Frontiers in Oncology (Jul 2023)

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

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

DOI
https://doi.org/10.3389/fonc.2023.1200815
Journal volume & issue
Vol. 13

Abstract

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IntroductionGlioblastoma (GBM), the most lethal primary brain malignancy, is divided into histological (hist-GBM) and molecular (mol-GBM) subtypes according to the 2021 World Health Organization classification of central nervous system tumors. This study aimed to characterize the clinical, radiological, molecular, and survival features of GBM under the current classification scheme and explore survival determinants.MethodsWe 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.ResultsAmong 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.ConclusionThe definition of GBM and its clinical, radiological, molecular, and prognostic characteristics have been altered under the current classification.

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