Multicenter, prospective trial of non-endoscopic biomarker-driven detection of barrett’s esophagus and esophageal adenocarcinoma

BACKGROUND: Preliminary data suggest that an encapsulated balloon (EsoCheckTM), coupled with a two methylated DNA biomarker panel (EsoGuardTM), detects Barrett’s esophagus (BE) and esophageal adenocarcinoma (EAC) with high accuracy. The initial assay required sample freezing upon collection. AIM: Assess a next-generation EsoCheck sampling device and EsoGuard assay in a much-enlarged multicenter study clinically enhanced by utilizing a CLIA-compliant assay and samples maintained at room temperature. METHODS: Cases with nondysplastic BE (NDBE), dysplastic BE (indefinite=IND, low grade dysplasia = LGD, high grade dysplasia = HGD), EAC, junctional adenocarcinoma (JAC), plus endoscopy controls without esophageal intestinal metaplasia, were prospectively enrolled. Medical assistants at six institutions delivered the encapsulated balloon per orally, with inflation in the stomach. The inflated balloon sampled the distal 5 cm of the esophagus, then was deflated and retracted into the capsule, preventing sample contamination. EsoGuard bisulfite sequencing assayed levels of methylated Vimentin (mVIM) and methylated Cyclin A1 (mCCNA1). RESULTS: A total of 243 evaluable patients – 88 cases (median age 68, 78% men, 92% white) and 155 controls (median age 57, 41% men, 88% white) – underwent adequate EsoCheck sampling. Mean procedural time was approximately 3 minutes. Cases included 31 NDBE, 16 IND/LGD, 23 HGD, and 18 EAC/JAC. Thirty-seven (53%) non-dysplastic and dysplastic BE cases were short segment BE (SSBE; < 3 cm). Overall sensitivity was 85% (95% CI= 0.78-0.93), and specificity was 85% (95% CI=0.79-0.90). Sensitivity for NDBE was 84%. EsoCheck/EsoGuard detected 100% of cancers (n=18). CONCLUSION: EsoCheck/EsoGuard demonstrated high sensitivity and specificity in detecting BE and BE-related neoplasia.