Glioblastoma, IDH-wild type is the most common malignant primary central nervous system (CNS) tumor and is associated with a dramatically poor prognosis. Despite progress in the understanding of the molecular underpinnings of glioblastomas, the standard treatment approach has predominantly relied on a combination of radiotherapy and alkylating agents, with no significant breakthrough in improving patient outcomes.

The most recent World Health Organization (WHO) 2021 classification of tumors of the central nervous system defines glioblastomas as diffuse astrocytic gliomas that are IDH-wildtype and H3-wildtype, exhibiting one or more of the following histologic or molecular features: microvascular proliferation, necrosis, TERT promoter mutation, EGFR amplification, or concurrent gain of whole chromosome 7 and loss of whole chromosome 10 [1], [2.], [3.]. These updated criteria recognize the fundamental biological differences between glioblastomas and IDH-mutant tumors and allow for a glioblastoma diagnosis in biopsy samples not representative of higher-grade areas.

Aside from the signature diagnostic molecular alterations, glioblastomas are heterogeneous with regards to additional genetic profiles, which has prompted efforts to stratify favorable and unfavorable molecular groups in terms of survival, particularly those associated with specific molecular alterations that can be targeted by novel therapeutic agents. In this study, we established a cohort of sequential glioblastomas at a tertiary hospital and conducted clinical and molecular characterization to investigate correlations between molecular features and survival data, aiming to identify subgroups with improved outcomes.