Author: Young-Bin Cho, Robert Timmerman 👨🔬
Affiliation: Department of Radiation Oncology, UT Southwestern Medical Center, Cleveland Clinic 🌍
Purpose: Immunologically hot (MC38) and cold (LLC) tumor in mouse were treated with radiation and/or immunotherapy agent for the study of Personalized Ultrafractionated Stereotactic Adaptive Radiotherapy (PULSAR). Scheduling radiation and immunotherapy was known to greatly affect the dynamics of tumor response and the success of treatment. This study presents the modelling of PULSA response using the Radio-immune (RI) model.
Methods: RI response model was constructed by 4 ordinary difference equations (ODE) as a function of biomedical variables including the amount of tumor antigen naturally released by tumor, the activation of cytotoxic T-lymphocytes (CTL) by radiation, immune suppression by tumor volume and the use of immunotherapy drugs. These parameters were tuned to fit tumor volume response in single fraction of radiation with/without immunotherapy for each hot and cold tumor types in PULSAR study. The tumor response under different treatment condition (application of the fractionation of radiation with different interval and different immunotherapy schedule) were evaluated. Biomedical parameters extracted during the tunning process were compared between the two different tumor types.
Results: The rate of tumor cell killing by immune response and the amount of radiation induced immune response is 5 and 4.3 times in MC38 hot tumor compared to cold tumor from the tunned RI model. Immune suppression capability of cold tumor was 1.7 times of hot tumor. Tumor volume of both hot and cold type was well predicted with the proposed RI model under all different treatment conditions in PULSA study, demonstrating the feasibility of personalized adaptive radiotherapy.
Conclusion: Tumor response for PULSAR study was well predicted with the proposed RI model under all different treatment conditions, indicating the feasibility of personalized adaptive radiotherapy with PULSAR and RI model.