braf mutations in advanced cancers clinical characteristics and outcomesbraf突变先进的癌症的临床特征和治疗效果.pdfVIP

BRAF Mutations in Advanced Cancers: Clinical Characteristics and Outcomes 1 1 1 1 1 2 Hazem El-Osta , Gerald Falchook , Apostolia Tsimberidou , David Hong , Aung Naing , Kevin Kim , 3 1 1 Sijin Wen , Filip Janku , Razelle Kurzrock * 1 Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America, 2 Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America, 3 Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America Abstract Background: Oncogenic BRAF mutations have been found in diverse malignancies and activate RAF/MEK/ERK signaling, a critical pathway of tumorigenesis. We examined the clinical characteristics and outcomes of patients with mutant (mut) BRAF advanced cancer referred to phase 1 clinic. Methods: We reviewed the records of 80 consecutive patients with mutBRAF advanced malignancies and 149 with wild-type (wt) BRAF (matched by tumor type) referred to the Clinical Center for Targeted Therapy and analyzed their outcome. Results: Of 80 patients with mutBRAF advanced cancer, 56 had melanoma, 10 colorectal, 11 papillary thyroid, 2 ovarian and 1 esophageal cancer. Mutations in codon 600 were found in 77 patients (62, V600E; 13, V600K; 1, V600R; 1, unreported). Multivariate analysis showed less soft tissue (Odds ratio (OR) = 0.39, 95%CI: 0.20–0.77, P = 0.007), lung (OR = 0.38, 95%CI: 0.19–0.73, p = 0.004) and retroperitoneal metastases (OR = 0.34, 95%CI: 0.13–0.86, p = 0.024) and more brain m