P04.31 Defining Tumor Treating Fields (TTFields) dosimetry using Power Density Loss and related measures

Abstract

Tumor Treating Fields (TTFields) are alternating electric fields known to inhibit cancer cell growth. TTFields are approved for the treatment of Glioblastoma Multiforme. Historically, TTFields dose has been quantified using the magnitude of the electric field, which is indicative of the force that the field applies on charged objects. However, when considering the dose of a physical modality such as TTFields, it is important to consider the amount of energy transferred from the modality to the tissue. This is because, the extent to which the modality can alter the state of the objects on which it operates depends on the amount of energy that the modality transfers to those objects. Power loss density quantifies the energy transferred by an electric field to tissue through electric conductance. Here analyze how power density loss can be used to quantify TTFields dose, shedding new light on the mechanism of action of this anti-cancer modality. The power density loss of TTFields is defined as, L=12σE2 where, L represents power loss density, σ is the conductivity of tissue and E is the magnitude of the electric field. The unit for measuring the power loss density of TTFields is milli-Watts per cubic centimeter (mW/cm3). To examine the distribution of power loss density when delivering TTFields to the brain, we numerically simulated delivery of TTFields to realistic head models of Glioblastoma patients. We then created colormaps that visualized the field intensity distribution and the power loss density distribution within the models and qualitatively compared the two. Finally, we calculated the total power loss within the models to gain a measure of the power delivered by TTFields to the brain during treatment. The electric field intensity tends to increase in regions of low conductivity, such as white matter, and tends to be lowest in regions of high conductivity such as the ventricles and resection cavities. However, the power loss density tends to increase in regions of higher conductivity. Within the highly conductive ventricles and resection cavity, it can take on values comparable to those observed in other tissue types. The average power loss density within the gross tumor volumes of all patients was 5 mw/cm^3. The total power loss of TTFields within the simulated cases was between 20–40 Watts, which is equivalent to 412–825 Kcalories per day, on-par with the resting metabolic rate of the brain (about 20% of the body’s resting metabolic rate). This analysis shows that power loss density is a viable physical measurement to accurately quantify TTFields dose in treatment planning. The analysis also shows that the power delivered by TTFields to cells is comparable to the metabolic rate of the cells. This observation could lead to new hypotheses about the mechanism of action of TTFields.