The oncologist · 2026
Identification of new prognostic molecular markers in glioblastoma: a single-center retrospective study.
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Meola Adèle, Segier Bertille, Siegfried Aurore, Lusque Amélie, Evrard Solène, Pouessel Damien, Dghayem Delphine, Roux Franck-Emmanuel, Soares Sandra, Guillaumey Maïlys, Blazevic Ilfad, Moyal Elizabeth Cohen-Jonathan, Larrieu Delphine
Аннотация
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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).
CONCLUSION: 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.
METHODS: 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.
RESULTS: 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).
CONCLUSION: 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.