Modeling of dose and sensitivity heterogeneities in radiation therapy

The increased interest in the use of light ion therapy is due to the high dose conformity to the target and the dense energy deposition along the tracks resulting in increased relative biological effectiveness compared to conventional radiation therapy. In spite of the good clinical experience, fundamental research on the characteristics of the ion beams is still needed in order to be able to fully explore their use. Therefore, a Monte Carlo track structure code, KITrack, simulating the transport of electrons in liquid water, has been developed and used for calculation of parameters of interest for beam characterization. The influence of the choice of the cross sections for the physical processes on the electron tracks has also been explored. As an alternative to Monte Carlo calculations a semi-analytical approach to calculate the radial dose distribution from ions, has been derived and validated. In advanced radiation therapy, accurate characterization of the beams has to be complemented by comprehensive radiobiological models, which relate the dose deposition into the cells to the outcome of the treatment. The second part of the study has therefore explored the influence of heterogeneity in the dose deposition into the cells as well as the heterogeneity in the cells sensitivity to radiation on the probability of controlling the tumor. Analytical expressions for tumor control probability including heterogeneous dose depositions or variation of radiation sensitivity of cells and tumors have been derived and validated with numerical simulations. The more realistic case of a combination of these effects has also been explored through numerical simulations. The MC code KITrack has evolved into an extremely useful tool for beam characterization. The tumor control probability, given by the analytical derived expression, can help improve radiation therapy. A novel anisotropy index has been proposed. It is a measure of the absence of isotropy and provides deeper understanding of the relationship between beam quality and biological effects.At the time of the doctoral defense, the following paper was unpublished and had a status as follows: Paper 4: Manuscript.