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bone metastases

Etiology: 1) prostate cancer (80%) 2) lung cancer 3) breast cancer 4) thyroid cancer 5) kidney cancer Physical examination: - digital rectal examination (men) Clinical manifestations: - most commonly spine, pelvis, ribs, skull, upper arm & long bones of the leg involved [4] - bone pain is often the first symptom [3] - the pain often comes and goes at first - it tends to be worse at night & may be relieved by movement - later on, it can become constant & may be worse during activity - pathologic bone fracture may occur - spinal cord compression may occur Laboratory: - serum chemistries - serum calcium may be high - serum alkaline phosphatase may be high - serum protein electrophoresis - urinalysis - urine protein electrophoresis - N-telopeptide in urine - complete blood count - anemia may occur if sufficient amounts of marrow effected - serum prostate-specific antigen (men) Radiology: - radiography - computed tomography - most sensitive study to detect bone destruction [5] - magnetic resonance imaging - most sensitive study for assessment intramedullary & extraosseous involvement [5] - bone scan - very sensitive study for detection of occult lesions & assessment of lesion activity Management: 1) symptomatic relief of pain from uncomplicated bone metastases - radiotherapy: 8 Gy treatment to the appropriate target once - effective benefit covered by hospice - investigational FLASH proton radiotherapy can be delivered at 1000 times the dose rate of conventional-dose-rate photon radiotherapy for its potential normal tissue-sparing effects [9,10] 2) see spinal cord compression for vertebral metastases 3) intravenous radiopharmaceutical a) indication: targeted radiotherapy not feasible or practical b) strontium-89 is 148 mBq (4mCi) IV over 1-2 minutes with hydration (> 500 mL) c) samarium-153 is 37 mBq/kg (1 mCi/kg) IV over 1-2 minutes with hydration (> 500 mL) d) intravenous radium-223 (50 kBq/kg) improves symptoms & overall survival in patients with bone-limited or bone-predominant metastatic prostate cancer [6,7] 4) dexamethasone 4 mg PO/IV every 6-12 hours in conjunction with radiotherapy, duration ? [1] a) decreases neuropathic pain & bone pain b) reduces vasogenic edema 5) prophylactic radiation to asymptomatic, high-risk bone metastases reduces pathologic fractures, spinal cord compression, orthopedic surgery, or palliative radiation therapy & hospitalizations in patients with lung cancer, breast cancer, prostate cancer & other cancers [13] 6) not useful - epidural glucocorticoids: lack of evidence supporting use in patients with pain from bone metastases - calcitonin: evidence does not support use to control pain from bone metastases [12] 7) bisphosphonate to prevent bone fractures - denosumab may be alternative to bisphosphonate (NGC)

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metastasis

References

  1. Geriatric Review Syllabus, 7th edition Parada JT et al (eds) American Geriatrics Society, 2010
  2. Taylor JW, Schiff D. Metastatic epidural spinal cord compression. Semin Neurol. 2010 Jul;30(3):245-53. PMID: 20577931
  3. American Cancer Society Bone Metastasis http://www.cancer.org/treatment/understandingyourdiagnosis/bonemetastasis/bone-metastasis-detailed-guide-toc
  4. OrthoInfo Metastatic Bone Disease http://orthoinfo.aaos.org/topic.cfm?topic=a00093
  5. Chansky HA, Gellman H Medscape: Metastatic Bone Disease http://emedicine.medscape.com/article/1253331-overview
  6. Parker C et al. Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med 2013 Jul 18; 369:213 PMID: 23863050 http://www.nejm.org/doi/full/10.1056/NEJMoa1213755 - Vapiwala N and Glatstein E. Fighting prostate cancer with radium-223 - Not your madame's isotope. N Engl J Med 2013 Jul 18; 369:276 PMID: 23863055 http://www.nejm.org/doi/full/10.1056/NEJMe1304041
  7. Medical Knowledge Self Assessment Program (MKSAP) 17, American College of Physicians, Philadelphia 2015
  8. Handkiewicz-Junak D, Poeppel TD, Bodei L, et al. EANM guidelines for radionuclide therapy of bone metastases with beta-emitting radionuclides. Eur J Nucl Med Mol Imaging. 2018 Feb 16. PMID: 29453701 https://link.springer.com/article/10.1007%2Fs00259-018-3947-x
  9. Mascia AE, Daugherty EC, Zhang Y et al Proton FLASH Radiotherapy for the Treatment of Symptomatic Bone Metastases. The FAST-01 Nonrandomized Trial. JAMA Oncol. Published online October 23, 2022 PMID: 36273324 https://jamanetwork.com/journals/jamaoncology/fullarticle/2797843 - Jarvis LA, Zhang R, Pogue BW The First FLASH Clinical Trial - The Journey of a Thousand Miles Begins With 1 Step. JAMA Oncol. Published online October 23, 2022 PMID: 36273321 https://jamanetwork.com/journals/jamaoncology/fullarticle/2797844
  10. Daugherty EC, Mascia AE, Zhang Y et al FLASH Radiotherapy for the Treatment of Symptomatic Bone Metastases (FAST-01): Protocol for the First Prospective Feasibility Study. JMIR Res Protoc. 2022 Oct 4. PMID: 36206189 Free article
  11. Chow E, Meyer RM, Ding K et al Dexamethasone in the prophylaxis of radiation-induced pain flare after palliative radiotherapy for bone metastases: a double-blind, randomised placebo-controlled, phase 3 trial. Lancet Oncol. 2015 Nov;16(15):1463-1472 PMID: 26489389 Clinical Trial.
  12. Martinez-Zapata MJ, Roque M, Alonso-Coello P, Catala E. Calcitonin for metastatic bone pain. Cochrane Database Syst Rev. 2006 Jul 19;2006(3):CD003223. PMID: 16856000 PMCID: PMC9676422 Free PMC article
  13. Gillespie EF et al. Prophylactic radiation therapy versus standard of care for patients with high-risk asymptomatic bone metastases: A multicenter, randomized phase ii clinical trial. J Clin Oncol 2024 Jan 1; 42:38. PMID: 37748124 PMCID: PMC10730067 (available on 2025-01-01) https://ascopubs.org/doi/10.1200/JCO.23.00753
  14. Hsu SH, Wang SY. Trends in Provision of Palliative Radiotherapy and Chemotherapy Among Hospices in the United States, 2011-2018. JAMA Oncol. 2020 Jul 1;6(7):1106-1108. PMID: 32352492 PMCID: PMC7193522 Free PMC article.