Objective:To analyze the clinical characteristics of long-term survival patients with advanced non-small cell lung cancer (NSCLC) treated with chemotherapy combined with primary tumor radiotherapy, and to establish a Nomogram prognostic model, aiming to provide a certain reference for making a decision about the treatment of advanced NSCLC.Methods:A retrospective analysis was made on the data of 260 NSCLC patients who participated in two prospective clinical studies from January 2003 to May 2012 and the data of 138 NSCLC patients admitted to the Affiliated Cancer Hospital of Guizhou Medical University from January 2014 to August 2020. The former 260 cases were used as a training set and the latter 138 cases were used as the validation set. The overall survival (OS) of ≥ 18 months was defined as long-term survival (LTS). The clinical characteristics of LTS patients were compared with those with OS less than 18 months. The clinical characteristics and treatment-related parameters between the two types of patients were compared using the χ2 test. A multivariate analysis was made using logistic regression, and a nomogram model was built using RStudio. Results:The median OS of the training set was 13.4 months (95% CI: 11.9-14.9), with 1-, 2-, and 3-year OS rates of 55.4%, 19.1%, and 11.9%, respectively. In the training set, 87 cases had LTS and were classified as the LTS group, while 173 cases had OS less than 18 months and were classified as the non-LTS group. The univariate analysis showed that the prognostic factors affecting LST included the KPS score, T status, the number of metastatic organs, the number of metastatic lesions, brain metastasis, bone metastasis, the number of chemotherapy cycles, the biologically effective dose (BED) to the primary tumor, hemoglobin level, platelet count, plasma D-dimer, fibrinogen level, lactate dehydrogenase, and lung immune prognostic index (LIPI; χ2=4.72-12.63, P < 0.05). The multivariable analysis showed that the independent prognostic factors of LTS included a number of chemotherapy cycles ≥ 4, BED ≥ 70 Gy, platelets ≤ 220×10 9/L, D-dimer ≤ 0.5 mg/L, and a good LIPI score ( P= 0.002, 0.036, 0.005, 0.008, and 0.002). A nomogram model was established using the meaningful parameters obtained in the multivariable analysis, determining that the training and validation sets had a consistency index (C-index) of 0.750 and 0.727, respectively. As shown by the analytical result of the corrected curves, for the advanced NSCLC patients treated with thoracic radiotherapy, their LTS probability predicted using the nomogram prognostic model was highly consistent with their actual LTS probability. Both the analytical result of the receiver operating characteristic (ROC) curves and the decision curve analysis (DCA) result showed that the composite prediction model was more beneficial than a single prediction model. Conclusions:For patients with advanced NSCLC treated with thoracic radiotherapy, the independent prognostic factors of LTS included the number of chemotherapy cycles, BED, platelet count, pre-chemotherapy D-dimer, and LIPI score. The Nomogram prognostic model built based on these prognostic factors is a convenient, intuitive, and personalized prediction model used to screen patients who can benefit from thoracic radiotherapy.

Objective:To study the relationship between endoplasmic reticulum stress (ERS) and apoptotic protein and myocardial pathological changes in rats after endostar combined with low-dose X-ray irradiation.Methods:Forty SD rats were evenly divided into four groups: control group (intraperitoneal injection of equal volume physiological saline, once per day, 14 d), endostar group (intraperitoneal injection of endostar 6 mg/kg, once per day, 14 d), irradiation group (15 Gy divided into 3 times X-ray irradiation) and combination group (intraperitoneal injection of endostar after irradiation at the same dose and time as the endostar group). At 1 and 6 months after treatment, myocardial tissues of rats were prepared for HE staining and Masson staining to observe the myocardial histological changes. TUNEL assay was used to detect myocardial cell apoptosis, and ImageJ software was utilized to calculate myocardial collagen volume fraction (CVF). The expression levels of ERS and apoptotic protein glucose-regulated protein 78 (GRP78), protein kinase-like endoplasmic reticulum kinases (PERK), CCAAT/enhancer binding protein homologous protein (CHOP) and cysteine-containing aspartate-specific protease-12 (Caspase-12) were detected by Western blot. One-way ANOVA was conducted using GraphPad Prism 8.0.1 software, and comparison between two groups was conducted using t-test. Results:At 6 months after treatment, the myocardial interstitium in the irradiation and combination groups was widened, showing strip-like or reticular fibrosis changes, and the myocardial interstitium had diffuse collagen fiber deposition. Compared with the control group, CVF was increased significantly (both P<0.01). At 1 and 6 months after treatment, the apoptotic index of myocardial cells in the combination group was significantly higher than that in the control group ( P<0.05, <0.001). At 1 and 6 months after treatment, the expression levels of GRP78 protein in the irradiation and combination groups were increased (all P<0.01), and the expression levels of PERK and CHOP proteins in the combination group were increased compared to those in the control group (both P<0.05). At 6 months after treatment, the expression levels of PERK and CHOP proteins in the irradiation group were increased compared to those in the control group (both P<0.05). Compared with the control group, Caspase-12 expression levels at 1 and 6 months after treatment were increased in the endostar, irradiation and combination groups (all P<0.05). Conclusions:The expression levels of ERS and apoptotic proteins are related to cardiac injury caused by irradiation in rats. After low-dose X-ray combined with endostar treatment, ERS is aggravated and myocardial apoptosis is increased.

Objective:To explore the characteristics of failure patterns of three-dimensional radiotherapy combined with first-line drug therapy for primary tumors of stage Ⅳ non-small cell lung cancer(NSCLC)and investigate the influence of radiotherapy-related factors.Methods:708 patients newly-diagnosed with stage Ⅳ NSCLC from March 2003 to July 2020 were selected. Chi-square test was used for univariate analysis of failure patterns. Kaplan-Meier method, Log-rank test and Cox regression model were employed for multivariate analysis. Results:The incidence of first-line treatment failure in 708 cases was 71.2%, and the incidence of treatment failure was 22.7%, 28.8%, 13.3%, and 6.4% for ≤6 months, >6-12 months, >12-24 months, and>24 months, respectively, and the median survival time was 7.2, 13.4, 22.2, and 37.6 months, which was significantly different( χ2=226.013, P<0.001). The incidence of recurrence failure(RF)was 21.3%.There was no significant difference in the incidence of RF between oligometastasis(OM)and non-oligometastasis(NOM). The incidence of DF was 66.3% and the order of incidence was brain>bone>lung>pleural cavity>liver>distant lymph nodes>adrenal gland>other sites, occurring in approximately 1/2 of AM and 1/3 of PSM cases. Metastatic status, time to treatment failure, pathological type, gender, combined treatment intensity were the independent influencing factors for predicting prognosis. Conclusions:The failure pattern of radiotherapy for primary tumors of stage Ⅳ NSCLC is different from that of first-line drug therapy, with significantly lower local failure and predominantly metastatic failure. The incidence of brain metastasis is the highest. The later time to treatment failure, the longer the overall survival(OS). OM, female, non-squamous cell carcinoma, late treatment failure, 4-6 cycles of chemotherapy over the same period ≥63 Gy are the independent prognostic factors for prolonging survival.

Objective:To analyze the mediastinal displacement of target volume in the postoperative radiotherapy (PORT) process for non-small cell lung cancer (NSCLC) and the value of mid-term evaluation.Methods:For 100 patients with postoperativeN 2 stage NSCLC, R 1-2 and any N staging, bone anatomy was utilized to measure the change of the first and second CT localization on the same level. Statistical analysis were performed using the WilCoxon, Kruskal-Wallis and χ2 tests. The cut-off values were calculated with the receiver operating characteristic (ROC) curve. Results:Among the included patients, in the PORT process, the mediastinal displacement in the x (front and rear), Y (left and right) and Z (upper and lower) directions were 0.04-0.53 cm, 0.00-0.84 cm and 0.00-1.27 cm, respectively, and the order of mediastinal displacement distance wasz > Y> X,respectively. According to the ROC curve calculation, the cut-off values were 0.263, 0.352 and 0.405, respectively, which were greater than the cut-off values in 25 cases (25%), 30 cases (30%) and 30 cases (30%), respectively. There was significant difference in the three-dimensionalmediastinal displacement ( P=0.007, <0.001 and<0.001). The mediastinal displacement in thex, Y and Z directions had no statistical significance regarding resection site ( P=0.355, 0.239 and 0.256) and operation mode ( P=0.241, 0.110 and 0.064). Comparative analysis of modified whole group mediastinal shift> and cut-off values, medium-simulation (m-S) and the originally planned radiotherapy shown that there was no significant difference in the incidence of radiation esophagitis (RE) and radiation pneumonitis in PORT patients (all P>0.05); however, the incidence of ≥grade 3 RE in the modified plan after m-S was significantly lower than that in the originally planned PORT patients, which were 0 and 7%, respectively ( P<0.001). Conclusions:Mediastinal displacement exists in the PORT process of N 2 or/and R 1-2 cases after radical operation of NSCLC, and obvious movement occurs in 20%-30% of patients. Relocating and modifying the target volume and radiotherapy plan in the middle of the PORT process is beneficial to quality assurance and quality control.

Objective:To investigate the implication of micro RNA-21(miR-21) in Endostar combined with X-ray irradiation of cardiac fibroblasts (CF).Methods:Rat CFs were used in this experiment and been divided into the blank control group, 10 Gy X-ray irradiation group, Endostar group, 10 Gy X-ray+ Endostar group, 10 Gy X-ray+ Endostar+ NC mimic group (negative control 1), 10 Gy X-ray+ Endostar+ miR-21 mimic group, 10 Gy X-ray+ Endostar+ NC inhibitor group (negative control 2) and 10 Gy X-ray+ Endostar+ miR-21 inhibitor group. The proliferation of CF was determined by Methyl thiazolyl tetrazolium (MTT) assay. The expression level of Collagen Ⅰ protein was analyzed by Western blot. The expression levels of Collagen Ⅰ and miR-21 mRNA were assayed by real-time quantitative polymerase chain reaction (q-PCR).Results:In the 10 Gy X-ray+ Endostar+ miR-21 mimic group, the CF proliferation, Collagen Ⅰ and miR-21 mRNA were increased significantly compared with those in the blank control group, 10 Gy X-ray+ Endostar group, and negative control group 1 (all P<0.05). In the 10 Gy X-ray+ Endostar+ miR-21 inhibitor group, the CF proliferation and expression levels of Collagen Ⅰ mRNA were decreased significantly compared with those in the blank control group, 10 Gy X-ray+ Endostar group and negative control group 2(all P<0.05). Conclusions:The CF proliferation and Collagen Ⅰ expression are increased when the expression level of miR-21 gene is simulated. When inhibiting the expression of miR-21 gene, the CF proliferation and Collagen Ⅰ expression are reduced.

Objective:To analyze the radiotherapy-related factors affecting the survival of non-small cell lung cancer (NSCLC) patients complicated with malignant pleural effusion (MPE)(MPE-NSCLC).Methods:From 2007 to 2019, 256 patients pathologically diagnosed with MPE-NSCLC received primary treatment. Among them, 117 cases were enrolled in this study. All patients were divided into two groups according to the radiation dose (<63 Gy and≥63 Gy). Propensity score matching (PSM) was performed to further adjust the confounding factors (Calipers value=0.1). The impact of radiotherapy-related factors on the overall survival (OS) was analyzed by Kaplan—Meier method, log-rank test and Cox’s regression model. Results:Primary tumor radiotherapy significantly prolonged the OS ( P<0.001). The radiation dose escalation (36.0-44.1 Gy, 45.0-62.1 Gy, 63.0-71.1 Gy) of primary tumor significantly prolonged the OS ( P<0.001). The corresponding median OS were 5, 13 and 18 months, respectively. Before the PSM, univariate analysis suggested that radiation dose ≥63 Gy, gross tumor volume (GTV)<157.7 cm 3 and stations of metastatic lymph node (S-mlN)≤5 were significantly associated with better OS (all P<0.05) and T 4N 3 was significantly associated with worse OS ( P=0.018). After the PSM, univariate analysis indicated that radiation dose ≥63 Gy was significantly associated with better OS ( P=0.013) and S-mlN ≤5 had a tendency to prolong the OS ( P=0.098). Prior to the PSM, multivariate analysis showed that radiation dose ≥63 Gy was an independent favorable factor of OS ( HR=0.566, 95% CI 0.368-0.871, P=0.010) and GTV<157.7 cm 3 had a tendency to prolong the OS ( HR=0.679, 95% CI 0.450-1.024, P=0.065). After the PSM, multivariate analysis revealed that radiation dose ≥63 Gy was still an independent favorable factor of OS ( HR=0.547, 95% CI 0.333~0.899, P=0.017). No ≥grade 4 radiation toxicity occurred. The incidence rates of grade 3 radiation esophagitis and pneumonitis were 9.4% and 5.1%, respectively. Conclusion:For MPE-NSCLC, radiotherapy dose of primary tumor may play a key role in improving OS on the basis of controllable MPE.

The prognosis of patients with brain metastases from non-small cell lung cancer (NSCLC) is poor. Tyrosine kinase inhibitor (TKI) significantly improves the prognosis of patients with epidermal growth factor receptor (EGFR) sensitive mutation. EGFR sensitive mutations are associated with the incidence of brain metastases in NSCLC and may affect the efficacy of radiotherapy and TKI therapy. Both EGFR-TKI and radiotherapy are effective for EGFR-mutant NSCLC with brain metastases. Whether the combination of EGFR-TKI and radiotherapy may improve the prognosis compared with EGFR-TKI or radiotherapy alone has been studied. Retrospective studies have indicated that upfront radiotherapy, especially upfront stereotaxic radiosurgery combined with EGFR-TKI may be more advantageous in improving the prognosis, but it is still controversial. Therefore, clinical research progresses on the radiotherapy for EGFR-mutant NSCLC patients with brain metastases were reviewed.

Objective:To assess the effects of recombinant human endostatin (rh-ES) on radiation-induced myocardial fibrosis.Methods:Totally 40 SD rats were randomly divided into 4 groups, including A group as normal control, B group receiving rh-ES with a dosage of 6 mg·kg -1·d -1, in traperitoneal injection, for 14 consecutive days, C group with local heart irradiation delivered to the precordial region of rats in five fractions with a dose of 25 Gy, D group receiving rh-ES as the same as B group and local heart irradiation as C group. At 1 and 3 months after irradiation, five rats were killed under anesthesia. Mason staining was used to observe myocardial injury and fibrosis. Western blotting was used to detect the expression of TGF-β1, CTGF and COL-I in myocardium. Results:Masson staining showed that no obvious myocardial fibrosis was found in group B at 1 month and 3 months after irradiation, while collagen fibers were distributed in myocardium in groups C and D. One month after irradiation, the result of semi-quantitative analysis showed that the CVF in group A was (5.20 ±0.75)%, which was significantly lower than that in group C (10.12 ±2.17)% ( t=4.74、4.93, P<0.01) and the CVF in group D (10.32 ±1.36), and the CVF of group C was similar to that of group D ( P<0.01). Three months after irradiation, CVF in group C (13.17±2.67)% was still higher than that in group A (5.23 ±1.32)% ( t=4.49, P<0.01), but lower than that in group D (16.92 ±3.58)% ( t=3.19, P<0.05). One month after irradiation, the expression of TGF-β1 in group A was 0.441 ±0.063, lower than that in group C (0.817 ±0.079, t=5.81, P<0.01). Three months after irradiation, the expression of TGF-β1 in group A was 0.501 ±0.110, lower than that in group C (0.832 ±0.150, t=4.19, P<0.01), and the expression of TGF-β1 in group D was 1.403 ±0.133, which was significantly higher than that in group C ( t=7.24, P<0.01). Conclusions:Radiation can cause the formation of myocardial fibrosis, and recombinant human endostatin may aggravate the formation of late radiation fibrosis.

Objective:To retrospectively analyze the clinical efficacy and safety of three-dimensional radiotherapy for the primary tumors in patients with stage Ⅳ non-small cell lung cancer complicated with malignant pleural effusion (MPE-NSCLC).Methods:A total of 198 patients who were initially pathologically diagnosed with MPE-NSCLC from January 2007 to April 2018 were enrolled and divided into the untreated group ( n=45), drug group ( n=57) and radiotherapy group ( n=96), respectively. The short-term efficacy, overall survival (OS) and adverse events in the drug and radiotherapy groups were analyzed. The OS rate was analyzed by Kaplan-Meier method and log-rank test. Clinical prognosis was evaluated by multivariate Cox′s regression model. Results:In the radiotherapy group, the objective response rate and non-response rate was 54% and 46%, significantly better than 25% and 75% in the drug group ( P=0.007). In the radiotherapy group, the 1-, 2-, 3-, 5-year OS and median survival was 47%, 18%, 6%, 1% and 12 months, remarkably higher than 15%, 3%, 2%, 0% and 5 months in the drug group, respectively (all P<0.001). Multivariate Cox′s regression analysis showed that radiotherapy for the primary tumors was an independent prognostic factor to prolong the OS ( P<0.001). Radiotherapy at a dose of ≥63 Gy and 4-6 cycles of chemotherapy tended to prolong the OS ( P=0.063 and 0.071). The OS of patients with EGFR mutation receiving radiotherapy combined with molecular target therapy was significantly better than that of those with unknown EGFR status treated with radiotherapy and chemotherapy ( P=0.007). Addition of radiotherapy for the primary tumors did not significantly increase the incidence of adverse events ( P>0.05). Conclusion:Addition of three-dimensional radiotherapy for the primary tumors in MPE-NSCLC patients may prolong the OS and yield tolerable adverse events.

Objective:To investigate the primary tumor volume change and timing of radiotherapy for patients with stage Ⅳ non-small cell lung cancer with EGFR mutation during molecular targeted therapy.Methods:Simulated CT scanning measurement and analysis were performed to observe the volume changes of primary tumors before and after treatment with a time interval of 10 days in this prospective study. Positioning and volume measurement were terminated when the volume change was 5% or less between two time points before and after treatment or 90 days after treatment. Primary tumor radiation therapy was then performed, acute radiation-induced injury was recorded, and the implementation and simulation of related parameters of radiotherapy plans were compared.Results:Twenty-nine of 30 cases were included in the analysis (1 case dropped off). After EGFR-TKIs treatment, the volume of all primary tumors was decreased, but the shrinking rate was inconsistent with the speed. Until the last simulated CT scanning, the maximum and minimum shrinking rates were 90% and 28%, respectively. There was no case of termination within 30 days of treatment, and the average tumor volume was significantly decreased within 40 days and the average tumor volume significantly differed every 10 days ( P<0.001). After 40 days, the volume shrinking rate of primary tumors ≤5% gradually appeared, and one patient presented with a volume shrinking rate of >5% on 90 days. During this time, the average volume shrinking rate slowed down and became stable, ranging from 49.15% to 54.77%. Moreover, the average volume continued to gradually shrink after slight increase at 70 days. There was no significant difference in the average volume every 10 days ( P>0.05). After the termination of simulated CT scanning, the dose of primary tumor was (69±7) Gy for patients receiving radiotherapy. Two patients had grade 2 acute radiation-induced pneumonitis and 3 patients had grade 3 acute radiation-induced pneumonitis. In addition, 1 patient had grade 2 radiation-induced esophagitis. According to the technology and dose parameters of radiotherapy plan, simulated radiotherapy plans before and 40 days after EGFR-TKIs treatment were designed. The timing of implementation plan was significantly better than that before EGFR-TKIs treatment (all P<0.05), whereas it was similar to that at 40 days after EGFR-TKI treatment ( P>0.05). Conclusions:The primary tumor shrinking rate is gradually slowed down over time after EGFR-TKIs treatment in patients with stage Ⅳ non-small cell lung cancer. The average tumor volume is significantly decreased within 40 days and then the shrinking rate becomes slow. The tumor shrinking rate of each case is inconsistent. Radiotherapy at 40 days after treatment is probably the optimal timing to obtain high dose and control radiation-induced injury.