Radiation Therapy for Metastatic Disease

  • Dirk Rades
Part of the Medical Radiology book series (MEDRAD)


Bone metastases occur in up to 40% of NSCLC patients. If associated with pathological fractures or metastatic spinal cord compression (MSCC), they are considered “complicated” lesions. Otherwise, they are considered “uncomplicated”. 1x8 Gy of radiation therapy (RT) can be considered the standard treatment of most uncomplicated painful bone metastases. Single-fraction RT requires re-RT more often than multi-fraction RT regimens. However, re-RT after 1x8 Gy is safe and effective. If re-RT is required after longer-course RT with 10x3 Gy or 20x2 Gy, the second RT course should be delivered using high-precision techniques. For a pathological fracture, surgical stabilisation followed by RT should be performed. Remineralization of the osteolytic bone is better after multi-fraction RT. For MSCC, short-course RT is as effective as longer RT programs regarding motor function. Local control of MSCC is better after longer-course RT. Patients with MSCC from NSCLC and a favorable survival prognosis may be considered candidates for decompressive surgery followed by longer-course RT. Decompressive surgery would also be the first choice for a local recurrence of MSCC after longercourse RT. A recurrence after short-course RT can be safely treated with another short-course of RT. Brain metastases occur in 20–40% of cancer patients. NSCLC is the most common primary tumor and which accounts for at least 40% or more of these patients. Most patients have multiple (4) lesions and usually receive whole-brain radiotherapy (WBRT) alone. Patients with a poor survival prognosis should receive 5x4 Gy in one week, whereas patients with a more favourable prognosis are candidates for longer-course WBRT. Patients with 1–3 brain metastases have a considerably better survival prognosis and may benefit from more intensive treatments including radiosurgery or surgery. WBRT in addition to radiosurgery or surgery leads to improved local control. The non-invasive regimen radiosurgery + WBRT is at least as effective as surgery + WBRT, and, therefore, preferable. Most data of SBRT of liver metastases have been obtained from colorectal cancer patients bur can be “extrapolated” to liver metastases from NSCLC. SBRT if used for a limited number of liver metastases can lead to high local control rates and considered a reasonable alternative to other local treatments. If SBRT is used for the treatment of lung metastases, lung tissue density correction during treatment planning is very important. In the treatment of a limited number of lung metastases, SBRT can result in excellent local control rates and median survival times of more than three years. In summery, radiation therapy if appropriately tailored to the individual patient with metastasis from NSCLC can provide valuable results in terms of relief of symptoms and improvement of the patient’s prognosis.


Brain Metastasis Stereotactic Body Radiation Therapy Local Control Rate Biologically Effective Dose Survival Prognosis 
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.


  1. Amouzegar-Hashemi F, Behrouzi H, Kazemian A et al (2008) Single versus multiple fractions of palliative radiotherapy for bone metastases: a randomized clinical trial in Iranian patients. Curr Oncol 15:36–39CrossRefGoogle Scholar
  2. Antonadou D, Paraskevaidis M, Sarris G et al (2002) Phase II randomized trial of temozolomide and concurrent radiotherapy in patients with brain metastases. J Clin Oncol 20:3644–3650PubMedCrossRefGoogle Scholar
  3. Aoyama H, Shirato H, Tago M et al (2006) Stereotactic radiosurgery plus whole-brain radiation therapy vs. stereotactic radiosurgery alone for treatment of brain metastases. A randomized controlled trial. JAMA 295:2483–2491PubMedCrossRefGoogle Scholar
  4. Aoyama H, Tago M, Kato N et al (2007) Neurocognitive function of patients with brain metastasis who received either whole brain radiotherapy plus stereotactic radiosurgery or radiosurgery alone. Int J Radiat Oncol Biol Phys 68:1388–1395PubMedCrossRefGoogle Scholar
  5. Bach F, Larsen BH, Rohde K et al (1990) Metastatic spinal cord compression. Occurrence, symptoms, clinical presentations, and prognosis in 398 patients with spinal cord compression. Acta Neurochir 107:37–43PubMedCrossRefGoogle Scholar
  6. Blomgren H, Lax I, Naslund I et al (1995) Stereotactic high dose fractionation radiation therapy of extracranial tumors using an accelerator. Clinical experience of the first thirty-one patients. Acta Oncol 34:861–870PubMedCrossRefGoogle Scholar
  7. 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 52:111–121CrossRefGoogle Scholar
  8. Borgelt B, Gelber R, Kramer S et al (1980) The palliation of brain metastases: final results of the first two studies by the Radiation Therapy Oncology Group. Int J Radiat Oncol Biol Phys 6:1–9PubMedCrossRefGoogle Scholar
  9. Borgelt B, Gelber R, Karson M et al (1981) Ultra-rapid high dose irradiation schedules for the palliation of brain metastases: final results of the first two studies by the radiation therapy oncology group. Int J Radiat Oncol Biol Phys 7:1633–1638PubMedCrossRefGoogle Scholar
  10. Chatani M, Matayoshi Y, Masaki N et al (1994) Radiation therapy for brain metastases from lung carcinoma. Prospective randomized trial according to the level of lactate dehydrogenase. Strahlenther Onkol 170:155–161PubMedGoogle Scholar
  11. Chow E, Loblaw A, Harris K et al (2007a) Dexamethasone for the prophylaxis of radiation-induced pain flare after palliative radiotherapy for bone metastases—a pilot study. Support Care Cancer 15:643–647Google Scholar
  12. Chow E, Harris K, Fan G et al (2007b) Palliative radiotherapy trials for bone metastases: a systematic review. J Clin Oncol 25:1423–1436Google Scholar
  13. Coleman RE (2006) Clinical features of metastatic bone disease and risk of skeletal morbidity. Clin Cancer Res 12(Suppl.):6243 s–6249 sGoogle Scholar
  14. Coleman RE, Rubens R (1987) The clinical course of bone metastases in breast cancer. Br J Cancer 77:336–340CrossRefGoogle Scholar
  15. De Angelis LM, Mandell LR, Thaler HAT et al (1989) The role of postoperative radiotherapy after resection of single brain metastasis. Neurosurgery 24:798–805CrossRefGoogle Scholar
  16. Foro Arnalot P, Fontanais AV, Galceran JC 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 89:150–155PubMedCrossRefGoogle Scholar
  17. Gaspar LE, Scott C, Rotman M et al (1997) Recursive partitioning analysis (RPA) of prognostic factors in three radiation therapy oncology group (RTOG) brain metastases trials. Int J Radiat Oncol Biol Phys 37:745–751PubMedCrossRefGoogle Scholar
  18. Gaze MN, Kelly CG, Kerr GR et al (1997) Pain relief and quality of life following radiotherapy for bone metastases: a randomised trial of two fractionation schedules. Radiother Oncol 45:106–116CrossRefGoogle Scholar
  19. Gerszten PC, Burton SA, Ozhasoglu C et al (2007) Radiosurgery for spinal metastases: clinical experience in 500 cases from a single institution. Spine 32:193–199PubMedCrossRefGoogle Scholar
  20. Gilbert RW, Kim JH, Posner JB (1978) Epidural spinal cord compression from metastatic tumor: diagnosis and treatment. Ann Neurol 3:40–51PubMedCrossRefGoogle Scholar
  21. Hara R, Itami J, Kondo T et al (2002) Stereotactic single high dose irradiation of ling tumors under respiratory gating. Radiother Oncol 63:159–163PubMedCrossRefGoogle Scholar
  22. Hartsell WF, Scott CB, Bruner DW 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
  23. Harwood AR, Simson WJ (1977) Radiation therapy of cerebral metastases: a randomized prospective clinical trial. Int J Radiat Oncol Biol Phys 2:1091–1094PubMedCrossRefGoogle Scholar
  24. Herfarth KK, Debus J, Lohr F et al (2001) Stereotactic single-dose radiation therapy of liver tumors: results of a phase I/II trial. J Clin Oncol 19:164–170PubMedGoogle Scholar
  25. Hoskin PJ, Price P, Easton D 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
  26. Hoyer M, Henrik R, Traberg-Hansen A (2006) Phase II study on stereotactic body radiotherapy of colorectal metastases. Acta Oncol 45:823–830PubMedCrossRefGoogle Scholar
  27. Jeremic B, Shibamoto Y, Acimovic L 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
  28. Jeremic B, Shibamoto Y, Igrutinovic I (1999) Single 4 Gy re-irradiation for painful bone metastases following single fraction radiotherapy. Radiother Oncol 52:123–127PubMedCrossRefGoogle Scholar
  29. Katagiri H, Takahashi M, Wakai K et al (2005) Prognostic factors and a scoring system for patients with skeletal metastasis. J Bone Joint Surg Br 87:698–703PubMedGoogle Scholar
  30. Katz AW, Carey-Simpson M, Muhs AG et al (2007) Hypofractionated stereotactic body radiation therapy (SBRT) for limited hepatic metastases. Int J Radiat Oncol Biol Phys 67:793–798PubMedCrossRefGoogle Scholar
  31. Kavanagh BD, Schefter TE, cardenes HR et al (2006) Interim analysis of a prospective phase I/II trial for liver metastases. Acta Oncol 45:848–855PubMedCrossRefGoogle Scholar
  32. Khuntia D, Brown P, Li J et al (2006) Whole-brain radiotherapy in the management of brain metastasis. J Clin Oncol 24:1295–1304PubMedCrossRefGoogle Scholar
  33. Knisely J, Strugar J (2006) Can decompressive surgery improve outcome in patients with metastatic epidural spinal-cord compression? Nat Clin Pract Oncol 3:14–15PubMedCrossRefGoogle Scholar
  34. Kocher M, Sofietti R, Abacioglu U et al (2011) Adjuvant whole-brain radiotherapy versus observation after radiosurgery or surgical resection of one to three cerebral metastases: results of the EORTC 22952-26001 study. J Clin Oncol 29:134–141PubMedCrossRefGoogle Scholar
  35. 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
  36. Kunkler I (2006) Surgical resection in metastatic spinal cord compression. Lancet 367:109PubMedCrossRefGoogle Scholar
  37. Lee SW, Choi EK, Park HJ et al (2003) Stereotactic body frame based fractionated radiosurgery on consecutive days for primary or metastatic tumors in the lung. Lung Cancer 40:309–315PubMedCrossRefGoogle Scholar
  38. Loblaw DA, Laperriere NJ, Mackillop WJA (2003) Population-based study of malignant spinal cord compression in Ontario. Clin Oncol 15:211–217CrossRefGoogle Scholar
  39. Ma S, Xu Y, Deng Q et al (2009) Treatment of brain metastasis from non-small cell lung cancer with whole brain radiotherapy and Gefitinib in a Chinese population. Lung Cancer 65:198–203PubMedCrossRefGoogle Scholar
  40. Maranzano E, Bellavita R, Rossi 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
  41. Maranzano E, Trippa F, Casale M et al (2009) 8 Gy 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
  42. Mendez Romero A, Wunderink W, Hussain SM et al (2006) Stereotactic body radiation therapy for primary and metastatic liver tumors: a single institution phase I–II study. Acta Oncol 45:831–837PubMedCrossRefGoogle Scholar
  43. Meyers CA, Smith JA, Bezjak A et al (2004) Neurocognitive function and progression in patients with brain metastases treated with whole-brain radiation and motexafin gadolinium: results of a randomized phase III trial. J Clin Oncol 22:157–165PubMedCrossRefGoogle Scholar
  44. Milker-Zabel S, Zabel A, Thilmann C et al (2003) Clinical results of retreatment of vertebral bone metastases by stereotactic conformal radiotherapy and intensity-modulated radiotherapy. Int J Radiat Oncol Biol Phys 55:162–167PubMedCrossRefGoogle Scholar
  45. Mintz AH, Kestle J, Rathbone MP et al (1996) A randomized trial to assess the efficacy of surgery in addition to radiotherapy in patients with a single cerebral metastasis. Cancer 78:1470–1476PubMedCrossRefGoogle Scholar
  46. Mithal N, Needham P, Hoskin P (1994) Retreatment with radiotherapy for painful bone metastases. Int J Radiat Oncol Biol Phys 29:1011–1014PubMedCrossRefGoogle Scholar
  47. Mornex F, Thomas L, Mohr P et al (2003) Randomized phase III trial of fotemustine plus whole brain irradiation in cerebral metastases of melanoma. Cancer Radiother 7:1–8PubMedCrossRefGoogle Scholar
  48. Nagata Y, Negoro Y, Aoki T et al (2002) Clinical outcomes of 3D conformal hypofractionated single high-dose radiotherapy for one or two lung tumors using a stereotactic body frame. Int J Radiat Oncol Biol Phys 52:1041–1046PubMedCrossRefGoogle Scholar
  49. Nakagawa K, Aoki Y, Tago M et al (2000) Megavoltage CT-assisted stereotactic radiosurgery for thoracic tumors: original research in the treatment of thoracic neoplasms. Int J Radiat Oncol Biol Phys 48:449–457PubMedCrossRefGoogle Scholar
  50. Nielsen OS, Bentzen SM, Sandberg E et al (1998) Randomized trial of single dose versus fractionated palliative radiotherapy of bone metastases. Radiother Oncol 47:233–240PubMedCrossRefGoogle Scholar
  51. Niewald M, Tkocz HJ, Abel U 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
  52. Norihisa Y, Nagata Y, Takayama K et al (2008) Stereotactic body radiotherapy for oligometastatic lung tumors. Int J Radiat Oncol Biol Phys 72:398–403PubMedCrossRefGoogle Scholar
  53. Okawa T, Kita M, Goto M et al (1988) Randomized prospective clinical study of small, large and twice-a-day fraction radiotherapy for painful bone metastases. Radiother Oncol 13:99–104PubMedCrossRefGoogle Scholar
  54. Okunieff P, Petersen AL, Philip A et al (2006) Stereotactic body radiation therapy (SBRT) for lung metastases. Acta Oncol 45:808–817PubMedCrossRefGoogle Scholar
  55. Patchell RA, Tibbs PA, Walsh JW et al (1990) A randomized trial of surgery in the treatment of single metastases of the brain. N Engl J Med 322:494–500PubMedCrossRefGoogle Scholar
  56. Patchell RA, Tibbs PA, Regine WF et al (1998) Postoperative radiotherapy in the treatment of single metastases to the brain. A randomised trial. JAMA 280:1485–1489PubMedCrossRefGoogle Scholar
  57. Patchell R, Tibbs PA, Regine WF et al (2005) Direct decompressive surgical resection in the treatment of spinal cord compression caused by metastatic cancer: a randomised trial. Lancet 366:643–648PubMedCrossRefGoogle Scholar
  58. Postmus PE, Haaxma-Reiche H, Smit EF et al (2000) Treatment of brain metastases of small-cell lung cancer: comparing teniposide and teniposide with whole brain radiotherapy––a phase II study of the European Organization for the Research and Treatment of Lung Cancer Cooperative Group. J Clin Oncol 18:3400–3408PubMedGoogle Scholar
  59. Prasad D, Schiff D (2005) Malignant spinal-cord compression. Lancet Oncol 6:15–24PubMedGoogle Scholar
  60. Priestman TJ, Dunn J, Brada M et al (1996) Final results of the Royal College of Radiologists trial comparing two different radiotherapy schedules in the treatment of cerebral metastases. Clin Oncol 8:308–315CrossRefGoogle Scholar
  61. Rades D, Dziggel L, Haatanen T et al (2011a) Scoring systems to estimate intracerebral control and survival rates of patients irradiated for brain metastases. Int J Radiat Oncol Biol Phys (in press)Google Scholar
  62. Rades D, Huttenlocher S, Bajrovic A et al (2011c) Surgery followed by radiotherapy versus radiotherapy alone for metastatic spinal cord compression from unfavorable tumors. Int J Radiat Oncol Biol Phys (in press)Google Scholar
  63. Rades D, Fehlauer F, Stalpers LJA et al (2004) A prospective evaluation of two radiation schedules with 10 versus 20 fractions for the treatment of metastatic spinal cord compression: final results of a multi-center study. Cancer 101:2687–2692PubMedCrossRefGoogle Scholar
  64. Rades D, Stalpers LJ, Veninga T et al (2005) Spinal reirradiation after short-course RT for metastatic spinal cord compression. Int J Radiat Oncol Biol Phys 63:872–875PubMedCrossRefGoogle Scholar
  65. Rades D, Stalpers LJA, Schulte R et al (2006) Defining the appropriate radiotherapy regimen for metastatic spinal cord compression (MSCC) in non-small cell lung cancer (NSCLC) patients. Eur J Cancer 42:1052–1056PubMedCrossRefGoogle Scholar
  66. Rades D, Schild SE, Lohynska R et al (2007a) Two radiation regimens and prognostic factors for brain metastases in nonsmall cell lung cancer patients. Cancer 110:1077–1082Google Scholar
  67. Rades D, Pluemer A, Veninga T et al (2007b) Whole-brain radiotherapy versus stereotactic radiosurgery for patients in recursive partitioning analysis classes 1 and 2 with 1 to 3 brain metastases. Cancer 110:2285–2292Google Scholar
  68. Rades D, Dunst J, Schild SE (2008a) The first score predicting overall survival in patients with metastatic spinal cord compression. Cancer 112:157–161Google Scholar
  69. Rades D, Rudat V, Veninga T et al (2008b) Prognostic factors for functional outcome and survival after re-irradiation for in-field recurrences of metastatic spinal cord compression. Cancer 113:1090–1096Google Scholar
  70. Rades D, Kieckebusch S, Haatanen T et al (2008c) Surgical resection followed by whole brain radiotherapy versus whole brain radiotherapy alone for single brain metastasis. Int J Radiat Oncol Biol Phys 70:1319–1324Google Scholar
  71. Rades D, Kueter JD, Hornung D, et al (2008d) Comparison of stereotactic radiosurgery (SRS) alone and whole brain radiotherapy (WBRT) plus a stereotactic boost (WBRT + SRS) for one to three brain metastases. Strahlenther Onkol 184:655–662Google Scholar
  72. Rades D, Kueter JD, Veninga T et al (2009) Whole brain radiotherapy plus stereotactic radiosurgery (WBRT + SRS) versus surgery plus whole brain radiotherapy (OP + WBRT) for 1–3 brain metastases: results of a matched pair analysis. Eur J Cancer 45:400–404PubMedCrossRefGoogle Scholar
  73. Rades D, Douglas S, Veninga T et al (2010a) Validation and simplification of a score predicting survival in patients irradiated for metastatic spinal cord compression. Cancer 116:3670–3673Google Scholar
  74. Rades D, Huttenlocher S, Dunst J et al (2010b) Matched pair analysis comparing surgery followed by radiotherapy and radiotherapy alone for metastatic spinal cord compression. J Clin Oncol 28:3597–3604Google Scholar
  75. Rades D, Lange M, Veninga T et al (2011b) Final results of a prospective study comparing the local control of short-course and long-course radiotherapy for metastatic spinal cord compression. Int J Radiat Oncol Biol Phys 79:524–530Google Scholar
  76. Rasmusson B, Vejborg I, Jensen AB 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
  77. Roos DE, Turner SL, O’Brien PC 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
  78. Rusthoven KE, Kavanagh BD, Burri SH et al (2009) Multi-institutional phase I/II trial of stereotactic body radiation therapy for lung metastases. J Clin Oncol 27:1579–1584PubMedCrossRefGoogle Scholar
  79. Schöggl A, Kitz K, Reddy M et al (2000) Defining the role of stereotactic radiosurgery versus microsurgery in the treatment of single brain metastases. Acta Neurochir (Wien) 142:621–626CrossRefGoogle Scholar
  80. Steenland E, Leer JW, van Houwelingen H 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
  81. Sundstrom JT, Minn H, Lertola KK et al (1998) Prognosis of patients treated for intracranial metastases with whole-brain irradiation. Ann Med 30:296–299PubMedCrossRefGoogle Scholar
  82. Sze WM, Shelley MD, Held I et al (2003) Palliation of metastatic bone pain (single fraction versus multifraction radiotherapy-a systematic review of randomised trials). Clin Oncol 15:345–352CrossRefGoogle Scholar
  83. Timmerman RD, Bizekis CS, Pass HI et al (2009) Local surgical, ablative, and radiation treatment of metastases. Ca Cancer J Clin 59:145–170PubMedCrossRefGoogle Scholar
  84. 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
  85. Uematsu M, Shioda A, Tahara K et al (1998) Focal, high dose, and fractionated modified stereotactic radiation therapy for lung carcinoma patients: a preliminary experience. Cancer 82:1062–1070PubMedCrossRefGoogle Scholar
  86. Van der Linden YM, Dijkstra SP, Vonk EJ et al (2005) Prediction of survival in patients with metastases in the spinal column. Results based on a randomized trial of radiotherapy. Cancer 103:320–328PubMedCrossRefGoogle Scholar
  87. Vecht CJ, Haaxma-Reiche H, Noordijk EM et al (1993) Treatment of single brain metastasis: radiotherapy alone or combined with neurosurgery? Ann Neurol 33:583–590PubMedCrossRefGoogle Scholar
  88. Wu JS, Wong R, Johnston M et al (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
  89. Wulf J, Hädinger U, Oppitz U et al (2001) Stereotactic radiotherapy of targets in the lung and liver. Strahlenther Onkol 177:645–655PubMedCrossRefGoogle Scholar
  90. Zimm S, Wampler GL, Stablein D et al (1981) Intracerebral metastases in solid tumor patients: natural history and results of treatment. Cancer 48:384–394PubMedCrossRefGoogle Scholar

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© Springer-Verlag Berlin Heidelberg 2011

Authors and Affiliations

  1. 1.Department of Radiation OncologyUniversity of LübeckLübeckGermany

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