Identification of new prognostic molecular markers in glioblastoma: a single-center retrospective study

Glioblastoma (GBM) is the most common and aggressive primary CNS tumor in adults and carries a poor prognosis. Although molecular classification has advanced, patient outcomes remain variable. Next-generation sequencing (NGS) can reveal genomic alterations that, while not yet treatment-guiding, offer prognostic and biological insight. The study aimed to investigate the association between molecular alterations in primary GBM tumors and patient survival outcomes.

This study analyzed medical records of consecutive GBM patients treated between November 1, 2018 and December 31, 2021 at a comprehensive cancer center, for whom NGS data from the tumor was available. Survival analyses were performed according to clinical, radiological, therapeutic, and molecular data.

Of 199 patients, 38 were excluded: 15 for recurrence-only data and 23 for incomplete molecular data after first progression. In the survival analysis of the cohort (n = 161) adjusted on surgical resection, MGMT promoter methylation status, number of alterations, age, tumor localization, MIB1 and performance status, EGFR substitutions were significantly associated with increased overall survival (OS) (HR = 0.43 [0.26; 0.72], P = .001), while CDKN2A/B loss and TP53 substitutions were associated with decreased OS (HR = 1.75 [1.08; 2.84], P = .023 and HR = 1.69 [1.04; 2.74], P = .034 respectively). NOTCH1 substitutions showed a trend towards improved progression-free survival (PFS) (HR = 0.55 [0.30; 1.01], P = .054).

We identified new prognostic markers in GBM, showing for the first time that EGFR substitutions improve OS. Validation in external cohorts and preclinical studies is needed.