**2.1 Clinical applications of microwave hyperthermia**

In Prague, the clinical applications of microwave hyperthermia for cancer treatment started in 1981, in cooperation with the Medical Faculty (the Charles University in Prague), the Radiotherapy Institute in Prague, and the Dept. of EM Field (the Czech Technical University in Prague). Since then, microwave hyperthermia has been clinically applied to more than 1000 cancer patients. Mostly added to radiotherapy (RT), a clinical study has been approved as a significantly positive contribution to RT treatment. Recently, a combination of hyperthermia added to proton therapy has been clinically applied in Prague.

Treatment of malignant tumors comprises several techniques usually. In some cases, tumors can be resected by surgery. Radiotherapy and/or chemotherapy can be applied when surgery is not possible or as part of a multidisciplinary approach. A less widely known treatment modality is hyperthermia. It is a therapeutic application of heat in which tumor temperatures are elevated in the range of 41–45°C. The heating of tumor tissue has a cell killing (cytotoxic) effect. However, the cytotoxic effect is small at temperatures below 45°C. Therefore, hyperthermia is always clinically combined with either radiotherapy or chemotherapy. The application of hyperthermia has been proven to increase the therapeutic effect of both radiotherapy and chemotherapy.

The effect of hyperthermia is strongly dependent on the achieved tumor temperatures and heating time. Preclinical research has shown that the cell-killing effect doubles every centigrade, e.g., 1 hour at 42°C is equivalent to half an hour at 43°C. Hypoxic tumors, i.e., tumors with a low level of oxygen, are more resistant to ionizing radiation than well-oxygenated tumors, while hyperthermia is particularly effective in hypoxic tumors.

Large solid tumors often contain hypoxic areas due to heterogeneous vascularization, making hyperthermia a useful addition to radiotherapy. The complementary effect of hyperthermia and radiotherapy is also because cells in the S-phase of the cell cycle are more sensitive to hyperthermia than the G1-phase, whereas cells are more resistant to radiotherapy in the S-phase.

Repair of DNA damage caused by radiotherapy is inhibited by hyperthermia. Hyperthermia also induces radiosensitization and chemosensitization. Furthermore, blood flow increases during hyperthermia improving tumor oxygenation and probably enhancing radiosensitivity. The increased blood flow also improves the uptake of cytostatics in tumor cells. Thus, the increased blood flow during hyperthermia is favorable for improving radiotherapy and chemotherapy effectiveness.

In clinical practice, we need to increase the temperature in a more or less circumscribed body region with tumor load. Treated volume ranges from a few cubic centimeters in case of thermoablation in lesions up to heating the whole body. Because of this, we need different types of applicators for each of the below-mentioned special cases. Thus, we can speak about different clinical modes of microwave hyperthermia.

First of all, we would like to offer an overview of the technical equipment needed for clinical applications of microwave thermotherapy in this chapter. Further, the main basic principles of EM field behavior inside the living biological system, selected from the point of view of physics related to microwave thermotherapy, will be mentioned. Moreover, we will provide the reader with references in literature, where detailed information on both physical and technical aspects of microwave thermotherapy (especially microwave hyperthermia) can be found.

#### **2.2 Classification of clinical modes of microwave thermotherapy**

According to ESHO guidelines following classification of different clinical modes of microwave hyperthermia (or thermotherapy in general) can be made:


of these indications were validated in prospective studies. Basic physical and technical descriptions will be given in the following text.

