Combined IDH1 mutation and MGMT methylation status on long-term survival of patients with cerebral low-grade glioma

• A consecutive series of 55 patients with low grade glioma (LGG, WHO grade II) treated in our institute between 1983 and 2013 were retrospectively reviewed to determine the prognostic factors for survival.
• A mutation in IDH1 was positively correlated with methylation of MGMT.
• A better prognosis was significantly associated with combined IDH1 mutation and MGMT methylation status, as well as histology and tumor size.

ObjectiveThe management of low-grade glioma (LGG) still remains controversial because the effectiveness of early and extensive resection is unclear, and the use of radiation therapy or chemotherapy is not well-defined. In particular, the importance of prognostic factors for survival remains a matter of discussion. The purpose of this study was to validate prognostic factors for survival in patients with LGG.Materials and methodsA consecutive series of 55 patients with WHO grade II LGG treated in our institute between 1983 and 2013 were retrospectively reviewed to determine the prognostic factors for survival. All data were retrospectively analyzed from the aspect of baseline characteristics, pathological findings, genetic change, surgical treatments, adjuvant therapies, and survival time. Cox multivariate analysis was performed to determine the prognostic factors for survival.ResultsThere were 28 patients with diffuse astrocytoma (DA), 21 patients with oligodendroglioma (OG), and 6 patients with oligoastrocytoma (OA) diagnosed on initial surgery. The median overall survival was 193 months and fifteen patients (27.3%) died. A mutation in isocitrate dehydrogenase-1 (IDH1) was found in 72.9% of LGG, and this mutation was positively correlated with methylation of O6-methylguanine-DNA methyltransferase (MGMT) (p = 0.02). A better prognosis was significantly associated with combined IDH1 mutation and MGMT methylation status (both positive vs both negative, HR 0.079 [95% CI 0.008–0.579], p = 0.012), as well as histology (OG vs DA and OA, HR 0.158 [95% CI 0.022–0.674], p = 0.011) and tumor size (<6 cm vs ≥6 cm, HR 0.120 [95% CI 0.017–0.595], p = 0.008).ConclusionsTumor histology, size and IDH-mutation status are important predictors for prolonged overall survival in patients with LGG and may provide a reliable tool for standardizing future treatment strategies.