Mathematical Modeling of the Synergetic Effect between Radiotherapy and Immunotherapy

TL;DR

This paper develops a mathematical model to understand the synergistic effects of radiotherapy and immunotherapy, focusing on the timing and immune response dynamics to optimize combined cancer treatments.

Contribution

It introduces a novel ODE-based framework that links radiation timing with immune response, aiding in the design of personalized ultra-fractionated radiotherapy strategies.

Findings

Model captures tumor-immune interaction dynamics

Provides insights into optimal radiation timing

Supports in-silico trial design for PULSAR

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.