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

Barrett Esophagus Clinical Trial

Official title:

Outcomes of Endoscopically Resected High-risk Mucosal Adenocarcinoma and Low- and High-risk Submucosal Adenocarcinoma Arising in Barrett's Esophagus: an International Multicenter Retrospective Cohort Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04818476
• Other study ID #: x
• Status: Recruiting
• Start date: February 10, 2020
• Est. completion date: December 31, 2022

Study information

• Verified date: March 2021
• Source: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Contact: Man Wai Chan, MD
• Phone: (0)20 4442432
• Email: m.w.chan[@]amsterdamumc.nl
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1000
• Est. completion date: December 31, 2022
• Est. primary completion date: December 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

• Adenocarcinoma
• Adenocarcinoma Esophagus
• Barrett Esophagus
• Esophageal Neoplasms
• High-risk Mucosal Esophageal Adenocarcinoma
• Submucosal Esophageal Adenocarcinoma

Intervention

Procedure:
• diagnostic endoscopic resection
diagnostic endoscopic resection

Locations

Country	Name	City	State
Australia	Westmead hospital	Sydney
Belgium	UZ Gasthuisberg	Leuven
France	CHU Nantes	Nantes
Germany	Universitätsklinikum Augsburg	Augsburg
Germany	EVK Duesseldorf	Duesseldorf
Germany	MRI TUM	Münich
Germany	Barmherzige Brüder Regensburg	Regensburg
Netherlands	Amsterdam UMC, location VUmc	Amsterdam
Netherlands	Catharina Hospital	Eindhoven
Netherlands	University Medical Center Groningen	Groningen
Netherlands	St. Antonius Hospital	Nieuwegein
Netherlands	Erasmus MC - University Medical Center	Rotterdam
Netherlands	Haga Medical Center	The Hague
Netherlands	Isala Clinics	Zwolle
Switzerland	Hirslanden private hospital group	Zürich
United Kingdom	University College London Hospital	London

Sponsors (1)

Lead Sponsor	Collaborator
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Countries where clinical trial is conducted

Australia,  Belgium,  France,  Germany,  Netherlands,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	lymph node metastasis rate	Confirmed by cytology and/or histology by performing FNA during EUS or biopsies	10 years
Primary	distant metastasis rate	Primary tumor of distant metastasis should be histopathologically evalueted by taking biopsies.	10 years
Primary	disease-specific mortality	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.	10 years
Primary	overall mortality	Overall mortality of study population (tumor-related + non-tumor-related deaths). Measured in numbers and percentages, survival analysis (KM).	10 years