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 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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Journal
Neuro-Oncology
Published
2026-09-16
DOI
https://doi.org/10.1093/neuonc/noag145
Primary Topic
Glioma Diagnosis and Treatment
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article
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article

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

Omar H. Butt, Murat Gökden, Maria A. Gubbiotti, G. F. Reis et al.
Neuro-Oncology
Glioma Diagnosis and Treatment
article

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

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

Abstract

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.

Neuro-Oncology
Northwestern University (US), University of North Carolina at Chapel Hill (US), University of Iowa (US), Brigham and Women's Hospital (US), Boston Children's Hospital (US), Loma Linda University Medical Center (US), University of Minnesota (US), UMass Memorial Health Care (US), St. Jude Children's Research Hospital (US), Beth Israel Deaconess Medical Center (US), Cleveland Clinic (US), Hackensack University Medical Center (US), RealNetworks (United States) (US), Barrow Neurological Institute (US), Allina Health (US), Walmart (United States) (US), Children's Hospital of Philadelphia (US), Children's National (US), Kaiser Permanente (US), The University of Texas MD Anderson Cancer Center (US), University of Wisconsin–Madison (US), University of Kentucky (US), Johns Hopkins University (US), University of Kansas (US), Emory University (US), University of San Diego (US), Oregon Health & Science University (US), University of California, San Francisco (US), Baylor College of Medicine (US), Virginia Commonwealth University (US), University of Washington (US), Norton Healthcare (US), SUNY Upstate Medical University (US), Washington University in St. Louis (US), Augusta University (US), Loma Linda University (US), University of Michigan (US), Worcester Memorial Hospital (US), Hospital of the University of Pennsylvania (US), Inova Fairfax Hospital (US), Mercy General Hospital (US), The University of Kansas Health System (US), Vancouver General Hospital (CA), Moffitt Cancer Center (US), University of California San Diego (US), University of Chicago (US), Massachusetts General Hospital (US), Fred Hutch Cancer Center (US), Memorial Medical Center (US), Lehigh Valley Health Network (US), Laboratório Bacchi (BR), Mount Sinai Medical Center (US), University of California, Irvine Medical Center (US), Virginia Cancer Institute (US), Mayo Clinic in Arizona (US), Kaiser Permanente West Los Angeles Medical Center (US), University of Kansas Medical Center (US), National Taiwan University Hospital (TW), National Cancer Institute (US), Beaumont Hospital (US), Memorial Regional Hospital (US), Boston Children's Museum (US), Joe DiMaggio Children's Hospital (US), University of Virginia (US), The Ohio State University (US), University of Nebraska Medical Center (US), Stony Brook University (US), National Institute of Mental Health and Neurosciences (IN), University of Arkansas for Medical Sciences (US), The University of Texas Southwestern Medical Center (US), University of Colorado Denver (US), Stanford University (US)
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Glioma Diagnosis and Treatment
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