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Dynamic Thermal Dosimetry for HT-RT

Hyperthermia is a cancer treatment where the tumor is exposed to elevated temperatures. In conjunction with radiotherapy, hyperthermia acts as a booster to the radiotherapy treatment when applied prior to or after irradiation. The mechanism through which hyperthermia achieves its synergistic effect is subject of ongoing research. Regardless of the exact principles of operation of hyperthermia, it is critical to be able to assess how much heating is required, for how long and at which temperature, in order to be able to predict the outcome, identify which treatment aspects are relevant and eventually to include hyperthermia in the dosimetric treatment planning that is already pervasive for radiotherapy.

 

In order to be able to specify a dose of the thermal effect, we model DNA damage and repair in silico using a system of differential equations that is rooted in well established radiobiological principles. Consistent with experimental observations, the effect of hyperthermia is accounted for by modeling the inactivation of DNA repair proteins at elevated temperatures.

 

In order to calibrate the model, we quantify DNA damage in a time-resolved manner after treating well characterised cancer cell lines with hyperthermia and radiation. Qunatification is done with single cell gel electrophoresis, a method that quantifies DNA damage on a per-cell basis. This DNA damage readout is then mapped to the model state variables; the error is minimized using evolutionary algorithms and other machine-learning techniques.

 

Once calibrated, this model-based approach allows us to predict how cancer cells will react to different treatment modalities, to quantify the effect of hyperthermia and eventually to determine the optimal treatment.