Title: BRIDE (Barrett’s Randomised Intervention for Dysplasia by Endoscopy) - a feasibility study
Funder: Department of Health (England)

Abstract: Background: Barrett's oesophagus (BE) is a changed gullet lining predisposing to adenocarcinoma, the fifth commonest UK cause of cancer death. Patients with BE undergo endoscopic surveillance to diagnose curable pre-cancerous high grade dysplasia (HGD) and early cancer. Surgery was the only option until recently but new endoscopic treatments have shown success in expert centres; however, most evidence is from cohort studies with no randomised comparison between treatments. The best evidence is for endoscopic resection (ER) alone or combined with radiofrequency ablation (RFA) or argon beam coagulation (APC); both burn away ('ablate') the gullet lining which can regenerate to normal. Both have advantages and disadvantages for the NHS and for patients- APC is cheaper, easier and may require fewer endoscopies but has a smaller evidence base than RFA, which is expensive, more standardisable but may have complications which adversely affect patients’ quality of life if extensive ER is required. The best treatment for patients (many are unfit for surgery) is uncertain as no direct comparative trial exists. After ER of HGD/early cancer, 20-30% recur during follow up, but this is reduced by BE ablation. Case series and a randomised trial show success for RFA (now recommended by NICE); APC effectively eradicates BE but the evidence from small retrospective cohort studies is insufficient to recommend it. Aims: To maximise the chances of successful recruitment and retention in subsequent proposed trials - BRIDE2 : randomised trial to compare ER plus RFA versus ER plus APC and BREST ( B arrett’s R andomised E ndotherapy versus S urgery T rial), we aim to: 1. gain information that will enable realistic estimation of recruitment/retention rates, and identify potential barriers to these by qualitative interviews with a purposive sample of these patients in up to 100 patients recruited over 1 year from 6 expert centres. 2. obtain preliminary estimates for sample size of BRIDE2. 3. determine cost data appropriate for cost economic calculations in BRIDE2 and BREST. 4. determine acceptability to patients and clinicians of a trial comparing surgery to endotherapy (BREST) to follow BRIDE2. 5. test feasibility of assuring equivalent treatment and histology interpretation in different centres. Plan of investigation: 0-3 months: Setup Participating endoscopists attend a workshop to assure consistency of endoscopic procedures Establish quality control for endotherapy and pathology 4 - 15 months: Recruit and randomise patients with HGD/early cancer suitable for endotherapy identified at local upper GI cancer Multi Disciplinary Team meeting (6 centres, 15-20 patients per centre per year). Treatment (5 sessions, T=0,2,4, 6 and 8 months): initial ER followed by ER and/or APC or ER/RFA Open-ended questionnaire to surgeons, and qualitative interviews of a purposive subsample of patients from recruiting centres to establish views on participating in trials involving surgery and endoscopic treatments for early oesophageal cancer. 16-27 months: Treatment completion (ER and APC or ER and RFA). Exit endoscopy at 12 months (assess clinical endpoints). Analysis of open-ended questionnaires and telephone interviews 28-33 months: Collate/analyse results to inform BRIDE2 and BREST. Benefit to patients and NHS: Benefits will arise from the proposed trials between both endotherapy options and surgery which BRIDE facilitates. These will identify the best most cost effective technique to cure early Barrett's cancer with the lowest risk of recurrence. Discussions with patients suggest that there may be benefits in determining the best ablation technique: fewer potentially stressful endoscopies with APC which unlike RFA can be carried out at the same session as ER. The size/extent of ER is not limited for APC treatment (unlike for RFA) and unpleasant complications (eg oesophageal laceration) may be less with APC. For RFA, travel to a providing centre is required.


Research activity codes: 6.4 SURGERY
Health categories: CANCER AND NEOPLASMS;ORAL AND GASTROINTESTINAL