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

Davison, Jon M.; Goldblum, John R.; Grewal, Udhayvir Singh; McGrath, Kevin; Fasanella, Kenneth E.; Deitrick, Christopher; DeWard, Aaron D.; Bossart, Emily A.; Hayward, Stephen L.; Zhang, Yi; Critchley-Thorne, Rebecca J.; Thota, Prashanthi N.

doi:10.14309/ajg.0000000000000556

Cited by 40 publications

(25 citation statements)

References 34 publications

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“…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 ).…”

Section: Discussionmentioning

confidence: 99%

“…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 ).…”

Section: Introductionmentioning

confidence: 99%

“…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.…”

Section: Introductionmentioning

confidence: 99%

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

Frei¹,

Konté²,

Bossart

et al. 2020

Clin Transl Gastroenterol

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Frei¹,

Konté²,

Bossart

et al. 2020

Clin Transl Gastroenterol

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“…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 .…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2021

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Background and study aims The TissueCypher Barrett’s Esophagus Assay is a novel tissue biomarker test, and has been validated to predict progression to high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC) in patients with Barrett’s esophagus (BE). The aim of this study was to evaluate the impact of TissueCypher on clinical decision-making in the management of BE. Patients and methods TissueCypher was ordered for 60 patients with non-dysplastic (ND, n = 18) BE, indefinite for dysplasia (IND, n = 25), and low-grade dysplasia (LGD, n = 17). TissueCypher reports a risk class (low, intermediate or high) for progression to HGD or EAC within 5 years. The impact of the test results on BE management decisions was assessed. Results Fifty-two of 60 patients were male, mean age 65.2 ± 11.8, and 43 of 60 had long segment BE. TissueCypher results impacted 55.0 % of management decisions. In 21.7 % of patients, the test upstaged the management approach, resulting in endoscopic eradication therapy (EET) or shorter surveillance interval. The test downstaged the management approach in 33.4 % of patients, leading to surveillance rather than EET. In the subset of patients whose management plan was changed, upstaging was associated with a high-risk TissueCypher result, and downstaging was associated with a low-risk result (P < 0.0001). Conclusions TissueCypher was used as an adjunct to support a surveillance-only approach in 33.4 % of patients. Upstaging occurred in 21.7 % of patients, leading to therapeutic intervention or increased surveillance. These results indicate that the TissueCypher test may enable physicians to target EET for TissueCypher high-risk BE patients, while reducing unnecessary procedures in TissueCypher low-risk patients.

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“…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.…”

Section: Introductionmentioning

confidence: 99%

Systematic Identification of Key Functional Modules and Genes in Esophageal Cancer

Zhuang

Sun

et al. 2020

Preprint

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Background: Esophageal cancer is associated with high incidence and mortality worldwide. Differential expression genes (DEGs) and weighted gene co-expression network analysis (WGCNA) are important methods to screen the core genes as bioinformatics methods.Methods: The DEGs and WGCNA were combined to screen the hub genes, and pathway enrichment analyses were performed on the hub module in the WGCNA. The CCNB1 was identified as the hub gene based on the intersection between DEGs and the greenyellow module in WGCNA. Expression levels and prognostic values of CCNB1 were verified in UALCAN, GEPIA2, HCMDB, Kaplan–Meier plotter, and TIMER databases.Results: We identified 1,044 DEGs form dataset GSE20347, 1,904 from GSE29001, and 2,722 from GSE111044, and 32 modules were revealed by WGCNA. The greenyellow module was identified as the hub module in the WGCNA. CCNB1 gene was identified as the hub gene, which was upregulated in tumour tissues. Moreover, esophageal cancer patients with higher expression of CCNB1 showed worse prognosis. However, CCNB1 doesn’t play an important role in immune cell infiltration.Conclusion Based on DEGs and key modules related to esophageal cancer, CCNB1 was identified as the hub gene, which offered novel insights into the development and treatment of esophageal cancer.

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

Cited by 40 publications

References 34 publications

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

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

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

Systematic Identification of Key Functional Modules and Genes in Esophageal Cancer

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