Abstract 5668: Preclinical efficacy of tumor treating fields (TTFields) for small cell lung carcinoma (SCLC)

Abstract Purpose: Small cell lung cancer (SCLC) is a highly aggressive malignant neoplasm, accounting for 10-15% of lung cancer cases, characterized by rapid growth, and early metastasis. The standard of care is combination chemotherapy with cisplatin or carboplatin plus etoposide, administered together with immunotherapy and concurrent chest radiotherapy. The current preclinical study aimed to investigate the efficacy of TTFields for treatment of SCLC and examine the effect of TTFields together with the standard-of-care chemotherapies. Methods: DMS-53 and H196 SCLC cells were treated with TTFields (1 V/cm RMS, 150 kHz, 72 h for DMS-53 cells; 1.62 V/cm RMS, 150 kHz, 120 h for H196 cells), alone or with the addition of different concentrations of cisplatin or etoposide. Efficacy was measured by analyzing cell count, colony formation, and apoptosis induction. The overall effect was calculated by multiplying cell count with colony formation. TTFields efficacy was further evaluated in vivo, in mice orthotopically inoculated with murine KP3 SCLC cells. 7 days after inoculation, TTFields or sham-heat were continuous applied for 9 days. Tumor volume was examined by magnetic resonance imaging (MRI) at treatment end. Results: TTFields reduced cell count, induced apoptosis, and provided an increased overall effect relative to control in both cell lines. Application of cisplatin or etoposide alongside TTFields showed a synergistic interaction in H196 cells, which was higher for the latter chemotherapy. In DMS-53 cells, the concomitant treatment of TTFields with either chemotherapy showed an additive interaction in cytotoxicity and a synergistic overall effect, which matched the relatively high levels of apoptosis in this cell line. Furthermore, TTFields significantly reduced tumor growth relative to control in the mouse model. Conclusions: Our results demonstrate efficacy for TTFields for the treatment of SCLC in preclinical models, and a potential advantage for TTFields concomitant with the standard-of-care chemotherapies for this malignancy. Future studies will test the effect of TTFields concomitant with both chemotherapies, in vitro and in vivo; and together with immunotherapy and chemotherapy. Citation Format: Rotem Engelman, Lina Somri-Gannam, Talya Borkum, Roni Blatt, Daria Gerasimova, Shay Cahal, Catherine Tempel Brami, Mai Shai, Eyal Dor-On, Itai Tzchori, Adi Haber, Moshe Giladi, Yoram Palti. Preclinical efficacy of tumor treating fields (TTFields) for small cell lung carcinoma (SCLC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5668.