Skip to main content

Advertisement

SpringerLink
Log in

Management of brain metastases

  • Published:
Current Neurology and Neuroscience Reports Aims and scope Submit manuscript

Abstract

Brain metastases represent a common and devastating complication of cancer. With advances in surgery, radiology, and medical and radiation oncology, the number of treatment options have greatly increased. In addition, the prognosis for patients can vary widely depending on factors such as the number of lesions, extent of extracranial disease, age, and functional status. Recently, the possible impairment of whole brain radiation therapy on neurocognitive function has been a subject of concern and debate. Thus, the use of whole brain radiation therapy in conjunction with other treatment modalities should be optimized to ensure the best outcomes with regard to tumor control and functional status. As a result, patient management has become controversial, with strong opinions often dictating “optimal” therapy. This review of the management of brain metastases focuses on whole brain radiation therapy, surgery, stereotactic radiosurgery, radiation sensitizers, and clinical trials.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References and Recommended Reading

  1. Greenberg H, Chandler WF, Sandler HM: Brain metastases. In Brain Tumors. Edited by Greenberg H, Chandler WF, Sandler HM. New York: Oxford University Press; 1999:299–317.

    Google Scholar 

  2. Wen PY, Black PM, Loeffler JS: Metastatic brain cancer. In Cancer: Principles and Practice of Oncology. Edited by DeVita V, Hellman S, Rosenberg SA. Philadelphia: Lippincott Williams & Wilkins; 2001:2655–2670.

    Google Scholar 

  3. Delattre JY, Krol G, Thaler HT, et al.: Distribution of brain metastases. Arch Neurol 1988, 45:741–744.

    PubMed  CAS  Google Scholar 

  4. Nussbaum ES, Djalilian HR, Cho K, et al.: Brain metastases. Histology, multiplicity, surgery and survival. Cancer 1996, 78:1781–1788.

    Article  PubMed  CAS  Google Scholar 

  5. Chang EL, Wefel JS, Maor MH, et al.: A pilot study of neurocognitive function in patients with one to three new brain metastases initially treated with stereotactic radiosurgery alone. Neurosurgery 2007, 60:277–284.

    PubMed  Google Scholar 

  6. Komaki R, Meyers CA, Shin DM, et al.: Evaluation of cognitive function in patients with limited small cell lung cancer prior to and shortly following prophylactic cranial irradiation. Int J Radiat Oncol Biol Phys 1995, 33:179–182.

    PubMed  CAS  Google Scholar 

  7. Meyers CA, Smith JA, Bezjak A, et al.: 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 2004, 22:157–165.

    Article  PubMed  CAS  Google Scholar 

  8. Richards P, McKissock W: Intracranial metastases. Br Med J 1963, 5322:15–18.

    Article  Google Scholar 

  9. Lang EF, Slater J: Metastatic brain tumors: results of surgical and nonsurgical treatment. Surg Clin North Am 1964, 44:865–872.

    PubMed  CAS  Google Scholar 

  10. Chao JH, Phillips R, Nickson JJ: Roentgen-ray therapy of cerebral metastases. Cancer 1954, 7:682–689.

    Article  PubMed  CAS  Google Scholar 

  11. Gaspar L, Scott C, Rotman M, et al.: Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy Oncology Group (RTOG) brain metastases trials. Int J Radiat Oncol Biol Phys 1997, 37:745–751.

    PubMed  CAS  Google Scholar 

  12. Videtic GM, Adelstein DJ, Mekhail TM, et al.: Validation of the RTOG recursive partitioning analysis (RPA) classification for small cell lung cancer-only brain metastases. Int J Radiat Oncol Biol Phys 2007, 67:240–243.

    PubMed  Google Scholar 

  13. Sperduto PW, Berkey B, Gaspar LE, et al.: A new prognostic index and comparison to three other indices for patients with brain metastases: an analysis of 1960 patients in the RTOG database. Int J Radiat Oncol Biol Phys 2008, 70:510–514.

    PubMed  Google Scholar 

  14. Kurtz JM, Gelber R, Brady LW, et al.: The palliation of brain metastases in a favorable patient population: a randomized clinical trial by the Radiation Therapy Oncology Group. Int J Radiat Oncol Biol Phys 1981, 7:891–895.

    PubMed  CAS  Google Scholar 

  15. Borgelt B, Gelber R, Kramer S, et al.: The palliation of brain metastases: final results of the first two studies by the Radiation Therapy Oncology Group. Int J Radiat Oncol Biol Phys 1980, 6:1–9.

    PubMed  CAS  Google Scholar 

  16. Borgelt B, Gelber R, Larson M, et al.: 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 1981, 7:1633–1638.

    PubMed  CAS  Google Scholar 

  17. Murray KJ, Scott C, Greenberg HM, et al.: A randomized phase III study of accelerated hyperfractionation versus standard in patients with unresected brain metastases: a report of the Radiation Therapy Oncology Group (RTOG) 9104. Int J Radiat Oncol Biol Phys 1997, 39:571–574.

    PubMed  CAS  Google Scholar 

  18. DeAngelis, LM, Delattre JY, Posner JB. Radiation-induced dementia in patients cured of brain metastases. Neurology 1989, 39:789–96.

    PubMed  CAS  Google Scholar 

  19. Regine WF, Scott C, Murray K, et al.: Neurocognitive outcome in brain metastases patients treated with acceleratedfractionation vs. accelerated-hyperfractionated radiotherapy: an analysis from Radiation Therapy Oncology Group Study 91-04. Int J Radiat Oncol Biol Phys 2001, 51:711–717.

    PubMed  CAS  Google Scholar 

  20. Gregor A, Cull A, Stephens RJ, et al.: Prophylactic cranial irradiation is indicated following complete response to induction therapy in small cell lung cancer: results of a multicentre randomised trial. United Kingdom Coordinating Committee for Cancer Research (UKCCCR) and the European Organization for Research and Treatment of Cancer (EORTC). Eur J Cancer 1997, 33:1752–1758.

    Article  PubMed  CAS  Google Scholar 

  21. Arriagada R, Le Chevalier T, Borie F, et al.: Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission. J Natl Cancer Inst 1995, 87:183–190.

    Article  PubMed  CAS  Google Scholar 

  22. van Oosterhout A, Boon P, Houx P, et al.: Follow up of cognitive functioning in patients with small cell lung cancer. Int J Radiat Oncol Biol Phys 1995, 31:911–914.

    PubMed  Google Scholar 

  23. Mehta MP, Rodrigus P, Terhaard CH, et al.: Survival and neurologic outcomes in a randomized trial of motexafin gadolinium and whole-brain radiation therapy in brain metastases. J Clin Oncol 2003, 21:2529–2536.

    Article  PubMed  CAS  Google Scholar 

  24. Meyers CA, Weitzner MA, Valentine AD, Levin VA: Methylphenidate therapy improves cognition, mood, and function of brain tumor patients. J Clin Oncol 1998, 16:2522–2527.

    PubMed  CAS  Google Scholar 

  25. Shaw EG, Rosdhal R, D’Agostino RB, et al.: Phase II study of donezepil in irradiated brain tumor patients: effect on cognitive function, mood and quality of life. J Clin Oncol 2006, 24:1415–1420.

    Article  PubMed  CAS  Google Scholar 

  26. Gehring K, Sitskoorn MM, Aaronson NK, et al.: Interventions for cognitive deficits in adult with brain tumours. Lancet Neurol 2008, 7:548–560.

    Article  PubMed  Google Scholar 

  27. Peissner W, Kocher M, Treuer H, et al.: Ionizing radiationinduced apoptosis of proliferating stem cells in the dentate gyrus of the adult rat hippocampus. Brain Res Mol Brain Res 1999, 71:61–68.

    Article  PubMed  CAS  Google Scholar 

  28. Mizumatsu S, Monje ML, Morhardt DR, et al.: Extreme sensitivity of adult neurogenesis to low doses of X-irradiation. Cancer Res 2003, 63:4021–4027.

    PubMed  CAS  Google Scholar 

  29. Ghia A, Tome WA, Thomas S, et al.: Distribution of brain metastasis in relation to the hippocampus: implications for neurocognitive functional preservation. Int J Radiat Oncol Biol Phys 2007, 68:971–977.

    PubMed  Google Scholar 

  30. Khuntia D, Mehta M: Motexafin gadolinium: a clinical review of a novel radioenhancer for brain tumors. Expert Rev Anticancer Ther 2004, 4:981–989.

    Article  PubMed  CAS  Google Scholar 

  31. Carde P, Timmerman R, Mehta MP, et al.: Multicenter phase Ib/II trial of the radiation enhancer motexafin gadolinium in patients with brain metastases. J Clin Oncol 2001, 19:2074–2083.

    PubMed  CAS  Google Scholar 

  32. Mehta MP, Shapiro WR, Glantz MJ, et al.: Lead-in phase to randomized trial of motexafin gadolinium and whole-brain radiation for patients with brain metastases: centralized assessment of magnetic resonance imaging, neurocognitive, and neurologic end points. J Clin Oncol 2002, 20:3445–3453.

    Article  PubMed  CAS  Google Scholar 

  33. Mehta MP, Carrie C, Mahe MA, et al.: Motexafin gadolinium (MGd) combined with prompt whole brain radiation therapy prolongs time to neurologic progression in non-small cell lung cancer (NSCLC) patients with brain metastases: results of a randomized phase 3 trial. Int J Radiat Oncol Biol Phys 2006, 66(Suppl):S23.

    Google Scholar 

  34. Kunert M, Liard J, Abraham D: RSR-13, an allosteric effector of hemoglobin, increases systemic and iliac vascular resistance in rats. Am J Physiol 1996, 271:H602–H613.

    PubMed  CAS  Google Scholar 

  35. Suh J: Efaproxiral: a novel radiation sensitizer. Expert Opin Investig Drugs 2004, 13:543–550.

    Article  PubMed  CAS  Google Scholar 

  36. Shaw E, Scott C, Suh J, et al.: RSR-13 plus cranial radiation therapy in patients with brain metastases: comparison with the Radiation Therapy Oncology Group Recursive Partitioning Analysis Brain Metastases Database. J Clin Oncol 2003, 21:2364–2371.

    Article  PubMed  CAS  Google Scholar 

  37. Suh JH, Stea B, Nabid A, et al.: Phase III study of efaproxiral as an adjunct to whole-brain radiation therapy for brain metastases. J Clin Oncol 2006, 24:106–114.

    Article  PubMed  CAS  Google Scholar 

  38. Suh JH, Stea B, Nabid A, et al.: Results of the phase III ENRICH (RT-016) study of efaproxiral administered concurrent with whole brain radiation therapy (WBRT) in women with brain metastases from breast cancer. Int J Radiat Oncol Biol Phys 2008, 72(Suppl):S110.

    Google Scholar 

  39. Berk L, Berkey B, Rich T, et al.: Randomized phase II trial of high-dose melatonin and radiation therapy for RPA class 2 patients with brain metastases (RTOG 0119). Int J Radiat Oncol Biol Phys 2007, 68:852–857.

    PubMed  CAS  Google Scholar 

  40. D’Amato RJ, Loughnan MS, Flynn E, et al.: Thalidomide is an inhibitor of angiogenesis. Proc Nat Acad Sci U S A 1994, 91:4082–4085.

    Article  Google Scholar 

  41. Knisely JP, Berkey B, Chakravarti A, et al.: A phase III study of conventional radiation therapy plus thalidomide versus conventional radiation therapy for multiple brain metastases (RTOG 0118). Int J Radiat Oncol Biol Phys 2008, 71:79–86.

    PubMed  CAS  Google Scholar 

  42. Patchell RA, Tibbs PA, Walsh JW, et al.: A randomized trial of surgery in the treatment of single metastases to the brain. N Engl J Med 1990, 322:494–500.

    PubMed  CAS  Google Scholar 

  43. Vecht CJ, Haaxma-Reiche H, Noordijk EM, et al.: Treatment of single brain metastasis: radiotherapy alone or combined with neurosurgery. Ann Neurol 1993, 33:583–590.

    Article  PubMed  CAS  Google Scholar 

  44. Mintz AH, Kestle J, Rathbone MP, et al.: A randomized trial to assess the efficacy of surgery in addition to radiotherapy in patients with a single cerebral metastasis. Cancer 1996, 78:1470–1476.

    Article  PubMed  CAS  Google Scholar 

  45. Patchell RA, Tibbs PA, Regine WF, et al.: Postoperative radiotherapy in the treatment of single metastases to the brain: a randomized trial. JAMA 1998, 280:1485–1489.

    Article  PubMed  CAS  Google Scholar 

  46. Shaw E, Scott C, Souhami L, et al.: Single dose radiosurgical treatment of recurrent irradiated primary brain tumors and brain metastases: final report of RTOG protocol 90-05. Int J Radiat Oncol Biol Phys 2000, 47:291–298.

    Article  PubMed  CAS  Google Scholar 

  47. Sanghavi SN, Miranpuri SS, Chappell R, et al.: Radiosurgery for patients with brain metastases: a multiinstitutional analysis, stratified by the RTOG recursive partitioning analysis method. Int J Radiat Oncol Biol Phys 2001, 51:426–434.

    PubMed  CAS  Google Scholar 

  48. Andrews DW, Scott CB, Sperduto PW, et al.: Whole brain radiation therapy with or without stereotactic radiosurgery boost for patients with one to three brain metastases: phase III results of the RTOG 9508 randomised trial. Lancet 2004, 363:1665–1672.

    Article  PubMed  Google Scholar 

  49. Kondziolka D, Patel A, Lunsford LD, et al.: Stereotactic radiosurgery plus whole brain radiotherapy versus radiotherapy alone for patients with multiple brain metastases. Int J Radiat Oncol Biol Phys 1999, 45:427–434.

    PubMed  CAS  Google Scholar 

  50. Sneed P, Suh J, Goetsch S, et al.: A multi-institutional review of radiosurgery alone vs. radiosurgery with whole brain radiotherapy as the initial management of brain metastases. Int J Radiat Oncol Biol Phys 2002, 53:519–526.

    PubMed  Google Scholar 

  51. Pirzkall A, Debus J, Lohr F, et al.: Radiosurgery alone or in combination with whole-brain radiotherapy for brain metastases. J Clin Oncol 1998, 16:3563–3569.

    PubMed  CAS  Google Scholar 

  52. Manon R, O’Neill A, Knisely J, et al.: Phase II trial of radiosurgery for one to three newly diagnosed brain metastases from renal cell carcinoma, melanoma, and sarcoma: an Eastern Cooperative Oncology Group study (E 6397). J Clin Oncol 2005, 23:8870–8876.

    Article  PubMed  Google Scholar 

  53. Aoyama H, Shirato H, Tago M, et al.: Stereotactic radiosurgery plus whole-brain radiation therapy vs stereotactic radiosurgery alone for treatment of brain metastases: a randomized controlled trial. JAMA 2006, 295:2483–2491.

    Article  PubMed  CAS  Google Scholar 

  54. Aoyama H, Tago M, Kato N, et al.: Neurocognitive function of patients with brain metastases who received either whole brain radiotherapy plus stereotactic radiosurgery or radiosurgery alone. Int J Radiat Oncol Biol Phys 2007, 68:1388–1395.

    PubMed  Google Scholar 

  55. Kim PL, Ellis TL, Stieber VW, et al.: Gamma knife surgery targeting the resection cavity of brain metastasis that has progressed after whole-brain radiotherapy. J Neurosurg (Suppl) 2006, 105:75–78.

    Google Scholar 

  56. Soltys SG, Adler JR, Lipani JD, et al.: Stereotactic radiosurgery of the postoperative resection cavity for brain metastases. Int J Radiat Oncol Biol Phys 2008, 70:187–193.

    PubMed  Google Scholar 

  57. Chao ST, Barnett GH, Liu SW, et al.: Five-year survivors of brain metastases: a single-institution report of 32 patients. Int J Radiat Oncol Biol Phys 2006, 66:801–809.

    PubMed  Google Scholar 

  58. Kondziolka D, Martin JJ, Flickinger JC, et al.: Longterm survivors after gamma knife radiosurgery for brain metastases. Cancer 2005, 104:2784–2791.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Radiation Oncology, Brain Tumor and Neuro-oncology Center, T28, 9500 Euclid Avenue, Cleveland, OH, 44195, USA

    John H. Suh

Authors
  1. John H. Suh
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Samuel T. Chao
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Michael A. Vogelbaum
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to John H. Suh.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Suh, J.H., Chao, S.T. & Vogelbaum, M.A. Management of brain metastases. Curr Neurol Neurosci Rep 9, 223–230 (2009). https://doi.org/10.1007/s11910-009-0033-6

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11910-009-0033-6

Keywords

Search

Navigation