‎microscopic rbe estimation in proton therapy using topas-nbio‎: ‎impact of physics models and dna damage energy threshold

Relative biological effectiveness (rbe) is a key factor in proton therapy, yet its current fixed clinical value of 1.1 may not adequately represent biological effects at the microscopic level. in this study, we employed the topas-nbio monte carlo toolkit to simulate dna damage and calculate rbe based on various biological endpoints, including direct and indirect double-strand breaks (dsbs), and simple versus complex dsbs. simulations were performed across multiple proton energies (1-64 mev) using three physics constructors and two energy threshold models for strand break induction. validation against reference and experimental data showed less than 5% deviation, with dna physics option 2 and a linear energy threshold of 5-37.5 ev yielding the most consistent results. similarly, dna physics option 4 and 6 with a fixed energy threshold of 17.5 ev align well with experimental and simulation reference data. rbe values were found to vary significantly with damage type and simulation parameters, with total dsbs providing the most biologically relevant estimates, reaching a maximum of 1.9 for low-energy protons. the study also revealed that both direct and indirect damage alone may underestimate biological effectiveness. differences in rbe across physics constructors reached up to 30.8%, emphasizing the need for careful model selection. these findings support replacing the fixed rbe with a more nuanced, dna damage-based approach in treatment planning systems. incorporating microscopic rbe modeling could enhance the biological accuracy of proton therapy and ultimately improve patient outcomes.