1.Concept of tumor thermotherapy Tumor thermotherapy refers to the application of various thermogenic sources to increase the temperature of tumor tissues and/or the whole body to treat malignant tumors by using thermal injury and its secondary effects. Some scholars call it “warm treatment of cancer”, “high heat treatment of cancer”, “heat penetration treatment of cancer” and so on. In terms of heat therapy itself, it is a purely physical treatment. When heating up the body, due to the unsound tissue structure of tumor, the heat dissipation is slower than normal tissue, so the temperature of tumor tissue is 5℃-10℃ higher than normal tissue, and malignant tumor cells are sensitive to high heat, as a result, tumor cells are killed or gradually apoptotic after high heat, while normal tissue is not damaged. The unique advantage of thermotherapy compared with radiotherapy and chemotherapy is that it has no obvious toxic side effects. At the same time, thermotherapy can also enhance the immune ability of the body, increase the efficacy of radiotherapy and chemotherapy, and cooperate with surgery and other means to treat cancer, which can reduce tumor recurrence, improve the quality of survival of tumor patients and prolong the survival period. Randomized studies at home and abroad for decades have confirmed that heat therapy combined with radiotherapy and chemotherapy can increase the local control rate of tumor by one or more times, and most studies have concluded that heat therapy has improved the cure rate and survival of patients with advanced tumors. The origin of thermotherapy for tumors The word thermotherapy originates from the Greek word, meaning hyperthermia or overheating. The history of heat therapy in the West can be traced back to 5,000 years ago, when Egyptian doctors used the heating method to treat breast tumors. Hippocrates, a famous ancient Greek doctor, also used heating therapy to treat tumors. He had a motto: “What cannot be cured by drugs can be treated by surgery, what cannot be cured by surgery can be cured by heat therapy, and what cannot be cured by heat therapy cannot be cured”. Since 1866, some patients with malignant tumors have been reported in the West to have their tumors regressed due to occasional dysentery, severe infection or history of high fever. Since then, scholars have been reporting many cases in which heat combined with other therapies have improved the efficacy of tumors or cured them. Thousands of years ago in China, people have been using medicinal baths, drug fumigation, hot water baths, hot spring baths, moxibustion, sand baths, and fire pots to treat diseases. Ancient Chinese physicians used acupuncture stones and fire to treat diseases, and in doing so created the art of acupuncture. It must be acknowledged that tumor heat therapy has not progressed much further from the ancient fire needles, moxibustion, branding irons, and medicinal baths to the use of whole-body heat therapy in the 19th century using infected tannins. After the 1990s, with the in-depth research on tumor thermotherapy and the rapid development of thermotherapy equipment, tumor thermotherapy has been developed in clinical practice. The tumors involved almost include all kinds of tumors in the whole body except brain tumors. (1) Direct effect of hyperthermia on tumor cells Research shows that hyperthermia can directly kill tumor cells. High heat can inhibit the synthesis of deoxyribonucleic acid, ribonucleic acid and protein, and the inhibition of protein synthesis also inhibits the proliferation of tumor cells and promotes the death of tumor cells; high heat can damage the normal function of cell membrane, change the permeability of cell membrane, cause protein overflow and change the structure of nuclear chromatin, which leads to the death of cancer cells. Because the internal structure of tumor tissues is not sound, the respiration of tumor cells is inhibited during hyperthermia, and the enhanced anaerobic enzymolysis causes the pH to drop, which in turn strengthens the activity of lysosomes, leading to the death of tumor cells by lysis. Since all of these are most sensitive to the S phase of cell proliferation, which can vary tens to hundreds of times compared to other phases. Therefore, the combination of other therapies such as radiation therapy and certain chemotherapeutic agents that have a significant effect on the cell proliferation cycle beyond the S phase has important therapeutic value in clinical practice. (2) Heat therapy increases the effect of radiotherapy Heat therapy and radiotherapy have different action sites in the cell proliferation cycle; heat therapy mainly acts on S-phase cells, while radiotherapy mainly acts on G1 and G2/M-phase cells, which have complementary effects in cell phase; heat therapy can also improve tumor hypoxia and increase the sensitivity of radiotherapy; heat therapy works well on low PH tumor cells, while radiotherapy does the opposite, so heat therapy and radiotherapy have complementary effects in the extracellular environment of tumor cells. Therefore, heat therapy and radiotherapy have complementary effects on the external environment of tumor cells. (3) Heat therapy increases the effect of chemotherapy The combined application of heat therapy and chemotherapy can obviously enhance the efficacy of chemotherapy, and at the same time, for some patients who are resistant to chemotherapy, the combined application with heat therapy can also obtain better results. The possible mechanisms include: heating destabilizes the cells and increases the permeability of the membrane, which is conducive to the penetration and absorption of chemical drugs; heating not only accelerates the uptake of drugs and the response of drugs, but also reduces the repair of DNA damage; heat improves the blood environment around the tumor and causes the expansion of blood vessels inside the tumor and accelerates the blood flow, which increases the concentration of chemotherapeutic drugs inside the tumor and enhances the chemotherapeutic response; heat promotes the binding of anti-cancer Heat can promote the binding of anti-cancer drugs to cancer cell DNA; heat can inhibit the expression of multidrug resistance P-glycoprotein, reduce and reverse the occurrence of drug resistance in tumor cells. After heat therapy, tumor tissues are often in a low pH state, and the effect of chemotherapy is more obvious at this time. (4) Heat therapy affects the body immunity and inhibits tumor angiogenesis Heat therapy can effectively activate the body immune activity and induce some apoptotic gene expression, and it can increase the efficacy of gene therapy. Heat can also reduce the expression of vascular endothelial growth factor, from inhibiting the formation of tumor neovascularization and reducing the chance of distant metastasis. (5) Heat therapy eliminates toxins from the body The human skin provides protection for the whole body, and it is both an absorbing and excreting organ. During whole-body heat therapy, the body excretes a large amount of sweat, and the pores that normally cannot be opened will be opened to the maximum extent, and the toxic substances absorbed by the body and skin will be excreted while a large amount of sweat is excreted, which prevents the body from being stimulated by toxic substances and achieves the purpose of disease prevention. (6) Other Heat therapy with surgery can reduce the residual tumor cells; with Chinese medicine, it can increase the anti-tumor effect of Chinese herbal medicine. (1) Whole-body thermotherapy refers to the method of heating all parts of the body to make the body temperature rise evenly and achieve the treatment temperature. There are three kinds of heating methods, i.e. heating by body surface, extracorporeal circulation method and biological method. Body surface heating can be divided into infrared radiation heating, microwave heating, etc., while the hot water bath, hot wax bath and electric blanket used in the 1980s are no longer used due to many defects. At present, infrared radiation heating is more commonly used in clinical practice because of its effectiveness, small side effects, easy monitoring and low cost. External circulation force heating refers to the method of using special equipment to pump part of the blood out of the body for heating to a predetermined temperature, and then instill it into the body to reach the treatment temperature, but it is not easy to be popularized because of the expensive equipment and cost. Biological method refers to the method of heating the body with biological agents, which is not easy to control the temperature and time, and is no longer used. (2) Regional thermal therapy is a method that heats a part of the body in a larger range than local heating. Heating methods include microwave, radiofrequency, regional thermal perfusion, etc. Since regional heating can also raise the temperature of the whole body, some scholars are now using regional heating for whole-body heat therapy. Regional heating can make the temperature of a certain area of the body reach 40℃-44℃, which is mostly used in combination with radiotherapy and chemotherapy to increase the effect of thermal therapy. The scope of treatment includes various early, middle and late malignant tumors of the trunk except head and neck tumors. (3) Local heat therapy The heating range is limited to the lesion and the surrounding normal tissues, and the whole body temperature does not increase significantly. The heat sources include microwave, radiofrequency, ultrasound, etc. Microwave is more frequently used in early local heat therapy. Local heat therapy is suitable for many kinds of superficial tumors, such as superficial lymph node metastasis, skin cancer, malignant melanoma and other tumors in superficial parts of the body.