MGMT Gene Promoter Methylation as a Potent Prognostic Factor in Glioblastoma Treated with Temozolomide-Based Chemoradiotherapy: A Single-Institution Study

Abstract

Purpose: Recently, cells deficient in O6-methylguanine–DNAmethyltransferase (MGMT) were found to show increased sensitivity totemozolomide (TMZ). We evaluated whether hypermethylation of MGMT wasassociated with survival in patients with glioblastoma multiforme (GBM).Methods and Materials: We retrospectively analyzed 93 patients withhistologically confirmed GBM and who received involved field radiotherapywith TMZ from 2001 to 2008. The median age was 58 years (range, 24-78).Surgical resection was total in 39 patients (42%), subtotal in 30 patients (32%),partial in 17 patients (18%), and only a biopsy was performed in seven patients(8%). Post-operative radiotherapy began within 3 weeks of surgery in 87% ofthe patients. Radiotherapy doses ranged from 50-74 Gy (median 70 Gy).MGMT gene methylation was determined in 78 patients; MGMT wasunmethylated in 43 patients (55%) and methylated in 35 patients (45%). Themedian follow-up period was 22 months (range, 3-88) for all patients.Results: The median overall survival (OS) was 22 months, and progression-freesurvival (PFS) was 11 months. MGMT gene methylation was an independentlysignificant prognostic factor for both OS (p=0.002) and PFS (p=0.008) inmultivariate analysis. The median OS was 29 months for the methylated group,and 20 months for the unmethylated group. In 35 patients with methylatedMGMT genes, the 2-year and 5-year OS rates were 54% and 31%, respectively.Six patients with combined prognostic factors of methylated MGMT genes,≤50 years, and total/subtotal resections are all alive 38-77 months afteroperation, whereas the median OS in eight patients with unmethylated MGMTgenes, >50 years, and less than subtotal resection was 13.2 months.Conclusion: We confirmed that MGMT gene methylation is a potentprognostic factor in patients with GBM. Our results suggest that earlypost-operative radiotherapy and a high total/subtotal resection rate might furtherimprove the outcome.