Ghosh Hia S, Patel Ruchit V, Woodward Eleanor, Greenwald Noah F, Bhave Varun M, Maury Eduardo A, Cello Gregory, Hoffman Samantha E, Li Yvonne, Gupta Hersh, Youssef Gilbert, Spurr Liam F, Vogelzang Jayne, Touat Mehdi, Dubois Frank, Cherniack Andrew D, Guo Xiaopeng, Tavakol Sherwin, Cioffi Gino, Lindeman Neal I, Ligon Azra H, Chiocca E Antonio, Reardon David A, Wen Patrick Y, Meredith David M, Santagata Sandro, Barnholtz-Sloan Jill S, Ligon Keith L, Beroukhim Rameen, Bi Wenya Linda
Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
School of Medicine, Stanford University, Palo Alto, California, USA.
Neuro Oncol. 2025 Jan 12;27(1):195-208. doi: 10.1093/neuonc/noae164.
With the significant shift in the classification, risk stratification, and standards of care for gliomas, we sought to understand how the overall survival of patients with these tumors is impacted by molecular features, clinical metrics, and treatment received.
We assembled a cohort of patients with histopathologically diagnosed glioma from The Cancer Genome Atlas (TCGA), Project Genomics Evidence Neoplasia Information Exchange, and Dana-Farber Cancer Institute/Brigham and Women's Hospital. This incorporated retrospective clinical, histological, and molecular data alongside a prospective assessment of patient survival.
Of 4400 gliomas were identified: 2195 glioblastomas, 1198 IDH1/2-mutant astrocytomas, 531 oligodendrogliomas, 271 other IDH1/2-wild-type gliomas, and 205 pediatric-type glioma. Molecular classification updated 27.2% of gliomas from their original histopathologic diagnosis. Examining the distribution of molecular alterations across glioma subtypes revealed mutually exclusive alterations within tumorigenic pathways. Non-TCGA patients had significantly improved overall survival compared to TCGA patients, with 26.7%, 55.6%, and 127.8% longer survival for glioblastoma, IDH1/2-mutant astrocytoma, and oligodendroglioma, respectively (all P < .01). Several prognostic features were characterized, including NF1 alteration and 21q loss in glioblastoma, and EGFR amplification and 22q loss in IDH1/2-mutant astrocytoma. Leveraging the size of this cohort, nomograms were generated to assess the probability of overall survival based on patient age, the molecular features of a tumor, and the treatment received.
By applying modern molecular criteria, we characterize the genomic diversity across glioma subtypes, identify clinically applicable prognostic features, and provide a contemporary update on patient survival to serve as a reference for ongoing investigations.
随着胶质瘤的分类、风险分层和治疗标准发生重大变化，我们试图了解这些肿瘤患者的总生存期如何受到分子特征、临床指标和所接受治疗的影响。
我们从癌症基因组图谱（TCGA）、肿瘤基因组证据肿瘤信息交换计划以及丹娜-法伯癌症研究所/布莱根妇女医院收集了一组经组织病理学诊断为胶质瘤的患者。这纳入了回顾性临床、组织学和分子数据以及对患者生存期的前瞻性评估。
共鉴定出4400例胶质瘤：2195例胶质母细胞瘤、1198例异柠檬酸脱氢酶1/2（IDH1/2）突变型星形细胞瘤、531例少突胶质细胞瘤、271例其他IDH1/2野生型胶质瘤和205例儿童型胶质瘤。分子分类使27.2%的胶质瘤从其最初的组织病理学诊断中得到更新。对胶质瘤亚型间分子改变分布的研究揭示了致瘤途径内相互排斥的改变。非TCGA患者的总生存期显著优于TCGA患者，胶质母细胞瘤、IDH1/2突变型星形细胞瘤和少突胶质细胞瘤的生存期分别长26.7%、55.6%和127.8%（均P < .01）。确定了几个预后特征，包括胶质母细胞瘤中的神经纤维瘤病1型（NF1）改变和21号染色体缺失，以及IDH1/2突变型星形细胞瘤中的表皮生长因子受体（EGFR）扩增和22号染色体缺失。利用该队列的规模，生成了列线图，以根据患者年龄、肿瘤的分子特征和所接受的治疗来评估总生存期的概率。
通过应用现代分子标准，我们描述了胶质瘤亚型间的基因组多样性，确定了临床适用的预后特征，并提供了患者生存期的当代最新情况，以供正在进行的研究参考。
