PATH-79. High-grade astrocytoma with piloid features (HGAP) comprehensive update: histological grading, molecular markers and clinical outcomes

Abstract BACKGROUND HGAP was first described in 2018. However, prognostic factors of clinical outcome are not well-understood secondary to recent recognition and paucity of data for this diagnostic entity. Here, we utilize a large HGAP cohort (n=252) to survey the genomic landscape and explore prognostic correlates. METHODS NIH DNA methylation profiling was performed to identify HGAP cases and combined with publicly available datasets. Evaluable molecular markers, patient demographics, tumor location, imaging reports, treatment history (e.g. temozolomide, targeted therapy, surgery, and radiation) and survival data were assessed. Kaplan-Meier analysis was performed. RESULTS The cohort included cases that matched to HGAP on the NIH/Bethesda methylation classifier at ≥0.9 confidence score. More males (60%) than females (40%) were in the cohort. Twenty-one percent of patients were known to have neurofibromatosis type 1. Posterior fossa location was predominant (57%, n=131). Common genomic findings included alterations in NF1 (58%), ATRX (50%), FGFR1 (15%), TP53 (9%) and PIK3CA (8%). CDKN2A/B homozygous deletion was identified in 80% of cases. MGMT promoter methylation was found in 55% of cases. Median progression free survival (mPFS) was 24 months (mo), and median overall survival (mOS) was 108 mo. Central histological review revealed 67% of cases were high-grade. High-grade histopathology (brisk mitotic activity) was not associated with survival. Immunohistochemical ATRX loss was associated with shorter mPFS (18.0 mo vs 35.5 mo, p=0.04) and mOS (93.7 mo vs not reached, p=0.04). The presence of ATRX genetic alterations was associated with shorter mOS (30 mo vs not reached, p=0.008). CDKN2A/B homozygous deletion and MGMT status were not correlative with patient outcome. CONCLUSION HGAP is a glial neoplasm that shows frequent tumor recurrence. The majority of HGAP cases are high-grade. Our analysis of correlates with patient outcome suggests immunohistochemical ATRX loss and molecular ATRX alteration may be important poor prognostic markers.

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Journal
Neuro-Oncology
Published
2025-11-01
DOI
https://doi.org/10.1093/neuonc/noaf201.1031
Primary Topic
Glioma Diagnosis and Treatment
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article
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article

PATH-79. High-grade astrocytoma with piloid features (HGAP) comprehensive update: histological grading, molecular markers and clinical outcomes

Murat Gökden, Maria A. Gubbiotti, Julieann C. Lee, Calixto‐Hope G. Lucas et al.
Neuro-Oncology
Glioma Diagnosis and Treatment
article

PATH-79. High-grade astrocytoma with piloid features (HGAP) comprehensive update: histological grading, molecular markers and clinical outcomes

Murat Gökden, Maria A. Gubbiotti, Julieann C. Lee, Calixto‐Hope G. Lucas, Omkar Singh, Robert Macaulay, Sahara Cathcart, Vanessa Goodwill, William H. Yong, Shuodan Zhang, William C. McDonald, Christopher Mount, Osório Lopes Abath Neto, Patrick J. Cimino, Abir Mukherjee, Peter Pytel, Zied Abdullaev, Stephen Yip, Janna H. Neltner, Koping Chang, Kenneth Aldape, Roberta Seidman, Karen Dazelle, Krishna Bharani, Hope Richard, Jennifer Eschbacher, Daniel Brown, Cristina Vincentelli, Linda J. Szymanski, Richard Green, Matthew D. Wood, Suash Sharma, Nelli S. Lakis
article en

Abstract

Abstract BACKGROUND HGAP was first described in 2018. However, prognostic factors of clinical outcome are not well-understood secondary to recent recognition and paucity of data for this diagnostic entity. Here, we utilize a large HGAP cohort (n=252) to survey the genomic landscape and explore prognostic correlates. METHODS NIH DNA methylation profiling was performed to identify HGAP cases and combined with publicly available datasets. Evaluable molecular markers, patient demographics, tumor location, imaging reports, treatment history (e.g. temozolomide, targeted therapy, surgery, and radiation) and survival data were assessed. Kaplan-Meier analysis was performed. RESULTS The cohort included cases that matched to HGAP on the NIH/Bethesda methylation classifier at ≥0.9 confidence score. More males (60%) than females (40%) were in the cohort. Twenty-one percent of patients were known to have neurofibromatosis type 1. Posterior fossa location was predominant (57%, n=131). Common genomic findings included alterations in NF1 (58%), ATRX (50%), FGFR1 (15%), TP53 (9%) and PIK3CA (8%). CDKN2A/B homozygous deletion was identified in 80% of cases. MGMT promoter methylation was found in 55% of cases. Median progression free survival (mPFS) was 24 months (mo), and median overall survival (mOS) was 108 mo. Central histological review revealed 67% of cases were high-grade. High-grade histopathology (brisk mitotic activity) was not associated with survival. Immunohistochemical ATRX loss was associated with shorter mPFS (18.0 mo vs 35.5 mo, p=0.04) and mOS (93.7 mo vs not reached, p=0.04). The presence of ATRX genetic alterations was associated with shorter mOS (30 mo vs not reached, p=0.008). CDKN2A/B homozygous deletion and MGMT status were not correlative with patient outcome. CONCLUSION HGAP is a glial neoplasm that shows frequent tumor recurrence. The majority of HGAP cases are high-grade. Our analysis of correlates with patient outcome suggests immunohistochemical ATRX loss and molecular ATRX alteration may be important poor prognostic markers.

Neuro-OncologyVol. 27(Supplement_5)
University of Iowa (US), National Institutes of Health (US), St. Jude Children's Research Hospital (US), Abbott Northwestern Hospital (US), Hackensack University Medical Center (US), St. Joseph's Hospital and Medical Center (US), Kaiser Permanente (US), The University of Texas MD Anderson Cancer Center (US), University of Kentucky (US), Johns Hopkins University (US), Oregon Health & Science University (US), Virginia Commonwealth University (US), Johns Hopkins Medicine (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), Augusta University Health (US), Stony Brook School (US), Massachusetts General Hospital (US), Lehigh Valley Health Network (US), Mount Sinai Medical Center (US), University of California, Irvine Medical Center (US), National Institute of Neurological Disorders and Stroke (US), Ennetix (United States) (US), Kaiser Permanente West Los Angeles Medical Center (US), National Taiwan University Hospital (TW), Stanford Medicine (US), National Cancer Institute (US), Seattle University (US), University of Nebraska Medical Center (US), Stony Brook University (US), University of Arkansas for Medical Sciences (US)
Openalex Percentile: Top 52%
Glioma Diagnosis and Treatment
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