Sa1204 COMPARATIVE OUTCOMES OF CRYOTHERAPY ABLATION FOR TREATMENT NAÏVE DYSPLASTIC BARRETT'S ESOPHAGUS STRATIFIED BY BASELINE HISTOLOGY

Background: Predicting progression in patients with Barrett's esophagus (BE) without conventional low-grade or high-grade dysplasia (LGD/HGD, in which dysplasia involves both the crypt and surface epithelium) is challenging.There is a need for tools to risk stratify these patients in order to prevent cancer development.Dysplasia initially develops in the bases of crypts ("crypt dysplasia", CD).However, the crypt bases in BE often show nuclear atypia that approaches, but does not reach, the diagnostic criteria of dysplasia.The predictive significance of crypt atypia grade is unknown.Multiple studies have shown that a risk prediction test (TissueCypher Barrett's Esophagus Assay) can predict progression in BE, but this test has not yet been evaluated in crypt atypia.Aim: To evaluate the histologic degree of crypt atypia to predict neoplastic progression in BE patients, and to evaluate TissueCypher in this regard.Methods: A nested case-control study was conducted with BE patients who progressed to HGD/EAC (n=39) and matched patients with surveillance showing no progression (n=179, median surveillance 7 years).Baseline biopsies without conventional LGD/HGD were tested blindly with the risk prediction test that stratifies patients into low-, intermediate-and high-risk for progression to HGD/EAC within 5 years.The same biopsies were scored blindly on a 4-point scale: 1. Grade 1 atypia (nuclear enlargement without stratification); 2. Grade 2 (partial stratification); 3. Grade 3 (full crypt stratification); Grade 4 (full stratification with marked pleomorphism).The predictive performance of the two risk stratification methods was compared.Results: Patients with grade 4 atypia progressed at a significantly higher rate than patients with grade 1, 2 or 3 (Fig. 1A,p=0.0008).The sensitivity of grade 4 atypia in identifying progressors was 8.8%.There was a trend towards increased rate of progression from grades 1-3, but this was not significant (p=0.09,Fig. 1A).The risk prediction test provided significant risk stratification (p=0.0003,Fig. 1B), and identified 2.5x as many progressors as grade 4 atypia with sensitivity of 22.4%.The test identified a subset of patients with grade 1/2 atypia that progressed at a higher rate (4.6%/ year) than patients with grade 3/4 atypia (1.6%/year).Multivariate Cox analysis showed that the high-risk class provided predictive power that was independent of clinical variables and atypia grade.Conclusions: The level of crypt atypia in BE patients without conventional LGD or HGD demonstrated predictive significance of progression to HGD/EAC.However, TissueCypher provided superior risk stratification that outperformed crypt atypia scores.The TC risk prediction test identified an "at-risk" subset of non-dysplastic BE patients that may benefit from increased surveillance and early therapeutic intervention.