Radiation-induced lung injury (RILI), including acute radiation pneumonitis and chronic radiation-induced pulmonary fibrosis (RIPF), is a side effect of radiotherapy for lung cancer and esophageal cancer. Pulmonary macrophages, as a kind of natural immune cells maintaining lung homeostasis, play a key role in the whole pathological process of RILI. In the early stage of RILI, classically activated M1 macrophages secrete proinflammatory cytokines to induce inflammation and produce massive reactive oxygen species (ROS) through ROS-induced cascade to further impair lung tissue. In the later stage of RILI, alternatively activated M2 macrophages secrete profibrotic cytokines to promote the development of RIPF. The roles of macrophage in the pathogenesis of RILI and the related potential clinical applications are summarized in this review.
Humans ; Lung/radiation effects* ; Lung Injury/physiopathology* ; Macrophages/metabolism* ; Radiation Injuries ; Radiation Pneumonitis/etiology* ; Radiotherapy/adverse effects*

Radiation-induced lung injury (RILI) is the most common complication of the radiotherapy for thoracic tumor. It can lower the ratio of local control and seriously affect the patients' quality of life. At present, the clinical management of RILI is not more than the use of glucocorticoid and anti-inflammatory agent for symptomatic treatments. These treatments do not have any preventive effect but cause much side reactions. In this paper, we review the data from the contigency researches on the mechanism of RILI, from the researches on gene therapy and stem cell-therapy, and we dicuss the more safe, more stable and more efficacious treatment of RILI.
Antioxidants ; therapeutic use ; Genetic Therapy ; methods ; Humans ; Lung ; pathology ; radiation effects ; Lung Neoplasms ; radiotherapy ; Mesenchymal Stem Cell Transplantation ; methods ; Radiation Injuries ; etiology ; therapy ; Radiation Pneumonitis ; etiology ; therapy ; Radiation-Protective Agents ; therapeutic use ; Radiotherapy, Conformal ; adverse effects

Carcinoma, Non-Small-Cell Lung ; pathology ; surgery ; Humans ; Lung Neoplasms ; pathology ; surgery ; Neoplasm Staging ; Radiation Pneumonitis ; etiology ; Radiosurgery ; adverse effects ; methods ; Radiotherapy, Image-Guided

BACKGROUNDPrevention is presently the only available method to limit radiation-induced lung morbidity. A good predictor is the key point of prevention. This study aimed to investigate if [(18)F]2-fluoro-2-deoxyglucose (FDG) uptake changes in the lung after radiotherapy could be used as a new predictor for acute radiation pneumonitis (RP).

METHODSForty-one patients with lung cancer underwent FDG positron emission tomography/computed tomography (FDG-PET/CT) imaging before and after radiotherapy. The mean standardized uptake value (SUV) was measured for the isodose regions of 0 - 9 Gy, 10 - 19 Gy, 20 - 29 Gy, 30 - 39 Gy, 40 - 49 Gy. The mean SUV of these regions after radiotherapy was compared with baseline. The mean SUV in patients who developed RP was also compared with that in those who did not. The statistical difference was determined by matched pair t test. The Radiation Therapy Oncology Group (RTOG) criteria were used for diagnosis and grading of RP.

RESULTSWith a median follow-up of 12 months, 11 (26.8%) of the 41 patients developed grade 2 and above acute RP. The mean SUV of regions (10 - 19 Gy, 20 - 29 Gy, 30 - 39 Gy, 40 - 49 Gy) increased after radiation therapy in all 41 patients. The mean SUVs after radiation therapy were 0.54, 0.68, 1.31, 1.74 and 2.27 for 0 - 9 Gy, 10 - 19 Gy, 20 - 29 Gy, 30 - 39 Gy and 40 - 49 Gy, respectively. Before the radiation therapy, the mean SUV in each region was 0.53, 0.52, 0.52, 0.53 and 0.54, respectively. These patients had significantly higher FDG activities in regions receiving 10 Gy or more (P < 0.001). Compared with their counterparts, the elevation of SUV was significantly greater in those patients who developed acute RP subsequently.

CONCLUSIONThe mean SUV of the lung tissue may be a useful predictor for the acute RP. FDG-PET/CT may play a new role in the study of the radiation damage of the lung.

Aged ; Aged, 80 and over ; Female ; Fluorodeoxyglucose F18 ; Humans ; Male ; Middle Aged ; Positron-Emission Tomography ; methods ; Radiation Pneumonitis ; diagnosis ; etiology ; Tomography, X-Ray Computed ; methods

OBJECTIVETo compare the treatment results of three-dimensional conformal radiotherapy (3D-CRT) and conventional radiotherapy (2D) for patients with locally advanced non-small-cell lung cancer (NSCLC).

METHODSFive hundred and twenty seven patients with stage III NSCLC treated between Jan 2000 and Dec 2006 were included in this study. Among them, 253 cases were treated with 3D-CRT, and 274 with conventional radiotherapy. In the 3D group, 159 (62.8%) patients received chemoradiotherapy, 77 with total radiotherapy dose of > 60 Gy, 49 with 50 - 60 Gy. In the 2D group, 127 (46.4%) patients received chemoradiotherapy, 48 with total radiotherapy dose of > 60 Gy, 75 with 50 - 60 Gy.

RESULTSThe 1-, 3-, 5-year overall survival rates (OS) and median survival time for patients treated with 3D-CRT were 73.3%, 26.1%, 14.4% and 20.1 months, respectively, and that of patients treated with 2D radiotherapy were 61.0%, 13.8%, 8.0% and 15.6 months, respectively (P = 0.002). The 1-, 3-, 5-year cause-specific survival rates (CSS) were 79.0%, 33.3%, and 20.8% for the 3D group and 65.1%, 16.7%, 11.2%, respectively, for the 2D group (P = 0.000). The 1-, 3-, and 5-year locoregional control rates were 71.6%, 34.3% and 31.0% for patients treated with 3D radiotherapy and 57.3%, 22.1% and 19.2%, respectively, for patients treated with 2D treatment (P = 0.002). The results of multivariate analysis showed that 3D-CRT, KPS, clinical tumor response and pretreatment hemoglobin level were independently associated with increased OS and CSS. No statistically significant differences were found between the radiation complications in the two groups.

CONCLUSIONSThe results of our study demonstrate that 3D-conformal radiotherapy improves the survival rate in patients with stage III NSCLC compared with that of 2D radiation therapy.

Aged ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; pathology ; radiotherapy ; Chemoradiotherapy ; Female ; Follow-Up Studies ; Hemoglobins ; metabolism ; Humans ; Lung Neoplasms ; drug therapy ; pathology ; radiotherapy ; Male ; Neoplasm Staging ; Radiation Pneumonitis ; etiology ; Radiotherapy Dosage ; Radiotherapy, Conformal ; adverse effects ; methods ; Survival Rate

OBJECTIVEThe purpose of this study was to investigate whether the associated diabetes mellitus exerts a certain effect on the development of radiation pneumonitis in patients with non-small cell lung cancer.

METHODS156 patients with non small cell lung cancer were treated with three-dimensional conformal radiation therapy in this study, including 52 associated with diabetes and 104 non-diabetic patients as a control group. All the patients were followed up for one year and the development of radiation pneumonitis was observed. Radiation pneumonitis was diagnosed according to the criteria of radiation therapy oncology group. The morbidities of radiation pneumonitis in the two groups were compared. The relationships between the morbidity of radiation pneumonitis and blood sugar level as well as diabetic history were analyzed by chi-square test.

RESULTSTwenty-one (40.4%) of 52 patients with diabetes had radiation pneumonitis (grade 2 or greater), while in the control group only 22 of 104 patients (21.2%) suffered from radiation pneumonitis. There was a statistically significant difference between the two groups in the morbidity of the radiation pneumonitis (P < 0.05), with a relative risk value of 2.05 (95% CI, 1.17, 3.58). The rate of the radiation pneumonitis in the patients with a lower blood sugar level (< 7 mmol/L) was significantly lower than that in those with a higher blood sugar level (30.6% vs. 62.5%, P < 0.05). However, the rate of radiation pneumonitis in the patients with a longer diabetic history was not significantly different from that in those with a shorter diabetic history (P > 0.05).

CONCLUSIONNon-small cell lung cancer patients with diabetes mellitus are more vulnerable than those without to radiation pneumonitis. Therefore, diabetes mellitus is a newly discovered risk factor to radiation pneumonitis, and the blood sugar level is positively correlated with the morbidity of radiation pneumonitis.

Adult ; Aged ; Blood Glucose ; analysis ; Carcinoma, Non-Small-Cell Lung ; blood ; complications ; radiotherapy ; Diabetes Mellitus ; blood ; Female ; Humans ; Lung Neoplasms ; blood ; complications ; radiotherapy ; Male ; Middle Aged ; Morbidity ; Radiation Pneumonitis ; epidemiology ; etiology ; Radiotherapy, Conformal ; adverse effects ; Risk Factors

BACKGROUND: The main manifestations of radiation pneumonitis are injury of alveolar epithelial and endothelial cells, abnormal expression of cytokines, abnormal proliferation of fibroblasts and synthesis of fibrous matrix. The occurrence of radiation pneumonitis is associated with multiplecytokine level abnormality. These cytokines can also be used as bio-markers to predict the occurrence of radiation pneumonitis. This study was to evaluate the correlation between the change of apurinic/apyrimidinic endonuclease 1/redox factor-1 (Ape1/Ref-1), intercellular adhesion molecules 1 (ICAM-1) and interleukin-17A (IL-17A) before and after radiotherapy and radiation pneumonitis for local advanced non-small cell lung cancer (NSCLC) patients with concurrent chemoradiotherapy. METHODS: NSCLC patients (68 cases) were treated with concurrent radiotherapy and chemotherapy, every patient's normal tissue were controlled with a same radation dose. 68 local advanced NSCLC patients with concurrent chemoradiotherapy were detected the levels of Ape1/Ref-1, ICAM-1 and IL-17A in serum by ELISA before radiotherapy and in the 14th week after radiotherapy. Acute and advanced radiation pulmonary injury was graded according to Radiation Therapy Oncology Group/European Organization For Research and Treatment (RTOG/EORTC) diagnostic and grading criteria. Grade 2 or more radiation pneumonitis was taken as the main end point. RESULTS: Eighteen cases out of 68 developed radiation pneumonitis, 50 of 68 cases have no radiation pneumonia development. There was no significant change of Ape1/Ref-1 levels before and after radiotherapy in radiation pneumonitis group (P>0.05). There was no significant change of Ape1/Ref-1 concentration in serum after radiotherapy between radiation pneumonitis group and non-radiation pneumonitis group (P>0.05). Compared with before radiotherapy, upregulation degree of ICAM-1 levels in radiation pneumonitis group was significantly higher than that in non- radiation pneumonitis group (P<0.05). There was no significant change of IL-17A concentration before and after radiotherapy in radiation pneumonitis group, but after radiotherapy IL-17A concentration in serum were remarkably higher than that in non-radiation pneumonitis group (P<0.05). Correlation analysis found that the change of ICAM-1 before and after radiotherapy has no obvious correlation with the incidence of radiation pneumonitis, and IL-17A change has obvious correlation with the incidence of radiation pneumonitis. CONCLUSIONS On the basis of strictly controlling radiation dose on normal tissue, IL-17A in serum could be the predictive factors of radiation pneumonitis for local advanced NSCLC patients with concurrent chemoradiotherapy.
Aged ; Carcinoma, Non-Small-Cell Lung ; blood ; drug therapy ; radiotherapy ; Chemoradiotherapy ; adverse effects ; DNA-(Apurinic or Apyrimidinic Site) Lyase ; blood ; Female ; Humans ; Intercellular Adhesion Molecule-1 ; blood ; Interleukin-17 ; blood ; Male ; Middle Aged ; Radiation Pneumonitis ; blood ; etiology

BACKGROUND: The incidence of symptomatic radiation pneumonitis (RP) and its relationship with dose-volume histogram (DVH) parameters in non-small cell lung cancer (NSCLC) patients receiving epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) and concurrent once-daily thoracic radiotherapy (TRT) remain unclear. We aim to analyze the values of clinical factors and dose-volume histogram (DVH) parameters to predict the risk for symptomatic RP in these patients. METHODS: Between 2011 and 2019, we retrospectively analyzed and identified 85 patients who had received EGFR-TKIs and once-daily TRT simultaneously (EGFR-TKIs group) and 129 patients who had received concurrent chemoradiotherapy (CCRT group). The symptomatic RP was recorded according to the Common Terminology Criteria for Adverse Event (CTCAE) criteria (grade 2 or above). Statistical analyses were performed using SPSS 26.0. RESULTS: In total, the incidences of symptomatic (grade≥2) and severe RP (grade≥3) were 43.5% (37/85) and 16.5% (14/85) in EGFR-TKIs group vs 27.1% (35/129) and 10.1% (13/129) in CCRT group respectively. After 1:1 ratio between EGFR-TKIs group and CCRT group was matched by propensity score matching, chi-square test suggested that the incidence of symptomatic RP in the MATCHED EGFR-TKIs group was higher than that in the matched CCRT group (χ2=4.469, P=0.035). In EGFR-TKIs group, univariate and multivariate analyses indicated that the percentage of ipsilateral lung volume receiving ≥30 Gy (ilV30) [odds ratio (OR): 1.163, 95%CI: 1.036-1.306, P=0.011] and the percentage of total lung volume receiving ≥20 Gy (tlV20) (OR: 1.171, 95%CI: 1.031-1.330, P=0.015), with chronic obstructive pulmonary disease (COPD) or not (OR: 0.158, 95%CI: 0.041-0.600, P=0.007), were independent predictors of symptomatic RP. Compared to patients with lower ilV30/tlV20 values (ilV30 and tlV20cut-off point values) and COPD had a significantly higher risk for developing symptomatic RP, with a hazard ratio (HR) of 1.350 (95%CI: 1.190-1.531, P<0.001). CONCLUSIONS Patients receiving both EGFR-TKIs and once-daily TRT were more likely to develop symptomatic RP than patients receiving concurrent chemoradiotherapy. The ilV30, tlV20, and comorbidity of COPD may predict the risk of symptomatic RP among NSCLC patients receiving EGFR-TKIs and conventionally fractionated TRT concurrently.
Carcinoma, Non-Small-Cell Lung/radiotherapy* ; ErbB Receptors/genetics* ; Humans ; Lung Neoplasms/radiotherapy* ; Protein Kinase Inhibitors/adverse effects* ; Pulmonary Disease, Chronic Obstructive/complications* ; Radiation Pneumonitis/etiology* ; Radiotherapy Dosage ; Retrospective Studies

OBJECTIVETo investigate the predictive value of low dose volume of the lung on acute radiation pneumonitis (RP) in patients with esophageal cancer treated with three-dimensional conformal radiotherapy (3D-CRT) only, and to analyze the relation of comprehensive parameters of the dose-volume V5, V20 and mean lung dose (MLD) with acute RP.

METHODSTwo hundred and twenty-two patients with esophageal cancer treated by 3D-CRT have been followed up. The V5-V30 and MLD were calculated from the dose-volume histogram system. The clinical factors and treatment parameters were collected and analyzed. The acute RP was evaluated according to the RTOG toxicity criteria.

RESULTSThe acute RP of grade 1, 2, 3 and 4 were observed in 68 (30.6%), 40 (18.0%), 8 (3.6%) and 1 (0.5%) cases, respectively. The univariate analysis of measurement data:The primary tumor length, radiation fields, MLD and lung V5-V30 had a significant relationship with the acute RP. The magnitude of the number of radiation fields, the volume of GTV, MLD and Lung V5-V30 had a significant difference in whether the ≥ grade 1 and ≥ grade 2 acute RP developed or not. Binary logistic regression analysis showed that MLD, Lung V5, V20 and V25 were independent risk factors of ≥ grade 1 acute RP, and the radiation fields, MLD and Lung V5 were independent risk factors of ≥ grade 2 acute RP. The ≥ grade 1 and ≥ grade 2 acute RP were significantly decreased when MLD less than 14 Gy, V5 and V20 were less than 60% and 28%,respectively. When the V20 ≤ 28%, the acute RP was significantly decreased in V5 ≤ 60% group. When the MLD was ≤ 14 Gy, the ≥ 1 grade acute RP was significantly decreased in the V5 ≤ 60% group. When the MLD was >14 Gy, the ≥ grade 2 acute RP was significantly decreased in the V5 ≤ 60% group.

CONCLUSIONSThe low dose volume of the lung is effective in predicting radiation pneumonitis in patients with esophageal cancer treated with 3D-CRT only. The comprehensive parameters combined with V5, V20 and MLD may increase the effect in predicting radiation pneumonitis.

Acute Disease ; Adult ; Aged ; Aged, 80 and over ; Carcinoma, Squamous Cell ; radiotherapy ; Dose-Response Relationship, Radiation ; Esophageal Neoplasms ; radiotherapy ; Female ; Follow-Up Studies ; Humans ; Lung ; radiation effects ; Male ; Middle Aged ; Radiation Pneumonitis ; etiology ; pathology ; Radiotherapy Dosage ; Radiotherapy, Conformal ; adverse effects ; Retrospective Studies

OBJECTIVETo study the differences of objective response rate (ORR), side effects and survival among patients with limited-stage small cell lung cancer (LD-SCLC), who received concurrent chemoradiotherapy, sequential chemoradiotherapy or chemotherapy alone, and to analyze the influencing factors on their survival.

METHODSOne hundred and sixty-six patients diagnosed as LD-SCLC in Peking Union Medical College Hospital from January 2000 to December 2009 were included in this study. The differences of objective response rates, side effects and survival rates were analyzed by χ2 test. Kaplan-Meier test was used to calculate the overall survival (OS) and progress-free survival (PFS). Cox regression was used to detect the influencing factors on survival time of the patients.

RESULTSThe patients were divided into three groups: concurrent chemoradiotherapy (49 cases), sequential chemoradiotherapy (62 cases) and chemotherapy alone (55 cases). The chemotherapy was based on CE/EP regimen, with an average cycle of 5.2. Radiotherapy was of a common or 3-dimensional conformal technology, for regular segmentation irradiation with an average dose of 49.6 Gy. The total ORR was 73.4%, OS and PFS were 22.9 months and 10.8 months, 1, 3, 5-year survival rates were 82.7%, 31.8%, 18.6%, respectively. For the concurrent group, sequential group and chemotherapy alone group, the ORR was 89.4%, 67.2% and 66.0%, respectively. Compared the chemotherapy alone group and concurrent group with the sequential group, there were significant differences (P<0.05). For the concurrent group, sequential group and chemotherapy alone group, the median OS was 29.7 months, 22.6 months, and 19.5 months; the median PFS was 12.7 months, 10.8 months, and 9.8 months, respectively, with a non-significant difference between each two groups (P>0.05). For the concurrent group, sequential group and chemotherapy alone group, the 1-year survival rates were 91.1%, 86.3%, and 65.6%, the 3-year survival rates were 44.2%, 28.3% and 22.8%, and the 5-year survival rates were 24.2%, 21.4% and 11.1%, respectively, with significant differences among them (P<0.05). The major side effects were myelosuppression, gastrointestinal reactions, radiation pneumonia and radiation esophagitis. For the concurrent group, sequential group and chemotherapy alone group, the incidence of myelosuppression were 84.4%, 76.8% and 60.0%, respectively, with a significant difference (P=0.008) between the concurrent group and chemotherapy alone group. For the concurrent group and sequential group, the incidences of radiation pneumonia were 22.2% and 22.9%, with a non-significant difference (P=0.940). The incidences of radiation esophagitis were 47.2% and 16.7%, respectively, with a significant difference (P=0.002). Multivariate analysis showed that OS was significantly associated with gender (P=0.018) and ECOG score (P=0.009), and PFS was significantly associated with gender (P=0.050).

CONCLUSIONSFor LD-SCLC, concurrent chemoradiotherapy can significantly increase the objective response rate. Concurrent chemoradiotherapy and sequential chemoradiotherapy compared with chemotherapy alone can extend survival, and concurrent chemoradiotherapy is better, but the differences among the three regimens are not significant. Gender and ECOG score are important influencing factors of survival.

Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Carboplatin ; therapeutic use ; Chemoradiotherapy ; Cisplatin ; therapeutic use ; Combined Modality Therapy ; Disease-Free Survival ; Epirubicin ; therapeutic use ; Esophagitis ; etiology ; Etoposide ; therapeutic use ; Female ; Humans ; Lung Neoplasms ; drug therapy ; pathology ; radiotherapy ; Male ; Middle Aged ; Myelopoiesis ; radiation effects ; Radiation Pneumonitis ; etiology ; Radiotherapy, Conformal ; adverse effects ; Remission Induction ; Small Cell Lung Carcinoma ; drug therapy ; pathology ; radiotherapy ; Survival Rate