First theoretical determination of relative biological effectiveness of very high energy electrons.

Very high energy electrons (VHEEs, E > 70 MeV) present promising clinical advantages over conventional beams due to their increased range, improved penumbra and relative insensitivity to tissue heterogeneities. They have recently garnered additional interest in their application to spatially fractionated radiotherapy or ultra-high dose rate (FLASH) therapy. However, the lack of radiobiological data limits their rapid development. This study aims to provide numerical biologically-relevant information by characterizing VHEE beams (100 and 300 MeV) against better-known beams (clinical energy electrons, photons, protons, carbon and neon ions). Their macro- and microdosimetric properties were compared, using the dose-averaged linear energy transfer ([Formula: see text]) as the macroscopic metric, and the dose-mean lineal energy [Formula: see text] and the dose-weighted lineal energy distribution, yd(y), as microscopic metrics. Finally, the modified microdosimetric kinetic model was used to calculate the respective cell survival curves and the theoretical RBE. From the macrodosimetric point of view, VHEEs presented a potential improved biological efficacy over clinical photon/electron beams due to their increased [Formula: see text]. The microdosimetric data, however, suggests no increased biological efficacy of VHEEs over clinical electron beams, resulting in RBE values of approximately 1, giving confidence to their clinical implementation. This study represents a first step to complement further radiobiological experiments.