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

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

Helen R Moinova  1 , Suman Verma  2 , John Dumot  1 , Ashley Faulx  1 , Prasad G Iyer  3 , Marcia Irene Canto  4 , Jean S Wang  5 , Nicholas J Shaheen  6 , Prashanthi N Thota  7 , Lishan Aklog  2 , Joseph E Willis  8   9 , Sanford D Markowitz  1   9   10 , Amitabh Chak  1   9
Affiliations
Multicenter Study

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

Helen R Moinova et al. Am J Gastroenterol. .

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.

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Conflict of interest statement

• Specific author contributions: S.D.M. and A.C. designed the study; A.C. wrote and submitted the clinical protocol; P.N.T, A.F., J.D., A.C., P.G.I., M.I.C., J.S.W., and N.J.S. recruited patients, treated patients, and obtained research tissue samples; J.E.W. performed pathology review of the biopsy samples; S.V. and L.A. oversaw biomarker assays; H.R.M. and S.D.M. analyzed the data; H.R.M., S.D.M., and A.C. wrote the manuscript. All authors reviewed and approved the final manuscript.

Author Conflict of Interest/Study Support:

• Guarantor of the article: Sanford D. Markowitz

• Potential competing interests: Drs. Chak, Willis, and Markowitz are scientific founders and stockholders of Lucid Diagnostics. Drs. Chak, Willis, Markowitz, and Moinova are consultants to Lucid Diagnostics. Drs. Chak, Markowitz, Willis and Moinova are inventors on patents assigned to Case Western Reserve University and licensed to Lucid Diagnostics. These include awarded patents on the use of methylated Vimentin for detection of Barrett’s esophagus and other GI cancers (SM, JW, AC), an awarded patent on a balloon-based device for non-endoscopic sampling of the esophagus (SM JW, AC); pending patents on methylated CCNA1 (SM, JW, AC, HM), and pending patents on composition of buffers for preserving DNA methylation (SM, HM). Patent interests are managed under institutional conflict of interest policies. Awarded patents include: U.S. Patent 9580754, Methods and Compositions for Detecting Gastrointestinal and Other Cancers; U.S. Patent 8415100, Methods and Compositions for Detecting Gastrointestinal and Other Cancers; U.S. Patent 8221977, Methods and Compositions for Detecting Colon Cancers; US Patent 10,660,621, Device for Collecting a Biological Sample. Pending patents include: PCT/US2010/030084, Digital quantification of DNA methylation; PCT/US2015/068131, Methods and compositions for detecting esophageal neoplasias and metaplasias; PCT/US2017/040708, Methods and compositions for detecting esophageal neoplasias and/or metaplasias in the esophagus. S.D.M also holds a sponsored research agreement with Lucid Diagnostics and has consulting relationships with Amgen. A.C. has consulting relationships with US Endoscopy and MicroTech and has research funding from C2 Therapeutics. N.J.S. consults for Shire, Ambu, Cook Medical, and Boston Scientific and has research funding from Medtronic, C2 Therapeutics, CSA Medical, EndoStim, CDx Medical, and Interpace Diagnostics. P.G.I. consults for Medtronic and has research funding from Exact Sciences, Intromedic, and C2 Therapeutics. M.I.C. consults for Pentax Medical Corporation and Cook Medical and has research funding from C2 Therapeutics, Inc. J.D. consults for US Endoscopy and CSA Medical and has research funding from C2 Therapeutics. SV and LA are employees and stockholders of Lucid Diagnostics. No other financial conflicts of interest pertain to the authors of this paper.

• ClinicalTrials.gov ID: NCT00288119 Genetic Determinants of Barrett’s Esophagus and Esophageal Adenocarcinoma (FBE).

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