Advertisement

Bone Metastases

  • Yvette van der Linden
  • Peter Hoskin
Chapter
Part of the Medical Radiology book series (MEDRAD)

Abstract

The treatment of bone metastases comprises a large part of the radiotherapy daily practice. Palliative radiotherapy has proven to be successful in treating pain caused by metastatic lesions in any bone and in treating neurological complaints caused by compression of the spinal cord due to lesions in the spinal column. In most prospective randomized trials on radiotherapy for bone pain, responses up to 70 % were reported. However, when survival was prolonged, recurrent pain was reported in up to 50 % of patients. It is to be expected for the future, since patients are living longer with disseminated disease, that symptoms may recur and therefore retreatment of bone metastases for palliative reasons will increase. In this chapter, the evidence-based outcomes for response and duration of response to initial and subsequent radiotherapy will be presented. Guidelines will be formulated for retreatment in bone metastases, with a focus on timing, expected complications, and preferred radiotherapy techniques. More intensive radiation techniques like intensity-modulated and stereotactic radiotherapy will be discussed for their role in retreatment of bone metastases.

Keywords

Bone Metastasis Spinal Cord Compression Single Fraction Spinal Metastasis Biologically Effective Dose 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. Ang KK, Jiang GL, Feng Y, Stephens LC, Tucker SL, Price RE (2001) Extent and kinetics of recovery of occult spinal cord injury. Int J Radiat Oncol Biol Phys 50:1013–1020PubMedCrossRefGoogle Scholar
  2. Bartels RH, van der Linden YM, van der Graaf WT (2008) Spinal extradural metastasis: review of current treatment options. CA Cancer J Clin 58:245–259PubMedCrossRefGoogle Scholar
  3. Barton R, Robinson G, Gutierrez E, Kirkbride P, McLean M (2002) Palliative radiation for vertebral metastases: the effect of variation in prescription parameters on the dose received at depth. Int J Radiat Oncol Biol Phys 52:1083–1091PubMedCrossRefGoogle Scholar
  4. Berg RS, Yilmaz MK, Hoyer M, Keldsen N, Nielsen OS, Ewertz M (2009) Half body irradiation of patients with multiple bone metastases: a phase II trial. Acta Oncol 48:556–561PubMedCrossRefGoogle Scholar
  5. Bhattacharya IS, Hoskin PJ (2015) Stereotactic body radiotherapy for spinal and bone metastases. Clin Oncol (R Coll Radiol) 27:298–306CrossRefGoogle Scholar
  6. Bone Pain Trial Working Party (1999) 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. Radiother Oncol 52(2):111–121Google Scholar
  7. Chang EL, Shiu AS, Mendel E, Mathews LA, Mahajan A, Allen PK et al (2007) Phase I/II study of stereotactic body radiotherapy for spinal metastasis and its pattern of failure. J Neurosurg Spine 7:151–160PubMedCrossRefGoogle Scholar
  8. Chi JH, Gokaslan Z, McCormick P, Tibbs PA, Kryscio RJ, Patchell RA (2009) Selecting treatment for patients with malignant epidural spinal cord compression-does age matter? Results from a randomized clinical trial. Spine (Phila Pa 1976) 34:431–435CrossRefGoogle Scholar
  9. Chow E, Wu J, Hoskin P, Coia L, Bentzen S, Blitzer P (2002) International consensus on palliative radiotherapy endpoints for future clinical trials in bone metastases. Radiother Oncol 64:275–280PubMedCrossRefGoogle Scholar
  10. Chow E, Ling A, Davis L, Panzarella T, Danjoux C (2005) Pain flare following external beam radiotherapy and meaningful change in pain scores in the treatment of bone metastases. Radiother Oncol 75:64–69PubMedCrossRefGoogle Scholar
  11. Chow E, Harris K, Fung K (2006) Successful validation of a survival prediction model in patients with metastases in the spinal column. Int J Radiat Oncol Biol Phys 65:1522–1527PubMedCrossRefGoogle Scholar
  12. Chow E, Harris K, Fan G, Tsao M, Sze WM (2007a) Palliative radiotherapy trials for bone metastases: a systematic review. J Clin Oncol 25:1423–1436PubMedCrossRefGoogle Scholar
  13. Chow E, Loblaw A, Harris K, Doyle M, Goh P, Chiu H et al (2007b) Dexamethasone for the prophylaxis of radiation-induced pain flare after palliative radiotherapy for bone metastases: a pilot study. Support Care Cancer 15:643–647PubMedCrossRefGoogle Scholar
  14. Chow E, Hoskin P, Mitera G, Zeng L, Lutz S, Roos D et al; International Bone Metastases Consensus Working Party (2012) Update of the international consensus on palliative radiotherapy endpoints for future clinical trials in bone metastases. Int J Radiat Oncol Biol Phys 82:1730–1737Google Scholar
  15. Chow E, van der Linden YM, Roos D, Hartsell WF, Hoskin P, Wu JS et al (2014a) Single versus multiple fractions of repeat radiation for painful bone metastases: a randomised, controlled, non-inferiority trial. Lancet Oncol 15:164–171PubMedCrossRefGoogle Scholar
  16. Chow E, Meyer RM, Chen BE, van der Linden YM, Roos D, Hartsell WF et al (2014b) Impact of reirradiation of painful osseous metastases on quality of life and function: a secondary analysis of the NCIC CTG SC.20 randomized trial. J Clin Oncol 32:3867–3873PubMedCrossRefPubMedCentralGoogle Scholar
  17. Chow E, Meyer RM, Ding K, Nabid A, Chabot P, Wong P et al (2015) 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 16:1463–1472PubMedCrossRefGoogle Scholar
  18. Chow E, Ding K, Parulekar WR, Wong RK, van der Linden YM, Roos D et al (2016) Revisiting classification of pain from bone metastases as mild, moderate, or severe based on correlation with function and quality of life. Support Care Cancer 24:1617–1623PubMedCrossRefGoogle Scholar
  19. Cole DJ (1989) A randomized trial of a single treatment versus conventional fractionation in the palliative radiotherapy of painful bone metastases. Clin Oncol (R Coll Radiol) 1:59–62CrossRefGoogle Scholar
  20. Coleman RE (1997) Skeletal complications of malignancy. Cancer 80(8 Suppl):1588–1594PubMedCrossRefGoogle Scholar
  21. Dupuy DE, Liu D, Hartfeil D, Hanna L, Blume JD, Ahrar K et al (2010) Percutaneous radiofrequency ablation of painful osseous metastases: a multicenter American College of Radiology Imaging Network trial. Cancer 116:989–997PubMedCrossRefPubMedCentralGoogle Scholar
  22. Falkmer U, Jarhult J, Wersall P, Cavallin-Stahl E (2003) A systematic overview of radiation therapy effects in skeletal metastases. Acta Oncol 42:620–633PubMedCrossRefGoogle Scholar
  23. 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 (Phila Pa 1976) 35:E1221–E1229CrossRefGoogle Scholar
  24. Foro AP, Fontanals AV, Galceran JC, Lynd F, Latiesas XS, de Dios NR et al (2008) 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 89:150–155CrossRefGoogle Scholar
  25. Galasko CS (1981) The anatomy and pathways of bone metastases. In: Weiss L, Gilbert A (eds) Bone metastases. GK Hall, Boston, pp 49–63Google Scholar
  26. Gaze MN, Kelly CG, Kerr GR, Cull A, Cowie VJ, Gregor A et al (1997) Pain relief and quality of life following radiotherapy for bone metastases: a randomised trial of two fractionation schedules. Radiother Oncol 45:109–116PubMedCrossRefGoogle Scholar
  27. Gerszten PC, Burton SA, Ozhasoglu C, Welch WC (2007) Radiosurgery for spinal metastases: clinical experience in 500 cases from a single institution. Spine (Phila Pa 1976) 32:193–199CrossRefGoogle Scholar
  28. Gibbs IC, Kamnerdsupaphon P, Ryu MR, Dodd R, Kiernan M, Chang SD et al (2007) Image-guided robotic radiosurgery for spinal metastases. Radiother Oncol 82:185–190PubMedCrossRefGoogle Scholar
  29. Goetz MP, Callstrom MR, Charboneau JW, Farrell MA, Maus TP, Welch TJ et al (2004) Percutaneous image-guided radiofrequency ablation of painful metastases involving bone: a multicenter study. J Clin Oncol 22:300–306PubMedCrossRefGoogle Scholar
  30. Haas RL, Betgen A, Wolfrat M, Panneman C, Remeijer P (2013) Cone beam CT assisted irradiation of painful vertebral metastases without prior virtual simulation: a quick and patient friendly procedure. Radiother Oncol 106:375–377PubMedCrossRefGoogle Scholar
  31. Haddad P, Cheung F, Pond G, Easton D, Cops F, Bezjak A et al (2006) Computerized tomographic simulation compared with clinical mark-up in palliative radiotherapy: a prospective study. Int J Radiat Oncol Biol Phys 65:824–829PubMedCrossRefGoogle Scholar
  32. Harrington KD (1986) Metastatic disease of the spine. J Bone Joint Surg Am 68:1110–1115PubMedCrossRefGoogle Scholar
  33. Hartsell WF, Konski AA, Scott CB, Bruner DW, Scarantino CW, Ivker RA et al (2005) Randomized trial of short- versus long-course radiotherapy for palliation of painful bone metastases. J Natl Cancer Inst 97:798–804PubMedCrossRefGoogle Scholar
  34. Harvey HA (1997) Issues concerning the role of chemotherapy and hormonal therapy of bone metastases from breast carcinoma. Cancer 80(8 Suppl):1646–1651PubMedCrossRefGoogle Scholar
  35. Heimdal K, Hirschberg H, Slettebo H, Watne K, Nome O (1992) High incidence of serious side effects of high-dose dexamethasone treatment in patients with epidural spinal cord compression. J Neurooncol 12:141–144PubMedCrossRefGoogle Scholar
  36. Hird A, Chow E, Zhang L, Wong R, Wu J, Sinclair E et al (2009a) Determining the incidence of pain flare following palliative radiotherapy for symptomatic bone metastases: results from three Canadian cancer centers. Int J Radiat Oncol Biol Phys 75:193–197PubMedCrossRefGoogle Scholar
  37. Hird A, Zhang L, Holt T, Fairchild A, Deangelis C, Loblaw A et al (2009b) Dexamethasone for the prophylaxis of radiation-induced pain flare after palliative radiotherapy for symptomatic bone metastases: a phase II study. Clin Oncol (R Coll Radiol) 21:329–335CrossRefGoogle Scholar
  38. Hirokawa Y, Wadasaki K, Kashiwado K (1988) A multi-institutional prospective randomized study of radiation therapy of bone metastases (Japanese). Nippon Igaku Hoshasen Gakkai Zasshi 48:1425–1431PubMedGoogle Scholar
  39. Hortobagyi GN, Theriault RL, Porter L, Blayney D, Lipton A, Sinoff C et al (1996) Efficacy of pamidronate in reducing skeletal complications in patients with breast cancer and lytic bone metastases. Protocol 19 Aredia Breast Cancer Study Group. N Engl J Med 335:1785–1791PubMedCrossRefGoogle Scholar
  40. Hoskin PJ (1988) Scientific and clinical aspects of radiotherapy in the relief of bone pain. Cancer Surv 7:69–86PubMedGoogle Scholar
  41. Hoskin PJ, Price P, Easton D, Regan J, Austin D, Palmer S et al (1992) A prospective randomised trial of 4 Gy or 8 Gy single doses in the treatment of metastatic bone pain. Radiother Oncol 23:74–78PubMedCrossRefGoogle Scholar
  42. Hoskin P, Grover A, Bhana R (2003) Metastatic spinal cord compression: radiotherapy outcome and dose fractionation. Radiother Oncol 68:175–180PubMedCrossRefGoogle Scholar
  43. Hoskin P, Rojas A, Fidarova E, Jalali R, Mena Merino A, Poitevin A et al (2015) IAEA randomised trial of optimal single dose radiotherapy in the treatment of painful bone metastases. Radiother Oncol 116:10–14PubMedCrossRefGoogle Scholar
  44. Huisman M, van den Bosch MA, Wijlemans JW, van Vulpen M, van der Linden YM, Verkooijen HM (2012) Effectiveness of reirradiation for painful bone metastases: a systematic review and meta-analysis. Int J Radiat Oncol Biol Phys 84:8–14PubMedCrossRefGoogle Scholar
  45. Jeremic B, Shibamoto Y, Acimovic L, Milicic B, Milisavljevic S, Nikolic N et al (1998) A randomized trial of three single-dose radiation therapy regimens in the treatment of metastatic bone pain. Int J Radiat Oncol Biol Phys 42:161–167PubMedCrossRefGoogle Scholar
  46. Jeremic B, Shibamoto Y, Igrutinovic I (1999) Single 4 Gy re-irradiation for painful bone metastasis following single fraction radiotherapy. Radiother Oncol 52:123–127PubMedCrossRefGoogle Scholar
  47. Jeremic B, Shibamoto Y, Igrutinovic I (2002) Second single 4 Gy reirradiation for painful bone metastasis. J Pain Symptom Manage 23:26–30PubMedCrossRefGoogle Scholar
  48. Jin JY, Chen Q, Jin R, Rock J, Anderson J, Li S et al (2007) Technical and clinical experience with spine radiosurgery: a new technology for management of localized spine metastases. Technol Cancer Res Treat 6:127–133PubMedCrossRefGoogle Scholar
  49. Kaasa S, Brenne E, Lund JA, Fayers P, Falkmer U, Holmberg M et al (2006) Prospective randomised multicenter trial on single fraction radiotherapy (8 Gy x 1) versus multiple fractions (3 Gy x 10) in the treatment of painful bone metastases. Radiother Oncol 79:278–284PubMedCrossRefGoogle Scholar
  50. Kagei K, Suyuki K, Sherato H (1990) Prospective randomized trial of single high dose versus multiple fraction radiation therapy for the treatment of bone metastasis. Gan No Rinsho 36:2553–2558PubMedGoogle Scholar
  51. Kallmes DF, Jensen ME (2003) Percutaneous vertebroplasty. Radiology 229:27–36PubMedCrossRefGoogle Scholar
  52. Kamby C, Vejborg I, Daugaard S, Guldhammer B, Dirksen H, Rossing N et al (1987) Clinical and radiologic characteristics of bone metastases in breast cancer. Cancer 60:2524–2531PubMedCrossRefGoogle Scholar
  53. Kirkbride P, Warde P, Panzarella A (2000a) A randomised trial comparing the efficacy of single fraction radiation therapy plus ondansetron with fractionated radiation therapy in the palliation of skeletal metastases (Abstract). Int J Radiat Oncol Biol Phys 48(3 Suppl):185CrossRefGoogle Scholar
  54. Kirkbride P, Bezjak A, Pater J, Zee B, Palmer MJ, Wong R et al (2000b) Dexamethasone for the prophylaxis of radiation-induced emesis: a National Cancer Institute of Canada Clinical Trials Group phase III study. J Clin Oncol 18:1960–1966PubMedCrossRefGoogle Scholar
  55. Kirkpatrick JP, van der Kogel AJ, Schultheiss TE (2010) Radiation dose-volume effects in the spinal cord. Int J Radiat Oncol Biol Phys 76(3 Suppl):S42–S49PubMedCrossRefGoogle Scholar
  56. Koswig S, Budach V (1999) Remineralization and pain relief in bone metastases after different radiotherapy fractions (10 times 3 Gy vs. 1 time 8 Gy). A prospective study. Strahlenther Onkol 175:500–508PubMedCrossRefGoogle Scholar
  57. Lee YT (1983) Breast carcinoma: pattern of metastasis at autopsy. J Surg Oncol 23:175–180PubMedCrossRefGoogle Scholar
  58. Letourneau D, Wong R, Moseley D, Sharpe MB, Ansell S, Gospodarowicz M et al (2007) Online planning and delivery technique for radiotherapy of spinal metastases using cone-beam CT: image quality and system performance. Int J Radiat Oncol Biol Phys 67:1229–1237PubMedCrossRefGoogle Scholar
  59. Li KK, Harris K, Hadi S, Chow E (2007) What should be the optimal cut points for mild, moderate, and severe pain? J Palliat Med 10:1338–1346PubMedCrossRefGoogle Scholar
  60. Li KK, Hadi S, Kirou-Mauro A, Chow E (2008) When should we define the response rates in the treatment of bone metastases by palliative radiotherapy? Clin Oncol (R Coll Radiol) 20:83–89CrossRefGoogle Scholar
  61. Lieberman I, Reinhardt MK (2003) Vertebroplasty and kyphoplasty for osteolytic vertebral collapse. Clin Orthop (415 Suppl):S176–S186Google Scholar
  62. Lipton A (2003) Bisphosphonates and metastatic breast carcinoma. Cancer 97(3 Suppl):848–853PubMedCrossRefGoogle Scholar
  63. Lipton A, Fizazi K, Stopeck AT, Henry DH, Smith MR, Shore N et al (2016) Effect of denosumab versus zoledronic acid in preventing skeletal-related events in patients with bone metastases by baseline characteristics. Eur J Cancer 53:75–83PubMedCrossRefGoogle Scholar
  64. Loblaw DA, Wu JS, Kirkbride P, Panzarella T, Smith K, Aslanidis J et al (2007) Pain flare in patients with bone metastases after palliative radiotherapy–a nested randomized control trial. Support Care Cancer 15:451–455PubMedCrossRefGoogle Scholar
  65. Macbeth FR, Wheldon TE, Girling DJ, Stephens RJ, Machin D, Bleehen NM et al (1996) Radiation myelopathy: estimates of risk in 1048 patients in three randomized trials of palliative radiotherapy for non-small cell lung cancer. The Medical Research Council Lung Cancer Working Party. Clin Oncol (R Coll Radiol) 8:176–181CrossRefGoogle Scholar
  66. Madsen EL (1983) Painful bone metastasis: efficacy of radiotherapy assessed by the patients: a randomized trial comparing 4 Gy X 6 versus 10 Gy X 2. Int J Radiat Oncol Biol Phys 9:1775–1779PubMedCrossRefGoogle Scholar
  67. Mancosu P, Navarria P, Bignardi M, Cozzi L, Fogliata A, Lattuada P et al (2010) Re-irradiation of metastatic spinal cord compression: a feasibility study by volumetric-modulated arc radiotherapy for in-field recurrence creating a dosimetric hole on the central canal. Radiother Oncol 94:67–70PubMedCrossRefGoogle Scholar
  68. Maranzano E, Latini P (1995) Effectiveness of radiation therapy without surgery in metastatic spinal cord compression: final results from a prospective trial. Int J Radiat Oncol Biol Phys 32:959–967PubMedCrossRefGoogle Scholar
  69. Maranzano E, Latini P, Perrucci E, Beneventi S, Lupatelli M, Corgna E (1997) Short-course radiotherapy (8Gy x 2) in metastatic spinal cord compression: an effective and feasible treatment. Int J Radiat Oncol Biol Phys 38:1037–1044PubMedCrossRefGoogle Scholar
  70. Maranzano E, Bellavita R, Floridi P, Celani G, Righetti E, Lupattelli M et al (2001) Radiation-induced myelopathy in long-term surviving metastatic spinal cord compression patients after hypofractionated radiotherapy: a clinical and magnetic resonance imaging analysis. Radiother Oncol 60:281–288PubMedCrossRefGoogle Scholar
  71. Maranzano E, Bellavita R, Rossi R, De Angelis V, Frattegiani A, Bagnoli R et al (2005) Short-course versus split-course radiotherapy in metastatic spinal cord compression: results of a phase III, randomized, multicenter trial. J Clin Oncol 23:3358–3365PubMedCrossRefGoogle Scholar
  72. Maranzano E, Trippa F, Casale M, Costantini S, Lupattelli M, Bellavita R et al (2009) 8Gy single-dose radiotherapy is effective in metastatic spinal cord compression: results of a phase III randomized multicentre Italian trial. Radiother Oncol 93:174–179PubMedCrossRefGoogle Scholar
  73. Meeuse JJ, van der Linden YM, van Tienhoven G, Gans RO, Leer JW, Reyners AK (2010) Efficacy of radiotherapy for painful bone metastases during the last 12 weeks of life: results from the Dutch Bone Metastasis Study. Cancer 116:2716–2725PubMedGoogle Scholar
  74. Mercadante S (1997) Malignant bone pain: pathophysiology and treatment. Pain 69:1–18PubMedCrossRefGoogle Scholar
  75. Miller F, Whitehill R (1984) Carcinoma of the breast metastatic to the skeleton. Clin Orthop 184:121–127Google Scholar
  76. Mithal NP, Needham PR, Hoskin PJ (1994) Retreatment with radiotherapy for painful bone metastases. Int J Radiat Oncol Biol Phys 29:1011–1014PubMedCrossRefGoogle Scholar
  77. Nieder C, Grosu AL, Andratschke NH, Molls M (2005) Proposal of human spinal cord reirradiation dose based on collection of data from 40 patients. Int J Radiat Oncol Biol Phys 61:851–855PubMedCrossRefGoogle Scholar
  78. Nieder C, Grosu AL, Andratschke NH, Molls M (2006) Update of human spinal cord reirradiation tolerance based on additional data from 38 patients. Int J Radiat Oncol Biol Phys 66:1446–1449PubMedCrossRefGoogle Scholar
  79. Nielsen OS, Bentzen SM, Sandberg E, Gadeberg CC, Timothy AR (1998) Randomized trial of single dose versus fractionated palliative radiotherapy of bone metastases. Radiother Oncol 47:233–240PubMedCrossRefGoogle Scholar
  80. Niewald M, Tkocz HJ, Abel U, Scheib T, Walter K, Nieder C et al (1996) Rapid course radiation therapy vs. more standard treatment: a randomized trial for bone metastases. Int J Radiat Oncol Biol Phys 36:1085–1089PubMedCrossRefGoogle Scholar
  81. Okawa T, Kita M, Goto M, Nishijima H, Miyaji N (1988) Randomized prospective clinical study of small, large and twice-a-day fraction radiotherapy for painful bone metastases. Radiother Oncol 13:99–104PubMedCrossRefGoogle Scholar
  82. Patchell R, Tibbs PA, Regine WF, Payne R (2005) Direct decompressive surgical resection in the treatment of spinal cord compression caused by metastatic cancer: a randomised trial. Lancet 366:643–648PubMedCrossRefGoogle Scholar
  83. Payne R (2003) Mechanisms and management of bone pain. Cancer 80:1608–1613CrossRefGoogle Scholar
  84. Price P, Hoskin PJ, Easton D, Austin D, Palmer SG, Yarnold JR (1986) Prospective randomised trial of single and multifraction radiotherapy schedules in the treatment of painful bony metastases. Radiother Oncol 6:247–255PubMedCrossRefGoogle Scholar
  85. Price P, Hoskin PJ, Easton D, Austin D, Palmer S, Yarnold JR (1988) Low dose single fraction radiotherapy in the treatment of metastatic bone pain: a pilot study. Radiother Oncol 12:297–300PubMedCrossRefGoogle Scholar
  86. Quasim M (1981) Half body irradiation in metastatic carcinomas. Clin Radiol 32:215–219CrossRefGoogle Scholar
  87. Quilty PM, Kirk D, Bolger JJ (1994) A comparison of the palliative effects of strontium-89 and external beam radiotherapy in metastatic prostate cancer. Radiother Oncol 31:33–40PubMedCrossRefGoogle Scholar
  88. Rades D, Heidenreich F, Karstens JH (2002) Final results of a prospective study of the prognostic value of the time to develop motor deficits before irradiation in metastatic spinal cord compression. Int J Radiat Oncol Biol Phys 53:975–979PubMedCrossRefGoogle Scholar
  89. Rades D, Stalpers L, Veninga T (2005a) Evaluation of five radiation schedules and prognostic factors for metastatic spinal cord compression in a series of 1304 patients. J Clin Oncol 23:3366–3375PubMedCrossRefGoogle Scholar
  90. Rades D, Stalpers LJ, Veninga T, Hoskin PJ (2005b) Spinal reirradiation after short-course RT for metastatic spinal cord compression. Int J Radiat Oncol Biol Phys 63:872–875PubMedCrossRefGoogle Scholar
  91. Rades D, Hoskin PJ, Stalpers LJ, Schulte R, Poortmans P, Veninga T et al (2006) Short-course radiotherapy is not optimal for spinal cord compression due to myeloma. Int J Radiat Oncol Biol Phys 64:1452–1457PubMedCrossRefGoogle Scholar
  92. Rades D, Dunst J, Schild S (2008a) The first score predicting overall survival in patients with metastatic spinal cord compression. Cancer 112:157–161PubMedCrossRefGoogle Scholar
  93. Rades D, Rudat V, Veninga T, Stalpers LJ, Basic H, Karstens JH et al (2008b) A score predicting posttreatment ambulatory status in patients irradiated for metastatic spinal cord compression. Int J Radiat Oncol Biol Phys 72:905–908PubMedCrossRefGoogle Scholar
  94. Rades D, Rudat V, Veninga T, Stalpers LJ, Hoskin PJ, Schild SE (2008c) Prognostic factors for functional outcome and survival after reirradiation for in-field recurrences of metastatic spinal cord compression. Cancer 113:1090–1096PubMedCrossRefGoogle Scholar
  95. Rades D, Lange M, Veninga T, Rudat V, Bajrovic A, Stalpers LJ et al (2009) Preliminary results of spinal cord compression recurrence evaluation (score-1) study comparing short-course versus long-course radiotherapy for local control of malignant epidural spinal cord compression. Int J Radiat Oncol Biol Phys 73:228–234PubMedCrossRefGoogle Scholar
  96. Rades D, Huttenlocher S, Dunst J, Bajrovic A, Karstens JH, Rudat V et al (2010a) Matched pair analysis comparing surgery followed by radiotherapy and radiotherapy alone for metastatic spinal cord compression. J Clin Oncol 28:3597–3604PubMedCrossRefGoogle Scholar
  97. Rades D, Douglas S, Veninga T, Stalpers LJ, Hoskin PJ, Bajrovic A et al (2010b) Validation and simplification of a score predicting survival in patients irradiated for metastatic spinal cord compression. Cancer 116:3670–3673PubMedCrossRefGoogle Scholar
  98. Rades D, Douglas S, Huttenlocher S, Rudat V, Veninga T, Stalpers LJ et al (2011a) Validation of a score predicting post-treatment ambulatory status after radiotherapy for metastatic spinal cord compression. Int J Radiat Oncol Biol Phys 79:1503–1506PubMedCrossRefGoogle Scholar
  99. Rades D, Freundt K, Meyners T, Bajrovic A, Basic H, Karstens JH et al (2011b) Dose escalation for metastatic spinal cord compression in patients with relatively radioresistant tumors. Int J Radiat Oncol Biol Phys 80:1492–1497PubMedCrossRefGoogle Scholar
  100. Rades D, Šegedin B, Conde-Moreno AJ, Garcia R, Perpar A, Metz M et al (2016) Radiotherapy with 4 Gy × 5 versus 3 Gy × 10 for metastatic epidural spinal cord compression: final results of the SCORE-2 trial (ARO 2009/01). J Clin Oncol 34:597–602PubMedCrossRefGoogle Scholar
  101. Rasmusson B, Vejborg I, Jensen AB, Andersson M, Banning AM, Hoffmann T et al (1995) Irradiation of bone metastases in breast cancer patients: a randomized study with 1 year follow-up. Radiother Oncol 34:179–184PubMedCrossRefGoogle Scholar
  102. Ratanatharathorn V, Powers WE, Moss WT, Perez CA (1999) Bone metastasis: review and critical analysis of random allocation trials of local field treatment. Int J Radiat Oncol Biol Phys 44:1–18PubMedCrossRefGoogle Scholar
  103. Rogers MJ, Watts DJ, Russell RG (1997) Overview of bisphosphonates. Cancer 80(8 Suppl):1652–1657PubMedCrossRefGoogle Scholar
  104. Roos DE, O’Brien PC, Smith JG, Spry NA, Hoskin PJ, Burmeister BH et al (2000) A role for radiotherapy in neuropathic bone pain: preliminary response rates from a prospective trial (Trans-tasman radiation oncology group, TROG 96.05) [published erratum appears in Int J Radiat Oncol Biol Phys 2000;47:545]. Int J Radiat Oncol Biol Phys 46:975–981PubMedCrossRefGoogle Scholar
  105. Roos DE, Turner SL, O’Brien PC, Smith JG, Spry NA, Burmeister BH et al (2005) 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 75:54–63PubMedCrossRefGoogle Scholar
  106. Rosen LS, Gordon D, Simon Tchekmedyian N, Yanagihara R, Hirsh V, Krzakowski M et al (2004) Long term efficacy and safety of Zoledronic acid in the treatment of skeletal metastases in patients with non-small cell lung carcinoma and other solid tumors. A randomized, phase III, double-blind, placebo-controlled trial. Cancer 100:2613–2621PubMedCrossRefGoogle Scholar
  107. Ryu S, Fang YF, Rock J, Zhu J, Chu A, Kagan E et al (2003) Image-guided and intensity-modulated radiosurgery for patients with spinal metastasis. Cancer 97:2013–2018PubMedCrossRefGoogle Scholar
  108. Ryu S, Jin JY, Jin R, Rock J, Ajlouni M, Movsas B et al (2007) Partial volume tolerance of the spinal cord and complications of single-dose radiosurgery. Cancer 109:628–636PubMedCrossRefGoogle Scholar
  109. Ryu S, Pugh SL, Gerszten PC, Yin FF, Timmerman RD, Hitchcock YJ et al (2014) RTOG 0631 phase 2/3 study of image guided stereotactic radiosurgery for localized (1-3) spine metastases: phase 2 results. Pract Radiat Oncol 4:76–81PubMedCrossRefGoogle Scholar
  110. Sahgal A, Ma L, Weinberg V, Gibbs IC, Chao S, Chang UK et al (2012) Reirradiation human spinal cord tolerance for stereotactic body radiotherapy. Int J Radiat Oncol Biol Phys 82:107–116PubMedCrossRefGoogle Scholar
  111. Salazar OM, Rubin P, Hendrickson FR, Komaki R, Poulter C, Newall J et al (1986) Single-dose half-body irradiation for palliation of multiple bone metastases from solid tumors. Final Radiation Therapy Oncology Group report. Cancer 58:29–36PubMedCrossRefGoogle Scholar
  112. Salazar OM, Sandhu T, da Motta NW, Escutia MA, Lanzos-Gonzales E, Mouelle-Sone A et al (2001) Fractionated half-body irradiation (HBI) for the rapid palliation of widespread, symptomatic, metastatic bone disease: a randomized Phase III trial of the International Atomic Energy Agency (IAEA). Int J Radiat Oncol Biol Phys 50:765–775PubMedCrossRefGoogle Scholar
  113. Sartor O, Coleman R, Nilsson S, Heinrich D, Helle SI, O’Sullivan JM et al (2014) Effect of radium-223 dichloride on symptomatic skeletal events in patients with castration-resistant prostate cancer and bone metastases: results from a phase 3, double-blind, randomised trial. Lancet Oncol 15:738–746PubMedCrossRefGoogle Scholar
  114. Schultheiss TE (2008) The radiation dose-response of the human spinal cord. Int J Radiat Oncol Biol Phys 71:1455–1459PubMedCrossRefGoogle Scholar
  115. Sorensen S, Helweg-Larsen S, Mouridsen H, Hansen HH (1994) Effect of high-dose dexamethasone in carcinomatous metastatic spinal cord compression treated with radiotherapy: a randomised trial. Eur J Cancer 30A:22–27PubMedCrossRefGoogle Scholar
  116. Steenland E, Leer JW, van Houwelingen H, Post WJ, van den Hout WB, Kievit J 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 52:101–109PubMedCrossRefGoogle Scholar
  117. Sykes AJ, Kiltie AE, Stewart AL (1997) Ondansetron versus a chlorpromazine and dexamethasone combination for the prevention of nausea and vomiting: a prospective, randomised study to assess efficacy, cost effectiveness and quality of life following single-fraction radiotherapy. Support Care Cancer 5:500–503PubMedCrossRefGoogle Scholar
  118. Sze WM, Shelley MD, Held I, Wilt TJ, Mason MD (2003) Palliation of metastatic bone pain: single fraction versus multifraction radiotherapy. A systematic review of randomised trials. Clin Oncol (R Coll Radiol) 15:345–352CrossRefGoogle Scholar
  119. Sze WM, Shelley M, Held I, Mason M (2004) Palliation of metastatic bone pain: single fraction versus multifraction radiotherapy – a systematic review of the randomised trials. Cochrane Database Syst Rev (2):CD004721Google Scholar
  120. Tanck E, van Aken JB, van der Linden YM, Schreuder HW, Binkowski M, Huizenga H et al (2009) Pathological fracture prediction in patients with metastatic lesions can be improved with quantitative computed tomography based computer models. Bone 45:777–783PubMedCrossRefGoogle Scholar
  121. Tong D, Gillick L, Hendrickson FR (1982) The palliation of symptomatic osseous metastases: final results of the Study by the Radiation Therapy Oncology Group. Cancer 50:893–899PubMedCrossRefGoogle Scholar
  122. Uppelschoten JM, Wanders SL, de Jong JM (1995) Single-dose radiotherapy (6 Gy): palliation in painful bone metastases. Radiother Oncol 36:198–202PubMedCrossRefGoogle Scholar
  123. Vakaet LA, Boterberg T (2004) Pain control by ionizing radiation of bone metastasis. Int J Dev Biol 48:599–606PubMedCrossRefGoogle Scholar
  124. van der Linden YM, Kroon HM, Dijkstra PD, Lok JJ, Noordijk EM, Leer JWH et al (2003) Simple radiographic parameter predicts fracturing in metastatic femoral bone lesions: results from a randomized trial. Radiother Oncol 69:21–31PubMedCrossRefGoogle Scholar
  125. van der Linden YM, Dijkstra PD, Kroon HM, Lok JJ, Noordijk EM, Leer J et al (2004a) Comparative analysis of risk factors for pathological fracture with femoral metastases. Results based on a randomised trial of radiotherapy. J Bone Joint Surg Br 86:566–573PubMedGoogle Scholar
  126. van der Linden YM, Lok JJ, Steenland E, Martijn H, Houwelingen JC, Leer JWH et al (2004b) 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 59:528–537PubMedCrossRefGoogle Scholar
  127. van der Linden YM, Dijkstra PDS, Vonk EJA, Marijnen CAM, Leer JWH (2005) Prediction of survival in patients with metastases in the spinal column. Cancer 103:320–328PubMedCrossRefGoogle Scholar
  128. van der Linden YM, Steenland E, van Houwelingen H, Post WJ, Oei B, Marijnen CAM et al (2006) 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 48:245–253CrossRefGoogle Scholar
  129. van Helvoirt R, Bratelli K (2008) Both immediate and late retreatment with single fraction radiotherapy are effective in palliating patients with painful skeletal metastases: a prospective cohort analysis. Radiother Oncol 88(Suppl):S51Google Scholar
  130. Vecht CJ, Haaxma-Reiche H, van Putten WL, de Visser M, Vries EP, Twijnstra A (1989) Initial bolus of conventional versus high-dose dexamethasone in metastatic spinal cord compression. Neurology 39:1255–1257PubMedCrossRefGoogle Scholar
  131. Wedin R, Bauer H, Rutqvist LE (2001) Surgical treatment for skeletal breast cancer metastases. A population-based study of 641 patients. Cancer 92:257–262PubMedCrossRefGoogle Scholar
  132. Westhoff PG, de Graeff A, Geerling JI, Reyners AK, van der Linden YM (2014) Dexamethasone for the prevention of a pain flare after palliative radiotherapy for painful bone metastases: a multicenter double-blind placebo-controlled randomized trial. BMC Cancer 14:347PubMedCrossRefPubMedCentralGoogle Scholar
  133. Wu JS, Wong R, Johnston M, Bezjak A, Whelan T (2003) Meta-analysis of dose-fractionation radiotherapy trials for the palliation of painful bone metastases. Int J Radiat Oncol Biol Phys 55:594–605PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  1. 1.Department of RadiotherapyLeiden University Medical CentreLeidenThe Netherlands
  2. 2.Department of RadiotherapyMount Vernon HospitalLondonUK

Personalised recommendations