External Beam Radiotherapy in the Treatment of Painful Bone Metastases

  • Candice JohnstoneEmail author
  • Amol J. Ghia
  • Anussara Prayongrat


The management of bone metastases is a multidisciplinary effort. External beam radiotherapy (EBRT) remains an effective and efficient method by which to palliate pain and prevent pathologic fracture. Various regimens have been utilized in the treatment of bone metastasis. The most commonly used and guideline-supported regimens range from 8 Gy in a single fraction to 30 Gy in 10 fractions. These regimens provide equivalent pain relief with minimal side effects. Stereotactic body radiation therapy (SBRT), a form of high-dose, highly conformal radiation therapy, shows promise in the treatment of selected patients. Due to the expense and complexity, the most appropriate indications for this technology are yet to be determined through continued accrual to ongoing clinical trials. National guidelines and quality metrics help define the use of EBRT in the treatment of uncomplicated bone metastasis.


External beam radiotherapy (EBRT) Bone metastases Fractionation Pain Highly conformal therapy Stereotactic body radiation therapy (SBRT) 


  1. 1.
    Galasko CS. Then anatomy and pathways of bone metastasis. In: Weiss L, Gilbert A, editors. Bone metastasis. Boston: GK Hall; 1981. p. 49–63.Google Scholar
  2. 2.
    Laufer I, Rubin DG, Lis E, Cox BW, Stubblefield MD, Yamada Y, et al. The NOMS framework: approach to the treatment of spinal metastatic tumors. Oncologist. 2013;18(6):744–51. PubMed PMID: 23709750. Pubmed Central PMCID: 4063402. eng.PubMedPubMedCentralCrossRefGoogle Scholar
  3. 3.
    Coleman RE. Skeletal complications of malignancy. Cancer. 1997;80(8 Suppl):1588–94. PubMed PMID: 9362426. Epub 1997/11/15. eng.PubMedCrossRefGoogle Scholar
  4. 4.
    Kamby C, Vejborg I, Daugaard S, Guldhammer B, Dirksen H, Rossing N, et al. Clinical and radiologic characteristics of bone metastases in breast cancer. Cancer. 1987;60(10):2524–31. PubMed PMID: 3664434. Epub 1987/11/15. eng.PubMedCrossRefGoogle Scholar
  5. 5.
    Chow E, Harris K, Fan G, Tsao M, Sze WM. Palliative radiotherapy trials for bone metastases: a systematic review. J Clin Oncol. 2007;25(11):1423–36.PubMedPubMedCentralCrossRefGoogle Scholar
  6. 6.
    Chow E, Zeng L, Salvo N, Dennis K, Tsao M, Lutz S. Update on the systematic review of palliative radiotherapy trials for bone metastases. Clin Oncol (R Coll Radiol). 2012;24(2):112–24. PubMed PMID: 22130630. Epub 2011/12/02. engCrossRefGoogle Scholar
  7. 7.
    van der Linden YM, Lok JJ, Steenland E, Martijn H, van Houwelingen H, Marijnen CAM, et al. Single fraction radiotherapy is efficacious: a further analysis of the Dutch bone metastasis study controlling for the influence of retreatment. Int J Radiat Oncol Biol Phys. 2004;59(2):528–37. PubMed PMID: 15145173PubMedCrossRefGoogle Scholar
  8. 8.
    WHO. World Health Organization Pain Ladder 2010 [cited 2013 9 Feb 3013]. Available from:
  9. 9.
    van der Linden YM, Steenland E, van Houwelingen HC, Post WJ, Oei B, Marijnen CAM, et al. Patients with a favourable prognosis are equally palliated with single and multiple fraction radiotherapy: results on survival in the Dutch bone metastasis study. Radiother Oncol. 2006;78(3):245–53.PubMedCrossRefGoogle Scholar
  10. 10.
    Chow E, van der Linden YM, Roos D, Hartsell WF, Hoskin P, Wu JS, et al. Single versus multiple fractions of repeat radiation for painful bone metastases: a randomised, controlled, non-inferiority trial. Lancet Oncol. 2014;15(2):164–71. PubMed PMID: 24369114.PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    Nielsen OS, Munro AJ, Tannock IF. Bone metastases: pathophysiology and management policy. J Clin Oncol. 1991;9(3):509–24.PubMedCrossRefGoogle Scholar
  12. 12.
    Springfield D. Pathologic fractures. Rockwood and Green’s fractures in adults. 5th ed. Philadelphia: Lippincott Williams Wilkins; 2001.Google Scholar
  13. 13.
    Koswig S, Budach V. [Remineralization and pain relief in bone metastases after after different radiotherapy fractions (10 times 3 Gy vs. 1 time 8 Gy). A prospective study]. Strahlentherapie und Onkologie : Organ der Deutschen. Rontgengesellschaft [et al]. 1999 Oct;175(10):500–8. PubMed PMID: 10554645. Epub 1999/11/11. Remineralisation und Schmerzlinderung von Knochenmetastasen nach unterschiedlich fraktionierter Strahlentherapie (10 mal 3 Gy vs. 1 mal 8 Gy). Eine prospektive Studie. ger.Google Scholar
  14. 14.
    Townsend PW, Smalley SR, Cozad SC, Rosenthal HG, Hassanein RE. Role of postoperative radiation therapy after stabilization of fractures caused by metastatic disease. Int J Radiat Oncol Biol Phys. 1995;31(1):43–9. PubMed PMID: 7995767. Epub 1995/01/01. engPubMedCrossRefGoogle Scholar
  15. 15.
    Harrington KD. Impending pathologic fractures from metastatic malignancy: evaluation and management. Instr Course Lect. 1986;35:357–81. PubMed PMID: 3819423.PubMedGoogle Scholar
  16. 16.
    Mirels H. Metastatic disease in long bones. A proposed scoring system for diagnosing impending pathologic fractures. Clin Orthop Relat Res. 1989;249:256–64. PubMed PMID: 2684463.Google Scholar
  17. 17.
    Fourney DR, Frangou EM, Ryken TC, Dipaola CP, Shaffrey CI, Berven SH, et al. Spinal instability neoplastic score: an analysis of reliability and validity from the spine oncology study group. J Clin Oncol. 2011;29(22):3072–7. PubMed PMID: 21709187.PubMedCrossRefGoogle Scholar
  18. 18.
    Bilsky MH, Laufer I, Fourney DR, Groff M, Schmidt MH, Varga PP, et al. Reliability analysis of the epidural spinal cord compression scale. J Neurosurg Spine. 2010;13(3):324–8. PubMed PMID: 20809724. eng.PubMedCrossRefGoogle Scholar
  19. 19.
    Ryu S, Rock J, Jain R, Lu M, Anderson J, Jin JY, et al. Radiosurgical decompression of metastatic epidural compression. Cancer. 2010;116(9):2250–7. PubMed PMID: 20209611. eng.PubMedGoogle Scholar
  20. 20.
    Maranzano E, Bellavita R, Rossi R, De Angelis V, Frattegiani A, Bagnoli R, et al. Short-course versus split-course radiotherapy in metastatic spinal cord compression: results of a phase III, randomized, multicenter trial. J Clin Oncol. 2005;23(15):3358–65. PubMed PMID: 15738534.PubMedCrossRefGoogle Scholar
  21. 21.
    Maranzano E, Latini P, Perrucci E, Beneventi S, Lupattelli M, Corgna E. Short-course radiotherapy (8 Gy x 2) in metastatic spinal cord compression: an effective and feasible treatment. Int J Radiat Oncol Biol Phys. 1997;38(5):1037–44. PubMed PMID: 9276370.PubMedCrossRefGoogle Scholar
  22. 22.
    Fairchild A, Barnes E, Ghosh S, Ben-Josef E, Roos D, Hartsell W, et al. International patterns of practice in palliative radiotherapy for painful bone metastases: evidence-based practice? Int J Radiat Oncol Biol Phys. 2009;75(5):1501–10. PubMed PMID: 19464820. Epub 2009/05/26. eng.PubMedPubMedCentralCrossRefGoogle Scholar
  23. 23.
    Jeremic B, Shibamoto Y, Acimovic L, Milicic B, Milisavljevic S, Nikolic N, et al. A randomized trial of three single-dose radiation therapy regimens in the treatment of metastatic bone pain. Int J Radiat Oncol Biol Phys. 1998;42(1):161–7. PubMed PMID: 9747834.PubMedCrossRefGoogle Scholar
  24. 24.
    Hartsell WF, Scott CB, Bruner DW, Scarantino CW, Ivker RA, Roach M, et al. Randomized trial of short- versus long-course radiotherapy for palliation of painful bone metastases. J Natl Cancer Inst. 2005;97(11):798–804.PubMedCrossRefGoogle Scholar
  25. 25.
    Party BPTW. 8 Gy single fraction radiotherapy for the treatment of metastatic skeletal pain: randomised comparison with a multifraction schedule over 12 months of patient follow-up. Bone Pain Trial Working Party. Radiother Oncol. 1999;52(2):111–21. PubMed PMID: 10577696.CrossRefGoogle Scholar
  26. 26.
    Steenland E, Leer JW, van Houwelingen H, Post WJ, van den Hout WB, Kievit J, et al. 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. 1999;52(2):101–9. PubMed PMID: 10577695.PubMedCrossRefGoogle Scholar
  27. 27.
    Foro Arnalot P, Fontanals AV, Galceran JC, Lynd F, Latiesas XS, de Dios NR, et al. Randomized clinical trial with two palliative radiotherapy regimens in painful bone metastases: 30 Gy in 10 fractions compared with 8 Gy in single fraction. Radiother Oncol. 2008;89(2):150–5. PubMed PMID: 18556080. Epub 2008/06/17. engPubMedCrossRefGoogle Scholar
  28. 28.
    Hartsell WF, Desilvio M, Bruner DW, Scarantino C, Ivker R, Roach M 3rd, et al. Can physicians accurately predict survival time in patients with metastatic cancer? Analysis of RTOG 97-14. J Palliat Med. 2008;11(5):723–8. PubMed PMID: 18588404. Epub 2008/07/01. eng.PubMedCrossRefGoogle Scholar
  29. 29.
    Van der Linden YM, Dijkstra PD, Kroon HM, Lok JJ, Noordijk EM, Leer JW, et al. Comparative analysis of risk factors for pathological fracture with femoral metastases. J Bone Joint Surg. 2004;86(4):566–73. PubMed PMID: 15174555. Epub 2004/06/04. engCrossRefGoogle Scholar
  30. 30.
    Roos DE, Turner SL, O’Brien PC, Smith JG, Spry NA, Burmeister BH, et al. Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic pain due to bone metastases (Trans-Tasman Radiation Oncology Group, TROG 96.05). Radiother Oncol. 2005;75(1):54–63. PubMed PMID: 15878101. Epub 2005/05/10. eng.PubMedCrossRefGoogle Scholar
  31. 31.
    Maranzano E, Trippa F, Casale M, Costantini S, Lupattelli M, Bellavita R, et al. 8Gy single-dose radiotherapy is effective in metastatic spinal cord compression: results of a phase III randomized multicentre Italian trial. Radiother Oncol. 2009;93(2):174–9. PubMed PMID: 19520448.PubMedCrossRefGoogle Scholar
  32. 32.
    Hartsell W, Scott C, Bruner DW, et al. Phase III randomized trial of 8 Gy in 1 fraction vs. 30 Gy in 10 fractions for palliation of painful bone metastases: preliminary results of RTOG 97–14. Int J Radiat Oncol Biol Phys. 2003;57(Supplement):124.CrossRefGoogle Scholar
  33. 33.
    Loblaw DA, Wu JS, Kirkbride P, Panzarella T, Smith K, Aslanidis J, et al. Pain flare in patients with bone metastases after palliative radiotherapy—a nested randomized control trial. Support Care Cancer. 2007;15(4):451–5. PubMed PMID: 17093912. Epub 2006/11/10. engPubMedCrossRefGoogle Scholar
  34. 34.
    Chow E, Hoskin P, Mitera G, Zeng L, Lutz S, Roos D, et al. Update of the international consensus on palliative radiotherapy endpoints for future clinical trials in bone metastases. Int J Radiat Oncol Biol Phys. 2012;82(5):1730–7. PubMed PMID: 21489705. Epub 2011/04/15. eng.PubMedCrossRefGoogle Scholar
  35. 35.
    Huisman M, van den Bosch MA, Wijlemans JW, van Vulpen M, van der Linden YM, Verkooijen HM. Effectiveness of reirradiation for painful bone metastases: a systematic review and meta-analysis. Int J Radiat Oncol Biol Phys. 2012;84(1):8–14. PubMed PMID: 22300568.PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Lo SS, Fakiris AJ, Chang EL, Mayr NA, Wang JZ, Papiez L, et al. Stereotactic body radiation therapy: a novel treatment modality. Nat Rev Clin Oncol. 2010;7(1):44–54. PubMed PMID: 19997074. Epub 2009/12/10. eng.PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Jaffray D, Kupelian P, Djemil T, Macklis RM. Review of image-guided radiation therapy. Expert Rev Anticancer Ther. 2007;7(1):89–103. PubMed PMID: 17187523. Epub 2006/12/26. engPubMedCrossRefGoogle Scholar
  38. 38.
    Allen AM, Pawlicki T, Dong L, Fourkal E, Buyyounouski M, Cengel K, et al. An evidence based review of proton beam therapy: the report of ASTRO’s emerging technology committee. Radiother Oncol. 2012;103(1):8–11. PubMed PMID: 22405807. Epub 2012/03/13. eng.PubMedCrossRefGoogle Scholar
  39. 39.
    Sahgal A, Larson DA, Chang EL. Stereotactic body radiosurgery for spinal metastases: a critical review. Int J Radiat Oncol Biol Phys. 2008;71(3):652–65. PubMed PMID: 18514775. Epub 2008/06/03. engCrossRefGoogle Scholar
  40. 40.
    Wang XS, Rhines LD, Shiu AS, Yang JN, Selek U, Gning I, et al. Stereotactic body radiation therapy for management of spinal metastases in patients without spinal cord compression: a phase 1−2 trial. Lancet Oncol. 2012;13(4):395–402. PubMed PMID: 22285199. Epub 2012/01/31. engPubMedPubMedCentralCrossRefGoogle Scholar
  41. 41.
    Garg AK, Shiu AS, Yang J, Wang XS, Allen P, Brown BW, et al. Phase 1/2 trial of single-session stereotactic body radiotherapy for previously unirradiated spinal metastases. Cancer. 2012;118(20):5069–77. PubMed PMID: 22511344. Epub 2012/04/19. eng.PubMedPubMedCentralCrossRefGoogle Scholar
  42. 42.
    Jhaveri PM, Teh BS, Paulino AC, Blanco AI, Lo SS, Butler EB, et al. A dose-response relationship for time to bone pain resolution after stereotactic body radiotherapy (SBRT) for renal cell carcinoma (RCC) bony metastases. Acta Oncol. 2012;51(5):584–8. PubMed PMID: 22248089. Epub 2012/01/18. eng.PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
  44. 44.
    Lo SS, Sahgal A, Chang EL, Mayr NA, Teh BS, Huang Z, et al. Serious complications associated with stereotactic ablative radiotherapy and strategies to mitigate the risk. Clin Oncol (R Coll Radiol). 2013;25(6):378–87.PubMedCrossRefGoogle Scholar
  45. 45.
    Brown JMCD, Brenner DJ. The tumor radiobiology of SRS and SBRT: are more than the 5 Rs involved? Int J Radiat Oncol Biol Phys. 2014;88(2):254–62.PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    Song CW, Kim MS, Cho LC, Dusenbery K, Sperduto PW. Radiobiological basis of SBRT and SRS. Int J Clin Oncol. 2014;19(4):570–8. PubMed PMID: 24993673. eng.PubMedCrossRefGoogle Scholar
  47. 47.
    Song CW, Cho LC, Yuan J, Dusenbery KE, Griffin RJ, Levitt SH. Radiobiology of stereotactic body radiation therapy/stereotactic radiosurgery and the linear-quadratic model. Int J Radiat Oncol Biol Phys. 2013;87(1):18–9. PubMed PMID: 23608235. eng.PubMedCrossRefGoogle Scholar
  48. 48.
    Kirkpatrick JP, KMJ M, Marks LB. The linear-quadratic model is inappropriate to model high dose per fraction effects in radiosurgery. Semin Radiat Oncol. 2008;18(4):240–3. 20080826 DCOM- 20081009. eng.PubMedCrossRefGoogle Scholar
  49. 49.
    Yu HH, Hoffe SE. Beyond the conventional role of external-beam radiation therapy for skeletal metastases: new technologies and stereotactic directions. Cancer Control. 2012;19(2):129–36. PubMed PMID: 22487975. Epub 2012/04/11. eng.PubMedCrossRefGoogle Scholar
  50. 50.
    Lutz S, Lo SS, Chow E, Sahgal A, Hoskin P. Radiotherapy for metastatic bone disease: current standards and future prospectus. Expert Rev Anticancer Ther. 2010;10(5):683–95. PubMed PMID: 20470001.PubMedCrossRefGoogle Scholar
  51. 51.
    Guckenberger M, Sweeney RA, Flickinger JC, Gerszten PC, Kersh R, Sheehan J, et al. Clinical practice of image-guided spine radiosurgery—results from an international research consortium. Radiat Oncol. 2011 20120227 DCOM- 20120615;6(1748-717X (Electronic)):172. PubMed PMID: 22172095. Pubmed Central PMCID: 3286433. eng.Google Scholar
  52. 52.
    Sahgal A, Bilsky M, Chang EL, Ma L, Yamada Y, Rhines LD, et al. Stereotactic body radiotherapy for spinal metastases: current status, with a focus on its application in the postoperative patient. J Neurosurg Spine. 2011;14(2):151–66. PubMed PMID: 21184635. Epub 2010/12/28. eng.PubMedCrossRefGoogle Scholar
  53. 53.
    Sahgal A, Roberge D, Schellenberg D, Purdie TG, Swaminath A, Pantarotto J, et al. The Canadian Association of Radiation Oncology scope of practice guidelines for lung, liver and spine stereotactic body radiotherapy. Clin Oncol (R Coll Radiol). 2012;24(9):629–39. PubMed PMID: 22633542. eng.CrossRefGoogle Scholar
  54. 54.
    Sohn S, Chung CK. The role of stereotactic radiosurgery in metastasis to the spine. J Korean Neurosurg Soc. 2012;51(1):1–7. PubMed PMID: 22396835. Pubmed Central PMCID: 3291699. eng.PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    Chawla S, Schell MC, Milano MT. Stereotactic body radiation for the spine: a review. Am J Clin Oncol. 2013;36(6):630–6. PubMed PMID: 22134513. Epub 2011/12/03. engPubMedCrossRefGoogle Scholar
  56. 56.
    Ejima Y, Matsuo Y, Sasaki R. The current status and future of radiotherapy for spinal bone metastases. J Orthop Sci. 2015.; (1436–2023 (Electronic)). PubMed PMID: 25860575. eng.Google Scholar
  57. 57.
    Ryu S, Yoon H, Stessin A, Gutman F, Rosiello A, Davis R. Contemporary treatment with radiosurgery for spine metastasis and spinal cord compression in 2015. Radiat Oncol J. 2015;33(1):1–11. PubMed PMID: 25874172. Pubmed Central PMCID: 4394063. eng.PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    Park HJ, Kim HJ, Won JH, Lee SC, Chang AR. Stereotactic body radiotherapy (SBRT) for spinal metastases: who will benefit the most from SBRT? Technol Cancer Res Treat. 2015;14(2):159–67. PubMed PMID: 24502552. Epub 2014/02/08. eng.PubMedCrossRefGoogle Scholar
  59. 59.
    Gerszten PC, Mendel E, Yamada Y. Radiotherapy and radiosurgery for metastatic spine disease: what are the options, indications, and outcomes? Spine. 2009;15(22 Suppl):S78–92. 20091015 DCOM- 20100126. eng.CrossRefGoogle Scholar
  60. 60.
    Bauer HWR. Survival after surgery for spinal and extremity metastases. Acta Orthop Scand. 1995;66(2):143–6.PubMedCrossRefGoogle Scholar
  61. 61.
    Wibmer C, Leithner A, Hofmann G, Clar H, Kapitan M, Berghold A, et al. Survival analysis of 254 patients after manifestation of spinal metastases: evaluation of seven preoperative scoring systems. Spine. 2011;36(23):1977–86. PubMed PMID: 21304424. eng.PubMedCrossRefGoogle Scholar
  62. 62.
    Leithner A, Radl R, Gruber G, Hochegger M, Leithner K, Welkerling H, et al. Predictive value of seven preoperative prognostic scoring systems for spinal metastases. Eur Spine J. 2008;17(11):1488–95. PubMed PMID: 18787846. Pubmed Central PMCID: 2583181. eng.PubMedPubMedCentralCrossRefGoogle Scholar
  63. 63.
    Tomita K, Kawahara N, Kobayashi T, Yoshida A, Murakami H, Akamaru T. Surgical strategy for spinal metastases. Spine. 2001;26(3):298–306. PubMed PMID: 11224867. eng.PubMedCrossRefGoogle Scholar
  64. 64.
    Tokuhashi Y, Matsuzaki H, Toriyama S, Kawano H, Ohsaka S. Scoring system for the preoperative evaluation of metastatic spine tumor prognosis. Spine. 1990;15(11):1110–3. PubMed PMID: WOS:A1990EJ57700005. English.PubMedCrossRefGoogle Scholar
  65. 65.
    Arana E Kovacs FM, Royuela A, Asenjo B, Pérez-Ramírez Ú, Zamora J; Spanish Back Pain Research Network Task Force for the improvement of inter-disciplinary management of spinal metastasis. Agreement in the assessment of metastatic spine disease using scoring systems. Radiother Oncol. 115(1):135-140 2015 20150516:pii: S0167-8140(15)00155-3. doi: [Epub ahead of print]. Eng.PubMedCrossRefGoogle Scholar
  66. 66.
    Tokuhashi Y, Matsuzaki H, Oda H, Oshima M, Ryu J. A revised scoring system for preoperative evaluation of metastatic spine tumor prognosis. Spine. 2005;30(19):2186–91. PubMed PMID: 16205345. eng.PubMedCrossRefGoogle Scholar
  67. 67.
    Wang M, Bunger CE, Li HS, Wu CS, Hoy K, Niedermann B, et al. Predictive value of Tokuhashi scoring systems in spinal metastases, focusing on various primary tumor groups evaluation of 448 patients in the Aarhus spinal metastases database. Spine. 2012;37(7):573–82. PubMed PMID: WOS:000302266400014. English.PubMedCrossRefGoogle Scholar
  68. 68.
    Krishnan MS, Epstein-Peterson Z, Chen YH, Tseng YD, Wright AA, Temel JS, et al. Predicting life expectancy in patients with metastatic cancer receiving palliative radiotherapy: the TEACHH model. Cancer. 2014;120(1):134–41. PubMed PMID: 24122413.PubMedCrossRefGoogle Scholar
  69. 69.
    Chow E, Abdolell M, Panzarella T, Harris K, Bezjak A, Warde P, et al. Validation of a predictive model for survival in metastatic cancer patients attending an outpatient palliative radiotherapy clinic. Int J Radiat Oncol Biol Phys. 2009;73(1):280–7. PubMed PMID: 18676092.PubMedCrossRefGoogle Scholar
  70. 70.
    Chao ST, Koyfman SA, Woody N, Angelov L, Soeder SL, Reddy CA, Rybicki LA, Djemil T, Suh JH. Recursive partitioning analysis index is predictive for overall survival in patients undergoing spine stereotactic body radiation therapy for spinal metastases. Int J Radiat Oncol Biol Phys. 2012;82(5):1738–43. 20120320 DCOM- 20120511. eng.PubMedCrossRefGoogle Scholar
  71. 71.
    Tang C, Hess K, Bishop AJ, Pan HY, Christensen EN, Yang JN, et al. Creation of a prognostic index for spine metastasis to stratify survival in patients treated with spinal stereotactic radiosurgery: secondary analysis of mature prospective trials. Int J Radiat Oncol Biol Phys. 2015;93(1):118–25. PubMed PMID: 26130231. eng.PubMedCrossRefGoogle Scholar
  72. 72.
    Kim H, Rajagopalan MS, Beriwal S, Huq MS, Smith KJ. Cost-effectiveness analysis of single fraction of stereotactic body radiation therapy compared with single fraction of external beam radiation therapy for palliation of vertebral bone metastases. Int J Radiat Oncol Biol Phys. 2015;91(3):556–63. PubMed PMID: 25680599. eng.PubMedCrossRefGoogle Scholar
  73. 73.
    RTOG. RTOG 0631: a phase II/III study of image-guided radiosurgery/SBRT for localized spine metastasis—RTOG CCOP study 2006 [Jan 31 2016]. Available from:
  74. 74.
    Gerszten PC, Burton SA, Ozhasoglu C, Vogel WJ, Welch WC, Baar J, et al. Stereotactic radiosurgery for spinal metastases from renal cell carcinoma. J Neurosurg Spine. 2005;3(4):288–95. PubMed PMID: 16266070. eng.PubMedCrossRefGoogle Scholar
  75. 75.
    Gerszten PC, Burton SA, Quinn AE, Agarwala SS, Kirkwood JM. Radiosurgery for the treatment of spinal melanoma metastases. Stereotact Funct Neurosurg. 2005;83(5–6):213–21. 20060407 DCOM- 20060829. PubMed PMID: 16534253. eng.PubMedCrossRefGoogle Scholar
  76. 76.
    Sohn SCC, Sohn MJ, Chang UK, Kim SH, Kim J, Park E. Stereotactic radiosurgery compared with external radiation therapy as a primary treatment in spine metastasis from renal cell carcinoma: a multicenter, matched-pair study. J Neuro-Oncol. 2014;119(1):121–8. 20140812 DCOM- 20151019. eng.CrossRefGoogle Scholar
  77. 77.
    Chang UK, Cho WI, Lee DH, Kim MS, Cho CK, Lee SY, et al. Stereotactic radiosurgery for primary and metastatic sarcomas involving the spine. J Neuro-Oncol. 2012;107(3):551–7. PubMed PMID: 22246201. eng.CrossRefGoogle Scholar
  78. 78.
    Maranzano E, Trippa F, Pacchiarini D, Chirico L, Basagni ML, Rossi R, et al. Re-irradiation of brain metastases and metastatic spinal cord compression: clinical practice suggestions. Tumori. 2005;91(4):325–30. PubMed PMID: 16277098. eng.PubMedGoogle Scholar
  79. 79.
    Nieder C, Grosu AL, Andratschke NH, Molls M. Update of human spinal cord reirradiation tolerance based on additional data from 38 patients. Int J Radiat Oncol Biol Phys. 2006;66(5):1446–9. PubMed PMID: 17084560.PubMedPubMedCentralCrossRefGoogle Scholar
  80. 80.
    Ryu S, Rock J, Rosenblum M, Kim JH. Patterns of failure after single-dose radiosurgery for spinal metastasis. J Neurosurg. 2004;101(Suppl 3) (0022–3085 (Print)):402–5. PubMed PMID: 15537196. eng.Google Scholar
  81. 81.
    Hamilton AJ, Lulu BA, Fosmire H, Stea B, Cassady JR. Preliminary clinical experience with linear accelerator-based spinal stereotactic radiosurgery. Neurosurgery. 1995;36(2):311–9. PubMed PMID: 7731511. eng.PubMedCrossRefGoogle Scholar
  82. 82.
    Milker-Zabel S, Zabel A, Thilmann C, Schlegel W, Wannenmacher M, Debus J. Clinical results of retreatment of vertebral bone metastases by stereotactic conformal radiotherapy and intensity-modulated radiotherapy. Int J Radiat Oncol Biol Phys. 2003;55(1):162–7. PubMed PMID: 12504049. eng.PubMedCrossRefGoogle Scholar
  83. 83.
    Mahan SL, Ramsey CR, Scaperoth DD, Chase DJ, Byrne TE. Evaluation of image-guided helical tomotherapy for the retreatment of spinal metastasis. Int J Radiat Oncol Biol Phys. 2005;63(5):1576–83. PubMed PMID: 16125871. eng.PubMedCrossRefGoogle Scholar
  84. 84.
    Yamada Y, Lovelock DM, Yenice KM, Bilsky MH, Hunt MA, Zatcky J, et al. Multifractionated image-guided and stereotactic intensity-modulated radiotherapy of paraspinal tumors: a preliminary report. Int J Radiat Oncol Biol Phys. 2005;62(1):53–61. PubMed PMID: 15850902. eng.PubMedCrossRefGoogle Scholar
  85. 85.
    Chang EL, Shiu AS, Mendel E, Mathews LA, Mahajan A, Allen PK, et al. Phase I/II study of stereotactic body radiotherapy for spinal metastasis and its pattern of failure. J Neurosurg Spine. 2007;7(2):151–60. PubMed PMID: 17688054. eng.PubMedCrossRefGoogle Scholar
  86. 86.
    Gerszten PC, Burton SA, Ozhasoglu C, Welch WC. Radiosurgery for spinal metastases: clinical experience in 500 cases from a single institution. Spine. 2007;32(2):193–9. PubMed PMID: 17224814. eng.PubMedCrossRefGoogle Scholar
  87. 87.
    Gibbs IC, Kamnerdsupaphon P, Ryu MR, Dodd R, Kiernan M, Chang SD, et al. Image-guided robotic radiosurgery for spinal metastases. Radiother Oncol. 2007;82(2):185–90. PubMed PMID: 17257702. eng.PubMedPubMedCentralCrossRefGoogle Scholar
  88. 88.
    Sahgal A, Chou D, Ames C, Ma L, Chuang C, Lambom K, et al. Proximity of spinous/paraspinous radiosurgery metastatic targets to the spinal cord versus risk of local failure. Int J Radiat Oncol. 2007;69(3):S243. PubMed PMID: WOS:000249950200431. English.CrossRefGoogle Scholar
  89. 89.
    Wang XS, Rhines LD, Shiu AS, Yang JN, Selek U, Gning I, Liu P, Allen PK, Azeem SS, Brown PD, Sharp HJ, Weksberg DC, Cleeland CS, Chang EL. Stereotactic body radiation therapy for management of spinal metastases in patients without spinal cord compression: a phase 1–2 trial. Lancet Oncol. 2012;13(4):395–402. 20120403 DCOM- 20120622. eng.PubMedPubMedCentralCrossRefGoogle Scholar
  90. 90.
    Supe SS, Ganesh KM, Naveen T, Jacob S, Sankar BN. Spinal cord response to altered fractionation and re-irradiation: radiobiological considerations and role of bioeffect models. J Cancer Res Ther. 2006;2(3):105–18. PubMed PMID: 17998688. eng.PubMedCrossRefGoogle Scholar
  91. 91.
    Gerszten PC, Germanwala A, Burton SA, Welch WC, Ozhasoglu C, Vogel WJ. Combination kyphoplasty and spinal radiosurgery: a new treatment paradigm for pathological fractures. J Neurosurg Spine. 2005;3(4):296–301. 20051103 DCOM- 20051115. eng.PubMedCrossRefGoogle Scholar
  92. 92.
    Moulding HD, Elder JB, Lis E, Lovelock DM, Zhang Z, Yamada Y, et al. Local disease control after decompressive surgery and adjuvant high-dose single-fraction radiosurgery for spine metastases. J Neurosurg Spine. 2010;13(1):87–93. PubMed PMID: 20594023. eng.PubMedCrossRefGoogle Scholar
  93. 93.
    Rock JP, Ryu S, Shukairy MS, Yin FF, Sharif A, Schreiber F, et al. Postoperative radiosurgery for malignant spinal tumors. Neurosurgery. 2006;58(5):891–8. discussion -8. PubMed PMID: 16639323. eng.PubMedCrossRefGoogle Scholar
  94. 94.
    Ryu S, Pugh SL, Gerszten PC, Yin FF, Timmerman RD, Hitchcock YJ, et al. RTOG 0631 phase 2/3 study of image guided stereotactic radiosurgery for localized (1-3) spine metastases: phase 2 results. Pract Radiat Oncol. 2014;4(2):76–81. PubMed PMID: 24890347. Pubmed Central PMCID: 3711083.PubMedCrossRefGoogle Scholar
  95. 95.
    Degen JW, Gagnon GJ, Voyadzis JM, McRae DA, Lunsden M, Dieterich S, et al. CyberKnife stereotactic radiosurgical treatment of spinal tumors for pain control and quality of life. J Neurosurg Spine. 2005;2(5):540–9. PubMed PMID: 15945428. eng.PubMedCrossRefGoogle Scholar
  96. 96.
    Sahgal A, Chou D, Ames C, Ma L, Lamborn K, Huang K, et al. Image-guided robotic stereotactic body radiotherapy for benign spinal tumors: the University of California San Francisco preliminary experience. Technol Cancer Res Treat. 2007;6(6):595–604. PubMed PMID: 17994789. eng.PubMedCrossRefGoogle Scholar
  97. 97.
    Pan HY, Allen PK, Wang XS, Chang EL, Rhines LD, Tatsui CE, et al. Incidence and predictive factors of pain flare after spine stereotactic body radiation therapy: secondary analysis of phase 1/2 trials. Int J Radiat Oncol Biol Phys. 2014;90(4):870–6. PubMed PMID: 25227497. Epub 2014/09/18. engPubMedCrossRefGoogle Scholar
  98. 98.
    Chiang A, Zeng L, Zhang L, Lochray F, Korol R, Loblaw A, et al. Pain flare is a common adverse event in steroid-naive patients after spine stereotactic body radiation therapy: a prospective clinical trial. Int J Radiat Oncol Biol Phys. 2013;86(4):638–42. PubMed PMID: 23664326. Epub 2013/05/15. eng.PubMedPubMedCentralCrossRefGoogle Scholar
  99. 99.
    Ryu S, Fang Yin F, Rock J, Zhu J, Chu A, Kagan E, et al. Image-guided and intensity-modulated radiosurgery for patients with spinal metastasis. Cancer. 2003;97(8):2013–8. PubMed PMID: 12673732. eng.PubMedCrossRefGoogle Scholar
  100. 100.
    Rades D, Stalpers LJ, Veninga T, Hoskin PJ. Spinal reirradiation after short-course RT for metastatic spinal cord compression. Int J Radiat Oncol Biol Phys. 2005;63(3):872–5. PubMed PMID: 15939549. eng.PubMedCrossRefGoogle Scholar
  101. 101.
    Hall WA, Stapleford LJ, Hadjipanayis CG, Curran WJ, Crocker I, Shu HK. Stereotactic body radiosurgery for spinal metastatic disease: an evidence-based review. Int J Surg Oncol. 2011 20120207 DCOM- 20120823;2011(2090–1410 (Electronic)):979214. PubMed PMID: 22312536. Pubmed Central PMCID: 3263656. eng.Google Scholar
  102. 102.
    Sahgal A, Whyne CM, Ma L, Larson DA, Fehlings MG. Vertebral compression fracture after stereotactic body radiotherapy for spinal metastases. Lancet Oncol. 2013;14(8):e310–20. PubMed PMID: 23816297. eng.PubMedCrossRefGoogle Scholar
  103. 103.
    Rose PS, Laufer I, Boland PJ, Hanover A, Bilsky MH, Yamada J, et al. Risk of fracture after single fraction image-guided intensity-modulated radiation therapy to spinal metastases. J Clin Oncol. 2009;27(30):5075–9. PubMed PMID: 19738130. Pubmed Central PMCID: 3664037. eng.PubMedPubMedCentralCrossRefGoogle Scholar
  104. 104.
    Cunha MV, Al-Omair A, Atenafu EG, Masucci GL, Letourneau D, Korol R, et al. Vertebral compression fracture (VCF) after spine stereotactic body radiation therapy (SBRT): analysis of predictive factors. Int J Radiat Oncol Biol Phys. 2012;84(3):e343–9. PubMed PMID: 22658511. eng.PubMedCrossRefGoogle Scholar
  105. 105.
    Boehling NS, Grosshans DR, Allen PK, McAleer MF, Burton AW, Azeem S, et al. Vertebral compression fracture risk after stereotactic body radiotherapy for spinal metastases. J Neurosurg Spine. 2012;16(4):379–86. PubMed PMID: 22225488. eng.PubMedCrossRefGoogle Scholar
  106. 106.
    Thibault I, Al-Omair A, Masucci GL, Masson-Cote L, Lochray F, Korol R, et al. Spine stereotactic body radiotherapy for renal cell cancer spinal metastases: analysis of outcomes and risk of vertebral compression fracture. J Neurosurg Spine. 2014;21(5):711–8. PubMed PMID: 25170656. eng.PubMedCrossRefGoogle Scholar
  107. 107.
    Lo SS, Lutz ST, Chang EL, Galanopoulos N, Howell DD, Kim EY, et al. ACR Appropriateness Criteria((R)) spinal bone metastases. J Palliat Med. 2013;16(1):9–19. PubMed PMID: 23167547. Epub 2012/11/22. eng.PubMedCrossRefGoogle Scholar
  108. 108.
    Lutz S, Berk L, Chang E, Chow E, Hahn C, Hoskin P, et al. Palliative radiotherapy for bone metastases: an ASTRO evidence-based guideline. Int J Radiat Oncol Biol Phys. 2011;79(4):965–76. PubMed PMID: 21277118. Epub 2011/02/01. engCrossRefGoogle Scholar
  109. 109.
    Lutz ST, Lo SS, Chang EL, Galanopoulos N, Howell DD, Kim EY, et al. ACR appropriateness criteria(R) non-spine bone metastases. J Palliat Med. 2012;15(5):521–6. PubMed PMID: 22536988. Epub 2012/04/28. engPubMedPubMedCentralCrossRefGoogle Scholar
  110. 110.
    NQF. #1822 External beam radiotherapy for bone metastasis. American Society for radiation oncology; Fairfax VA USA. 2012; pp. 1–23.Google Scholar
  111. 111.
    “Choosing Wisely” ABIM foundation; Philadelphia PA USA. 2014.Google Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Candice Johnstone
    • 1
    Email author
  • Amol J. Ghia
    • 2
  • Anussara Prayongrat
    • 3
  1. 1.Department of Radiation OncologyMedical College of WisconsinMilwaukeeUSA
  2. 2.University of Texas MD Anderson Cancer Center, Department of Radiation OncologyHoustonUSA
  3. 3.King Chulalongkorn Memorial Hospital and Chulalongkorn University, Department of Radiation OncologyBangkokThailand

Personalised recommendations