Room: AAPM ePoster Library
Purpose: To develop a simple biophysical DNA double-strand-break (DSB) induction model for proton therapy and explore its possible uses in radiobiologically constrained inverse plan optimization.
Methods: A probabilistic single particle interaction model was developed to quantify the yield of DSBs for a given voxelized energy spectrum. Parametric fitting was performed to Monte Carlo DSB counts calculated under hypoxic conditions in a first approximation, limiting the effects of chemical repair and oxygen fixation. Monte Carlo simulations were performed for a range of nominal proton pencil beam energies between 60 and 120 MeV. Energy spectra were extracted from 1 mm cubed voxels in a water phantom and used to calculate mean DSB counts per voxel. Similarly, DSB counts were collected from a uniform 10 x 10 cm 6MV photon field for comparison. A restricted relative biological effect (RBE), based only on DSB induction, was then calculated by dividing the proton beam DSB counts by the photon beam counts.
Results: DSB counts were shown to increase similarly to the linear energy transfer (LET) as a function of depth, reaching an inflection point at the distal edge of the Bragg peak. The RBE in the entrance region was 1.1 on average, and reached between 1.8 and 2.4 at the distal edge. Furthermore, the maximum RBE achieved was shown to increase with decreasing beam energy.
Conclusion: A simple DSB induction model, developed from first principles, has provided RBE estimates that are in line with experimental findings in the literature. The model excludes physicochemical processes such as oxygen fixation and DNA repair, but captures the physical principles behind the argument for variable RBE. As DSB counts estimated using this model scale linearly with dose, standard inverse optimization can be performed with precalculated RBE-weighted pencil beam doses.
Funding Support, Disclosures, and Conflict of Interest: MB is supported by Cancer Research UK Grant No. C2195/A25197, through a CRUK Oxford Centre DPhil Prize Studentship, AV by Cancer Research UK Grant: ArtNET: Number C309/A21993, and FVdH by a Cancer Centre grant CRUK C2195/A25014 and CRUK OIRO Number C5255/A23755.