Amplitude-modulated electromagnetic fields for the treatment of cancer: Discovery of tumor-specific frequencies and assessment of a novel therapeutic approach

Following a period of search and discovery of novel tumor-specific frequencies, outpatient treatment of patients with advanced cancer was initiated in Switzerland and Brazil on a compassionate basis, free of charge. Patients self-administered treatment for 60 min, three times a day. Oral informed consent was provided by seven patients. All other patients signed a written informed consent approved by a local human subject committee in compliance with the Helsinki declaration and the protocol was registered, clinicaltrials.gov identifier # NCT00805337. All patients had histologically confirmed diagnosis of cancer. Except for patients with a diagnosis of ovarian cancer, measurable disease was required. For patients with ovarian cancer, CA 125 level was used as a surrogate marker of measurable disease and a 50% increase in baseline level considered evidence of disease progression. All anticancer therapies had to be discontinued for at least one month prior to treatment initiation. Other eligibility criteria included an Eastern Cooperative Group performance status (PS) of 0 to 2 and an estimated life expectancy of at least 3 months.

Objective response in patients with measurable disease was assessed using the Response Evaluation Criteria in Solid Tumors group classification [14]. Two of us (B.B. and R.F.M.) independently reviewed all imaging studies.

Patients were evaluated for treatment-related toxicity at a minimum every two months as per the National Cancer Institute Common Toxicity Criteria version 2.0. The worst grade of toxicity per patient was recorded.

A total of 115 patients were examined in Switzerland, 48 in Brazil (Table 1). There were 76 females and 87 males. The median age was 59 years (range 19 – 84). The most common tumor types were hepatocellular carcinoma (46), breast cancer (32), colorectal cancer (19), and prostate cancer (17).

Compassionate treatment with tumor-specific frequencies was offered to 28 patients (Table 2). Twenty six patients were treated in Switzerland and two patients were treated in Brazil. All patients were white, and 63% (n = 17) were female. Patients ranged in age from 30 to 82 years (median, 61 years) and 75% (n = 21) had PS of 1 (vs 0 or 2). Seventy-nine percent (n = 22) of patients had received at least one prior systemic therapy, 57% (n = 17) had received at least two prior systemic therapies (Table 2).

Once disease progression was observed, most patients elected to resume or initiate chemotherapy and/or targeted therapy. Seven (25%) patients requested to continue experimental treatment in combination with chemotherapy. Continuation of experimental treatment was allowed if desired by the patient and approved by the patient's oncologist.

The exact duration of each examination was not recorded but lasted on average three hours. Each patient was examined an average of 3.3 ± 3.4 times (range 1 – 26). Frequency discovery was performed in patients with disease progression, stable disease or partial response. In general, we found more frequencies in patients with evidence of disease progression and large tumor bulk than in patients with stable disease, small tumor bulk or evidence of response. When we restrict the analysis of patients examined in 2006 and 2007, i.e. at a time when we had gathered more than 80% of the common tumor frequencies, we found that patients with evidence of disease progression had positive biofeedback responses to 70% or more of the frequencies previously discovered in patients with the same disease. Conversely, patients with evidence of response to their current therapy had biofeedback responses to 20% or less of the frequencies previously discovered in patients with the same disease. We also observed that patients examined on repeated occasions developed biofeedback responses to an increasing number of tumor-specific frequencies over time whenever there was evidence of disease progression. Whenever feasible, all frequencies were individually retested at each frequency detection session. These findings suggest that a larger number of frequencies are identified at the time of disease progression.

A total of 1524 frequencies ranging from 0.1 to 114 kHz were identified during a total of 467 frequency detection sessions (Table 1). The number of frequencies identified in each tumor type ranges from two for thymoma to 278 for ovarian cancer. Overall, 1183 (77.6%) of these frequencies were tumor-specific, i.e. they were only identified in patients with the same tumor type. The proportion of tumor-specific frequencies ranged from 56.7% for neuroendocrine tumors to 91.7% for renal cell cancer. A total of 341 (22.4%) frequencies were common to at least two different tumor types. The number of frequencies identified was not proportional to either the total number of patients studied or the number of frequency detection sessions (Table 1).

Twenty eight patients received a total of 278.4 months of experimental treatment. Median treatment duration was 4.1 months per patient; range 1 to +50.5. Patients treated in Switzerland were re-examined on average every other month for frequency detection; patients treated in Brazil were only examined once. Novel frequencies discovered upon re-examination were added to the treatment program of patients receiving experimental treatment. The first treatment programs consisted of combinations of less than ten frequencies while the most recent treatment programs exceed 280 frequencies (Figure 2).

The evolution of treatment programs through incremental addition of tumor-specific frequencies is illustrated by the case of a 51 year old woman with ovarian cancer. This patient was diagnosed with FIGO stage III (G2–G3) ovarian cancer in October 1997 and had received multiple courses of palliative chemotherapy until 2005. As seen on Figure 2, the initial treatment consisting of 15 frequencies did not yield any response. Upon re-examination, 11 additional frequencies (total of 26) were added to the treatment program in August 05. Because of disease progression, treatment with single agent bevacizumab was initiated in November 05. Interestingly, the CA 125 level had decreased by 200 units between October and November 2005, prior to the initiation of bevacizumab. Combined treatment with amplitude-modulated electromagnetic fields and bevacizumab resulted in a decrease in CA 125 level from 2140 to 540 in May 06. Treatment was supplemented with cyclophosphamide from March to September 07. The patient was hospitalized with pneumonia and elected to only receive amplitude-modulated electromagnetic fields since September 07. As of April 1, 2009 the patient has stable disease and is asymptomatic. She has been receiving experimental treatment without interruption for a total of +50.5 months.

This case provides empirical evidence that adding tumor-specific frequencies may yield disease stabilization in patients with evidence of disease progression. However, addition of frequencies over time does not appear to be a requirement for therapeutic efficacy. This is illustrated by the case of a 59 yo postmenopausal female with ER/PR positive, ERBB2 negative breast cancer with biopsy confirmed metastasis to the left ischium and right adrenal gland (Figure 3A, Figure 3C, Figure 3D). She had been previously treated with radiation therapy to the left ischium, had received five different hormonal manipulations (tamoxifen, anastrozole, exemestane, fulvestran and megestrol). She had also received capecitabine, which had been discontinued because of gastrointestinal side effects. The patient was examined only once. In June 2006, at the time of treatment initiation, the patient complained of severe left hip pain, which was limiting her mobility despite the intake of opioids. Within two weeks of experimental treatment initiation with breast cancer-specific frequencies, the patient reported complete disappearance of her pain and discontinued the use of pain medications. She also reported a significant improvement in her overall condition. As seen on Figure 3B and 3E, PET-CT obtained three months after treatment initiation showed complete disappearance of the right adrenal and left ischium lesions. The complete response lasted 11 months. Intriguingly, the patient had developed intermittent vaginal spotting in the months preceding experimental treatment initiation. A minimally enhancing uterine lesion was observed on PET-CT prior to treatment initiation. Upon follow-up, FDG uptake increased significantly (Figure 3B) and the patient was diagnosed with uterine cancer by hysteroscopy. The patient underwent hysterectomy, which revealed endometrial adenocarcinoma. Hence, while treatment with breast cancer specific frequencies resulted in a complete response, it did not affect the growth of endometrial adenocarcinoma. This observation suggests that breast cancer frequencies are tumor-specific as a response of the metastatic breast cancer was observed while a uterine tumor progressed.

As seen in Table 3, sixteen patients were evaluable for response by RECIST criteria. A complete response was observed in a patient with hormone-refractory breast cancer metastatic to the adrenal gland and bone (Figure 3), which lasted 11 months. A partial response was observed in a patient with hormone-refractory breast cancer metastatic to bone and liver, which lasted 13.5 months. Five patients had stable disease for +34.1 months (thyroid cancer with biopsy-proven lung metastases), 6.0 months (mesothelioma metastatic to the abdomen), 5.1 months (non-small cell lung cancer), and 4.1 months (pancreatic cancer with biopsy-proven liver metastases). As of April 1, 2009 two patients are still receiving experimental treatment and four patients are alive.

No patients receiving experimental therapy reported any side effect of significance and no patient discontinued treatment because of adverse effects. Three patients (10.7%) reported grade I fatigue after receiving treatment. One patient (3.6%) reported grade I mucositis after long-term use (26 months) of the experimental device and concomitant chemotherapy. Two patients with severe bony pain prior to initiation of experimental treatment reported significant symptomatic improvement. Both patients had breast cancer metastatic to the skeleton.