Clinical trial NCT07022886: INCIDENCE, PREVALENCE AND OVERALL RISK OF ESOPHAGEAL CANCER IN ACHALASIA: A PROPENSITY-MATCHED POPULATION-BASED STUDY FROM A LARGE MULTICENTER DATABASE
Official title: INCIDENCE, PREVALENCE AND OVERALL RISK OF ESOPHAGEAL CANCER IN ACHALASIA: A PROPENSITY-MATCHED POPULATION-BASED STUDY FROM A LARGE MULTICENTER DATABASE
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Achalasia Cardia
Esophageal Cancer (EsC)
Keywords: achalasia
esophageal cancer
Lead sponsor: IRCCS San Raffaele
Sponsor class: OTHER
Collaborators: name: TriNetX, LLC
name: Vita-Salute San Raffaele University
First posted: 2025-06-15
Enrollment: 47000
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Achalasia diagnosis according to guidelines as stated in Electronic Health Records (EHR) data.

Brief summary: Esophageal Achalasia has been investigated as a potential risk factor for esophageal cancer (EC). Longstanding disease, repeated treatment, age and male sex seem the most relevant risk factors, but no clear effect size estimation from large sample cohorts has been provided so far. The aim of the investigators is to estimate EC risk in large sample-size population, and to provide sub-analyses per cancer type and treatment impact on EC risk.

Detailed description: Achalasia is a chronic idiopathic condition characterized by the absence of esophageal peristalsis and reduced relaxation of the lower esophageal sphincter, causing progressive dysphagia and weight loss. Achalasia has been investigated as a potential risk factor for esophageal cancer (EC); squamous cancer due to chronic inflammation related to stasis due to poor esophageal emptying and adenocarcinoma due to uncontrolled gastroesophageal reflux after treatment. Longstanding disease, repeated treatment, age and male sex have been addressed as the most relevant risk factors, but no clear effect size estimation from large sample cohorts has been provided so far.

The authors conducted a retrospective cohort study, accessing the global federated health research network "TriNetX", that provides access to electronic medical records from approximately a hundred million patients across large healthcare organizations (HCOs). The analysis will be performed on achalasia patients, based on the ICD-10 code (K22.0), from January 1st 2000 until May 31st 2025. The incidence rate (cases/1000 persons-year) and cumulative prevalence of EC in an achalasia cohort in a span of 25 years will be firstly assessed. Then the absolute and time-to-event risk of EC, by comparing the achalasia cohort with control cohort, after propensity score nearest neighbor greedy matching, for relevant covariates. Kaplan-Meyer (KM) analysis with censoring, Hazard Ratios (HRs) and Risk Ratio (RR) and Risk Difference (RD) estimation for EC risk will be calculated. Log Rank test will be used to compare KM curves. Further sub-group analysis will be implemented between two population of achalasia patients, treated (with endoscopic/surgical myotomy or pneumatic dilation) and treatment-naïve. Further in-depth analyses between histologic type of EC, esophageal localization and comparing different achalasia treatment (myotomy vs pneumatic dilation) will be performed, in order to categorize the risk of EC, if more linked to treatment and therefore to the development of reflux, Barrett esophagus eventually leading to adenocarcinoma, or towards squamous cell cancer driven by chronic stasis and degeneration of the squamous esophageal epithelium

Eligibility criteria: Inclusion Criteria:

* Esophageal achalasia diagnosed according to guidelines (ICD-10-K22.0)

Exclusion Criteria:

* Primary esophaeal and pharyngeal motility disorders (ICD-10-J39.2)

Primary outcomes:
measure: Hazard Ratio
timeFrame: from Jan 1st 2000 to June 3rd 2025
measure: Incidence proportion, prevalence and incidence rate
timeFrame: Jan 1st 2000- June 3rd 2025
Secondary outcomes:
measure: Risk Ratio
timeFrame: Jan 1st 2000-Jun 3rd 2025
measure: Risk Difference
timeFrame: Jan 1st 2000-June 3rd 2025
measure: Hazard Ratio (HR) with Kaplan Meyer (KM) analysis of EC occurrence
timeFrame: Jan 1st 2000- June 3rd 2025
Other outcomes:
Locations:
city: Milan
country: Italy
facility: IRCCS San Raffaele Hospital
state: Lombardia
Study officials:
affiliation: Department of Gastroenterology, Amsterdam UMC Location AMC, Amsterdam, The Netherlands
name: Albert Jan Bredenoord, MD, PhD, Prof
role: STUDY_DIRECTOR
References:
citation: Ponds FA, Moonen A, Smout AJPM, Rohof WOA, Tack J, van Gool S, Bisschops R, Bredenoord AJ, Boeckxstaens GE. Screening for dysplasia with Lugol chromoendoscopy in longstanding idiopathic achalasia. Am J Gastroenterol. 2018 Jun;113(6):855-862. doi: 10.1038/s41395-018-0064-1.
citation: Tustumi F, Bernardo WM, da Rocha JRM, Szachnowicz S, Seguro FC, Bianchi ET, Sallum RAA, Cecconello I. Esophageal achalasia: a risk factor for carcinoma. A systematic review and meta-analysis. Dis Esophagus. 2017 Oct 1;30(10):1-8. doi: 10.1093/dote/dox072.
citation: Gillies CL, Farrukh A, Abrams KR, Mayberry JF. Risk of esophageal cancer in achalasia cardia: A meta-analysis. JGH Open. 2019 Feb 8;3(3):196-200. doi: 10.1002/jgh3.12132. eCollection 2019 Jun.