Spatiotemporal Study of a Risk-Stratification Epigenetic-Based Biomarker Assay in Barrett's Esophagus Patients.

Abstract

Background: Barrett's esophagus (BE) is the strongest known risk factor for developing esophageal adenocarcinoma (EAC), the second-most lethal cancer in the United States. Esopredict is a novel validated methylation-based biomarker assay that provides precise quantification of neoplastic progression risk in BE patients. Inherit challenges, including tissue heterogeneity, sampling error, interobserver variability, and inconsistent adherence to surveillance biopsy guidelines may impact Esopredicts' predictive value results obtained at different anatomic locations or different sampling time points.

Methods: To investigate the spatiotemporal performance of Esopredict across multiple spatiotemporal sampling points, we profiled 220 biopsies obtained from 58 BE patients, including 11 patients with overlapping spatial and temporal biopsies. We focused on spatial profiling (i.e., multiple biopsies obtained at several anatomic locations during a single endoscopy and temporal profiling (i.e., biopsies obtained from multiple endoscopies performed at different time points). Each patient had an initial histologic diagnosis of nondysplastic Barrett's esophagus (NDBE), indefinite for dysplasia (IND), or low-grade dysplasia (LGD). Final follow-up (endpoint) biopsies showed either HGD or EAC (progressors); or NDBE, IND, or LGD (non-progressors). Biopsies were analyzed with Esopredict to compute a progression risk score, which quantified the likelihood of future progression to HGD or EAC within 5 years.

Results: In 52 spatially profiled patients, Esopredict demonstrated a sensitivity of 81% (17/21 progressor patients), based on the highest-scoring biopsy from each patient; sensitivity increased to 100% (12/12) when endpoint biopsies occurred within 5 years of the index (initial) biopsy. In 28 temporally profiled patients, sensitivity was 100% (8/8 patients), based on the biopsy performed at the timepoint closest to the endpoint biopsy.

Conclusion: Esopredict showed high predictive performance in multiple spatiotemporal samples in BE patients. These data further support the use of Esopredict as a robust test to distinguish high-risk BE patients, who may benefit from endoscopic eradication therapy or increased surveillance frequency, from low-risk patients, who may be candidates for less frequent surveillance and non-interventive observation.