Stratifying Risk in Barrett's Esophagus: A Pilot Study for Biomarker-based Patient Management
Condition: Barrett's Esophagus; Esophageal Adenocarcinoma; Intestinal Metaplasia; Dysplasia
MeSH terms: Adenocarcinoma; Barrett Esophagus; Metaplasia
Study type: Observational

Summary: 
      Subjects enrolled in this study will have biopsies obtained and sent to Dr. Fitzgerald's lab
      for analysis of a validated biomarker panel. Subjects will be stratified to either high or
      low risk of progression to esophageal adenocarcinoma (EAC) based on biomarker panel results.
      Biomarker panel results will not be communicated to sites. Subjects with low grade dysplasia
      will be offered the option of treatment (radiofrequency ablation (RFA)) as part of routine
      care. Subjects with low grade dysplasia who do not want RFA and subjects with no dysplasia
      will receive surveillance endoscopy in 1 year per routine care. All subjects will be
      administered a questionnaire seeking information about hypothetical willingness to be
      randomized to treatment or surveillance.
    

Detailed description: 
      The Investigators have previously completed a validation study in which they have identified
      a panel of biomarkers that can predict progression of subjects with BE and no dysplasia or
      low-grade dysplasia to esophageal adenocarcinoma (EAC). The biomarker panel, performed by the
      Fitzgerald lab, included ploidy (by image cytometry), AOL (histochemistry (IHC)), p53 (IHC),
      cyclin A (IHC), and dysplasia. These markers have been validated and demonstrated to be
      highly predictive of both progression to EAC, as well as the presence of occult malignancy
      elsewhere in the specimen (field effect). The final panel of validated biomarkers will be
      used in this study to identify patients at high risk of developing EAC.

      The study will recruit 100 patients across 4 sites (University of North Carolina, Case
      Western Reserve University, University of Cambridge, and Academic Medical Center in
      Amsterdam). The specific aims of this pilot study are to:

        1. Demonstrate that the international, multicenter team can work together,

        2. Define the logistics of assaying biomarkers in real time such that in the future
           interventional trial, results could influence clinical decision-making, and,

        3. Provide further data to inform a power calculation for the full trial.

      Subjects enrolled in the study will complete a questionnaire gathering hypothetical
      willingness to be randomized to receive endoscopic treatment intervention (RFA) or
      surveillance endoscopy.

      Biopsy samples will be obtained from all subjects and tested for all biomarkers in the panel.
      Results of the biomarker panel will not be communicated to sites. Subjects with low grade
      dysplasia will be offered the option of receiving radiofrequency ablation (RFA) as part of
      routine care. Subjects with low grade dysplasia who agree to RFA will receive RFA as part of
      routine care. Subjects with no dysplasia and subjects with low grade dysplasia who do not
      want to receive RFA will receive a surveillance endoscopy in 1 year as part of routine care.

      The goals of this pilot study are to ascertain the proportion of subjects in the high risk
      arm, to demonstrate the plausibility of performing the biomarker analysis efficiently in a
      sizable group of patients, to demonstrate the feasibility of delivering the endoscopic
      intervention (RFA), to obtain 1 year pilot data regarding progression in the high risk arm
      for use in sample size calculations, and to document collaboration among the centers.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Subjects with Barrett's Esophagus, coming into clinics for routine care surveillance upper
        endoscopy procedures.
      
Biospecimen description: 
      Paraffin embedded esophageal biopsies
    
Keywords: Barrett's Esophagus; Esophageal Adenocarcinoma