Title: Selective Use of Postoperative Radiotherapy AftEr MastectOmy G0400170
Funder: Department of Health and Social Care

Abstract: The role of adjuvant postmastectomy radiotherapy (PMRT) in women with intermediate risk breast cancer is uncertain. SUPREMO is a phase III randomised international clinical trial assessing the role of PMRT and, if appropriate, systemic therapy in women (pT 1 ,NI,M0 or pT 1 ,NI,MO) with 1-3 involved nodes or node negative with other risk factors (grade 3 and/or lymphovascular invasion). The primary end point is overall survival.Secondary endpoints are disease free survival, acute and late morbidity, quality of life, molecular markers of radiation sensitivity and cost effectiveness.Patients will be randomised to PMRT or no PMRT.Target accrual is 3700 patients over 4 years, allowing 5% for attrition, with 5 years of follow up. The sample size is sufficient to detect a statistically significant difference (p 0.05) between 5 year survival rates of 75% and 79%. The trial is underpinned by a quality assurance programme. A biological substudy (TRANS-SUPREMO) aims to define a molecular signature for chest wall relapse, identifying which patients may or may not benefit from PMRT. Molecular profiles of relapse identified from the Scottish Conservation trial (Forrest et al,l996) will be used to identify key molecular/biochemical pathways relevant to relapse and radiosensitivity in SUPREMO.Tissue microarrays will be collected from paraffin blocks from mastectomy specimens from all patients. A Quality of Life substudy of 800 UK patients, the primary endpoints are fatigue (EORTC,QLQ-C30), physical functioning (QLQ-C30), chest wall, shoulder and arm symptoms (EORTC BR23) and the Body Image Scale (BIS).Descriptive data will be collected for role functioning,social and sexual functioning, pain, nausea and vomiting, anxiety and depression (HADS). In a cardiac substudy the role of serum brain natriuretic peptide (BNP) will be studied in assessing the impact of chemotherapy (CT) and PMRT on treatment induced cardiac damage. BNP levels with be measured before CT/RT,post CT, post RT and at 1 and 5 years. In a health economic substudy the cost effectiveness of PMRT will be measured in all UK patients.Usage of community and health service resources will be collected at follow up supplemented by review of hospital records.The primary analysis will determine the extent to which the costs between the two arms of the trial differ. A secondary analysis will model the determinants of difference in cost between individual patients.Cost per life year saved will be calculated as the measure of cost effectiveness.

Lay abstract: Breast cancer is a major and growing health care burden with over 40,000 new cases per year in the UK. About two thirds of patients with operable breast cancer are managed by conservation and one third by mastectomy. In Scotland a 20% rise in incidence in breast cancer is projected over the next decade (Cancer Scenarios, 2001). The role of adjuvant postmastectomy radiotherapy (PMRT) in women with intermediate risk breast cancer is uncertain. SUPREMO is a phase III randomised international clinical trial assessing the role of PMRT and, if appropriate, systemic therapy in women with 1-3 involved nodes or node negative with other risk factors. The primary end point is overall survival. Secondary endpoints are disease free survival, acute and late morbidity, quality of life, molecular markers of radiation sensitivity and cost effectiveness. Patients will be randomised to PMRT or no PMRT.Target accrual is 3700 patients over 4 years, with 5 years of follow up. The trial is underpinned by a quality assurance programme.

Research activity codes: 6.1 PHARMACEUTICALS;6.5 RADIOTHERAPY AND OTHER NON-INVASIVE THERAPIES
Health categories: CANCER AND NEOPLASMS