The use of stereotactic body radiation therapy employing few large fractions of radiation dose for the treatment of non-small cell lung cancer has been proven very successful, high values of tumour control probability (TCP) being clinically achieved. In spite of the success of the fractionation schedules currently used, there is a tendency towards reducing the number of fractions for economical and practical reasons, and also for maximizing the comfort of the patients. It is therefore the main aim of this thesis to investigate the impact of a severely reduced number of fractions on the tumour control probability for tumours that contain hypoxic areas. The impact on TCP of other factors such as hypoxic fraction, distribution of the oxygen partial pressure and location of the hypoxic volume within the tumour were also investigated. The effect of tumour motion due to breathing was included and evaluated using Cone Beam Computed Tomography (CBCT) data from patients imaged with internal markers in the liver and pancreas. The results clearly showed that in the presence of hypoxia, TCP is seriously compromised if there is not enough time for reoxygenation between fractions. A reduction in the number of fractions of just one fraction may require an increase of several Gy per fraction to obtain a similar TCP. The diaphragmatic tumour motion range showed little influence on TCP provided that the PTV encompassed all tumour positions. The dose delivered to the PTV margin was found not to be the only factor that is significant for local control, the average dose correlated better with TCP. The agreement of the results of this work with clinical results also serve as a strong indicator that inter-fraction reoxygenation is an important process in real-life patients treated with stereotactic body radiotherapy.

Radiation therapy with light ions improves treatment outcome for a number of tumor types. The advantageous dose distributions of light ion beams en-able exceptional target conformity, which assures high dose delivery to the tumor while minimizing the dose to surrounding normal tissues. The demand of high target conformity necessitates development of accurate methods to calculate absorbed dose distributions. This is especially important for heavy charged particle irradiation, where the patient is exposed to a complex radia-tion field of primary and secondary ions. The presented approach combines accurate Monte Carlo calculations using the SHIELD-HIT07 code with a fast analytical pencil beam model, to pro-vide dose distributions of light ions. The developed model allows for ana-lytical descriptions of multiple scattering and energy loss straggling proc-esses of both primary ions and fragments, transported in tissue equivalent media. By applied parameterization of the radial spread of fragments, im-proved description of radial dose distributions at every depth is obtained. The model provides a fast and accurate tool of practical value in clinical work. Compared to conventional radiation modalities, an enhanced tissue response is seen after light ion irradiation and biological optimization calls for accu-rate model description and prediction of the biological effects of ion expo-sure. In a joint study, the performance of some radiobiological models is compared for facilitating the development towards more robust and precise models. Specifically, cell survival after exposure to various ion species is modeled by a fast analytical cellular track structure approach in conjunction with a simple track-segment model of ion beam transport. Although the stud-ies show that descriptions of complex biological effects of ion beams, as given by simple radiobiological models, are approximate, the models may yet be useful in analyzing clinical results and designing new strategies for ion therapy.