Molecular pathology, Glioblastoma, WHO CNS 5, Prognosis, Predictive marker, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

Abstract Purpose The 2021 WHO classification of central nervous system tumors introduced molecular criteria to stratify Grade 4 gliomas, which remain heterogeneous. This study aims to elucidate the clinical, radiological, and molecular characteristics of WHO Grade 4 gliomas, focusing on their prognostic implications and the development of a predictive model for astrocytoma IDH-mutant WHO Grade 4 (A4). Methods A retrospective cohort of 223 patients from Beijing Tiantan Hospital was analyzed. Clinical, radiological, and histopathological data were combined with molecular profiling, focusing on IDH mutations, TERT promoter mutations, and MGMT methylation. A predictive model was developed using LASSO regression to distinguish A4 from glioblastomas and validated with an external dataset from UCSF. Results The cohort included 201 glioblastomas (90.1%) and 22 A4 cases (9.9%). A4 tumors were associated with younger age, higher MGMT promoter methylation, lower rates of TERT mutations, and distinct radiological features, such as cortical non-enhancing tumor infiltration (CnCE). Patients with A4 demonstrated significantly better survival outcomes compared to glioblastoma patients (p