P3264 - The Tissue Systems Pathology Test Predicts Risk of Progression in Medicare-Eligible Patients with Barrett’s Esophagus

Award: Presidential Poster Award

Harshit S. Khara, MD¹, Jon M.. Davison, MD², John Goldblum, MD³, Prashanthi N. Thota, MD⁴, Lucas C.. Duits, MD, PhD⁵, Amir Khoshiwal, MSc⁵, Jacques J.. Bergman, MD, PhD⁵, Gary Falk, MD, MS, FACG⁶, Christian Smolko, PhD⁷, Mary Hall, MBA, PhD⁷, Jennifer J. Siegel, MA, PhD⁸, Rebecca J. Critchley-Thorne, PhD⁷, David L. Diehl, MD^1
1Geisinger Medical Center, Danville, PA; ²University of Pittsburgh School of Medicine, Pittsburgh, PA; ³Cleveland Clinic, Cleveland, OH; ⁴Cleveland Clinic Foundation, Cleveland, OH; ⁵Amsterdam University Medical Center, Amsterdam, Noord-Holland, Netherlands; ⁶University of Pennsylvania Perelman School of Medicine, Philadelphia, PA; ⁷Castle Biosciences, Pittsburgh, PA; ⁸Castle Biosciences, Friendswood, TX

Introduction: Accurate prediction of risk of progression to esophageal adenocarcinoma (EAC) is needed in patients with Barrett’s esophagus (BE), which disproportionately affects patients ≥ 65 years of age (Medicare-eligible), representing the majority of EAC cases diagnosed each year in the U.S. Multiple studies have validated that the tissue systems pathology (TSP-9) test predicts risk of neoplastic progression in patients with BE. This study evaluated the performance of TSP-9 for predicting risk of progression to high-grade dysplasia (HGD) or EAC in Medicare-eligible BE patients.

Methods: A pooled analysis was performed on data from 5 studies of 290 BE patients who were ≥ 65 years old with known outcomes, including 84 patients who progressed to HGD/EAC in 2.4 years (median; IQR 1.3 - 3.5). Data were also analyzed from a second cohort on clinical use of the TSP-9 test ordered by 356 physicians at 251 clinical sites for 2,078 BE patients ≥ 65 years old. The risk stratification performance of TSP-9 results and clinicopathologic variables was evaluated.

Results: In the pooled analysis of patients with known outcomes, TSP-9 demonstrated significantly higher sensitivity (64.0%; 95% CI 53.3 - 74.7) than expert pathology and real-world pathology (22.6%; 95% CI 13.3 - 33.3 and 38.7%; 95% CI 28.0 - 49.3, respectively; P < 0.05) in detecting patients who progressed to HGD/EAC. In multivariable analyses with clinicopathologic variables, TSP-9 was the strongest, independent predictor of progression to HGD/EAC (HR 7.2; 95% CI 4.2 - 14.2; P < 0.0001; Table, Fig. 1A). In the clinical use cohort, TSP-9 provided significant risk stratification in all evaluated subsets, identifying 17.7% of patients as high/intermediate risk for progression to HGD/EAC (Fig. 1B-E). Patients with NDBE who scored TSP-9 high risk had a higher 5-year progression risk (16.6%; IQR 13.7 - 25.0) than patients with LGD (6.1%; IQR 3.0 - 14.5; Fig. 1B).

Discussion: The TSP-9 test risk-stratifies BE patients ≥ 65 years old independently of clinicopathologic variables and has significantly higher sensitivity for detection of progressors than pathology diagnosis of LGD. In clinical use, the TSP-9 test identified a high-risk subset of NDBE patients who had a higher progression risk than patients with LGD, enabling early detection of patients requiring escalation of care to reduce the incidence of EAC. TSP-9 provides clinically impactful risk prediction in patients ≥ 65 years old to guide risk-aligned care for improved health outcomes.



Disclosures:


Harshit S. Khara, MD¹, Jon M.. Davison, MD², John Goldblum, MD³, Prashanthi N. Thota, MD⁴, Lucas C.. Duits, MD, PhD⁵, Amir Khoshiwal, MSc⁵, Jacques J.. Bergman, MD, PhD⁵, Gary Falk, MD, MS, FACG⁶, Christian Smolko, PhD⁷, Mary Hall, MBA, PhD⁷, Jennifer J. Siegel, MA, PhD⁸, Rebecca J. Critchley-Thorne, PhD⁷, David L. Diehl, MD¹. P3264 - The Tissue Systems Pathology Test Predicts Risk of Progression in Medicare-Eligible Patients with Barrett’s Esophagus, ACG 2023 Annual Scientific Meeting Abstracts. Vancouver, BC, Canada: American College of Gastroenterology.