Predicting acute radiation toxicity in breast cancer

After surgery, radiotherapy is the second most commonly used treatment for breast cancer. Radiotherapy reduces local recurrence rates with a modest improvement in long-term overall survival. However, up to 20 % of patients may experience clinically significant side-effects (toxicity). Radiation toxicity can impact negatively on a patient’s surgical outcomes and on quality of life. There are currently no clinically useful predictive tests for toxicity capable of personalising breastradiotherapy. It is also not known how patients’ treatment decision-making may be influenced by prior knowledge of their personal risk of side-effects from radiotherapy. With a focus on skin toxicity, this study was designed to explore how acute radiation toxicity in the breast can be predicted more accurately, in order to give patients and clinicians better information to plan treatment. Breast cancer patients were recruited prospectively at Leicester and seven other European and North American centres into the REQUITE cohort study. Data on acute toxicity and QoL were correlated with patient and treatment variables to identify those side-effects that could have a significant impact on QoL. Patients participating in the REQUITE study in Leicester were then interviewed to explore their attitudes towards predictive testing and whether a test for acute toxicity would influence their treatment decision-making.The predictive power of known clinical variables associated with acute desquamation was analysed in a combination of three existing Radiogenomics cohorts. In order to investigate the addition of genetic markers to improve predictive model performance, a systematic review and meta-analysis was undertaken, which identified a number of genetic variants associated with acute breast skin toxicity. The clinical prediction model and genetic markers of acute breast toxicity failed to validate in the REQUITE breast cancer cohort, but this analysis confirmed an association of acute ulceration with SNPs near the REV3L gene.<br

The Patient Perspective on Radiogenomics Testing for Breast Radiation Toxicity.

AIMS: In the field of radiogenomics, several potential predictive genetic markers have been identified that are associated with individual susceptibility to radiation toxicity. Predictive models of radiation toxicity incorporating radiogenomics and other biomarkers are being developed as part of the ongoing multicentre REQUITE trial. The purpose of this study was to explore patient attitudes towards future predictive radiogenomics testing for breast radiation toxicity. PATIENTS AND METHODS: Twenty-one semi-structured interviews were conducted with breast cancer patients taking part in the REQUITE study at one centre. We used inductive thematic analysis to generate common themes. RESULTS: We identified three emerging themes describing attitudes and feelings towards a predictive radiogenomics test for breast radiation toxicity: theme 1 - willingness to undergo a test (subthemes - information, trusted expert); theme 2 - implications of a test (subthemes - preparation and planning, anxiety without recourse); theme 3 - impact on treatment decision-making (subthemes - prioritising cancer cure, preserving breast integrity, patient preferences). CONCLUSIONS: Results from the present study indicate that patients support and have confidence in the validity of a radiogenomics test for breast radiation toxicity, but they would prefer the result be provided to healthcare professionals. Except in cases of significant chronic symptoms and pain or significant end-organ damage, participants in this study rarely felt that advance knowledge of their personal risk of breast radiation toxicity would influence their treatment decision-making. These findings provide a number of insights that will allow us to anticipate how patients are likely to engage with predictive radiogenomics testing in the future

The TeaM (Therapeutic Mammaplasty) study: Protocol for a prospective multi-centre cohort study to evaluate the practice and outcomes of therapeutic mammaplasty

Wide local excision and adjuvant radiotherapy is the standard of care for early breast cancer. For large tumours, however, mastectomy is frequently recommended as conventional breast-conserving techniques often result in poor cosmetic outcomes. Therapeutic mammaplasty (TM) may extend the boundaries of breast-conserving surgery by combining breast reduction and mastopexy techniques with tumour excision, preserving a natural breast shape and avoiding the need for mastectomy. The prevalence of this operative option among surgeons in the UK and its success rate are unknown. The TeaM study is a multicentre prospective study that aims to investigate the practice and outcomes of TM. Methods and analysis Breast centres performing TM will be invited to participate through the research collaborative network and the professional associations. All patients undergoing TM between September 2016 and March 2017 will be included. Demographic, operative, oncological and complication data within 30-days of surgery will be collected. The primary outcome will be unplanned re-operation for complications. Secondary outcomes will include unplanned readmission, re-excision rates and time to adjuvant therapy. Prospective data on 500 patients from 50 centres are anticipated. Exploratory analyses will identify predictors for complications and inform the design of a definitive study. Ethics and dissemination Research ethics approval is not required for this study. This has been confirmed by the on-line Health Research Authority decision tool. This study will provide novel information regarding the practice and outcomes of TM in the UK. This will inform decision-making for patients and surgeons and inform future research. Dissemination of the study protocol will be via the Mammary Fold Academic and Research Collaborative, the Reconstructive Surgery Trials Network and the professional associations, the Association of Breast Surgery and British Association of Plastic, Reconstructive and Aesthetic Surgeons. Results will be presented at relevant surgical conferences and published in peer-reviewed journals