Purpose: Patients with grade II/III diffuse glioma (lower grade glioma, LGG) with isocitrate dehydrogenase wild-type (IDH-wt) and telomerase reverse-transcriptase promoter mutation (TERTp-mut) experience shorter overall survival (OS) time than IDH mutant patients. The optimal treatment strategy for these patients is unclear. We compared the effects of radiotherapy (RT) alone vs. RT concurrent with temozolomide (TMZ) followed by adjuvant TMZ in these LGG patients. Patients and methods: Thirty-seven LGG patients with IDH-wt and TERTp-mut were randomly allocated to either RT alone treatment (RT group, n = 18; 60 Gy in 30 daily fractions) or RT concurrent with TMZ (75 mg/m(2)/d, 7 d/week) followed by adjuvant TMZ (CRT group, n = 19). The median follow-up duration was 17 months. Log-rank test was used for OS and PFS comparisons. Results: The 1-year OS rate was 94.1% [95% confidence interval (CI) 82.9-100] in the CRT group and 74.6% (95% CI, 52.9-96.4) in the RT group. The median OS values in the CRT and RT groups were statistically different [25 vs. 17 months, respectively; hazard ratio (HR) 0.271; 95% CI, 0.092-0.793; P = 0.017], while PFS values were not (16 vs. 7 months, respectively; HR, 0.917; 95% CI, 0.397-2.120; P = 0.840). Multivariate analysis indicated that CRT treatment and female sex were associated with significantly longer OS (P = 0.001, P = 0.016, respectively). Conclusion: CRT treatment for IDH-wt/TERTp-mut grade II/III gliomas resulted in significantly longer OS than RT alone. Female sex was a significant favorable prognostic factor. (C) 2021 The Authors. Published by Elsevier B.V.