Abstract Low-grade glioma (LGG) with infiltrative nature and frequent growth in eloquent area in brain often makes total resection impossible. Although post-radiation adjuvant temozolomide (TMZ) is the standard of care for high-grade gliomas, and radiotherapy and/or TMZ are recommended for the treatment of residue low-grade gliomas, the efficacy of combined radiotherapy with adjuvant TMZ for residue LGG remains to be defined. We have initiated a randomized clinical trial in 2012 to test whether radiotherapy with subsequent TMZ chemotherapy will improve survival of patients with residue LGG compared to radiotherapy alone. This study was approved by the Ethics Committee of the Sun Yat-sen University Cancer Center, Guangzhou, China (approval No. 5010-2012-03) and was registered with ClinicalTrials.gov (NCT01649830). Inclusion Criteria: Patients age of 18 years to 60 years, with incompletely resected supratentorial WHO grade 2 astrocytoma, oligodendroglioma or oligodendroastrocytoma. Enrolled patients were randomized into: radiation therapy alone (RT) or radiotherapy with subsequent TMZ chemotherapy (RC) group. Start Date: July 2012, Estimated Primary Completion Date:August 2025. Radiation therapy will start within 8 weeks after neurosurgical procedures, with a total dose of 54.0 Gy in 27 - 30 fractions over 6 - 7 weeks. Four weeks after radiotherapy, patients in RC group will receive 6 cycle of TMZ dosed at 200 mg/m2 daily for 5 consecutive days, repeated every 28 days. We have completed enrollment on December 2018 with valid cases of 248 patients. Up to last follow-up date of Feb. 2023, 204 cases were analyzed (see table). There is no significant difference between RT group and RC group on both PFS and OS (5-year PFS 68.9% vs 75.2%, p=0.680; 5-year OS 92.0% vs 86.0%, p=0.400). Longer follow-up and molecular subgroup analysis are currently on the way, which could show benefit in special molecular subgroup.