Radiation lung injury is caused by ionizing radiation 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 in the chest, including acute radiation pneumonia and radiation pulmonary fibrosis, and is the most important dose-limiting factor in radiation therapy for chest tumors.
I. Occurrence mechanism
Radiation lung injury is mainly caused by the local cytokine production in the irradiated field, resulting in lung fibrosis. The mechanism of occurrence.
1, small blood vessels and lung type II cell injury
The pathological changes in the acute phase mostly occur 1 to 2 months after radiation therapy, manifesting as capillary damage resulting in congestion, edema cell infiltration, and reduced alveolar type II cell regeneration, weakening the inhibitory effect on fibroblast growth and causing fibroblast proliferation.
2.Increased free radical production
It was found that after lung irradiation, the free radical content in lung increased progressively, which may be the direct cause of lung tissue damage after irradiation.
3.Increased cytokine content
Fibroblast growth factor and chemokines act together in the irradiated area to cause damage to lung tissue.
4 Multiple original factors
The occurrence of radiation pneumonia is multiprogenic, in which macrophages, mast cells, fibroblasts, and lung type II cells are involved in the formation process.
II. Pathophysiology
The pathological changes of radiation lung injury are due to free radicals generated by radioactive ionization, which damage cell membranes and DNA, leading to cellular malfunction and death. Six to nine months after radiation treatment, the pathological changes of the lung are mainly the gradual development of fibrosis, alveolar extensive fibrosis, but most of them do not produce symptoms, if accompanied by infection then produce symptoms, that is, radiation pneumonia, but the symptoms vary in severity. After active treatment, the symptoms disappear in 2-3 months and gradually turn into chronic pulmonary fibrosis.
Third, the clinical manifestations.
1.Radiation pneumonia
It usually appears within 1 to 3 months after the completion of radiotherapy, and the symptoms may appear before the imaging changes. Radiation pneumonia can occur in the course of radiotherapy for any disease in the chest, and the condition varies greatly from lack of clinical manifestations in mild cases to rapid onset of respiratory failure and acute pulmonary heart disease within a few days in severe cases, and is life-threatening. The most common clinical manifestations are shortness of breath and cough, which varies in severity and usually presents 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 include neutrophilia and accelerated erythrocyte sedimentation rate.
2.Radiation pulmonary fibrosis
It is a clinical syndrome caused by the occurrence of chronic lung damage, and the process of permanent pulmonary fibrosis occurs for about 6 to 24 months. Pulmonary fibrosis may occur without a history of acute pneumonia, and patients may be asymptomatic or only show 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, but some irradiated areas may have altered breath sounds and percussion turbidities.
3. X-ray chest film
Acute radiation pneumonia is seen in the lung radiation field in the form of lamellar uniform density blurred shadow, multiple small patchy shadows with unclear boundaries, the edge of the lesion is consistent with the radiation treatment field, and there is a clear demarcation with normal lung tissue, this is the characteristic manifestation of the disease.
4. CT performance
Early manifestation of radiation pneumonia is a scattered small patchy faint density shadow in the irradiated field, with blurred edges, accompanied by thickened blood vessels, bronchial shadow, the surrounding pleura is still bright and neat. In the middle stage, solid lung lesions with bronchial signs, alveolar sacs and stellate edges may be seen, which may extend beyond the radiation field; the surrounding thick and long stripes may be seen, and the pleura near the chest wall may be thickened and stretched. Late stage manifests as large lamellar hyperdense shadow in the irradiation field with sharp edges, increased fibrous striae, thickened lobular spaces, ipsilateral pleural thickening, mediastinal shift, and lung volume reduction 3.3 Staging and grading.
IV. Treatment strategy.
1.Treatment principles
The radiological lung injury with only imaging manifestations without clinical symptoms can be treated without special treatment. 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.
2. Adrenocorticosteroids
It 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 methylprednisolone is 40-80mg/d, after the symptoms improve, the dose is gradually reduced to 10-15mg/d, and finally replaced by oral prednisone until it is stopped, the total course of treatment is 4-8 weeks.
3.Anti-infection Radiation pneumonia is very easy to combine with bacterial infection, if there is high fever, high blood white blood cell count and neutrophils, 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 quickly effective.
4.Chinese medicine treatment
According to the traditional Chinese medicine, radiation is the evil of heat and toxicity, and heat can turn into fire. 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 medicine, it can significantly relieve symptoms, improve the pathological changes of pulmonary fibrosis after radiotherapy, and accelerate the recovery of lung function.
V. Susceptibility factors.
1. Radiation dosimetry factors
Radiation absorbed dose is related to the degree of lung injury, but its effect is significantly influenced by the size of daily segmentation. When patients with non-small cell lung cancer receive radiotherapy, the incidence of 2-year radiation pneumonia is 0, 7%, 13% and 36% when V20 (i.e., the volume of lung receiving >20GY irradiation to total volume ratio) is <22%, 22%-30%, 31%-40% and >40%, respectively. Therefore, to avoid severe radiation pneumonia, it is recommended that V20 should be <25%.
2.Understand previous treatment history
The risk of radiation lung injury is significantly increased with or without signs and symptoms of radiation injury. If the manifestation of radiation pneumonia occurs with the first treatment, the second treatment may cause serious reactions. Many chemotherapeutic agents not only have direct pulmonary toxic effects, but also may aggravate the lung injury effects of radiotherapy. Bleomycin, when used concurrently with radiotherapy, will be more toxic than either one of them alone. Other chemotherapeutic drugs that can increase the degree of lung injury from radiotherapy include actinomycin, cyclophosphamide, vincristine, adriamycin and gemcitabine, etc. The toxicity of simultaneous use is greater than that of alternate use.
3, close observation of changes in the condition
During the course of radiation therapy, patients should be closely observed for respiratory symptoms and elevated body temperature. The pneumonia found in the imaging examination should immediately stop radiation therapy. Once severe radiation pneumonia occurs, it is often irreversible, which shows the importance of prevention. In addition, prevention of colds and flu, smoking cessation, and active treatment of chronic lung diseases should be carried out.