Reinforced risk appraisal of medical exposure is needed due to an extensive use of ionising radiation for diagnosis and therapy. The main objective of the 4-year SINFONIA project is to develop novel methodologies and tools that will provide a comprehensive a risk appraisal for detrimental effects of radiation exposure on patients, workers, carers and comforters, the public and the environment during the management of patients suspected or diagnosed with lymphoma and brain tumours. The scientific work will (1) develop novel AI-powered personalised dosimetry and risk appraisal methods and tools to estimate the radiation burden on patients undergoing state-of-the-art radiological, nuclear medicine and radiation therapy procedures, (2) reinforce risk appraisal for exposed staff, comforters, the public and the environment during nuclear medicine and proton therapy procedures, (3) determine the degree of patient variability in radiation sensitivity for the risk of developing secondary malignancies and (4) design and develop data management techniques for managing data from imaging and non-imaging examinations and radiation therapy sessions. A data repository will be developed for storing data as well as for the deployment of AI algorithms on an online platform. SINFONIA research outcomes for the two clinical examples, lymphoma and brain tumours, will be also applicable to other diseases. AI-powered personalised dosimetry tools will provide advanced knowledge on parameters affecting radiation detriment. This will help balancing risks and benefits of ionising radiation procedures and developing dose optimisation strategies. Additionally, radiation biology studies will identify individuals with increased susceptibility of developing cancer from ionising radiation exposure. SINFONIA also will organise highlevel multidisciplinary training in the field of radiation dosimetry, risk appraisal and radiation protection and develop recommendations on radiological protection.