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      Emerging medical applications based on non-ionizing electromagnetic fields from 0 Hz to 10 THz

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          Abstract

          The potential for using non-ionizing electromagnetic fields (EMF; at frequencies from 0 Hz up to the THz range) for medical purposes has been of interest since many decades. A number of established and familiar methods are in use all over the world. This review, however, provides an overview of applications that already play some clinical role or are in earlier stages of development. The covered methods include modalities used for bone healing, cancer treatment, neurological conditions, and diathermy. In addition, certain other potential clinical areas are touched upon. Most of the reviewed technologies deal with therapy, whereas just a few diagnostic approaches are mentioned. None of the discussed methods are having such a strong impact in their field of use that they would be expected to replace conventional methods. Partly this is due to a knowledge base that lacks mechanistic explanations for EMF effects at low-intensity levels, which often are used in the applications. Thus, the possible optimal use of EMF approaches is restricted. Other reasons for the limited impact include a scarcity of well-performed randomized clinical trials that convincingly show the efficacy of the methods and that standardized user protocols are mostly lacking. Presently, it seems that some EMF-based methods can have a niche role in treatment and diagnostics of certain conditions, mostly as a complement to or in combination with other, more established, methods. Further development and a stronger impact of these technologies need a better understanding of the interaction mechanisms between EMF and biological systems at lower intensity levels. The importance of the different physical parameters of the EMF exposure needs also further investigations.

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          Most cited references171

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          Hyperthermia in combined treatment of cancer.

          Hyperthermia, the procedure of raising the temperature of tumour-loaded tissue to 40-43 degrees C, is applied as an adjunctive therapy with various established cancer treatments such as radiotherapy and chemotherapy. The potential to control power distributions in vivo has been significantly improved lately by the development of planning systems and other modelling tools. This increased understanding has led to the design of multiantenna applicators (including their transforming networks) and implementation of systems for monitoring of E-fields (eg, electro-optical sensors) and temperature (particularly, on-line magnetic resonance tomography). Several phase III trials comparing radiotherapy alone or with hyperthermia have shown a beneficial effect of hyperthermia (with existing standard equipment) in terms of local control (eg, recurrent breast cancer and malignant melanoma) and survival (eg, head and neck lymph-node metastases, glioblastoma, cervical carcinoma). Therefore, further development of existing technology and elucidation of molecular mechanisms are justified. In recent molecular and biological investigations there have been novel applications such as gene therapy or immunotherapy (vaccination) with temperature acting as an enhancer, to trigger or to switch mechanisms on and off. However, for every particular temperature-dependent interaction exploited for clinical purposes, sophisticated control of temperature, spatially as well as temporally, in deep body regions will further improve the potential.
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            Alternating electric fields arrest cell proliferation in animal tumor models and human brain tumors.

            We have recently shown that low intensity, intermediate frequency, electric fields inhibit by an anti-microtubule mechanism of action, cancerous cell growth in vitro. Using implanted electrodes, these fields were also shown to inhibit the growth of dermal tumors in mice. The present study extends these findings to additional cell lines [human breast carcinoma; MDA-MB-231, and human non-small-cell lung carcinoma (H1299)] and to animal tumor models (intradermal B16F1 melanoma and intracranial F-98 glioma) using external insulated electrodes. These findings led to the initiation of a pilot clinical trial of the effects of TTFields in 10 patients with recurrent glioblastoma (GBM). Median time to disease progression in these patients was 26.1 weeks and median overall survival was 62.2 weeks. These time to disease progression and OS values are more than double the reported medians of historical control patients. No device-related serious adverse events were seen after >70 months of cumulative treatment in all of the patients. The only device-related side effect seen was a mild to moderate contact dermatitis beneath the field delivering electrodes. We conclude that TTFields are a safe and effective new treatment modality which effectively slows down tumor growth in vitro, in vivo and, as demonstrated here, in human cancer patients.
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              Heating the patient: a promising approach?

              There is a clear rationale for using hyperthermia in cancer treatment. Treatment at temperatures between 40 and 44 degrees C is cytotoxic for cells in an environment with a low pO(2) and low pH, conditions that are found specifically within tumour tissue, due to insufficient blood perfusion. Under such conditions radiotherapy is less effective, and systemically applied cytotoxic agents will reach such areas in lower concentrations than in well perfused areas. Therefore, the addition of hyperthermia to radiotherapy or chemotherapy will result in at least an additive effect. Furthermore, the effects of both radiotherapy and many drugs are enhanced at an increased temperature. Hyperthermia can be applied by several methods: local hyperthermia by external or internal energy sources, regional hyperthermia by perfusion of organs or limbs, or by irrigation of body cavities, and whole body hyperthermia. The use of hyperthermia alone has resulted in complete overall response rates of 13%. The clinical value of hyperthermia in addition to other treatment modalities has been shown in randomised trials. Significant improvement in clinical outcome has been demonstrated for tumours of the head and neck, breast, brain, bladder, cervix, rectum, lung, oesophagus, vulva and vagina, and also for melanoma. Additional hyperthermia resulted in remarkably higher (complete) response rates, accompanied by improved local tumour control rates, better palliative effects and/or better overall survival rates. Generally, when combined with radiotherapy, no increase in radiation toxicity could be demonstrated. Whether toxicity from chemotherapy is enhanced depends on sequence of the two modalities, and on which tissues are heated. Toxicity from hyperthermia cannot always be avoided, but is usually of limited clinical relevance. Recent developments include improvements in heating techniques and thermometry, development of hyperthermia treatment planning models, studies on heat shock proteins and an effect on anti-cancer immune responses, drug targeting to tumours, bone marrow purging, combination with drugs targeting tumour vasculature, and the role of hyperthermia in gene therapy. The clinical results achieved to date have confirmed the expectations raised by results from experimental studies. These findings justify using hyperthermia as part of standard treatment in tumour sites for which its efficacy has been proven and, furthermore, to initiate new studies with other tumours. Hyperthermia is certainly a promising approach and deserves more attention than it has received until now.
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                Author and article information

                Journal
                Med Devices (Auckl)
                Med Devices (Auckl)
                MDER
                mder
                Medical Devices (Auckland, N.Z.)
                Dove
                1179-1470
                12 September 2019
                2019
                : 12
                : 347-368
                Affiliations
                [1 ]SciProof International AB , Östersund, Sweden
                [2 ]Strömstad Akademi, Institute for Advanced Studies , Strömstad, Sweden
                Author notes
                Correspondence: Mats-Olof MattssonSciProof International AB , Vaktpoststigen 4, ÖstersundS-83132, SwedenTel +36 202 350 5825Email mats-olof.mattsson@sciproof- international.se
                Article
                214152
                10.2147/MDER.S214152
                6746309
                31565000
                294f6f2c-e2da-48d1-9df1-57f95e2e6ea5
                © 2019 Mattsson and Simkó.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                : 01 May 2019
                : 23 August 2019
                Page count
                Tables: 3, References: 185, Pages: 22
                Categories
                Review

                Biotechnology
                pulsed electromagnetic fields,low frequency electromagnetic fields,high frequency electromagnetic fields,millimeter waves,thz waves,bone healing,cancer treatment,neurological treatment,diathermy

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