AB003. Clinical analysis of central nervous system (CNS) World Health Organization (WHO) grade 4 gliomas with IDH-mutant versus IDH-wildtype focused on CDKN2A homozygous deletion.

BACKGROUND: We are primarily investigating the prognostic role of cell-cycle-dependent kinase inhibitor (CDKN)-2A homozygous deletion in central nervous system (CNS) World Health Organization (WHO) grade 4 gliomas. Additionally, traditional prognostic factors for grade 4 gliomas will be examined, and our results will be validated.

METHODS: We conducted a retrospective analysis of glioma cohorts in our institute. Medical records were reviewed for 142 glioblastoma patients for 15 years, and pathological slides were examined again for the updated diagnosis according to the 2021 WHO classification of CNS tumors. The isocitrate dehydrase (IDH) mutation and CDKN2A deletion were examined by next generation sequencing (NGS) analysis using ONCO accuPanel®. Traditional prognostic factors including age, WHO performance status, extent of resection, and O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation were examined.

RESULTS: After the exclusion of 6 patients with poor status of pathologic samples, 136 glioblastoma that were diagnosed by previous WHO criteria were changed into 29 (21.3%) astrocytoma, IDH-mutant, CNS WHO grade 4 and 107 (78.7%) glioblastoma, IDH-wildtype, CNS WHO grade 4. Among them, 61 patients (56.0%) had CDKN2A deletion. Group A with IDH-wildtype and CDKN2A deletion had a mean overall survival (OS) of 15.70 months [95% confident interval (CI): 13.86-17.54], group B with IDH-mutant and CDKN2A deletion had a mean OS of 19.37 months (95% CI: 13.43-25.30), group C with IDH-wildtype and intact CDKN2A had a mean OS of 22.63 months (95% CI: 20.10-25.17), and group D with IDH-mutant and intact CDKN2A had a mean OS of 33.38 months (95% CI: 29.35-37.40). Multifactor analysis showed following factors were independently associated with OS: age [≥50 vs. <50 years; hazard ratio (HR) 4.642], extent of resection (gross total resection vs. others; HR 5.523), WHO performance (0, 1 vs. 2; HR 5.007), MGMT promoter methylation, (methylated vs. unmethylated; HR 5.075), IDH mutation (mutant vs. wildtype; HR 6.358), and CDKN2A deletion (absence vs. presence; HR 13.452).

CONCLUSIONS: The presenting study suggests that CDKN2A deletion should play a powerful prognostic role in CNS WHO grade 4 gliomas as well as low-grade glioma. Even if CNS WHO grade 4 gliomas had mutant IDH, they can have poor clinical outcomes due to CDKN2A deletion.