Abstract
IDH-mutant lower-grade gliomas (LGGs, grade 2 or 3) eventually transform into secondary grade 4 astrocytomas (sA<sub>IDHmut/G4</sub>). Here, we sought to describe the transformation time, risk factors, and outcomes in malignant transformation of IDH-mutant LGGs. We screened data for 108 patients with sA<sub>IDHmut/G4</sub> 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<sub>IDHmut/G4</sub>, and associated risk factors and outcomes. Malignant transformation was defined as pathological confirmation of grade 4 astrocytoma. 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; <i>P</i> = 0.001] and non-A blood type (HR, 0.37; 95% CI, 0.203-0.680; <i>P</i> = 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; <i>P</i> = 0.008), overall survival (HR, 0.50; 95% CI, 0.265-0.972; <i>P</i> = 0.041), and progression-free survival (HR, 0.25; 95% CI, 0.133-0.479; <i>P</i> < 0.0001) in patients with IDH-mutant gliomas. Radiotherapy is associated with delayed malignant transformation and improved survival in patients with IDH-mutant gliomas.
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