IDH mutation and MGMT promoter methylation are associated with the pseudoprogression and improved prognosis of glioblastoma multiforme patients who have undergone concurrent and adjuvant temozolomide-based chemoradiotherapy

Abstract

Purpose: This study aimed to investigate the potential association between IDH mutation and O⁶-methyl-guanine methyl transferase (MGMT) gene promoter methylation and pseudoprogression disease (psPD) in glioblastoma multiforme (GBM) patients after concurrent temozolomide (TMZ)-based chemoradiotherapy.

Methods: A total of 157 GBM patients who received concurrent TMZ-based chemoradiotherapy were included in this retrospective study. The association between psPD and a number of demographic and genetic factors, including IDH mutation and MGMT promoter methylation, were analyzed based on logistic regression, Cox regression, and multivariate analysis.

Results: Of the 157 GBM patients, 145 (92.36%) patients, including 38 patients with psPD, 38 patients with early progression (ePD), and 69 patients with non-progression (non-PD), were followed up for six to 56 months. We identified a higher rate of MGMT promoter methylation and IDH1 mutation in psPD patients compared with ePD patients (P=0.002). In addition, MGMT promoter methylation and IDH1 mutation predicted a high probability of psPD development in GBM patients (P=0.001 and P<0.001, respectively). MGMT promoter methylation, IDH1 mutation, Karnofsky performance score (KPS) ≥70, and psPD were associated with a significantly longer overall survival of GBM patients (P=0.001, 0.001, 0.002, and P<0.001, respectively). Both of MGMT promoter methylation and IDH mutation had a cumulative effect on the OS of GBM patients. GBM patients with psPD (39.2±2.1months, P<0.001) had a longer median survival (MS) than GBM patients with ePD (11.9±1.1months) or with non-PD (24.4±2.4months).

Conclusion: MGMT promoter methylation and IDH1 mutation were associated with PsPD and predicted a longer median survival in GBM patients after TMZ-based chemoradiotherapy. Genetic analyses of the MGMT promoter and IDH1 may allow us to effectively treat GBM patients.

Keywords: Chemotherapy; Glioblastoma; IDH mutation; MGMT; Molecular genetics; Pseudoprogression.