Epidermal Growth Factor Receptor (EGFR) Amplification and Survival in Patients With Glioblastoma: A Systematic Review...

Glioblastoma has been described as the most common and aggressive primary brain neoplasm in adults, with limited survival despite multimodal therapy. The prognostic impact of epidermal growth factor receptor (EGFR) amplification and its interaction with isocitrate dehydrogenase (IDH) mutation and O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation remains unclear. This systematic review and meta-analysis examined how EGFR amplification level and molecular profile affect overall survival (OS) in glioblastoma. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, a systematic review was performed for studies reporting OS stratified by EGFR amplification, MGMT methylation, or IDH mutation. Using a random-effects model, pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated, and I² statistics were employed to assess heterogeneity. Nine studies including 1,766 subjects were analyzed. Low or moderate EGFR amplification showed no OS impact (HR=0.98 (95% CI: 0.88-1.09); HR=0.94 (95% CI: 0.81-1.10)), whereas high amplification predicted worse survival (HR=1.19; 95% CI: 1.14-1.24; p<0.00001). EGFR amplification with MGMT methylation correlated with poorer outcomes (HR=1.38; 95% CI: 1.33-1.44), while EGFR amplification with unmethylated MGMT showed improved survival (HR=0.68; 95% CI: 0.61-0.76). Stratification by IDH status identified EGFR-negative/IDH-mutant tumors as the most favorable group (HR=0.44; 95% CI: 0.29-0.67) and EGFR-positive/IDH-wildtype as the least favorable (HR=1.33; 95% CI: 0.89-2.00). High EGFR amplification independently predicts worse survival in glioblastoma, particularly with MGMT promoter methylation and IDH-wildtype status. Integrating EGFR, MGMT, and IDH profiles refines prognostic assessment and supports personalized therapeutic strategies.