Melanoma brain metastasis: the impact of stereotactic radiosurgery, BRAF mutational status, and targeted and/or immune-based therapies on treatment outcome

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The goal of this study was to investigate the impact of stereotactic radiosurgery (SRS), BRAF status, and targeted and immune-based therapies on the recurrence patterns and factors associated with overall survival (OS) among patients with melanoma brain metastasis (MBM).


A total of 366 patients were treated for 1336 MBMs; a lesion-based analysis was performed on 793 SRS lesions. The BRAF status was available for 78 patients: 35 had BRAFmut and 43 had BRAF wild-type (BRAF-WT) lesions. The Kaplan-Meier method evaluated unadjusted OS; cumulative incidence analysis determined the incidences of local failure (LF), distant failure, and radiation necrosis (RN), with death as a competing risk.


The 12-month OS was 24% (95% CI 20%–29%). On multivariate analysis, younger age, lack of extracranial metastases, better Karnofsky Performance Status score, and fewer MBMs, as well as treatment with BRAF inhibitors (BRAFi), anti–PD-1/CTLA-4 therapy, or cytokine therapy were significantly associated with OS. For patients who underwent SRS, the 12-month LF rate was lower among those with BRAFmut lesions (6%, 95% CI 2%–11%) compared with those with BRAF-WT lesions (22%, 95% CI 13%–32%; p < 0.01). The 12-month LF rates among lesions treated with BRAFi and PD-1/CTLA-4 agents were 1% (95% CI 1%–4%) and 7% (95% CI 1%–13%), respectively. On multivariate analysis, BRAF inhibition within 30 days of SRS was protective against LF (HR 0.08, 95% CI 0.01–0.55; p = 0.01). The 12-month rates of RN were low among lesions treated with BRAFi (0%, 95% CI 0%–0%), PD-1/CTLA-4 inhibitors (2%, 95% CI 1%–5%), and cytokine therapies (6%, 95% CI 1%–13%).


Prognostic schema should incorporate BRAFi or immunotherapy status and use of targeted therapies. Treatment with a BRAF inhibitor within 4 weeks of SRS improves local control without an increased risk of RN.

ABBREVIATIONS BRAFi = BRAF inhibitors; DF = distant failure; GPA = graded prognostic assessment; KPS = Karnofsky Performance Status; LF = local failure; MBM = melanoma brain metastasis; OS = overall survival; RN = radiation necrosis; SRS = stereotactic radiosurgery; WBRT = whole-brain radiation therapy; WT = wild type.

Article Information

Correspondence Manmeet S. Ahluwalia, Department of Hematology/Oncology, Taussig Cancer Institute, Rose Ella Burkhardt Brain Tumor and Neuro-Oncology Center, Cleveland Clinic Main Campus, Mail Code S73, 9500 Euclid Ave., Cleveland, OH 44195. email:

INCLUDE WHEN CITING Published online August 11, 2017; DOI: 10.3171/2017.1.JNS162797.

Disclosures Dr. Suh received consulting payment from Varian Medical Systems; had travel and lodging paid for by Elekta; and received speaking fees from Philips. Dr. Ahluwalia received a consulting payment and grant from Elekta; grant support from Boehringer Ingelheim, Bristol-Myers Squibb, Novartis, Spectrum Pharmaceuticals, Tracon Pharmaceuticals, and Novocure; and is a consultant for Merck, Genentech/Roche, Incyte, Caris Lifesciences, Monteris Medical, MRI Interventions Inc., Bristol-Myers Squibb, Astrazeneca, and Abbvie. He received support of non–study-related clinical or research efforts that he oversaw from Novartis, Novocure, and Bristol-Myers Squibb. Dr. Kotecha is on the medical advisory board of Varian Medical Systems.

© AANS, except where prohibited by US copyright law.



  • View in gallery

    Graphs showing estimates of (A) cumulative incidence of intracranial progression; (B) cumulative incidence of distant intracranial progression; and OS from the time of diagnosis of brain metastasis for patients with melanoma, stratified by (C) BRAF mutational status and (D) use of BRAFi. Values on the x axis denote the number of months postdiagnosis. inhib. = inhibitor; unt. = untested.

  • View in gallery

    Graphs showing cumulative incidences of LF for MBM undergoing SRS, stratified by (A) BRAF mutational status, (B) treatment with BRAFi, and (C) treatment with PD-1/CTLA-4 inhibitors.

  • View in gallery

    Graphs showing cumulative incidences of RN for MBM treated with SRS, stratified by (A) BRAF status and (B) treatment with BRAFi and PD-1/CTLA-4 inhibitors.


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