P05.07.A IDENTIFICATION OF NEW PROGNOSTIC MOLECULAR MARKERS IN GLIOBLASTOMA: A SINGLE-CENTER RETROSPECTIVE STUDY

Abstract BACKGROUND Glioblastoma (GBM) is the most common and aggressive primary CNS tumor in adults, with a poor prognosis. Despite molecular advances, outcome heterogeneity persists. Next-generation sequencing (NGS) helps identify key genomic alterations, offering insights into prognosis and biology. The study aimed to investigate the association between molecular alterations in primary GBM tumors and patient survival outcomes. MATERIAL AND METHODS This study analyzed medical records of 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. RESULTS Of 199 patients, 15 were excluded due to molecular data being available only for recurrence, and 23 due to pending data after first progression, despite primary tumor sampling. In the survival analysis of the final cohort (n = 161), all survival results were adjusted for surgical resection, MGMT promoter methylation status, number of alterations, age, tumor localization, MIB1 and performance status (PS). EGFR substitutions were significantly associated with increased overall survival (OS) (HR = 0.41 [0.25; 0.69], p < 0.001), while CDKN2A/B loss and TP53 substitution were associated with decreased OS (HR = 1.78 [1.10; 2.86], p = 0.018 and HR = 1.75 [1.08; 2.84], p = 0.023 respectively). NOTCH1 substitutions showed a trend towards improved progression-free survival (PFS) (HR = 0.55 [0.30; 1;01], p = 0.055). CONCLUSION Our study identified new prognostic markers in GBM patients, demonstrating for the first time a positive prognostic impact of EGFR substitutions on OS. These factors require validation in external cohorts, and the underlying pathophysiological mechanisms should be investigated using preclinical models.