A comprehensive model for heat-induced radio-sensitisation

Area of Science:

• Oncology
• Radiation Oncology
• Biophysics

Background:

• Combined radiotherapy (RT) and hyperthermia (HT) show potential for improved cancer treatment outcomes through heat-induced radio-sensitization.
• The precise mechanisms of radio-sensitization by heat, particularly concerning DNA damage repair, require further elucidation.

Purpose of the Study:

• To propose and validate an empirical cell survival model, the AlphaR model, for describing multimodality therapy combining RT and HT.
• To investigate the dependence of clonogenic survival on treatment temperature and thermal dose.
• To derive the relative biological effectiveness (RBE) of HT treatments and assess thermal dose as an indicator of heat-induced radio-sensitization.

Main Methods:

• Development of the AlphaR model, positing that heat reduces DNA damage repair capacity up to a threshold.
• Fitting the AlphaR model to experimental cell survival data from HCT116, Cal27, BHK, and CHO cell lines under HT and combined RT-HT conditions.
• Analysis of survival curves, parameter dependencies on temperature, and calculation of RBE values.

Main Results:

• The AlphaR model demonstrated a good fit (R² ≥ 0.95) for all experimental data.
• For HT alone, two model parameters increased exponentially with temperature, allowing for RBE derivation.
• Thermal dose was confirmed as a valid indicator of heat-induced radio-sensitization in combined RT-HT treatments.

Conclusions:

• The AlphaR model offers a flexible framework for describing cell survival curves under combined RT-HT.
• The model aids in quantifying heat-induced radio-sensitization and thermal dose, potentially improving treatment planning.
• Further research can refine the model for broader clinical application in optimizing cancer therapy.