Independent Validation of a Tissue Systems Pathology Assay to Predict Future Progression in Nondysplastic Barrett's Esophagus: A Spatial-Temporal Analysis

Abstract

INTRODUCTION: An automated risk prediction assay has previously been shown to objectively identify patients with nondysplastic Barrett's esophagus (NDBE) who are at increased risk of malignant progression. To evaluate the predictive performance of the assay in 76 patients with NDBE of which 38 progressed to high-grade dysplasia/esophageal adenocarcinoma (progressors) and 38 did not (nonprogressors) and to determine whether assessment of additional (spatial) levels per endoscopy and/or multiple (temporal) time points improves assay performance. METHODS: In a blinded, nested case-control cohort, progressors and nonprogressors were matched (age, sex, and Barrett's esophagus length). All random biopsy levels from the baseline endoscopy (spatial samples) and all available previous endoscopies back to 10 years before progression (temporal samples) were assayed. Because the 1:1 ratio of progressors to nonprogressors does not reflect the real-world Barrett's population, negative and positive predictive values were adjusted for prevalence. RESULTS: Seventy-six patients (58 men), mean age of 63 ± 9 years, were studied. A high-risk score was associated with a prevalence-adjusted annual progression rate of 6.9%. The assay identified 31% of progressors when assessing a single biopsy level from the baseline endoscopy. Sensitivity increased to 50% and 69% in spatial and temporal analyses, respectively, while specificity remained at 95%. DISCUSSION: The assay identified a significant subset of NDBE patients who progress at a rate comparable with published estimates for expert-confirmed low-grade dysplasia. Assessing additional spatial and temporal biopsies increased the predictive accuracy, allowing for identification of most future progressors. Additional studies will evaluate the predictive performance of the assay in low-prevalence settings.

Barrett's esophagus: The pathomorphological and molecular genetic keystones of neoplastic progression

“…Use of TissueCypher in patients with NDBE is of great interest: rate of progression in high-risk patients established by TissueCypher is comparable to rate of progression in patients with LGD. 166,167 These results allow us to choose personalized treatment for patients with BE. In a prospective study, TissueCypher result influenced management decisions for choosing surveillance interval or method of treatment (endoscopic eradication therapy) in 55% cases.…”

Today’s Mistakes and Tomorrow’s Wisdom in Development and Use of Biomarkers for Barrett’s Esophagus

“…Additionally, more insights in expression of biomarkers over time (temporal distribution) may be useful in personalizing surveillance intervals. If a biomarker predicts progression early and reliable with little variation over time, patients with a low risk of progression may undergo more lenient surveillance [41]. One of the first studies evaluating biomarker over space and time was published by Li et al in 2014 [42].…”

“…Interestingly, sensitivity increased to 50% when multiple levels were assessed. This underlines the importance for future research to either identify a biomarker represented in the majority of the BE segment or to collect material from a wider area than with four-quadrant forceps biopsies, which are prone to sampling error [41].…”

Implications of Recent Revelations from Basic and Clinical Studies of Barrett’s Esophagus for Screening and Surveillance Strategies

“…These results have been validated further in several subsequent case-control and retrospective cohort studies. [34][35][36] Promising as these results are, American GI societies have not yet endorsed the use of biomarkers for routine management of patients with Barrett esophagus.…”