Title: Palliative radiotherapy in addition to self-expanding metal stent for improving outcomes of dysphagia and survival in advanced oesophageal cancer: ROCS (Radiotherapy after Oesophageal Cancer Stenting) Study
Funder: Health and Care Research Wales (Welsh Government)

Abstract: Does the administration of palliative oesophageal radiotherapy after the insertion of a self-expanding metal stent for dysphagia improve outcome in advanced oesophageal cancer? Methodology A phase III trial in which patients with oesophageal cancer requiring immediate insertion of a self-expanding metal stent (SEMS) are randomised on a 1:1 ratio between Arm A (stent insertion alone) and Arm B (stent insertion and radiotherapy). All patients will receive best supportive care. The patient group are likely to be frail and elderly. To ensure that the study conduct is optimal an initial pilot phase will be conducted. This will require that at least 70% of screened patients undergoing stent for dysphagia are considered eligible for the trial and at least 50% of these eligible patients consent to randomisation. There will also be a qualitative component for a small sub-set of patients to explore the problems of trial recruitment and to explore the participants’ experience of the interventions. This will be a 6 year study which will involve approximately 10 participating UK radiotherapy treatment centres with additional linked centres performing stent insertion and follow up. Sample Group Patients with histologically confirmed oesophageal carcinoma who are not suitable for radical treatment, and require a stent as the first treatment for dysphagia. The treatment decision for these patients will have been made by an upper GI multi-disciplinary team, and the patient will have been assessed as being able to attend for radiotherapy and having an expected survival of at least 12 weeks. Outcome Measures The primary objective is to assess the impact of radiotherapy in addition to stent placement on time to progression of patient-reported dysphagia in a patient population unable to undergo radical therapy. Secondary objectives are to: 1. Assess the impact of the addition of radiotherapy on core components of health related quality of life 2. Assess the impact of radiotherapy in addition to stent placement on overall survival 3. Determine morbidity and quality of life associated with both interventions 4. Measure re-intervention rates 5. Assess the cost of the addition of radiotherapy to SEMS placement ********** Study Design: A pragmatic, randomised controlled trial of external beam radiotherapy in addition to self expanding metal stent (SEMS) versus SEMS alone in patients clinically assessed as requiring stent insertion for relief of dysphagia caused by oesophageal cancer. Target Population: Patients selected for palliation of malignant dysphagia with an oesophageal SEMS. Settings: Secondary care, including cancer centres and district general hospitals from ten participating centres. Health Technologies to be assessed: SEMS: insertion will be according to local protocol; the length, and type can be selected by the clinician. External Beam Radiotherapyu (EBRT: will commence within four weeks of stent placement. Two radiotherapy schedules may be used: 20Gy in five daily fractions over one week or 30Gy in ten daily fractions over two weeks, both prescribed to midplane dose. The aim is to standardise the critical aspects of the radiotherapy delivered within the study, following the centre’s own protocol as closely as possible. Outcome Measures: Baseline data prior to SEMS and follow up data 4 weekly until death. Dedicated research staff will visit patients at home. Primary Outcome: (i) Patient–reported dysphagia: measured using the EORTC QLQ-OG25 questionnaire. Secondary Outcomes: (i) Quality of life: measured using the EORTC QLQ-C30 , EORTC QLQ-OG25 and EQ-5D. ii) Patient experience of trial recruitment and interventions and perception of treatment effects: Patient interviews will be undertaken to understand both interventions from the patient’s point of view and how they make sense of this in the context of their daily life and illness experience. The methodology used will be Interpretative Phenomenological Analysis (IPA). (iii) Survival: Notification of death will be collected and overall survival calculated from date of randomisation. (iv) Morbidity: Length of hospital stay, complication rates and re-intervention rates will be gathered from case notes and captured in the CRFs. Pain, eating restrictions and physical functioning via EORTC QLQ-C30 and QLQ-OG25. (v) Cost effectiveness: Total NHS resource use will be monitored prospectively. Due to likely skewness, cost data will be bootstrapped. Effectiveness will be measured using EQ-5D which produces a single utility based index score and has been used in patients with inoperable oesophageal cancer. Differences between trial arms will be assessed using the area under the curve method. Proposed Sample Size: Sample Size based on a time to event analysis, to detect an increase in median time to deterioration in dysphagia of four weeks: from twelve to sixteen weeks (equivalent to HR of 0.75 and a difference in 12 week event rate of 50% vs. 60%)

Lay abstract: The single most distressing symptom for more than 70% of patients with oesophageal (gullet) cancer is difficulty in swallowing (dysphagia) caused by blockage of the gullet by a tumour. This causes severe restrictions on food intake, physical activity, social functioning and overall quality of life. Amongst the more effective treatments for improving swallowing, is the insertion of a metal stent (Self Expanding Metal Stent or SEMS) across the blocked part, which then self-expands to open up the gullet. The addition of radiotherapy may help to improve the problems caused by the tumour and provide an additional survival benefit. The purpose of this study is to test the impact of adding radiotherapy to stent insertion on: i) the length of time swallowing remains improved for ii) quality of life iii) survival Patients will be eligible to take part in the trial if they have oesophageal cancer not suitable for radical treatment, are in need of a stent because of dysphagia, are aged 16 years or older, have been clinically assessed to be able to receive radiotherapy, have an expected survival of at least 12 weeks and are able to give written informed consent. Four hundred and ninety-six patients will be randomised to receive either stent alone or stent with radiotherapy. The radiotherapy will be given as an outpatient either as five treatments (one per day) over one week, or ten treatments over two weeks. Questionnaires will be completed before treatment, within one week of stent insertion and then four weeks after stent insertion until death to assess quality of life and cost. Interviews will be held with a small subset of trial participants at three time points to explore their experiences whilst on the trial. Interviews will also be held with patients who do not consent to take part in the trial to explore their reasons for non-consent.

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