1.Concept of tumor thermotherapy Hyperthermia is a method of applying various heat sources to treat malignant tumors by applying modern medical technology and ICU technology. Some scholars call it “warm heat treatment for cancer”, “hyperthermia treatment for cancer”, “hyperthermia treatment for cancer” and so on. In terms of heat therapy itself, it is a purely physical treatment, with heat sources including high frequency electromagnetic waves, infrared rays, ultrasonic waves and hot water baths. When heating up the body, due to the unsound tissue structure of tumor tissues, the heat dissipation is slower than normal tissues, so the temperature of tumor tissues is 5℃～10℃ higher than normal tissues, while malignant tumor cells are sensitive to high heat, as a result, tumor cells are killed or gradually apoptotic after high heat, while normal tissues are not damaged. The unique advantage of thermotherapy compared with radiotherapy and chemotherapy is that it has no toxic side effects. At the same time, thermotherapy can 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 survival quality of tumor patients and prolong the survival period. 2. Five major anti-tumor effects of heat therapy (1) Direct effect of hyperthermia on tumor cells Research shows that hyperthermia can directly kill tumor cells and inhibit the synthesis of deoxyribonucleic acid (DNA), ribonucleic acid (RNA) and protein; hyperthermia can damage the normal function of cell membrane, change the permeability of cell membrane, cause protein spillover and change the structure of nuclear chromatin, leading 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 pH drops due to the enhancement of anaerobic enzymes, which in turn strengthens the activity of lysosomes and causes tumor cells to lyse and die; the inhibition of protein synthesis also inhibits the proliferation of tumor cells and causes them to die. All these are most sensitive to the S phase of cell proliferation, which can be tens to hundreds of times different from other phases. This is because radiation therapy and many drugs are effective against cell proliferation cycles beyond the S phase. Such a complementary and synergistic relationship has important therapeutic value in clinical practice. (2) Heat therapy increases the effect of chemotherapy Studies have shown that 42°C in vitro for 120 minutes can enhance the cancer-killing effect of some chemotherapy drugs by 10 to 100 times. In clinical practice, the combined application of heat therapy and chemotherapy is far more effective than the sum of the two therapeutic effects. In the case of achieving the same efficacy index, the dosage of chemotherapy drugs can be reduced, thus reducing the harm to human body. (3) Heat therapy increases the effect of radiotherapy Heat therapy and radiotherapy have different sites of action in the cell proliferation cycle, i.e. the cell cycle sensitive to heat therapy is not sensitive to radiotherapy treatment, so that a complementary relationship is formed, and heat therapy changes the histological and physiological properties of the tumor at the same time, and these can enhance the effect of radiotherapy. (4) Heat therapy affects the immunity of the body. In the special biological characteristics of tumor tissues there is a different response from normal tissues, which results in accelerating the death of tumor tissues. (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 the whole body heat therapy, the human body discharges a large amount of sweat, and the pores that normally cannot be opened will be opened to the maximum extent, while a large amount of sweat is discharged, the toxic substances absorbed by the body and skin will be discharged, which makes the body free from the stimulation of toxic substances and achieves the purpose of disease prevention. (1) Superficial tumors Because superficial tumors are easy to heat, easy to observe and relatively easy to measure or control temperature, so most of the tumors treated by heat therapy in early stage are superficial tumors. Superficial tumors can be divided into primary and metastatic, skin cancer, breast cancer, melanoma, soft tissue sarcoma, etc. are all primary tumors; cancerous metastasis of superficial lymph nodes and other superficial metastatic tumors are all metastatic tumors. 1.1. Skin cancer Skin cancer is a common malignant tumor, which usually occurs in the exposed parts of head and neck, upper limbs, inside the mouth, vulva and other parts. Squamous cell carcinoma is more common in young people and basal cell carcinoma is more common in old people. The clinical symptoms of the former are mostly local red and hard lumps with rapid ulceration and local lymph node metastasis, often accompanied by infection and pain; the clinical symptoms of the latter are mostly plaque-like papules or wart-like elevations with a harder base, later ulceration and slower growth, and less metastasis. Therapeutic analysis: Among the non-surgical treatment methods, thermotherapy can enhance the sensitivity of radiotherapy, and the thermal enhancement ratio can be up to 1:1.4. In the head and neck area, thermotherapy can reduce the dose of radiotherapy and maintain the cosmetic effect; for patients with larger area and cannot be operated and radiotherapy, whole body thermotherapy can be carried out to improve the efficacy. 1.2, Breast Cancer Breast cancer is the malignant tumor with the highest incidence in women and has a complex pathological typing. As it is a systemic disease, systemic metastasis can appear earlier when the cell differentiation is low. Efficacy analysis: It is mainly used for patients with stage II or above. Combining chemotherapy and radiotherapy can enhance the sensitivity of treatment and improve the control rate of tumor; radiotherapy sensitization for recurrent breast cancer has stronger advantages. When breast cancer patients have skin damage, such as orange peel-like appearance or rupture, or upper limb lymphedema, chemotherapy combined with thermotherapy can significantly improve the efficacy. In advanced stage with extensive metastasis in lung, liver and bone and pain, whole body thermotherapy can significantly improve symptoms, reduce pain and improve quality of life. Melanoma and soft tissue sarcoma Melanoma is a kind of skin malignant tumor with high malignancy, which grows rapidly and has extremely bad biological behavior, and like soft tissue sarcoma, it is prone to hematogenous metastasis. It is characterized by a high risk of recurrence after surgery and is insensitive to radiotherapy and chemotherapy. Efficacy analysis: For localized malignant melanoma, especially those occurring in the limbs, localized regional thermal perfusion chemotherapy is more effective, with an overall efficiency of 80% to 90% and a complete remission rate of 55% to 65%; for patients with systemic metastases of malignant melanoma, systemic thermal therapy is also effective as long as the systemic condition allows; the thermal therapy for soft tissue sarcoma is similar to that for melanoma. In the application of both tumors, good results have been obtained. 1.4. Metastatic tumors For some superficial metastatic tumors, radiotherapy together with thermotherapy can significantly improve the control rate of tumors. The most common superficial metastatic tumors are recurrence of breast cancer in the chest wall after surgery and metastasis of lymph nodes in the neck of nasopharyngeal cancer. Among the patients with recurrent breast cancer, 3/5 of them present with chest wall and local recurrence, often with pain, ulceration, bleeding and other symptoms, especially since most of them have already undergone local radiotherapy, which makes further control extremely difficult. In addition, the efficacy analysis: the control rate is greatly improved with comprehensive treatment, which can improve the survival rate and survival quality of patients with metastatic tumors. (2) Head and neck malignant tumors Early stage head and neck tumors are mainly treated by surgery; for patients with inoperable early and middle and late stages, radiotherapy is mainly used; for stage III and IV and recurrent metastases, thermal chemotherapy is added on top of local treatment to improve control rate and reduce recurrence rate. Efficacy analysis: Adding thermotherapy to radiation therapy can increase the sensitivity of radiation therapy, reduce the dose of radiation therapy and improve the tumor control rate; for head and neck malignant tumors with large lesions and inoperable, systemic thermochemotherapy is feasible; it has achieved remarkable efficacy in the treatment of brain tumor, nasopharyngeal cancer, thyroid cancer, parotid cancer, laryngeal cancer, oropharyngeal cancer and lip cancer. (3) Lung cancer A variety of thermal therapies can be applied to lung cancer, but whether it is interstitial coagulation thermal therapy or extracorporeal heating, it is difficult to form an effective therapeutic temperature in the tumor when applied alone, so it is usually combined with radiotherapy, chemotherapy and Chinese medicine for comprehensive treatment. Efficacy analysis: Intrathoracic thermal perfusion therapy is effective for those with cancerous pleural effusion and pleural dissemination of lung cancer. The treatment of cancerous pleural effusion with DDP or VitB17 combined with extracorporeal circulation of hot saline at 43℃ is more than 80% effective. Intrathoracic thermal perfusion chemotherapy for unresectable metastatic lung cancer has also received good efficacy. (4) Esophageal cancer is a common malignant tumor in China. The main symptoms are progressive dysphagia and pain behind the sternum, etc. The pathological type is mainly squamous carcinoma, and the five-year survival rate after surgery is not more than 30%, and only about l/3 of patients can be treated surgically. Efficacy analysis: In the late 1970s, intracavitary microwave thermotherapy combined with radiation therapy was firstly started, and its efficacy caused a sensation in the international arena, followed by the triple combination of thermoradiotherapy, thermoradiotherapy before surgery and thermochemotherapy, which also received good efficacy. (5) Gastric cancer occupies the second place in the incidence of gastrointestinal malignant tumors. The pathological type of gastric cancer is mainly adenocarcinoma, and the early symptoms are not obvious, but in the middle and late stages, symptoms such as epigastric mass, poor nutrition, emaciation, anemia, bleeding and left supraclavicular lymph node metastasis often appear. Analysis of efficacy: Heat therapy is mainly applied to patients whose tumors are found to invade beyond the plasma membrane layer and cannot be resected radically, then intraoperative heat perfusion therapy is feasible; preoperative heat perfusion chemotherapy can improve the surgical resection rate; for postoperative recurrent gastric cancer patients and patients with liver or abdominal lymph node metastasis, peritoneal heat perfusion therapy is more effective. (6) Hepatocellular carcinoma is characterized by insidious onset, rapid progress, short course and short-term recurrence. Efficacy analysis: surgery and intervention combined with various forms of thermal therapy can improve the survival rate of patients. (7) Colorectal cancer Colorectal cancer includes colon cancer and rectal cancer. The pathological type of colorectal cancer is mainly adenocarcinoma, and the treatment method is mainly surgery, supplemented by radiotherapy and chemotherapy. Efficacy analysis: intraoperative thermoperfusion chemotherapy can prevent implantation metastasis and treat surgically unresected lesions; local thermotherapy for patients with obstruction can help relieve obstruction; prophylactic systemic chemotherapy plus systemic thermotherapy can help improve control rate. It has been reported that the efficiency of treating advanced recurrent rectal and colon cancer with thermal radiotherapy triple therapy is 54%. Among them, 94% of patients had pain relief, 33% of patients created the opportunity for re-operation, and the 1-year survival rate after treatment was 80%, and the 3-year survival rate was 34%. (8) Pancreatic cancer is a common malignant tumor of the digestive system, with insidious onset, poor prognosis, small success rate of treatment, only a few cases (15%-20%) can have a chance of surgery, poor sensitivity to radiotherapy and tricky treatment. The pathological types of pancreatic cancer are mainly ductal adenocarcinoma and alveolar cell carcinoma. Efficacy analysis: intraoperative thermal perfusion therapy helps to improve the control rate; advanced pancreatic cancer with intraperitoneal thermal perfusion of chemotherapeutic drugs or VitB17 etc. can relieve pain and slow down the progression of the disease. (9) Bladder cancer is a common malignant tumor of the urinary system. The earliest clinical symptom is painless hematuria, and once urinary frequency, urinary urgency or difficulty in urination occurs, it can indicate that the tumor is highly malignant or in advanced stage, and the recurrence rate is extremely high. The pathological types are mostly papillary carcinoma and metastatic epithelial carcinoma, but squamous adenocarcinoma is rare. The 3-year survival rate is 100% for those with good cell differentiation and about 40% for those with grade 3. Efficacy analysis: For those who underwent bladder perfusion chemotherapy after surgery, if combined with heat therapy can significantly reduce the risk of metastatic recurrence; in the comprehensive treatment of patients with intermediate and advanced stages, combining heat therapy can significantly improve the efficacy of drug and radiation therapy. (10) Prostate cancer is a common malignant tumor in elderly men. For early stage cases, radical surgery and radical radiotherapy are mostly used; for more advanced cases and those who cannot tolerate surgery, endocrine therapy and radiotherapy are mostly used to prolong the survival period. Efficacy analysis: ultrasound focused (HIFU) has advantages in treating prostate cancer; local ultra-high-temperature heat therapy such as microwave has obvious efficacy; various local heat therapy or transthermal therapy with radiotherapy is better than single treatment. The simultaneous local heat therapy and radiotherapy for recurrent prostate can improve the control rate and survival quality. (11) Cervical cancer Cervical cancer is a common malignant tumor in women, second only to breast cancer in terms of incidence. The pathological type is mainly squamous cell carcinoma, which often invades the pelvic organs and vaginal bladder triangle and is prone to regional metastasis. The treatment of cervical cancer is mainly surgery and radiotherapy, while systemic or regional chemotherapy is performed for patients with systemic metastasis or advanced stage. Efficacy analysis: radiotherapy plus intracavitary microwave thermotherapy can reduce the dose of radiotherapy or avoid intracavitary radiotherapy and reduce the occurrence of corresponding side effects; the addition of thermotherapy can significantly improve the treatment effect of patients with recurrence. The overall remission rate of patients with pelvic and abdominal metastases of mid- to late-stage cervical cancer was 83% after the administration of radiofrequency regional extracorporeal heating and thermal perfusion chemotherapy with artificial ascites, and there were no obvious toxic side effects. (12) Endometrial cancer Endometrial cancer is also a common female malignant tumor, which is hormone-dependent. The main treatment means are surgery, radiotherapy, endocrine therapy and chemotherapy. Analysis of efficacy: application of thermal perfusion chemotherapy before surgery can improve the surgical resection rate; intraoperative application can reduce the recurrence rate and remove the cancer cells that may spread in the pelvic and abdominal cavities; for advanced tumor invading the outer membrane or spreading in the abdominal cavity and intra-abdominal lymph node metastasis, peritoneal thermal perfusion chemotherapy has the irreplaceable advantages of other therapies. (13) Ovarian cancer is second only to breast cancer and cervical cancer in terms of incidence. It is characterized by complex pathological types and diverse symptoms, with early symptoms of lower abdominal discomfort and abdominal distension, and late symptoms such as massive ascites, pain, bleeding, anemia and cachexia. Surgery, radiotherapy and chemotherapy are commonly used, and thermotherapy can be combined with the first three treatments to improve the clinical cure rate. Analysis of the efficacy: abdominal thermal perfusion chemotherapy applied in preoperative can increase the chance of surgical resection; applied in intraoperative can significantly reduce the chance of abdominal tumor dissemination; applied in advanced stage with ascites can improve the efficacy; systemic thermal chemotherapy can significantly increase the efficiency of chemotherapeutic drugs.