Prognostic significance of CDKN2A/B hemizygous deletion in IDH-mutant astrocytomas : a systematic review and meta-analysis

Abstract

The prognostic significance of CDKN2A/B hemizygous deletion (HemD) in IDH-mutant astrocytomas (A-IDHm) remains unclear. We conducted a systematic review and WHO grade-specific meta-analysis of primary tumors following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Effect sizes included hazard ratios (HRs) and restricted mean survival time (RMST) for overall survival. The pooled frequency of HemD in grade 2 A-IDHm was 13.8% (95% confidence interval [CI]: 8.5–21.7%; 12 studies; I2 = 23.6%), lower than that in grade 3 tumors (25.2% [CI: 20.5–30.5%; 12 studies; I2 = 0%]) and grade 4 tumors with CDKN2A/B non-homozygous deletion (29.5% [CI: 23.3–36.6%]; 11 studies; I2 = 0%). Stratification by WHO grade revealed a significant association in grade 2 tumors (pooled HR [pHR]: 1.98 [CI: 1.03–3.80]; four studies; 369 patients; P = 0.04; I2 = 0%), but no significant association in grade 3 (pHR: 1.78 [CI: 0.99–3.20]; five studies, 239 patients; P = 0.054; I2 = 0%) or grade 4 tumors (pHR: 1.39 [CI: 0.85–2.26]; five studies; 192 patients; P = 0.18; I2 = 0%). The RMST difference reached statistical significance only in WHO grade 2 tumors, suggesting a potential prognostic effect of HemD in low-grade A-IDHm.