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

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ID: 328713
2026
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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.
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Authors Shuodan Zhang, Omkar Singh, Karen Dazelle, Martha Quezado, Patrick J. Cimino, Zied Abdullaev, Jing Wu, Calixto-Hope Lucas, Karisa C Schreck, Matthias Holdhoff, Peter Pytel, Vanessa Goodwill, Rob Macaulay, William McDonald, Roberta Seidman, Matthew Wood, Krishna Bharani, Janna Neltner, Hope Richard, Koping Chang, Linda Szymanski, Stephen Yip, Abir Mukherjee, Osório Lopes Abath Neto, Suash J. Sharma, Richard Green, Daniel Brown, Maria A. Gubbiotti, Leomar Y. Ballester, Jennifer Eschbacher, Matthew Smith-Cohn, Murat Gökden, Cristina Vincentelli, William Yong, Julieann Lee, Christopher Mount, Joseph Fulmer, Michael Sun, K. Ligon, Mariarita Santi, Emily Ling-Lin Pai, Gabrielle Yeaney, Sanda Alexandrescu, Ravi Raghavan, Igor Fernandes, G. F. Reis, Jacob Mandel, Dario Caccamo, Shilpa Rao, Omar H. Butt, Sonika Dahiya, Sara Stone, Kyle Conway, MacLean P. Nasrallah, Christine Fuller, Angus Toland, Rimas V Lukas, David Cachia, Erik Uhlmann, Matthew McCord, Jeffrey Helgager, Karam Han, Arie Perry, Sandra Perez, Elena Daoud, Darby Bedell, Hilary Highfield, Peter Kobalka, J Stephen Nix, Edjah Nduom, Stewart Neill, Mark Gilbert, Nelli Lakis, Adriana Fonseca, Colette Shen, Rebecca Yoda, Lenore Monterroza, Adam L. Cohen, Sahara Cathcart, M D Al Amin, Jian Campian, Kenneth Aldape
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Journal journal of neuro-oncology
Year 2026
DOI
10.1093/neuonc/noag145
URL
https://doi.org/10.1093/neuonc/noag145
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