Determination of the Effective Local Lethal Function for the NanOx Model.

Area of Science:

• Biophysics
• Radiation Oncology
• Cellular Biology

Background:

• Hadrontherapy utilizes ionizing radiation to treat cancer, necessitating accurate prediction of cell survival.
• Existing models may not fully capture the complex cellular responses to radiation at different scales.
• The NanOx model was developed to address these limitations by considering distinct biological events.

Purpose of the Study:

• To refine the modeling of local lethal events within the NanOx biophysical model.
• To characterize cell line response to restricted specific energy using an effective local lethal function (F).
• To validate the improved model by benchmarking predicted cell survival curves against experimental data.

Main Methods:

• Modeled local lethal events via inactivation of nanometric targets using an effective local lethal function (F).
• Determined F as a linear combination of basis functions, then applied a parametric expression to capture threshold and saturation.
• Applied the strategy to three cell lines irradiated with different ions and energies, comparing predicted α(LET) curves to experimental data.

Main Results:

• Developed a parametric effective local lethal function (F) that captures key features like threshold and saturation.
• Successfully reduced the number of free parameters in the model.
• Benchmarked predicted α(LET) curves against experimental data for multiple cell lines and ion types, showing good agreement.

Conclusions:

• The refined modeling of local lethal events provides a more accurate representation of cell response to ionizing radiation.
• The NanOx model, with its enhanced local lethal event function, shows promise for improving hadrontherapy treatment planning.
• This approach offers a robust method for benchmarking biophysical models against experimental outcomes in radiation biology.