title: BRAF V600E mutation and BRAF kinase inhibitors in conjunction with stereotactic radiosurgery for intracranial melanoma metastases.
abstract: OBJECTIVE Recent advancements in molecular biology have identified the BRAF mutation as a common mutation in melanoma. The wide use of BRAF kinase inhibitor ( BRAFi) in patients with metastatic melanoma has been established. The objective of this study was to examine the impact of BRAF mutation status and use of BRAFi in conjunction with stereotactic radiosurgery (SRS). METHODS This was a single-center retrospective study. Patient's charts and electronic records were reviewed for date of diagnosis of primary malignancy, BRAF mutation status, chemotherapies used, date of the diagnosis of CNS metastases, date of SRS, survival, local tumor control after SRS, and adverse events. Patients were divided into 3 groups: Group A, those with mutant BRAF without BRAFi treatment (13 patients); Group B, those with mutant BRAF with BRAFi treatment (17 patients); and Group C, those with wild-type BRAF (35 patients). Within a cohort of 65 patients with the known BRAF mutation status and treated with SRS between 2010 and 2014, 436 individual brain metastases (BMs) were identified. Kaplan-Meier methodology was then used to compare survival based on each binary parameter. RESULTS Median survival times after the diagnosis of melanoma BM and after SRS were favorable in patients with a BRAF mutation and treated with SRS in conjunction with BRAFi (Group B) compared with the patients with wild-type BRAF (Group C, 23 vs 8 months and 13 vs 5 months, respectively; p < 0.01, log-rank test). SRS provided a local tumor control rate of 89.4% in the entire cohort of patients. Furthermore, the local control rate was improved in the patients treated with SRS in conjunction with BRAFi (Group B) compared with patients with wild-type (Group C) or with BRAF mutation but no BRAFi (Group A) as an adjunct treatment for BMs. CONCLUSIONS BRAF mutation status appears to play an important role as a potent prognostic factor in patients harboring melanoma BM. BRAFi in conjunction with SRS may benefit this group of patients in terms of BM survival and SRS with an acceptable safety profile.
authors.affiliation: Departments of 1 Neurological Surgery and.
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Departments of 1 Neurological Surgery and.|Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital.|School of Medicine, National Yang-Ming University, Taipei; and.
authors.forename: Cheng-Chia
authors.initials: CC
authors.lastname: Lee
authors.affiliation: Departments of 1 Neurological Surgery and.
authors.forename: Arjun
authors.initials: A
authors.lastname: Ramesh
authors.affiliation: Radiation Oncology, University of Virginia, Charlottesville, Virginia.
authors.forename: Adam C
authors.initials: AC
authors.lastname: Mueller
authors.affiliation: Departments of 1 Neurological Surgery and.|Radiation Oncology, University of Virginia, Charlottesville, Virginia.
authors.forename: David
authors.initials: D
authors.lastname: Schlesinger
authors.affiliation: Departments of 1 Neurological Surgery and.
authors.forename: Or
authors.initials: O
authors.lastname: Cohen-Inbar
authors.affiliation: Taichung Veterans General Hospital, Taichung, Taiwan, Republic of China.
authors.forename: Han-Hsun
authors.initials: HH
authors.lastname: Shih
authors.affiliation: Departments of 1 Neurological Surgery and.|Radiation Oncology, University of Virginia, Charlottesville, Virginia.
authors.forename: Jason P
authors.initials: JP
authors.lastname: Sheehan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics; D001932:Brain Neoplasms / Q000201:enzymology / Q000235:genetics / Q000556:secondary* / Q000628:therapy*; D059248:Chemoradiotherapy; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000201:enzymology / Q000235:genetics / Q000473:pathology* / Q000628:therapy*; D008875:Middle Aged; D011379:Prognosis; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors* / Q000235:genetics; D016634:Radiosurgery; D012189:Retrospective Studies; D016019:Survival Analysis; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf
keywords: ARE = adverse radiation effect; BM = brain metastasis; BRAF kinase inhibitor; BRAF mutation; BRAFi = BRAF kinase inhibitor; DS-GPA = disease-specific graded prognostic assessment; GKRS = Gamma Knife radiosurgery; KPS = Karnofsky Performance Scale; MEK = mitogen-activated protein kinase; OS = overall survival; SRS = stereotactic radiosurgery; WBRT = whole brain radiation therapy; brain metastases; melanoma; oncology; stereotactic radiosurgery