Methylation of MGMT promoter does not predict response to temozolomide in patients with glioblastoma in Donostia Hospital

Larraitz Egaña,Nicolas Samprón,Jorge Villanua,Jaione Auzmendi-Iriarte,Joaquin Andermatten,Arrate Querejeta,Alejandro Elua-Pinin,Paula Aldaz,Felix Zubia,Irune Ruiz,Ander Matheu,Cristina Sarasqueta

doi:10.1038/s41598-020-75477-9

Abstract

O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status has been considered a prognostic factor in newly diagnosed glioblastoma (GBM). In this study, we evaluated the prognostic and predictive value of MGMT promoter methylation in patients with glioblastoma in Donostia Hospital. Surprisingly, methylation of MGMT promoter did not predict response to temozolomide in patients with glioblastoma in Donostia Hospital. Specifically, overall survival (OS) and progression-free survival (PFS) did not differ significantly by MGMT methylation status in our cohort. In contrast, both were longer in patients who received treatment, received more TMZ cycles, had a better general status and perform at least a partial resection. No association was detected between methylation of MGMT promoter and molecular markers such as ATRX, IDH, p53 and Ki67. These results indicate that MGMT methylation did not influence in patient survival in our cohort.

Highlights

We sought to assess whether methylation of the MGMT promoter was a predictor of response to TMZ in patients diagnosed with GBM in our hospital; we wanted to determine whether its predictive value is independent of age, functional status and relevant molecular markers
We excluded cases of GBM initially diagnosed as low-grade glioma that evolved to GBM over time. 18 of 334 patients were anaplastic astrocytoma, the rest were glioblastoma or
The median progression-free survival (PFS) was 6 months

Summary

Introduction

We sought to assess whether methylation of the MGMT promoter was a predictor of response to TMZ in patients diagnosed with GBM in our hospital; we wanted to determine whether its predictive value is independent of age, functional status and relevant molecular markers. The older the age the greater the probability of having methylated MGMT (61.1% among patients ≥ 65 years old, 45.8% among those between 50 and 64 years old, and 34.7% among under-50-yearolds, p < 0.043), the differences were not found to be significant in the multivariate analysis (Tables 2 and 3).

Results

Conclusion