Evaluating Very High Energy Electron RBE from nanodosimetric pBR322 plasmid DNA damage

This paper presents the first plasmid DNA irradiations carried out with Very High Energy Electrons (VHEE) over 100-200 MeV at the CLEAR user facility to determine the Relative Biological Effectiveness (RBE) of VHEE. DNA damage yields were measured in dry and wet environments to determine that ~99% of total DNA breaks were caused by indirect effects, consistent with other published measurements for protons and photons. Double-Strand Break (DSB) yield was used as the biological endpoint for RBE calculation, with values found to be consistent with established radiotherapy modalities. Similarities in physical damage between VHEE and conventional modalities gives confidence that biological effects of VHEE will also be similar – key for clinical implementation. Damage yields were used as a baseline for track structure simulations of VHEE plasmid irradiation using GEANT4-DNA. Current models for DSB yield have shown reasonable agreement with experimental values. The growing interest in FLASH radiotherapy motivated a study into DSB yield variation with dose rate following VHEE irradiation. No significant variations were observed between conventional and FLASH dose rate irradiations, indicating that a FLASH effect is not related to DNA damage under these conditions.