Thorax radiotherapy using 18F-positron emission tomography/computed tomography-guided precision radiotherapy is a prognostic factor for survival in patients with extracranial oligometastatic non-small cell lung cancer:A two-center propensity score-matched analysis.

Background: This retrospective study compared positron emission tomography (PET)/computed tomography (CT) and CT in the treatment of extracranial oligometastatic non-small-cell lung cancer (NSCLC) and explored the impact of thorax radiotherapy (TRT) on patient survival. Methods: We reviewed the medical records of Chinese patients with stage IV extracranial oligometastatic NSCLC who underwent PET/CT or CT at two centers. Propensity score matching (PSM) was used to control differences in patient characteristics between the maintenance chemotherapy alone and TRT plus maintenance chemotherapy groups. Results: We analyzed 192 eligible patients. The median survival time was better in patients who received PET/CT than in those who only received CT (n = 192, 16 months vs. 6 months, p<0.001). Subgroup analysis showed the median survival time was significantly longer in the TRT plus maintenance group than in the chemotherapy alone group in patients who underwent PET/CT examinations (n = 94, 25 months vs. 11 months, p<0.001). However, there was no statistical difference in survival between both groups in patients who underwent CT examinations (n = 98, 8 months vs. 5 months, p = 0.180). A multifactorial analysis revealed a more favorable prognosis in patients who underwent PET/CT evaluation (HR: 0.343, 95% CI: 0.250-0.471, p <0.001) and TRT (HR: 0.624, 95% CI: 0.464-0.840, p = 0.002), than in those who did not. PSM was consistent with these results. Conclusions: PET/CT-guided TRT is associated with improved clinical outcomes in patients with stage IV extracranial oligometastatic NSCLC.

Treatment patterns and survival after 18F-fluorodeoxyglucose positron emission tomography/computed tomography-guided local consolidation therapy for oligometastatic non-small cell lung cancer: a two-center propensity score-matched analysis.

PURPOSE: In this retrospective study, we evaluated the treatment patterns and survival after positron emission tomography-computed tomography (PET/CT)-guided local consolidation therapy (LCT) for oligometastatic non-small cell lung cancer (NSCLC). METHODS: We reviewed the medical records of Chinese patients with oligometastatic stage IV non-small cell lung cancer (≤ 5 metastases) who had undergone PET/CT and were eligible for systemic therapy at two centers between May 2005 and August 2019. Propensity score matching (1:1) was used to reduce selection bias and imbalanced distribution of confounding factors. RESULTS: We identified 84 eligible patients and used propensity scores to create well-matched groups of 35 patients who did or did not undergo LCT. Among all patients, the 1-year overall survival (OS) rate was 47.6% and the 2-year OS rate was 22.6%. Relative to the group that did not receive LCT, the LCT group had a significantly higher OS rate (13 months vs. 7 months, p = 0.002). The two groups had similar incidences and classifications of LCT-related side effects. In multivariable analysis, LCT was found to be strongly associated with a favorable OS (hazard ratio: 0.508, 95% confidence interval: 0.311-0.828, p = 0.001). CONCLUSION: We concluded that LCT was significantly associated with improved clinical outcomes among the Chinese patients with oligometastatic NSCLC who were eligible for systemic treatment and could undergo PET/CT evaluation.

Electrospun Poly (Aspartic Acid)-Modified Zein Nanofibers for Promoting Bone Regeneration.

BACKGROUND: Critical-sized bone defects raise great challenges. Zein is of interest for bone regeneration, but it has limited ability to stimulate cell proliferation. In this regard, a poly (aspartic acid) (PAsp)-zein hybrid is promising, as PAsp can promote rat bone marrow stromal cell (rBMSCs) proliferation and osteogenic differentiation. This research aimed to develop electrospun PAsp-modified zein nanofibers to realize critical-sized bone defects repair. METHODS: Three groups of PAsp-modified zein nanofibers were prepared, they were PAsp grafting percentages of 0% (zein), 5.32% (ZPAA-1), and 7.63% (ZPAA-2). Using rBMSCs as in vitro cell model and SD rats as in vivo animal model, fluorescence staining, SEM, CCK-8, ALP, ARS staining, µCT and histological analysis were performed to verify the biological and osteogenic activities for PAsp-modified zein nanofibers. RESULTS: As the Asp content increased from 0% to 7.63%, the water contact angle decreased from 129.8 ± 2.3° to 105.5 ± 2.5°. SEM, fluorescence staining and CCK-8 assay showed that ZPAA-2 nanofibers had a superior effect on rBMSCs spreading and proliferation than did zein and ZPAA-1 nanofibers, ALP activity and ARS staining showed that ZPAA-2 can improve rBMSCs osteogenic differentiation. In vivo osteogenic activities was evaluated by µCT analysis, HE, Masson and immunohistochemical staining, indicating accelerated bone formation in ZPAA-2 SD rats after 4 and 8 weeks treatment, with a rank order of ZPAA-2 > ZPAA-1 > zein group. Moreover, the semiquantitative results of the Masson staining revealed that the maturity of the new bone was higher in the ZPAA-2 group than in the other groups. CONCLUSION: Electrospun PAsp-modified zein can provide a suitable microenvironment for osteogenic differentiation of rBMSCs, as well as for bone regeneration; the optimal membrane appears to have a PAsp grafting percentage of 7.63%.

Clinical efficacy of gemcitabine and cisplatin-based transcatheter arterial chemoembolization combined with radiotherapy in hilar cholangiocarcinoma.

BACKGROUND: Radical surgical resection is regarded as the best treatment for hepatic hilar cholangiocarcinoma. However, 60%-70% of patients have lost the chance of surgery at the time of diagnosis. Simple biliary stent or drainage tube placement may fail in a short time due to tumor invasion or overgrowth, bile accumulation, or biofilm formation. Effective palliative treatments to extend the effective drainage time are of great significance for improving the quality of life of patients and changing the prognosis of patients. AIM: To investigate the clinical efficacy of gemcitabine and cisplatin-based transcatheter arterial chemoembolization (TACE) combined with radiotherapy in hilar cholangiocarcinoma. METHODS: A retrospective analysis was conducted on patients clinically diagnosed with hilar cholangiocarcinoma from June 2014 to January 2017 at the Liaoning Provincial Cancer Hospital. Patients were evaluated by specialists, and those who were not suitable for surgery or unwilling to undergo surgery and met the inclusion criteria were included in the study. There were a total of 72 patients (34 males and 38 females) with an average age of 59.9 years (range, 40-72 years). According to percutaneous transhepatic biliary angiography and the patients' wishes, stent implantation or biliary drainage tube implantation was used to relieve biliary obstruction. The patients were divided into either a control group or a combined treatment group according to their follow-up treatment. The control group consisted of a total of 35 patients who received simple biliary drainage tube placement and biliary stent implantation (7 patients with bilateral stents and 6 with a unilateral stent) and 22 patients receiving biliary drainage tube placement alone. The combined treatment group received TACE and extracorporeal radiotherapy after biliary drainage or biliary stent implantation and consisted of a total of 37 patients, including 21 patients receiving combined treatment after biliary stent placement (14 patients with bilateral stents and 7 with a unilateral stent) and 16 undergoing combined therapy after implanting the biliary drainage tube. In the combination treatment group, the TACE chemotherapy regimen employed gemcitabine and cisplatin, and the embolic agent was iodized oil. A particular dose was determined according to the patient's body surface area and the tumor staining indicated by DSA. In vitro radiotherapy was performed with intensity-modulated radiotherapy or three-dimensional conformal radiotherapy at an average dose of 48.3 Gy. Both groups were followed from stent implantation or drainage tube implantation until the patient quitted or died. The median length of follow-up observation was 13 mo. The differences in overall survival time and the effect of different jaundice reducing methods (single stent, double stent, or biliary drainage) on the patency time and survival time of biliary stents were compared between the two groups; the related factors affecting overall survival time were analyzed. RESULTS: The median survival time of the control group was 10.5 mo; the median survival time of patients with biliary stent implantation and those with percutaneous biliary drainage was 9.6 mo and 11.4 mo, respectively, and there was no statistically significant difference between them. The median survival time of the combined treatment group was 20.0 mo, which was significantly higher than that of the control group (P < 0.05). Among patients in the combined treatment group, the median survival time of patients who underwent biliary stent implantation and those who accepted percutaneous biliary drainage before the combination therapy was 19.5 mo and 20.1 mo, respectively, and there was no significant difference between them. In the combination treatment group, the mean time of median stent patency was 15.6 mo, which was significantly higher than that of the control group (7.0 mo; P < 0.05). The independent factors affecting survival time included age, whether to receive combination therapy, percutaneous biliary drainage tube implantation, and Bismuth-Corlette classification as type IV. CONCLUSION: Gemcitabine and cisplatin-based TACE combined with radiotherapy can prolong the survival of patients with hilar cholangiocarcinoma. Independent predictors of survival include selection of combination therapy, Bismuth-Corlette classification as type IV, selection of percutaneous biliary drainage tube implantation, and age.

Dual-specificity phosphatase 6 genetic variants associated with risk of lung squamous cell carcinoma in Han Chinese.

BACKGROUND: Nonsmall cell lung cancer (NSCLC) mainly contains adenocarcinoma (AC) and squamous cell carcinoma (SqCC). This study investigated single nucleotide polymorphism (SNP) of topoisomerase II alpha (TOP2A) and dual-specificity phosphatase 6 (DUSP6) in a hospital-based case and control cohort of individuals for association with risk of different histological subtypes of NSCLC. MATERIALS AND METHODS: A total of 454 (237 SqCC and 217 AC) NSCLC patients, and 454 healthy controls were recruited for analysis of TOP2A rs471692 and DUSP6 rs2279574 genotypes using the TaqMan polymerase chain reaction technique. RESULTS: TOP2A rs471692 and DUSP6 rs2279574 SNPs were in complete linkage disequilibrium; however, frequency of DUSP6 rs2279574 genotype was significantly different between the case and control, that is, DUSP6 rs2279574a/A and A/C genotypes might contribute to an increased risk of lung squamous carcinoma compared with the C/C genotype. Moreover, DUSP6 rs2279574 AA genotype was also significantly associated with advanced stages of lung cancer. In contrast, frequency of the TOP2A rs471692 genotype had no association between cases and controls (P = 0.906). Genotype frequency of DUSP6 rs2279574 was 11.9% for C/C, 43.6% for C/A, and 44.5% for A/A in the case versus 16.7% C/C, 43.4% C/A, and 39.9% A/A in the control population (χ2 = 3.136, P= 0.077 by Hardy-Weinberg equilibrium test [HWE]). The genotype frequency of TOP2A rs471692 was 50.0% for C/C, 41.6% for C/T, and 8.4% for T/T in the case versus 50.2% C/C, 43.0% C/T, and 6.8% T/T in the control populations (χ2 = 0.023, P= 0.879 by HWE test). CONCLUSION: Individuals are carrying DUSP6 rs2279574 AA and AC genotypes associated with an increased risk in developing lung squamous carcinoma in Han Chinese and with advanced NSCLC stages.

Association of Topoisomerase II (TOP2A) and Dual-Specificity Phosphatase 6 (DUSP6) Single Nucleotide Polymorphisms with Radiation Treatment Response and Prognosis of Lung Cancer in Han Chinese.

BACKGROUND Mutations of DNA topoisomerase II (TOP2A) are associated with chemotherapy resistance, whereas dual-specificity phosphatase 6 (DUSP6) negatively regulates members of the mitogen-activated protein (MAP) kinase superfamily to control cell proliferation. This study assessed TOP2A and DUSP6 single nucleotide polymorphisms (SNPs) in non-small cell lung cancer (NSCLC) patients for association with chemoradiotherapy responses and prognosis. MATERIAL AND METHODS A total of 140 Chinese patients with histologically confirmed NSCLC were enrolled and subjected to genotyping of TOP2A rs471692 and DUSP6 rs2279574 using Taqman PCR. An independent sample t test was used to analyze differences in tumor regression after radiotherapy versus SNP risk factors. Kaplan-Meier curves analyzed overall survival, followed by the log-rank test and Cox proportional hazard models. RESULTS There were no significant associations of TOP2A rs471692 and DUSP6 rs2279574 polymorphisms or clinicopathological variables with response to chemoradiotherapy (p>0.05). Comparing overall survival of 87 patients with stage I-III NSCLC treated with radiotherapy or chemoradiotherapy to clinicopathological variables, the data showed that tumor regression, weight loss, clinical stage, and cigarette smoking were independent prognostic predictors (p=0.009, 0.043, 0.004, and 0.025, respectively). Tumor regression rate >0.34 was associated with patent survival versus tumor regression rate ≤0.34 (p=0.007). CONCLUSIONS TOP2A rs471692 and DUSP6 rs2279574 SNPs were not associated with chemoradiotherapy response, whereas tumor regression, weight loss, clinical stage, and cigarette smoking were independent prognostic predictors for these Chinese patients with NSCLC.

Dual Specificity Phosphatase 6 (DUSP6) Polymorphism Predicts Prognosis of Inoperable Non-Small Cell Lung Cancer after Chemoradiotherapy.

BACKGROUND: Dual-specificity phosphatase 6 (DUSP6) inactivates different target kinases to regulate cell proliferation and differentiation. Altered DUSP6 expressions or gene polymorphisms are associated with human cancer development including non-small cell lung cancer (NSCLC). DNA topoisomerase II alpha (TOP2A) regulates chromosome condensation and chromatid separation, and altered TOP2A expressions are associated with drug resistance development. This study assessed DUSP6 and TOP2A single nucleotide polymorphisms (SNPs) associated with NSCLC patient survival. METHODS: This study included 152 surgically resected NSCLC patients and 277 chemoradiotherapy treated inoperable cases. DNA samples from each patient were genotyped for DUSP6 and TOP2A SNPs. Kaplan-Meier survival analysis, log-rank test, and Cox proportional hazard model were used to evaluate the association between these variants and NSCLC overall survival. RESULTS: DUSP6 rs2279574 A/A genotype was associated with significantly poor inoperable NSCLC patient overall survival (A/A vs. C/C, adjusted HR = 1.549, 95% CI = 1.019-2.355). Stratification analysis against clinical stage, histology, weight loss, and ECOG performance status revealed that the DUSP6 rs2279574 A/A variant homozygous genotype is associated with a decrease in survival of stage IV NSCLC patients compared to those with the C/C genotype (log-rank, p = 0.003). No association was found among histology, weight loss, and ECOG performance status. Moreover, there was no association of TOP2A SNPs between clinicopathological and survival data. CONCLUSIONS: Data obtained from the current study demonstrated that functional DUSP6 rs2279574 polymorphism was able to predict inoperable NSCLC patient survival after chemoradiotherapy.

PARP-1 rs3219073 polymorphism may contribute to susceptibility to lung cancer.

OBJECTIVE: To investigate the relationship between the PARP-1 rs3219073 C>G polymorphism and susceptibility to lung cancer in Chinese people. METHODS: In accordance with the case-control study principle, 645 of the patients had histologically recognized primary lung cancer, among them 240 had squamous carcinoma, 217 had adenocarcinoma, and 188 had small-cell lung cancer. The control group consisted of 643 healthy subjects who had received a physical examination. Extracts of peripheral blood were taken from all subjects, and genomic DNA was extracted by the phenol-chloroform method. RESULTS: After adjusting for age and smoking status, the results show significant association between genetic variations in the rs3219073 C/C genotype and an increased risk of lung cancer (p=0.045, odds ratio [OR]=0.625). After combining C/G, G/G is still statistically significant (p=0.042, OR=0.637). Hierarchical analysis found that the number of subjects with a G/G genotype in the adenocarcinoma group is lower than in the control group (p=0.015, OR=0.543). After combining C/G, G/G is still statistically significant (p=0.027, OR=0.595). After correcting for age and smoking status, the group with C/G genotype and the group with G/G genotype both appear to have a reduced risk for lung cancer compared with the control group (p=0.045, OR=0.566; p=0.013, OR=0.489). The combination of C/G and G/G displays a more statistically significant difference (p=0.018, OR=0.528). CONCLUSIONS: The study found that PARP-1 rs3219073 C>G polymorphism is indeed associated with lung cancer susceptibility. The carriers of G alleles may have reduced risk of lung cancer, especially adenocarcinoma.