Abstract
BACKGROUND: Isocitrate dehydrogenase-mutant astrocytomas (A-IDHm) with the homozygous deletion of cyclin-dependent kinase 2A/B (CDKN2A/B-HD) have been classified as grade 4 in the WHO 2021 classification (WHO2021). This study aimed to find survival differences in subgroups stratified by CDKN2A/B status and traditional histological grades (hGs). METHODS: The frequency and prognostication of CDKN2A/B-HD in primary A-IDHm were analyzed based on hGs. A systematic review and meta-analysis were performed following the PRISMA guidelines using three databases (registration CRD42024570409). Effect sizes were evaluated using the hazard ratio (HR) and restricted mean survival time (RMST) for overall survival (OS). RESULTS: Thirty-three articles with 3739 A-IDHm patients were included. The pooled frequencies of CDKN2A/B-HD were 3.3% [95% confidence interval (CI): 1.9-5.8], 11.0% [CI: 8.6-14.0], and 39.1% [CI: 34.0-44.5] in hG-II, hG-III, and hG-IV, respectively, after excluding the outliers. CDKN2A/B-HD significantly impaired OS in patients with hG-III (pooled HR (pHR), 3.61; CI, 2.72-4.78) and hG-IV (pHR, 1.93; CI, 1.43-2.61), and it was not evident in hG-II due to the paucity of the data. pHR showed better survival in patients with grade-2 tumors over grade-3 (WHO2021) (pHR 1.44, CI 1.09-1.90, P = .01, 1184 patients), although the RMST difference was only 7.1 months at 100 months (N = 1162). Among the grade-4 tumors, CDKN2A/B-HD hG-IV had the worst survival (RMST at 60 months, 32 months). CONCLUSION: The prognosis of A-IDHm can be stratified by hG and CDKN2A/B-HD. However, evidence is insufficient for the classification of hG-II with CDKN2A/B-HD.