BURDEN OF ESOPHAGEAL CANCER IN EOSINOPHILIC ESOPHAGITIS (ESCAPE STUDY)

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	Yes
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Observational
Eligible Ages	N/A and Over
Gender	All

More Inclusion & Exclusion Criteria

Inclusion Criteria:

- EoE diagnosed patients according to ICD-10 code K20.

Exclusion Criteria:

- Patients diagnosed with other EGIDs (- K52.81: Eosinophilic Gastritis or Gastroenteritis.

- K52.82: Eosinophilic Colitis.

- K558.4: Eosinophilic gastroenteritis and colitis)

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT07102329
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	IRCCS San Raffaele
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	Alberto Barchi, MD
Principal Investigator Affiliation	IRCCS San Raffaele Hospital
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Other
Overall Status	Active, not recruiting
Countries	Italy
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Eosinophilic Esophagitis (EoE)

Additional Details

Eosinophilic esophagitis (EoE) is a chronic, immune-mediated inflammatory disease of the esophagus, often presenting with symptoms such as dysphagia and food impaction. Recent literature has raised concerns about a potential association between EoE and the development of esophageal cancer (EC), though findings are inconsistent and possibly confounded by coexisting gastroesophageal reflux disease (GERD) or Barrett's esophagus (BE). The objective of this study was to assess whether EoE independently increases the risk of esophageal cancer, or whether any observed risk is primarily driven by overlapping conditions such as GERD or BE. This was a retrospective, multicenter cohort study utilizing TriNetX, a global federated health research network that provides access to real-world data from electronic medical records (EMRs) of over 100 million patients across more than 100 large healthcare organizations (HCOs), predominantly located in the United States. The network supports cohort design, real-time analytics, and privacy-preserving analytics within a federated data environment. Patients were selected based on the ICD-10 diagnosis code for eosinophilic esophagitis (K20.0) recorded between January 1, 2000, and March 31, 2025. To isolate the specific contribution of EoE to cancer risk, two distinct EoE cohorts were defined: Cohort A: All patients with a diagnosis of EoE, excluding only other eosinophilic gastrointestinal disorders (EGIDs), thereby including individuals with coexisting GERD or BE Cohort B: A more stringently defined "pure EoE" group, excluding patients with any diagnosis of GERD, BE, or other EGIDs, in order to assess the cancer risk attributable to EoE in isolation. Each EoE cohort was compared to a control cohort comprising patients who had outpatient encounters for non-specific or undefined reasons (ICD-10 Z00), and who had no recorded diagnosis of EoE and any instance of EC or BE before the index event. To reduce bias and account for confounding factors, a 1:1 propensity score matching was performed using a nearest-neighbor greedy algorithm, with several matching variables. Time-to-event analysis was designed using Kaplan-Meier survival curves, with censoring applied at the last clinical encounter. Comparative analysis of cancer incidence between groups was planned through log-rank testing, and both hazard ratios (HRs) and risk differences (RDs) were to be calculated. This study design aims to provide a clearer understanding of whether EoE itself constitutes an independent risk factor for esophageal cancer, after accounting for potential confounding conditions.

Arms & Interventions

Arms

: 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.

Interventions

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International Sites

IRCCS San Raffaele Hospital, Milan, Lombardia, Italy

Status

Address

IRCCS San Raffaele Hospital

Milan, Lombardia, 20132

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