Purpose: Variable RBE in carbon radiotherapy may be calculated using several models, including the microdosimetric kinetic model (MKM), adapted stochastic MKM (SMKM), and repair misrepair fixation (RMF) model. This work compares the sensitivity of each of these models to variations in input biological and reference parameters.
Methods: Geant4 Monte Carlo was used to simulate clinically realistic monoenergetic carbon beams (ranges 5/15/25 cm) incident on a water phantom. Input parameters for RBE models (microdosimetric spectra, double strand break yield, physical dose) were scored. Data were used along with cellular and model specific parameters to calculate carbon linear (α) and quadratic (β) components, which were combined with reference α and β values and physical dose to calculate RBE. Model sensitivity to various parameters were quantified by statistically introducing uncertainty into independent parameters over 1000 iterations and sampling resultant RBE. Reference cell lines were also varied to assess RBE differences due to histology.
Results: The sensitivity study demonstrated that microdosimetric models had greater sensitivity to changes in reference α, β, and physical dose than RMF. Within microdosimetric models, changes in cellular domain radius had the largest effect on RBE. Within RMF, the double strand break yield of reference radiation had the greatest impact. When varying cell lines within a single model, RBE varied by 15% and 77% on average, for each microdosimetric models and RMF. Using different published reference data sets for a single cell line yielded an average RBE difference of 50% across all four reference data sets.
Conclusion: While focus is largely placed on comparing models, the variation within each based on reference parameters alone is drastic. This study gives insight on the robustness of various models to measured and assumed input parameters, and emphasizes the need for continued computational and in vitro RBE research.
TH- External Beam- Particle/high LET therapy: Other particle therapy