Journal article
High-grade astrocytoma with piloid features: a clinical and genomic analysis of prognostic factors using a large cohort
Neuro-oncology (Charlottesville, Va.), Vol.28(10), pp.2435-2448
09/16/2026
DOI: 10.1093/neuonc/noag145
PMCID: PMC13635591
PMID: 42747321
Abstract
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.
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.
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.
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.
Details
- Title: Subtitle
- High-grade astrocytoma with piloid features: a clinical and genomic analysis of prognostic factors using a large cohort
- Creators
- Shuodan Zhang - Johns Hopkins UniversityOmkar Singh - National Cancer InstituteKaren Dazelle - National Cancer InstituteMartha Quezado - National Cancer InstitutePatrick J Cimino - National Cancer InstituteZied Abdullaev - National Cancer InstituteJing Wu - National Cancer InstituteCalixto-Hope Lucas - Johns Hopkins UniversityKarisa C Schreck - Johns Hopkins UniversityMatthias Holdhoff - Johns Hopkins UniversityPeter Pytel - University of ChicagoVanessa Goodwill - University of San DiegoRob Macaulay - Moffitt Cancer CenterWilliam McDonald - Allina HealthRoberta Seidman - Stony Brook UniversityMatthew Wood - Oregon Health & Science UniversityKrishna Bharani - Stanford UniversityJanna Neltner - University of KentuckyHope Richard - Virginia Commonwealth UniversityKoping Chang - National Taiwan University HospitalLinda Szymanski - Hackensack University Medical CenterStephen Yip - Vancouver General HospitalAbir Mukherjee - Lehigh Valley Health NetworkOsorio Lopes Abath Neto - University of IowaSuash J Sharma - Augusta UniversityRichard Green - Kaiser PermanenteDaniel Brown - RealNetworks (United States)Maria A Gubbiotti - The University of Texas MD Anderson Cancer CenterLeomar Y Ballester - The University of Texas MD Anderson Cancer CenterJennifer Eschbacher - Barrow Neurological InstituteMatthew Smith-Cohn - Barrow Neurological InstituteMurat Gokden - University of Arkansas for Medical SciencesCristina Vincentelli - Mount Sinai Medical CenterWilliam Yong - University of California, Irvine Medical CenterJulieann Lee - St. Jude Children's Research HospitalChristopher Mount - Massachusetts General HospitalJoseph Fulmer - Beaumont HospitalMichael Sun - Brigham and Women's HospitalKeith Ligon - Brigham and Women's HospitalMariarita Santi - Children's Hospital of PhiladelphiaEmily Ling-Lin Pai - Children's Hospital of PhiladelphiaGabrielle Yeaney - Cleveland ClinicSanda Alexandrescu - Boston Children's HospitalRavi Raghavan - Loma Linda University Medical CenterIgor Fernandes - Laboratório BacchiGerald Feliz Reis - Memorial Regional HospitalJacob Mandel - Baylor College of MedicineDario Caccamo - Mercy General HospitalShilpa Rao - National Institute of Mental Health and NeurosciencesOmar H Butt - Washington University in St. LouisSonika Dahiya - Washington University in St. LouisSara Stone - University of MichiganKyle Conway - University of MichiganMacLean P Nasrallah - Hospital of the University of PennsylvaniaChristine Fuller - SUNY Upstate Medical UniversityAngus Toland - University of Colorado DenverRimas V Lukas - Northwestern UniversityDavid Cachia - UMass Memorial Health CareErik Uhlmann - Beth Israel Deaconess Medical CenterMatthew McCord - University of VirginiaJeffrey Helgager - University of Wisconsin–MadisonKaram Han - University of Wisconsin–MadisonArie Perry - University of California, San FranciscoSandra Perez - University of California, San FranciscoElena Daoud - The University of Texas Southwestern Medical CenterDarby BeDell - University of MinnesotaHilary Highfield - Norton HealthcarePeter Kobalka - The Ohio State UniversityJ Stephen Nix - Walmart (United States)Edjah Nduom - Emory UniversityStewart Neill - Emory UniversityMark Gilbert - Fred Hutch Cancer CenterNelli Lakis - The University of Kansas Health SystemAdriana Fonseca - Children's NationalColette Shen - University of North Carolina at Chapel HillRebecca Yoda - University of WashingtonLenore Monterroza - Inova Fairfax HospitalAdam L Cohen - Virginia Cancer InstituteSahara Cathcart - University of Nebraska Medical CenterM D Al Amin - Mayo Clinic in ArizonaJian Campian - Mayo Clinic in ArizonaKenneth Aldape - Mayo Clinic in Arizona
- Resource Type
- Journal article
- Publication Details
- Neuro-oncology (Charlottesville, Va.), Vol.28(10), pp.2435-2448
- DOI
- 10.1093/neuonc/noag145
- PMID
- 42747321
- PMCID
- PMC13635591
- NLM abbreviation
- Neuro Oncol
- ISSN
- 1523-5866
- eISSN
- 1523-5866
- Publisher
- Oxford University Press
- Grant note
- U.S. Department of Health and Human Services National Institutes of Health
Open Access funding is provided by the National Institutes of Health (NIH). This research was supported (in part) by the Intramural Research Program of the NIH. The contributions of the NIH authors were made as part of their official duties as NIH federal employees, are in compliance with agency policy requirements, and are considered Works of the United States Government. However, the findings and conclusions presented in this paper are those of the authors and do not necessarily reflect the views of the NIH or the U.S. Department of Health and Human Services.
- Language
- English
- Electronic publication date
- 09/16/2026
- Academic Unit
- Pathology
- Record Identifier
- 9985230785102771
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