title: Impact on overall survival of the combination of BRAF inhibitors and stereotactic radiosurgery in patients with melanoma brain metastases.
abstract: The aim of this study was to evaluate the impact of BRAF inhibitors on survival outcomes in patients receiving stereotactic radiosurgery (SRS) for melanoma brain metastases. We prospectively collected treatment parameters and outcomes for 80 patients with melanoma brain metastases who underwent SRS. Thirty-five patients harbored the BRAF mutation (BRAF-M) and 45 patients did not (BRAF-WT). Univariate and multivariate analyses were performed to identify predictors of overall survival. The median overall survival from first SRS procedure was 6.7, 11.2 months if treated with a BRAF inhibitor and 4.5 months for BRAF-WT. Actuarial survival rates for BRAF-M patients on an inhibitor were 54 % at 6 months and 41 % at 12 months from the time of SRS. In contrast, BRAF-WT had overall survival rates of 28 % at 6 months and 19 % at 12 months. Overall survival was extended for patients on a BRAF inhibitor at or after the first SRS. The median time to intracranial progression was 3.9 months on a BRAF inhibitor and 1.7 months without. The local control rate for all treated tumors was 92.5 %, with no difference based on BRAF status. Patients with higher KPS, fewer treated intracranial metastases, controlled systemic disease, RPA Class 1 and BRAF-M patients had extended overall survival. Overall, patients with BRAF-M treated with both SRS and BRAF inhibitors, at or after SRS, have increased overall survival from the time of SRS. As patients live longer as a result of more effective systemic and local therapies, close surveillance and early management of intracranial disease with SRS will become increasingly important.
authors: Departments of Neurosurgery, Laura and Isaac Perlmutter Cancer Center, NYU Langone Medical Center, New York University, Suite 8R, 530 First Avenue, New York, NY, 10016, USA.
authors: Amparo
authors: A
authors: Wolf
authors: Departments of Neurosurgery, Laura and Isaac Perlmutter Cancer Center, NYU Langone Medical Center, New York University, Suite 8R, 530 First Avenue, New York, NY, 10016, USA.
authors: Sayyad
authors: S
authors: Zia
authors: Departments of Neurosurgery, Laura and Isaac Perlmutter Cancer Center, NYU Langone Medical Center, New York University, Suite 8R, 530 First Avenue, New York, NY, 10016, USA.
authors: Rashika
authors: R
authors: Verma
authors: Medical Oncology, Laura and Isaac Perlmutter Cancer Center, NYU Langone Medical Center, New York University, New York, NY, USA.
authors: Anna
authors: A
authors: Pavlick
authors: Medical Oncology, Laura and Isaac Perlmutter Cancer Center, NYU Langone Medical Center, New York University, New York, NY, USA.
authors: Melissa
authors: M
authors: Wilson
authors: Departments of Neurosurgery, Laura and Isaac Perlmutter Cancer Center, NYU Langone Medical Center, New York University, Suite 8R, 530 First Avenue, New York, NY, 10016, USA.
authors: John G
authors: JG
authors: Golfinos
authors: Radiation Oncology, Laura and Isaac Perlmutter Cancer Center, NYU Langone Medical Center, New York University, New York, NY, USA.
authors: Joshua S
authors: JS
authors: Silverman
authors: Departments of Neurosurgery, Laura and Isaac Perlmutter Cancer Center, NYU Langone Medical Center, New York University, Suite 8R, 530 First Avenue, New York, NY, 10016, USA. douglas.kondziolka@nyumc.org.
authors: Douglas
authors: D
authors: Kondziolka
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000401:mortality* / Q000556:secondary / Q000628:therapy; D003131:Combined Modality Therapy; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008545:Melanoma / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors* / Q000235:genetics; D016634:Radiosurgery / Q000401:mortality*; D015996:Survival Rate
chemical_list: C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf
keywords: BRAF inhibitors; BRAF mutation; Brain metastasis; Metastatic melanoma; Stereotactic radiosurgery