Current practice in radiation therapy is based on physical optimisation of the dose distribution according to the anatomical information regarding the localisation and the extent of the tumour and the normal tissue. The routine planning in the clinical radiation treatment does not generally take into account the particular radiation sensitivity of either the tumour or the individual patient, or the spatial and temporal heterogeneity of the tumour resistance. However, it is well known that these aspects may be the cause for treatment failure, as the standard dose prescription does not ensure curative doses to counteract the radiation resistance of the tumour. The general aim of this research project is to use information from morphological and functional imaging methods in order to individualise the radiation dose delivery with high accuracy using advanced treatment planning techniques such as biologically optimized intensity-modulated radiotherapy.

The use of stereotactic radiosurgery employing one large fraction of radiation has continuously increased due to the technical development and the progress in dose delivery complemented by the positive clinical experience. This project aims to analyse and quantify a multiobserver variability of target and organs at risk delineation for radiosurgery targets and to evaluate the potential impact of the differences in delineation with respect to tumour control probability, contribute to the establishment of delineation guidelines for organs at risk (OARs) as well as to develop a robust method for estimating the accurate target based on multiple delineations and to investigate the possibility of accounting for the uncertainty in target delineation through probabilistic and robust treatment planning.

Stereotactic body radiation therapy outcome is highly dependent on the tumour microenvironmental conditions. One question is how efficient is SBRT particularly for the case of tumours with hypoxic regions. The optimal number of fractions in which the SBRT has to be delivered must therefore be customised for each patient depending not only on the intrinsic sensitivity of the cells to radiation but also on the oxygenation of the tumour. Thus, the specific aim of this project is to analyse of the impact of the fractionation schedule in which the prescribed dose is delivered in SBRT on the tumour control probability depending on the intrinsic sensitivity of the cells to radiation and the oxygenation of the tumour.

There are very few, if any, clinical trials comparing photons with protons or ions heavier than protons such as C-ions. Currently, the selection of the patients for proton therapy is based on the assumed better physical conformity of the proton plans in comparison to photons. The specific aim of this project is to create the framework and perform in silico clinical trials protons versus photons that would provide objective criteria to select patients for proton therapy including the analysis of the robustness of the photon and proton plans to uncertainties in the physical and biological parameters, the optimisation of the proton plans with respect to LET and the optimisation of the plans with respect to the adverse radiobiological features.