Predicting the Tumour Response to Radiation by Modelling the Five Rs of Radiotherapy Using PET Images.

ABSTRACT

Despite the intensive use of radiotherapy in clinical practice, its effectiveness depends on several factors. Several studies showed that the tumour response to radiation differs from one patient to another. The non-uniform response of the tumour is mainly caused by multiple interactions between the tumour microenvironment and healthy cells. To understand these interactions, five major biologic concepts called the "5 Rs" have emerged. These concepts include reoxygenation, DNA damage repair, cell cycle redistribution, cellular radiosensitivity and cellular repopulation. In this study, we used a multi-scale model, which included the five Rs of radiotherapy, to predict the effects of radiation on tumour growth. In this model, the oxygen level was varied in both time and space. When radiotherapy was given, the sensitivity of cells depending on their location in the cell cycle was taken in account. This model also considered the repair of cells by giving a different probability of survival after radiation for tumour and normal cells. Here, we developed four fractionation protocol schemes. We used simulated and positron emission tomography (PET) imaging with the hypoxia tracer 18F-flortanidazole (18F-HX4) images as input data of our model. In addition, tumour control probability curves were simulated. The result showed the evolution of tumours and normal cells. The increase in the cell number after radiation was seen in both normal and malignant cells, which proves that repopulation was included in this model. The proposed model predicts the tumour response to radiation and forms the basis for a more patient-specific clinical tool where related biological data will be included.