BURDEN OF ESOPHAGEAL CANCER IN EOSINOPHILIC ESOPHAGITIS (ESCAPE STUDY)

NCT07102329 | Completed

• 1 other identifier: ESCAPE-1
• Study Type: observational
• Target: 100,000
• Locations: 1 country
• Sites: 1

Brief Summary

Eosinophilic esophagitis (EoE) is a chronic, immune-mediated inflammatory disorder of the esophagus that can lead to symptoms such as dysphagia and food impaction. In recent years, a potential association between EoE and esophageal cancer (EC) has been proposed, though evidence remains inconsistent and may be influenced by overlapping conditions like gastroesophageal reflux disease (GERD) and Barrett's esophagus (BE). The purpose of this study was to determine whether patients with EoE are at increased risk of developing esophageal cancer, and to clarify whether any observed risk is intrinsic to EoE or instead related to coexisting GERD or BE. The main research question was: Is eosinophilic esophagitis independently associated with an increased risk of esophageal cancer, or is this risk mediated by overlapping conditions such as GERD or Barrett's esophagus? To address this, we conducted a retrospective, multicenter cohort study using real-world data from TriNetX, a global federated health research network aggregating electronic medical records from approximately 100 million patients.

Conditions

Eosinophilic Esophagitis (EoE)

Keywords

Eosinophilic Esophagitis; Esophageal Cancer; Gastroesophageal Reflux Disease; Barrett Esophagus; Risk

Outcome Measures

Primary Outcomes (1)

• Hazard Ratio (HR) of esophageal cancer (EC) in EoE cohort A versus controls

  Hazard ratios (HRs) and 95% confidence intervals (CIs) for EC development in cohort A versus controls, derived from Cox proportional hazards models, where cohort assignment served as the primary covariate. The proportional hazards assumption was evaluated using the generalized Schoenfeld residuals method.

  from January 2000 to July 2025

Secondary Outcomes (3)

• Hazard Ratio (HR) of esophageal cancer (EC) in EoE cohort B versus controls

  From January 2000 to July 2025

• Hazard Ratio (HR) of adenocarcinoma (EAC) or squamous cell carcijoma (SCC in EoE cohort A versus controls

  from January 2000 to July 2025

• Hazard Ratio (HR) of adenocarcinoma (EAC) or squamous cell carcijoma (SCC in pure EoE cohort B versus controls

  from January 2000 to July 2025

Other Outcomes (3)

• Hazard Ratio (HR) and Risk Difference (RD) of EC, SCC and EAC in cohort A vs cohort B

  from January 2000 to July 2025

• Estimate the incidence, prevalence proportion (/100,000 persons) and incidence rate (100,000 persons/year) for EC overall, EAC and SCC in cohort A and cohort B

  from January 2000 to July 2025

• Estimate the incidence, prevalence proportion (/100,000 persons) and incidence rate (100,000 persons/year) for GERD and BE in cohort A

  from January 2000 to July 2025

Study Arms (3)

A) primary cohort of EoE patients

The primary cohort of the main analysis was built to include all eosinophilic esophagitis (EoE) patients, therefore implementing the ICD-10 code specific for the disease (K20.0). In order not to include other eosinophilic gastrointestinal disorders (EGIDs) primary cohort was built excluding the following ICD-10(ICD-9) codes: * K52.81: Eosinophilic Gastritis or Gastroenteritis * K52.82: Eosinophilic Colitis * K558.4: Eosinophilic gastroenteritis and colitis Following diagnosis were excluded if happened on or before the index event: * ICD-10-K22.7 Barrett Esophagus * ICD-10-K22.71 Barrett Esophagus with dysplasia * ICD-10-K22.711 Barrett Esophagus with high-grade dysplasia * ICD-10-K22.719 Barrett Esophagus with dysplasia, unspecified * ICD-10-K22.710 Barrett Esophagus with low-grade dysplasia * ICD-10-K22.1 Ulcer of the esophagus * ICD-10-K22.10 Ulcer of the esophagus without bleeding * ICD-10-K22.11 Ulcer of the esophagus with bleeding * ICD-10-C15 Esophageal cancer

Cohort B: Pure EoE without BE/GERD

The secondary cohort (Cohort B) of the main analysis was built to include all eosinophilic esophagitis (EoE) patients, therefore implementing the ICD-10 code specific for the disease (K20.0). In order not to include other eosinophilic gastrointestinal disorders (EGIDs) leading to confounding clinical profiles, this primary cohort was built excluding the following ICD-10(ICD-9) codes: * K52.81: Eosinophilic Gastritis or Gastroenteritis * K52.82: Eosinophilic Colitis * K558.4: Eosinophilic gastroenteritis and colitis To eliminate the confounding effect of BE and objective GERD was built with the exclusion from cohort A of the following diagnosis: * ICD-10-K22.7 Barrett Esophagus * ICD-10-K22.71 Barrett Esophagus with dysplasia * ICD-10-K22.711 Barrett Esophagus with high-grade dysplasia * ICD-10-K22.719 Barrett Esophagus with dysplasia, unspecified * ICD-10-K22.710 Barrett Esophagus with low-grade dysplasia * ICD-10-K22.1 Ulcer of the esophagus * ICD-10-K22.11 Ulcer of the esophagus with bleeding

Control group

The control group cohort was built in order to minimize the risk of selection bias, using the general code for "encounter for general examination without complaint, suspected or reported diagnosis" ICD-10 Z00 with the exclusion of the following codes related to EoE diagnosis (ICD10-K20.0). In order to minimize the overestimation of time-to-event risk of primary outcome, the following diagnosis were excluded if happened on or before the index event: * ICD-10-K22.7 Barrett Esophagus * ICD-10-K22.71 Barrett Esophagus with dysplasia * ICD-10-K22.711 Barrett Esophagus with high-grade dysplasia * ICD-10-K22.719 Barrett Esophagus with dysplasia, unspecified * ICD-10-K22.710 Barrett Esophagus with low-grade dysplasia * ICD-10-K22.1 Ulcer of the esophagus * ICD-10-K22.10 Ulcer of the esophagus without bleeding * ICD-10-K22.11 Ulcer of the esophagus with bleeding * ICD-10-C15 Esophageal cancer To restrict the number of patients in the control group only patients with an "ambulatory" encounter.

Eligibility Criteria

• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

\- EoE diagnosed patients according to ICD-10 code K20, compared to control population

You may qualify if:

• EoE diagnosed patients according to ICD-10 code K20

You may not qualify if:

• Patients diagnosed with other EGIDs (- K52.81: Eosinophilic Gastritis or Gastroenteritis
• K52.82: Eosinophilic Colitis
• K558.4: Eosinophilic gastroenteritis and colitis)

Sponsors & Collaborators

• IRCCS San Raffaele: lead
• TriNetX, LLC: collaborator
• Vita-Salute San Raffaele University: collaborator

Study Sites (1)

IRCCS San Raffaele Hospital

Milan, Lombardy, 20132, Italy

Location

MeSH Terms

Conditions

Eosinophilic Esophagitis; Esophageal Neoplasms; Gastroesophageal Reflux; Barrett Esophagus

Condition Hierarchy (Ancestors)

Esophagitis; Esophageal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Gastroenteritis; Eosinophilia; Leukocyte Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Esophageal Motility Disorders; Deglutition Disorders; Precancerous Conditions

Study Officials

• Alberto Barchi, MD

  IRCCS San Raffaele Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Doctor

Study Record Dates

• First Submitted: July 28, 2025
• First Posted: August 3, 2025
• Study Start: July 23, 2025
• Primary Completion: July 30, 2025
• Study Completion: November 30, 2025
• Last Updated: March 11, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)