Dabrafenib in patients with recurrent, BRAF V600E mutated malignant glioma and leptomeningeal disease.
Dabrafenib in patients with recurrent, BRAF V600E mutated malignant glioma and leptomeningeal disease.
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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。
DOI：
10.3892/or.2017.6013
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发表时间：
2017-12
期刊：
影响因子：
4.2
通讯作者：
Bähr O
中科院分区：
文献类型：
--
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
BRAF V600E突变在恶性黑色素瘤中经常发生，但在大多数恶性胶质瘤亚型中很少见。此外，更多的良性脑肿瘤，如神经节胶质瘤、胚胎发育不良的神经上皮细胞瘤和幕上毛细胞星形细胞瘤，只有多形性黄色星形细胞瘤(50%-78%)和上皮样胶质母细胞瘤(50%)经常出现BRAF突变。在目前的研究中，我们报告了三名携带BRAF V600E突变的复发恶性胶质瘤患者。所有患者在复发时均表现为明显播散性软脑膜病变，并在放射治疗和烷化化疗后进展。因此，复发时的估计预期寿命为几周。所有三名患者都接受了达普拉非尼作为单一药物的治疗，所有患者都表现出完全或几乎完全有效。治疗正在进行中，患者分别稳定了27个月、7个月和3个月。一名患者在治疗一周后表现出显著的放射学和临床反应。我们能够从一名患者的脑脊液中产生体外肿瘤细胞培养。体外培养的细胞用达普拉非尼处理后，细胞密度降低，ERK的磷酸化受到抑制。到目前为止，这是第一个用达普拉非尼单一疗法治疗BRAF突变的恶性胶质瘤和软脑膜播散的成人患者的系列。所有患者都表现出戏剧性的反应，其中一名患者持续反应超过两年。
BRAF V600E mutations occur frequently in malignant melanoma, but are rare in most malignant glioma subtypes. Besides, more benign brain tumors such as ganglioglioma, dysembryoblastic neuroepithelial tumours and supratentorial pilocytic astrocytomas, only pleomorphic xanthoastrocytomas (50–78%) and epitheloid glioblastoma (50%) regularly exhibit BRAF mutations. In the present study, we report on three patients with recurrent malignant gliomas harbouring a BRAF V600E mutation. All patients presented with markedly disseminated leptomeningeal disease at recurrence and had progressed after radiotherapy and alkylating chemotherapy. Therefore, estimated life expectancy at recurrence was a few weeks. All three patients received dabrafenib as a single agent and all showed a complete or nearly complete response. Treatment is ongoing and patients are stable for 27 months, 7 months and 3 months, respectively. One patient showed a dramatic radiologic and clinical response after one week of treatment. We were able to generate an ex vivo tumor cell culture from CSF in one patient. Treatment of this cell culture with dabrafenib resulted in reduced cell density and inhibition of ERK phosphorylation in vitro. To date, this is the first series on adult patients with BRAF-mutated malignant glioma and leptomeningeal dissemination treated with dabrafenib monotherapy. All patients showed a dramatic response with one patient showing an ongoing response for more than two years.
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影响因子：
7.4
作者：
del Bufalo, Francesca;Carai, Andrea;Mastronuzzi, Angela
通讯作者：
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