Handling of beam spectra in training and application of proton RBE models.

Published data from cell survival experiments are frequently used as training data for models of proton relative biological effectiveness (RBE). The publications rarely provide full information about the primary particle spectrum of the used beam, or its content of heavy secondary particles. The purpose of this paper is to assess to what extent heavy secondary particles may have been present in published cell survival experiments, and to investigate the impact of non-primary protons for RBE calculations in treatment planning. We used the Monte Carlo code Geant4 to calculate the occurrence of non-primary protons and heavier secondary particles for clinical protons beams in water for four incident energies in the [100, 250] MeV interval. We used the resulting spectra together with a conservative RBE parameterization and an RBE model to map both the rise of RBE at the beam entry surface due to heavy secondary particle buildup, and the difference in estimated RBE if non-primary protons are included or not in the beam quality metric. If included, non-primary protons cause a difference of 2% of the RBE in the plateau region of an spread out Bragg peak and 1% in the Bragg peak. Including non-primary protons specifically for RBE calculations will consequently have a negligible impact and can be ignored. A buildup distance in water of one millimeter was sufficient to reach an equilibrium state of RBE for the four incident energies selected. For the investigated experimental data, 83 out of the 86 data points were found to have been determined with at least that amount of buildup material. Hence, RBE model training data should be interpreted to include the contribution of heavy secondaries.