Molecular Classification of CNS Tumours: A Radiation Oncologist’s Perspective

Abstract

Molecular classification has transformed central nervous system (CNS) tumour diagnosis by integrating genetic and epigenetic information with histopathology and imaging. The 2021 WHO classification made molecular alterations defining criteria for several tumour entities, creating direct and emerging implications for radiation oncology. This review examines how molecular information affects diagnostic grading, risk stratification, systemic-therapy selection, radiation de-escalation, and target-volume delineation. CDKN2A/B homozygous deletion can molecularly upgrade IDH-mutant astrocytoma to WHO grade 4, while IDH mutation with 1p/19q codeletion defines oligodendroglioma. MGMT promoter methylation is primarily a predictive biomarker for alkylating chemotherapy benefit rather than an independent marker of radiosensitivity. Molecular subgroups of medulloblastoma, meningioma, and ependymoma refine prognostic assessment and may support future treatment adaptation. In contrast, current CNS radiotherapy remains predominantly anatomy-, imaging-, surgical-, and clinically driven. Molecularly guided dose reduction, margin modification, and adaptive radiotherapy remain areas for prospective validation. Precision CNS radiotherapy will therefore depend on integrating molecular biology with imaging, surgical findings, patterns of spread, patient factors, and prospective evidence. Keywords: CNS tumours; molecular classification; radiotherapy; IDH; 1p/19q; MGMT; medulloblastoma; meningioma; ependymoma; precision radiotherapy