Biological Impact of Target Fragments from 10 MeV - 20 GeV Proton Beams: Relevance to Proton Therapy and Space...

The interaction of proton beams with matter produces secondary protons and high-LET ions through nuclear reactions, modifying the absorbed depth-dose profile and the beam's relative biological effectiveness (RBE). However, the separate contributions of primary and secondary particles have never been systematically quantitatively analyzed. To address this, we performed Monte Carlo transport simulations using the FLUKA code for proton beams at 25 different primary energies (10 MeV-20 GeV) in water, providing spectral information for each produced component. The biological effects of the resulting mixed field were evaluated using mixed radiation calculator (MiRaCal) developed at GSI, Darmstadt, Germany. MiRaCal integrates monochromatic RBE data from the local effect model (LEM IV) using the low-energy adaption (LEA) into a representative RBE value, accounting for all spectral components. The RBE was assessed for eight αγ/βγ ratios (1-20 Gy) to represent different cell sensitivities for all primary energies. We show that for low αγ/βγ ratios, a crossover energy exists above which secondary particles dominate the biological effect, despite their minor contribution to fluence and absorbed dose. We then demonstrate that 80-100 MeV protons exhibit minimal effectiveness. Additionally, we show that fragment-associated effects support the use of a global RBE of 1.1 for organs at risk that are not irradiated by the spread-out Bragg peak but lie in the entrance channel of the treatment fields. Furthermore, the enhanced RBE at high primary proton energies due to fragments is particularly relevant for space radiation protection, where protons with energies from < 1 MeV up to tens of GeV account for most of the particle spectra, especially inside a space habitat. Finally, we show that LETd is not a good unique predictor for RBE, but its use in proton therapy clinical practice as a surrogate for RBE is justified under certain controlled conditions.