Abstract 306: The efficacy of the combined treatment of 150 KHz tumor treating fields (TTFields) and Sorafenib in hepatocellular carcinoma in vitro and in vivo
Authors: Voloshin Tali , Davidi Shiri , Tempel-Brami Catherine , Munster Mijal , Gotlib Karnit , Zeevi Einav , Schneiderman Rosa S. , Giladi Moshe , Kinzel Adrian , Kirson Eilon D. , Weinberg Uri , Palti Yoram 
Published: August 2019

Abstract
Hepatocellular carcinoma (HCC) is the third cause of cancer related mortality and the primary cause of cancer death. Sorafenib, an oral multikinase inhibitor is approved for patients with advanced HCC, yet its survival benefit is still limited. Tumor Treating Fields (TTFields) therapy is an effective anti-neoplastic treatment modality delivered via noninvasive application of low intensity, intermediate frequency, alternating electric fields. The aim of this work is to explore the potential of the use of TTFields alone and in combination with Sorafenib as a treatment for HCC. HepG2 and Huh-7D12 cells were treated with various TTFields frequencies for 72 hours using the inovitro system. Efficacy of the combined treatment of TTFields and Sorafenib (36-3000 nM) was tested by applying TTFields at the optimal frequency together with various drug concentrations. Cell counts, induction of apoptosis, cell cycle and clonogenic potential were determined. N1S1 HCC cells were injected to the left lobe of the liver of SD rats. After 1 week, TTFields (1.2 V/cm) and Sorafenib (10 mg/kg) were applied for 6 days and tumor growth was followed using MRI. Healthy rats were used to study safety of the use of TTFields (150 kHz) applied to the abdomen. The optimal TTFields frequency was found to be 150 kHz for both cell lines. TTFields application (1.0 - 1.7 V/cm, 72 hours) at 150 kHz led to 53-64% reduction in cell counts and to additional reduction of over 70% in the clonogenic potential. The combined treatment of TTFields and Sorafenib led to a significant reduction in the number of cells (2-way ANOVA, p&lt;0.001) as compared to each treatment alone. Tumor growth was significantly reduced by the combined group compared to the control group (student t test, p&lt;0.01). Moreover, the averaged tumor volume fold increase of the combination treatment group (1.6) was significantly lower than the one observed in the : control group (5.9, p &lt;0.0001), the TTFields group (3.3, p &lt;0.01) and the Sorafenib group (2.3, p &lt;0.05). Safety studies did not reveal any adverse event associated with TTFields application to the rat abdomen. The results presented in this work demonstrate that TTFields can be a safe and effective treatment against HCC cells and that the combination with Sorafenib may further enhance treatment efficacy.
Citation Format: Tali Voloshin, Shiri Davidi, Catherine Tempel-Brami, Mijal Munster, Karnit Gotlib, Einav Zeevi, Rosa S. Schneiderman, Moshe Giladi, Adrian Kinzel, Eilon D. Kirson, Uri Weinberg, Yoram Palti. The efficacy of the combined treatment of 150 KHz tumor treating fields (TTFields) and Sorafenib in hepatocellular carcinoma in vitro and in vivo [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 306.