Report of treatment intensity and survival outcomes in older patients with glioblastoma diagnosed according to WHO CNS 5 classification

PURPOSE: Glioblastoma is the most common primary brain cancer in adults, with half of cases diagnosed in patients aged ≥ 65 years. However, definitions of older adults vary, resulting in treatment variation between centres. This study aimed to report on the treatment intensity and survival outcomes in older patients with glioblastoma diagnosed according to WHO CNS 5 classification. METHODS: We conducted a retrospective, multicentre cohort study (Histo-Mol GBM Collaborative) of consecutive patients with pathologically confirmed glioblastoma, IDH-wildtype diagnosed in 2021, according to the 2021 WHO CNS 5 classification, across 52 centres in the UK, Ireland, New Zealand, and Australia. Demographic, molecular, treatment, and survival data were analysed. RESULTS: Of 1,857 patients, 863 (46.5%) were aged ≥ 65 years. Older patients had worse performance status, were more likely to have a biopsy, and received less intensive oncological therapy. Molecular testing was less comprehensive for older patients, but in those patients tested there was no difference with older age. Median overall survival declined with older age, with the steepest reduction in patients ≥ 70 years. Patients aged 65-69 derived comparable benefit from conventionally fractionated chemoradiation to adults aged < 65, whereas outcomes in those aged ≥ 70 were equivalent when treated with hypofractionated or conventionally fractionated chemoradiation. In multivariate analysis, oncological treatment intensity, completion of adjuvant therapy, and MGMT promoter methylation were independent predictors of survival. CONCLUSIONS: This international clinical dataset of adults diagnosed with glioblastoma since the introduction of the WHO CNS 5 criteria supports the use of conventionally fractionated chemoradiation in fit patients < 70, while hypofractionated regimens are appropriate for those ≥ 70. Surgical extent, treatment intensity, and MGMT methylation remain key determinants of survival in older patients with glioblastoma.