Clinical trial NCT04818476: Outcomes of Endoscopically Resected High-risk Mucosal and Low- and High-risk Submucosal Adenocarcinoma Arising in Barrett's Esophagus
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
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Barrett Esophagus
Adenocarcinoma Esophagus
Submucosal Esophageal Adenocarcinoma
High-risk Mucosal Esophageal Adenocarcinoma
Keywords: Barrett Esophagus
Submucosal esophageal adenocarcinoma
Endoscopic treatment
Endoscopic follow-up
High-risk mucosal esophageal adenocarcinoma
Lead sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Sponsor class: OTHER
First posted: 2021-03-26
Enrollment: 1000
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients who underwent a diagnostic ER for Barrett's related HR T1a or T1b EAC in one of the participating centers, from 1/1/2008 up to the moment of data collection.

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.

Eligibility criteria: 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

Primary outcomes:
measure: lymph node metastasis rate
timeFrame: 10 years
measure: distant metastasis rate
timeFrame: 10 years
measure: disease-specific mortality
timeFrame: 10 years
measure: overall mortality
timeFrame: 10 years
Secondary outcomes:
Other outcomes:
Locations:
city: Sydney
country: Australia
facility: Westmead hospital
city: Leuven
country: Belgium
facility: UZ Gasthuisberg
city: Nantes
country: France
facility: CHU Nantes
city: Augsburg
country: Germany
facility: Universitätsklinikum Augsburg
city: Duesseldorf
country: Germany
facility: EVK Duesseldorf
city: Münich
country: Germany
facility: MRI TUM
city: Regensburg
country: Germany
facility: Barmherzige Brüder Regensburg
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC, location VUmc
city: Eindhoven
country: Netherlands
facility: Catharina Hospital
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
city: Nieuwegein
country: Netherlands
facility: St. Antonius Hospital
city: Rotterdam
country: Netherlands
facility: Erasmus MC - University Medical Center
city: The Hague
country: Netherlands
facility: Haga Medical Center
city: Zwolle
country: Netherlands
facility: Isala Clinics
city: Zürich
country: Switzerland
facility: Hirslanden private hospital group
city: London
country: United Kingdom
facility: University College London Hospital
Study officials:
affiliation: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
name: R.E. Pouw, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: