Molecularly diagnosed glioblastoma: clinical presentation and outcomes

The 2021 WHO classification permits diagnosis of glioblastoma in IDH-wildtype diffuse astrocytic tumors with TERT promoter mutation, EGFR amplification, or chromosome 7 gain/10 loss, even without necrosis or microvascular proliferation. The clinical behavior of these molecularly defined glioblastomas (molGBM) remains uncertain.

We retrospectively analyzed patients with molGBM treated at Hannover Medical School between 2017 and 2024. A contemporaneous histologically defined glioblastoma cohort (hisGBM) served as a control group in an approximately 1:3 ratio. MolGBM were stratified by histological grade and additionally compared with IDH-mutant astrocytomas of corresponding grade. Survival was assessed using Kaplan-Meier analysis, Cox regression, and propensity score matching.

Thirty-four patients with molGBM and 103 with hisGBM were included. Compared with hisGBM, molGBM patients were younger (p < 0.001), had higher Karnofsky Performance Status (p < 0.001), and more often presented with seizures (p = 0.006), whereas focal neurological deficits were more frequent in hisGBM. MolGBM showed less contrast enhancement (p < 0.001) and lower Ki-67 indices (p < 0.001). Median overall survival was longer in molGBM (539 vs. 374 days; p = 0.032), but tumor group was not independently associated with survival after adjustment for age and KPS (HR 1.21, 95% CI 0.77-1.90; p = 0.411). In the matched cohort, overall survival did not differ significantly (517 vs. 468 days; p = 0.670). MolGBM had inferior survival to grade-corresponding IDH-mutant astrocytomas (p < 0.001).

MolGBM shows a distinct clinical-radiological phenotype, while its apparent survival advantage over hisGBM is influenced by baseline clinical differences.

Not applicable.