Radiation protection and safety measures are essential to ensure adequate quality & safety in radiotherapy (RT). Side effects are systematically mitigated through optimisation and individualisation. Breast cancer (Bca) is the most common cancer in women in Europe, leading to millions of BCa survivors in Europe; this group is projected to increase in the next decades. Randomised trials established the role of RT following breast surgery. Careful RT planning and delivery allow targeting the breast while minimising the dose to organs at risk. Yet, some doses unavoidably reach the lung and the heart, putting BCa patients at risk for severe cardiac and pulmonary disease and second cancers. Quantitative personalised risk scores for late severe cardiac/pulmonary disease/second cancers following RT would reveal opportunities to further mitigate the risk of side effects at the individual patient level. Risk scores would provide a quantitative guide when shaping the patients’ follow-up and screening program to assess the risk or presence of subclinical diseases. Within TETRIS, we propose to design and test quantitative personalised low-level risk scores based on dose-response relationships already published in the literature and refined risk scores which merge patient-specific features (from imaging, genetics and transcriptomics) with RT dose. The project also proposes to explore the opportunities and challenges of applying digital twins (DTs) in RT safety. We will use the historical cohort to develop the prototypes and evaluate the gain we can have using digital twins for risk assessment instead of model-based risk scores. Using a prospective collection of detailed patient data, we will demonstrate the possibility of refining DTs, allowing a deeper description of the single patient and a broader description of the patient’s follow-up. The value of the refined DTs could shape investments in data collection and computational resources for radioprotection.