Background

Non-small cell lung cancer (NSCLC) accounts for the majority of lung cancer cases, with a significant proportion of patients presenting with distant metastases at diagnosis. While immune checkpoint inhibitors and targeted therapies have extended survival, long-term efficacy remains limited by drug resistance and tumor heterogeneity. Tumor treating fields (TTFields), a non-invasive alternating electric field-based modality, have recently received FDA approval for metastatic NSCLC, yet the relative contributions of field intensity and exposure duration from a dosimetric perspective remain poorly understood.

New method

This study employed three TTFields regimens with distinct intensity-duration configurations (0.4 V/cm for 24 h, 0.8 V/cm for 6 h, and 1.6 V/cm for 3 h) applied to H460 and A549 NSCLC cell lines. Both short-term (48 h) and long-term (7-day) responses were assessed through cell viability, clonogenic survival, migration, apoptosis, and western blotting analyses.

Results

TTFields significantly reduced cell viability, clonogenic survival, and migratory capacity while increasing apoptotic susceptibility across all conditions. Different intensity-duration combinations produced partially overlapping inhibitory effects, with the strongest suppression observed at 1.6 V/cm for 3 h. These findings suggest an intensity-duration trade-off governed by overall energy delivery.

Comparison with existing methods 

Most prior NSCLC studies adopted TTFields parameters optimized for glioblastoma without accounting for NSCLC-specific biophysical differences. This study systematically evaluated dose-schedule dependency in NSCLC, providing a quantitative dosimetric framework that better reflects the combined influence of intensity and duration on antitumor efficacy.

Conclusions

NSCLC cells respond to TTFields in a dosimetry-dependent manner, supporting the feasibility of flexible exposure strategies. These findings provide preliminary evidence for alternative intensity-duration configurations that may improve patient adherence while maintaining antitumor activity, pending energy-matched in vivo validation.

Authors & Affiliations

1. Department of Bio-medical Engineering, Korea University, Seoul, Republic of Korea — Jinju Heo, Myonggeun Yoon
2. Research and Development Center, FieldCure Ltd., Seoul, Republic of Korea — Myonggeun Yoon

Journal: Oncology Letters, Vol. 31, Article 238, 2026  Received: December 2, 2025 |  Accepted: February 27, 2026  DOI: 10.3892/ol.2026.15593