P12.16.A PROGNOSTIC IMPLICATION OF CDKN2A/B HOMOZYGOUS DELETION ON HISTOLOGICAL GRADES IN IDH-MUTANT ASTROCYTOMAS: A SYSTEMATIC REVIEW AND META-ANALYSIS

Abstract BACKGROUND IDH-mutant astrocytomas (A-IDHm) with the homozygous deletion of CDKN2A/B (CDKN-HD) have been classified as grade 4 in the WHO 2021 classification (WHO2021). However, the results of previous studies that investigated the prognostic role of CDKN-HD in A-IDHm were mostly obtained by combining traditional histological grade (hG) II and -III or all grades. Thus, this present study determines how traditional hGs affect survival in patients with A-IDHm that were classified using CDKN-HD in accordance with the WHO2021. MATERIAL AND METHODS The frequency and prognostication of CDKN-HD in primary A-IDHm were analyzed based on hGs. A systematic review and meta-analysis were performed in accordance with the PRISMA guidelines using three databases. Effect sizes were evaluated using the hazard ratio (HR) and restricted mean survival time (RMST) for overall survival (OS). Individual patient data (IPD) were recorded if available, and relevant statistical data from the IPD were recalculated. Individual patient survival data was also extracted from the Kaplan-Meier curves. The risk of bias was assessed using the Joanna Briggs Institute’s critical appraisal checklist. RESULTS Thirty-three articles with 3739 A-IDHm patients were included. The pooled frequencies of CDKN-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. There was considerable between-study variance (τ2 = 1.06), and potential publication bias was identified in hG-II tumors compared to those in higher grades. CDKN-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), but it was not evident in hG-II due to the paucity of data. pHR showed better survival in patients with grade-2 tumors over grade-3 (WHO2021) (pHR 1.44, CI 1.09-1.90, P = 0.01), although the RMST difference was only 7.1 months at 100 months. In contrast, the RMST difference in the grade 4 group was larger by 10.2-20.6 months; the survival was the worst in hG-IV with CDKN-HD, middle in hG-III with CDKN-HD, and better in hG-IV without CDKN-HD. CONCLUSION CDKN-HD was rarely found in hG-II A-IDHm. The frequency of CDKN-HD increased with the hG and reached 39.1% in hG-IV. Although the prognosis of A-IDHm can be stratified by hG and CDKN-HD, evidence is insufficient for the classification of hG-II with CDKN-HD.