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Controversies in the Management of Solid Tumor Bone Metastases

  • Andrew M. FarachEmail author
  • E. Brian Butler
  • Bin S. Teh
Part of the Medical Radiology book series


Bone metastases from solid tumor origin are challenging to manage and require a coordinated multi-specialist effort. Skeletal related events result in a significant societal burden and the predominant goal of the orthopedic oncologist is palliation of pain and preservation of function. Given the wide range of clinical scenarios that may be encountered, controversies exist both within and among specialties. This chapter reviews the current landscape in the management of bone metastases with a focus on commonly encountered sub-sites including long bones, spine, and periacetabular metastases.


  1. Balain BA, Jaiswal A, Trivedi JM, Eisenstein SM, Kuiper JH, Jaffray DC (2013) The Oswestry Risk Index: an aid in the treatment of metastatic disease of the spine. Bone Joint J 95-B(2):210–216Google Scholar
  2. Barzilai O, Amato MK, McLaughlin L, Reiner AS, Ogilvie SQ, Lis E, Yamada Y, Bilsky MH, Laufer I (2018) Hybrid surgery-radiosurgery therapy for metastatic epidural spinal cord compression: a prospective evaluation using patient-reported outcomes. Neurooncol Pract 5(2):104–113Google Scholar
  3. Barzilai O, Versteeg AL, Sahgal A, Rhines LD, Bilsky MH, Sciubba DM et al (2019) Survival, local control, and health-related quality of life in patients with oligometastatic and polymetastatic spinal tumors: A multicenter, international study. Cancer 125(5):770–778Google Scholar
  4. Berenson J, Pflugmacher R, Jarzem P, Zonder J, Schechtman K, Tillman JB, Bastian L, Ashraf T, Vrionis F, Cancer Patient Fracture Evaluation (CAFE) Investigators (2011) Balloon kyphoplasty versus non-surgical fracture management for treatment of painful vertebral body compression fractures in patients with cancer: a multicentre, randomised controlled trial. Lancet Oncol 12(3):225–235Google Scholar
  5. Bilsky MH, Laufer I, Burch S (2005) Shifting paradigms in the treatment of metastatic spine disease. Spine 34(22):S101–S107Google Scholar
  6. Breast Cancer NCCN Evidence Blocks (2018) NCCN clinical practice guidelines in oncology (NCCN Guidelines®) Version 3.2018 – Nov. 13, 2018Google Scholar
  7. Capanna R, Campanacci DA (2001) The treatment of metastases in the appendicular skeleton. J Bone Joint Surg (Br) 83(4):471–481Google Scholar
  8. Cassidy JT, Baker JF, Lenehan B (2018) The role of prognostic scoring systems in assessing surgical candidacy for patients with vertebral metastasis: a narrative review. Global Spine J 8(6):638–651Google Scholar
  9. Cheon PM, Wong E, Thavarajah N, Dennis K, Lutz S et al (2015) A definition of “uncomplicated bone metastases” based on previous bone metastases radiation trials comparing single-fractions and multi-fraction radiation therapy. J Bone Oncol 4(1):13–17Google Scholar
  10. Choosing Wisely, American Society for Radiation Oncology (ASTRO) (2015).
  11. Choudhury KB, Mallik C, Sharma S, Choudhury DB, Maiti S et al (2011) A randomized controlled trial to compare the efficacy of bisphosphonates in the management of painful bone metastasis. Indian J Palliat Care 17(3):210–218Google Scholar
  12. Chow E, Zeng L, Salvo N, Dennis K, Tsao M, Lutz S (2012) Update on the systematic review of palliative radiotherapy trials for bone metastases. Clin Oncol 24:112–124Google Scholar
  13. Chow E, van der Linden YM, Roos D, Hartsell WF, Hoskin P, Wu JS et al (2014) Single versus multiple fractions of repeat radiation for painful bone metastases: a randomised, controlled, non-inferiority trial. Lancet Oncol 15(2):164–171Google Scholar
  14. Enneking W, Dunham W, Gebhardt M, Malawar M, Pritchard D (1990) A system for the classification of skeletal resections. Chir Organi Mov 75(1):217–240Google Scholar
  15. Lutz ST, Lo SSM, Chang EL, Galanopoulos N, et al. Expert Panel on Radiation Oncology-Bone Metastases (2012) ACR appropriateness criteria® non-spine bone metastases. J Palliat Med 15(5)Google Scholar
  16. Fisher CG, DiPaola CP, Ryken TC, Bilsky MH, Shaffrey CI, Berven SH et al (2010) A novel classification system for spinal instability in neoplastic disease: an evidence-based approach and expert consensus from the Spine Oncology Study Group. Spine 35(22):E1221–E1229Google Scholar
  17. Fizazi K, Carducci M, Smith M, Damião R, Brown J, Karsh L, Milecki P, Shore N, Rader M, Wang H, Jiang Q, Tadros S, Dansey R, Goessl C (2011) Denosumab versus zoledronic acid for treatment of bone metastases in men with castration-resistant prostate cancer: a randomised, double-blind study. Lancet 377(9768):813–822Google Scholar
  18. Fourney DR, Frangou EM, Ryken TC, Dipaola CP, Shaffrey CI, Berven SH et al (2011) Spinal instability neoplastic score: an analysis of reliability and validity from the spine oncology study group. J Clin Oncol 29(22):3072–3077Google Scholar
  19. Gerszten PC, Burton SA, Ozhasoglu C, Welch WC (2007) Radiosurgery for spinal metastases: clinical experience in 500 cases from a single institution. Spine 32(2):193–199Google Scholar
  20. Gravalos C, Rodriguez C, Sabino A, Segui MA, Virizuela JA, Carmona A, Cassinello J, Isla D, Jara C, Martin M (2016) SEOM clinical guideline for bone metastases from solid tumours. Clin Transl Oncol 18(12):1243–1253Google Scholar
  21. Hansen-Algenstaedt N, Kwan MK, Algenstaedt P, Chiu CK, Viezens L, Chan TS, Lee CK, Wellbrock J, Chan CYW, Schaefer C (2017a) Comparison between minimally invasive surgery and conventional open surgery for patients with spinal metastasis: a prospective propensity score-matched study. Spine 42(10):789–797Google Scholar
  22. Hansen-Algenstaedt N, Kwan MK, Algenstaedt P, Chiu CK, Viezens L et al (2017b) Comparison between minimally invasive surgery and conventional open surgery for patients with spinal metastasis: a prospective propensity score-matched study. Spine 42(10):789–797Google Scholar
  23. Harel R, Angelov L (2010) Spine metastases: current treatments and future directions. Eur J Cancer 46(15):2696–2707Google Scholar
  24. Harrington KD (1981) The management of acetabular insufficiency secondary to metastatic malignant disease. J Bone Joint Surg Am 63(4):653–664Google Scholar
  25. Henry D, Vadhan-Raj S, Hirsh V, von Moos R, Hungria V, Costa L, Woll PJ, Scagliotti G, Smith G, Feng A, Jun S, Dansey R, Yeh H (2014) Delaying skeletal-related events in a randomized phase 3 study of denosumab versus zoledronic acid in patients with advanced cancer: an analysis of data from patients with solid tumors. Support Care Cancer 22(3):679–687Google Scholar
  26. Hernandez RK, Adhia A, Wade SW, O’Connor E, Arellano J, Francis K, Alvrtsyan H, Million RP, Liede A (2015) Prevalence of bone metastases and bone-targeting agent using solid tumor patients in the United States. Clin Epidemiol 7:335–345Google Scholar
  27. Hernandez RK, Wade SW, Reich A, Pirolli M, Liede A, Lyman GH (2018) Incidence of bone metastases in patients with solid tumors: analysis of oncology electronic medical records in the United States. BMC Cancer 18:44Google Scholar
  28. Himelstein AL, Qin R, Novotny PJ, Seisler DK, Khatcheressian JL, Roberts JD et al (2015) CALGB 70604 (Alliance): a randomized phase III study of standard dosing vs. longer interval dosing of zoledronic acid in metastatic cancer. J Clin Oncol 33(suppl):abstr 9501Google Scholar
  29. Hortobayi GN, Lipton A, Chew HC, Gradishar WJ, Sauter N, Mohanlal R et al (2014) Efficacy and safety of continued zoledronic acid every 4 weeks versus every 12 weeks in women with bone metastases from breast cancer: results of the OPTIMIZE-2 trial. J Clin Oncol 32:5sGoogle Scholar
  30. Hoskin P, Sundar S, Reczko K, Forsyth S, Mithal N et al (2015) A multicenter randomized trial of ibandronate compared with single-dose radiotherapy for localized metastatic bone pain in prostate cancer. J Natl Cancer Inst 107(10)Google Scholar
  31. Hospital Outpatient Quality Reporting Program (2016) Fact Sheet for OP-33: External Beam Radiotherapy for Bone Metastases.
  32. Ji T, Guo W, Yang R-L, Tang S, Sun X (2011) Clinical outcome and quality of life after surgery for peri-acetabular metastases. J Bone Joint Surg (Br) 93-B:1104–1110Google Scholar
  33. Johnson S (2018) What percentage of bones in the body comprise the axial skeleton? Sciencing, Accessed 16 Nov 2018
  34. Kohno N, Aogi K, Minami H, Nakamura S, Asaga T, Iino Y, Watanabe T, Goessl C, Ohashi Y, Takashima S (2005) Zoledronic acid significantly reduces skeletal complications compared with placebo in Japanese women with bone metastases from breast cancer: a randomized, placebo-controlled trial. J Clin Oncol 23(15):3314–3321Google Scholar
  35. Konski A (2004) Radiotherapy is a cost-effective palliative treatment for patients with bone metastasis from prostate cancer. Int J Radiat Oncol Biol Phys 60(5):1373–1378Google Scholar
  36. Leithner A, Radl R, Gruber G, Hochegger M, Leithner K, Welkerling H, Rehak P, Windhager R (2008) Predictive value of seven preoperative prognostic scoring systems for spinal metastases. Eur Spine J 17(11):1488–1495Google Scholar
  37. Lovelock DM, Zhang Z, Jackson A, Keam J, Bekelman J et al (2010) Correlation of local failure with measures of dose insufficiency in the high-dose single-fraction treatment of bony metastases. Int J Radiat Oncol Biol Phys 77(4):1282–1287Google Scholar
  38. Lutz S, Balboni T, Jones J, Lo S, Petit J, Rich SE, Wong R, Hahn C (2017) Palliative radiation therapy for bone metastases: Update of an ASTRO Evidence-Based Guideline. Pract Radiat Oncol 7:4–12Google Scholar
  39. Marco RAW (2018) Metastatic spine disease: a guide to diagnosis and management. Springer, BerlinGoogle Scholar
  40. Mirels H (1989) Metastatic disease in long bones. A proposed scoring system for diagnosing impending pathologic fractures. Clin Orthop Relat Res 249:256–264Google Scholar
  41. Muller DA, Capanna R (2015) The surgical treatment of pelvic bone metastases. Adv Orthop 2015:525363Google Scholar
  42. Patchell RA, Tibbs PA, Regine WF, Payne R et al (2005) Direct decompressive surgical resection in the treatment of spinal cord compression caused by metastatic cancer: a randomised trial. Lancet 366(9486):643–648Google Scholar
  43. Rades D, Rudat V, Veninga T, Stalpers LJ, Basic H et al (2008a) A score predicting post treatment ambulatory status in patients irradiated for metastatic spinal cord compression. Int J Radiat Oncol Biol Phys 72(3):905–908Google Scholar
  44. Rades D, Dunst J, Schild SE (2008b) The first score predicting overall survival in patients with metastatic spinal cord compression. Cancer 112(1):157–161Google Scholar
  45. Rades D, Douglas S, Huttenlocher S, Rudat V, Veninga T et al (2011) Validation of a score predicting post-treatment ambulatory status after radiotherapy for metastatic spinal cord compression. Int J Radiat Oncol Biol Phys 79(5):1503–1506Google Scholar
  46. Roos DE (2000) Continuing reluctance to use single fractions of radiotherapy for metastatic bone pain: an Australian and New Zealand practice survey and literature review. Radiother Oncol 56:315–322Google Scholar
  47. Rosen LS, Gordon D, Tchekmedyian NS, Yanagihara R, Hirsh V, Krzakowski M, Pawlicki M, De Souza P, Zheng M, Urbanowitz G, Reitsma D, Seaman J (2004) Long-term efficacy and safety of zoledronic acid in the treatment of skeletal metastases in patients with nonsmall cell lung carcinoma and other solid tumors: a randomized, phase III, double-blind, placebo-controlled trial. Cancer 100(12):2613–2621Google Scholar
  48. Rutter CE, Yu JB, Wilson LD, Park HS (2015) Assessment of national practice for palliative radiation therapy for bone metastases suggests marked underutilization of single-fraction regimens in the United States. Int J Radiat Oncol Biol Phys 91(3):548–555Google Scholar
  49. Saad F, Gleason DM, Murray R, Tchekmedyian S, Venner P, Lacombe L, Chin JL, Vinholes JJ, Goas JA, Zheng M, Zoledronic Acid Prostate Cancer Study Group (2004) Long-term efficacy of zoledronic acid for the prevention of skeletal complications in patients with metastatic hormone-refractory prostate cancer. J Natl Cancer Inst 96(11):879–882Google Scholar
  50. Scagliotti GV, Hirsh V, Siena S, Henry DH, Woll PJ, Manegold C, Solal-Celigny P, Rodriguez G, Krzakowski M, Mehta ND, Lipton L, García-Sáenz JA, Pereira JR, Prabhash K, Ciuleanu TE, Kanarev V, Wang H, Balakumaran A, Jacobs I (2012a) Overall survival improvement in patients with lung cancer and bone metastases treated with denosumab versus zoledronic acid: subgroup analysis from a randomized phase 3 study. J Thorac Oncol 7(12):1823–1829Google Scholar
  51. Scagliotti GV, Hirsh V, Siena S, Henry DH, Woll PJ et al (2012b) Overall survival improvement in patients with lung cancer and bone metastases treated with denosumab versus zoledronic acid: subgroup analysis from a randomized phase 3 study. J Thorac Oncol 7(12):1823–1829Google Scholar
  52. Steenland E, Leer J, van Houwelingen H, Post WJ, van den Hout WB et al (1999) The effect of a single fraction compared to multiple fractions on painful bone metastases: a global analysis of the Dutch Bone Metastasis Study. Radiother Oncol 52:101–109Google Scholar
  53. Stopeck AT, Lipton A, Body JJ, Steger GG, Tonkin K, de Boer RH, Lichinitser M, Fujiwara Y, Yardley DA, Viniegra M, Fan M, Jiang Q, Dansey R, Jun S, Braun A (2010) Denosumab compared with zoledronic acid for the treatment of bone metastases in patients with advanced breast cancer: a randomized, double-blind study. J Clin Oncol 28(35):5132–5139Google Scholar
  54. Tokuhashi Y, Matsuzaki H, Oda H, Oshima M, Ryu J (2005) A revised scoring system for preoperative evaluation of metastatic spine tumor prognosis. Spine 30(19):2186–2191Google Scholar
  55. Tomita K, Kawahara N, Kobayashi T, Yoshida A, Murakami H, Akamaru T (2001) Surgical strategy for spinal metastases. Spine 26(3):298–306Google Scholar
  56. Townsend PW, Smalley SR, Cozad SC, Rosenthal HG, Hassanein RES (1995) Role of postoperative radiation therapy after stabilization of fractures caused by metastatic disease. Int J Radiat Oncol Biol Phys 31(1):43–49Google Scholar
  57. Wilkinson AN, Viola R, Brundage MD (2008) Managing skeletal related events resulting from bone metastases. BMJ 337:A2041Google Scholar
  58. Wood TJ, Racano A, Yeung H, Farrokhyar F, Ghert M, Deheshi BM (2014) Surgical management of bone metastases: quality of evidence and systematic review. Ann Surg Oncol 21(13):4081–4089Google Scholar
  59. Yamada Y, Bilsky MH, Lovelock DM, Venkatraman ES, Toner S et al (2008) High-dose, single-fraction image-guided intensity-modulated radiotherapy for metastatic spinal lesions. Int J Radiat Oncol Biol Phys 71(2):484–490Google Scholar
  60. Yamada Y, Cox B, Zelefsky MJ et al (2011) An analysis of prognostic factors for local control of malignant spine tumors treated with spine radiosurgery. Int J Radiat Oncol Biol Phys 81:S132–S133Google Scholar
  61. Yamada K, Yoshimura M, Kaise H, Ogata A, Ueda N et al (2012) Concurrent use of Sr-89 chloride with zoledronic acid is safe and effective for breast cancer patients with painful bone metastases. Exp Ther Med 3(2):226–230Google Scholar
  62. Zuckerman SL, Laufer I, Sahgal A, Yamada YJ, Schmidt MH et al (2016) When less is more: the indications for MIS techniques and separation surgery in metastatic spine disease. Spine 41(20):S246–S253Google Scholar

Copyright information

© Springer Nature Switzerland AG  2019

Authors and Affiliations

  • Andrew M. Farach
    • 1
    Email author
  • E. Brian Butler
    • 1
  • Bin S. Teh
    • 1
  1. 1.Department of Radiation OncologyHouston Methodist HospitalHoustonUSA

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