Impact of EGFRA289T/V mutation on relapse pattern in glioblastoma

Abstract

Background: Molecular factors influence relapse patterns in glioblastoma. The hotspot mutation located at position 289 of the extracellular domain of the epidermal growth factor receptor (EGFR^A289mut) is associated with a more infiltrative phenotype. The primary objective of this study was to explore the impact of the EGFR^A289 mutation on the pattern of relapse after chemoradiotherapy-based treatment of patients suffering from newly diagnosed glioblastoma.

Patients and methods: An ancillary study from a prospective cohort of patients suffering from glioblastoma was conducted. All patients received radiotherapy and concomitant temozolomide. The population was divided into two groups according to EGFR^A289 status (mutated versus wild-type). The primary endpoint was the overlap score (varying from 0 to 1) between the initial irradiated tumor volume (Vinit) and the relapse volume (Vr). Secondary endpoints explored the impact of EGFR^A289mut on survival.

Results: One hundred twenty-eight patients were included and analyzed: 11% had EGFR^A289mut glioblastoma (n = 14/128). EGFR^A289mut glioblastomas had a relapse pattern that was more marginal than EGFR^A289wt glioblastomas: a median overlap score Vinit/Vr of 0.96 was observed in the EGFR^A289mut group versus 1 in the EGFR^A289wt group (P = 0.05). Half of the population with EGFR^A289mut tumor (n = 7/14) had a marginal relapse (i.e. overlap score^Vr/Vinit ≤ 0.95) compared to 23.7% (n = 27/114) in the EGFR^A289wt group, P = 0.035. EGFR^A289mut did not influence survival.

Conclusion: We highlighted a link between the EGFR^A289 mutation and the relapse pattern in glioblastoma. The independent role of EGFR^A289mut and its clinical implication should now be explored in further studies.

Keywords: EGFR; glioblastoma; mutation; overlap score; radiotherapy; relapse pattern.