The REQUITE-AB study: Validating predictive models and biomarkers of radiotherapy toxicity to reduce side-effects and improve quality of life in breast cancer patients

Abstract

Background: Clinically significant side-effects from radiotherapy affect around a quarter of breast cancer patients and may have a considerable impact on outcomes from breast surgery. An increasing number of replicated genetic associations for radiotherapy-induced adverse effects are being reported. The purpose of the EU-funded REQUITE consortium is to validate genetic markers and known clinical factors implicated in radiotoxicity to personalise cancer care in the future. The aim of the REQUITE-AB project is to develop an integrated set of predictors for radiotherapy side-effects in breast cancer patients as the primary component of a decision-making tool for clinicians and patients. Methods: As part of the REQUITE multi-centre observational cohort study >1,900 patients eligible for adjuvant breast radiotherapy will be recruited in nine centres across Europe and North America between April 2014 and August 2016, with centralised data management, biobanking and two years' prospective follow-up using a standardised protocol. Primary endpoints of the REQUITE-AB project are acute skin toxicity (CTC-AE v4.0) and change in patient-reported outcome (PRO) scores on completion of radiotherapy and at 3 months from start of radiotherapy. Secondary endpoints are late side-effects including fibrosis. Results: 1,206 breast cancer patients have been recruited to date with standardized documentation of toxicity and PROs. On completion of radiotherapy, 22.5% of patients recruited so far developed grade 2 skin toxicity (brisk erythema) with a further 1.7% displaying grade 3 toxicity (moist desquamation). PRO questionnaire completion rates at baseline and end of treatment are 85.8% and 88.6%, respectively. Conclusion: The REQUITE study includes the largest radiogenomics cohort of breast cancer patients recruited to date under a single standardised protocol. Genotyping will take place in 2016. The ability of clinical and genetic variables to predict both clinical outcomes and PROs will be examined. Findings of the REQUITE-AB project are likely to inform the development of future interventional biomarker trials in breast cancer care and breast reconstruction.