Research Article

Safety and Efficacy of amplitude-modulated radiofrequency electromagnetic fields in advanced hepatocellular carcinoma

¹ Department of Radiation Oncology, Wake Forest Baptist Medical Center, Winston-Salem, NC 27157, USA
² Wake Forest Baptist Comprehensive Cancer Center, Winston-Salem, NC 27157, USA
³ Division of Hematology/Oncology, Northwestern Medical Group, Chicago, IL 60611, USA
⁴ Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka 577-8502, Japan
⁵ Department of Cancer Biology, Wake Forest Baptist Medical Center, Winston-Salem, NC 27157, USA
⁶ Genolier Cancer Center, Genolier 1272, Switzerland
⁷ Department of Social Sciences and Health Policy, Wake Forest University Health Service, Winston-Salem, NC 27157, USA
⁸ Department of Biostatistics and Data Science, Wake Forest Baptist Medical Center, Winston-Salem, NC 27157, USA
⁹ TheraBionic Inc., Winston-Salem, NC 27106, USA
¹⁰ TheraBionic GmbH, Ettlingen 76275, Germany

^* Corresponding author: bpasche@wakehealth.edu

Received: 23 June 2021
Accepted: 2 July 2021

Abstract

Importance: Hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide. Despite the recent approval of several new agents, long-term disease control remains elusive for most patients. Administration of 27.12 MHz radiofrequency (RF) electromagnetic fields (EMF) by means of a spoon-shaped antenna (TheraBionic P1 device) placed on the anterior part of the tongue results in systemic delivery of low and safe levels of RF EMF from head to toe.

Objective: To report treatment outcomes and adverse events associated with treatment with the TheraBionic P1 device in comparison to suitable historical placebo and actively treated controls.

Design: Pooled case series with comparison to historical controls.

Participants: Patients with advanced HCC receiving this treatment, 18 real-world patients and 41 patients from a previously reported phase II study. Historical controls from previously conducted clinical trials.

Interventions: Three hours daily treatment with the TheraBionic P1 device compared with standard of care as received by historical controls in the previously conducted trials.

Main outcomes and measures: Overall survival (OS), time to progression, response rate, and adverse events in the combined pooled patients and in appropriate subgroups comparable to the historical control groups.

Results: In the pooled treatment group, median OS of patients with Child-Pugh A disease (n = 32) was 10.36 (95% CI 5.42–14.07) months, 4.44 (95% CI 1.64–7.13) months for patients with Child-Pugh B disease (n = 25), and 1.99 (95% CI 0.76–3.22) months for patients with Child-Pugh C disease (n = 2). Median OS for Child-Pugh A patients was 2.62 (33.9%) months longer than the 7.74 months OS of comparable historical controls (p = 0.036). The 4.73 (95% CI 1.18–8.28) months median OS for Child-Pugh B patients receiving TheraBionic P1 device as first line therapy is slightly higher than the 4.6 months median OS of historical controls receiving Sorafenib as first line therapy. Only grade 1 mucositis and fatigue were reported by patients using the device, even among Child-Pugh B and C patients. No patients discontinued treatment because of adverse events.

Conclusions and Relevance: Treatment of advanced HCC with the TheraBionic P1 device is well tolerated, even in patients with severely impaired liver function, and results in improved overall survival compared to historical controls without any significant adverse events, even after many years of continuous treatment. This treatment modality appears to be well suited for patients who have failed or are intolerant to currently approved therapies.