Qualitative Comparison of the Cytotoxic and Immunologic Consequences of Spatially Homogeneous and Heterogeneous Radiation Dosing

In radiotherapy the standard of care (SOC) is homogeneous tumor dosing. Spatially fractionated dosing (GRID) has recently been studied in the clinic. Radiation induces cytotoxicity on both tumor and immune cells, but it is hypothesized that it also elicits an immune response. To explore radiation-induced immunity, three tumors of similar mass were grown in silico and radiated with SOC homogeneous and GRID dose distributions. A stochastic agent based model described the dynamic interactions between the cancer and immune cells. This was supplemented with an ODE approach. All simulations without radiation-induced immunity did not control tumors. Simulations under conventional dosing with radiation-induced immunity resulted in tumor control. GRID radiation with large single doses correlated with lower cancer to immune cell ratios. Simulations revealed that in addition to inducing a powerful immune response, the tumor did not decrease in mass without radiation-induced immunity. GRID dosing may be effective in treatment of tumors assuming robust immune response. High dose, single GRID fractions showed promise in reducing tumor burden due to the large number of immune cells generated and spared.