CDKN2A/B status and histological grade independently predict post-recurrence survival in recurrent IDH-mutant...

Homozygous deletions of cyclin-dependent kinase inhibitor 2 A/B (CDKN2A/B) are recognized as poor prognostic markers in newly diagnosed IDH-mutant astrocytomas. However, a standardized definition of CDKN2A/B homozygous deletion has not yet been established. Furthermore, the prognostic significance of CDKN2A/B homozygous and hemizygous deletions at recurrence remains unclear. In this study, we investigated the prognostic impact of CDKN2A/B homozygous and hemizygous deletions in patients with recurrent IDH-mutant astrocytomas. We conducted a retrospective review of 32 patients treated at our institution between January 2006 and March 2023. CDKN2A/B homozygous and hemizygous deletions were defined as relative CDKN2A/B copy numbers of < 0.4 and < 0.7, respectively, as determined by multiplex ligation-dependent probe amplification. Univariate analysis demonstrated that both homozygous and hemizygous deletions at first recurrence were associated with shorter post-recurrence survival. Multivariable analysis identified both deletion types and histological grade at first recurrence as independent prognostic factors. Risk stratification based on histological grade and CDKN2A/B status effectively predicted survival outcomes following recurrence. In conclusion, CDKN2A/B status, alongside histological grading, represents an independent prognostic indicator in recurrent IDH-mutant astrocytoma.