Investigation of relative biological effectiveness for protons, carbon and oxygen ion beams by DNA damage calculations in a fractal fibroblast cell geometry.

The relative biological effectiveness (RBE) was established to quantitatively compare the biological impact of different radiation types. While clinical proton therapy typically employs an RBE of 1.1, significant variability exists in experimental determinations making the establishment of a definitive proton RBE value challenging. This study investigates RBE of protons (62 MeV), carbon ions (112.5 MeV/n) and oxygen ions (131.5 MeV/n) by analyzing DNA damage complexity and cell survival in a fractal fibroblast cell nucleus (as an optimized cellular geometry) using Geant4 simulations. Our results demonstrate that carbon and oxygen ions induce significantly greater DNA damage than protons, particularly complex double-strand breaks. Simulated RBEs reached maxima of 5.71 and 7.54 for carbon and oxygen ions, respectively, which were validated against experimental data (for C-12) over a wide LET range, successfully reproducing the characteristic overkill effect for carbon ions. The dense ionization patterns of heavy ions produce clustered DNA damage, while protons yield more dispersed, reparable lesions. While proton RBE remained below 1.5 across the primary depths analyzed, carbon and oxygen ions exhibited substantially higher values at the same depths, aligning with experimental observations. Oxygen ions showed superior tumor cell killing to carbon ions, requiring lower doses (1.01 vs. 1.28 Gy at the Bragg peak) to achieve 10% cell survival. RBE calculations derived from cell survival curves closely matched those from complex DSB analysis. The study underscores the need for RBE models that integrate both complex DNA damage metrics and survival endpoints to improve treatment planning for proton and heavy ion radiotherapy.