AUTHOR=Gallaher Ian S. , Watanabe Yoichi , DeFor Todd E. , Dusenbery Kathryn E. , Lee Chung K. , Hunt Matthew A. , Lin Hong-Yiou , Yuan Jianling 

TITLE=BRAF Mutation Is Associated with Improved Local Control of Melanoma Brain Metastases Treated with Gamma Knife Radiosurgery

JOURNAL=Frontiers in Oncology

VOLUME=6

YEAR=2016

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2016.00107

DOI=10.3389/fonc.2016.00107

ISSN=2234-943X

ABSTRACT=<sec id="ST1"><title>Objectives</title><p>Evidence has implicated a possible role of tumor mutation status on local control (LC) with radiotherapy. <italic>BRAF</italic> is a proto-oncogene that is mutated in approximately 50% of patients with melanoma. We sought to analyze the influence of <italic>BRAF</italic> status on LC of melanoma brain metastases (MBM) following Gamma Knife radiosurgery (GK).</p></sec><sec id="ST2"><title>Methods</title><p>Among 125 patients treated with GK for MBM at our institution between 2006 and 2015, we identified 19 patients with 69 evaluable metastases whose <italic>BRAF</italic> mutation status was known and follow-up imaging was available. LC of individual metastases was compared based on <italic>BRAF</italic> mutation status using statistical techniques to control for measurements of multiple metastases within each patient. CNS progression was defined as either local failure or development of new lesions.</p></sec><sec id="ST3"><title>Results</title><p>Of the 69 metastases, <italic>BRAF</italic> was mutated in 30 and wild-type in 39. With a median follow-up of 30 months for all patients and a median follow-up of 5.5 months for treated lesions, 1-year LC was significantly better among metastases with mutated vs. wild-type <italic>BRAF</italic> (69 vs. 34%, RR = 0.3, 95% CI = 0.1–0.7, <italic>p</italic> = 0.01). <italic>BRAF</italic> mutation was found to be a significant predictor of LC after stereotactic radiosurgery (SRS) in both univariate [RR = 0.3 (95% CI 0.1–0.7, <italic>p</italic> = 0.01)] and multivariate [RR = 0.2 (95% CI 0.1–0.7, <italic>p</italic> = 0.01)] analyses. There was also a trend toward improved CNS progression free survival (PFS) at 1 year (26 vs. 0%, <italic>p</italic> = 0.06), favoring <italic>BRAF</italic>-mutated patients.</p></sec><sec id="ST4"><title>Conclusion</title><p>In this retrospective study, MBM treated with GK had significantly improved LC for patients with <italic>BRAF</italic> mutation vs. wild-type. Our data suggest that <italic>BRAF</italic> mutation may sensitize tumors to radiosurgery, and that <italic>BRAF</italic> wild-type tumors may be more radioresistant.</p></sec>