In MGMT-related subgroup analysis, temozolomide plus interferon alfa treatment showed significant improvement in the median OS of patients with MGMT unmethylation (24.7 [95% CI, 20.5-28.8] months in the temozolomide plus interferon alfa group vs 17.4 [95% CI, 14.1-20.7] months in the temozolomide group; HR, 0.57 [95% CI, 0.37-0.87]; P = .008) (Figure 3A)....In this randomized clinical trial, therapy consisting of temozolomide combined with interferon alfa prolonged the survival time of patients with newly diagnosed HGG, especially those with MGMT unmethylated tumors...we suggest that patients with MGMT unmethylated HGG receive temozolomide plus interferon alfa combination treatment.