Abstract
Abstract Purpose: High-grade glioma (HGG), the most common form of primary brain tumor, is highly lethal and treatment options remain limited. Despite advances in genomic technologies, there are few molecular biomarkers to guide precision medicine for HGG. Here, we aimed to identify the clinicogenomic features associated with HGG prognosis and recurrence patterns. Methods: Our single-institution retrospective analysis included 220 patients initially diagnosed with adult HGG (grade 3 or 4) who underwent next-generation sequencing targeting 82 brain tumor-relevant genes. The patients were categorized according to the 2021 WHO classification and their clinical status, survival, genomic profile, and recurrence patterns were analyzed. Results: At a median follow-up of 23 months (ranges, 2-59 months), 180 patients (82%) showed either progression or recurrence. A total of 15% of patients were reclassified under the 2021 WHO classification, revealing a clear separation of progression-free survival (PFS) and overall survival (OS) curves between grades 3 and 4 gliomas. We found that TP53 mutations were significantly associated with the occurrence of distant progression, especially in grade 4 gliomas. Additionally, TP53 mutations were more common in patients with higher Ki67 index and subependymal/leptomeningeal seeding, indicating an increased risk of distant progression in TP53-mutated grade 4 glioma patients. Following multivariate Cox regression analysis, TP53 mutations were independent predictors of OS (hazard ratio [HR]=1.47, P=0.039) and distant PFS (HR=1.71, P=0.005). Conclusion: Considering the elevated risk of distant progression in grade 4 gliomas with TP53 mutations, our results underscore the necessity for additional research into the most effective treatment approaches for these patients. Keywords: high-grade glioma, TP53, pattern of failure, distant progression, next-generation sequencing Citation Format: Byung-Hee Kang, Seungbok Lee, Joo Ho Lee. Clinicogenomic anlaysis reveals a role for TP53 mutations in distant progression of high-grade glioma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7656.
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