Il cancro è una delle cause di morte più comuni in tutto il mondo e ha rappresentato 8,2 milioni di morti nel 2012 1. Si prevede che il numero di decessi correlati al cancro aumenterà a oltre 11 milioni entro il 2030 2. I tipi di cancro con la più alta incidenza sono polmone (1,59 milioni di persone), fegato (745.000), stomaco (723.000), colon e retto (694.000), seno (521.000) ed esofago (400.000) 1. In oncologia, la selezione della corretta strategia di trattamento, nelle prime fasi della malattia, è fondamentale per aumentare la probabilità di remissione e migliorare la sopravvivenza. I trattamenti antitumorali disponibili includono chemioterapia, immunoterapia o terapia a base di anticorpi, radioterapia e chirurgia 3. La strategia terapeutica viene scelta tenendo conto della valutazione medica del singolo paziente, del tipo di cancro, della posizione e dello stadio 4 della malattia. I trattamenti multimodali sono spesso necessari per ridurre gli effetti collaterali indotti dalla terapia 5 relativi a approcci farmacologici e di altro tipo, tra cui la chirurgia 6. Gli effetti collaterali indotti dalla chemioterapia dipendono da varie variabili come il farmaco impiegato, il suo dosaggio e la durata del trattamento. Questi effetti collaterali includono dolore, affaticamento, piaghe alla gola e alla bocca, diarrea, nausea, vomito, stitichezza e disturbi del sangue. Gli effetti collaterali che colpiscono il sistema nervoso sono comunemente sperimentati con la chemioterapia e includono disfunzione cognitiva, mal di testa, vertigini, perdita della vista e disturbi della vista come visione offuscata o doppia, cambiamenti nell'apprendimento e nella memoria, disfunzione sessuale, atassia e neuropatia periferica 7-11. Eruzioni cutanee, febbre, ipotensione, colite o altri problemi gastrointestinali e disfunzioni tiroidee sono effetti collaterali correlati all'immunoterapia 12. I principali effetti collaterali indotti dalla radioterapia sono secchezza delle fauci e delle gengive, rigidità della mascella, nausea, linfedema, difficoltà di deglutizione, mancanza di respiro, dolore al seno o al capezzolo, sanguinamento rettale, incontinenza, irritazione della vescica e disfunzione ipofisaria 13. Le tecniche chirurgiche, come la chirurgia mini-invasiva, provocano anche dolore, affaticamento, perdita di appetito, gonfiore e lividi intorno al sito dell'intervento chirurgico, sanguinamento, infezione, linfedema e disfunzione d'organo 14. Numerosi studi supportano lo sviluppo di nuovi trattamenti in oncologia da aggiungere ai protocolli tradizionali per aumentare l'efficacia dei trattamenti disponibili, riducendo il profilo degli effetti collaterali e la qualità della vita dei pazienti 15-18. Tali risorse includono la medicina tradizionale cinese, la medicina ayurvedica, l'omeopatia e la naturopatia 19. Mentre la medicina complementare e alternativa (CAM) non è generalmente considerata parte della medicina convenzionale, è stata ampiamente utilizzata in campo oncologico come terapia aggiuntiva per controllare i sintomi dei pazienti e migliorare la loro qualità di vita 20-26. L'inizio del 20 ° secolo ha visto le prime applicazioni terapeutiche delle terapie CAM per il trattamento del cancro; queste terapie includono l'agopuntura, la cromoterapia, il tocco terapeutico (reiki) e la terapia del campo elettromagnetico pulsato (PEMF) 4, 15, 27-30. In questa recensione, ci siamo concentrati sulla terapia PEMF, una tecnica non invasiva caratterizzata da elettromagnetic campi che inducono microcorrenti a tutto il corpo o localmente per colpire specifici tessuti corporei. L'esposizione a PEMF nella gamma 0-300 Hz è uno strumento terapeutico ampiamente utilizzato per il trattamento di diverse patologie tra cui l'osteoartrite, il morbo di Parkinson, il dolore postchirurgico e l'edema, il trattamento delle ferite croniche e la facilitazione della vasodilatazione e dell'angiogenesi che producono una stimolazione diretta alle cellule eccitabili tra cui le cellule nervose e muscolari 31-34 . La stimolazione con intensità e durata sufficienti induce una corrente attraverso le membrane cellulari mirate, attivando cellule nervose o muscoli per propagare i potenziali d'azione 35-37. Infatti, la terapia PEMF può essere utilizzata come trattamento adiuvante alla chemioterapia e alla radioterapia con l'obiettivo di ridurne il dosaggio, mitigare eventuali effetti collaterali secondari dannosi e migliorare la prognosi del paziente 15, 35, 38-40.
Abbiamo esaminato studi in vitro, in vivo e clinici che impiegano la terapia PEMF per il trattamento del cancro pubblicati tra il 1976 e il 2016. Abbiamo cercato Pubmed/Medline, Embase, Web of Science e Scopus utilizzando le parole chiave "PEMF", "cancro", "magnetoterapia", "frequenze specifiche del tumore" e "oncologia" da sole o combinate. Questa revisione mira a descrivere lo stato dell'arte della terapia PEMF, discutendo l'attuale comprensione dei meccanismi sottostanti e delineando le prospettive terapeutiche future in oncologia.
La terapia PEMF è stata ampiamente studiata in vitro utilizzando varie linee cellulari tumorali umane, come il feocromocitoma derivato (PC12), il cancro al seno (ad esempio, MCF7, MDA-MB-231 e T47D) e il cancro del colon (SW-480 e HCT-116) 41-45. Questi studi hanno dimostrato che la terapia con PEMF può esercitare l'inibizione proliferativa e l'interruzione del fuso mitotico 18, 40, bloccare lo sviluppo della neovascolarizzazione necessaria per l'apporto tumorale 46-48 ed esacerbare un'instabilità genetica intrinseca o indotta riducendo il rigore del checkpoint 49 del ciclo tardivo (G2). Mentre la chemioterapia non è specifica per le cellule tumorali e prende di mira tutte le cellule in rapida divisione 50-52, le PEMF esercitano un effetto citotossico selettivo sulle cellule neoplastiche 15, 40, 53-55 rendendo questa terapia una strategia molto promettente.
Nei prossimi commi, esamineremo gli studi che impiegano la terapia PEMF in diverse linee cellulari come modello per studiare specifici tipi di cancro (Tabella 1).
Tabella 1. Studi in vitro della terapia PEMF in oncologia| Author(s), year | Cell type | Treatment | Main findings | References |
|---|---|---|---|---|
| Crocetti et al., 2013 | Human breast adenocarcinoma cells (MCF7) and nontumorigenic cells (MCF10) | Daily 60-min PEMF therapy session (20 Hz; 3 mT) for 3 days | PEMFs increased apoptosis in MCF7 cells but had no effect on MCF10 cells | 38 |
| Filipovic et al., 2014 | Human breast cancer (MDA-MB-231) and colon cancer (SW-480 and HCT-116) cell lines | 24 and 72 h exposure to PEMF therapy (50 Hz; 10 mT) | 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 | 58 |
| Morabito et al., 2010 | Undifferentiated PC12 pheochromocytoma cells and differentiated PC12 cells | Short PEMF therapy session (50 Hz, 0.1–1.0 mT) for 30 min, and long-term PEMF session (50 Hz, 0.1–1.0 mT) for 7 days | 30-min PEMF session in undifferentiated PC12 cells increased ROS levels and decreased catalase activity. No change in intracellular Ca2+ concentration was observed. 7-day PEMF therapy session in undifferentiated PC12 cells resulted in increased intracellular Ca2+ concentration and increased catalase activity. No significant findings were observed in differentiated PC12 cells | 41 |
A study by Crocetti and coworkers 38 investigated whether ultra-low intensity and frequency PEMF therapy could induce apoptosis in human breast adenocarcinoma cells (MCF7). PEMF exposure was cytotoxic to MCF7 cells, but not to normal breast epithelial cells (MCF10). Both MCF7 and MCF10 cells were exposed to PEMF therapy and the cytotoxic indices were measured in order to design PEMF paradigms that could reduce selectively 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. Four independent methods of monitoring cancer-induced apoptosis (trypan blue assay, apoptosis determination by DNA strand break detection, analysis of cellular electrical properties by means of impedance microflow cytometer, and apoptosis determination by Annexin V staining) showed that this specific set of PEMF parameters was cytotoxic to breast cancer cells. While this treatment selectively induced apoptosis of MCF7 cells, it had no effect on MCF10 cells that were more resistant to apoptosis in response to PEMFs. Although these results are encouraging, PEMF exposure was limited to 3 days. Long-term PEMF exposure needs to be assessed in further studies based on the concept that PEMF effectiveness is strictly linked to the signal parameters, exposure magnitude, duration, signal shape, duration of treatment as well as the type of cells exposed to the magnetic field 56, 57.
The antineoplastic effect of PEMFs has also been investigated in human breast cancer MDA-MB-231, colon cancer SW-480, and HCT-116 cell lines. These cells were exposed to 50 Hz PEMFs for 24 and 72 h 58. PEMFs decreased the number of viable cells in all the cell lines tested, reaching 55% after 24 h and 20% after 72 h in the MDA-MB-231 cell line, 11% after 24 h and 6% after 72 h in the SW480 cell line, and 2% after 24 h and 3% after 72 h in the HCT-116 cell line, compared with unexposed cancer cell lines used as controls, as assessed by a computer reaction-diffusion model, a mathematical model widely employed to study cell proliferation and infiltration 59. The lower percentage inhibition of neoplastic cell proliferation was observed after 72 h, showing that PEMF therapy had antiproliferative activity which decreased over time. This action is exerted in vitro by interfering with microtubule spindle polymerization. Indeed, PEMF exposure reduces the fraction of polymerized microtubules, disrupts the mitotic spindle structure, inhibits cell division, thereby leading to chromosome mis-segregation and cancer-induced apoptosis 60. In summary, studies in human breast and colon cancer cell lines are promising and warrant further investigations.
PEMF signal parameters have been extensively utilized on diverse cell types to determine in vitro effectiveness 61, 62. For example, Morabito and coworkers 41 investigated cell responsiveness and in vitro neuritogenesis following PEMF exposure. They specifically focused on PEMF ability to modify morphology, proliferation, and differentiation in PC12 pheochromocytoma cells. Furthermore, they assessed whether PEMFs can induce variable and species-specific alterations in the oxidative stress pathway such as Ca2+-dependent oxidative stress which enhances free radical production, particularly via the Fenton reaction, leading to apoptotic cell death 63-69. Undifferentiated and differentiated [supplemented with 50 ng/mL of nerve growth factor (NGF)] PC12 cells were exposed to 50 Hz PEMF therapy (0.1–1.0 mT), and cell growth and viability were evaluated after immediate (30 min) or long-term exposure (7 days), using colorimetric and morphological assays. The long-lasting exposure to PEMFs did not affect the biological response in terms of proliferation and neuritogenesis. Thirty-minute PEMF exposure at 1.0 mT in undifferentiated PC12 cells increased the levels of reactive oxygen species (ROS) and decreased catalase activity, an indicator of oxidative stress. Conversely, long-term PEMF exposure of undifferentiated PC12 cells also increased catalase activity that could reflect the absence of ROS accumulation and a possible adaptation cell response to PEMFs. During immediate PEMF exposure in undifferentiated PC12 cells, no change in intracellular Ca2+ concentration was observed, while it increased after long-term exposure. This enhanced calcium level could activate, through voltage-gated (L-type) calcium channels, signaling pathways and lead to the expression of genes modulating cell differentiation, survival, and apoptosis such as extracellular signal-regulated kinases, c-Jun N-terminal protein kinase/stress-activated protein kinase, and p38 70-73. In particular, the undifferentiated PC12 cells were more sensitive to PEMFs exposure, while the differentiated PC12 cells were more stable and resistant to stress, probably due to the action of the cell surface NGF receptors such as p75NR 74.
Further studies are necessary to identify the ROS/intracellular Ca2+ cross-talking pathway activated by PEMF therapy. However, the study by Morabito and coworkers supports the hypothesis that ROS and Ca2+ could be the cellular “primum movens” of PEMF therapy-induced effects, as observed in pheochromocytoma cells.
Several studies investigated the antineoplastic effect of PEMFs using widely employed animal models of several types of cancer, including breast cancer, hepatocellular carcinoma (HCC), and melanoma (Table 2) 4, 48, 75-78.
Table 2. In vivo studies of PEMF therapy in oncology| Author(s), year | Animal model (number of animals, study design) | Route of administration | Treatment | Main findings | References |
|---|---|---|---|---|---|
| Tatarov et al., 2011 | 12 T-cell-immunodeficient Swiss outbred female nude mice (Cr:NIH(S)-nu/nu), divided into 4 groups (n = 3 each) | Orthotopic injection of metastatic mouse breast tumor cell line [EpH4-MEK Bcl213 cells (1 × 106)] into the mammary fat pad | Group 1, 2 and 3 were exposed to PEMFs (1 Hz, 100 mT) daily for 60, 180, or 360 min, respectively, for 4 weeks; group 4 did not receive any treatment and was used as control | Mice exposed for 60 and 180 min daily showed a 30% and 70% tumor reduction, respectively, at week 4, if compared to baseline | 85 |
| Emara et al., 2013 | 60 rats (strain not reported) divided into 6 groups | Intraperitoneal administration of a carcinogenic agent, DEN | Group 1 (naive rats) received PEMF therapy (2-3 Hz, 0.004 T) for 30 min/day for 6 days/week for 4 weeks; group 2 (naive rats) received PEMF therapy (<1 Hz, 0.6 T) 15 min/day for 6 days/week for 4 weeks; group 3 (naive rats) was left untreated; group 4 (HCC rats) received PEMF therapy (2-3 Hz, 0.004 T) for 30 min/day for 6 days/week for 4 weeks; group 5 (HCC rats) received PEMF therapy (<1 Hz, 0.6 T) 15 min/day for 6 days/week for 4 weeks; group 6 (HCC rats) was left untreated. | A significant decrease in serum AFP level and a slight improvement in dielectric properties of liver tissues was observed in HCC rats treated with PEMFs. These results were confirmed by electron microscopy and histological analysis showing HCC regression. No changes in histopathology and dielectric properties of liver tissue were observed in naive rats exposed to PEMFs. | 91 |
| Nuccitelli et al., 2006 | 23 SKH-1 immunocompetent, hairless, albino mice | Single subcutaneous injection of B16 murine melanoma cells (1 × 105) on the dorsal side of the mouse ear | 30-min PEMF therapy session (0.5 Hz, 0.2 T) three times a day for 6 days | All mice exhibited significant pyknosis, shrinkage of the tumor cell nuclei by 54% within a few minutes after PEMF therapy and by 68% within 3 h and reduction in the blood flow in about 15 min following PEMF therapy | 95 |
| Nuccitelli et al., 2010 | Four female immunodeficient, hairless, albino Nu/Nu mice | Single subcutaneous injection of murine melanoma cells (B16-F10-eGFP, 1 × 105) on the mouse skin | Daily 6-min PEMF session (5–7 Hz, 0.2 T) for 10 days | Melanoma cells shrank within an hour post PEMF therapy, exhibiting pyknosis within 24 h post treatment. PEMFs-treated mice showed complete remission of melanoma | 100 |
PEMF therapy effectiveness on tumor growth and viability has been tested in mouse models of breast cancer. For example, xenograft mouse models are widely used to study breast cancer. This model is obtained by injection of human breast cancer cells including estrogen-negative (MDA-MB-231) and estrogen-positive (MCF7) breast carcinoma cell lines or mouse breast cancer cells including EpH4 mammary epithelial cells or mitogen-activated protein kinase (MEK)-transformed EpH4 cells subcutaneously, intravenously, intracardially, or orthotopically, four times every 5 days, into the mammary fat pad of immunocompromised mice 79, 80. The injected cells are highly invasive in vitro and tumorigenic when transplanted into the mammary fat pad. After a week from the last injection, the mouse is palpated biweekly for mammary tumors and the dimensions of tumors are measured using an external caliper daily. Mice are euthanized when the tumor size becomes ulcerated with macro-metastases, mainly in liver, bone, and brain 81-84. For example, EpH4-MEK Bcl213 cells (1 × 106) transfected with a luciferase expression vector (pβP2-PolII-luciferase) were injected into the mammary fat pad in 12 T-cell-immunodeficient Swiss outbred female nude mice (Cr:NIH(S)-nu/nu) 85. Mice were divided into four groups (n = 3 each). Group 1, 2, and 3 were exposed to PEMF therapy (1 Hz, 100 mT) daily for 60, 180, or 360 min, respectively, for 4 weeks, while group 4 did not receive PEMF therapy and was used as control. All mice were monitored for tumor growth by body bioluminescence imaging once every 2 to 4 days for 4 weeks. Then, all the mice were sacrificed and skin, liver, lung, and spleen samples were collected for histopathologic analysis. Mice exposed to PEMFs for 60 and 180 min daily showed a 30% and 70% breast tumor reduction, respectively, at week 4, if compared to baseline. Mice exposed to PEMFs for 360 min daily, showed a suppression of tumor growth at week 4. In summary, this study shows that the time of PEMF exposure is critical to determine its effectiveness. Mice exposed for longer duration (360 min daily for 4 weeks) showed a significant reduction in tumor size, due probabily to the inhibition of angiogenesis that may suppress the formation of blood vessels in tumor tissues, reducing the tumor growth.
Chemically induced HCC is a widely used model of hepatocarcinogenesis that mimics the development of fibrosis and cirrhosis. This model is obtained by intraperitoneal administration of a carcinogenic agent, N-diethylnitrosamine (DEN; 50–100 mg/kg mouse body weight) alone or followed by oral administration of a nongenotoxic liver tumor promoter [phenobarbital (PB)]. DEN induces damage to DNA, proteins, and lipids, leading to hepatocyte death 86. It is hydroxylated to α-hydroxylnitrosamine, mediated by cytochrome P450 enzymes which are primarily located in the centrilobural hepatocytes. Then, an electrophilic ethyldiazonium ion is formed and causes DNA damage by reacting with nucleophiles. Three to four weeks following the last injection, mice receive drinking water containing PB (0.07%) that increases the expression of cytochrome P450, inducing oxidative stress and resulting in HCC development after 6 months from PB administration 86-90. Emara and coworkers evaluated the safety and effectiveness of PEMFs with different intensity and frequency in a rat model of DEN-induced HCC (75 mg/kg body weight, once a week for 3 weeks) 91. Sixty rats were divided into six groups: Group 1 (naive rats) received PEMF therapy (2-3 Hz, 0.004 T) for 30 min/day for 6 days/week for 4 weeks; group 2 (naive rats) received PEMF therapy (<1 Hz, 0.6 T) 15 min/day for 6 days/week for 4 weeks; group 3 (naive rats) was left untreated; group 4 (HCC rats) received PEMF therapy (2-3 Hz, 0.004 T) for 30 min/day for 6 days/week for 4 weeks; group 5 (HCC rats) received PEMF therapy (<1 Hz, 0.6 T) 15 min/day for 6 days/week for 4 weeks; group 6 (HCC rats) was left untreated. No changes in histopathology and dielectric properties of liver tissue were observed in naive rats exposed to PEMFs supporting its safety. In HCC rats exposed to PEMFs, a significant decrease in AFP level (AFP is a serum glycoprotein often elevated in HCC patients and used as a carcinoma marker in the clinic) was reported together with a slight improvement in dielectric properties of liver tissue. These results were confirmed by electron microscopy and histological analysis showing HCC regression. Altogether this evidence supports the antineoplastic activity of PEMF therapy in the rat model of DEN-induced HCC and warrants further investigations.
The most frequently used murine melanoma model is the syngeneic B16 model. It is obtained by a single subcutaneous injection of 1 × 105 B16 murine melanoma cells on the dorsal side of the mouse ear. Melanoma nodules 5–6 mm in diameter develop 7 days post-injection 92-94. The melanoma model in SKH-1 hairless mice has been used to investigate the effectiveness of PEMF therapy (0.5 Hz, 0.2 T, 30 min/day). Mice (n = 23) received 1–3 PEMF treatments daily for 6 days and were monitored for tumor growth, daily, by optical methods, such as transillumination and power Doppler ultrasound reconstructions that display blood flow images for each tumor 95. Then, all the mice were sacrificed and skin tissues were collected for histopathological analysis. All mice exposed to PEMFs exhibited significant pyknosis, shrinkage of the tumor cell nuclei by 54% within a few minutes after PEMF therapy and by 68% within 3 h and reduction in the blood flow in about 15 min following PEMF therapy. These effects may be due to PEMF therapy that stimulates murine melanoma to self-destruct by triggering rapid pyknosis of tumor cell nuclei and reducing blood flow 96-99. A further study 100 optimized the PEMF therapy parameters pulse number, amplitude, and frequency to completely suppress melanoma with a single treatment. In this study, four female immunodeficient, hairless, albino Nu/Nu mice received a single PEMF treatment for 6 min using the following parameters: 2.700 pulses, amplitude of 30 kV/cm and frequency of 5–7 Hz for 10 days. After 2–4 weeks, mice were sacrificed and skin samples were processed for histology. Melanoma cells shrank within an hour post PEMF therapy, exhibiting pyknosis within 24 h post PEMFs and showing a complete remission of melanoma in all the mice, as assessed by in vivo imaging (transillumination and photography). To evaluate the safety of PEMF therapy, the authors recorded the physiological parameters and introduced a miniature thermocouple into the tumor for simultaneous measurement of intratumoral temperature during PEMF treatment; body temperature and systolic blood pressure showed no significant changes, while the intratumoral temperature was ~6–7°C, evidencing that, by limiting the frequency to 7 Hz or less, it was possible to avoid heating the tumor to hyperthermia temperatures potentially leading to damage of the surrounding tissues. Evidence of efficacy of a single PEMF treatment on mouse skin cancer resulting in suppression of tumor growth and induction of apoptosis is promising for translational applications.
The use of PEMF therapy in oncology is still limited (Table 3) 4. The first study utilizing PEMF therapy was conducted by Barbault and coworkers who hypothesized that a combination of specific frequencies, defined tumor-specific frequencies, may display therapeutic effectiveness for localized treatment of tumors 15. They identified a total of 1524 tumor-specific frequencies, ranging from 0.1 to 114 kHz, consisting in the measurement of variations in skin electrical resistance, pulse amplitude, and blood pressure in 163 patients affected by different types of cancer including brain tumors, colorectal cancer, HCC carcinoma, pancreatic, colorectal, ovarian, breast, prostate, lung, thyroid, and bladder cancer and exposed to the radiofrequency system. Self-administered PEMF therapy for 60 min, three times a day, for an average of 278.4 months was offered to only 28 patients with advanced cancer (breast cancer [n = 7], ovarian cancer [n = 5], pancreatic cancer [n = 3], colorectal cancer [n = 2], prostate cancer [n = 2], glioblastoma multiforme [n = 1], HCC carcinoma [n = 1], mesothelioma [n = 1], neuroendocrine tumor [n = 1], non-small-cell lung cancer [n = 1], oligodendroglioma [n = 1], small-cell lung cancer [n = 1], sarcoma [n = 1] and thyroid tumor [n = 1]). None of the patients who received PEMF therapy reported any side effects; four patients presented stable disease for 3 years (thyroid cancer with biopsy-proven lung metastases), 6 months (mesothelioma metastatic to the abdomen), 5 months (non-small-cell lung cancer), and 4 months (pancreatic cancer with biopsy-proven liver metastases), respectively.
Table 3. Clinical studies of PEMF therapy in oncology| Author(s), year | Study design | Number of patients | Pathology | Treatment | Outcomes | Side effects | References |
|---|---|---|---|---|---|---|---|
| Barbault et al., 2009 | Compassionate and investigational clinical trial | 28 | Glioblastoma multiforme, mesothelioma, oligodendroglioma, sarcoma, HCC and breast, colorectal, lung, neuroendocrine, ovarian, pancreatic, prostate and thyroid cancers | 60-min PEMF session (0.1 Hz–114 kHz, 1.5 T) three times a day for 278.4 months | One patient with thyroid cancer, one patient with mesothelioma metastatic to the abdomen, one patient with non-small-cell lung cancer and one patient with pancreatic cancer with biopsy-proven liver metastases presented stable disease for 3 years, 6 months, 5 months and 4 months, respectively | None reported | 15 |
| Costa et al., 2007 | A single-group, open-label, phase I/II clinical trial | 41 | Advanced HCC | Daily 60-min PEMF session (100 Hz–21 kHz, 1.5 T) three times a day for 6 months | Five patients reported complete disappearance and two patients reported decrease in pain shortly after treatment. Four patients showed a partial response to treatment, while 16 patients had stable disease for more than 12 weeks | None reported | 102 |
PEMF therapy has also been employed for the treatment of HCC. Therapies for this disease are needed, especially for patients at an advanced disease stage who cannot tolerate chemotherapy or intrahepatic interventions because of impaired liver function 101. The feasibility of PEMF therapy for treatment of HCC has also been investigated in a single-group, open-label, phase I/II clinical study 102. Forty-one patients with advanced HCC received very low levels of PEMFs modulated at HCC-specific frequencies (100 Hz–21 kHz) and received three-daily 60 min outpatient treatments. No adverse reactions were observed during PEMF treatment. Five patients reported complete disappearance and two patients reported decrease in pain shortly after beginning of treatment. Four patients showed a partial response to treatment, while 16 patients (39%) had stable disease for more than 12 weeks. This study shows that PEMF therapy provides a safe and well-tolerated treatment, as well as evidence of antineoplastic effects in patients with HCC.
In summary, encouraging findings warrant randomized clinical studies to determine the effectiveness of amplitude-modulated PEMF therapy that can delay cancer progression and increase overall survival in patients. The increased knowledge of tumor-specific frequencies and the preliminary evidence that additional tumor-specific frequencies may yield a therapeutic benefit provide a strong rationale for the novel concept that administration of a large number of these frequencies may result in successful long-term disease management.
In vitro studies support antineoplastic and antiangiogenic effects of PEMF therapy. Several mechanisms of PEMF therapy have been elucidated. For example, PEMFs inhibit cancer growth by disrupting the mitotic spindle in a process mediated by interference of spindle tubulin orientation and induction of dielectrophoresis. Furthermore, PEMF therapy modulates gene expression and protein synthesis interacting with specific DNA sequences within gene promoter regions 18, 38, 40,