Radiation oncology is a special discipline in clinical medicine that deals with the treatment of malignant tumors and certain benign diseases by means of ionizing radiation. The development of the discipline is dependent on advances in radiation physics, radiobiology, and clinical medicine. There are many treatment methods for malignant tumors, including surgery, radiotherapy, chemotherapy, Chinese medicine, immunotherapy and gene therapy, etc., while the first three are widely used and more mature treatment methods. About 2/3 of malignant tumor patients have applied radiotherapy at different stages of the disease to improve the quality of life and therapeutic efficacy. Radiotherapy is a localized treatment, and its efficacy can be expressed by the local control rate. If the tumor is limited to local development, radiotherapy can be applied to achieve the goal of eradication; if distant metastasis has occurred, radiotherapy can only play the role of palliative treatment to reduce symptoms and improve the quality of life. Due to the infiltrative and metastatic characteristics of the tumor, clinically it is often necessary to carry out a variety of methods of integrated treatment, especially the integrated treatment of surgery, radiotherapy and chemotherapy. I. Physical basis of radiotherapy (I) Types of radioactive sources There are three types of radioactive sources used in radiotherapy: first, α, p and γ rays emitted by radioisotopes; second, X-ray therapy machines and various gas pedals produce X-rays with different energies; and third, all kinds of gas pedals produce beams of electrons, proton beams, negative meson beams and other heavy particle beams. (B) the mode of radiation therapy 1, long-distance irradiation radioactive sources located outside the body at a certain distance, focusing on irradiation of a part of the human body, in addition to the traditional fixed source of dermatomes and fixed or rotating source of axial distance irradiation, but also includes stereotactic radiation therapy, the so-called γ-knife or X-knife, as well as the three-dimensional conformal radiation therapy (3D conformal radiation thempy) and intensity-modulation therapy (IMRT) Intensity Modulation Radiated Therapy (IMRT). 2, brachytherapy The radioisotope is sealed and placed directly into the tissue to be treated or the natural cavity, respectively, known as inter-tissue irradiation and intracavitary therapy, in addition to intraoperative placement of postoperative treatment and mold therapy. 3, internal radioisotope: radioisotopes are injected into the body orally or intravenously for treatment. (C) radiation therapy equipment 1, X-ray therapy machine X-rays are generated by high-speed movement of electrons hitting the target material. According to the energy level can be divided into X-ray: critical X-ray (6-11kV), contact X-ray (10-60kV), superficial X-ray (60-160kV), deep x-ray (180-400kV) and high-voltage X-ray (400kV-lMV). Superficial X-ray and deep X-ray are commonly used in clinical practice to treat superficial tumors. x-ray therapy machines have low energy compared to 60Co and gas pedals. Depth dose is small, easy to scatter, poor dose distribution, its highest dose point in the body surface, more absorption in bone tissue. But cheap, simple structure, easy to operate and maintain. 2, 60Co therapeutic machine The first 60Co therapeutic machine was manufactured in 1951 by Canada, is now widely used in developing countries and regions. Radioisotope 60Co can produce two kinds of rays, namely, the energy of 0.31MeV beta ray and the average energy of 1.25MeV ray. The latter is used in clinical radiotherapy and has a half-life of 5.27 years. Compared with deep X-ray therapy machines, it is high energy, monoenergetic, with high penetration, the highest dose point is 0.5 cm below the skin, so it helps to protect the skin, and bone and soft tissues have the same absorbed dose, with less side scattering. Compared with the gas pedal, it is economical and reliable, simple in structure and easy to maintain. But its penumbra is larger, and the need for regular replacement of cobalt source. 3, medical gas pedal from the early 50s gas pedal for clinical use. There are mainly three types: First, the electronic induction gas pedal, electron acceleration in the ring vacuum box, can produce X-ray and electron beam, but the X-ray output rate is low, the output stability is not high, the clinical use of its electronic line. Second, the electron linear gas pedal, with a microwave electric field to accelerate the electrons to high energy, if the direct lead for the electron beam therapy; if the strike target, then the X-ray therapy. Electron linear gas pedal has two main types: low-energy single-photon (4-6MV) linear gas pedal high-energy single / two-photon band electron beam linear gas pedal. The former can meet the treatment needs of 80% of the depth of the tumor, the latter is used for deeper parts of the tumor, and the electron wire can be used to treat shallower off-set tumors. Thirdly, electron concave cyclotron, which has both the economy of induction gas pedal and the high output rate of electron linear gas pedal. Its electron and X-ray energy can be ideal for medical use and can be adjusted within a wide range, simple structure, small size, low cost, is the future direction of development of medical high-energy gas pedal. 4, radiation therapy auxiliary equipment Radiation therapy auxiliary equipment refers to the positioning and implementation of radiotherapy-related equipment, including diagnostic imaging instruments CT (computerized tomography) and MRI (magnetic resonance imaging); simulator (simulator): simulation of the geometric conditions of radiation therapy X-ray fluoroscopy, filming or CT devices; treatment planning system (TPS, treatment) Treatment planning system (TPS, treatment planning system); CT or MRI images into the microcomputer, through the corresponding software to calculate the distribution of isodose curves, so as to propose the best treatment plan, and can be stored and printed. (D) treatment plan design and implementation 1, radiation dosimetry (1) absorbed dose: radiation through the material, its energy is absorbed by the material through which it is gradually weakened, so it is called absorbed dose. Dose unit of radiation therapy is Gray (Gy), which represents the average energy absorbed per unit mass of material (J/kg). (2) The clinical dosimetric principle of radiation therapy: under the premise of irradiating as little as possible the surrounding normal tissues, especially the vital organs and tissues with high radiosensitivity, the absorbed dose to the tumor tissues should be increased as much as possible. Therefore, a good treatment plan should meet the following conditions: the tumor dose is accurate, the irradiation field must be aligned with the target area to be treated, which should include the tumor foci and subclinical foci when radical treatment is carried out; the dose distribution in the treated tumor area should be uniform, and the dose change gradient should not be more than 10%, i.e., 90% of the dose distribution should be achieved; the field should be designed to increase the dose in the treatment area as much as possible, and to decrease the dose absorbed by the normal tissues of irradiated area; the normal tissues around the tumor should be protected, and the dose received should be increased as much as possible. The radiation field should be designed to increase the dose in the treatment area as much as possible and reduce the normal tissues in the irradiated area; the important organs around the tumor should be protected from irradiation or should not exceed the tolerance range. According to the relationship between the radioactive source and the position of the human body, the external irradiation is divided into fixed-source skin-distance irradiation, isocentric fixed-angle irradiation and rotational irradiation. In the process of implementation, different kinds of rays or different energy rays can be used in conjunction with the single field or multiple field irradiation, and there are fashionable fillers, lead blocking blocks or wedge filters for dose modification, and attention should be paid to the articulation of adjacent field irradiation to avoid “hot spots” or “cold spots”. The implementation and quality of the treatment plan. Implementation and quality control of treatment plan There are three main factors affecting the dosimetric accuracy of radiation therapy: patient’s condition, including the external contour of irradiated area, tumor location and tissue density; physical factors, including inaccuracy of dosimetric distribution measurement; inaccuracy of the important organs around the tumor and the range of determination, bad repeatability of the position and the movement of the patient’s body position. Therefore, close collaboration between radiotherapists, physicists and technologists is required during the implementation of radiation therapy. The radiotherapist designs the treatment plan, evaluates the treatment plan and supervises the execution of the plan; the physicist optimizes the dose on the TPS, ensures the accuracy of the dosimetry, is responsible for the protection and maintenance of the treatment equipment, and ensures the safety and protection of the staff and the patient; the technician is responsible for the execution of the plan, and ensures the accuracy of the patient’s positioning and other operations. Second, the radiochemical basis of radiation reaction and the biological basis of radiation therapy (a) radiochemical reaction Radiochemical reaction occurs immediately after the body is irradiated by radiation, the mechanism is that the organism contains about 70% of the water, and the role of rays and water to produce a number of free radicals, such as H-, OH-, hydrogen peroxide, and so on, and then cause energy absorption. Therefore, the presence of organic oxygen during irradiation is the most important modifier of the radiation reaction. (B) the biological basis of radiation therapy A series of biological effects occur in the organism after irradiation, according to the level of tissue structure of the organism can be divided into the following three types of radiation effects: 1, tissue level radiation effects The tissue that the cellular population will produce morphological and functional changes after irradiation, a variety of tissues are made up of cells in different phases of the cell cycle, and different phases of the cellular radiosensitivity, most of the Most mammalian cells are most sensitive in the G2 and M phases, while Gl and S phases are less sensitive, and G0 cells are resistant to radiation. After radiation, anoxic cell reoxygenation, cell cycle redistribution, cell repopulation, cell damage repair and cell replenishment occur. Expressed as the prolongation of the cell proliferation cycle or delayed division, some cell groups lose the ability to divide. 2, the cell level of radiation effects of radiobiology that cells lose the ability to unlimited proliferation is death. According to the period of death, radiation-induced cell death can be divided into interphase death and proliferation death. According to cell morphology, cell death can be categorized into cell necrosis and apoptosis. Radiation-induced apoptosis can be divided into pre-division apoptosis and post-division apoptosis. Selective increase of apoptosis may increase the anti-tumor efficacy of certain treatments, on the other hand, selective inhibition of apoptosis may reduce the complications brought about by tumor treatment. Radiation effect at molecular level In the genome, DNA radiation damage has selectivity and uneven distribution, in various forms of DNA damage, double strand break (DSB) has been paid special attention to, because it is closely related to cell survival. a certain form of repair can occur after DSB, but most of them are incorrect repairs, or the formation of double-stranded chromosomes and lethal, or the occurrence of chromosomal symmetric ectopia, the activation of Proto-oncogenes, such as can induce leukemia or lymphoma; or gene deletion, so that oncogenes are lost or inactivated, such as can induce solid tumors. Changes in the cell cycle after irradiation are regulated by cytokines. There are 3 checkpoints in the cell cycle, i.e., G1/S, S/G2, and G2/M checkpoints, which are regulated by different cyclins to regulate the activity of P34 to ensure the correctness and timeliness of each cell cycle transition. Genes related to apoptosis include bcl-2, myc and ras. Irradiated cells also cause changes in cell signaling, and the early response genes include c-fas, c-jun, etc. The microactivation of early response genes triggers cell signaling. The microactivation of early response genes triggers the activation of late response genes, thus expressing important effector proteins, such as tumor necrosis factor (TNF) and transforming growth factor (TGFβ), etc., the latter of which is thought to be related to radiation pulmonary fibrosis. (III) Radiosensitivity and radiotolerance A tissue such as bone marrow, small intestinal epithelium, squamous epithelium and migratory epithelium is roughly composed of 3 types of interconnected cells. ① Stem cell: This is a cell that can divide many times until it differentiates and matures into a functional cell, or it can become a daughter cell (same as a daughter cell) of the parent cell without differentiating after division. ② Differentiated cells or functional cells: such as the villous cells of the small intestinal membrane, which can no longer divide and die through senescence. (iii) Tend to mature differentiated cells: between the above two, is the progeny of stem cells, not yet fully differentiated, is completing the process of class differentiation. Generally speaking, the sensitivity of stem cells is the highest, with the increase of differentiation and maturity, its sensitivity gradually decreases, and the sensitivity of fully differentiated cells that are no longer dividing is the lowest. 1, radiosensitivity In a certain dose, time and irradiation field, all kinds of tissue cells are affected by radiation and produce different degrees of change. Tumor tissue is usually expressed by radiosensitivity, while normal tissue is mostly called radiation tolerance. Radiosensitive tumors are those in which the dose of radiation that causes such tumors to disappear is much lower than the amount tolerated by normal tissues, such as malignant lymphomas and seminomas: such tumors tend to be highly malignant and may have distant metastases in the early stages. Radiation-insensitive tumors are mostly originated from cells and tissues that are often in a static state, such as bone, cartilage, rhabdomyosarcoma and nerves, etc. This kind of tumors can not be controlled by giving a higher dose of radiation, which can cause irreparable damages to the neighboring normal tissues. However, with the development of radiobiology, radiation sensitivity can also be improved by changing the treatment plan, such as melanoma, by increasing the split dose each time (500-600cGy/dose, twice a week) to improve the efficacy. Those in between are called moderately sensitive tumors, in which the tumor’s lethal dose is close to the tolerance of normal tissues. Therefore, early detection and treatment of these tumors is desirable. These tumors are usually located in superficial parts of the body or visible natural cavities, such as skin, neck, nasopharyngeal, oral cavity and lip cancers, and their pathological types are mostly squamous epithelial cell carcinoma. There are many factors affecting the radiosensitivity of tumors, including the location of the tumor, the type of surrounding normal tissues and the relationship between the tumor tissues and normal tissues, the early and late stages of the disease, and the general condition of the patients, in addition to the source of tissues, the type of pathology and the degree of differentiation. The oxygenation state of cells is one of the important factors affecting the radiosensitivity of cells, and other factors include the distribution of the cell cycle, the difference between the proliferation rate of tumor tissues and that of normal tissues during divided irradiation, the proportion of clonogenic cells, the inherent radiosensitivity of cells, the repair of cellular damage and the relationship between the host and the tumor. The sensitivity of human tissue to radiation is directly proportional to its proliferation ability and inversely proportional to its differentiation degree. Under a certain dose, the sensitivity is positively correlated with the irradiated area. The performance of radiation damage ultimately depends on the degree of depletion of the stem cell population in the tissue. In recent years, according to the development of experimental radiotherapeutics and radiobiology, normal tissues are classified into early-responsive and late-responsive tissues, while tumors basically belong to early-responsive tissues. According to the L-Q model (linear quadratic equation), the γ/β value of early radiation-responsive tissues is larger, around 10Gy: the γ/β value of late radiation-responsive tissues is smaller, at 2-3Gy. (1) Early radiation-responsive tissues: the radiation response occurs during the period of radiotherapy, i.e., within 2 months after the beginning of radiotherapy, such as radioactive esophagitis, mucositis, and acute injury to the skin, and is characterized by the fact that it is able to proliferate under normal condition, and can accelerate repopulation after the irradiation. It is characterized by proliferation under normal conditions and accelerated repopulation after irradiation. (2) late radiation response tissue: radiation response (injury) occurs in the months or years after the end of radiation, this kind of tissue, including; brain, spinal cord, lungs, subcutaneous connective tissue and adult bone, these tissues have lost or have a very weak ability to proliferate, the compensation for radiation damage is mainly achieved by repair. Many organs can show both early radiation damage and late radiation damage. For example, the early radiation damage to the skin for the red shift, hyperpigmentation, dry desquamation and wet desquamation; late damage to the skin surface capillary expansion, skin and subcutaneous tissue atrophy and fibrosis. The reason for this is that the early response is damage to the hair growth cells in the basal layer of the skin, while the late damage is damage to the dermal tissue under the skin. (3) Normal tissue tolerance: TD5/5 and TD50/5 are commonly used. The former refers to the dose under the condition of routine divided irradiation (2Gy/times/d, 5 times/week), which is less than or equal to the dose in which complications occur in 5% of the cases within 5 years after treatment. The latter is the dose at which serious complications occur in 50% of cases within 5 years. The tolerance of normal tissues can be divided into the following different levels according to the local irradiation dose: irradiation of 20Gy affects radiosensitive tissues, including ovaries, zaibatsu, developing mammary glands, growing bone and cartilage, bone marrow and crystals. The entire digestive system, most or all of the stomach, small intestine and colon were not seriously complicated by irradiation at 20-45 Gy. Irradiation of both kidneys and whole lungs at 25Gy or more, a certain percentage of radioactive nephritis and radioactive pneumonia occurred. Whole liver and whole heart irradiated more than 40Gy occurred a certain proportion of radioactive damage. For irradiation of 50-70Gy, 1%-5% of the skin, oral mucosa, salivary glands, esophagus, pancreas, rectum and bladder will have serious radioactive damage. Irradiation of more than 75Gy still do not occur serious complications of the fallopian tube, uterus, adult mammary glands, adult muscle, blood, bile ducts, articular cartilage, peripheral nerves and lung apices. Third, clinical radiotherapy In the clinic about 70% of tumor patients need radiation therapy. According to the different purposes of treatment, radiation therapy can be divided into curative radiotherapy, which targets clinically detected tumors, and prophylactic radiotherapy, which targets potential lesions. Among them, therapeutic radiotherapy can be categorized into simple radiotherapy and integrated therapy. Radiotherapy alone can be further divided into radical radiotherapy and palliative radiotherapy in clinical practice. Radical radiotherapy refers to the long-term or permanent disappearance of the tumor in the diseased area by means of radiation, but without producing fatal injury to the surrounding normal tissues and organs often using external radiation or supplemented by brachytherapy. It is used for those who have the possibility of cure and whose tumors are sensitive or moderately sensitive to radiation. Palliative treatment is used for patients who have lost the possibility of radical treatment of the tumor for various reasons. Its purpose is to reduce the symptoms caused by the tumor, improve the quality of life and prolong the life expectancy, but on the premise of not increasing the patient’s pain and toxic side effects. Such as superior vena cava compression, brain metastasis, bone metastasis. Comprehensive treatment mainly includes integrated treatment of radiation and surgery and integrated treatment of radiation and chemotherapy. According to the sequence of radiotherapy and surgery, the former can be divided into the following three categories: preoperative, intraoperative and postoperative radiotherapy. The basic principle of combined surgery and radiation therapy is that the mechanisms of the two approaches are different. Radiation therapy tends to be ineffective in the center of the tumor, where the concentration of tumor clonogenic cells is highest and in a hypoxic environment. Surgery is ineffective when the tumor spreads beyond the resection area and invades adjacent tissues to form foci that are not observable by microscopy. Radiation therapy kills tumors with good vascular supply and low tumor cell counts; surgery removes large tumors with huge foci of necrosis. The advantages of preoperative radiotherapy are that the tissues are not destroyed, and fields can be set up according to the extent of the tumor and the clinically possible routes of dissemination; it reduces the size of the tumor, and turns a tumor that would otherwise be technically unresectable into an operable one. The disadvantage of preoperative radiotherapy is the lack of precise pathological diagnosis of the tumor extent, which affects the repair of normal tissues after surgery. The disadvantage of postoperative radiotherapy is the need to treat all tissues that are potentially contaminated during surgery. In addition, viable tumor cells may have spread beyond the treatment volume during surgery. The combination of surgery and radiation significantly improves local control of many progressive tumors and reduces the incidence of complications associated with excessive single-form therapy. Intraoperative radiotherapy: is mostly used for tumors of the digestive tract, such as gastric, pancreatic and rectal cancers. After surgical removal of a large tumor, irradiation of the tumor and the surrounding lymphatic drainage area improves the rate of local control of the tumor. Its advantage is that the radiation range is exposed and the radiosensitive organs such as small intestine are moved to the field to be protected. Combined application of radiotherapy and chemotherapy: radiotherapy acts locally, while chemotherapy acts systemically, therefore, for some tumors that are easy to occur hematogenous dissemination (e.g. lung cancer) or tumors that are easy to occur in multiple centers (e.g. malignant lymphoma), chemotherapy is to eliminate distant metastases that have already been disseminated, and radiotherapy is to control the local primary tumors. In this way, the combination of radiotherapy and chemotherapy can help to improve the local control rate, reduce or delay the emergence of distant metastases, and thus improve the survival rate. Chemotherapy is used in patients with large local tumor volume, aiming at reducing tumor cells, so that the number of tumor cells that should be killed by radiation will be reduced, and the total radiation dose will be reduced. Hedge Section II Characteristics and Complications Prevention and Control of Elderly Tumors Elderly tumors have some common characteristics of geriatric diseases. Clinical manifestations are atypical. Most of them are asymptomatic at the early stage of the disease, so early diagnosis is difficult. Elderly patients are prone to multi-system diseases, therefore, the clinical symptoms often overlap and cover each other or are complicated. The causative factors are often unknown, and the disease progresses unconsciously in the body, with a lingering course and no special treatment. Due to the weakening of the body of the elderly, complications are likely to occur, such as dehydration, contracture, decubitus ulcers, urinary and fecal incontinence and so on. Elderly people have poor compensatory capacity and are prone to failure. Elderly due to multiple diseases and medication is also more, coupled with organ function decline, detoxification and excretion function is poor, so the drug is prone to cause side effects, so the dose of medication is appropriately reduced, and the duration of the medication should not be too long. Advanced age can enable the accumulation of gene mutations caused by environmental factors, and the immune system’s function of immune surveillance against tumors decreases, therefore, elderly patients with tumors have a greater tendency to develop double cancers. All patients undergoing radiotherapy will experience some side effects. The magnitude of side effects depends on the site of treatment, the size of the field of fire, treatment factors-including total dose, field energy, split dose, and dose rate, whether chemotherapy is combined, and whether surgery is performed. Combination of radiotherapy, whether applied simultaneously or followed by chemotherapy, enhances the effect of radiation. Surgery also increases the incidence of radiotherapy side effects, e.g. multiple laparotomies increase the incidence of small bowel obstruction after pelvic radiotherapy. Radiotherapy of various organs leads to acute and chronic side effects. The former occurs days to weeks after radiotherapy, usually associated with edema, stem cell death or loss and inflammatory changes; the latter occurs months to years after radiotherapy, often associated with mesenchymal changes, such as fibrosis. Systemic reactions: in addition to systemic radiotherapy, radiotherapy is a localized treatment modality, and side effects are mostly limited to the irradiated local area. However, many patients do experience some systemic symptoms such as malaise, fatigue, loss of appetite and depression. The cause of these symptoms is unknown. They may be due to psychological and emotional changes during the treatment of the tumor or to organic changes induced by the treatment. Emotional support and clarification that these are a normal part of the treatment process are necessary. Blood reaction: Bone marrow and lymphocytes are highly sensitive to radiation, and the most obvious reaction is a decrease in white blood cells and platelets, while red blood cells are not sensitive. Differences in hematologic response are related to the following factors: the size of the irradiated area, whether the spleen and bone marrow are irradiated, and whether chemotherapy is used before and during radiotherapy. If a very small part of the body is irradiated, such as skin cancer, there is little or no change in the blood picture and regular blood tests are not necessary. However, if the radiation field is large and irradiates deeper parts of the body cavity or even includes the spleen, the hematopoietic system will react more and weekly blood tests will be needed. White blood cell and platelet counts are a limiting factor in treatment. It is generally believed that the safe lower limit of treatment is 3×109/L for white blood cells and 8×1010/L for platelets. Radiotherapy is an important means of cancer treatment, which has the dual effects of treatment and symptom relief, especially for the old and frail elderly patients, when they cannot undergo surgery and chemotherapy, it is still a beneficial treatment choice. In clinical practice, doctors often under-dose elderly patients due to concerns about toxic side effects at the full irradiation dose. Due to the aging of the population, more and more elderly tumor patients are receiving radiation therapy. A large body of literature reports that radiation therapy is safe and effective for frail elderly tumor patients, especially for head, neck, and thoracic tumors. The irradiation field should be appropriately reduced for pelvic tumors. Weight maintenance is extremely important for radiation therapy, and it is important to improve diet, measure weight weekly, and adjust the quality and quantity of diet in time. Advanced age is not an anti-indication for radiotherapy, but the general condition of patients is an important factor affecting the prognosis of radiotherapy. Reasons for interruption of radiotherapy in elderly patients include weight loss due to diarrhea, dysphagia, and disease progression. The greatest cause of treatment interruption may be large irradiation fields. Patients in good general condition tolerate acute dermatitis, mucositis, pharyngitis, esophagitis, and cystitis of 2-3 degrees. Small bowel reactions (diarrhea) and pharyngeal mucositis in elderly patients deserve special attention and appropriate supportive therapy.