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