Stratifying Risk in Barrett's Esophagus: A Pilot Study for Biomarker-based Patient Management

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.

Inclusion Criteria:

- Able to read, comprehend, and complete the consent form.

- Aged 18 to 80.

- Diagnosed with at least 3 centimeters (>3cm) of Barrett's Esophagus (BE) AND no
dysplasia or low grade dysplasia per review by pathologist.

Exclusion Criteria:

- Pregnant women.

- Current use of blood thinners such as coumadin, warfarin, heparin and/or low
molecular weight heparin (requires discontinuation of medication 5 days prior to and
6 days after EGD).

- Known bleeding disorder.

- Status post partial or complete esophageal resection.

- Current or past diagnosis of invasive esophageal cancer (previous intramucosal cancer
is allowable, if removed by endoscopic mucosal resection with histologically
confirmed negative lateral and deep margins).

- Prior ablative therapy of the esophagus including prior radiofrequency ablation
(RFA), photodynamic therapy (PDT), spray cryotherapy, and other ablation therapies.
Prior endoscopic mucosal resection (EMR) is acceptable.