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Tumor Rapid Fire Abstract

Tumor

Contemporary Molecular Landscape, Improved Survival, and Novel Prognostic Factors in 4,400 Gliomas

Sunday, May 5, 2024
2:45 PM – 2:47 PM CT
Location:  S405a
Disclosure(s):
Ruchit V. Patel, BS: No financial relationships to disclose
Wenya Linda Bi, MD, PhD: Stryker: Consultant (Ongoing)
E. Chiocca, MD, PhD: Alliance for Cancer Gene Therapy: Grant/Research Support (Ongoing); Bionaut Labs: Advisor (Ongoing), Stock Shareholder (excluding mutual funds) (Ongoing); Department of Defense: Grant/Research Support (Ongoing); Immunomic Therapeutics: Stock Shareholder (excluding mutual funds) (Ongoing); InSightec: Advisor (Ongoing); NIH: Grant/Research Support (Ongoing); Seneca Therapeutics: Advisor (Ongoing), Stock Shareholder (excluding mutual funds) (Ongoing); Ternalys Therapeutics: Board Member/Officer/Trustee (Ongoing), Stock Shareholder (excluding mutual funds) (Ongoing); Theriva: Advisor (Ongoing)
Patrick Y. Wen, MD: anheart: Consultant (Terminated, November 23, 2024)
Introduction: Molecular glioma classification and advances in treatments have refined therapeutic options for patients. We sought to capture the genomic landscape and characterize prognostic features for gliomas, while exploring the age-dependent variability seen in glioma patient outcomes.

Methods: We assembled patients from TCGA (n=772) and multi-institutional datasets (n=3,628) that assayed somatic mutations and copy number/structural variants, of which nearly 60% harbored overall survival data. All gliomas were classified using molecular definitions (WHO 2021/cIMPACT-NOW). We identified correlated genes through permutations testing and prognostic features through multivariate cox models with backwards elimination.

Results: 4,400 patients were identified (median age 52yrs): 2,195 glioblastoma, 1,198 IDH1/2-mutant astrocytoma, 531 oligodendroglioma, 271 other IDH1/2-wildtype glioma, and 205 pediatric-type glioma. Molecular classification shifted 27.2% of gliomas from their original histopathologic designation. Genetic alterations showed unique correlations with clinical features. Non-TCGA patients had improved overall survival compared to TCGA patients, with 26.7%, 55.6%, and 127.8% longer survival for glioblastoma, IDH1/2-mutant astrocytoma, and oligodendroglioma respectively (p < 0.001). In the non-TCGA cohort, median survival of grade 2/3 IDH1/2-mutant astrocytomas more than doubled that of grade 4. Across subtypes, patients ≥65 years had lower median survival compared to younger patients. IDH1/2-mutation prevalence decreased with age while MGMT-methylation remained stable. In glioblastoma, increasing age, CDKN2A/B heterozygous or homozygous deletion, NF1 alteration, and PIK3CA/3R1 alteration were negatively prognostic. Receipt of chemotherapy, MGMT-methylation, 19q-gain, 21q-loss, and RB1 alteration were positively prognostic. In IDH1/2-mutant astrocytoma, negative prognostic features were CCND2 alteration, CDKN2A/B heterozygous or homozygous deletion, EGFR amplification, PDGFRA alteration, and 22q loss. White race was the only positively prognostic feature in IDH1/2-mutant astrocytomas. An aggressive subtype of IDH1/2-mutant astrocytoma was identified containing many of the identified negative prognostic features.

Conclusion : Survival of glioma patients has significantly changed over time, with new subtype-specific prognostic features emerging. These data establish an updated benchmark for comparison of future investigations and guiding patients.