A DNA damage calculation method for large-scale tumor models in boron neutron capture therapy

Area of Science:

• Medical Physics
• Radiation Oncology
• Computational Biology

Background:

• Boron Neutron Capture Therapy (BNCT) is a targeted radiotherapy for cancer treatment.
• Conventional methods for calculating DNA damage in BNCT are computationally intensive, limiting studies to single-cell models.
• Accurate simulation of DNA damage distribution in clinically relevant tumor volumes is essential for treatment optimization.

Purpose of the Study:

• To develop a computationally efficient method for evaluating DNA damage yields induced by alpha and 7Li particles in BNCT.
• To enable quantitative assessment of DNA damage in large-scale tumor models at an acceptable computational cost.
• To compare the efficacy of different boron-containing agents (BPA vs. BSH) in terms of DNA damage induction.

Main Methods:

• Developed a framework using Geant4 and Geant4-DNA to simulate particle transport and DNA damage.
• Created an energy-dependent DNA damage yield database for alpha and 7Li particles.
• Integrated the database into a customized Geant4 program for rapid damage estimation in centimeter-scale models.

Main Results:

• The proposed method allows computation of DNA damage yields for over a million particles within tens of hours.
• Boronophenylalanine (BPA) distribution resulted in higher DNA damage yields and probabilities compared to Boronophenylalanine (BSH).
• In a centimeter-scale tumor model, BPA showed higher overall damage than BSH, though the difference was less pronounced than in single-cell models.

Conclusions:

• This study presents the first application of a rapid DNA damage evaluation method to large-scale tumor models in BNCT.
• The findings demonstrate the feasibility of estimating nanoscale DNA damage yields at acceptable computational costs.
• This approach supports further analysis of DNA damage spatial distribution for optimizing clinical BNCT treatments.