title: Vemurafenib and radiation therapy in melanoma brain metastases.
abstract: Brain metastases in malignant melanoma carries a poor prognosis with minimal response to any therapy. The purpose of this pilot analysis was to find the effectiveness of vemurafenib, an oral BRAF inhibitor, and radiation therapy in V600 mutated melanoma with brain metastases. BRAF mutation status of the melanoma patients was determined by real-time PCR assay. Retrospective analysis was performed on twelve patients who had the mutation and were treated with either stereotactic radiosurgery or whole brain radiation therapy prior to or along with vemurafenib at a dose of 960 mg orally twice a day. Clinical and radiological responses, development of new brain metastases, overall survival and toxicity were assessed. Improvement in neurological symptoms was seen in 7/11 (64 %) following therapy. Radiographic responses were noted in 36/48 (75 %) of index lesions with 23 (48 %) complete responses and 13 (27 %) partial responses. Six month local control, freedom from new brain metastases and overall survival were 75, 57 and 92 %. Four patients had intra-tumoral bleed prior to therapy and two patients developed steroid dependence. One patient experienced radiation necrosis. This retrospective study suggests that melanoma patients with brain metastases harboring BRAF mutation appear to be a distinct sub-group with a favorable response to vemurafenib and radiation therapy and acceptable morbidity.
authors.affiliation: Department of Radiation Oncology, New York University Langone Medical Center, 566 First Avenue HC-107, New York, NY 10016, USA. ashwatha.narayana@greenwichhospital.org
authors.forename: Ashwatha
authors.initials: A
authors.lastname: Narayana
authors.forename: Maya
authors.initials: M
authors.lastname: Mathew
authors.forename: Moses
authors.initials: M
authors.lastname: Tam
authors.forename: Rajni
authors.initials: R
authors.lastname: Kannan
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Madden
authors.forename: John G
authors.initials: JG
authors.lastname: Golfinos
authors.forename: Erik C
authors.initials: EC
authors.lastname: Parker
authors.forename: Patrick A
authors.initials: PA
authors.lastname: Ott
authors.forename: Anna C
authors.initials: AC
authors.lastname: Pavlick
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001932:Brain Neoplasms / Q000401:mortality / Q000556:secondary / Q000628:therapy*; D003131:Combined Modality Therapy; D016371:Cranial Irradiation; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D008297:Male; D008545:Melanoma / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009364:Neoplasm Recurrence, Local / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D011379:Prognosis; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors / Q000235:genetics; D016634:Radiosurgery; D012189:Retrospective Studies; D013449:Sulfonamides / Q000627:therapeutic use*; D015996:Survival Rate; D000077484:Vemurafenib
chemical_list: D007211:Indoles; D013449:Sulfonamides; D000077484:Vemurafenib; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf