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      Magnetic hyperthermia therapy for the treatment of glioblastoma: a review of the therapy’s history, efficacy and application in humans

      1 , 1 , 1 , 2 , 1 , 3
      International Journal of Hyperthermia
      Informa UK Limited

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          Abstract

          <p class="first" id="P1">Hyperthermia therapy (HT) is the exposure of a region of the body to elevated temperatures to achieve a therapeutic effect. HT anticancer properties and its potential as a cancer treatment have been studied for decades. Techniques used to achieve a localised hyperthermic effect include radiofrequency, ultrasound, microwave, laser and magnetic nanoparticles (MNPs). The use of MNPs for therapeutic hyperthermia generation is known as magnetic hyperthermia therapy (MHT) and was first attempted as a cancer therapy in 1957. However, despite more recent advancements, MHT has still not become part of the standard of care for cancer treatment. Certain challenges, such as accurate thermometry within the tumour mass and precise tumour heating, preclude its widespread application as a treatment modality for cancer. MHT is especially attractive for the treatment of glioblastoma (GBM), the most common and aggressive primary brain cancer in adults, which has no cure. In this review, the application of MHT as a therapeutic modality for GBM will be discussed. Its therapeutic efficacy, technical details, and major experimental and clinical findings will be reviewed and analysed. Finally, current limitations, areas of improvement, and future directions will be discussed in depth. </p>

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          Most cited references96

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          Analysis of tissue and arterial blood temperatures in the resting human forearm.

          H H PENNES (1948)
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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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              Convection-enhanced delivery of macromolecules in the brain.

              For many compounds (neurotrophic factors, antibodies, growth factors, genetic vectors, enzymes) slow diffusion in the brain severely limits drug distribution and effect after direct drug administration into brain parenchyma. We investigated convection as a means to enhance the distribution of the large and small molecules 111In-labeled transferrin (111In-Tf; M(r), 80,000) and [14C]sucrose (M(r), 359) over centimeter distances by maintaining a pressure gradient during interstitial infusion into white matter to generate bulk flow through the brain interstitium. The volume of distribution (Vd) containing > or = 1% concentration of infusion solution increased linearly with the infusion volume (Vi) for 111In-Tf(Vd/Vi, 6:1) and [14C]sucrose (Vd/Vi, 13:1). Twenty-four hours after infusion, the distribution of 111In-Tf was increased and more homogeneous, and penetration into gray matter had occurred. By using convection to supplement simple diffusion, enhanced distribution of large and small molecules can be obtained in the brain while achieving drug concentrations orders of magnitude greater than systemic levels.
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                Author and article information

                Journal
                International Journal of Hyperthermia
                International Journal of Hyperthermia
                Informa UK Limited
                0265-6736
                1464-5157
                April 18 2018
                November 17 2018
                February 06 2018
                November 17 2018
                : 34
                : 8
                : 1316-1328
                Affiliations
                [1 ] Department of Neurosurgery, Brain Tumor Nanotechnology Laboratory, Tisch Cancer Institute at Mount Sinai, New York, NY, USA;
                [2 ] Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine Baltimore, MD, USA;
                [3 ] Department of Neurosurgery, Mount Sinai Beth Israel, New York, NY, USA
                Article
                10.1080/02656736.2018.1430867
                6078833
                29353516
                7f79f436-6285-450b-95f9-becb8f4eb9da
                © 2018
                History

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