A Precision Tumor Growth Model Integrating Time-Resolved Flow Cytometry: Predicting Fractionation Efficacy and Immunotherapy Scheduling

OBJECTIVE: Current mathematical models of tumor growth are often limited by a scarcity of quantitative immune data, leading to imprecise characterizations of tumor progression. To address this limitation, we developed a novel coupled Tumor-Immune-Radiotherapy dynamics model by integrating time-resolved flow cytometry data. Approach: An MC38 tumor-bearing mouse model was established to evaluate distinct radiotherapy fractionation regimens (Control, 5 Gy × 5, and 8 Gy × 3). Flow cytometry was employed to dynamically quantify the temporal evolution of tumor-infiltrating lymphocytes. By integrating the Linear-Quadratic model and immune cytotoxicity into the Gompertz equation, a dynamic coupled mathematical model was formulated. Least squares fitting was applied to experimental data to calibrate parameters governing immune-mediated tumor suppression and promotion. Main results: The proposed immune-growth coupled framework demonstrated superior goodness-of-fit compared to conventional models for both hypofractionated (8 Gy × 3) and medium-dose (5 Gy × 5) regimens. Notably, the incorporation of a dynamic temporal dimension facilitated the estimation of immune intervention timing, revealing that the onset of immune synergy is distinct and critically dictated by the selected dose fractionation strategy. Significance: The coupled model established herein not only accurately predicts tumor growth dynamics but also serves as a robust, biologically validated computational tool for predicting the efficacy of fractionation schemes and providing strategic recommendations for immunotherapy scheduling. .