Hydrogel and Skin Conductivity Impacts Dose from Tumor Treating Fields Running head: Hydrogel Effects on TTFields

Edwin Lok ^1,2* Olivia Liang ^1,2 Monika Haack ¹ Eric T Wong ^2,3*

• ¹ Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States
• ² Warren Alpert Medical School, Brown University, Providence, Rhode Island, United States
• ³ Department of Neurology, Warren Alpert Medical School, Brown University, Providence, Rhode Island, United States

Purpose: Tumor Treating Fields (TTFields) are delivered by transducer arrays applied to scalp or body surface for treatment of multiple malignancies. Dermatologic complications are thought to be related to hydrogel situated between the electrodes and scalp or skin to facilitate electric field penetration.High intensity of TTFields on these surfaces may also be a contributing factor. We explored conductivity changes in the hydrogel and skin to improve TTFields coverage and penetration. Methods: Magnetic resonance imaging datasets from 12 glioblastoma patients and attenuation-corrected positron emission tomography-computed tomography datasets from 3 non-small cell lung and 2 ovarian carcinoma patients were used to segment anatomic structures. Finite element mesh models were generated and solved for distribution of applied electric fields, rate of energy deposition, and current density at the gross tumor volume (GTV) and clinical target volume (CTV). Electric field-volume, specific absorption rate-volume, and current density-volume histograms were generated, by which plan quality metrics were used to evaluate relative differences in field coverage between models at various hydrogel and skin conductivities. Results: By varying conductivity of hydrogel, TTFields coverage at GTV or CTV increased up to 0.5 S/m for head and 1.0 S/m for thorax and pelvis models, and no additional increase was observed beyond these saturation points. Although scalp hotspots increased or decreased by +1.5%, -0.1%, and -0.9% in E5%, SAR5%, and CD5%, the skin hotspots increased by as much as +23.5%, +45.7%, and +20.6%, respectively. When altering conductivity of the entire scalp, TTFields coverage peaked near 1 S/m at the GTV or CTV for the head models. TTFields coverage in both the GTV and scalp increased up to 1 S/m for the head models but plateaued thereafter. Contouring under the scalp increased scalp hotspots by +316% in E5% at 1 S/m compared to altering the conductivity of the entire scalp. GTV hotspots decreased by +17% in E5% at 1 S/m. Conclusions: TTFields delivery can be modulated by the conductivity of hydrogel and skin at the transducer-scalp or transducer-skin interface.