3015 - Evaluation of Usage Schedules and Interruption Patterns on Tumor Treating Fields (TTFields) Efficacy in Cancer Preclinical Models

Purpose/Objective(s): Tumor Treating Fields (TTFields) therapy administers low-intensity, alternating electric fields that interfere with mitosis and suppress tumor cell proliferation. Clinical findings demonstrate a positive association between device usage and outcomes. Although patients are advised to maintain high average monthly usage, guidance regarding the optimal handling of treatment interruptions within a given month is lacking. This study investigated how the duration, distribution, and timing of treatment breaks influence TTFields efficacy in vitro.

Materials/Methods: Human NSCLC (A549) and GBM (U87 MG) cell lines were treated with TTFields (150 and 200 kHz, respectively; 1 V/cm RMS) using predefined schedules incorporating planned interruptions. Continuous exposure for 48 or 72 hours was first compared with a cumulative 48-hour exposure delivered within a 72-hour window, including either one 24-hour mid-course interruption or three separate 8-hour daily breaks. Break timing was subsequently evaluated by positioning a 24-hour interruption at the start, midpoint, or end of the 72-hour period. The duration of a mid-course interruption was then extended to 24, 48, or 72 hours (total experimental durations of 72, 96, and 120 hours, respectively). Finally, the 72-hour interruption was distributed across the 120-hour period. Efficacy was determined by final cell counts, normalized to untreated time-matched controls and expressed as percentage of control.

Results: Interruptions totaling up to 24 hours within a 72-hour experimental period produced efficacy comparable to uninterrupted exposure with the same cumulative 48-hour treatment duration. Similar effects were observed whether the 24-hour pause was delivered as a single continuous interval or divided into three 8-hour segments. Altering the timing of the 24-hour interruption—at the beginning, middle, or end—did not significantly modify response. Extending the mid-course interruption from 24 (of 72) to 48 (of 96) to 72 (of 120) hours had minimal impact on U87 MG cells, whereas a 72-hour continuous interruption substantially reduced efficacy in A549 cells. Distributing the 72-hour interruption across the 120-hour experimental period partially restored efficacy in A549 cells.

Conclusion: TTFields’ efficacy is maintained in the presence of short or fractionated 24-hour interruptions but decreases with prolonged uninterrupted treatment gaps. Defining acceptable interruption patterns and supporting sustained device usage may help preserve therapeutic benefit while potentially reducing treatment burden.