Hyperthermia’s history starts from the ancient times when it was described as a cancer treatment in the ancient Indian epic, the Ramayana. Hyperthermia has been mentioned by the great Greek physician, Hippocrates (400 B.C.), Cornelius Celsus Aulus, Roman encyclopedic doctor (25 BC - 50 AD) and by Gallen (200 A.D.), Roman physician and philosopher (1). The description by Hippocrates that “if a tumor cannot be cut, it should burned. If it cannot be burned, then it is incurable” actually holds relevant to many types of cancers even today (1). 

In the middle ages, instruments were designed and shaped for application of heat to kill tumours or cauterize bleeding.  Hyperthermia in the middle ages have been described by Leonidas - Nicolaus Leonicenus (1428- 1524), a professor of medicine in Padua (2). After the Renaissance period, there were reports that patients with smallpox, influenza, tuberculosis and malaria experienced spontaneous tumor regression. However in 1537, Ambroise Paré, military surgeon described the adverse consequences of medical treatment by cauterization which led to declining interest in Hyperthermia. In 1779, the effect of malaria on malignant tumours was described by Dr Kizowitz (2).

In modern times, the German physician Busch’s observation in 1887 that erysipelas resulted in disappearance of sarcoma on the face in a patient rekindled the interest in Hyperthermia. An American doctor W.B. Colley used bacterial toxin as to artificially create fever thereby producing heat to treat tumours. Westermark in 1898 used circulating high temperature water for the treatment of an inoperable cancer of uterine cervix with good results.  After the advent of electricity, electric current started to be used for delivering heat to the diseased tissues and it was termed galvanocautery.  John Byrne (1825 – 1902) invented a special liquid storage battery to supply electric current to cauterize pathological changes of the uterus and the results of his twenty year study on the effects of treatment of the uterus and cervix tumors in 367 patients were complied in a text in 1889. Enrico Bottini in 1874 invented a device for firing prostate cancer cauterization named as "cauterio termogalvanico" (2). Then high frequency currents using electromagnetism were employed to induce heat. Despite sporadic reports of hyperthermia being used for cancer treatment was doing rounds for several ages, the lack of advanced methods to apply heat and measure temperature accurately were not available leading to the mixed results in early clinical applications of hyperthermia for cancer treatment (2).

After the World War II, as radiotherapy gained attention for treatment of tumours, interest in hyperthermia began to decline further but there were still research going on hyperthermia. The growing consensus in the 1970s that heat increases radiation damage to cells in vitro led to the First International Symposium on heat and radiation to treat cancer in Washington in 1975 but the symposium had only 70 attendees. However the 5th symposium held in Japan in 1988 had more than 800 participants.

A hyperthermia group was formed in the US in 1981 and an Institute was established in Europe in 1983. In Japan, hyperthermia research started in 1978 with the establishment of the Japanese Society of Hyperthermia Oncology in 1984. The research in identification of the most appropriate heating devices for hyperthermia first saw the advent of the microwave heating techniques and ultrasound techniques for hyperthermia. Early microwave devices had limitations like under heating problems and the longer wavelength at the frequencies at which these devices operate made it difficult to focus on tumours (3). The disadvantages with the use of ultrasound are bone heating, large reflection in bone-tissue interfaces, high impedance mismatch between air and soft tissues, unsuitability for lung and abdominal cancers and requirement of coupling (4).

It was then that intensive research was undertaken to design a device with ability to heat both superficial and deep tissue and the result of these intensive researches was the development of Thermotron- RF8 capacitive heating device which uses radiofrequency waves for inducing hyperthermia. Seven Clinical trials were undertaken to arrive at continuous improvements in the Thermotron RF 8. Thermotron RF 8 was approved by the Ministry of Health, Labour and Welfare of Japan as a cancer treatment apparatus in 1984. A seven institution trial in 1990 on the Thermotron RF 8 hyperthermia treatment given to 177 patients with deep-seated tumors in combination with radiation therapy alone (96 patients) or with radiochemotherapy (81 patients) indicated that hyperthermia was one of the most effective treatment techniques for advanced or inoperable cases and that response rates and symptomatic improvement were perceived to be higher than expected for historical controls treated with radiation therapy or chemotherapy alone (5, 6). The Thermotron RF 8 is now being used worldwide as a clinical hyperthermia system.

References:

Glazer ES, Curley SA. The ongoing history of thermal therapy for cancer. Surg Oncol Clin N Am. 2011 Apr;20(2):229-35, vii. doi: 10.1016/j.soc.2010.11.001. Epub 2010 Dec 13. Piotr GAS. Essential Facts on the History of Hyperthermia and their Connections with Electromedicine. PRZEGLĄD ELEKTROTECHNICZNY (Electrical Review), ISSN 0033-2097, R. 87 NR 12b/2011 Riadh Habash. Bioeffects and Therapeutic Applications of Electromagnetic Energy. 1st Edition. ISBN-13: 978-1420062847 Cheung AY, Neyzari A. Deep local hyperthermia for cancer therapy: external electromagnetic and ultrasound techniques. Cancer Res. 1984 Oct;44(10 Suppl):4736s-4744s. Holland-Frei Cancer Medicine. 5th edition. Bast RC Jr, Kufe DW, Pollock RE, et al., editors. Hamilton (ON): BC Decker; 2000. Kakehi M, Ueda K, Mukojima T, Hiraoka M, Seto O, Akanuma A, Nakatsugawa S. Multi-institutional clinical studies on hyperthermia combined with radiotherapy or chemotherapy in advanced cancer of deep-seated organs. Int J Hyperthermia. 1990;6:719–740