Validation of an Epigenetic Prognostic Assay to Accurately Risk-Stratify Patients With Barrett Esophagus

• Published in: The American journal of gastroenterology
• Main Authors: Laun, Sarah E., Kann, Lisa, Braun, Jerome, Gilbert, Stacey, Lunz, Daniel, Pierre, Francia, Kalra, Andrew, Ma, Ke, Tsai, Hua-Ling, Wang, Hao, Jit, Simran, Cheng, Yulan, Ahmed, Yousra, Wang, Kenneth K., Leggett, Cadman L., Cellini, Ashley, Ioffe, Olga B., Zaidi, Ali H., Omstead, Ashten N., Jobe, Blair, Korman, Louis, Cornish, Drew, Zellenrath, Pauline, Spaander, Manon, Kuipers, Ernst, Perpetua, Lorrie, Greenwald, Bruce D., Maddala, Tara, Meltzer, Stephen J.
• Format: Journal Article
• Language: English
• Published: 14.08.2024
• ISSN: 0002-9270; 1572-0241
• DOI: 10.14309/ajg.0000000000003030

INTRODUCTION: Esophageal adenocarcinoma (EAC) is the second-most lethal cancer in the United States, with Barrett esophagus (BE) being the strongest risk factor. Assessing the future risk of neoplastic progression in patients with BE is difficult; however, high-grade dysplasia (HGD) and early EAC are treatable by endoscopic eradication therapy (EET), with survival rates of 90%. Thus, it would be beneficial to develop a molecular assay to identify high-risk patients, who merit more frequent endoscopic surveillance or EET, as well as low-risk patients, who can avoid EET and undergo less frequent surveillance. METHODS: Deidentified endoscopic biopsies were acquired from 240 patients with BE at 6 centers and confirmed as future progressors or nonprogressors. Tissues were analyzed by a set of methylation-specific biomarker assays. Test performance was assessed in an independent validation set using 4 stratification levels: low risks, low-moderate risks, high-moderate risks, and high risks. RESULTS: Relative to patients in the low-risk group, high-risk patients were 15.2 times more likely to progress within 5 years to HGD or EAC. For patients in the high-risk category, the average risk of progressing to HGD or EAC within 5 years was 21.5%, 4-fold the BE population prevalence within 5 years, whereas low-risk patients had a progression risk of only 1.85%. DISCUSSION: This clinical assay, Esopredict, stratifies future neoplastic progression risk to identify higher-risk patients with BE who can benefit from EET or more frequent surveillance and lower-risk patients who can benefit from reduced surveillance.