Calculation of the DNA damage yield and relative biological effectiveness in boron neutron capture therapy via the Monte Carlo track structure simulation.

Boron neutron capture therapy (BNCT) is an advanced cellular-level hadron therapy that has exhibited remarkable therapeutic efficacy in the treatment of locally invasive malignancies. Despite its clinical success, the intricate nature of relative biological effectiveness (RBE) and mechanisms responsible for DNA damage remains elusive. This work aims to quantify the RBE of compound particles (i.e., alpha and lithium) in BNCT based on the calculation of DNA damage yields via the Monte Carlo track structure (MCTS) simulation. Approach: The TOPAS-nBio toolkit was employed to conduct MCTS simulations. The calculations encompassed four steps: determination of the angle and energy spectra on the nuclear membrane, quantification of the database containing DNA damage yields for ions with specific angle and energy, accumulation of the database and spectra to obtain the DNA damage yields of compound particles, and calculation of the RBE by comparison yields of double-strand break (DSB) with the reference gamma-ray. Furthermore, the impact of cell size and microscopic boron distribution was thoroughly discussed. Main results: The DSB yields induced by compound particles in three types of spherical cells (radius equal to 10, 8, and 6 μm) were found to be 13.28, 17.34, 22.15 /Gy/Gbp for boronophenylalanine (BPA), and 1.07, 3.45, 8.32 /Gy/Gbp for sodium borocaptate (BSH). The corresponding DSB-based RBE values were determined to be 1.90, 2.48, 3.16 for BPA and 0.15, 0.49, 1.19 for BSH. The calculated DSB-based RBE showed agreement with experimentally values of compound biological effectiveness for melanoma and gliosarcoma. Besides, the DNA damage yield and DSB-based RBE value exhibited an increasing trend as the cell radius decreased. The impact of the boron concentration ratio on RBE diminished once the drug enrichment surpasses a certain threshold. Significance: This work is potential to provide valuable guidance for accurate biological-weighted dose evaluation in BNCT.