Abstract
Alternating electric fields (AEF), also known as tumor treating fields (TTFields), have emerged as a non-invasive anticancer modality; however, their clinical benefit in non-small cell lung cancer (NSCLC) still depends heavily on prolonged daily wear time, which often limits patient adherence due to discomfort and skin irritation. Despite recent Food and Drug Administration approval of TTFields for metastatic NSCLC, the relative contributions of field intensity and exposure duration, particularly from a quantitative and dosimetric perspective, have not been systematically evaluated. In the present study, H460 and A549 NSCLC cell lines were exposed to three TTFields regimens combining different 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), and short-(48 h) and long-term (7-day) responses were assessed. TTFields significantly reduced cell viability, clonogenic survival and migratory capacity while increasing apoptotic susceptibility. Notably, treatment conditions with different intensity-duration combinations produced partially overlapping inhibitory effects, suggesting that overall exposure may contribute to the observed responses. These findings indicated that NSCLC cells respond to TTFields in a dosimetry-dependent manner and support the existence of an intensity-duration trade-off. The present study provided preliminary evidence for flexible TTFields exposure strategies while underscoring the need for energy-matched and in vivo validation in future research to refine treatment scheduling in NSCLC.