Neurosurgical Management of Single Brain Metastases

  • Sherise D. FergusonEmail author
  • Richard G. Everson
  • Kathryn M. Wagner
  • Debra Nana Yeboa
  • Ian E. McCutcheon
  • Raymond Sawaya


Brain metastasis is the most common type of intracranial tumor. The contemporary management of brain metastasis is a challenging issue and carries a poor prognosis, as traditionally it occurs in the setting of advanced systemic disease. Yet, as advances in systemic cancer treatment cause an increasing number of patients to develop brain metastases in the setting of limited systemic disease, the means for effectively treating them becomes more important. Surgery and stereotactic radiosurgery provide excellent therapeutic options for many such patients with single brain metastases. Concepts in managing brain metastasis are advancing, particularly with the judicious use of available techniques being applied as multimodal therapy tailored to the individual patient, which has now become the standard of care.


Brain metastasis Brain metastases Gross-total resection Stereotactic radiosurgery Whole-brain radiation therapy 



We thank David M. Wildrick, PhD, for editorial assistance.

Conflict of Interest

 The authors declare that they have no conflicts of interest.


  1. 1.
    Sul J, Posner JB. Brain metastases: epidemiology and pathophysiology. Cancer Treat Res. 2007;136:1–21.Google Scholar
  2. 2.
    Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2008. CA Cancer J Clin. 2008;58(2):71–96.Google Scholar
  3. 3.
    Fox BD, Cheung VJ, Patel AJ, et al. Epidemiology of metastatic brain tumors. Neurosurg Clin N Am. 2011;22(1):1–6, v.Google Scholar
  4. 4.
    Nayak L, Lee EQ, Wen PY. Epidemiology of brain metastases. Curr Oncol Rep. 2012;14(1):48–54.Google Scholar
  5. 5.
    Brastianos PK, Curry WT, Oh KS. Clinical discussion and review of the management of brain metastases. J Natl Compr Cancer Netw. 2013;11(9):1153–64.Google Scholar
  6. 6.
    Eichler AF, Chung E, Kodack DP, et al. The biology of brain metastases-translation to new therapies. Nat Rev Clin Oncol. 2011;8(6):344–56.Google Scholar
  7. 7.
    Kibbi N, Kluger H. The treatment of melanoma brain metastases. Curr Oncol Rep. 2016;18(12):73.Google Scholar
  8. 8.
    Delattre JY, Krol G, Thaler HT, et al. Distribution of brain metastases. Arch Neurol. 1988;45(7):741–4.Google Scholar
  9. 9.
    Gavrilovic IT, Posner JB. Brain metastases: epidemiology and pathophysiology. J Neurooncol. 2005;75(1):5–14.Google Scholar
  10. 10.
    Rostami R, Mittal S, Rostami P, et al. Brain metastasis in breast cancer: a comprehensive literature review. J Neurooncol. 2016;127(3):407–14.Google Scholar
  11. 11.
    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.Google Scholar
  12. 12.
    Vecht CJ, Haaxma-Reiche H, Noordijk EM, et al. Treatment of single brain metastasis: radiotherapy alone or combined with neurosurgery. Ann Neurol. 1993;33(6):583–90.Google Scholar
  13. 13.
    Schödel P, Schebesch KM, Brawanski A, et al. Surgical resection of brain metastases-impact on neurological outcome. Int J Mol Sci. 2013;14(5):8708–18.Google Scholar
  14. 14.
    Forsyth PA, Weaver S, Fulton D, et al. Prophylactic anticonvulsants in patients with brain tumour. Can J Neurol Sci. 2003;30(2):106–12.Google Scholar
  15. 15.
    Franceschetti S, Binelli S, Casazza M, et al. Influence of surgery and antiepileptic drugs on seizures symptomatic of cerebral tumours. Acta Neurochir. 1990;103(1–2):47–51.Google Scholar
  16. 16.
    Glantz MJ, Cole BF, Friedberg MH, et al. A randomized, blinded, placebo-controlled trial of divalproex sodium prophylaxis in adults with newly diagnosed brain tumors. Neurology. 1996;46(4):985–91.Google Scholar
  17. 17.
    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. 2010;96(1):103–14.Google Scholar
  18. 18.
    Tendulkar RD, Liu SW, Barnett GH, et al. RPA classification has prognostic significance for surgically resected single brain metastasis. Int J Radiat Oncol Biol Phys. 2006;66(3):810–7.Google Scholar
  19. 19.
    Lee CH, Kim DG, Kim JW, et al. The role of surgical resection in the management of brain metastasis: a 17-year longitudinal study. Acta Neurochir. 2013;155(3):389–97.Google Scholar
  20. 20.
    Pessina F, Navarria P, Cozzi L, et al. Role of surgical resection in patients with single large brain metastases: feasibility, morbidity, and local control evaluation. World Neurosurg. 2016;94:6–12.Google Scholar
  21. 21.
    Paek SH, Audu PB, Sperling MR, et al. Reevaluation of surgery for the treatment of brain metastases: review of 208 patients with single or multiple brain metastases treated at one institution with modern neurosurgical techniques. Neurosurgery. 2005;56(5):1021–34.Google Scholar
  22. 22.
    Arita H, Narita Y, Miyakita Y, et al. Risk factors for early death after surgery in patients with brain metastases: reevaluation of the indications for and role of surgery. J Neurooncol. 2014;116(1):145–52.Google Scholar
  23. 23.
    Obermueller T, Schaeffner M, Gerhardt J, et al. Risks of postoperative paresis in motor eloquently and non-eloquently located brain metastases. BMC Cancer. 2014;14:21.Google Scholar
  24. 24.
    Schackert G, Schmiedel K, Lindner C, et al. Surgery of recurrent brain metastases: retrospective analysis of 67 patients. Acta Neurochir. 2013;155(10):1823–32.Google Scholar
  25. 25.
    Sperduto CM, Watanabe Y, Mullan J, et al. A validation study of a new prognostic index for patients with brain metastases: the graded prognostic assessment. J Neurosurg. 2008;109(Suppl):87–9.Google Scholar
  26. 26.
    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.Google Scholar
  27. 27.
    Estabrook NC, Lutz ST, Johnson CS, et al. Does graded prognostic assessment outperform recursive partitioning analysis in patients with moderate prognosis brain metastases? CNS Oncol. 2016;5(2):69–76.Google Scholar
  28. 28.
    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.Google Scholar
  29. 29.
    Antoni D, Clavier JB, Pop M, et al. Institutional, retrospective analysis of 777 patients with brain metastases: treatment outcomes and diagnosis-specific prognostic factors. Int J Radiat Oncol Biol Phys. 2013;86(4):630–7.Google Scholar
  30. 30.
    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.Google Scholar
  31. 31.
    Baumert BG, Rutten I, Dehing-Oberije C, et al. A pathology-based substrate for target definition in radiosurgery of brain metastases. Int J Radiat Oncol Biol Phys. 2006;66(1):187–94.Google Scholar
  32. 32.
    Kamp MA, Dibue M, Niemann L, et al. Proof of principle: supramarginal resection of cerebral metastases in eloquent brain areas. Acta Neurochir. 2012;154(11):1981–6.Google Scholar
  33. 33.
    Yoo H, Kim YZ, Nam BH, et al. Reduced local recurrence of a single brain metastasis through microscopic total resection. J Neurosurg. 2009;110(4):730–6.Google Scholar
  34. 34.
    Patel AJ, Suki D, Hatiboglu MA, et al. Impact of surgical methodology on the complication rate and functional outcome of patients with a single brain metastasis. J Neurosurg. 2015;122(5):1132–43.Google Scholar
  35. 35.
    Patel AJ, Suki D, Hatiboglu MA, et al. Factors influencing the risk of local recurrence after resection of a single brain metastasis. J Neurosurg. 2010;113(2):181–9.Google Scholar
  36. 36.
    Ahn JH, Lee SH, Kim S, et al. Risk for leptomeningeal seeding after resection for brain metastases: implication of tumor location with mode of resection. J Neurosurg. 2012;116(5):984–93.Google Scholar
  37. 37.
    Suki D, Abouassi H, Patel AJ, et al. Comparative risk of leptomeningeal disease after resection or stereotactic radiosurgery for solid tumor metastasis to the posterior fossa. J Neurosurg. 2008;108(2):248–57.Google Scholar
  38. 38.
    Siam L, Bleckmann A, Chaung HN, et al. The metastatic infiltration at the metastasis/brain parenchyma-interface is very heterogeneous and has a significant impact on survival in a prospective study. Oncotarget. 2015;6(30):29254–67.Google Scholar
  39. 39.
    Berghoff AS, Rajky O, Winkler F, et al. Invasion patterns in brain metastases of solid cancers. Neuro Oncol. 2013;15(12):1664–72.Google Scholar
  40. 40.
    Kamp MA, Rapp M, Slotty PJ, et al. Incidence of local in-brain progression after supramarginal resection of cerebral metastases. Acta Neurochir. 2015;157(6):905–10; discussion 10-1.Google Scholar
  41. 41.
    Hendrix P, Senger S, Griessenauer CJ, et al. Preoperative navigated transcranial magnetic stimulation in patients with motor eloquent lesions with emphasis on metastasis. Clin Anat. 2016;29(7):925–31.Google Scholar
  42. 42.
    Huberfeld G, Trebuchon A, Capelle L, et al. Preoperative and intraoperative neurophysiological investigations for surgical resections in functional areas. Neurochirurgie. 2017;63(3):142–9.Google Scholar
  43. 43.
    Sollmann N, Wildschuetz N, Kelm A, et al. Associations between clinical outcome and navigated transcranial magnetic stimulation characteristics in patients with motor-eloquent brain lesions: a combined navigated transcranial magnetic stimulation-diffusion tensor imaging fiber tracking approach. J Neurosurg. 2018;128:800–10.Google Scholar
  44. 44.
    Sanmillan JL, Fernandez-Coello A, Fernandez-Conejero I, et al. Functional approach using intraoperative brain mapping and neurophysiological monitoring for the surgical treatment of brain metastases in the central region. J Neurosurg. 2017;126:698–707.Google Scholar
  45. 45.
    Kellogg RG, Munoz LF. Selective excision of cerebral metastases from the precentral gyrus. Surg Neurol Int. 2013;4:66.Google Scholar
  46. 46.
    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.Google Scholar
  47. 47.
    Nieder C, Astner ST, Grosu AL, et al. The role of postoperative radiotherapy after resection of a single brain metastasis. Combined analysis of 643 patients. Strahlenther Onkol. 2007;183(10):576–80.Google Scholar
  48. 48.
    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.Google Scholar
  49. 49.
    Tallet AV, Azria D, Barlesi F, et al. Neurocognitive function impairment after whole brain radiotherapy for brain metastases: actual assessment. Radiat Oncol. 2012;7(1):77.Google Scholar
  50. 50.
    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.Google Scholar
  51. 51.
    Auchter RM, Lamond JP, Alexander E, et al. A multiinstitutional outcome and prognostic factor analysis of radiosurgery for resectable single brain metastasis. Int J Radiat Oncol Biol Phys. 1996;35(1):27–35.Google Scholar
  52. 52.
    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.Google Scholar
  53. 53.
    Ebner D, Rava P, Gorovets D, et al. Stereotactic radiosurgery for large brain metastases. J Clin Neurosci. 2015;22(10):1650–4.Google Scholar
  54. 54.
    Molenaar R, Wiggenraad R, Verbeek-de Kanter A, et al. Relationship between volume, dose and local control in stereotactic radiosurgery of brain metastasis. Br J Neurosurg. 2009;23(2):170–8.Google Scholar
  55. 55.
    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.Google Scholar
  56. 56.
    Selek U, Chang EL, Hassenbusch SJ III, et al. Stereotactic radiosurgical treatment in 103 patients for 153 cerebral melanoma metastases. Int J Radiat Oncol Biol Phys. 2004;59(4):1097–106.Google Scholar
  57. 57.
    Blonigen BJ, Steinmetz RD, Levin L, et al. Irradiated volume as a predictor of brain radionecrosis after linear accelerator stereotactic radiosurgery. Int J Radiat Oncol Biol Phys. 2010;77(4):996–1001.Google Scholar
  58. 58.
    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.Google Scholar
  59. 59.
    Sneed PK, Mendez J, Vemer-van den Hoek JG, et al. Adverse radiation effect after stereotactic radiosurgery for brain metastases: incidence, time course, and risk factors. J Neurosurg. 2015;123(2):373–86.Google Scholar
  60. 60.
    Hasegawa T, Kato T, Yamamoto T, et al. Multisession gamma knife surgery for large brain metastases. J Neurooncol. 2017;131(3):517–24.Google Scholar
  61. 61.
    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.Google Scholar
  62. 62.
    Yomo S, Hayashi M, Nicholson C. A prospective pilot study of two-session Gamma Knife surgery for large metastatic brain tumors. J Neurooncol. 2012;109(1):159–65.Google Scholar
  63. 63.
    Trifiletti DM, Lee CC, Winardi W, et al. Brainstem metastases treated with stereotactic radiosurgery: safety, efficacy, and dose response. J Neurooncol. 2015;125(2):385–92.Google Scholar
  64. 64.
    Trifiletti DM, Lee CC, Kano H, et al. Stereotactic radiosurgery for brainstem metastases: an international cooperative study to define response and toxicity. Int J Radiat Oncol Biol Phys. 2016;96(2):280–8.Google Scholar
  65. 65.
    Gans JH, Raper DM, Shah AH, et al. The role of radiosurgery to the tumor bed after resection of brain metastases. Neurosurgery. 2013;72(3):317–25; discussion 25–6.Google Scholar
  66. 66.
    Joshi R, Johnson MD, Maitz A, et al. Utility of graded prognostic assessment in evaluation of patients with brainstem metastases treated with radiosurgery. Clin Neurol Neurosurg. 2016;147:30–3.Google Scholar
  67. 67.
    Park CY, Choi HY, Lee SR, et al. Neurological change after gamma knife radiosurgery for brain metastases involving the motor cortex. Brain Tumor Res Treat. 2016;4(2):111–5.Google Scholar
  68. 68.
    Caruso JP, Moosa S, Fezeu F, et al. A cost comparative study of Gamma Knife radiosurgery versus open surgery for intracranial pathology. J Clin Neurosci. 2015;22(1):184–8.Google Scholar
  69. 69.
    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.Google Scholar
  70. 70.
    Chow E, Davis L, Holden L, et al. Prospective assessment of patient-rated symptoms following whole brain radiotherapy for brain metastases. J Pain Symptom Manag. 2005;30(1):18–23.Google Scholar
  71. 71.
    McDuff SG, Taich ZJ, Lawson JD, et al. Neurocognitive assessment following whole brain radiation therapy and radiosurgery for patients with cerebral metastases. J Neurol Neurosurg Psychiatry. 2013;84(12):1384–91.Google Scholar
  72. 72.
    Pulenzas N, Khan L, Tsao M, et al. Fatigue scores in patients with brain metastases receiving whole brain radiotherapy. Support Care Cancer. 2014;22(7):1757–63.Google Scholar
  73. 73.
    Taillibert S, Le Rhun E, Chamberlain MC. Chemotherapy-related neurotoxicity. Curr Neurol Neurosci Rep. 2016;16(9):81.Google Scholar
  74. 74.
    Mathieu D, Kondziolka D, Flickinger JC, et al. Tumor bed radiosurgery after resection of cerebral metastases. Neurosurgery. 2008;62(4):817–23; discussion 23–4.Google Scholar
  75. 75.
    Jagannathan J, Yen CP, Ray DK, et al. Gamma Knife radiosurgery to the surgical cavity following resection of brain metastases. J Neurosurg. 2009;111(3):431–8.Google Scholar
  76. 76.
    Jensen CA, Chan MD, McCoy TP, et al. Cavity-directed radiosurgery as adjuvant therapy after resection of a brain metastasis. J Neurosurg. 2011;114(6):1585–91.Google Scholar
  77. 77.
    Choi CY, Chang SD, Gibbs IC, et al. Stereotactic radiosurgery of the postoperative resection cavity for brain metastases: prospective evaluation of target margin on tumor control. Int J Radiat Oncol Biol Phys. 2012;84(2):336–42.Google Scholar
  78. 78.
    Robbins JR, Ryu S, Kalkanis S, et al. Radiosurgery to the surgical cavity as adjuvant therapy for resected brain metastasis. Neurosurgery. 2012;71(5):937–43.Google Scholar
  79. 79.
    Atalar B, Modlin LA, Choi CY, et al. Risk of leptomeningeal disease in patients treated with stereotactic radiosurgery targeting the postoperative resection cavity for brain metastases. Int J Radiat Oncol Biol Phys. 2013;87(4):713–8.Google Scholar
  80. 80.
    Brennan C, Yang TJ, Hilden P, et al. A phase 2 trial of stereotactic radiosurgery boost after surgical resection for brain metastases. Int J Radiat Oncol Biol Phys. 2014;88(1):130–6.Google Scholar
  81. 81.
    Ojerholm E, Lee JY, Thawani JP, et al. Stereotactic radiosurgery to the resection bed for intracranial metastases and risk of leptomeningeal carcinomatosis. J Neurosurg. 2014;121(Suppl):75–83.Google Scholar
  82. 82.
    Iorio-Morin C, Masson-Cote L, Ezahr Y, et al. Early Gamma Knife stereotactic radiosurgery to the tumor bed of resected brain metastasis for improved local control. J Neurosurg. 2014;121(Suppl):69–74.Google Scholar
  83. 83.
    Mahajan A, Ahmed S, McAleer MF, et al. Post-operative stereotactic radiosurgery versus observation for completely resected brain metastases: a single-Centre, randomised, controlled, phase 3 trial. Lancet Oncol. 2017;18(8):1040–8.Google Scholar
  84. 84.
    Brown PD, Ballman KV, Cerhan JH, et al. Postoperative stereotactic radiosurgery compared with whole brain radiotherapy for resected metastatic brain disease (NCCTG N107C/CEC.3): a multicentre, randomised, controlled, phase 3 trial. Lancet Oncol. 2017;18(8):1049–60.Google Scholar
  85. 85.
    Asher AL, Burri SH, Wiggins WF, et al. A new treatment paradigm: neoadjuvant radiosurgery before surgical resection of brain metastases with analysis of local tumor recurrence. Int J Radiat Oncol Biol Phys. 2014;88(4):899–906.Google Scholar
  86. 86.
    Patel KR, Burri SH, Asher AL, et al. Comparing preoperative with postoperative stereotactic radiosurgery for resectable brain metastases: a multi-institutional analysis. Neurosurgery. 2016;79(2):279–85.Google Scholar
  87. 87.
    Patel KR, Burri SH, Boselli D, et al. Comparing pre-operative stereotactic radiosurgery (SRS) to post-operative whole brain radiation therapy (WBRT) for resectable brain metastases: a multi-institutional analysis. J Neurooncol. 2017;131(3):611–8.Google Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Sherise D. Ferguson
    • 1
    Email author
  • Richard G. Everson
    • 2
  • Kathryn M. Wagner
    • 3
  • Debra Nana Yeboa
    • 4
  • Ian E. McCutcheon
    • 1
  • Raymond Sawaya
    • 1
  1. 1.Department of NeurosurgeryThe University of Texas MD Anderson Cancer CenterHoustonUSA
  2. 2.Department of NeurosurgeryUCLA Medical CenterLos AngelesUSA
  3. 3.Department of NeurosurgeryBaylor College of MedicineHoustonUSA
  4. 4.Department of Radiation OncologyThe University of Texas MD Anderson Cancer CenterHoustonUSA

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