Angi-19. Leptomeningeal Disease and Intraparenchymal Dissemination in Patients With Glioblastoma and Idh-Mutant High-Grade Astrocytoma Harboring Cdkn2a/B Homozygous Deletion: A Case Series

INTRODUCTION CDKN2A/B homozygous deletion is associated with poor prognosis and aggressive tumor behavior. It is a marker of high proliferative potential, which may facilitate invasion beyond the primary tumor site, including the leptomeninges. The incidence and clinical behavior of leptomeningeal disease (LMD) in these patients is not well defined. METHODS In this retrospective single-institution review, we analyzed deceased adult patients with glioblastoma IDH-wildtype (GBM) and IDH-mutant astrocytoma grade 4 (AIDHm) harboring CDKN2A/B homozygous deletion who were evaluated at Jersey Shore University Medical Center from January 2022 through April 2025. All deletions were identified through next-generation sequencing in all patients at diagnosis. RESULTS We identified 28 patients harboring CDKN2A/B homozygous deletion (26 GBM patients and 2 AIDHm patients). Median age was 67 (28-83); 21 were male. Radiographically LMD was diagnosed in 8/28 (28%): 7/26 (27%) GBM patients and 1/2 (50%) AIDHm patients. 3/8 patient with LMD underwent lumbar puncture; all had negative cytology. Mean overall survival (OS) for the GBM cohort was 12.2 months (2–25). Mean OS for GBM with LMD was 9.2 months (3–15). Mean time from diagnosis to LMD was 6.9 months (1–14), with mean OS of 2.4 months (0.4–9) after LMD diagnosis. Out of the 2 AIDHm patients, 1 developed LMD 15 months from diagnosis and died 7 months later, and 1 developed extracranial osseous metastasis 11 months from diagnosis and died one month later. 9/28 (32%) patients developed multifocal dissemination at progression and 8/28 (28%) presented with multifocal disease. CONCLUSION Leptomeningeal disease occurred in 28% of glioma patients harboring CDKN2A/B homozygous deletion and multifocal disease occurred in 60% of the patients either at diagnosis or progression. These findings suggest CDKN2A/B homozygous deletion may contribute to aggressive dissemination and poor survival. These results underscore the need for early surveillance strategies and further research into dissemination mechanisms.