Temperature control in TTFields therapy of GBM: impact on the duty cycle and tissue temperature

In TTFields therapy, Optune(& xfffd;) is used to deliver the electric field to the tumor via 4 transducer arrays. This device monitors the temperature of the transducers and reduces the current whenever a transducer reaches 41 & xfffd;C. Our aim is to quantify Optune?s duty cycle and to predict the steady-state temperature distribution in the head during GBM treatment. We used a realistic head model and the finite element method to solve Pennes equation and to simulate how Optune operates considering that current reduces to zero when the thermal limit is reached. The thermal impact was evaluated considering the maximum temperature reached by each tissue and using the CEM 43 & xfffd;C metric. We observed that Optune switches the current on and off intermittently. In our model, one transducer reached the temperature limit quicker than the others and consequently it was the one that controlled current injection. This led to different duty cycles for the anterior?posterior and left?right array pairs. The thermal analysis indicated that the highest temperature in the model, 41.7 & xfffd;C, was reached on the scalp under a transducer. However, TTFields may lead to significant changes only at the brain level such as BBB permeability increase, cerebral blood flow variation and changes in the concentration of some neurotransmitters. The duty cycle may be increased, e.g. by controlling the current at the transducer level. These predictions should be validated by comparison with experimental data and reconciled with the lack of evidence of thermal impact in clinical trials.