Yang Peter H, Tao Yu, Luo Jingqin, Paturu Mounica, Lu Hsiang-Chih, Ramkissoon Shakti, Heusel Jonathan W, Leuthardt Eric C, Chicoine Michael R, Dowling Joshua L, Dunn Gavin P, Duncavage Eric, Dahiya Sonika, Chattherjee Arindam R, Kim Albert H
Department of Neurological Surgery, Washington University School of Medicine in St. Louis, St. Louis, Missouri, USA.
Department of Surgery, Public Health Sciences Division, Washington University School of Medicine in St. Louis, St. Louis, Missouri, USA.
Neurooncol Adv. 2022 Jan 10;4(1):vdac002. doi: 10.1093/noajnl/vdac002. eCollection 2022 Jan-Dec.
Many factors impact survival in patients with glioblastoma, including age, Karnofsky Performance Status, postoperative chemoradiation, mutation status, promoter methylation status, and extent of resection. High-throughput next-generation sequencing is a widely available diagnostic tool, but the independent impact of tumors harboring specific mutant genes on survival and the efficacy of extent of resection are not clear.
We utilized a widely available diagnostic platform (FoundationOne CDx) to perform high-throughput next-generation sequencing on 185 patients with newly diagnosed glioblastoma in our tertiary care center. We performed multivariate analysis to control for clinical parameters with known impact on survival to elucidate the independent prognostic value of prevalent mutant genes and the independent impact of gross total resection.
When controlling for factors with known prognostic significance including mutation and after multiple comparisons analysis, and mutations were associated with reduced overall survival while mutation was associated with improved overall survival. Gross total resection, compared to other extent of resection, was associated with improved overall survival in patients with tumors harboring mutations in , , , , promoter, and . All patients possessed at least one of these 6 mutant genes.
This study verifies the independent prognostic value of several mutant genes in glioblastoma. Six commonly found mutant genes were associated with improved survival when gross total resection was achieved. Thus, even when accounting for known predictors of survival and multiple mutant gene comparisons, extent of resection continues to be strongly associated with survival.
许多因素影响胶质母细胞瘤患者的生存，包括年龄、卡诺夫斯基功能状态、术后放化疗、突变状态、启动子甲基化状态和切除范围。高通量下一代测序是一种广泛可用的诊断工具，但携带特定突变基因的肿瘤对生存的独立影响以及切除范围的疗效尚不清楚。
我们利用一个广泛可用的诊断平台（FoundationOne CDx）对我们三级医疗中心的185例新诊断的胶质母细胞瘤患者进行高通量下一代测序。我们进行多变量分析以控制对生存有已知影响的临床参数，以阐明常见突变基因的独立预后价值和全切除的独立影响。
在控制包括突变在内的具有已知预后意义的因素并经过多次比较分析后， 和 突变与总生存期缩短相关，而 突变与总生存期改善相关。与其他切除范围相比，全切除与携带 、 、 、 、 启动子和 突变的肿瘤患者的总生存期改善相关。所有患者至少拥有这6种突变基因中的一种。
本研究验证了胶质母细胞瘤中几种突变基因的独立预后价值。当实现全切除时，6种常见的突变基因与生存改善相关。因此，即使考虑到已知的生存预测因素和多个突变基因比较，切除范围仍然与生存密切相关。
