Histological and molecular glioblastoma, IDH-wildtype: a real-world landscape using the 2021 WHO classification of central nervous system tumors

组织学和分子胶质母细胞瘤,IDH-野生型:使用 2021 年 WHO 中枢神经系统肿瘤分类的真实世界景观

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作者:Xiaopeng Guo, Lingui Gu, Yilin Li, Zhiyao Zheng, Wenlin Chen, Yaning Wang, Yuekun Wang, Hao Xing, Yixin Shi, Delin Liu, Tianrui Yang, Yu Xia, Junlin Li, Jiaming Wu, Kun Zhang, Tingyu Liang, Hai Wang, Qianshu Liu, Shanmu Jin, Tian Qu, Siying Guo, Huanzhang Li, Yu Wang, Wenbin Ma

Conclusion

The definition of GBM and its clinical, radiological, molecular, and prognostic characteristics have been altered under the current classification.

Methods

We re-examined the genetic alterations of IDH-wildtype diffuse gliomas at our institute from 2011 to 2022, and enrolled GBMs for analysis after re-classification. Univariable and multivariable analyses were used to identify survival determinants.

Results

Among 209 IDH-wildtype gliomas, 191 were GBMs, including 146 hist-GBMs (76%) and 45 mol-GBMs (24%). Patients with mol-GBMs were younger, less likely to develop preoperative motor dysfunction, and more likely to develop epilepsy than hist-GBMs. Mol-GBMs exhibited lower radiographic incidences of contrast enhancement and intratumoral necrosis. Common molecular features included copy-number changes in chromosomes 1, 7, 9, 10, and 19, as well as alterations in EGFR, TERT, CDKN2A/B, and PTEN, with distinct patterns observed between the two subtypes. The median overall survival (mOS) of GMB was 12.6 months. Mol-GBMs had a higher mOS than hist-GBMs, although not statistically significant (15.6 vs. 11.4 months, p=0.17). Older age, male sex, tumor involvement of deep brain structure or functional area, and genetic alterations in CDK4, CDK6, CIC, FGFR3, KMT5B, and MYB were predictors for a worse prognosis, while MGMT promoter methylation, maximal tumor resection, and treatment based on the Stupp protocol were predictive for better survival.

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