Mathematical modeling in radiotherapy for cancer: a comprehensive narrative review

Mathematical modeling has long been a cornerstone of radiotherapy for cancer, guiding treatment prescription, planning, and delivery through versatile applications. As we enter the era of medical big data, where the integration of molecular, imaging, and clinical data at both the tumor and patient levels could promise more precise and personalized cancer treatment, the role of mathematical modeling has become even more critical. This comprehensive narrative review aims to summarize the main applications of mathematical modeling in radiotherapy, bridging the gap between classical models and the latest advancements. The review covers a wide range of applications, including radiobiology, clinical workflows, stereotactic radiosurgery/stereotactic body radiotherapy (SRS/SBRT), spatially fractionated radiotherapy (SFRT), FLASH radiotherapy (FLASH-RT), immune-radiotherapy, and the emerging concept of radiotherapy digital twins. Each of these areas is explored in depth, with a particular focus on how newer trends and innovations are shaping the future of radiation cancer treatment. By examining these diverse applications, this review provides a comprehensive overview of the current state of mathematical modeling in radiotherapy. It also highlights the growing importance of these models in the context of personalized medicine and multi-scale, multi-modal data integration, offering insights into how they can be leveraged to enhance treatment precision and patient outcomes. As radiotherapy continues to evolve, the insights gained from this review will help guide future research and clinical practice, ensuring that mathematical modeling continues to propel innovations in radiation cancer treatment.