Radiation pneumonia is an inflammatory reaction caused by damage to normal lung tissue in the radiation field after radiation therapy for lung cancer, breast cancer, esophageal cancer, malignant lymphoma or other malignant tumors of the chest. In mild cases, there are no symptoms and the inflammation can dissipate on its own; in severe cases, extensive fibrosis occurs in the lungs, leading to respiratory impairment and even respiratory failure. Therefore, radiation pneumonia has gradually attracted the attention of clinical workers, this paper reviews the recent literature, its etiology and diagnostic and therapeutic advances are reviewed as follows.
1.Risk factors
1.1 Factors related to radiotherapy The occurrence and severity of radiation pneumonia are closely related to the method of radiation, the amount of radiation, the area of radiation, and the speed of radiation. Since different segmentation irradiation methods are used in the process of radiation therapy for tumors, such as conventional irradiation, super-segmentation irradiation, conformal irradiation, etc., in order to compare the biological effects of different radiotherapy methods, it is suggested to normalize the biological effects by mathematical models.
According to the statistics of Zhongshan Hospital of Shanghai Medical University, radiation pneumonia rarely occurs in those whose radiation dose is less than 2000 rad within 6 weeks, while the radiation pneumonia increases significantly in those whose dose exceeds 4000 rad, and in those whose radiation dose exceeds 6000 rad, there must be radiation pneumonia. The larger the radiation field, the higher the incidence, the more serious the lung tissue damage of large area radiation than local radiation; the faster the irradiation speed, the more likely to produce lung damage; the chance of radiation pneumonia occurring in conventional irradiation than super-segmented irradiation and conformal irradiation.
1.2 Other factors The occurrence of radiation pneumonia is also related to cold and flu, combined chemotherapy, history of chronic lung disease, history of smoking, and age. The application of chemotherapeutic drugs may also reduce the tolerance of the lung and increase the radiation damage to the lung, and some chemotherapeutic drugs may aggravate the radiation treatment response of the lung. Poor tolerance to radiation, pre-existing lung lesions such as pneumonia, chronic bronchitis, chronic obstructive pulmonary disease, and re-radiation therapy all contribute to the development of radiation pneumonia. Poor tolerance to radiation therapy.
2.Occurrence mechanism
2.1 Traditional theory The conventional view is that radiation pneumonia is mainly due to the local cytokine production in the irradiated field caused by radiation, resulting in lung fibrosis. The mechanisms of occurrence are.
① Small vessel and lung type II cell injury The pathological changes in the acute phase mostly occur 1 to 2 months after radiation therapy, manifested as capillary injury resulting in congestion, edema cell infiltration, and decreased alveolar type II cell regeneration, weakening the inhibitory effect on fibroblast growth and causing fibroblast proliferation.
②Increased production of free radicals: animal experiments revealed a progressive increase in the content of free radicals in the lung after irradiation, which may be a direct cause of lung tissue damage after irradiation.
(③) Increased cytokine content: Fibroblast growth factor and chemokine act together in the irradiated area to cause lung tissue damage.
④Multiprogenitor factors: The occurrence of radiation pneumonia is multiprogenitor in nature, in which macrophages, mast cells, fibroblasts, and lung type II cells are involved in the formation process.
2.2 Disseminated theory The theory of disseminated radiation pneumonia suggests that the disease is an immune-mediated reaction that produces bilateral lymphocytic alveolitis and local radiation field. The pathological changes are due to free radicals produced by radiation ionization, which damage cell membranes and DNA, leading to cellular malfunction and death. Six to nine months after radiation therapy, the pathological changes in the lung are mainly progressive fibrosis, with extensive alveolar fibrosis, but most of them do not produce symptoms, and if accompanied by infection, they produce symptoms, i.e., radiation pneumonia, but the symptoms vary in severity. The symptoms disappear in 2-3 months after active treatment, and gradually turn into chronic pulmonary fibrosis.
3.Diagnosis overview
3.1 Clinical manifestations
3.1.1 Radiation pneumonia: There is an incubation period after exposure to radiation, usually 1 to 3 months between the completion of radiotherapy and the appearance of symptoms, and the symptoms may appear before the imaging changes. Radiation pneumonia can occur during radiotherapy for any disease in the chest and varies greatly from lack of clinical manifestations in mild cases to rapid and life-threatening respiratory failure and acute pulmonary heart disease within a few days in severe cases. The most common clinical manifestations are shortness of breath and cough, which varies in severity, usually presenting as a dry cough, with sputum blood (filaments) in the later stages. Physical examination is usually unremarkable. Occasionally, wet rales and pleural friction sounds can be heard in the irradiated area. Skin changes may occur in the radiation field. Laboratory tests in the acute phase lack specificity and may
There may be neutrophilia and accelerated erythrocyte sedimentation rate.
3.1.2 Radiation pulmonary fibrosis: It is a clinical syndrome caused by the occurrence of chronic lung damage, and the process of permanent pulmonary fibrosis takes about 6 to 24 months. There may be no history of acute pneumonia before the onset of pulmonary fibrosis, and patients may be asymptomatic or present only with shortness of breath. Patients with Ohno irradiation may develop chronic pulmonary insufficiency and eventually chronic pulmonary heart disease and pulmonary hypertension. In patients with mild symptoms, there may be no obvious abnormalities on physical examination, and some irradiated areas may have altered breath sounds and percussion turbidities.
3.1.3 Fine bronchiectasis occlusive mechanized pneumonia: only a few cases have been reported in the literature, all of which occurred in breast cancer patients who received radiotherapy and may appear 1.5-6.0 months after the end of radiotherapy. Lymphocytosis is seen on bronchoalveolar lavage fluid (BAL) examination, and the pathogenesis is unclear.
3.2 Imaging manifestations
3.2.1 X-ray chest radiograph [14]: acute radiation pneumonitis occurs near the end of radiotherapy to within 2 months after radiotherapy, and is seen as a lamellar homogeneous density blurred shadow in the lung radiation field, with multiple small patchy shadows with unclear borders, and the edge of the lesion is consistent with the radiation treatment field, and there is a clear demarcation with normal lung tissue.
Radiation pulmonary fibrosis begins as a slender reticulated or thin striped shadow in the radiation field, which can gradually increase after 1 month, with higher density, and the lesions can expand and fuse into a dense mass.
The main features of X-ray performance are
①fibrous cord shadow: varying in length, thickness, with dotted hyperdensity shadow in the middle, lung texture disorder, chest wall and pleural hypertrophy;
②Sheet-like shadow: lung upper irradiation field sheet-like shadow with clear proximal edge;
③ pleural changes: pleural hypertrophy adhesions, blurred rib-diaphragm angle, pleural effusion;
④Pulmonary atelectasis: may be manifested as segmental or lobar atelectasis;
⑤ Mediastinal displacement: it shows displacement to the left or right, and sometimes it only shows twisted displacement of trachea.
3.2.2 CT manifestation: The early stage of radiation pneumonia shows small scattered patches of faint density shadow in the irradiated field with blurred edges, accompanied by thickened blood vessels and bronchial shadow, and the surrounding pleura is still bright and neat. In the middle stage, solid lung changes are seen, including bronchial signs and alveolar sacs, and some of the edges may be stellate, which may extend beyond the radiation field; the surrounding thick and long stripes are seen, and the local pleura near the chest wall is thickened and pulled. The late stage shows large lamellar hyperdense shadow in the irradiated field with sharp edges, increased fibrous striae, thickened lobular spaces, ipsilateral pleural thickening, mediastinal shift, and lung volume reduction [15].CT is better than X-ray plain film in showing the internal subtle structures of radiographic pneumonia shadow, such as showing vascular signs, bronchial inflation signs, large alveoli, and bronchial dilatation.
3.3 Staging and grading
3.3.1 Clinical staging The development of typical radiation pneumonia can be divided into 4 stages.
① Early stage: 0.5 to 1 month, mainly exudate;
②Middle stage: 2-3 months, predominantly granulomatous growth;
③Late stage: 3 to 6 months, mainly fibroplasia, ;
④Late stage: after 6 months, mainly fibrotic lesions.
3.3.2 Grading criteria According to the grading criteria for acute radiation pneumonia developed by the American Cancer Research Collaborative Group (RTOG) in 1995 Grading:
①Grade 0: no change;
②Grade 1: mild dry cough or dyspnea on exertion;
③Grade 2: persistent cough requiring narcotic cough suppressants, dyspnea with mild exertion, no change on X-ray or slight cotton wool or flaky shadow;
Grade 3: severe cough, ineffective narcotic cough suppressant, dyspnea with quietness, dense X-ray image, requiring intermittent oxygen or hormone therapy;
⑤ Grade 4: respiratory insufficiency, requiring continuous oxygenation or assisted mechanical ventilation;
Grade 5: fatal respiratory distress.
4.Treatment strategy
4.1 Treatment principles No special treatment can be given for radiation pneumonia with only imaging manifestations and no clinical symptoms. If there is mild cough and sputum, symptomatic treatment is sufficient. Antibiotics are given for secondary lung infections, early application of glucocorticoids is effective, anticoagulation therapy is given, and oxygen inhalation can improve hypoxemia.
4.2 Adrenocorticosteroids are commonly used and effective drugs in the treatment of radiation pneumonia, especially in the early stage. They can reduce the degree of damage to lung parenchymal cells and microvessels, reduce lung tissue exudation and edema, and effectively improve symptoms. The initial dose of prednisone is 60-100mg/d orally in divided doses, and the dose is gradually reduced to 10-15mg/d after the symptoms improve, for a total duration of 3-6 weeks. In severe cases, dexamethasone can be administered intravenously at 10-15mg/d, and then orally at 15mg three times a day after the symptoms are relieved. Dexamethasone can also be used for nebulized inhalation, which is effective in reducing systemic reactions.
4.3 Anti-infection Radiation pneumonia is very easy to combine with bacterial infection, if there is high fever, high total white blood cell and neutrophil count, coughing yellow pus sputum, in the use of glucocorticoids at the same time, should be given a sufficient amount of effective broad-spectrum antibiotic treatment, can be more effective.
4.4 Non-steroidal drugs indomethacin and aspirin can effectively reduce vascular endothelial cell injury and inhibit the production of prostaglandins and leukotrienes, thus reducing the clinical symptoms of radiation pneumonia, which can play an auxiliary role [17].
4.5 Reduction and prevention of pulmonary fibrosis D-penicillamine, which has a significant affinity for lung tissue, is a chelating agent that prevents the maturation of salt-soluble collagen in vivo, and has a good effect on improving the subjective symptoms and lung function of patients with pulmonary fibrosis. It can delay the occurrence of radiation pneumonia and prolong the survival period.
4.6 Chinese medicine treatment According to the traditional Chinese medicine, radiation is a heat and poisonous evil, heat can turn fire, and cancer patients mostly have insufficient positive energy and internal stasis of blood, so the treatment should adopt the method of nourishing Yin and moistening the lung, as well as reducing poison and eliminating stasis. Modern pharmacological research proves that north sage has antipyretic and analgesic effects; maidenhair, Zhi Mu, pollen, raw earth, Xuan Shen and gardenia have antibacterial and anti-inflammatory effects; lily and maidenhair have anti-hypoxic effects; salvia has the effect of preventing radioactive lung injury. Combined with western drugs, they can significantly relieve symptoms, improve the pathological changes of pulmonary fibrosis after radiotherapy, and accelerate the recovery of lung function [18,19].
5. Preventive measures
5.1 Mastering the total irradiation dose The absorbed radiation dose correlates with the degree of lung injury, but its effect is significantly influenced by the daily split size. a study by Graham et al [ 4 ] showed that patients with non-small cell lung cancer underwent radiotherapy when V20 (i.e., the volume of the lung receiving >20 GY irradiation to total volume ratio) was <22%, 22%-30%, 31%-40% and >40%, respectively The incidence of radiation pneumonia in 2 years is 0, 7%, 13% and 36% respectively, so in order to avoid severe radiation pneumonia, it is recommended that V20 should be <25%.
5.2 Mastering the number of splits/dose ratio Splits reduce the biological effects of radiation and are a major factor affecting late radiation damage. Multicenter studies have shown that the segmentation range, number of segments and total radiation dose are significantly associated with the risk of radiation pneumonia, with segmentation range >2.67Gy being the most important risk factor for radiation pneumonia. The total radiation dose is the same, and compared with a single exposure, 2 exposures divided per day can reduce the hazard of radiation. Therefore, the total radiation dose and its single dose distribution and the size of the irradiation field should be strictly controlled. It is better to perform tangential projection for breast cancer radiation therapy to avoid lung damage as much as possible.
5.3 Control of irradiation volume Usually the lung irradiation range <25% has the possibility of local damage to the lung, but does not cause radiation pneumonia. Smaller fields, especially functionally important and volumetrically larger lower lung fields, may produce clinical symptoms with high dose irradiation (>50Gy). The incidence of radiation pneumonia will be significantly higher if the lung irradiation range is >50%, especially if both lungs are irradiated simultaneously. Irradiation of both lungs >30Gy is a lethal dose, but death has been reported at doses as low as 13Gy. However, treatment of non-small cell lung cancer requires an irradiation dose >60Gy to achieve better results. According to the study protocol of the Oncology Radiotherapy Group, irradiation should be limited to within 50 px of the primary tumor and the affected lymph nodes, beyond which the degree of lung injury increases significantly.
5.4 Knowing the history of previous treatment The risk of radiation lung injury is significantly increased with or without previous radiation injury symptoms or signs. If radiation pneumonia is present at the first treatment, the second treatment may cause a serious reaction. Many chemotherapeutic agents not only have direct pulmonary toxic effects, but also may aggravate the lung injury effects of radiotherapy. Bleomycin, when used in conjunction with radiotherapy, will be more toxic than either one of them alone. Other chemotherapeutic agents that can increase the degree of lung injury from radiotherapy are actinomycin, cyclophosphamide, vincristine and adriamycin, etc. The toxicity of simultaneous use is again greater than that of alternate use. If the above-mentioned conditions exist, special care is needed in the formulation of radiation therapy plans and in the implementation of radiation therapy.
5.5 Close observation of changes in condition In the course of radiation therapy, patients should be closely observed for respiratory symptoms and elevated body temperature. x-ray examination reveals pneumonia, radiation therapy should be stopped immediately. Once radiation pneumonia occurs, it is often irreversible, which shows the importance of prevention. In addition, it is important to prevent colds, stop smoking, and actively treat chronic lung diseases.
In conclusion, the occurrence of radiation pneumonia is the result of multiple factors, and once it has progressed to the stage of pulmonary fibrosis, it is often irreversible, so prevention and early treatment are essential. With the continuous updating of imaging equipment and the development of diagnostic imaging technology, earlier detection of radiation pneumonia is expected.