FLASH PROTON THERAPY: the biological response and the oxygen depletion effect of high dose rate

FLASH radiotherapy is attracting an increasing interest in the radiation oncology community due to the great potential clinical benefit resulting from the low damage to normal tissues, whilst preserving the required tumour control. Since the use of proton beams at conventional dose rate also spare critical organs by reducing the dose delivered, the use of proton beams for FLASH radiotherapy is an interesting subject of investigation. Although some preliminary investigations have been carried out, in the current literature there is still a great lack of experimental data, simulations and modelling work for what concern FLASH protons. This project aims at supporting the development of a new FLASH proton-therapy technique by investigating the proton-specific radiobiological mechanisms underpinning it. Our goals are: to relate the biological effects of high-dose rate radiation to the different chemical conditions under which the cells find themselves and to investigate the role of oxygen and free radical species. For in-vitro experiments, different cell types will be used employing conventional radiobiology techniques such as clonogenic assays - for studying the impact on cell killing at variable doses - and immunofluorescence - for DNA break/repair detection. An irradiation chamber has been developed with the aim to irradiate cells in different conditions of oxygenation to investigate the role of oxygen level on the FLASH effect and, therefore investigate the oxygen depletion hypothesis. The simulation part will be carried out using the Geant4 extension for radiobiology, Geant4-DNA, which provides tools to model the biological damages induced by ionising radiation at the DNA scale and the chemical processes for water radiolysis. Experiments will be combined with modelling activities to study if a correlation exists between the amount of free radicals’ production, under different oxygen levels, and the biological response of normal and tumour cells.
{"references":["Vozenin et al., 2019, Radiotherapy and Oncology 139","Vozenin et al, 2019, Clinical Oncology 31","Durante et al., 2018, Br J Radiol 91: 20170628","Boscolo et al., 2020, Int J Mol Sci 21:424","Cancer Research UK (CRUK)"]}