Deng Jiaojiao, Sun Shuchen, Chen Jiawei, Wang Daijun, Cheng Haixia, Chen Hong, Xie Qing, Hua Lingyang, Gong Ye
Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China.
Institute of Neurosurgery, Fudan University, Shanghai, China.
Front Oncol. 2021 Oct 29;11:747592. doi: 10.3389/fonc.2021.747592. eCollection 2021.
Adjuvant radiotherapy (RT) is one of the most commonly used treatments for high-grade meningiomas (HGMs) after surgery, but genetic determinants of clinical benefit are poorly characterized.
We describe efforts to integrate clinical genomics to discover predictive biomarkers that would inform adjuvant treatment decisions in HGMs.
We undertook a retrospective analysis of 37 patients with HGMs following RT. Clinical hybrid capture-based sequencing assay covering 184 genes was performed in all cases. Associations between tumor clinical/genomic characteristics and RT response were assessed. Overall survival (OS) and progression-free survival (PFS) curves were plotted using the Kaplan-Meier method.
Among the 172 HGMs from a single institution, 42 cases (37 WHO grade 2 meningiomas and five WHO grade 3 meningiomas) were identified as HGMs following RT. Only mutations [62.5% C228T; 25% C250T; 12.5% copy number amplification (CN amp.)] were significantly associated with tumor progression after postoperative RT (adjusted = 0.003). Potential different somatic interactions between and other tested genes were not identified. Furthermore, alterations (-alt) were the predictor of tumor progression (Fisher's exact tests, = 0.003) and were associated with decreased PFS (log-rank test, = 0.0114) in HGMs after RT.
Our findings suggest that -alt is associated with tumor progression and poor outcome of newly diagnosed HGM patients after postoperative RT.
辅助放疗（RT）是术后高级别脑膜瘤（HGM）最常用的治疗方法之一，但临床获益的基因决定因素尚不明确。
我们描述了整合临床基因组学以发现预测生物标志物的努力，这些生物标志物将为HGM的辅助治疗决策提供依据。
我们对37例接受RT治疗的HGM患者进行了回顾性分析。所有病例均进行了基于临床杂交捕获的测序分析，覆盖184个基因。评估肿瘤临床/基因组特征与RT反应之间的关联。使用Kaplan-Meier方法绘制总生存（OS）和无进展生存（PFS）曲线。
在来自单一机构的172例HGM中，42例（37例世界卫生组织2级脑膜瘤和5例世界卫生组织3级脑膜瘤）被确定为接受RT治疗后的HGM。只有 突变[62.5% C228T；25% C250T；12.5%拷贝数扩增（CN amp.）]与术后RT后肿瘤进展显著相关（校正 = 0.003）。未发现 与其他测试基因之间潜在的不同体细胞相互作用。此外， 改变（-alt）是肿瘤进展的预测指标（Fisher精确检验， = 0.003），并且与RT后HGM的PFS降低相关（对数秩检验， = 0.0114）。
我们的研究结果表明，-alt与新诊断的HGM患者术后RT后的肿瘤进展和不良预后相关。
