Therapeutic and Prognostic Implications of BRAF V600E in Pediatric Low-Grade Gliomas
Therapeutic and Prognostic Implications of BRAF V600E in Pediatric Low-Grade Gliomas
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DOI：
10.1200/jco.2016.71.8726
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发表时间：
2017-09-01
影响因子：
45.3
通讯作者：
Tabori, Uri
中科院分区：
文献类型：
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作者：
Lassaletta, Alvaro;Zapotocky, Michal;Tabori, Uri
目的BRAF V600 E是在儿童低级别胶质瘤（PLGG）亚组中检测到的潜在高度靶向突变。它的生物学和临床效果在这个不同的肿瘤组仍然unknowed.Patients和方法相结合的临床和遗传机构的研究PLGG患者进行了长期随访（N = 510）。将BRAF V600E突变型PLGG患者（n = 99）的临床和治疗数据与BRAF V600E突变型PLGG患者（n = 180）的大型国际独立队列进行比较。其在临床实践中通常不进行常规活组织检查。BRAF V600 E PLGG患者在化疗和放疗后表现出不良结局，BRAF V600 E和野生型PLGG的10年无进展生存率分别为27%（95% CI，12.1%至41.9%）和60.2%（95% CI，53.3%至67.1%）（P <0.001）。额外的多变量临床和分子分层显示，切除程度和CDKN2A缺失独立导致BRAF V600 E PLGG的不良结局。在独立队列中观察到CDKN 2A和切除对结局具有类似的独立作用。定量影像学分析显示，大多数BRAF V600 E PLGG患者病情进展，对常规化疗缺乏反应。结论BRAF V600 E PLGG是一种独特的实体，在目前的辅助治疗下预后不良。(C)2017年美国临床肿瘤学会
Purpose BRAF V600E is a potentially highly targetable mutation detected in a subset of pediatric low-grade gliomas (PLGGs). Its biologic and clinical effect within this diverse group of tumors remains unknown.Patients and Methods A combined clinical and genetic institutional study of patients with PLGGs with long-term follow-up was performed (N = 510). Clinical and treatment data of patients with BRAF V600E mutated PLGG (n = 99) were compared with a large international independent cohort of patients with BRAF V600E mutated-PLGG (n = 180).Results BRAF V600E mutation was detected in 69 of 405 patients (17%) with PLGG across a broad spectrum of histologies and sites, including midline locations, which are not often routinely biopsied in clinical practice. Patients with BRAF V600E PLGG exhibited poor outcomes after chemotherapy and radiation therapies that resulted in a 10-year progression-free survival of 27% (95% CI, 12.1% to 41.9%) and 60.2% (95% CI, 53.3% to 67.1%) for BRAF V600E and wild-type PLGG, respectively (P < .001). Additional multivariable clinical and molecular stratification revealed that the extent of resection and CDKN2A deletion contributed independently to poor outcome in BRAF V600E PLGG. A similar independent role for CDKN2A and resection on outcome were observed in the independent cohort. Quantitative imaging analysis revealed progressive disease and a lack of response to conventional chemotherapy in most patients with BRAF V600E PLGG.Conclusion BRAF V600E PLGG constitutes a distinct entity with poor prognosis when treated with current adjuvant therapy. (C) 2017 by American Society of Clinical Oncology