ESTRO 2023 - Abstract Book

S1868

Digital Posters

ESTRO 2023

Medicine, University of Liverpool, Department of Molecular and Clinical Cancer Medicine, Liverpool, United Kingdom; 5 Clinical University Hospital of Santiago, Department of Medical Physics, Santiago de Compostela, Spain Purpose or Objective Radioimmunotherapy is a novel treatment strategy that aims at exploiting the synergy between radiotherapy and immunotherapy to increase the tumor control rates achieved with either modality alone. The linear-quadratic (LQ) model has played a paramount role in the development of radiotherapy, assisting in the design of novel fractionations. However, because the LQ model only considers direct damage associated with radiation, it cannot be used to model response to radioimmunotherapy. There is a need to develop radiobiological models to describe the dose- effect of radioimmunotherapy treatments. Materials and Methods We present a biomathematical model of tumor response to radioimmunotherapy, which uses the LQ/LQL models to account for direct radiation damage, and includes an immune effect. The model is written as a set of delay differential equations, with mathematical delays accounting for biological delays associated with cell death and immune cell activation and migration. The model is based on our previous work (Gonzalez-Crespo et al. 2022, DOI: 10.1109/TCBB.2022.3174454). The model has been used to fit and analyze preclinical data (mice) of tumor response to radiotherapy combined with checkpoint inhibitors α PDL1/ α CTLA4 (Deng et al. 2014, DOI: 10.1172/JCI67313; Dewan et al. 2009, DOI: 10.1158/1078- 0432.CCR-09-0265). Results The model provides good fits to experimental volume dynamics and control data of tumors treated with radioimmunotherapy (Figure 1). Based on the results of these fits, we have investigated optimal combination schedules for radiotherapy+immunotherapy. This study suggests that the interplay between biological delays and the kinetics of the immunotherapy is important to design optimal radioimmunotherapy schedules: the combined effect seems to be lower if the immunotherapy is delivered too early or too late after radiotherapy (Figure 2).