Novel Electromagnetic Field Device for Advanced Hepatocellular Carcinoma
Boris Pasche, MD, PhD, Karmanos Cancer Institute, Detroit, Michigan, discusses the results from a study evaluating the TheraBionic device, a novel battery-operated portable device which emits electromagnetic fields that are amplitude-modulated at hepatocellular carcinoma frequencies. According to this study, there is a reasonable assurance of safety and probable benefit from this device among patients with advanced hepatocellular carcinoma who have failed in the first- or second-line setting.
Transcript:
My name is Boris Pasche. I am the president and CEO of the Karmanos Cancer Institute in Detroit, and I'm also the co-founder and co-developer of the TheraBionic technology, as well as the CEO of TheraBionic Inc. And TheraBionic GMBH.
So my partner, Alexandre Barbault, a Frenchman with whom I've worked for decades, had worked on the use of radiofrequency electromagnetic fields for the treatment of insomnia. We published multiple articles in the 1990s, and this technology had helped us identify a way to detect body reaction to radiofrequency electromagnetic fields. What we were using were changes in pulse amplitude. In other words, simpler words, the difference between the systolic and diastolic blood pressure would increase with certain frequencies.
In the early 2000s, we decided to move into the field of oncology and began examining patients with a diagnosis of cancer to look for such frequencies. What we found is that these frequencies were very different from the frequencies where we're finding in patient with insomnia and they were in general higher frequencies and they were very precise. We realized that we were getting the narrower. We came to a certain frequency, the stronger the response, the response being measured as a higher pulse change and a higher number of beats of these pulse change.
Using this approach, we developed novel devices that were very precise that could go down to 10 to the minus hertz in term of precision, and began examining a large number of patients with cancer. Then the major leap was we found that these frequencies were always the same with patient, with the same tumor type. For example, a patient with lung cancer, men or women, Black, Caucasian, Asian, had exactly the same frequencies. So suddenly we started to discover that we were finding tumor specific frequencies and they were not different from one patient to the other. However, a different tumor type was quite different. For example, breast cancer frequencies would be essentially completely different from the liver cancer frequencies, with the exception maybe a few percent.
The next step was can these frequency be used for therapeutic purpose? So we had to developed a small portable device which emits 27 megahertz radiofrequency electromagnetic fields and use this device to deliver these frequencies. And you wonder why 27 megahertz; 27 megahertz is approved for medical use and has the unique property of having a wavelength of 11 meters. What we know in biophysics is that the optimal absorption of these frequencies is at one quarter of the wavelength, which is about 2.5 meter, which is very close to the size of the human body. In other words, by having the device connected to a spoon that would be placed in the mouth of the patient. That's the spoon. The whole body becomes an antenna so you can deliver the signal to the entire body. So that was the theory and we started to treat patient.
We conducted a feasibility study on 28 of the patients that we had examined. The study demonstrated that it had activity, so we demonstrate 2 things. First of all, we had 2 patients with stage 4 breast cancer that had a response while using only the device. One patient had a complete response with disappearance of bone metastasis and adrenal gland metastasis. Another patient had partial response, which meant decrease in the tumor size by 30% of more in the liver. This had proven the point that we could with the right frequencies, shrink the tumor and control the tumor for an extended period of time. These 2 patients, 1 of them had a response lasting 11 months, the other one 13 months. So that was very encouraging.
Next step, we had looked at hepatocellular carcinoma, liver cancer. In those days there were no drugs. Sorafenib was being tested. We conducted a study at a center that was running a study on sorafenib and 41 patients with advanced hepatocellular carcinoma were enrolled. What we found is that when we use hepatocellular carcinoma frequencies, 10% of these patients had shrinkage of the tumor, which was about four times higher than what sorafenib was doing or other TKIs [tyrosine kinase inhibitors], and at the same time we saw some very long-term survivors. And third, we saw that it was very well tolerated even in patient with poor liver function.
That led us to develop a novel device, which is the one that has been FDA-approved, to learn from the experience of these clinical studies. For example, we used what's for a docking station, which is a unit that is placed underneath the device right here. You see the device itself and a docking station to wirelessly charge the device, so it minimized the risk of electrocution. This is a 5 volt battery and it allowed us also to insert a chip card which can go into the slot here to prescribe the treatment for 1 month.
The device was then further developed and in 2018 we received European approval for the device and began discussing with the FDA. That was in 2019. The FDA subsequently recommended us to provide all the data of all the patients we had ever treated and suggested multiple analysis in addition to the one that we had already done and published. This was summarized in a paper that was published in 2021, where we documented a significant increase in survival in patients that were treated with this device compared with historical control from placebo studies that were being done at the same time. It was quite substantial. It was 34% increase in overall survival.
And then the FDA asked us, we want look at patient who have failed first-line and second-line therapy, and that was what the data that were presented at ASCO GI. What we found is that patient who had failed first line and second line therapy had a survival that was also significantly longer than you would expect. When you look at all the 3 studies that led to FDA approval of second-line agents, the median overall survival of patient once they failed the second line therapy was six months. What we found is that patient that received TheraBionic after 2 lines of therapy lived 9.50 months, so almost 50% increase in overall survival. Then the FDA ask additional question: let's look at all the patients that failed 2 line of therapy, but that never received anything but TheraBionic until they died and that confirmed further the data, showing a survival of greater than 9 months and for the Child-Pugh A patient it was even longer. These are the data.
Then what we did also at the request of the FDA look at the adverse events, we did not expect adverse events because the level of radiofrequency electromagnetic field delivered by the device is about 200 times less than what you get with your cell phone. It’s at a level that is expectedly safe. However, we compare the data with the sorafenib studies since they were done side by side and showed that the side effect profile was significantly better than sorafenib for several aspects: nausea, anorexia, and hand-foot syndrome. Then we compare the side effect with the TheraBionic device with the placebo arm of the study and found no difference. In other words, there was strong evidence of safety and strong evidence of benefits in patients that had failed first-line and second-line therapy.
We requested from the FDA for the device to be approved for patient who failed all lines of therapy. Actually they said, no, we'll expand the application: Anybody who has failed two line of therapy will be eligible for your therapy, which was a very nice surprise. The approval came in late 2023. Given the fact that it's an entirely novel technology, we sought a new CPT [Current Procedural Terminology) code, called aHCPCS [Healthcare Common Procedure Coding System] code for novel technology, which was awarded last year in August and became effective in October. The first patient began treatments in November of last year, and we have already several patient responding to therapy who had failed 2 line of therapy.
The implication of these finding are twofold. First, this is the first FDA-approved therapy as third line, for patient who have failed 2 lines of therapy, and it's the only proof therapy for that. Second, it can be used safely even in patients with very poor liver function. During our study, we included even patient with Child-Pugh C, which is really impending liver failure. None of them had any adverse event and some of them had a good response to the therapy. Some of the patients that have already been treated since the FDA approval had very poor liver function. So that's really the only option for patient that have poor liver function and seems to be very well tolerated with no side effect.
What we found also in our studies, which has just been confirmed in the early clinical experience post-FDA approval, is that sometime patients have pain associated with their cancer. In the phase one, phase two, we had 11 patients that had significant pain at the outset of their treatment. What we found is the majority of patients had either disappearance of pain, 45% of them the pain completely disappeared, or a decrease in pain. And interestingly, 1 of the first patient post-approval had severe abdominal pain. The pain entirely disappeared within 1 month of treatment.
It’s very encouraging data. We are now entering the larger markets since now it's already prescribed in several states. We'll be conducting a post-approval study at multiple centers to validate further this data. We have also planned to expand in first-line and second-line in hepatocellular carcinoma, and we currently have 1 ongoing study in stage four pancreatic cancer with pancreatic cancer specific frequencies.
Are there any specific considerations for providers treating patients with this device?
The only advice I would say is that we have identified the mechanism of action of these frequencies, and we know that they are sensed by a calcium channel receptor named CACNA1H, also called the Cav3.2 T-type calcium channel. We demonstrated in vitro that if you use drugs that block these channels, you may not have the benefits of the therapy. Patients need to be checked for the use of calcium channel blockers or any other drugs that would block calcium channels. And since most of these drugs are not absolutely necessary, they can be switched to other drugs. That's the only, I would say contraindication we have found. There are no other medical contraindication, whether patient have other comorbidities, heart disease or other issues. We have not seen anything that would preclude the use of this device. Even patient with implantable devices, such as a pacemaker or insulin pump, can use this device safely. It will not interact with their proper functioning.
What are the next steps for researching this device?
The next step, as frequently in oncology, you start with a patient that have very few options and you try to find whether a therapy is safe and effective. It appears that in patients with advanced capital cell carcinoma, the safety has been well documented and there is quite good evidence that it provides benefits. Obviously, given the fact that it has a limited side effect profile — I don't pretend we know all the side effects, but so far we don't seem to see any adverse effect of significance — it could be easily added to existing regimens.
For example, the pancreatic cancer study is a good example. We are starting treatment with chemotherapy. We use an FDA approved first-line treatment: the gemcitabine, nab-paclitaxel, and TheraBionic is added to that regimen. I think that's the future is that we're going to move up this technology to the first line and expand into other tumor types. We have identified other frequencies in other tumor types and already demonstrated in some cases responses that's breast cancer, that's pancreatic cancer, ovarian cancer, prostate cancer, these are four other tumor types where we have good evidence that it may be helpful, but of course we'll need additional studies.
Is there anything you would like to add about this device?
It’s an entirely novel technology that is based on entirely novel premises. We examined patients with a patient-based discovery of tumor-specific frequencies and then use of these patient-based tumor-specific frequency to treat the tumor. It was a wild hypothesis. Could that work? As I told you, that was a hypothesis we had about 15 years ago, and now we have a good proof of principle that it works in hepatocellular carcinoma and good indication that it may well work in other diseases.
As a practicing oncologist, I would say that's the dream come true. It's a therapy that is targeted, that is systemic — it targets both the primary tumor and the metastases — and is devoid of adverse events. For patient who have already gone through chemotherapy, sometimes surgery, radiation therapy or TKI, we are offering a treatment option that is very well tolerated and that can expand the overall survival and their quality of life.
Source:
Pasche B, Benson III A, Kudo M, et al. Development and regulatory approval of a new systemic targeted therapy for advanced hepatocellular carcinoma. Presented at the 2025 ASCO Gastrointestinal Cancers Symposium. February 13-15, 2025; San Francisco, CA. Abstract 613.
