Study of the impact of CT/CT image fusion radiotherapy on V_(20) and radiation pneumonitis of non-small cell lung cancer

Objective:The aim of our study was to investigate the value of CT/CT image fusion radiation treatment planning in non-small cell lung cancer(NSCLC) and the impact on V20 and radiation pneumonitis(RP).Methods:Patients who were pathologically or cytologically diagnosed of stage IIIA and IIIB NSCLC were treated with three-dimensional conformal radiation therapy(4000 cGy).Forty patients got at least 25% tumor reduction were randomly divided into two groups:group A of regular shrink field radiotherapy(20 cases) and group B of CT/CT image fused shrink field radiotherapy(20 cases).Dosage reached 6600 cGy.Clinical data,V20 and RP were observed within 3 months after radiotherapy.Statistical analysis was conducted for the NSCLC patients.Results:22.5%(9/40) patients got RP during follow-up.Group A accounted for 6 cases(30%),and group B had 3 cases(15%).There was no marked difference between the two groups(P = 0.256),univariate analysis revealed that the IV20 of A and B groups,and IV20 and CV20 of all patients were statistically related to the incidence of RP(P < 0.05).With Wilcoxon method assay,the ipsilateral lung V20 and contralateral lung V20 had statistical significance between the two groups(P < 0.05).Conclusion:The CT/CT image infusion treatment planning could increase the radical dosage with better tumor control probability but won't increase adverse reaction.

Treatment of Non-Small Cell Lung Cancer (NSCLC) Using CT in Combination with a PET Examination to Minimize the Clinical Target Volume of the Mediastinum

OBJECTIVE To decrease radiation injury of the esophagus and lungs by utilizing a CT scan in combination with PET tumor imaging in order to minimize the clinical target area of locally advanced non-small cell lung can-cer, without preventive radiation on the lymphatic drainage area. METHODS Of 76 patients with locally advanced non-small cell lung cancer (NSCLC), 32 received a PET examination before radiotherapy. Preventive radiation was not conducted in the mediastinum area without lymphatic metastasis, which was confirmed by CT and PET. For the other 44 patients, preventive radiation was performed in the lymphatic drainage area. PET examinations showed that the clinical target volume of the patients was decreased on average to about one third. The radiation therapy for patients of the two groups was the same, i.e. the dose for accelerated fractionated irradiation was 3 Gy/time and 5 time/week. The preventive dose was 42 to 45 Gy/time, 14 to 15 time/week, with 3-week treatment, and the therapeu- tic dose was 60 to 63 Gy/time, 20 to 21 time/week, with a period of 4 to 5 weeks. RESULTS The rate of missed lymph nodes beyond the irradiation field was 6.3% and 4.5% respectively in the group with and without PET exami- nation (P = 0.831). The incidence of acute radioactive esophagitis was 15.6 % and 45.5% in the two groups respectively (P = 0.006). The incidence of acute radiation pneumonia and long-term pulmonary fibrosis in the two groups was 6.3% and 9.1%, and 68.8% and 75.0%, respectively (P = 0.982 and P = 0.547). CONCLUSION The recurrence rate in the lymph nodes beyond the tar-get area was not increased after minimizing the clinical target volume (CTV), whereas radioactive injury to the lungs and esophageal injury was reduced, and especially with a significant decrease in the rate of acute radioactive esophagitis. The method of CT in combination with PET for minimizing the mediastinal CTV is superior to the conventional preventive radiation of the mediastinum.

Quantitative monitoring and mutations of ctDNA before and after non-small cell lung cancer radical surgery

Objective The aim of this study was to study the quantitative expression of circulating tumour DNA(ctDNA) in patients with non-small cell lung cancer(NSCLC) before and after radical operation and to explore the correlation between gene mutations in non-small cell lung cancer tissues and those in ctDNA.Methods We randomly assigned 5 NSCLC patients from the Department of Thoracic Surgery of Fujian Medical University Union Hospital. All the patients had undergone radical surgery. Venous blood samples were collected from the 5 NSCLC patients at two time points(before the operation and 21–37 days after the operation) for monitoring ctDNA levels. This was done by isolating plasma from venous blood using high velocity centrifugation, extracting DNA from the plasma using the QIAamp Circulating Nucleic Acid kit, and then quantifying the ctDNA levels. The results were analyzed using the Wilcoxon Rank Sum Test. Moreover, the ctDNA levels were compared with those of carcinoembryonic antigen(CEA), which was detected simultaneously with the ctDNA. Then, DNA samples from the tumor tissues and peripheral blood cells and ctDNA were sequenced using the Hiseq2000 sequencing platform(Illumina) and the mutant genes were screened out. Mutations that occurred within the tumor tissues were used as positive control, whereas those found in the pre-operative blood cells were used as a negative control. Based on the mutational analysis of ctDNA genes, a total of 508 cancer-related genes were screened. Results The median values of the pre-and post-operative ctDNA levels in the 5 patients with NSCLC were 0.612(0.518–0.876) and 0.430(0.372–0.612) ng/μL, respectively. There was a significant difference between the two groups(P < 0.05). The pre-operative CEA level was slightly higher than the post-operative level(P > 0.05). In one of the cases, LC tissues showed multiple mutations, consistent with pre-operative ctDNA. Moreover, isogenic mutations of the same type were not detected in post-operative ctDNA or peripheral blood cells. Conclusion Mutations found in the lung cancer(LC) ctDNA gene were consistent with the mutation type of LC tissue. Hence, the quantitative and qualitative analysis of ctDNA is a promising novel molecular biomarker for the evaluation of tumor burden changes in NSCLC.

Correlation study between CT perfusion parameters of non-small cell lung cancer and angiogenesis, cell proliferation as well as tumor load

Objective:To study the correlation between CT perfusion parameters of non-small cell lung cancer and angiogenesis, cell proliferation as well as tumor load.Methods: Patients diagnosed with non-small cell lung cancer in our hospital between May 2012 and December 2015 were selected, CT perfusion was used to measure the blood volume (BV), blood flow (BF) and time to peak (TTP) of lung cancer lesions and unaffected-side lung tissue, and the lung cancer tissue and para-carcinoma tissue were collected to determine the expression of angiogenesis and cell proliferation molecules.Results:BV and BF of non-small cell lung cancer tissue were significantly higher than those of unaffected-side lung tissue while TTP was significantly shorter than that of unaffected-side lung tissue;PCDGF, bFGF, FGFR, VEGF, VEGFR, TCF3, Skp2, Livin and Survivin expression in non-small cell lung cancer tissue were significantly higher than those in para-carcinoma tissue, positively correlated with BV and BF, and negatively correlated with TTP.Conclusion:CT perfusion parameters BV, BF and TTP are closely related to the expression of angiogenesis molecules and cell proliferation molecules in non-small cell lung cancer lesions, and are valuable for the assessment of angiogenesis and cell proliferation.

Analysis and Review of Downregulated Actin Cytoskeletal Proteins in Non-Small Cell Lung Cancer

Actin, a highly conserved protein, plays a dominant role in Non-small cell lung cancer (NSCLC). Late diagnosis and the aggressive nature of NSCLC pose a significant threat. Studying the clinic pathological properties of NSCLC proteins is a potential alternative for developing treatment strategies. Towards this, 35 downregulated actin cytoskeletal proteins on NSCLC prognosis and treatment were studied by examining their protein-protein interactions, gene ontology enrichment terms, and signaling pathways. Using PubMed, various proteins in NSCLC were identified. The protein-protein interactions and functional associations of these proteins were examined using the STRING database. The focal adhesion signaling pathway was selected from all available KEGG and Wiki pathways because of its role in regulating gene expression, facilitating cell movement and reproduction, and significantly impacting NSCLC. The protein-protein interaction network of the 35 downregulated actin cytoskeleton proteins revealed that ACTG1, ACTR2, ACTR3, ANXA2, ARPC4, FLNA, TLN1, CALD1, MYL6, MYH9, MYH10, TPM1, TPM3, TPM4, PFN1, IQGAP1, MSN, and ZXY exhibited the highest number of interactions. Whereas HSPB1, CTNNA1, KRT17, KRT7, FLNB, SEPT2, and TUBA1B displayed medium interactions, while UTRN, TUBA1B, and DUSP23 had relatively fewer interactions. It was discovered that focal adhesions are critical in connecting membrane receptors with the actin cytoskeleton. In addition, protein kinases, phosphatases, and adapter proteins were identified as key signaling molecules in this process, greatly influencing cell shape, motility, and gene expression. Our analysis shows that the focal adhesion pathway plays a crucial role in NSCLC and is essential for developing effective treatment strategies and improving patient outcomes.

Chemotherapy combined with bevacizumab for small cell lung cancer with brain metastases:A case report

BACKGROUND Small cell lung cancer(SCLC)is a common and aggressive subtype of lung cancer.It is characterized by rapid growth and a high mortality rate.Approximately 10%of patients with SCLC present with brain metastases at the time of diagnosis,which is associated with a median survival of 5 mo.This study aimed to summarize the effect of bevacizumab on the progression-free survival(PFS)and overall survival of patients with brain metastasis of SCLC.CASE SUMMARY A 62-year-old man was referred to our hospital in February 2023 because of dizziness and numbness of the right lower extremity without headache or fever for more than four weeks.The patient was diagnosed with limited-stage SCLC.He received 8 cycles of chemotherapy combined with maintenance bevacizumab therapy and achieved a PFS of over 7 mo.CONCLUSION The combination of bevacizumab and irinotecan effectively alleviated brain metastasis in SCLC and prolonged PFS.

Stage Ⅳ non-small cell lung cancer with multiple metastases to the small intestine leading to intussusception: A case report

BACKGROUND Gastrointestinal tract metastasis from lung cancer is rare and compared to small cell lung cancer(SCLC),non-SCLC(NSCLC)is even less likely to metastasize in this manner.Additionally,small intestinal tumors can also present with diverse complications,some of which require urgent intervention.CASE SUMMARY In this report,we detail a unique case of stage IV lung cancer,where the presence of small intestine tumors led to intussusception.Subsequent to a small intestine resection,pathology confirmed that all three tumors within the small intestine were metastases from adenocarcinoma of the lung.The postoperative follow-up period extended beyond 14 mo.CONCLUSION In patients with stage IV NSCLC,local tumor control can be achieved with various treatments.However,if small intestinal metastasis occurs,surgical intervention remains necessary,as it may improve survival.

Immunotherapy for Small Cell Lung Cancer

Small cell lung cancer (SCLC) is a poorly differentiated, highly malignant neuroendocrine tumor characterized by rapid growth, aggressiveness, and easy recurrence. It is usually found in late clinical stage and the opportunity for surgery is lost. Therefore, surgery is often not used in clinical treatment. Although it is sensitive to chemoradiotherapy, it has a high recurrence rate and lacks effective treatment methods at present. Following chemotherapy and radiotherapy, immunotherapy for small cell lung cancer has become the mainstream research direction. Immunotherapy is profoundly changing the approach to cancer treatment due to its tolerable safety profile, sustained treatment response due to the production of immune memory, and effectiveness in a broad patient population. Immunotherapy for small cell lung cancer is one of the effective treatment methods for small cell lung cancer, and relevant studies are not rare, but there are still shortcomings such as intolerance of side effects and inaccurate evaluation of treatment timing. This article reviews the history of immunotherapy, the mechanism of action of immunodrugs, and the current immunodrugs used in the first-line treatment of extensive small cell lung cancer.

Optimal timing of thoracic irradiation for limited stage small cell lung cancer:Current evidence and future prospects

Lung cancer is a global health concern as the leading cause of cancer related mortality worldwide.Small cell lung cancer(SCLC)poses a formidable challenge to the treating physicians with the worst prognosis among all lung cancers.However,limited stage SCLC(LS-SCLC)has a relatively better outcome with multimodality management.Efforts have been focused on optimal integration of treatment modalities to achieve an improved therapeutic ratio for patients with LS-SCLC.While chemotherapy and thoracic radiation therapy(TRT)are primary components of initial management for LS-SCLC,there is no consensus on optimal timing of TRT.Within this context,we herein provide a concise overview of current evidence and future prospects regarding the optimal timing of thoracic irradiation for LS-SCLC in light of the literature.

Efficacy and Safety of Primary Radiotherapy in Combination with EGFR-TKIs for Non-Small Cell Lung Cancer Harboring EGFR Mutation

Objective: To evaluate the efficacy and safety of EGFR-TKI with the radiotherapy in EGFR mutant metastatic NSCLC. Methods: Retrospective analysis of 72 patients with stage IV lung cancer with EGFR-sensitive mutation. Patients in the A group were treated with the first-generation EGFR-TKI (Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor) combined with radiotherapy for primary tumors (34 cases). The B group was treated with the first-generation EGFR-TKI alone until the disease progressed (38 cases). PFS, OS, pulmonary infection and hematological toxicity during treatment were commented in both groups. Results: The objective remission rate was 47.1% (16/34) in the A group and 21.1% (8/38) in the B group. There was a significant difference between the two groups. There was no significant difference in hematological toxicity between the A group and the B group. There were 10 patients (29.4%) with degree II pulmonary infection in the A group and 3 patients (7.9%) in the B group. The difference between the two groups was statistically significant, suggesting that the incidence of pneumonia in the A group was higher than that in the B group. The median PFS (Progression-Free Survival)) and OS (Overall Survival) of the A group were significantly longer than those of the B group (16.5 months vs 9 months) and the median OS (36 months vs 19 months). The PFS and OS in the A group were significantly longer than those in the B group. Conclusion: EGFR-TKI combined with primary radiotherapy can significantly prolong the drug resistance time of EGFR mutant metastatic NSCLC.

Improvement of Quality of Life with Shenfu Injection (参附注射液) in Non Small Cell Lung Cancer Patients Treated with Gemcitabine plus Cisplatin Regimen

Objective： To observe the effect of Shenfu injection （参附注射液, SFI） in treating non small cell lung cancer （NSCLC） patients on quality of life with gemcitabine （GEM） plus cisplatin （GP） regimen. Methods： Thirty-four patients were ready to receive GP regimen chemotherapy for treating NSCLC disease, according to lot-drawing, they were divided into SFI pre-treatment group （18 cases） and SFI post-treatment group （ 16 cases）. SFI pre-treatment group： During the first treatment course, chemotherapy was begun with SFI 60 ml, intravenous dripping on the 3rd day, once daily, consecutively for 10 days; on the 1st day, GP regimen （GEM 1250 mg/m^2 , intravenous dripping, on the 1st and 8th day; cisplatin 70 mg/m^2 on the 2nd day; 21 days as one cycle） was carried out; in the second treatment course GP regimen was merely given to serve as the self-control. SFI post-treatment group： the medicament sequence order was reversed from that of pre-treatment group. Using dual international quality of life （QOL） scores, the effect of SFI on the patients＂ QOL was observed through randomized self pre- and post- crossover control. Results： The QOL in the 34 patients after being treated by SFI in combination with GP chemotherapy regimen in one group, and GP chemotherapy regimen alone in the other, was improved in different degrees, with significant difference （P〈0.01）; comparision of SFI combined with GP chemotherapy regimen with GP chemotherapy alone showed that QOL in patients was significantly different （P〈0.01）. Conclusion： SFI could improve QOL in patients with NSCLC who were treated with GP regimen.

Clinical Features and Prognostic Factors of Small Cell Lung Cancer:A Retrospective Study in 148 Patients

To better understand the outcomes of small cell lung cancer（SCLC）,we examined the clinical features and prognostic factors of SCLC in this study.A total of 148 patients who were diagnosed as having SCLC between January 2009 and December 2013 in Cancer Center of Union Hospital,Wuhan,China,were enrolled and their clinical features and prognostic factors were retrospectively analyzed.Log-rank test and Cox regression model were employed for analysis of prognostic factors.The 1-and 2-year overall survival（OS） rates were 59.7% and 25.7%,respectively,for limited disease（LD） patients whose median survival time（MST） was 16 months.The 1-and 2-year OS rates were 29.5% and 5.3%,respectively,for extensive disease（ED） patients whose MST was 10 months.The univariate analysis and multivariate analysis revealed that age,tumor stage,serum CEA and Ki-67 antigen were significantly correlated to the outcomes of SCLC,and they were significant prognostic factors for SCLC.

Shenqi Fuzheng injection combined with GP chemotherapy in the treatment of advanced non-small cell lung cancer： a meta-analysis

Objective： To evaluate the clinical efficacy of Shenqi Fuzheng injection combined with gemcitabine plus cisplatin（GP） in the treatment of advanced non-small cell lung cancer （NSCLC）. Methods： we performed a systematicsearch in the electronic databases such as Cochrane Library, Pubmed, Embase, Chinese Journal Full-text Database,Chinese Biomedical Literature Database, Chinese Science and Technology Periodical Full-text Database andWanfang Database up to 30 January 2017. Randomized controlled trials （RCT） of Shenqi Fuzheng Injectioncombined with GP chemotherapy in the treatment of advanced NSCLC were searched, and all the RCTs wereconducted on methodological quality assessment. Data extraction and data analysis were according to standards ofCochrane systematic review. Results： Eight trials were included including a total of 701 patients. Meta-analysisresults： Shenqi Fuzheng injection combined with GP chemotherapy could significantly improve the functionalstatus of patients with NSCLC （OR = 3.44, 95% CI [2.26, 5.25], P 〈 0.0001） and clinical treatment efficacy （OR =（OR = 0.31, 95%CI [0.20, 0.47], P 〈 0.0001. The rate of leukopenia （OR = .31, 95%CI [0.20,0.47], P 〈 0.0001）,thrombocytopenia （OR = 0.58, 95%CI [0.37, 0.91], P = 0.020）, hemoglobin decline （（OR = 0.31, 95%CI [0.16,0.59], P = 0.0004） and incidence of gastrointestinal reactions （OR = 0.58,P 〈 0.05） could be reduced. Conclusion：Shenqi Fuzheng injection combined with GP chemotherapy in the treatment of advanced NSCLC obtainedsignificantly clinical efficacy. The quality of the literature incorporated is low, the conclusion requires high-qualityresearch to further prove.

Clinical characteristics and response to tyrosine kinase inhibitors of patients with non-small cell lung cancer harboring uncommon epidermal growth factor receptor mutations

Objective： To investigate the clinical features of patients with non-small cell lung cancer（NSCLC） harboring uncommon epidermal growth factor receptor（EGFR） mutations, and the treatment outcomes of EGFR tyrosine kinase inhibitors（TKIs） in these patients.Methods： We retrospectively analyzed the data of 128 NSCLC patients pathologically diagnosed with uncommon EGFR mutation in the Department of Pathology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences ＆ Peking Union Medical College and Beijing Hospital from January 2010 to December 2015, including 40 advanced patients who received EGFR-TKI.Results： Among the total 128 patients, 11 patients were non-adenocarcinoma, including squamous carcinoma（3.9%）, adenosquamous carcinoma（2.3%）, large cell carcinoma（0.8%）, and composite neuroendocrine carcinoma（1.6%）. Single mutations accounted for 75.0%（96/128）, including G719X（29.7%）, S768I（18.0%）, 20 exon insertion（13.3%）, L861Q（12.5%）, De novo T790M（0.8%）, and T725（0.8%）. Thirty-two patients harbored complex mutations. Forty advanced patients received EGFR-TKI, the objective response rate（ORR） was 20.0%,the disease control rate（DCR） was 85.0%, and the progression-free survival（PFS） was 6.4 [95% confidence interval（95% CI）, 4.8–7.9] months. The exploratory analysis of tumor response and PFS in 33 patients with G719X/S768I/L861 Q subtypes showed that ORR was 21.2%（7/33）, the DCR was 93.9%（31/33）, and PFS was 7.6（95% CI, 5.8–9.4） months. Patients with exon 20 insertion mutation and De novo T790 M experienced rapid disease progression with PFS no more than 2.7 months.Conclusions： Uncommon EGFR-mutant NSCLCs are heterogeneous, EGFR-TKIs can have different efficacy in this specific subtype, and thus further individual assessment is required for each case.

A phaseⅠtrial of an oral subtype-selective histone deacetylase inhibitor,chidamide,in combination with paclitaxel and carboplatin in patients with advanced non-small cell lung cancer

Objective： This phase I study was to evaluate safety, maximum tolerated dose, pharmacokinetics and preliminary antitumor activity of chidamide, a novel subtype-selective histone deacetylase （HDAC） inhibitor, in combination with paclitaxel and carboplatin in patients with advanced non-small cell lung cancer （NSCLC）. Methods： Ten patients received oral chidamide 20, 25, or 30 mg twice per week continuously with paclitaxel （175 mg/m2） and carboplatin [area under the curve （AUC） 5 mg/mL/min] administered in a 3-week cycle. Patients with response and stable disease after four cycles maintained chidamide monotherapy until disease progression or unacceptable toxicity. Blood samples were collected for pharmacoldnetic analysis after the first single oral of chidamide and first combination treatment in cycle 1 from all patients. Results： Two dose-limiting toxicities were recorded in the 30 mg cohort, including thrombocytopenia and prolonged neutropenia in the first cycle. Grade 3/4 neutropenia in any cycle was observed in all patients, but was not associated with significant complications. Other grade 3/4 hematologic toxicities included thrombocytopenia and leucopenia. No significant changes were observed in pharmacokinetic parameters for both chidamide and paclitaxel. One patient in the 20 mg cohort had confirmed partial response （PR）. Two out of 5 patients with brain metastases had intracranial complete remission after 4-cycle treatment. Conclusions： Chidamide combined with paclitaxel and carboplatin was generally tolerated without unanticipated toxicities or clinically relevant pharmacokinetic interactions. The recommended dose for chidamide in this combination was established at 20 mg, and a phase II trial is ongoing with this regimen in patients with advanced NSCLC.

Vascular Invasion as An Independent Prognostic Indicator in Radically Resected Non-small Cell Lung Cancer

Objective： A retrospective study was performed to analyze the impact of vascular invasion on prognosis in a series of radically resected non-small cell lung cancer （NSCLC） and the subgroup of T1-4 nodal negative NSCLC patients. Methods： A total of 259 NSCLC patients who had undergone radical resection were entered into this study. Detailed clinical data including five-year survival were obtained for all the patients. The tumors were reviewed for the presence or absence of vascular invasion. Fisher＇s exact tests were used to assess the relationship between vascular invasion and other clinicopathological variables. Survival time was defined as the interval from the date of operation to either death from lung cancer or the last follow-up. Univariate analysis of survival curve was performed by the Kaplan-Meier method using the Log rank test. Multivariate survival analysis was carried out by Cox regression. P〈0.05 was considered statistically significant. Results： In 259 patients, 33 cases were diagnosed as having vascular invasion. The overall 5-year survival was 37.5%. Patients with vascular invasion had a median survival of 20 months compared with 43 months for those without vascular invasion （P〈0.01）. Multivariate analysis indicated that vascular invasion was a significant independent prognostic predictor for shortened cancer-related survival in the patients. The relative risk for cancer-related survival was 2.2-fold greater in patients with vascular invasion （95% CI： 1.45-3.32）. Subgroup analysis revealed that patients with vascular invasion had a 5-year survival of 11.1% compared with 57.1% for those without vascular invasion in the resected lung cancer patients at T1-4N0M0 （P=0.002）. Conclusion： Vascular invasion can serve as an independent prognostic factor in radically resected NSCLC.

Comparative study of induction chemotherapy and chemoradiotherapy in the treatment of limited-disease small cell lung cancer with ipsilateral pleural effusion

Objective:The aim of the study was to explore the effects and side effects of induction chemotherapy followed by chemoradiotherapy for limited-disease small cell lung cancer (LD-SCLC) patients with ipsilateral pleural effusion.Methods:From January 2005 to May 2009,52 LD-SCLC patients with ipsilateral pleural effusion were treated with induction chemotherapy first.The regimen was taken as follows:etoposide 100 mg iv,d1-d5,cisplatin 25 mg/m2 iv,d1-d3 or CBP AUC 4 iv,d1.Three-week therapy was a cycle.According to pleural effusion status after 2-4 cycles induction chemotherapy,patients got disappearance of pleural effusion after chemotherapy were underwent thoracic radiotherapy (TRT;50 Gy/25 fraction) or same chemotherapy regimen;patients without disappearance or with increasing of pleural effusion after chemotherapy were given same chemotherapy regimen.Therapeutic effect was evaluated every two cycles according to RECIST 1.0 and side-effects were evaluated every cycle according to NCI-CTC AE Grades.All patients were followed up,and the median follow-up time was 26 months.Results:The response rate of patients was 80.7% (42/52) after induction chemotherapy and 34 patients got disappearance of pleural effusion.The median survival time,1-and 2-year survival rates were 15.4 months,76.9% (40 /52) and 38.5% (20 /52) respectively.The median survival time,1-and 2-year survival rates of patients with pleural effusion remission received chest radiotherapy (A group,n=20),patients with pleural effusion remission received chemotherapy (B group,n=14) and patients without pleural effusion remission received chemotherapy (C group,n=18) were 21.5 months,14.4 months,12.5 months,80.0%,64.3%,55.6% and 35%,21.4%,11.1%,respectively.Main side effects were grades 1-2,including myelosuppression,fatigue,nausea and vomiting.No therapeutic related death was occurred.Conclusion:Induction chemotherapy plus chemoradiotherapy has shown better effect in prolonging survival of small cell lung cancer (SCLC) patients with ipsilateral pleural effusion than chemotherapy alone.The patients with decreased ipsilateral pleural effusion may receive benefit from subsequent TRT.

Expression and Clinical Significance of Semaphorin4D in Non-small Cell Lung Cancer and Its Impact on Malignant Behaviors of A549 Lung Cancer Cells

This study aimed to explore Semaphrin4D（Sema4D） expression and clinical significance in non-small cell lung cancer（NSCLC）, and to define the roles and mechanisms of Sema4 D in regulating the malignant behaviors of A549 cells by small interfering RNA（siRNA）. Firstly, immunohistochemistry revealed that Sema4 D was more frequently expressed in NSCLC than in lung benign lesion（P〈0.05） and its overexprssion was associated with low differentiation（P〈0.05）, poor pTNM staging（P〈0.05） and occurrence of lymph node（LN） metastasis（P〈0.05）. Endogenous Sema4 D expression was suppressed by Sema4 D siRNA in A549 cells overexpressing Sema4 D. Protein levels of Sema4 D, total Akt and p-Akt were examined by Western blotting. Cell proliferation, migration and invasion abilities were measured by MTT assay and Transwell assay respectively. Results showed that Sema4 D siRNA significantly suppressed phosphorylation of AKT in A549 cells, but it did not alter total AKT expression. In addition, efficient down-regulation of SemaD significantly inhibit cell proliferation（P〈0.05）, migration（P〈0.05） and invasion（P〈0.05） in A549 cells. These findings suggest that Sema4 D might serve as a reliable tool for early prediction of NSCLC poor prognosis. Sema4 D could play an important role in promoting tumor proliferation, migration and metastasis in the NSCLC, by influencing the Akt protein phosphorylation. Inhibition of Sema4 D may be a useful approach for the treatment of NSCLC.

Recursive Partitioning Analysis Classification and Graded Prognostic Assessment for Non-Small Cell Lung Cancer Patients with Brain Metastasis:A Retrospective Cohort Study

Objective：To assess prognostic factors and validate the effectiveness of recursive partitioning analysis （RPA） classes and graded prognostic assessment （GPA） in 290 non-small cell lung cancer （NSCLC） patients with brain metastasis （BM）.Methods：From Jan 2008 to Dec 2009,the clinical data of 290 NSCLC cases with BM treated with multiple modalities including brain irradiation,systemic chemotherapy and tyrosine kinase inhibitors （TKIs） in two institutes were analyzed.Survival was estimated by Kaplan-Meier method.The differences of survival rates in subgroups were assayed using log-rank test.Multivariate Cox＇s regression method was used to analyze the impact of prognostic factors on survival.Two prognostic indexes models （RPA and GPA） were validated respectively.Results：All patients were followed up for 1-44 months,the median survival time after brain irradiation and its corresponding 95% confidence interval （95% CI） was 14 （12.3-15.8） months.1-,2-and 3-year survival rates in the whole group were 56.0%,28.3%,and 12.0%,respectively.The survival curves of subgroups,stratified by both RPA and GPA,were significantly different （P0.001）.In the multivariate analysis as RPA and GPA entered Cox＇s regression model,Karnofsky performance status （KPS） ≥ 70,adenocarcinoma subtype,longer administration of TKIs remained their prognostic significance,RPA classes and GPA also appeared in the prognostic model.Conclusion：KPS ≥70,adenocarcinoma subtype,longer treatment of molecular targeted drug,and RPA classes and GPA are the independent prognostic factors affecting the survival rates of NSCLC patients with BM.

Activation of Toll-like receptors signaling in non-small cell lung cancer cell line induced by tumor-associated macrophages

Background： Inflammation is often linked with the progress and poor outcome of lung cancer. The understanding of the relationship between tumor-associated macrophages （TAMs） and lung cancer cells involves in the underlying mechanism of inflammatory cytokine production. Toll-like receptors （TLRs） are engaged in promoting the production of pro-inflammatory cytokines and play an important role in tumor immunology. Methods： To investigate the mechanisms by which TAMs influence the production of pro-inflammatory cytoldnes in lung cancer cells, we established an in vitro coculture system using TAMs and human non- small cell lung cancer （NSCLC） cell line SPC-A1. Levels of interleukin （IL）-113, IL-6 and IL-8 in SPC-A1 were evaluated by RT-PCR and cytometric bead array assay after being cocultured with TAMs. Expression changes of TLRs and TLRs signaling pathway proteins in SPC-Al were further confirmed by RT-PCR and western blot. The level changes of IL-1β, IL-6 and IL-8 in SPC-Al were also detected after the stimulation of TLRs agonists. Results： We found that the phenotype markers of TAMs were highly expressed after stimulating human monocyte cell line THP-1 by phorbol-12-myristate-β-acetate （PMA）. Higher mRNA and supernate secretion levels of IL-1β, IL-6 and IL-8 were detected in SPC-A1 after being eocultured with TAMs. We also found that TLR1, TLR6 and TLR7 were up-regulated in SPC-A1 in the coculture system with TAMs. Meanwhile, TLRs signaling pathway proteins were also significantly activated. Moreover, pre-treatment with agonist ligands for TLR1, TLR6 and TLR7 could dramatically promote inductions of IL-1β, IL-6 and IL-8. Conclusions： These findings demonstrated that TAMs may enhance IL-1β, IL-6 and IL-8 expressions via TLRs signaling pathway. We conclude that TAMs contribute to maintain the inflammation microenvironment and ultimately promote the development and progression of lung cancer.