Impact of EGFR(A289T/V) mutation on relapse pattern in glioblastoma

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.