2649 - Survival Impact of Histological vs. Molecular Glioblastoma: A Propensity Score-Matched Analysis

Purpose/Objective(s): Glioblastoma (GBM) is the most aggressive primary brain tumor, characterized by poor survival despite advancements in multimodal therapy. The incorporation of molecular classification has significantly reshaped prognostic assessment and treatment strategies. However, the survival impact of molecularly defined GBM (mGBM) compared to histologically classified GBM (hGBM) remains unclear. This study applies propensity score matching (PSM) to evaluate survival differences between hGBM and mGBM while adjusting for key clinical confounders.

Materials/Methods: We conducted a retrospective analysis of GBM patients, employing 1:1 nearest-neighbor PSM to balance cohorts based on age (<64 vs. =64 years), MGMT methylation status, and radiotherapy (RT) dose. Standardized mean differences were used to assess pre- and post-matching balance between groups. Kaplan-Meier survival estimates and log-rank tests were used to compare overall survival (OS) and progression-free survival (PFS).

Results: The matched cohort included 27 hGBM and 27 mGBM patients. The median OS for the entire cohort was 13.3 months. Among hGBM patients, median OS was 13.2 months for those <64 years and 11.7 months for those =64 years (p=0.571), while for mGBM patients, median OS was 19.5 months and 10.9 months, respectively (p=0.672). Significant OS differences were observed in MGMT-unmethylated patients, where mGBM conferred a survival advantage over hGBM (p=0.025). In contrast, no significant OS difference was observed in MGMT-methylated patients (p=0.497). RT dose also significantly influenced outcomes, with patients receiving RT 60/30 demonstrating superior OS (p=0.016). Notably, in patients receiving RT 40/15, hGBM demonstrated a significant advantage in PFS (p=0.012).

Conclusion: This study highlights the prognostic importance of molecular classification in GBM, particularly in MGMT-unmethylated patients, where mGBM demonstrates improved survival. Additionally, RT dose remains a crucial factor influencing survival, emphasizing the need for individualized treatment strategies. These findings support the ongoing evolution toward precision oncology in GBM management. Further validation in larger cohorts is warranted to refine molecularly guided therapeutic strategies and optimize patient outcomes.