Prognostic Value of EGFR Amplification in Glioblastoma Patients Treated with Radiation Therapy and Concurrent Temozolomide

Methylguanine methyltransferase (MGMT) promotor methylation status has been identified as a prognostic as well as predictive biomarker in glioblastoma (GBM) patients treated with temozolomide. Epidermal growth factor receptor (EGFR) amplification has been investigated in GBM; however, the role of EGFR as a prognostic marker remains controversial in the literature, especially in the context of MGMT status. In this study, we evaluated the prognostic effect of EGFR amplification in GBM patients and explored its interaction with the MGMT status. Eligibility criteria included glioblastoma with known MGMT promotor methylation and EGFR amplification status, who received standard radiation therapy (RT) and temozolomide between 2010 and 2018. Glioblastomas with IDH mutations were excluded. The MGMT promotor methylation was detected by methylation specific PCR whereas EGFR amplification was detected by fluorescence in situ hybridization (FISH) or next generation sequencing. Chi-square test was performed to evaluate the association between MGMT and EGFR status. Overall survival (OS) rates were analyzed with Kaplan-Meier method. Cox regression analyses were performed to determine if EGFR was associated with survival and to explore statistical interaction with MGMT status. A total of 202 patients with IDH-wildtype GBM were included in the analysis. Ninety-one patients (45.0%) had EGFR amplification. The median OS of the entire cohort was 14.3 months (95% CI 11.9-16.6). When stratified by the EGFR status, the median OS was not significantly different between those with EGFR amplification vs those without: 15.3 months (95% CI 10.6-19.9) vs 13.9 months (95% CI 10.9-17.0), respectively, p = 0.56. There was no association between EGFR amplification and MGMT methylation (p = 0.56). If stratified by MGMT status, EGFR amplification was still not prognostic for OS (MGMT methylated subset: HR: 1.44, 95% CI 0.78-2.66, p = 0.24; MGMT unmethylated subset: HR: 0.88, 95% CI: 0.58-1.34, p = 0.55). On multivariate Cox analysis for OS, EGFR amplification showed no significant interaction with MGMT status. EGFR amplification status does not appear to be prognostic for IDH-wildtype GBM treated neither with standard chemoradiotherapy nor to have any statistical interaction with MGMT status.