imaging alone will suffice for the diagnosis of metastatic bone disease.<br /> <br /> ==Treatment==<br /> There are a variety of therapeutic interventions available to patients presenting with bone metastases, but consideration must be given to several patient-specific and tumour-dependent parameters, which include&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11738947/&lt;/ref&gt; (but are not limited to):<br /> <br /> *Lesion site(s) (localised or widespread)<br /> *Presence of extraskeletal metastasis<br /> *Tumour type and features (like receptors)<br /> *Prior treatment history (and response)<br /> *Clinical symptoms<br /> *Performance status<br /> <br /> === Radiotherapy ===<br /> Radiation therapy can provide effective <br /> <br /> === Bisphosphonates ===<br /> -<br /> <br /> === Denosumab ===<br /> -<br /> <br /> === Analgesia ===<br /> -<br /> <br /> === Chemotherapy ===<br /> -<br /> <br /> === Hormonal therapies ===<br /> -<br /> <br /> === Surgery ===<br /> -<br /> <br /> === Bone cement ===<br /> -<br /> <br /> ==Living with bone metastases==<br /> Pain, mobility and safety, survival&lt;references /&gt;</div>

Alex https://oncopaedia.net/w/index.php?title=Articles:Bone_metastases&diff=281 2020-04-07T14:31:03Z

<p>Alex: </p> <hr /> <div>Metastases within bone can cause extreme and debilitating pain. Bone metastases are far more common than primary bone cancer, and many different cancer types can spread to the bone. The most common types of cancer which spread to bone are:<br /> <br /> *Breast<br /> *Prostate<br /> *Lung<br /> *Kidney<br /> *Thyroid<br /> <br /> Cancer can theoretically metastasize to any bone in the body, but in reality there is a predilection for certain sites. The most common sites are the vertebrae, ribs, pelvis, sternum, and the skull.<br /> <br /> ==Classification==<br /> A bone is a rigid organ, but it is far from physiologically static. To maintain bone strength, there is continuous breakdown and simultaneous reformation of bone, two processes which must finely balance for good bone health.<br /> <br /> '''Osteoblastic''' (or '''sclerotic''') metastases are characterised by the deposition of new bone. These are present most commonly in prostate cancer, but also occur in carcinoid, small cell lung cancer, medulloblastoma, and Hodgkin lymphoma. The molecular crosstalk between tumour and bone cells involves osteoblast-generating proteins such as Transforming Growth Factor, Bone Morphogenic Proteins (BMPs), and Endothelin-1&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12085970&lt;/ref&gt;.<br /> <br /> '''Osteolytic''' (or '''lytic''') metastases are characterised by the destruction and breakdown of normal bone. These often occur when breast cancer spreads to bone, which is primarily mediated by osteoclasts (bone cells that breaks down bone tissue) and is not a direct effect of metastasized tumour cells&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8086233/&lt;/ref&gt;. Other tumour types with osteolytic metastases include multiple myeloma, non-small cell lung cancer, thyroid cancer, non-Hodgkin lymphoma, and Langerhans' cell histiocytosis. Osteolytic metastases are more common than osteoblastic metastases.<br /> <br /> '''Mixed''' metastases are characterised by the presence of both osteolytic and osteoblastic lesions together in the same area of bone. These metastases are usually present in metastatic gastrointestinal and squamous cancers, as well as in secondary breast cancer. Although breast cancer gives rise to predominantly lytic lesions, around 15–20% of women have sclerotic or both types of lesions&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/11346860/&lt;/ref&gt;.<br /> <br /> ==Diagnosis==<br /> <br /> ===Signs and symptoms===<br /> Bone metastases cause major morbidity, and high clinical suspicion should be kept for any patient with cancer that presents with:<br /> <br /> *Severe pain (poorly localised, worse at night)<br /> *Impaired mobility<br /> *[[Pathological fracture|Bone fracture]]<br /> *Bone marrow aplasia<br /> *Symptoms of (metastatic) [[Metastatic spinal cord compression|spinal cord compression]] (MSCC)<br /> *Symptoms in keeping with [[hypercalcaemia]]:<br /> **Constipation<br /> **Fatigue<br /> **Polyuria/polydipsia<br /> **Acute kidney injury (AKI)<br /> **Cardiac arrhythmia<br /> <br /> ===Bloods===<br /> When a patient with cancer presents with any of the signs or symptoms above, basic screening in the form of simple blood testing must be undertaken&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/24782453/&lt;/ref&gt; and complemented with appropriate imaging tests&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/15978828/&lt;/ref&gt;:<br /> <br /> *Full evaluation of bone turnover and potential hypercalcaemia:<br /> **Serum calcium<br /> **Serum phosphate<br /> **25-Hydroxyvitamin D<br /> **Thyroid-stimulating hormone (TSH)<br /> **Parathyroid hormone (PTH)<br /> **Serum creatinine<br /> **Alkaline phosphatase (ALP)<br /> *Full blood count (myelosuppression, anaemia)<br /> *Serum protein electrophoresis (SPEP; myeloma screen)<br /> *Tumour markers (such as PSA in prostate cancer)<br /> <br /> ===Imaging===<br /> Radiological tests are an essential component of diagnosing bony metastases. One or more imaging modalities may be required to confirm suspected cancerous spread to bone.<br /> <br /> '''Plain radiographs''' (X-ray scans) are quick, cost-effective, and widely-available, and should be the initial diagnostic test of choice when investigating bone pain. They are highly specific but lack sensitivity (44-50%) because early-stage metastatic lesions, particularly those up to 1 cm, may be more difficult to visualise. More than 50% of the trabecular bone must be involved before the lesion will be apparent on film and, due to the poor contrast of trabecular bone, lesions within the medulla are often less evident than those within cortical bone&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9025785/&lt;/ref&gt;. As outlined above, sclerotic metastases will appear more radiopaque than the surrounding bone, whereas lytic metastases will appear more radiolucent.<br /> <br /> '''Bone scintigraphy''' (bone scans) on the other hand is highly sensitive but with low specificity. Data from Technetium-99m (&lt;sup&gt;99m&lt;/sup&gt;Tc) scintigraphy have shown false-negative rates as low as 11 to 38% (good sensitivity), with false-positive rates as high as 40% (poor specificity). It thus provides a non-specific osteoblastic indication of bone status, be it inflammatory, traumatic, or neoplastic in origin. Scintigraphy is still more specific and sensitive than either plain radiography or computed tomography, whilst magnetic resonance imaging is more efficacious in assessing vertebral metastases&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/2028061/&lt;/ref&gt;.<br /> <br /> '''Computed tomography''' (CT scans) has a high sensitivity, ranging from 71 to 100%, for the detection of metastatic bone lesions&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/9362427/&lt;/ref&gt;. Because of the excellent soft tissue resolution of the images produced by CT, it is a particularly helpful modality to distinguish lytic and sclerotic metastases and to visualise their precise location(s) for biopsy.<br /> <br /> '''Magnetic resonance imaging''' (MRI scans) is useful in assessing bone marrow infiltration by tumour deposits, and is required (whole spine) for the proper diagnosis of [[Metastatic spinal cord compression|MSCC]]. It has similarly high specificity (73 to 100%) and sensitivity (82 to 100%) in screening for bone metastases&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10964746/&lt;/ref&gt;.<br /> <br /> '''Positron emission tomography''' (PET scans) detects tumour indirectly by measuring metabolic activity in the form of fluorodeoxyglucose (&lt;sup&gt;18&lt;/sup&gt;F) tissue uptake. As such, its use is not limited to visualising only bony metastases, as &lt;sup&gt;18&lt;/sup&gt;F PET will reveal non-bony metastatic spread also&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/8638000/&lt;/ref&gt;. The accuracy of PET is highly dependent on the primary tumour site from which imaged metastases originate. As a modality it is superior to scintigraphy in the screening of bony metastases from breast (specificity 94%, sensitivity 95%)&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/12073051/&lt;/ref&gt; and lung (specificity 99%, sensitivity 92%)&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10478250/&lt;/ref&gt; malignancies, but has lower sensitivity in detecting the comparatively slower-growing bone metastases of prostate and renal cancers&lt;ref&gt;https://www.ncbi.nlm.nih.gov/pubmed/10520701/&lt;/ref&gt;. <br /> <br /> ===Biopsy===<br /> Sometimes it is necessary to diagnose metastases histologically, by removing cells or tissue from the bone lesion(s) directly. Usually this is in the form of a needle or surgical biopsy, and may be indicated if a primary cancer is not known. If the patient has a known primary cancer, then often imaging alone will suffice for the diagnosis of metastatic bone disease.<br /> <br /> ==Treatment==<br /> There are a variety of therapeutic interventions available to patients presenting with bone metastases, but consideration must be given to several patient-specific and tumour-dependent parameters, which include (but are not limited to):<br /> <br /> * Site (localised or widespread)<br /> * Presence of extraskeletal metastasis<br /> * Tumour type and features (like receptors)<br /> * Prior treatment history (and response)<br /> * Symptoms<br /> * Performance status<br /> <br /> Radiation, bisphosphonates, denosumab, analgesia, chemo, hormonal therapies, surgery, bone cement<br /> <br /> ==Living with bone metastases==<br /> Pain, mobility and safety, survival&lt;references /&gt;</div>

Alex