Hyperthermia therapy: Difference between revisions

Hyperthermia therapy
Hyperthermia therapy
	Whole-body suit used in hyperthermia therapy.
ICD-10-PCS	6A3
ICD-9-CM	93.35, 99.85
MeSH	D006979
OPS-301 code	8–60
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Hyperthermia therapy (or hyperthermia, or thermotherapy) is a type of medical treatment in which body tissue is exposed to temperatures above body temperature, in the region of 40–45 °C (104–113 °F). Hyperthermia is usually applied as an adjuvant to radiotherapy or chemotherapy, to which it works as a sensitizer, in an effort to treat cancer.^[1]^[2]

Hyperthermia uses higher temperatures than diathermy and lower temperatures than ablation.^[3] When combined with radiation therapy, it can be called thermoradiotherapy.

Definition

Hyperthermia is defined as supra-normal body temperatures. There is no consensus as to what is the safest or most effective target temperature for the whole body. During treatment the body temperature reaches a level between 39.5 and 40.5 °C (103.1 and 104.9 °F).^[4] However, other researchers define hyperthermia between 41.8–42 °C (107.2–107.6 °F) (Europe, USA) to near 43–44 °C (109–111 °F) (Japan, Russia).^[5]

Types

Local hyperthermia heats a very small area and is typically used for cancers near or on the skin or near natural openings in the body (e.g., the mouth).^[6] In some instances, the goal is to kill the tumor by heating it, without damaging anything else. The heat may be created with microwave, radiofrequency, ultrasound energy or using magnetic hyperthermia (also known as magnetic fluid hyperthermia)^[7]^[8]^[9]). Depending on the location of the tumor, the heat may be applied to the surface of the body (superficial hyperthermia), inside normal body cavities (intraluminal hyperthermia), or deep in tissue through the use of needles or probes (interstitial hyperthermia). It should not be confused with ablation of small tumors, where higher temperatures (>55 °C) are applied with an aim to kill the tumor cells.^[10]
Regional hyperthermia heats a larger part of the body, such as an entire organ or limb. Usually, the goal is to weaken cancer cells so that they are more likely to be killed by radiation and chemotherapeutic medications. This may use the same techniques as local hyperthermia treatment, or it may rely on blood perfusion.^[6] In blood perfusion, the patient's blood is removed from the body, heated up, and returned to blood vessels that lead directly through the desired body part. Normally, chemotherapy drugs are infused at the same time. One specialized type of this approach is continuous hyperthermic peritoneal perfusion (CHPP), which is used to treat difficult cancers within the peritoneal cavity (the abdomen), including primary peritoneal mesothelioma and stomach cancer. Hot chemotherapy drugs are pumped directly into the peritoneal cavity to kill the cancer cells.^[10]
Whole-body hyperthermia heats the entire body to temperatures of about 39 to 43 °C (102 to 109 °F), with some advocating even higher temperatures. It is typically used to treat metastatic cancer (cancer that spread to many parts of the body).^[6] Techniques include infrared hyperthermia domes which include the whole body or the body apart from the head, putting the patient in a very hot room/chamber, or wrapping the patient in hot, wet blankets or a water tubing suit.^[6]^[10]

Treatment

Research has shown that hyperthermia, when administered with other treatments, can shrink tumours and may assist other treatments kill cancer cells.^[1]

Localized hyperthermia treatment is a well-established cancer treatment method with a simple basic principle: If a temperature elevation to 40 °C (104 °F) can be maintained for one hour within a cancer tumor, the cancer cells will be destroyed.^[11]

The schedule for treatments has varied between study centers. After being heated, cells develop resistance to heat, which persists for about three days and reduces the likelihood that they will die from direct effects of the heat.^[12] Some even suggest maximum treatment schedule of twice a week.^[13] Japanese researchers treated people with "cycles" up to four times a week apart.^[14] Radiosensitivity may be achieved with hyperthermia, and using heat with every radiation treatment may drive the treatment schedule.^[12] Moderate hyperthermia treatments usually maintain the temperature for approximately an hour.^[13]

Before the advent of modern antiretroviral therapy extracorporeal whole body hyperthermia was tried as a treatment for HIV/AIDS, with some positive outcomes.^[15]

Adverse effects

External application of heat may cause surface burns.^[13] Tissue damage to a target organ with a regional treatment will vary with what tissue is heated (e.g. brain treated directly may injure the brain, lung tissue treated directly may cause pulmonary problems). Whole body hyperthermia can cause swelling, blood clots, and bleeding.^[12] Systemic shock, may result, but is highly dependent upon method difference in achieving it. It may also cause cardiovascular toxicity.^[10] All techniques are often combined with radiation or chemotherapy, muddying how much toxicity is the result of those treatments versus the temperature elevation achieved.

Technique

Heat sources

There are many techniques by which heat may be delivered. Some of the most common involve the use of focused ultrasound (FUS or HIFU), RF sources, infrared sauna, microwave heating, induction heating, magnetic hyperthermia, infusion of warmed liquids, or direct application of heat such as through sitting in a hot room or wrapping a patient in hot blankets.

Controlling temperature

One of the challenges in thermal therapy is delivering the appropriate amount of heat to the correct part of the patient's body. For this technique to be effective, the temperatures must be high enough, and the temperatures must be sustained long enough, to damage or kill the cancer cells. However, if the temperatures are too high, or if they are kept elevated for too long, then serious side effects, including death, can result. The smaller the place that is heated, and the shorter the treatment time, the lower the side effects. Conversely, tumor treated too slowly or at too low a temperature will not achieve therapeutic goals. The human body is a collection of tissues with differing heat capacities, all connected by a dynamic circulatory system with variable relationship to skin or lung surfaces designed to shed heat energy. All methods of inducing higher temperature in the body are countered by the thermo-regulatory mechanisms of the body. The body as a whole relies mostly on simple radiation of energy to the surrounding air from the skin (50% of heat lost this way) which is augmented by convection (blood shunting) and vaporization through sweat and respiration. Regional methods of heating may be more or less difficult based on the anatomic relationships, and tissue components of the particular body part being treated. Measuring temperatures in various parts of the body may be very difficult, and temperatures may locally vary even within a region of the body.

To minimize damage to healthy tissue and other adverse effects, attempts are made to monitor temperatures.^[10] The goal is to keep local temperatures in tumor bearing tissue under 44 °C (111 °F) to avoid damage to surrounding tissues. These temperatures have been derived from cell culture and animal studies. The body keeps itself normal human body temperature, near 37.6 °C (99.7 °F). Unless a needle probe can be placed with accuracy in every tumor site amenable to measurement, there is an inherent technical difficulty in how to actually reach whatever a treating center defines as an "adequate" thermal dose. Since there is also no consensus as to what parts of the body need to be monitored (common clinically measured sites are ear drums, oral, skin, rectal, bladder, esophagus, blood probes, or even tissue needles). Clinicians have advocated various combinations for these measurements. These issues complicate the ability of comparing different studies and coming up with a definition of exactly what a thermal dose actually should be for tumor, and what dose is toxic to what tissues in human beings. Clinicians may be able to apply advanced imaging techniques, instead of probes, to monitor heat treatments in real time; heat-induced changes in tissue are sometimes perceptible using these imaging instruments.

There is the further difficulty inherent in the devices delivering energy. Regional devices may not uniformly heat a target area, even without taking into account compensatory mechanisms of the body. A great deal of current research focuses on how one might precisely position heat-delivery devices (catheters, microwave and ultrasound applicators, etc.) using ultrasound or magnetic resonance imaging, as well as developing new types of nanoparticles that can more evenly distribute heat within a target tissue.

Among hyperthermia therapy methods, magnetic hyperthermia is well known as the one that produce a controllable heat inside the body. Because of using magnetic fluid in this method, temperature distribution can be controlled by the velocity, size of nanoparticles and distribution of them inside the body.^[8] These materials upon application of external, alternating magnetic field convert electromagnetic energy into thermal energy and induce temperature rises.^[16]

Mechanism

Hyperthermia can kill cells directly, but its more important use is in combination with other treatments for cancer.^[12] Hyperthermia increases blood flow to the warmed area, perhaps doubling perfusion in tumors, while increasing perfusion in normal tissue by ten times or even more.^[12] This enhances the delivery of medications. Hyperthermia also increases oxygen delivery to the area, which may make radiation more likely to damage and kill cells, as well as preventing cells from repairing the damage induced during the radiation session.^[13]

Cancerous cells are not inherently more susceptible to the effects of heat.^[12] When compared in in vitro studies, normal cells and cancer cells show the same responses to heat. However, the vascular disorganization of a solid tumor results in an unfavorable microenvironment inside tumors. Consequently, the tumor cells are already stressed by low oxygen, higher than normal acid concentrations, and insufficient nutrients, and are thus significantly less able to tolerate the added stress of heat than a healthy cell in normal tissue.^[12]

Mild hyperthermia, which provides temperatures equal to that of a naturally high fever, may stimulate natural immunological attacks against the tumor. However, it is also induces a natural physiological response called thermotolerance, which tends to protect the treated tumor.^[12]

Moderate hyperthermia, which heats cells in the range of 40 to 42 °C (104 to 108 °F), damages cells directly, in addition to making the cells radiosensitive and increasing the pore size to improve delivery of large-molecule chemotherapeutic and immunotherapeutic agents (molecular weight greater than 1,000 daltons), such as monoclonal antibodies and liposome-encapsulated drugs.^[12] Cellular uptake of certain small molecule drugs is also increased.^[12]

Very high temperatures, above 50 °C (122 °F), are used for ablation (direct destruction) of some tumors.^[13] This generally involves inserting a metal tube directly into the tumor, and heating the tip until the tissue next to the tube has been killed.

History

The application of heat to treat certain conditions, including possible tumors, has a long history. Ancient Greeks, Romans, and Egyptians used heat to treat breast masses; this is still a recommended self-care treatment for breast engorgement. Medical practitioners in ancient India used regional and whole-body hyperthermia as treatments.^[17]

During the 19th century, tumor shrinkage after a high fever due to infection had been reported in a small number of cases.^[13] Typically, the reports documented the rare regression of a soft tissue sarcoma after erysipelas (an acute streptococcus bacterial infection of the skin; a different presentation of an infection by "flesh-eating bacteria") was noted. Efforts to deliberately recreate this effect led to the development of Coley's toxin.^[17] A sustained high fever after induction of illness was considered critical to treatment success.^[17] This treatment is generally considered^{[by whom?]} both less effective than modern treatments and, when it includes live bacteria, inappropriately dangerous.

Around the same period Westermark used localized hyperthermia to produce tumor regression in patients.^[18] Encouraging results were also reported by Warren when he treated patients with advanced cancer of various types with a combination of heat, induced with pyrogenic substance, and x-ray therapy. Out of 32 patients, 29 improved for 1 to 6 months.^[19]

Properly controlled clinical trials on deliberately induced hyperthermia began in the 1970s.^[13]

Future directions

Hyperthermia may be combined with gene therapy, particularly using the heat shock protein 70 promoter.^[12]

Two major technological challenges make hyperthermia therapy complicated: the ability to achieve a uniform temperature in a tumor, and the ability to precisely monitor the temperatures of both the tumor and the surrounding tissue.^[12] Advances in devices to deliver uniform levels of the precise amount of heat desired, and devices to measure the total dose of heat received, are hoped for.^[12]

In locally advanced adenocarcinoma of middle and lower rectum, regional hyperthermia added to chemoradiotherapy achieved good results in terms of rate of sphincter sparing surgery.^[20]

Magnetic hyperthermia

Magnetic hyperthermia is an experimental treatment for cancer, based on the fact that magnetic nanoparticles can transform electromagnetic energy from an external high-frequency field to heat.^[21] This is due to the magnetic hysteresis of the material when it is subjected to an alternating magnetic field.^[22] The area enclosed by the hysteresis loop represents losses, which are commonly dissipated as thermal energy.^[21] In many industrial applications this heat is undesirable, however it is the basis for magnetic hyperthermia treatment.^{[citation needed]}

As a result, if magnetic nanoparticles are put inside a tumor and the whole patient is placed in an alternating magnetic field, the temperature of the tumor will rise. This elevation of temperature may enhance tumor oxygenation and radio- and chemosensitivity, hopefully shrinking tumors.^[23] This experimental cancer treatment has also been investigated for the aid of other ailments, such as bacterial infections.^{[citation needed]}

Magnetic hyperthermia is defined by specific absorption rate (SAR) and it is usually expressed in watts per gram of nanoparticles.^[24]

References

^ ^a ^b "Hyperthermia in Cancer Treatment". National Cancer Institute. 9 September 2011. Retrieved 7 November 2017.
^ "Hyperthermia". European Society of Hyperthermic Oncology. Retrieved 28 January 2021.
^ This article incorporates public domain material from Dictionary of Cancer Terms. U.S. National Cancer Institute.: Hyperthermia therapy entry in the public domain NCI Dictionary of Cancer Terms
^ Wolf, Peter (2008). Innovations in biological cancer therapy, a guide for patients and their relatives. Hannover: Naturasanitas. pp. 31–3. ISBN 978-3-9812416-1-7.
^ Baronzio, Gian Franco; Hager, E. Dieter (2006). Hyperthermia in Cancer Treatment: A Primer. Medical Intelligence Unit. doi:10.1007/978-0-387-33441-7. ISBN 978-0-387-33440-0.^{[page needed]}
^ ^a ^b ^c ^d Mallory M, Gogineni E, Jones GC, Greer L, Simone CB 2nd (August 2015). "Therapeutic hyperthermia: The old, the new, and the upcoming". Crit Rev Oncol Hematol. 97 (15): 30018–4. doi:10.1016/j.critrevonc.2015.08.003. PMID 26315383.{{cite journal}}: CS1 maint: multiple names: authors list (link) CS1 maint: numeric names: authors list (link)
^ Javidi, Mehrdad; Heydari, Morteza; Attar, Mohammad Mahdi; Haghpanahi, Mohammad; Karimi, Alireza; Navidbakhsh, Mahdi; Amanpour, Saeid (19 December 2014). "Cylindrical agar gel with fluid flow subjected to an alternating magnetic field during hyperthermia". International Journal of Hyperthermia. 31 (1): 33–39. doi:10.3109/02656736.2014.988661. PMID 25523967. S2CID 881157.
^ ^a ^b Javidi, M; Heydari, M; Karimi, A; Haghpanahi, M; Navidbakhsh, M; Razmkon, A (15 December 2014). "Evaluation of the Effects of Injection Velocity and Different Gel Concentrations on Nanoparticles in Hyperthermia Therapy". Journal of Biomedical Physics & Engineering. 4 (4): 151–162. PMC 4289522. PMID 25599061.
^ HEYDARI, MORTEZA; JAVIDI, MEHRDAD; ATTAR, MOHAMMAD MAHDI; KARIMI, ALIREZA; NAVIDBAKHSH, MAHDI; HAGHPANAHI, MOHAMMAD; AMANPOUR, SAEID (October 2015). "Magnetic Fluid Hyperthermia in a Cylindrical Gel Contains Water Flow". Journal of Mechanics in Medicine and Biology. 15 (5): 1550088. doi:10.1142/S0219519415500888.
^ ^a ^b ^c ^d ^e Information from the U.S. National Cancer Institute
^ "Hyperthermia Cancer Treatment - CancerTutor.com". Cancer Tutor. 6 December 2016. Retrieved 25 April 2019.
^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k ^l ^m Carolyn Freeman; Halperin, Edward C.; Brady, Luther W.; David E. Wazer (2008). Perez and Brady's Principles and Practice of Radiation Oncology. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins. pp. 637–644. ISBN 978-0-7817-6369-1.
^ ^a ^b ^c ^d ^e ^f ^g Dollinger, Malin (2008). Everyone's Guide to Cancer Therapy; Revised 5th Edition: How Cancer Is Diagnosed, Treated, and Managed Day to Day. Kansas City, MO: Andrews McMeel Publishing. pp. 98–100. ISBN 978-0-7407-6857-6.
^ Maeta M, Koga S, Wada J, et al. (March 1987). "Clinical evaluation of total-body hyperthermia combined with anticancer chemotherapy for far-advanced miscellaneous cancer in Japan". Cancer. 59 (6): 1101–6. doi:10.1002/1097-0142(19870315)59:6<1101::AID-CNCR2820590610>3.0.CO;2-G. PMID 3815283.
^ Ash, S. R.; Steinhart, C. R.; Curfman, M. F.; Gingrich, C. H.; Sapir, D. A.; Ash, E. L.; Fausset, J. M.; Yatvin, M. B. (September 1997). "Extracorporeal whole body hyperthermia treatments for HIV infection and AIDS". ASAIO Journal (American Society for Artificial Internal Organs: 1992). 43 (5): M830–838. doi:10.1097/00002480-199703000-00123. ISSN 1058-2916. PMID 9360163.
^ John, Łukasz; Janeta, Mateusz; Szafert, Sławomir (2017). "Designing of macroporous magnetic bioscaffold based on functionalized methacrylate network covered by hydroxyapatites and doped with nano-MgFe 2 O 4 for potential cancer hyperthermia therapy". Materials Science and Engineering: C. 78: 901–911. doi:10.1016/j.msec.2017.04.133. PMID 28576066.
^ ^a ^b ^c Gian F. Baronzio (2006). "Introduction". Hyperthermia In Cancer Treatment: A Primer. Medical Intelligence Unit. Berlin: Springer. ISBN 0-387-33440-8.^{[page needed]}
^ Westermark F (1898). "Uber die Behandlung des Ulcerirended Cervixcarcinoms. Mittel Konstanter Warme". ZBL Gynakol. 22: 1335.
^ Warren SL (1935). "Preliminary study of the effect of artificial fever upon hopeless tumor cases". Am J Roentgenol. 33: 75.
^ Maluta S, Romano M, Dall'oglio S, et al. (2010). "Regional hyperthermia added to intensified preoperative chemo-radiation in locally advanced adenocarcinoma of middle and lower rectum". International Journal of Hyperthermia. 26 (2): 108–17. doi:10.3109/02656730903333958. PMID 20146565. S2CID 33333237.
^ ^a ^b Périgo, E. A.; Hemery, G.; Sandre, O.; Ortega, D.; Garaio, E.; Plazaola, F.; Teran, F. J. (30 November 2015). "Fundamentals and advances in magnetic hyperthermia". Applied Physics Reviews. 2 (4): 041302. arXiv:1510.06383. Bibcode:2015ApPRv...2d1302P. doi:10.1063/1.4935688. S2CID 53355982.
^ Midura, M.; Wróblewski, P.; Wanta, D.; Kryszyn, J.; Smolik, W. T.; Domański, G.; Wieteska, M.; Obrębski, W.; Piątkowska-Janko, E.; Bogorodzki, P. (17 November 2022). "The Hybrid System for the Magnetic Characterization of Superparamagnetic Nanoparticles". Sensors. 22 (22): 8879. Bibcode:2022Senso..22.8879M. doi:10.3390/s22228879. PMC 9695308. PMID 36433476.
^ Kumar, CS; Mohammad, F (14 August 2011). "Magnetic nanomaterials for hyperthermia-based therapy and controlled drug delivery". Advanced Drug Delivery Reviews. 63 (9): 789–808. doi:10.1016/j.addr.2011.03.008. PMC 3138885. PMID 21447363.
^ Carrey, J.; Mehdaoui, B.; Respaud, M. (15 April 2011). "Simple models for dynamic hysteresis loop calculations of magnetic single-domain nanoparticles: Application to magnetic hyperthermia optimization". Journal of Applied Physics. 109 (8): 083921–083921–17. arXiv:1007.2009. Bibcode:2011JAP...109h3921C. doi:10.1063/1.3551582. S2CID 119228529.

External links

Hyperthermia to Treat Cancer Information from the American Cancer Society
Transurethral Microwave Thermotherapy of the Prostate (TUMT) at eMedicine
Society of Thermal Medicine
European Society of Hyperthermic Oncology

[NIH2017-1] "Hyperthermia in Cancer Treatment". National Cancer Institute. 9 September 2011. Retrieved 7 November 2017.

[ESHO2021-2] "Hyperthermia". European Society of Hyperthermic Oncology. Retrieved 28 January 2021.

[3] This article incorporates public domain material from Dictionary of Cancer Terms. U.S. National Cancer Institute.: Hyperthermia therapy entry in the public domain NCI Dictionary of Cancer Terms

[Wolf2008p31-3-4] Wolf, Peter (2008). Innovations in biological cancer therapy, a guide for patients and their relatives. Hannover: Naturasanitas. pp. 31–3. ISBN 978-3-9812416-1-7.

[5] Baronzio, Gian Franco; Hager, E. Dieter (2006). Hyperthermia in Cancer Treatment: A Primer. Medical Intelligence Unit. doi:10.1007/978-0-387-33441-7. ISBN 978-0-387-33440-0.^{[page needed]}

[Mallory2015-6] Mallory M, Gogineni E, Jones GC, Greer L, Simone CB 2nd (August 2015). "Therapeutic hyperthermia: The old, the new, and the upcoming". Crit Rev Oncol Hematol. 97 (15): 30018–4. doi:10.1016/j.critrevonc.2015.08.003. PMID 26315383.{{cite journal}}: CS1 maint: multiple names: authors list (link) CS1 maint: numeric names: authors list (link)

[7] Javidi, Mehrdad; Heydari, Morteza; Attar, Mohammad Mahdi; Haghpanahi, Mohammad; Karimi, Alireza; Navidbakhsh, Mahdi; Amanpour, Saeid (19 December 2014). "Cylindrical agar gel with fluid flow subjected to an alternating magnetic field during hyperthermia". International Journal of Hyperthermia. 31 (1): 33–39. doi:10.3109/02656736.2014.988661. PMID 25523967. S2CID 881157.

[cite_journal_|pmc=4289522-8] Javidi, M; Heydari, M; Karimi, A; Haghpanahi, M; Navidbakhsh, M; Razmkon, A (15 December 2014). "Evaluation of the Effects of Injection Velocity and Different Gel Concentrations on Nanoparticles in Hyperthermia Therapy". Journal of Biomedical Physics & Engineering. 4 (4): 151–162. PMC 4289522. PMID 25599061.

[9] HEYDARI, MORTEZA; JAVIDI, MEHRDAD; ATTAR, MOHAMMAD MAHDI; KARIMI, ALIREZA; NAVIDBAKHSH, MAHDI; HAGHPANAHI, MOHAMMAD; AMANPOUR, SAEID (October 2015). "Magnetic Fluid Hyperthermia in a Cylindrical Gel Contains Water Flow". Journal of Mechanics in Medicine and Biology. 15 (5): 1550088. doi:10.1142/S0219519415500888.

[NCI-10] Information from the U.S. National Cancer Institute

[11] "Hyperthermia Cancer Treatment - CancerTutor.com". Cancer Tutor. 6 December 2016. Retrieved 25 April 2019.

[PerezBrady08-12] ^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k ^l ^m Carolyn Freeman; Halperin, Edward C.; Brady, Luther W.; David E. Wazer (2008). Perez and Brady's Principles and Practice of Radiation Oncology. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins. pp. 637–644. ISBN 978-0-7817-6369-1.

[Dollinger08-13] ^ ^a ^b ^c ^d ^e ^f ^g Dollinger, Malin (2008). Everyone's Guide to Cancer Therapy; Revised 5th Edition: How Cancer Is Diagnosed, Treated, and Managed Day to Day. Kansas City, MO: Andrews McMeel Publishing. pp. 98–100. ISBN 978-0-7407-6857-6.

[14] Maeta M, Koga S, Wada J, et al. (March 1987). "Clinical evaluation of total-body hyperthermia combined with anticancer chemotherapy for far-advanced miscellaneous cancer in Japan". Cancer. 59 (6): 1101–6. doi:10.1002/1097-0142(19870315)59:6<1101::AID-CNCR2820590610>3.0.CO;2-G. PMID 3815283.

[15] Ash, S. R.; Steinhart, C. R.; Curfman, M. F.; Gingrich, C. H.; Sapir, D. A.; Ash, E. L.; Fausset, J. M.; Yatvin, M. B. (September 1997). "Extracorporeal whole body hyperthermia treatments for HIV infection and AIDS". ASAIO Journal (American Society for Artificial Internal Organs: 1992). 43 (5): M830–838. doi:10.1097/00002480-199703000-00123. ISSN 1058-2916. PMID 9360163.

[16] John, Łukasz; Janeta, Mateusz; Szafert, Sławomir (2017). "Designing of macroporous magnetic bioscaffold based on functionalized methacrylate network covered by hydroxyapatites and doped with nano-MgFe 2 O 4 for potential cancer hyperthermia therapy". Materials Science and Engineering: C. 78: 901–911. doi:10.1016/j.msec.2017.04.133. PMID 28576066.

[isbn0-387-33440-8-17] Gian F. Baronzio (2006). "Introduction". Hyperthermia In Cancer Treatment: A Primer. Medical Intelligence Unit. Berlin: Springer. ISBN 0-387-33440-8.^{[page needed]}

[18] Westermark F (1898). "Uber die Behandlung des Ulcerirended Cervixcarcinoms. Mittel Konstanter Warme". ZBL Gynakol. 22: 1335.

[19] Warren SL (1935). "Preliminary study of the effect of artificial fever upon hopeless tumor cases". Am J Roentgenol. 33: 75.

[20] Maluta S, Romano M, Dall'oglio S, et al. (2010). "Regional hyperthermia added to intensified preoperative chemo-radiation in locally advanced adenocarcinoma of middle and lower rectum". International Journal of Hyperthermia. 26 (2): 108–17. doi:10.3109/02656730903333958. PMID 20146565. S2CID 33333237.

[:0-21] Périgo, E. A.; Hemery, G.; Sandre, O.; Ortega, D.; Garaio, E.; Plazaola, F.; Teran, F. J. (30 November 2015). "Fundamentals and advances in magnetic hyperthermia". Applied Physics Reviews. 2 (4): 041302. arXiv:1510.06383. Bibcode:2015ApPRv...2d1302P. doi:10.1063/1.4935688. S2CID 53355982.

[22] Midura, M.; Wróblewski, P.; Wanta, D.; Kryszyn, J.; Smolik, W. T.; Domański, G.; Wieteska, M.; Obrębski, W.; Piątkowska-Janko, E.; Bogorodzki, P. (17 November 2022). "The Hybrid System for the Magnetic Characterization of Superparamagnetic Nanoparticles". Sensors. 22 (22): 8879. Bibcode:2022Senso..22.8879M. doi:10.3390/s22228879. PMC 9695308. PMID 36433476.

[23] Kumar, CS; Mohammad, F (14 August 2011). "Magnetic nanomaterials for hyperthermia-based therapy and controlled drug delivery". Advanced Drug Delivery Reviews. 63 (9): 789–808. doi:10.1016/j.addr.2011.03.008. PMC 3138885. PMID 21447363.

[JAP-Carrey-24] Carrey, J.; Mehdaoui, B.; Respaud, M. (15 April 2011). "Simple models for dynamic hysteresis loop calculations of magnetic single-domain nanoparticles: Application to magnetic hyperthermia optimization". Journal of Applied Physics. 109 (8): 083921–083921–17. arXiv:1007.2009. Bibcode:2011JAP...109h3921C. doi:10.1063/1.3551582. S2CID 119228529.

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@@ Line 1: / Line 1: @@
-{{For|other health treatments involving application of [[heat]]|Heat therapy}}
+{{about|using increased temperatures to treat cancer|other health treatments involving application of heat|Heat therapy|use of elevated body temperature to treat infections|Pyrotherapy}}
+{{multiple issues|
-'''Hyperthermia therapy''' is a type of medical treatment in which [[body tissue]] is exposed to high [[temperatures]] to damage and kill [[cancer cells]] or to make cancer cells more sensitive to the effects of [[Radiation therapy|radiation]] and certain [[chemotherapy|anti-cancer drug]]s.<ref>{{NCI-cancer-dict}}: [http://www.cancer.gov/Templates/db_alpha.aspx?CdrID=46263 Hyperthermia therapy] entry in the public domain NCI Dictionary of Cancer Terms</ref>  When combined with [[radiation therapy]], it is called '''thermoradiography'''.
+  {{Fringe theories|date=October 2016}}
+  {{POV|date=October 2016}}
+}}
+{{Use dmy dates|date=October 2019}}
+{{Infobox medical intervention
+|  Name        = Hyperthermia therapy
+|  Image = Nci-vol-1954-300 hyperthermia therapy.jpg
+|  Caption = Whole-body suit used in hyperthermia therapy.
+|  ICD10       = {{ICD10PCS|6A3|6/A/3}}
+|  ICD9        = {{ICD9proc|93.35}}, {{ICD9proc|99.85}}
+|  MeshID      = D006979
+|  OPS301      = {{OPS301|8–60}}
+|  OtherCodes  =
+|  HCPCSlevel2 =
+}}
+'''Hyperthermia therapy''' ''(or hyperthermia, or thermotherapy)'' is a type of [[medical treatment]] in which [[Tissue (biology)|body tissue]] is exposed to [[temperature]]s above [[body temperature]], in the region of {{convert|40|–|45|C|F}}. Hyperthermia is usually applied as an adjuvant to [[radiotherapy]] or [[chemotherapy]], to which it works as a sensitizer, in an effort to treat [[cancer]].<ref name=NIH2017>{{cite web|access-date=2017-11-07|title=Hyperthermia in Cancer Treatment|url=https://www.cancer.gov/about-cancer/treatment/types/surgery/hyperthermia-fact-sheet|website=National Cancer Institute|date=2011-09-09}}</ref><ref name=ESHO2021>{{cite web|access-date=2021-01-28|title=Hyperthermia|url=https://www.esho.info/index.php?id=101|website=European Society of Hyperthermic Oncology}}</ref>
-Local hyperthermia for certain small tumors is generally accepted, similar to surgically removing a tumor.  Whole-body hyperthermia is generally considered to be a promising but [[experimental cancer treatment]].
+Hyperthermia uses higher temperatures than [[diathermy]] and lower temperatures than [[ablation]].<ref>{{NCI-cancer-dict}}: [http://www.cancer.gov/dictionary?CdrID=46263 Hyperthermia therapy] entry in the public domain NCI Dictionary of Cancer Terms</ref>  When combined with [[radiation therapy]], it can be called '''thermoradiotherapy'''.
-Hyperthermia is only useful for certain kinds of cancer, and is not in widespread use.  Hyperthermia is most effective when used alongside conventional therapies, so it is normally used as an [[adjuvant]] therapy.  The most effective uses are currently being studied.
-==Mechanism==
+==Definition==
+Hyperthermia is defined as supra-normal body temperatures. There is no consensus as to what is the safest or most effective target temperature for the whole body. During treatment the body temperature reaches a level between {{convert|39.5|and|40.5|°C}}.<ref name=Wolf2008p31-3>{{cite book |last=Wolf |first=Peter |title=Innovations in biological cancer therapy, a guide for patients and their relatives |year=2008 |publisher=Naturasanitas |location=Hannover |isbn=978-3-9812416-1-7 |pages=31–3}}</ref> However, other researchers define hyperthermia between {{convert|41.8|–|42|°C}} (Europe, USA) to near {{convert|43|–|44|°C}} (Japan, Russia).<ref>{{cite book |doi=10.1007/978-0-387-33441-7|title=Hyperthermia in Cancer Treatment: A Primer|series=Medical Intelligence Unit|year=2006|isbn=978-0-387-33440-0|last1=Baronzio|first1=Gian Franco|last2=Hager|first2=E. Dieter}}{{page needed|date=April 2014}}</ref>
-Hyperthermia may kill or weaken [[tumor]] cells, and is controlled to limit effects on healthy cells. Tumor cells, with a disorganized and compact [[Blood vessel|vascular]] structure, have difficulty dissipating heat. Hyperthermia may therefore cause cancerous cells to undergo [[apoptosis]] in direct response to applied heat, while healthy tissues can more easily maintain a normal temperature.
+===Types===
-Even if the cancerous cells do not die outright, they may become more susceptible to ionizing [[radiation therapy]] or to certain [[chemotherapy]] drugs, which may allow such therapy to be given in smaller doses.
+[[File:Hyperthemia machine.jpg|thumb|Patient is undergoing local hyperthermia treatment for head and neck cancer.]]
+* ''Local hyperthermia'' heats a very small area and is typically used for cancers near or on the skin or near natural openings in the body (e.g., the mouth).<ref name="Mallory2015">{{cite journal| author=Mallory M, Gogineni E, Jones GC, Greer L, Simone CB 2nd|title=Therapeutic hyperthermia: The old, the new, and the upcoming|journal=Crit Rev Oncol Hematol|volume=97|issue=15|pages=30018–4|date=August 2015|pmid=26315383|doi=10.1016/j.critrevonc.2015.08.003}}</ref>  In some instances, the goal is to kill the tumor by heating it, without damaging anything else. The heat may be created with microwave, radiofrequency, ultrasound energy or using [[#Magnetic hyperthermia|magnetic hyperthermia]] (also known as magnetic fluid hyperthermia)<ref>{{cite journal|last1=Javidi|first1=Mehrdad|last2=Heydari|first2=Morteza|last3=Attar|first3=Mohammad Mahdi|last4=Haghpanahi|first4=Mohammad|last5=Karimi|first5=Alireza|last6=Navidbakhsh|first6=Mahdi|last7=Amanpour|first7=Saeid|title=Cylindrical agar gel with fluid flow subjected to an alternating magnetic field during hyperthermia|journal=International Journal of Hyperthermia|date=19 December 2014|volume=31|issue=1|pages=33–39|doi=10.3109/02656736.2014.988661|pmid=25523967|s2cid=881157|doi-access=free}}</ref><ref name="cite journal |pmc=4289522">{{cite journal|last1=Javidi|first1=M|last2=Heydari|first2=M|last3=Karimi|first3=A|last4=Haghpanahi|first4=M|last5=Navidbakhsh|first5=M|last6=Razmkon|first6=A|title=Evaluation of the Effects of Injection Velocity and Different Gel Concentrations on Nanoparticles in Hyperthermia Therapy|journal=Journal of Biomedical Physics & Engineering|date=15 December 2014|volume=4|issue=4|pages=151–162|pmc=4289522 |pmid=25599061}}</ref><ref>{{cite journal|last1=HEYDARI|first1=MORTEZA|last2=JAVIDI|first2=MEHRDAD|last3=ATTAR|first3=MOHAMMAD MAHDI|last4=KARIMI|first4=ALIREZA|last5=NAVIDBAKHSH|first5=MAHDI|last6=HAGHPANAHI|first6=MOHAMMAD|last7=AMANPOUR|first7=SAEID|title=Magnetic Fluid Hyperthermia in a Cylindrical Gel Contains Water Flow|journal=[[Journal of Mechanics in Medicine and Biology]]|date=October 2015|volume=15|issue=5|pages=1550088|doi=10.1142/S0219519415500888}}</ref>). Depending on the location of the tumor, the heat may be applied to the surface of the body ''(superficial hyperthermia)'', inside normal body cavities ''(intraluminal hyperthermia)'', or deep in tissue through the use of needles or probes ''(interstitial hyperthermia)''. It should not be confused with [[ablation]] of small tumors, where higher temperatures (>55&nbsp;°C) are applied with an aim to kill the tumor cells.<ref name=NCI>[http://www.cancer.gov/cancertopics/factsheet/Therapy/hyperthermia Information] from the U.S. [[National Cancer Institute]]</ref>
-Intense heating will cause [[denaturation (biochemistry)|denaturation]] and coagulation of [[cell (biology)|cellular]] [[protein]]s, rapidly killing cells within a tumour.  More prolonged moderate heating to temperatures just a few degrees above normal can cause more subtle changes.  A mild heat treatment combined with other stresses can cause cell death by [[apoptosis]].  There are many biochemical consequences to the [[heat shock protein|heat shock response]] within in cell, including slowed cell division and increased sensitivity to ionizing [[radiation therapy]].
+* ''Regional hyperthermia'' heats a larger part of the body, such as an entire organ or limb. Usually, the goal is to weaken cancer cells so that they are more likely to be killed by radiation and chemotherapeutic medications. This may use the same techniques as local hyperthermia treatment, or it may rely on blood [[perfusion]].<ref name="Mallory2015"/>  In blood perfusion, the patient's blood is removed from the body, heated up, and returned to blood vessels that lead directly through the desired body part. Normally, chemotherapy drugs are infused at the same time. One specialized type of this approach is [[continuous hyperthermic peritoneal perfusion]] (CHPP), which is used to treat difficult cancers within the [[peritoneal cavity]] (the abdomen), including primary [[peritoneal mesothelioma]] and stomach cancer. Hot chemotherapy drugs are pumped directly into the peritoneal cavity to kill the cancer cells.<ref name=NCI />
+* ''Whole-body hyperthermia'' heats the entire body to temperatures of about {{convert|39|to|43|°C}}, with some advocating even higher temperatures. It is typically used to treat [[metastatic cancer]] (cancer that spread to many parts of the body).<ref name="Mallory2015"/>  Techniques include infrared hyperthermia domes which include the whole body or the body apart from the head, putting the patient in a very hot room/chamber, or wrapping the patient in hot, wet blankets or a water tubing suit.<ref name="Mallory2015"/><ref name=NCI />
+==Treatment==
-Hyperthermia can kill cells directly, but its more important use is in combination with other treatments for cancer.<ref name="isbn0-7817-6369-X" />  Hyperthermia increases blood flow to the warmed area, perhaps doubling perfusion in tumors, while increasing perfusion in normal tissue by ten times or even more.<ref name="isbn0-7817-6369-X" />  This enhances the delivery of medications.  Hyperthermia also increases oxygen delivery to the area, which may make radiation more likely to damage and kill cells, as well as preventing cells from repairing the damage induced during the radiation session.<ref name="isbn0-7407-6857-3"/>
+Research has shown that hyperthermia, when administered with other treatments, can shrink tumours and may assist other treatments kill cancer cells.<ref name="NIH2017" />
+Localized hyperthermia treatment is a well-established cancer treatment method with a simple basic principle: If a temperature elevation to {{convert|40|°C|°F|abbr=on}} can be maintained for one hour within a cancer tumor, the cancer cells will be destroyed.<ref>{{Cite web|url=https://www.cancertutor.com/hyperthermia/|title=Hyperthermia Cancer Treatment - CancerTutor.com|date=2016-12-06|website=Cancer Tutor|language=en-US|access-date=2019-04-25}}</ref>
-Cancerous cells are not inherently more susceptible to the effects of heat.<ref name="isbn0-7817-6369-X" />  When compared in ''in vitro'' studies, normal cells and cancer cells show the same responses to heat.  However, the vascular disorganzation of a solid tumor results in an unfavorable microenvironment inside tumors.  Consequently, the tumor cells are already stressed by low oxygen, higher than normal acid concentrations, and insufficient nutrients, and are thus significantly less able to tolerate the added stress of heat than a healthy cell in normal tissue.<ref name="isbn0-7817-6369-X" />
+The schedule for treatments has varied between study centers. After being heated, cells develop resistance to heat, which persists for about three days and reduces the likelihood that they will die from direct effects of the heat.<ref name=PerezBrady08 /> Some even suggest maximum treatment schedule of twice a week.<ref name=Dollinger08/> Japanese researchers treated people with "cycles" up to four times a week apart.<ref>{{cite journal  |vauthors=Maeta M, Koga S, Wada J, etal |title=Clinical evaluation of total-body hyperthermia combined with anticancer chemotherapy for far-advanced miscellaneous cancer in Japan |journal=Cancer |volume=59 |issue=6 |pages=1101–6 |date=March 1987  |pmid=3815283 |doi=10.1002/1097-0142(19870315)59:6<1101::AID-CNCR2820590610>3.0.CO;2-G|doi-access=free }}</ref> Radiosensitivity may be achieved with hyperthermia, and using heat with every radiation treatment may drive the treatment schedule.<ref name=PerezBrady08 /> Moderate hyperthermia treatments usually maintain the temperature for approximately an hour.<ref name=Dollinger08/>
-Mild hyperthermia, which provides temperatures equal to that of a naturally high [[fever]], may stimulate natural immunological attacks against the tumor, as part of a natural physiological response called [[thermotolerance]].<ref name="isbn0-7817-6369-X" />
+Before the advent of modern antiretroviral therapy extracorporeal whole body hyperthermia was tried as a treatment for HIV/AIDS, with some positive outcomes.<ref>{{Cite journal |last1=Ash |first1=S. R. |last2=Steinhart |first2=C. R. |last3=Curfman |first3=M. F. |last4=Gingrich |first4=C. H. |last5=Sapir |first5=D. A. |last6=Ash |first6=E. L. |last7=Fausset |first7=J. M. |last8=Yatvin |first8=M. B. |date=September 1997 |title=Extracorporeal whole body hyperthermia treatments for HIV infection and AIDS |journal=ASAIO Journal (American Society for Artificial Internal Organs: 1992) |volume=43 |issue=5 |pages=M830–838 |doi=10.1097/00002480-199703000-00123 |issn=1058-2916 |pmid=9360163|doi-access=free }}</ref>
-Moderate hyperthermia, which heats cells in the range of 40 to 42 °C, damages cells directly, in addition to making the cells radiosensitive and increasing the pore size to improve delivery of large-molecule chemotherapeutic and immunotherapeutic agents (molecular weight greater than 1,000 [[atomic mass unit|Daltons]]), such as [[monoclonal antibodies]] and liposome-encapsulated drugs.<ref name="isbn0-7817-6369-X" />  Cellular uptake of certain small molecule drugs is also increased.<ref name="isbn0-7817-6369-X" />  Most local and regional cancer treatments are in this temperature range.
+==Adverse effects==
-Very high temperatures, above 50 C (122 F), are used for [[ablation]] (direct destruction) of some tumors.<ref name="isbn0-7407-6857-3"/>  This generally involves inserting a metal tube directly into the tumor, and heating the tip until the tissue next to the tube has been killed.
+External application of heat may cause surface burns.<ref name=Dollinger08/> Tissue damage to a target organ with a regional treatment will vary with what tissue is heated (e.g. brain treated directly may injure the brain, lung tissue treated directly may cause pulmonary problems).  Whole body hyperthermia can cause swelling, blood clots, and bleeding.<ref name=PerezBrady08 />  Systemic shock, may result, but is highly dependent upon method difference in achieving it. It may also cause cardiovascular toxicity.<ref name=NCI /> All techniques are often combined with radiation or chemotherapy, muddying how much toxicity is the result of those treatments versus the temperature elevation achieved.
-==Heat sources==
+==Technique==
-There are many techniques by which heat may be delivered. Some of the most common involve the use of focused [[ultrasound]] (FUS or [[HIFU]]), [[infrared]] sauna, [[microwave]] heating, [[induction heating]], [[magnetic hyperthermia]], infusion of warmed liquids, or direct application of heat such as through sitting in a hot room or wrapping a patient in hot blankets.
-==Types==
+===Heat sources===
+There are many techniques by which heat may be delivered. Some of the most common involve the use of focused [[ultrasound]] (FUS or [[HIFU]]), [[RF]] sources, [[infrared sauna]], [[Microwave thermotherapy|microwave heating]], [[induction heating]], [[magnetic hyperthermia]], infusion of warmed liquids, or direct application of heat such as through sitting in a hot room or wrapping a patient in hot blankets.
-* ''Local hyperthermia'' heats a very small area, usually the tumor itself.  In some instances, the goal is to kill the tumor by "cooking" it, without damaging anything else.  The heat may be created with microwave, radiofrequency, ultrasound energy or using [[magnetic hyperthermia]]. Depending on the location of the tumor, the heat may be applied to the surface of the body, inside normal body cavities, or deep in tissue through the use of needles or probes.  One relatively common type is [[radiofrequency ablation]] of small tumors.<ref name=NCI>[http://www.cancer.gov/cancertopics/factsheet/Therapy/hyperthermia Information] from the U.S. [[National Cancer Institute]]  </ref>  This is easiest to achieve when the tumor is on a superficial part of the body, which is called ''superficial hyperthermia'', or when needles or probes are inserted directly into the tumor, which is called ''interstitial hyperthermia''.
-* ''Regional hyperthermia'' heats a larger part of the body, such as an entire organ or limb.  Usually, the goal is to weaken cancer cells so that they are more likely to be killed by radiation and chemotherapeutic medications.  This may use the same techniques as local hyperthermia treatment, or it may rely on blood [[perfusion]].  In blood perfusion, the patient's blood is removed from the body, heated up, and returned to blood vessels that lead directly through the desired body part.  Normally, chemotherapy drugs are infused at the same time.  One specialized type of this approach is [[continuous hyperthermic peritoneal perfusion]] (CHPP), which is used to treat difficult cancers within the [[peritoneal cavity]] (the abdomen), including primary [[peritoneal mesothelioma]] and stomach cancer.  Hot chemotherapy drugs are pumped directly into the peritoneal cavity to kill the cancer cells.<ref name=NCI />
-* ''Whole-body hyperthermia'' heats the entire body.  It is typically used to treat [[metastatic cancer]] (cancer that spread to many parts of the body).  Techniques include putting the patient in a very hot room, or wrapping the patient in hot, wet blankets.<ref name=NCI />
+===Controlling temperature===
-==Treatment==
+One of the challenges in thermal therapy is delivering the appropriate amount of heat to the correct part of the patient's body. For this technique to be effective, the temperatures must be high enough, and the temperatures must be sustained long enough, to damage or kill the cancer cells. However, if the temperatures are too high, or if they are kept elevated for too long, then serious side effects, including death, can result. The smaller the place that is heated, and the shorter the treatment time, the lower the side effects. Conversely, tumor treated too slowly or at too low a temperature will not achieve therapeutic goals. The human body is a collection of tissues with differing heat capacities, all connected by a dynamic circulatory system with variable relationship to skin or lung surfaces designed to shed heat energy. All methods of inducing higher temperature in the body are countered by the [[Thermoregulation|thermo-regulatory mechanisms of the body]]. The body as a whole relies mostly on simple radiation of energy to the surrounding air from the skin (50% of heat lost this way) which is augmented by convection (blood shunting) and vaporization through sweat and respiration. Regional methods of heating may be more or less difficult based on the anatomic relationships, and tissue components of the particular body part being treated. Measuring temperatures in various parts of the body may be very difficult, and temperatures may locally vary even within a region of the body.
-Moderate hyperthermia treatments usually maintain the temperature for about an hour or so.<ref name="isbn0-7407-6857-3"/>
+To minimize damage to healthy tissue and other adverse effects, attempts are made to monitor temperatures.<ref name=NCI />  The goal is to keep local temperatures in tumor bearing tissue under {{convert|44|°C}} to avoid damage to surrounding tissues. These temperatures have been derived from cell culture and animal studies. The body keeps itself [[normal human body temperature]], near {{convert|37.6|°C}}. Unless a needle probe can be placed with accuracy in every tumor site amenable to measurement, there is an inherent technical difficulty in how to actually reach whatever a treating center defines as an "adequate" thermal dose. Since there is also no consensus as to what parts of the body need to be monitored (common clinically measured sites are ear drums, oral, skin, rectal, bladder, esophagus, blood probes, or even tissue needles). Clinicians have advocated various combinations for these measurements. These issues complicate the ability of comparing different studies and coming up with a definition of exactly what a thermal dose actually should be for tumor, and what dose is toxic to what tissues in human beings. Clinicians may be able to apply advanced imaging techniques, instead of probes, to monitor heat treatments in real time; heat-induced changes in [[biological tissue|tissue]] are sometimes perceptible using these imaging instruments.
-The schedule for treatments depends on the effect desired.  After being heated, cells develop resistance to heat, which persists for about three days and reduces the likelihood that they will die from direct cytotoxic effects of the heat.<ref name="isbn0-7817-6369-X" />  This suggests a maximum treatment schedule of about twice a week.<ref name="isbn0-7407-6857-3"/>  However, if the desired goal is increased radiosensitivity in a poorly oxygenated tumor, rather than directly killing the cells, then application of heat with every radiation treatment is acceptable.<ref name="isbn0-7817-6369-X" />
+There is the further difficulty inherent in the devices delivering energy. Regional devices may not uniformly heat a target area, even without taking into account compensatory mechanisms of the body. A great deal of current research focuses on how one might precisely position heat-delivery devices (catheters, microwave and ultrasound applicators, etc.) using ultrasound or [[magnetic resonance imaging]], as well as developing new types of nanoparticles that can more evenly distribute heat within a target tissue.
-==Controlling temperatures==
-One of the challenges in thermal therapy is delivering the appropriate amount of heat to the correct part of the patient's body.  For this technique to be effective, the temperatures must be high enough, and the temperatures must by sustained long enough, to damage or kill the cancer cells.  However, if the temperatures are too high, or if they are kept elevated for too long, then serious side effects, including death, can result.  The smaller the place that is heated, and the shorter the treatment time, the lower the side effects.
+Among hyperthermia therapy methods, [[magnetic hyperthermia]] is well known as the one that produce a controllable heat inside the body. Because of using magnetic fluid in this method, temperature distribution can be controlled by the velocity, size of [[nanoparticles]] and distribution of them inside the body.<ref name="cite journal |pmc=4289522"/> These materials upon application of external, alternating magnetic field convert electromagnetic energy into thermal energy and induce temperature rises.<ref>{{Cite journal|last1=John|first1=Łukasz|last2=Janeta|first2=Mateusz|last3=Szafert|first3=Sławomir|title=Designing of macroporous magnetic bioscaffold based on functionalized methacrylate network covered by hydroxyapatites and doped with nano-MgFe 2 O 4 for potential cancer hyperthermia therapy|journal=Materials Science and Engineering: C|volume=78|pages=901–911|doi=10.1016/j.msec.2017.04.133|pmid=28576066|year=2017}}</ref>
-To minimize damage to healthy tissue and other adverse effects, physicians carefully monitor the temperature of the affected area.<ref name=NCI />  The goal is to keep local temperatures under 44 °C (111 °F) to avoid damage to surrounding tissues, and the whole body temperatures under 42 °C (108 °F), which is the upper limit compatible with life.  These temperatures compare to the [[normal human body temperature]], taken internally, of about 37.6 °C (99.6 °F).
+==Mechanism==
-A great deal of current research focuses on precisely positioning heat-delivery devices (catheters, microwave and ultrasound applicators, etc.) using ultrasound or [[magnetic resonance imaging]], as well as developing new types of nanoparticles that make them particularly efficient absorbers while offering little or no concerns about toxicity to other tissues. Clinicians also hope to use advanced imaging techniques to monitor heat treatments in real time; heat-induced changes in [[biological tissue|tissue]] are sometimes perceptible using these imaging instruments.
+Hyperthermia can kill cells directly, but its more important use is in combination with other treatments for cancer.<ref name=PerezBrady08>{{cite book |author1=Carolyn Freeman |author2=Halperin, Edward C. |author3=Brady, Luther W. |author4=David E. Wazer |title=Perez and Brady's Principles and Practice of Radiation Oncology |publisher=Wolters Kluwer Health/Lippincott Williams & Wilkins |location=Philadelphia |year=2008 |pages=637–644 <!-- More stuff in this great chapter; this is as far as I've read --> |isbn=978-0-7817-6369-1 }}</ref>  Hyperthermia increases blood flow to the warmed area, perhaps doubling perfusion in tumors, while increasing perfusion in normal tissue by ten times or even more.<ref name=PerezBrady08 />  This enhances the delivery of medications. Hyperthermia also increases oxygen delivery to the area, which may make radiation more likely to damage and kill cells, as well as preventing cells from repairing the damage induced during the radiation session.<ref name=Dollinger08/>
-==Adverse effects==
-External application of heat may cause blisters, which generally heal quickly, and burns, which do not.<ref name="isbn0-7407-6857-3"/>  All techniques may result in pain or fatigue.  Perfusion and moderate or high levels of hyperthermia can cause swelling, blood clots, and bleeding.<ref name="isbn0-7817-6369-X" />  Whole-body hyperthermia, which is the riskiest treatment, usually results in diarrhea, nausea, vomiting, fatigue, and other symptoms of [[sunstroke]]; it may also cause cardiovascular problems.<ref name=NCI />
+Cancerous cells are not inherently more susceptible to the effects of heat.<ref name=PerezBrady08 />  When compared in ''in vitro'' studies, normal cells and cancer cells show the same responses to heat. However, the vascular disorganization of a solid tumor results in an unfavorable microenvironment inside tumors. Consequently, the tumor cells are already stressed by low oxygen, higher than normal acid concentrations, and insufficient nutrients, and are thus significantly less able to tolerate the added stress of heat than a healthy cell in normal tissue.<ref name=PerezBrady08 />
-==Effectiveness==
-[[Monotherapy|By itself]], hyperthermia is generally ineffective, with only small numbers of patients receiving lasting benefit.<ref name="isbn0-7407-6857-3"/>  However, it may significantly increase the effectiveness of other treatments.<ref name="isbn0-7407-6857-3"/>
+Mild hyperthermia, which provides temperatures equal to that of a naturally high [[fever]], may stimulate natural immunological attacks against the tumor. However, it is also induces a natural physiological response called [[thermotolerance]], which tends to protect the treated tumor.<ref name=PerezBrady08 />
-When combined with radiation, hyperthermia is particularly effective at increasing the damage to acidic, poorly oxygenated parts of a tumor,<ref name="isbn0-7817-6369-X" /> and cells that are preparing to divide.<ref name="isbn0-7407-6857-3"/>  Hyperthermia treatment is most effective when provided at the same time, or within an hour, of the radiation.<ref name="isbn0-7407-6857-3"/>
+Moderate hyperthermia, which heats cells in the range of {{convert|40|to|42|°C}}, damages cells directly, in addition to making the cells radiosensitive and increasing the pore size to improve delivery of large-molecule chemotherapeutic and immunotherapeutic agents (molecular weight greater than 1,000 [[Dalton (unit)|daltons]]), such as [[monoclonal antibodies]] and liposome-encapsulated drugs.<ref name=PerezBrady08 />  Cellular uptake of certain small molecule drugs is also increased.<ref name=PerezBrady08 />
-Whole body hyperthermia cannot safely reach the temperatures necessary to improve the effectiveness of radiation, and thus is not used with radiation,<ref name="isbn0-7817-6369-X">{{cite book |author=Carolyn Freeman; Halperin, Edward C.; Brady, Luther W.; David E. Wazer |title=Perez and Brady's Principles and practice of radiation oncology |publisher=Wolters Kluwer Health/Lippincott Williams & Wilkins |location=Philadelphia |year=2008 |pages=637-644 <!-- More stuff in this great chapter; this is as far as I've read --> |isbn=0-7817-6369-X |oclc= }}</ref> but itmay be useful for chemotherapy and immunotherapy.<ref name="isbn0-7407-6857-3"/>
+Very high temperatures, above {{convert|50|°C}}, are used for [[ablation]] (direct destruction) of some tumors.<ref name=Dollinger08/>  This generally involves inserting a metal tube directly into the tumor, and heating the tip until the tissue next to the tube has been killed.
 ==History==
-The application of heat to treat certain conditions, including possible tumors, has a long history.  Ancient Greeks, Romans, and Egyptians used heat to treat breast masses; this is still a recommended self-care treatment for [[breast engorgement]].  Medical practitioners in ancient India used regional and whole-body hyperthermia as treatments.<ref name="isbn0-387-33440-8">{{cite book |author=Gian F. Baronzio |title=Hyperthermia In Cancer Treatment: A Primer (Medical Intelligence Unit) |publisher=Springer |location=Berlin |year=2006 |pages= Introduction (no page numbers) |isbn=0-387-33440-8 }}</ref>
+The application of heat to treat certain conditions, including possible tumors, has a long history. Ancient Greeks, Romans, and Egyptians used heat to treat breast masses; this is still a recommended self-care treatment for [[breast engorgement]]. Medical practitioners in ancient India used regional and whole-body hyperthermia as treatments.<ref name="isbn0-387-33440-8">{{cite book |author=Gian F. Baronzio |title=Hyperthermia In Cancer Treatment: A Primer |series=Medical Intelligence Unit |publisher=Springer |location=Berlin |year=2006 |chapter=Introduction |isbn=0-387-33440-8}}{{page needed|date=April 2014}}</ref>
-During the 19th century, tumor shrinkage after a high fever due to infection had been reported a small number of cases.<ref name="isbn0-7407-6857-3">{{cite book |author=Dollinger, Malin |title=Everyone's Guide to Cancer Therapy; Revised 5th Edition: How Cancer Is Diagnosed, Treated, and Managed Day to Day |publisher=Andrews McMeel Publishing |location=Kansas City, MO |year=2008 |pages= 98-100 |isbn=0-7407-6857-3 |oclc= |doi= }}</ref>  Typically, the reports documented the rare regression of a soft-tissue sarcoma after [[erysipelas]] (an acute streptococcus bacterial infection of the skin; a different presentation of an infection by [[Necrotizing fasciitis|"flesh-eating bacteria"]]) was noted.  Efforts to deliberately recreate this effect led to the development of [[Coley's toxin]].<ref name="isbn0-387-33440-8" />  A sustained high fever after induction of illness was considered critical to treatment success.<ref name="isbn0-387-33440-8" />  This treatment is generally considered both less effective than modern treatments and, when it includes live bacteria, inappropriately dangerous.
+During the 19th century, tumor shrinkage after a high fever due to infection had been reported in a small number of cases.<ref name=Dollinger08>{{cite book |author=Dollinger, Malin |title=Everyone's Guide to Cancer Therapy; Revised 5th Edition: How Cancer Is Diagnosed, Treated, and Managed Day to Day |publisher=Andrews McMeel Publishing |location=Kansas City, MO |year=2008 |pages=[https://archive.org/details/everyonesguideto00koan/page/98 98–100] |isbn=978-0-7407-6857-6 |url-access=registration |url=https://archive.org/details/everyonesguideto00koan/page/98 }}</ref>  Typically, the reports documented the rare regression of a [[soft tissue sarcoma]] after [[erysipelas]] (an acute streptococcus bacterial infection of the skin; a different presentation of an infection by [[Necrotizing fasciitis|"flesh-eating bacteria"]]) was noted. Efforts to deliberately recreate this effect led to the development of [[Coley's toxin]].<ref name="isbn0-387-33440-8" />  A sustained high fever after induction of illness was considered critical to treatment success.<ref name="isbn0-387-33440-8" />  This treatment is generally considered{{by whom|date=December 2020}} both less effective than modern treatments and, when it includes live bacteria, inappropriately dangerous.
+Around the same period Westermark used localized hyperthermia to produce tumor regression in patients.<ref>{{cite journal |author=Westermark F |title=Uber die Behandlung des Ulcerirended Cervixcarcinoms. Mittel Konstanter Warme |journal=ZBL Gynakol |volume=22 |page=1335 |year=1898 }}</ref>  Encouraging results were also reported by Warren when he treated patients with advanced cancer of various types with a combination of heat, induced with pyrogenic substance, and x-ray therapy. Out of 32 patients, 29 improved for 1 to 6 months.<ref>{{cite journal |author=Warren SL |title=Preliminary study of the effect of artificial fever upon hopeless tumor cases |journal=Am J Roentgenol |volume=33 |page=75 |year=1935 }}</ref>
-Properly controlled [[clinical trial]]s on deliberately induced hyperthermia began in the 1970s.<ref name="isbn0-7407-6857-3"/>
+Properly controlled [[clinical trial]]s on deliberately induced hyperthermia began in the 1970s.<ref name=Dollinger08/>
 ==Future directions==
-Hyperthermia may be combined with gene therapy, particularly using the [[heat shock protein]] 70 promoter.<ref name="isbn0-7817-6369-X" />
+Hyperthermia may be combined with gene therapy, particularly using the [[heat shock protein]] 70 promoter.<ref name=PerezBrady08 />
+Two major technological challenges make hyperthermia therapy complicated: the ability to achieve a uniform temperature in a tumor, and the ability to precisely monitor the temperatures of both the tumor and the surrounding tissue.<ref name=PerezBrady08 />  Advances in devices to deliver uniform levels of the precise amount of heat desired, and devices to measure the total dose of heat received, are hoped for.<ref name=PerezBrady08 />
+In locally advanced adenocarcinoma of middle and lower rectum, regional hyperthermia added to chemoradiotherapy achieved good results in terms of rate of sphincter sparing surgery.<ref>{{cite journal  |vauthors=Maluta S, Romano M, Dall'oglio S, etal |title=Regional hyperthermia added to intensified preoperative chemo-radiation in locally advanced adenocarcinoma of middle and lower rectum |journal=International Journal of Hyperthermia |volume=26 |issue=2 |pages=108–17 |year=2010 |pmid=20146565 |doi=10.3109/02656730903333958|s2cid=33333237 |doi-access=free }}</ref>
+=== Magnetic hyperthermia ===
+Magnetic hyperthermia is an experimental treatment for cancer, based on the fact that [[magnetic nanoparticles]] can transform electromagnetic energy from an external high-frequency field to heat.<ref name=":0">{{Cite journal|last1=Périgo|first1=E. A.|last2=Hemery|first2=G.|last3=Sandre|first3=O.|last4=Ortega|first4=D.|last5=Garaio|first5=E.|last6=Plazaola|first6=F.|last7=Teran|first7=F. J.|date=2015-11-30|title=Fundamentals and advances in magnetic hyperthermia|url=https://aip.scitation.org/doi/10.1063/1.4935688|journal=Applied Physics Reviews|volume=2|issue=4|pages=041302|doi=10.1063/1.4935688|arxiv=1510.06383|bibcode=2015ApPRv...2d1302P|s2cid=53355982}}</ref> This is due to the [[magnetic hysteresis]] of the material when it is subjected to an alternating magnetic field.<ref>{{Cite journal|last1=Midura|first1=M. |last2=Wróblewski|first2=P.|last3=Wanta|first3=D. |last4=Kryszyn|first4=J.|last5=Smolik|first5=W. T. |last6=Domański|first6=G. |last7=Wieteska|first7=M. |last8=Obrębski|first8=W. |last9=Piątkowska-Janko|first9=E. |last10=Bogorodzki|first10=P. |date=2022-11-17|title=The Hybrid System for the Magnetic Characterization of Superparamagnetic Nanoparticles|journal=Sensors|volume=22|issue=22|pages=8879|doi=10.3390/s22228879|pmid=36433476 |pmc=9695308 |bibcode=2022Senso..22.8879M |doi-access=free}}</ref> The area enclosed by the hysteresis loop represents losses, which are commonly dissipated as thermal energy.<ref name=":0" /> In many industrial applications this heat is undesirable, however it is the basis for magnetic hyperthermia treatment.{{citation needed|date=October 2019}}
+As a result, if magnetic nanoparticles are put inside a tumor and the whole patient is placed in an alternating magnetic field, the temperature of the tumor will rise. This elevation of temperature may enhance tumor oxygenation and radio- and chemosensitivity, hopefully shrinking tumors.<ref>{{cite journal|last1=Kumar|first1=CS|last2=Mohammad|first2=F|title=Magnetic nanomaterials for hyperthermia-based therapy and controlled drug delivery.|journal=Advanced Drug Delivery Reviews|date=14 August 2011|volume=63|issue=9|pages=789–808|pmid=21447363|pmc=3138885|doi=10.1016/j.addr.2011.03.008}}</ref> This [[experimental cancer treatment]] has also been investigated for the aid of other ailments, such as bacterial infections.{{citation needed|date=October 2019}}
+Magnetic hyperthermia is defined by [[specific absorption rate]] (SAR) and it is usually expressed in watts per gram of nanoparticles.<ref name="JAP-Carrey">{{cite journal|last1=Carrey|first1=J.|last2=Mehdaoui|first2=B.|last3=Respaud|first3=M.|title=Simple models for dynamic hysteresis loop calculations of magnetic single-domain nanoparticles: Application to magnetic hyperthermia optimization|journal=Journal of Applied Physics|date=15 April 2011|volume=109|issue=8|pages=083921–083921–17|doi=10.1063/1.3551582|bibcode=2011JAP...109h3921C|s2cid=119228529|url=http://aip.scitation.org/doi/pdf/10.1063/1.3617122|arxiv=1007.2009}}</ref>
-Two major technological challenges make hyperthermia therapy complicated:  the ability to achieve a uniform temperature in a tumor, and the ability to precisely monitor the temperatures of both the tumor and the surrounding tissue.<ref name="isbn0-7817-6369-X" />  Advances in devices to deliver uniform levels of the precise amount of heat desired, and devices to measure the total dose of heat received, are hoped for.<ref name="isbn0-7817-6369-X" />
 ==See also==
-* [[Thermotherapy]], use of heat for treating other conditions
+* [[Microwave thermotherapy]], use of microwave heating to treat cancer
 * [[Photothermal Therapy]], use of infrared radiation to treat cancer <!-- Should probably be merged into this article-->
+* [[Thermotherapy]], use of heat for treating other conditions
-* [[Photodynamic therapy]], which uses light but not heat
+* [[Coley's toxins]], a bacteria mixture used to generate fevers as an [[alternative cancer treatment]]
+* [[Tronado machine]], a device that uses microwave radiation to generate hyperthermia for cancer (no evidence of benefit)
+* [[Pyrotherapy]], a method of treating infections by raising the body temperature
 ==References==
@@ Line 75: / Line 105: @@
 == External links ==
-* [http://www.cancer.org/docroot/ETO/content/ETO_5_3X_Heat_Therapy.asp Information] from the [[American Cancer Society]]
+* [https://www.cancer.org/treatment/treatments-and-side-effects/treatment-types/hyperthermia.html Hyperthermia to Treat Cancer] Information from the [[American Cancer Society]]
 * {{eMedicine|med|3070|Transurethral Microwave Thermotherapy of the Prostate (TUMT)}}
+*  [http://psfebus.allenpress.com/eBusSFTM/ Society of Thermal Medicine]
+*  [https://www.esho.info/ European Society of Hyperthermic Oncology]
+[[Category:Oncothermia]]
-[[Category:Cancer treatments]]
-[[cs:Mikrovlnná termoterapie]]
-[[fa:گرماافزایی]]