Medulloblastoma (MB) is one of the most common brain tumors in children and most patients will survive their disease if treated with surgery, radio- and chemotherapy. This has resulted in a growing number of MB survivors who are at risk of developing severe late complications related to the aggressive anti-cancer therapy. Some of the most important late complications for these patients include secondary malignancies, cardiac events and neurocognitive decline. Much of the late complication risk can be attributed the craniospinal irradiation which is part of standard management, since this results in irradiating a large volume of healthy tissue in these young patients. The general aim of this thesis is reducing the risk of late treatment toxicity through risk-based advanced radiotherapy optimization. We specifically investigated the use of radiobiological models to estimate late complication risks, developed a mathematical framework for comparing different risks on a common scale and the assessed the potential clinical benefit of sparing critical neurological structures during cranial irradiation. We also developed a mathematical tumor control model for standard-risk MB to assess the effect on treatment efficacy from applying different risk-based treatment strategies.