Chemoradiotherapy with temozolomide vs. radiotherapy alone in patients with IDH wild-type and TERT promoter mutation histological grade 2/3 gliomas: An extension retrospective analysis of a randomized controlled trial

Abstract

Background: Given the poor prognosis of IDH wild-type (IDH-wt) and telomerase reverse transcriptase promoter mutation (TERTp-mut) histological grade 2 to 3 gliomas, the World Health Organization has reclassified it as molecular glioblastoma. However, the effectiveness of chemoradiotherapy (CRT) in these patients remains unclear, especially in comparison to radiotherapy alone (RT). This study aims to assess CRT's efficacy in this population. Methods: A prospective randomized study was conducted at Beijing Tiantan Hospital from 2016 to 2019, enrolling 37 patients with histologically confirmed grade 2/3 IDH-wt/TERTp-mutant gliomas. Patients were randomly assigned to receive either RT (n = 18) or CRT (n = 19). After preliminary analysis showed a significant overall survival (OS) benefit in the CRT group, the study cohort was expanded from 2020 to 2022 by recruiting an additional 21 patients who all received CRT. Primary endpoints were OS and progression-free survival (PFS). Results: The final cohort comprised 58 patients (RT, 18; CRT, 40) with a median follow-up of 43.7 months (range, 7.9–75.1). CRT significantly improved OS compared to RT alone, with a median OS of 25.8 versus 17.2 months (hazard ratio, 0.31; 95% CI, 0.16–0.62; p =.001) and 2-year OS rate of 63.0% versus 16.7%. PFS also favored CRT, showing median PFS of 14.2 versus 7.1 months (hazard ratio, 0.38; 95% CI, 0.21–0.70; p =.002) and 1-year PFS rate of 56.6% versus 33.3%. Multivariable analysis confirmed CRT benefits were independent of O6-methylguanine-DNA methyl-transferase (MGMT) status (OS, p =.001; PFS, p =.002). Treatment was well-tolerated with no grade ≥3 toxicities in the CRT group. Conclusion: CRT significantly improves survival in IDH-wt/TERTp-mut grade 2 to 3 gliomas with favorable safety. Clinical trial registration: Trial registry name: CCRT With Temozolomide Versus RT Alone in Patients With IDH Wild-type/TERT Promoter Mutation Grade II/III Gliomas. Registration identification number: NCT02766270. URL for the registry: https://clinicaltrials.gov/study/NCT02766270?cond=NCT02766270&rank=1.