Predicting acute radiation toxicity in breast cancer
thesisposted on 13.11.2019, 11:06 by Tim Rattay
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.