title: Alternating electric fields (TTFields) inhibit metastatic spread of solid tumors to the lungs.
abstract: Tumor treating fields (TTFields) are low intensity, intermediate frequency, alternating electric fields used to treat cancerous tumors. This novel treatment modality effectively inhibits the growth of solid tumors in vivo and has shown promise in pilot clinical trials in patients with advanced stage solid tumors. TTFields were tested for their potential to inhibit metastatic spread of solid tumors to the lungs in two animal models: (1) Mice injected with malignant melanoma cells (B16F10) into the tail vein, (2) New Zealand White rabbits implanted with VX-2 tumors within the kidney capsule. Mice and rabbits were treated using two-directional TTFields at 100-200 kHz. Animals were either monitored for survival, or sacrificed for pathological and histological analysis of the lungs. The total number of lung surface metastases and the absolute weight of the lungs were both significantly lower in TTFields treated mice then in sham control mice. TTFields treated rabbits survived longer than sham control animals. This extension in survival was found to be due to an inhibition of metastatic spread, seeding or growth in the lungs of TTFields treated rabbits compared to controls. Histologically, extensive peri- and intra-tumoral immune cell infiltration was seen in TTFields treated rabbits only. These results raise the possibility that in addition to their proven inhibitory effect on the growth of solid tumors, TTFields may also have clinical benefit in the prevention of metastatic spread from primary tumors.
authors.affiliation: NovoCure Limited, Matam Advanced Technology Centre, 31905, Haifa, Israel. Eilon@novo-cure.com
authors.forename: Eilon D
authors.initials: ED
authors.lastname: Kirson
authors.forename: Moshe
authors.initials: M
authors.lastname: Giladi
authors.forename: Zoya
authors.initials: Z
authors.lastname: Gurvich
authors.forename: Aviran
authors.initials: A
authors.lastname: Itzhaki
authors.forename: Daniel
authors.initials: D
authors.lastname: Mordechovich
authors.forename: Rosa S
authors.initials: RS
authors.lastname: Schneiderman
authors.forename: Yoram
authors.initials: Y
authors.lastname: Wasserman
authors.forename: Bernhard
authors.initials: B
authors.lastname: Ryffel
authors.forename: Dorit
authors.initials: D
authors.lastname: Goldsher
authors.forename: Yoram
authors.initials: Y
authors.lastname: Palti
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004560:Electricity; D005260:Female; D008175:Lung Neoplasms / Q000556:secondary*; D008545:Melanoma / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis / Q000517:prevention & control*; D009368:Neoplasm Transplantation; D011817:Rabbits