Optimizing Radiation Therapy Treatments by Exploring Tumour Ecosystem Dynamics in – silico

In this contribution, we propose a system-level compartmental population dynamics model of tumour cells that interact with the patient (innate) immune system under the impact of radiation therapy (RT). The resulting in silico model enables us to analyse the system-level impact of radiation on the tumour ecosystem. The Tumour Control Probability (TCP) was calculated for varying conditions concerning therapy fractionation schemes, radio-sensitivity of tumour sub-clones, tumour population doubling time, repair speed and immunological elimination parameters. The simulations exhibit a therapeutic benefit when applying the initial 3 fractions in an interval of 2 days instead of daily delivered fractions. This effect disappears for fastgrowing tumours and in the case of incomplete repair. The results suggest some optimisation potential for combined hyperthermia-radiotherapy. Regarding the sensitivity of the proposed model, cellular repair of radiation-induced damages is a key factor for tumour control. In contrast to this, the radio-sensitivity of immune cells does not influence the TCP as long as the radio-sensitivity is higher than those for tumour cells. The influence of the tumour sub-clone structure is small (if no competition is included). This work demonstrates the usefulness of in silico – modelling for identifying optimisation potentials.