Mathematical Modeling of the Synergetic Effect between Radiotherapy and Immunotherapy

Abstract: Achieving effective synergy between radiotherapy and immunotherapy is critical for optimizing tumor control and treatment outcomes. To explore the underlying mechanisms of this synergy, we have investigated a novel treatment approach known as personalized ultra-fractionated stereotactic adaptive radiation therapy (PULSAR), which emphasizes the impact of radiation timing on treatment efficacy. However, the precise mechanism remains unclear. Building on insights from small animal PULSAR studies, we developed a mathematical framework consisting of multiple ordinary differential equations to elucidate the temporal dynamics of tumor control resulting from radiation and the adaptive immune response. The model accounts for the migration and infiltration of T-cells within the tumor microenvironment. This proposed model establishes a causal and quantitative link between radiation therapy and immunotherapy, providing a valuable in-silico analysis tool for designing future PULSAR trials.