A Pulsed Tumor Treating Fields Protocol to Improve Glioblastoma Therapy.

Abstract

Tumor Treating Fields (TTFields) utilize alternating fields (AC fields) within 100-300 kHz and electric field strengths above 1 V/cm for glioblastoma (GBM) treatment. However, the electric field is often reduced to a relatively low value (below 1 V/cm) due to the unavoidable thermal effects induced by Joule heating on the patient's skin. This study proposes a pulsed TTFields to enhance therapy effect, while reducing thermal effects. This work designed a TTFields generator to output 200 kHz AC fields. Cell experiments were conducted to compare cell viability between pulsed and conventional TTFields. A gel platform was used to measure temperature rises under clinical parameters of TTFields. A realistic head model with a tumor was simulated to analyze electric field and thermal distributions. The designed generator can output two separate TTFields signals with 100 V voltage amplitude and 2000 mA current amplitude, meeting clinical trial requirements. Pulsed TTFields (10% duty cycle, 3.37 V/cm) achieved significantly lower cell viability (53.07%) than continuous TTFields (1.07 V/cm, 84.76%) while maintaining similar temperature rises. Gel experiments confirmed comparable temperature rises for both protocols. Simulations on a realistic head model demonstrated that pulsed TTFields achieved broader tumor coverage (electric field >1 V/cm) compared to continuous TTFields under equivalent thermal conditions. Pulsed TTFields can generate higher electric fields in targeted regions, significantly inhibiting cell proliferation while reducing thermal risks compared to continuous TTFields. The proposed pulsed TTFields may provide an optimized treatment method to enhance GBM therapy efficacy.