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Abstract

Radiotherapy is a crucial pillar of cancer therapy and ion beams promise superior dose conformity and potentially enhanced biological effectiveness in comparison to conventional radiation modalities. However, several factors are known to modify the biological effect of radiation. The capability to model their impact within a unified description of radiation action in conventional and ion beam fields would greatly enhance the ability to prescribe the optimal treatment and improve the knowledge of underlying mechanisms. To this end, the initial developments of the mechanistic UNIfied and VERSatile bio response Engine (UNIVERSE) are presented in this work. The effects of radiosensitizing drugs and mutations as well as DNA repair kinetics were modeled for each radiation quality. For sparsely ionizing radiation, the sparing effects at ultra-high dose-rates (uHDR) applied in FLASH radiotherapy were introduced based on oxygen depletion rates approaching measured values. Benchmarks against own or literature data are presented for each development. Challenges concerning the transition of oxygen and uHDR effects to ion beams as well as the vision of personalized biomarker-based patient plan adaptation based on UNIVERSE are discussed. UNIVERSE offers clinically relevant insights into radiobiological interdependencies and its versatility will allow it to follow future trends in radiotherapy.