Clinical, radiological and genomic features and targeted therapy in BRAF V600E mutant adult glioblastoma.
Clinical, radiological and genomic features and targeted therapy in BRAF V600E mutant adult glioblastoma.
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DOI：
10.1007/s11060-021-03719-5
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发表时间：
2021-05
影响因子：
3.9
通讯作者：
Arrillaga-Romany I
中科院分区：
文献类型：
--
作者：
Lim-Fat MJ;Song KW;Iorgulescu JB;Andersen BM;Forst DA;Jordan JT;Gerstner ER;Reardon DA;Wen PY;Arrillaga-Romany I
尽管不常见，但由于分子诊断的广泛应用和BRAF/MEK抑制剂的治疗活性的提高，在成年胶质母细胞瘤患者中检测BRAF V600E突变已变得越来越重要。我们对2011年1月至2019年7月在丹娜-法伯癌症研究所/布里格姆妇女医院或马萨诸塞州总医院接受治疗的成年胶质母细胞瘤患者进行了回顾性研究，通过免疫组织化学或分子检测确定了BRAF V600E突变。分析患者特征、分子基因组学和术前MRI。19例胶质母细胞瘤患者，诊断时的中位年龄为41岁（范围22-69岁）。只有1/18是idh1 /2突变体；10/17有MGMT未甲基化肿瘤。最常见的附加分子改变是CDKN2A/2B双等位基因缺失/功能缺失（10/13,76.9%）、7号多体体（8/12,66.7%）、10号单体（5/12,41.7%）、PTEN双等位基因缺失/功能缺失（5/13,38.5%）和TERT启动子突变（5/15,33.3%）。大多数肿瘤边界清晰（11/14），MRI造影增强。12例患者最终发展为室管膜下播散或脑膜轻散。6例患者在标准护理治疗后疾病进展后接受BRAF/MEK抑制治疗，其中4/6患者表现出部分反应或疾病稳定为最佳反应。BRAF/MEK抑制后的中位进展时间为6.0个月（95% CI 1.2-11.8）。2例患者出现1级皮疹，但无其他不良事件报道。整个队列的中位OS为24.1个月（95% CI 15.7-38.9）。了解BRAF V600E胶质母细胞瘤的自然历史和特征可能有助于更好地识别BRAF/MEK抑制患者并选择治疗策略。
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. 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. 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). Understanding the natural history and features of BRAF V600E glioblastoma may help better identify patients for BRAF/MEK inhibition and select therapeutic strategies.
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dabrafenib患有复发性，BRAF V600E突变的恶性神经胶质瘤和瘦脑脑疾病的患者。
影响因子：
4.2
作者：
Burger MC;Ronellenfitsch MW;Lorenz NI;Wagner M;Voss M;Capper D;Tzaridis T;Herrlinger U;Steinbach JP;Stoffels G;Langen KJ;Brandts C;Senft C;Harter PN;Bähr O
通讯作者：
Bähr O
DOI：
10.6004/jnccn.2017.7052
发表时间：
2018-04-01
影响因子：
13.4
作者：
Schreck, Karisa C.;Guajardo, Andrew;Grossman, Stuart A.
通讯作者：
Grossman, Stuart A.
影响因子：
158.5
作者：
Long, G. V.;Stroyakovskiy, D.;Flaherty, K.
通讯作者：
Flaherty, K.
影响因子：
6.4
作者：
Korshunov, Andrey;Chavez, Lukas;von Deimling, Andreas
通讯作者：
von Deimling, Andreas
影响因子：
2.4
作者：
ARITA, N;TANEDA, M;HAYAKAWA, T
通讯作者：
HAYAKAWA, T