Title: IMPORT: Joint trial of IMPORT HIGH and IMPORT LOW
Funder: Cancer Research UK

Abstract: Randomised trial testing intensity modulated radiotherapy and partial organ radiotherapy following breast conservation surgery for early breast cancer to test partial breast radiotherapy delivered using intensity modulated techniques following complete local tumour excision of low risk early stage breast cancer. Study design: Prospective randomised controlled clinical trial for patients at low risk of local recurrence (< 1% annual risk local recurrence after radiotherapy) The primary endpoint is local tumour control in the ipsilateral breast. Secondary endpoints include location of tumour relapse, contralateral primary tumours, regional and distant metastases, late adverse effects in normal tissues, quality of life (QL) and economic evaluation. BACKGROUND Breast cancer mortality and iatrogenic morbidity can be reduced further The Early Breast Cancer Trialists Collaborative Group (EBCTCG) systematic overview confirms a 75% reduction in local tumour recurrence risk after radiotherapy in patients treated by breast conservation surgery for early breast cancer. The overview shows that the prevention of 4 local tumour recurrences prevents 1 breast cancer death at 10 years, corresponding to 1-5 fewer deaths per 100 node negative women and 5-10 fewer deaths per 100 node positive patients treated. These observations are strengthened by the 2000 systematic overview of radiotherapy effects by the EBCTCG (unpublished). For the majority of women with small screen-detected cancers, late complications of radiotherapy rather than local cancer recurrence are now the dominant hazard. Exposure of non-target tissues to ugh doses of radiotherapy predisposes to a wide range of morbidities, including lung fibrosis, heart injury (left-sided cases), rib fracture, shoulder stiffness, breast shrinkage, tissue hardness, pain and tenderness with consequent effects on physical functioning and quality of life. Complication risk is increased by the widespread use of radiotherapy planning techniques based on standard wedge compensators that fail to meet international dosimetric guidelines in a majority of patients. The morbidity of radiotherapy would be significantly reduced by eliminating unplanned dose variation across the breast and reducing the dose to parts of the breast remote from the tumour bed at very low risk of recurrence. Radiotherapy target volume and dose intensity are poorly adapted to local recurrence risk: Standard guidelines for radiotherapy in early breast cancer fail to discriminate between different risk groups. Women with low-grade screen-detected cancers a few millimetres in diameter receive the same radiotherapy regimen as women with higher risk tumours. They share the same risk of complications as women with high risk tumours, but have less to gain in terms of local tumour control. For women with low risk disease, the challenge is to reduce the morbidity of therapy without compromising cure. Applications of recent technical advances in radiotherapy should achieve more effective exploitation of radiotherapy dose- response, fractionation sensitivity and partial volume effects without loss of departmental working efficiency. The first step in testing risk-adapted radiotherapy in low risk patients is to confirm that women with low and high risk tumours can be reliably identified. Low and high risk subgroups can be distinguished: Data from four prospective randomised trials testing radiotherapy after breast conservation surgery have reported on factors associated with local recurrence risk. Last updated 18/02/2008


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