Contribution of Nuclear Fragmentation to Dose and RBE in Carbon-Ion Radiotherapy.

Variable relative biological effectiveness (RBE) of carbon radiotherapy may be calculated using several models, including the microdosimetric kinetic model (MKM), stochastic MKM (SMKM), repair-misrepair-fixation (RMF) model, and local effect model I (LEM), which have not been thoroughly compared. In this work, we compared how these four models handle carbon beam fragmentation, providing insight into where model differences arise. Monoenergetic and spread-out Bragg peak carbon beams incident on a water phantom were simulated using Monte Carlo. Using these beams, input parameters for each model (microdosimetric spectra, DNA double-strand break yield, kinetic energy spectra, physical dose fragment contributions) were calculated for each contributing carbon beam fragment (hydrogen, helium, lithium, beryllium, boron, secondary carbon, primary carbon, electrons, and "other"). Scored input parameters for each fragment were used to calculate linear (α) and quadratic (β) parameters according to each model, which were combined with reference α and β values and absorbed physical dose to calculate RBE. Contributions from secondary fragments were found to exceed 30% of the total physical dose. Using identical beam parameters, the four models produced not only different RBE values but also different RBE trends. In all models, RBE was highest for secondary carbon ions. Beyond secondary carbons, the RBE magnitude typically increased with the atomic number of the fragment, but RBE trends differed dramatically by model and beamline region (entrance, spread-out Bragg peak, and tail). Variations in fragment RBE were large enough to be apparent in biological dose predictions. This study demonstrated that fragmentation is a nonnegligible consideration in carbon radiotherapy. Our findings identified differences in RBE among specific fragments and the four models, contributing to variability in the total biological dose across models. Because these findings emphasize differences in how various models handle carbon beam fragments, greater care should be taken in characterization of secondary fragments in particle therapy.