期刊
JOURNAL OF NEURO-ONCOLOGY
卷 152, 期 3, 页码 515-522出版社
SPRINGER
DOI: 10.1007/s11060-021-03719-5
关键词
Glioblastoma; BRAF; Molecular targeted therapy; MEK inhibitor; BRAF inhibitor
资金
- NCI NIH HHS [K12 CA090354] Funding Source: Medline
A retrospective study of 19 adult glioblastoma patients with BRAF V600E mutations showed that this mutation is not common in these patients. Some patients were treated with BRAF/MEK inhibitors, showing partial response or stability in disease progression, which could be a potential therapeutic option.
Purpose Although uncommon, detection of BRAF V600E mutations in adult patients with glioblastoma has become increasingly relevant given the widespread application of molecular diagnostics and encouraging therapeutic activity of BRAF/MEK inhibitors. Methods We performed a retrospective study of adult glioblastoma patients treated at Dana-Farber Cancer Institute/Brigham and Women's Hospital or Massachusetts General Hospital from January 2011 to July 2019 with an identified BRAF V600E mutation by either immunohistochemistry or molecular testing. Patient characteristics, molecular genomics, and preoperative MRI were analyzed. Results Nineteen glioblastoma patients were included, with median age at diagnosis of 41-years-old (range 22-69). Only 1/18 was IDH1/2-mutant; 10/17 had MGMT unmethylated tumors. The most common additional molecular alterations were CDKN2A/2B biallelic loss/loss-of-function (10/13, 76.9%), polysomy 7 (8/12, 66.7%), monosomy 10 (5/12, 41.7%), PTEN biallelic loss/loss-of-function (5/13, 38.5%) and TERT promoter mutations (5/15, 33.3%). Most tumors were well-circumscribed (11/14) and all were contrast-enhancing on MRI. Twelve patients eventually developed subependymal or leptomeningeal dissemination. Six patients were treated with BRAF/MEK inhibition following disease progression after standard of care therapy, with 4/6 patients showing partial response or stable disease as best response. Median time to progression after BRAF/MEK inhibition was 6.0 months (95% CI 1.2-11.8). Grade 1 skin rash was present in 2 patients, but no other adverse events were reported. Median OS for the entire cohort was 24.1 months (95% CI 15.7-38.9). Conclusion Understanding the natural history and features of BRAF V600E glioblastoma may help better identify patients for BRAF/MEK inhibition and select therapeutic strategies.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据