Title: The BioStent study: Biodegradable oesophageal stents plus radiotherapy in carcinoma of the oesophagus
Funder: Department of Health and Social Care

Abstract: BACKGROUND The current standard of care for the palliation of dysphagia in patients with advanced oesophageal cancer is placement of a self expanding metal stent (SEMS). SEMS provide rapid palliation of dysphagia (1) but are associated with complications such as slippage or blockage which may necessitate removal and/or replacement. We therefore need to explore better treatment options for the palliation of dysphagia in oesophageal cancer. For some time, short courses of radiotherapy (RT) have been used to to palliate dysphagia from oesophageal cancer (5)and may give more long lasting palliation as compared to stents, but the improvement in dysphagia is slower to be realised with RT than with stents, and dysphagia may worsen initially after RT. Biodegradable (BD) stents are a new development (6). They are placed in the same way as SEMS but dissolve in-situ over 3-4 months. They are currently licensed for the treatment of benign oesophageal strictures, but not for oesophageal cancer which would ordinarily be exepcted to cause recurrent dysphagia once the stent had disolved. We suggest that the combination of a BD stent followed by a short (1-2 week) course of radiotherapy will give palliation both quickly, as a result of the stent, but also of long duration, from RT, which would be anticipated to have caused tumour regression by the time the stent loses its structural integrity. This treatment strategy has not yet been evaluated. Ultimately we would wish to compare it with the standard of care, currently SEMS, but we feel that we need to obtain an initial estimate of efficacy before embarking on a randomised study. A separate UK study is in set up, which will recruit the same group of patients as this study, and randomise between SEMS alone and SEMS plus RT. Although not inter-dependent, these studies will be complementary, and if SEMS+RT emerges as new standard of care, then a study of SEMS+RT vs BD stent+RT would be proposed. AIMS The aim of this project is to determine whether a treatment consisting of BD stent plus RT is adequately effective in the palliation of dysphagia from oesophageal cancer such that it would be worthwhile investigating further in a randomised trial. The primary endpoint is the need for a further intervention for dysphagia. We would consider the treatment worthy of further investigation if no more than 15% of patients require some form of re-intervention for dysphagia by 4 months post placement of BD stent. Secondary endpoints relate to a description of stent related symptoms, feasibility of collecting quality of life, nutrition and anxiety/depression, and a description of these scores, and overall survival. PLAN OF INVESTIGATION Up to 59 patients in Southampton and Manchester who would otherwise be treated with a SEMS for the palliation of dysphagia in oesophageal cancer will instead be offered participation in this non-randomised study. The study treatment comprises insertion of a BD stent then a 1-2 week course of RT. Patients will be assessed prior to insertion of the stent, then before RT, then at regular intervals following RT. As well as determining if a further intervention for the treatment of dysphagia has taken place, assessments will comprise symptom assessments, and assessments of quality of life, nutrition, and anxiety/depression. The study design is a Simon 2-stage phase 2 study (8). It is powered to exclude a re-intervention rate of more than 15% at the chosen time point. POTENTIAL BENEFITS As compared to the current standard of SEMS: Reduced need for readmission for uncomfortable, disruptive and costly repeat procedures associated with slipped metal stents Reduced symptoms and improved quality of life as compared to permanent metal stents.

Lay abstract: Background The commonest symptom of oesophagus (gullet/food pipe) cancer is difficuly swallowing due to blockage of the oesophagus by cancer. Patients unsuitable for curative treatment can have a wire mesh tube (metal stent) inserted to open up the oesophagus, quickly improving swallowing. Metal stents have side effects including pain and back flow of stomach contents. They can slip, become blocked, and may require removal or replacement. We therefore need to explore alternative treatments. Radiotherapy (high energy X-ray treatment) can improve swallowing, often for longer than stents, but improvement in swallowing is slower to start following radiotherapy, and swallowing may worsen at first. Biodegradable oesophageal stents are placed like metal stents but dissolve within 3-4 months. They are currently used for non-cancerous causes of oesophageal narrowing but not cancer. The placement of a biodegradable stent followed by a short course of radiotherapy may give both quick (from the stent) and longer-term (from radiotherapy) relief of swallowing problems and avoid some of the side effects associated with metal stents Aim To test the effectiveness of biodegradable stents plus radiotherapy in patients with swallowing problems from incurable oesophagus cancer. Methods Patients will be invited to have a biodegradable stent placed instead of a metal stent, then have a 1-2 week course of radiotherapy. We would consider the treatment promising if no more than 15% of patients require another procedure to help their swallowing within 4 months of this treatment. We will also ask patients about symptoms (particularly swallowing), their quality of life, their diet and their mood. Research Team The research team includes people with expertise in oesophageal stenting, oncologists (cancer specialists), a dietitian, a specialist nurse in oesophagus cancers and a statistician. A patient with relevant personal experience and a nursing background is also part of the team.

Research activity codes: 6.5 RADIOTHERAPY AND OTHER NON-INVASIVE THERAPIES;6.3 MEDICAL DEVICES
Health categories: CANCER AND NEOPLASMS