Incorporating oxygenation levels in analytical DNA-damage models-quantifying the oxygen fixation mechanism

Area of Science:

• Radiation Oncology
• Medical Physics
• Radiobiology

Background:

• Oxygen levels significantly impact radiation therapy effectiveness by influencing DNA damage.
• Current treatment planning often simplifies or ignores these oxygenation effects.
• A universal framework is needed to integrate oxygenation's role across diverse radiation modalities.

Purpose of the Study:

• To develop a universal framework for incorporating oxygenation effects into radiation therapy treatment planning.
• To predict DNA damage differences under variable oxygenation levels for all radiation modalities and energy spectra.
• To create a model applicable to polyenergetic beams and various oxygen concentrations.

Main Methods:

• A statistical model of DNA damage (complex and simple) was developed, incorporating oxygen fixation.
• A linear transformation extended the model to all energies and modalities, resulting in a rational polynomial expression.
• Validation involved Microdosimetric Monte Carlo Damage Simulation (MCDS) and comparison with proton beam experiments and FLUKA simulations.

Main Results:

• The framework accurately parameterized complex DNA damage across modalities (electrons, protons) within 0.3% of MCDS calculations.
• Oxygen Enhancement Ratio (OER) variations were observed in proton beams depending on position within the Spread Out Bragg Peak (SOBP).
• Environmental oxygenation emerged as a more critical variable than beam characteristics for OER.

Conclusions:

• An effective analytical expression for complex DNA damage, considering modality, energy, and oxygenation, has been developed.
• This model can be integrated into treatment planning software to account for variable oxygenation.
• It represents a foundational step toward biologically optimized radiation therapy.