Abstract A057: High-grade astrocytoma with piloid features: a clinical and genomic analysis of prognostic factors using a large cohort

Abstract Background: High-grade astrocytoma with piloid features (HGAP) is a recently defined tumor type that is not well-understood. Prognostic factors of clinical outcome are not well-established. Methods: Samples were processed at the National Cancer Institute (NCI) Laboratory of Pathology, and published samples were included (n=421). Methylation classifier scores of ≥0.90 to the HGAP class on the NCI-Bethesda classifier were included. Clinical features were collected from the medical record. Kaplan-Meier survival analysis as well as Cox-proportional hazards was performed. Results: The cohort comprised 421 patients. There was a high rate of ATRX alteration (62%), CDKN2A/B loss (78%) and MGMT promoter methylation (53%). MAPK alterations were identified in 74% of samples. The median age was 46 years, and posterior fossa location was predominant (52%). The median overall survival (OS) was 88 months. Older age (p = 0.01) and the presence of an ATRX alteration (p = 0.04) were found to be poorly prognostic. The presence of cystic features on magnetic resonance imaging (MRI) was found to be favorably prognostic (p = 0.01). Factors that were not significantly associated with survival included histologic anaplasia, CDKN2A/B homozygous deletion, MGMT promoter methylation and surgery type. Conclusions: Utilizing a relatively large cohort of HGAP cases, this work establishes relative frequencies of several important markers, and additionally suggests older age, the presence of an ATRX alteration, and cystic features on MRI as prognostic. Our work may aid in identifying treatment regiments for patients with this tumor type. Citation Format: Shuodan Zhang, Omkar Singh, Karen Dazelle, HGAP manuscript co-authors, Kenneth Aldape. High-grade astrocytoma with piloid features: a clinical and genomic analysis of prognostic factors using a large cohort [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Brain Cancer; 2026 Mar 23-25; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2026;86(6_Suppl):Abstract nr A057.