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

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

doi:10.3389/fonc.2023.1200815

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

Front Oncol. 2023 Jul 6:13:1200815. doi: 10.3389/fonc.2023.1200815. eCollection 2023.

Authors

Xiaopeng Guo^{1

2}, Lingui Gu¹, Yilin Li^{1

3}, Zhiyao Zheng^{1

4

5}, Wenlin Chen¹, Yaning Wang¹, Yuekun Wang¹, Hao Xing¹, Yixin Shi^{1

6}, Delin Liu^{1

6}, Tianrui Yang^{1

6}, Yu Xia^{1

6}, Junlin Li^{1

6}, Jiaming Wu^{1

6}, Kun Zhang^{1

6}, Tingyu Liang¹, Hai Wang¹, Qianshu Liu^{1

6}, Shanmu Jin^{1

3}, Tian Qu^{1

6}, Siying Guo^{1

6}, Huanzhang Li^{1

6}, Yu Wang^{1

2}, Wenbin Ma^{1

2}

Affiliations

¹ Department of Neurosurgery, Center for Malignant Brain Tumors, National Glioma MDT Alliance, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
² China Anti-Cancer Association Specialty Committee of Glioma, Peking Union Medical College Hospital, Beijing, China.
³ '4 + 4' Medical Doctor Program, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
⁴ Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
⁵ Research Unit of Accurate Diagnosis, Treatment, and Translational Medicine of Brain Tumors (No.2019RU011), Chinese Academy of Medical Sciences, Beijing, China.
⁶ Eight-year Medical Doctor Program, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Abstract

Introduction: Glioblastoma (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.

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.

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

Keywords: chromosome copy number variation; glioblastoma; histological glioblastoma; molecular alteration; molecular glioblastoma.

Grants and funding

This work was funded by the National Natural Science Foundation of China (82203527), the Fundamental Research Funds for the Central Universities (3332022009), and the China Postdoctoral Science Foundation (2022M710451) for XG, and by the Beijing Municipal Natural Science Foundation (7202150) and the National High Level Hospital Clinical Research Funding (2022-PUMCH-A-019) for YW, and by the National High Level Hospital Clinical Research Funding (2022-PUMCH-B-113), the Tsinghua University-Peking Union Medical College Hospital Initiative Scientific Research Program (2019ZLH101) and the Beijing Municipal Natural Science Foundation (19JCZDJC64200[Z]) for WM.