BRAF V600E mutation and BRAF kinase inhibitors in conjunction with stereotactic radiosurgery for intracranial melanoma metastases
Autor: | Or Cohen-Inbar, Adam C. Mueller, Jason P. Sheehan, Han-Hsun Shih, Zhiyuan Xu, David Schlesinger, Cheng-Chia Lee, Arjun Ramesh |
---|---|
Rok vydání: | 2017 |
Předmět: |
Adult
Male Proto-Oncogene Proteins B-raf medicine.medical_treatment Antineoplastic Agents Radiosurgery Young Adult 03 medical and health sciences 0302 clinical medicine Biomarkers Tumor medicine Humans Adverse effect Melanoma neoplasms Aged Retrospective Studies Aged 80 and over Brain Neoplasms Kinase business.industry Retrospective cohort study Chemoradiotherapy General Medicine Intracranial Melanoma Middle Aged Prognosis medicine.disease Survival Analysis digestive system diseases BRAF V600E 030220 oncology & carcinogenesis Mutation (genetic algorithm) Cancer research Female business 030217 neurology & neurosurgery |
Zdroj: | Journal of Neurosurgery. 126:726-734 |
ISSN: | 1933-0693 0022-3085 |
Popis: | 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. |
Databáze: | OpenAIRE |
Externí odkaz: |