Radiotherapy delays malignant transformation and prolongs survival in patients with IDH-mutant gliomas

OBJECTIVE: IDH-mutant lower-grade gliomas (LGGs, grade 2 or 3) eventually transform into secondary grade 4 astrocytomas (sA(IDHmut/G4)). Here, we sought to describe the transformation time, risk factors, and outcomes in malignant transformation of IDH-mutant LGGs. METHODS: We screened data for 108 patients with sA(IDHmut/G4) in the Chinese Glioma Genome Atlas who had initial IDH-mutant LGGs and underwent reoperation during 2005–2021. We evaluated the transformation time from IDH-mutant LGGs to sA(IDHmut/G4), and associated risk factors and outcomes. Malignant transformation was defined as pathological confirmation of grade 4 astrocytoma. RESULTS: The median age of the 108 patients with IDH-mutant LGGs was 35 years (range, 19–54); the median age at transformation was 40 years (range, 25–62); and the median follow-up time for all patients was 146 months (range, 121–171). The average transformation time was 58.8 months for all patients with LGGs (range, 5.9–208.1); 63.5 and 51.9 months for grade 2 and 3 gliomas, respectively; and 58.4 and 78.1 months for IDH-mutant/1p/19q-non-codeleted astrocytomas and IDH-mutant/1p/19q-codeleted oligodendrogliomas, respectively. Univariate and multivariate analysis indicated that radiotherapy [hazard ratio (HR), 0.29; 95% confidence interval (CI), 0.137–0.595; P = 0.001] and non-A blood type (HR, 0.37; 95% CI, 0.203–0.680; P = 0.001) were protective factors against delayed malignant transformation. Radiotherapy was associated with improved survival after transformation (HR, 0.44; 95% CI, 0.241–0.803; P = 0.008), overall survival (HR, 0.50; 95% CI, 0.265–0.972; P = 0.041), and progression-free survival (HR, 0.25; 95% CI, 0.133–0.479; P < 0.0001) in patients with IDH-mutant gliomas. CONCLUSIONS: Radiotherapy is associated with delayed malignant transformation and improved survival in patients with IDH-mutant gliomas.