Abstract— This is a broad overview of tumor growth and treatment concerning electromagnetic fields. This paper will cover cancer risks from mobile phone use, treatment methods using EMF/PEMF, if non-ionizing radiation actually causes cancer, reviews of tumor-specific frequencies,

Index Terms— pemf, pulsed electromagnetic fields, NIR, Non-Ionizing Radiation, Electrohypersensitivity, (EHS)

I. INTRODUCTIONElectromagnetic fields have been an abstract concept since their inception. In today’s society we are surround by EMF. Exposure has become ubiquitous and for the scientific community it is concerning since this is a new variable interacting with our biology and we haven’t been able to produce an evolutionary response if exposure happens to be negative. A lot of superstition is centered around electromagnetic fields and cancer. There are disorders such as electrohypersensitivity that can affect an individual’s way of life.

Another area of concern is that we haven’t had enough time to research effects of EMF’s since some cancers can take up to 10 years to manifest themselves. With the rise of mobile phones, it will be a challenge to find reasonable control groups.

On the positive side treatment with EMF/PEMF’s has shown some promise. Given the rising costs of healthcare treating tumors with RF might be a viable alternative. New research is continually being done to uncover potential lifesaving processes through RF treatments.

II. RISKS OF ONCOGENICITY AND EMF

A. Cell Phones and Cancer Risks: Epidemiological Studies

Cell phones causing cancer have always been a common old wives’ tale. Due to the enigmatic nature of radio frequencies it is understandable many people can hold these opinions. My goal is to shed light on this subject and hopefully dispel some rumors that we are in danger from our beloved

phones. Due to the nature of RF signals I believe epidemiologic studies give the best insight on the safety of cell phone signals.

A study conducted by the International Commission for Non-Ionizing Radiation Protection conducted an epidemiological study on mobile phones and tumor risks is one of the most comprehensive studies I’ve read on this subject. The emphasis of our review, and of the majority of recently published studies, is on tumors of the brain and other sites in the head that have the highest exposure from mobile phones held against the ear. These include the glial and meningeal tissue close to the surface of the head, the vestibular portion of the eighth cranial nerve where acoustic neuromas (vestibular Schwannomas) develop, and the parotid gland [1].

Mobile phones became prevalent in the early 1990s, since then we’ve been exposed to them consistently throughout our daily lives. Exposure levels can vary greatly due to adaptive power levels when an individual is inside or far away from the base station. The importance of the various usage circumstances may vary with geographic location and over time.2,3 In addition to system characteristics, the radiofrequency exposure also depends on the characteristics of the phone itself, including the type and location of the antenna (eg, pull-out rod or built-in) and the tilt of the phone relative to the head. The spatial distribution of RF energy in the brain has been studied using measurements made on phantoms [1]. Nearly all of the energy (97%–99%) is absorbed in the brain hemisphere on the side where the phone is used, mainly (50% 60%) in the temporal lobe [1]. More considerations should be taken on how studies were conducted also. Was the data obtained directly by the participants? Or was it provided by the network operators? Do users overestimate their time on the phone? Etc. Data collected cannot always be reliable so risk estimates can be diluted. Considering multiple studies can be more reliable. Another important aspect of this study and all epidemiologic studies in this topic is induction and latency periods. Because mobile phones are a new

A review of Oncogenicity and EMFJoshua Asmussen

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technology, there is epidemiologic evidence on cancer risk only for relatively short periods since first exposure; data on exposures more than 10 years before cancer diagnosis are still limited. Most types of cancer occur many years, or even decades, after initial exposure to known carcinogens [1]. So, like always any risk assessment can be taken with a grain of salt. 50 years down the road we might discover cell phones can be as deadly as asbestos, although highly unlikely. Epidemiologic studies are based on diagnosed tumors, whose identification depends not just on the induction period (period between exposure and initiation of disease) but also on their latency (ie, how long they are present before being detected). Latency is likely to be short for fast-growing malignancies, but could be decades for less aggressive tumors such as acoustic neuromas and benign meningiomas. Hence for glioma (or at least the subset of gliomas that are fast-growing) information on risks 10 or 15 years after first exposure could provide meaningful information for determining whether mobile phone use has an etiologic effect, although this may not be true for slower-growing tumors [1].

A possible glaring error in almost all studies on this topic is the control groups. There’s an estimated 7 billion active mobile devices in the world, with more than half the world’s population owning their own mobile phone. Finding a control group poses a significant challenge and control groups that are used can be debatable since many humans receive significant exposure throughout their lifetime.

Glioma Results and Interpretation

Glioblastoma (GBM) is the most common primary malignant brain tumor, comprising 16% of all primary brain and central nervous system neoplasms. The average age-adjusted incidence rate is 3.2 per 100,000 population [2]. Out of the 14 studies conducted most found risk estimates to or below unity, besides 2 studies. These studies found that short-term exposure increases risks with odds ratios between 1.2 and 1.7. Analyzing table. 1:

Studies with elevated risks: The most recent study by Hardell found increased risks in all categories of time since first use, with an OR of 1.6 (1.1–2.4) within 5 years based on 100 exposed cases. Hours et al38 found an OR of 2.0 (0.7–5.2) for 3.8 or more

years since first use, which was the maximum exposure category analyzed in this French Interphone study. Takebayashi also reported an elevated OR after intermediate term exposure duration, but found a reduced OR after longer term exposure (_6.5 years). Both the Hours et al and Takebayashi et al studies included few exposed cases. For at least 10 years since first exposure, Hardell found a more than 3-fold risk increase (OR _ 3.6 _1.7–7.5_ for digital use) and Schuz reported a 2-fold risk increase based on 12 exposed cases (2.2 _0.9– 5.1_) [1].

Referencing table 1 it is apparent that a lot of the studies with increased risks are outweighed by those that are close to or below unity with only one serious outlier, Hardell 2006. The studies by Hardell et al are particularly problematic because of variation across their publications in the exact constitution of case groups, criteria for exclusion, exposure definitions, and the selection of results for presentation in the multiple overlapping publications. In our view, the series of decisions in methods, analysis, and presentation provide the most plausible explanation for the deviation of the findings of the Hardell studies from those of other investigators. This does not address the other positive reports, but they seem to fit more in the distribution of results expected given random error across studies [1]. Summarizing the data, there doesn’t seem to be a causal link to mobile phone use and increased risk of glioma. There remains some uncertainty due to inconsistencies across the studies, as well as the recognized problems of exposure misclassification and potential for bias due to selective participation. As discussed previously, nonparticipation in the Interphone studies has been estimated to result in a 10% downward bias of the odds ratios, which can not explain all of the observed risk reduction. In addition, the period between exposure to a causal agent and manifestation of glioma may range from 5 to 20 years or more, judging from the intervals observed between ionizing radiation exposure and tumor diagnosis [1]. I also agree with the author, keeping in mind the data obtained is not always reliable, if mobile phone use did cause glioma it would of manifested itself in many other studies not just the outliers.

Meningioma: Results and Interpretation

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Table 2 contains the results of eleven case-control studies and 2 pooled analyses. Much of the data mirrors the previous study even the Hardell study follows the same pattern as being one of the extreme outliers. Many of the methodologic studies concerning the glioma study apply to this one so considering each study besides the Hardell study there is no considerable risk of meningioma for mobile phone users.

B. Ionizing Radiation and CancerThere is an ongoing debate on whether or not EMF’s are able to cause cancer. One group adheres to the concept that, the only harmful effects associated with RF and MW radiation are due to heating, and that below thermal guidelines, this energy is safe [6]. This group relies on the well-established theory that non-ionizing radiation (NIR) does not have enough energy to dislodge electrons

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and therefore is unable to cause cancer [6]. The other group believes that NIR is harmful at levels well below thermal guidelines, levels that are now ubiquitous in urban centers. They believe that NIR causes cancer, reproductive problems, and a range of symptoms that have been classified as electrohypersensitivity (EHS) or idiopathic environmental intolerance according to the WHO; that children and pregnant women are particularly vulnerable; and that many of the chronic illnesses common in our society are due, in part, to electromagnetic pollution or electrosmog exposure [6].

The statement non-ionizing radiation doesn’t have enough energy to dislodge electrons and thus cannot cause cancer, this assumption is flawed. Models of chemicals and ionizing radiation (IR) are repeatedlyand inappropriately used to interpret the effects of NIR. With IR, photon energy is the critical criterion. With chemical toxicants, speciation and the dose are critical. With NIR we have evidence of effects within narrow intensity and frequency windows and evidence that waveform and modulation are biologically important [6].

When RF causes cancer it dislodges electrons, which create free radicals in the system. Since non-ionizing radiation doesn’t have the energy to dislodge these electrons it is easy to assume they don’t cause cancer but studies have shown that NIR interfere with the production of anti-oxidants. Ninety-three of the 100 available peer-reviewed studies, dealing with oxidative effects with low-intensity RF exposure, confirmed that RF induces oxidative stress in biological systems. The research includes studies with humans, plants and animals. conclude that low intensity RFR is an oxidative agent for living cells and is one of the primary mechanisms accounting for the biological activity of this kind of radiation [6]. A preponderance of scientific evidence clearly indicates that NIR, both ELF and RF, causes oxidative stress in living cells. This oxidative stress, while not the only mechanism, may be the key mechanism involved in carcinogenicity and it may also be involved with other effects including symptoms of electrohypersensitivity (EHS) and reproductive problems due to impaired sperm. The damage isgenerated not by direct ionization of atoms and molecules but rather by interference with anti-oxidant repair mechanisms [6]. Another possible

mechanism of production of free radicals produced by NIR is the introduction of heat shock proteins; altered calcium flux and intracellular calcium signaling; induced ornithine decarboxylase activity; increased permeability of the blood brain barrier; reduced oncostatic effect of melatonin; single and double strand DNA breaks; as well as other mechanisms have been documented [6]. Since The International Agency for Research on Cancer (IARC) states RFR and ELF magnetic fields are a possible human carcinogen rather than probable based on the fact there is no biologically plausible mechanism to support a carcinogenic effect of non-ionizing RF waves. There is some evidence this claim is wrong and should be reviewed.

From the sources I cited the author is from this article is clearly for limited NIR. Looking through some of the sources reveals that the Hardell 2006 epidemiological study was used. A study that I reviewed and agreed it was flawed especially since it was a major outlier. I think it is worth considering many of the studies and possibly reevaluating the effects of NIR, but regardless of the results I don’t see humanity or myself putting down the mobile phones.

III. THERAPEUTIC TREATMENTS

A. Biological Responses to Radiation TherapyRadiation therapy is an integral part of cancer

treatment. Approximately 50% of all patients with localized malignant tumors are treated with radiation at some point in the course of their disease [3]. The biological effectiveness of radiation depends on the linear energy transfer (LET), total dose, number of fractions and radio sensitivity of the targeted cells or tissues [3].

Radiation therapy is applied in a course of multiple fractions over several weeks to reduce the normal cell toxicity, with an estimation of about 40% toward the curative treatment [3]. Radiation therapy is also a cost-effective treatment, so any

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improvement to the therapy will greatly benefit patients. Radiation therapy uses linear energy transfer radiations to efficiently kill tumor cells while minimizing doses to healthy tissues. Linear energy transfer is the measurement of ionizations that radiation causes per unit distance as it travels through the biological material. Typically X-rays, gamma rays, and charged particles are the most used radiation. Low LET radiations (X-rays, gamma rays and beta particles) deposit a relatively small quantity of energy. On the other hand, radiation particles either negatively charged (electrons), positively charged (protons, alpha rays, and other heavy ions) deposits more energy on the targeted areas called the Bragg peak and causes more biological effects than the low LET radiations. However, tumors have developed multiple strategies to resist radiation damage. The following (1) Tumor burden (2) Tumor microenvironment/hypoxia (3) Inherent or acquired treatment resistance and (4) Repopulations during the treatment are the major mechanisms involved in the treatment resistance [3]. Ionizing radiations can kill any tumor but the problem is it can kill healthy tissue.

Direct EffectsUnder the target-cell damage, the major effect of

ionizing radiation on tissues are the direct cell killing mostly by damaging the DNA, resulting in the depopulation of cell populations and subsequent functional deficiency. Radiation induced ionizations can act directly on the cellular molecules and cause damage. Also, can act indirectly, producing free radicals which are derived from the ionization or excitation of the water component (80% of a cell is composed of water) of the cells. For ionizing radiations such as low LET X-rays and gamma-rays, 60% of cellular damage is caused by the indirect effects. Radiation induced double strand breaks (DSBs) represent the most lethal types of DNA damage, leading to cell death, if unrepaired. However, DNA damage response mechanisms represent a vital line of defense against exogenous and endogenous damage caused by radiation and promote two distinct outcomes: survival and the maintenance of genomic stability [3]. This figure below is an illustration of the two methods DNA is damaged.

Several experiments were performed indicating that the DNA of cancer cells repair more slowly and also produce more DNA breaks (single strand break and double strand breaks) than the normal cells. Furthermore, various proteins involved in cell death and DNA damage mechanisms decrease the radio resistance of the fast doubling cancer cells, while increase in radio resistance of slow doubling normal cells [3]. p53 is a transcription factor and also one of the most commonly mutated genes in cancer responds to ionizing radiation by initiating cell cycle arrest, senescence, apoptosis and DNA damage repair. However, whether p53 induces apoptosis or cell cycle arrest for the DNA damage repair is a complex process and partly depends on the abundance of the p53 protein (low protein levels lead to cell cycle arrest and high protein levels lead to apoptosis). However, various DNA repair mechanisms within the tumor cells interfere with the radiation induced damage and further increase

the radio resistance of cancer cells. Furthermore, inhibition of DNA repair proteins such as ATM or DNA-dependent protein kinase (DNA-PK) have been shown to sensitize the cancer cells to radiation treatment [3]. The figure below illustrates these mechanisms.

Radiation therapy seems to be a somewhat viable approach to limit cancer tumor growth. This paper introduced many issues with radiation therapy. Like tumors acquiring radio resistance during these treatments or tumors that are radio resistant from the beginning. To overcome these issues a better understanding of the biological methods need to be understood.

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B. Mechanisms and Therapeutic Effectiveness of Pulsed Electromagnetic Field Therapy in Oncology

PEMF therapies provide a new alternative to cancer treatment. Current treatments come with a lot of side effects and are not always 100 percent effective. PEMF therapy presents several potential advantages including non-invasiveness, safety, lack of toxicity for non-cancerous cells, and the possibility of being combined with other available therapies [4]. This treatment has been in use for various types of cancer including skin, breast, prostate, hepatocellular, lung, ovarian, pancreatic, bladder, thyroid, and colon cancer in vitro and in vivo but only limited applications of PEMF have been documented in humans. This review focuses on PEMF therapy which is considered an alternative therapy for cancer treatments. The frequency is between 0-300 Hz, and the fields are usually used for treatments that I have written about in the past such as osteoarthritis or vasodilation. PEMF therapy can be used as an adjuvant treatment to chemotherapy and radiotherapy with the aim of reducing their dosage, mitigating any harmful secondary side effects, and enhancing patient’s prognosis [4].

Studies of PEMF therapy in human breast cancer and colon cancer cell lines

PEMF exposure was cytotoxic to adenocarcinoma cells (MCF7) but not to normal breast cells (MCF10). This was an attempt to set PEMF paradigms to limit neoplastic cell proliferation. The PEMF parameters tested were: (1) frequency of 20 Hz, (2) intensity of 3 mT and (3) exposure time of 60 min/day for up to 3 days.

For MCF7 cells treated with 60-min PEMF sessions at 20 Hz, 3mT for 3 days: PEMFs increased apoptosis in MCF7 cells but had no effect on MCF10 cells.

For human breast cancer (MDA-MB-231) and colon cancer (SW-480 and HCT-116) cells treated with 24-72 h exposure at 50 Hz and 10mt: PEMFs increased apoptosis in MDA-MB- 231 (55% and 20%), SW480 (11% and 6%), and HCT-116 cell lines (2% and 3%) after 24 and 72 h exposure, respectively, compared with untreated control cancer cell lines [4].

PEMF therapy effectiveness in mouse models of breast cancer

This model is obtained by injecting human breast cancer cells: estrogen-negative (MDA-MB-231) and estrogen positive (MCF7) breast carcinoma cell lines or mouse breast cancer cells. These treatments are administered four times a day for 5 days. Mice were divided into 4 groups. 3 groups received PEMF treatments at 1 Hz 100mT daily for 60, 180, or 360 mins, for 4 weeks. Group 4 received no treatments. Mice exposed for 60, 180 mins showed a 30% to 70% reduction. Mice at 360 mins showed a suppression of tumor growth. This experiment shows PEMF exposure is critical to effectiveness. Mice exposed for longer duration (360 min daily for 4 weeks) showed a significant reduction in tumor size, due probably to the inhibition of angiogenesis that may suppress the formation of blood vessels in tumor tissues, reducing the tumor growth [4].

Clinical Studies

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These clinical studies simply state a stable disease

was observed or a complete disappearance. Based on the table below PEMF obviously need more research for clinical trials.

With more research PEMF for cancer treatment could possibly be a safer alternative to current treatments. This journal gives some reasons why PEMF is effective the specific claim, supported by the described in vivo studies, is that all treated groups showed slower tumor growth rate if compared with untreated control group, confirming that PEMF therapy can modulate the physiology and electrochemistry of cancer cells and influence cell membrane systems and mitosis. In addition, PEMFs induce some changes in membrane transport capacity through impacting the osmotic potential, ionic valves and leading to reduction in cellular stress factors, increase in the rate of DNA transcription, and modulation of immune response [4]. PEMFs have also an immunomodulatory effect, as supported by in vivo evidence showing an increase in tumor necrosis factor alpha levels that induce an anti-tumoral response, leading to the activation of a proapoptotic pathway induced by

caspase-8 interaction with Fas-associated death domain, in the spleen of the murine melanoma mouse model after a 16-day therapy [4]. With only two clinical studies done it’s hard to say if these treatments will be viable but in-vivo studies have shown a lot of promise. Animal studies have also shown a lot of potential too. Establishing a better paradigm for PEMF should be focused on so it can be assured the PEMF’s being used for clinical trials are the most effective.

C. Tumor-Specific Frequencies

Given the advantageous safety profile of athermal, non-ionizing radiofrequency electromagnetic fields and the emerging evidence that low levels of electromagnetic or electric fields may modify the growth of tumor cells, we hypothesized that the growth of human tumors might be sensitive to different but specific modulation frequencies [5]. The patients that were examined all had biopsy-proven cancer. Patients with the same type of tumors exhibited the same biofeedback responses at the same precise frequencies while patients with different tumors had different responses at that frequency. 163 tumor-specific frequencies were identified.

Frequency discovery consists in the measurement of variations in skin electrical resistance, pulse amplitude and blood pressure. These measurements

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are conducted while individuals are exposed to low and safe levels of amplitude-modulated frequencies emitted by handheld devices [5]. The exposure levels are deemed safe by the international electromagnetic safety limits. Patients lied on their back and were exposed to modulation frequencies. Variations in the amplitude of the radial pulse were used as the primary method for frequency detection. They were defined as an increase in the amplitude of the pulse for one or more beats during scanning of frequencies from 0.1 to 114,000 Hz using increments of 100 Hz. Whenever a change in the amplitude of the pulse is observed, scanning is repeated using increasingly smaller steps, down to 10-3 Hz. Frequencies eliciting the best biofeedback responses, defined by the magnitude of increased amplitude and/or the number of beats with increased amplitude, were selected as tumor-specific frequencies [5]. I’m not sure how amplitude of the radial pulse will identify a tumor-specific frequency. To elaborate, what does a tumor have to do with the amplitude of a heartbeat?

Frequencies were identified in the 1,000 to 15,000 Hz range and the signal synthesizer was tested with a precision of frequency of 10-7.

Results

A total of 115 patients were examined in Switzerland, 48 in Brazil. 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) [1]. The results are on the table on page 8.

Looking at the table multiple tumor-specific frequencies were identified, and there were frequencies common in two or more types of tumors.

Discovery of Tumor-Specific Frequencies

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 [5]. A total of 1524 frequencies were used ranging from 0.1 114 kHz and 1183 were identified as tumor-specific (77.6%).

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Table above shows frequency discovery.

Table on the left shows tumor-specific frequency responses

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Treatment with tumor-specific amplitude-modulated electromagnetic fields

Referencing the bottom table on page 8. 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 [5].

One studies provides empirical evidence that adding tumor-specific frequencies may yield diseases stabilization in patients showing evidence of disease progression. Noting that these patients also receive drugs to treat their caner as well. So, a control study would be needed to prove this. Another study showed empirical evidence of tumor-specific frequencies. A patient with breast cancer exhibited a complete response to tumor-specific frequencies but later on the patient was diagnosed with uterine cancer.

Concluding Remarks on Tumor-Specific Frequencies

Of the seven patients with metastatic breast cancer, one had a complete response lasting 11 months, another one a partial response lasting 13.5 months. The increased knowledge of tumor-specific frequencies and the preliminary evidence that additional tumor-specific frequencies may yield a therapeutic benefit provides a strong rationale for the novel concept that administration of a large number of tumor-specific frequencies obtained through the follow-up of numerous patients may result in long-term disease control. This hypothesis is partially supported by two long-term survivors reported in this study, a patient with thyroid cancer metastatic to the lung with stable disease for +34.1

months and a heavily pretreated patient with ovarian carcinoma and peritoneal carcinomatosis with stable disease for +50.5 months [5]. This study is drawing the conclusions based off a small number of successful trials. And I’m not convinced it could purely be from the RF therapies. This topic will need more research to draw any viable conclusions.

IV. CONCLUDING REMARKS

The goal of this paper was to provide a light review of contemporary research and biological methods of EMF and oncogenicity. Sometimes the superstitions that EMF’s causing cancer aren’t always as baseless as some of us might like to assume. That being said, for the most part, EMF’s do not cause cancer. It is hard to pinpoint the exact reason someone develops cancerous tumors and it is even harder to pinpoint something as complicated as EMF’s to be a direct cause. My pragmatic opinion says that given the benefits of mobile phone use in today’s society the risks associated with mobile phone use is outweighed.

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REFERENCES

[1] Ahlbom, Anders, et al. “Epidemiologic Evidence on Mobile Phones and Tumor Risk.” Epidemiology, vol. 20, no. 5, 2009, pp. 639–652., doi:10.1097/ede.0b013e3181b0927d.

[2] Davis, Mary. “Glioblastoma: Overview of Disease and Treatment.” Clinical Journal of Oncology Nursing, vol. 20, no. 5, Jan. 2016, doi:10.1188/16.cjon.s1.2-8.

[3] Baskar, Rajamanickam, et al. “Biological Response of Cancer Cells to Radiation Treatment.” Frontiers in Molecular Biosciences, vol. 1, 2014, doi:10.3389/fmolb.2014.00024.

[4] Vadalà, M., Morales-Medina, J. C., Vallelunga, A., Palmieri, B., Laurino, C., & Iannitti, T. (2016). Mechanisms and therapeutic effectiveness of pulsed electromagnetic field therapy in oncology. Cancer Medicine, 5(11), 3128-3139. doi:10.1002/cam4.861

[5] Barbault, A., Costa, F. P., Bottger, B., Munden, R. F., Bomholt, F., Kuster, N., & Pasche, B. (2009). Amplitude-modulated electromagnetic fields for the treatment of cancer: Discovery of tumor-specific frequencies and assessment of a novel therapeutic approach. Journal of Experimental & Clinical Cancer Research,28(1), 51. doi:10.1186/1756-9966-28-51

[6] Havas, Magda. “When Theory and Observation Collide: Can Non-Ionizing Radiation Cause Cancer?” Environmental Pollution, vol. 221, 2017, pp. 501–505., doi:10.1016/j.envpol.2016.10.018.

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