Indications for Stereotactic Radiosurgery: Multiple Brain Metastases

  • Anurag Saraf
  • Tony J. C. WangEmail author


Brain metastasis (BM) is the most common intracranial malignancy, and most patients present with multiple brain metastases at time of diagnosis. Whole brain radiation therapy (WBRT) has been the standard of care for multiple BM; however, recent studies have shown that stereotactic radiosurgery (SRS) may have similar outcomes and better toxicity profile than WBRT in the setting of multiple BM.

SRS has worse distant brain failure for patients with multiple BM than with the addition of WBRT. However, with frequent follow-up and surveillance imaging for salvage treatment (with SRS, surgery, or WBRT), studies find that SRS has similar overall survival to WBRT in the treatment of multiple BM. On the other hand, WBRT leads to worsening neurocognitive decline and worse quality of life and, therefore, the toxicity profile may not be an appropriate choice for patients compared to SRS alone.


Brain metastases Radiation therapy Stereotactic radiosurgery Whole brain radiation therapy Radiation necrosis Neurocognition Gamma Knife stereotactic radiosurgery Cyberknife radiosurgery 


  1. 1.
    Wen PY, Loeffler JS. Management of brain metastases. Oncology (Williston Park). 1999;13(7):941–54, 957–61; discussion 961–2, 9.Google Scholar
  2. 2.
    Johnson JD, Young B. Demographics of brain metastasis. Neurosurg Clin N Am. 1996;7(3):337–44.PubMedCrossRefGoogle Scholar
  3. 3.
    Villa S, et al. Validation of the new graded prognostic assessment scale for brain metastases: a multicenter prospective study. Radiat Oncol. 2011;6:23.PubMedPubMedCentralCrossRefGoogle Scholar
  4. 4.
    Stelzer KJ. Epidemiology and prognosis of brain metastases. Surg Neurol Int. 2013;4(Suppl 4):S192–202.PubMedPubMedCentralCrossRefGoogle Scholar
  5. 5.
    Tabouret E, et al. Recent trends in epidemiology of brain metastases: an overview. Anticancer Res. 2012;32(11):4655–62.PubMedPubMedCentralGoogle Scholar
  6. 6.
    Andrews DW, 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.PubMedPubMedCentralCrossRefGoogle Scholar
  7. 7.
    Sperduto PW, et al. Secondary analysis of RTOG 9508, a phase 3 randomized trial of whole-brain radiation therapy versus WBRT plus stereotactic radiosurgery in patients with 1-3 brain metastases; poststratified by the graded prognostic assessment (GPA). Int J Radiat Oncol Biol Phys. 2014;90(3):526–31.PubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    Yamamoto M, et al. Stereotactic radiosurgery for patients with multiple brain metastases (JLGK0901): a multi-institutional prospective observational study. Lancet Oncol. 2014;15(4):387–95.PubMedCrossRefGoogle Scholar
  9. 9.
    Chang EL, 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(2):277–83; discussion 283–4.PubMedCrossRefGoogle Scholar
  10. 10.
    Brown PD, et al. Effect of radiosurgery alone vs radiosurgery with whole brain radiation therapy on cognitive function in patients with 1 to 3 brain metastases: a randomized clinical trial. JAMA. 2016;316(4):401–9.PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    Tsao MN, et al. Whole brain radiotherapy for the treatment of multiple brain metastases. Cochrane Database Syst Rev. 2006;(3):CD003869.Google Scholar
  12. 12.
    Borgelt B, 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.PubMedCrossRefGoogle Scholar
  13. 13.
    Suzuki H, et al. Spontaneous haemorrhage into metastatic brain tumours after stereotactic radiosurgery using a linear accelerator. J Neurol Neurosurg Psychiatry. 2003;74(7):908–12.PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    Muller-Riemenschneider F, et al. Medical and health economic assessment of radiosurgery for the treatment of brain metastasis. GMS Health Technol Assess. 2009;5:Doc03.PubMedPubMedCentralGoogle Scholar
  15. 15.
    Hall MD, et al. Cost-effectiveness of stereotactic radiosurgery with and without whole-brain radiotherapy for the treatment of newly diagnosed brain metastases. J Neurosurg. 2014;121(Suppl):84–90.PubMedCrossRefGoogle Scholar
  16. 16.
    Chang EL, 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.PubMedCrossRefGoogle Scholar
  17. 17.
    Kocher M, 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. 2011;29(2):134–41.CrossRefPubMedGoogle Scholar
  18. 18.
    Aoyama H, 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.PubMedCrossRefGoogle Scholar
  19. 19.
    Gaspar L, 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.CrossRefPubMedGoogle Scholar
  20. 20.
    Weltman E, et al. Radiosurgery for brain metastases: a score index for predicting prognosis. Int J Radiat Oncol Biol Phys. 2000;46(5):1155–61.PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Lorenzoni J, et al. Radiosurgery for treatment of brain metastases: estimation of patient eligibility using three stratification systems. Int J Radiat Oncol Biol Phys. 2004;60(1):218–24.PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    Lagerwaard FJ, et al. Identification of prognostic factors in patients with brain metastases: a review of 1292 patients. Int J Radiat Oncol Biol Phys. 1999;43(4):795–803.PubMedCrossRefGoogle Scholar
  23. 23.
    Golden DW, et al. Prognostic factors and grading systems for overall survival in patients treated with radiosurgery for brain metastases: variation by primary site. J Neurosurg. 2008;109(Suppl):77–86.PubMedPubMedCentralCrossRefGoogle Scholar
  24. 24.
    Sperduto PW, et al. A new prognostic index and comparison to three other indices for patients with brain metastases: an analysis of 1,960 patients in the RTOG database. Int J Radiat Oncol Biol Phys. 2008;70(2):510–4.CrossRefPubMedGoogle Scholar
  25. 25.
    Sperduto PW, 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. 2010;77(3):655–61.PubMedPubMedCentralCrossRefGoogle Scholar
  26. 26.
    Sperduto PW, et al. Summary report on the graded prognostic assessment: an accurate and facile diagnosis-specific tool to estimate survival for patients with brain metastases. J Clin Oncol. 2012;30(4):419–25.PubMedCrossRefGoogle Scholar
  27. 27.
    Subbiah IM, et al. Validation and development of a modified breast graded prognostic assessment as a tool for survival in patients with breast Cancer and brain metastases. J Clin Oncol. 2015;33(20):2239–45.PubMedPubMedCentralCrossRefGoogle Scholar
  28. 28.
    Sperduto PW, et al. Estimating survival in patients with lung cancer and brain metastases: an update of the graded prognostic assessment for lung cancer using molecular markers (lung-molGPA). JAMA Oncol. 2017;3(6):827–31.PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Hughes RT, et al. Initial SRS for patients with 5 to 15 brain metastases: results of a multi-institutional experience. Int J Radiat Oncol Biol Phys. 2019;104:1091–8.PubMedCrossRefGoogle Scholar
  30. 30.
    Chang WS, et al. Analysis of radiosurgical results in patients with brain metastases according to the number of brain lesions: is stereotactic radiosurgery effective for multiple brain metastases? J Neurosurg. 2010;113(Suppl):73–8.PubMedCrossRefGoogle Scholar
  31. 31.
    Salvetti DJ, et al. Gamma Knife surgery for the treatment of 5 to 15 metastases to the brain: clinical article. J Neurosurg. 2013;118(6):1250–7.PubMedCrossRefGoogle Scholar
  32. 32.
    Aoyama H, et al. Stereotactic radiosurgery with or without whole-brain radiotherapy for brain metastases: secondary analysis of the JROSG 99-1 randomized clinical trial. JAMA Oncol. 2015;1(4):457–64.PubMedCrossRefGoogle Scholar
  33. 33.
    Saraf A, et al. Breast cancer subtype and stage are prognostic of time from breast cancer diagnosis to brain metastasis development. J Neuro-Oncol. 2017;134(2):453–63.CrossRefGoogle Scholar
  34. 34.
    Tai CH, et al. Single institution validation of a modified graded prognostic assessment of patients with breast cancer brain metastases. CNS Oncol. 2018;7(1):25–34.PubMedPubMedCentralCrossRefGoogle Scholar
  35. 35.
    Mohammadi AM, et al. Role of Gamma Knife surgery in patients with 5 or more brain metastases. J Neurosurg. 2012;117(Suppl):5–12.PubMedCrossRefGoogle Scholar
  36. 36.
    Bhatnagar AK, et al. Stereotactic radiosurgery for four or more intracranial metastases. Int J Radiat Oncol Biol Phys. 2006;64(3):898–903.PubMedCrossRefGoogle Scholar
  37. 37.
    Tsao MN, et al. Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es): an American Society for Radiation Oncology evidence-based guideline. Pract Radiat Oncol. 2012;2(3):210–25.PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Lippitz B, et al. Stereotactic radiosurgery in the treatment of brain metastases: the current evidence. Cancer Treat Rev. 2014;40(1):48–59.PubMedCrossRefGoogle Scholar
  39. 39.
    Vecht CJ, et al. Treatment of single brain metastasis: radiotherapy alone or combined with neurosurgery? Ann Neurol. 1993;33(6):583–90.PubMedCrossRefGoogle Scholar
  40. 40.
    Patchell RA, 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.CrossRefPubMedGoogle Scholar
  41. 41.
    Grandhi R, et al. Stereotactic radiosurgery using the Leksell Gamma Knife Perfexion unit in the management of patients with 10 or more brain metastases. J Neurosurg. 2012;117(2):237–45.PubMedCrossRefGoogle Scholar
  42. 42.
    Ma L, et al. Apparatus dependence of normal brain tissue dose in stereotactic radiosurgery for multiple brain metastases. J Neurosurg. 2011;114(6):1580–4.PubMedCrossRefGoogle Scholar
  43. 43.
    Ma L, et al. Variable dose interplay effects across radiosurgical apparatus in treating multiple brain metastases. Int J Comput Assist Radiol Surg. 2014;9(6):1079–86.PubMedPubMedCentralCrossRefGoogle Scholar
  44. 44.
    McDonald D, et al. Comparison of radiation dose spillage from the Gamma Knife Perfexion with that from volumetric modulated arc radiosurgery during treatment of multiple brain metastases in a single fraction. J Neurosurg. 2014;121(Suppl):51–9.PubMedCrossRefGoogle Scholar
  45. 45.
    Dong P, et al. Minimizing normal tissue dose spillage via broad-range optimization of hundreds of intensity modulated beams for treating multiple brain targets. J Radiosurg SBRT. 2016;4(2):107–15.PubMedPubMedCentralGoogle Scholar
  46. 46.
    Sahgal A, et al. Prescription dose guideline based on physical criterion for multiple metastatic brain tumors treated with stereotactic radiosurgery. Int J Radiat Oncol Biol Phys. 2010;78(2):605–8.PubMedCrossRefGoogle Scholar
  47. 47.
    Shaw E, et al. Single dose radiosurgical treatment of recurrent previously irradiated primary brain tumors and brain metastases: final report of RTOG protocol 90-05. Int J Radiat Oncol Biol Phys. 2000;47(2):291–8.CrossRefPubMedGoogle Scholar
  48. 48.
    Mulvenna P, et al. Dexamethasone and supportive care with or without whole brain radiotherapy in treating patients with non-small cell lung cancer with brain metastases unsuitable for resection or stereotactic radiotherapy (QUARTZ): results from a phase 3, non-inferiority, randomised trial. Lancet. 2016;388(10055):2004–14.PubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    Zindler JD, et al. Whole brain radiotherapy versus stereotactic radiosurgery for 4-10 brain metastases: a phase III randomised multicentre trial. BMC Cancer. 2017;17(1):500.PubMedPubMedCentralCrossRefGoogle Scholar
  50. 50.
    Brown PD, et al. Memantine for the prevention of cognitive dysfunction in patients receiving whole-brain radiotherapy: a randomized, double-blind, placebo-controlled trial. Neuro-Oncology. 2013;15(10):1429–37.PubMedPubMedCentralCrossRefGoogle Scholar
  51. 51.
    Rapp SR, et al. Donepezil for irradiated brain tumor survivors: a phase III randomized placebo-controlled clinical trial. J Clin Oncol. 2015;33(15):1653–9.PubMedPubMedCentralCrossRefGoogle Scholar

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© Springer Nature Switzerland AG 2020

Authors and Affiliations

  1. 1.Department of Radiation OncologyMassachusetts General HospitalBostonUSA
  2. 2.Department of Radiation OncologyColumbia University Irving Medical CenterNew YorkUSA

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