title: Impact of BRAF mutation and BRAF inhibition on melanoma brain metastases.
abstract: The impact of BRAF mutations in metastatic melanoma on the incidence of brain metastases and melanoma prognosis and the effect of BRAF inhibitors on the incidence of brain metastases has not been defined. Therefore, a retrospective analysis of patients with metastatic melanoma treated at three institutions was carried out to examine the impact of BRAF mutations and a BRAF inhibitor, vemurafenib, on the incidence of brain metastases. A retrospective review of 436 records revealed no difference in the incidence of brain metastases between patients with BRAF-mutated tumors versus those without (incidence rate ratio=1.11, 95% confidence interval: 0.80-1.53; P=0.53). A lower incidence of brain metastases was observed in patients with BRAF-mutated tumors who took vemurafenib before the development of brain metastases versus those who did not (incidence rate ratio=0.51, 95% confidence interval: 0.30-0.86; P=0.009). Although treatment with vemurafenib led to improvement in extracranial disease control, it did not significantly affect progression of existing intracranial disease and survival in these patients (P=0.7). Although our previous preclinical data have indicated that penetration of vemurafenib into the brain is limited, our retrospective analysis showed that there was a lower incidence of brain metastases in patients with BRAF-mutated tumors who took vemurafenib before the diagnosis of brain metastases.
authors.affiliation: aMasonic Cancer Center, University of Minnesota, Minneapolis bDepartment of Medical Oncology, Mayo Clinic cMidwest Melanoma Partnership, Rochester, Minnesota dDivision of Hematology/Oncology, University of Illinois Cancer Center, Chicago, Illinois, USA eIstituto Oncologico, Veneto, Padova, Italy.
authors.forename: Tulasi
authors.initials: T
authors.lastname: Gummadi
authors.forename: Ben Y
authors.initials: BY
authors.lastname: Zhang
authors.forename: Sara
authors.initials: S
authors.lastname: Valpione
authors.forename: Chul
authors.initials: C
authors.lastname: Kim
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Kottschade
authors.forename: Rajendar K
authors.initials: RK
authors.lastname: Mittapalli
authors.forename: Vanna
authors.initials: V
authors.lastname: Chiarion-Sileni
authors.forename: Jacopo
authors.initials: J
authors.lastname: Pigozzo
authors.forename: William F
authors.initials: WF
authors.lastname: Elmquist
authors.forename: Arkadiusz Z
authors.initials: AZ
authors.lastname: Dudek
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage; D001921:Brain / Q000473:pathology; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D015994:Incidence; D007211:Indoles / Q000008:administration & dosage; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D009154:Mutation; D009362:Neoplasm Metastasis; D011379:Prognosis; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D012189:Retrospective Studies; D013449:Sulfonamides / Q000008:administration & dosage; D016896:Treatment Outcome; D000077484:Vemurafenib
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D013449:Sulfonamides; D000077484:Vemurafenib; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf