Radiobiological end-points for the theoretical evaluation of the effectiveness of carbon ions and photons in treating tumours with dynamic hypoxia

Abstract: Tumours are characterised by unorganised vasculature, which often results in hypoxic regions. Hypoxia is a common cause for photon radiotherapy (RT) treatment failure, as hypoxic cells require up to 2-3 times higher doses compared to well-oxygenated cells for the same effect in terms of cell kill. The increase in dose that would be required to treat the tumours of cancer patients is limited by the radiation sensitivity of surrounding normal tissues. Using carbon ions instead of photons, the radiation dose can be conformed to the tumour to a much higher degree, resulting in an improved sparing of normal tissues. In addition, carbon ions have a much higher radiobiological effectiveness near the end of their range, which is positioned in the tumour. Also, the radiation modes of action leading to cell death when carbon ions interact with living tissues, are less sensitive to the oxygen status compared with the action modes of photons.The focus of this thesis lies in the development of models for the computation of the cell surviving fraction and tumour control probability (TCP) in hypoxic tumours after photon and carbon ion RT. The impact of fractionation was evaluated with regard to possible spatial changes in oxygenation, both for stereotactic body RT and for carbon ion RT. The feasibility of a method to determine and deliver the optimal photon dose for achieving a high TCP according to spatial variations in radiation sensitivity was evaluated in a treatment planning study. The radiobiological models were finally used for the theoretical quantification of the gain in using carbon ions instead of photons.The results show that there are great possibilities to increase the number of positive outcomes of radiation treatment of tumours if the key influential factors are taken into account, such as level and distribution of hypoxia, radiation quality and choice of fractionation schedule.