Prognostic implications of epidermal and platelet-derived growth factor receptor alterations in 2 cohorts of IDHwt glioblastoma

Background: Glioblastoma remains a deadly brain cancer with dismal prognosis. Genetic alterations, including IDH mutations, 1p19q co-deletion status and MGMT promoter methylation have been proven to be prognostic and predictive to response to treatment in gliomas. In this manuscript, we aimed to correlate other mutations and genetic alterations with various clinical endpoints in patients with IDH-wild-type (IDHwt) glioblastoma. Methods: We compiled a comprehensive clinically annotated database of IDHwt GBM patients treated at the Ohio State University Wexner Medical Center for whom we had mutational data through a CLIA-certified genomic laboratory. We then added data that is publicly available from Memorial Sloan Kettering Cancer Center through cBioPortal. Each of the genetic alterations (mutations, deletions, and amplifications) served as a variable in univariate and multivariate Cox proportional hazard models. Results: A total of 175 IDHwt GBM patients with available MGMT promoter methylation data from both cohorts were included in the analysis. As expected, MGMT promoter methylation was significantly associated with improved overall survival (OS). Median OS for MGMT promoter methylated and unmethylated GBM was 26.5 and 18 months, respectively (HR 0.45; P =. 003). Moreover, EGFR/ERBB alterations were associated with favorable outcome (HR of 0.37 (P =. 003), but only in MGMT promoter unmethylated GBM. We further found that patients with EGFR/ERBB alterations who also harbored PDGFRA amplification had a significantly worse outcome (HR 7.89; P =. 025). Conclusions: Our data provide further insight into the impact of genetic alterations on various clinical outcomes in IDHwt GBM in 2 cohorts of patients with detailed clinical information and inspire new therapeutic strategies for IDHwt GBM.