Algorithm Training and Testing for a Nonendoscopic Barrett’s Esophagus Detection Test in Prospective Multicenter Cohorts

• Published in: Clinical gastroenterology and hepatology Vol. 22; no. 8; pp. 1596 - 1604.e4
• Main Authors: Iyer, Prasad G., Slettedahl, Seth W., Mahoney, Douglas W., Giakoumopoulos, Maria, Olson, Marilyn C., Krockenberger, Martin, Taylor, William R., Foote, Patrick, Berger, Calise, Leggett, Cadman, Wu, Tsung-Teh, Antpack, Eduardo, Falk, Gary W., Ginsberg, Gregory G., Abrams, Julian A., Lightdale, Charles J., Ramirez, Francisco, Kahn, Allon, Wolfsen, Herbert, Konda, Vani, Trindade, Arvind J., Kisiel, John B.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.08.2024
• Subjects: Adenocarcinoma - diagnosis; Adenocarcinoma - pathology; Adult; Aged; Algorithms; Barrett Esophagus - diagnosis; Barrett Esophagus - pathology; Cohort Studies; Endoscopy; Esophageal Cancer; Esophageal Neoplasms - diagnosis; Esophageal Neoplasms - pathology; Female; Gastroenterology and Hepatology; Humans; Male; Middle Aged; Prognosis; Prospective Studies; Risk; Screening; Sensitivity and Specificity; IMGEJ; SS-NDBE; Prognosis; BE; HGD; IM; CCD; LS-NDBE; CI; EAC; LGD; Risk; GEJ; Screening; MDM; Esophageal Cancer; IND; intestinal metaplasia of the gastroesophageal junction; short-segment nondysplastic Barrett’s esophagus; long-segment nondysplastic Barrett’s esophagus; low-grade dysplasia; Barrett’s esophagus; indefinite for dysplasia; high-grade dysplasia; gastroesophageal junction; encapsulated sponge cell collection device; methylated DNA marker; esophageal adenocarcinoma; intestinal metaplasia; confidence interval
• ISSN: 1542-3565; 1542-7714; 1542-7714
• DOI: 10.1016/j.cgh.2024.03.003

Endoscopic Barrett’s esophagus (BE) and esophageal adenocarcinoma (EAC) detection is invasive and expensive. Nonendoscopic BE/EAC detection tools are guideline-endorsed alternatives. We previously described a 5-methylated DNA marker (MDM) panel assayed on encapsulated sponge cell collection device (CCD) specimens. We aimed to train a new algorithm using a 3-MDM panel and test its performance in an independent cohort. Algorithm training and test samples were from 2 prospective multicenter cohorts. All BE cases had esophageal intestinal metaplasia (with or without dysplasia/EAC); control subjects had no endoscopic evidence of BE. The CCD procedure was followed by endoscopy. From CCD cell lysates, DNA was extracted, bisulfite treated, and MDMs were blindly assayed. The algorithm was set and locked using cross-validated logistic regression (training set) and its performance was assessed in an independent test set. Training (N = 352) and test (N = 125) set clinical characteristics were comparable. The final panel included 3 MDMs (NDRG4, VAV3, ZNF682). Overall sensitivity was 82% (95% CI, 68%–94%) at 90% (79%–98%) specificity and 88% (78%–94%) sensitivity at 84% (70%–93%) specificity in training and test sets, respectively. Sensitivity was 90% and 68% for all long- and short-segment BE, respectively. Sensitivity for BE with high-grade dysplasia and EAC was 100% in training and test sets. Overall sensitivity for nondysplastic BE was 82%. Areas under the receiver operating characteristic curves for BE detection were 0.92 and 0.94 in the training and test sets, respectively. A locked 3-MDM panel algorithm for BE/EAC detection using a nonendoscopic CCD demonstrated excellent sensitivity for high-risk BE cases in independent validation samples. (Clinical trials.gov: NCT02560623, NCT03060642.) [Display omitted]