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01-02-2012 | Neuro-oncology (M Gilbert, Section Editor)

Management of Brain Metastasis: Past Lessons, Modern Management, and Future Considerations

Authors: Eugene Koay, Erik P. Sulman

Published in: Current Oncology Reports | Issue 1/2012

Abstract

Brain metastasis is a major challenge for patients, physicians, and the broader health care system, with approximately 170,000 new cases per year. After a diagnosis of brain metastasis, patients have a poor prognosis, but modern management has made significant advances in the past two decades to improve palliative efficacy and patient survival through a multidisciplinary approach. A number of factors must be taken into consideration in the treatment approach, including the number of intracranial lesions, the control of extracranial disease, and the patient’s overall health, while weighing the benefits of treatment against the toxicities, both acute and chronic. With quality of life as an emphasis, emerging concepts for modern management of brain metastasis have sought to minimize long-term toxicities. The economic impact of such strategies for patients and the health care system has been demonstrated in some studies, but has not been a consistent area of focus. Each of these strategies, as well as novel therapeutics, has embraced the concept of personalized treatment. This review will discuss the current knowledge of modern multidisciplinary management of brain metastasis and look forward to emerging concepts.

•• 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(9422):1665–72. Seminal clinical trial to define the use of stereotactic radiosurgery in combination with whole brain radiation. PubMedCrossRef

Hasegawa T, Kondziolka D, Flickinger JC, et al. Brain metastases treated with radiosurgery alone: an alternative to whole brain radiotherapy? Neurosurgery. 2003;52(6):1318–26. discussion 1326.PubMedCrossRef

Shaffrey ME, Mut M, Asher AL, et al. Brain metastases. Curr Probl Surg. 2004;41(8):665–741.PubMedCrossRef

Thomas SS, Dunbar EM. Modern multidisciplinary management of brain metastases. Curr Oncol Rep. 12(1):34–40.

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):1–9.PubMed

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(12):1633–8.PubMedCrossRef

Chatani M, Matayoshi Y, Masaki N, Inoue T. Radiation therapy for brain metastases from lung carcinoma. Prospective randomized trial according to the level of lactate dehydrogenase. Strahlenther Onkol. 1994;170(3):155–61.PubMed

Haie-Meder C, Pellae-Cosset B, Laplanche A, et al. Results of a randomized clinical trial comparing two radiation schedules in the palliative treatment of brain metastases. Radiother Oncol. 1993;26(2):111–6.PubMedCrossRef

Harwood AR, Simson WJ. Radiation therapy of cerebral metastases: a randomized prospective clinical trial. Int J Radiat Oncol Biol Phys. 1977;2(11–12):1091–4.PubMed

10.

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(7):891–5.PubMedCrossRef

11.

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(3):571–4.PubMedCrossRef

12.

Suh JH, Videtic GM, Aref AM, et al. ACR Appropriateness Criteria: single brain metastasis. Curr Probl Cancer. 34(3):162–74.

13.

Casanova N, Mazouni Z, Bieri S, et al. Whole brain radiotherapy with a conformational external beam radiation boost for lung cancer patients with 1–3 brain metastasis: a multi institutional study. Radiat Oncol. 2010;5:13.PubMedCrossRef

14.

DeAngelis LM, Delattre JY, Posner JB. Radiation-induced dementia in patients cured of brain metastases. Neurology. 1989;39(6):789–96.PubMed

15.

Komaki R, Cox JD, Whitson W. Risk of brain metastasis from small cell carcinoma of the lung related to length of survival and prophylactic irradiation. Cancer Treat Rep. 1981;65(9–10):811–4.PubMed

16.

•• 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(4):745–51. Describes the most widely utilized prognostic classification scheme for brain metastases.PubMedCrossRef

17.

• Sperduto PW, Chao ST, Sneed PK, et al. Diagnosis-specific prognostic factors, indexes, and treatment outcomes for patients with newly diagnosed brain metastases: a multi-institutional analysis of 4,259 patients. Int J Radiat Oncol Biol Phys. 77(3):655–61. An updated prognostic classification of brain metastases that incorporates tumor histologic type.

18.

Komosinska K, Kepka L, Niwinska A, et al. Prospective evaluation of the palliative effect of whole-brain radiotherapy in patients with brain metastases and poor performance status. Acta Oncol. 49(3):382–8.

19.

Paumier A, Cuenca X, Le Pechoux C. Prophylactic cranial irradiation in lung cancer. Cancer Treat Rev. 37(4):261–5.

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(11):1752–8. Large trial to demonstrate the survival benefit for prophylactic cranial irradiation of patients with limited-stage small cell lung cancer.PubMedCrossRef

21.

• Slotman B, Faivre-Finn C, Kramer G, et al. Prophylactic cranial irradiation in extensive small-cell lung cancer. N Engl J Med. 2007;357(7):664–72. Similar to Gregor et al. [20•], this trial demonstrated a survival benefit of prophylactic cranial irradiation, but in extensive-stage small cell lung cancer. Both trials established the standard of care for these patients. PubMedCrossRef

22.

Auperin A, Arriagada R, Pignon JP, et al. Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission. Prophylactic Cranial Irradiation Overview Collaborative Group. N Engl J Med. 1999;341(7):476–84.PubMedCrossRef

23.

Meert AP, Paesmans M, Berghmans T, et al. Prophylactic cranial irradiation in small cell lung cancer: a systematic review of the literature with meta-analysis. BMC Cancer. 2001;1:5.PubMedCrossRef

24.

Gore EM, Bae K, Wong SJ, et al. Phase III comparison of prophylactic cranial irradiation versus observation in patients with locally advanced non-small-cell lung cancer: primary analysis of radiation therapy oncology group study RTOG 0214. J Clin Oncol. 2011;29(3):272–8.PubMedCrossRef

25.

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(8):494–500.PubMedCrossRef

26.

Mikkelsen T, Anderson J, Doyle TJ, et al. Phase I/II dose escalation trial of concurrent temozolomide and whole brain radiation therapy for multiple brain metastasis. J Neurooncol. 100(2):241–7.

27.

Liu R, Wang X, Ma B, et al. Concomitant or adjuvant temozolomide with whole-brain irradiation for brain metastases: a meta-analysis. Anticancer Drugs 21(1):120–8.

28.

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(13):2529–36.PubMedCrossRef

29.

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(1):79–86.PubMedCrossRef

30.

Neuhaus T, Ko Y, Muller RP, et al. A phase III trial of topotecan and whole brain radiation therapy for patients with CNS-metastases due to lung cancer. Br J Cancer. 2009;100(2):291–7.PubMedCrossRef

31.

Phillips TL, Scott CB, Leibel SA, et al. Results of a randomized comparison of radiotherapy and bromodeoxyuridine with radiotherapy alone for brain metastases: report of RTOG trial 89–05. Int J Radiat Oncol Biol Phys. 1995;33(2):339–48.PubMedCrossRef

32.

Sampson JH, Carter Jr JH, Friedman AH, Seigler HF. Demographics, prognosis, and therapy in 702 patients with brain metastases from malignant melanoma. J Neurosurg. 1998;88(1):11–20.PubMedCrossRef

33.

Rades D, Heisterkamp C, Schild SE. Do patients receiving whole-brain radiotherapy for brain metastases from renal cell carcinoma benefit from escalation of the radiation dose? Int J Radiat Oncol Biol Phys. 78(2):398–403.

34.

Cannady SB, Cavanaugh KA, Lee SY, et al. Results of whole brain radiotherapy and recursive partitioning analysis in patients with brain metastases from renal cell carcinoma: a retrospective study. Int J Radiat Oncol Biol Phys. 2004;58(1):253–8.PubMedCrossRef

35.

Wronski M, Maor MH, Davis BJ, et al. External radiation of brain metastases from renal carcinoma: a retrospective study of 119 patients from the M. D. Anderson Cancer Center. Int J Radiat Oncol Biol Phys. 1997;37(4):753–9.PubMedCrossRef

36.

Onufrey V, Mohiuddin M. Radiation therapy in the treatment of metastatic renal cell carcinoma. Int J Radiat Oncol Biol Phys. 1985;11(11):2007–9.PubMedCrossRef

37.

Meyners T, Heisterkamp C, Kueter JD, et al. Prognostic factors for outcomes after whole-brain irradiation of brain metastases from relatively radioresistant tumors: a retrospective analysis. BMC Cancer. 10:582.

38.

Rades D, Heisterkamp C, Huttenlocher S, et al. Dose escalation of whole-brain radiotherapy for brain metastases from melanoma. Int J Radiat Oncol Biol Phys. 77(2):537–41.

39.

Ziegler JC, Cooper JS. Brain metastases from malignant melanoma: conventional vs. high-dose-per-fraction radiotherapy. Int J Radiat Oncol Biol Phys. 1986;12(10):1839–42.PubMedCrossRef

40.

Fogarty G, Morton RL, Vardy J, et al. Whole brain radiotherapy after local treatment of brain metastases in melanoma patients—a randomised phase III trial. BMC Cancer. 11(1):142.

41.

Bindal AK, Bindal RK, Hess KR, et al. Surgery versus radiosurgery in the treatment of brain metastasis. J Neurosurg. 1996;84(5):748–54.PubMedCrossRef

42.

O’Neill BP, Iturria NJ, Link MJ, et al. A comparison of surgical resection and stereotactic radiosurgery in the treatment of solitary brain metastases. Int J Radiat Oncol Biol Phys. 2003;55(5):1169–76.PubMedCrossRef

43.

Kienast Y, Winkler F. Therapy and prophylaxis of brain metastases. Expert Rev Anticancer Ther. 10(11):1763–77.

44.

Al-Shamy G, Sawaya R. Management of brain metastases: the indispensable role of surgery. J Neurooncol. 2009;92(3):275–82.PubMedCrossRef

45.

Stieber VW, Bourland JD, Tome WA, Mehta MP. Gentlemen (and ladies), choose your weapons: Gamma knife vs. linear accelerator radiosurgery. Technol Cancer Res Treat. 2003;2(2):79–86.PubMed

46.

Swinson BM, Friedman WA. Linear accelerator stereotactic radiosurgery for metastatic brain tumors: 17 years of experience at the University of Florida. Neurosurgery. 2008;62(5):1018–31. discussion 1031–1012.PubMedCrossRef

47.

Suh JH. Stereotactic radiosurgery for the management of brain metastases. N Engl J Med. 2010;362(12):1119–27.PubMedCrossRef

48.

Cooper JS, Steinfeld AD, Lerch IA. Cerebral metastases: value of reirradiation in selected patients. Radiology. 1990;174(3 Pt 1):883–5.PubMed

49.

Hazuka MB, Kinzie JJ. Brain metastases: results and effects of re-irradiation. Int J Radiat Oncol Biol Phys. 1988;15(2):433–7.PubMedCrossRef

50.

Kurup P, Reddy S, Hendrickson FR. Results of re-irradiation for cerebral metastases. Cancer. 1980;46(12):2587–9.PubMedCrossRef

51.

Wong WW, Schild SE, Sawyer TE, Shaw EG. Analysis of outcome in patients reirradiated for brain metastases. Int J Radiat Oncol Biol Phys. 1996;34(3):585–90.PubMedCrossRef

52.

Son CH, Jimenez R, Niemierko A, et al. Outcomes after whole brain reirradiation in patients with brain metastases. Int J Radiat Oncol Biol Phys. 2011.

53.

Sneed PK, Lamborn KR, Forstner JM, et al. Radiosurgery for brain metastases: is whole brain radiotherapy necessary? Int J Radiat Oncol Biol Phys. 1999;43(3):549–58.PubMedCrossRef

54.

Chang EL, Wefel JS, Hess KR, et al. Neurocognition in patients with brain metastases treated with radiosurgery or radiosurgery plus whole-brain irradiation: a randomised controlled trial. Lancet Oncol. 2009;10(11):1037–44.PubMedCrossRef

55.

Noordijk EM, Vecht CJ, Haaxma-Reiche H, et al. The choice of treatment of single brain metastasis should be based on extracranial tumor activity and age. Int J Radiat Oncol Biol Phys. 1994;29(4):711–7.PubMedCrossRef

56.

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(17):1485–9.PubMedCrossRef

57.

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(21):2483–91.PubMedCrossRef

58.

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(11):3563–9.PubMed

59.

Kocher M, Soffietti R, Abacioglu U, et al. 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(2):134–41.

60.

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(1):187–93.PubMedCrossRef

61.

Nataf F, Schlienger M, Liu Z, et al. Radiosurgery with or without A 2-mm margin for 93 single brain metastases. Int J Radiat Oncol Biol Phys. 2008;70(3):766–72.PubMedCrossRef

62.

Mehta MP, Tsao MN, Whelan TJ, et al. The American Society for Therapeutic Radiology and Oncology (ASTRO) evidence-based review of the role of radiosurgery for brain metastases. Int J Radiat Oncol Biol Phys. 2005;63(1):37–46.PubMedCrossRef

63.

Phase III randomized study of stereotactic radiosurgery with versus without whole-brain radiotherapy in patients with cerebral metastases [http://www.cancer.gov/clinicaltrials/search/view?cdrid=499633&version=healthprofessional].

64.

Coller BS. Realigning incentives to achieve health care reform. JAMA. 2011;306(2):204–5.PubMedCrossRef

65.

Okma KG, Marmor TR, Oberlander J. Managed competition for medicare? Sobering lessons from the Netherlands. N Engl J Med. 2011.

66.

Jost TS. Consensus and conflict in health system reform–the Republican budget plan and the ACA. N Engl J Med. 2011;364(19):e40.PubMedCrossRef

67.

Lal LS, Byfield SD, Chang EL, et al. Cost-effectiveness analysis of a randomized study comparing radiosurgery with radiosurgery and whole brain radiation therapy in patients with 1 to 3 brain metastases. Am J Clin Oncol.

68.

Lal LS, Franzini L, Panchal J, et al. Economic impact of stereotactic radiosurgery for malignant intracranial brain tumors. Expert Rev Pharmacoecon Outcomes Res. 11(2):195–204.

69.

Mehta M, Noyes W, Craig B, et al. A cost-effectiveness and cost-utility analysis of radiosurgery vs. resection for single-brain metastases. Int J Radiat Oncol Biol Phys. 1997;39(2):445–54.PubMedCrossRef

70.

Wen PY, Loeffler JS. Brain metastases. Curr Treat Options Oncol. 2000;1(5):447–58.PubMedCrossRef

71.

Ryken TC, McDermott M, Robinson PD, et al. The role of steroids in the management of brain metastases: a systematic review and evidence-based clinical practice guideline. J Neurooncol. 96(1):103–14.

72.

Butler Jr JM, Case LD, Atkins J, et al. A phase III, double-blind, placebo-controlled prospective randomized clinical trial of d-threo-methylphenidate HCl in brain tumor patients receiving radiation therapy. Int J Radiat Oncol Biol Phys. 2007;69(5):1496–501.PubMedCrossRef

73.

Aoyama H, Tago M, Kato N, et al. 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. 2007;68(5):1388–95.PubMedCrossRef

74.

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(1):157–65.PubMedCrossRef

75.

Li J, Bentzen SM, Renschler M, Mehta MP. Regression after whole-brain radiation therapy for brain metastases correlates with survival and improved neurocognitive function. J Clin Oncol. 2007;25(10):1260–6.PubMedCrossRef

76.

Sheline GE, Wara WM, Smith V. Therapeutic irradiation and brain injury. Int J Radiat Oncol Biol Phys. 1980;6(9):1215–28.PubMedCrossRef

77.

Uzal D, Ozyar E, Hayran M, et al. Reduced incidence of the somnolence syndrome after prophylactic cranial irradiation in children with acute lymphoblastic leukemia. Radiother Oncol. 1998;48(1):29–32.PubMedCrossRef

78.

Ghia A, Tome WA, Thomas S, et al. Distribution of brain metastases in relation to the hippocampus: implications for neurocognitive functional preservation. Int J Radiat Oncol Biol Phys. 2007;68(4):971–7.PubMedCrossRef

79.

Marsh JC, Herskovic AM, Gielda BT, et al. Intracranial metastatic disease spares the limbic circuit: a review of 697 metastatic lesions in 107 patients. Int J Radiat Oncol Biol Phys. 76(2):504–12.

80.

Gondi V, Tome WA, Mehta MP. Why avoid the hippocampus? A comprehensive review. Radiother Oncol. 2010;97(3):370–6.PubMedCrossRef

81.

Bender ET, Mehta MP, Tome WA. On the estimation of the location of the hippocampus in the context of hippocampal avoidance whole brain radiotherapy treatment planning. Technol Cancer Res Treat. 2009;8(6):425–32.PubMed

82.

• Gondi V, Tolakanahalli R, Mehta MP, et al. Hippocampal-sparing whole-brain radiotherapy: a “how-to” technique using helical tomotherapy and linear accelerator-based intensity-modulated radiotherapy. Int J Radiat Oncol Biol Phys. 2010;78(4):1244–52. Describes technique and rationale for hippocampal-sparing whole brain radiation. PubMedCrossRef

83.

Marsh JC, Godbole RH, Herskovic AM, et al. Sparing of the neural stem cell compartment during whole-brain radiation therapy: a dosimetric study using helical tomotherapy. Int J Radiat Oncol Biol Phys. 78(3):946–54.

84.

Bonner JA, Harari PM, Giralt J, et al. Radiotherapy plus cetuximab for locoregionally advanced head and neck cancer: 5-year survival data from a phase 3 randomised trial, and relation between cetuximab-induced rash and survival. Lancet Oncol. 2010;11(1):21–8.PubMedCrossRef

85.

Ceresoli GL, Cappuzzo F, Gregorc V, et al. Gefitinib in patients with brain metastases from non-small-cell lung cancer: a prospective trial. Ann Oncol. 2004;15(7):1042–7.PubMedCrossRef

86.

Tsai C, Chiu C, Liou J, et al. Gefitinib is active in patients with brain metastasis from non-small cell lung cancer. Zhongguo Fei Ai Za Zhi. 2004;7(4):298–304.PubMed

87.

Hotta K, Kiura K, Ueoka H, et al. Effect of gefitinib (‘Iressa’, ZD1839) on brain metastases in patients with advanced non-small-cell lung cancer. Lung Cancer. 2004;46(2):255–61.PubMedCrossRef

88.

Namba Y, Kijima T, Yokota S, et al. Gefitinib in patients with brain metastases from non-small-cell lung cancer: review of 15 clinical cases. Clin Lung Cancer. 2004;6(2):123–8.PubMedCrossRef

89.

Shimato S, Mitsudomi T, Kosaka T, et al. EGFR mutations in patients with brain metastases from lung cancer: association with the efficacy of gefitinib. Neuro Oncol. 2006;8(2):137–44.PubMedCrossRef

90.

Wu C, Li YL, Wang ZM, et al. Gefitinib as palliative therapy for lung adenocarcinoma metastatic to the brain. Lung Cancer. 2007;57(3):359–64.PubMedCrossRef

91.

Long GV, Kefford RF, Carr PJA, et al. Phase 1/2 study of GSK2118436, a selective inhibitor of V600 mutant (mut) BRAF kinase: evidence of activity in melanoma brain metastases (mets) (LBA27). In: European Society of Medical Oncology: 2010; Milan, Italy: Oxford University Press; 2010: viii12.

92.

Cruz-Munoz W, Kerbel RS. Preclinical approaches to study the biology and treatment of brain metastases. Semin Cancer Biol. 2011;21(2):123–30.PubMedCrossRef

Title: Management of Brain Metastasis: Past Lessons, Modern Management, and Future Considerations
Authors: Eugene Koay
Erik P. Sulman
Publication date: 01-02-2012
Publisher: Current Science Inc.
Published in: Current Oncology Reports / Issue 1/2012
Print ISSN: 1523-3790
Electronic ISSN: 1534-6269
DOI: https://doi.org/10.1007/s11912-011-0205-9

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