Abstract：
Recurrent and anaplastic pleomorphic xanthoastrocytoma (r&aPXA) is a rare primary brain tumor that is challenging to treat. Two-thirds of PXA tumors harbor a BRAF gene mutation. BRAF inhibitors have been shown to improve tumor control. However, resistance to BRAF inhibition develops in most cases. Concurrent therapy with MEK inhibitors may improve tumor control and patient survival. In this study, we identified 5 patients diagnosed with BRAF-mutated PXA who received BRAF and MEK inhibitors over a 10-year interval at our institution. Patient records were evaluated, including treatments, adverse effects (AEs), outcomes, pathology, next-generation sequencing, and MRI. The median age was 22 years (range, 14-66 years), 60% male, and 60% anaplastic PXA. Median overall survival was 72 months (range, 19-112 months); 1 patient died of tumor-related hemorrhage while off therapy, and the other 4 experienced long-term disease control (21, 72, 98, and 112 months, respectively). Dual BRAF/MEK inhibitors were well tolerated, with only grade 1-2 AEs, including rash, neutropenia, fatigue, abdominal discomfort, and diarrhea. No grade 3-5 AEs were detected. A literature review was also performed of patients diagnosed with BRAF-mutated PXA and treated with BRAF and/or MEK inhibitors through August 2021, with a total of 32 cases identified. The median age was 29 years (range, 8-57 years) and the median PFS and OS were 8.5 months (range, 2-35 months) and 35 months (range, 10-80 months), respectively. The most common AEs were grade 1-2 fatigue and skin rash. Results of this case series and literature review indicate that dual-drug therapy with BRAF and MEK inhibitors for r&aPXA with BRAF V600E mutation may delay tumor progression without unexpected AEs.
摘要：
复发性和间变性多形性黄色星形细胞瘤（r＆aPXA）是一种罕见的原发性脑肿瘤，具有挑战性的治疗。三分之二的PXA肿瘤具有BRAF基因突变。BRAF抑制剂已显示可改善肿瘤控制。然而,对BRAF抑制的抗性在大多数情况下发展。MEK抑制剂的同时治疗可以改善肿瘤控制和患者生存率。在这项研究中,我们确定了5例诊断为BRAF突变PXA的患者,这些患者在我们机构接受了BRAF和MEK抑制剂治疗10年.评估患者记录，包括治疗,不良反应（AE），结果，病理学,下一代测序，MRI。中位年龄为22岁(范围，14-66岁），60%男性,和60%间变性PXA。中位总生存期为72个月(范围，19-112个月）；1例患者在停止治疗时死于肿瘤相关出血，其他4人经历了长期的疾病控制(21、72、98和112个月，分别)。双重BRAF/MEK抑制剂耐受性良好，只有1-2级AE，包括皮疹,中性粒细胞减少症,疲劳,腹部不适,和腹泻。未检测到3-5级AE。到2021年8月，还对诊断为BRAF突变的PXA并接受BRAF和/或MEK抑制剂治疗的患者进行了文献综述，共确定32例。中位年龄为29岁(范围，8-57年)，中位PFS和OS为8.5个月(范围，2-35个月)和35个月(范围，10-80个月），分别。最常见的不良事件是1-2级疲劳和皮疹。本病例系列和文献综述的结果表明，BRAF和MEK抑制剂对具有BRAFV600E突变的r＆aPXA的双药治疗可能会延迟肿瘤进展，而不会出现意外的AE。
