Independent Blinded Validation of a Tissue Systems Pathology Test to Predict Progression in Patients With Barrett's Esophagus

Abstract

INTRODUCTION: A risk prediction test was previously validated to predict progression to high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC) in patients with Barrett's esophagus (BE). The aim of our study was to independently validate this test to predict the risk of progression to HGD/EAC in BE patients with nondysplastic (ND), indefinite for dysplasia and low-grade dysplasia (LGD). METHODS: A single-blinded, case-control study was conducted to stratify patients with BE as low, intermediate, or high risk for progression to HGD/EAC within 5 years using a previously described risk prediction test. Patients with BE who progressed to HGD/EAC after at least 1 year (n = 58) were matched to patients undergoing surveillance without progression (n = 210, median surveillance 7 years). Baseline biopsies with subspecialist diagnoses of ND, indefinite for dysplasia, or LGD were tested in a blinded manner, and the predictive performance of the test was assessed. RESULTS: This risk prediction test stratified patients with BE based on progression risk with the high-risk group at 4.7-fold increased risk for HGD/EAC compared with the low-risk group (95% confidence interval 2.5–8.8, P < 0.0001). Prevalence-adjusted positive predictive value at 5 years was 23%. The high-risk class and male sex provided predictive power that was independent of pathologic diagnosis, age, segment length, and hiatal hernia. Patients with ND BE who scored high risk progressed at a higher rate (26%) than patients with subspecialist-confirmed LGD (21.8%) at 5 years. DISCUSSION: A risk prediction test identifies patients with ND BE who are at high risk for progression to HGD/EAC and may benefit from early endoscopic therapy or increased surveillance.

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

“…Applying this risk prediction assay on all NDBE cases would thus allow prophylactic treatment of 50% of all cancer progressors and significantly reduce the risk of the remaining patients. In addition to a recent study ( 14 ), we demonstrate a persistent high specificity in parallel with increasing sensitivity while testing multiple levels, thus patients will not be harmed (for example by a false-positive high-risk score) by testing additional levels. A recent study used Markov decision modeling and simulation to evaluate the cost-effectiveness of care guided by this risk prediction assay vs the current standard of care from the perspective of a large US health care system ( 26 ).…”

“…Finally, a multivariable classifier integrates the quantitative features to produce a risk score that ranges from 0 to 10 and risk classes (low, intermediate, or high risk) for progression to HGD/EAC within 5 years. This computational pathology approach has been demonstrated to objectively identify NDBE patients who are at increased risk of incident progression independent from other clinical risk factors ( 13 , 14 ). Moreover, recent findings suggest that this risk prediction assay may capture a field effect because BE patients with prevalent HGD/EAC were discriminated from patients with no evidence of HGD/EAC ( 15 ).…”

“…Moreover, recent findings suggest that this risk prediction assay may capture a field effect because BE patients with prevalent HGD/EAC were discriminated from patients with no evidence of HGD/EAC ( 15 ). Although the most recent of these studies evaluated the spatial distribution of the assay results in a subset of the evaluated patients ( 14 ), the spatial distribution and temporal distribution of the assay results in NDBE patients have not been well characterized.…”

TissueCypher Barrett’s esophagus assay impacts clinical decisions in the management of patients with Barrett’s esophagus

“…The TissueCypher Barrett’s Esophagus Assay has been developed and validated in five multi-institutional studies to predict progression from ND, IND, and LGD to HGD and EAC, and also to detect prevalence of HGD/EAC in BE that can be missed on surveillance endoscopy 20 21 22 23 24 . TissueCypher utilizes a multiplexed fluorescence imaging platform that objectively extracts quantitative data on multiple epithelial, stromal, and morphometric features in intact tissue specimens 25 26 .…”

Systematic Identification of Key Functional Modules and Genes in Esophageal Cancer

“…The reliability of such approaches encounter limitation due to variation in endoscopic sampling site and observer's experience, and may lead to unnecessary biopsies, costs, and high false-positive rates. Even the molecular and cellular changes may appear indolent in endoscopic histology to avoid surveillance [10,11]. Thus, it's of extremely urgent to explore novel approaches or biomarkers to ameliorate the early detection, treatment guidance and prognosis prediction for patients.…”