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.

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.

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)

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

No IPD used