At present, the incidence of lung cancer is showing a rapid upward trend in the world, and the mortality rate ranks first in malignant tumors in the world[21, 22]. Lung cancer has become the first cause of death from malignant tumors in China, accounting for 22.7% of all malignant tumor deaths[23, 24]. Synchronous radiotherapy and chemotherapy for non-small cell lung cancer that is not suitable for surgery has become the current standard treatment mode, and RILI is a common complication of lung cancer radiotherapy[25, 26]. RILI not only poses a great threat to the patient's prognosis and quality of life, but also hinders the clinical application of effective radiation dose[27, 28]. It is one of the dose limiting factors of chest radiotherapy and an important factor affecting the failure of local tumor control[29].
Radiotherapy is one of the main methods for the treatment of lung cancer, but due to serious complications of radiation pneumonitis, the dose of radiotherapy has decreased and the local recurrence rate has increased[30]. With the emergence of three-dimensional conformal radiotherapy and three-dimensional conformal intensity-modulated radiotherapy, the incidence of radiation pneumonitis has decreased compared with the previous. However, the data show that radiation pneumonitis with clinical symptoms occurred 7% -32%, severe radiation pneumonitis occurred 2.6% -18.0%, and death occurred 0–2%[31–33]. The occurrence of radiation pneumonitis reduces the patient's quality of life and even endangers the patient's life.
There are two manifestations of RILI, divided into two stages, namely acute radiation pneumonia and radiation pulmonary fibrosis[14, 34]. Early research believed that these two stages were a gradual process, that is, radiation pulmonary fibrosis was gradually evolved and developed from radiation pneumonia[28]. Typical radiation pneumonia generally occurs during radiotherapy or 1 to 3 months after radiotherapy. Congestion and edema of the lung tissue, increased exudation of alveolar fibrin, and thickening of the lung interstitial. Its clinical manifestation is almost no different from that of general pneumonia. Its particularity is that it is not caused by pathogenic microorganism infection, so it is often called radiation lung disease. Once diagnosed, it is often irreversible, and the clinical manifestations are mainly dry cough, less sputum, chest tightness, and chest pain[35]. Wet rales can be heard in the lung field where the lesion is occurring, and the breath sounds are rough. Severe cases will be accompanied by varying degrees of dyspnea, low fever, and normal blood leukocytes, which are not effective after antibacterial treatment[36]. The incidence of radiation-induced pulmonary fibrosis is more than 6 months after radiotherapy, and the fibrosis of the alveolar septum is accompanied by atrophy of the alveoli. Replaced and filled by fibrous connective tissue, the lung function is severely damaged and eventually leads to dyspnea and death. The percussion of the lung field where the lesion occurred showed dullness, the breathing sound was low or the fine wet rales were heard.
The results of univariate analysis in this study showed that lung function before radiotherapy was associated with RILI. RILI is mostly a latent and hidden development process. RILI with symptoms occurs in 13–37% of patients undergoing chest radiotherapy. The incidence of RILI in this study is 26%, which is consistent with it. At present, the research related to the clinical factors affecting RILI is more controversial. Some researchers believe that low KPS score[37], smoking[38], chronic obstructive pulmonary disease (COPD) [10], lung function status before radiotherapy[39], lower lung lobe tumors[40], and concurrent radiotherapy and chemotherapy can increase the risk of RILI.
So far, the academic community has not formed a unified opinion on whether the basic lung function before radiotherapy is closely related to the occurrence of radiation pneumonia. Some researchers believe that before radiotherapy, there is no direct correlation between basic pulmonary diseases such as COPD and radiation pneumonia[10]. However, some studies have pointed out that the state of lung function before radiotherapy is the main factor affecting the occurrence of RILI, even its independent risk factor[41]. The results of this study showed that patients with higher FEV1/FVC before radiation therapy had 1.855 times the risk of RILI than those with relatively lower patients. The results of the study suggest that FEV1/FVC is an independent risk factor affecting the occurrence of RILI before radiotherapy. Vdose (eg V5, V10, V15) refers to the volume of lung tissue that is irradiated above a certain dose (5 Gy, 10 Gy, 15 Gy), as a percentage of the total lung volume. Graham et al [42] research confirmed that V20 is the only independent factor that affects the occurrence of RILI. Kim et al [43] reported that V20, V30, V50 and MLD are related to the occurrence of RILI. This study also found that all DVH parameters are involved in the occurrence of RILI. Among them, multivariate analysis confirmed that V15 is the only independent factor that affects the occurrence of RILI. And V15 ≥ 25% may be an independent predictor of dosimetric occurrence of RILI.