Articles:Bone metastases - Revision history

Alex at 16:56, 14 August 2020

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Alex at 13:37, 24 April 2020

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Alex at 14:04, 23 April 2020

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Alex at 15:08, 22 April 2020

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Alex at 14:49, 22 April 2020

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 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.
-'''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<ref>https://www.ncbi.nlm.nih.gov/pubmed/12085970</ref>.
+'''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<ref>https://pubmed.ncbi.nlm.nih.gov/12085970/</ref>.
-'''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<ref>https://www.ncbi.nlm.nih.gov/pubmed/8086233/</ref>. 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.
+'''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<ref>https://pubmed.ncbi.nlm.nih.gov/8086233/</ref>. 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.
-'''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<ref>https://www.ncbi.nlm.nih.gov/pubmed/11346860/</ref>.
+'''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<ref>https://pubmed.ncbi.nlm.nih.gov/11346860/</ref>.
 ==Diagnosis==
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 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.
-'''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<ref>https://www.ncbi.nlm.nih.gov/pubmed/9025785/</ref>. As outlined above, sclerotic metastases will appear more radiopaque than the surrounding bone, whereas lytic metastases will appear more radiolucent.
+'''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<ref>https://pubmed.ncbi.nlm.nih.gov/9025785/</ref>. As outlined above, sclerotic metastases will appear more radiopaque than the surrounding bone, whereas lytic metastases will appear more radiolucent.
-'''Bone scintigraphy''' (bone scans) on the other hand is highly sensitive but with low specificity. Data from Technetium-99m ('''<sup>99m</sup>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<ref>https://www.ncbi.nlm.nih.gov/pubmed/2028061/</ref>.
+'''Bone scintigraphy''' (bone scans) on the other hand is highly sensitive but with low specificity. Data from Technetium-99m ('''<sup>99m</sup>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<ref>https://pubmed.ncbi.nlm.nih.gov/2028061/</ref>.
-'''Computed tomography''' (CT scans) has a high sensitivity, ranging from 71 to 100%, for the detection of metastatic bone lesions<ref>https://www.ncbi.nlm.nih.gov/pubmed/9362427/</ref>. 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.
+'''Computed tomography''' (CT scans) has a high sensitivity, ranging from 71 to 100%, for the detection of metastatic bone lesions<ref>https://pubmed.ncbi.nlm.nih.gov/9362427/</ref>. 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.
-'''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<ref>https://www.ncbi.nlm.nih.gov/pubmed/10964746/</ref>.
+'''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<ref>https://pubmed.ncbi.nlm.nih.gov/10964746/</ref>.
-'''Positron emission tomography''' (PET scans) detects tumour indirectly by measuring metabolic activity in the form of fluorodeoxyglucose ('''<sup>18</sup>F''') tissue uptake. As such, its use is not limited to visualising only bony metastases, as <sup>18</sup>F PET will reveal non-bony metastatic spread also<ref>https://www.ncbi.nlm.nih.gov/pubmed/8638000/</ref>. 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%)<ref>https://www.ncbi.nlm.nih.gov/pubmed/12073051/</ref> and lung (specificity 99%, sensitivity 92%)<ref>https://www.ncbi.nlm.nih.gov/pubmed/10478250/</ref> malignancies, but has lower sensitivity in detecting the comparatively slower-growing bone metastases of prostate and renal  cancers<ref>https://www.ncbi.nlm.nih.gov/pubmed/10520701/</ref>.
+'''Positron emission tomography''' (PET scans) detects tumour indirectly by measuring metabolic activity in the form of fluorodeoxyglucose ('''<sup>18</sup>F''') tissue uptake. As such, its use is not limited to visualising only bony metastases, as <sup>18</sup>F PET will reveal non-bony metastatic spread also<ref>https://pubmed.ncbi.nlm.nih.gov/8638000/</ref>. 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%)<ref>https://pubmed.ncbi.nlm.nih.gov/12073051/</ref> and lung (specificity 99%, sensitivity 92%)<ref>https://pubmed.ncbi.nlm.nih.gov/10478250/</ref> malignancies, but has lower sensitivity in detecting the comparatively slower-growing bone metastases of prostate and renal  cancers<ref>https://pubmed.ncbi.nlm.nih.gov/10520701/</ref>.
 ===Biopsy===
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 ==Treatment==
-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<ref>https://www.ncbi.nlm.nih.gov/pubmed/11738947/</ref> (but are not limited to):
+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<ref>https://pubmed.ncbi.nlm.nih.gov/11738947/</ref> (but are not limited to):
 *Lesion site(s) (localised or widespread)
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 ===Radiotherapy===
-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<ref>https://www.ncbi.nlm.nih.gov/pubmed/24782453/</ref>. Other than localised bone pain, additional indications for radiotherapy include [[Metastatic spinal cord compression|MSCC]] and bones at high risk for [[pathological fracture]]<ref>https://www.ncbi.nlm.nih.gov/pubmed/15978828/</ref>. 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).
+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<ref>https://pubmed.ncbi.nlm.nih.gov/24782453/</ref>. Other than localised bone pain, additional indications for radiotherapy include [[Metastatic spinal cord compression|MSCC]] and bones at high risk for [[pathological fracture]]<ref>https://pubmed.ncbi.nlm.nih.gov/15978828/</ref>. 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).
-'''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%<ref>https://www.ncbi.nlm.nih.gov/pubmed/6178497/</ref>. 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<ref>https://www.ncbi.nlm.nih.gov/pubmed/9681885</ref>, 24 Gy<ref>https://www.ncbi.nlm.nih.gov/pubmed/10577695</ref>, and 30 Gy<ref>https://www.ncbi.nlm.nih.gov/pubmed/10577696</ref>.
+'''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%<ref>https://pubmed.ncbi.nlm.nih.gov/6178497/</ref>. 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<ref>https://www.ncbi.nlm.nih.gov/pubmed/9681885</ref>, 24 Gy<ref>https://www.ncbi.nlm.nih.gov/pubmed/10577695</ref>, and 30 Gy<ref>https://www.ncbi.nlm.nih.gov/pubmed/10577696</ref>.
 '''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<ref>https://www.ncbi.nlm.nih.gov/pubmed/8823257</ref>, that increasing doses beyond 8 Gy does not improve overall pain responses<ref>https://www.ncbi.nlm.nih.gov/pubmed/11395246</ref>, 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<ref>https://www.ncbi.nlm.nih.gov/pubmed/1374061</ref>. 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<ref>https://www.ncbi.nlm.nih.gov/pubmed/6178497/</ref>. Any treatments must be delivered with fields shaped to minimise irradiation of organs at risk, such as lung, liver, kidney and bowel.

← Older revision		Revision as of 13:37, 24 April 2020
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	==Living with bone metastases==		==Living with bone metastases==
−	Pain, ~~mobility~~ and safety, survival<references />	+	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.
		+
		+	'''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.
		+
		+	'''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.
		+
		+	'''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.<references />

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 '''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<ref>https://www.ncbi.nlm.nih.gov/pubmed/21629403</ref>. Depending on where cementoplasty is used, it may be termed differently:
-* Osteoplasty (generic term, into non-axial bones)
+*Osteoplasty (generic term, injection into non-axial bone lesions)
-* Vertebroplasty (into an affected vertebra)
+*Vertebroplasty (injection into a vertebral lesion)
-* Kyphoplasty (mostly for vertebral fractures, this is vertebroplasty with use of balloon inflation beforehand to restore vertebral height)
+*Kyphoplasty (mostly for vertebral fractures, this is vertebroplasty with use of intravertebral balloon inflation beforehand to restore vertebral height)
-* Sacroplasty (into a sacral lesion)
+*Sacroplasty (injection into a sacral lesion)
 ===Surgery===

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 '''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<ref>https://www.ncbi.nlm.nih.gov/pubmed/21785102/</ref>. Complications rates for each procedure are low, but localised infection and enduring neuropathic pain have been reported.
-percutaneous cementoplasty (bone cement)
+'''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<ref>https://www.ncbi.nlm.nih.gov/pubmed/21629403</ref>. Depending on where cementoplasty is used, it may be termed differently:
 ===Surgery===

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 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''<nowiki/>'; small-molecules: '-''golix''<nowiki/>'), GnRH receptor agonists ('-''relin''<nowiki/>'), 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.
 ===Interventional radiology===
-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.
+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.
 '''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<ref>https://www.ncbi.nlm.nih.gov/pubmed/21785102/</ref>. Complications rates for each procedure are low, but localised infection and enduring neuropathic pain have been reported.

@@ Line 104: / Line 104: @@
 ===Surgery===
+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.
 ==Living with bone metastases==
 Pain, mobility and safety, survival<references />

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 ===Hormone therapies===
 ===Interventional radiology===
 Ablation (inc. RFA), percutaneous cementoplasty (bone cement)