Calculation of DNA damage at different depths of proton SOBP based on a new method and its applications

In examining the biological effects of proton radiation, DNA is the primary sensitive target. This study utilizes Monte Carlo simulations to efficiently calculate DNA damage yields at various proton depths to analyze the biological effects of protons and their variability on different scales. A new method, the "Coefficient Method" is used to replace the complete chemical processes by adjusting parameters to obtain suitable values for simulating DNA damage yields at different SOBP depths of low-energy protons, and these parameters are then applied to high-energy proton simulations based on a mesh-type cell model. We computed two RBE at two different scales: RBE_max (at 0 Gy per fraction) and RBE_DSB (based on DNA damage yields). The results confirm the feasibility of the "Coefficient Method," with deviations in Y_DSBs (the yields of double-strand breaks) and Y_DSBc (the yields of complex double-strand breaks) ranging from 0.60%-3.79% and 1.45%-4.1%, respectively, and a clear advantage in simulation efficiency. For high-energy protons, Y_SSBs (the yields of single-strand breaks) decreases with depth, while Y_DSBs and Y_DSBc increase. What's more, the differences in RBE across different scales are substantial. At 1 cm depth for 70_SOBP MeV protons, RBEmax is 1.53 vs. RBE_DSB of 1.45; at the beam end, RBE_max reaches 10.45 vs. RBE_DSB of 2.36. Mesh thickness has negligible impact on RBEmax. It is confirmed that using the "Coefficient Method" to obtain DNA damage yields at different depths for high-energy protons is reliable. The RBE_DSB values based on this method show significant differences compared to the traditional RBEmax values. This indicates the importance of investigating the biological effects of proton radiation at the DNA scale and further emphasizes the significance of exploring the relationship between proton radiation quality and the target of interest.