Liquid Biopsies in Esophageal Adenocarcinoma: Barrett's Esophagus and Esophageal Adenocarcinoma, Searching for Reliable Diagnostic RNA Plasma-based Biomarkers
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Esophageal Neoplasms
- Sponsor
- University Hospital, Ghent
- Enrollment
- 100
- Locations
- 1
- Primary Endpoint
- Identification of plasma biomarkers (micro RNAs) for early detection of esophageal adenocarcinoma
- Status
- Recruiting
- Last Updated
- last year
Overview
Brief Summary
This study is designed to perform a explorative search of the transcriptome to detect new circulating diagnostic sensitive and specific biomarkers in patients with Barrett's esophagus or esophageal adenocarcinoma.
Detailed Description
By developing new tools for risk-assessing of Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) in a population at risk, the investigators expect that diagnosis can be done in an earlier stage resulting in an improved 5-year survival. A proof-of-concept RNA profiling study will be done in 20 BE and EAC patients where 2 biomaterials (tissue and plasma) and 2 RNA biotopes (micro RNA and messenger RNA) will be compared. Previously validated methodology on small RNA and messenger RNA capture sequencing on both tissue and plasma will be used to obtain high-quality data. Differential expression analysis will be done on tissue and plasma sample data. Additional in-depth data-mining will be done, amongst other focusing on structural information encoded in the transcriptome and building a multifeature classifier. These findings will be validated in a large validation cohort, followed by development of a clinical-grade quantitative Polymerase Chain Reaction (qPCR) test, ready for testing in an independent cohort.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Barrett's Esophagus with length \> 3cm OR esophageal adenocarcinoma histologically proven
- •Adequate mental faculty, allowing to understand the proposed treatment protocol and provide informed consent
- •Age over 18 years
- •No other concurrent malignant disease
- •No inclusion in other clinical trials interfering with the study protocol
- •No concurrent chronic systemic immune or hormone therapy, except neoadjuvant chemotherapy
- •Absence of any severe organ insufficiency
- •No pregnancy or breast feeding
- •Written informed consent
Exclusion Criteria
- •Pregnancy or breast feeding
- •Active bacterial, viral or fungal infection
- •Parenchymal liver disease (any stage cirrhosis)
- •High risk of bleeding during biopsy (anticoagulants, esophageal varices)
- •Esophageal squamous cell carcinoma
- •Helicobacter pylori positive at the time of biopsy sampling
- •Radiofrequency ablation of the oesophagus
- •Psychiatric pathology capable of affecting comprehension and judgement faculty
Outcomes
Primary Outcomes
Identification of plasma biomarkers (micro RNAs) for early detection of esophageal adenocarcinoma
Time Frame: 4 years
Identification of micro RNAs in plasma and tissue of patients with (non-)dysplastic Barrett's esophagus and EAC that are differentially abundant, compared to healthy plasma (healthy volunteers) or healthy tissue (patient-matched healthy esophagus biopsies).
Identification of plasma biomarkers (messenger RNAs) for early detection of esophageal adenocarcinoma
Time Frame: 4 years
Identification of messenger RNAs in plasma and tissue of patients with (non-)dysplastic Barrett's esophagus and EAC that are differentially abundant, compared to healthy plasma (healthy volunteers) or healthy tissue (patient-matched healthy esophagus biopsies).
Identification of biomarkers (messenger RNAs) for therapy response prediction
Time Frame: 2 years
Identification of a set of messenger RNAs that change during treatment (using longitudinally collected plasma samples) and that separate responders from non-responders to neo-adjuvant radiochemotherapy.
Secondary Outcomes
- Development of a quantitative Polymerase Chain Reaction (qPCR) test for clinical use(1 year)