PULSAR Effect: Revealing Potential Synergies in Combined Radiation Therapy and Immunotherapy via Differential Equations

TL;DR

This paper develops a mathematical model to understand how the timing of radiation pulses in PULSAR therapy influences its synergy with immunotherapy, aiming to optimize treatment scheduling based on pre-clinical data.

Contribution

The study introduces a novel differential equation model that captures the timing-dependent synergy between PULSAR radiotherapy and immunotherapy, aiding clinical trial design.

Findings

Model replicates pre-clinical tumor response data

Optimal pulse spacing enhances synergistic effects

Model is simple to implement and adaptable

Abstract

PULSAR (personalized ultrafractionated stereotactic adaptive radiotherapy) is a form of radiotherapy method where a patient is given a large dose or pulse of radiation a couple of weeks apart rather than daily small doses. The tumor response is then monitored to determine when the subsequent pulse should be given. Pre-clinical trials have shown better tumor response in mice that received immunotherapy along with pulses spaced 10 days apart. However, this was not the case when the pulses were 1 day apart. Therefore, a synergistic effect between immunotherapy and PULSAR is observed when the pulses are spaced out by a certain number of days. In our study, we aimed to develop a mathematical model that can capture the synergistic effect by considering a time-dependent weight function that takes into account the spacing between pulses. By determining feasible parameters, and applying reasonable conditions, we utilize our model to simulate murine trials with varying sequencing of pulses. We successfully demonstrate that our model is simple to implement and can generate tumor volume data that is consistent with the pre-clinical trial data. Our model has the potential to aid in the development of clinical trials of PULSAR therapy.