Multiple Brain Metastases

  • Isabella Zhang
  • Masaaki Yamamoto
  • Jonathan P. S. KniselyEmail author


In the United States every year, estimates of cancer patients diagnosed with brain metastases range from just under 100,000 to nearly 200,000; they affect 20–40% of all patients with cancer within their lifetimes. Patients with a limited number of metastases are candidates for surgery or stereotactic radiosurgery (SRS), with surgery preferred for larger, acutely symptomatic tumors. Patients with more numerous metastases can be treated with SRS or whole brain radiation therapy (WBRT), with the latter approach or supportive care preferred for patients with worse prognoses.

Prognostication systems developed to help guide management decisions in patients with brain metastases have identified important factors such as patient performance status, age, tumor histology, intracranial disease volume, and extracranial tumor control. In addition to local necrosis from SRS, neurocognitive decline is a more recently recognized adverse effect that may occur after SRS alone or after whole brain radiation has been employed. Two approaches have recently emerged to reduce these neurocognitive consequences in patients requiring irradiation of brain metastases, including dose sparing of the hippocampi and pharmacologically decreasing radiation-induced neuronal excitotoxicity.

Optimal brain metastasis management and the integration of focal treatments with a changing landscape of systemic management approaches present challenges for oncologists. Better knowledge and better tools facilitate better choices.


Multiple brain metastases Stereotactic radiosurgery Whole brain radiation therapy 



Delayed radiation-induced vasculitic leukoencephalopathy


Fractionated SRS


Karnofsky performance status


Optimal supportive care


Quality-adjusted life year


Quality of life


Stereotactic radiosurgery


Whole brain radiation therapy


  1. 1.
    Wen PY, Loeffler J. Management of brain metastases. Oncology (Williston Park, NY). 1999;13(7):941–54, 57–61; discussion 61–2, 9.Google Scholar
  2. 2.
    Barnholtz-Sloan JS, Sloan AE, Davis FG, et al. Incidence proportions of brain metastases in patients diagnosed (1973 to 2001) in the Metropolitan Detroit Cancer Surveillance System. J Clin Oncol. 2004;22(14):2865–72.CrossRefPubMedGoogle Scholar
  3. 3.
    Delattre JY, Krol G, Thaler HT, et al. Distribution of brain metastases. Arch Neurol. 1988;45(7):741–4.CrossRefPubMedGoogle Scholar
  4. 4.
    Arbit E, Wronski M, Burt M, et al. The treatment of patients with recurrent brain metastases. A retrospective analysis of 109 patients with nonsmall cell lung cancer. Cancer. 1995;76(5):765–73.CrossRefPubMedGoogle Scholar
  5. 5.
    Chamberlain MC. Leptomeningeal metastasis. Semin Neurol. 2010;30(3):236–44.CrossRefPubMedGoogle Scholar
  6. 6.
    Priedigkeit N, Hartmaier RJ, Chen Y, et al. Intrinsic subtype switching and acquired ERBB2/HER2 amplifications and mutations in breast cancer brain metastases. JAMA Oncol. 2017;3(5):666–71.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Zimm S, Wampler GL, Stablein D, et al. Intracerebral metastases in solid-tumor patients: natural history and results of treatment. Cancer. 1981;48(2):384–94.CrossRefPubMedGoogle Scholar
  8. 8.
    Mulvenna P, Nankivell M, Barton R, 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.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    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.CrossRefPubMedGoogle Scholar
  10. 10.
    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 1,960 patients in the RTOG database. Int J Radiat Oncol Biol Phys. 2008;70(2):510–4.CrossRefPubMedGoogle Scholar
  11. 11.
    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. 2010;77(3):655–61.CrossRefPubMedGoogle Scholar
  12. 12.
    Sperduto PW, Yang TJ, Beal K, 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.CrossRefPubMedGoogle Scholar
  13. 13.
    Yamamoto M, Serizawa T, Shuto T, et al. Stereotactic radiosurgery for patients with multiple brain metastases (JLGK0901): a multi-institutional prospective observational study. Lancet Oncol. 2014;15(4):387–95.CrossRefPubMedGoogle Scholar
  14. 14.
    Skeie BS, Skeie GO, Enger PO, et al. Gamma Knife surgery in brain melanomas: absence of extracranial metastases and tumor volume strongest indicators of prolonged survival. World Neurosurg. 2011;75(5–6):684–91. discussion 598–603CrossRefPubMedGoogle Scholar
  15. 15.
    Baschnagel AM, Meyer KD, Chen PY, et al. Tumor volume as a predictor of survival and local control in patients with brain metastases treated with Gamma Knife surgery. J Neurosurg. 2013;119(5):1139–44.CrossRefPubMedGoogle Scholar
  16. 16.
    Twycross RG. Palliative care formulary. Oxford: Radcliffe Publishing; 2002.Google Scholar
  17. 17.
    Bindal AK, Bindal RK, Hess KR, et al. Surgery versus radiosurgery in the treatment of brain metastasis. J Neurosurg. 1996;84(5):748–54.CrossRefPubMedGoogle Scholar
  18. 18.
    Bindal RK, Sawaya R, Leavens ME, et al. Surgical treatment of multiple brain metastases. J Neurosurg. 1993;79(2):210–6.CrossRefPubMedGoogle Scholar
  19. 19.
    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.CrossRefPubMedGoogle Scholar
  20. 20.
    McPherson CM, Suki D, Feiz-Erfan I, et al. Adjuvant whole-brain radiation therapy after surgical resection of single brain metastases. Neuro Oncol. 2010;12(7):711–9.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    McTyre E, Scott J, Chinnaiyan P. Whole brain radiotherapy for brain metastasis. Surg Neurol Int. 2013;4(Suppl 4):S236–44.PubMedPubMedCentralGoogle Scholar
  22. 22.
    Tsao MN, Lloyd N, Wong RK, et al. Whole brain radiotherapy for the treatment of newly diagnosed multiple brain metastases. Cochrane Database Syst Rev 2012;(4):CD003869.Google Scholar
  23. 23.
    Gondi V, Pugh SL, Tome WA, et al. Preservation of memory with conformal avoidance of the hippocampal neural stem-cell compartment during whole-brain radiotherapy for brain metastases (RTOG 0933): a phase II multi-institutional trial. J Clin Oncol. 2014;32(34):3810–6.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Brown PD, Pugh S, Laack NN, et al. Memantine for the prevention of cognitive dysfunction in patients receiving whole-brain radiotherapy: a randomized, double-blind, placebo-controlled trial. Neuro Oncol. 2013;15(10):1429–37.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Horton J, Baxter DH, Olson KB. The management of metastases to the brain by irradiation and corticosteroids. Am J Roentgenol Radium Therapy Nucl Med. 1971;111(2):334–6.CrossRefGoogle Scholar
  26. 26.
    Wong WW, Schild SE, Sawyer TE, et al. Analysis of outcome in patients reirradiated for brain metastases. Int J Radiat Oncol Biol Phys. 1996;34(3):585–90.CrossRefPubMedGoogle Scholar
  27. 27.
    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.CrossRefPubMedGoogle Scholar
  28. 28.
    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(2):427–34.CrossRefPubMedGoogle Scholar
  29. 29.
    Sneed PK, Suh JH, Goetsch SJ, 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(3):519–26.CrossRefPubMedGoogle Scholar
  30. 30.
    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.CrossRefPubMedGoogle Scholar
  31. 31.
    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. 2011;29(2):134–41.CrossRefPubMedGoogle Scholar
  32. 32.
    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.CrossRefPubMedGoogle Scholar
  33. 33.
    Brown PD, Jaeckle K, Ballman KV, 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.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Aoyama H, Tago M, Shirato H. 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.CrossRefPubMedGoogle Scholar
  35. 35.
    Churilla TM, Ballman KV, Brown PD, et al. Stereotactic radiosurgery with or without whole-brain radiation therapy for limited brain metastases: a secondary analysis of the North Central Cancer Treatment Group N0574 (Alliance) randomized controlled trial. Int J Radiat Oncol Biol Phys. 2017;99:1173.CrossRefPubMedGoogle Scholar
  36. 36.
    Churilla TM, Handorf E, Collette S, et al. Whole brain radiotherapy after stereotactic radiosurgery or surgical resection among patients with one to three brain metastases and favorable prognoses: a secondary analysis of EORTC 22952-26001. Ann Oncol. 2017;28(10):2588–94.CrossRefPubMedGoogle Scholar
  37. 37.
    Soffietti R, Kocher M, Abacioglu UM, et al. A European Organisation for Research and Treatment of Cancer phase III trial of adjuvant whole-brain radiotherapy versus observation in patients with one to three brain metastases from solid tumors after surgical resection or radiosurgery: quality-of-life results. J Clin Oncol. 2013;31(1):65–72.CrossRefPubMedGoogle Scholar
  38. 38.
    Sahgal A, Aoyama H, Kocher M, et al. Phase 3 trials of stereotactic radiosurgery with or without whole-brain radiation therapy for 1 to 4 brain metastases: individual patient data meta-analysis. Int J Radiat Oncol Biol Phys. 2015;91(4):710–7.CrossRefPubMedGoogle Scholar
  39. 39.
    NCC Network. Central nervous system cancers (Version 1.2016). [February 7, 2017]; Available from:
  40. 40.
    Choosing Wisely. American Society for Radiation Oncology. [updated June 21, 2016; June 9, 2017]; Available from:
  41. 41.
    Mehta MP, Aoyama H, Gondi V. The changing role of whole-brain radiotherapy: demise or time for selective usage? JAMA Oncol. 2017;3:1021.CrossRefPubMedGoogle Scholar
  42. 42.
    Knisely JP, Yamamoto M, Gross CP, et al. Radiosurgery alone for 5 or more brain metastases: expert opinion survey. J Neurosurg. 2010;113(Suppl):84–9.PubMedGoogle Scholar
  43. 43.
    Korytko T, Radivoyevitch T, Colussi V, et al. 12 Gy Gamma Knife radiosurgical volume is a predictor for radiation necrosis in non-AVM intracranial tumors. Int J Radiat Oncol Biol Phys. 2006;64(2):419–24.CrossRefPubMedGoogle Scholar
  44. 44.
    Shaw E, Scott C, Souhami L, 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
  45. 45.
    Yamamoto M, Serizawa T, Higuchi Y, et al. A multi-institutional prospective observational study of stereotactic radiosurgery for patients with multiple brain metastases (JLGK0901 study update): irradiation-related complications and long-term maintenance of mini-mental state examination scores. Int J Radiat Oncol Biol Phys. 2017;99(1):31–40.CrossRefPubMedGoogle Scholar
  46. 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 31-2.CrossRefPubMedGoogle Scholar
  47. 47.
    Varlotto JM, Flickinger JC, Niranjan A, et al. The impact of whole-brain radiation therapy on the long-term control and morbidity of patients surviving more than one year after Gamma Knife radiosurgery for brain metastases. Int J Radiat Oncol Biol Phys. 2005;62(4):1125–32.CrossRefPubMedGoogle Scholar
  48. 48.
    Jawahar A, Matthew RE, Minagar A, et al. Gamma Knife surgery in the management of brain metastases from lung carcinoma: a retrospective analysis of survival, local tumor control, and freedom from new brain metastasis. J Neurosurg. 2004;100(5):842–7.CrossRefPubMedGoogle Scholar
  49. 49.
    Skeie BS, Enger PO, Ganz JC, et al. Gamma Knife surgery of colorectal brain metastases: a high prescription dose of 25 Gy may improve growth control. World Neurosurg. 2013;79(3–4):525–36.CrossRefPubMedGoogle Scholar
  50. 50.
    Surgeons AAoNSaCoN. Statement on coding and reimbursement for stereotactic radiosurgery. 2008 [January 1, 2017.]; Available from:
  51. 51.
    Higuchi Y, Serizawa T, Nagano O, et al. Three-staged stereotactic radiotherapy without whole brain irradiation for large metastatic brain tumors. Int J Radiat Oncol Biol Phys. 2009;74(5):1543–8.CrossRefPubMedGoogle Scholar
  52. 52.
    Kim YJ, Cho KH, Kim JY, et al. Single-dose versus fractionated stereotactic radiotherapy for brain metastases. Int J Radiat Oncol Biol Phys. 2011;81(2):483–9.CrossRefPubMedGoogle Scholar
  53. 53.
    Minniti G, Scaringi C, Paolini S, et al. Single-fraction versus multifraction (3 x 9 Gy) stereotactic radiosurgery for large (>2 cm) brain metastases: a comparative analysis of local control and risk of radiation-induced brain necrosis. Int J Radiat Oncol Biol Phys. 2016;95(4):1142–8.CrossRefPubMedGoogle Scholar
  54. 54.
    Ernst-Stecken A, Ganslandt O, Lambrecht U, et al. Phase II trial of hypofractionated stereotactic radiotherapy for brain metastases: results and toxicity. Radiother Oncol. 2006;81(1):18–24.CrossRefPubMedGoogle Scholar
  55. 55.
    Fokas E, Henzel M, Surber G, et al. Stereotactic radiosurgery and fractionated stereotactic radiotherapy: comparison of efficacy and toxicity in 260 patients with brain metastases. J Neurooncol. 2012;109(1):91–8.CrossRefPubMedGoogle Scholar
  56. 56.
    Demaria S, Coleman CN, Formenti SC. Radiotherapy: changing the game in immunotherapy. Trends Cancer. 2016;2(6):286–94.CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Grimaldi AM, Simeone E, Giannarelli D, et al. Abscopal effects of radiotherapy on advanced melanoma patients who progressed after ipilimumab immunotherapy. Oncoimmunology. 2014;3:e28780.CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Schaue D, Ratikan JA, Iwamoto KS, et al. Maximizing tumor immunity with fractionated radiation. Int J Radiat Oncol Biol Phys. 2012;83(4):1306–10.CrossRefPubMedGoogle Scholar
  59. 59.
    Dewan MZ, Galloway AE, Kawashima N, et al. Fractionated but not single-dose radiotherapy induces an immune-mediated abscopal effect when combined with anti-CTLA-4 antibody. Clin Cancer Res. 2009;15(17):5379–88.CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    Tsao MN, Rades D, Wirth A, 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.CrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    Knisely JP, Yu JB, Flanigan J, et al. Radiosurgery for melanoma brain metastases in the ipilimumab era and the possibility of longer survival. J Neurosurg. 2012;117(2):227–33.CrossRefPubMedPubMedCentralGoogle Scholar
  62. 62.
    Rauch PJ, Park HS, Knisely JP, et al. Delayed radiation-induced vasculitic leukoencephalopathy. Int J Radiat Oncol Biol Phys. 2012;83(1):369–75.CrossRefPubMedGoogle Scholar
  63. 63.
    Cohen JV, Kluger HM. Systemic immunotherapy for the treatment of brain metastases. Front Oncol. 2016;6:49.CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Colaco RJ, Martin P, Kluger HM, et al. Does immunotherapy increase the rate of radiation necrosis after radiosurgical treatment of brain metastases? J Neurosurg. 2016;125(1):17–23.CrossRefPubMedGoogle Scholar
  65. 65.
    Kim JM, Miller JA, Kotecha R, et al. The risk of radiation necrosis following stereotactic radiosurgery with concurrent systemic therapies. J Neurooncol. 2017;133(2):357–68. Scholar
  66. 66.
    Long GV, Atkinson V, Lo S, et al. Combination nivolumab and ipilimumab or nivolumab alone in melanoma brain metastases: a multicentre randomised phase 2 study. Lancet Oncol. 2018;19(5):672–81.CrossRefPubMedGoogle Scholar
  67. 67.
    Magnuson WJ, Yeung JT, Guillod PD, et al. Impact of deferring radiation therapy in patients with epidermal growth factor receptor-mutant non-small cell lung cancer who develop brain metastases. Int J Radiat Oncol Biol Phys. 2016;95(2):673–9.CrossRefPubMedGoogle Scholar
  68. 68.
    Yomo S, Hayashi M. Is stereotactic radiosurgery a rational treatment option for brain metastases from small cell lung cancer? A retrospective analysis of 70 consecutive patients. BMC Cancer. 2015;15:95.CrossRefPubMedPubMedCentralGoogle Scholar
  69. 69.
    Doyle DM, Einhorn LH. Delayed effects of whole brain radiotherapy in germ cell tumor patients with central nervous system metastases. Int J Radiat Oncol Biol Phys. 2008;70(5):1361–4.CrossRefPubMedGoogle Scholar
  70. 70.
    Oechsle K, Bokemeyer C. Treatment of brain metastases from germ cell tumors. Hematol Oncol Clin North Am. 2011;25(3):605–13, ix.CrossRefPubMedGoogle Scholar
  71. 71.
    Gilligan T. Decision making in a data-poor environment: management of brain metastases from testicular and extragonadal germ cell tumors. J Clin Oncol. 2016;34(4):303–6.CrossRefPubMedGoogle Scholar
  72. 72.
    Feldman DR, Lorch A, Kramar A, et al. Brain metastases in patients with germ cell tumors: prognostic factors and treatment options--an analysis from the global germ cell cancer group. J Clin Oncol. 2016;34(4):345–51.CrossRefPubMedGoogle Scholar
  73. 73.
    Motzer RJ, Bosl GJ. Hemorrhage: a complication of metastatic testicular choriocarcinoma. Urology. 1987;30(2):119–22.CrossRefPubMedGoogle Scholar
  74. 74.
    Huang TY, Arita N, Hayakawa T, et al. ACNU, MTX and 5-FU penetration of rat brain tissue and tumors. J Neurooncol. 1999;45(1):9–17.CrossRefPubMedGoogle Scholar
  75. 75.
    Bertke MH, Burton EC, Shaughnessy JN. Stereotactic radiosurgery as part of multimodal treatment in a bulky leptomeningeal recurrence of breast cancer. Cureus. 2016;8(3):e523.PubMedPubMedCentralGoogle Scholar
  76. 76.
    Shiau CY, Sneed PK, Shu HK, et al. Radiosurgery for brain metastases: relationship of dose and pattern of enhancement to local control. Int J Radiat Oncol Biol Phys. 1997;37(2):375–83.CrossRefPubMedGoogle Scholar
  77. 77.
    Kano H, Iyer A, Kondziolka D, et al. Outcome predictors of Gamma Knife radiosurgery for renal cell carcinoma metastases. Neurosurgery. 2011;69(6):1232–9.CrossRefPubMedGoogle Scholar
  78. 78.
    Mathieu D, Kondziolka D, Cooper PB, et al. Gamma knife radiosurgery in the management of malignant melanoma brain metastases. Neurosurgery. 2007;60(3):471–81. discussion 81–2CrossRefPubMedGoogle Scholar
  79. 79.
    Garsa AA, Badiyan SN, DeWees T, et al. Predictors of individual tumor local control after stereotactic radiosurgery for non-small cell lung cancer brain metastases. Int J Radiat Oncol Biol Phys. 2014;90(2):407–13.CrossRefPubMedGoogle Scholar
  80. 80.
    Sheline GE, Wara WM, Smith V. Therapeutic irradiation and brain injury. Int J Radiat Oncol Biol Phys. 1980;6(9):1215–28.CrossRefPubMedGoogle Scholar
  81. 81.
    Minniti G, Clarke E, Lanzetta G, et al. Stereotactic radiosurgery for brain metastases: analysis of outcome and risk of brain radionecrosis. Radiat Oncol. 2011;6:48.CrossRefPubMedPubMedCentralGoogle Scholar
  82. 82.
    Walker AJ, Ruzevick J, Malayeri AA, et al. Postradiation imaging changes in the CNS: how can we differentiate between treatment effect and disease progression? Future Oncol. 2014;10(7):1277–97.CrossRefPubMedPubMedCentralGoogle Scholar
  83. 83.
    Gonzalez J, Kumar AJ, Conrad CA, et al. Effect of bevacizumab on radiation necrosis of the brain. Int J Radiat Oncol Biol Phys. 2007;67(2):323–6.CrossRefPubMedGoogle Scholar
  84. 84.
    Chaunzwa TL, Deng D, Leuthardt EC, et al. Laser thermal ablation for metastases failing radiosurgery: a multicentered retrospective study. Neurosurgery. 2018;82(1):56–63.CrossRefPubMedGoogle Scholar
  85. 85.
    Sharma M, Balasubramanian S, Silva D, et al. Laser interstitial thermal therapy in the management of brain metastasis and radiation necrosis after radiosurgery: an overview. Expert Rev Neurother. 2016;16(2):223–32.CrossRefPubMedGoogle Scholar
  86. 86.
    Danesh-Meyer HV. Radiation-induced optic neuropathy. J Clin Neurosci. 2008;15(2):95–100.CrossRefPubMedGoogle Scholar
  87. 87.
    Leavitt JA, Stafford SL, Link MJ, et al. Long-term evaluation of radiation-induced optic neuropathy after single-fraction stereotactic radiosurgery. Int J Radiat Oncol Biol Phys. 2013;87(3):524–7.CrossRefPubMedGoogle Scholar
  88. 88.
    Mayo C, Martel MK, Marks LB, et al. Radiation dose-volume effects of optic nerves and chiasm. Int J Radiat Oncol Biol Phys. 2010;76(3 Suppl):S28–35.CrossRefPubMedGoogle Scholar
  89. 89.
    Kano H, Kondziolka D, Khan A, et al. Predictors of hearing preservation after stereotactic radiosurgery for acoustic neuroma. J Neurosurg. 2009;111(4):863–73.CrossRefPubMedGoogle Scholar
  90. 90.
    Benedict SH, Yenice KM, Followill D, et al. Stereotactic body radiation therapy: the report of AAPM Task Group 101. Med Phys. 2010;37(8):4078–101.CrossRefPubMedGoogle Scholar
  91. 91.
    Gondi V, Tome WA, Mehta MP. Why avoid the hippocampus? A comprehensive review. Radiother Oncol. 2010;97(3):370–6.CrossRefPubMedPubMedCentralGoogle Scholar
  92. 92.
    Patel TR, McHugh BJ, Bi WL, et al. A comprehensive review of MR imaging changes following radiosurgery to 500 brain metastases. AJNR Am J Neuroradiol. 2011;32(10):1885–92.CrossRefPubMedGoogle Scholar
  93. 93.
    Kano H, Kondziolka D, Lobato-Polo J, et al. T1/T2 matching to differentiate tumor growth from radiation effects after stereotactic radiosurgery. Neurosurgery. 2010;66(3):486–91; discussion 91–2.CrossRefPubMedGoogle Scholar
  94. 94.
    Weybright P, Sundgren PC, Maly P, et al. Differentiation between brain tumor recurrence and radiation injury using MR spectroscopy. AJR Am J Roentgenol. 2005;185(6):1471–6.CrossRefPubMedGoogle Scholar
  95. 95.
    Momose T, Nariai T, Kawabe T, et al. Clinical benefit of 11C methionine PET imaging as a planning modality for radiosurgery of previously irradiated recurrent brain metastases. Clin Nucl Med. 2014;39(11):939–43.CrossRefPubMedGoogle Scholar
  96. 96.
    Kwon KY, Kong DS, Lee JI, et al. Outcome of repeated radiosurgery for recurrent metastatic brain tumors. Clin Neurol Neurosurg. 2007;109(2):132–7.CrossRefPubMedGoogle Scholar
  97. 97.
    Koiso T, Yamamoto M, Kawabe T, et al. Follow-up results of brain metastasis patients undergoing repeat Gamma Knife radiosurgery. J Neurosurg. 2016;125(Suppl 1):2–10.PubMedGoogle Scholar
  98. 98.
    Guo S, Balagamwala EH, Reddy C, et al. Clinical and radiographic outcomes from repeat whole-brain radiation therapy for brain metastases in the age of stereotactic radiosurgery. Am J Clin Oncol. 2016;39(3):288–93.CrossRefPubMedGoogle Scholar
  99. 99.
    Nieder C, Norum J, Dalhaug A, et al. Radiotherapy versus best supportive care in patients with brain metastases and adverse prognostic factors. Clin Exp Metastasis. 2013;30(6):723–9.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Isabella Zhang
    • 1
  • Masaaki Yamamoto
    • 2
  • Jonathan P. S. Knisely
    • 3
    Email author
  1. 1.Department of Radiation MedicineNorthwell HealthLake SuccessUSA
  2. 2.Department of NeurosurgeryKatsuta Hospital Mito GammaHouseHitachi-nakaJapan
  3. 3.Department of Radiation Oncology, Weill Cornell School of MedicineNew York Presbyterian HospitalNew YorkUSA

Personalised recommendations