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