High-grade astrocytoma with piloid features: a clinical and genomic analysis of prognostic factors using a large cohort.
Publication/Presentation Date
9-16-2026
Abstract
BACKGROUND: High-grade astrocytoma with piloid features (HGAP) is a recently defined tumor type that is not well-understood. Prognostic factors of clinical outcomes are not well-established.
METHODS: Methylation profiling was performed on tumor samples, many at the National Cancer Institute (NCI) Laboratory of Pathology, and others from publicly available sources. Methylation classifier scores of ≥ 0.90 to the HGAP class on the NCI-Bethesda classifier version 3 were included. Clinical features were collected from the medical record. Survival analyses were performed using the Kaplan-Meier and Cox-proportional hazards methods.
RESULTS: The cohort comprised 421 patients. There were high rates of ATRX alteration (62%), CDKN2A/B homozygous loss (78%) and MGMT promoter methylation (53%). MAPK alterations were identified in 74% of evaluable 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 negative prognostic factors. 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 prognosis included histologic high-grade features, CDKN2A/B homozygous deletion, MGMT promoter methylation, extent of resection, and presence of NF1 syndrome.
CONCLUSIONS: This large cohort establishes relative frequencies of several important markers. Additionally, older age, the presence of an ATRX alteration, and cystic features on MRI were found to be prognostic. Our work may aid in optimizing treatment regimens for patients with this tumor type.
ISSN
1523-5866
Published In/Presented At
Zhang, S., Singh, O., Dazelle, K., Quezado, M., Cimino, P. J., Abdullaev, Z., Wu, J., Lucas, C. H., Schreck, K. C., Holdhoff, M., Pytel, P., Goodwill, V., Macaulay, R., McDonald, W., Seidman, R., Wood, M., Bharani, K., Neltner, J., Richard, H., Chang, K., … Aldape, K. (2026). High-grade astrocytoma with piloid features: a clinical and genomic analysis of prognostic factors using a large cohort. Neuro-oncology, noag145. Advance online publication. https://doi.org/10.1093/neuonc/noag145
Disciplines
Medicine and Health Sciences
PubMedID
42747321
Department(s)
Department of Pathology and Laboratory Medicine
Document Type
Article