Tumor Treating Fields for Treatment of Spinal Metastasis

Abstract

INTRODUCTION: Tumor treating fields(TTF) has never been described for treatment of spinal metastasis. We investigate the anti-mitotic effect of TTF to inhibit the growth of human cancer using cells in vitro and in vivo models of spinal metastasis. METHODS: In-vitro: human derived osteosarcoma (Krib-Luc-1) and lund adenocarcinoma (A549-Luc) cells were seeded in 5x5mm human demineralized bone grafts kept in culture while treated with 0 KHz (control) or 150 KHz of TTF for 14 days. Bioluminescence images (BLI) were obtained at baseline and 14 days. In-vivo: Krib-Luc-1 cells were surgically implanted via trasperitoneal approach to the L3 vertebra in nude mice. Animals were treated with 0 KHz or 150 KHz of TTF for 30 days or until paralysis. BLI were obtained at day 0 and every 7 days. MRI was obtained at day 22. Histological analysis was performed at the end of the experiment. Control and TTF treated groups were compared with two-tailed t-tests. RESULTS: In vitro: BLI of the control grafts demonstrated a median value of 1×10^10 photons/sec at 14 days, significantly higher than 1×10^8 photons/sec observed in the 150 KHz group (p < 0.0001). In Vivo: median time to paralysis in control animals was 25 days, all animals treated with TTF at 150 KHz reached the 30 day mark without deficits. BLI of the control group was 3.5×10^9 photons/sec significantly higher than 1×10^9 photons/sec in the 150 KHz TTF group (p = 0.0212). MRI and histological analysis confirmed significant smaller tumors in the treated group when compared to controls. CONCLUSIONS: Application of TTF 150 KHz reduced cellular proliferation in both in vitro and in vivo models of spinal metastasis. We believe TTF could become a groundbreaking treatment for spinal metastasis.