Outcomes of Endoscopically Resected High-risk Mucosal and Low- and High-risk Submucosal Adenocarcinoma Arising in Barrett's Esophagus

• Conditions: Submucosal Esophageal Adenocarcinoma; High-risk Mucosal Esophageal Adenocarcinoma; Barrett Esophagus; Adenocarcinoma Esophagus
• Interventions: Procedure: diagnostic endoscopic resection

• Registration Number: NCT04818476
• Lead Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Brief Summary

The purpose of this study is to assess lymph node metastasis rate, distant metastasis rate, disease-specific mortality, and overall mortality in patients with Barrett's related T1b and high risk T1a esophageal adenocarcinoma (EAC) who underwent a diagnostic endoscopic resection.

Detailed Description

The incidence of esophageal adenocarcinoma (EAC) has increased six-fold over the last three decades, making it the most rapidly rising cancer in the Western world. The main histologic risk factor for development of EAC is the presence of Barrett's esophagus (BE). BE can develop from non-dysplastic BE, to low (LGD) and high grade dysplasia (HGD) and, eventually, EAC.

The past two decades minimally invasive endoscopic resection (ER) has replaced surgical esophagectomy as first-choice therapy for the treatment of early neoplastic lesions in Barrett's esophagus. ER provides adequate tissue specimens, allowing for accurate histopathological staging of a lesion, by assessment of invasion depth, differentiation grade, presence of lympho-vascular invasion (LVI), and radicality of the resection. Endoscopic resection thus similarly fulfils a diagnostic and therapeutic role in the management of Barrett's neoplasia.

However, ER offers local treatment and does not include lymph node dissection as is still standard of care during esophagectomy. Therefore, the choice to perform endoscopic follow-up after a radical ER of an early EAC, or to refer a patient for additional surgery, is guided by the assumed risk of lymph node metastasis (LNM).

Data from previous studies show that the risk of LNM is only 1% in patients with low risk mucosal EAC after endoscopic treatment (i.e., infiltration depth limited to the mucosa, G1-G2, without LVI), and \<2% in low risk submucosal EAC (i.e., infiltration depth \<500μm, good to moderate differentiation grade (G1-G2), without LVI). In high risk submucosal EAC (i.e., infiltration depth ≥500 μm, and/or G3-G4, and/or LVI), the LNM risk is estimated to be much higher (16-44%). Nevertheless, these numbers are mainly based on old surgical series.

Current data is limited in terms of small and heterogeneous patient cohorts, and data for patients with high risk T1a EAC is not available at all. Therefore, we would like to conduct an international multicenter retrospective cohort study in \>10 centers to evaluate the safety and efficacy of endoscopic treatment and follow-up of patients with high risk mucosal and submucosal EAC. Our main focus will be the presence of lymph node metastasis and EAC related death.

Aim of this registration study is to collect data of the above-mentioned group of patients and thereby assess lymph node metastasis rate, disease-specific mortality, and overall mortality.

This study will be conducted according to the principles of the Declaration of Helsinki and in accordance with the Medical Research Involving Human Subjects Act (WMO), the Medical Treatment Contracts Act (WGBO) and the Dutch Personal Data Protection Act (WBP). The investigators will perform the study in accordance with this protocol and will make sure that participants do not object to using their data. Collection, recording, and reporting of data will be accurate and will ensure the privacy, health, and welfare of research subjects during and after the study.

Study Timeline

• Study Start: 2020-02-10
• Status Verified: 2021-03
• Study First Submitted: 2021-03-24
• Study First Submitted QC: 2021-03-24
• Last Update Submitted: 2021-03-24
• Study First Posted: 2021-03-26
• Last Update Posted: 2021-03-26
• Primary Completion: 2022-12-31
• Study Completion: 2022-12-31

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 1000

Inclusion Criteria

1. Males or females, all ages
2. Endoscopic resection of a histologically proven high risk T1a, low risk T1b EAC, or high risk T1b EAC
3. Between 1/1/2008 and 1/1/2019
4. Endoscopic resection and endoscopic FU (or other treatment after ER) have taken place in the participating center
5. No written or oral refusal to use subject's data

Exclusion Criterium:

Objection against participation in this study

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
LR-T1b	diagnostic endoscopic resection	Patients who were treated by radical endoscopic resection for a low-risk submucosal EAC (LR-T1b N0M0)
HR-T1b	diagnostic endoscopic resection	Patients who were treated by radical endoscopic resection for a high-risk submucosal EAC (HR-T1b N0M0)
HR-T1a	diagnostic endoscopic resection	Patients who weretreated by radical endoscopic resection for a high-risk mucosal EAC (HR-T1a N0M0)

Primary Outcome Measures

Name	Time	Method
lymph node metastasis rate	10 years	Confirmed by cytology and/or histology by performing FNA during EUS or biopsies
distant metastasis rate	10 years	Primary tumor of distant metastasis should be histopathologically evalueted by taking biopsies.
disease-specific mortality	10 years	Disease specific mortality is decribed as mortality directly linked to the esophageal adenocarcinoma (i.e., metastasized EAC, metastasized disease with a simultaneously primary cancer present and it cannot be ruled out (based on histology) that the metastases are related to the other primary cancer, death due to complications of the endoscopic procedure, death due to complications after surgery or CRT, no clear cause of death in patients who have metastases or untreated local recurrence). If patients are diagnosed with distant metastases, and subsequently die of a non-tumor related cause, patients will still be documented as tumor-related death. Will be measured in number of patients and percentages. Survival analysis using Kaplan Meier will be performed.
overall mortality	10 years	Overall mortality of study population (tumor-related + non-tumor-related deaths). Measured in numbers and percentages, survival analysis (KM).

Trial Locations

Locations (16)

Amsterdam UMC, location VUmc; 🇳🇱 Amsterdam, Netherlands

Catharina Hospital; 🇳🇱 Eindhoven, Netherlands

UZ Gasthuisberg; 🇧🇪 Leuven, Belgium

St. Antonius Hospital; 🇳🇱 Nieuwegein, Netherlands

Westmead hospital; 🇦🇺 Sydney, Australia

EVK Duesseldorf; 🇩🇪 Duesseldorf, Germany

Universitätsklinikum Augsburg; 🇩🇪 Augsburg, Germany

MRI TUM; 🇩🇪 Münich, Germany

CHU Nantes; 🇫🇷 Nantes, France

Barmherzige Brüder Regensburg; 🇩🇪 Regensburg, Germany

University Medical Center Groningen; 🇳🇱 Groningen, Netherlands

Erasmus MC - University Medical Center; 🇳🇱 Rotterdam, Netherlands

Haga Medical Center; 🇳🇱 The Hague, Netherlands

Isala Clinics; 🇳🇱 Zwolle, Netherlands

Hirslanden private hospital group; 🇨🇭 Zürich, Switzerland

University College London Hospital; 🇬🇧 London, United Kingdom