Multicenter, Prospective Trial of Nonendoscopic Biomarker-Driven Detection of Barrett's Esophagus and Esophageal Adenocarcinoma

Helen R Moinova; Suman Verma; John Dumot; Ashley Faulx; Prasad G Iyer; Marcia Irene Canto; Jean S Wang; Nicholas J Shaheen; Prashanthi N Thota; Lishan Aklog; Joseph E Willis; Sanford D Markowitz; Amitabh Chak

doi:10.14309/ajg.0000000000002850

Multicenter, Prospective Trial of Nonendoscopic Biomarker-Driven Detection of Barrett's Esophagus and Esophageal Adenocarcinoma

Am J Gastroenterol. 2024 Nov 1;119(11):2206-2214. doi: 10.14309/ajg.0000000000002850. Epub 2024 Apr 30.

Authors

Helen R Moinova¹, Suman Verma², John Dumot¹, Ashley Faulx¹, Prasad G Iyer³, Marcia Irene Canto⁴, Jean S Wang⁵, Nicholas J Shaheen⁶, Prashanthi N Thota⁷, Lishan Aklog², Joseph E Willis^{8

9}, Sanford D Markowitz^{1

9

10}, Amitabh Chak^{1

9}

Affiliations

¹ Department of Medicine, Case Western Reserve University, and University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA.
² Lucid Diagnostics, New York, New York, USA.
³ Barrett's Esophagus Unit, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA.
⁴ Division of Gastroenterology and Hepatology, Department of Medicine, The Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
⁵ Division of Gastroenterology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.
⁶ Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, University of North Carolina, Chapel Hill, North Carolina, USA.
⁷ Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio, USA.
⁸ Department of Pathology, Case Western Reserve University, and University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA.
⁹ Seidman Cancer Center, University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA.
¹⁰ Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, Ohio, USA .

PMID: 38686933
PMCID: PMC11534537 (available on 2025-11-01)
DOI: 10.14309/ajg.0000000000002850

Abstract

Introduction: Preliminary data suggest that an encapsulated balloon (EsoCheck), coupled with a 2 methylated DNA biomarker panel (EsoGuard), detects Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) with high accuracy. The initial assay requires sample freezing upon collection. The purpose of this study was to assess a next-generation EsoCheck sampling device and EsoGuard assay in a much-enlarged multicenter study clinically enhanced by using a Clinical Laboratory Improvement Amendments of 1988-compliant assay and samples maintained at room temperature.

Methods: Cases with nondysplastic BE (NDBE), dysplastic BE (indefinite for dysplasia, low-grade dysplasia, high-grade dysplasia), EAC, junctional adenocarcinoma, plus endoscopy controls without esophageal intestinal metaplasia, were prospectively enrolled. Medical assistants at 6 institutions delivered the encapsulated balloon per orally with inflation in the stomach. The inflated balloon sampled the distal 5 cm of the esophagus and then was deflated and retracted into the capsule, preventing sample contamination. EsoGuard bisulfite sequencing assayed levels of methylated vimentin and methylated cyclin A1.

Results: A total of 243 evaluable patients-88 cases (median age 68 years, 78% men, 92% White) and 155 controls (median age 57 years, 41% men, 88% White)-underwent adequate EsoCheck sampling. The mean procedural time was approximately 3 minutes. Cases included 31 with NDBE, 16 with indefinite for dysplasia/low-grade dysplasia, 23 with high-grade dysplasia, and 18 with EAC/junctional adenocarcinoma. Thirty-seven NDBE and dysplastic BE cases (53%) were short-segment BE (<3 cm). Overall sensitivity was 85% (95% confidence interval 0.78-0.93) and specificity was 85% (95% confidence interval 0.79-0.90). Sensitivity for NDBE was 84%. EsoCheck/EsoGuard detected 100% of cancers (n = 18).

Discussion: EsoCheck/EsoGuard demonstrated high sensitivity and specificity in detecting BE and BE-related neoplasia.

Trial registration: ClinicalTrials.gov NCT00288119.

Publication types

Multicenter Study

MeSH terms

Adenocarcinoma* / diagnosis
Adenocarcinoma* / genetics
Adenocarcinoma* / pathology
Aged
Barrett Esophagus* / diagnosis
Barrett Esophagus* / genetics
Barrett Esophagus* / pathology
Biomarkers, Tumor / genetics
DNA Methylation*
Esophageal Neoplasms* / diagnosis
Esophageal Neoplasms* / genetics
Esophageal Neoplasms* / pathology
Female
Humans
Male
Middle Aged
Prospective Studies
Sensitivity and Specificity
Vimentin / metabolism

Substances

Biomarkers, Tumor
Vimentin

Supplementary concepts

Adenocarcinoma Of Esophagus

Associated data

ClinicalTrials.gov/NCT00288119