Treatment of advanced hepatocellular carcinoma with very low levels of amplitude-modulated electromagnetic fields

Abstract

Background: Therapeutic options for patients with advanced hepatocellular carcinoma (HCC) are limited. There is emerging evidence that the growth of cancer cells may be altered by very low levels of electromagnetic fields modulated at specific frequencies.

Methods: A single-group, open-label, phase I/II study was performed to assess the safety and effectiveness of the intrabuccal administration of very low levels of electromagnetic fields amplitude modulated at HCC-specific frequencies in 41 patients with advanced HCC and limited therapeutic options. Three-daily 60-min outpatient treatments were administered until disease progression or death. Imaging studies were performed every 8 weeks. The primary efficacy end point was progression-free survival 6 months. Secondary efficacy end points were progression-free survival and overall survival.

Results: Treatment was well tolerated and there were no NCI grade 2, 3 or 4 toxicities. In all, 14 patients (34.1%) had stable disease for more than 6 months. Median progression-free survival was 4.4 months (95% CI 2.1-5.3) and median overall survival was 6.7 months (95% CI 3.0-10.2). There were three partial and one near complete responses.

Conclusion: Treatment with intrabuccally administered amplitude-modulated electromagnetic fields is safe, well tolerated, and shows evidence of antitumour effects in patients with advanced HCC.

Conflict of interest statement

AB and BP have filed a patent related to the use of electromagnetic fields for the diagnosis and treatment of cancer. AB and BP are founding members of TheraBionic LLC.

Figures

Figure 1

Delivery of HCC-specific modulation frequencies. (A) The generator of AM EMFs is a battery-driven RF EMF generator connected to a spoon-shaped mouthpiece. (B) Schematic description of AM EMFs. The carrier frequency (27.12 MHz) is sinusoidally modulated at specific frequencies. (C) Patient receiving treatment with RF AM EMF. (D) HCC treatment programme consisting of sequential emission of 194 modulation frequencies for 60 min.

Figure 2

CONSORT diagram.

Figure 3

Progression-free and overall survival. (A) Median progression-free survival was 4.4 months (95% CI 2.1–5.3). (B) Median overall survival was 6.7 months (95% CI 3.0–10.2). (C) Long-term partial response in a patient with biopsy-proven hepatocellular carcinoma. A 76-year-old woman with hepatitis C and Child–Pugh A5, BCLC C, biopsy-proven hepatocellular carcinoma with bilateral pulmonary metastases, who had evidence of disease progression (+36% by Response Evaluation Criteria in Solid Tumours (RECIST) criteria) between 3 May 2006 (first column) and 26 July 2006 (second column) while enrolled in the SHARP study (Llovet et al, 2008b). Treatment with AM EMFs was initiated on 9 August 2006. Subsequent restaging multiphasic contrast-enhanced computed tomographies (CTs) with images from corresponding levels (across rows) are demonstrated in the third and fourth columns over the course of 57 months. Note that the hypervascularity of the focal hepatic lesions (arrows in first two rows) became relatively hypoenhancing on arterial phase (20 August 2008). The patient developed main portal vein thrombosis with cavernous transformation as a complication of her cirrhosis. However, the intrahepatic lesion size is stable regardless of enhancement pattern. Note also that the left lung base lesion resolved (4th row), and the right lung base lesion remained stable (3rd row) over the duration of treatment. (D) Alpha-fetoprotein response in a 67-year-old patient with Child–Pugh A5, BCLC C HCC and hepatitis C (hepatitis B negative).

Figure 4

A 70-year-old man with recurrent thyroid cancer metastatic to the lungs: stable disease at 57.5 months. Long-term stable disease in a 70-year-old man with recurrent biopsy-proven thyroid carcinoma metastatic to the lungs enrolled in the previously published feasibility study (Barbault et al, 2009). Treatment with AM EMFs was initiated on 20 August 2006. As of 9 June 2011, the patient is asymptomatic and still receiving treatment with no evidence of disease progression. Images through the target metastatic lesion in the right hilum demonstrate minimal size change over the 4 years, given differences in computed tomography acquisition techniques over that time interval.