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  1. High expression of △Np73 predicts poor prognosis in NSCLC cancer patients

    Institute of Scientific and Technical Information of China (English)

    HE Yong; FAN Shi-zhi; JIANG Yao-guang; CHEN Jian-ming; HU Yi-jie

    2007-01-01

    Objective:To study the expression of △Np73,an isoform of the p53 homologue p73,in the different stages of human non-small-cell lung cancer (NSCLC) and the association of △Np73 expression with in patient survival.Methods:Semi-quantitative reverse transcriptase polymerase chain reaction (RTPCR) was used to study the expression of △Np73 mRNA in 51 resected NSCLC tissues.Its relation to clinicopathological factors and survival outcome were analyzed.Results:The positive rate and expression level of △Np73 mRNA in the cancer tissues were significantly higher than that in the matched non-cancer lung tissues.The incidence of positive expression of △Np73 was 50.0%,52.6%,and 87.5% in patients with stage Ⅰ,Ⅱ,and Ⅲ, respectively.Positive expression of △Np73 was associated with pathological TNM stage (P=0.046),while not with age,gender,histological type and differentiation status.Survival rate of patients with high △Np73 mRNA was significantly poorer than those with low △Np73 mRNA levels (P<0.001).Multivariate analysis revealed that △Np73 mRNA levels were a significant prognostic factor,independent of the other conventional prognostic factors.Conclusion:NSCLC has over-expression of △Np73 mRNA,which is closely related to TNM stages and prognosis of patients with NSCLC.These resuits suggest that measurement of △Np73 mRNA levels in tumor tissues might be useful as a promising predictor for the prognosis of patients with NSCLC.

  2. Mortality in asymptomatic vs. symptomatic patients surgically treated for non-small cell lung cancer (NSCLC)

    DEFF Research Database (Denmark)

    Madsen, Kirsten Riis; Bødtger, Uffe

    Introduction: Compared to incidentally found lung cancer, the presence of symptoms (eg. cough, haemoptysis, pain, weight loss) at diagnosis is associated with a 50% reduction in median survival. In surgically treated patients, it is unknown whether presence of symptoms has prognostic significance....... Aim: We wanted to ascertain if symptoms at time of NSCLC diagnosis lowered 12-months mortality after surgery. Methods: Retrospective analysis of all patients with localised NSCLC referred from our department between 2009-2011 for intended curative surgery Data on age, sex, tobacco pack years, Charlson......, tobacco pack years, or FEV1. Former malignancy was significantly more prevalent among asymptomatic than symptomatic subjects (33 % vs. 11%), with insignificant differences in prevalence of other co-morbidities or in post-surgical TNM (82% vs 85% in stages IA-IIB). 12-months mortality was insignificantly...

  3. Chemotherapy with cisplatin and vinorelbine for elderly patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC)

    International Nuclear Information System (INIS)

    Although modest improvements in the survival of patients with non-small cell lung cancer (NSCLC) can be achieved with cisplatin-based chemotherapy (CT), its value is disputed in the geriatric setting. In this study, we evaluate the feasibility of vinorelbine/cisplatin CT for elderly NSCLC patients. In this pilot phase I/II trial, all patients received CT with vinorelbine 25 mg/m2, on day 1 and 8, and cisplatin on day 1, in 28 days-cycles. After stratification for age (up to 75 years), younger patients were sequentially allocated to moderate cisplatin doses (80 mg/m2 or 90 mg/m2), and older patients were allocated to lower cisplatin doses (60 mg/m2 or 70 mg/m2). We recruited patients aged over 70 years with newly diagnosed NSCLC, clinical stage III or IV, Karnofsky performance status ≥ 70%, normal serum creatinine, peripheral neuropathy ≤ grade 1, and no prior cancer therapy. Analysis was by intention to treat. Main toxicities (grade 3–4) was as follows: neutropenia, 20%; anemia, 11%; and thrombocytopenia, 2%; alopecia, 55%; fatigue, 11%; and peripheral neurotoxicity, 2%. No grade 3–4 emesis or renal toxicity occurred. Global median time to progression (TTP) and overall survival (OS) were 27.0 (95% CI: 10.1 to 43.7) weeks and 30.1 (95% CI: 24.4 to 35.8) weeks; 1- and 2-year survival rates were 36.3% and 13.2%, respectively. Overall response rate was 50.0% (95% CI: 35.4% to 64.5%), with 1 complete response; no difference on response rate was noticed according to cisplatin dose. Median overall survival was 30.1 weeks, with 1- and 2-year survival rates of 36.3% and 13.2%, respectively. Age does not preclude assessment on the role of cisplatin-vinorelbine CT for elderly NSCLC patients with good performance status and adequate bodily functions

  4. CT-guided permanent brachytherapy for patients with medically inoperable early-stage non-small cell lung cancer (NSCLC).

    Science.gov (United States)

    Martínez-Monge, Rafael; Pagola, María; Vivas, Isabel; López-Picazo, José María

    2008-08-01

    Seven patients with early stage T1N0M0 NSCLC who had medical contraindications for surgical resection were treated with CT-guided percutaneous implantation of (103)Pd or (125)I seeds. After the procedure, two patients developed pneumothorax and hemo/pneumothorax that was managed with aspirative drainage. One patient developed a focal pneumonitis 3 months after the procedure. After a median follow-up of 13 months (4.6-41.0+ months), no patient has developed local or regional failure. PMID:18243409

  5. TMPRSS4 induces cancer stem cell-like properties in lung cancer cells and correlates with ALDH expression in NSCLC patients.

    Science.gov (United States)

    de Aberasturi, Arrate L; Redrado, Miriam; Villalba, Maria; Larzabal, Leyre; Pajares, Maria J; Garcia, Javier; Evans, Stephanie R; Garcia-Ros, David; Bodegas, Maria Elena; Lopez, Lissett; Montuenga, Luis; Calvo, Alfonso

    2016-01-28

    Metastasis involves a series of changes in cancer cells that promote their escape from the primary tumor and colonization to a new organ. This process is related to the transition from an epithelial to a mesenchymal phenotype (EMT). Recently, some authors have shown that migratory cells with an EMT phenotype share properties of cancer stem cells (CSCs), which allow them to form a new tumor mass. The type II transmembrane serine protease TMPRSS4 is highly expressed in some solid tumors, promotes metastasis and confers EMT features to cancer cells. We hypothesized that TMPRSS4 could also provide CSC properties. Overexpression of TMPRSS4 reduces E-cadherin and induces N-cadherin and vimentin in A549 lung cancer cells, supporting an EMT phenotype. These changes are accompanied by enhanced migration, invasion and tumorigenicity in vivo. TMPRSS4 expression was highly increased in a panel of lung cancer cells cultured as tumorspheres (a typical assay to enrich for CSCs). H358 and H441 cells with knocked-down TMPRSS4 levels were significantly less able to form primary and secondary tumorspheres than control cells. Moreover, they showed a lower proportion of ALDH+ cells (examined by FACS analysis) and lower expression of some CSC markers than controls. A549 cells overexpressing TMPRSS4 conferred the opposite phenotype and were also more sensitive to the CSC-targeted drug salinomycin than control cells, but were more resistant to regular chemotherapeutic drugs (cisplatin, gemcitabine and 5-fluorouracil). Analysis of 70 NSCLC samples from patients revealed a very significant correlation between TMPRSS4 expression and CSC markers ALDH (p = 0.0018) and OCT4 (p = 0.0004), suggesting that TMPRSS4 is associated with a CSC phenotype in patients' tumors. These results show that TMPRSS4, in addition to inducing EMT, can also promote CSC features in lung cancer; therefore, CSC-targeting drugs could be an appropriate treatment for TMPRSS4+ tumors. PMID:26546046

  6. Is second-line systemic chemotherapy beneficial in patients with non-small cell lung cancer (NSCLC)? A multicenter data evaluation by the Anatolian Society of Medical Oncology.

    Science.gov (United States)

    Odabas, Hatice; Ulas, Arife; Aydin, Kubra; Inanc, Mevlude; Aksoy, Asude; Yazilitas, Dogan; Turkeli, Mehmet; Yuksel, Sinemis; Inal, Ali; Ekinci, Ahmet S; Sevinc, Alper; Demirci, Nebi S; Uysal, Mukremin; Alkis, Necati; Dane, Faysal; Aliustaoglu, Mehmet; Gumus, Mahmut

    2015-12-01

    Patients with advanced non-small cell lung cancer (NSCLC) generally require second-line treatment although their prognosis is poor. In this multicenter study, we aimed to detect the characteristics related to patients and disease that can predict the response to second-line treatments in advanced NSCLC. Data of 904 patients who have progressed after receiving first-line platinum-based chemotherapy in 11 centers with the diagnosis of stage IIIB and IV NSCLC and who were evaluated for second-line treatment were retrospectively analyzed. The role of different factors in determining the benefit of second-line treatment was analyzed. Median age of patients was 57 years (range 19-86). Docetaxel was the most commonly used (20.9 %, n = 189) single agent, while gemcitabine-platinum was the most commonly used (6.7 %, n = 61) combination chemotherapy regimen in second-line setting. According to survival analysis, median progression-free survival after first-line treatment (PFS2) was 3.5 months (standard error (SE) 0.2; 95 % confidence interval (CI), 3.2-3.9), median overall survival (OS) was 6.7 months (SE 0.3; 95 % CI, 6.0-7.3). In multivariate analysis, independent factors affecting PFS2 were found to be hemoglobin (Hb) level over 12 g/dl and treatment-free interval (TFI) longer than 3 months (p = 0.006 and 0.003, respectively). Similarly, in OS analysis, Hb level over 12 g/dl and time elapsed after the first-line treatment that is longer than 3 months were found to be independent prognostic factors (p = 0.0001 and 0.045, respectively). In light of these findings, determining and using the parameters for which the treatment will be beneficial prior to second-line treatment can increase success rate.

  7. Validation of an algorithm able to differentiate small-cell lung cancer (SCLC) from non-small-cell lung cancer (NSCLC) patients by means of a tumour marker panel: analysis of the errors.

    OpenAIRE

    Paone, G; De Angelis, G.; Portalone, L.; Greco, S.; Giosué, S.; Taglienti, A.; Bisetti, A; Ameglio, F.

    1997-01-01

    By means of a mathematical score previously generated by discriminant analysis on 90 lung cancer patients, a new and larger group of 261 subjects [209 with non-small-cell lung cancer (NSCLC) and 52 with small-cell lung cancer (SCLC)] was analysed to confirm the ability of the method to distinguish between these two types of cancers. The score, which included the serum neuron-specific enolase (NSE) and CYFRA-21.1 levels, permitted correct classification of 93% of the patients. When the misclas...

  8. Early reduction in tumour [{sup 18}F]fluorothymidine (FLT) uptake in patients with non-small cell lung cancer (NSCLC) treated with radiotherapy alone

    Energy Technology Data Exchange (ETDEWEB)

    Trigonis, Ioannis; Tamal, Mahbubunnabi; Anton-Rodriguez, Jose; Jackson, Alan; Asselin, Marie-Claude [The University of Manchester, Institute of Population Health, Wolfson Molecular Imaging Centre, Manchester Academic Health Sciences Centre, Manchester (United Kingdom); Koh, Pek Keng [The University of Manchester, Manchester Cancer Research Centre, Manchester Academic Health Sciences Centre, Manchester (United Kingdom); Taylor, Ben; Ryder, David; Earl, Mark [The Christie NHS Foundation Trust, Manchester (United Kingdom); Haslett, Kate; Faivre-Finn, Corinne; Blackhall, Fiona [The University of Manchester, Manchester Cancer Research Centre, Manchester Academic Health Sciences Centre, Manchester (United Kingdom); The Christie NHS Foundation Trust, Manchester (United Kingdom); Young, Helen [AstraZeneca Pharmaceuticals, Macclesfield (United Kingdom)

    2014-04-15

    Changes in tumour 3'-deoxy-3'-[{sup 18}F]fluorothymidine (FLT) uptake during concurrent chemo-radiotherapy in patients with non-small cell lung cancer (NSCLC) have been reported, at variable time points, in two pilot positron emission tomography (PET) studies. The aim of this study was to assess whether FLT changes occur early in response to radiotherapy (RT) without concurrent chemotherapy and whether such changes exceed test-retest variability. Sixteen patients with NSCLC, scheduled to have radical RT, underwent FLT PET once/twice at baseline to assess reproducibility and/or after 5-11 RT fractions to evaluate response. Primary and nodal malignant lesions were manually delineated on CT and volume, mean and maximum standardized uptake values (SUV{sub mean} and SUV{sub max}) estimated. Analysis included descriptive statistics and parameter fitting to a mixed-effects model accounting for patients having different numbers of evaluable lesions. In all, 35 FLT PET scans from 7 patients with a total of 18 lesions and 12 patients with a total of 30 lesions were evaluated for reproducibility and response, respectively. SUV{sub mean} reproducibility in primary tumours (SD 8.9 %) was better than SUV{sub max} reproducibility (SD 12.6 %). In nodes, SUV{sub mean} and SUV{sub max} reproducibilities (SD 18.0 and 17.2 %) were comparable but worse than for primary tumours. After 5-11 RT fractions, primary tumour SUV{sub mean} decreased significantly by 25 % (p = 0.0001) in the absence of significant volumetric change, whereas metastatic nodes decreased in volume by 31 % (p = 0.020) with a larger SUV{sub mean} decrease of 40 % (p < 0.0001). Similar changes were found for SUV{sub max}. Across this group of NSCLC patients, RT induced an early, significant decrease in lesion FLT uptake exceeding test-retest variability. This effect is variable between patients, appears distinct between primary and metastatic nodal lesions, and in primary tumours is lower than previously

  9. Evaluation of elastix-based propagated align algorithm for VOI- and voxel-based analysis of longitudinal F-18-FDG PET/CT data from patients with non-small cell lung cancer (NSCLC)

    NARCIS (Netherlands)

    Kerner, Gerald S. M. A.; Fischer, Alexander; Koole, Michel J. B.; Pruim, Jan; Groen, Harry J. M.

    2015-01-01

    Background: Deformable image registration allows volume of interest (VOI)- and voxel-based analysis of longitudinal changes in fluorodeoxyglucose (FDG) tumor uptake in patients with non-small cell lung cancer (NSCLC). This study evaluates the performance of the elastix toolbox deformable image regis

  10. Cost effectivenes of erlotinib versus chemotherapy for first-line treatment of non small cell lung cancer (NSCLC) in fit elderly patients participating in a prospective phase 2 study (GFPC 0504)

    OpenAIRE

    Christos Chouaid; Hervé Le; Chrystelle Locher; Cecile Dujon; Pascal Thomas; Jean Bernard Auliac; Isabelle Monnet; Alain Vergnenegre

    2012-01-01

    Abstract Background The median age of newly diagnosed patients with non-small cell lung cancer (NSCLC) is 67 years, and one-third of patients are older than 75 years. Elderly patients are more vulnerable to the adverse effects of chemotherapy, and targeted therapy might thus be a relevant alternative. The objective of this study was to assess the cost-effectiveness of erlotinib followed by chemotherapy after progression, compared to the reverse strategy, in fit elderly patients with advanced ...

  11. The Predictive Value of Germline Polymorphisms in Patients with NSCLC

    DEFF Research Database (Denmark)

    Nygaard, Anneli Dowler; Spindler, Karen-Lise Garm; Andersen, Rikke Fredslund;

    2010-01-01

    urgently needed. Single Nucleotide Polymorphisms (SNPs) are stable markers of potential clinical value and the study aimed at evaluating their use in lung cancer patients given standard chemotherapy. Genomic DNA was extracted from a pre-treatment blood sample drawn from patients with advanced Non......-Small Celled Lung Cancer (NSCLC), referred to palliative chemotherapy (Carboplatin and Vinorelbine) at the Department of Oncology, Vejle Hospital, between 2007 and 2010. Eighty-seven patients were included in a test cohort, and 161 patients in an independent validation cohort. A panel of 107 SNPs in the EGF......, VEGF and DNA-excision repair systems was investigated. The primary endpoint was response rates (RR). Secondary endpoints were progression free survival (PFS) and overall survival (OS). SNPs with significant association to outcome in the test cohort were further tested in the validation cohort...

  12. Heavy Metal Content in Thoracic Tissue Samples from Patients with and without NSCLC

    Directory of Open Access Journals (Sweden)

    Jessica Q. Tran

    2014-01-01

    Full Text Available Objectives. Environmental factors expose an individual to heavy metals that may stimulate cancer growth preclinically including non-small cell lung cancer (NSCLC cells. Here, we examine the prevalence of four heavy metals present in postsurgical tissues from individuals with and without NSCLC. Materials and Methods. Thoracic tissue samples from two separate sample sets were analyzed for cadmium (Cd, arsenic (As, mercury (Hg, and lead (Pb content. Results. In the first sample set, there was no significant measurable amount of Pb and Hg found in either NSCLC tissue or nonmalignant lung tissue samples. Cd was the most prevalent heavy metal and As was present in moderate amounts. In the second sample set, Cd was measurable across all tissue types taken from 28 NSCLC patients and significantly higher Cd was measurable in noncancer benign lung (n=9. In the NSCLC samples, As was measurable in moderate amounts, while Hg and Pb amounts were negligible. Conclusion. Cd and As are present in lung tissues for patients with NSCLC. With existing preclinical evidence of their tumorigenecity, it is plausible that Cd and/or As may have an impact on NSCLC development. Additional studies examining the prevalence and association between smokers and nonsmokers are suggested.

  13. Integrative discovery of epigenetically derepressed cancer testis antigens in NSCLC.

    Directory of Open Access Journals (Sweden)

    Chad A Glazer

    Full Text Available BACKGROUND: Cancer/testis antigens (CTAs were first discovered as immunogenic targets normally expressed in germline cells, but differentially expressed in a variety of human cancers. In this study, we used an integrative epigenetic screening approach to identify coordinately expressed genes in human non-small cell lung cancer (NSCLC whose transcription is driven by promoter demethylation. METHODOLOGY/PRINCIPAL FINDINGS: Our screening approach found 290 significant genes from the over 47,000 transcripts incorporated in the Affymetrix Human Genome U133 Plus 2.0 expression array. Of the top 55 candidates, 10 showed both differential overexpression and promoter region hypomethylation in NSCLC. Surprisingly, 6 of the 10 genes discovered by this approach were CTAs. Using a separate cohort of primary tumor and normal tissue, we validated NSCLC promoter hypomethylation and increased expression by quantitative RT-PCR for all 10 genes. We noted significant, coordinated coexpression of multiple target genes, as well as coordinated promoter demethylation, in a large set of individual tumors that was associated with the SCC subtype of NSCLC. In addition, we identified 2 novel target genes that exhibited growth-promoting effects in multiple cell lines. CONCLUSIONS/SIGNIFICANCE: Coordinated promoter demethylation in NSCLC is associated with aberrant expression of CTAs and potential, novel candidate protooncogenes that can be identified using integrative discovery techniques. These findings have significant implications for discovery of novel CTAs and CT antigen directed immunotherapy.

  14. Predictive factors associated with prolonged survival in patients with advanced non-small-cell lung cancer (NSCLC) treated with gefitinib

    OpenAIRE

    Satouchi, M; Negoro, S; Funada, Y; Urata, Y.; Shimada, T; Yoshimura, S.; Kotani, Y.; Sakuma, T.; Watanabe, H.(Max-Planck-Institut für Kernphysik, 69117, Heidelberg, Germany); Adachi, S.; Takada, Y.; Y. Yatabe; Mitsudomi, T.

    2007-01-01

    This study aimed to identify predictive factors associated with prognostic benefits of gefitinib. A total of 221 Japanese patients who received gefitinib (250 mg day−1) were examined retrospectively and potential predictive factors analysed. Overall response rate (ORR) was 24.4% and median survival time (MST) was 8.0 months. In a log-rank test, survival was significantly better in females, patients with adenocarcinoma, never-smokers, favourable performance status (PS) and patients with epider...

  15. ERCC1 and histopathology in advanced NSCLC patients randomized in a large multicenter phase III trial

    DEFF Research Database (Denmark)

    Vilmar, Adam Christian; Santoni-Rugiu, E; Sørensen, J B

    2010-01-01

    Customized chemotherapy is likely to improve outcome in patients with advanced non-small-cell lung cancer (NSCLC). Excision repair cross-complementation group 1 (ERCC1) is a promising biomarker; however, current evidence is inadequate. Impact of ERCC1 status was evaluated among patients participa...

  16. Lineage tracing of metastasis in a mouse model for Non-small cell lung cancer (NSCLC)

    OpenAIRE

    Thakur, Chitra

    2012-01-01

    Non-small cell lung cancer (NSCLC) is the deadliest form of lung cancer and has a poor prognosis due to its high rate of metastasis. Notably, metastasis is one of the leading causes of death among cancer patients. Despite the clinical importance, the cellular and molecular mechanisms that govern the initiation, establishment and progression of metastasis remain unclear. Moreover, knowledge gained on metastatic process was largely based on cultured or in vitro manipulated cells that were reint...

  17. RAGE genetic polymorphisms are associated with risk, chemotherapy response and prognosis in patients with advanced NSCLC.

    Directory of Open Access Journals (Sweden)

    Xiang Wang

    Full Text Available AIM: To explore the association between genetic polymorphisms of the receptor for advanced glycation end-products (RAGE and susceptibility, chemotherapy response rate and prognosis of non-small cell lung cancer (NSCLC. METHOD: This is a prospective study in which 562 patients with NSCLC and 764 healthy controls were enrolled. Three RAGE genetic polymorphisms, namely, -429T/C, -374T/A and 82G/S were genotyped. Platinum-based chemotherapy was given to 432 subjects with advanced inoperable NSCLC and their responses to chemotherapy were evaluated. RESULTS: All the polymorphic genotypes of RAGE polymorphisms were associated with susceptibility for NSCLC. Only the 82G/S polymorphisms denoted a significant difference between responders and non-responders to chemotherapy. The 82SS genotype and 82S allele distribution not only increased the NSCLC risk, but also was associated with a lower chemotherapy response rate and poor prognosis, indicated by overall survival and progression free survival. CONCLUSION: The 82G/S genetic polymorphism of RAGE gene might be used as a genetic marker to screen for patients sensitive to thermotherapy and to predict the prognosis of NSCLC.

  18. CyberKnife with tumor tracking: An effective alternative to wedge resection for high-risk surgical patients with stage I non-small cell lung cancer (NSCLC

    Directory of Open Access Journals (Sweden)

    Sean eCollins

    2012-02-01

    Full Text Available Published data suggests that wedge resection for stage I NSCLC results in improved overall survival compared to stereotactic body radiation therapy (SBRT. We report CyberKnife outcomes for high-risk surgical patients with biopsy-proven stage I NSCLC. PET/CT imaging was completed for staging. Three-to-five gold fiducial markers were implanted in or near tumors to serve as targeting references. Gross tumor volumes (GTVs were contoured using lung windows; the margins were expanded by 5 mm to establish the planning treatment volume (PTV. Treatment plans were designed using hundreds of pencil beams. Doses delivered to the PTV ranged from 42-60 Gy in 3 fractions. The 30-Gy isodose contour extended at least 1cm from the GTV to eradicate microscopic disease. Treatments were delivered using the CyberKnife system with tumor tracking. Examination and PET/CT imaging occurred at 3-month follow-up intervals. Forty patients (median age 76 with a median maximum tumor diameter of 2.6 cm (range, 1.4-5.0 cm and a mean post-bronchodilator percent predicted forced expiratory volume in 1 second (FEV1 of 57% (range, 21 - 111% were treated. A mean dose of 50 Gy was delivered to the PTV over 3 to 13 days (median, 7 days. The 30-Gy isodose contour extended a mean 1.9 cm from the GTV. At a median 44 months (range, 12 -72 months follow-up, the 3-year Kaplan-Meier locoregional control and overall survival estimates compare favorably with contemporary wedge resection outcomes at 91% and 75% , respectively. CyberKnife is an effective treatment approach for stage I NSCLC that is similar to wedge resection, eradicating tumors with 1 to 2 cm margins in order to preserve lung function. Prospective randomized trials comparing CyberKnife with wedge resection are necessary to confirm equivalence.

  19. Quantification of Cell-Free mSHOX2 Plasma DNA for Therapy Monitoring in Advanced Stage Non-Small Cell (NSCLC) and Small-Cell Lung Cancer (SCLC) Patients

    OpenAIRE

    Schmidt, Bernd; Beyer, Julia; Dietrich, Dimo; Bork, Ines; Liebenberg, Volker; Fleischhacker, Michael

    2015-01-01

    Purpose Most patients suffering from advanced lung cancer die within a few months. To exploit new therapy regimens we need better methods for the assessment of a therapy response. Material and Methods In a pilot study we prospectively enrolled 36 patients with advanced NSCLC and SCLC (34 stage IV, 2 stage IIIB) of whom 34 received standard platinum-based chemo/radiotherapy and two were treated with a tyrosine kinase inhibitor. We measured the levels of extracellular methylated SHOX2 DNA (mSHO...

  20. Effect of daily administration of oral etoposide for patients with stage III non-small cell lung cancer (NSCLC) treated with concurrent radiation therapy

    International Nuclear Information System (INIS)

    Purpose: The purpose of this study is to explore the effect of daily administration of oral etoposide(25mg) for patients with stage III NSCLC treated with concurrent radiation therapy. Planned endpoints were response, survival and toxicities. Material and Methods: Between (8(92)) and (9(95)), 37 stage III NSCLC patients were randomized to daily oral etoposide(25mg) with concurrent radiation therapy group(ERT) in 21 and radiation therapy alone group(RT) in 16. Etoposide was administered in the morning throughout radiation therapy. Median total irradiated dose, fraction size and time were 61.9Gy, 34.2 fractions and 48.8 days, respectively. Results: TO Monovariate survival analysis between ERT and RT showed no significant difference(p=0.10), but multivariate analysis confirmed that administration of oral etoposide is independent prognostic factor (p=0.009), together with T factor and N factor. Conclusion: ERT was better in local response but poorer in survival than RT. We concluded that complications of ERT was severe enough to cause death in some patients. We should design some methods to decrease these complications to make use of good local response acquired with ERT

  1. [F-18] FDG-PET/CT parameters as predictors of outcome in inoperable NSCLC patients

    Directory of Open Access Journals (Sweden)

    Nappi Antonio

    2015-12-01

    Full Text Available Background. We evaluated the prognostic significance of standardized uptake value (SUVmax, metabolic tumour volume (MTV, and total lesion glycolysis (TLG in [F-18] FDG PET/CT findings in patients with inoperable non-small-cell lung cancer (NSCLC.

  2. Chemotherapy and quality of life in NSCLC PS 2 patients

    DEFF Research Database (Denmark)

    Helbekkmo, Nina; Strøm, Hans H; Sundstrøm, Stein H;

    2009-01-01

    INTRODUCTION: Nearly 40% of patients with advanced NSCLC are in performance status (PS) 2. These patients have a shorter life expectancy than PS 0/1 patients and they are underrepresented in clinical trials. Data on how platinum-based combination chemotherapy affects Health Related Quality of Life...... (HRQOL) of patients with PS 2 are scarce and the treatment of this important group of patients is controversial. METHODS: A national multicenter phase III study on platinum based chemotherapy to 432 advanced NSCLC patients included 123 patients with PS 2. To explore the treatment impact on HRQOL......: Whereas the demographic data at baseline were well balanced between the groups, the PS 2 patients had significantly worse function and more severe symptoms than the PS 0/1 patients. In response to combination chemotherapy, the PS 2 patients had a more profound improvement of global QOL, cognitive function...

  3. EGFR CA repeat polymorphism predict clinical outcome in EGFR mutation positive NSCLC patients treated with erlotinib

    DEFF Research Database (Denmark)

    Winther Larsen, Anne; Nissen, Peter Henrik; Meldgaard, Peter;

    2014-01-01

    OBJECTIVES: Somatic mutations in the epidermal growth factor receptor (EGFR) are predictors of efficacy for treatment with the EGFR tyrosine kinase inhibitor erlotinib in non-small cell lung cancer (NSCLC). A CA repeat polymorphism in intron 1 of the EGFR gene influences the transcription...... of the EGFR gene. This study evaluates the association between the CA repeat polymorphism and outcome in NSCLC patients treated with erlotinib.MATERIALS AND METHODS: Number of CA repeats in the EGFR gene was evaluated with PCR-fragment length analysis by capillary electrophoresis in 432 advanced NSCLC...... patients treated with erlotinib irrespective of EGFR mutation status. Patients were dichotomized into harboring short allele (CA≤16 in any allele) or long alleles (CA>16 in both alleles). Number of repeats was correlated with clinical characteristic and outcome. A subgroup analysis was performed based...

  4. Economic Evaluation of Positron Emission Tomography (PET) in Non Small Cell Lung Cancer (NSCLC), CHERE Working Paper 2007/6

    OpenAIRE

    Alex Bird; Richard Norman; Stephen Goodall

    2007-01-01

    Background: There are several perceived benefits from introducing positron emission tomography (PET) scanning into the staging of non small lung cancer (NSCLC). However, its greatest primary benefit is the role it can potential perform in reducing the number of unnecessary diagnostic examinations and futile surgeries. Objectives: To evaluate the economic impact and cost effectiveness of PET scanning in the management of potentially operable NSCLC patients using a cost-utility model. Methods: ...

  5. FDG-PET/CT response evaluation during EGFR-TKI treatment in patients with NSCLC

    Institute of Scientific and Technical Information of China (English)

    Matthijs; H; van; Gool; Tjeerd; S; Aukema; Koen; J; Hartemink; Renato; A; Valdés; Olmos; Houke; M; Klomp; Harm; van; Tinteren

    2014-01-01

    Over recent years,[18F]-fluorodeoxyglucose positron emission tomography acquired together with low dose computed tomography(FDG-PET/CT)has proven its role as a staging modality in patients with non-small cell lung cancer(NSCLC).The purpose of this review was to present the evidence to use FDG-PET/CT for response evaluation in patients with NSCLC,treated with epidermal growth factor receptor(EGFR)-tyrosine kinase inhibitors(TKI).All published articles from 1November 2003 to 1 November 2013 reporting on 18FFDG-PET response evaluation during EGFR-TKI treatment in patients with NSCLC were collected.In total 7studies,including data of 210 patients were eligible for analyses.Our report shows that FDG-PET/CT responseduring EGFR-TKI therapy has potential in targeted treatment for NSCLC.FDG-PET/CT response is associated with clinical and radiologic response and with survival.Furthermore FDG-PET/CT response monitoring can be performed as early as 1-2 wk after initiation of EGFR-TKI treatment.Patients with substantial decrease of metabolic activity during EGFR-TKI treatment will probably benefit from continued treatment.If metabolic response does not occur within the first weeks of EGFR-TKI treatment,patients may be spared(further)unnecessary toxicity of ineffective treatment.Refining FDG-PET response criteria may help the clinician to decide on continuation or discontinuation of targeted treatment.

  6. Correlation of the apparent diffusion coefficient (ADC with the standardized uptake value (SUV in lymph node metastases of non-small cell lung cancer (NSCLC patients using hybrid 18F-FDG PET/MRI.

    Directory of Open Access Journals (Sweden)

    Benedikt Michael Schaarschmidt

    Full Text Available To compare the apparent diffusion coefficient (ADC in lymph node metastases of non-small cell lung cancer (NSCLC patients with standardized uptake values (SUV derived from combined 18F-fluoro-deoxy-glucose-positron emission tomography/magnetic resonance imaging (18F-FDG PET/MRI.38 patients with histopathologically proven NSCLC (mean age 60.1 ± 9.5 y received whole-body PET/CT (Siemens mCT™ 60 min after injection of a mean dose of 280 ± 50 MBq 18F-FDG and subsequent PET/MRI (mean time after tracer injection: 139 ± 26 min, Siemens Biograph mMR. During PET acquisition, simultaneous diffusion-weighted imaging (DWI, b values: 0, 500, 1000 s/mm² was performed. A maximum of 10 lymph nodes per patient suspicious for malignancy were analyzed. Regions of interest (ROI were drawn covering the entire lymph node on the attenuation-corrected PET-image and the monoexponential ADC-map. According to histopathology or radiological follow-up, lymph nodes were classified as benign or malignant. Pearson's correlation coefficients were calculated for all lymph node metastases correlating SUVmax and SUVmean with ADCmean.A total of 146 suspicious lymph nodes were found in 25 patients. One hundred lymph nodes were eligible for final analysis. Ninety-one lymph nodes were classified as malignant and 9 as benign according to the reference standard. In malignant lesions, mean SUVmax was 9.1 ± 3.8 and mean SUVmean was 6.0 ± 2.5 while mean ADCmean was 877.0 ± 128.6 x10(-5 mm²/s in PET/MRI. For all malignant lymph nodes, a weak, inverse correlation between SUVmax and ADCmean as well as SUVmean and ADCmean (r = -0.30, p<0.05 and r = -0.36, p<0.05 existed.The present data show a weak inverse correlation between increased glucose-metabolism and cellularity in lymph node metastases of NSCLC patients. 18F-FDG-PET and DWI thus may offer complementary information for the evaluation of treatment response in lymph node metastases of NSCLC.

  7. Phase II trial of second-line erlotinib and digoxin for nonsmall cell lung cancer (NSCLC

    Directory of Open Access Journals (Sweden)

    Fadi Kayali

    2011-02-01

    Full Text Available Fadi Kayali, Muhamad A Janjua, Damian A Laber, Donald Miller, Goetz H KloeckerUniversity of Louisville, James Graham Brown Cancer Center, Louisville, KY, USABackground: In vitro digoxin sensitizes cancer cells to the induction of apoptosis by chemotherapy. Inhibition of the Na/K-ATPase enzyme by ouabain disturbs the intracellular ion composition of cancer cells, altering cellular homeostasis. This suggests that inhibition of the Na/K pump results in cellular sensitization of malignant but not benign cells to the induction of apoptosis. Epidemiologic studies have also shown beneficial effects of digitalis in breast cancer incidence. At ASCO (American Society of Clinical Oncology 2007 our group presented a Phase II study showing encouraging results by adding digoxin to biochemotherapy for melanoma. Erlotinib is one of the standard second-line treatments for nonsmall cell lung cancer (NSCLC, with a response rate (RR of 10%. This study's hypothesis was that adding digoxin to erlotinib will improve the RR and time to progression (TTP in NSCLC.Methods: Patients with progressive disease (PD after chemotherapy were enrolled if they had an ECOG (Eastern Cooperative Oncology Group score from 0 to 2 and good organ function. Daily erlotinib 150 mg and digoxin 0.25 mg were taken by mouth. The digoxin dose was adjusted to keep levels between 1 and 2 ng/mL. Computed tomography scans were done every 6 weeks. Treatment continued until PD or significant toxicity occurred.Results: Patient accrual lasted from March 2006 until August 2008 and was stopped early at the time of interim analysis. Twenty-eight patients were enrolled, and 24 who completed at least 6 weeks of therapy are presented here. All patients had unresectable NSCLC stage III/IV at diagnosis. Median age was 61 (34–78, 14 were female, 17 had prior radiation (not involving the target lesions, 23 had one prior chemotherapy, and one subject had two. Only one patient was a never-smoker. Histologies were

  8. Plasma PGE-2 levels and altered cytokine profiles in adherent peripheral blood mononuclear cells in non-small cell lung cancer (NSCLC

    Directory of Open Access Journals (Sweden)

    Hirschowitz Edward A

    2002-11-01

    Full Text Available Abstract Introduction PGE-2 is constitutively produced by many non-small cell lung cancers (NSCLC and its immunosuppressive effects have been linked to altered immune responses in lung cancer. We asked whether elevated levels of plasma PGE-2 correlated with monocyte IL10 production in the NSCLC environment. Looking for correlation in NSCLC patient blood we assayed plasma from NSCLC patients for PGE2 and IL10; we further evaluated production of IL10 by adherent mononuclear cells from a subset of these patients looking for an altered cytokine profile. Results Our initial in vitro experiments show that monocyte IL10 induction correlates with tumor cell PGE-2 production, confirming similar reports in the literature. Data show plasma PGE-2 levels in 38 NSCLC patients are elevated compared to normal controls. Plasma IL10 levels were not significantly elevated; however, adherent monocytes derived from NSCLC patient blood did produce significantly more IL10 in 24 hr primary culture than those from normal controls (p Conclusions Elevated plasma PGE-2 and monocyte IL10 production are associated with NSCLC. The biological significance to elevated PGE-2 levels in NSCLC are unclear. Further investigation of each as a nonspecific marker for NSCLC tumor is warranted.

  9. SIRT1 expression is associated with the chemotherapy response and prognosis of patients with advanced NSCLC.

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    Tao Zhang

    Full Text Available AIM: The role of Sirtuin 1 (SIRT 1 in carcinogenesis is controversial. This study was to explore the association between the SIRT1 expression and the clinical characteristics, the responsiveness to chemotherapy and prognosis in Non-small cell lung cancer (NSCLC. METHODS: We enrolled 295 patients with inoperable advanced stage of NSCLC, namely, stage III (A+B and IV NSCLC. All patients had received platinum-based chemotherapy after diagnosis and the chemotherapy response were evaluated. All patients were followed up for overall survival (OS and progression free survival (PFS. In vitro, H292 cells were tranfected with SIRT1 small interfering RNA (siRNA. The cell biological behaviors and chemosensitivity to cisplatin treatment were studied. The in vivo tumorgenesis and metastasis assays were performed in nude mice. RESULTS: We found that the SIRT1 expressions were significantly associated with the tumor stage, tumor size and differentiation status. Patients with high SIRT 1 expressions had a significantly higher chance to be resistant to chemotherapy than those with low SIRT 1 expression. Patients with high expression of SIRT1 had significantly shorter OS and DFS than those with low expression. Cox analyses confirmed that the SIRT 1 expression was a strong predictor for a poor OS and PFS in NSCLC patients underwent Platinum-based chemotherapy. In vitro studies revealed that the reduced expression SIRT 1 by siRNA technique significantly inhibited cell proliferation, migration and invasion. More importantly, SIRT1 si-RNA significantly enhanced the chemosensitivity of H292 cells to cisplatin treatment. The in vivo tumorgenesis and metastasis assays showed that SIRT1 knockdown dramatically reduced the tumor volume and the metastatic ability in nude mice. CONCLUSION: Collectively, our data suggest that the SIRT1 expression may be a molecular marker associated with the NSLCLC clinical features, treatment responsiveness and prognosis of advanced NSCLC.

  10. A Novel Method for Detecting p53 Autoantibodies in Sera of Patients with NSCLC

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    Kai TANG

    2009-09-01

    Full Text Available Background and objective Serum autoantibody detection is useful means for the early diagnosis and prognosis of cancer. So our objective was to synthesize peptide array to analyse p53 autoantibodies in the sera of patients with non small cell lung cancer (NSCLC. Methods Cellulose-bound overlapping peptides (12 mers derived from p53 wild type protein were synthesized using SOPTs synthesis technique by an AutoSpot robot –ASP SL (Intavis, Germany. The membrane was incubated with 1/400 dilutions of p53 monoclonal antibody (Sc-53394 to establish a new approach to detect p53 antibody, and the epitopes of the p53 monoclonal antibody is already known. We analysed the p53 autoantibodies from the sera of NSCLC and controls by peptide array and ELISA. Results We synthesized on cellulose membranes twelve-amino-acid overlapping peptides which included all of the sequences of the polypeptide chain of p53. The p53 autoantibody was positive in seven cases of thirty patients’ sera with NSCLC and was negative in sera of the controls, with the same result of ELISA. Conclusion The peptide array could be applied not only to detect the autoantibodies in the sera of patients with lung cancer, but also to map the epitopes of the autoantibodies which might be useful for the early diagnosis and prognosis of cancer.

  11. Effects of DMSO, glycerol, betaine and their combinations in detecting single nucleotide polymorphisms of epidermal growth factor receptor (EGFR) gene promoter sequence in non-small-cell lung cancer (NSCLC) patients.

    Science.gov (United States)

    Jurišić, Vladimir; Obradović, Jasmina; Tošić, Natasa; Pavlović, Sonja; Kulić, Milan; Djordjević, Nataša

    2016-09-01

    The aim of the study was to examine the effects of frequently used polymerase chain reaction (PCR) additives DMSO, glycerol and betaine on amplification of GC-rich epidermal growth factor receptor (EGFR) gene promoter region, in order to detect the presence of -216G>T and -191C>A gene variations in non-small-cell lung cancer (NSCLC) patients. PCR products and restriction fragments were detected by electrophoresis on 8% polyacrylamide gel and 3% agarose gel. Our analysis shows that single used additives including DMSO in concentration of 7% and 10%, glycerol in concentration of 10%, 15% and 20%, as well as betaine in concentration of 1M, 1.5M and 2M significantly enhanced the yield and specificity of PCR reaction. In addition, the combination of 10% DMSO with 15% glycerol has shown positive effects, whereas other analyzed combinations of additives failed to amplify the EGFR promoter region. PMID:27284695

  12. Systemic treatment in EGFR-ALK NSCLC patients: second line therapy and beyond

    International Nuclear Information System (INIS)

    Lung cancer is the most frequently diagnosed cancer and a leading cause of cancer mortality worldwide, with adenocarcinoma being the most common histological subtype. Deeper understanding of the pathobiology of non-small cell lung cancer (NSCLC) has led to the development of small molecules that target genetic mutations known to play critical roles in progression to metastatic disease and to influence response to targeted therapies. The principle goal of precision medicine is to define those patient populations most likely to respond to targeted therapies. However, the cancer genome landscape is composed of relatively few “mountains” [representing the most commonly mutated genes like KRAS, epidermal growth factor (EGFR), and anaplastic lymphoma kinase (ALK)] and a vast number of “hills” (representing low frequency but potentially actionable mutations). Low-frequency lesions that affect a druggable gene product allow a relatively small population of cancer patients for targeted therapy to be selected

  13. Preliminary Study of MALDI-TOF Mass Spectrometry-based Screening of Patients with the NSCLC Serum-Specific Peptides

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    Juan AN

    2013-05-01

    Full Text Available Background and objective The improved survival of patients with lung cancer depends on early diagnosis of lung cancer. However, the traditional diagnostic techniques have several limitations. Mass spectrometry (MS has been applied as a core technology for cancer diagnosis in preliminary proteomic studies. The aim of this study is to explore the differences in the serum peptide levels of patients with non-small cell lung cancer (NSCLC and healthy individuals using matrix-assisted laser desorption/ionization (MALDI-time-of-flight (TOF-MS. A NSCLC serum classification model was then established. Methods One hundred and thirty three cases of patients with NSCLC serum specimens and 132 cases of healthy human serum specimens were randomly divided into two groups in accordance with the ratio of three to one without age and gender differences. The training group was used to establish the classification model, this group included serum samples from 100 NSCLC cases and 100 healthy individuals. The test group for validating the proposed model was composed of the remaining serum samples from 33 NSCLC cases and 32 healthy individuals. Peptides were extracted from the samples using magnetic beads- immobilized metal affinity capture - copper, and their mass spectra were obtained using an automated MALDI-TOF-MS system. The MS data from the training group was analyzed using the ClinproToolTM software to identify the individual peptide fragments and establish the classification model. The sensitivity and specificity of the model were verified by blind testing with the test group. Results Among the 131 different peptide peaks, ranging from m/z 1,000 Da to 10,000 Da, 14 peaks were significantly different in the NSCLC samples of the training group, as compared with the controls (P<0.000,001; AUC≥0.9; these included 2 higher peaks and 12 lower peaks. The classification model was established, and the test group was verified for only 3 peptide peaks (7,478.59, 2

  14. Resistance gene expression determines the in vitro chemosensitivity of non-small cell lung cancer (NSCLC

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    Amer Khalid

    2009-08-01

    Full Text Available Abstract Background NSCLC exhibits considerable heterogeneity in its sensitivity to chemotherapy and similar heterogeneity is noted in vitro in a variety of model systems. This study has tested the hypothesis that the molecular basis of the observed in vitro chemosensitivity of NSCLC lies within the known resistance mechanisms inherent to these patients' tumors. Methods The chemosensitivity of a series of 49 NSCLC tumors was assessed using the ATP-based tumor chemosensitivity assay (ATP-TCA and compared with quantitative expression of resistance genes measured by RT-PCR in a Taqman Array™ following extraction of RNA from formalin-fixed paraffin-embedded (FFPE tissue. Results There was considerable heterogeneity between tumors within the ATP-TCA, and while this showed no direct correlation with individual gene expression, there was strong correlation of multi-gene signatures for many of the single agents and combinations tested. For instance, docetaxel activity showed some dependence on the expression of drug pumps, while cisplatin activity showed some dependence on DNA repair enzyme expression. Activity of both drugs was influenced more strongly still by the expression of anti- and pro-apoptotic genes by the tumor for both docetaxel and cisplatin. The doublet combinations of cisplatin with gemcitabine and cisplatin with docetaxel showed gene expression signatures incorporating resistance mechanisms for both agents. Conclusion Genes predicted to be involved in known mechanisms drug sensitivity and resistance correlate well with in vitro chemosensitivity and may allow the definition of predictive signatures to guide individualized chemotherapy in lung cancer.

  15. Quantification of cell-free mSHOX2 Plasma DNA for therapy monitoring in advanced stage non-small cell (NSCLC and small-cell lung cancer (SCLC patients.

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    Bernd Schmidt

    Full Text Available Most patients suffering from advanced lung cancer die within a few months. To exploit new therapy regimens we need better methods for the assessment of a therapy response.In a pilot study we prospectively enrolled 36 patients with advanced NSCLC and SCLC (34 stage IV, 2 stage IIIB of whom 34 received standard platinum-based chemo/radiotherapy and two were treated with a tyrosine kinase inhibitor. We measured the levels of extracellular methylated SHOX2 DNA (mSHOX2 in plasma before and during therapy until re-staging. The mSHOX2 analysis was blinded with respect to the clinical data making it an observational study.According to the re-staging of 31 first-line patients, 19 patients were classified as non-responders while 12 patients were in the responder group. We observed a tight correlation between radiological data and the change of plasma mSHOX2 level as the equivalent for a therapy response. A ROC analysis showed a high discriminatory power for both patient groups already one week after therapy start (AUC 0.844. Additionally, a Kaplan-Meier and Cox Proportional Hazards analyses revealed a strong relationship between survival and plasma mSHOX2 value p ≤ 0.001 (hazard ratio 11.08 providing some evidence for mSHOX2 also being a predictive marker.The longitudinal measurement of extracellular plasma mSHOX2 DNA yields information about the response to cytotoxic treatment and allows an early assessment of treatment response for lung cancer patients. If confirmed in a larger study this would be a valuable tool for selecting and guiding a cytotoxic treatment.

  16. Quantification of Cell-Free mSHOX2 Plasma DNA for Therapy Monitoring in Advanced Stage Non-Small Cell (NSCLC) and Small-Cell Lung Cancer (SCLC) Patients

    Science.gov (United States)

    Schmidt, Bernd; Beyer, Julia; Dietrich, Dimo; Bork, Ines; Liebenberg, Volker; Fleischhacker, Michael

    2015-01-01

    Purpose Most patients suffering from advanced lung cancer die within a few months. To exploit new therapy regimens we need better methods for the assessment of a therapy response. Material and Methods In a pilot study we prospectively enrolled 36 patients with advanced NSCLC and SCLC (34 stage IV, 2 stage IIIB) of whom 34 received standard platinum-based chemo/radiotherapy and two were treated with a tyrosine kinase inhibitor. We measured the levels of extracellular methylated SHOX2 DNA (mSHOX2) in plasma before and during therapy until re-staging. The mSHOX2 analysis was blinded with respect to the clinical data making it an observational study. Results According to the re-staging of 31 first-line patients, 19 patients were classified as non-responders while 12 patients were in the responder group. We observed a tight correlation between radiological data and the change of plasma mSHOX2 level as the equivalent for a therapy response. A ROC analysis showed a high discriminatory power for both patient groups already one week after therapy start (AUC 0.844). Additionally, a Kaplan-Meier and Cox Proportional Hazards analyses revealed a strong relationship between survival and plasma mSHOX2 value p≤0.001 (hazard ratio 11.08) providing some evidence for mSHOX2 also being a predictive marker. Conclusion The longitudinal measurement of extracellular plasma mSHOX2 DNA yields information about the response to cytotoxic treatment and allows an early assessment of treatment response for lung cancer patients. If confirmed in a larger study this would be a valuable tool for selecting and guiding a cytotoxic treatment. PMID:25675432

  17. Distribution Characteristics of Syndrome Types in TCM in Patients with Advanced Non-Small Cell Lung Cancer (NSCLC)%207例晚期非小细胞肺癌中医证型分布特点

    Institute of Scientific and Technical Information of China (English)

    杨小兵; 龙顺钦; 邓宏; 刘伟; 河文峰; 潘宗奇; 周宇姝; 蔡姣芝; 欧阳育树

    2013-01-01

    Objective: To investigate the distribution characteristics of TCM syndrome types in patients with advanced non-smallcell lung cancer ( NSCLC ) . Methods; Patients were selected with the inclusion criteria, retrospective method was used to observe the distribution. TCM syndromes were generalized according to pre-designed forms and diagnostic criteria for clinical syndromes, inputting the questionnaire data into database, the statistical analysis was conducted. Results : Total of 207 patients with advanced NSCLC ( stage Ⅲ B and Ⅳ ) were collected. The distribution of TCM syndromes were as follows: Qi-deficiency with damp-phlegm type was the most common type, accounted for 76.3%; Qi-yin deficiency type followed, accounted for 9.2%; Qi stagnation with blood stasis type, Yin asthenia and excess toxin and heat type and toxic heat flourishing type were 5.8%, 5.8% and 2.9%, respectively. Conclusion; The study suggests that Qi-deficiency with damp-phlegm type was the most common type in patients with advanced non-small cell lung cancer ( stage Ⅲ B and Ⅳ ) .%目的:探讨晚期(ⅢB及Ⅳ期)非小细胞肺癌的中医证型分布特点.方法:采用回顾性的研究方法,按照纳入标准筛选病例,根据预先设计的观察表和临床证型诊断标准,归纳证型,将调查表数据输入数据库,进行统计学分析.结果:共收集到207例晚期非小细胞肺癌患者,各证型构成如下:气虚痰湿型最多,占76.3%,其次为气阴两虚型,占9.2%,气滞血瘀型、阴虚毒热型及热毒炽盛型分别占5.8%、5.8%、2.9%.结论:晚期(ⅢB及Ⅳ期)非小细胞肺癌的中医证型以气虚痰湿型为主.

  18. Anti-angiogenic drugs for second-line treatment of NSCLC patients: just new pawns on the chessboard?

    Science.gov (United States)

    Bronte, Giuseppe; Passiglia, Francesco; Galvano, Antonio; Russo, Antonio

    2016-01-01

    Tumor angiogenesis is one of the main pathways targeted to treat cancer. Bevacizumab added survival benefit when combined with platinum-based chemotherapy in NSCLC. Recently, Phase III trials showed survival benefit when anti-angiogenic drugs are added to docetaxel as second-line treatment for NSCLC. These anti-angiogenic agents include nintedanib and ramucirumab, a tyrosine-kinase inhibitor and a monoclonal antibody, respectively, which target receptors involved in angiogenesis. These studies have some similarities and differences. We propose a new algorithm for treatment sequences in performance status 0-1 patients with non-oncogene-addicted NSCLC type adenocarcinoma. Indeed clearer scientific evidences are available for this subgroup of patients.

  19. Plasma cell-free DNA levels and integrity in patients with chest radiological findings: NSCLC versus benign lung nodules.

    Science.gov (United States)

    Szpechcinski, Adam; Rudzinski, Piotr; Kupis, Wlodzimierz; Langfort, Renata; Orlowski, Tadeusz; Chorostowska-Wynimko, Joanna

    2016-05-01

    Effective discrimination between lung cancer and benign tumours is a common clinical problem in the differential diagnosis of solitary pulmonary nodules. The analysis of cell-free DNA (cfDNA) in blood may greatly aid the early detection of lung cancer by evaluating cancer-related alterations. The plasma cfDNA levels and integrity were analysed in 65 non-small cell lung cancer (NSCLC) patients, 28 subjects with benign lung tumours, and 16 healthy controls using real-time PCR. The NSCLC patients demonstrated significantly higher mean plasma cfDNA levels compared with those with benign tumours (P = 0.0009) and healthy controls (P 2.8 ng/ml provided 86.4% sensitivity and 61.4% specificity in discriminating NSCLC from benign lung pathologies and healthy controls. cfDNA integrity showed better discriminatory power (91% sensitivity, 68.2% specificity). These data demonstrate that plasma cfDNA concentration and integrity analyses can significantly differentiate between NSCLC and benign lung tumours. The diagnostic capacity of the quantitative cfDNA assay is comparable to the values presented by conventional imaging modalities used in clinical practice. PMID:26854716

  20. Re-Treatment with EGFR-TKIs in NSCLC Patients Who Developed Acquired Resistance

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    Wen-Shuo Wu

    2014-06-01

    Full Text Available In the era of personalized medicine, epidermal growth factor receptor (EGFR inhibition with tyrosine kinase inhibitor (TKI has been a mainstay of treatment for non-small cell lung cancer (NSCLC patients with an EGFR mutation. Acquired resistance, especially substitution of methionine for threonine at position 790 (T790M, which has accounted for more than half of the cases, developed inevitably in patients who were previously treated with EGFR-TKI. At present, there is no standard treatment for patients who have developed a resistance to EGFR-TKI. Several strategies have been developed or suggested to treat such patients. This article aimsto review the EGFR-TKI re-treatment strategy and the efficacy of different generations of EGFR-TKIs in patients with acquired resistance to prior EGFR-TKI.

  1. Metastatic squamous cell non-small-cell lung cancer (NSCLC): disrupting the drug treatment paradigm with immunotherapies

    OpenAIRE

    Scarpace, Sarah L

    2015-01-01

    Lung cancer is the third most commonly diagnosed cancer and the leading cause of cancer-related death in the United States. Unlike non-squamous NSCLC, squamous NSCLC rarely harbor epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) mutations for which there are directed therapies, and until the recent approval of immunotherapies for squamous NSCLC, a limited number of traditional cytotoxic chemotherapy drugs have been FDA-approved for use in the treatment of advanced ...

  2. Planned FDG PET-CT Scan in Follow-Up Detects Disease Progression in Patients With Locally Advanced NSCLC Receiving Curative Chemoradiotherapy Earlier Than Standard CT

    DEFF Research Database (Denmark)

    Pan, Yi; Brink, Carsten; Schytte, Tine;

    2015-01-01

    The role of positron emission tomography-computed tomography (PET-CT) in surveillance of patients with nonsmall cell lung cancer (NSCLC) treated with curatively intended chemoradiotherapy remains controversial. However, conventional chest X-ray and computed tomography (CT) are of limited value...... in discriminating postradiotherapy changes from tumor relapse. The aim of this study was to evaluate the clinical value of PET-CT scan in the follow-up for patients with locally advanced (LA) NSCLC receiving concomitant chemoradiotherapy (CCRT).Between 2009 and 2013, eligible patients with stages IIB-IIIB NSCLC...... were enrolled in the clinical trial NARLAL and treated in Odense University Hospital (OUH). All patients had a PET-CT scan scheduled 9 months (PET-CT9) after the start of the radiation treatment in addition to standard follow-up (group A). Patients who presented with same clinical stage of NSCLC...

  3. An Evidence-Based Approach to the Use of Predictive Biomarkers in the Treatment of Non- Small Cell Lung Cancer (NSCLC)

    Energy Technology Data Exchange (ETDEWEB)

    Quinton, Cindy [Juravinski Cancer Centre, 699 Concession, St Hamilton, Hamilton, ON L8V 5C2 (Canada); Ellis, Peter M., E-mail: peter.ellis@jcc.hhsc.ca [Juravinski Cancer Centre, 699 Concession, St Hamilton, Hamilton, ON L8V 5C2 (Canada); Department of Oncology, McMaster University Hamilton, ON L8S 4L8 (Canada)

    2011-09-13

    Recent advances in the treatment of non-small cell lung cancer (NSCLC) have led to improvements in patient survival and quality of life. It is unclear whether molecular abnormalities associated with NSCLC cell survival, growth and proliferation are useful in predicting treatment benefit. We conducted a systematic review to establish which biomarkers contribute meaningfully to the management of NSCLC. A team of researchers searched PubMed and conference proceedings (ASCO, ESMO, IASLC, USCAP) using MESH terms for NSCLC and randomized trials (RCT), plus keywords for variables of interest. Evidence from multiple RCTs confirmed that histologic subtype is prognostic for survival and predictive of treatment efficacy and/or toxicity in NSCLC. Likewise, activating mutations of the epidermal growth factor receptor (EGFR) are associated with benefit from EGFR tyrosine kinase inhibitors in patients with advanced non-squamous NSCLC and should be assessed routinely. No biomarkers to date reliably predict response to anti-Vascular Endothelial Growth Factor (VEGF) therapies. There are inconsistent data on the role of ERCC1, BRCA, Beta tubulin III, RRM1, K-RAS, or TP-53 in treatment decisions. These tests should not be routinely used in selecting treatment at this time, whereas EML4/ALK translocations predict responses to specific targeted agents, the optimal assessment of this molecular abnormality has yet to be established. Personalized care of patients with NSCLC based on biomarkers is increasingly important to both clinical practice and research.

  4. Acute esophagitis for patients with Local-regional Advanced NSCLC treated with concurrent chemoradiotherapy

    DEFF Research Database (Denmark)

    Pan, Y.; Brink, C.; Knap, M.;

    2015-01-01

    and clinical and dosimetric parameters in the patients with local advanced NSCLC receiving IMRT and concomitant chemotherapy (CCT). Materials and Methods: Between 2009 and 2013, 117 patients with stages IIB-IIIB NSCLC enrolled in the multi institution clinical trial NARLAL. All patients were treated with 2......Purpose/Objective: Esophagitis are one of the acute treatment related toxicities to definitive radiotherapy for NSCLC. Most current researches about the risk factors for acute esophagitis are based on 3DCRT. The purpose of this study was to estimate the dose-effect relationship between esophagitis...

  5. Prediction models for platinum-based chemotherapy response and toxicity in advanced NSCLC patients.

    Science.gov (United States)

    Yin, Ji-Ye; Li, Xi; Li, Xiang-Ping; Xiao, Ling; Zheng, Wei; Chen, Juan; Mao, Chen-Xue; Fang, Chao; Cui, Jia-Jia; Guo, Cheng-Xian; Zhang, Wei; Gao, Yang; Zhang, Chun-Fang; Chen, Zi-Hua; Zhou, Hui; Zhou, Hong-Hao; Liu, Zhao-Qian

    2016-07-10

    In this study, we aimed to establish a platinum-based chemotherapy response and toxicity prediction model in advanced non-small cell lung cancer (NSCLC) patients. 416 single nucleotide polymorphisms (SNPs) in 185 genes were genotyped, and their association with drug response and toxicity were estimated using logistic regression. Nine data mining techniques were employed to establish the prediction model; the sensitivity, specificity, overall accuracy and receiver operating characteristic (ROC) curve were used to assess the models' performance. Finally, selected models were validated in an independent cohort. The models established by naïve Bayesian algorithm had the best performance. The response prediction model achieved a sensitivity of 0.90 and a specificity of 0.47 with the ROC area under curve (AUC) of 0.80. The overall toxicity prediction model achieved a sensitivity of 0.86 and a specificity of 0.46 with the ROC AUC of 0.73. The hematological toxicity prediction model achieved a sensitivity of 0.89 and a specificity of 0.39 with the ROC AUC of 0.76. The gastrointestinal toxicity prediction model achieved a sensitivity of 0.93 and a specificity of 0.35 with the ROC AUC of 0.80. In conclusion, we provided platinum-based chemotherapy response and toxicity prediction models for advanced NSCLC patients. PMID:27126360

  6. Does VMAT for treatment of NSCLC patients increase the risk of pneumonitis compared to IMRT ? - a planning study

    DEFF Research Database (Denmark)

    Bertelsen, Anders; Hansen, Olfred; Brink, Carsten

    2012-01-01

    Volumetric modulated arc therapy (VMAT) for treatment of non-small cell lung cancer (NSCLC) patients potentially changes the risk of radiation-induced pneumonitis (RP) compared to intensity modulated radiation therapy (IMRT) if the dose to the healthy lung is changed significantly. In this study......, clinical IMRT plans were used as starting point for VMAT optimization and differences in risk estimates of RP between the two plan types were evaluated....

  7. Alectinib induced CNS radiation necrosis in an ALK+NSCLC patient with a remote (7 years) history of brain radiation.

    Science.gov (United States)

    Ou, Sai-Hong Ignatius; Weitz, Michael; Jalas, John R; Kelly, Daniel F; Wong, Vanessa; Azada, Michele C; Quines, Oliver; Klempner, Samuel J

    2016-06-01

    Alectinib is a second generation ALK inhibitor that has significant clinical activity in central nervous system (CNS) metastases in anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC). Pseudoprogression (PsP) due to radiation necrosis during alecitnib treatment of central nervous system (CNS) metastases from ALK-rearranged NSCLC as been reported. Hence, distinguishing radiation-related PsP from alectinib-induced radiographic changes is important to avoid erroneous early trial discontinuation and abandonment of an effective treatment. However, it remains difficult to assess casuality of radiation necrosis is related to recent direct radiation or induced by alectinib treatment or both. It is also unknown how long from previous radiation can alectinib still induce radiation necrosis. Here we reported a crizotinib-refractory ALK-positive NSCLC patient who develop radiation necrosis in one of his metastatic CNS lesions after approximately 12 months of alectinib treatment who otherwise had on-going CNS response on alectinib. His most recent radiation to his CNS metastases was 7 years prior to the start of alectinib. This case illustrates that in the setting of pror CNS radiation, given the significant clinical activity of alectinib in CNS metastases in ALK-positive NSCLC patients the risk of CNS radiation necrosis remains long after previous radiation to the CNS metastases has been completed and can occur after durable response of treatment. PMID:27133743

  8. Cancer Associated Fibroblasts in Stage I-IIIA NSCLC: Prognostic Impact and Their Correlations with Tumor Molecular Markers.

    Directory of Open Access Journals (Sweden)

    Thomas K Kilvaer

    Full Text Available Cancer Associated Fibroblasts (CAFs are thought to regulate tumor growth and metastasis. Fibroblast Activating Protein 1 (FAP-1 is a marker for fibroblast activation and by many recognized as the main marker of CAFs. Alpha Smooth Muscle Actin (α-SMA is a general myofibroblast marker, and can be used to identify CAFs. This study investigates the prognostic impact of FAP-1 and α-SMA in non-small cell lung cancer (NSCLC patients and correlates their expression to 105 proteins investigated in the same cohort.Tumor specimens from 536 NSCLC patients were obtained and tissue micro-arrays were constructed. Immunohistochemistry was used to evaluate the expression of FAP-1 and α-SMA and explore their impact on survival and association with other tumor molecular markers in NSCLC patients.High expression of FAP-1, but not α-SMA, in squamous cell carcinoma (SCC, P = 0.043, HR = 0.63 95% CI 0.40-0.99 was significantly associated with increased disease-specific survival. FAP-1 and α-SMA were not significantly correlated to each other. Analyses of FAP-1 and α-SMA associated with other tumor-related proteins revealed histotype-specific correlation patterns.The presence of FAP-1 expressing CAFs is an indicator of positive outcome for NSCLC-SCC patients. In addition, correlation analyses suggest FAP-1 and α-SMA to label different subsets of fibroblasts and their associations with other tumor-related proteins diverge according to histological subtype.

  9. The microRNA miR-34a inhibits non-small cell lung cancer (NSCLC) growth and the CD44hi stem-like NSCLC cells.

    Science.gov (United States)

    Shi, Yang; Liu, Can; Liu, Xin; Tang, Dean G; Wang, Junchen

    2014-01-01

    Lung cancer is among the most lethal malignancies with a high metastasis and recurrence rate, which is probably due to the existence of lung cancer stem cells (CSCs). CSCs in many tumors including non-small cell lung cancer (NSCLC) have been identified using adhesion molecular CD44, either individually or in combination with other marker(s). MicroRNAs (miRNAs) regulate both normal stem cells and CSCs and dysregulation of miRNAs has been implicated in tumorigenesis. Recently, miR-34a was found to be downregulated in NSCLC cells but the biological functions of miR-34a in regulating NSCLC cell behavior have not been extensively studied. Here we show that transfection of synthetic miR-34a, but not the negative control (NC) miRNA oligonucleotides (oligos) in three NSCLC cell lines, i.e., A549, H460, and H1299, inhibited their holoclone formation, clonogenic expansion, and tumor regeneration in vivo. Furthermore, the lentiviral vector-mediated overexpression of miR-34a in purified CD44hi H460 cells also inhibited tumor outgrowth. In contrast, expression of miR-34a antagomirs (i.e., antisense oligos) in the CD44lo H460 cells promoted tumor development. Our study shows that miR-34a is a negative regulator of the tumorigenic properties of NSCLC cells and CD44hi lung CSCs, and establishes a strong rationale for developing miR-34a as a novel therapeutic agent against NSCLC. PMID:24595209

  10. The microRNA miR-34a inhibits non-small cell lung cancer (NSCLC growth and the CD44hi stem-like NSCLC cells.

    Directory of Open Access Journals (Sweden)

    Yang Shi

    Full Text Available Lung cancer is among the most lethal malignancies with a high metastasis and recurrence rate, which is probably due to the existence of lung cancer stem cells (CSCs. CSCs in many tumors including non-small cell lung cancer (NSCLC have been identified using adhesion molecular CD44, either individually or in combination with other marker(s. MicroRNAs (miRNAs regulate both normal stem cells and CSCs and dysregulation of miRNAs has been implicated in tumorigenesis. Recently, miR-34a was found to be downregulated in NSCLC cells but the biological functions of miR-34a in regulating NSCLC cell behavior have not been extensively studied. Here we show that transfection of synthetic miR-34a, but not the negative control (NC miRNA oligonucleotides (oligos in three NSCLC cell lines, i.e., A549, H460, and H1299, inhibited their holoclone formation, clonogenic expansion, and tumor regeneration in vivo. Furthermore, the lentiviral vector-mediated overexpression of miR-34a in purified CD44hi H460 cells also inhibited tumor outgrowth. In contrast, expression of miR-34a antagomirs (i.e., antisense oligos in the CD44lo H460 cells promoted tumor development. Our study shows that miR-34a is a negative regulator of the tumorigenic properties of NSCLC cells and CD44hi lung CSCs, and establishes a strong rationale for developing miR-34a as a novel therapeutic agent against NSCLC.

  11. Vinorelbine and gemcitabine vs vinorelbine and carboplatin as first-line treatment of advanced NSCLC. A phase III randomised controlled trial by the Norwegian Lung Cancer Study Group

    DEFF Research Database (Denmark)

    Fløtten, Ø; Grønberg, B H; Bremnes, R;

    2012-01-01

    BACKGROUND: Platinum-based doublet chemotherapy is the standard first-line treatment for advanced non-small cell lung cancer (NSCLC), but earlier studies have suggested that non-platinum combinations are equally effective and better tolerated. We conducted a national, randomised study to compare...... a non-platinum with a platinum combination. METHODS: Eligible patients had stage IIIB/IV NSCLC and performance status (PS) 0-2. Patients received up to three cycles of vinorelbine 60 mg m(-2) p.o.+gemcitabine 1000 mg m(-2) i.v. day 1 and 8 (VG) or vinorelbine 60 mg m(-2) p.o. day 1 and 8+carboplatin...

  12. Treatment outcome in performance status 2 advanced NSCLC patients administered platinum-based combination chemotherapy

    DEFF Research Database (Denmark)

    Helbekkmo, Nina; Aasebø, Ulf; Sundstrøm, Stein H;

    2008-01-01

    BACKGROUND: There is no consensus regarding chemotherapy to patients with advanced NSCLC (ANSCLC) and performance status (PS) 2. Using data from a national multicenter study comparing two third-generation carboplatin-based regimens in ANSCLC patients, we evaluated the outcome of PS 2 patients. PA...

  13. The microRNA miR-34a Inhibits Non-Small Cell Lung Cancer (NSCLC) Growth and the CD44hi Stem-Like NSCLC Cells

    OpenAIRE

    Shi, Yang; Liu, Can; Liu, Xin; Tang, Dean G.; Wang, Junchen

    2014-01-01

    Lung cancer is among the most lethal malignancies with a high metastasis and recurrence rate, which is probably due to the existence of lung cancer stem cells (CSCs). CSCs in many tumors including non-small cell lung cancer (NSCLC) have been identified using adhesion molecular CD44, either individually or in combination with other marker(s). MicroRNAs (miRNAs) regulate both normal stem cells and CSCs and dysregulation of miRNAs has been implicated in tumorigenesis. Recently, miR-34a was found...

  14. LKB1 deficiency enhances sensitivity to energetic stress induced by erlotinib treatment in non-small cell lung cancer (NSCLC) cells

    OpenAIRE

    Whang, Young Mi; Park, Serk In; Trenary, Irina A.; Egnatchik, Robert A.; Fessel, Joshua P.; Kaufman, Jacob M.; Carbone, David P.; Young, Jamey D.

    2015-01-01

    The tumor suppressor serine/threonine kinase 11 (STK11 or LKB1) is mutated in 20–30% of non-small cell lung cancer (NSCLC) patient tumors. Loss of LKB1-AMPK signaling confers sensitivity to metabolic inhibition or stress-induced mitochondrial insults. We tested the hypothesis that loss of LKB1 sensitizes NSCLC cells to energetic stress induced by treatment with erlotinib. LKB1-deficient cells exhibited enhanced sensitivity to erlotinib in vitro and in vivo that was associated with alterations...

  15. EGFR, KRAS, BRAF, and HER-2 molecular status in brain metastases from 77 NSCLC patients

    OpenAIRE

    Villalva, Claire; Duranton-Tanneur, Valérie; Guilloteau, Karline; Burel-Vandenbos, Fanny; Wager, Michel; Doyen, Jérôme,; Levillain, Pierre Marie; Fontaine, Denys; Blons, Hélène; Pedeutour, Florence; Karayan-Tapon, Lucie

    2013-01-01

    The aim of this study was to determine the frequency of EGFR, KRAS, BRAF, and HER-2 mutations in brain metastases from non-small cell lung carcinomas (BM-NSCLC). A total of 77 samples of BM-NSCLC were included and 19 samples of BM from breast, kidney, and colorectal tumors were also studied as controls. These samples were collected from patients followed between 2008 and 2011 at Poitiers and Nice University Hospitals in France. The frequencies of EGFR, KRAS, BRAF, and HER-2 mutations in BM-NS...

  16. Review article: Heat shock protein 70 (Hsp70 peptide activated Natural Killer (NK cells for the treatment of patients with non-small cell lung cancer (NSCLC after radiochemotherapy (RCTx – from preclinical studies to a clinical phase II trial

    Directory of Open Access Journals (Sweden)

    Hanno M Specht

    2015-04-01

    Full Text Available Heat shock protein 70 (Hsp70 is frequently overexpressed in tumor cells. An unusual cell surface localization could be demonstrated on a large variety of solid tumors including lung, colorectal, breast, squamous cell carcinomas of the head and neck, prostate and pancreatic carcinomas, glioblastomas, sarcomas and hematological malignancies, but not on corresponding normal tissues. A membrane (mHsp70-positive phenotype can be determined either directly on single cell suspensions of tumor biopsies by flow cytometry using cmHsp70.1 monoclonal antibody or indirectly in the serum of patients using a novel lipHsp70 ELISA. A mHsp70-positive tumor phenotype has been associated with highly aggressive tumors, causing invasion and metastases and resistance to cell death. However, natural killer (NK, but not T cells were found to kill mHsp70-positive tumor cells after activation with a naturally occurring Hsp70 peptide (TKD plus low dose IL-2 (TKD/IL-2. Safety and tolerability of ex vivo TKD/IL-2 stimulated, autologous NK cells has been demonstrated in patients with metastasized colorectal and NSCLC in a phase I clinical trial. Based on promising clinical results of the previous study, a phase II randomized clinical study was initiated in 2015. The primary objective of this multicenter proof-of-concept trial is to examine whether an adjuvant treatment of NSCLC patients after platinum based radiochemotherapy with TKD/IL-2 activated, autologous NK cells is clinically effective. As a mHsp70-positive tumor phenotype is associated with poor clinical outcome only mHsp70-positive tumor patients will be recruited into the trial. The primary endpoint of this study will be the comparison of the progression-free survival of patients treated with ex vivo activated NK cells compared to patients who were treated with radiochemotherapy alone. As secondary endpoints overall survival, toxicity, quality-of-life and biological responses will be determined in both study groups.

  17. Clinicopathologic Features of Advanced Squamous NSCLC.

    Science.gov (United States)

    Socinski, Mark A; Obasaju, Coleman; Gandara, David; Hirsch, Fred R; Bonomi, Philip; Bunn, Paul; Kim, Edward S; Langer, Corey J; Natale, Ronald B; Novello, Silvia; Paz-Ares, Luis; Pérol, Maurice; Reck, Martin; Ramalingam, Suresh S; Reynolds, Craig H; Spigel, David R; Stinchcombe, Thomas E; Wakelee, Heather; Mayo, Carlos; Thatcher, Nick

    2016-09-01

    Lung cancer remains the leading cause of cancer-related death worldwide. NSCLC accounts for more than 85% of all lung cancers, and the prognosis for advanced-stage disease is typically poor. In recent years, the importance of histologic subtypes of NSCLC has been recognized, and the distinction between squamous and other NSCLC histologic subtypes is now critical to patient management. Squamous cell lung cancer (sqCLC) represents approximately 25% to 30% of NSCLC. The prognosis for patients with advanced NSCLC is poorer for those with sqCLC than for those with adenocarcinoma. This is partly due to a number of clinical characteristics that distinguish sqCLC from other NSCLC histologic subtypes, such as smoking history, comorbid diseases, age, and molecular profile. Together, these factors make sqCLC an especially challenging disease to manage. Herein, we review some of the key clinicopathologic features of sqCLC. Understanding these features to optimally address many of the unique therapeutic challenges of this disease is likely to be central to ultimately improving outcomes for patients with squamous NSCLC.

  18. 1,25-Dihydroxyvitamin D3 (1,25(OH2D3 Signaling Capacity and the Epithelial-Mesenchymal Transition in Non-Small Cell Lung Cancer (NSCLC: Implications for Use of 1,25(OH2D3 in NSCLC Treatment

    Directory of Open Access Journals (Sweden)

    Pamela A. Hershberger

    2013-11-01

    Full Text Available 1,25-dihydroxyvitamin D3 (1,25(OH2D3 exerts anti-proliferative activity by binding to the vitamin D receptor (VDR and regulating gene expression. We previously reported that non-small cell lung cancer (NSCLC cells which harbor epidermal growth factor receptor (EGFR mutations display elevated VDR expression (VDRhigh and are vitamin D-sensitive. Conversely, those with K-ras mutations are VDRlow and vitamin D-refractory. Because EGFR mutations are found predominately in NSCLC cells with an epithelial phenotype and K-ras mutations are more common in cells with a mesenchymal phenotype, we investigated the relationship between vitamin D signaling capacity and the epithelial mesenchymal transition (EMT. Using NSCLC cell lines and publically available lung cancer cell line microarray data, we identified a relationship between VDR expression, 1,25(OH2D3 sensitivity, and EMT phenotype. Further, we discovered that 1,25(OH2D3 induces E-cadherin and decreases EMT-related molecules SNAIL, ZEB1, and vimentin in NSCLC cells. 1,25(OH2D3-mediated changes in gene expression are associated with a significant decrease in cell migration and maintenance of epithelial morphology. These data indicate that 1,25(OH2D3 opposes EMT in NSCLC cells. Because EMT is associated with increased migration, invasion, and chemoresistance, our data imply that 1,25(OH2D3 may prevent lung cancer progression in a molecularly defined subset of NSCLC patients.

  19. SU-E-J-266: Cone Beam Computed Tomography (CBCT) Inter-Scan and Inter-Observer Tumor Volume Variability Assessment in Patients Treated with Stereotactic Body Radiation Therapy (SBRT) for Early Stage Non-Small Cell Lung Cancer (NSCLC)

    Energy Technology Data Exchange (ETDEWEB)

    Hou, Y; Aileen, C; Kozono, D; Killoran, J; Wagar, M; Lee, S; Hacker, F; Aerts, H; Lewis, J; Mak, R [Brigham and Women’s Hospital, Boston, MA (United States)

    2015-06-15

    Purpose: Quantification of volume changes on CBCT during SBRT for NSCLC may provide a useful radiological marker for radiation response and adaptive treatment planning, but the reproducibility of CBCT volume delineation is a concern. This study is to quantify inter-scan/inter-observer variability in tumor volume delineation on CBCT. Methods: Twenty earlystage (stage I and II) NSCLC patients were included in this analysis. All patients were treated with SBRT with a median dose of 54 Gy in 3 to 5 fractions. Two physicians independently manually contoured the primary gross tumor volume on CBCTs taken immediately before SBRT treatment (Pre) and after the same SBRT treatment (Post). Absolute volume differences (AVD) were calculated between the Pre and Post CBCTs for a given treatment to quantify inter-scan variability, and then between the two observers for a given CBCT to quantify inter-observer variability. AVD was also normalized with respect to average volume to obtain relative volume differences (RVD). Bland-Altman approach was used to evaluate variability. All statistics were calculated with SAS version 9.4. Results: The 95% limit of agreement (mean ± 2SD) on AVD and RVD measurements between Pre and Post scans were −0.32cc to 0.32cc and −0.5% to 0.5% versus −1.9 cc to 1.8 cc and −15.9% to 15.3% for the two observers respectively. The 95% limit of agreement of AVD and RVD between the two observers were −3.3 cc to 2.3 cc and −42.4% to 28.2% respectively. The greatest variability in inter-scan RVD was observed with very small tumors (< 5 cc). Conclusion: Inter-scan variability in RVD is greatest with small tumors. Inter-observer variability was larger than inter-scan variability. The 95% limit of agreement for inter-observer and inter-scan variability (∼15–30%) helps define a threshold for clinically meaningful change in tumor volume to assess SBRT response, with larger thresholds needed for very small tumors. Part of the work was funded by a Kaye

  20. ERCC1, toxicity and quality of life in advanced NSCLC patients randomized in a large multicentre phase III trial

    DEFF Research Database (Denmark)

    Vilmar, Adam Christian; Santoni-Rugiu, Eric; Sørensen, Jens Benn

    2010-01-01

    Excision repair cross complementation group 1 (ERCC1) is a promising biomarker in advanced non-small cell lung cancer (NSCLC). However, current evidence regarding the impact of ERCC1 on toxicity and quality of life (QOL) is limited.......Excision repair cross complementation group 1 (ERCC1) is a promising biomarker in advanced non-small cell lung cancer (NSCLC). However, current evidence regarding the impact of ERCC1 on toxicity and quality of life (QOL) is limited....

  1. Analysis of Prognostic Factors of 80 Advanced NSCLC Patients Treated with Gefitinib for more than 6 Months

    Directory of Open Access Journals (Sweden)

    Ling DAI

    2010-11-01

    Full Text Available Background and objective Some clinical predictors can be used to evaluate the efficacy of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI therapy for non-small cell lung cancer (NSCLC, including female, East-Asian, non-smoker, adenocarcinoma, skin rash, etc. The aim of this study is to explore the prognosis of advanced NSCLC patients treated with gefitinib for more than 6 months. Methods Eighty advanced NSCLC patients treated with gefitinib for more than 6 months were collected from January, 2005 to March, 2010. The association of their clinical characteristics with median progression-free survival time (PFS was analysed. Results Significantly longer median PFS were found in patients with > 70 years old, earlier clinical stage (IIIb, non-bone metastasis (27 months vs 12 months; 32 months vs 12 months; 16 months vs 10 months, P < 0.05. There was no significant difference in median PFS between ECOG performance status 0-1 group and 2-4 group, between more than 4 cycles of chemotherapy and 1-4 cycles, between PFS of chemotherapy > 6 months group and ≤6 months group, however, ECOG 0-1 group and more than 4 cycles of chemotherapy or PFS of chemotherapy > 6 months group seemed to have longer median PFS (15 months vs 10 months; 16 months vs 12 months; 14months vs 12 months. Compared with no skin rash and grade 0-I rash group, the patients with rash or grade ≥II rash had longer median PFS (16 months vs 13 months, P=0.171; 19 months vs 11 months, P=0.085. The median PFS was not related with sex, smoking index, pathological types, metastatic sites except bone, treatment strategy, etc (P > 0.05. Conclusion For gefitinib treatment, longer median PFS is likely to be obtained in patients with > 70 years old, earlier clinical stage (IIIb, non-bone metastasis.

  2. Maximal Oxygen Uptake--Risk Predictor of NSCLC Resection in Patients With Comorbid Emphysema: Lessons From NETT.

    Science.gov (United States)

    Makey, Ian; Berger, Robert L; Cabral, Howard J; Celli, Bartolome; Folch, Erik; Whyte, Richard I

    2015-01-01

    We compared VO2 max values from ACCP Guidelines and from NETT's homogenous NULPD surrogate for predicting operative mortalities. Estimated mid and long-term non-cancer related survival in NETT's subset was also obtained. NETT and ACCP Guideline VO2 max values were similar in the "low" and "mid" risk operative mortality categories but NETT's "high" risk subset showed lower mortality (14% vs. 26%). Estimated non-cancer related survival in NETT "low", "mid" and "high" risk VO2 max categories at two and eight years were 100%, 74%, 59% and 48%, 26%, 14%, respectively. The lower predicted risk in NETT's "high- risk" subset raises the possibility of extending indications for potential curative resection in selected patients. The NETT surrogate also provides hitherto unavailable estimate on long-term non-cancer related survival after potential curative resection of NSCLC and suggests that the operation does not shorten eight-year longevity.

  3. MicroRNA-187-5p suppresses cancer cell progression in non-small cell lung cancer (NSCLC) through down-regulation of CYP1B1.

    Science.gov (United States)

    Mao, Ming; Wu, Zhouqing; Chen, Jiakuan

    2016-09-16

    Lung cancer remains a leading cause of cancer-associated mortality worldwide and non-small lung cancer (NSCLC) is responsible for over 80% of lung cancer-related deaths. Identifying novel molecular biomarker that can inhibit the progression of lung cancer will facilitate the development of new treatment strategies. Herein, we demonstrated that miR-187-5p is a tumor-suppressor miRNA in NSCLC progression. We found that expression of miR-187-5p was decreased obviously in NSCLC tissues. Down-regulation of miR-187-5p was associated with TNM stage and postoperative survival. Overexpression of miR-187-5p inhibited the growth and metastasis of NSCLC cells. The CYP1B1 was a direct target of miR-187-5p and promoted the growth and metastasis of NSCLC cells. Further study showed that CYP1B1 could reverse the inhibitory effect of miR-187-5p on growth and metastasis of NSCLC cells. Taken together, our data highlight the pivotal role of miR-187-5p in the progression of NSCLC. Thus, miR-187-5p may be a potential prognostic marker and of treatment relevance for NSCLC progression intervention. PMID:27495872

  4. Stromal Caveolin-1 Is Associated With Response and Survival in a Phase II Trial of nab-Paclitaxel With Carboplatin for Advanced NSCLC Patients

    Science.gov (United States)

    Bertino, Erin M.; Williams, Terence M.; Nana-Sinkam, S. Patrick; Shilo, Konstantin; Chatterjee, Moumita; Mo, Xiaokui; Rahmani, Meliha; Phillips, Gary S.; Villalona-Calero, Miguel A.; Otterson, Gregory A.

    2016-01-01

    In this phase II trial, carboplatin with nanoparticle albumin-bound (nab)-paclitaxel as first-line therapy for advanced non–small-cell lung cancer (NSCLC) was evaluated. Most patients had squamous cell histology. Tumor-associated stromal caveolin-1 (Cav-1) expression was correlated with improved response rate and survival in NSCLC patients who received nab-paclitaxel in this phase II trial. These results suggest Cav-1 might serve as a potential biomarker in this patient population. Background The combination of bevacizumab with platinum-based chemotherapy results in greater response rate (RR) and overall survival (OS) in advanced non–small-cell lung cancer (NSCLC). Bevacizumab is contraindicated in patients with squamous histology or hemoptysis. Nanoparticle albumin-bound (nab)-paclitaxel is a novel formulation of paclitaxel with greater dose tolerance and improved efficacy. We hypothesized that nab-paclitaxel and carboplatin would be superior to alternative doublets in advanced NSCLC patients ineligible for bevacizumab. Patients and Methods We conducted a single-arm phase II trial (NCT00729612) with carboplatin and nab-paclitaxel on day 1 of a 21-day cycle to evaluate RR (primary end point), safety, toxicity, and OS. Eligibility included: squamous histology, hemoptysis, or ongoing anticoagulation. Correlative studies included immunohistochemistry for secreted protein acid rich in cysteine (SPARC) and caveolin-1 (Cav-1). Results Sixty-three patients were enrolled. Most patients had squamous cell carcinoma (n = 48); other reasons for eligibility included hemoptysis (n = 11) and anticoagulation (n = 2). Toxicity Grade ≥ 3/4 included neuropathy, cytopenias, and fatigue. RR was 38% (24 partial response/0 complete response); 20 patients had stable disease (32%). Median progression-free survival was 5 months and median OS was 9.7 months. Immunohistochemistry for SPARC and Cav-1 was performed in 38 and 37 patients respectively. Although no association was found for

  5. Clinical efficacy of percutaneous vertebroplasty combined with intensity-modulated radiotherapy for spinal metastases in patients with NSCLC

    Directory of Open Access Journals (Sweden)

    Li Y

    2015-08-01

    Full Text Available Yi Li,1,2 Yi Qing,1 Zhimin Zhang,3 Mengxia Li,1 Jiaying Xie,1 Ge Wang,1 Dong Wang1 1Department of Cancer Center, Research Institute of Surgery, Daping Hospital, Third Military Medical University, 2Department of Oncology, Beibei Traditional Chinese Medical Hospital, Chongqing, 3Department of Oncology, Wuhan General Hospital of Guangzhou Command, People’s Liberation Army, Wuhan, Hubei, People’s Republic of China Objective: This study aimed to evaluate the safety and efficacy of percutaneous vertebroplasty (PVP combined with intensity-modulated radiotherapy (IMRT for metastatic lesions of patients with non-small-cell lung cancer (NSCLC at centrum vertebrae.Methods: A total of 39 patients with spinal metastatic NSCLC (stage IV were treated with PVP followed by IMRT (30 Gy/10F/2 W for metastatic lesion at centrum vertebrae under local anesthesia. Retrospective analysis was done with medical records and radiological data. The change of visual analog scale (VAS, activities of daily living, and kyphotic angle was measured preoperatively. The presence of complications was assessed preoperatively (baseline at 24 hours, 1 week, and 1, 3, 6, 12, and 24 months postoperatively, or until the patient died or was lost to follow-up. Survival was assessed in the group.Results: A total of 39 consecutive patients were successfully treated with PVP via a translateral approach and IMRT. Their mean VAS score decreased from 7.93±1.09 preoperatively to 4.14±1.15 by the 24-hour postoperative time point and was 3.92±1.23 at 1 week, 4.27±1.93 at 1 month, 3.24±1.35 at 3 months, 2.27±0.96 at 6 months, and 2.59±1.55 at 12 months after the procedure. The mean VAS score at all of the postoperative time points was decreased significantly from the preoperative baseline score (P<0.05. Activities of daily living evaluation showed that the patients had a significantly high life quality after the combined approach (50.9±11.7 vs 82.3±9.9, P<0.05. No severe complications

  6. 非含铂双药和非含铂单药治疗老年和/或PS差的非小细胞肺癌病人疗效:荟萃分析%Non-platinum doublets versus single agents in non-small cell lung cancer (NSCLC) patients with elderly age and/or poor performance status:a meta-analysis

    Institute of Scientific and Technical Information of China (English)

    Huijuan Qiu; Fang Wang; Guifang Guo; Feifei Zhou; Wenzhuo He; Liangping Xia

    2011-01-01

    Objective:The aim of the study was to compare the efficacies and toxicities of non-platinum doublets (doublets group) with a non-platinum single agent (single-agent group) in previously untreated advanced non-small cell lung cancer (NSCLC) patients with elderly age and/or poor performance status (PS).Methods:The PubMed database was screened.Subsequently,the hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS),relative risks (RRs) for overall response rate (ORR) and one-year survival,and odds ratios (ORs) for the different types of toxicities were pooled using the Review Manager 5.0 package.Results:This study comprised of 1427 patients enrolled in four randomized controlled trials.The pooled HR showed that the doublet group could increase ORR (P = 0.002) with no heterogeneity (P = 0.64),and might improve OS (P = 0.01 / P = 0.06) with heterogeneity (P < 0.001).There was no significant difference in PFS (P = 0.16) and one-year survival (P = 0.25) between two treatment groups.The doublet group led to more grade 3/4 neutropenia and thrombocytopenia than the single-agent group (P = 0.02 and P = 0.000,respectively).The incidences of grade 3/4 anemia,vomiting,mucositis,constipation,diarrhea,neurotoxicity,allergy,and fatigue between the two treatment groups were insignificant.Conclusion:Except for neutropenia and thrombocytopenia,the non-platinum doublets could increase ORR,and might improve OS for NSCLC patients with elderly age and/or poor PS without addition of more side effects;however,the doublets showed an increased rate of neutropenia and thrombocytopenia.The addition of doublets may not improve PFS and one-year survival.

  7. DCE-MRI Perfusion and Permeability Parameters as predictors of tumor response to CCRT in Patients with locally advanced NSCLC

    Science.gov (United States)

    Tao, Xiuli; Wang, Lvhua; Hui, Zhouguang; Liu, Li; Ye, Feng; Song, Ying; Tang, Yu; Men, Yu; Lambrou, Tryphon; Su, Zihua; Xu, Xiao; Ouyang, Han; Wu, Ning

    2016-01-01

    In this prospective study, 36 patients with stage III non-small cell lung cancers (NSCLC), who underwent dynamic contrast-enhanced MRI (DCE-MRI) before concurrent chemo-radiotherapy (CCRT) were enrolled. Pharmacokinetic analysis was carried out after non-rigid motion registration. The perfusion parameters [including Blood Flow (BF), Blood Volume (BV), Mean Transit Time (MTT)] and permeability parameters [including endothelial transfer constant (Ktrans), reflux rate (Kep), fractional extravascular extracellular space volume (Ve), fractional plasma volume (Vp)] were calculated, and their relationship with tumor regression was evaluated. The value of these parameters on predicting responders were calculated by receiver operating characteristic (ROC) curve. Multivariate logistic regression analysis was conducted to find the independent variables. Tumor regression rate is negatively correlated with Ve and its standard variation Ve_SD and positively correlated with Ktrans and Kep. Significant differences between responders and non-responders existed in Ktrans, Kep, Ve, Ve_SD, MTT, BV_SD and MTT_SD (P < 0.05). ROC indicated that Ve < 0.24 gave the largest area under curve of 0.865 to predict responders. Multivariate logistic regression analysis also showed Ve was a significant predictor. Baseline perfusion and permeability parameters calculated from DCE-MRI were seen to be a viable tool for predicting the early treatment response after CCRT of NSCLC. PMID:27762331

  8. Evaluation of Circulating Tumor Cells and Related Events as Prognostic Factors and Surrogate Biomarkers in Advanced NSCLC Patients Receiving First-Line Systemic Treatment.

    Science.gov (United States)

    Muinelo-Romay, Laura; Vieito, Maria; Abalo, Alicia; Nocelo, Marta Alonso; Barón, Francisco; Anido, Urbano; Brozos, Elena; Vázquez, Francisca; Aguín, Santiago; Abal, Miguel; López, Rafael López

    2014-01-01

    In the present study we investigated the prognostic value of Circulating Tumour Cells (CTC) and their utility for therapy monitoring in non-small cell lung cancer (NSCLC). A total of 43 patients newly diagnosed with NSCLC were prospectively enrolled. Blood samples were obtained before the 1st, 2nd and 5th cycles of chemotherapy and analyzed using CellSearch technology. Both CTC and CTC-related objects (not morphological standard or broken epithelial cells) were counted. At baseline 18 (41.9%) patients were positive for intact CTC count and 10 (23.2%) of them had ≥5 CTC, while CK positive events were found in 79.1% of patients. The group of patients with CTC ³5 at baseline presented worse PFS and OS than those with <5 CTC (p = 0.034 and p = 0.008, respectively). Additionally, high levels of total CK positive events were associated with poor prognosis in the group of patients with <5 CTC. Regarding therapy monitoring, patients presenting increased levels of CTC during the treatment demonstrated lower OS and PFS rates. All these data supported the value of CTC as a prognostic biomarker and as a surrogate indicator of chemotherapy effectiveness in advanced NSCLC patients, with the additional value of analyzing other "objects" such as apoptotic CTC or CK fragments to guide the clinical management of these patients.

  9. Evaluation of Circulating Tumor Cells and Related Events as Prognostic Factors and Surrogate Biomarkers in Advanced NSCLC Patients Receiving First-Line Systemic Treatment

    Energy Technology Data Exchange (ETDEWEB)

    Muinelo-Romay, Laura; Vieito, Maria; Abalo, Alicia; Alonso Nocelo, Marta; Barón, Francisco; Anido, Urbano; Brozos, Elena; Vázquez, Francisca; Aguín, Santiago; Abal, Miguel; López López, Rafael, E-mail: rafael.lopez.lopez@sergas.es [Translational Medical Oncology, Health Research Institute of Santiago (IDIS), Complexo Hospitalario Universitario de Santiago de Compostela (SERGAS), Trav. Choupana s/n 15706 Santiago de Compostela (Spain)

    2014-01-21

    In the present study we investigated the prognostic value of Circulating Tumour Cells (CTC) and their utility for therapy monitoring in non-small cell lung cancer (NSCLC). A total of 43 patients newly diagnosed with NSCLC were prospectively enrolled. Blood samples were obtained before the 1st, 2nd and 5th cycles of chemotherapy and analyzed using CellSearch technology. Both CTC and CTC-related objects (not morphological standard or broken epithelial cells) were counted. At baseline 18 (41.9%) patients were positive for intact CTC count and 10 (23.2%) of them had ≥5 CTC, while CK positive events were found in 79.1% of patients. The group of patients with CTC ≥5 at baseline presented worse PFS and OS than those with <5 CTC (p = 0.034 and p = 0.008, respectively). Additionally, high levels of total CK positive events were associated with poor prognosis in the group of patients with <5 CTC. Regarding therapy monitoring, patients presenting increased levels of CTC during the treatment demonstrated lower OS and PFS rates. All these data supported the value of CTC as a prognostic biomarker and as a surrogate indicator of chemotherapy effectiveness in advanced NSCLC patients, with the additional value of analyzing other “objects” such as apoptotic CTC or CK fragments to guide the clinical management of these patients.

  10. Evaluation of Circulating Tumor Cells and Related Events as Prognostic Factors and Surrogate Biomarkers in Advanced NSCLC Patients Receiving First-Line Systemic Treatment

    Directory of Open Access Journals (Sweden)

    Laura Muinelo-Romay

    2014-01-01

    Full Text Available In the present study we investigated the prognostic value of Circulating Tumour Cells (CTC and their utility for therapy monitoring in non-small cell lung cancer (NSCLC. A total of 43 patients newly diagnosed with NSCLC were prospectively enrolled. Blood samples were obtained before the 1st, 2nd and 5th cycles of chemotherapy and analyzed using CellSearch technology. Both CTC and CTC-related objects (not morphological standard or broken epithelial cells were counted. At baseline 18 (41.9% patients were positive for intact CTC count and 10 (23.2% of them had ≥5 CTC, while CK positive events were found in 79.1% of patients. The group of patients with CTC ³5 at baseline presented worse PFS and OS than those with <5 CTC (p = 0.034 and p = 0.008, respectively. Additionally, high levels of total CK positive events were associated with poor prognosis in the group of patients with <5 CTC. Regarding therapy monitoring, patients presenting increased levels of CTC during the treatment demonstrated lower OS and PFS rates. All these data supported the value of CTC as a prognostic biomarker and as a surrogate indicator of chemotherapy effectiveness in advanced NSCLC patients, with the additional value of analyzing other “objects” such as apoptotic CTC or CK fragments to guide the clinical management of these patients.

  11. EGFR testing and clinical management of advanced NSCLC: a Galician Lung Cancer Group study (GGCP 048-10

    Directory of Open Access Journals (Sweden)

    Vázquez S

    2016-02-01

    Full Text Available Sergio Vázquez,1 Joaquín Casal,2 Francisco Javier Afonso Afonso,3 José Luis Fírvida,4 Lucía Santomé,5 Francisco Barón,6 Martín Lázaro,7 Carolina Pena,7 Margarita Amenedo,8 Ihab Abdulkader,9 Carmen González-Arenas,10 Laura Fachal,11 Ana Vega11 On behalf of the Galician Lung Cancer Group (GGCP1Medical Oncology Department, Lucus Augusti University Hospital, Lugo, 2Medical Oncology Department, University Hospital Complex of Vigo, Pontevedra, 3Medical Oncology Department, University Hospital Complex of Ferrol, Ferrol, 4Medical Oncology Department, University Hospital Complex of Ourense, Ourense, 5Medical Oncology Department Povisa Hospital, Vigo, 6Medical Oncology Department, University Hospital Complex of Santiago de Compostela, Santiago de Compostela, 7Medical Oncology Department, Hospital Complex of Pontevedra, Pontevedra, 8Medical Oncology Department, Oncology Center of Galicia, A Coruña, 9Anatomical Pathology Department, University Hospital Complex of Santiago de Compostela, Santiago de Compostela, 10AstraZeneca, Madrid, 11Galician Public Foundation of Genomic Medicine-SERGAS, Santiago de Compostela Clinic Hospital, Santiago de Compostela, Spain Purpose: This study aimed to assess the incidence of mutations in the epidermal growth factor receptor (EGFR gene in non-small-cell lung cancer (NSCLC patients in the Galician region of Spain and the clinical management and outcome of patients carrying EGFR mutations. Patients and methods: All newly diagnosed advanced or metastatic NSCLC patients were screened for EGFR mutations in matched tumor samples (tissue or cytology specimens and serum samples. Results: Of 198 patients screened for EGFR mutations in tumor samples, 184 had evaluable data and, of these, 25 (13.6% had EGFR mutations (84% sensitizing mutations. EGFR mutation was found in serum in 14 (8.1% patients (of 174 evaluable. Compared to matched tumor tissue, serum EGFR mutation testing specificity and sensitivity were 99% and 52

  12. A Phase III Study of Durvalumab (MEDI4736) With or Without Tremelimumab for Previously Treated Patients With Advanced NSCLC: Rationale and Protocol Design of the ARCTIC Study.

    Science.gov (United States)

    Planchard, David; Yokoi, Takashi; McCleod, Michael J; Fischer, Jürgen R; Kim, Young-Chul; Ballas, Marc; Shi, Kelvin; Soria, Jean-Charles

    2016-05-01

    Anti-programmed cell death-1 and anti-programmed cell death ligand-1 (PD-L1) monotherapies have shown promising clinical activity in advanced, refractory non-small-cell lung cancer (NSCLC), but antitumor activity appears to be greater in patients with PD-L1(+) tumors compared with patients harboring PD-L1(-) tumors. Combining the anti-PD-L1 antibody durvalumab and the anti-cytotoxic T-lymphocyte antigen 4 antibody tremelimumab offers the potential for antitumor activity in patients with advanced NSCLC, regardless of PD-L1 tumor status. ARCTIC (NCT02352948) is a global, phase III, randomized, open-label multicenter study in patients with advanced NSCLC assessing the safety and clinical activity of durvalumab versus standard of care (SoC; erlotinib, gemcitabine, or vinorelbine) in patients with PD-L1(+) tumors (≥25% of tumor cells with membrane staining using VENTANA PD-L1 [SP263] CDx Assay) (Sub-study A) and the combination of durvalumab + tremelimumab or either agent as monotherapy versus SoC in patients with PD-L1(-) tumors (Sub-study B). Eligible patients are those with locally advanced or metastatic NSCLC (Stage IIIB/IV), without epidermal growth factor receptor tyrosine kinase activating mutations or anaplastic lymphoma kinase rearrangements, who have received at least 2 prior systemic regimens, including 1 platinum-based chemotherapy regimen. Co-primary endpoints are progression-free survival and overall survival. Secondary endpoints include the proportion of patients alive at 12 months, objective response rate, duration of response, progression-free survival at 6 and 12 months, safety and tolerability, pharmacokinetics, immunogenicity, and quality of life. The exploratory endpoints will assess potential biomarkers of treatment response. Recruitment started in January 2015 and is ongoing.

  13. 1,25-Dihydroxyvitamin D{sub 3} (1,25(OH){sub 2}D{sub 3}) Signaling Capacity and the Epithelial-Mesenchymal Transition in Non-Small Cell Lung Cancer (NSCLC): Implications for Use of 1,25(OH){sub 2}D{sub 3} in NSCLC Treatment

    Energy Technology Data Exchange (ETDEWEB)

    Upadhyay, Santosh Kumar; Verone, Alissa; Shoemaker, Suzanne [Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263 (United States); Qin, Maochun; Liu, Song [Department of Biostatistics and Bioinformatics, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263 (United States); Campbell, Moray; Hershberger, Pamela A., E-mail: pamela.hershberger@roswellpark.org [Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263 (United States)

    2013-11-08

    1,25-dihydroxyvitamin D{sub 3} (1,25(OH){sub 2}D{sub 3}) exerts anti-proliferative activity by binding to the vitamin D receptor (VDR) and regulating gene expression. We previously reported that non-small cell lung cancer (NSCLC) cells which harbor epidermal growth factor receptor (EGFR) mutations display elevated VDR expression (VDR{sup high}) and are vitamin D-sensitive. Conversely, those with K-ras mutations are VDR{sup low} and vitamin D-refractory. Because EGFR mutations are found predominately in NSCLC cells with an epithelial phenotype and K-ras mutations are more common in cells with a mesenchymal phenotype, we investigated the relationship between vitamin D signaling capacity and the epithelial mesenchymal transition (EMT). Using NSCLC cell lines and publically available lung cancer cell line microarray data, we identified a relationship between VDR expression, 1,25(OH){sub 2}D{sub 3} sensitivity, and EMT phenotype. Further, we discovered that 1,25(OH){sub 2}D{sub 3} induces E-cadherin and decreases EMT-related molecules SNAIL, ZEB1, and vimentin in NSCLC cells. 1,25(OH){sub 2}D{sub 3}-mediated changes in gene expression are associated with a significant decrease in cell migration and maintenance of epithelial morphology. These data indicate that 1,25(OH){sub 2}D{sub 3} opposes EMT in NSCLC cells. Because EMT is associated with increased migration, invasion, and chemoresistance, our data imply that 1,25(OH){sub 2}D{sub 3} may prevent lung cancer progression in a molecularly defined subset of NSCLC patients.

  14. LAPTM4B is associated with poor prognosis in NSCLC and promotes the NRF2-mediated stress response pathway in lung cancer cells.

    Science.gov (United States)

    Maki, Yuho; Fujimoto, Junya; Lang, Wenhua; Xu, Li; Behrens, Carmen; Wistuba, Ignacio I; Kadara, Humam

    2015-01-01

    We recently demonstrated that lysosomal protein transmembrane 4 beta (LAPTM4B) is elevated in non-small cell lung cancers (NSCLCs) and in the surrounding premalignant airway field of cancerization. In the present study, we sought to begin to understand the relevance of LAPTM4B expression and signaling to NSCLC pathogenesis. In situ hybridization analysis of LAPTM4B transcript in tissue microarrays comprised of 368 NSCLCs demonstrated that LAPTM4B expression was significantly increased in smoker compared to non-smoker lung adenocarcinoma tumors (P P < 0.05) in adenocarcinoma patients. Knockdown of LAPTM4B expression inhibited cell growth, induced cellular apoptosis and decreased cellular autophagy in serum starved lung cancer cells. Expression profiling coupled with pathways analysis revealed decreased activation of the nuclear factor erythroid 2-like 2 (NRF2) stress response pathway following LAPTM4B knockdown. Further analysis demonstrated that LAPTM4B augmented the expression and nuclear translocation of the NRF2 transcription factor following serum deprivation as well as increased the expression of NRF2 target genes such as heme oxygenase 1/HMOX1). Our study points to the relevance of LAPTM4B expression to NSCLC pathogenesis as well as to the probable role of LAPTM4B/NRF2 signaling in promoting lung cancer cell survival. PMID:26343532

  15. Urokinase receptor forms in serum from non-small cell lung cancer patients

    DEFF Research Database (Denmark)

    Almasi, Charlotte Elberling; Christensen, Ib Jarle; Høyer-Hansen, Gunilla;

    2011-01-01

    To study the prognostic impact of the different forms of the receptor for urokinase plasminogen activator (uPAR) in serum from 171 non-small cell lung cancer (NSCLC) patients.......To study the prognostic impact of the different forms of the receptor for urokinase plasminogen activator (uPAR) in serum from 171 non-small cell lung cancer (NSCLC) patients....

  16. Improved radiotherapy for locally advanced Non-Small Cell Lung Carcinoma (NSCLC) patients

    DEFF Research Database (Denmark)

    Ottosson, Wiviann

    be reduced by the DIBH method for the lung cancer patients. The overall aim of the clinical part of this thesis was to clarify the potential benefit of offering DIBH gating, compared to free-breathing (FB), for lung cancer patients. Particularly, the benefits for locally advanced non-small cell lung cancer...... in the phantom. Severe dose deviations were observed, especially for small tumor sizes ≤ 2 cm in diameter. Our results imply that there exist severe tumor-size dependency, which potentially could have implications on the radiotherapy treatment planning of lung cancer. This thesis concludes that the clinical gain......Lung cancer is worldwide one of the most common cancer diseases with a high mortality rate. There is thus an urgent need for improving radiotherapy for these patients. Radiotherapy for lung cancer patients is challenging because the tumor and organs at risk (OARs) move with the breathing motion...

  17. Overexpression of Wnt5a Promotes Angiogenesis in NSCLC

    Directory of Open Access Journals (Sweden)

    Lingli Yao

    2014-01-01

    Full Text Available To evaluate Wnt5a expression and its role in angiogenesis of non-small-cell lung cancer (NSCLC, immunohistochemistry and CD31/PAS double staining were performed to examine the Wnt5a expression and we analyze the relationships between Wnt5a and microvessel density (MVD, vasculogenic mimicry (VM, and some related proteins. About 61.95% of cases of 205 NSCLC specimens exhibited high expression of Wnt5a. Wnt5a expression level was upregulated in the majority of NSCLC tissues, especially in squamous cell carcinoma, while its expression level in adenocarcinoma was the lowest. Wnt5a was also found more frequently expressed in male patients than in female patients. Except for histological classification and gender, little association was found between Wnt5a and clinicopathological features. Moreover, Wnt5a was significantly correlated with prognosis. Overall, Wnt5a-positive expression in patients with NSCLC indicated shorter survival time. As for vascularization in NSCLC, Wnt5a showed close association with VM and MVD. In addition, Wnt5a was positively related with β-catenin-nu, VE-cadherin, MMP2, and MMP9. The results demonstrated that overexpression of Wnt5a may play an important role in NSCLC angiogenesis and it may function via canonical Wnt signal pathway. This study will provide evidence for further research on NSCLC and also will provide new possible target for NSCLC diagnosis and therapeutic strategies.

  18. Estrogen and its signaling pathway in non-small cell lung cancer(NSCLC)

    Institute of Scientific and Technical Information of China (English)

    Ruitong Xu; Yongqian Shu

    2009-01-01

    Lung cancer is the most common cancer in the world. It is a highly lethal disease in women and men, and new treatments are urgently needed. Several studies have implicated a role of estrogens and estrogen receptors in lung cancer progression. This review will investigate the biological significance of estrogens in lung cancer cells, the expression and molecular mechanisms of estrogen receptors(ER α and ER β, elucidate the prognostic significance of estrogens and their receptors in lung carcinomas and provide new options for patients afflicted with lung malignancies.

  19. A Laboratory Prognostic Index Model for Patients with Advanced Non-Small Cell Lung Cancer

    OpenAIRE

    Arife Ulas; Fatma Paksoy Turkoz; Kamile Silay; Saadet Tokluoglu; Nilufer Avci; Berna Oksuzoglu; Necati Alkis

    2014-01-01

    Purpose We aimed to establish a laboratory prognostic index (LPI) in advanced non-small cell lung cancer (NSCLC) patients based on hematologic and biochemical parameters and to analyze the predictive value of LPI on NSCLC survival. Patients and Methods The study retrospectively reviewed 462 patients with advanced NSCLC diagnosed between 2000 and 2010 in a single institution. We developed an LPI that included serum levels of white blood cells (WBC), lactate dehydrogenase (LDH), albumin, calciu...

  20. Intercalated chemotherapy and erlotinib for advanced NSCLC: high proportion of complete remissions and prolonged progression-free survival among patients with EGFR activating mutations

    Directory of Open Access Journals (Sweden)

    Zwitter Matjaz

    2014-12-01

    Full Text Available Background. Pharmaco-dynamic separation of cytotoxic and targeted drugs might avoid their mutual antagonistic effect in the treatment of advanced non-small cell lung cancer (NSCLC.

  1. Immunohistochemical detections of EGFR status in NSCLC

    Directory of Open Access Journals (Sweden)

    Jie WANG

    2015-04-01

    Full Text Available Background and objective Patients with non-small cell lung cancer (NSCLC harboring mutations of the epidermal growth factor receptor (EGFR respond well to EGFR-tyrosine kinase inhibitor therapy. Immunohistochemistry (IHC is a simple and widely used technique in clinical pathology laboratories. IHC also features cost effectiveness and rapid detection of EGFR mutations compared with molecular methods. This study aims to determine the accuracy of IHC for EGFR mutation detection in NSCLC. Methods Specimens (obtained from surgery or biopsy from 97 NSCLC cases were stained through IHC with mutation-specific antibodies. The clinicopathological features of patients with positive immunostaining results were analyzed. Positive specimens were subjected to liquid chip technology to detect the actual EGFR status. Forty NSCLC specimens obtained from surgery and confirmed to have EGFR mutations through liquid chip technology were collected. These specimens were then subjected to IHC analyses with mutation-specific antibodies. The sensitivity of IHC in detecting EGFR mutations was calculated. Results Seventeen of the 97 NSCLC specimens were stained positive, and positive results were mostly observed in females, patients with adenocarcinoma, and non-smokers. About 76.9% of specimens with positive IHC results harbored mutations. The sensitivity of IHC was 40% among the 40 cases identified as containing EGFR mutations through liquid chip technology. Conclusion The strong positive immunostaining result is accurate, but the sensitivity of the method may not be optimal and significantly varies in different studies. The widespread application of IHC in clinics must be further investigated.

  2. Quality of Life (QOL) Analysis of a Randomized Radiation Dose Escalation Non-Small Cell Lung Cancer (NSCLC) Study: Radiation Therapy Oncology Group (RTOG) Trial 0617

    Science.gov (United States)

    Movsas, Benjamin; Hu, Chen; Sloan, Jeffrey; Bradley, Jeffrey; Komaki, Ritsuko; Masters, Gregory; Kavadi, Vivek; Narayan, Samir; Michalski, Jeff; Johnson, Douglas W.; Koprowski, Christopher; Curran, Walter J.; Garces, Yolanda I.; Gaur, Rakesh; Wynn, Raymond B.; Schallenkamp, John; Gelblum, Daphna Y.; MacRae, Robert M; Paulus, Rebecca; Choy, Hak

    2015-01-01

    Importance A recent randomized radiation dose escalation trial in unresectable stage III NSCLC showed a lower survival in the high-dose arm (74Gy vs. 60Gy) with concurrent chemotherapy. Quality of life (QOL), an important secondary endpoint, is presented here. Objective The primary QOL hypothesis predicted a clinically meaningful decline (CMD) in QOL via the Functional Assessment of Cancer Therapy-Lung Cancer Subscale (FACT-LCS) in the high-dose RT-arm at 3 months. Design RTOG 0617 was a randomized phase III study (conducted from Nov 2007 to Nov 2011) in stage III NSCLC using a 2×2 factorial design and stratified by histology, PET staging, performance status and radiation technique (3D-conformal RT [3DCRT] vs. intensity-modulated radiation [IMRT]). Setting 185 institutions in the USA and Canada. Participants Of 424 eligible stage III NSCLC patients randomized, 360 (85%) consented to QOL, of whom 313 (88%) completed baseline QOL assessments. Intervention for Clinical Trials 74Gy vs. 60Gy with concurrent and consolidation carboplatin/paclitaxel +/− cetuximab. Main Outcomes and Measures QOL was collected prospectively via FACT-Trial Outcome Index (FACT-TOI), equaling Physical-Well-Being (PWB) + Functional-Well-Being (FWB) + Lung Cancer Subscale (LCS). Data are presented at baseline & 3 and 12 months via minimal clinically meaningful changes of >=2 points for PWB, FWB or LCS or >=5 points for TOI. Results Patient demographics and baseline QOL scores were comparable between the 74Gy and 60Gy arms. Two-hundred-nineteen (72%) of living patients who completed QOL at baseline did so at 3 months and 137 (57%) of living patients did so at 12 months. Significantly more patients on 74Gy arm had clinically meaningful decline in FACT-LCS at 3 months than on the 60Gy arm (45% vs. 30%, p=0.02). At 12 months, fewer patients who received IMRT (vs 3DCRT) had clinically meaningful decline in FACT-LCS (21% vs 46%, p=0.003). Baseline FACT-TOI was associated with overall survival in

  3. Single-agent maintenance therapy for advanced non-small cell lung cancer (NSCLC): a systematic review and Bayesian network meta-analysis of 26 randomized controlled trials

    Science.gov (United States)

    Zeng, Xiaoning; Ma, Yuan

    2016-01-01

    Background The benefit of maintenance therapy has been confirmed in patients with non-progressing non-small cell lung cancer (NSCLC) after first-line therapy by many trials and meta-analyses. However, since few head-to-head trials between different regimens have been reported, clinicians still have little guidance on how to select the most efficacious single-agent regimen. Hence, we present a network meta-analysis to assess the comparative treatment efficacy of several single-agent maintenance therapy regimens for stage III/IV NSCLC. Methods A comprehensive literature search of public databases and conference proceedings was performed. Randomized clinical trials (RCTs) meeting the eligible criteria were integrated into a Bayesian network meta-analysis. The primary outcome was overall survival (OS) and the secondary outcome was progression free survival (PFS). Results A total of 26 trials covering 7,839 patients were identified, of which 24 trials were included in the OS analysis, while 23 trials were included in the PFS analysis. Switch-racotumomab-alum vaccine and switch-pemetrexed were identified as the most efficacious regimens based on OS (HR, 0.64; 95% CrI, 0.45–0.92) and PFS (HR, 0.54; 95% CrI, 0.26–1.04) separately. According to the rank order based on OS, switch-racotumomab-alum vaccine had the highest probability as the most effective regimen (52%), while switch-pemetrexed ranked first (34%) based on PFS. Conclusions Several single-agent maintenance therapy regimens can prolong OS and PFS for stage III/IV NSCLC. Switch-racotumomab-alum vaccine maintenance therapy may be the most optimal regimen, but should be confirmed by additional evidence.

  4. Living with a diagnosis of non-small cell lung cancer: patients' lived experiences.

    LENUS (Irish Health Repository)

    McCarthy, Ita

    2012-01-31

    The aim of this study was to explore patients\\' experience of living with non-small cell lung cancer (NSCLC). Patients diagnosed with NSCLC know that their treatment is not with curative intent and can expect distressing symptoms. In this phenomenological study, six adults with a diagnosis of NSCLC were interviewed. Data was analysed guided by van Manen\\'s six-step process. Four main themes were interpreted: \\'Maintaining my life\\'; \\'The enemy within\\'; \\'Staying on the train\\

  5. Texture analysis of advanced non-small cell lung cancer (NSCLC) on contrast-enhanced computed tomography: prediction of the response to the first-line chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Farina, Davide; Morassi, Mauro; Maroldi, Roberto [University of Brescia, Department of Radiology, Brescia (Italy); Roca, Elisa; Tassi, Gianfranco [University of Brescia, Department of Pneumology, Brescia (Italy); Cavalleri, Giuseppe [University of Brescia, Department of Electronic Engineering, Brescia (Italy)

    2013-12-15

    To assess whether tumour heterogeneity, quantified by texture analysis (TA) on contrast-enhanced computed tomography (CECT), can predict response to chemotherapy in advanced non-small cell lung cancer (NSCLC). Fifty-three CECT studies of patients with advanced NSCLC who had undergone first-line chemotherapy were retrospectively reviewed. Response to chemotherapy was evaluated according to RECIST1.1. Tumour uniformity was assessed by a TA method based on Laplacian of Gaussian filtering. The resulting parameters were correlated with treatment response and overall survival by multivariate analysis. Thirty-one out of 53 patients were non-responders and 22 were responders. Average overall survival was 13 months (4-35), minimum follow-up was 12 months. In the adenocarcinoma group (n = 31), the product of tumour uniformity and grey level (GL*U) was the unique independent variable correlating with treatment response. Dividing the GL*U (range 8.5-46.6) into tertiles, lesions belonging to the second and the third tertiles had an 8.3-fold higher probability of treatment response compared with those in the first tertile. No association between texture features and response to treatment was observed in the non-adenocarcinoma group (n = 22). GL*U did not correlate with overall survival. TA on CECT images in advanced lung adenocarcinoma provides an independent predictive indicator of response to first-line chemotherapy. (orig.)

  6. Metformin and salinomycin as the best combination for the eradication of NSCLC monolayer cells and their alveospheres (cancer stem cells) irrespective of EGFR, KRAS, EML4/ALK and LKB1 status.

    Science.gov (United States)

    Xiao, Zhiguang; Sperl, Bianca; Ullrich, Axel; Knyazev, Pjotr

    2014-12-30

    The presence of cancer stem cells (CSCs) is linked to preexisting or acquired drug resistance and tumor relapse. Therefore, targeting both differentiated tumor cells and CSCs was suggested as an effective approach for non-small cell lung cancer (NSCLC) treatment. After screening of chemotherapeutic agents, tyrosine kinase inhibitors (TKIs) or monoclonal antibody in combination with the putative stem cell killer Salinomycin (SAL), we found Metformin (METF), which modestly exerted a growth inhibitory effect on monolayer cells and alveospheres/CSCs of 5 NSCLC cell lines regardless of their EGFR, KRAS, EML4/ALK and LKB1 status, interacted synergistically with SAL to effectively promote cell death. Inhibition of EGFR (AKT, ERK1/2) and mTOR (p70 s6k) signaling with the combination of METF and SAL can be augmented beyond that achieved using each agent individually. Phospho-kinase assay further suggested the multiple roles of this combination in reducing oncogenic effects of modules, such as ß-catenin, Src family kinases (Src, Lyn, Yes), Chk-2 and FAK. Remarkably, significant reduction of sphere formation was seen under combinatorial treatment in all investigated NSCLC cell lines. In conclusion, METF in combination with SAL could be a promising treatment option for patients with advanced NSCLC irrespective of their EGFR, KRAS, EML4/ALK and LKB1 status. PMID:25375092

  7. Assessment of EGFR mutations in circulating tumor cell preparations from NSCLC patients by next generation sequencing: toward a real-time liquid biopsy for treatment.

    Directory of Open Access Journals (Sweden)

    Antonio Marchetti

    Full Text Available Assessment of EGFR mutation in non-small cell lung cancer (NSCLC patients is mandatory for optimization of pharmacologic treatment. In this respect, mutation analysis of circulating tumor cells (CTCs may be desirable since they may provide real-time information on patient's disease status.Blood samples were collected from 37 patients enrolled in the TRIGGER study, a prospective phase II multi-center trial of erlotinib treatment in advanced NSCLC patients with activating EGFR mutations in tumor tissue. 10 CTC preparations from breast cancer patients without EGFR mutations in their primary tumors and 12 blood samples from healthy subjects were analyzed as negative controls. CTC preparations, obtained by the Veridex CellSearch System, were subjected to ultra-deep next generation sequencing (NGS on the Roche 454 GS junior platform.CTCs fulfilling all Veridex criteria were present in 41% of the patients examined, ranging in number between 1 and 29. In addition to validated CTCs, potential neoplastic elements were seen in 33 cases. These included cells not fulfilling all Veridex criteria (also known as "suspicious objects" found in 5 (13% of 37 cases, and isolated or clustered large naked nuclei with irregular shape observed in 33 (89% cases. EGFR mutations were identified by NGS in CTC preparations of 31 (84% patients, corresponding to those present in matching tumor tissue. Twenty-five (96% of 26 deletions at exon 19 and 6 (55% of 11 mutations at exon 21 were detectable (P = 0.005. In 4 (13% cases, multiple EGFR mutations, suggesting CTC heterogeneity, were documented. No mutations were found in control samples.We report for the first time that the CellSearch System coupled with NGS is a very sensitive and specific diagnostic tool for EGFR mutation analysis in CTC preparations with potential clinical impact.

  8. Triaging early-stage lung cancer patients into non-surgical pathways: who, when, and what?

    OpenAIRE

    Sroufe, Rameses; Kong, Feng-Ming

    2015-01-01

    More lung cancer patients are being diagnosed at an earlier stage due to improved diagnostic imaging techniques, a trend that is expected to accelerate with the dissemination of lung cancer screening. Surgical resection has always been considered the standard treatment for patients with early-stage non-small cell lung cancer (NSCLC). However, non-surgical treatment options for patients with early-stage NSCLC have evolved significantly over the past decade with many new and exciting alternativ...

  9. Incidental Prophylactic Nodal Irradiation and Patterns of Nodal Relapse in Inoperable Early Stage NSCLC Patients Treated With SBRT: A Case-Matched Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Lao, Louis [Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Department of Radiation Oncology, Auckland City Hospital, Auckland (New Zealand); Hope, Andrew J. [Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Maganti, Manjula [Department of Biostatistics, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Brade, Anthony; Bezjak, Andrea; Saibishkumar, Elantholi P.; Giuliani, Meredith; Sun, Alexander [Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Cho, B. C. John, E-mail: john.cho@rmp.uhn.on.ca [Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada)

    2014-09-01

    Purpose: Reported rates of non-small cell lung cancer (NSCLC) nodal failure following stereotactic body radiation therapy (SBRT) are lower than those reported in the surgical series when matched for stage. We hypothesized that this effect was due to incidental prophylactic nodal irradiation. Methods and Materials: A prospectively collected group of medically inoperable early stage NSCLC patients from 2004 to 2010 was used to identify cases with nodal relapses. Controls were matched to cases, 2:1, controlling for tumor volume (ie, same or greater) and tumor location (ie, same lobe). Reference (normalized to equivalent dose for 2-Gy fractions [EQD2]) point doses at the ipsilateral hilum and carina, demographic data, and clinical outcomes were extracted from the medical records. Univariate conditional logistical regression analyses were performed with variables of interest. Results: Cases and controls were well matched except for size. The controls, as expected, had larger gross tumor volumes (P=.02). The mean ipsilateral hilar doses were 9.6 Gy and 22.4 Gy for cases and controls, respectively (P=.014). The mean carinal doses were 7.0 Gy and 9.2 Gy, respectively (P=.13). Mediastinal nodal relapses, with and without ipsilateral hilar relapse, were associated with mean ipsilateral hilar doses of 3.6 Gy and 19.8 Gy, respectively (P=.01). The conditional density plot appears to demonstrate an inverse dose-effect relationship between ipsilateral hilar normalized total dose and risk of ipsilateral hilar relapse. Conclusions: Incidental hilar dose greater than 20 Gy is significantly associated with fewer ipsilateral hilar relapses in inoperable early stage NSCLC patients treated with SBRT.

  10. miR-143 suppresses the proliferation of NSCLC cells by inhibiting the epidermal growth factor receptor

    Science.gov (United States)

    Zhang, Hong-Bo; Sun, Li-Chao; Ling, Lan; Cong, Lu-Hong; Lian, Rui

    2016-01-01

    MicroRNAs (miRs) regulate the proliferation and metastasis of numerous cancer cell types. It was previously reported that miR-143 levels were downregulated in non-small cell lung cancer (NSCLC) tissues and cell lines, and that the migration and invasion of NSCLC cells was inhibited upon suppression of cell proliferation and colony formation by the upregulation of miR-143. Epidermal growth factor receptor (EGFR), which is a vital factor in the promotion of cancer cell proliferation and has been investigated as a potential focus in cancer therapy, has been reported to be a possible target of miR-143. The present study aimed to investigate the role of miR-143 in NSCLC using NSCLC cell lines and primary cells from NSCLC patients. NSCLC cells were co-transfected with EGFR and miR-143, and the mRNA and protein expression of EGFR were analyzed. Furthermore, the activity of the transfected cancer cells with regard to colony formation, migration, invasion and apoptosis were evaluated. The levels of miR-143 were decreased in the NSCLC cell lines and primary cells from patients with NSCLC compared with the controls. Following transfection with miR-143, the ability of NSCLC cells to proliferate, form colonies, migrate and invade was inhibited. Similarly, knockdown of EGFR led to the suppression of NSCLC cell proliferation. The mRNA and protein expression levels of EGFR were significantly reduced following miR-143 overexpression, and the level of miR-143 was inversely correlated with that of EGFR in NSCLC cells. The results of the present study demonstrated that miR-143 was able to suppress NSCLC cell proliferation and invasion by inhibiting the effects of EGFR, suggesting that EGFR may be considered a potential target for NSCLC therapy. PMID:27602093

  11. Vinorelbine/carboplatin vs gemcitabine/carboplatin in advanced NSCLC shows similar efficacy, but different impact of toxicity

    DEFF Research Database (Denmark)

    Helbekkmo, N; Sundstrøm, S H; Aasebø, U;

    2007-01-01

    This randomised phase III study in advanced non-small cell lung cancer (NSCLC) patients was conducted to compare vinorelbine/carboplatin (VC) and gemcitabine/carboplatin (GC) regarding efficacy, health-related quality of life (HRQOL) and toxicity. Chemonaive patients with NSCLC stage IIIB...... and pain, showed no significant differences. More grade 3-4 anaemia (Pplatelets (P

  12. miR-25 modulates NSCLC cell radio-sensitivity through directly inhibiting BTG2 expression

    Energy Technology Data Exchange (ETDEWEB)

    He, Zhiwei, E-mail: carlhe@126.com; Liu, Yi, E-mail: cassieliu@126.com; Xiao, Bing, E-mail: rockg714@aliyun.com; Qian, Xiaosen, E-mail: xiaosenqian@126.com

    2015-02-13

    A large proportion of the NSCLC patients were insensitive to radiotherapy, but the exact mechanism is still unclear. This study explored the role of miR-25 in regulating sensitivity of NSCLC cells to ionizing radiation (IR) and its downstream targets. Based on measurement in tumor samples from NSCLC patients, this study found that miR-25 expression is upregulated in both NSCLC and radio-resistant NSCLC patients compared the healthy and radio-sensitive controls. In addition, BTG expression was found negatively correlated with miR-25a expression in the both tissues and cells. By applying luciferase reporter assay, we verified two putative binding sites between miR-25 and BTG2. Therefore, BTG2 is a directly target of miR-25 in NSCLC cancer. By applying loss-and-gain function analysis in NSCLC cell lines, we demonstrated that miR-25-BTG2 axis could directly regulated BTG2 expression and affect radiotherapy sensitivity of NSCLC cells. - Highlights: • miR-25 is upregulated, while BTG2 is downregulated in radioresistant NSCLC patients. • miR-25 modulates sensitivity to radiation induced apoptosis. • miR-25 directly targets BTG2 and suppresses its expression. • miR-25 modulates sensitivity to radiotherapy through inhibiting BTG2 expression.

  13. Pharmacogenomics of platinum-based chemotherapy sensitivity in NSCLC: toward precision medicine.

    Science.gov (United States)

    Yin, Ji-Ye; Li, Xi; Zhou, Hong-Hao; Liu, Zhao-Qian

    2016-08-01

    Lung cancer is one of the leading causes of cancer-related death in the world. Platinum-based chemotherapy is the first-line treatment for non-small-cell lung cancer (NSCLC), however, the therapeutic efficiency varies remarkably among individuals. A large number of pharmacogenomics studies aimed to identify genetic variations which can be used to predict platinum response. Those studies are leading NSCLC treatment to the new era of precision medicine. In the current review, we provided a comprehensive update on the main recent findings of genetic variations which can be used to predict platinum sensitivity in the NSCLC patients.

  14. Survival of primary irradiated patients with NSCLC in dependence of the pretherapeutical haemoglobin level

    International Nuclear Information System (INIS)

    We have analysed the files of 96 primary radiated patients to evaluate the pre-therapeutic haemoglobin level as well as sex, age, histopathology, total dose and fractionation. The analysis of Karnofsky-status or patient condition was not performed as there was a lack of sufficient data in the patient files. Histopathology, sex, age as well as total dose and fractionation of the radiation treatment were similar in the cohort building 3 groups: Hb15 g/dl. The investigation resulted in the observation, that lower levels of initial serum haemoglobin concentration compared to levels over 15 g/dl are negative prognostic factors. Higher initial haemoglobin concentration is a high significant positive prognostic factor (p=0,0001). The applied total dose (>30 Gy, >50 Gy, >55 Gy) was not a significant prognostic factor in this patient material, where two thirds of the patients had an advanced cancer (stage IIIB or Stage IV). (orig./MG)

  15. Cost-effective analysis of PET application in NSCLC

    International Nuclear Information System (INIS)

    Objective: To evaluate the cost-effectiveness of PET and CT application for diagnosis of non-small cell lung cancer (NSCLC) in China. Methods: Using decision analysis method the diagnostic efficiency of PET and CT for diagnosis of NSCLC in china was analysed. And also the value of cost for accurate diagnosis (CAD), cost for accurate staging (CAS) and cost for effective therapy (CAT) was calculated. Results: (1) For the accurate diagnosis, CT was much more cost-effective than PET. (2) For the accurate staging, CT was still more cost-effective than PET. (3) For the all over diagnostic and therapeutic cost, PET was more cost-effective than CT. (4) The priority of PET to CT was for the diagnosis of stage I NSCLC. Conclusion: For the management of NSCLC patient in China, CT is more cost-effective for screening, whereas PET for clinical staging and monitoring therapeutic effect. (authors)

  16. Phase I Study of Oral Vinorelbine in Combination with Erlotinib in Advanced Non-Small Cell Lung Cancer (NSCLC Using Two Different Schedules.

    Directory of Open Access Journals (Sweden)

    Natalia Sutiman

    Full Text Available This study aimed to evaluate the safety, tolerability and pharmacokinetics of the combination of oral vinorelbine with erlotinib using the conventional (CSV and metronomic (MSV dosing schedules in patients with advanced non-small cell lung cancer (NSCLC.This was an open-label, multiple dose-escalation phase I study. An alternating 3+3 phase I design was employed to allow each schedule to enroll three patients sequentially at each dose level. Thirty patients with Stage IIIB/IV NSCLC were treated with escalating doses of oral vinorelbine starting at 40 mg/m2 on day 1 and 8 in the CSV group (N = 16 and at 100 mg/week in the MSV group (N = 14. Erlotinib was administered orally daily.The maximum tolerated dose was vinorelbine 80 mg/m2 with erlotinib 100 mg in the CSV group and vinorelbine 120 mg/week with erlotinib 100 mg in the MSV group. Grade 3/4 toxicities included neutropenia (N = 2; 13% and hyponatremia (N = 1; 6% in the CSV group, and neutropenia (N = 5; 36% in the MSV group. Objective response was achieved in 38% and 29% in the CSV and MSV groups respectively. Vinorelbine co-administration did not significantly affect the pharmacokinetics of erlotinib and OSI-420 after initial dose. However, at steady-state, significantly higher Cmax, higher Cmin and lower CL/F of erlotinib were observed with increasing dose levels of vinorelbine in the CSV group. Significantly higher steady-state Cmin, Cavg and AUCss of erlotinib were observed with increasing dose levels of vinorelbine in the MSV group.Combination of oral vinorelbine with erlotinib is feasible and tolerable in both the CSV and MSV groups.ClinicalTrials.gov NCT00702182.

  17. Rationale and Study Design of the IRENE-Trial (NVALT-16) : A Phase II Trial to Evaluate Iressa Rechallenge in Advanced NSCLC Patients With an Activating EGFR Mutation Who Responded to an EGFR-TKI Used As First-Line or Previous Treatment

    NARCIS (Netherlands)

    Kuiper, Justine L.; Heideman, Danielle A. M.; Wurdinger, Tom; Grunberg, Katrien; Groen, Harry J. M.; Smit, Egbert F.

    2015-01-01

    Background: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have shown improved progression-free survival (PFS) and overall survival (OS) over chemotherapy in a molecularly defined subgroup of advanced non-small-cell lung cancer (NSCLC) patients (ie, patients with an activa

  18. Vitamin D-Related Gene Polymorphisms, Plasma 25-Hydroxy-Vitamin D, Cigarette Smoke and Non-Small Cell Lung Cancer (NSCLC) Risk.

    Science.gov (United States)

    Wu, Xiayu; Cheng, Jiaoni; Yang, Kaiyun

    2016-01-01

    Epidemiological studies regarding the relationship between vitamin D, genetic polymorphisms in the vitamin D metabolism, cigarette smoke and non-small cell lung cancer (NSCLC) risk have not been investigated comprehensively. To search for additional evidence, the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique and radioimmunoassay method were utilized to evaluate 5 single-nucleotide polymorphisms (SNPs) in vitamin D receptor (VDR), 6 SNPs in 24-hydroxylase (CYP24A1), 2 SNPs in 1α-hydroxylase (CYP27B1) and 2 SNPs in vitamin D-binding protein (group-specific component, GC) and plasma vitamin D levels in 426 NSCLC cases and 445 controls from China. Exposure to cigarette smoke was ascertained through questionnaire information. Multivariable linear regressions and mixed effects models were used in statistical analysis. The results showed that Reference SNP rs6068816 in CYP24A1, rs1544410 and rs731236 in VDR and rs7041 in GC were statistically significant in relation to reduction in NSCLC risk (p vitamin D concentration, the more the genetic variations in CYP24A1, VDR and GC genes may be associated with NSCLC risk. In addition, there are significant joint associations of cigarette smoking and vitamin D deficiency on NSCLC risk. PMID:27669215

  19. Predictive impact of RRM1 protein expression on vinorelbine efficacy in NSCLC patients randomly assigned in a chemotherapy phase III trial

    DEFF Research Database (Denmark)

    Vilmar, A C; Santoni-Rugiu, E; Sørensen, Jens Benn

    2013-01-01

    Platinum-based doublets (PBDs) remain the cornerstone of treatment in non-small-cell lung cancer (NSCLC) and may include gemcitabine. A biomarker predicting sensitivity to this antimetabolite would represent a major step forward. Accordingly, we explored the predictive role of ribonucleotide...

  20. Progress in standard of care therapy and modest survival benefits in the treatment of non-small cell lung cancer patients in the Netherlands in the last 20 years.

    NARCIS (Netherlands)

    Drift, M.A. van der; Karim-Kos, H.E.; Siesling, S.; Groen, H.J.; Wouters, M.W.; Coebergh, J.W.W.; Vries, E. de; Janssen-Heijnen, M.L.

    2012-01-01

    INTRODUCTION: Lung cancer is the leading cause of cancer mortality worldwide. We analyzed changes in treatment and their potential effect on survival of non-small cell lung cancer (NSCLC) patients in the Netherlands. METHODS: All NSCLC patients diagnosed during 1989-2009 (n=147,760) were selected fr

  1. Progress in Standard of Care Therapy and Modest Survival Benefits in the Treatment of Non-small Cell Lung Cancer Patients in the Netherlands in the Last 20 Years

    NARCIS (Netherlands)

    Drift, van der M.A.; Karim-Kos, H.E.; Siesling, S.; Groen, H.J.M.; Wouters, M.W.J.M.; Coebergh, J.W.W.; Vries, de E.; Janssen-Heijnen, M.L.G.

    2012-01-01

    Introduction: Lung cancer is the leading cause of cancer mortality worldwide. We analyzed changes in treatment and their potential effect on survival of non-small cell lung cancer (NSCLC) patients in the Netherlands. Methods: All NSCLC patients diagnosed during 1989–2009 (n=147,760) were selecte

  2. Progress in Standard of Care Therapy and Modest Survival Benefits in the Treatment of Non-small Cell Lung Cancer Patients in the Netherlands in the Last 20 Years

    NARCIS (Netherlands)

    van der Drift, Miep A.; Karim-Kos, Henrike E.; Siesling, Sabine; Groen, Harry J. M.; Wouters, Michel W. J. M.; Coebergh, Jan-Willem; de Vries, Esther; Janssen-Heijnen, Maryska L. G.

    2012-01-01

    Introduction: Lung cancer is the leading cause of cancer mortality worldwide. We analyzed changes in treatment and their potential effect on survival of non-small cell lung cancer (NSCLC) patients in the Netherlands. Methods: All NSCLC patients diagnosed during 1989-2009 (n = 147,760) were selected

  3. Variations in Serum CEA and CYFRA21-1 Levels Before and After Surgery Facilitate Prognosis of Non-small Cell Lung Cancer Patients

    OpenAIRE

    Xinchun DUAN; Cui, Yong; Gong, Min; Tian, Feng; Guan SHI; Wu, Bingqun; Liu, Mingliang; Jiayun GUO; Kong, Yuanyuan

    2015-01-01

    Background and objective Serum carcinoembryonic antigen (CEA) and the soluble fragment of cytokeratin 19 (CYFRA21-1) are important tumor markers (TMs) in the preoperative examination of patients with non-small cell lung cancer (NSCLC). However, the prognostic role of these markers in NSCLC patients remains controversial. The aim of the study was to investigate the clinical significance of serum CEA variances and CYFRA21-1 levels for the prognosis of NSCLC patients following surgery. Methods T...

  4. Examination of 12-lipoxygenase (12-LOX) as a therapeutic target in non-small cell lung cancer (NSCLC): Mechanisms controlling survival and induction of apoptosis following selective inhibition

    LENUS (Irish Health Repository)

    Cathcart, Mary Clare

    2011-06-01

    Background: Platelet-type 12-LOX is an arachidonic acid metabolising enzyme resulting in the formation of 12(S)-HETE, which stimulates tumour cell adhesion, invasion and metastasis. This study aimed to examine the expression profile and role of this enzyme in NSCLC, and determine if it is a potential target for intervention. Methods: A panel of retrospective resected lung tumours was stained for 12-LOX expression by IHC. Levels of the 12-LOX metabolite, 12(S)-HETE, were examined in 50 NSCLC serum samples, and correlated with serum VEGF. A panel of NSCLC cell lines were treated with baicalein (10 uM), a selective inhibitor of 12-LOX, or 12(S)-HETE (100 ng\\/ml) and cell survival\\/proliferation examined by BrdU. Apoptosis following 12-LOX inhibition was examined by HCS and validated by FACS and DNA laddering. The effect of 12-LOX inhibition on NSCLC tumour growth and survival was examined in-vivo using an athymic nude mouse model. Gene alterations following 12-LOX inhibition in NSCLC cell lines were assessed by qPCR arrays and validated by RT-PCR. Transient transfection methods were used to examine the effects of 12-LOX overexpression in NSCLC cells. Results: 12-LOX expression was observed to a varying degree in human lung cancers of varying histological subtypes. 12(S)-HETE levels were correlated (p<0.05) with those of VEGF. Baicalein inhibited proliferation\\/survival in all cell lines, while 12(S)-HETE increased proliferation. 12-LOX inhibition increased apoptosis, indicated by a reduction in f-actin content and mitochondrial mass potential. Treatment with baicalein significantly reduced the growth of NSCLC tumours and increased overall survival in athymic nude mice. qPCR array data implicated a number of apoptosis\\/angiogenesis genes regulating these effects, including bcl-2, VEGF, integrin A2 and A4. 12-LOX overexpression resulted in an increase in VEGF secretion, confirming qPCR observations. Conclusions: 12-LOX is a survival factor\\/potential target in

  5. Emerging treatments and combinations in the management of NSCLC

    DEFF Research Database (Denmark)

    Reck, Martin; Mellemgaard, Anders

    2015-01-01

    There remains an unmet need for effective, well-tolerated treatment options in advanced non-small cell lung cancer (NSCLC) to alleviate the disease burden for a broad selection of patients. Nintedanib is a potent, oral, triple angiokinase inhibitor of vascular endothelial growth factor, fibroblast...... growth factor, and platelet-derived growth factor, and was recently approved in Europe for use in combination with docetaxel for the treatment of adults with locally advanced, metastatic, or locally recurrent NSCLC of adenocarcinoma tumor histology, following first-line chemotherapy. Nintedanib has been...... investigated extensively in preclinical research and in a number of clinical studies, the most important of which was the Phase III LUME-Lung 1 study, which investigated nintedanib in combination with docetaxel in patients with advanced NSCLC after failure of first-line chemotherapy. In this study, which led...

  6. Prognostic significance of CDH13 hypermethylation and mRNA in NSCLC

    Directory of Open Access Journals (Sweden)

    Xue R

    2014-10-01

    Full Text Available Ruilin Xue,1 Cuili Yang,1 Fang Zhao,2 Dejia Li1 1Global Health Institute, School of Public Health, 2Zhongnan Hospital, Wuhan University, Wuhan, People's Republic of ChinaAbstract: Aberrant methylation of CpG dinucleotides is a commonly observed epigenetic modification in human cancer. Thus, detection of aberrant gene promoter methylation as a tool for diagnosis of tumors or as a prognostic marker has been widely described for many types of cancers, including nonsmall cell lung cancer (NSCLC. Emerging evidence indicates that CDH13 is a candidate tumor suppressor in several types of human tumors, including NSCLC. However, the correlation between CDH13 hypermethylation and clinicopathological characteristics of NSCLC remains unclear. In the current study, we conducted a systematic review and meta-analysis to quantitatively evaluate the effects of CDH13 hypermethylation on the incidence of NSCLC and clinicopathological characteristics. Final analysis of 803 NSCLC patients from eleven eligible studies was performed. CDH13 hypermethylation was observed to be significantly higher in NSCLC than in normal lung tissue, with the pooled odds ratio (OR from seven studies including 448 NSCLC and 345 normal lung tissue (OR, 7.85; 95% confidence interval, 5.12–12.03; P<0.00001. CDH13 hypermethylation was also associated with pathological types. The pooled OR was obtained from four studies, including 111 squamous cell carcinoma and 106 adenocarcinoma (OR, 0.35; 95% confidence interval, 0.19–0.66; P=0.001, which indicated that CDH13 hypermethylation plays a more important role in the pathogenesis of adenocarcinoma. NSCLC with CDH13 hypermethylation was found more frequently in poorly differentiated NSCLC patients. NSCLC patients with CDH13 hypermethylation had a lower survival rate than those without CDH13 hypermethylation. In addition, CDH13 mRNA high expression was found to correlate with better overall survival for all NSCLC patients followed for 20 years

  7. A phase Ⅱ clinical trial of celecoxib combined with platinum-based chemotherapy in the treatment of patients with advanced NSCLC as first-line treatment

    Directory of Open Access Journals (Sweden)

    Zhijie WANG

    2008-06-01

    Full Text Available Background and objective Currently, platinum-based regimes are standard first-line chemotherapy for non-small cell lung cancer. The aim of this study is to evaluate the efficacy, influencing factors and adverse events of celecoxib plus platinum-based chemotherapy in advanced non-small cell lung cancer as first-line treatment. Methods Previously untreated patients of advanced non-small cell lung cancer with COX-2 positive, confirmed by immunohistochemical staining, were randomized to receive GP, NP or TP regimens. Celecoxib of 400 mg Bid was given, po 5-7 days before chemotherapy,and not stopped until evidence of disease progression or toxicity. Adverse events were cirtified according to NCI-CTC criteria. Kaplan-Meier method was used to analyze the survival rate. COX regression was used to define the predictive factors. Primary endpoint: median survival time, 1-year survival rate and median progression free survival time. Secondary endpoint: response rate and toxicity. Results Forty-four evaluable patients were enrolled in the study from February 2005 to March 2007. Response rate was 45%, disease control rate 59%. Median progression free survival time and median survival time were 6months (95%CI: 4-8 months and 18 months (95%CI: 9-27months, respectively. One-year survival rate was 68%. Numbers of chemotherapy cycles and overall evaluation were the predictive factors for PFS in COX model (P=0.023 and 0.000. No factor was defined to affect survival time. Neutropenia and nausea/vomit were the most common toxicity. Conclusion Celecoxib combined with platinum-based chemotherapy appears to be well tolerated and demonstrates encouraging activity in patients of previously untreated advanced NSCLC.

  8. Effect of Amifostine on Locally Advanced Non-small Cell Lung Cancer Patients Treated with Radiotherapy: A Meta-analysis of Randomized Controlled Trials

    OpenAIRE

    Wang, Shengye; Zhang, Yiping; Zhang, Suzhan; Ma, Shenglin

    2012-01-01

    Background and objective Controversy exists on whether amifostine can reduce the efficacy and decrease the side effects of non-small cell lung cancer (NSCLC) treated by radiotherapy. The aim of this meta-analysis is to evaluate the efficacy and side effects of amifostine in NSCLC patients treated with radiotherapy. Methods Open published randomized controlled trials on the efficacy and side effects of amifostine in NSCLC patients treated with radiotherapy were collected from Medline, Cochrane...

  9. Activation of insulin-like growth factor 1 receptor in patients with non-small cell lung cancer.

    Science.gov (United States)

    Kim, Jin-Soo; Kim, Edward S; Liu, Diane; Lee, J Jack; Behrens, Carmen; Lippman, Scott M; Hong, Waun Ki; Wistuba, Ignacio I; Lee, Euni; Lee, Ho-Young

    2015-06-30

    According to previous reports demonstrating the implication of insulin-like growth factor receptor (IGF-1R) signaling in non-small cell lung cancer (NSCLC), in this study, the potential prognostic values of IGF-1R expression/activation were analyzed. The expression and activation of IGF-1R were evaluated in two tissue microarray (TMA) sets from NSCLC patients (N = 352 for TMA I, and N = 353 for TMA II). Alterations in IGF-1R protein or mRNA expression in NSCLC patients were evaluated using publicly available data from The Cancer Genome Atlas (TCGA). We found that membranous and cytoplasmic IGF-1R expressions were significantly associated with squamous cell carcinoma (SCC) in both of the TMAs. Analysis of the TCGA data revealed increased mRNA levels in NSCLC patients, which was significantly associated with reductions in overall survival (OS) (median survival 26.51 vs. 47.77 months, P = 0.017) and disease-free survival (median survival 17.44 vs. 37.65 months, P = 0.045) only in NSCLC patients with adenocarcinoma (ADC). These data suggest that IGF-1R is activated in patients with NSCLC, particularly those with SCC. IGF-1R mRNA expression is a potential prognostic factor in patients with NSCLC, especially those with ADC. Further studies are warranted to investigate the prognostic value of IGF-1R in NSCLC patients. PMID:25944691

  10. First-line erlotinib and bevacizumab in patients with locally advanced and/or metastatic non-small-cell lung cancer : a phase II study including molecular imaging

    NARCIS (Netherlands)

    Dingemans, A. -M. C.; de Langen, A. J.; van den Boogaart, V.; Marcus, J. T.; Backes, W. H.; Scholtens, H. T. G. M.; van Tinteren, H.; Hoekstra, O. S.; Pruim, J.; Brans, B.; Thunnissen, F. B.; Smit, E. F.; Groen, H. J. M.

    2011-01-01

    Background: Both bevacizumab and erlotinib have clinical activity in non-small-cell lung cancer (NSCLC). Preclinical data suggest synergistic activity. Patients and methods: Chemonaive patients with stage IIIb or IV non-squamous NSCLC were treated with bevacizumab 15 mg/kg every 3 weeks and erlotini

  11. Prediction of outcome of non-small cell lung cancer patients treated with chemotherapy and bortezomib by time-course MALDI-TOF-MS serum peptide profiling

    NARCIS (Netherlands)

    Voortman, J.; Pham, T.V.; Knol, J.C.; Giaccone, G.; Jimenez, C.R.

    2009-01-01

    Background: Only a minority of patients with advanced non-small cell lung cancer (NSCLC) benefit from chemotherapy. Serum peptide profiling of NSCLC patients was performed to investigate patterns associated with treatment outcome. Using magnetic bead-assisted serum peptide capture coupled to matrix-

  12. Metformin increases antitumor activity of MEK inhibitors through GLI1 downregulation in LKB1 positive human NSCLC cancer cells

    Science.gov (United States)

    Della Corte, Carminia Maria; Ciaramella, Vincenza; Mauro, Concetta Di; Castellone, Maria Domenica; Papaccio, Federica; Fasano, Morena; Sasso, Ferdinando Carlo; Martinelli, Erika; Troiani, Teresa; De Vita, Ferdinando; Orditura, Michele; Bianco, Roberto; Ciardiello, Fortunato; Morgillo, Floriana

    2016-01-01

    Purpose Metformin, widely used as antidiabetic drug, showed antitumoral effects expecially in combination with chemotherapy. Our group recently has demonstrated that metformin and gefitinib are synergistic in LKB1-wild-type NSCLC cells. In these models, metformin as single agent induced an activation and phosphorylation of mitogen-activated-protein-kinase (MAPK) through an increased C-RAF/B-RAF heterodimerization. Experimental design Since single agent metformin enhances proliferating signals through the RAS/RAF/MAPK pathway, and several MEK inhibitors (MEK-I) demonstrated clinical efficacy in combination with other agents in NSCLC, we tested the effects of metformin plus MEK-I (selumetinib or pimasertib) on proliferation, invasiveness, migration abilities in vitro and in vivo in LKB1 positive NSCLC models harboring KRAS wild type and mutated gene. Results The combination of metformin with MEK-I showed a strong anti-proliferative and proapoptotic effect in Calu-3, H1299, H358 and H1975 human NSCLC cell lines, independently from the KRAS mutational status. The combination reduced the metastatic behaviour of NSCLC cells, via a downregulation of GLI1 trascritional activity, thus affecting the transition from an epithelial to a mesenchymal phenotype. Metformin and MEK-Is combinations also decreased the production and activity of MMP-2 and MMP-9 by reducing the NF-jB (p65) binding to MMP-2 and MMP-9 promoters. Conclusions Metformin potentiates the antitumor activity of MEK-Is in human LKB1-wild-type NSCLC cell lines, independently from the KRAS mutational status, through GLI1 downregulation and by reducing the NF-jB (p65)-mediated transcription of MMP-2 and MMP-9. PMID:26673006

  13. 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

    Institute of Scientific and Technical Information of China (English)

    Yusheng Shi; Xiaogang Deng; Longhua Chen

    2007-01-01

    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 cancer, 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 therapeutic 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 examination (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 target 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.

  14. Targeted therapies forpatients withadvanced NSCLC harboring wild-type EGFR:what’s new andwhat’s enough

    Institute of Scientific and Technical Information of China (English)

    FeiZhou; Cai-CunZhou

    2015-01-01

    Historically, non‑small cell lung cancer (NSCLC) is divided into squamous and nonsquamous subtypes based on histo‑logic features. With a growing number of oncogenic drivers being identiifed in squamous and nonsquamous NSCLC, this malignancy has been recently divided into several distinct subtypes according to the speciifc molecular altera‑tions. This new paradigm has substantially highlighted the treatment of advanced NSCLC, shifting it from standard chemotherapy according to speciifc histologic subtypes to targeted therapy according to speciifc oncogenic drivers. The application of epidermal growth factor receptor (EGFR)‑tyrosine kinase inhibitors (TKIs) in NSCLC patients harbor‑ing activatingEGFR mutations has been a representative model of precise medicine in the treatment of NSCLC. As the role of EGFR‑TKIs in routine management of patients with advanced NSCLC has been well established, this review provides an overview of alternative targeted therapy in the treatment of NSCLC, including EGFR‑TKIs for patients with wild‑typeEGFR NSCLC, as well as other targeted agents either clinical available or in early‑ to late‑stage development.

  15. Toxicity-adjusted dose (TAD) administration of chemotherapy: Effect of baseline and nadir neutrophil count in patients with breast, ovarian, and lung cancer?

    DEFF Research Database (Denmark)

    Carus, Andreas; Donskov, Frede; Gebski, Val;

    2011-01-01

    .I-IV, non-small cell lung cancer (NSCLC) st.II-IV, and small-cell lung cancer (SCLC) treated from 1997 to 2005 at Westmead Hospital, Sydney, with complete medical records of the first 3 cycles of chemotherapy and a full set of baseline and nadir laboratory data were collected from patient medical files.......Survival data were updated 2010. Results: A total of 819 patients were identified, comprising 507 patients with breast cancer, 118 patients with ovarian cancer, 115 patients with NSCLC and 79 patients with SCLC. Median survival for ovarian cancer patients obtaining nadir neutropenia below 2.0 x 109/l was 56...

  16. Comparison Study of Elemene Combinde with Temozolomide,Temozolomide Alone Maintenance Therapy after Radiotherapy in Patients of NSCLC with Brain Metastases%榄香烯联合替莫唑胺与单药替莫唑胺在 NSCLC 脑转移放疗后维持治疗中的比较研究

    Institute of Scientific and Technical Information of China (English)

    欧鹏举; 安煜致

    2014-01-01

    To investigate the maintenance therapy effect of elemene in combination with temozolomide after radiotherapy in patients of non-small cell lung cancer (NSCLC ) combined with brain metastases .46 patients with brain metastases after radiotherapy in NSCLC were randomly divided into two groups :combined treatment group and control group ,respectively elemene plus temozolomide or temozolomide alone were observed efficacy ,immune parameters , adverse reactions and survival analysis .Results of two groups'progression-free survival and overall survival were not significant (P> 0 .05) . The overall response rate and KPS significant difference between the two groups (P<0 .05) ,quality of life in patients of the combined treatment group were improved and adverse effects after chemotherapy were reduced .Elemene combined temozolomide maintenance therapy can improved overall response rate in patients of NSCLC with brain metastases after radiotherapy ,improved quality of life ,reduced the adverse effects of chemotherapy ,and were application security .%探讨榄香烯注射液联合替莫唑胺在非小细胞肺癌(NSCLC)脑转移患者放疗后维持治疗的疗效,将46例NSCLC脑转移放疗后患者,随机分为联合治疗组和对照组,分别采用榄香烯联合替莫唑胺和单药替莫唑胺维持化疗,观察两组疗效、免疫指标、不良反应及生存分析。结果显示两组无进展生存期(PFS)、总生存期(OS)差异无统计学意义(P>0.05)。总缓解率及卡氏功能状态评分(KPS)两组比较差异有统计学意义(P<0.05)。联合治疗组免疫功能提高,化疗不良反应减轻。榄香烯联合替莫唑胺维持治疗可以提高NSCLC脑转移患者放疗后的总缓解率,改善生活质量,减轻化疗的不良反应,应用安全。

  17. Montreal prognostic score: estimating survival of patients with non-small cell lung cancer using clinical biomarkers

    OpenAIRE

    Gagnon, B.; Agulnik, J S; Gioulbasanis, I; Kasymjanova, G.; Morris, D.; Macdonald, N.

    2013-01-01

    Background: For evidence-based medical practice, well-defined risk scoring systems are essential to identify patients with a poor prognosis. The objective of this study was to develop a prognostic score, the Montreal prognostic score (MPS), to improve prognostication of patients with incurable non-small cell lung cancer (NSCLC) in everyday practice. Methods: A training cohort (TC) and a confirmatory cohort (CC) of newly diagnosed patients with NSCLC planning to receive chemotherapy were used ...

  18. Docetaxel plus nintedanib versus docetaxel plus placebo in patients with previously treated non-small-cell lung cancer (LUME-Lung 1)

    DEFF Research Database (Denmark)

    Reck, Martin; Kaiser, Rolf; Mellemgaard, Anders;

    2014-01-01

    BACKGROUND: The phase 3 LUME-Lung 1 study assessed the efficacy and safety of docetaxel plus nintedanib as second-line therapy for non-small-cell lung cancer (NSCLC). METHODS: Patients from 211 centres in 27 countries with stage IIIB/IV recurrent NSCLC progressing after first-line chemotherapy...

  19. Investigations of 99mTc-labeled glucarate as a SPECT radiotracer for non-small cell lung cancer (NSCLC) and potential tumor uptake mechanism

    International Nuclear Information System (INIS)

    This study attempted to evaluate the feasibility of 99mTc-labeled glucarate (99mTc-GLA) imaging in non-small cell lung cancer (NSCLC) and the potential tumor uptake mechanism. Cell lysates from two NSCLC cell lines, H292 and H1975, were immunoblotted with anti-glucose transporter 5 (GLUT5) antibody for Western blotting. Thereafter, the two cell lines were used to examine cellular uptake of 99mTc-GLA with or without fructose. SPECT/CT imaging studies were performed on small animals bearing H292 and H1975 tumors. Biodistribution studies were also conducted to achieve accurate tissue uptake of this tracer in two tumor models. Hematoxylin & eosin (H&E) staining and GLUT5, Ki67 and cytokeratin-7 (CK-7) immunohistochemistry (IHC) analysis were further investigated on tumor tissues. In Western blotting, H292 cells showed higher levels of GLUT5 compared to the H1975 cells. Meanwhile, the in vitro cell assays indicated GLUT5-dependent uptake of 99mTc-GLA in H292 and H1975 cells. The fructose competition assays showed a significant decrease in 99mTc-GLA uptake by H292 and H1975 cells when fructose was added. The 99mTc-GLA accumulation was as much as two-fold higher in H292 implanted tumors than in H1975 implanted tumors. 99mTc-GLA exhibited rapid clearance pharmacokinetics and reasonable uptake in human NSCLC H292 (1.69 ± 0.37 ID%/g) and H1975 (0.89 ± 0.06 ID%/g) implanted tumors at 30 min post injection. Finally, the expression of GLUT5, Ki67 and CK-7 on tumor tissues also exhibited positive correlation with the in vitro cell test results and in vivo SPECT/CT imaging results in xenograft tumors. Both in vitro and ex vivo studies demonstrated that the uptake of 99mTc-GLA in NSCLC is highly related to GLUT5 expression. Imaging and further IHC results support that 99mTc-GLA could be a promising SPECT imaging agent for NSCLC diagnosis and prognosis evaluation

  20. Concomitant expression of far upstream element (FUSE) binding protein (FBP) interacting repressor (FIR) and its splice variants induce migration and invasion of non-small cell lung cancer (NSCLC) cells.

    Science.gov (United States)

    Müller, Benedikt; Bovet, Michael; Yin, Yi; Stichel, Damian; Malz, Mona; González-Vallinas, Margarita; Middleton, Alistair; Ehemann, Volker; Schmitt, Jennifer; Muley, Thomas; Meister, Michael; Herpel, Esther; Singer, Stephan; Warth, Arne; Schirmacher, Peter; Drasdo, Dirk; Matthäus, Franziska; Breuhahn, Kai

    2015-11-01

    Transcription factors integrate a variety of oncogenic input information, facilitate tumour growth and cell dissemination, and therefore represent promising therapeutic target structures. Because over-expression of DNA-interacting far upstream element binding protein (FBP) supports non-small cell lung cancer (NSCLC) migration, we asked whether its repressor, FBP-interacting repressor (FIR) is functionally inactivated and how FIR might affect NSCLC cell biology. Different FIR splice variants were highly expressed in the majority of NSCLCs, with the highest levels in tumours carrying genomic gains of chromosome 8q24.3, which contained the FIR gene locus. Nuclear FIR expression was significantly enriched at the invasion front of primary NSCLCs, but this did not correlate with tumour cell proliferation. FIR accumulation was associated with worse patient survival and tumour recurrence; in addition, FIR over-expression significantly correlated with lymph node metastasis in squamous cell carcinomas (SCCs). In vitro, we applied newly developed methods and modelling approaches for the quantitative and time-resolved description of the pro-migratory and pro-invasive capacities of SCC cells. siRNA-mediated silencing of all FIR variants significantly reduced the speed and directional movement of tumour cells in all phases of migration. Furthermore, sprouting efficiency and single cell invasiveness were diminished following FIR inhibition. Interestingly, the silencing of FIR isoforms lacking exon 2 (FIR(Δexon2)) alone was sufficient to reduce lateral migration and invasion. In summary, by using scale-spanning data derived from primary human tissues, quantitative cellular analyses and mathematical modelling, we have demonstrated that concomitant over-expression of FIR and its splice variants drives NSCLC migration and dissemination.

  1. The relationship between glasgow prognostic score and serum tumor markers in patients with advanced non-small cell lung cancer

    International Nuclear Information System (INIS)

    Glasgow Prognostic Score (GPS) has been reported as a powerful prognostic tool for patients with advanced non–small cell lung cancer (NSCLC). The aim of this study was to assess the relationship between GPS and prognosis related tumor markers in patients with advanced NSCLC. We included 138 advanced NSCLC patients and twenty healthy controls in the study. GPS was calculated by combined serum C-reactive protein (CRP) and albumin. Three serum tumor markers, which included cytokeratin 19 fragment antigen 21-1 (CYFRA21–1), carcinoembryonic antigen (CEA) and tissue polypeptide specific antigen (TPS), were detected by enzyme-linked immunosorbent assay (ELISA). GPS and tumor markers were all assessed before chemotherapy. All patients received at least 2 courses of cisplatin-based chemotherapy. After that, 2 to 5 years follow-up was conducted. Median levels of CYFRA21–1 were 1.5 ng/ml (0.1–3.1 ng/ml) in healthy controls, and 4.6 ng/ml (0.7–35.2 ng/ml) in GPS 0 advanced NSCLC, 11.2 ng/ml (0.4–89.2) ng/ml in GPS 1 advanced NSCLC, and 15.7 ng/ml (2.9–134.6 ng/ml) in GPS 2 advanced NSCLC, respectively. Median levels of CYFRA21-1 were higher in NSCLC patients than in healthy controls, and CYFRA21-1 increased gradually according to GPS category in NSCLC patients (P < 0.05). Similar results were found for median levels of CEA and TPS in healthy controls and NSCLC patients (P < 0.05). In NSCLC patients, positive correlations were found between CYFRA21-1 and GPS, CEA and GPS, TPS and GPS. The Spearman’s rank correlation coefficient were 0.67 (P < 0.05), 0.61 (P < 0.05) and 0.55 (P < 0.05), respectively. Survival analyses showed GPS was an independent prognostic factor for advanced NSCLC. CYFRA21-1(>3.3 ng/ml) and TPS (>80 U/l) were related with the prognosis of advanced NSCLC by univariate analyses, but multivariate analyses showed CYFRA21-1, TPS and CEA were not the independent prognostic factors for advanced NSCLC. Our results showed GPS were positive correlated

  2. Second-line Treatment of Stage III/IV Non-Small-Cell Lung Cancer (NSCLC with pemetrexed in routine clinical practice: Evaluation of performance status and health-related quality of life

    Directory of Open Access Journals (Sweden)

    Schuette Wolfgang

    2012-01-01

    Full Text Available Abstract Background Second-line treatment of advanced non-small-cell lung cancer (NSCLC improves overall survival. There is a lack of data regarding the impact on patients' overall health condition. This prospective, non-interventional study evaluated performance status (PS and health-related quality of life (HR-QoL during second-line pemetrexed treatment in routine clinical practice. Methods Stage III/IV NSCLC patients who initiated second-line pemetrexed (standard vitamin and dexamethasone supplementation were observed for a maximum of 9 treatment cycles. The primary objective was to evaluate the proportion of patients achieving improvement of Karnofsky Index (KI of ≥ 10% (absolute or maintaining KI ≥ 80% after the second treatment cycle ("KI benefit response". HR-QoL was self-rated using the EuroQoL-5D questionnaire (EQ-5D. Factors potentially associated with KI benefit response were evaluated using logistic regression models. Results Of 521 eligible patients (73.5% Stage IV, median age 66.3 yrs, 36.1% ≥ 70 yrs, 62.0% with KI ≥ 80%, 471 (90.4% completed at least 2 treatment cycles. 58.0% (95%CI 53.6%;62.2% achieved KI benefit response after the second cycle. Patients with baseline KI ≥ 80%, no Grade 3/4 toxicities during the first 2 cycles, or combination regimen as prior first-line therapy were more likely to achieve a KI benefit response. EQ-5D scores improved over time. Grade 3/4 toxicities were reported in 23.8% of patients (mainly fatigue/asthenia 15.9%, neutropenia 8.7%. Conclusions In this large prospective, non-interventional study of second-line pemetrexed treatment in patients with advanced NSCLC, including 36% elderly patients ( ≥ 70 years, physician-rated PS and self-rated HR-QoL were maintained or improved in the majority of patients. Trial registration Registered on ClinicalTrials.gov (NCT00540241 on October 4, 2007

  3. Rapamycin Enhances the Anti-Cancer Effect of Dasatinib by Suppressing Src/PI3K/mTOR Pathway in NSCLC Cells.

    Directory of Open Access Journals (Sweden)

    Bin Chen

    Full Text Available Src and the mammalian target of rapamycin (mTOR signaling are commonly activated in non-small cell lung cancer (NSCLC and hence potential targets for chemotherapy. Although the combined use of Src inhibitor Dasatinib with other chemotherapeutic agents has shown superior efficacy for cancer treatment, the mechanisms that lead to enhanced sensitivity of Dasatinib are not completely understood. In this study, we found that Rapamycin dramatically enhanced Dasatinib-induced cell growth inhibition and cell cycle G1 arrest in human lung adenocarcinoma A549 cells without affecting apoptosis. The synergistic effects were consistently correlated with the up-regulation of cyclin-dependent kinases inhibitor proteins, including p16, p19, p21, and p27, as well as the repression of Cdk4 expression and nuclear translocation. Mechanistic investigations demonstrated that FoxO1/FoxO3a and p70S6K/4E-BP1, the molecules at downstream of Src-PI3K-Akt and mTOR signaling, were significantly suppressed by the combined use of Dasatinib and Rapamycin. Restraining Src and mTOR with small interfering RNA in A549 cells further confirmed that the Src/PI3K/mTOR Pathway played a crucial role in enhancing the anticancer effect of Dasatinib. In addition, this finding was also validated by a series of assays using another two NSCLC cell lines, NCI-H1706 and NCI-H460. Conclusively, our results suggested that the combinatory application of Src and mTOR inhibitors might be a promising therapeutic strategy for NSCLC treatment.

  4. Effective avoidance of a functional spect-perfused lung using intensity modulated radiotherapy (IMRT) for non-small cell lung cancer (NSCLC): an update of a planning study.

    Science.gov (United States)

    Lavrenkov, Konstantin; Singh, Shalini; Christian, Judith A; Partridge, Mike; Nioutsikou, Elena; Cook, Gary; Bedford, James L; Brada, Michael

    2009-06-01

    IMRT and 3-dimensional conformal radiotherapy (3-DCRT) plans of 25 patients with non-small cell lung (NSCLC) were compared in terms of planning target volume (PTV) coverage and sparing of functional lung (FL) defined by a SPECT perfusion scan. IMRT resulted in significant reduction of functional V(20) and mean lung dose in stage III patients with inhomogeneous hypoperfusion. If the dose to FL is shown to be the determinant of lung toxicity, IMRT would allow for effective dose escalation by specific avoidance of functional lung. PMID:18995919

  5. Effective avoidance of a functional spect-perfused lung using intensity modulated radiotherapy (IMRT) for non-small cell lung cancer (NSCLC): An update of a planning study

    International Nuclear Information System (INIS)

    IMRT and 3-dimensional conformal radiotherapy (3-DCRT) plans of 25 patients with non-small cell lung (NSCLC) were compared in terms of planning target volume (PTV) coverage and sparing of functional lung (FL) defined by a SPECT perfusion scan. IMRT resulted in significant reduction of functional V20 and mean lung dose in stage III patients with inhomogeneous hypoperfusion. If the dose to FL is shown to be the determinant of lung toxicity, IMRT would allow for effective dose escalation by specific avoidance of functional lung.

  6. 非小细胞肺癌组织成纤维细胞P-gp的表达及意义%P-glycoprotein expression in non-small cell lung cancer(NSCLC)and its significance

    Institute of Scientific and Technical Information of China (English)

    李绍鹏; 汪礼旭; 赵勇; 洪琼川

    2012-01-01

    目的:研究非小细胞肺癌组织中成纤维细胞P-gp的表达与临床病理特征的关系,探讨其对患者术后早期复发或远处转移的影响.方法:应用Max VisionTM快捷免疫组化检测48例非小细胞肺癌组织和10例非癌肺组织中成纤维细胞P-gp的表达,随访患者并研究其表达水平与术后早期复发的相关性.结果:非小细胞肺癌组织中成纤维细胞P-gp的表达阳性率为70.8%,明显高于非癌肺组织(P<0.01);成纤维细胞P-gp的表达与患者年龄、肿瘤分化程度、临床分期和有无淋巴结转移有关(P<0.05);与患者性别、大小和肿瘤组织类型无关(P>0.05),P-gp阳性患者术后1年内复发或远处转移率明显高于P-gp阴性患者.结论:P-gp参与了肿瘤细胞的耐药性的形成,肿瘤组织成纤维细胞P-gp的表达水平在患者术后早期复发及远处转移中具有重要意义.%Objective: To study clinical pathological significance of P - gp expression in non - small cell lung cancer and examine the impact of the P - glycoprotein expression level in non - small cell lung cancer tumor - associated fibroblast to the early recurrence of postoperative patients. Methods: P - gp of lung cancer tissue and normal lung tissue were detected by using Max - Vision TMimmunohistochemical method, to observe the p - gp expression level in TAF of NSCLC lung cancer tissue and normal lung tissue, and followed up the patient, to find the relation between the expression level with the recurrence or distant metastasis of postoperative patients. Results:The positive rate of P - gp expression in TAF of 48 NSCLC patients was 70. 8% , higher than the normal lung tissue (P 0.05 ). The postoperative patients with p - gp strongly positive expression hade higher rate of recurrence or distant metastasis than the negative or weakly positive of NSCLC within one year. Conclusion: P - gp promotes the formation of tumor drug resistance. The expression level of P - gp in the

  7. Diffusion weighted MRI and 18F-FDG PET/CT in non-small cell lung cancer (NSCLC): Does the apparent diffusion coefficient (ADC) correlate with tracer uptake (SUV)?

    Energy Technology Data Exchange (ETDEWEB)

    Regier, M., E-mail: mregier@uke.uni-hamburg.de [Center for Radiology and Endoscopy, Department of Diagnostic and Interventional Radiology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg (Germany); Derlin, T. [Center for Radiology and Endoscopy, Department of Nuclear Medicine, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg (Germany); Schwarz, D.; Laqmani, A.; Henes, F.O.; Groth, M.; Buhk, J.-H. [Center for Radiology and Endoscopy, Department of Diagnostic and Interventional Radiology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg (Germany); Kooijman, H. [Philips Healthcare, Clinical Application, Luebeckertordamm 5, 20099 Hamburg (Germany); Adam, G. [Center for Radiology and Endoscopy, Department of Diagnostic and Interventional Radiology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg (Germany)

    2012-10-15

    Introduction: To investigate the potential correlation of the apparent diffusion coefficient assessed by diffusion-weighted MRI (DWI) and glucose metabolism determined by the standardized uptake value (SUV) at 18F-FDG PET/CT in non-small cell lung cancer (NSCLC). Materials and methods: 18F-FDG PET/CT and DWI (TR/TE, 2000/66 ms; b-values, 0 and 500 s/mm{sup 2}) were performed in 41 consecutive patients with histologically verified NSCLC. Analysing the PET-CT data calculation of the mean (SUV{sub mean}) and maximum (SUV{sub max}) SUV was performed. By placing a region-of-interest (ROI) encovering the entire tumor mean (ADC{sub mean}) and minimum ADC (ADC{sub min}) were determined by two independent radiologists. Results of 18F-FDG PET-CT and DWI were compared on a per-patient basis. For statistical analysis Pearson's correlation coefficient, Bland–Altman and regression analysis were assessed. Results: Data analysis revealed a significant inverse correlation of the ADC{sub min} and SUV{sub max} (r = −0.46; p = 0.032). Testing the correlation of the ADC{sub min} and SUV{sub max} for each histological subtype separately revealed that the inverse correlation was good for both adenocarcinomas (r = −0.47; p = 0.03) and squamouscell carcinomas (r = −0.71; p = 0.002), respectively. No significant correlation was found for the comparison of ADC{sub min} and SUV{sub mean} (r = −0.29; p = 0.27), ADC{sub mean} vs. SUV{sub mean} (r = −0.28; p = 0.31) or ADC{sub mean} vs. SUV{sub max} (r = −0.33; p = 0.23). The κ-value of 0.88 indicated a good agreement between both observers. Conclusion: This preliminary study is the first to verify the relation between the SUV and the ADC in NSCLC. The significant inverse correlation of these two quantitative imaging approaches points out the association of metabolic activity and tumor cellularity. Therefore, DWI with ADC measurement might represent a new prognostic marker in NSCLC.

  8. hnRNP B1mRNA在非小细胞肺癌患者外周血中手术前后的表达变化及临床意义%The perioperative change and clinical significance of the expression level of peripheral blood hnRNP B1 mRNA in NSCLC patients

    Institute of Scientific and Technical Information of China (English)

    Jun Lu; Jingmin Ding; Jiashun Wang; Wendong Wang

    2012-01-01

    Objective: The aim of this study was to investigate the perioperative expression of the peripheral blood hnRNP B1 mRNA in non-small-cell lung cancer (NSCLC) patients and its clinical significance. Methods: Using real time FQ-RT-PCR, we detected the expression of peripheral blood hnRNP B1 mRNA in 30 NSCLC patients on preoperative d3 and postoperative d3, d5, and d10, respectively. Results: The ΔΔCt value of hnRNP B1 in NSCLC patients on preoperative d3 was significantly different from those on postoperative d5 and d10 (P = 0.00), but not different from postoperative d3 (P = 0.12). The ΔΔCt values of patients with squamous cell carcinoma were significantly different from those with other pathological types on preoperative d3 (P = 0.02) and postoperative d3 (P = 0.01). Whereas, the ΔΔCt values were not related to gender, pathological stage and lymph node metastasis (P > 0.05). ΔΔCt values in patients with different pathology classifications had no differences on postoperative d5 and d10 (P > 0.05). Conclusion: The expression of peripheral blood hnRNP B1 mRNA in NSCLC patients decreased gradually after operation, which may be used in assessment of the therapeutic efficacy of the operation and prognosis, and the monitor of the tumor recurrence. In addition, preoperative and early postoperative expression of peripheral blood hnRNP B1 mRNA in NSCLC patients may be related to pathological types.

  9. HBP1 promoter methylation augments the oncogenic β-catenin to correlate with prognosis in NSCLC

    Science.gov (United States)

    Tseng, Ruo-Chia; Huang, Way-Ren; Lin, Su-Feng; Wu, Pei-Chen; Hsu, Han-Shui; Wang, Yi-Ching

    2014-01-01

    β-catenin nuclear accumulation is frequently identified in human non-small cell lung cancer (NSCLC). The HMG-box transcription factor 1 (HBP1) is a known repressor of β-catenin transactivation. However, the role of HBP1 in relation to β-catenin nuclear accumulation has not been addressed in human cancer patients. In addition, the mechanism of HBP1 gene alteration in NSCLC remains unclear, although HBP1 mutation and gene deletion of HBP1 are reported in breast and colon cancers. Here, we demonstrate that HBP1 acts as a tumour suppressor and serves as a prognostic biomarker in NSCLC clinical and cell models. The immunohistochemistry data indicated that 30.5% (25/82) of tumours from NSCLC patients showed absence or low expression of HBP1 protein. A significant inverse correlation between mRNA/protein expression and promoter hypermethylation suggested that promoter hypermethylation is responsible for low expression of HBP1 in NSCLC patients. Reactivation of HBP1 expression by demethylation reagent or ectopic expression of HBP1 suppressed β-catenin transactivation. Conversely, HBP1 knockdown increased β-catenin transactivation. Importantly, preserved expression of HBP1 had a significantly protective effect on prognosis in patients with β-catenin nuclear accumulation, suggesting that low expression of HBP1 in NSCLC patients with β-catenin nuclear accumulation was one of the major determinants of prognosis. Our data from cellular and clinical models suggest that HBP1 is a suppressor of cancer progression, making it a potential prognostic predictor and therapeutic target to attenuate lung cancer progression. PMID:24895061

  10. Increased Expression of TGFβR2 Is Associated with the Clinical Outcome of Non-Small Cell Lung Cancer Patients Treated with Chemotherapy

    OpenAIRE

    Han, Yang; Jia, Chengyou; Cong, Xianling; Yu, Fei; Cai, Haidong; Fang, Suyun; Cai, Li; Yang, Huiqiong; Sun, Yu; Li, Dan; Liu, Jin; Xie, Ruting; Yuan, Xueyu; Zhong, Xiaoming; LI Ming

    2015-01-01

    To investigate the prognostic significance of TGFβR2 expression and chemotherapy in Chinese non-small cell lung cancer (NSCLC) patients, TGFβR2 expression NSCLC was analyzed in silico using the Oncomine database, and subsequently analyzed with quantitative RT-PCR in 308 NSCLC biopsies, 42 of which were paired with adjacent non-neoplastic tissues. Our results show that TGFβR2 expression was also increased in NSCLC biopsies relative to normal tissue samples and correlated with poor prognosis. T...

  11. Expression of DNA repair and replication genes in non-small cell lung cancer (NSCLC: a role for thymidylate synthetase (TYMS

    Directory of Open Access Journals (Sweden)

    Kotoula Vassiliki

    2012-08-01

    Full Text Available Abstract Background BRCA1 (B, ERCC1 (E, RRM1 (R and TYMS (T mRNA expression has been extensively studied with respect to NSCLC patient outcome upon various chemotherapy agents. However, these markers have not been introduced into clinical practice yet. One of the reasons seems to be lack of a standard approach for the classification of the reported high/low mRNA expression. The aim of this study was to determine the prognostic/predictive impact of B, E, R, T in routinely-treated NSCLC patients by taking into account the expression of these genes in the normal lung parenchyma. Methods B, E, R, T mRNA expression was examined in 276 NSCLC samples (real-time PCR. The normal range of B, E, R, T transcript levels was first determined in matched tumor – normal pairs and then applied to the entire tumor series. Four main chemotherapy categories were examined: taxanes-without-platinum (Tax; platinum-without-taxanes (Plat; taxanes/platinum doublets (Tax/Plat; and, all-other combinations. Results In comparison to remotely located normal lung parenchyma, B, E, R, T mRNA expression was generally increased in matched tumors, as well as in the entire tumor series. Therefore, tumors were classified as expressing normal or aberrant B, E, R, T mRNA. In general, no marker was associated with overall and progression free survival (OS, PFS. Upon multivariate analysis, aberrant intratumoral TYMS predicted for shorter PFS than normal TYMS in 1st line chemo-naïve treated patients (p = 0.012. In the same setting, specific interactions were observed for aberrant TYMS with Plat and Tax/Plat (p = 0.003 and p = 0.006, respectively. Corresponding patients had longer PFS in comparison to those treated with Tax (Plat: HR = 0.234, 95% CI:0.108-0.506, Wald’s p  Conclusion Classifying intratumoral B, E, R, T mRNA expression in comparison to normal lung may facilitate standardization of these parameters for prospective studies. With this approach, NSCLC

  12. Changes in Health-Related Quality of Life During Rehabilitation in Patients With Operable Lung Cancer

    DEFF Research Database (Denmark)

    Sommer, Maja S; Trier, Karen; Vibe-Petersen, Jette;

    2016-01-01

    year after surgery in patients with NSCLC participating in a rehabilitation program. METHODS: Forty patients with NSCLC in disease stage I to IIIa, referred for surgical resection at the Department of Cardiothoracic Surgery RT, Rigshospitalet, were included in the study. The rehabilitation program...... comprised supervised group exercise program, 2 hours weekly for 12 weeks, combined with individual counseling. The study endpoints were self-reported HRQoL (Functional Assessment of Cancer Therapy-Lung, European Organization for Research and Treatment in Cancer-Quality of Life Questionnaire-QLQ-C30, Short....... RESULTS: Forty patients were included, 73% of whom completed rehabilitation. Results on emotional well-being (P

  13. Functional role of eukaryotic translation initiation factor 4 gamma 1 (EIF4G1) in NSCLC

    Science.gov (United States)

    Cao, Yueyu; Wei, Mengdan; Li, Bing; Liu, Yali; Lu, Ying; Tang, Zhipeng; Lu, Tianbao; Yin, Yujiao; Qin, Zhiqiang; Xu, Zengguang

    2016-01-01

    Eukaryotic translation initiation factor 4 gamma 1(EIF4G1) is related to tumorigenesis and tumor progression. However, its role and the underlying mechanisms in the regulation of tumor development in non–small cell lung cancers (NSCLC) remain largely unknown. Here we report that the levels of EIF4G1 expression are much higher in NSCLC cell lines and tumor tissues than those in the normal lung cells and adjacent normal tissues from the same patients. Using shRNA to knock down EIF4G1 expression stably, we found EIF4G1 required for NSCLC cell proliferation, anchorage-independent growth, migration and invasion. Furthermore, silencing of EIF4G1 induces NSCLC cell apoptosis and causes G0/G1 cell cycle arrest. To identify the partner protein network of EIF4G1 in NSCLC cells, we found that Ubiquitin-specific protease 10 (USP10) can directly interacts with EIF4G1, while acting as a negative regulator for EIF4G1-mediated functions. Together, our results indicate that EIF4G1 functions as an oncoprotein during NSCLC development, which may represent a novel and promising therapeutic target in lung cancer. PMID:27003362

  14. Relationship between estrogen receptor α and β expression and clinicopathological characteristics in elderly patients with non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    李琳

    2013-01-01

    Objective To evaluate estrogen receptor(ER)α and β expressions in elderly patients with non-small cell lung cancer(NSCLC) in China and their relationship with clinical and pathological characteristics

  15. An analysis of impact of argon helium cryoablation (AHC) on tumor metastasis and complications of elderly patients with III, IV stage of non-small-cell carcinoma (NSCLC)

    Institute of Scientific and Technical Information of China (English)

    Mao-Hong Liu; Hong Zhang; Qiong Zhang

    2015-01-01

    Objective:To study the impact of argon helium cryoablation (AHC) on tumor metastasis and complications of elderly patients with III, IV stage of non-small-cell carcinoma (NSCLC). Method:Selected 60 cases of elderly patients with III, IV stage of NSCLC who received treatment in our hospital from May, 2011 to Jan. 2014 as research subjects. They were divided into the observation group and the control group by adopting the numbering approach, 30 cases in each group. Chemotherapy was applied only for patients in the control group, and AHC combining with chemotherapy was applied for patients in the observation group. Clinical efficacy was compared three months after the treatment, tumor metastasis one year after follow-up treatment, relapse, survival status and complications occurrence status of patients in the two groups.Results:The total effective rate and clinical benefit rate of the observation group three months after the treatment are significantly higher than those of the control group. After one year follow-up visit, the relapse rate and tumor metastasis rate of the observation group are significantly lower than those of the control group, and one year survival rate is significantly higher than that of the control group. The occurrence rate of complications, such as postoperative hemoptysis, blood-stained sputum, pneumothorax and pyrexia of the two groups has no statistical difference.Conclusion: Compared with single chemotherapy, AHC combining with chemotherapy has better clinical effects on treatment of elderly patients with III, IV stage of NSCLC. Besides, AHC is safer and more reliable, and can reduce tumor metastasis. Thus it is worthy of clinical recommendations.

  16. Identification of ATP synthase beta subunit (ATPB on the cell surface as a non-small cell lung cancer (NSCLC associated antigen

    Directory of Open Access Journals (Sweden)

    Qian Zhi

    2009-01-01

    Full Text Available Abstract Background Antibody-based immuneotherapy has achieved some success for cancer. But the main problem is that only a few tumor-associated antigens or therapeutic targets have been known to us so far. It is essential to identify more immunogenic antigens (especially cellular membrane markers for tumor diagnosis and therapy. Methods The membrane proteins of lung adenocarcinoma cell line A549 were used to immunize the BALB/c mice. A monoclonal antibody 4E7 (McAb4E7 was produced with hybridoma technique. MTT cell proliferation assay was carried out to evaluate the inhibitory effect of McAb4E7 on A549 cells. Flow cytometric assay, immunohistochemistry, western blot and proteomic technologies based on 2-DE and mass spectrometry were employed to detect and identify the corresponding antigen of McAb4E7. Results The monoclonal antibody 4E7 (McAb4E7 specific against A549 cells was produced, which exhibited inhibitory effect on the proliferation of A549 cells. By the proteomic technologies, we identified that ATP synthase beta subunit (ATPB was the corresponding antigen of McAb4E7. Then, flow cytometric analysis demonstrated the localization of the targeting antigen of McAb4E7 was on the A549 cells surface. Furthermore, immunohistochemstry showed that the antigen of McAb4E7 mainly aberrantly expressed in tumor cellular membrane in non-small cell lung cancer (NSCLC, but not in small cell lung cancer (SCLC. The rate of ectopic expressed ATPB in the cellular membrane in lung adenocarcinoma, squamous carcinoma and their adjacent nontumourous lung tissues was 71.88%, 66.67% and 25.81% respectively. Conclusion In the present study, we identified that the ectopic ATPB in tumor cellular membrane was the non-small cell lung cancer (NSCLC associated antigen. ATPB may be a potential biomarker and therapeutic target for the immunotherapy of NSCLC.

  17. Levels of cell-free DNA and plasma KRAS during treatment of advanced NSCLC

    DEFF Research Database (Denmark)

    Dowler Nygaard, Anneli; Spindler, Karen-Lise Garm; Pallisgaard, Niels;

    2014-01-01

    Non-small cell lung cancer (NSCLC) is one of the most common malignant tumours in the western world and is associated with a poor prognosis. Biomarkers predicting prognosis and therapeutic effects are highly required, and cell-free DNA (cfDNA) may be a feasible option. Genetic mutations can be...... analysed in plasma and may increase the scientific use of such measurements. In the present study, we investigated: i) the dynamics of cfDNA and plasma mutated KRAS (pmKRAS) during the treatment of patients with advanced NSCLC; and ii) the prognostic value of baseline cfDNA and pmKRAS. Sixty‑nine patients...... were included in a prospective biomarker trial. Inclusion criteria included advanced NSCLC, candidate for first-line treatment, no previous cancer within the five years prior to this study. Blood samples were drawn at baseline, day 8 and at progression. Analyses of cfDNA and KRAS mutations in plasma...

  18. Five-fraction stereotactic radiosurgery (SRS) for single inoperable high-risk non-small cell lung cancer (NSCLC) brain metastases

    International Nuclear Information System (INIS)

    Achieving durable local control while limiting normal tissue toxicity with definitive radiation therapy in the management of high-risk brain metastases remains a radiobiological challenge. The objective of this study was to examine the local control and toxicity of a 5-fraction stereotactic radiosurgical approach for treatment of patients with inoperable single high-risk NSCLC brain metastases. This retrospective analysis examines 20 patients who were deemed to have “high-risk” brain metastases. High-risk tumors were defined as those with a maximum diameter greater than 2 cm and/or those located within an eloquent cortex. Patients were evaluated by a neurosurgeon prior to treatment and determined to be inoperable due to tumor or patient characteristics. Patients were treated using the CyberKnife® SRS system in 5 fractions to a total dose of 30 Gy, 35 Gy, or 40 Gy. Twenty patients with a median age of 65.5 years were treated from April 2010 to August 2014 in 5 fractions to a median total dose of 35 Gy. At a median follow up of 11.3 months local tumor control was observed in 18 of 20 metastases (90 %). Both local failures were observed in patients receiving a lower dose of 30 Gy. Median pre-treatment dexamethasone dose was 10 mg/day and median post-treatment nadir dose was 0 mg/day. Salvage intracranial therapy was required in 45 % of patients. Symptomatic radionecrosis was observed in 4 of 20 patients (20 %), two of which were treated to 40 Gy and the remainder to 35 Gy. Kaplan-Meier 1-year, 2-year, and median survival were calculated to be 45 %, 20 %, and 13.2 months, respectively. Five-fraction SRS to a total dose of 35 Gy appears to be a safe and effective management strategy for single high-risk NSCLC brain metastases, while a total dose of 40 Gy leads to an excess risk of neurotoxicity

  19. Collaborative care in NSCLC; the role of early palliative care

    Directory of Open Access Journals (Sweden)

    Marnie eHowe

    2014-07-01

    Full Text Available The management of non-small-cell-lung-cancer (NSCLC has evolved into a multidisciplinary team approach that traditionally has involved medical oncology, radiation oncology and thoracic surgery. However, in the era of personalized medicine the importance of molecular diagnostics requires adequate tissue for histologic subtyping and molecular testing and thus requires the engagement of other subspecialties such as pathology, respirology and interventional radiology. Unfortunately in 2014 the majority of patients presenting with NSCLC will succumb to their disease and the early integration of palliative care into the treatment strategy will improve the quality of life (QoL and end of life (EOL care of our patients and may in fact improve their overall survival.

  20. A randomized trial comparing adjuvant chemotherapy with gemcitabine plus cisplatin with docetaxel plus cisplatin in patients with completely resected non-small-cell lung cancer with quality of life as the primary objective

    OpenAIRE

    Barlesi, Fabrice; Chouaid, Christos; Crequit, Jacky; Le Caer, Hervé; Pujol, Jean Louis; Legodec, Julien; Vergnenegre, Alain; Le Treut, Jacques; Fabre-Guillevin, Elizabeth; Loundou, Anderson; Auquier, Pascal; Simeoni, Marie-Claude; Thomas, Pascal A

    2015-01-01

    International audience OBJECTIVES: Adjuvant chemotherapy with vinorelbine plus cisplatin (VC) improves survival in resected non-small-cell lung cancer (NSCLC), but has negative impact on quality of life (QoL). In advanced NSCLC, gemcitabine plus cisplatin (GC) and docetaxel plus cisplatin (DC) exhibit comparable efficacy, with possibly superior QoL compared to VC. This trial investigated these regimens in the adjuvant setting. METHODS: Patients with Stage IB to III NSCLC were eligible foll...

  1. CRIPTO1 expression in EGFR-mutant NSCLC elicits intrinsic EGFR-inhibitor resistance.

    Science.gov (United States)

    Park, Kang-Seo; Raffeld, Mark; Moon, Yong Wha; Xi, Liqiang; Bianco, Caterina; Pham, Trung; Lee, Liam C; Mitsudomi, Tetsuya; Yatabe, Yasushi; Okamoto, Isamu; Subramaniam, Deepa; Mok, Tony; Rosell, Rafael; Luo, Ji; Salomon, David S; Wang, Yisong; Giaccone, Giuseppe

    2014-07-01

    The majority of non-small cell lung cancer (NSCLC) patients harbor EGFR-activating mutations that can be therapeutically targeted by EGFR tyrosine kinase inhibitors (EGFR-TKI), such as erlotinib and gefitinib. Unfortunately, a subset of patients with EGFR mutations are refractory to EGFR-TKIs. Resistance to EGFR inhibitors reportedly involves SRC activation and induction of epithelial-to-mesenchymal transition (EMT). Here, we have demonstrated that overexpression of CRIPTO1, an EGF-CFC protein family member, renders EGFR-TKI-sensitive and EGFR-mutated NSCLC cells resistant to erlotinib in culture and in murine xenograft models. Furthermore, tumors from NSCLC patients with EGFR-activating mutations that were intrinsically resistant to EGFR-TKIs expressed higher levels of CRIPTO1 compared with tumors from patients that were sensitive to EGFR-TKIs. Primary NSCLC cells derived from a patient with EGFR-mutated NSCLC that was intrinsically erlotinib resistant were CRIPTO1 positive, but gained erlotinib sensitivity upon loss of CRIPTO1 expression during culture. CRIPTO1 activated SRC and ZEB1 to promote EMT via microRNA-205 (miR-205) downregulation. While miR-205 depletion induced erlotinib resistance, miR-205 overexpression inhibited CRIPTO1-dependent ZEB1 and SRC activation, restoring erlotinib sensitivity. CRIPTO1-induced erlotinib resistance was directly mediated through SRC but not ZEB1; therefore, cotargeting EGFR and SRC synergistically attenuated growth of erlotinib-resistant, CRIPTO1-positive, EGFR-mutated NSCLC cells in vitro and in vivo, suggesting that this combination may overcome intrinsic EGFR-inhibitor resistance in patients with CRIPTO1-positive, EGFR-mutated NSCLC. PMID:24911146

  2. Patterns of recurrence and survival after surgery or stereotactic radiotherapy for early stage NSCLC

    NARCIS (Netherlands)

    van den Berg, Liseth L.; Klinkenberg, Theo J.; Groen, Harry J. M.; Widder, Joachim

    2015-01-01

    Introduction: Surgery is the standard treatment for early stage non-small-cell lung cancer (NSCLC). For medically inoperable patients, stereotactic ablative radiotherapy (SABR) has emerged as widely used standard treatment. The aim of this study was to analyze survival and patterns of tumor recurren

  3. Cardiac Toxicity after definitive Radiotherapy of locally advanced NSCLC

    DEFF Research Database (Denmark)

    Schytte, Tine; Hansen, Olfred; Stohlberg-Rohr, Thomine;

    2010-01-01

    report the heart toxicities in locally-regionally advanced NSCLC (LA-NSCLC) patients (pts) treated with RT in our centre.   Methods and material: From 01.01.1995-30.11.2007, 287 pts with LA-NSCLC (stage IIB-IIIB) were treated with RT at our centre with planned dose 60-66 Gy. All RT was applied as 3D RT......    Cardiac Toxicity after definitive Radiotherapy of locally advanced NSCLC Tine Schytte, Olfred Hansen, Thomine Stolberg-Rohr* and Carsten Brink*. Dept. Oncology and Radiophysic Lab.* Odense University Hospital, Denmark   Keyword: Radiotherapy, Locally advanced NSCLC, Cardiac toxicity...

  4. Exercise and relaxation intervention for patients with advanced lung cancer

    DEFF Research Database (Denmark)

    Adamsen, Lis; Stage, M; Laursen, J;

    2012-01-01

    Lung cancer patients experience loss of physical capacity, dyspnea, pain, reduced energy and psychological distress. The aim of this study was to explore feasibility, health benefits and barriers of exercise in former sedentary patients with advanced stage lung cancer, non-small cell lung cancer...... (NSCLC) (III-IV) and small cell lung cancer (SCLC) (ED), undergoing chemotherapy. The intervention consisted of a hospital-based, supervised, group exercise and relaxation program comprising resistance-, cardiovascular- and relaxation training 4 h weekly, 6 weeks, and a concurrent unsupervised home...... exercise and relaxation intervention showed an adherence rate of 76%, whereas the patients failed to comply with the home-based exercise. The hospital-based intervention initiated at time of diagnosis encouraged former sedentary lung cancer patients to participation and was undertaken safely by cancer...

  5. Analysis of GAGE, NY-ESO-1 and SP17 cancer/testis antigen expression in early stage non-small cell lung carcinoma

    DEFF Research Database (Denmark)

    Gjerstorff, Morten F; Pøhl, Mette; Olsen, Karen E;

    2013-01-01

    NSCLC has shown promising results. However, little is known about the expression of other cancer/testis antigens in NSCLC. In the present study the expression of cancer/testis antigens GAGE, NY-ESO-1 and SP17 was investigated in patients with completely resected, early stage, primary NSCLC....

  6. Improving chemotherapy for patients with advanced non-small cell lung cancer

    DEFF Research Database (Denmark)

    von Plessen, Christian

    2011-01-01

    . MATERIALS AND METHODS: The thesis combines methods from different knowledge domains. In a randomised trial, we compared three with six courses of platinum-based chemotherapy for advanced NSCLC. In a quality improvement study, we used logistic improvement tools, qualitative and quantitative patient and staff....... The general section of the thesis describes approaches to system-wide improvements and introduces a quality improvement matrix. CONCLUSION: We conclude from our randomised trial and related research that chemotherapy beyond three courses is not beneficial for patients with advanced NSCLC. The report from......INTRODUCTION: Lung cancer is the third most common mortal disease in industrialised countries and the prognosis has been slow to improve. The largest subgroup has locally advanced or metastatic non-small cell lung cancer (NSCLC). Unfortunately, these patients can usually not be cured and the main...

  7. Prognostic value of serum cytokeratin 19 fragments (Cyfra 21-1) in patients with non-small cell lung cancer.

    Science.gov (United States)

    Xu, Youtao; Xu, Lei; Qiu, Mantang; Wang, Jie; Zhou, Qing; Xu, Lin; Wang, Jian; Yin, Rong

    2015-01-01

    The role of serum CYFRA 21-1 level in patients with non-small cell lung cancer (NSCLC) remains to be defined. To re-evaluate the impact of serum CYFRA 21-1 in NSCLC survival, we performed this meta-analysis. Databases were searched to identify relevant studies reported after the publication of a meta-analysis in 2004. Totally, 31 studies with 6394 patients were included in this meta-analysis. The pooled Hazard ratios (HRs) indicated that high CYFRA 21-1 level was associated with poor prognosis on overall survival (OS) in patients with NSCLC (HR = 1.60; 95%CI = 1.36-1.89; P CYFRA 21-1 related to PFS was performed and pooled HR was 1.41 (95%CI = 1.19-1.69; P CYFRA 21-1 is a negative prognostic indicator of patients with NSCLC. PMID:25901419

  8. Treating patients with ALK-positive non-small cell lung cancer: latest evidence and management strategy

    OpenAIRE

    Liao, Bin-Chi; Lin, Chia-Chi; Shih, Jin-Yuan; Yang, James Chih-Hsin

    2015-01-01

    Rearrangements in anaplastic lymphoma kinase (ALK) gene and echinoderm microtubule-associated protein-like 4 (EML4) gene were first described in a small portion of patients with non-small cell lung cancer (NSCLC) in 2007. Fluorescence in situ hybridization is used as the diagnostic test for detecting an EML4–ALK rearrangement. Crizotinib, an ALK inhibitor, is effective in treating advanced ALK-positive NSCLC, and the US Food and Drug Administration approved it for treating ALK-positive NSCLC ...

  9. Manifestation of leukoencephalopathy in a patient with advanced non-small cell lung cancer following treatment with gefitinib

    Institute of Scientific and Technical Information of China (English)

    HUANG Yi-sheng; HUANG Biao; WU Yi-long

    2011-01-01

    The present case is a patient with advanced non-small cell lung cancer (NSCLC) who developed leukoencephalopathy following radiotherapy and gefitinib treatments.There are rarely reports of such incidences because the median survival period of advanced NSCLC is only ten months.The features of leukoencephalopathy in this case were atypical for radiation leukoencephalopathy,so it was suspected that the leukoencephalopathy was associated with gefitinib.

  10. Combined Targeted DNA Sequencing in Non-Small Cell Lung Cancer (NSCLC Using UNCseq and NGScopy, and RNA Sequencing Using UNCqeR for the Detection of Genetic Aberrations in NSCLC.

    Directory of Open Access Journals (Sweden)

    Xiaobei Zhao

    Full Text Available The recent FDA approval of the MiSeqDx platform provides a unique opportunity to develop targeted next generation sequencing (NGS panels for human disease, including cancer. We have developed a scalable, targeted panel-based assay termed UNCseq, which involves a NGS panel of over 200 cancer-associated genes and a standardized downstream bioinformatics pipeline for detection of single nucleotide variations (SNV as well as small insertions and deletions (indel. In addition, we developed a novel algorithm, NGScopy, designed for samples with sparse sequencing coverage to detect large-scale copy number variations (CNV, similar to human SNP Array 6.0 as well as small-scale intragenic CNV. Overall, we applied this assay to 100 snap-frozen lung cancer specimens lacking same-patient germline DNA (07-0120 tissue cohort and validated our results against Sanger sequencing, SNP Array, and our recently published integrated DNA-seq/RNA-seq assay, UNCqeR, where RNA-seq of same-patient tumor specimens confirmed SNV detected by DNA-seq, if RNA-seq coverage depth was adequate. In addition, we applied the UNCseq assay on an independent lung cancer tumor tissue collection with available same-patient germline DNA (11-1115 tissue cohort and confirmed mutations using assays performed in a CLIA-certified laboratory. We conclude that UNCseq can identify SNV, indel, and CNV in tumor specimens lacking germline DNA in a cost-efficient fashion.

  11. The prognostic value of positron emission tomography in non-small cell lung cancer : Analysis of 266 cases

    NARCIS (Netherlands)

    Kramer, H.; Post, W.J.; Pruim, J.; Groen, H.J.M.

    2006-01-01

    Positron emission tomography (PET) is more accurate than computed tomography (CT) in the staging of non-small cell lung cancer (NSCLC). We analyzed the prognostic value of PET for survival in NSCLC patients. Methods: Consecutive patients with proven NSCLC with PET for staging were selected. Staging

  12. Clinical Analysis of Lung Cancer Patients Younger Than 30 Years

    Directory of Open Access Journals (Sweden)

    Guangjie HOU

    2011-05-01

    Full Text Available Background and objective It is common recognized that young patients of lung cancer have poor prognosis due to relatively higher malignancy and more invasive growth. In the past most studies on young patients of lung cancer selected patients younger than 40 or 45 years old, and there were few clinical materials for younger patients under 30 years. This study retrospectively described the the disease history, stage, treatment and pathology features of lung cancer patients younger than 30 years and aimed to provide references for these patients. Methods Those patients younger than 30 years, once admitted in the General Hospital of the People's Liberation Army for lung cancer from 1993 to date, were sought in medical record system, and 53 patients were found in total. In this group, there were 34 non-small cell lung cancer (NSCLC patients and 19 small cell lung cacer (SCLC patients. The male/female ratio was 1.5:1. In the NSCLC patients, there were 27 adenocarcinomas, 6 squamous carcinomas and 1 adenosquamous carcinoma, with no large cell carcinoma involved. In these patients, 12 patients received operations while 38 patients got chemo- and/or radiotherapy and 3 quited any treatment. Results There was no death in hospital, however, in the 12 patients who got operation, only 8 patients got complete resection while 4 patients got palliative resection. Conclusion Lung cancer patients younger than 30 years had a high fraction of adenocarcinoma and small cell type pathologically and most of them were in late stage when presenting with symptoms in hospital and would have a dismal prognosis. The routine health examination and early diagnosis should be emphasized to improve the prognosis of these patients.

  13. Diagnostic utility of LunX mRNA in peripheral blood and pleural fluid in patients with primary non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Tian Zhigang

    2008-05-01

    Full Text Available Abstract Background Progress in lung cancer is hampered by the lack of clinically useful diagnostic markers. The goal of this study was to provide a detailed evaluation of lung cancer tumor markers indicative of molecular abnormalities and to assess their diagnostic utility in non-small cell lung cancer (NSCLC patients. Methods Quantitative real-time RT-PCR was used to determine LunX, CK19, CEA, VEGF-C and hnRNP A2/B1 mRNA levels in peripheral blood and pleural fluid from NSCLC patients, compared with those from patients with other epithelial cancer (esophagus cancer and breast cancer, benign lung disease (pneumonia and tuberculo pleurisy and from healthy volunteers. Results In peripheral blood LunX mRNA was detectable in 75.0% (33/44 of patients with NSCLC, but not in patients with other epithelial cancer (0/28, benign lung disease (0/10 or in healthy volunteers (0/15. In contrast, all other genetic markers were detected in patients with either NSCLC, other epithelia cancer or benign lung disease, and in healthy volunteers. The expression level and positive rate of LunX mRNA in peripheral blood correlated with the pathologic stage of NSCLC (P LunX mRNA was detected in 92.9% (13/14 of malignant pleural fluid samples and was the only marker whose expression level was significantly different between malignant and benign pleural fluid (P LunX mRNA in the peripheral blood of NSCLC patients decreased shortly after clinical treatment (P = 0.005. Conclusion Of several commonly used genetic markers, LunX mRNA is the most specific gene marker for lung cancer and has potential diagnostic utility when measured in the peripheral blood and pleural fluid of NSCLC patients.

  14. [Expression and clinical significance of IL-33 in patients with non-small cell lung cancer].

    Science.gov (United States)

    Feng, Yuehua; Zhu, Yibei; Luo, Guanghua; Wang, Zhigang; Yu, Pengyi; Zheng, Liang

    2016-06-01

    Objective To investigate the expression of interleukin 33 (IL-33) in cancer and adjacent non-cancerous tissues from patients with non-small cell lung cancer (NSCLC). Methods Real-time quantitative PCR was performed to detect the mRNA expression of IL-33 in 61 pairs of cancerous and adjacent non-cancerous tissues. In addition, immunohistochemistry was used to evaluate the expression and location of IL-33 on paraffin sections in selected 12 cases with different pathological types, to analyze the correlation of IL-33 expression with clinicopathological variables and overall survival. Results The expression of IL-33 mRNA in cancer tissues was significantly lower than that in adjacent non-cancerous tissues. The immunohistochemical results showed that IL-33 protein was mainly localized in the nucleus, and was obviously down-regulated in NSCLC. Besides, the expression of IL-33 was associated with histological type, but was not associated with age, gender, smoking history, differentiation status and pathological TNM stage. According to the Kaplan-Meier analysis, the expression of IL-33 mRNA was evidently associated with post-operative overall survival of patients suffering from NSCLC. Conclusion IL-33 may play an important role in the development of NSCLC and the targeted therapy. PMID:27371849

  15. Evaluation of setup accuracy for NSCLC patients; studying the impact of different types of cone-beam CT matches based on whole thorax, columna vertebralis, and GTV

    DEFF Research Database (Denmark)

    Ottosson, W.; Baker, M.; Hedman, Mattias;

    2010-01-01

    Purpose. The aim of this study is to evaluate the patient setup accuracy by investigating the impact of different types of CBCT matches, performed with 3 (translations only) or 6 (including rotations) degrees-of-freedom (DOF). The purpose is also to calculate and compare CTV to PTV margins based...... on the various CBCT matches, setups using 2D kV planar imaging or setups using skin markers only (non-IGRT). Material and methods. Setup images from 16 NSCLC patients with weekly CBCT and daily 2D kV planar imaging were analyzed retrospectively. The CBCT matches were based on the columna vertebralis (CV...... degrees. The calculated margins for non-IGRT, about 10 mm, were reduced to approximately 4 mm, regardless of using IGRT setup by CBCT or 2D kV imaging on CV. However, if using WT CBCT setup, the margin in LNG direction was slightly larger, approximately 6 mm. Conclusion. IGRT for NSCLC is an essential...

  16. Effect of Chemotherapy Alternately Targeted Drugs on PFS and OS in EGFR Mutation Positive Patients with Advanced NSCLC%化疗交替靶向药物治疗对 EGFR 突变阳性的晚期 NSCLC 患者PFS及 OS的影响

    Institute of Scientific and Technical Information of China (English)

    林顺欢; 刘淳; 蔡彦敏; 郑锐年

    2015-01-01

    Objective To observe the effect of chemotherapy alternately targeted drugs on progression free survival ( PFS) and overall survival( OS) in EGFR mutation positive patients with advanced non-small cell lung cancer ( NSCLC) .Meth-ods 100 cases of EGFR mutation positive patients with advanced NSCLC were chosen as the research object,and were divided into 2 groups,group A received gemcitabine +cisplatin /carboplatin chemotherapy alternated with gefitinib, and group B re-ceived the single use of gefitinib.Tolerance,adverse reaction rates and total remission rates( ORR) during the treatment process were compared;PFS,OS and quality of life score( QoL) were contrasted between group A and B.Results The rates of adverse reactions of the 2 groups showed no statistical difference(P>0.05).During the treatment,due to the severity of adverse reaction 5 patients in group A quitted,and 4 in group B quitted;ORR of group A was 68.89%,and that of group B was 47.86%,there had significant difference(P<0.05).PFS,OS and QoL of patients in group A were higher than those of group B,there had signif-icant difference(P<0.05).Conclusion Chemotherapy alternately targeted drugs for EGFR mutation positive patients with ad-vanced NSCLC has significant clinical efficacy,it is worthy of clinical promotion and application.%目的:观察化疗交替靶向药物治疗对EGFR突变阳性的晚期非小细胞肺癌患者PFS及OS的影响。方法选取100例EGFR突变阳性的晚期NSCLC患者作为研究对象,将患者分为2组,A组为吉西他滨+顺铂/卡铂化疗交替吉非替尼组,B组为单用吉非替尼组。比较患者治疗过程中的耐受情况、不良反应的发生率和总缓解率( ORR);对比A、B组患者的肿瘤无进展生存期( PFS)、总生存期( OS)和患者生活质量评分( QoL)。结果2组患者的不良反应发生率无统计学差异(P>0.05),治疗期间A组5例患者因无法耐受不良反应而退出,B组4

  17. Long non-coding RNA MEG3 inhibits NSCLC cells proliferation and induces apoptosis by affecting p53 expression

    International Nuclear Information System (INIS)

    Long non-coding RNAs play an important role in tumorigenesis, hence, identification of cancer-associated lncRNAs and investigation of their biological functions and molecular mechanisms are important for understanding the development and progression of cancer. Recently, the downregulation of lncRNA MEG3 has been observed in various human cancers. However, its role in non-small cell lung cancer (NSCLC) is unknown. The aim of this study was to examine the expression pattern of MEG3 in NSCLC and to evaluate its biological role and clinical significance in tumor progression. Expression of MEG3 was analyzed in 44 NSCLC tissues and 7 NSCLC cell lines by qRT-PCR. Over-expression approaches were used to investigate the biological functions of MEG3 in NSCLC cells. Bisulfite sequencing was used to investigate DNA methylation on MEG3 expression. The effect of MEG3 on proliferation was evaluated by MTT and colony formation assays, and cell apoptosis was evaluated by Hoechst staining and Flow-cytometric analysis. NSCLC cells transfected with pCDNA-MEG3 were injection into nude mice to study the effect of MEG3 on tumorigenesis in vivo . Protein levels of MEG3 targets were determined by western blot analysis. Differences between groups were tested for significance using Student’s t-test (two-tailed). MEG3 expression was decreased in non-small cell lung cancer (NSCLC) tumor tissues compared with normal tissues, and associated with advanced pathologic stage, and tumor size. Moreover, patients with lower levels of MEG3 expression had a relatively poor prognosis. Overexpression of MEG3 decreased NSCLC cells proliferation and induced apoptosis in vitro and impeded tumorigenesis in vivo. MDM2 and p53 protein levels were affected by MEG3 over-expression in vitro. Our findings indicate that MEG3 is significantly down-regulated in NSCLC tissues that could be affected by DNA methylation, and regulates NSCLC cell proliferation and apoptosis, partially via the activition of p53. Thus, MEG3

  18. [Research Progress of EGFR-TKI Therapy for Patients with Central Nervous System 
Metastases from Non-small Cell Lung Cancer].

    Science.gov (United States)

    Jin, Yinghua; Xin, Tao

    2016-08-20

    Approximately half of all patients with non-small cell lung cancer (NSCLC) develop central nervous system metastases during the course of their disease which indicate poor prognosis. A part of NSCLC patients demonstrates activating epidermal growth factor receptor gene (EGFR) mutations who represent effectiveness and well tolerance of EGFR-specific tyrosine kinase inhibitors (TKIs) therapy. Although the systemic efficacy of targeted agents is established, the efficacy of central nervous system (CNS) metastases is not as well characterized. In this article, we review recent data on the use of EGFR inhibitors for treatment of patients with NSCLC and CNS metastases. PMID:27561797

  19. The role of Gefitinib in patients with non-small-cell lung cancer in India

    Directory of Open Access Journals (Sweden)

    Asmita Anilkumar Mehta

    2013-01-01

    Full Text Available Background: Gefitinib, an epidermal growth factor receptor-tyrosine kinase inhibitor, represents a new treatment option for patients with advanced non-small-cell lung cancer (NSCLC. We analyzed the data of patients who received Gefitinib for NSCLC in a tertiary care center in South India. Materials and Methods: Sixty-three patients with advanced NSCLC who had received Gefitinib either after failure of conventional chemotherapy or were previously not treated as they were unfit or unwilling for conventional treatment were included in the analysis. Results: The median follow-up for the cohort was 311 days (range 11-1544 days. Median time to progression was 161 (range 9-883 days. Complete and partial remission was seen in 1 (2% and 6 (9% patients, respectively, with overall response rate of 11%. Twenty-four (38% patients had stable disease. Gefitinib was well tolerated with no significant side effects. Conclusion: Gefitinib shows anti-tumor activity in pretreated or previously untreated patients with advanced NSCLC. It has a favorable toxicity profile and is well tolerated. Gefitinib should be considered as a viable therapy in patients with NSCLC.

  20. miR-638 is a new biomarker for outcome prediction of non-small cell lung cancer patients receiving chemotherapy

    OpenAIRE

    Wang, Fang; Lou, Jian-fang; Cao, Yan; Shi, Xin-hui; Wang, Peng; Xu, Jian; Xie, Er-fu; Xu, Ting; Sun, Rui-hong; Rao, Jian-Yu; Huang, Pu-wen; Pan, Shi-yang; Wang, Hong

    2015-01-01

    MicroRNAs (miRNAs), a class of small non-coding RNAs, mediate gene expression by either cleaving target mRNAs or inhibiting their translation. They have key roles in the tumorigenesis of several cancers, including non-small cell lung cancer (NSCLC). The aim of this study was to investigate the clinical significance of miR-638 in the evaluation of NSCLC patient prognosis in response to chemotherapy. First, we detected miR-638 expression levels in vitro in the culture supernatants of the NSCLC ...

  1. Elevated Pretreatment Serum Concentration of YKL-40-An Independent Prognostic Biomarker for Poor Survival in Patients With Metastatic Nonsmall Cell Lung Cancer

    DEFF Research Database (Denmark)

    Thom, I.; Andritzky, B.; Schuch, G.;

    2010-01-01

    YKL-40 has not been established in non-small cell lung cancer (NSCLC). METHODS: Pretreatment serum levels of YKL-40 were determined in 189 patients with NSCLC (143 men and 46 women; median age, 62 years;, age range, 41-76 years). Twelve percent of patients had stage IIIB disease, and 88% had stage IV......BACKGROUND: The glycoprotein YKL-40 is synthesized both by cancer cells and by tumor-associated macrophages and plays a functional role in tumor progression. Consequently, high serum YKL-40 levels have been associated with a poor prognosis in patients with several cancer types. However, the role of...... was identified as a new, independent prognostic biomarker in patients with metastatic NSCLC and may help to determine the individual prognosis of these patients. Cancer 2010;116:4114-21. (C) 2010 American Cancer Society...

  2. 培美曲塞联合奈达铂治疗晚期非鳞状 NSCLC 的疗效分析%Clinical Efficacy of Pemetrexed and Nedaplatin for Patients with Advanced Non Squamous Non-Small Cell Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    朱方; 徐瀚峰; 郑勤; 张全安

    2014-01-01

    Objective To evaluate the efficacy and safety of pemetrexed ( PEM) and nedaplatin ( NDP) as first-line and second-line chemotherapy for advanced non squamous non-small cell lung cancer .Methods 82 patients with non squamous non-small cell lung cancer who were treated with pemetrexed and nedaplatin were divided into 2 groups.Team A(36 cases) received chemotherapy as first-line treatment while team B (46 cases) received chemotherapy as seconed-line treatment.The response rate ( RR)、disease control rate ( DCR)、time to progression ( TTP)、1-year survival rate of the 2 groups were evlauated after at least 2 cycles,and adverse reactions were observed .Results Among the 82 cases,there were 1 CR (1.22%),17 PR (20.73%),25 SD (30.49%),and 39 PD (47.56%).The overall response rate was 21.95% (18/82),and DCR was 52.44%,mTTP was 10.3 months and 1-year survival rate was 76.59%.The effect of group A was better than that of the group B ,there was statistical difference .The adverse reactions were tolerable .Conclusion Pemetrexed and nedaplatin is effective first-line and second-line therapy for advanced non squamous non-small cell lung cancer ,it is worthy of clinical application .%目的:评价培美曲塞(pemetrexed,PEM)联合奈达铂(nedaplatin,NDP)方案一线和二线治疗晚期(Ⅲb和Ⅳ期)非鳞状非小细胞肺癌( NSCLC)的疗效及安全性。方法采用培美曲塞联合奈达铂治疗82例晚期非鳞状NSCLC患者,分为A、B两组:A组36例患者,一线采用培美曲塞( PEM )联合奈达铂化疗; B组46例患者,为一线治疗进展后患者,方案同上。所有患者化疗至少2个周期后评价近期有效率( RR)、疾病控制率( DCR)、疾病进展时间( TTP)、1年生存率;并观察患者的不良反应及耐受性。结果82例患者中完全缓解1例(1.22%),部分缓解17例(20.73%),稳定25例(30.49%),进展39例(47.56%),总有效率为21.95

  3. Improved local control without elective nodal radiotherapy in patients with unresectable NSCLC treated by 3D-CRT

    Institute of Scientific and Technical Information of China (English)

    YANG Kunyu; CAO Fengjun; WANG Jianhua; LIU Li; ZHANG Tao; WU Gang

    2007-01-01

    To investigate the influence of prophylactic elective nodal irradiation on the therapeutic results of definitive radiotherapy for patients with stage IliA or stage IIIB unresectable non-small-cell lung cancer,55 patients with clinically inoperable advanced non-small-cell lung cancer were studied.After four cycles of induction chemotherapy,the patients were divided into two groups at random.In one group,the elective nodal irradiation was included in clinical tumor volume(CTV)of definitive radiotherapy(ENI group);and in the other group,elective nodal irradiation was not included in CTV(non-ENI group).For the patients in the ENI group,the mean prescription dose for gross tumor volumes was 58.4 Gy,while for the patients in the non-ENI group,it was 65.8 Gy(P<0.05).The responsive rates were 45.8% and 74.0%(P<0.05),and the rate of the elective nodal failure (ENF)was 4.2% and 11.1%,respectively.Kaplan-Meier analysis showed that the mean local-progression-free survival time was 11.0 and 15.0 months,and one-year local-failure rates were 51.9% and 24.5%(P<0.05).The median overall survival time was 13.0 and 15.0 months,respectively (P=0.084).The one-year survival rates were 55.7% and 72.5%,and two-year survival rates were 0% and 19.9%.There was no significant difference in the occurrences of radiation-associated complications between the two groups.Our results showed that omitting elective nodal irradiation did not result in a high incidence of elective nodal failure.On the contrary,it decreased local failure by increasing prescription doses to the primary diseases and lymphadenopaphy,and thereby it may further prolong the patients' survival.

  4. PDCD5在晚期非小细胞肺癌患者血清中的表达及与化疗药物敏感性的相关性研究%The expression of PDCD5 in the serum of patients with advanced NSCLC and the correlation study of its sensitivity to chemotherapy drugs

    Institute of Scientific and Technical Information of China (English)

    赵丹宁; 李焕焕; 林芷伊; 李晶; 苏帆; 巩平

    2015-01-01

    目的:研究程序化细胞死亡分子5(PDCD5)在晚期非小细胞肺癌(NSCLC)患者血清中的表达,探讨其与化疗药物敏感性的关系。方法收集经病理证实为晚期 NSCLC 患者40例作为肺癌组,体检健康者20例为正常组。肺癌组给予铂类药物联合其他化疗药物进行化疗,治疗周期为21 d,治疗2周期后进行疗效评估,分为有效组和无效组。采用ELISA 法分别检测肺癌组化疗前后及正常组血清中 PDCD5蛋白的水平,并分析其与疗效、临床特征的关系。结果正常组血清中 PDCD5蛋白的水平高于肺癌组,差异有统计学意义(P 0.05)。结论晚期 NSCLC 患者血清中 PDCD5蛋白的水平有望成为化疗敏感性的预测因子,其表达水平降低可能与肺癌的发生有关,也可能为晚期 NSCLC 患者不良预后因素。%Objective To investigate the expression level of programmed cell death 5(PDCD5) in advanced non-small cell lung cancer ( NSCLC), and to explore the correlation study of its sensitivity to chemotherapy drugs. Methods 40 advanced non-small cell lung cancer patients were collected and confirmed by pathological examina-tion and designated them as lung cancer group. Another 20 persons whose physical examinations were healthy were collected as normal group. Patients in lung cancer group were given platinum drugs combined with other chemother-apy drugs. The chemotherapy cycle was 21 days and curative effect evaluation was made after 2 cycles of treatment. According to efficacy they were divided into effective group and ineffective group. ELISA was used to detect the ser-um PDCD5 concentration in lung cancer group and normal control group, and its relationship with curative effect and clinical significance was analysed. Results The serum PDCD5 protein level in the normal group was higher than the lung cancer group and the difference was statistically (P 0. 05). Conclusion PDCD5 protein level in serum of patients with advanced NSCLC is

  5. LDA-SVM-Based EGFR Mutation Model for NSCLC Brain Metastases

    Science.gov (United States)

    Hu, Nan; Wang, Ge; Wu, Yu-Hao; Chen, Shi-Feng; Liu, Guo-Dong; Chen, Chuan; Wang, Dong; He, Zhong-Shi; Yang, Xue-Qin; He, Yong; Xiao, Hua-Liang; Huang, Ding-De; Xiong, Kun-Lin; Wu, Yan; Huang, Ming; Yang, Zhen-Zhou

    2015-01-01

    Abstract Epidermal growth factor receptor (EGFR) activating mutations are a predictor of tyrosine kinase inhibitor effectiveness in the treatment of non–small-cell lung cancer (NSCLC). The objective of this study is to build a model for predicting the EGFR mutation status of brain metastasis in patients with NSCLC. Observation and model set-up. This study was conducted between January 2003 and December 2011 in 6 medical centers in Southwest China. The study included 31 NSCLC patients with brain metastases. Eligibility requirements were histological proof of NSCLC, as well as sufficient quantity of paraffin-embedded lung and brain metastases specimens for EGFR mutation detection. The linear discriminant analysis (LDA) method was used for analyzing the dimensional reduction of clinical features, and a support vector machine (SVM) algorithm was employed to generate an EGFR mutation model for NSCLC brain metastases. Training-testing-validation (3 : 1 : 1) processes were applied to find the best fit in 12 patients (validation test set) with NSCLC and brain metastases treated with a tyrosine kinase inhibitor and whole-brain radiotherapy. Primary and secondary outcome measures: EGFR mutation analysis in patients with NSCLC and brain metastases and the development of a LDA-SVM-based EGFR mutation model for NSCLC brain metastases patients. EGFR mutation discordance between the primary lung tumor and brain metastases was found in 5 patients. Using LDA, 13 clinical features were transformed into 9 characteristics, and 3 were selected as primary vectors. The EGFR mutation model constructed with SVM algorithms had an accuracy, sensitivity, and specificity for determining the mutation status of brain metastases of 0.879, 0.886, and 0.875, respectively. Furthermore, the replicability of our model was confirmed by testing 100 random combinations of input values. The LDA-SVM-based model developed in this study could predict the EGFR status of brain metastases in this

  6. LDA-SVM-based EGFR mutation model for NSCLC brain metastases: an observational study.

    Science.gov (United States)

    Hu, Nan; Wang, Ge; Wu, Yu-Hao; Chen, Shi-Feng; Liu, Guo-Dong; Chen, Chuan; Wang, Dong; He, Zhong-Shi; Yang, Xue-Qin; He, Yong; Xiao, Hua-Liang; Huang, Ding-De; Xiong, Kun-Lin; Wu, Yan; Huang, Ming; Yang, Zhen-Zhou

    2015-02-01

    Epidermal growth factor receptor (EGFR) activating mutations are a predictor of tyrosine kinase inhibitor effectiveness in the treatment of non-small-cell lung cancer (NSCLC). The objective of this study is to build a model for predicting the EGFR mutation status of brain metastasis in patients with NSCLC. Observation and model set-up. This study was conducted between January 2003 and December 2011 in 6 medical centers in Southwest China. The study included 31 NSCLC patients with brain metastases. Eligibility requirements were histological proof of NSCLC, as well as sufficient quantity of paraffin-embedded lung and brain metastases specimens for EGFR mutation detection. The linear discriminant analysis (LDA) method was used for analyzing the dimensional reduction of clinical features, and a support vector machine (SVM) algorithm was employed to generate an EGFR mutation model for NSCLC brain metastases. Training-testing-validation (3 : 1 : 1) processes were applied to find the best fit in 12 patients (validation test set) with NSCLC and brain metastases treated with a tyrosine kinase inhibitor and whole-brain radiotherapy. Primary and secondary outcome measures: EGFR mutation analysis in patients with NSCLC and brain metastases and the development of a LDA-SVM-based EGFR mutation model for NSCLC brain metastases patients. EGFR mutation discordance between the primary lung tumor and brain metastases was found in 5 patients. Using LDA, 13 clinical features were transformed into 9 characteristics, and 3 were selected as primary vectors. The EGFR mutation model constructed with SVM algorithms had an accuracy, sensitivity, and specificity for determining the mutation status of brain metastases of 0.879, 0.886, and 0.875, respectively. Furthermore, the replicability of our model was confirmed by testing 100 random combinations of input values. The LDA-SVM-based model developed in this study could predict the EGFR status of brain metastases in this small cohort of

  7. Nintedanib in NSCLC: evidence to date and place in therapy.

    Science.gov (United States)

    Bronte, Giuseppe; Passiglia, Francesco; Galvano, Antonio; Barraco, Nadia; Listì, Angela; Castiglia, Marta; Rizzo, Sergio; Fiorentino, Eugenio; Bazan, Viviana; Russo, Antonio

    2016-05-01

    The treatment of advanced non-small cell lung cancer (NSCLC) is currently driven by the detection of targetable oncogenic drivers, i.e. epidermal growth factor receptor, echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase, etc. Those patients who are wildtype for known and valuable oncogenes can receive standard chemotherapy as first-line treatment, with the possibility of adding bevacizumab. With regard to second-line treatment, nintedanib can improve the efficacy of docetaxel. Nintedanib is a tyrosine kinase inhibitor targeting three angiogenesis-related transmembrane receptors. The usefulness of nintedanib as an anticancer agent for NSCLC has been proved by both preclinical and clinical phase I and II trials; however, its approval for the use in clinical practice has been possible because of the positive results of the LUME-Lung 1 trial (nintedanib + docetaxel versus docetaxel alone) in terms of progression-free survival and overall survival, and a manageable tolerability profile. Therefore, the good results seen in the clinical trials with nintedanib in the second-line setting for NSCLC patients with adenocarcinoma subtype are encouraging enough to recommend it in clinical practice.

  8. Immunoproteasomes and immunotherapy-a smoking gun for lung cancer?

    Science.gov (United States)

    Spits, Menno; Neefjes, Jacques

    2016-07-01

    Lung cancer is the second most prevalent cancer in both women and men with some 221,200 new cases and 158,040 deaths reported in 2015. Almost 90% of these are non-small cell lung cancer (NSCLC) and these patients have a very poor prognosis. Recently a new treatment option for NSCLC appeared that strongly improved treatment responses-immunotherapy. Here we review the various forms of immunotherapy and how immune modification of proteasomes in lung cancer may support the immune system in controlling NSCLC. These immunoproteasomes then support recognition of NSCLC and may act as a biomarker for selecting responding patients to immunotherapy. PMID:27501321

  9. Immunoproteasomes and immunotherapy—a smoking gun for lung cancer?

    Science.gov (United States)

    Spits, Menno

    2016-01-01

    Lung cancer is the second most prevalent cancer in both women and men with some 221,200 new cases and 158,040 deaths reported in 2015. Almost 90% of these are non-small cell lung cancer (NSCLC) and these patients have a very poor prognosis. Recently a new treatment option for NSCLC appeared that strongly improved treatment responses—immunotherapy. Here we review the various forms of immunotherapy and how immune modification of proteasomes in lung cancer may support the immune system in controlling NSCLC. These immunoproteasomes then support recognition of NSCLC and may act as a biomarker for selecting responding patients to immunotherapy. PMID:27501321

  10. Promoter Methylation Primarily Occurs in Tumor Cells of Patients with Non-small Cell Lung Cancer

    NARCIS (Netherlands)

    De Jong, Wouter K.; Verpooten, Gonda F.; Kramer, Henk; Louwagie, Joost; Groen, Harry J. M.

    2009-01-01

    Background: The distribution of promoter methylation throughout the lungs of patients with non-small cell lung cancer (NSCLC) is unknown. In this explorative study, we assessed the methylation status of the promoter region of 11 genes in brush samples of 3 well-defined endobronchial locations in pat

  11. Tumor-specific cytotoxic t cells are crucial for efficacy of immunomodulatory antibodies in patients with lung cancer

    NARCIS (Netherlands)

    J.G.J.V. Aerts (Joachim); J.P.J.J. Hegmans (Joost)

    2013-01-01

    textabstractThere is growing evidence that activation of the immune system may be an effective treatment for patients with either small cell lung cancer or non-small cell lung cancer (NSCLC). Immunomodulatory antibodies directed against cytotoxic T cell-associated antigen 4 (CTLA-4/CD152) and progra

  12. Research on pharmacokinetics of high-dose tamoxifen in non-small cell lung cancer patients

    Institute of Scientific and Technical Information of China (English)

    陈玲; 李旭; 李蓉; 赵新汉; 李睿; 郑晓辉; 王嗣岑

    2007-01-01

    Objective To study the pharmacokinetics of tamoxifen at a high dosage, which will offer a theoretical support for an appropriate clinical use of the medicine in non-small cell lung cancer (NSCLC) patients. Methods Three qualified NSCLC patients are selected and given tamoxifen (TAM) 160 mg per Os. Blood samples were collected at different times and then analyzed by high-performance liguid chromatography. The PK-GRAPH program was used to obtain the parameters. Results The concentration-time courses of the TA...

  13. Effect of integrated Chinese medical treatment on the survival time of patients with advanced non-small-cell lung cancer: a clinical study

    Institute of Scientific and Technical Information of China (English)

    刘苓霜

    2014-01-01

    Objective To observe clinical effect of integrated Chinese medical(CM)treatment(as maintenance therapy)on the progression-free survival(PFS)and overall survival(OS)in patients with advanced non-small-cell lung cancer(NSCLC)after first-line chemotherapy.Methods The study was a prospective,randomized,controlled clinical trial.Totally 69 non-progressive advanced NSCLC patients treated with first-line chemotherapy were

  14. The Possibility of Traditional Chinese Medicine as Maintenance Therapy for Advanced Nonsmall Cell Lung Cancer

    OpenAIRE

    2014-01-01

    Lung cancer has become the leading cause of cancer deaths, with nonsmall cell lung cancer (NSCLC) accounting for around 80% of lung cancer cases. Chemotherapy is the main conventional therapy for advanced NSCLC. However, the disease control achieved with classical chemotherapy in advanced NSCLC is usually restricted to only a few months. Thus, sustaining the therapeutic effect of first-line chemotherapy is an important problem that requires study. Maintenance therapy is given for patients wit...

  15. 肺癌病人生活质量及认知改变分析%Change of quality of life and cognitive function of patients with NSCLC

    Institute of Scientific and Technical Information of China (English)

    莫梦姣; 胡先纬; 毛玉巧; 胡杰贵

    2015-01-01

    目的:评估晚期非小细胞肺癌病人化疗前后生活质量及认知改变,分析相关影响因素;方法用 QLQ-LC43、MoCA、HAMA 及 HAMD 对41例肺癌病人化疗前、化疗后的生活质量及认知功能评价,同时对30例对照组进行认知评估,统计分析相关因素。结果治疗组在化疗4周期后呼吸困难症状得分降低,但其他症状量表得分未见下降,功能量表得分呈下降趋势;在认知领域,与健康对照组相比肺癌病人化疗前已出现认知损害,化疗后认知损害程度加重,与血红蛋白水平相关。结论化疗可以部分改善肺癌患者症状,认知改变与疾病本身、化疗药物及血红蛋白水平、年龄等因素相关。%Objective To evaluate the variation of quality of life and cognitive function of patients with NSCLC. Methods 41 NSCLC patients and 30 control subjects were selected. Their cognitive states were investiga-ted by Montreal Cognitive Assessment (MoCA), Hamilton Depression Scale (HAMD) and Hamilton Anxiety Scale (HAMA), and their quality of life was investigated by QLQLC-43. Results 4 cycles after chemotherapy, only the score of dyspnea symptom and functional scale declined. Their cognitive state was damaged seriously after chemother-apy, and the damage was correlated with the level of hemoglobin. Conclusion The cognitive impairment has existed before chemotherapy in advanced NSCLC patients. Chemotherapy can improve their quality of life at some extent, and their cognitive impairment was related with age, chemotherapeutics and hemoglobin.

  16. Weekly administration of paclitaxel and carboplatin with concurrent thoracic radiation in previously untreated elderly patients with locally advanced non-small-cell lung cancer: A case series of 20 patients

    OpenAIRE

    Takeshita, Jumpei; MASAGO, KATSUHIRO; FUJITA, SHIRO; Hata, Akito; Kaji, Reiko; KAWAMURA, TAKAHISA; Tamai, Koji; Matsumoto, Takeshi; NAGATA, KAZUMA; Otsuka, Kyoko; Nakagawa, Atsushi; OTSUKA, KOJIRO; Tomii, Keisuke; Shintani, Takashi; Takayama, Kenji

    2014-01-01

    Elderly patients with stage III non-small-cell lung cancer (NSCLC) are frequently underrepresented in clinical trials that evaluate chemoradiotherapy, due to their poor functional status, coexisting illnesses and limited life expectancy. The Japan Clinical Oncology Group 0301 trial (JCOG0301) was the first study to demonstrate that thoracic radiation therapy (TRT) with daily low-dose carboplatin may improve the outcome of elderly patients with stage III NSCLC. However, the efficacy and safety...

  17. Recent Advances in Targetable Therapeutics in Metastatic Non-Squamous NSCLC

    Directory of Open Access Journals (Sweden)

    Pranshu eBansal

    2016-05-01

    Full Text Available Lung adenocarcinoma is the most common subtype of non-small cell lung cancer (NSCLC. With the discovery of epidermal growth factor receptor (EGFR mutations, anaplastic lymphoma kinase (ALK rearrangements and effective targeted therapies, therapeutic options are expanding for patients with lung adenocarcinoma. Here, we review novel therapies in non-squamous NSCLC, which are directed against oncogenic targets, including EGFR, ALK, ROS1, BRAF, MET, human epidermal growth factor receptor 2 (HER2, vascular endothelial growth factor receptor 2 (VEGFR2, RET and NTRK. With the rapidly evolving molecular testing and development of new targeted agents, our ability to further personalize therapy in non-squamous NSCLC is rapidly expanding.

  18. Recent advances in epigenomics in NSCLC: real-time detection and therapeutic implications.

    Science.gov (United States)

    Di Paolo, Antonello; Del Re, Marzia; Petrini, Iacopo; Altavilla, Giuseppe; Danesi, Romano

    2016-08-01

    NSCLC is an aggressive disease with one of the poorer prognosis among cancers. The disappointing response to chemotherapy drives the search for genetic biomarkers aimed at both attaining an earlier diagnosis and choosing the most appropriate chemotherapy. In this scenario, epigenomic markers, such as DNA methylation, histone acetylation and the expression of noncoding RNAs, have been demonstrated to be reliable for the stratification of NSCLC patients. Newest techniques with increased sensitivity and the isolation of nucleic acids from plasma may allow an early diagnosis and then monitoring the efficacy over time. However, prospective confirmatory studies are still lacking. This article presents an overview of the epigenetic markers evaluated in NSCLC and discusses the role of their real-time detection in the clinical management of the disease.

  19. Maintenance Therapy for NSCLC: Consensus and Controversy

    Institute of Scientific and Technical Information of China (English)

    Shun Lu; Yong-feng Yu

    2011-01-01

    Nowadays,advanced non-small cell lung cancer (NSCLC) is still an incurable disease.However,recent researches on maintenance therapy have led to considerable progress.Recently,pemetrexed and erlotinib have been approved for maintenance chemotherapy by both the U.S.Food and Drug Administration and European Medicines Agency.However,there are not adequate data to support the maintenance therapy as the standard treatment for advanced NSCLC and there has been no conclusive predictor of who will get benefit from maintenance chemotherapy and what type of maintenance,continuation or switch,is preferred.This article reviews the main studies on maintenance therapy of advanced NSCLC and discusses the results available to date.

  20. ANGPTL4 Correlates with NSCLC Progression and Regulates Epithelial-Mesenchymal Transition via ERK Pathway.

    Science.gov (United States)

    Zhu, Xiaoming; Guo, Xiaobin; Wu, Sen; Wei, Li

    2016-08-01

    Purpose Lung cancer remains the leading cause of cancer deaths with intricate mechanisms. In the present study, we evaluated the clinical significance and biological role of ANGPTL4 in non-small cell lung cancer (NSCLC), the most common lung cancer subtype. Methods Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used for examining the mRNA level of ANGPTL4 in NSCLC tissues and adjacent non-tumor tissues, NSCLC cell lines, and the immortalized human bronchial epithelial cell line HBE, respectively. A tissue microarray was used for analyzing the relationship between ANGPTL4 expression and the clinicopathological parameters of NSCLC patients. Commercial lentivirus expressing shRNAs was used for silencing ANGPTL4. Cell Counting Kit-8 (CCK-8) was employed for evaluating the cell proliferation ability and transwell with or without matrigel was used for cell migration and invasion assay. Results As the result, ANGPTL4 was over-expressed in NSCLC tissues compared with benign lung tissues. Silencing ANGPTL4 expression strongly inhibited the proliferation, migration, and invasion of A549 and H520 cells, which was in accordance with the increase of epithelial marker E-cadherin and decrease of mesenchymal marker vimentin. By screening the ERK, AKT, EGFR, and STAT3 pathways, we found that cell growth, migration, and invasion arrest induced by loss of ANGPTL4 expression was partially attributable to down-regulation of ERK signaling. Conclusion These results suggested that ANGPTL4 was essential for proliferation and metastasis of lung cancer cells and might serve as a novel target for the treatment of lung cancer. PMID:27166634

  1. Gefitinib: a pharmacoeconomic profile of its use in patients with Non Small Cell Lung Cancer EGFR+

    Directory of Open Access Journals (Sweden)

    Viola Sacchi

    2011-06-01

    Full Text Available Lung cancer is the most common form of cancer with the highest incidence worldwide. The mortality rates are highest in males and second highest in females, after breast cancer. The genetic predisposition to Non Small Cell Lung Cancer (NSCLC is still under investigation, however, studies have shown that the Epidermal Growth Factor Receptor (EGFR, a receptor tyrosine kinase is frequently over-expressed and activated to a phosphorylated state in NSCLC. The activity of EGFR in cancer cells results in the phosphorylation of downstream proteins that promote cell proliferation, invasion, metastasis, and inhibition of apoptosis. Targeting the EGFR pathway therefore constitutes a relevant strategy for cancer therapy. Gefitinib is a selective inhibitor of the EGFR tyrosine kinase and is indicated for the treatment of adult patients with locally advanced or metastatic NSCLC with activating mutations of EGFR-TK. From the pharmacoeconomic point of view gefitinib is dominant (more effective and less expensive compared to the alternatives. In conclusion, gefitinib is a treatment option for NSCLC tumors with a high clinical and economic value in the Italian setting.

  2. Emerging treatments and combinations in the management of NSCLC: clinical potential of nintedanib

    Directory of Open Access Journals (Sweden)

    Reck M

    2015-07-01

    Full Text Available Martin Reck,1 Anders Mellemgaard2 1Department of Thoracic Oncology, Lung Clinic Grosshansdorf, and member of the Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany; 2Department of Oncology, Herlev University Hospital, Copenhagen, Denmark Abstract: There remains an unmet need for effective, well-tolerated treatment options in advanced non-small cell lung cancer (NSCLC to alleviate the disease burden for a broad selection of patients. Nintedanib is a potent, oral, triple angiokinase inhibitor of vascular endothelial growth factor, fibroblast growth factor, and platelet-derived growth factor, and was recently approved in Europe for use in combination with docetaxel for the treatment of adults with locally advanced, metastatic, or locally recurrent NSCLC of adenocarcinoma tumor histology, following first-line chemotherapy. Nintedanib has been investigated extensively in preclinical research and in a number of clinical studies, the most important of which was the Phase III LUME-Lung 1 study, which investigated nintedanib in combination with docetaxel in patients with advanced NSCLC after failure of first-line chemotherapy. In this study, which led to the approval of nintedanib, addition of nintedanib to docetaxel significantly improved overall survival in patients with adenocarcinoma histology. Nintedanib demonstrated a manageable safety profile in combination with docetaxel. This review focuses on the clinical experience with nintedanib in NSCLC and discusses the clinical potential of this agent for use in combination with chemotherapy. Keywords: nintedanib, non-small cell lung cancer, second-line treatment, docetaxel, adenocarcinoma, antiangiogenesis

  3. Identifying Structures in Social Conversations in NSCLC Patients through the Semi-Automatic extraction of Topical Taxonomies

    Directory of Open Access Journals (Sweden)

    Giancarlo Crocetti

    2016-01-01

    Full Text Available The exploration of social conversations for addressing patient’s needs is an important analytical task in which many scholarly publications are contributing to fill the knowledge gap in this area. The main difficulty remains the inability to turn such contributions into pragmatic processes the pharmaceutical industry can leverage in order to generate insight from social media data, which can be considered as one of the most challenging source of information available today due to its sheer volume and noise. This study is based on the work by Scott Spangler and Jeffrey Kreulen and applies it to identify structure in social media through the extraction of a topical taxonomy able to capture the latent knowledge in social conversations in health-related sites. The mechanism for automatically identifying and generating a taxonomy from social conversations is developed and pressured tested using public data from media sites focused on the needs of cancer patients and their families. Moreover, a novel method for generating the category’s label and the determination of an optimal number of categories is presented which extends Scott and Jeffrey’s research in a meaningful way. We assume the reader is familiar with taxonomies, what they are and how they are used.

  4. Advanced NSCLC First Pass Perfusion at 64-slice CT: Reproducibility of Volume-based Quantitative Measurement

    Directory of Open Access Journals (Sweden)

    Jie HU

    2010-05-01

    Full Text Available Background and objective The aim of this study is to explore the reproducibility of volume-based quantitative measurement of non-small cell lung cancer (NSCLC perfusion at 64-slice CT. Methods Fourteen patients with proved advanced NSCLC were enrolled in this dynamic first pass volume-based CT perfusion (CTP study (8×5 mm collimation, and they underwent the second scan within 24 h. According to the longest diameters, those patients were classified to ≤3 cm and >3 cm groups, and each group had 7 patients. Intraclass correlation coefficient (ICC and Bland-Altman statistics were used to evaluate the reproducibility of CTP imaging. Results In both groups of advanced NSCLC, the reproducibility with BF, BV, and PS values were good (ICC >0.75 for all, but mean transit time (MTT values. For advanced NSCLC (≤3 cm, repeatability coefficient (RC values with blood flow (BF, blood volume (BV, MTT and permeability surface area product (PS values were 56%, 45%, 114%, and 78%, respectively, and the 95% change intervals of RC were -39%-53%, -29%-62%, -83%-145%, and -57%-98%, respectively. For advanced NSCLC (>3 cm, those values were 46%, 30%, 59%, and 33%, respectively, and the 95% change intervals of RC were -48%-45%, -33%-26%, -54%-64%, and -18%-48%. Conclusion There is greater reproducibility of tumor size >3 cm than that of ≤3 cm. BF and BV could be addressed for reliable clinical application in antiangiogenesis therapeutic monitoring with advanced NSCLC patients.

  5. CRIPTO1 expression in EGFR-mutant NSCLC elicits intrinsic EGFR-inhibitor resistance

    OpenAIRE

    Park, Kang-Seo; Raffeld, Mark; Moon, Yong Wha; Xi, Liqiang; Bianco, Caterina; Van Pham, Trung; Lee, Liam C.; Mitsudomi, Tetsuya; Yatabe, Yasushi; Okamoto, Isamu; Subramaniam, Deepa; Mok, Tony; Rosell, Rafael; Luo, Ji; Salomon, David S.

    2014-01-01

    The majority of non–small cell lung cancer (NSCLC) patients harbor EGFR-activating mutations that can be therapeutically targeted by EGFR tyrosine kinase inhibitors (EGFR-TKI), such as erlotinib and gefitinib. Unfortunately, a subset of patients with EGFR mutations are refractory to EGFR-TKIs. Resistance to EGFR inhibitors reportedly involves SRC activation and induction of epithelial-to-mesenchymal transition (EMT). Here, we have demonstrated that overexpression of CRIPTO1, an EGF-CFC protei...

  6. BRAF mutations in patients with non-small cell lung cancer: a systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Dong Chen

    Full Text Available BRAF mutations have been well described in non-small cell lung cancer (NSCLC for several years, but the clinical features of patients harboring BRAF mutations are still not well described. We performed a meta-analysis to identify common clinical features in NSCLC patients carrying BRAF mutations.We identified clinical studies that examined the association between BRAF mutations and features of NSCLC within PubMed, Embase and ISI Science Citation Index database up to October 2013. The effect size of clinical features was estimated by odds ratios (ORs with 95% confidence interval (CI for each study, using a fixed-effects or random-effects model.Ten studies with a total of 5599 NSCLC patients were included. There was a 3% (170/5599 BRAF mutation rate. BRAF mutations in NSCLC were significantly associated with adenocarcinomas (ADCs (compared with non-ADCs, OR = 4.96, 95%CI = 2.29-10.75. There were no significant differences in gender, smoking and stage in patients with and without BRAF mutations. The BRAFV600E mutation was more frequent in women than non-BRAFV600E mutations (OR = 0.27, 95%CI = 0.12-0.59, and was closely related to never smokers (OR = 0.14, 95%CI = 0.05-0.42.These findings have important implications for the prediction of the NSCLC sub-types more accurately combined with other genetic changes.

  7. Acute esophagitis for patients with local-regional advanced non small cell lung cancer treated with concurrent chemoradiotherapy

    DEFF Research Database (Denmark)

    Pan, Yi; Brink, Carsten; Knap, Marianne;

    2016-01-01

    PURPOSE: Esophagitis is common in patients treated with definitive radiotherapy for local-regional advanced non small cell lung cancer (NSCLC). The purpose of this study was to estimate the dose-effect relationship using clinical and dosimetric parameters in patients receiving intensity modulated...

  8. Platinum-based doublet chemotherapy plus bevacizumab without bevacizumab maintenance in advanced non-small cell lung cancer (NSCLC)

    DEFF Research Database (Denmark)

    Nørøxe, Dorte Schou; Wallerek, Sandra; Sørensen, Jens Benn

    2013-01-01

    We report on a retrospective, consecutive non-randomized group of patients who received bevacizumab plus chemotherapy without bevazicumab maintenance.......We report on a retrospective, consecutive non-randomized group of patients who received bevacizumab plus chemotherapy without bevazicumab maintenance....

  9. Advancements in radiotherapy for lung cancer in China

    Institute of Scientific and Technical Information of China (English)

    Lujun Zhao; Luhua Wang

    2015-01-01

    Lung cancer is the leading cause of death due to cancer in China. In recent years, great progress has been made in radiotherapy for lung cancer patients in China. The main advance-ments include the fol owing aspects:(1) stereotactic ablative radiotherapy for early stage non-smal cel lung cancer (NSCLC), (2) post-operative radiotherapy for NSCLC, (3) combined chemotherapy and radiotherapy for local y advanced NSCLC, (4) improved radiotherapy for advanced NSCLC, and 5) prediction of radiation-induced lung toxicity.

  10. Class III β-tubulin in advanced NSCLC of adenocarcinoma subtype predicts superior outcome in a randomized trial

    DEFF Research Database (Denmark)

    Vilmar, Adam Christian; Santoni-Rugiu, Eric; Sørensen, Jens Benn

    2011-01-01

    Platinum-based doublets are the cornerstone of treatment in advanced non-small-cell lung cancer (NSCLC) and often include vinorelbine or taxanes. A predictive biomarker is greatly needed to select chemotherapy-sensitive patients for these microtubule-interfering agents. Class III ß-tubulin (TUBB3...

  11. Class III β-tubulin in advanced NSCLC of adenocarcinoma subtype predicts superior outcome in a randomized trial

    DEFF Research Database (Denmark)

    Vilmar, Adam Christian; Santoni-Rugiu, Eric; Sørensen, Jens Benn

    2011-01-01

    Platinum-based doublets are the cornerstone of treatment in advanced non-small-cell lung cancer (NSCLC) and often include vinorelbine or taxanes. A predictive biomarker is greatly needed to select chemotherapy-sensitive patients for these microtubule-interfering agents. Class III β-tubulin (TUBB3...

  12. Cancer-associated fibroblasts from human NSCLC survive ablative doses of radiation but their invasive capacity is reduced

    Directory of Open Access Journals (Sweden)

    Hellevik Turid

    2012-04-01

    Full Text Available Abstract Background Cancer-Associated Fibroblasts (CAFs are significant components of solid malignancies and play central roles in cancer sustainability, invasion and metastasis. In this study we have investigated the invasive capacity and matrix remodelling properties of human lung CAFs after exposure to ablative doses of ionizing radiation (AIR, equivalent to single fractions delivered by stereotactic ablative radiotherapy (SART for medically inoperable stage-I/II non-small-cell lung cancers. Methods CAFs were isolated from lung tumour specimens from 16 donors. Initially, intrinsic radiosensitivity was evaluated by checking viability and extent of DNA-damage response (DDR at different radiation doses. The migrative and invasive capacities of CAFs were thereafter determined after a sub-lethal single radiation dose of 18 Gy. To ascertain the mechanisms behind the altered invasive capacity of cells, expression of matrix metalloproteinases (MMPs and their endogenous inhibitors (TIMPs were measured in the conditioned media several days post-irradiation, along with expression of cell surface integrins and dynamics of focal contacts by vinculin-staining. Results Exposing CAFs to 1 × 18 Gy resulted in a potent induction of multiple nuclear DDR foci (> 9/cell with little resolution after 120 h, induced premature cellular senescence and inhibition of the proliferative, migrative and invasive capacity. AIR promoted MMP-3 and inhibited MMP-1 appearance to some extent, but did not affect expression of other major MMPs. Furthermore, surface expression of integrins α2, β1 and α5 was consistently enhanced, and a dramatic augmentation and redistribution of focal contacts was observed. Conclusions Our data indicate that ablative doses of radiation exert advantageous inhibitory effects on the proliferative, migratory and invasive capacity of lung CAFs. The reduced motility of irradiated CAFs might be a consequence of stabilized focal contacts via integrins.

  13. Depression in Cancer Patients

    Directory of Open Access Journals (Sweden)

    Beyhan Bag

    2014-06-01

    Full Text Available It is not enough to consider treatment and care depression in the oncology that is the most common psychiatric illness in cancer patient affects of cancer treatment and the patient`s quality of life negatively, which is determined through researches in the field. With development of psycho-oncology it has been demonstrated to establish an important link between the cancer patient`s treatment as well as psycho-social support for the patient and psychiatric treatment and care for the if it is needed. With this connection between them it has been proposed to use of bio-psycho-social-model in cancer patient to improve their care. To achieve this goal, it is expected from medical personnel to realize patients psychosocial need und if he/she has a psychiatric disorders or syndromes. For the medical personnel that work in oncology services, it is inevitable to organize in order to raise the awareness of depression in the cancer patients. In the present study, it is focused on raising the awareness of depression in cancer patient for the medical personnel. [Psikiyatride Guncel Yaklasimlar - Current Approaches in Psychiatry 2014; 6(2.000: 186-198

  14. Nomogram Predicting Clinical Outcomes in Non-small Cell Lung Cancer Patients Treated with Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors

    OpenAIRE

    Keam, Bhumsuk; Kim, Dong-Wan; Park, Jin Hyun; Lee, Jeong-Ok; Kim, Tae Min; Lee, Se-Hoon; Chung, Doo Hyun; Heo, Dae Seog

    2014-01-01

    Purpose The aim of this study was to develop a pragmatic nomogram for prediction of progressionfree survival (PFS) for the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) in EGFR mutant non-small cell lung cancer (NSCLC). Materials and Methods A total of 306 recurred or metastatic NSCLC patients with EGFR mutation, who received EGFR TKIs, were enrolled in this study. We developed the nomogram, using a Cox proportional hazard regression model for PFS. Results The median...

  15. An introduction to flow cytometric analysis for measuring activated cyclic endothelial cells in the peripheral blood of NSCLC patients%流式细胞仪检测非小细胞肺癌患者活性循环内皮细胞初探

    Institute of Scientific and Technical Information of China (English)

    孙洪岩; 张爱梅; 操乐杰; 李庆; 徐修才

    2011-01-01

    目的 建立流式细胞仪技术检测成熟循环内皮细胞(CECs)及活性循环内 皮细胞(aCECs)方法,了解非小细胞肺癌(NSCLC)患者及健康人群的CECs和aCECs数量上的差异.方法 采用淋巴细胞分离技术提取外周血单个核细胞,用CD45-PC5 、CD146-PE、CD106-FITC抗体标记60例肺癌患者(NSCLC 56例)及30例健康人,用流式细胞仪检测CECs及aCECs.结果 采用上述标记抗体通过流式细胞仪可顺利检测出外周血CECs及aCECs,而NSCLC患者外周血CECs及aCECs的数量[(2 573±2 019)个/mL,(784±914)个/mL]明显高于健康人群[(273±210)个/mL,(35±61)个/mL],差异有统计 学意义(P0.05).CECs、aCECs的数量与NSCLC肿瘤大小、血CEA之间无明显相关性(P>0.05).结论 采用流式细胞仪可以快速、方便检测出CECs及aCECs.CECs及aC Ecs的数量在NSCLC患者外周血均有明显升高,它可以作为反映NSCLC的血管生成状况及抗血管生成治疗疗效的标志物.%Objective To establish the flow cytometric method for circulating endothelial cells (CECs) and activated circulating endothelial cells (aCECs), for finding out the quantitative difference of CECs and aCECs between NSCLC patients and healthy controls. Methods We adopted the method of Lymphocyte separation to prepare mononuclear cell samples; CECs and aCECs were enumerated in 60 lung cancer patients (56 NSCLC) and 30 healthy controls by flow cytometry using PC5-labelled anti-CD45, FITC-labelled anti-CD106 and PE-labelled anti-CD146. Results Adopting the above method can successfully detect the numbers of CECs and aCECs. The counts of CECs and aCECs were significantly higher in NSCLC patients[ (2 573± 2 019)/mL, (784 ± 914)/mL] than in healthy volunteers[ (273 ± 210)/mL, (35 ± 61 )/mL] (P < 0.001 ). CECs was onlya smallpart of aCECs; aCECs percent was higher in NSCLC patients than that in healthy volunteers (P<0.001). There was no difference in the amounts of CECs and aCECs in terms of pathology type and

  16. Determination of EGFR and KRAS mutational status in Greek non-small-cell lung cancer patients

    OpenAIRE

    Papadopoulou, Eirini; TSOULOS, NIKOLAOS; TSIRIGOTI, ANGELIKI; Apessos, Angela; AGIANNITOPOULOS, KONSTANTINOS; Metaxa-Mariatou, Vasiliki; Zarogoulidis, Konstantinos; Zarogoulidis, Pavlos; KASARAKIS, DIMITRIOS; KAKOLYRIS, STYLIANOS; Dahabreh, Jubrail; VLASTOS, FOTIS; ZOUBLIOS, CHARALAMPOS; Rapti, Aggeliki; PAPAGEORGIOU, NIKI GEORGATOU

    2015-01-01

    It has been reported that certain patients with non-small-cell lung cancer (NSCLC) that harbor activating somatic mutations within the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) gene may be effectively treated using targeted therapy. The use of EGFR inhibitors in patient therapy has been demonstrated to improve response and survival rates; therefore, it was suggested that clinical screening for EGFR mutations should be performed for all patients. Numerous clinicopat...

  17. Effects of multidisciplinary team care on the survival of patients with different stages of non-small cell lung cancer: a national cohort study.

    Directory of Open Access Journals (Sweden)

    Chien-Chou Pan

    Full Text Available In Taiwan, cancer is the top cause of death, and the mortality rate of lung cancer is the highest of all cancers. Some studies have demonstrated that multidisciplinary team (MDT care can improve survival rates of non-small cell lung cancer (NSCLC patients. However, no study has discussed the effect of MDT care on different stages of NSCLC. The target population for this study consisted of patients with NSCLC newly diagnosed in the 2005-2010 Cancer Registry. The data was linked with the 2002-2011 National Health Insurance Research Database and the 2005-2011 Cause of Death Statistics Database. The multivariate Cox proportional hazards model was used to explore whether the involvement of MDT care had an effect on survival. This study applied the propensity score as a control variable to reduce selection bias between patients with and without involvement of MDT care. The adjusted hazard ratio (HR of death of MDT participants with stage III & IV NSCLC was significantly lower than that of MDT non-participants (adjusted HR = 0.87, 95% confidence interval = 0.84-0.90. This study revealed that MDT care are significantly associated with higher survival rate of patients with stage III and IV NSCLC, and thus MDT care should be used in the treatment of these patients.

  18. ENO1 Protein Levels in the Tumor Tissues and Circulating Plasma Samples of Non-small Cell Lung Cancer Patients

    Directory of Open Access Journals (Sweden)

    Ying ZHANG

    2010-12-01

    Full Text Available Background and objective Proper tumor markers are useful to diagnosis, prognosis and treatment for lung cancer. The aim of this study is to examine the levels of alpha-enolase (ENO1 protein in the tumor tissues and peripheral plasma samples obtained from non-small cell lung cancer (NSCLC patients, and evaluate its potential clinical significance. Methods The ENO1 protein levels in the tumor tissues and corresponding normal tissues from 16 cases of lung squamous cell carcinoma were analyzed by Western blot. The ENO1 protein levels in the plasma samples from 42 healthy individuals, 34 patients with lung benign disease and 84 patients with NSCLC were measured by double antibody sandwich enzyme-linked immunosorbent assay. Results For 87.5% (14/16 of the patients with lung squamous cell carcinoma, the ENO1 protein level in the tumor tissues was higher than that in the corresponding normal lung tissues. The ENO1 protein level in the plasma of NSCLC patients was significantly higher than that in the plasma of healthy individuals (P=0.031 and patients with lung benign disease (P=0.019. Furthermore, the ENO1 protein level was significantly higher in the plasma of patients with lung adenocarcinoma than that of patients with lung squamous cell carcinoma. Conclusion The elevated levels of ENO1 protein in the tumor tissues and the plasma samples from NSCLC patients indicate ENO1 may be a candidate biomarker of lung cancer.

  19. Chemotherapy options for the elderly patient with advanced non-small cell lung cancer.

    LENUS (Irish Health Repository)

    Hennessy, B T

    2012-02-03

    Combination chemotherapy has been shown to improve overall survival compared with best supportive care in patients with advanced non-small cell lung cancer (NSCLC). The survival advantage is modest and was initially demonstrated with cisplatin-containing regimens in a large meta-analysis of randomized trials reported in 1995. Newer chemotherapy combinations have been shown to be better tolerated than older cisplatin-based combinations, and some trials have also shown greater efficacy and survival benefits with these newer combinations. Combination chemotherapy is, therefore, the currently accepted standard of care for patients with good performance statuses aged less than 70 years with advanced NSCLC. However, there are limited data from clinical trials to support the use of combination chemotherapy in elderly patients over 70 years of age with advanced NSCLC. Subgroup analyses of large randomized phase III trials suggest that elderly patients with good performance statuses do as well as younger patients treated with combination chemotherapy. There are few randomized trials reported that evaluate chemotherapy in patients aged greater than 70 years only. Based on data from trials performed by an Italian group, single-agent vinorelbine has been shown to have significant activity in elderly patients with advanced NSCLC and to be well tolerated by those patients with Eastern Cooperative Oncology Group performance statuses of two or less, with associated improvements in measures of global health.

  20. Prognostic significance of RNA-dependent protein kinase (PKR) on non-small cell lung cancer patients

    Science.gov (United States)

    Pataer, Abujiang; Raso, Maria Gabriela; Correa, Arlene M; Behrens, Carmen; Tsuta, Koji; Solis, Luisa; Fang, Bingliang; Roth, Jack A.; Wistuba, Ignacio I.; Swisher, Stephen G.

    2011-01-01

    Purpose The role of RNA-dependent protein kinase (PKR) in antiviral defence mechanisms and in cellular differentiation, growth, and apoptosis is well known, but the role of PKR in human lung cancer remains poorly understood. To explore the role of PKR in human lung cancer, we evaluated PKR’s expression in tissue microarray specimens from both non-small cell lung cancer (NSCLC) and normal human bronchial epithelium tissue. Experimental Design Tissue microarray samples (TMA-1) from 231 lung cancers were stained with PKR antibody and validated on TMA-2 from 224 lung cancers. Immunohistochemical expression score was quantified by three pathologists independently. Survival probability was computed by the Kaplan-Meier method. Results The NSCLC cells showed lower levels of PKR expression than normal bronchial epithelium cells did. We also found a significant association between lower levels of PKR expression and lymph node metastasis. We found that loss of PKR expression is correlated with a more aggressive behavior, and that a high PKR expression predicts a subgroup of patients with a favorable outcome. Univariate and multivariate Cox proportional hazards regression models showed that a lower level of PKR expression was significantly associated with shorter survival in NSCLC patients. We further validated and confirmed that PKR to be a powerful prognostic factor in TMA-2 lung cancer (HR=0.22, P<0.0001). Conclusions Our findings first indicate that PKR expression is an independent prognostic variable in NSCLC patients. PMID:20930042

  1. Progress in Clinical Studies of the Gefitinib Uesd in the Treatment of Non-small cell lung cancer(NSCLC)%吉非替尼治疗非小细胞肺癌的临床研究进展

    Institute of Scientific and Technical Information of China (English)

    戴青; 马荔

    2014-01-01

    Lung cancer is the most common cause of death,85%of non-small cell lung cancer,and most patients with advanced performance,generating 5-year rate was 1%~5%.In recent years,successfully developed tyrosine ki-nase inhibitors,opened a new era of smallmolecule targeted cancer therapy.Especially the Gefitinib which is devel-oped and launched by Astra Zeneca,provides another effective treatment for patients with advanced NSCLC.This pa-per gived an overview of worldwide clinical studies of Gefitinib in the treatment of non-small cell lung cancer,which included the monotherapy of Gefitinib in first-line, second-line and maintenance treatment, also the combination chemotherapy in non-small cell lung cancer.%肺癌是肿瘤死亡的最常见原因,其中85%为非小细胞肺癌,且大多数患者有晚期的表现,患者5年的生成率仅为1%~5%,近年研发成功的酪氨酸激酶抑制剂,开启了肿瘤小分子靶向治疗的新时代,尤其是由阿斯利康公司研制并推出的吉非替尼,为晚期 NSCLC患者又提供了一种有效的治疗药物。本文对吉非替尼治疗非小细胞肺癌的临床研究进展进行综述,其中包括全球范围内吉非替尼单药二线、一线和维持治疗,以及联合化疗治疗非小细胞肺癌的临床研究进展。

  2. Combined effects of EGFR tyrosine kinase inhibitors and vATPase inhibitors in NSCLC cells

    Energy Technology Data Exchange (ETDEWEB)

    Jin, Hyeon-Ok [KIRAMS Radiation Biobank, Korea Institute of Radiological and Medical Sciences, 75 Nowon-ro, Nowon-gu, Seoul, 139–706 (Korea, Republic of); Hong, Sung-Eun [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, 75 Nowon-ro, Nowon-gu, Seoul, 139–706 (Korea, Republic of); Kim, Chang Soon [Department of Microbiological Engineering, Kon-Kuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul, 143–701 (Korea, Republic of); Park, Jin-Ah; Kim, Jin-Hee; Kim, Ji-Young; Kim, Bora [KIRAMS Radiation Biobank, Korea Institute of Radiological and Medical Sciences, 75 Nowon-ro, Nowon-gu, Seoul, 139–706 (Korea, Republic of); Chang, Yoon Hwan; Hong, Seok-Il; Hong, Young Jun [Department of Laboratory Medicine, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, 75 Nowon-ro, Nowon-gu, Seoul, 139–706 (Korea, Republic of); Park, In-Chul, E-mail: parkic@kirams.re.kr [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, 75 Nowon-ro, Nowon-gu, Seoul, 139–706 (Korea, Republic of); Lee, Jin Kyung, E-mail: jklee@kirams.re.kr [KIRAMS Radiation Biobank, Korea Institute of Radiological and Medical Sciences, 75 Nowon-ro, Nowon-gu, Seoul, 139–706 (Korea, Republic of); Department of Laboratory Medicine, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, 75 Nowon-ro, Nowon-gu, Seoul, 139–706 (Korea, Republic of)

    2015-08-15

    Despite excellent initial clinical responses of non-small cell lung cancer (NSCLC) patients to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), many patients eventually develop resistance. According to a recent report, vacuolar H + ATPase (vATPase) is overexpressed and is associated with chemotherapy drug resistance in NSCLC. We investigated the combined effects of EGFR TKIs and vATPase inhibitors and their underlying mechanisms in the regulation of NSCLC cell death. We found that combined treatment with EGFR TKIs (erlotinib, gefitinib, or lapatinib) and vATPase inhibitors (bafilomycin A1 or concanamycin A) enhanced synergistic cell death compared to treatments with each drug alone. Treatment with bafilomycin A1 or concanamycin A led to the induction of Bnip3 expression in an Hif-1α dependent manner. Knock-down of Hif-1α or Bnip3 by siRNA further enhanced cell death induced by bafilomycin A1, suggesting that Hif-1α/Bnip3 induction promoted resistance to cell death induced by the vATPase inhibitors. EGFR TKIs suppressed Hif-1α and Bnip3 expression induced by the vATPase inhibitors, suggesting that they enhanced the sensitivity of the cells to these inhibitors by decreasing Hif-1α/Bnip3 expression. Taken together, we conclude that EGFR TKIs enhance the sensitivity of NSCLC cells to vATPase inhibitors by decreasing Hif-1α/Bnip3 expression. We suggest that combined treatment with EGFR TKIs and vATPase inhibitors is potentially effective for the treatment of NSCLC. - Highlights: • Co-treatment with EGFR TKIs and vATPase inhibitors induces synergistic cell death • EGFR TKIs enhance cell sensitivity to vATPase inhibitors via Hif-1α downregulation • Co-treatment of these inhibitors is potentially effective for the treatment of NSCLC.

  3. [Nutrition and cancer patients].

    Science.gov (United States)

    Katsuramaki, T; Hirata, K; Isobe, M

    1998-03-01

    Nutritional therapy for cancer patients includes various objectives such as improvement of cachexia, elucidation of the mechanism of malnutrition, development of therapy for anorexia, nutrition support during chemotherapy or radiotherapy, and inhibition of tumor growth under controlled caloric intake. This review describes recent remarkable developments in nutritional therapy for cancer patients. Cytokines such as interleukin (IL)-1, IL-6, and tumor necrosis factor which induce proteolysis and lipolysis are involved in the cause of malnutrition and cachexia in cancer patients. IL-1 also plays a significant role in the development of cancer anorexia via direct action in the brain. For anorexia therapy, progestogens have been shown to improve appetite and food intake in cancer patients. Moreover, glutamine supplementation improves the host protein metabolism without enhancement of tumor growth during chemotherapy. Among the effects of caloric intake on anticancer therapy, AO-90, a methionine-free intravenous amino acid solution, has been shown to increase the antitumor effect of 5-fluorouracil in clinical studies. From these observations, recent progress in nutritional therapy for cancer patients has been remarkable. Further study of nutritional therapy is required in order to maintain or improve the quality of life of cancer patients in the future.

  4. Comparison of Survival Rate in Primary Non-Small-Cell Lung Cancer Among Elderly Patients Treated With Radiofrequency Ablation, Surgery, or Chemotherapy

    International Nuclear Information System (INIS)

    Purpose: We retrospectively compared the survival rate in patients with non-small-cell lung cancer (NSCLC) treated with radiofrequency ablation (RFA), surgery, or chemotherapy according to lung cancer staging. Materials and Methods: From 2000 to 2004, 77 NSCLC patients, all of whom had WHO performance status 0–2 and were >60 years old, were enrolled in a cancer registry and retrospectively evaluated. RFA was performed on patients who had medical contraindications to surgery/unsuitability for surgery, such as advanced lung cancer or refusal of surgery. In the RFA group, 40 patients with inoperable NSCLC underwent RFA under computed tomography (CT) guidance. These included 16 patients with stage I to II cancer and 24 patients with stage III to IV cancer who underwent RFA in an adjuvant setting. In the comparison group (n = 37), 13 patients with stage I to II cancer underwent surgery; 18 patients with stage III to IV cancer underwent chemotherapy; and 6 patients with stage III to IV cancer were not actively treated. The survival curves for RFA, surgery, and chemotherapy in these patients were calculated using Kaplan–Meier method. Results: Median survival times for patients treated with (1) surgery alone and (2) RFA alone for stage I to II lung cancer were 33.8 and 28.2 months, respectively (P = 0.426). Median survival times for patients treated with (1) chemotherapy alone and (2) RFA with chemotherapy for stage III to IV cancer were 29 and 42 months, respectively (P = 0.03). Conclusion: RFA can be used as an alternative treatment to surgery for older NSCLC patients with stage I to II inoperable cancer and can play a role as adjuvant therapy with chemotherapy for patients with stage III to IV lung cancer.

  5. Clinical effect study of chemical therapy combined with Endostar treatment on late stage NSCLC patients with the expression of ERCC1%化疗联合恩度治疗ERCC1阳性晚期 NSCLC的临床疗效

    Institute of Scientific and Technical Information of China (English)

    任柏沉; 李燕宏; 孙建; 曾小飞

    2015-01-01

    Objective To investigate the clinical efficacy of chemical therapy with or without Endostar treatment for late‐stage non‐small cell lung cancer (NSCLC) with the expression of excision repair cross‐complementing group 1 (ERCC1) .Methods Three hundred and one NSCLC patients of IV stage from 2012 June to 2013 June were enrolled in our hospital and the expression of ERCC1 was detected by immunohistochemical staining in tissue samples ,then the patients were divided into chemotherapy alone group and chemotherapy with Endostar group ,the recent curative effect and patients′survival in two groups were evaluated .Results Among 301 NSCLC patients ,166 patients had a positive expression of ERCC1 and account to 55 .1% .The efficacy rate in ERCC1+ NSCLC patients was significantly lower than that in ERCC1‐NSCLC patients .In ERCC1+ NSCLC patients ,compared with the chemotherapy alone group ,the response rate in the chemotherapy with Endostar group was increased ,and the median survival time (MST) and median time to progress(TTP) were also extended .Conclusion chemotherapy with Endostar increased the recent cura‐tive effect of NSCLC patients and might conducive to improving the quality of life .%目的:探讨化疗联合恩度在核苷酸切除修复交叉互补基因1(ERCC1)阳性晚期非小细胞肺癌(NSCLC)中的临床疗效。方法选取2012年6月至2013年6月在该院经组织学确诊的Ⅳ期NSCLC患者301例,根据ERCC1的表达将患者分为单纯化疗组和化疗联合恩度组,比较不同治疗方案的疗效及患者的生存率。结果在301例NSCLC患者中,ERCC1阳性患者166例,阳性率为55.1%。在所有接受治疗的患者中,ERCC1阳性患者治疗的效果低于 ERCC1阴性患者;但与单纯化疗组相比,化疗联合恩度组能够显著提高ERCC1阳性患者的治疗效果,且其中位生存时间和疾病进展时间也显著延长( P<0.05)。结论化疗联合恩度治疗可有效增加NSCLC患者的疗效。

  6. Diagnostic Value of Single and Combined Determination of Serum TPS Cyfra21-1 and Ferritin in patients with NSCLC%血清肿瘤标记物对非小细胞肺癌的诊断价值

    Institute of Scientific and Technical Information of China (English)

    刘广军; 谢宗涛

    2012-01-01

    Objective: To investigate the diagnostic value of single and combined determination of serum tissue polypeptide specific antigen( TPS ), cytokeratin 19 fragment(Cyfra21-1 ) and ferritin in patients with non-small cell lung cancer( NSCLC ). Method: The levels of serum TPS were detected in 108 patients with NSCLC and 86 cases of healthy adults by enzyme-linked immunosorbent assay( ELASA ),and the levels of Cyfra21-1 and ferritin were detected by electrochemiluminescence. Result: The serum levels and positive rates of the three tumor markers in lung cancer group were significantly higher than those in healthy adults( P <0. 01 ). TPS showed higher sensitivity than the other two tumor markers in the diagnosis of pulmonary ade-nocarcinoma( P<0. 05 );The serum levels and positive rates of Cyfra21-1 in squamous carcinoma group were significantly higher than those in adenocarcinoma group( P<0. 01 ). TPS showed the highest sensitivity and Cyfra21-1 showed the highest sensitivity in single tumor marker detection; Their combined detection could reduce the specificity to a certain extent,but could significantly improve the sensitivity and the accuracy( P< 0. 01 ). Conclusion: The single and combined detection TPS,cyfra21-l and ferritin has high clinical value in the diagnosis of NSCLC and the differentiation of pathology types.%目的 探讨血清组织多肽特异性抗原( TPS)、细胞角蛋白19片段(Cyfra21-1)和铁蛋白(Ferritin)单项及联合检测对非小细胞肺癌的诊断价值.方法 采用酶联免疫吸附(ELISA)法测定108例NSCLC患者和86例健康人的血清中TPS水平,同时用电化学发光法测定Cyfra21-1和Ferritin水平.结果 肺癌组三项血清肿瘤标记物水平及阳性率均显著高于健康对照组(P<0.01).TPS诊断肺腺癌的敏感性优于其他两项肿瘤标记物(P<0.05);Cyfra21-1在鳞癌组血清浓度及阳性率明显高于腺癌组(P<0.01).三项肿瘤标记物单项检测时,TPS的敏感性最高,Cyfra21-1的特异性

  7. A multicentre phase II randomised trial of weekly docetaxel/gemcitabine followed by erlotinib on progression, vs the reverse sequence, in elderly patients with advanced non small-cell lung cancer selected with a comprehensive geriatric assessment (the GFPC 0504 study)

    OpenAIRE

    LeCaer, H; Barlesi, F.; Corre, R; Jullian, H; Bota, S; Falchero, L; Vergnenegre, A.; Dujon, C; Delhoume, J Y; Chouaid, C; ,

    2011-01-01

    Background: Elderly cancer patients form a heterogeneous population in which therapeutic decision-making is often difficult. The aim of this randomised phase II trial was to evaluate the feasibility and activity of weekly docetaxel/gemcitabine (DG) followed by erlotinib after progression (arm A) vs erlotinib followed by DG after progression (arm B) in fit elderly patients with advanced non small-cell lung cancer (NSCLC). Methods: Elderly chemotherapy-naive patients with stage IIIB/IV NSCLC we...

  8. Clinical observation of docetaxel combined with lobaplatin for elderly patients with advanced NSCLC%多西他赛联合洛铂治疗老年晚期非小细胞肺癌临床观察

    Institute of Scientific and Technical Information of China (English)

    阮寒光; 吴永华; 邬蒙

    2014-01-01

    Objective To study the toxicity and efficacy of chemotherapy with docetaxel (TAX) combined with lobaplatin (LBP) for elderly patients with advanced non-small cell lung cancer(NSCLC). Methods From January 2011 to December 2012,26 elderly patients with advanced NSCLC were treated with TL(TAX combined with LBP) for chemotherapy regimens. TAX 75 mg/m2 was dissolved in 250 mL normal saline(NS) or 250 mL 5%glucose solution for 1-h intravenous drip;LBP 30 mg/m2 was dissolved in 250 mL 5%glucose solution for 3-h intravenous drip. 3 weeks was taken as a period. Results Among the 26 pa-tients,4 cases got partial remission(15.4%),13 cases got stable(50.0%) and 9 cases got progressive(34.6%) with the effective rate of 15.4%and disease control rate of 65.4%. The main toxicities were myelosuppression ,especially thrombocytopenia. Serious renal toxicity did not appeared. Conclusion This combination therapy of TAX and LBP has good effect for elderly patients with advanced NSCLC,but hematopoietic factor support should be strengthened when the therapy is adopted in clinic.%目的:观察多西他赛(TAX)和洛铂(LBP)组成的TL化疗方案治疗老年晚期非小细胞肺癌(NSCLC)的疗效和毒性反应。方法选择2011年1月至2012年12月南昌市第三医院采用TL(TAX联合LBP)化疗方案治疗的26例老年晚期NSCLC患者,将TAX 75 mg/m2溶于生理盐水250 mL或5%葡萄糖溶液250 mL中,静脉滴注1 h;另将LBP 30 mg/m2溶于5%葡萄糖溶液250 mL中,静脉滴注3 h;3周为1个周期。结果所有患者中无一例完全缓解,获部分缓解4例(15.4%),稳定13例(50.0%),进展9例(34.6%),有效率为15.4%,肿瘤控制率为65.4%;主要毒性反应为骨髓抑制,尤以血小板减少为重,未发现明显的肾功能损伤。结论 TAX联合LBP治疗老年晚期NSCLC的疗效较好,但临床上采用该方案治疗的同时应加强血细胞监测及造血因子支持。

  9. Successful Chemotherapy with Nab-Paclitaxel in a Heavily Treated Non-Small Cell Lung Cancer Patient: A Case Report

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    Mikiko Ishihara

    2014-06-01

    Full Text Available Non-small cell lung cancer (NSCLC accounts for the majority of all lung cancers. A 69-year-old female with postoperatively recurrent NSCLC was treated weekly with nanoparticle-albumin-bound paclitaxel (nab-paclitaxel monotherapy every 4 weeks as a tenth line chemotherapy, and stable disease was achieved by seven cycles of this regimen. The patient developed grade 4 neutropenia and grade 3 leukopenia, but none of the other toxicities, including febrile neutropenia and peripheral neuropathy, were severe, and thus she was able to tolerate this salvage chemotherapy. To our knowledge this is the first report of the efficacy of nab-paclitaxel monotherapy in a heavily treated NSCLC patient.

  10. Multicenter Phase II Study Evaluating Two Cycles of Docetaxel, Cisplatin and Cetuximab as Induction Regimen Prior to Surgery in Chemotherapy-Naive Patients with NSCLC Stage IB-IIIA (INN06-Study.

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    Wolfgang Hilbe

    Full Text Available Different strategies for neoadjuvant chemotherapy in patients with early stage NSCLC have already been evaluated. The aim of this study was to evaluate the tolerability and efficacy of a chemoimmunotherapy when limited to two cycles.Between 01/2007 and 03/2010 41 patients with primarily resectable NSCLC stage IB to IIIA were included. Treatment consisted of two cycles cisplatin (40 mg/m2 d1+2 and docetaxel (75 mg/m2 d1 q3 weeks, accompanied by the administration of cetuximab (400 mg/m2 d1, then 250 mg weekly. The primary endpoint was radiological response according to RECIST.40 patients were evaluable for toxicity, 39 for response. The main grade 3/4 toxicities were: neutropenia 25%, leucopenia 11%, febrile neutropenia 6%, nausea 8% and rash 8%. 20 patients achieved a partial response, 17 a stable disease, 2 were not evaluable. 37 patients (95% underwent surgery and in three of them a complete pathological response was achieved. At a median follow-up of 44.2 months, 41% of the patients had died, median progression-free survival was 22.5 months.Two cycles of cisplatin/ docetaxel/ cetuximab showed promising efficacy in the neoadjuvant treatment of early-stage NSCLC and rapid operation was possible in 95% of patients. Toxicities were manageable and as expected.EU Clinical Trials Register; Eudract-Nr: 2006-004639-31.

  11. Sarcopenia in Cancer Patients.

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    Chindapasirt, Jarin

    2015-01-01

    Sarcopenia, characterized by a decline of skeletal muscle plus low muscle strength and/or physical performance, has emerged to be an important prognostic factor for advanced cancer patients. It is associated with poor performance status, toxicity from chemotherapy, and shorter time of tumor control. There is limited data about sarcopenia in cancer patients and associated factors. Moreover, the knowledge about the changes of muscle mass during chemotherapy and its impact to response and toxicity to chemotherapy is still lacking. This review aimed to provide understanding about sarcopenia and to emphasize its importance to cancer treatment.

  12. The relationship between chemotherapy tolerance and CA125、CEA levels of patients with advanced NSCLC%晚期NSCLC患者血清CA125、CEA水平与化疗耐受的关系及意义

    Institute of Scientific and Technical Information of China (English)

    张秀萍; 熊新华; 瞿少刚

    2011-01-01

    目的:糖类抗原125(carbohydrate antigen,CAl25)、癌胚抗原(carcinoembryonic antigen,CEA)是最早被应用于临床的肿瘤标志物.对于肺癌患者,监测它们主要用于早期诊断和疗效评价,且两者联合其他指标具有较高的灵敏度和准确性,但其对疗效的具体影响目前还不清楚.为此我们研究了晚期非小细胞肺癌(NSCLC)患者血清CA125、CEA水平及其与化疗耐受次数的关系,从化疗耐受的角度初步探讨其对化疗的影响.方法:应用回顾性分析,观察274例晚期NSCLC患者化疗前血清CA125水平、化疗耐受次数和其中110例患者血清CEA水平,计算患者CA125和CEA阳性率,并将化疗耐受次数与化疗前血清CA125、CEA水平用SPAA10.0软件进行统计学处理.结果:部分晚期NSCLC患者CA125、CEA水平升高,且CA125阳性率(62.4%)高于CEA阳性率(40%);化疗前CA125水平对NSCLC化疗的耐受次数有统计学意义(P0.05).结论:对于晚期NSCLC患者,CA125具有更高的灵敏度,且其化疗前水平在一定程度上可预测患者的化疗耐受,监测CA125比CEA更有利于对患者进行化疗耐受评估,指导临床选择治疗手段.%Objective CA125 and CEA are the first tumor markers to be used for clinical purpose. For patients with lung cancer, These markers are mainly used for early diagnosis and monitoring the efficacy of therapy, and there be high sensitivity and accuracy in combination with other tumor markers ,but their detailed therapeutic effects are unclear. So we study the relationship between chemotherapy tolerance and CA125、CEA levels of patients with advanced NSCLC to find how their impact on chemotherapy from a chemotherapeutic tolerance perspective. Methods By retrospective analysis, we observe the serum CA125 level of 274 advanced NSCLC patients before chemotherapy, tracking the number of their tolerance of chemotherapy, and gather the level of serum CEA of 110 cases among them. Then we calculated the positive rate of CA

  13. Retrospective analysis of third-line chemotherapy in advanced non-small cell lung cancer

    OpenAIRE

    Ali Murat Tatli; Deniz Arslan; Mukremin Uysal; Sema Sezgin Goksu; Seyda Gulenay Gunduz; Hasan Senol Coskun; Mustafa Ozdogan; Burhan Savas; Hakan Sat Bozcuk

    2015-01-01

    Background: First- and second-line chemotherapies have been demonstrated to be effective in treatment of patients with inoperable, advanced non-small cell lung cancer (NSCLC), although the role of third-line chemotherapy remains unclear. The present investigation assessed treatment outcomes in patients with advanced NSCLC who received third-line and higher chemotherapy. Patients and Methods: This retrospective study included consecutive patients with advanced NSCLC who received at least t...

  14. Triaging early-stage lung cancer patients into non-surgical pathways: who, when, and what?

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    Sroufe, Rameses; Kong, Feng-Ming Spring

    2015-08-01

    More lung cancer patients are being diagnosed at an earlier stage due to improved diagnostic imaging techniques, a trend that is expected to accelerate with the dissemination of lung cancer screening. Surgical resection has always been considered the standard treatment for patients with early-stage non-small cell lung cancer (NSCLC). However, non-surgical treatment options for patients with early-stage NSCLC have evolved significantly over the past decade with many new and exciting alternative treatments now available. These alternative treatments include radiofrequency ablation (RFA), microwave ablation (MWA), percutaneous cryoablation therapy (PCT), photodynamic therapy (PDT) and external beam radiation therapy (EBRT), including stereotactic body radiation therapy (SBRT) and accelerated hypofractionated radiation therapy. We describe the established alternatives to surgical resection, their advantages and disadvantages, potential complications and efficacy. We then describe the optimal treatment approach for patients with early-stage NSCLC based on tumor operability, size and location. Finally, we discuss future directions and whether any alternative therapies will challenge surgical resection as the treatment of choice for patients with operable early-stage lung cancer. PMID:26380185

  15. Dysphagia in Tongue Cancer Patients

    OpenAIRE

    Son, Yu Ri; Choi, Kyoung Hyo; Kim, Tae Gyun

    2015-01-01

    Objective To identify risk factors for dysphagia in tongue cancer patients. Dysphagia is a common complication of surgery, radiotherapy, and chemotherapy in tongue cancer patients. Previous studies have attempted to identify risk factors for dysphagia in patients with head and neck cancer, but no studies have focused specifically on tongue cancer patients. Methods This study was conducted on 133 patients who were diagnosed with tongue cancer and who underwent a videofluoroscopy swallowing stu...

  16. Comparison of the utility of whole-body MRI with and without contrast-enhanced Quick 3D and double RF fat suppression techniques, conventional whole-body MRI, PET/CT and conventional examination for assessment of recurrence in NSCLC patients

    Energy Technology Data Exchange (ETDEWEB)

    Ohno, Yoshiharu, E-mail: yosirad@kobe-u.ac.jp [Advanced Biomedical Imaging Research Center, Kobe University Graduate School of Medicine (Japan); Division of Functional and Diagnostic Imaging Research, Department of Radiology, Kobe University Graduate School of Medicine, Kobe (Japan); Nishio, Mizuho [Advanced Biomedical Imaging Research Center, Kobe University Graduate School of Medicine (Japan); Division of Functional and Diagnostic Imaging Research, Department of Radiology, Kobe University Graduate School of Medicine, Kobe (Japan); Koyama, Hisanobu [Division of Radiology, Department of Radiology, Kobe University Graduate School of Medicine, Kobe (Japan); Yoshikawa, Takeshi; Matsumoto, Sumiaki [Advanced Biomedical Imaging Research Center, Kobe University Graduate School of Medicine (Japan); Division of Functional and Diagnostic Imaging Research, Department of Radiology, Kobe University Graduate School of Medicine, Kobe (Japan); Takenaka, Daisuke [Division of Radiology, Department of Radiology, Kobe University Graduate School of Medicine, Kobe (Japan); Department of Radiology, Hyogo Cancer Center, Akashi (Japan); Seki, Shinichiro [Division of Radiology, Department of Radiology, Kobe University Graduate School of Medicine, Kobe (Japan); Tsubakimoto, Maho [Division of Radiology, Department of Radiology, Kobe University Graduate School of Medicine, Kobe (Japan); Department of Radiology, Graduate School of Medical Science, University of the Ryukyus, Nishihara, Okinawa (Japan); Sugimura, Kazuro [Division of Radiology, Department of Radiology, Kobe University Graduate School of Medicine, Kobe (Japan)

    2013-11-01

    Purpose: The purpose of this study was to compare diagnostic capabilities for assessment of recurrence in non-small cell lung cancer (NSCLC) patients by contrast-enhanced whole-body MRI (CE-WB-MRI) with and without CE-Quick 3D and double RF fat suppression technique (DFS), FDG-PET/CT and conventional radiological examinations. Materials and methods: A total of 134 pathologically proven and completely resected NSCLC patients (78 males, 56 females; mean age: 72 years) underwent FDG-PET/CT, CE-WB-MRI with and without Quick 3D and DFS at 3 T as well as conventional radiological examinations. The probability of recurrence was assessed with a 5-point scoring system on a per-patient basis, and final diagnosis was made by consensus between two readers. The capability for overall recurrence assessment by all the methods was compared by means of ROC analysis and their sensitivity, specificity and accuracy by means of McNemar's test. Results: Although areas under the curve did not show any significant differences, specificity (100%) and accuracy (95.5%) of CE-WB-MRI with CE-Quick 3D and DFS were significantly higher than those of FDG-PET/CT (specificity: 93.6%, p = 0.02; accuracy: 89.6%, p = 0.01) and conventional radiological examinations (specificity: 92.7%, p = 0.01; accuracy: 91.0%, p = 0.03). In addition, specificity of CE-WB-MRI without CE-Quick 3D and DFS (100%) was significantly higher than that of FDG-PET/CT (p = 0.02) and conventional radiological examinations (p = 0.01). Conclusion: Specificity and accuracy of CE-WB-MRI with CE-Quick 3D and DFS for assessment of recurrence in NSCLC patients are at least as high as, or higher than those of others.

  17. Evaluation of reverse phase protein array (RPPA)-based pathway-activation profiling in 84 non-small cell lung cancer (NSCLC) cell lines as platform for cancer proteomics and biomarker discovery.

    Science.gov (United States)

    Ummanni, Ramesh; Mannsperger, Heiko A; Sonntag, Johanna; Oswald, Marcus; Sharma, Ashwini K; König, Rainer; Korf, Ulrike

    2014-05-01

    The reverse phase protein array (RPPA) approach was employed for a quantitative analysis of 71 cancer-relevant proteins and phosphoproteins in 84 non-small cell lung cancer (NSCLC) cell lines and by monitoring the activation state of selected receptor tyrosine kinases, PI3K/AKT and MEK/ERK1/2 signaling, cell cycle control, apoptosis, and DNA damage. Additional information on NSCLC cell lines such as that of transcriptomic data, genomic aberrations, and drug sensitivity was analyzed in the context of proteomic data using supervised and non-supervised approaches for data analysis. First, the unsupervised analysis of proteomic data indicated that proteins clustering closely together reflect well-known signaling modules, e.g. PI3K/AKT- and RAS/RAF/ERK-signaling, cell cycle regulation, and apoptosis. However, mutations of EGFR, ERBB2, RAF, RAS, TP53, and PI3K were found dispersed across different signaling pathway clusters. Merely cell lines with an amplification of EGFR and/or ERBB2 clustered closely together on the proteomic, but not on the transcriptomic level. Secondly, supervised data analysis revealed that sensitivity towards anti-EGFR drugs generally correlated better with high level EGFR phosphorylation than with EGFR abundance itself. High level phosphorylation of RB and high abundance of AURKA were identified as candidates that can potentially predict sensitivity towards the aurora kinase inhibitor VX680. Examples shown demonstrate that the RPPA approach presents a useful platform for targeted proteomics with high potential for biomarker discovery. This article is part of a Special Issue entitled: Biomarkers: A Proteomic Challenge. PMID:24361481

  18. Clinical Observation of Icotinib Hydrochloride for Advanced Non-small Cell Lung Cancer Patients with EGFR Status Identified

    Directory of Open Access Journals (Sweden)

    Xi LI

    2015-12-01

    Full Text Available Background and objective Icotinib is the first self-developed small molecular drug in China for targeted therapy of lung cancer. Compared to the other two commercially available epidermal growth factor receptor (EGFR tyrosine kinase inhibitors, gefitinib and erlotinib, icotinib is similar to them in chemical structure, mechanism of activity and therapeutic effects. To explore the efficacy and side effects of icotinib hydrochloride in the treatment of the advanced non-small cell lung cancer (NSCLC patients with EGFR mutation and wild-type. Methods Patients with advanced NSCLC who were treated with icotinib hydrochloride in Beijing Chest Hospital were retrospective analyzed from March 2009 to December 2014. Results The clinical data of 124 patients (99 with EGFR mutation and 25 with wild type with advanced NSCLC were enrolled in this study. The patients’ overall objective response rate (ORR was 51.6 % and the disease control rate (DCR was 79.8%; The patients with EGFR mutation, ORR was 63.6%, DCR was 93.9%. The ORR was 4.0% and the DCR was 24.0% in the wild-type patients. Median progression-free survival (PFS with icotinib treatment in EGFR mutation patients was 10.5 months and 1.0 month in wild-type patients. The major adverse events were mild skin rash (30.6% and diarrhea (16.1%. Conclusion Monotherapy with icotinib hydrochloride is effective and tolerable for the advanced NSCLC EGFR mutation patients.

  19. Metastatic spinal cord compression in non-small cell lung cancer patients. Prognostic factors in a series of 356 patients

    Energy Technology Data Exchange (ETDEWEB)

    Rades, D.; Douglas, S. [Luebeck Univ. (Germany). Dept. of Radiation Oncology; Veninga, T. [Dr. Bernard Verbeeten Institute Tilburg (Netherlands). Dept. of Radiation Oncology; Bajrovic, A. [University Medical Center Hamburg-Eppendorf, Hamburg (Germany). Dept. of Radiation Oncology; Stalpers, L.J.A. [Academic Medical Center Amsterdam (Netherlands). Dept. of Radiotherapy; Hoskin, P.J. [Mount Vernon Centre for Cancer Treatment, Northwood (United Kingdom). Dept. of Clinical Oncology; Rudat, V. [Saad Specialist Hospital Al-Khobar (Saudi Arabia). Dept. of Radiation Oncology; Schild, S.E. [Mayo Clinic Scottsdale, Scottsdale, AZ (United States). Dept. of Radiation Oncology

    2012-06-15

    Patients with metastatic spinal cord compression (MSCC) from non-small cell lung cancer (NSCLC) have an unfavorable prognosis compared to most other MSCC patients. This study was performed to identify prognostic factors for functional outcome and survival in these patients after radiotherapy (RT) alone. Data of 356 patients irradiated for MSCC from NSCLC were retrospectively analyzed. Ten potential prognostic factors were investigated including age, gender, Eastern cooperative Oncology Group performance score (ECOG-PS), number of involved vertebrae, pre-RT ambulatory status, other bone metastases, visceral metastases, interval from cancer diagnosis to RT of MSCC, time developing motor deficits before RT, and the radiation schedule. On multivariate analysis, better functional outcome was associated with pre-RT ambulatory status (estimate: -0.84, p = 0.022), no visceral metastases (estimate: -1.15, p < 0.001), interval from cancer diagnosis to RT of > 15 months (estimate: +0.48, p = 0.019), and slower (> 7 days) development of motor deficits (estimate: +1.56, p < 0.001). On multivariate analysis, improved survival was significantly associated with female gender (risk ratio (RR) 1.32, p = 0.043), ECOG-PS 1-2 (RR 1.45, p = 0.034), pre-RT ambulatory status (RR 0.58, p < 0.001), no other bone metastases (RR 1.38, p = 0.010), no visceral metastases (RR 2.87, p < 0.001), interval from cancer diagnosis to RT of > 15 months (RR 0.84, p = 0.035), and slower (> 7 days) development of motor deficits (RR 0.78, p < 0.001). This study identified additional independent prognostic factors for outcomes after radiotherapy of MSCC from NSCLC. These prognostic factors can be used for stratification in future trials and can help develop prognostic scores for MSCC from NSCLC. (orig.)

  20. Role of gefitinib in the targeted treatment of non-small-cell lung cancer in Chinese patients

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    Li MJ

    2016-03-01

    Full Text Available Meng-Jiao Li, Qing He, Mei Li, Feng Luo, Yong-Song Guan Department of Oncology, Center of Oncology, West China Hospital of Sichuan University, Chengdu, People’s Republic of China Abstract: Non-small-cell lung cancer (NSCLC is the most common type of lung cancer. Conventional treatment options have limited efficacy because most cases are in the advanced stage at the time of diagnosis. In recent years, gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor, has shown its good antitumor activities in treating NSCLC in a number of studies. This paper reviews its role in the targeted treatment of NSCLC in Chinese patients. Keywords: pulmonary carcinoma, therapy, EGFR-TK inhibitor, status, People’s Republic of China 

  1. Rapid and dramatic response to alectinib in an anaplastic lymphoma kinase rearranged non-small-cell lung cancer patient who is critically ill.

    Science.gov (United States)

    Yoshida, Tatsuya; Hida, Toyoaki; Yatabe, Yasushi

    2016-07-01

    Anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) have shown promising clinical activity in the treatment of non-small-cell lung cancer (NSCLC) that harbors ALK rearrangement. The next-generation ALK-TKI, alectinib, has been reported to have potent efficacy in ALK-positive NSCLC patients including on mutations that confer resistance to crizotinib, which was the first ALK-TKI approved for ALK-positive NSCLC. The efficacy and safety of ALK-TKIs, including crizotinib and alectinib, as the first-line treatment in critically ill patients is unclear. We report one ALK-positive NSCLC patient with poor performance status (PS) and disseminated intravascular coagulation because of respiratory failure and multiple metastases, and experienced the rapid and dramatic response to alectinib without adverse events that can lead to discontinuation and dose reduction of the drug. After a couple of months of treatment with alectinib, radiological review indicated a complete response. The present case is the first reported case of rapid and marked response to alectinib in ALK-positive NSCLC patients who had poor PS and severe organ dysfunction, such as disseminated intravascular coagulation. Further investigation of the safety and efficacy of ALK-TKI for ALK-positive NSCLC patients who are critically ill is warranted. PMID:26938871

  2. [Physiotherapy of cancer patients].

    Science.gov (United States)

    Gomez, Izabella; Szekanecz, Éva; Szekanecz, Zoltán; Bender, Tamás

    2016-07-01

    Physiotherapy of cancer patients is one of the most controversial issues in our country. Malignant diseases are firstly mentioned as a contraindication of physiotherapy. Until now, physiotherapy was not suggested (or only in limited accessibility) for those patients who had malignant disease in medical history. International medical practice was less restrictive in managing this topic. The development of imaging techniques put this question in a new light. On the basis of evidence, the majority of articles have reported beneficial effects of physiotherapy in cancer patients, and only few articles mentioned it as harmful. Of course, each patient requires an individual assessment, however, if we exclude the possibility of tumor recurrence and metastasis, most of physiotherapy procedures can be used safely. One of the aims of this review is to support the physicians' decisions when to prescribe treatments, in such a way, that more patients could receive physiotherapy. Orv. Hetil., 2016, 157(31), 1224-1231.

  3. Insomnia in cancer patients.

    Science.gov (United States)

    O'Donnell, Joseph F

    2004-01-01

    Insomnia affects up to 50% of patients with cancer, but has received little attention from the oncology community compared with other symptoms such as pain and fatigue. Insomnia and subsequent sleep disturbances can lead to fatigue, mood disturbances, and contribute to immunosuppression, which can have a profound impact on quality of life and perhaps affect the course of disease. Insomnia in cancer patients must be distinguished from cancer-related fatigue. Although they are 2 distinct conditions, insomnia and fatigue are interrelated. Insomnia often leads to daytime fatigue that interferes with normal functioning. Conversely, daytime fatigue can lead to behaviors such as napping, which result in insomnia. The primary goal of insomnia treatment should first be to relieve any underlying disorder (eg, cancer pain, depression, anxiety) that may be causing the sleep disturbance. Because insomnia in this patient population may be due to a variety of causes, treatment must be multimodal and include both pharmacologic and nonpharmacologic therapies. A plan that combines attention to sleep hygiene and cognitive-behavioral therapy with prescription of hypnotic medications can help relieve the symptoms of insomnia in cancer patients and improve their quality of life. PMID:15675652

  4. PI3K pathway in NSCLC

    Directory of Open Access Journals (Sweden)

    Alex eMartínez Martí

    2012-01-01

    Full Text Available The phosphatidylinositol 3-kinases (PI3Ks are members of a family of intracellular lipid kinases that phosphorylate the 3’-hydroxyl group of phosphatidylinositol and phosphoinositides. PI3K regulate signaling pathways for neoplasia, including cell proliferation, adhesion, survival and motility. Different classes of PI3K have distinct roles in cellular signal transduction. PI3K pathway is activated by several different mechanisms in cancers, including, somatic mutation and gene amplification. In this review, we examine the literature addressing PI3K mutation status and gene amplification, with an emphasis on non-small cell lung cancer (NSCLC.

  5. Severity of lung fibrosis affects early surgical outcomes of lung cancer among patients with combined pulmonary fibrosis and emphysema.

    Science.gov (United States)

    Mimae, Takahiro; Suzuki, Kenji; Tsuboi, Masahiro; Ikeda, Norihiko; Takamochi, Kazuya; Aokage, Keiju; Shimada, Yoshihisa; Miyata, Yoshihiro; Okada, Morihito

    2016-07-01

    Combined pulmonary fibrosis and emphysema (CPFE) is defined as upper lobe emphysema and lower lobe fibrosis, which are representative lung disorders that increase the prevalence of lung cancer. This unique disorder may affect the morbidity and mortality during the early period after surgery. The present study aimed to identify which clinicopathological features significantly affect early surgical outcomes after lung resection in nonsmall cell lung cancer (NSCLC) patients and in those with CPFE.We retrospectively assessed 2295 patients with NSCLC and found that 151 (6.6%) had CPFE. All were surgically treated between January 2008 and December 2010 at 4 institutions.The postoperative complication rates for patients with and without CPFE were 39% and 17%, respectively. The 90-day mortality rates were higher among patients with than without CPFE (7.9% vs 1%). Acute exacerbation of interstitial pneumonia was the main cause of death among 12 patients with CPFE who died within 90 days after surgery. Multivariate logistic regression analysis selected CPFE, gender, age, and clinical stage as independent predictive factors for postoperative complications, and CPFE, clinical stage, and sex for 90-day mortality. The severity of lung fibrosis on preoperative CT images was an independent predictive factor for 90-day mortality among patients with CPFE.The key predictive factor for postoperative mortality and complications of lung resection for NSCLC was CPFE. The severity of lung fibrosis was the principal predictor of early outcomes after lung surgery among patients with CPFE and NSCLC.

  6. Survival Analysis of Non-Small Cell Lung Cancer in Patients Aged 70 and over

    Directory of Open Access Journals (Sweden)

    Jiankun SUN

    2008-04-01

    Full Text Available Background and Objective With a trend of worldwide increasing incidence of elderly population, more and more people pay close attention to diseases in the elderly. Lung cancer is a typical disease of the elderly patients. Around one-third of all patients with non-small cell lung cancer (NSCLC are over the age of 70. Many authors use the age 70 to define the elderly patients in lung cancer. The objective of this study is to evaluate the survival of patients older than 70 with NSCLC and explore the independent prognostic factors in this group of patients. Methods 148 elderly patients with NSCLC were reviewed. All the potential prognostic factors, including sex, age, smoke, symptoms, pathological types, clinical stage, ECOG performance status, complication, focus resection, radiotherapy and chemotherapy were analyzed by COX regression in SPSS 13.0 software. Results After 5-168 months follow-up, 119 patients died, the overall survival rate was 19.6%. 1,2,3,5-year survival rates were 43.2%, 19.0%, 9.0% and 5.4% respectively. Median survival time (MST was 9.29 moths. COX regression showed clinical stage (P=0.002, ECOG performance status (P=0.000, focus resection (P=0.012 and radiotherapy of primary site (P=0.012 were the independent prognostic factors. Conclusion The elderly patients with NSCLC in early stage and good performance status tend to have longer life expectance, whereas resection and radiotherapy of primary site can prolong the survival time (P<0.05.

  7. The importance of multidisciplinary team management of patients with non-small-cell lung cancer.

    Science.gov (United States)

    Ellis, P M

    2012-06-01

    Historically, a simple approach to the treatment of non-small-cell lung cancer (nsclc) was applicable to nearly all patients. Recently, a more complex treatment algorithm has emerged, driven by both pathologic and molecular phenotype. This increasing complexity underscores the importance of a multidisciplinary team approach to the diagnosis, treatment, and supportive care of patients with nsclc. A team approach to management is important at all points: from diagnosis, through treatment, to end-of-life care. It also needs to be patient-centred and must involve the patient in decision-making concerning treatment. Multidisciplinary case conferencing is becoming an integral part of care. Early integration of palliative care into the team approach appears to contribute significantly to quality of life and potentially extends overall survival for these patients. Supportive approaches, including psychosocial and nutrition support, should be routinely incorporated into the team approach. Challenges to the implementation of multidisciplinary care require institutional commitment and support.

  8. Systemic treatment in EGFR-ALK NSCLC patients:second line therapy and beyond

    Institute of Scientific and Technical Information of China (English)

    Niki Karachaliou; Rafael Rosell

    2014-01-01

    Lung cancer is the most frequently diagnosed cancer and a leading cause of cancer mortality worldwide, with adenocarcinoma being the most common histological subtype. Deeper understanding of the pathobiology of non-small cell lung cancer (NSCLC) has led to the development of small molecules that target genetic mutations known to play critical roles in progression to metastatic disease and to inlfuence response to targeted therapies. hTe principle goal of precision medicine is to deifne those patient populations most likely to respond to targeted therapies. However, the cancer genome landscape is composed of relatively few “mountains” [representing the most commonly mutated genes like KARS, epidermal growth factor (EGFR), and anaplastic lymphoma kinase (ALK)] and a vast number of “hills” (representing low frequency but potentially actionable mutations). Low-frequency lesions that affect a druggable gene product allow a relatively small population of cancer patients for targeted therapy to be selected.

  9. Clinic Characteristics and Prognosis in 102 Non-small Cell Lung Cancer Patients 
Less than 40 Years Old

    Directory of Open Access Journals (Sweden)

    Lili QU

    2013-02-01

    Full Text Available Background and objective The incidence of young non-small cell lung cancer (NSCLC annually increases. The aim of this study is to analyze the clinical pathological characteristics of young (less than 40 years old NSCLC patients. Methods The data of 102 young NSCLC were retrospectively analyzed. Results Among the 102 patients, 43.1% were women and 29.4% were smokers. The male-to-female ratio was 1.32:1. The most frequent histologic type was adenocarcinoma (77.5%. Tumor differentiation was mostly poor (64.1%, and 87.8% had stages IIIb and IV diseases. The median recurrence time of 6 patients who had tumor resection was 13.5 months. The objective response rate (ORR of 87 patients who received first-line chemotherapy was 46.0%, the disease control rate (DCR was 79.3%, and the median time to progression (TTP was 5.0 months. The ORR of 38 patients who received epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI therapy was 40.0%, with a DCR of 65.7% and a median TTP of 5.5 months. The DCR of 12 patients who received EGFR-TKI twice or more times was 66.7%, with a median TTP of 3.0 months. Conclusion The time from the first presenting symptom until diagnosis was usually long. The female proportion presented an upward trend and the correlation became attenuated between young NSCLC patients and smoking. Most of the young NSCLC patients had adenocarcinoma and poor tumor differentiation. Multidisciplinary and systematic therapies were needed to improve the poor prognosis of the young NSCLC patients.

  10. Application value of Cisplatin chrono-chemotherapy for Advanced Non-small Cell Lung Cancer%顺铂时辰化疗在晚期 NSCLC 治疗中的应用价值

    Institute of Scientific and Technical Information of China (English)

    徐成伟; 陈威龙

    2014-01-01

    Objective To evaluate the clinical value and toxicities of cisplatin chrono-chemotherapy for advanced non-small cell lung cancer ( NSCLC) .Methods 64 patients with advanced NSCLC were divided into chrono-chemotherapy group and conventional chemotherapy group .Clinical efficacy and toxicities of the 2 groups were evaluated .Results There was no signifi-cant difference in total response rate between chrono-chemotherapy group ( 53.13%) and conventional chemotherapy group (50.00%).The rates of leucopenia and neutropenia in chrono-chemotherapy group were 9.38%(3/32)and 9.38%(3/32);and the rates of leucopenia and neutropenia in conventional chemotherapy group were 40.63%(13/32) and 37.50%(12/32), there was significant difference between the 2 groups(P<0.05).The rate of gastrointestinal toxicity (nausea) in chrono-chemo-therapy group and in conventional chemotherapy group were 18.75%(6/32)and 62.50%(20/32),there was statistical difference (P<0.05).Conclusion Efficacy of cisplatin chrono-chemotherapy and conventional chemotherapy for advanced non -small cell lung cancer has no difference ,but chrono-chemotherapy has less adverse reactions ,and it is superior to conventional chemothera-py.%目的:探讨顺铂时辰化疗在晚期非小细胞肺癌( NSCLC)治疗中的临床应用价值及不良反应。方法选择晚期NSCLC患者64例,根据数字随机法将患者分为时辰化疗组和常规化疗组,各32例,评价2组临床应用价值和不良反应的差异。结果有效率时辰化疗组为53.13%,常规化疗组为50.00%,2组差异无统计学意义( P>0.05)。时辰化疗组严重白细胞下降者及严重中性粒细胞下降者分别为9.38%(3/32)、9.38%(3/32),常规化疗组分别为40.63%(13/32)、37.50%(12/32),差异有统计学意义(P<0.05)。消化道副作用(恶心)发生者,时辰化疗组为18.75%(6/32),常规化疗组为62.50%(20/32),

  11. Exhaled volatile organic compounds in patients with non-small cell lung cancer: cross sectional and nested short-term follow-up study

    OpenAIRE

    Acampa Olga; Goldoni Matteo; Corradi Massimo; Carbognani Paolo; Poli Diana; Balbi Bruno; Bianchi Luca; Rusca Michele; Mutti Antonio

    2005-01-01

    Abstract Background Non-invasive diagnostic strategies aimed at identifying biomarkers of lung cancer are of great interest for early cancer detection. The aim of this study was to set up a new method for identifying and quantifying volatile organic compounds (VOCs) in exhaled air of patients with non-small cells lung cancer (NSCLC), by comparing the levels with those obtained from healthy smokers and non-smokers, and patients with chronic obstructive pulmonary disease. The VOC collection and...

  12. Fluorescence in situ hybridization and immunohistochemistry as diagnostic methods for ALK positive non-small cell lung cancer patients.

    Directory of Open Access Journals (Sweden)

    Pablo Martinez

    Full Text Available BACKGROUND: Anaplastic Lymphoma Kinase (ALK positivity represents a novel molecular target in a subset of Non-Small Cell Lung Cancers (NSCLC. We explore Fluorescence in situ Hybridization (FISH and Immunohistochemistry (IHC as diagnostic methods for ALK positive patients and to describe its prevalence and outcomes in a population of NSCLC patients. METHODS: NSCLC patients previously screened for Epidermal Growth Factor Receptor (EGFR at our institution were selected. ALK positive patients were identified by FISH and the value of IHC (D5F3 was explored. RESULTS: ninety-nine patients were identified. Median age was 61.5 years (range 35-83, all were caucasians, eighty percent were adenocarcinomas, fifty-one percent were male and thirty-eight percent were current smokers. Seven (7.1% patients were ALK positive by FISH, thirteen (13.1% were EGFR mutant, and 65 (65.6% were negative/Wild Type (WT for both ALK and EGFR. ALK positivity and EGFR mutations were mutually exclusive. ALK positive patients tend to be younger than EGFR mutated or wt patients. ALK positive patients were predominantly never smokers (71.4% and adenocarcinoma (71.4%. ALK positive and EGFR mutant patients have a better outcome than negative/WT. All patients with ALK FISH negative tumours were negative for ALK IHC. Out of 6 patients positive for ALK FISH with more tissue available, 5 were positive for ALK IHC and 1 negative. CONCLUSIONS: ALK positive patients represent 7.1% of a population of selected NSCLC. ALK positive patients have different clinical features and a better outcome than EGFR WT and ALK negative patients. IHC is a promising method for detecting ALK positive NSCLC patients.

  13. Prediction of pulmonary complications after a lobectomy in patients with non-small cell lung cancer

    OpenAIRE

    Uramoto, H; Nakanishi, R.; Fujino, Y; Imoto, H; Takenoyama, M; Yoshimatsu, T.; Oyama, T; Osaki, T.; Yasumoto, K

    2001-01-01

    BACKGROUND—Although the preoperative prediction of pulmonary complications after lung major surgery has been reported in various papers, it still remains unclear.
METHODS—Eighty nine patients with stage I-IIIA non-small cell lung cancer (NSCLC) who underwent a complete resection at our institute from 1994-8 were evaluated for the feasibility of making a preoperative prediction of pulmonary complications. All had either a predicted postoperative forced vital capacity (FVC)...

  14. Gefitinib-induced disseminated intravascular coagulation in a patient with non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    YUAN Guang-jin; KE Qin-hua; XU Xi-ming; YANG Ji-yuan; SU Xiao-yan

    2010-01-01

    @@ In February 2005, Gefitinib (Iressa), a small-molecular epidermal growth factor receptor and tyrosine kinase inhibitor, was approved in China as an anticancer agent for patients with advanced (local or metastatic) non-small cell lung cancer (NSCLC), who failed prior chemotherapy. The common adverse events of the drug include acne-like skin rash, paronychia, pruritus, diarrhea, nausea/vomiting, anorexia, hepatitis, and hyperbilirubinemia.~1

  15. Diagnostic value of Cyfra21-1, SCC and CEA for differentiation of early-stage NSCLC from benign lung disease

    OpenAIRE

    Chen, Feng; Wang, Xiu-Ying; Han, Xiao-Hong; Wang, Hai; Qi, Jun

    2015-01-01

    Non-small cell lung cancer (NSCLC), which account for the most of lung carcinoma, is sometimes difficult to differentiate from benign lung diseases presented with nodular shadow in imaging scan. There is a need to find another non-invasive way to diagnosis early-stage NSCLC. To examine the potential diagnostic value of SCC, CFYRA 21-1 and CEA for the differentiation of early-stage NCSCL from benign lung diseases, we analyzed serum levels of tumor markers in 278 patients, including 248 patient...

  16. Pemetrexed clinical studies in performance status 2 patients with non-small cell lung cancer (Review).

    Science.gov (United States)

    Zinner, Ralph; Visseren-Grul, Carla; Spigel, David R; Obasaju, Coleman

    2016-01-01

    Because poor performance status (PS) is an independent prognostic factor in non-small cell lung cancer (NSCLC), PS scores are widely used by oncologists to make treatment decisions. Advanced NSCLC patients with an Eastern Cooperative Oncology Group PS of 2 have poor prognoses and are frequently excluded from clinical trials. This article reviews the efficacy and safety of pemetrexed in this patient group. We identified English-language literature (through March 2015) involving completed and ongoing studies through searches of PubMed, meeting abstracts, ClinicalTrials.gov and the European Clinical Trials Register; search terms included 'pemetrexed,' 'NSCLC' and 'PS2'. Only studies reporting ≥1 subset analysis of PS2 patients receiving pemetrexed were chosen. Our search identified a total of ten pemetrexed studies in PS2 patients. Eight studies included only chemonaive patients, one study included both chemonaive patients and patients with one prior chemotherapy regimen and one study included only patients with one prior regimen. In subset analyses in these studies, PS2 patients had worse outcomes than PS0-1 patients regardless of treatment. In a phase 3 study, chemonaive advanced NSCLC patients with PS2 receiving pemetrexed‑carboplatin versus pemetrexed experienced improved overall survival [hazard ratio (HR)=0.62; P=0.001], progression-free survival (HR=0.46; Pstudies, PS2 patients treated with pemetrexed plus carboplatin as first-line therapy had improved response rates and survival. Additional research on PS2 patients is needed.

  17. Exploring Spatial Overlap of High-Uptake Regions Derived From Dual Tracer Positron Emission Tomography–Computer Tomography Imaging Using 18F-Fluorodeoxyglucose and 18F-Fluorodeoxythymidine in Nonsmall Cell Lung Cancer Patients

    OpenAIRE

    Liu, Jing; Li, Chengqiang; Hu, Man; Lu, Jie; Shi, Xiaorong; XING, LIGANG; Sun, Xindong; FU, ZHENG; YU, JINMING; MENG, XUE

    2015-01-01

    Abstract Interest is growing in radiotherapy to nonuniformly boost radioresistant regions within nonsmall cell lung cancer (NSCLC) using molecular imaging techniques. The complexity of tumor behavior is beyond the ability of any single radiotracer to reveal. We hold dual tracer positron emission tomography–computer tomography (PET/CT) imaging with fluorodeoxyglucose (FDG) and fluorodeoxythymidine (FLT) for NSCLC patients to offer an integrated overlook of tumor biological behaviors quantitati...

  18. Increased Expression of TGFβR2 Is Associated with the Clinical Outcome of Non-Small Cell Lung Cancer Patients Treated with Chemotherapy.

    Directory of Open Access Journals (Sweden)

    Yang Han

    Full Text Available To investigate the prognostic significance of TGFβR2 expression and chemotherapy in Chinese non-small cell lung cancer (NSCLC patients, TGFβR2 expression NSCLC was analyzed in silico using the Oncomine database, and subsequently analyzed with quantitative RT-PCR in 308 NSCLC biopsies, 42 of which were paired with adjacent non-neoplastic tissues. Our results show that TGFβR2 expression was also increased in NSCLC biopsies relative to normal tissue samples and correlated with poor prognosis. TGFβR2 expression was also significantly correlated with other clinical parameters such as tumor differentiation, invasion of lung membrane, and chemotherapy. Moreover, overall survival (OS and disease free survival (DFS was increased in patients with low TGFβR2 expressing NSCLC and who had undergone chemotherapy. Thus, high expression of TGFβR2 is a significant risk factor for decreased OS and DFS in NSCLC patients. Thus, TGFβR2 is a potential prognostic tumor biomarker for chemotherapy.

  19. Increased Expression of TGFβR2 Is Associated with the Clinical Outcome of Non-Small Cell Lung Cancer Patients Treated with Chemotherapy

    Science.gov (United States)

    Yu, Fei; Cai, Haidong; Fang, Suyun; Cai, Li; Yang, Huiqiong; Sun, Yu; Li, Dan; Liu, Jin; Xie, Ruting; Yuan, Xueyu; Zhong, Xiaoming; Li, Ming; Wei, Qing; Lv, Zhongwei; Fu, Da; Ma, Yushui

    2015-01-01

    To investigate the prognostic significance of TGFβR2 expression and chemotherapy in Chinese non-small cell lung cancer (NSCLC) patients, TGFβR2 expression NSCLC was analyzed in silico using the Oncomine database, and subsequently analyzed with quantitative RT-PCR in 308 NSCLC biopsies, 42 of which were paired with adjacent non-neoplastic tissues. Our results show that TGFβR2 expression was also increased in NSCLC biopsies relative to normal tissue samples and correlated with poor prognosis. TGFβR2 expression was also significantly correlated with other clinical parameters such as tumor differentiation, invasion of lung membrane, and chemotherapy. Moreover, overall survival (OS) and disease free survival (DFS) was increased in patients with low TGFβR2 expressing NSCLC and who had undergone chemotherapy. Thus, high expression of TGFβR2 is a significant risk factor for decreased OS and DFS in NSCLC patients. Thus, TGFβR2 is a potential prognostic tumor biomarker for chemotherapy. PMID:26252213

  20. Keratin 34betaE12/keratin7 expression is a prognostic factor of cancer-specific and overall survival in patients with early stage non-small cell lung cancer

    DEFF Research Database (Denmark)

    Pøhl, Mette; Olsen, Karen Ege; Holst, Rene;

    2016-01-01

    proliferation, migration, and possibly cancer invasion, factors impacting prognosis in early stage non-small cell lung cancer (NSCLC). MATERIAL AND METHODS: Tumor tissue from a retrospective Danish cohort of 177 patients with completely resected NSCLC, stage I-IIIA tumors, were analyzed for keratin 7 (K7......BACKGROUND: Carcinomas and their metastases often retain the keratin patterns of their epithelial origin, and are therefore useful as lineage-specific markers in diagnostic pathology. Recently, it has become clear that intermediate filaments composed by keratins play a role in modulation of cell...

  1. Economics of Treatments for Non-Small Cell Lung Cancer

    OpenAIRE

    Christos Chouaid; Kukovi Atsou; Gilles Hejblum; Alain Vergnenegre

    2009-01-01

    The purpose of this article is to review the economics of treatments for non-small cell lung cancer (NSCLC). We systematically analysed the cost effectiveness of treatments for the different stages of NSCLC, with particular emphasis on more recently approved agents. Numerous economic analyses in NSCLC have been conducted, with a variety of methods and in a number of countries. In patients with localized disease, adjuvant chemotherapy appears to have greater cost effectiveness than observation...

  2. Overexpression of ubiquitin-specific protease 22 predicts poor survival in patients with early-stage non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    J. Ning

    2012-11-01

    Full Text Available Ubiquitin-specific protease 22 (USP22, a novel ubiquitin hydrolase, has been implicated in oncogenesis and cancer progression in various types of human cancer. However, the clinical significance of USP22 expression in non-small cell lung cancer (NSCLC has not been determined. In the present study, USP22 messenger RNA (mRNA and protein levels were analyzed by quantitative real-time polymerase chain reaction (PCR and western blot analysis in 30 cases of NSCLC and in corresponding non-tumor tissue samples. Furthermore, immunohistochemistry was performed to detect USP22 protein expression in 86 primary tumor tissues derived from clinically annotated NSCLC cases at stage I-II. In our analysis we found that both USP22 mRNA and protein levels in NSCLC tissues were significantly higher than those in corresponding non-tumor tissues and that there was a significant correlation between the expression of USP22 mRNA and protein (P=0.000, κ=0.732. In addition, a high-level of USP22 expression was observed in 53.3% (39 out of 86 cases and it was correlated with large tumor size (P=0.029 and lymph node metastasis (P=0.026. Patients with tumors displaying a high-level of USP22 expression showed significantly shorter survival (P=0.006, log-rank test. Importantly, multivariate analysis showed that high USP22 protein expression was an independent prognostic factor for NSCLC patients (P=0.003. In sum, our data suggest that USP22 plays an important role in NSCLC progression at the early stage, and that overexpression of USP22 in tumor tissues could be used as a potential prognostic marker for patients with early clinical stage of NSCLC.

  3. EGFR mutations in patients with brain metastases from lung cancer: Association with the efficacy of gefitinib

    OpenAIRE

    Shimato, Shinji; Mitsudomi, Tetsuya; Kosaka, Takayuki; Yatabe, Yasushi; Wakabayashi, Toshihiko; Mizuno, Masaaki; NAKAHARA, NORIMOTO; Hatano, Hisashi; Natsume, Atsushi; Ishii, Dai; YOSHIDA, Jun

    2006-01-01

    Gefitinib—a specific inhibitor of epidermal growth factor receptor (EGFR)-associated tyrosine kinase—has demonstrated efficacy in a subgroup of patients with non-small-cell lung carcinoma (NSCLC) who fail conventional chemotherapy. It is also reported to have an antitumor effect in brain metastases from NSCLC. Additionally, EGFR mutations have shown a strong association with gefitinib sensitivity for NSCLC. Here, we assessed the efficacy of gefitinib in brain metastases from NSCLC and evaluat...

  4. Cancer risks in thyroid cancer patients.

    OpenAIRE

    Hall, P.; Holm, L E; Lundell, G.; Bjelkengren, G.; Larsson, L. G.; Lindberg, S.; Tennvall, J.; Wicklund, H.; Boice, J. D.

    1991-01-01

    Cancer risks were studied in 834 thyroid cancer patients given 131I (4,551 MBq, average) and in 1,121 patients treated by other means in Sweden between 1950 and 1975. Record-linkage with the Swedish Cancer Register identified 99 new cancers more than 2 years after 131I therapy [standardised incidence ratio (SIR) = 1.43; 95% confidence interval (CI) 1.17-1.75] vs 122 (SIR = 1.19; 95% CI 0.88-1.42) in patients not receiving 131I. In females treated with 131I overall SIR was 1.45 (95% CI 1.14-1....

  5. Low claudin-6 expression correlates with poor prognosis in patients with non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Wang Q

    2015-07-01

    Full Text Available Qiang Wang,1 Yan Zhang,1 Tao Zhang,2 Zhi-Gang Han,1 Li Shan1 1Department of Thoracic Oncology, The Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi, Xinjiang Province, 2Department of Oncology, First Hospital of Lanzhou University, Lanzhou, Gansu Province, People’s Republic of China Objective: Claudins are found in junctional complexes mediating cell adhesion and are involved in the attachment of tight junctions to the underlying cytoskeleton. Abnormal claudin-6 expression has been observed for a variety of malignant solid tumors, but the expression of claudin-6 in non-small cell lung cancer (NSCLC has not yet been characterized.Methods: Immunohistochemistry, reverse transcription-polymerase chain reaction (RT-PCR, and western blot analysis were used to quantify claudin-6 expression in 123 cases of NSCLC and non-cancerous adjacent tissue. We analyzed the relationship between claudin-6 expression and clinicopathological features of NSCLC. The Kaplan–Meier method was used to analyze postoperative survival rates, and the log-rank test was used to assess differences in survival rates. The Cox regression model was used to perform multivariate analysis.Results: Claudin-6 expression was low for 61 of 123 (49.6% NSCLC tissue samples and for 33 of 123 (26.8% normal adjacent tissue samples. RT-PCR and western blot analyses confirmed the immunohistochemistry results. Claudin-6 expression was associated with lymph node metastasis (P<0.001 and TNM stage (P=0.007. Kaplan–Meier analysis indicated that patients with low claudin-6 expression had significantly lower survival rates than those with high claudin-6 expression. Multivariate analysis suggested that low claudin-6 expression was an independent indicator of prognosis in NSCLC patients.Conclusion: Low claudin-6 expression is an independent prognostic biomarker that indicates a worse prognosis in patients with NSCLC. Keywords: NSCLC, claudin-6, immunohistochemistry, RT-PCR, western

  6. The Efficacy Evaluation of Serum Tumor Marker in Advanced Non-small Cell Lung Cancer%血清肿瘤标志物对晚期 NSCLC 放疗疗效的评估价值

    Institute of Scientific and Technical Information of China (English)

    王杰; 胡学宁; 陈大兴

    2014-01-01

    目的:探讨放疗近期疗效与血清肿瘤标志物含量的关系。方法回顾性分析196例晚期非小细胞肺癌( non-small-cell carcinoma ,NSCLC)患者放疗前后血清中CEA、CYFAR21-1、SCC、CA125的水平变化,同时通过临床症状等资料评价放疗的近期效果,以此探讨放疗的近期疗效与肿瘤标志物变化的关系。结果196例患者中有109例在接受放疗后有效,总有效率为55.61%。放疗有效的患者在放疗后常规检查血清中CEA、CYFAR21-1、SCC、CA125含量与放疗前比较,明显减少,且差异具有统计学意义(P<0.05);接受放疗后肿瘤标志物降低组的110例患者近期疗效显著好于升高组,差异具有统计学意义(P<0.05)。结论血清肿瘤标志物CEA、CYFAR21-1、SCC、CA125的含量或可以用来评价放疗对晚期NSCLC的近期效果。%Objective To investigate the relation between short-term efficacy of radiotherapy and serum levels of tumor markers in advanced non-small cell lung cancer before and after radiotherapy in patients with serum CEA , CYFAR21-1, SCC, CA125 levels change.Methods Serum levels of CEA,CYFAR21-1,SCC,CA125 in 196 cases of advanced non-small cell lung cancer patients before and after radiotherapy were retrospectively analyzed .Short-term effects were evaluated by clinical symp-toms,and the relationship between the short-term efficacy of radiotherapy and tumor markers changes was investigated .Results Among the 196 patients,109 cases of patients were effective after radiotherapy ,the total effective rate was 53.06%.The routine examination of effective cases showed that serum levels of CEA ,CYFAR21-1,SCC,CA125 significantly reduced after radiothera-py,the difference was statistically significant (P<0.05);serum levels of CEA,CYFAR21-1,SCC,CA125 significantly reduced af-ter radiotherapy in 110 patients,and their short-term efficacy was better than that those patients with increased serum tumor mark

  7. Decreased levels of serum cytokeratin 19 fragment CYFRA 21-1 predict objective response to chemotherapy in patients with non-small cell lung cancer

    OpenAIRE

    Pang, Li; Jing WANG; Jiang, Yanwen; Chen, Liangan

    2013-01-01

    Diagnostic tools capable of predicting early responses to chemotherapy are required to improve the individual management of cancer patients. The present study aimed to evaluate the prognostic significance of the serum tumor markers CYFRA 21-1, carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), carbohydrate antigen (CA) 125, and CA 19-9 for predicting responses to different chemotherapy regimens in patients with non-small cell lung cancer (NSCLC). A total of 276 patients with posto...

  8. 苦参注射液联合紫杉醇同步调强放疗对局部晚期非小细胞肺癌患者生活质量的影响%Effects of concurrent chemoradiotherapy of KUSHEN injection plus paclitaxel with IMRT radiotherapy on quality of life in late stage NSCLC patients

    Institute of Scientific and Technical Information of China (English)

    陆红; 周涛; 佘文莉

    2011-01-01

    目的:观察复方苦参注射液联合周剂量紫杉醇同步调强放射(intensity modulated radiation therapy,IMRT)治疗局部晚期非小细胞肺癌(non-small lung cancer,NSCLC)的放射性肺损伤及对生活质量的影响.方法:64例局部晚期非小细胞肺癌患者随机分为治疗组及对照组,32例治疗组应用复方苦参注射液联合周剂量紫杉醇同步IMRT,32例对照组应用周剂量紫杉醇同步IMRT.结果:所有的患者均完成了放疗计划,按照RTOG放疗毒副反应评价标准,治疗组Ⅰ-Ⅱ级急性放射性肺损伤及慢性放射性肺损伤的发生率明显低于对照组(P<0.05);放射治疗过程中,生活质量除社会家庭状况及情感状况外其他领域均有明显差异(P<0.05),放射治疗结束后生活质量的功能状况、附加关注及量表总分比较有显著性差异(P<0.05).结论:复方苦参注射液联合调强放射治疗局部晚期非小细胞肺癌,可以减少放射性肺损伤的放射率,提高患者放射治疗过程中及放射治疗后的生活质量.%Aim: To observe effects of concurrent chemoradiotherapy of palitaxel and KUSHEN with IMRT( intensity modulated radiation therapy, IMRT) radiotherapy on quality of life in late stage NSCLC (non-small lung cancer, NSCLC) patients. Methods: Sixty-four NSCLC patients were randomly divided into treatment and control groups. The thirty -two cases treatment group was treated by kushen injection plus paclitaxel with IMRT radiotherapy, and the control group was treated by paclitaxel with IMRT radiotherapy.Results: After treatment, the radiotherapy side effects was recorded according to the RTOG grading. It showed that the rate of grade Ⅰ-Ⅱ radiotherapy side effects in treatment group was less than that of control( P < 0.05 ), and during the radiotherapy the quality of life in these patients was better than that of control(P <0.05 ), and after treatment the assay showed that the quality of life in these patients was better

  9. Nutrition in Cancer Patients

    OpenAIRE

    Dintinjana, Renata Dobrila; Redžović, Arnela; Čubranić, Aleksandar; Dintinjana, Marin; Vanis, Nenad

    2014-01-01

    Cachexia is defi ned as an unintended loss of stable weight exceeding 10%. Patients with advanced cachexia express anorexia, early satiety, severe weight loss, weakness, anemia, and edema. Anorexia represents the result of a failure of the usual appetite signals whereas cachexia is the debilitating state of involuntary weight loss. This syndrome, referred to as the »cancer anorexia-cachexia syndrome« (CACS) and usually consists of a combination of anorexia, tissue wasting, malnutr...

  10. THE EFFECTS OF MRP GENE mRNA OVEREXPRESSION ON THE PROGNOSIS IN LUNG CANCER PATIENTS

    Institute of Scientific and Technical Information of China (English)

    单根法; 钟竑; 张辅贤

    2000-01-01

    Objectire To study the effects of multi-drug resistance associated protein gene (MRP gene)overexpression on the prognosis of patients with lung cancer. Methods Paraffin- embedded tissues taken from radical resection of 47 cases suffering from non- small cell lung cancer (NSCLC) were determined for the expression of MRP gene mRNA by in situ hybridization using labelled digoxigenin probes combined with immunohistochemistry. All the patients had been followed-up from 6 months to 3 years. Results The overexpression of MRP gene mRNA of all the 47 lung cancer specimens was found to be obviously related with survival time, effects of chemotherapy, recurrence or metastases after surgery, but not related with histology, tumor size, node metastases, TNM stages, age and sex. Conclusion MRP gene mRNA expression is correlated with the prognosis of lung cancer patients and may be regarded as an indicator to forecast the prognosis and to choose the chemotherapy for lung cancer patients.

  11. Time evolution of regional CT density changes in normal lung after IMRT for NSCLC

    International Nuclear Information System (INIS)

    Purpose: This study investigates the clinical radiobiology of radiation induced lung disease in terms of regional computed tomography (CT) density changes following intensity modulated radiotherapy (IMRT) for non-small-cell lung cancer (NSCLC). Methods: A total of 387 follow-up CT scans in 131 NSCLC patients receiving IMRT to a prescribed dose of 60 or 66 Gy in 2 Gy fractions were analyzed. The dose-dependent temporal evolution of the density change was analyzed using a two-component model, a superposition of an early, transient component and a late, persistent component. Results: The CT density of healthy lung tissue was observed to increase significantly (p 12 months. Conclusions: The radiobiology of lung injury may be analyzed in terms of CT density change. The initial transient change in density is consistent with radiation pneumonitis, while the subsequent stabilization of the density is consistent with pulmonary fibrosis

  12. The influence of the pituitary tumor transforming gene-1 (PTTG-1 on survival of patients with small cell lung cancer and non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Geddert Helene

    2006-01-01

    Full Text Available Abstract Background PTTG-1 (pituitary tumor transforming gene is a novel oncogene that is overexpressed in tumors, such as pituitary adenoma, breast and gastrointestinal cancers as well as in leukemia. In this study, we examined the role of PTTG-1 expression in lung cancer with regard to histological subtype, the correlation of PTTG-1 to clinical parameters and relation on patients' survival. Methods Expression of PTTG-1 was examined immunohistochemically on formalin-fixed, paraffin-embedded tissue sections of 136 patients with small cell lung cancer (SCLC and 91 patients with non-small cell lung cancer (NSCLC, retrospectively. The intensity of PTTG-1 expression as well as the proportion of PTTG-1 positive cells within a tumor was used for univariate and multivariate analysis. Results PTTG-1 expression was observed in 64% of SCLC tumors and in 97.8% of NSCLC tumors. In patients with SCLC, negative or low PTTG-1 expression was associated with a shorter mean survival time compared with patients with strong PTTG-1 expression (265 ± 18 days vs. 379 ± 66 days; p = 0.0291. Using the Cox regression model for multivariate analysis, PTTG-1 expression was a significant predictor for survival next to performance status, tumor stage, LDH and hemoglobin. In contrast, in patients with NSCLC an inverse correlation between survival and PTTG-1 expression was seen. Strong PTTG-1 expression was associated with a shorter mean survival of 306 ± 58 days compared with 463 ± 55 days for those patients with no or low PTTG-1 intensities (p = 0.0386. Further, PTTG-1 expression was associated with a more aggressive NSCLC phenotype with an advanced pathological stage, extensive lymph node metastases, distant metastases and increased LDH level. Multivariate analysis using Cox regression confirmed the prognostic relevance of PTTG-1 expression next to performance status and tumor stage in patients with NSCLC. Conclusion Lung cancers belong to the group of tumors expressing

  13. A rehabilitation program for lung cancer patients during postthoracotomy chemotherapy

    Directory of Open Access Journals (Sweden)

    Hoffman AJ

    2014-03-01

    Full Text Available Amy J Hoffman,1 Ruth Ann Brintnall,2 Alexander von Eye,3 Lee W Jones,4 Gordon Alderink,5 Lawrence H Patzelt,6 Jean K Brown7 1College of Nursing, Michigan State University, East Lansing, MI, USA; 2Kirkhof College of Nursing, Grand Valley State University, Grand Rapids, MI, USA; 3Psychology Department, Michigan State University, East Lansing, MI, USA; 4Duke Center for Cancer Survivorship Department of Radiation Oncology, Duke University Medical Center, Durham, NC, USA; 5Frederik Meijer Honors College, Grand Valley State University, Grand Rapids, MI, USA; 6Spectrum Health, Grand Rapids, MI, USA and College of Human Medicine, Michigan State University, East Lansing, MI, USA; 7School of Nursing, University at Buffalo, the State University of New York, Buffalo, NY, USA Objective: The objective of this pilot study was to describe the effects of a 16-week home-based rehabilitative exercise program on cancer-related fatigue (CRF, other symptoms, functional status, and quality of life (QOL for patients with non-small cell lung cancer (NSCLC after thoracotomy starting within days after hospital discharge and continuing through the initiation and completion of chemotherapy. Materials and methods: Five patients with NSCLC completed the Brief Fatigue Inventory (measuring CRF severity and the MD Anderson Symptom Inventory (measuring symptom severity before and after thoractomy, and at the end of each week of the 16-week exercise program. Additionally, the Medical Outcomes Study Short Form-36 (measuring physical and mental functional status and the Quality of Life Index (measuring QOL were completed before and after thoracotomy, after weeks 3, 6, 12, and 16 (the end of the exercise program. Further, the 6-minute walk test (measuring functional capacity was administered before thoracotomy, prior to the initiation of chemotherapy and/or radiation therapy, and at the end of the 16-week exercise program, after completion of chemotherapy. Results: Participants had a

  14. Expression of Ribonucleotide Reductase Subunit-2 and Thymidylate Synthase Correlates with Poor Prognosis in Patients with Resected Stages I–III Non-Small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Francesco Grossi

    2015-01-01

    Full Text Available Biomarkers can help to identify patients with early-stages or locally advanced non-small cell lung cancer (NSCLC who have high risk of relapse and poor prognosis. To correlate the expression of seven biomarkers involved in DNA synthesis and repair and in cell division with clinical outcome, we consecutively collected 82 tumour tissues from radically resected NSCLC patients. The following biomarkers were investigated using IHC and qRT-PCR: excision repair cross-complementation group 1 (ERCC1, breast cancer 1 (BRCA1, ribonucleotide reductase subunits M1 and M2 (RRM1 and RRM2, subunit p53R2, thymidylate synthase (TS, and class III beta-tubulin (TUBB3. Gene expression levels were also validated in an available NSCLC microarray dataset. Multivariate analysis identified the protein overexpression of RRM2 and TS as independent prognostic factors of shorter overall survival (OS. Kaplan-Meier analysis showed a trend in shorter OS for patients with RRM2, TS, and ERCC1, BRCA1 overexpressed tumours. For all of the biomarkers except TUBB3, the OS trends relative to the gene expression levels were in agreement with those relative to the protein expression levels. The NSCLC microarray dataset showed RRM2 and TS as biomarkers significantly associated with OS. This study suggests that high expression levels of RRM2 and TS might be negative prognostic factors for resected NSCLC patients.

  15. The Role of Epidermal Growth Factor Receptor Mutations and Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors in the Treatment of Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Shih-Chieh [Department of Internal Medicine, National Yang-Ming University Hospital, Yilan 260, Taiwan (China); Chang, Cheng-Yu [Department of Chest Medicine, Far Eastern Memorial Hospital, Taipei 220, Taiwan (China); Shih, Jin-Yuan, E-mail: jyshih@ntu.edu.tw [Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei 100, Taiwan (China)

    2011-06-10

    Lung cancer is the leading cause of cancer-related deaths worldwide. Non-small-cell lung cancer (NSCLC) cases comprise approximately 85% of the lung cancer cases. Before the era of target therapy, platinum-based doublet chemotherapy only led to a median survival of 8–9 months and a one-year survival of 30%–40% in patients with advanced NSCLC. In July 2002, gefitinib, a small-molecule epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), was approved for the treatment of patients with advanced NSCLC in Japan. After the widespread use of gefitinib in the treatment of NSCLC, there have been many new studies regarding the association between the clinical anticancer efficacy of gefitinib and the somatic EGFR mutation status in patients with NSCLC. This article summarizes the role of EGFR mutations in lung cancer and the use of EGFR antagonists in the treatment of lung cancer and its associated adverse effects.

  16. Genetic variants in ABCG1 are associated with survival of nonsmall-cell lung cancer patients.

    Science.gov (United States)

    Wang, Yanru; Liu, Hongliang; Ready, Neal E; Su, Li; Wei, Yongyue; Christiani, David C; Wei, Qingyi

    2016-06-01

    Cell membrane transporters and metabolic enzymes play a crucial role in the transportation of a wide variety of substrates that maintain homeostasis in biological processes. We explored associations between genetic variants in these genes and survival of nonsmall-cell lung cancer (NSCLC) patients by reanalyzing two datasets from published genome-wide association studies (GWASs). In the discovery by using the GWAS dataset of the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, we evaluated associations of 1,245 single-nucleotide polymorphisms (SNPs) in genes of four transporter families and two metabolic enzyme families with survival of 1,185 NSCLC patients. We then performed a replication analysis in the Harvard University Lung Cancer study (LCS) with 984 NSCLC patients. Multivariate Cox proportional hazards regression and false discovery rate (FDR) corrections were performed to evaluate the associations. We identified that 21 genotyped SNPs in eight gene regions were significantly associated with survival with FDR ≤ 0.1 in the discovery dataset. Subsequently, we confirmed six SNPs, which were putative functional, in ABCG1 of the ATP-binding cassette transporter family in the replication dataset. In the pooled analysis, two tagging (at r(2)  > 0.8 for linkage disequilibrium with other replicated SNPs)/functional SNPs were independently associated with survival: rs225388 G > A [adjusted hazards ratio (HR) = 1.12, 95% confidence interval (CI) = 1.03-1.20, Ptrend  = 4.6 × 10(-3)] and rs225390 A > G (adjusted HR = 1.16, 95% CI = 1.07-1.25, Ptrend  = 3.8 × 10(-4) ). Our results indicated that genetic variants of ABCG1 may be predictors of survival of NSCLC patients.

  17. Venous thromboembolism in cancer patients

    Directory of Open Access Journals (Sweden)

    Mehmet Fuat Eren

    2013-09-01

    Full Text Available Venous thromboembolism (VTE is a major complication of cancer and represents an important cause of morbidity and mortality. The incidence of VTE is 0.6-7.8% in patients with cancer more than double the incidence of VTE in patients without cancer. The risk of VTE which includes deep venous thrombosis (DVT and pulmonary embolism (PE is increased two to seven fold in patients with cancer. VTE risk is especially high among certain groups such as hospitalized patients with cancer and those receiving active antineoplastic therapy. Also cancer patients, who undergoing major surgery, are increased risk of VTE. Trauma, long-haul travel, increased age, obesity, previous VTE and genetic component are also predisposing factors for VTE. Patients with cancer who develop VTE should be managed multidisciplinary treatment guidelines. The primary goal of thromboprophylaxis in patients with cancer is to prevent VTE. The large majority of cancer patients should be treated with therapeutic doses of unfractioned heparin (UFH or low molecular weight heparin (LMWH. Prophylaxis should include cancer patients who underwent major surgery for cancer and patients with a history of VTE.

  18. miR-125a-3p targets MTA1 to suppress NSCLC cell proliferation, migration, and invasion.

    Science.gov (United States)

    Zhang, Hong; Zhu, Xiaoxia; Li, Na; Li, Dianhe; Sha, Zhou; Zheng, Xiaokang; Wang, Haofei

    2015-07-01

    Metastasis-associated gene 1 (MTA1) is associated with cell growth, metastasis, and survival in non-small-cell lung cancer (NSCLC). Several previous reports have demonstrated that microRNAs affect gene expression through interaction between their seed region and the 3'-untranslated region of the target mRNA, resulting in post-transcriptional regulation. The aim of this study was to identify miRNAs that suppress malignancy in NSCLC cells by targeting MTA1. Two human NSCLC cell lines were analyzed for the expression of MTA1 by quantitative RT-PCR and western blotting after transfection with MTA1 mimics. A luciferase reporter assay was established to test the direct connection between MTA1 and its upstream miRNAs. Cell proliferation was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, 5-ethynyl-2'-deoxyuridine analysis, and colony formation assay. Cell migration and invasive capacity were evaluated by wound-healing assay and transwell assay. The miRNA/MTA1 axis was also probed by quantitative RT-PCR and western blotting in samples from eight NSCLC patients. Among the candidate miRNAs, miR-125a-3p was shown to post-transcriptionally regulate MTA1 in NSCLC cells. These data were reinforced by the luciferase reporter assay, in addition to the demonstration that MTA1 is inversely correlated with miR-125a-3p in NSCLC tissues. Furthermore, miR-125a-3p was found to inhibit NSCLC cell proliferation, migration, and invasion, through the same mechanisms of down-regulated MTA1. Our report demonstrates that miR-125a-3p inhibits the proliferation, migration, and invasion of NSCLC cells through down-regulation of MTA1, indicating the role of the miR-125a-3p/MTA1 axis in NSCLC, and may provide novel insight into the molecular mechanisms underpinning the disease and potential therapeutic targets. PMID:25998575

  19. Patient characteristics, treatment and survival in pulmonary carcinoid tumours: an analysis from the UK National Lung Cancer Audit

    Science.gov (United States)

    Hobbins, Stephanie; West, Doug; Peake, Michael; Beckett, Paul; Woolhouse, Ian

    2016-01-01

    Objectives Pulmonary carcinoid (PC) is a rare tumour with good prognosis following surgical resection. However, little is known regarding patient characteristics and use of other treatments modalities. Our objective was to review patient characteristics, treatment and survival for patients with PC and contrast these results with other forms of non-small cell lung cancer (NSCLC). Setting Audit data from UK National Lung Cancer Audit (NLCA) 2008–2013. Participants 184 906 lung cancer cases were submitted to the NLCA. Outcome measures Primary outcome—survival rates between PC and NSCLC. Secondary outcome—differences in performance status, lung function and treatment modality between PC and NSCLC. Results PC histology was recorded in 1341 (0.73%) patients and non-carcinoid NSCLC histology in 162 959 (87.4%) cases. 91% of patients with PC had good performance status (Eastern Cooperative Oncology Group (ECOG) 0–1), compared with only 53% of NSCLC. 66% of PC had localised disease. Of all PC cases, 77% were treated with surgery, 6.2% received chemotherapy and 3.6% received radiotherapy, with the remainder treated with best supportive care. Overall 1-year and 3-year survival rates for PC were 92% and 84.7%, respectively. In contrast, 1-year and 3-year survival rates for NSCLC were 36.2% and 15.6%, However, 3-year survival for PC markedly decreased with worsening performance status and advanced disease to 23.8% for performance status ECOG 3–4 and 33.6% for stage IV disease. Conclusions In contrast to other forms of NSCLC, the majority of patients with PC present with good performance status, preserved lung function and early stage disease amenable to surgical resection. However, 1 in 5 patients with PC has metastatic disease which is associated with poor prognosis, as is poor performance status at presentation. We believe these data will help clinicians provide accurate prognostic predictions stratified according to patient characteristics at presentation, as

  20. Outcome of surgical resection for brain metastases and radical treatment of the primary tumor in Chinese non–small-cell lung cancer patients

    Directory of Open Access Journals (Sweden)

    Li Z

    2015-04-01

    Full Text Available Zhenye Li,1,3,* Xiangheng Zhang,1,* Xiaobing Jiang,1 Chengcheng Guo,1 Ke Sai,1 Qunying Yang,1 Zhenqiang He,1 Yang Wang,1 Zhongping Chen,1 Wei Li,2 Yonggao Mou1 1Department of Neurosurgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China; 2Department of Anesthesiology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China; 3Beijing Neurosurgical Institute, Capital Medical University, Beijing, People’s Republic of China *These authors have contributed equally to this work Purpose: Brain metastasis is the most common complication of brain cancer; nevertheless, primary lung cancer accounts for approximately 20%–40% of brain metastases cases. Surgical resection is the preferred treatment for brain metastases. However, no studies have reported the outcome of surgical resection of brain metastases from non–small-cell lung cancer (NSCLC in the People’s Republic of China. Moreover, the optimal treatment for primary NSCLC in patients with synchronous brain metastases is hitherto controversial. Patients and methods: We retrospectively analyzed the cases of NSCLC patients with brain metastases who underwent neurosurgical resection at the Sun Yat-sen University Cancer Center, and assessed the efficacy of surgical resection and the necessity of aggressive treatment for primary NSCLC in synchronous brain metastases patients. Results: A total of 62 patients, including 47 men and 15 women, with brain metastases from NSCLC were enrolled in the study. The median age at the time of craniotomy was 54 years (range 29–76 years. At the final follow-up evaluation, 50 patients had died. The median OS time was 15.1 months, and the survival rates were 70% and 37% at 1 and 2 years, respectively. The median OS

  1. Perioperative Rehabilitation in Operable Lung Cancer Patients (PROLUCA)

    DEFF Research Database (Denmark)

    Sommer, Maja S; Trier, Karen; Vibe-Petersen, Jette;

    2016-01-01

    Introduction Surgical resection in patients with non-small cell lung cancer (NSCLC) may be associated with significant morbidity, functional limitations, and decreased quality of life. Objectives The safety and feasibility of a preoperative and early postoperative rehabilitation program in patients...... randomly assigned to 1 of 4 groups (3 intervention groups and 1 control group). The preoperative intervention consisted of a home-based exercise program, while the postoperative exercise program comprised a supervised group exercise program involving resistance and high-intensity interval cardiorespiratory......% of the patients randomized to this intervention. No adverse events were observed, indicating that the early postoperative exercise program is safe. The preoperative home-based exercise program was not feasible due to interfering diagnostic procedures and fast-track surgery that left only 1 to 2 weeks between...

  2. Pain in patients with cancer

    NARCIS (Netherlands)

    Vissers, K.C.P.; Besse, K.; Wagemans, M.; Zuurmond, W.; Giezeman, M.J.; Lataster, A.; Mekhail, N.; Burton, A.W.; Kleef, M. van; Huygen, F.

    2011-01-01

    Pain in patients with cancer can be refractory to pharmacological treatment or intolerable side effects of pharmacological treatment may seriously disturb patients' quality of life. Specific interventional pain management techniques can be an effective alternative for those patients. The appropriate

  3. Endoscopic ultrasonography/fine-needle aspiration and endobronchial ultrasonography/fine-needle aspiration for lung cancer staging.

    Science.gov (United States)

    Lankarani, Ali; Wallace, Michael B

    2012-04-01

    This article reviews different techniques available for diagnosis and staging of patients with non-small cell lung cancer (NSCLC). The advantages and disadvantages of each staging method are highlighted. The role of the gastroenterologist in NSCLC staging is explored. A new algorithm is proposed for the staging of NSCLC that incorporates endoscopic and endobronchial ultrasonography for mediastinal staging in patients with intrathoracic disease. PMID:22632944

  4. The prognostic value of KRAS mutated plasma DNA in advanced non-small cell lung cancer

    DEFF Research Database (Denmark)

    Nygaard, Anneli Dowler; Garm Spindler, Karen-Lise; Pallisgaard, Niels;

    2013-01-01

    DNA) in the blood allows for tumour specific analyses, including KRAS-mutations, and the aim of the study was to investigate the possible prognostic value of plasma mutated KRAS (pmKRAS) in patients with non-small cell lung cancer (NSCLC). MATERIAL AND METHODS: Patients with newly diagnosed, advanced NSCLC eligible...

  5. Analysis of the Factors Associated with Abnormal Coagulation and Prognosis
in Patients with Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Yanhua LI

    2014-11-01

    Full Text Available Background and objective The activation of coagulation and fibrinolysis is frequently encountered among cancer patients. Such tumors are associated with high risk of invasion, metastases, and negative final outcomes. Non-small cell lung cancer (NSCLC accounts for approximately 80% to 85% of all lung malignancies. This study aims to investigate the prognostic value of blood coagulation tests for NSCLC and provide a reference to patients on the prevention and treatment of thrombophilia. Methods Data were collected from 604 cases of hospitalized patients with histologically confirmed NSCLC from January 2009 to December 2012 at the Fourth Hospital of Hebei Medical University. Data included the related indexes of coagulation function in patients before treatment [(i.e., prothrombin time (PT, prothrombin time activity (PTA, international normalized ratio (INR, activated partial thromboplastin time (APTT, fibrinogen (Fib, D-dimer, and platelet count], as well as sex, age, pathological type, TNM stage, and lymph node status. Fifty control subjects without cancer were included in the analysis. Statistical analysis was conducted by using SPSS 13.0 software. Results The plasma level of all coagulation tests including D-dimer, Fib, PT, APTT, INR, and platelet counts revealed statistically significant differences between the patient and control group (P<0.001 for all variables; P=0.001,5 and P=0.004,5 for Fib and platelet counts, respectively. The squamous subtype exhibited high plasma Fib levels (P<0.001 compared with adenocarcinoma cell lung cancer patients. Fib and PLT levels increased (P<0.001 and P=0.014, respectively, and aPTT decreased (P<0.001 in patients at stages III and IV compared with those in patients at stages I and II. aPTT decreased significantly (P<0.001, and Fib and D-dimer levels increased (P<0.001 and P=0.048, respectively in N1-3 patients with NSCLC compared with those of N0 patients. Prolonged PT and INR, high plasma Fib levels, and

  6. Relationship between EGFR and KRAS mutations and prognosis in Chinese patients with non-small cell lung cancer:a mutation analysis with real-time polymerase chain reaction using scorpion amplification refractory mutation system

    Institute of Scientific and Technical Information of China (English)

    高洁

    2012-01-01

    Objective To investigate the gene mutation of EGFR and KRAS in Chinese patients with non-small cell lung cancer (NSCLC) ,and to analyze the relationship between the gene mutations and the clinicopathological features and EGFR-TKI efficiency. Methods EGFR mutation was detected in 120 patients and KRAS mutation in 104 patients

  7. Monocarboxylate transporters 1-4 in NSCLC: MCT1 is an independent prognostic marker for survival.

    Directory of Open Access Journals (Sweden)

    Marte Eilertsen

    Full Text Available INTRODUCTION: Monocarboxylate transporters (MCTs 1-4 are lactate transporters crucial for cancers cells adaption to upregulated glycolysis. Herein, we aimed to explore their prognostic impact on disease-specific survival (DSS in both cancer and tumor stromal cells in NSCLC. METHODS: Tissue micro arrays (TMAs were constructed, representing both cancer and stromal tumor tissue from 335 unselected patients diagnosed with stage I-IIIA NSCLC. Immunohistochemistry was used to evaluate the expression of MCT1-4. RESULTS: In univariate analyses; ↓ MCT1 (P = 0.021 and ↑ MCT4 (P = 0.027 expression in cancer cells, and ↑ MCT1 (P = 0.003, ↓ MCT2 (P = 0.006, ↓ MCT3 (P = 0.020 expression in stromal cells correlated significantly with a poor DSS. In multivariate analyses; ↓ MCT1 expression in cancer cells (HR: 1.9, CI 95%: 1.3-2.8, P = 0.001, ↓ MCT2 (HR: 2.4, CI 95%: 1.5-3.9, P<0.001, ↓ MCT3 (HR: 1.9, CI 95%: 1.1-3.5, P = 0.031 and ↑ MCT1 expression in stromal cells (HR: 1.7, CI 95%: 1.1-2.7, P = 0.016 were significant independent poor prognostic markers for DSS. CONCLUSIONS: We provide novel information of MCT1 as a candidate marker for prognostic stratification in NSCLC. Interestingly, MCT1 shows diverging, independent prognostic impact in the cancer cell and stromal cell compartments.

  8. Nomogram to Predict Occult N2 Lymph Nodes Metastases in Patients With Squamous Nonsmall Cell Lung Cancer

    OpenAIRE

    Jiang, Long; Jiang, Shanshan; Lin, Yongbin; Yang, Han; Xie, Zehua; Lin, Yaobin; Long, Hao

    2015-01-01

    Abstract For nonsmall cell lung cancer (NSCLC) patients without distant metastases, occult involvement of N2 lymph nodes would be of the utmost importance in determining both treatment and survival. The key to optimal treatment strategies relied on accurate diagnosis, in particular accurate clinical tumor staging. Patients with clinical N0 or N1 staging preoperatively had a sizeable risk to have occult N2 lymph nodes metastases. From November 2004 to March 2007, the entire database in a terti...

  9. Elevated Pretreatment Serum Concentration of YKL-40-An Independent Prognostic Biomarker for Poor Survival in Patients With Metastatic Nonsmall Cell Lung Cancer

    DEFF Research Database (Denmark)

    Thom, I.; Andritzky, B.; Schuch, G.;

    2010-01-01

    BACKGROUND: The glycoprotein YKL-40 is synthesized both by cancer cells and by tumor-associated macrophages and plays a functional role in tumor progression. Consequently, high serum YKL-40 levels have been associated with a poor prognosis in patients with several cancer types. However, the role ...... was identified as a new, independent prognostic biomarker in patients with metastatic NSCLC and may help to determine the individual prognosis of these patients. Cancer 2010;116:4114-21. (C) 2010 American Cancer Society......BACKGROUND: The glycoprotein YKL-40 is synthesized both by cancer cells and by tumor-associated macrophages and plays a functional role in tumor progression. Consequently, high serum YKL-40 levels have been associated with a poor prognosis in patients with several cancer types. However, the role of...... YKL-40 has not been established in non-small cell lung cancer (NSCLC). METHODS: Pretreatment serum levels of YKL-40 were determined in 189 patients with NSCLC (143 men and 46 women; median age, 62 years;, age range, 41-76 years). Twelve percent of patients had stage IIIB disease, and 88% had stage IV...

  10. Afatinib: emerging next-generation tyrosine kinase inhibitor for NSCLC

    Directory of Open Access Journals (Sweden)

    Nelson V

    2013-03-01

    Full Text Available Valerie Nelson, Jacqueline Ziehr, Mark Agulnik, Melissa JohnsonRobert H Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, USAAbstract: The discovery of epidermal growth-factor receptor (EGFR-activating mutations and the introduction of oral EGFR tyrosine kinase inhibitors (EGFR-TKIs have expanded the treatment options for patients with non-small cell lung cancer. The first two reversible EGFR-TKIs, erlotinib and gefitinib, are approved for use in the first-line setting in patients with known EGFR-activating mutations and in the second- and third-line settings for all NSCLC patients. These first-generation EGFR-TKIs improve progression-free survival when compared to chemotherapy in patients with EGFR-activating mutations in the first-line setting. However, nearly all patients develop resistance to EGFR-directed agents. There is a need for further therapy options for patients with disease progression after treatment with reversible EGFR-TKIs. Afatinib is an irreversible ErbB family blocker that inhibits EGFR, HER2, and HER4. In vitro and in vivo, afatinib have shown increased inhibition of the common EGFR-activating mutations as well as the T790M resistance mutation when compared to erlotinib and gefitinib. Clinically, afatinib has been evaluated in the LUX-Lung series of trials, with improvement in progression-free survival reported in patients with EGFR-activating mutations in both first- and second-/third-line settings when compared to chemotherapy. Further investigation is needed to determine the precise role that afatinib will play in the treatment of patients with non-small cell lung cancer and EGFR-activating mutations.Keywords: afatinib, EGFR, irreversible EGFR inhibitor, EGPR-TKIs, LUX lung, resistance mutation, targeted therapy

  11. Prediction of lung density changes after radiotherapy by cone beam computed tomography response markers and pre-treatment factors for non-small cell lung cancer patients

    DEFF Research Database (Denmark)

    Bernchou, Uffe; Hansen, Olfred; Schytte, Tine;

    2015-01-01

    BACKGROUND AND PURPOSE: This study investigates the ability of pre-treatment factors and response markers extracted from standard cone-beam computed tomography (CBCT) images to predict the lung density changes induced by radiotherapy for non-small cell lung cancer (NSCLC) patients. METHODS...

  12. Multivariable normal-tissue complication modeling of acute esophageal toxicity in advanced stage non-small cell lung cancer patients treated with intensity-modulated (chemo-)radiotherapy

    NARCIS (Netherlands)

    Wijsman, R.; Dankers, F.; Troost, E.G.; Hoffman, A.L.; Heijden, E. van der; Geus-Oei, L.F. de; Bussink, J.

    2015-01-01

    BACKGROUND AND PURPOSE: The majority of normal-tissue complication probability (NTCP) models for acute esophageal toxicity (AET) in advanced stage non-small cell lung cancer (AS-NSCLC) patients treated with (chemo-)radiotherapy are based on three-dimensional conformal radiotherapy (3D-CRT). Due to d

  13. Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer

    DEFF Research Database (Denmark)

    Scagliotti, G.V.; Parikh, P.; Pawel, J. von;

    2008-01-01

    Purpose Cisplatin plus gemcitabine is a standard regimen for first-line treatment of advanced non-small-cell lung cancer (NSCLC). Phase II studies of pemetrexed plus platinum compounds have also shown activity in this setting. Patients and Methods This noninferiority, phase III, randomized study ...... neutropenia (P = .002); and alopecia (P

  14. Influence of comorbidity on survival, toxicity and health-related quality of life in patients with advanced non-small-cell lung cancer receiving platinum-doublet chemotherapy

    DEFF Research Database (Denmark)

    Grønberg, Bjørn H; Sundstrøm, Stein; Kaasa, Stein;

    2010-01-01

    AIM OF THE STUDY: To investigate whether patients with severe comorbidity receiving platinum-based chemotherapy for advanced non-small-cell lung cancer (NSCLC) have a shorter overall survival, experience more toxicity or more deterioration of health-related quality of life (HRQoL) than other...

  15. Gemcitabine plus best supportive care (BSC) vs BSC in inoperable non-small cell lung cancer--a randomized trial with quality of life as the primary outcome. UK NSCLC Gemcitabine Group. Non-Small Cell Lung Cancer.

    Science.gov (United States)

    Anderson, H; Hopwood, P; Stephens, R J; Thatcher, N; Cottier, B; Nicholson, M; Milroy, R; Maughan, T S; Falk, S J; Bond, M G; Burt, P A; Connolly, C K; McIllmurray, M B; Carmichael, J

    2000-08-01

    Three hundred patients with symptomatic, locally advanced or metastatic NSCLC not requiring immediate radiotherapy were enrolled into this randomized multicentre trial comparing gemcitabine + BSC vs BSC alone. Patients allocated gemcitabine received 1000 mg/m2 on days 1, 8 and 15 of a 28-day cycle, for a maximum of six cycles. The main aim of this trial was to compare patient assessment of a predefined subset of commonly reported symptoms (SS14) from the EORTC QLQ-C30 and LC13 scales. The primary end-points were defined as (1) the percentage change in mean SS14 score between baseline and 2 months and (2) the proportion of patients with a marked (> or = 25%) improvement in SS14 score between baseline and 2 months sustained for > or =4 weeks. The secondary objectives were to compare treatments with respect to overall survival, and multidimensional QL parameters. The treatment groups were balanced with regard to age, gender, Karnofsky performance status (KPS) and disease stage (40% had metastatic disease). The percentage change in mean SS14 score from baseline to 2 months was a 10% decrease (i.e. improvement) for gemcitabine plus BSC and a 1% increase (i.e. deterioration) for BSC alone (P = 0.113, two-sample t-test). A sustained (> or = 4 weeks) improvement (> or =25%) on SS14 was recorded in a significantly higher proportion of gemcitabine + BSC patients (22%) than in BSC alone patients (9%) (P = 0.0014, Pearson's chi-squared test). The QLQ-C30 and L13 subscales showed greater improvement in the gemcitabine plus BSC arm (in 11 domains) than in the BSC arm (one symptom item). There was greater deterioration in the BSC alone arm (six domains/items) than in the gemcitabine + BSC arm (three QL domains). Tumour response occurred in 19% (95% CI 13-27) of gemcitabine patients. There was no difference in overall survival: median 5.7 months (95% CI 4.6-7.6) for gemcitabine + BSC patients and 5.9 months (95% CI 5.0-7.9) (log-rank, P = 0.84) for BSC patients, and 1 -year

  16. Preoperative CYFRA 21-1 and CEA as Prognostic Factors in Patients with Stage I Non-Small Cell Lung Cancer

    OpenAIRE

    Blankenburg, Florian; Hatz, Rudolf; Nagel, Dorothea; Ankerst, Donna Pauler; Reinmiedl, Judith; Gruber, Christine; Seidel, Dietrich; Stieber, Petra

    2008-01-01

    Objective: To validate the prognostic value of preoperative levels of CYFRA 21-1, CEA and the corresponding tumor marker index (TMI) in patients with stage I non-small cell lung cancer (NSCLC). Methods: Two hundred forty stage I NSCLC patients (80 in pT1 and 160 in pT2; 100 squamous cell carcinomas, 91 adenocarcinomas, 32 large-cell carcinomas, 17 with other histologies; 171 males and 69 females) who had complete resection (R0) between 1986 and 2004 were included in the analysis. CYFRA 21-1 a...

  17. Clinical Significance of Serum Cytokeratin 19 Fragment in the Prediction of Chemotherapy Efficacy and Prognosis in Patients with Advanced Non-small Cell Lung Cancer

    OpenAIRE

    Chong'an XU; Liu, Jiali; Xing, Lili; Liu, Shu

    2010-01-01

    Background and objective RECIST (Response Evaluation Criteria in Solid Tumors) criteria could not be used to detect viable tumor tissue and is not an accurate tool for evaluation of objective response (OR) in non-small cell lung cancer (NSCLC) patients without measurable lesions. The aim of this study is to detect the pre- and post-chemotherapy serum cytokeratin 19 fragment (CYFRA21-1) expression levels in advanced NSCLC patients to evaluate the clinical value of CYFRA21-1 in the prediction o...

  18. Association between different EGFR mutation status and survival in pemetrexed-based chemotherapy for advanced non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    郏博

    2014-01-01

    Objective To explore the association between different epidermal growth factor receptor(EGFR)mutation status and survival in pemetrexed-based chemotherapy for advanced non-small-cell lung cancer(NSCLC).Methods A retrospective cohort study was performed to assess146 patients with advanced NSCLC at Cancer

  19. First-line single agent treatment with gefitinib in patients with advanced non-small-cell lung cancer

    Directory of Open Access Journals (Sweden)

    Shu Yong-Qian

    2010-09-01

    Full Text Available Abstract Background Lung cancer is a malignant carcinoma which has the highest morbidity and mortality in Chinese population. Gefitinib, a tyrosine kinase (TK inhibitor of epidermal growth factor receptor (EGFR, displays anti-tumor activity. The present data regarding first-line treatment with single agent gefitinib against non-small-cell lung cancer (NSCLC in Chinese population are not sufficient. Purpose To assess the efficacy and toxicity of gefitinib in Chinese patients with advanced non-small-cell lung cancer (NSCLC, a study of single agent treatment with gefitinib in Chinese patients was conducted. Methods 45 patients with advanced NSCLC were treated with gefitinib (250 mg daily until the disease progression or intolerable toxicity. Results Among the 45 patients, 15 patients achieved partial response (PR, 17 patients experienced stable disease (SD, and 13 patients developed progression disease (PD. None of the patients achieved complete response (CR. The tumor response rate and disease control rate was 33% and 71.1%, respectively. Symptom remission rate was 72.5%, and median remission time was 8 days. Median overall survival and median progression-free survival was 15.3 months and 6.0 months, respectively. The main induced toxicities by gefitinib were skin rash and diarrhea (53.3% and 33.3%, respectively. The minor induced toxicities included dehydration and pruritus of skin (26.7% and 22.2%, respectively. In addition, hepatic toxicity and oral ulceration occurred in few patients (6.7% and 4.4%2, respectively. Conclusions Single agent treatment with gefitinib is effective and well tolerated in Chinese patients with advanced NSCLC.

  20. Serum level of microRNA-147 as diagnostic biomarker in human non-small cell lung cancer.

    Science.gov (United States)

    Chu, Guangmin; Zhang, Jianbo; Chen, Xiaobing

    2016-08-01

    Objectives In this study, we intended to examine the gene expression level and the clinical significance of microRNA-147 (miR-147) in cancer tissues and sera of patients with non-small cell lung cancer (NSCLC). Methods Quantitative real-time PCR (qRT-PCR) was used to investigate the expression levels of miR-147 in 32 paired NSCLC tissues and their adjacent normal lung tissues, sera of 122 control and 87 NSCLC patients. The correlation of serum miR-147 expression level with clinicopathological characteristics, and the prognosis of NSCLC patients was statistically evaluated. Results MiR-147 was significantly down-regulated in NSCLC tissues than in paired adjacent normal tissues, and in sera of NSCLC patients than in sera of control patients. In addition, serum miR-147 was markedly down-regulated in advanced NSCLC patients and the patients with lymph node metastasis (LNM). Low serum miR-147 expression level was found to be significantly correlated with tumor, lymph node, metastasis stage, LNM, and tumor size. Statistical analysis showed that patients with low serum miR-147 had much worse overall survival, and low serum miR-147 expression level was an independent prognostic factor for poor prognosis for NSCLC. Conclusion Low serum miR-147 expression level may be a useful biomarker for patients with NSCLC. PMID:26581116

  1. In vivo synergistic cytogenetic effects of aminophylline on lymphocyte cultures from patients with lung cancer undergoing chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Mylonaki, Effie; Manika, Katerina [Pulmonary Department, “G.Papanikolaou” General Hospital, Aristotle University of Thessaloniki (Greece); Zarogoulidis, Paul, E-mail: pzarog@hotmail.com [Pulmonary Department, “G.Papanikolaou” General Hospital, Aristotle University of Thessaloniki (Greece); Domvri, Kalliopi; Voutsas, Vasilis; Zarogoulidis, Kostas [Pulmonary Department, “G.Papanikolaou” General Hospital, Aristotle University of Thessaloniki (Greece); Mourelatos, Dionysios [Biology and Genetics, Medical School, Aristotle University of Thessaloniki (Greece)

    2012-12-15

    Highlights: ► SCEs in vivo, a possible predictor of tumor chemoresponse. ► In vivo exposure to combined treatment, applying the SCE assay. ► Aminophylline enhances DNA instability induced by chemotherapy in vivo. ► In vivo synergistic effect of Aminophylline with the chemotherapeutic agents. - Abstract: Background: The anti-cancer and cytogenetic effects of aminophylline (AM) have been demonstrated in several clinical trials. The aim of the present study was to investigate the in vivo cytogenetic effects of AM in newly diagnosed patients with small cell (SCLC) and non-small cell lung cancer (NSCLC), receiving chemotherapy for the first time. Methods: Sister chromatid exchanges (SCEs) and proliferation rate index (PRI) were evaluated in peripheral blood lymphocyte cultures from six patients with SCLC and six patients with NSCLC after the in vitro addition of AM and after the in vivo administration of AM in patients receiving chemotherapy. Results: The in vitro addition of AM significantly increased SCEs only in SCLC patients (p < 0.001). The in vivo administration of AM after chemotherapy increased SCEs in both cancer types (SCLC: p < 0.001, NSCLC: p = 0.003) and this increase was synergistic, the rates of SCEs in the presence of AM were higher than the expected SCE values if the increases above background for chemotherapy and AM were independent and additive (SCLC: p < 0.001, NSCLC: p = 0.008). Although in both groups of patients cell division delays were observed after the combined chemotherapy plus in vivo AM treatment, the correlation between the magnitude of the SCE response and the PRI depression was not statistically significant (p > 0.05). Conclusions: These observations suggest that AM enhances the results of concurrently administered chemotherapy by synergistically increasing its cytogenetic effects in patients with lung cancer.

  2. Muscle dysfunction in cancer patients

    DEFF Research Database (Denmark)

    Christensen, Jesper Frank; Jones, L W; Andersen, J L;

    2014-01-01

    implications of muscle dysfunction in cancer patients. The efficacy of exercise training to prevent and/or mitigate cancer-related muscle dysfunction is also discussed. DESIGN: We identified 194 studies examining muscular outcomes in cancer patients by searching PubMed and EMBASE databases. RESULTS: Muscle...... dysfunction is evident across all stages of the cancer trajectory. The causes of cancer-related muscle dysfunction are complex, but may involve a wide range of tumor-, therapy- and/or lifestyle-related factors, depending on the clinical setting of the individual patient. The main importance of muscle...... dysfunction in cancer patients lies in the correlation to vital clinical end points such as cancer-specific and all-cause mortality, therapy complications and quality of life (QoL). Such associations strongly emphasize the need for effective therapeutic countermeasures to be developed and implemented...

  3. Efficacy and safety evaluation of icotinib in patients with advanced non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    Aiqin Gu; Chunlei Shi; Liwen Xiong; Tianqing Chu; Jun Pei; Baohui Han

    2013-01-01

    To evaluate the efficacy and safety of icotinib hydrochloride in patients with advanced non-small cell lung cancer (NSCLC).Methods:A total of 89 patients with stage ⅢB or Ⅳ NSCLC received icotinib at a dose of 125 mg admimstered 3 times a day.Icotinib treatment was continued until disease progression or development of unacceptable toxicity.Results:A total of 89 patients were assessable.In patients treated with icotinib,the overall response rate (RR) was 36.0% (32/89),and the disease control rate (DCR) was 69.7% (62/89).RR and DCR were significantly improved in patients with adenocarcinoma versus non-adenocarcinoma (P<0.05).The symptom improvement rate was 57.3% (51/89),and the main symptoms improved were cough,pain,chest distress,dyspnea,and Eastern Cooperative Oncology Group performance status.The main toxic effects were rash [30/89 (33.7 %)] and diarrhea [15/89 (16.9%)].The level of toxicity was typically low.Conclusions:The use of icotinib hydrochloride in the treatment of advanced NSCLC is efficacious and safe,and its toxic effects are tolerable.

  4. Stereotactic body radiotherapy for centrally located early-stage non-small cell lung cancer or lung metastases from the RSSearch® patient registry

    International Nuclear Information System (INIS)

    The purpose of this study was to evaluate treatment patterns and outcomes of stereotactic body radiotherapy (SBRT) for centrally located primary non-small cell lung cancer (NSCLC) or lung metastases from the RSSearch® Patient Registry, an international, multi-center patient registry dedicated to radiosurgery and SBRT. Eligible patients included those with centrally located lung tumors clinically staged T1-T2 N0, M0, biopsy-confirmed NSCLC or lung metastases treated with SBRT between November 2004 and January 2014. Descriptive analysis was used to report patient demographics and treatment patterns. Overall survival (OS) and local control (LC) were determined using Kaplan-Meier method. Toxicity was reported using the Common Terminology Criteria for Adverse Events version 3.0. In total, 111 patients with 114 centrally located lung tumors (48 T1-T2,N0,M0 NSCLC and 66 lung metastases) were treated with SBRT at 19 academic and community-based radiotherapy centers in the US and Germany. Median follow-up was 17 months (range, 1–72). Median age was 74 years for primary NSCLC patients and 65 years for lung metastases patients (p < 0.001). SBRT dose varied from 16 – 60 Gy (median 48 Gy) delivered in 1–5 fractions (median 4 fractions). Median dose to centrally located primary NSCLC was 48 Gy compared to 37.5 Gy for lung metastases (p = 0.0001) and median BED10 was 105.6 Gy for primary NSCLC and 93.6 Gy for lung metastases (p = 0.0005). Two-year OS for T1N0M0 and T2N0M0 NSCLC was 79 and 32.1 %, respectively (p = 0.009) and 2-year OS for lung metastases was 49.6 %. Two-year LC was 76.4 and 69.8 % for primary NSCLC and lung metastases, respectively. Toxicity was low with no Grade 3 or higher acute or late toxicities. Overall, patients with centrally located primary NSCLC were older and received higher doses of SBRT than those with lung metastases. Despite these differences, LC and OS was favorable for patients with central lung tumors treated with SBRT. Reported toxicity

  5. XIAP inhibits mature Smac-induced apoptosis by degrading it through ubiquitination in NSCLC

    Science.gov (United States)

    Qin, Sida; Yang, Chengcheng; Zhang, Boxiang; Li, Xiang; Sun, Xin; Li, Gang; Zhang, Jing; Xiao, Guodong; Gao, Xiao; Huang, Guanghong; Wang, Peili; Ren, Hong

    2016-01-01

    X-linked inhibitor of apoptosis protein (XIAP) and second mitochondrial-derived activator of caspase (Smac) are two important prognostic biomarkers for cancer. They are negatively correlated in many types of cancer. However, their relationship is still unknown in lung cancer. In the present study, we found that there was a negative correlation between Smac and XIAP at the level of protein but not mRNA in NSCLC patients. However, XIAP overexpression had no effect on degrading endogenous Smac in lung cancer cell lines. Therefore, we constructed plasmids with full length of Smac (fSmac) and mature Smac (mSmac) which located in cytoplasm instead of original mitochondrial location, and was confirmed by immunofluorescence. Subsequently, we found that mSmac rather than fSmac was degraded by XIAP and inhibited cell viability. CHX chase assay and ubiquitin assay were performed to illustrate XIAP degraded mSmac through ubiquitin pathway. Overexpression of XIAP partially reverted apoptotic induction and cell viability inhibition by mSmac, which was due to inhibiting caspase-3 activation. In nude mouse xenograft experiments, mSmac inhibited Ki-67 expression and slowed down lung cancer growth, while XIAP partially reversed the effect of mSmac by degrading it. In conclusion, XIAP inhibits mature Smac-induced apoptosis by degrading it through ubiquitination in NSCLC. PMID:27498621

  6. Long-Term Excess Mortality for Survivors of Non-small Cell Lung Cancer in the Netherlands

    NARCIS (Netherlands)

    Janssen-Heijnen, Maryska L.; van Steenbergen, Liza N.; Steyerberg, Ewout; Visser, Otto; De Ruysscher, Dirk K.; Groen, Harry J.

    2012-01-01

    Introduction: Most patients diagnosed with non-small cell lung cancer (NSCLC) die within the first few years after diagnosis. However, only little is known about those who have survived these first years. We aimed to study conditional 5-year relative survival rates for NSCLC patients during long-ter

  7. Upregulation of MiR-1280 Expression in Non-small Cell Lung Cancer Tissues

    Institute of Scientific and Technical Information of China (English)

    Li-Min Xu; Li-Qin Li; Jing Li; Hong-Wei Li; Qi-Bin Shen; Jin-Liang Ping; Zhi-Hong Ma

    2015-01-01

    Background:Non-small cell lung cancer (NSCLC) is a prolific and high-mortality disease with few effective treatments.Although the detection and surgical techniques for NSCLC continue to advance,the survival rate for the patients with NSCLC remains poor.Enhanced predictive biomarkers such as microRNAs (miRNAs) are needed at the time of diagnosis to better tailor therapies for patients.This study focused on the expression ofmiR-1280 in NSCLC tissues and distal normal tissues in order to explore the association between miR-1280 expression and NSCLC.Methods:A total of 72 newly diagnosed primary NSCLC patients were enrolled in this study.Quantitative real-time polymerase chain reaction (PCR) was performed to identify the expression level ofmiR-1280 in the NSCLC tissues and distal normal tissues of these patients.Results:The miR-1280 expression was significantly higher in the NSCLC tissues (0.084 ± 0.099) than distal normal tissues (0.014 ± 0.015,P =0.009).In 54 patients (75%),the miR-1280 expression in the NSCLC tissues was upregulated (2-△△ct > 2),and no case showed a downregulation of miR-1280 expression.Conclusions:The expression level ofmiR-1280 could be regarded as a biomarker for NSCLC.

  8. FHIT promoter methylation status, low protein and high mRNA levels in patients with non-small cell lung cancer.

    Science.gov (United States)

    Czarnecka, Karolina H; Migdalska-Sęk, Monika; Domańska, Daria; Pastuszak-Lewandoska, Dorota; Dutkowska, Agata; Kordiak, Jacek; Nawrot, Ewa; Kiszałkiewicz, Justyna; Antczak, Adam; Brzeziańska-Lasota, Ewa

    2016-09-01

    FHIT is a tumor suppressor gene that is frequently silenced in non-small cell lung cancer (NSCLC) and also in preneoplastic lesions. Promoter hypermethylation was previously observed in NSCLC, and its epigenetic silencing, observed on mRNA or protein level, was proposed to predict NSCLC outcome. In the present study we evaluated the relationship between FHIT expression on mRNA level and promoter methylation, or immunoexpression level. The aim of this study was to analyze the usefulness of FHIT as early differentiating biomarker in NSCLC patients. Lung tissue specimens were obtained from 59 patients with diagnosed NSCLC (SCC=34, AC=20, LCC=5). FHIT promoter methylation was assessed in methylation-specific PCR. Relative expression analysis of FHIT was performed in real-time PCR (qPCR) and protein immunoexpression by ELISA assay. Significant differences in FHIT expression between NSCLC histopathological groups (SCC, AC, LCC) were observed (p=0.000009), with the lowest level in SCC. FHIT expression was significantly higher (p=0.034) in men vs. women. Methylated FHIT alleles were present both in NSCLC and control specimens. Mean MI value was higher in control tissue vs. neoplasm, and in men vs. women and it increased with patient age. Significant increase in MI level was observed in N0 group vs. N1 and N2, according to the TNM staging (p=0.0073). Differences in FHIT expression levels between AC, LCC and SCC indicated the usefulness of this gene as a diagnostic marker for NSCLC subtype differentiation. FHIT promoter hypermethylation both in cancer and control tissue indicated the presence of epigenetic alterations in early stage of NSCLC development. Differences in gene promoter methylation between cancer patients with and without node infiltration might be considered as a prognostic marker. Significantly lower FHIT protein immunoexpression was revealed in the group with long and intense history of smoking assessed as PYs (PY<40 vs. PY≥40, p=0.01). These results

  9. Repurposing Cationic Amphiphilic Antihistamines for Cancer Treatment

    Directory of Open Access Journals (Sweden)

    Anne-Marie Ellegaard

    2016-07-01

    Full Text Available Non-small cell lung cancer (NSCLC is one of the deadliest cancers worldwide. In search for new NSCLC treatment options, we screened a cationic amphiphilic drug (CAD library for cytotoxicity against NSCLC cells and identified several CAD antihistamines as inducers of lysosomal cell death. We then performed a cohort study on the effect of CAD antihistamine use on mortality of patients diagnosed with non-localized cancer in Denmark between 1995 and 2011. The use of the most commonly prescribed CAD antihistamine, loratadine, was associated with significantly reduced all-cause mortality among patients with non-localized NSCLC or any non-localized cancer when compared with use of non-CAD antihistamines and adjusted for potential confounders. Of the less frequently described CAD antihistamines, astemizole showed a similar significant association with reduced mortality as loratadine among patients with any non-localized cancer, and ebastine use showed a similar tendency. The association between CAD antihistamine use and reduced mortality was stronger among patients with records of concurrent chemotherapy than among those without such records. In line with this, sub-micromolar concentrations of loratadine, astemizole and ebastine sensitized NSCLC cells to chemotherapy and reverted multidrug resistance in NSCLC, breast and prostate cancer cells. Thus, CAD antihistamines may improve the efficacy of cancer chemotherapy.

  10. Repurposing Cationic Amphiphilic Antihistamines for Cancer Treatment.

    Science.gov (United States)

    Ellegaard, Anne-Marie; Dehlendorff, Christian; Vind, Anna C; Anand, Atul; Cederkvist, Luise; Petersen, Nikolaj H T; Nylandsted, Jesper; Stenvang, Jan; Mellemgaard, Anders; Østerlind, Kell; Friis, Søren; Jäättelä, Marja

    2016-07-01

    Non-small cell lung cancer (NSCLC) is one of the deadliest cancers worldwide. In search for new NSCLC treatment options, we screened a cationic amphiphilic drug (CAD) library for cytotoxicity against NSCLC cells and identified several CAD antihistamines as inducers of lysosomal cell death. We then performed a cohort study on the effect of CAD antihistamine use on mortality of patients diagnosed with non-localized cancer in Denmark between 1995 and 2011. The use of the most commonly prescribed CAD antihistamine, loratadine, was associated with significantly reduced all-cause mortality among patients with non-localized NSCLC or any non-localized cancer when compared with use of non-CAD antihistamines and adjusted for potential confounders. Of the less frequently described CAD antihistamines, astemizole showed a similar significant association with reduced mortality as loratadine among patients with any non-localized cancer, and ebastine use showed a similar tendency. The association between CAD antihistamine use and reduced mortality was stronger among patients with records of concurrent chemotherapy than among those without such records. In line with this, sub-micromolar concentrations of loratadine, astemizole and ebastine sensitized NSCLC cells to chemotherapy and reverted multidrug resistance in NSCLC, breast and prostate cancer cells. Thus, CAD antihistamines may improve the efficacy of cancer chemotherapy. PMID:27333030

  11. Association of TERT Polymorphisms with Clinical Outcome of Non-Small Cell Lung Cancer Patients.

    Directory of Open Access Journals (Sweden)

    Xueying Zhao

    Full Text Available TERT is of great importance in cancer initiation and progression. Many studies have demonstrated the TERT polymorphisms as risk factors for many cancer types, including lung cancer. However, the impacts of TERT variants on cancer progression and treatment efficacy have remained controversial. This study aimed to investigate the association of TERT polymorphisms with clinical outcome of advanced non-small cell lung cancer (NSCLC patients receiving first-line platinum-based chemotherapy, including response rate, clinical benefit, progression-free survival (PFS, overall survival (OS, and grade 3 or 4 toxicity. Seven polymorphisms of TERT were assessed, and a total of 1004 inoperable advanced NSCLC patients treated with platinum-based chemotherapy were enrolled. It is exhibited that the variant heterozygote of rs4975605 showed significant association with a low rate of clinical benefit, and displayed a much stronger effect in never-smoking female subset, leading to the clinical benefit rate decreased from 82.9% (C/C genotype to 56.4% (C/A genotype; adjusted OR, 3.58; P=1.40×10(-4. It is also observed that the polymorphism rs2736109 showed significant correlation with PFS (log-rank P=0.023. In age > 58 subgroup, patients carrying the heterozygous genotype had a longer median PFS than those carrying the wild-type genotypes (P=0.002. The results from the current study, for the first time to our knowledge, provide suggestive evidence of an effect of TERT polymorphisms on disease progression variability among Chinese patients with platinum-treated advanced NSCLC.

  12. Impact of physical size on gefitinib efficacy in patients with non-small cell lung cancer harboring EGFR mutations.

    Science.gov (United States)

    Ichihara, Eiki; Hotta, Katsuyuki; Takigawa, Nagio; Kudo, Kenichiro; Kato, Yuka; Honda, Yoshihiro; Hayakawa, Hiromi; Minami, Daisuke; Sato, Akiko; Tabata, Masahiro; Tanimoto, Mitsune; Kiura, Katsuyuki

    2013-09-01

    Gefitinib is an essential drug for the treatment of non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) gene mutations. The approved dosage is 250 mg/body/day without adjustment for physical size such as body surface area (BSA), and the impact of physical size on the efficacy of gefitinib has not been evaluated. Here, we sought to clarify this issue using a retrospective cohort. We reviewed the medical records of patients with consecutive advanced NSCLC harboring EGFR mutations who underwent gefitinib monotherapy at Okayama University Hospital. In total, 101 patients were included in this study, and the median BSA in this cohort was 1.5 m(2). The median progression-free survival (PFS) of the patients with higher BSA (≥1.5 m(2)) was significantly worse than that of those with lower BSA (BSA on PFS (hazards ratio, 2.34; 95% confidence interval, 1.78-2.89; p = 0.002). By contrast, no significant association between BSA and PFS was observed in those undergoing cytotoxic chemotherapy (4.0 vs. 5.1 months; p = 0.989, log-rank test), suggesting that BSA is a predictive, rather than a prognostic, marker for gefitinib therapy in EGFR-mutated NSCLC. In conclusion, BSA affected PFS in patients with EGFR-mutated NSCLC who underwent gefitinib monotherapy, suggesting the need for appraisal of BSA-based dose adjustment, even for this molecular target-based therapy.

  13. Clinical and Metabolic Parameters in Non-Small Cell Lung Carcinoma and Colorectal Cancer Patients with and without KRAS Mutations

    Directory of Open Access Journals (Sweden)

    Ahmet Yilmaz

    2014-08-01

    Full Text Available Lung cancer (LC and colorectal cancer (CRC are the first and second deadliest types of cancer worldwide. EGFR-based therapy has been used in the treatment of these cancers with variable success. Presence of mutations in the KRAS driver oncogene, possibly induced by environmental factors such as carcinogens in diet and cigarette smoke, may confer worse prognosis and resistance to treatment for reasons not fully understood. Data on possible associations between KRAS mutational status and clinical and metabolic parameters, which may help in clinical management, as well as in identifying risk factors for developing these cancers, are limited in the current literature. We sequenced the KRAS gene and investigated the associations of variations in 108 patients with non-small cell lung carcinoma (NSCLC, the most common form of LC, and in 116 patients with CRC. All of the mutations originated from the guanosine nucleotide and over half of all transversions in NSCLC and CRC were c.34 G>T and c.35 G>T, respectively. c.35 G>A was the most frequent type of transition in both cancers. Excluding smoking, the clinical and metabolic parameters in patients carrying mutant and wild type KRAS were similar except that the CRC patients with transversion mutations were 8.6 years younger than those carrying the transitions (P < 0.01. Dyslipidemia, hypertension, family cancer history, and age of diagnosis older than 60 years were more frequent in NSCLC than CRC (P ≤ 0.04. These results suggest that most of the clinical and metabolic parameters investigated in this study are probably not associated with the more aggressive phenotype and differences in response to EGFR-based treatment previously reported in patients with KRAS mutations. However, the increased rates of abnormal metabolic parameters in patients with NSCLC in comparison to CRC indicate that these parameters may be more important in the management of NSCLC. CRC patients carrying transition mutations are

  14. Survival of patients with small cell lung cancer undergoing lung resection in England, 1998-2009

    DEFF Research Database (Denmark)

    Lüchtenborg, Margreet; Riaz, Sharma P; Lim, Eric;

    2014-01-01

    INTRODUCTION: Chemotherapy or chemoradiotherapy is the recommended treatment for small cell lung cancer (SCLC), except in stage I disease where clinical guidelines state there may be a role for surgery based on favourable outcomes in case series. Evidence supporting adjuvant chemotherapy...... in resected SCLC is limited but this is widely offered. METHODS: Data on 359 873 patients who were diagnosed with a first primary lung cancer in England between 1998 and 2009 were grouped according to histology (SCLC or non-SCLC (NSCLC)) and whether they underwent a surgical resection. We explored...

  15. Glutathione S-transferase pi polymorphism contributes to the treatment outcomes of advanced non-small cell lung cancer patients in a Chinese population.

    Science.gov (United States)

    Chen, J B; Wang, F; Wu, J J; Cai, M

    2016-01-01

    We analyzed the association between polymorphisms in three glutathione S-transferase genes (GSTP1, GSTM1, and GSTT1) and the treatment outcome for advanced non-small cell lung cancer (NSCLC). We recruited 284 NSCLC patients at advanced stage from Department of Radiotherapy in Peace Hospital Attached to Changzhi Medical College between May 2009 and May 2011, who had received cisplatin-based chemotherapy. The GSTP1, GSTM1, and GSTT1 genotyping for was determined using DNA pyrosequencing on an ABI Prism 3100 DNA analyzer. In the Cox proportional hazards model, the IIe/Val and Val/Val genotypes of GSTP1 were associated with lower risk of disease progression compared with the IIe/IIe genotype, and the HRs (95%CIs) were 0.37 (0.18-0.74) and 0.15 (0.06-0.35), respectively. The IIe/Val and Val/Val genotypes significantly decreased risk of death from all causes in patients with NSCLC, and the HRs (95%CIs) were 0.52 (0.29-0.92) and 0.37 (0.17- 0.79), respectively No significant association was observed between GSTM1 and GSTT1 polymorphisms and progression-free survival and overall survival in the NSCLC patients. In summary, we suggest that GSTP1 polymorphisms might influence the treatment outcome of advanced NSCLC patients, and our results could help improve individualized therapy. PMID:27525853

  16. Pembrolizumab Shows Promise for NSCLC.

    Science.gov (United States)

    2015-06-01

    Data from the KEYNOTE-001 trial show that pembrolizumab improves clinical outcomes for patients with advanced non-small cell lung cancer, and is well tolerated. PD-L1 expression in at least 50% of tumor cells correlated with improved efficacy.

  17. A retrospective quality of life analysis using the lung cancer symptom scale in patients treated with palliative radiotherapy for advanced nonsmall cell lung cancer

    International Nuclear Information System (INIS)

    Purpose: To measure symptom palliation in patients treated with radiation therapy for advanced nonsmall cell lung cancer (NSCLC). Methods and Materials: Five hundred thirty patients with NSCLC were treated at the Medical College of Virginia between 1988 and 1993. Sixty-three patients with the least favorable prognostic features received palliative radiation to 30 Gy in 10 or 12 fractions for symptoms related to the presence of intrathoracic tumor. The observer portion of the Lung Cancer Symptom Scale (LCSS) was employed in a retrospective chart review, scoring measures of appetite, fatigue, cough, dyspnea, hemoptysis, and pain. Results: In 54 evaluable patients, median survival was 4 months and was independent of age, stage, performance status, or histology. Ninety-six percent of the patients had at least one LCSS symptom at presentation. Fatigue was unaffected by therapy. Improvements in appetite (p = 0.68) and pain (p = 0.61) were not statistically significant. There was, however, a statistically significant reduction in cough (p = 0.01), hemoptysis (p = 0.001), and dyspnea (p 0.0003). Self-limiting acute side effects included transient esophagitis in 37% of patients, though no severe toxicities were noted. Conclusions: These results suggest symptomatic benefit from radiotherapy even in those NSCLC patients with advanced disease and a limited life expectancy. Treatment should be given to patients whose symptoms are most amenable to palliation. A site-specific quality of life instrument such as the LCSS should be included within any future clinical trial of NSCLC management so that symptom control may be scored as a treatment outcome in addition to disease-free survival

  18. Metagenes Associated with Survival in Non-Small Cell Lung Cancer

    OpenAIRE

    Egon Urgard; Tõnu Vooder; Urmo Võsa; Kristjan Välk; Mingming Liu; Cheng Luo; Fabian Hoti; Retlav Roosipuu; Tarmo Annilo; Jukka Laine; Frenz, Christopher M.; Liqing Zhang; Andres Metspalu

    2011-01-01

    NSCLC (non-small cell lung cancer) comprises about 80% of all lung cancer cases worldwide. Surgery is most effective treatment for patients with early-stage disease. However, 30%–55% of these patients develop recurrence within 5 years. Therefore, markers that can be used to accurately classify early-stage NSCLC patients into different prognostic groups may be helpful in selecting patients who should receive specific therapies. A previously published dataset was used to evaluate gene expressio...

  19. Clinical Review of Iressa for the Treatment of NSCLC

    Institute of Scientific and Technical Information of China (English)

    Gang Cheng

    2005-01-01

    ABSTRACT Following development of basic science and the advancement of tumor molecular biology, molecular-target therapy has evolved as a new field for cancer treatment. The agents used act at specific target points such as receptors, kinases and signal transduction systems which are related to tumor growth. These actions result in inhibting proliferation, metastasis, vascularization, and promoting tumor apoptosis. Iressa (gefitinib) which is used for the treatment of NSCLC is a small molecular weight agent acting by inhibition of epidermal growth factor receptor-tyrosine kinase. Iressa was the first approved agent for target therapy for the treatment of NSCLC. This article focuses on the results from clinicai trials and the potential of Iressa for the treatment of NSCLC.

  20. Clinicopathological significance of fascin-1 expression in patients with non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Ling XL

    2015-06-01

    Full Text Available Xiao-Ling Ling,* Tao Zhang,* Xiao-Ming Hou, Da Zhao Department of Oncology, The First Hospital of Lanzhou University (The Branch Hospital of Donggang, Lanzhou, Gansu Province, People’s Republic of China *These authors contributed equally to this work Purpose: Fascin-1 promotes the formation of filopodia, lamellipodia, and microspikes of cell membrane after its cross-linking with F-actin, thereby enhancing the cell movement and metastasis and invasion of tumor cells. This study explored the fascin-1 protein’s expression in non-small cell lung cancer (NSCLC tissues and its relationship with clinical pathology and prognostic indicators.Methods: Immunohistochemical analysis was used to determine the expression of fascin-1 in NSCLC tissues. We used quantitative real-time polymerase chain reaction and western blot analysis to further verify the results. The fascin-1 expression and statistical method for clinical pathological parameters are examined by χ2. Kaplan–Meier method is used for survival analysis. Cox’s Proportional Hazard Model was used to conduct a combined-effect analysis for each covariate.Results: In 73 of the 128 cases, NSCLC cancer tissues (57.0% were found with high expression of fascin-1, which was significantly higher than the adjacent tissues (35/128, 27.3%. The results suggested that the high expression of fascin-1 was significantly correlated with lymph node metastasis (P=0.022 and TNM stage (P=0.042. The high fascin-1 expression patients survived shorter than those NSCLC patients with low fascin-1 expression (P<0.05. Univariate analysis revealed that lymph node metastasis, TNM stage, and fascin-1 expression status were correlated with the overall survival. Similarly, lymph node metastasis, TNM stage, and fascin-1 expression status were significantly associated with the overall survival in multivariate analyses by using the Cox regression model.Conclusion: The fascin-1 protein may be a useful prognostic indicator and

  1. Radiolabeled cetuximab plus whole-brain irradiation (WBI) for the treatment of brain metastases from non-small cell lung cancer (NSCLC)

    International Nuclear Information System (INIS)

    Background and Purpose: The addition of systemic drugs to whole-brain irradiation has not improved the survival of patients with multiple brain metastases, most likely because the agents did not readily cross the blood-brain barrier (BBB). Radiolabeling of cetuximab was performed to investigate whether this antibody crosses the BBB. Case Report: A patient with multiple brain lesions from non-small cell lung cancer was investigated. The largest metastasis (40 x 33 x 27 mm) was selected the reference lesion. On day 1, 200 mg/m2 cetuximab (0.25% hot and 99.75% cold antibody) were given. On day 3, 200 mg/m2 cetuximab (cold antibody) were given. Weekly doses of 250 mg/m2 cetuximab were administered for 3 months. Results: The reference lesion showed enhancement of radiolabeled cetuximab (123I-Erbi) on scintigraphy; 123I-Erbi crossed the BBB and accumulated in the lesion. The reference lesion measured 31 x 22 x 21 mm at 4 months. Enhancement of contrast medium was less pronounced. Conclusion: This is the first demonstration of cetuximab crossing the BBB and accumulating in brain metastasis. (orig.)

  2. WT1 Enhances Proliferation and Impedes Apoptosis in KRAS Mutant NSCLC via Targeting cMyc

    OpenAIRE

    Wu, Chen; Wang, Sihan; Xu, Caihua; Tyler, Andreas; Li, Xingru; Andersson, Charlotta; Oji, Yusuke; Sugiyama, Haruo; Chen, Yijiang; Li, Aihong

    2015-01-01

    Background: A novel link between oncogenic KRAS signalling and WT1 was recently identified. We sought to investigate the role of WT1 and KRAS in proliferation and apoptosis. Methods: KRAS mutations and WT1 (cMyc) expression were detected using Sanger sequencing and real-time PCR in 77 patients with non-small cell lung cancer (NSCLC). Overexpression and knockdown of WT1 were generated with plasmid and siRNA via transient transfection technology in H1299 and H1568 cells. MTT assay for detection...

  3. Textural features in pre-treatment [F18]-FDG-PET/CT are correlated with risk of local recurrence and disease-specific survival in early stage NSCLC patients receiving primary stereotactic radiation therapy

    International Nuclear Information System (INIS)

    Textural features in FDG-PET have been shown to provide prognostic information in a variety of tumor entities. Here we evaluate their predictive value for recurrence and prognosis in NSCLC patients receiving primary stereotactic radiation therapy (SBRT). 45 patients with early stage NSCLC (T1 or T2 tumor, no lymph node or distant metastases) were included in this retrospective study and followed over a median of 21.4 months (range 3.1–71.1). All patients were considered non-operable due to concomitant disease and referred to SBRT as the primary treatment modality. Pre-treatment FDG-PET/CT scans were obtained from all patients. SUV and volume-based analysis as well as extraction of textural features based on neighborhood gray-tone difference matrices (NGTDM) and gray-level co-occurence matrices (GLCM) were performed using InterView Fusion™ (Mediso Inc., Budapest). The ability to predict local recurrence (LR), lymph node (LN) and distant metastases (DM) was measured using the receiver operating characteristic (ROC). Univariate and multivariate analysis of overall and disease-specific survival were executed. 7 out of 45 patients (16%) experienced LR, 11 (24%) LN and 11 (24%) DM. ROC revealed a significant correlation of several textural parameters with LR with an AUC value for entropy of 0.872. While there was also a significant correlation of LR with tumor size in the overall cohort, only texture was predictive when examining T1 (tumor diameter < = 3 cm) and T2 (>3 cm) subgroups. No correlation of the examined PET parameters with LN or DM was shown. In univariate survival analysis, both heterogeneity and tumor size were predictive for disease-specific survival, but only texture determined by entropy was determined as an independent factor in multivariate analysis (hazard ratio 7.48, p = .016). Overall survival was not significantly correlated to any examined parameter, most likely due to the high comorbidity in our cohort. Our study adds to the growing evidence

  4. Therapeutic pathomorphosis of advanced NSCLC as a criteria for effectiveness of induction chemotherapy.

    Directory of Open Access Journals (Sweden)

    Kosse V.A.

    2007-01-01

    Full Text Available The aim of the study was the investigation of therapeutic pathomorphosis (ThP of non-small cell lung cancer (NSCLC and definition of its role as a criteria for effectiveness of induction chemotherapy (ICT. In the context of investigation there were 152 patients with IIIA st. NSCLC, being treated with ICT (102 pts and without it (50 pts. The analysis of qualitative and quantitative pathomorphological changes in tumors after platinum-based ICT was performed. Patients’ operability in the group with ICT was significantly higher than in control group (72.6% versus 56.0% that proves the effectiveness of ICT as a method of induction influence. The ICT estimation has to be complex, that means – the clinical effect should be verified by pathomorphological studies. Under the influence of ICT in NSCLC noticed the different ThP: 1 st. – 51%, 2-3 st. – 48%, 4 st. – 1% with better response rate in low-differentiation tumor. Being influenced by ICT, the part of viable tumors’ paren-chyma and its proliferating activity has significantly decreased, that is the essential component of further prognosis. The tu-mors’ resectability correlated with the level of its ThP, which serves the basis for necessity of reaching the maximal clinical effect of ICT.

  5. SU-F-BRF-07: Impact of Different Patient Setup Strategies in Adaptive Radiation Therapy with Simultaneous Integrated Volume-Adapted Boost of NSCLC

    Energy Technology Data Exchange (ETDEWEB)

    Balik, S [Cleveland Clinic Foundation, Cleveland, OH (United States); Weiss, E; Sleeman, W; Wu, Y; Hugo, G [Virginia Commonwealth University, Richmond, VA (United States); Dogan, N [University of Miami, Miami, FL (United States); Fatyga, M [Mayo Clinic, AZ, Phoenix, AZ (United States)

    2014-06-15

    Purpose: To evaluate the potential impact of several setup error correction strategies on a proposed image-guided adaptive radiotherapy strategy for locally advanced lung cancer. Methods: Daily 4D cone-beam CT and weekly 4D fan-beam CT images were acquired from 9 lung cancer patients undergoing concurrent chemoradiation therapy. Initial planning CT was deformably registered to daily CBCT images to generate synthetic treatment courses. An adaptive radiation therapy course was simulated using the weekly CT images with replanning twice and a hypofractionated, simultaneous integrated boost to a total dose of 66 Gy to the original PTV and either a 66 Gy (no boost) or 82 Gy (boost) dose to the boost PTV (ITV + 3mm) in 33 fractions with IMRT or VMAT. Lymph nodes (LN) were not boosted (prescribed to 66 Gy in both plans). Synthetic images were rigidly, bony (BN) or tumor and carina (TC), registered to the corresponding plan CT, dose was computed on these from adaptive replans (PLAN) and deformably accumulated back to the original planning CT. Cumulative D98% of CTV of PT (ITV for 82Gy) and LN, and normal tissue dose changes were analyzed. Results: Two patients were removed from the study due to large registration errors. For the remaining 7 patients, D98% for CTV-PT (ITV-PT for 82 Gy) and CTV-LN was within 1 Gy of PLAN for both 66 Gy and 82 Gy plans with both setup techniques. Overall, TC based setup provided better results, especially for LN coverage (p = 0.1 for 66Gy plan and p = 0.2 for 82 Gy plan, comparison of BN and TC), though not significant. Normal tissue dose constraints violated for some patients if constraint was barely achieved in PLAN. Conclusion: The hypofractionated adaptive strategy appears to be deliverable with soft tissue alignment for the evaluated margins and planning parameters. Research was supported by NIH P01CA116602.

  6. The Proangiogenic Phenotype of Natural Killer Cells in Patients with Non-Small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Antonino Bruno

    2013-02-01

    Full Text Available The tumor microenvironment can polarize innate immune cells to a proangiogenic phenotype. Decidual natural killer (dNK cells show an angiogenic phenotype, yet the role for NK innate lymphoid cells in tumor angiogenesis remains to be defined. We investigated NK cells from patients with surgically resected non-small cell lung cancer (NSCLC and controls using flow cytometric and functional analyses. The CD56+CD16- NK subset in NSCLC patients, which represents the predominant NK subset in tumors and a minor subset in adjacent lung and peripheral blood, was associated with vascular endothelial growth factor (VEGF, placental growth factor (PIGF, and interleukin-8 (IL-8/CXCL8 production. Peripheral blood CD56+CD16- NK cells from patients with the squamous cell carcinoma (SCC subtype showed higher VEGF and PlGF production compared to those from patients with adenocarcinoma (AdC and controls. Higher IL-8 production was found for both SCC and AdC compared to controls. Supernatants derived from NSCLC CD56+CD16- NK cells induced endothelial cell chemotaxis and formation of capillary-like structures in vitro, particularly evident in SCC patients and absent from controls. Finally, exposure to transforming growth factor-β1 (TGFβ1, a cytokine associated with dNK polarization, upregulated VEGF and PlGF in peripheral blood CD56+CD16- NK cells from healthy subjects. Our data suggest that NK cells in NSCLC act as proangiogenic cells, particularly evident for SCC and in part mediated by TGFβ1.

  7. Targeting HDAC with a novel inhibitor effectively reverses paclitaxel resistance in non-small cell lung cancer via multiple mechanisms

    OpenAIRE

    Wang, L.; Li, H.; Ren, Y; Zou, S; FANG, W.; Jiang, X.; L. Jia; M. Li; Liu, X.; Yuan, X.; G. Chen; Yang, J; Wu, C.

    2016-01-01

    Chemotherapy paclitaxel yields significant reductions in tumor burden in the majority of advanced non-small cell lung cancer (NSCLC) patients. However, acquired resistance limits its clinical use. Here we demonstrated that the histone deacetylase (HDAC) was activated in paclitaxel-resistant NSCLC cells, and its activation promoted proliferation and tumorigenesis of paclitaxel-resistant NSCLC cells in vitro and in vivo. By contrast, knockdown of HDAC1, a primary isoform of HDAC, sensitized res...

  8. Mitochondrial translocation of EGFR regulates mitochondria dynamics and promotes metastasis in NSCLC.

    Science.gov (United States)

    Che, Ting-Fang; Lin, Ching-Wen; Wu, Yi-Ying; Chen, Yu-Ju; Han, Chia-Li; Chang, Yih-leong; Wu, Chen-Tu; Hsiao, Tzu-Hung; Hong, Tse-Ming; Yang, Pan-Chyr

    2015-11-10

    Dysfunction of the mitochondria is well-known for being associated with cancer progression. In the present study, we analyzed the mitochondria proteomics of lung cancer cell lines with different invasion abilities and found that EGFR is highly expressed in the mitochondria of highly invasive non-small-cell lung cancer (NSCLC) cells. EGF induces the mitochondrial translocation of EGFR; further, it leads to mitochondrial fission and redistribution in the lamellipodia, upregulates cellular ATP production, and enhances motility in vitro and in vivo. Moreover, EGFR can regulate mitochondrial dynamics by interacting with Mfn1 and disturbing Mfn1 polymerization. Overexpression of Mfn1 reverses the phenotypes resulting from EGFR mitochondrial translocation. We show that the mitochondrial EGFR expressions are higher in paired samples of the metastatic lymph node as compared with primary lung tumor and are inversely correlated with the overall survival in NSCLC patients. Therefore, our results demonstrate that besides the canonical role of EGFR as a receptor tyrosine, the mitochondrial translocation of EGFR may enhance cancer invasion and metastasis through regulating mitochondria dynamics.

  9. Elderly Patients with Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Andromachi S Kougioumtzopoulou

    2014-07-01

    Full Text Available Pancreatic cancer marked significant increase of incidence during the last decades in the elderly population. Despite the certain increase of incidence there are no international guidelines for elderly patients who are suffering from pancreatic cancer. During the ASCO Annual Meeting 2014, two abstracts focusing on elderly patients suffering from different histological types of pancreatic cancer were presented. The first retrospective study (Abstract # 4119 showed the benefit of the systemic treatment on overall survival for elderly patients with stage IV pancreatic adenocarcinoma. The second retrospective study (Abstract # 4112 demonstrates the positive effect of somatostatin analogue (octreotide-LAR treatment on overall survival for elderly patients with neuroendocrine pancreatic carcinoma.

  10. Analysis of Prognostic Factors in 541 Female Patients with Advanced Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Meina WU

    2011-03-01

    Full Text Available Background and objective As there is a sharp increase in the incidence of lung cancer in women in recent years, it has brought broad concerns with its unique clinical and epidemiological characteristics and better prognosis. The aim of this study is to analyze the clinical data of women with advanced non-small cell lung cancer (NSCLC retrospectively to explore the prognostic factors. Methods Clinical data of 541 female patients with advanced NSCLC were collected and followed up till death. The primary endpoint is overall survival (OS. SPSS 11.0 statistical analysis software was used for univariate and multivariate analysis. Results The mean age is 59 years (20 years-86 years, adenocarcinoma account for 80.2% (434/541. The median OS was 15 months (95%CI: 13.87-16.13, and 1, 2, 5-year survival rates were 58.8%, 23.7% and 3.20% respectively. Univariate analysis showed that clinical stage, ECOG score, weight loss, clinical symptoms, liver/bone/brain metastasis and received more than one chemotherapy regimen, good response to the first-line chemotherapy, EGFR-TKI targeted therapy and radiotherapy treatment were significantly correlated with the OS and survival rate (P < 0.05. Combined with multivariate analysis, weight loss before treatment, ECOG score, received EGFR-TKI targeted therapy and response to first-line chemotherapy were independent prognostic factor for survival (P < 0.05. Conclusion There is a higher percentage of adenocarcinoma in female NSCLC. Weight loss before treatment, ECOG score, EGFR-TKI targeted therapy and response to first-line chemotherapy may become independent prognostic factors for survival of female patients with advanced NSCLC.

  11. Research on pharmacokinetics of high-dose tamoxifen in non-small cell lung cancer patients

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective To study the pharmacokinetics of tamoxifen at a high dosage, which will offer a theoretical support for an appropriate clinical use of the medicine in non-small cell lung cancer (NSCLC) patients. Methods Three qualified NSCLC patients are selected and given tamoxifen (TAM) 160 mg per Os. Blood samples were collected at different times and then analyzed by high-performance liguid chromatography. The PK-GRAPH program was used to obtain the parameters. Results The concentration-time courses of the TAM 160 mg were fitted to one-compartment model. The pharmacokinetic parameters were estimated as follows: Tmax (6.35±1.24)h, Cmax (217.39±7.71)ng/Ml, AUC (12 127.39±636.16)ng·h/Ml and T1/2ke (34.13±2.97)h. Conclusion TAM 160mg one day per Os cannot reach the effective maintenance concentration in vivo required for reversing MDR in vitro. Loading-maintenance dose strategy is recommended to study the pharmacodynamics of tamoxifen at a high dosage in NSCLC patients.

  12. Current Research on Consolidation Therapy and Follow-up Health Care in Advanced Non-small Cell Lung Cancer Patients

    Institute of Scientific and Technical Information of China (English)

    Runbo Zhong; Baohui Han; Bo Jin

    2008-01-01

    ABSTRACT Following concurrent radio-chemotherapy or first-line chemotherapy for advanced non-small cell lung cancer(NSCLC), continuous maintenance therapy given to patients with stable disease (SD) and follow-up treatment is called consolidation therapy. Concerning NSCLC patients with a non-operable dry Stage-ⅢB (N3) disease, I.e. Contra-lateral mediastinal and hilar lymph node, or homolateral/contra-lateral scalene and Troisier sign, a 2 or 3-course of standard-dosage Taxotere consolidation therapy can be performed after concurrent radio-chemotherapy. In pursuance of evidence-based medicine (EBM), low-dose Taxoteremaintenance therapy, and biological targeted therapy of patients with appropriate symptoms are suitable for second-line therapy for moist of the Stage-ⅢB (malignant pleural effusion) and Ⅳpatients.

  13. Re-challenge chemotherapy with gemcitabine plus carboplatin in patients with non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    Khurum Khan; Gerard G. Hanna; Lynn Campbell; Paula Scullin; Adnan Hussain; Ruth L. Eakin; Jonathan McAleese

    2013-01-01

    Despite recent improvements to current therapies and the emergence of novel agents to manage advanced non-smal celllung cancer (NSCLC), the patients′overal survival remains poor. Re-chal enging with first-line chemotherapy upon relapse is common in the management of smal celllung cancer but is not wel reported for advanced NSCLC. NSCLC relapse has been attributed to acquired drug resistance, but the repopulation of sensitive clones may also play a role, in which case re-chal enge may be appropriate. Here, we report the results of re-chal enge with gemcitabine plus carboplatin in 22 patients from a single institution who had previously received gemcitabine plus platinum in the first-line setting and had either partial response or a progression-free interval of longer than 6 months. In this retrospective study, the charts of patients who underwent second-line chemotherapy for NSCLC in our cancer center between January 2005 and April 2010 were reviewed. Al the patients who received a combination of gemcitabine and carboplatin for re-challenge were included in the study. These patients were offered second-line treatment on confirmation of clear radiological disease progression. The overall response rate was 15%and disease control rate was 75%. The median survival time was 10.4 months, with 46%of patients alive at 1 year. These results suggest that re-chal enge chemotherapy should be considered in selected patients with radiological partial response or a progression-free survival of longer than 6 months to the initial therapy.

  14. Prognostic value of tissue inhibitor of metalloproteinase-2 expression in patients with non-small cell lung cancer: a systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Lin Zhu

    Full Text Available Tissue inhibitor of metalloproteinase-2 (TIMP-2 is a small secretory glycoprotein with anti-matrix metalloproteinase activity. Data on the value of TIMP-2 as a prognostic factor in non-small cell lung cancer (NSCLC are discordant and remain controversial. A systematic review and meta-analysis was performed to explore this issue.We identified the relevant literature by searching the PubMed, EMBASE, Web of Science, China National Knowledge Infrastructure, SinoMed, and Wanfang Data databases (search terms: "non-small cell lung cancer" or "NSCLC" or "Lung Carcinoma, Non-Small-Cell", "Tissue Inhibitor of Metalloproteinase-2" or "TIMP-2", and "prognosis" or "prognostic" or "survive" for updates prior to March 1, 2014. The pooled hazard ratio (HR of overall survival with a 95% confidence interval (95% CI was used to evaluate the strength of the association between positive TIMP-2 expression and survival in patients with NSCLC.We included 12 studies in our systematic review; five studies involving 399 patients with NSCLC were meta-analyzed. The pooled HR of all included patients was 0.57 (95% CI: 0.43-0.77, and the HRs of subgroup analysis according to stage (I-IV, testing method (immunohistochemistry and high TIMP-2 expression percentage (<50% were 0.63 (95% CI: 0.43-0.92, 0.55 (95% CI: 0.41-0.74, and 0.50 (95% CI: 0.28-0.88, respectively. These data suggested that high TIMP-2 expression is associated with favorable prognosis in NSCLC. The meta-analysis did not reveal heterogeneity or publication bias.TIMP-2 expression indicates favorable prognosis in patients with NSCLC; as a protective factor, it could help predict outcome and may guide clinical therapy in the future.

  15. Setting up a wide panel of patient-derived tumor xenografts of non–small cell lung cancer by improving the preanalytical steps

    International Nuclear Information System (INIS)

    With the ongoing need to improve therapy for non–small cell lung cancer (NSCLC) there has been increasing interest in developing reliable preclinical models to test novel therapeutics. Patient-derived tumor xenografts (PDX) are considered to be interesting candidates. However, the establishment of such model systems requires highly specialized research facilities and introduces logistic challenges. We aimed to establish an extensive well-characterized panel of NSCLC xenograft models in the context of a long-distance research network after careful control of the preanalytical steps. One hundred fresh surgically resected NSCLC specimens were shipped in survival medium at room temperature from a hospital-integrated biobank to animal facilities. Within 24 h post-surgery, tumor fragments were subcutaneously xenografted into immunodeficient mice. PDX characterization was performed by histopathological, immunohistochemical, aCGH and next-generation sequencing approaches. For this model system, the tumor take rate was 35%, with higher rates for squamous carcinoma (60%) than for adenocarcinoma (13%). Patients for whom PDX tumors were obtained had a significantly shorter disease-free survival (DFS) compared to patients for whom no PDX tumors (P = 0.039) were obtained. We established a large panel of PDX NSCLC models with a high frequency of mutations (29%) in EGFR, KRAS, NRAS, MEK1, BRAF, PTEN, and PI3KCA genes and with gene amplification (20%) of c-MET and FGFR1. This new patient-derived NSCLC xenograft collection, established regardless of the considerable time required and the distance between the clinic and the animal facilities, recapitulated the histopathology and molecular diversity of NSCLC and provides stable and reliable preclinical models for human lung cancer research

  16. Bone health in cancer patients

    DEFF Research Database (Denmark)

    Coleman, R; Body, J J; Aapro, M;

    2014-01-01

    cancer for many patients resulting in a major reduction in skeletal complications, reduced bone pain and improved quality of life. Secondly, many of the treatments we use to treat cancer patients have effects on reproductive hormones, which are critical for the maintenance of normal bone remodelling...... in the metastatic processes required for cancer dissemination, and there are emerging data showing that, at least in some clinical situations, the use of bone-targeted treatments can reduce metastasis to bone and has potential impact on patient survival.......There are three distinct areas of cancer management that make bone health in cancer patients of increasing clinical importance. First, bone metastases are common in many solid tumours, notably those arising from the breast, prostate and lung, as well as multiple myeloma, and may cause major...

  17. Psychodynamic Psychotherapy for Cancer Patients

    OpenAIRE

    Straker, Norman

    1998-01-01

    Psychodynamic psychotherapy is effective as an approach to understanding the psychological conflicts and the psychiatric symptoms of cancer patients as well as to planning useful psychological interventions. The author recommends that the psychotherapist who treats cancer patients be familiar with the following: 1) the natural course and treatment of the illness, 2) a flexible approach in accord with the medical status of the patient, 3) a common sense approach to defenses, 4) a concern with ...

  18. Digital PCR analysis of plasma cell-free DNA for non-invasive detection of drug resistance mechanisms in EGFR mutant NSCLC: Correlation with paired tumor samples

    Science.gov (United States)

    Ishii, Hidenobu; Azuma, Koichi; Sakai, Kazuko; Kawahara, Akihiko; Yamada, Kazuhiko; Tokito, Takaaki; Okamoto, Isamu; Nishio, Kazuto; Hoshino, Tomoaki

    2015-01-01

    As the development of resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) has become an issue of concern, identification of the mechanisms responsible has become an urgent priority. However, for research purposes, it is not easy to obtain tumor samples from patients with EGFR mutation-positive non-small-cell lung cancer (NSCLC) that has relapsed after treatment with EGFR-TKIs. Here, using digital PCR assay as an alternative and noninvasive method, we examined plasma and tumor samples from patients with relapsed NSCLC to establish the inter-relationships existing among T790M mutation, activating EGFR mutations, HER2 amplification, and MET amplification. Paired samples of tumor and blood were obtained from a total of 18 patients with NSCLC after they had developed resistance to EGFR-TKI treatment, and the mechanisms of resistance were analyzed by digital PCR. Digital PCR analysis of T790M mutation in plasma had a sensitivity of 81.8% and specificity of 85.7%, the overall concordance between plasma and tissue samples being 83.3%. MET gene copy number gain in tumor DNA was observed by digital PCR in three patients, of whom one exhibited positivity for MET amplification by FISH, whereas no patient demonstrated MET and HER2 copy number gain in plasma DNA. Digital PCR analysis of plasma is feasible and accurate for detection of T790M mutation in NSCLC that becomes resistant to treatment with EGFR-TKIs. PMID:26334838

  19. Cigarette Smoking, BPDE-DNA Adducts, and Aberrant Promoter Methylations of Tumor Suppressor Genes (TSGs) in NSCLC from Chinese Population.

    Science.gov (United States)

    Jin, Yongtang; Xu, Peiwei; Liu, Xinneng; Zhang, Chunye; Tan, Cong; Chen, Chunmei; Sun, Xiaoyu; Xu, Yingchun

    2016-01-01

    Non-small cell lung cancer (NSCLC) is related to the genetic and epigenetic factors. The goal of this study was to determine association of cigarette smoking and BPDE-DNA adducts with promoter methylations of several genes in NSCLC. Methylation of the promoters of p16, RARβ, DAPK, MGMT, and TIMP-3 genes of tumor tissues from 199 lung cancer patients was analyzed with methylation-specific PCR (MSP), and BPDE-DNA adduct level in lung cancer tissue was obtained by ELISA. Level of BPDE-DNA adduct increased significantly in males, aged people (over 60 years), and smokers; however, no significant difference was found while comparing the BPDE-DNA adduct levels among different tumor types, locations, and stages. Cigarette smoking was also associated with increased BPDE-DNA adducts level (OR = 2.43, p > .05) and increased methylation level in at least 1 gene (OR = 5.22, p smoking also significantly increase the risk of p16 or DAPK methylation (OR = 3.02, p smoking for more than 40 pack-years (OR = 4.21, p smoking is significantly associated with the increase of BPDE-DNA adduct level, promoter hypermethylation of p16 and DAPK genes, while BPDE-DNA adduct was not significantly related to abnormal promoter hypermethylation in TSGs, suggesting that BPDE-DNA adducts and TSGs methylations play independent roles in NSCLC.

  20. IGFBP2/FAK pathway is causally associated with dasatinib resistance in non-small Cell Lung Cancer Cells

    OpenAIRE

    Lu, Haibo; Wang, Li; Gao, Wen; Meng, Jieru; Dai, Bingbing; Wu, Shuhong; Minna, John; Roth, Jack A.; Hofstetter, Wayne L.; Swisher, Stephen G.; Fang, Bingliang

    2013-01-01

    IGFBP2 expression is increased in various types of cancers, including in a subset of lung cancer patients. Because IGFBP2 is involved in signal transduction of some critical cancer related pathways, we analyzed the association between IGFBP2 and response to pathway-targeted agents in seven human non–small cell lung cancer (NSCLC) cell lines. Western blot analysis and enzyme-linked immunosorbent assay (ELISA) showed that four of the seven NSCLC cell lines analyzed expressed high levels of IGFB...

  1. Circulating long noncoding RNA GAS5 is a novel biomarker for the diagnosis of nonsmall cell lung cancer.

    Science.gov (United States)

    Liang, Wenjun; Lv, Tangfeng; Shi, Xuefei; Liu, Hongbing; Zhu, Qingqing; Zeng, Junli; Yang, Wen; Yin, Jie; Song, Yong

    2016-09-01

    The recently discovered long noncoding RNAs have the potential to regulate many biological processes, which are aberrantly expressed in many tumor types. Our previous study showed that the long noncoding RNA-growth arrest-specific transcript 5 (GAS5) was decreased in lung cancer tissue, which contributed to the proliferation and apoptosis of nonsmall cell lung cancer (NSCLC). GAS5 was also associated with the prognosis of lung cancer patients. These results suggest that GAS5 may represent a novel prognostic indicator and a target for gene therapy in NSCLC. However, the expression and diagnosis significance of GAS5 in the plasma of NSCLC patients was unknown. The plasma samples were more readily available than the tissue samples in clinical, so we designed the study to investigate the diagnosis value of GAS5 in blood samples. In our study, 90 patients with NSCLC and 33 healthy controls were included. Blood samples were collected before surgery and therapy. We extracted the free RNA in the plasma and analyzed the expression of GAS5 with quantitative reverse transcription PCR. Suitable statistics methods were used to compare the plasma GAS5 levels of preoperative and postoperative plasma samples between the NSCLC patients and healthy controls. Receiver-operating characteristic curve analysis was used to evaluate the diagnostic sensitivity and specificity of plasma GAS5 in NSCLC. The results showed that GAS5 was detectable and stable in the plasma of NSCLC patients. Furthermore, the plasma levels of GAS5 were significantly down-regulated in NSCLC patients compared with healthy controls (P = 0.000). Moreover, GAS5 levels increased markedly on the seventh day after surgery compared with preoperative GAS5 levels in NSCLC patients (P = 0.003). GAS5 expression levels could be used to distinguish NSCLC patients from control patients with an area under the curve of 0.832 (P ideal biomarker for the diagnosis of NSCLC. PMID:27631209

  2. Prognostic significance of systemic inflammation-based lymphocyte- monocyte ratio in patients with lung cancer: based on a large cohort study.

    Directory of Open Access Journals (Sweden)

    Pingping Hu

    Full Text Available Increasing evidence indicates cancer-related inflammatory biomarkers show great promise for predicting the outcome of cancer patients. The lymphocyte- monocyte ratio (LMR was demonstrated to be independent prognostic factor mainly in hematologic tumor. The aim of the present study was to investigate the prognostic value of LMR in operable lung cancer. We retrospectively enrolled a large cohort of patients with primary lung cancer who underwent complete resection at our institution from 2006 to 2011. Inflammatory biomarkers including lymphocyte count and monocyte count were collected from routinely performed preoperative blood tests and the LMR was calculated. Survival analyses were calculated for overall survival (OS and disease-free survival (DFS. A total of 1453 patients were enrolled in the study. The LMR was significantly associated with OS and DFS in multivariate analyses of the whole cohort (HR = 1.522, 95% CI: 1.275-1.816 for OS, and HR = 1.338, 95% CI: 1.152-1.556 for DFS. Univariate subgroup analyses disclosed that the prognostic value was limited to patients with non-small-cell lung cancer (NSCLC (HR: 1.824, 95% CI: 1.520-2.190, in contrast to patients with small cell lung cancer (HR: 1.718, 95% CI: 0.946-3.122. Multivariate analyses demonstrated that LMR was still an independent prognostic factor in NSCLC. LMR can be considered as a useful independent prognostic marker in patients with NSCLC after complete resection. This will provide a reliable and convenient biomarker to stratify high risk of death in patients with operable NSCLC.

  3. [Sexy cancer--sexuality for cancer patients].

    Science.gov (United States)

    Peleg-Nesher, Sharon; Yachini, Brurya; Inbar, Moshe

    2009-09-01

    Sexuality is a basic need for every human being as long as he or she is alive, irrespective of age or health status. Approximately 23,500 individuals are diagnosed with cancer each year in Israel and join the 120,000 cancer patients currently living in Israel. The results of cancer treatments are traditionally assessed and based on the outcome regarding mortality versus survival. An equally important aspect to be addressed in this assessment must relate to quality of life. One of the more painful insults to the quality of life of cancer patients relates to the deleterious effects on sexuality. This article aims to present physicians with the spectrum of sexuality-related issues which are encountered by cancer patients and their partners, starting from the moment of diagnosis, throughout the various stages of treatment and to provide basic knowledge. Many individuals contracting cancer have difficulty dealing with the issue of sexuality. They are typically embarrassed and feel uneasy when asking health care providers about such a non-life threatening issue. Partners similarly feel both shame and guilt. In many cases sexuality, intimacy and emotional attachment are important aspects and may be essential for survival. Addressing these issues during treatment can provide patients with a sense of security, avoiding embarrassment and further exacerbation of such problems. Unfortunately, little has been done to develop an optimal interventional program, although standard sexual treatments have often been applied. Prospective clinical research and outcomes are missing. The physician can use the well-known PLISSIT model (1978): to provide sexuality involvement on different levels. The very new BETTER model (2004) can help emphasize that cancer treatment and the disease have an influence on intimacy and sexuality. PMID:20070056

  4. Novel Molecular Tumor Cell Markers in Regional Lymph Nodes and Blood Samples from Patients Undergoing Surgery for Non-Small Cell Lung Cancer

    OpenAIRE

    Oddmund Nordgård; Gurpartap Singh; Steinar Solberg; Lars Jørgensen; Ann Rita Halvorsen; Rune Smaaland; Odd Terje Brustugun; Åslaug Helland

    2013-01-01

    INTRODUCTION: Recent evidence suggests that microscopic lymph node metastases and circulating tumor cells may have clinical importance in lung cancer. The purpose of this study was to identify new molecular markers for tumor cells in regional lymph nodes (LNs) and peripheral blood (PB) from patients with non-small cell lung cancer (NSCLC). METHODS: Candidate markers were selected based on digital transcript profiling and previous literature. KRT19, CEACAM5, EPCAM, DSG3, SFTPA, SFTPC and SFTPB...

  5. Repurposing Cationic Amphiphilic Antihistamines for Cancer Treatment

    DEFF Research Database (Denmark)

    Ellegaard, Anne-Marie; Dehlendorff, Christian; Vind, Anna C.;

    2016-01-01

    Non-small cell lung cancer (NSCLC) is one of the deadliest cancers worldwide. In search for new NSCLC treatment options, we screened a cationic amphiphilic drug (CAD) library for cytotoxicity against NSCLC cells and identified several CAD antihistamines as inducers of lysosomal cell death. We the...... of loratadine, astemizole and ebastine sensitized NSCLC cells to chemotherapy and reverted multidrug resistance in NSCLC, breast and prostate cancer cells. Thus, CAD antihistamines may improve the efficacy of cancer chemotherapy...... then performed a cohort study on the effect of CAD antihistamine use on mortality of patients diagnosed with non-localized cancer in Denmark between 1995 and 2011. The use of the most commonly prescribed CAD antihistamine, loratadine, was associated with significantly reduced all-cause mortality among patients...... with non-localized NSCLC or any non-localized cancer when compared with use of non-CAD antihistamines and adjusted for potential confounders. Of the less frequently described CAD antihistamines, astemizole showed a similar significant association with reduced mortality as loratadine among patients with any...

  6. Time evolution of regional CT density changes in normal lung after IMRT for NSCLC

    DEFF Research Database (Denmark)

    Bernchou, Uffe; Schytte, Tine; Bertelsen, Anders;

    2013-01-01

    This study investigates the clinical radiobiology of radiation induced lung disease in terms of regional computed tomography (CT) density changes following intensity modulated radiotherapy (IMRT) for non-small-cell lung cancer (NSCLC).......This study investigates the clinical radiobiology of radiation induced lung disease in terms of regional computed tomography (CT) density changes following intensity modulated radiotherapy (IMRT) for non-small-cell lung cancer (NSCLC)....

  7. The Analysis of Erlotinib on Brain Metastases in Patients with Non-small-cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Baohui HAN

    2009-12-01

    Full Text Available Background and objective Brain metastases are common in non-small-cell lung cancer (NSCLC and the prognosis is poor. Erlotinib is a specific inhibitor of the epidermal growth factor receptor-associated tyrosine kinase (EGFRTKI, which has been gradually used in the treatment for advanced NSCLC. The aim of this study is to evaluate the antitumor efficacy and its relevant factors of erlotinib in NSCLC patients with brain metastases. Methods The clinical data of 30 NSCLC patients with brain metastases were reviewed retrospectively. All of them were treated with erlotinib, given orally 150mg daily. These patients discontinued administration of erlotinib until disease progression, death or intolerable side effects. Results In terms of intracranial lesions, partial response (PR was observed in 2 patients (6.7%, with stable disease (SD in 17 patients (56.7%, for overall disease control rate (DCR of 63.4%. As for systemic disease, PR was observed in 2 patients (6.7%, with SD in 5 patients (16.7%, for overall DCR of 23.4%. There was no statistical difference in DCR among different subtypes of age, gender, smoking history, histology, PS score, the number of brain metastases, the onset of brain metastases, chemotherapy, brain radiotherapy and side effects. The median time to disease progression (MTTP and median survival time (MST was 2.4 months and 7.7 months respectively. The 1 and 2 year survival rate was 38.4% and 15.2%. The univariate analysis showed that the survival time was related to the patients’ PS score, smoking history, brain radiotherapy and chemotherapy. The multivariate analysis indicated that brain radiotherapy was the independent prognostic factor and the relationship between the survival time and smoking history was near to statistical significance. Conclusion The patients receiving brain radiotherapy may have better survival benefit. Non-smokers have a trend to survive longer than smokers. Erlotinib may be effective on brain metastases

  8. Expressions of c-Cbl, Cbl-b and EGFR and Its Role of Prognosis in NSCLC

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    Xin JIAO

    2011-06-01

    Full Text Available Background and objective Epidermal growth factor receptor (EGFR is closely correlated with the progression of lung cancer. Its activity is modulated by Casitas B-lineage lymphoma (Cbl family. The aim of this study is to investigate the expression and clinical relevance of c-Cbl, Cbl-b and EGFR in non-small cell lung cancer (NSCLC. Methods Expressions of c-Cbl, Cbl-b and EGFR protein were detected with tissue microarrays and immunohistochemistry technique in 94 cases of NSCLC. The correlations between the expression of the three proteins and clinicopathological parameters were analyzed. Results The positive expression rates of EGFR, c-Cbl and Cbl-b were 60.6% (57/94, 30.9% (29/94 and 84.0% (79/94, respectively. The expression of EGFR, c-Cbl and Cbl-b was not associated with age, pathological type, TNM stage, lymph node metastasis, and smoking history. c-Cbl and Cbl-b status was not significantly correlated with overall survival. Subgroup analyses showed that c-Cbl-positive patients had longer survival than c-Cbl-negative patients in EGFR-positive group (P=0.014. Conclusion Detection of c-Cbl protein levels might contribute to the prognosis evaluation of EGFR-positive NSCLC.

  9. Monitoring of epidermal growth factor receptor tyrosine kinase inhibitor-sensitizing and resistance mutations in the plasma DNA of patients with advanced non-small cell lung cancer during treatment with erlotinib

    DEFF Research Database (Denmark)

    Sorensen, Boe S; Wu, Lin; Wei, Wen;

    2014-01-01

    BACKGROUND: The feasibility of monitoring epidermal growth factor receptor (EGFR) mutations in plasma DNA from patients with advanced non-small cell lung cancer (NSCLC) during treatment with erlotinib and its relation to disease progression was investigated. METHODS: The amount of EGFR-mutant DNA...... was tested in plasma DNA from patients with advanced NSCLC with allele-specific polymerase chain reaction assays. Blood samples from 23 patients with adenocarcinoma of NSCLC that carried tyrosine kinase inhibitor-sensitizing EGFR mutations were taken immediately before treatment with erlotinib. Additional...... blood samples were taken at timed intervals until erlotinib treatment was withdrawn. RESULTS: The amount of plasma DNA with sensitizing EGFR mutations was found to be reduced after the first cycle of erlotinib treatment in 22 of 23 patients (96%). No patients presented with the resistant T790M mutation...

  10. High plasma fibrinogen concentration and platelet count unfavorably impact survival in non-small cell lung cancer patients with brain metastases

    Institute of Scientific and Technical Information of China (English)

    Jian-Fei Zhu; Ling Cai; Xue-Wen Zhang; Yin-Sheng Wen; Xiao-Dong Su; Tie-Hua Rong; Lan-Jun Zhang

    2014-01-01

    High expression of fibrinogen and platelets are often observed in non-smal celllung cancer (NSCLC) patients with local regional or distant metastasis. However, the role of these factors remains unclear. The aims of this study were to evaluate the prognostic significance of plasma fibrinogen concentration and platelet count, as wel as to determine the overal survival of NSCLC patients with brain metastases. A total of 275 NSCLC patients with brain metastasis were enrolled into this study. Univariate analysis showed that high plasma fibrinogen concentration was associated with age≥65 years (P = 0.011), smoking status (P = 0.009), intracranial symptoms (P = 0.022), clinical T category (P = 0.010), clinical N category (P = 0.003), increased partial thromboplastin time (P < 0.001), and platelet count (P < 0.001). Patients with low plasma fibrinogen concentration demonstrated longer overall survival compared with those with high plasma fibrinogen concentration (median, 17.3 months versus 11.1 months;P≤0.001). A similar result was observed for platelet counts (median, 16.3 months versus 11.4 months;P = 0.004). Multivariate analysis showed that both plasma fibrinogen concentration and platelet count were independent prognostic factors for NSCLC with brain metastases (R2 = 1.698,P < 0.001 andR2 = 1.699,P < 0.001, respectively). Our results suggest that high plasma fibrinogen concentration and platelet count indicate poor prognosis for NSCLC patients with brain metastases. Thus, these two biomarkers might be independent prognostic predictors for this subgroup of NSCLC patients.

  11. Brief versions of the FACIT-fatigue and FAACT subscales for patients with non-small cell lung cancer cachexia

    OpenAIRE

    Salsman, John M.; Beaumont, Jennifer L.; WORTMAN, KATY; Yan, Ying; Friend, John; Cella, David

    2014-01-01

    Purpose Cancer anorexia-cachexia syndrome (CACS) is common in advanced cancer patients and associated with weight loss, fatigue, impaired quality of life (QoL), and poor prognosis. The goal of this project was to identify the most responsive items from two QoL measures in the ROMANA 2 (NCT01387282) phase III global study evaluating anamorelin HCl in the treatment of non-small cell lung cancer (NSCLC) cachexia: the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) and the Func...

  12. Randomize Trial of Cisplatin plus Gemcitabine with either Sorafenib or Placebo as First-line Therapy for Non-small Cell Lung Cancer

    OpenAIRE

    Yan WANG; Wang, Lin; Liu, Yutao; Shufei YU; Xiangru ZHANG; Shi, Yuankai; Sun, Yan

    2011-01-01

    Background and objective Platinum-based chemotherapy doublets reached an efficacy plateau in nonsmall-cell lung cancer (NSCLC). This randomized controlled study prospectively assessed the efficacy and safety of cisplatin plus gemcitabine with either Sorafenib or placebo as first-line therapy for NSCLC. Methods Thirty patients, which were confirmed advanced NSCLC histologically or cytologically, were randomly assigned to receive up to six cycles of cisplatin plus gemcitabine with sorafenib or ...

  13. α-Tocopheryl succinate potentiates the paclitaxel-induced apoptosis through enforced caspase 8 activation in human H460 lung cancer cells

    OpenAIRE

    Lim, Soo-Jeong; Choi, Moon Kyung; Kim, Min Jung; Kim, Joo Kyoung

    2009-01-01

    Paclitaxel is one of the chemotheraputic drugs widely used for the treatment of nonsmall cell lung cancer (NSCLC) patients. Here, we tested the ability of α-tocopheryl succinate (TOS), another promising anticancer agent, to enhance the paclitaxel response in NSCLC cells. We found that sub-apoptotic doses of TOS greatly enhanced paclitaxel-induced growth suppression and apoptosis in the human H460 NSCLC cell lines. Our data revealed that this was accounted for primarily by an augmented cleavag...

  14. Nutritional Considerations for Cancer Patients

    OpenAIRE

    Chen, Angela

    1985-01-01

    Although weight loss is a frequent, though not invariable, component of the cancer syndrome, the associated malnutrition is a poor prognostic sign among both children and adults. This article describes the possible mechanisms of cancer cachexia; reviews the present state of nutritional support in cancer patients; identifies nutritional problems and workable approaches during the pre- and post-treatment periods; discusses the unconventional nutritional practices commonly encountered and lists ...

  15. Treating advanced non-small-cell lung cancer in Chinese patients: focus on icotinib

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    Liang JL

    2014-05-01

    Full Text Available Jun-Li Liang,1 Xiao-Cang Ren,2 Qiang Lin2 1Department of Radiation Oncology, Hebei Medical University Fourth Hospital, Shijiazhuang, People’s Republic of China; 2Department of Oncology, North China Petroleum Bureau General Hospital of Hebei Medical University, Renqiu, Hebei Province, People’s Republic of China Abstract: Icotinib hydrochloride is an orally administered small-molecule reversible tyrosine kinase inhibitor that has been independently researched and developed and has independent intellectual property rights in the People’s Republic of China. Clinical trials have demonstrated that the response to icotinib among advanced non-small-cell lung cancer (NSCLC patients who received at least one platinum-based chemotherapy regimen was not inferior to gefitinib. Since being launched August 2011 in the People’s Republic of China, icotinib has been widely used in clinics, and has become an important treatment option for Chinese patients with advanced NSCLC. The present study presents the Phase I, II, and III clinical trials of icotinib and discusses current clinical applications in the People’s Republic of China and future research directions. Keywords: targeted therapy, EGFR-TKI, NSCLC

  16. A laboratory prognostic index model for patients with advanced non-small cell lung cancer.

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    Arife Ulas

    Full Text Available We aimed to establish a laboratory prognostic index (LPI in advanced non-small cell lung cancer (NSCLC patients based on hematologic and biochemical parameters and to analyze the predictive value of LPI on NSCLC survival.The study retrospectively reviewed 462 patients with advanced NSCLC diagnosed between 2000 and 2010 in a single institution. We developed an LPI that included serum levels of white blood cells (WBC, lactate dehydrogenase (LDH, albumin, calcium, and alkaline phosphatase (ALP, based on the results of a Cox regression analysis. The patients were classified into 3 LPI groups as follows: LPI 0: normal; LPI 1: one abnormal laboratory finding; and LPI 2: at least 2 abnormal laboratory findings.The median follow up period was 44 months; the median overall survival (OS and median progression-free survival (PFS were 11 and 6 months, respectively. A multivariate analysis revealed that the following could be used as independent prognostic factors: an Eastern Cooperative Oncology Group performance status score (ECOG PS ≥2, a high LDH level, serum albumin 10.5 g/dL, number of metastases>2, presence of liver metastases, malignant pleural effusion, or receiving chemotherapy ≥4 cycles. The 1-year OS rates according to LPI 0, LPI 1, and LPI 2 were 54%, 34%, and 17% (p<0.001, respectively and 6-month PFS rates were 44%, 27%, and 15% (p<0.001, respectively. The LPI was a significant predictor for OS (Hazard Ratio (HR: 1.41; 1.05-1.88, p<0.001 and PFS (HR: 1.48; 1.14-1.93, p<0.001.An LPI is an inexpensive, easily accessible and independent prognostic index for advanced NSCLC and may be helpful in making individualized treatment plans and predicting survival rates when combined with clinical parameters.

  17. Cancer Cell Growth Inhibitory Effect of Bee Venom via Increase of Death Receptor 3 Expression and Inactivation of NF-kappa B in NSCLC Cells

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    Kyung Eun Choi

    2014-07-01

    Full Text Available Our previous findings have demonstrated that bee venom (BV has anti-cancer activity in several cancer cells. However, the effects of BV on lung cancer cell growth have not been reported. Cell viability was determined with trypan blue uptake, soft agar formation as well as DAPI and TUNEL assay. Cell death related protein expression was determined with Western blotting. An EMSA was used for nuclear factor kappaB (NF-κB activity assay. BV (1–5 μg/mL inhibited growth of lung cancer cells by induction of apoptosis in a dose dependent manner in lung cancer cell lines A549 and NCI-H460. Consistent with apoptotic cell death, expression of DR3 and DR6 was significantly increased. However, deletion of DRs by small interfering RNA significantly reversed BV induced cell growth inhibitory effects. Expression of pro-apoptotic proteins (caspase-3 and Bax was concomitantly increased, but the NF-κB activity and expression of Bcl-2 were inhibited. A combination treatment of tumor necrosis factor (TNF-like weak inducer of apoptosis, TNF-related apoptosis-inducing ligand, docetaxel and cisplatin, with BV synergistically inhibited both A549 and NCI-H460 lung cancer cell growth with further down regulation of NF-κB activity. These results show that BV induces apoptotic cell death in lung cancer cells through the enhancement of DR3 expression and inhibition of NF-κB pathway.

  18. The expression of Lunx mRNA in Peripheral Blood of patients with NSCLC by RT-PCR and its Clinical significance%RT-PCR法检测非小细胞肺癌患者外周血Lunx mRNA的表达及临床意义

    Institute of Scientific and Technical Information of China (English)

    谢风; 李辉; 孙晓盈

    2009-01-01

    Objective To discuss the significance of diagnosis、treat and prognosticjudgement by detecting the expression of Lunx mRNA in peripheral blood of patients with nonsmall-cell lung cancer.Methods To detect the expression of Lunx mRNA in peripheral blood of the experimental and control groups by RT-PCR(reverse transcription PCR).Results there are significant deviation (P0.05) between micrometastasis and age、gender、smoking history and primartumor position.Conclusion RT-PCR is regarded as a effective method to detect the expression of Lunx mRNA in micrometastasis of NSCLC,Lunx mRNA is a new special tumor marker for the detecting micrometastasis of NSCLC,which is important for diagnosis、treat and prognostic judgement.%目的 通过检测非小细胞肺癌患者外周血Lunx mRNA的表达来探讨其对临床诊断、治疗及判断预后的意义.方法 采用 RT-PCR(逆转录PCR)技术分别对实验组及对照组外周血Lunx mRNA的表达进行检测分析.结果 NSCLC患者外周血微转移与病理类型、细胞分化程度及TNM分期均存在密切关系(P0.05).结论 应用RT-PCR技术建立了一种检测NSCLC微转移Lunx mRNA表达的实验方法,Lunx mRNA 是一种检测 NSCLC外周血微转移新型的、较好的特异性标记物,对判断病程发展和指导临床治疗具有重要意义.

  19. Five year survival of non-small cell lung cancer patients in Brunei Darussalam

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    Muhd Syafiq ABDULLAH

    2013-02-01

    Full Text Available Introduction: Lung cancer has been the leading cause of cancer deaths in Brunei Darussalam for the past five years. This study is the first to supply data for the 5-year survival of patients diagnosed with non-small cell lung cancer (NSCLC in Brunei Darussalam. Materials and Methods: From 2002 to 2009, 302 patients diagnosed with NSCLC were identified from the National Cancer Registry of Brunei Darussalam. Demographic and clinical data were retrospectively retrieved from the clinical notes. All deaths and dates of death were obtained and crosschecked with the National Birth and Death Registry at the Immigration Department. Data were analysed using SPSS statistical software and 5-year Kaplan-Meier survival curves were derived and analysed. Predictors of 5-year survival were analysed using Cox regression analysis. Results: Mean age of the 302 patients was 64.9 ± 12.8 (27.4–90.6 years with male to female ratio of 194:108. Racial distribution consisted of 84.4% (n=255 Malay, 12.5% (n=38 Chinese and 3.1% of other racial origin (indigenous and foreign nationals. Histological types of NSCLC consisted of 67.9% (n=205 adenocarcinoma, 16.2% (n=49 squamous cell carcinoma, 6.3% (n=19 large cell carcinoma, 5.3% (n=16 bronchioalveolar carcinoma and 4.3% of other origin. Only 13.9% of patients underwent surgical resection. At completion of follow-up, only 47 (15.5% patients were still alive. There were 255 deaths. Overall 5-year survival for the whole group was 3.6% with a median survival time of 6.5 ± 0.9 months (95% CI: 4.7-8.4 months but according to stage of disease was 60.9% for Stage IA, 29.9% for Stage IB, 10.0% for Stage IIB, 7% for Stage IIIB and 3% for Stage IV. Significant prognostic factors were younger age at diagnosis, surgical resection, tumour types and tumour stages. Conclusion: Overall 5-year survival of patients diagnosed with NSCLC in Brunei Darussalam is still generally poor but comparable to previously reported data. Significant

  20. Cancer Patients and Fungal Infections

    Science.gov (United States)

    ... site. Top of Page Preventing fungal infections in cancer patients Fungi are difficult to avoid because they are a natural part of the environment. Fungi live outdoors in soil, on plants, trees, and other vegetation. They are also on ...

  1. 焦磷酸测序技术检测63例晚期NSCLC患者血浆KRAS基因突变%KRAS mutation detection by pyrosequencing in plasma of 63 patients with advanced NSCLC

    Institute of Scientific and Technical Information of China (English)

    孙洁; 明华; 孙建国; 张晓晶; 王欣欣; 刘佳; 陈正堂

    2012-01-01

    Objective To evaluate the utility of pyrosequencing to detect KRAS mutations in plasma ,and to investigate the frequency and characteristic of plasma KRAS mutations of patients with advanced NSCLC .Methods We collected 63 blood samples from advanced NSCLC patients isolated plasma and extracted DNA .The mutations in codon 12 and 13 of KRAS were detected by pyrosequencing of the nested-PCR fragment .Results Somatic mutations in KRAS gene in plasma were identified from 3 cases of 63 (4 .76% ) patients .The frequency of KRAS mutations in plasma of advanced NSCLC in our center coincided with that in tumor of Asian population ,but was lower than that in Western population .The mutations were all one-base substitution ,of which two cases in codon 12 and one case in codon 13 .KRAS mutations did not relate with gender ,smoking history ,age,pathological type,tumor stage ,and PS score .Conclusion Pyrosequencing is a fast method with high-throughput .It can be used for detecting KRAS mutations in circulating DNA ,and is suitable for screening patients refractory with tyrosine kinase inhibitors .It is conductive to guide the patients to choose personalized therapy with molecular targeted agents .%目的 探讨应用焦磷酸测序技术检测血浆KRAS基因突变的实用性,了解晚期非小细胞肺癌(NSCLC)血浆KRAS基因突变率和突变特征.方法 收集63例晚期NSCLC患者的外周血标本,分离血浆并提取DNA,采用巢式PCR结合焦磷酸测序分析KRAS基因12和13号密码子突变.结果 在63例晚期NSCLC患者中,3例存在血浆KRAS基因突变(4.76%),突变率较低,与亚裔组织KRAS突变率一致,低于西方人KRAS突变率,其突变类型均为单碱基替换突变.其中2例为12密码子突变,1例为13密码子突变.统计学分析未发现血浆KRAS突变与性别、吸烟史、年龄、病理类型、肿瘤分期、体力状况(PS)评分存在相关性.结论 焦磷酸测序技术操作简便,可以快速、高通量地进行外周血

  2. Perioperative nutrition in cancer patients.

    Science.gov (United States)

    Daly, J M; Redmond, H P; Gallagher, H

    1992-01-01

    Cancer patients have the highest incidence of protein-calorie malnutrition seen in hospitalized patients, with significant malnutrition occurring in more than 30% of cancer patients undergoing major upper gastrointestinal procedures. Clinically significant malnutrition occurs as a result of diminished nutrient intake, increased nutrient losses, and tumor-induced derangements in host metabolism. In the absence of adequate exogenous nutrients, the body utilizes endogenous substrates to satisfy the ongoing requirements of both host and tumor for energy and protein. In those patients with malignant obstruction of the gastrointestinal tract, the tumor itself may induce diminished nutrient intake. Present day treatment modalities including gastrointestinal resection, chemotherapy, and radiotherapy compound these metabolic derangements, further increasing the risk of postoperative morbidity and death. The presence of malnutrition in cancer patients has prognostic importance. In a review of more than 3000 cancer patients, DeWys and colleagues identified significantly improved survival in those patients without weight loss compared with those had lost 6% of their body weight (Am J Med 69:491-497, 1980). Other investigators have noted increased postoperative morbidity and mortality associated with malnutrition. Early hypotheses suggested that reversal of weight loss would improve survival. The development and refinements of enteral and parenteral nutrition have provided the opportunity for studying the relationship between nutritional supplementation and postoperative prognosis. Nutrition support is therefore often instituted to improve nutritional status and thereby reduce the risks of postoperative complications. This article addresses the beneficial role of preoperative nutrition therapy in cancer patients.

  3. The role of positron emission tomography/computed tomography in radiation therapy planning for patients with lung cancer.

    Science.gov (United States)

    Mac Manus, Michael P; Hicks, Rodney J

    2012-09-01

    Positron emission tomography (PET)/computed tomography (CT) has rapidly assumed a critical role in the management of patients with locoregionally advanced lung cancers who are candidates for definitive radiation therapy (RT). Definitive RT is given with curative intent, but can only be successful in patients without distant metastasis and if all gross tumor is contained within the treated volume. An increasing body of evidence supports the use of PET-based imaging for selection of patients for both surgery and definitive RT. Similarly, the use of PET/CT images for accurate target volume definition in lung cancer is a dynamic area of research. Most available evidence on PET staging of lung cancer relates to non-small cell lung cancer (NSCLC). In general clinical use, (18)F-fluorodeoxyglucose (FDG) is the primary radiopharmaceutical useful in NSCLC. Other tracers, including proliferation markers and hypoxia tracers, may have significant roles in future. Much of the FDG-PET literature describing the impact of PET on actual patient management has concerned candidates for surgical resection. In the few prospective studies where PET was used for staging and patient selection in NSCLC candidates for definitive RT, 25%-30% of patients were denied definitive RT, generally because PET detected unsuspected advanced locoregional or distant metastatic disease. PET/CT and CT findings are often discordant in NSCLC but studies with clinical-pathological correlation always show that PET-assisted staging is more accurate than conventional assessment. In all studies in which "PET-defined" and "non-PET-defined" RT target volumes were compared, there were major differences between PET and non-PET volumes. Therefore, in cases where PET-assisted and non-PET staging are different and biopsy confirmation is unavailable, it is rational to use the most accurate modality (namely PET/CT) to define the target volume. The use of PET/CT in patient selection and target volume definition is likely

  4. Differential miRNA expressions in peripheral blood mononuclear cells for diagnosis of lung cancer.

    Science.gov (United States)

    Ma, Jie; Lin, Yanli; Zhan, Min; Mann, Dean L; Stass, Sanford A; Jiang, Feng

    2015-10-01

    Tremendous efforts have been made to develop cancer biomarkers by detecting circulating extracellular miRNAs directly released from tumors. Yet, none of the cell-free biomarkers has been accepted to be used for early detection of non-small cell lung cancer (NSCLC). Peripheral blood mononucleated cells (PBMCs) act as the first line of defense against malignancy in immune system, their dysfunction may occur as an early event in cancer immunogenicity or immune evasion. We proposed to investigate whether analysis of miRNA expressions of PBMCs has diagnostic value for NSCLC. We first used a microarray to analyze PBMCs of 16 stage I NSCLC patients and 16 cancer-free smokers, and identified seven PBMC miRNAs with a significantly altered expression level in NSCLC patients. In a training set of 84 NSCLC patients and 69 cancer-free smokers, a panel of two miRNAs (miRs-19b-3p and -29b-3p) were developed from the seven PBMC miRNAs, producing 72.62% sensitivity and 82.61% specificity in identifying NSCLC. Furthermore, the miRNAs could identify squamous cell lung carcinoma (SCC), a major type of NSCLC, with 80.00% sensitivity and 89.86% specificity. The expression levels of the miRNAs were independent of disease stage. In a testing set of 56 NSCLC patients and 46 controls, the performance of the biomarkers was reproducibly confirmed. The study presents the first in-depth analysis of PBMC miRNA profile of NSCLC patients. The assessment of PBMC miRNAs may provide a new diagnostic approach for the early detection of NSCLC.

  5. Intensity-modulated stereotactic body radiotherapy for stage I non-small cell lung cancer

    OpenAIRE

    Kim, Min-Jeong; Yeo, Seung-Gu; KIM, EUN SEOK; MIN, CHUL KEE; SE AN, PYUNG

    2012-01-01

    This study aimed to investigate the clinical outcomes of intensity-modulated radiotherapy (IMRT)-based stereotactic body radiotherapy (SBRT) for patients with stage I non-small cell lung cancer (NSCLC). A prospective database of 16 consecutive patients receiving SBRT for pathologically-proven and peripherally-located stage I NSCLC was reviewed. Fifteen patients were medically inoperable and one patient refused to undergo surgery. The median age of the patients was 76 years (range, 69–86). Tre...

  6. MDT lung cancer care: input from the Surgical Oncologist.

    Science.gov (United States)

    Kidane, Biniam; Toyooka, Shinichi; Yasufuku, Kazuhiro

    2015-10-01

    Although there have been many advancements in the multidisciplinary management of non-small cell lung cancer (NSCLC), surgery remains the primary modality of choice for resectable lung cancer when the patient is able to tolerate lung resection physiologically. There have been recent advances in surgical diagnosis and treatment of lung cancer. Increasing use of low-dose computed tomography (CT) screening for lung cancer has resulted in increased detection of small peripheral nodules or semi-solid ground glass opacities. Here, we review different modalities of localization techniques that have been used to aid surgical excisional biopsy when needle biopsy has failed to provide tissue diagnosis. We also report on the current debates regarding the use of sublobar resections for Stage I NSCLC as well as the surgical management of locally advanced NSCLC. Finally, we discuss the complex surgical management of T4 NSCLC lung cancers. PMID:26059591

  7. Bioinformatics Analyses of the Role of Vascular Endothelial Growth Factor in Patients with Non-Small Cell Lung Cancer.

    Directory of Open Access Journals (Sweden)

    Ying Wang

    Full Text Available This study was aimed to identify the expression pattern of vascular endothelial growth factor (VEGF in non-small cell lung cancer (NSCLC and to explore its potential correlation with the progression of NSCLC.Gene expression profile GSE39345 was downloaded from the Gene Expression Omnibus database. Twenty healthy controls and 32 NSCLC samples before chemotherapy were analyzed to identify the differentially expressed genes (DEGs. Then pathway enrichment analysis of the DEGs was performed and protein-protein interaction networks were constructed. Particularly, VEGF genes and the VEGF signaling pathway were analyzed. The sub-network was constructed followed by functional enrichment analysis.Total 1666 up-regulated and 1542 down-regulated DEGs were identified. The down-regulated DEGs were mainly enriched in the pathways associated with cancer. VEGFA and VEGFB were found to be the initiating factor of VEGF signaling pathway. In addition, in the epidermal growth factor receptor (EGFR, VEGFA and VEGFB associated sub-network, kinase insert domain receptor (KDR, fibronectin 1 (FN1, transforming growth factor beta induced (TGFBI and proliferating cell nuclear antigen (PCNA were found to interact with at least two of the three hub genes. The DEGs in this sub-network were mainly enriched in Gene Ontology terms related to cell proliferation.EGFR, KDR, FN1, TGFBI and PCNA may interact with VEGFA to play important roles in NSCLC tumorigenesis. These genes and corresponding proteins may have the potential to be used as the targets for either diagnosis or treatment of patients with NSCLC.

  8. Elevated serum levels of fetal antigen 1,a member of the epidermal growth factor superfamily, in patients with small cell lung cancer

    DEFF Research Database (Denmark)

    Harken Jensen, C; Drivsholm, L; Laursen, I;

    1999-01-01

    Serum levels of fetal antigen 1 (FA1) were quantified pretherapeutically in 16 patients with pneumonia, 30 patients with small cell lung cancer (SCLC) and 10 patients with non-small cell lung cancer (NSCLC) and compared to the normal reference interval (n = 177). Serum FA1 levels were significantly...... of limited/extensive disease. Immunohistochemical analysis of a biopsy from 1 SCLC patient with an elevated serum FA1 also showed the presence of FA1 in tumor cells. FA1 in serum from SCLC patients was identical to that of FA1 in normal serum/amniotic fluid with respect to size distribution and also revealed...

  9. Platelet VEGF and serum TGF-β1 levels predict chemotherapy response in non-small cell lung cancer patients.

    Science.gov (United States)

    Fu, Bao-Hong; Fu, Zhan-Zhao; Meng, Wei; Gu, Tao; Sun, Xiao-Dong; Zhang, Zhi

    2015-08-01

    We examined the levels of platelet vascular endothelial growth factor (VEGF(PLT)) and serum level of transforming growth factor beta 1 (TGF-β1) in non-small cell lung cancer (NSCLC) patients before and after chemotherapy to assess their clinical value as biomarkers. A total of 115 subjects were recruited at the First Hospital of Qinhuangdao between July 2012 and October 2013, including 65 NSCLC patients receiving chemotherapy (NSCLC group) and 50 healthy controls (control group). All NSCLC patients received gemcitabine plus cisplatin (GP regimen) for a total of two courses. VEGF(PLT) and serum TGF-β1 levels were measured before and after chemotherapy using enzyme-linked immunosorbent assay (ELISA). Platelet count was obtained using the Abbott CD-1600 auto blood analyzer. NSCLC group was categorized into complete response (CR) plus partial response (PR) group and stable disease (SD) plus progressive disease (PD) group based on the results of CT scans obtained 1 week after chemotherapy. Our results revealed that VEGF(PLT) and serum TGF-β1 levels were significantly higher in NSCLC group before chemotherapy, compared to the control group (VEGF(PLT), 0.813 ± 0.072 vs. 0.547 ± 0.024; t = 26.48; P VEGF(PLT) and serum TGF-β1 levels decreased significantly after chemotherapy in CR + PR group in comparison with before chemotherapy (VEGF(PLT), 0.453 ± 0.078 vs. 0.814 ± 0.127; t = 15.51; P VEGF(PLT) and serum TGF-β1 levels were markedly higher after chemotherapy in the SD + PD group in comparison with before chemotherapy (VEGF(PLT), 0.816 ± 0.043 vs. 1.065 ± 0.016; t = 22.38; P VEGF(PLT) and serum TGF-β1 levels, and VEGF(PLT) and TGF-β1 levels correlate with chemotherapy response to GP regimen. Therefore, VEGF(PLT) and serum TGF-β1 levels are valuable biomarkers in clinical monitoring of NSCLC patients. PMID:25820820

  10. Next-Generation Sequencing Workflow for NSCLC Critical Samples Using a Targeted Sequencing Approach by Ion Torrent PGM™ Platform

    Directory of Open Access Journals (Sweden)

    Irene Vanni

    2015-12-01

    Full Text Available Next-generation sequencing (NGS is a cost-effective technology capable of screening several genes simultaneously; however, its application in a clinical context requires an established workflow to acquire reliable sequencing results. Here, we report an optimized NGS workflow analyzing 22 lung cancer-related genes to sequence critical samples such as DNA from formalin-fixed paraffin-embedded (FFPE blocks and circulating free DNA (cfDNA. Snap frozen and matched FFPE gDNA from 12 non-small cell lung cancer (NSCLC patients, whose gDNA fragmentation status was previously evaluated using a multiplex PCR-based quality control, were successfully sequenced with Ion Torrent PGM™. The robust bioinformatic pipeline allowed us to correctly call both Single Nucleotide Variants (SNVs and indels with a detection limit of 5%, achieving 100% specificity and 96% sensitivity. This workflow was also validated in 13 FFPE NSCLC biopsies. Furthermore, a specific protocol for low input gDNA capable of producing good sequencing data with high coverage, high uniformity, and a low error rate was also optimized. In conclusion, we demonstrate the feasibility of obtaining gDNA from FFPE samples suitable for NGS by performing appropriate quality controls. The optimized workflow, capable of screening low input gDNA, highlights NGS as a potential tool in the detection, disease monitoring, and treatment of NSCLC.

  11. Role of gender in the survival of surgical patients with nonsmall cell lung cancer

    Directory of Open Access Journals (Sweden)

    Nóris C Scaglia

    2013-01-01

    Conclusions: Our results show female gender as a possible protective factor for better survival of stage I NSCLC patients, but not among stage II patients. This study adds data to the knowledge that combined both genders survival rates for NSCLC is not an adequate prognosis.

  12. Circulating Lymphocyte Subsets 
in Patients with Lung Cancer and Their Prognostic Value

    Directory of Open Access Journals (Sweden)

    Jun LUO

    2011-08-01

    Full Text Available Background and objective Lung cancer is one of the most common malignancies. The aim of this study is to investigate the relationship between the change of lymphocyte subsets in the peripheral blood of lung cancer patients and the survival rate. Methods Flow cytometry was used to measure the percentages of lymphocyte subsets (CD3+, CD4+, CD8+, CD4+/CD8+, CD19+, CD25+, CD44+, and NK cells in peripheral blood obtained from 221 patients with primary lung cancer without any treatment and from 96 healthy blood donors as the control group. The result was combined with clinical and follow-up data and statistical analysis was conducted. Results The levels of CD3+ and CD8+ in the patient group are significantly lower compared with the control group, whereas the levels of CD4+/CD8+, CD19+, CD25+, CD44+, and NK cells are significantly higher (P<0.05. CD8+ is significantly higher in the small cell lung cancer (SCLC group compared with the non-small cell lung cancer (NSCLC group. However, CD4+ and CD4+/CD8+ are lower in SCLC (P<0.05. There were no significant differences in different stages and differentiation (P>0.05 in the NSCLC group. The level of CD3+ was significantly higher compared with the pre-chemotherapy group, but NK cell, CD19+, and CD44+ were distinctly lower in the post-chemotherapy group (P<0.05. More survival opportunities will be obtained for patients with no increase in CD44+ after chemotherapy (P=0.021, but the other three indices have no obvious influence on survival. Conclusion Widespread changes of lymphocyte occur in the peripheral blood of patients with lung cancer. There is a significant correlation between the change of CD44+ and the prognosis after chemotherapy.

  13. High expression of MAGE-A9 in tumor and stromal cells of non-small cell lung cancer was correlated with patient poor survival.

    Science.gov (United States)

    Zhang, Siya; Zhai, Xiaolu; Wang, Gui; Feng, Jian; Zhu, Huijun; Xu, Liqin; Mao, Guoxin; Huang, Jianfei

    2015-01-01

    Melanoma associated antigen-A (MAGE-A) is an oncogene and correlated with tumor initiation and development. However the roles of MAGE-A9 in non-small cell lung cancer (NSCLC) are still unknown. We investigated MAGE-A9 mRNA expression in 18 tumor tissues of NSCLC by qRT-PCR and MAGE-A9 protein expression in 213 NSCLC samples of tissue arrays by immunohistochemical staining. We assessed the relationship between MAGE-A9 expression and clinical parameters. The results showed that the high expression of MAGE-A9 protein in NSCLC tumor cells were commonly present in squamous cell carcinomas (P = 0.030). It was also related to larger tumor diameter, lymph node metastasis and later stage grouping with TNM classification (all P cells was higher in squamous cell carcinomas as well. Cox regression univariate and multivariable analysis revealed that MAGE-A9 expression in tumor cells of NSCLC (P < 0.001) is an independent prognostic factor in five-year overall survival rate. We concluded that the molecular assessment of MAGEA9 could be considered to improve prognostic evaluation and to identify eligible patients for potential target therapy.

  14. Abnormal expression of VEGF and its gene transcription status as diagnostic indicators in patients with non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    Yun Shi; Yang Shi; Xuli Yang; Jianrong Chen; Qi Qian; Dengfu Yao; Guangzhou Wu

    2015-01-01

    Objective Angiogenesis is known to be essential for the survival, growth, invasion, and metastasis of lung cancer cells. Vascular endothelial growth factor (VEGF) is an important factor regulating angiogenesis of non-small cell lung cancer (NSCLC); however, its pathologic features and significance are unclear. In this study, the tissue VEGF expression levels and its gene transcriptional status, as well as circulating VEGF levels, were investigated in patients with lung disease.Methods VEGF protein and mRNA expression levels in 38 lung tissue samples were analyzed by immu-nohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR), respectively. Circulating VEGF levels were detected quantitatively by an enzyme linked immuno-sorbent assay. Results The level of VEGF expression was significantly higher in lung cancer tissue than in the corre-sponding paracancerous or non-cancerous tissues. The average level of VEGF-positive staining was 76% in tissue samples from NSCLC patients; the levels were 89% in tissue samples from stage Ⅲ patients and 92% in stage Ⅳ patients. High VEGF expression was also evident in cases with lymph node metastasis (84%), distant metastasis (90%), and lower differentiation degree (89%). VEGF mRNA in cancerous tis-sues was represented predominantly by the VEGF121 and VEGF165 isoforms. Circulating VEGF levels were significantly higher in NSCLC patients [(840 ± 324) pg/mL] than in patients with benign lung diseases [(308 ± 96) pg/mL] or in healthy individuals serving as controls [(252 ± 108) pg/mL]. Conclusion The over-expression of lung VEGF and its gene transcription status should be useful mo-lecular indicators for NSCLC diagnosis.

  15. Telomere length of tumor tissues and survival in patients with early stage non-small cell lung cancer.

    Science.gov (United States)

    Jeon, Hyo-Sung; Choi, Yi Young; Choi, Jin Eun; Lee, Won Kee; Lee, Eungbae; Yoo, Seung Soo; Lee, Shin Yup; Lee, Jaehee; Cha, Seung Ick; Kim, Chang Ho; Park, Jae Yong

    2014-04-01

    Telomere shortening leads to genomic instability that drives oncogenesis through the activation of telomerase and the generation of other mutations necessary for tumor progression. This study was conducted to determine the impact of telomere shortening on the survival of patients with early stage non-small cell lung cancer (NSCLC). Relative telomere length in tumor tissues was measured by quantitative polymerase chain reaction in 164 patients with surgically resected NSCLC. The association between telomere length and overall survival (OS) and disease-free survival (DFS) was analyzed. When the patients were categorized into quartiles based on telomere length, those patients with the 1st quartile (shortest) of telomere length had a significantly worse OS and DFS compared to patients with the 2nd to the 4th quartiles of telomere length (adjusted hazard ratio for OS = 2.67, 95% confidence interval = 1.50-4.75, P = 0.001; and adjusted hazard ratio for DFS = 1.92, 95% confidence interval = 1.17-3.14, P = 0.01). An association between telomere length and survival outcome was more pronounced in squamous cell carcinomas than adenocarcinomas (P-value of test for homogeneity for OS and DFS = 0.05 and 0.02, respectively). Telomere length of tumor tissues is an independent prognostic factor in patients with surgically resected early stage NSCLC.

  16. Diagnostic utility of serum and pleural fluid carcinoembryonic antigen, and cytokeratin 19 fragments in patients with effusion from nonsmall cell lung cancer

    OpenAIRE

    Sushil Kumar Sharma; Sanjay Bhat; Vikas Chandel; Mayank Sharma; Pulkit Sharma; Sakul Gupta; Sashank Sharma; Aijaz Ahmed Bhat

    2015-01-01

    Aims: To assess the diagnostic value of CEA and CYFRA 21-1 (cytokeratin 19 fragments) in serum and pleural fluid in non small cell lung cancer with malignant pleural effusion (MPE). Settings and Design: Two subsets of patients were recruited with lymphocytic exudative effusion, one subset constituted diagnosed patients of NSCLC with malignant pleural effusion and the other subset of constituted with Tubercular pleural effusion. Methods and Material : CYFRA 21-1 and CEA levels were measured us...

  17. Acute Esophagus Toxicity in Lung Cancer Patients After Intensity Modulated Radiation Therapy and Concurrent Chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Kwint, Margriet [Department of Radiation Oncology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Uyterlinde, Wilma [Department of Thoracic Oncology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Nijkamp, Jasper; Chen, Chun; Bois, Josien de; Sonke, Jan-Jakob [Department of Radiation Oncology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Heuvel, Michel van den [Department of Thoracic Oncology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Knegjens, Joost; Herk, Marcel van [Department of Radiation Oncology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Belderbos, Jose, E-mail: j.belderbos@nki.nl [Department of Radiation Oncology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands)

    2012-10-01

    Purpose: The purpose of this study was to investigate the dose-effect relation between acute esophageal toxicity (AET) and the dose-volume parameters of the esophagus after intensity modulated radiation therapy (IMRT) and concurrent chemotherapy for patients with non-small cell lung cancer (NSCLC). Patients and Methods: One hundred thirty-nine patients with inoperable NSCLC treated with IMRT and concurrent chemotherapy were prospectively analyzed. The fractionation scheme was 66 Gy in 24 fractions. All patients received concurrently a daily dose of cisplatin (6 mg/m Superscript-Two ). Maximum AET was scored according to Common Toxicity Criteria 3.0. Dose-volume parameters V5 to V70, D{sub mean} and D{sub max} of the esophagus were calculated. A logistic regression analysis was performed to analyze the dose-effect relation between these parameters and grade {>=}2 and grade {>=}3 AET. The outcome was compared with the clinically used esophagus V35 prediction model for grade {>=}2 after radical 3-dimensional conformal radiation therapy (3DCRT) treatment. Results: In our patient group, 9% did not experience AET, and 31% experienced grade 1 AET, 38% grade 2 AET, and 22% grade 3 AET. The incidence of grade 2 and grade 3 AET was not different from that in patients treated with CCRT using 3DCRT. The V50 turned out to be the most significant dosimetric predictor for grade {>=}3 AET (P=.012). The derived V50 model was shown to predict grade {>=}2 AET significantly better than the clinical V35 model (P<.001). Conclusions: For NSCLC patients treated with IMRT and concurrent chemotherapy, the V50 was identified as most accurate predictor of grade {>=}3 AET. There was no difference in the incidence of grade {>=}2 AET between 3DCRT and IMRT in patients treated with concurrent chemoradiation therapy.

  18. SU-E-J-172: A Quantitative Assessment of Lung Tumor Motion Using 4DCT Imaging Under Conditions of Controlled Breathing in the Management of Non-Small Cell Lung Cancer (NSCLC) Using Stereotactic Body Radiation Therapy (SBRT)

    Energy Technology Data Exchange (ETDEWEB)

    Mohatt, D; Gomez, J; Singh, A; Malhotra, H [Roswell Park Cancer Institute, Buffalo, NY (United States)

    2014-06-01

    Purpose: To study breathing related tumor motion amplitudes by lung lobe location under controlled breathing conditions used in Stereotactic Body Radiation Therapy (SBRT) for NSCLC. Methods: Sixty-five NSCLC SBRT patients since 2009 were investigated. Patients were categorized based on tumor anatomic location (RUL-17, RML-7, RLL-18, LUL-14, LLL-9). A 16-slice CT scanner [GE RT16 Pro] along with Varian Realtime Position Management (RPM) software was used to acquire the 4DCT data set using 1.25 mm slice width. Images were binned in 10 phases, T00 being at maximum inspiration ' T50 at maximum expiration phase. Tumor volume was segmented in T50 using the CT-lung window and its displacement were measured from phase to phase in all three axes; superiorinferior, anterior-posterior ' medial-lateral at the centroid level of the tumor. Results: The median tumor movement in each lobe was as follows: RUL= 3.8±2.0 mm (mean ITV: 9.5 cm{sup 3}), RML= 4.7±2.8 mm (mean ITV: 9.2 cm{sup 3}), RLL=6.6±2.6 mm (mean ITV: 12.3 cm{sup 3}), LUL=3.8±2.4 mm (mean ITV: 18.5 cm{sup 3}), ' LLL=4.7±2.5 mm (mean ITV: 11.9 cm{sup 3}). The median respiratory cycle for all patients was found to be 3.81 ± 1.08 seconds [minimum 2.50 seconds, maximum 7.07 seconds]. The tumor mobility incorporating breathing cycle was RUL = 0.95±0.49 mm/s, RML = 1.35±0.62 mm/s, RLL = 1.83±0.71 mm/s, LUL = 0.98 ±0.50 mm/s, and LLL = 1.15 ±0.53 mm/s. Conclusion: Our results show that tumor displacement is location dependent. The range of motion and mobility increases as the location of the tumor nears the diaphragm. Under abdominal compression, the magnitude of tumor motion is reduced by as much as a factor of 2 in comparison to reported tumor magnitudes under conventional free breathing conditions. This study demonstrates the utility of abdominal compression in reducing the tumor motion leading to reduced ITV and planning tumor volumes (PTV)

  19. Digital PCR analysis of plasma cell-free DNA for non-invasive detection of drug resistance mechanisms in EGFR mutant NSCLC: Correlation with paired tumor samples

    OpenAIRE

    Ishii, Hidenobu; Azuma, Koichi; Sakai, Kazuko; KAWAHARA, AKIHIKO; Yamada, Kazuhiko; Tokito, Takaaki; Okamoto, Isamu; Nishio, Kazuto; Hoshino, Tomoaki

    2015-01-01

    As the development of resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) has become an issue of concern, identification of the mechanisms responsible has become an urgent priority. However, for research purposes, it is not easy to obtain tumor samples from patients with EGFR mutation-positive non-small-cell lung cancer (NSCLC) that has relapsed after treatment with EGFR-TKIs. Here, using digital PCR assay as an alternative and noninvasive method, we examin...

  20. Genetic and Prognostic Differences of Non-small Cell Lung Cancer between Elderly Patients and Younger Counterparts.

    Science.gov (United States)

    Suda, Kenichi; Tomizawa, Kenji; Mizuuchi, Hiroshi; Ito, Simon; Kitahara, Hirokazu; Shimamatsu, Shinichiro; Kohno, Mikihiro; Yoshida, Tsukihisa; Okamoto, Tatsuro; Maehara, Yoshihiko; Yatabe, Yasushi; Mitsudomi, Tetsuya

    2012-12-01

    Many elderly patients suffer from lung cancers, but it is not clear if their lung cancers differ from those of younger patients. In this study, we compared genetic and prognostic characteristics of lung cancers of patients aged ≥75 years with those of patients aged ≤ 64 years. In the genetic analysis, we explored 292 surgically treated non-squamous cell lung cancers with known mutational status of epidermal growth factor (EGFR) and anaplastic lymphoma kinase (ALK). In the prognostic analysis, we retrospectively analyzed 405 surgically treated non-small cell lung cancers (NSCLCs) before the era of routine clinical application of post-surgical adjuvant chemotherapy. Postsurgical recurrence-free survival (RFS) was compared between elderly patients and younger counterparts. The genetic analysis showed elderly non-squamous cell lung cancer patients to have higher prevalence of EGFR mutations (53.1 % vs 42.0%, P = 0.15) and lower prevalence of the ALK translocation (0 % vs 4.5%, P = 0.23) than their younger counterparts. The prognostic analysis showed postsurgical RFS was similar between the elderly NSCLC patients and the younger patients. However in multivariate analysis, adjusting for gender, smoking status, pathological stage, and histology, elderly patients had significantly worse prognoses (HR 1.57, 95% CI, 1.08-2.29; P = 0.02) compared with younger patients. These results suggest differences in genetic and prognostic aspects between elderly lung cancer patients and younger lung cancer patients. PMID:23251849

  1. Serum HE4: An Independent Prognostic Factor in Non-Small Cell Lung Cancer

    OpenAIRE

    Pierre-Jean Lamy; Carine Plassot; Jean-Louis Pujol

    2015-01-01

    Human epididymis secretory protein 4 (HE4) is a secreted glycosylated protein encoded by the WAP four-disulfide core domain 2 (WFDC2) gene, located on a chromosome 20 segment that is frequently amplified in many cancers. This study aimed at determining serum HE4 prognostic value in non-small cell lung cancer (NSCLC), following the REMARK guidelines. Serum samples from 346 consecutive patients with histologically proven and previously untreated NSCLC and 41 patients with benign pulmonary disea...

  2. High expression of BCL-2 predicts favorable outcome in non-small cell lung cancer patients with non squamous histology

    International Nuclear Information System (INIS)

    Bcl-2 promotes cell survival by inhibiting adapters needed for the activation and cleavage of caspases thus blocking the proteolytic cascade that ultimately dismantles the cell. Bcl-2 has been investigated as a prognostic factor in non small cell lung cancer (NSCLC) patients with conflicting results. Here, we quantitatively assessed Bcl-2 expression in two large and independent cohorts to investigate the impact of Bcl-2 on survival. AQUA®, a fluorescent-based method for analysis of in situ protein expression, was used to measure Bcl-2 protein levels and classify tumors by Bcl-2 expression in a cohort of 180 NSCLC patients. An independent cohort of 354 NSCLC patients was used to validate Bcl-2 classification and evaluate outcome. Fifty % and 52% of the cases were classified as high expressers in training and validation cohorts respectively. Squamous cell carcinomas were more likely to be high expressers compared to adenocarcinomas (63% vs. 45%, p = 0.002); Bcl-2 was not associated with other clinical or pathological characteristics. Survival analysis showed that patients with high BCL-2 expression had a longer median survival compared to low expressers (22 vs. 17.5 months, log rank p = 0.014) especially in the subset of non-squamous tumors (25 vs. 13.8 months, log rank p = 0.04). Multivariate analysis revealed an independent lower risk for all patients with Bcl-2 expressing tumors (HR = 0.53, 95% CI 0.37-0.75, p = 0.0003) and for patients with non-squamous tumors (HR = 0.5, 95% CI 0.31-0.81, p = 0.005). Bcl-2 expression defines a subgroup of patients with a favorable outcome and may be useful for prognostic stratification of NSCLC patients

  3. Integration of gene dosage and gene expression in non-small cell lung cancer, identification of HSP90 as potential target.

    Directory of Open Access Journals (Sweden)

    Mariëlle I Gallegos Ruiz

    Full Text Available BACKGROUND: Lung cancer causes approximately 1.2 million deaths per year worldwide, and non-small cell lung cancer (NSCLC represents 85% of all lung cancers. Understanding the molecular events in non-small cell lung cancer (NSCLC is essential to improve early diagnosis and treatment for this disease. METHODOLOGY AND PRINCIPAL FINDINGS: In an attempt to identify novel NSCLC related genes, we performed a genome-wide screening of chromosomal copy number changes affecting gene expression using microarray based comparative genomic hybridization and gene expression arrays on 32 radically resected tumor samples from stage I and II NSCLC patients. An integrative analysis tool was applied to determine whether chromosomal copy number affects gene expression. We identified a deletion on 14q32.2-33 as a common alteration in NSCLC (44%, which significantly influenced gene expression for HSP90, residing on 14q32. This deletion was correlated with better overall survival (P = 0.008, survival was also longer in patients whose tumors had low expression levels of HSP90. We extended the analysis to three independent validation sets of NSCLC patients, and confirmed low HSP90 expression to be related with longer overall survival (P = 0.003, P = 0.07 and P = 0.04. Furthermore, in vitro treatment with an HSP90 inhibitor had potent antiproliferative activity in NSCLC cell lines. CONCLUSIONS: We suggest that targeting HSP90 will have clinical impact for NSCLC patients.

  4. Definitive surgery and intraoperative photodynamic therapy: a prospective study of local control and survival for patients with pleural dissemination of non-small cell lung cancer

    Science.gov (United States)

    Simone, Charles B.; Cengel, Keith A.

    2016-01-01

    Patients with non-small cell lung cancer (NSCLC) with pleural dissemination have very limited survivals often of just 6–9 months. Prior reports of aggressive surgical resection of pleural metastases have shown no consistent improvements in overall survival and very high rates of local recurrences. Based on this and the generally very diffuse pleural dissemination seen in patients, chemotherapy and palliative interventions are standard of care. By attempting to sterile microscopic residual disease after surgical resection, intraoperative photodynamic therapy (PDT) could improve local pleural control and overall survival compared with surgery alone for patients with NSCLC with pleural metastasis. Prior attempts to demonstrate an improvement in clinical outcomes with PDT as an intraoperative adjuvant combined with definitive surgery to treat pleural malignancies have not been successful, perhaps due, in part, to limited ability to perform real-time dosimetry and ensure adequate and even light distribution throughout the chest cavity. A stratified phase II trial assessed the efficacy of definitive surgery and intraoperative PDT with real-time dosimetry in patients with NSCLC with pleural dissemination demonstrated prolonged local control and a higher than expected 21.7-month median survival from the time of surgery and PDT among 22 enrolled patients. This is the first ever report describing optimal methods, techniques, and dosimetry that could be used to safely and reproducibly deliver intraoperative PDT to the chest cavity as part of multimodality therapy for NSCLC with pleural metastasis.

  5. Cancer patients' evaluation of communication

    DEFF Research Database (Denmark)

    Ross, Lone; Petersen, Morten Aagaard; Johnsen, Anna Thit;

    2013-01-01

    PURPOSE: The aims of this study were to assess how communication with health care staff is perceived by Danish cancer patients and to characterise those patients who report problems in communication. METHODS: In a cross-sectional survey, a nationally representative sample of 2,202 cancer patients...... consultations, and whether doctors criticised other doctors. RESULTS: A total of 1,490 cancer patients responded to the questionnaire. Of these, 24 % reported one or more problems with the areas of communication measured. The problem most frequently reported (by 12 %) was not having sufficient time for...... who had been in contact with a hospital department during the past year was invited to respond to a questionnaire. Communication with doctors and nurses was assessed separately as were their abilities as listeners, doctors' use of an understandable language, timing of the information, duration of...

  6. Mutant KRAS associated malic enzyme 1 expression is a predictive marker for radiation therapy response in non-small cell lung cancer

    International Nuclear Information System (INIS)

    Advanced non-small cell lung cancer (NSCLC) is an aggressive tumor that is treated with a combination of chemotherapy and radiation if the patient is not a candidate for surgery. Predictive biomarkers for response to radiotherapy are lacking in this patient population, making it a non-tailored therapy regimen with unknown outcome. Twenty to 30 % of NSCLC harbor an activating mutation in KRAS that may confer radioresistance. We hypothesized that mutant KRAS can regulate glutamine metabolism genes in NSCLC and maintain tumor redox balance through transamination reactions that generate cytosolic NADPH via malic enzyme 1 (ME1), which may contribute to radioresistance. A doxycycline-inducible mouse model of KRASG12D driven NSCLC and patient data was analyzed from multiple publicly accessible databases including TCGA, CCLE, NCBI GEO and Project Achilles. ME1 expression was found to be mutant KRAS associated in both a NSCLC mouse model and human NSCLC cancer cell lines. Perturbing glutamine metabolism sensitized mutant KRAS, but not wild-type KRAS NSCLC cell lines to radiation treatment. NSCLC survival analysis revealed that patients with elevated ME1 and GOT1 expression had significantly worse outcomes after radiotherapy, but this was not seen after chemotherapy alone. KRAS driven glutamine metabolism genes, specifically ME1 and GOT1 reactions, may be a predictive marker and potential therapeutic target for radiotherapy in NSCLC. The online version of this article (doi:10.1186/s13014-015-0457-x) contains supplementary material, which is available to authorized users

  7. Inhibitory effect of Disulfiram/copper complex on non-small cell lung cancer cells

    International Nuclear Information System (INIS)

    Highlights: • Disulfiram and copper synergistically inhibit lung cancer cell proliferation. • Lung cancer cell colony formation ability is inhibited by Disulfiram/copper. • Disulfiram/copper increases the sensitivity of cisplatin to lung cancer cells. • Lung cancer stem cells are specifically targeted by Disulfiram/copper complex. - Abstract: Non-small cell lung cancer (NSCLC) is the most common cause of cancer-related death in both men and women worldwide. Recently, Disulfiram has been reported to be able to inhibit glioblastoma, prostate, or breast cancer cell proliferation. In this study, the synergistic effect of Disulfiram and copper on NSCLC cell growth was investigated. Inhibition of cancer cell proliferation was detected by 1-(4,5-Dimethylthiazol-2-yl)-3,5-diphenylformazan (MTT) assay and cell cycle analysis. Liquid colony formation and tumor spheroid formation assays were used to evaluate their effect on cancer cell clonogenicity. Real-time PCR was performed to test the mRNA level of cancer stem cell related genes. We found that Disulfiram or copper alone did not potently inhibit NSCLC cell proliferation in vitro. However, the presence of copper significantly enhanced inhibitory effect of Disulfiram on NSCLC cell growth, indicating a synergistic effect between Disulfiram and copper. Cell cycle analysis showed that Disulfiram/copper complex caused NSCLC cell cycle arrest in G2/M phase. Furthermore, Disulfiram/copper significantly increased the sensitivity of cisplatin in NSCLC cells tested by MTT assay. Liquid colony formation assay revealed that copper dramatically increased the inhibitory effect of Disulfiram on NSCLC cell colony forming ability. Disulfiram combined with copper significantly attenuated NSCLC cell spheroid formation and recuded the mRNA expression of lung cancer stem cell related genes. Our data suggest that Disulfiram/copper complex alone or combined with other chemotherapy is a potential therapeutic strategy for NSCLC patients

  8. Inhibitory effect of Disulfiram/copper complex on non-small cell lung cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Duan, Lincan [Department of Thoracic Surgery, The Third Affiliated Hospital of Kunming Medical University, Kunming (China); Shen, Hongmei [Cancer Center of Integrative Medicine, The Third Affiliated Hospital of Kunming Medical University, Kunming (China); Zhao, Guangqiang [Department of Thoracic Surgery, The Third Affiliated Hospital of Kunming Medical University, Kunming (China); Yang, Runxiang [Cancer Chemotherapy Center, The Third Affiliated Hospital of Kunming Medical University, Kunming (China); Cai, Xinyi [Colorectal Cancer Center, The Third Affiliated Hospital of Kunming Medical University, Kunming (China); Zhang, Lijuan [Department of Pathology, The Third Affiliated Hospital of Kunming Medical University, Kunming (China); Jin, Congguo [Cancer Institute, The Third Affiliated Hospital of Kunming Medical University, Kunming (China); Huang, Yunchao, E-mail: daliduanlincan@163.com [Department of Thoracic Surgery, The Third Affiliated Hospital of Kunming Medical University, Kunming (China)

    2014-04-18

    Highlights: • Disulfiram and copper synergistically inhibit lung cancer cell proliferation. • Lung cancer cell colony formation ability is inhibited by Disulfiram/copper. • Disulfiram/copper increases the sensitivity of cisplatin to lung cancer cells. • Lung cancer stem cells are specifically targeted by Disulfiram/copper complex. - Abstract: Non-small cell lung cancer (NSCLC) is the most common cause of cancer-related death in both men and women worldwide. Recently, Disulfiram has been reported to be able to inhibit glioblastoma, prostate, or breast cancer cell proliferation. In this study, the synergistic effect of Disulfiram and copper on NSCLC cell growth was investigated. Inhibition of cancer cell proliferation was detected by 1-(4,5-Dimethylthiazol-2-yl)-3,5-diphenylformazan (MTT) assay and cell cycle analysis. Liquid colony formation and tumor spheroid formation assays were used to evaluate their effect on cancer cell clonogenicity. Real-time PCR was performed to test the mRNA level of cancer stem cell related genes. We found that Disulfiram or copper alone did not potently inhibit NSCLC cell proliferation in vitro. However, the presence of copper significantly enhanced inhibitory effect of Disulfiram on NSCLC cell growth, indicating a synergistic effect between Disulfiram and copper. Cell cycle analysis showed that Disulfiram/copper complex caused NSCLC cell cycle arrest in G2/M phase. Furthermore, Disulfiram/copper significantly increased the sensitivity of cisplatin in NSCLC cells tested by MTT assay. Liquid colony formation assay revealed that copper dramatically increased the inhibitory effect of Disulfiram on NSCLC cell colony forming ability. Disulfiram combined with copper significantly attenuated NSCLC cell spheroid formation and recuded the mRNA expression of lung cancer stem cell related genes. Our data suggest that Disulfiram/copper complex alone or combined with other chemotherapy is a potential therapeutic strategy for NSCLC patients.

  9. [Advances in Bevacizumab Therapy for Non-small Cell Lung Cancer 
with Brain Metastases].

    Science.gov (United States)

    Qu, Liyan; Geng, Rui; Song, Xia

    2016-08-20

    Brain metastases are frequently encountered in patients with non-small cell lung cancer (NSCLC) and are a significant cause of morbidity and mortality. Antiangiogenesis therapy plays a major role in the management of brain metastases in lung cancer. Bevacizumab have become the novel method for the treatment of lung cancer with brain metastases beyond the whole brain radiation therapy, stereotactic radiosurgery and chemotherapy. Recently, more and more studies and trials laid emphasis on the bevacizumab for NSCLC with brain metastases treatment. The key point is the efficacy and safety. In this review, bevacizumab therapy of NSCLC with brain metastases were summarized. PMID:27561800

  10. Economic sustainability of anti-PD-1 agents nivolumab and pembrolizumab in cancer patients: Recent insights and future challenges.

    Science.gov (United States)

    Tartari, Francesca; Santoni, Matteo; Burattini, Luciano; Mazzanti, Paola; Onofri, Azzurra; Berardi, Rossana

    2016-07-01

    Anti-programmed death (PD)-1 agents pembrolizumab and nivolumab have recently obtained enthusiastic results in terms of progression-free survival (PFS), overall survival (OS) and tolerability in cancer patients. Despite these promising data, the high cost of these agents needs careful consideration. Indeed, the evaluation of cost-effectiveness analysis (CEA) and quality-adjusted life year (QALY), as well as different drug reimbursement modalities, will represent fundamental tools in order to guarantee the economic sustainability of health system and the access to care for all cancer patients. In this review, we discussed the recent results obtained by immunotherapy in cancer patients and we evaluated the economic impact of recently approved nivolumab and pembrolizumab in patients with advanced melanoma, non-small cell lung cancer (NSCLC) and renal cell carcinoma (RCC).

  11. Economic analysis of combined endoscopic and endobronchial ultrasound in the evaluation of patients with suspected non-small cell lung cancer.

    LENUS (Irish Health Repository)

    Harewood, Gavin C

    2010-03-01

    Lung cancer remains the most common cause of cancer-related death in the United States. This study evaluated the costs of alternative diagnostic evaluations for patients with suspected non-small cell lung cancer (NSCLC). Researchers used a cost-minimization model to compare various diagnostic approaches in the evaluation of patients with NSCLC. It was less expensive to use an initial endoscopic ultrasound (EUS) with fine needle aspiration (FNA) to detect a mediastinal lymph node metastasis ($18,603 per patient), compared with combined EUS FNA and endobronchial ultrasound (EBUS) with FNA ($18,753). The results were sensitive to the prevalence of malignant mediastinal lymph nodes; EUS FNA remained least costly, if the probability of nodal metastases was <32.9%, as would occur in a patient without abnormal lymph nodes on computed tomography (CT). While EUS FNA combined with EBUS FNA was the most economical approach, if the rate of nodal metastases was higher, as would be the case in patients with abnormal lymph nodes on CT. Both of these strategies were less costly than bronchoscopy or mediastinoscopy. The pre-test probability of nodal metastases can determine the most cost-effective testing strategy for evaluation of a patient with NSCLC. Pre-procedure CT may be helpful in assessing probability of mediastinal nodal metastases.

  12. TIME- AND DOSE-DEPENDENT UP-REGULATION OF TNF-α mRNA AFTER IRRADIATION OF HUMAN NSCLC CELL LINES IN VITRO

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Objective: Even though radiotherapy plays a major role in the local treatment of non-small cell lung cancer (NSCLC), little is known about the molecular effects of irradiation in this tumor. In the present study, we examined two NSCLC cell lines for their endogenous production of TNF-α after irradiation. To investigate the radiation-induced TNF-α production in NSCLC cell lines. Methods: Two human NSCLC cell lines (A549: squamous; NCI-H596: adenosquamous) were investigated for their TNF-α mRNA (real-time RT-PCR) after exposure to different irradiation doses (2, 5, 10, 20, 30, 40 Gy) and time intervals (1, 3, 6, 12, 24, 48 or 72 h). The TNF-α mRNA expression was quantified by real-time RT-PCR. The clonogenic survival was evaluated after irradiation with 2, 4, 6 and 8 Gy. Results: Non-irradiated NSCLC cells exhibited no or very low TNF-α expression. For the NCI-H596 cell line, TNF-α expression was significantly elevated 1~12 h (maximum 6h: 568fold increase relative to unirradiated cells) in a time-dependent manner. The radiation-induced increase could be observed after irradiation with 2 Gy reaching maximal at 40 Gy, with 83 times higher than normal controls. The clonogenic survival of these cell lines was nearly identical. Conclusion: NCI-H596 cells produce significant quantities of TNF-α following irradiation in a time- and dose-dependent manner. The pro-inflammatory cytokine TNF-α is a key mediator for the pathogenesis of radiation pneumonitis. Radiation-induced endogenous TNF-α expression in NSCLC cells may affect the normal lung adjacent to the tumor and may be associated with an adverse clinical outcome of the patient.

  13. The Distribution of Human Stem Cell–like Memory T Cell in Lung Cancer

    Science.gov (United States)

    Hong, Hai; Gu, Yong; Sheng, Si Yuan; Lu, Chuan Gang; Zou, Jian Yong

    2016-01-01

    Human stem cell–like memory T (Tscm) cells are long-lived, self-renewing memory lymphocytes that can differentiate into effector cells and mediate strong antitumour response in murine model. The distribution and function of Tscm cells in human lung cancer remain unknown. In this study, we investigated the properties of human Tscm cells in the blood and lymph node of non–small cell lung cancer (NSCLC) patients. There were more CD4+ Tscm cells in blood from NSCLC patients than from healthy donors, fewer CD4+ and CD8+ TSCM cells in blood than in lymph node from NSCLC patients. To further analyze their properties, we stimulated peripheral blood mononuclear cells from NSCLC patients by mitogens to examine cytokine production. Our data suggest that both CD4 and CD8 Tscm cells in blood produced interferon-γ significantly increased in NSCLC patients compare with healthy subjects. In addition, fewer Tscm cells produced interferon-γ in lymph node than in blood from NSCLC patients. Our results strongly suggest that the distribution and function of CD4 Tscm cells in NSCLC patients is upregulated. Understanding of the properties of stem-like memory T cells will supply a good rationale for designing the new adoptive immunotherapy in cancer. PMID:27244531

  14. Interstitial lung abnormalities in treatment-naïve advanced non-small-cell lung cancer patients are associated with shorter survival

    International Nuclear Information System (INIS)

    Highlights: • Interstitial lung abnormalities were present in 14% of stage IV NSCLC patients. • ILA was more common in older patients with heavier smoking history. • ILA was associated with shorter survival after adjusting for smoking and therapy. • ILA could be an additional independent marker for survival in advanced NSCLC. - Abstract: Objective: Interstitial lung diseases are associated with increased risk of lung cancer. The prevalence of ILA at diagnosis of advanced non-small-cell lung cancer (NSCLC) and its impact on overall survival (OS) remain to be investigated. Materials and method: The study included 120 treatment-naïve stage IV NSCLC patients (53 males, 67 females). ILA was scored on CT prior to any systemic therapy using a 4-point scale [0 = no evidence of ILA, 1 = equivocal for ILA, 2 = suspicious for ILA, 3 = ILA] by a sequential reading method previously reported. ILA scores of 2 or 3 indicated the presence of ILA. Results: ILA was present in 17 patients (14%) with advanced NSCLC prior to any treatment (score3: n = 2, score2: n = 15). These 17 patients were significantly older (median age: 69 vs. 63, p = 0.04) and had a heavier smoking history (median: 40 vs. 15.5 pack-year, p = 0.003) than those with ILA score 0 or 1. Higher ILA scores were associated with shorter OS (p = 0.001). Median OS of the 17 patients with ILA was 7.2 months [95%CI: 2.9–9.4] compared to 14.8 months [95%CI: 11.1–18.4] in patients with ILA score 0 or 1 (p = 0.002). In a multivariate model, the presence of ILA remained significant for increased risk for death (HR = 2.09, p = 0.028) after adjusting for first-line systemic therapy (chemotherapy, p < 0.001; TKI, p < 0.001; each compared to no therapy) and pack years of smoking (p = 0.40). Conclusion: Radiographic ILA was present in 14% of treatment-naïve advanced NSCLC patients. Higher ILA scores were associated with shorter OS, indicating that ILA could be a marker of shorter survival in advanced NSCLC

  15. Interstitial lung abnormalities in treatment-naïve advanced non-small-cell lung cancer patients are associated with shorter survival

    Energy Technology Data Exchange (ETDEWEB)

    Nishino, Mizuki, E-mail: Mizuki_Nishino@DFCI.HARVARD.EDU [Department of Radiology, Brigham and Women' s Hospital, 75 Francis St., Boston, MA 02115 (United States); Department of Imaging, Dana-Farber Cancer Institute, 450 Brookline Ave., Boston, MA 02215 (United States); Cardarella, Stephanie [Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave., Boston, MA 02215, (United States); Dahlberg, Suzanne E. [Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, 450 Brookline Ave., Boston, MA 02215 (United States); Araki, Tetsuro [Department of Radiology, Brigham and Women' s Hospital, 75 Francis St., Boston, MA 02115 (United States); Lydon, Christine; Jackman, David M.; Rabin, Michael S. [Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave., Boston, MA 02215, (United States); Hatabu, Hiroto [Department of Radiology, Brigham and Women' s Hospital, 75 Francis St., Boston, MA 02115 (United States); Johnson, Bruce E. [Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave., Boston, MA 02215, (United States)

    2015-05-15

    Highlights: • Interstitial lung abnormalities were present in 14% of stage IV NSCLC patients. • ILA was more common in older patients with heavier smoking history. • ILA was associated with shorter survival after adjusting for smoking and therapy. • ILA could be an additional independent marker for survival in advanced NSCLC. - Abstract: Objective: Interstitial lung diseases are associated with increased risk of lung cancer. The prevalence of ILA at diagnosis of advanced non-small-cell lung cancer (NSCLC) and its impact on overall survival (OS) remain to be investigated. Materials and method: The study included 120 treatment-naïve stage IV NSCLC patients (53 males, 67 females). ILA was scored on CT prior to any systemic therapy using a 4-point scale [0 = no evidence of ILA, 1 = equivocal for ILA, 2 = suspicious for ILA, 3 = ILA] by a sequential reading method previously reported. ILA scores of 2 or 3 indicated the presence of ILA. Results: ILA was present in 17 patients (14%) with advanced NSCLC prior to any treatment (score3: n = 2, score2: n = 15). These 17 patients were significantly older (median age: 69 vs. 63, p = 0.04) and had a heavier smoking history (median: 40 vs. 15.5 pack-year, p = 0.003) than those with ILA score 0 or 1. Higher ILA scores were associated with shorter OS (p = 0.001). Median OS of the 17 patients with ILA was 7.2 months [95%CI: 2.9–9.4] compared to 14.8 months [95%CI: 11.1–18.4] in patients with ILA score 0 or 1 (p = 0.002). In a multivariate model, the presence of ILA remained significant for increased risk for death (HR = 2.09, p = 0.028) after adjusting for first-line systemic therapy (chemotherapy, p < 0.001; TKI, p < 0.001; each compared to no therapy) and pack years of smoking (p = 0.40). Conclusion: Radiographic ILA was present in 14% of treatment-naïve advanced NSCLC patients. Higher ILA scores were associated with shorter OS, indicating that ILA could be a marker of shorter survival in advanced NSCLC.

  16. Chemotherapy with or without gefitinib in patients with advanced non-small-cell lung cancer: a meta-analysis of 6844 patients

    Institute of Scientific and Technical Information of China (English)

    ZHOU Hang; ZENG Chao; WANG Li-yang; XIE Hua; ZHOU Jin; DIAO Peng; YAO Wen-xiu

    2013-01-01

    Background Gefitinib is widely used in patients with advanced non-small-cell lung cancer (NSCLC),in whom chemotherapy had failed.Previous trials reported inconsistent findings regarding the efficacy of gefitinib on overall survival (OS) and progression free survival (PFS).This study was to evaluate the effects of chemotherapy plus gefitinib versus chemotherapy alone on survival of patients with NSCLC.Methods We systematically searched Medline,EmBase,the Cochrane Central Register of Controlled Trials,reference lists of articles,and proceedings of major meetings for relevant literature.Randomized controlled trials (RCTs) comparing chemotherapy with and without gefitinib in the treatment of patients with advanced NSCLC were included in our analysis.The primary endpoints were OS and PFS.Results Of 182 relevant studies,12 were included in the final analysis,which consisted of 6844 patients with NSCLC.Overall,we noted that gefitinib therapy had an 8% improvement in the OS as compared to the gefltinib-free therapy,but this difference was not statistically significant (HR,0.92; 95% C/:0.85-1.00; P=0.051).Furthermore,gefltinib therapy had significantly longer PFS compared to gefitinib-free therapy (HR,0.72; 95% C/ 0.60-0.87,P=0.001).Patients receiving gefitinib therapy also had a more frequent objective response rate (ORR) than the control arm (OR,2.51; 95% C/,1.67-3.78,P <0.001).Rashes,diarrhea,dry skin,pruritus,paronychia,and abnormal hepatic function were more frequent in the gefitinib therapy group.Conclusions Treatment with gefitinib had a clear effect on PFS and ORR,and it might contribute considerably to the OS.Furthermore,there was some evidence of benefit for gefitinib therapy among patients with adenocarcinoma.

  17. Relationship between the Expression of NF-kappa B and Apoptosis in Non-Small Cell Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    Jianqun Ma; Zhenfa Zhang; Shidong Xu

    2008-01-01

    OBJECTIVE To study the expression of the nuclear factor kappa B (NF-kappa B)in non-small cell lung cancer(NSCLC),to explore the apoptotic ratio in NSCLC related to different NF-kappa Bs,and to understand the clinical significance of NF-kappa B in NSCLC apoptosis.METHODS NF-kappa B expression in 45 new samples of NSCLC,collected during a period from October to December,2005,was assayed using Western blots,and the apoptotic ratio of NSCLC was determined by the Tunel method.RESULTS Of the 45 patients,the average relative expressxon of NF-kappa B was 0.6047±0.3572.The expression of NF-kappa B was higher in the poorly differentiated lung cancer cells than in the well-differentiated tumors (P<0.05).The apoptotic ratio was 56.4%in the lung cancer cells with higher NF-kappa B expression,and was 76.7%in those with lower NF-kappa B expression(P<0.05).CONCLUSION The expression of NF-kappa B is correlated with the differentiation of NSCLC.NF-kappa B inhibits apoptosis in NSCLC.AS a transcription factor,NF-kappa B plays a very important role both in formation and in development of NSCLC.NF-kappa B might serve as a target for NSCLC gene therapy.

  18. Gene-expression signature predicts postoperative recurrence in stage I non-small cell lung cancer patients.

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    Yan Lu

    Full Text Available About 30% stage I non-small cell lung cancer (NSCLC patients undergoing resection will recur. Robust prognostic markers are required to better manage therapy options. The purpose of this study is to develop and validate a novel gene-expression signature that can predict tumor recurrence of stage I NSCLC patients. Cox proportional hazards regression analysis was performed to identify recurrence-related genes and a partial Cox regression model was used to generate a gene signature of recurrence in the training dataset -142 stage I lung adenocarcinomas without adjunctive therapy from the Director's Challenge Consortium. Four independent validation datasets, including GSE5843, GSE8894, and two other datasets provided by Mayo Clinic and Washington University, were used to assess the prediction accuracy by calculating the correlation between risk score estimated from gene expression and real recurrence-free survival time and AUC of time-dependent ROC analysis. Pathway-based survival analyses were also performed. 104 probesets correlated with recurrence in the training dataset. They are enriched in cell adhesion, apoptosis and regulation of cell proliferation. A 51-gene expression signature was identified to distinguish patients likely to develop tumor recurrence (Dxy = -0.83, P85%. Multiple pathways including leukocyte transendothelial migration and cell adhesion were highly correlated with recurrence-free survival. The gene signature is highly predictive of recurrence in stage I NSCLC patients, which has important prognostic and therapeutic implications for the future management of these patients.

  19. Time to treatment as a quality metric in lung cancer: Staging studies, time to treatment, and patient survival

    International Nuclear Information System (INIS)

    Purpose: Prompt staging and treatment are crucial for non-small cell lung cancer (NSCLC). We determined if predictors of treatment delay after diagnosis were associated with prognosis. Materials and methods: Medicare claims from 28,732 patients diagnosed with NSCLC in 2004–2007 were used to establish the diagnosis-to-treatment interval (ideally ⩽35 days) and identify staging studies during that interval. Factors associated with delay were identified with multivariate logistic regression, and associations between delay and survival by stage were tested with Cox proportional hazard regression. Results: Median diagnosis-to-treatment interval was 27 days. Receipt of PET was associated with delays (57.4% of patients with PET delayed [n = 6646/11,583] versus 22.8% of those without [n = 3908/17,149]; adjusted OR = 4.48, 95% CI 4.23–4.74, p < 0.001). Median diagnosis-to-PET interval was 15 days; PET-to-clinic, 5 days; and clinic-to-treatment, 12 days. Diagnosis-to-treatment intervals <35 days were associated with improved survival for patients with localized disease and those with distant disease surviving ⩾1 year but not for patients with distant disease surviving <1 year. Conclusion: Delays between diagnosing and treating NSCLC are common and associated with use of PET for staging. Reducing time to treatment may improve survival for patients with manageable disease at diagnosis

  20. Expression of Epidermal Growth Factor Receptor and the association with Demographic and Prognostic Factors in Patients with Non-small Cell Lung Cancer

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    Reza Basiri

    2015-06-01

    Full Text Available Introduction: Growth, proliferation, survival, and differentiation are the prominent characteristics of cells, which are affected by cancer. Epidermal growth factor receptor (EGFR plays a pivotal role in the effective control of these features. Given the significance of EGFR signaling pathway in non-small cell lung cancer (NSCLC, EGFR expression is influential on these cell characteristics. In this paper, we studied EGFR expression and its association with demographic factors, clinicopathological features, and prognosis of NSCLC patients. Materials and Methods: In this retrospective cohort study which was done during 2009-12 at Ghaem Hospital, Mashhad, Iran. EGFR expression was evaluated in 96 patients with formalin-fixed, paraffin-embedded NSCLC tissues (43 adenocarcinomas, 48 squamous-cell carcinomas, and 5 large-cell carcinomas using immunohistochemistry (IHC. Data analysis was performed by SPSS version 20.0. Results: Out of 96 specimens, approximately 53% were classified as positive for EGFR expression. The study group consisted of 68% (N=65 male and 32% (N=31 female subjects, with the mean age of 61.1±9.03 years. There was no difference between EGFR-positive and EGFR-negative patients in terms of the overall survival rate (P=0.49. In addition, no association was observed between tumor histology and EGFR expression (P=0.08, while EGFR-positive adenocarcinoma (N=28, 29% was more prevalent compared to other subtypes of NSCLC. Moreover, there were no differences between tumor subtypes and the overall survival rate of the patients (P=0.21, and no association was found between EGFR expression and the patients’ demographic factors (e.g. age and gender. Conclusion: The results of this study indicated that EGFR expression could not be a prognostic marker in NSCLC patients; however, it seems that using standardized IHC scoring is likely to yield more reliable data in this regard.

  1. Detection of EMI4-ALK fusion gene in non-small cell lung cancer and its clinicopathologic correlation

    Institute of Scientific and Technical Information of China (English)

    钟山

    2013-01-01

    Objective To investigate the frequency of EML4-ALK fusion gene in non small-cell lung cancer NSCLC patients,and its correlation with clinicopathologic features.Methods Real-time PCR was used to detect

  2. EGFR Mutations in Surgically Resected Fresh Specimens from 697 Consecutive Chinese Patients with Non-Small Cell Lung Cancer and Their Relationships with Clinical Features

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    Yuanyang Lai

    2013-12-01

    Full Text Available We aimed to reveal the true status of epidermal growth factor receptor (EGFR mutations in Chinese patients with non-small cell lung cancer (NSCLC after lung resections. EGFR mutations of surgically resected fresh tumor samples from 697 Chinese NSCLC patients were analyzed by Amplification Refractory Mutation System (ARMS. Correlations between EGFR mutation hotspots and clinical features were also explored. Of the 697 NSCLC patients, 235 (33.7% patients had tyrosine kinase inhibitor (TKIs sensitive EGFR mutations in 41 (14.5% of the 282 squamous carcinomas, 155 (52.9% of the 293 adenocarcinomas, 34 (39.5% of the 86 adenosquamous carcinomas, one (9.1% of the 11 large-cell carcinomas, 2 (11.1% of the 18 sarcomatoid carcinomas, and 2 (28.6% of the 7 mucoepidermoid carcinomas. TKIs sensitive EGFR mutations were more frequently found in female patients (p < 0.001, non-smokers (p = 0.047 and adenocarcinomas (p < 0.001. The rates of exon 19 deletion mutation (19-del, exon 21 L858R point mutation (L858R, exon 21 L861Q point mutation (L861Q, exon 18 G719X point mutations (G719X, including G719C, G719S, G719A were 43.4%, 48.1%, 1.7% and 6.8%, respectively. Exon 20 T790M point mutation (T790M was detected in 3 squamous carcinomas and 3 adenocarcinomas and exon 20 insertion mutation (20-ins was detected in 2 patients with adenocarcinoma. Our results show the rates of EGFR mutations are higher in all types of NSCLC in Chinese patients. 19-del and L858R are two of the more frequent mutations. EGFR mutation detection should be performed as a routine postoperative examination in Chinese NSCLC patients.

  3. [Fertility in testicular cancer patients].

    Science.gov (United States)

    Shin, Takeshi; Miyata, Akane; Arai, Gaku; Okada, Hiroshi

    2015-03-01

    Testicular cancer(TC)is the most common and curable cancer affecting men of reproductive age. Successful treatment approaches have resulted in longer life expectancy in TC survivors. The most frequently used treatment for TC is a combination of inguinal orchiectomy, and either radiotherapy or cisplatin-based chemotherapy. In many TC patients, sperm quality is already abnormal and there may even be a lack of viable spermatozoa at the time of diagnosis. Therefore, the effect of cancer treatment on fertility is a potentially significant issue. Fertility preservation in these men has become essential and needs to be discussed prior to the start of cancer treatment. The only currently established fertility preservation method is the cryopreservation of sperm before therapy. For most patients seeking cryopreservation, the semen sample is collected via masturbation. If the patient is unable to ejaculate for any reason, other techniques such as vibratory stimulation and electroejaculation can be performed. In azoospermic or severely oligozoospermic patients, testicular sperm extraction at the time of the inguinal orchiectomy is a useful technique for obtaining spermatozoa before cytotoxic therapy. We herein present an overview of the current topics on fertility in TC patients, including the effects of surgery, chemotherapy, and radiation therapy. We also describe the strategy for fertility preservation in these patients. PMID:25812494

  4. Thromboembolism in Patients with Cancer.

    Science.gov (United States)

    Büyükçelik, Abdullah; Akbulut, Hakan

    2004-03-01

    One hundred and forty years ago, Armand Trousseau described phlegmasia alba dolens as a sign of internal malignancy. Nowadays, it is commonly believed that the presence malignant tumaor increases the risk of venous thromboembolism (i.e deep vein thrombosis and pulmonary embolism) However, cancer is usually associated with other factors such as old age, extensive surgery,immobility, etc., which may predispose to thromboembolism. The majority of thrombotic events occur in the venous system; the incidence of arterial thrombosis is much lower.Recurrent thromboembolism in cancer patients frequently and diminishes the quality of life of the patients.Furthermore, if the thromboembolism is massive, destipte of early and aggressive treatment, it may result in death. In this article, we review thromboembolic complications in cancer patients.

  5. Treatment Choice for Advanced Non-small Cell Lung Cancer Patients Who Had Gradual Progression After EGFR-TKIs: 32 Cases Report

    Directory of Open Access Journals (Sweden)

    Lin LIN

    2013-10-01

    Full Text Available Background and objective The epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs have been widely used in the treatment of the advanced non-small cell lung cancer (NSCLC, especially in the adenocarcinoma patients with activating EGFR mutations. But there is no published overview of the following treatment. This report through observing the efficacy, toxicity and overall survival of different treatments to the advanced NSCLC patients who had gradual progression after EGFR-TKIs, evaluates the influence of the continued treatment and switching chemotherapy. Methods Retrospective review is conducted on 32 cases of advanced NSCLC patients who experienced treatment failure of EGFR-TKIs. One group accepted the continued treatment and the other group accepted the switching chemotherapy. Results The median overall survival of the continued treatment group is 36.0 months. The respose rate of the switching chemotherapy group is 43.75%, and clinical benefit rate (complete and partial response and stable disease is 87.5%. The median overall survival is 15.5 months. The main toxicities are nausea, vomiting and hematological toxicities. Conclusion For the advanced NSCLC patients who had gradual progression after EGFR-TKIs, the continued treatment is one of the acceptable choices.

  6. Prophylactic cranial irradiation may impose a detrimental effect on overall survival of patients with nonsmall cell lung cancer: a systematic review and meta-analysis.

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    Shuan-shuan Xie

    Full Text Available To determine the role of brain metastases (BM and overall survival (OS in patients with non-small cell lung cancer (NSCLC by performing a meta-analysis of the RCTs (randomized controlled clinical trials and non-RCTs (non-randomized controlled clinical trials published in the literature.A meta-analysis was performed using trials identified through PubMed, EMBASE and Cochrane databases. Two investigators independently assessed the quality of the trials and extracted data. The outcomes included BM, OS, median survival (MS, response rate (RR, Hazard ratios (HRs and odds ratios (ORs, and their 95% confidence intervals (CIs were pooled using ReMan software.Twelve trials (6 RCTs and 6 non-RCTs involving 1,718 NSCLC patients met the inclusion criteria. They were grouped on the basis of study design for separate Meta-analyses. The results showed that prophylactic cranial irradiation (PCI reduced the risk of BM as compared with non-PCI in NSCLC patients (OR = 0.30, 95% [CI]: 0.21-0.43, p<0.00001. However, HRs for OS favored non-PCI (HR = 1.19, 95% [CI]: 1.06-1.33, p = 0.004, without evidence of heterogeneity between the studies.Our results suggest that although PCI decreased the risk of BM, it may impose a detrimental effect on OS of NSCLC patients.

  7. Evaluation of Efficacy and Safety of Bevacizumab Combined with Chemotherapy 
for Chinese Patients with Advanced Non-small Cell Lung Cancer

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    Xiao ZHAO

    2012-01-01

    Full Text Available Background and objective The current study reported the result of bevacizumab treatment administered to 25 Chinese patients with advanced non-small cell lung cancer (NSCLC who were treated at the Peking Union Medical College Hospital as a part of the SAiL (MO19390 trial. This trial is an open, international multicenter, single-arm clinical study that assesses the safety and efficacy of first-line bevacizumab-based therapy in advanced NSCLC. Methods Twenty-five Chinese patients with advanced non-squamous NSCLC received bevacizumab (15 mg/kg combined with chemotherapy (carboplatin plus paclitaxel treatment from August 2007 to February 2008. Adverse effects (AEs, objective response rate (ORR, median time to progression (TTP, and overall survival (OS were measured. Results AEs were generally mild and reversible. The most frequent AEs were alopecia, peripheral neuropathy, rash, proteinuria, nausea/vomitting, fatigue, myalgia, bleeding, and hypertension. The partial remission and stable disease rates were 68% and 28%, respectively. The median TTP and OS of all patients were 11.2 and 19.3 months, respectively. Conclusion Bevacizumab combined with carboplatin-based chemotherapy may be well tolerated and beneficial for Chinese patients with non-squamous NSCLC.

  8. Hypertension in Patients with Cancer

    International Nuclear Information System (INIS)

    There is a known association between chemotherapy and radiotherapy for treatment of cancer patients and development or worsening of hypertension. The aim of this article is to review this association. A literature search was conducted for articles reporting this association on the databases PubMed, SciELO and LILACS between 1993 and 2013. There was a high coprevalence of hypertension and cancer, since both diseases share the same risk factors, such as sedentary lifestyle, obesity, smoking, unhealthy diet and alcohol abuse. The use of chemotherapy and adjuvant drugs effective in the treatment of cancer increased the survival rate of these patients and, consequently, increased the incidence of hypertension. We described the association between the use of angiogenesis inhibitors (bevacizumab, sorafenib and sunitinib), corticosteroids, erythropoietin and non-steroidal anti-inflammatory drugs with the development of hypertension. We also described the relationship between hypertension and carotid baroreceptor injury secondary to cervical radiotherapy. Morbidity and mortality increased in patients with cancer and hypertension without proper antihypertensive treatment. We concluded that there is need for early diagnosis, effective monitoring and treatment strategies for hypertension in cancer patients in order to reduce cardiovascular morbidity and mortality

  9. Hypertension in Patients with Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Souza, Vinicius Barbosa de; Silva, Eduardo Nani; Ribeiro, Mario Luiz; Martins, Wolney de Andrade, E-mail: wolney@cardiol.br [Curso de Pós-Graduação em Ciências Cardiovasculares da Universidade Federal Fluminense, Niterói, RJ (Brazil)

    2015-03-15

    There is a known association between chemotherapy and radiotherapy for treatment of cancer patients and development or worsening of hypertension. The aim of this article is to review this association. A literature search was conducted for articles reporting this association on the databases PubMed, SciELO and LILACS between 1993 and 2013. There was a high coprevalence of hypertension and cancer, since both diseases share the same risk factors, such as sedentary lifestyle, obesity, smoking, unhealthy diet and alcohol abuse. The use of chemotherapy and adjuvant drugs effective in the treatment of cancer increased the survival rate of these patients and, consequently, increased the incidence of hypertension. We described the association between the use of angiogenesis inhibitors (bevacizumab, sorafenib and sunitinib), corticosteroids, erythropoietin and non-steroidal anti-inflammatory drugs with the development of hypertension. We also described the relationship between hypertension and carotid baroreceptor injury secondary to cervical radiotherapy. Morbidity and mortality increased in patients with cancer and hypertension without proper antihypertensive treatment. We concluded that there is need for early diagnosis, effective monitoring and treatment strategies for hypertension in cancer patients in order to reduce cardiovascular morbidity and mortality.

  10. Characterization of FGFR1 Locus in sqNSCLC Reveals a Broad and Heterogeneous Amplicon.

    Science.gov (United States)

    Rooney, Claire; Geh, Catherine; Williams, Victoria; Heuckmann, Johannes M; Menon, Roopika; Schneider, Petra; Al-Kadhimi, Katherine; Dymond, Michael; Smith, Neil R; Baker, Dawn; French, Tim; Smith, Paul D; Harrington, Elizabeth A; Barrett, J Carl; Kilgour, Elaine

    2016-01-01

    FGFR1 amplification occurs in ~20% of sqNSCLC and trials with FGFR inhibitors have selected FGFR1 amplified patients by FISH. Lung cancer cell lines were profiled for sensitivity to AZD4547, a potent, selective inhibitor of FGFRs 1-3. Sensitivity to FGFR inhibition was associated with but not wholly predicted by increased FGFR1 gene copy number. Additional biomarker assays evaluating expression of FGFRs and correlation between amplification and expression in clinical tissues are therefore warranted. We validated nanoString for mRNA expression analysis of 194 genes, including FGFRs, from clinical tumour tissue. In a panel of sqNSCLC tumours 14.4% (13/90) were FGFR1 amplified by FISH. Although mean FGFR1 expression was significantly higher in amplified samples, there was significant overlap in the range of expression levels between the amplified and non-amplified cohorts with several non-amplified samples expressing FGFR1 to levels equivalent to amplified samples. Statistical analysis revealed increased expression of FGFR1 neighboring genes on the 8p12 amplicon (BAG4, LSM1 and WHSC1L1) in FGFR1 amplified tumours, suggesting a broad rather than focal amplicon and raises the potential for codependencies. High resolution aCGH analysis of pre-clinical and clinical samples supported the presence of a broad and heterogeneous amplicon around the FGFR1 locus. In conclusion, the range of FGFR1 expression levels in both FGFR1 amplified and non-amplified NSCLC tissues, together with the breadth and intra-patient heterogeneity of the 8p amplicon highlights the need for gene expression analysis of clinical samples to inform the understanding of determinants of response to FGFR inhibitors. In this respect the nanoString platform provides an attractive option for RNA analysis of FFPE clinical samples. PMID:26905262

  11. Characterization of FGFR1 Locus in sqNSCLC Reveals a Broad and Heterogeneous Amplicon.

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    Claire Rooney

    Full Text Available FGFR1 amplification occurs in ~20% of sqNSCLC and trials with FGFR inhibitors have selected FGFR1 amplified patients by FISH. Lung cancer cell lines were profiled for sensitivity to AZD4547, a potent, selective inhibitor of FGFRs 1-3. Sensitivity to FGFR inhibition was associated with but not wholly predicted by increased FGFR1 gene copy number. Additional biomarker assays evaluating expression of FGFRs and correlation between amplification and expression in clinical tissues are therefore warranted. We validated nanoString for mRNA expression analysis of 194 genes, including FGFRs, from clinical tumour tissue. In a panel of sqNSCLC tumours 14.4% (13/90 were FGFR1 amplified by FISH. Although mean FGFR1 expression was significantly higher in amplified samples, there was significant overlap in the range of expression levels between the amplified and non-amplified cohorts with several non-amplified samples expressing FGFR1 to levels equivalent to amplified samples. Statistical analysis revealed increased expression of FGFR1 neighboring genes on the 8p12 amplicon (BAG4, LSM1 and WHSC1L1 in FGFR1 amplified tumours, suggesting a broad rather than focal amplicon and raises the potential for codependencies. High resolution aCGH analysis of pre-clinical and clinical samples supported the presence of a broad and heterogeneous amplicon around the FGFR1 locus. In conclusion, the range of FGFR1 expression levels in both FGFR1 amplified and non-amplified NSCLC tissues, together with the breadth and intra-patient heterogeneity of the 8p amplicon highlights the need for gene expression analysis of clinical samples to inform the understanding of determinants of response to FGFR inhibitors. In this respect the nanoString platform provides an attractive option for RNA analysis of FFPE clinical samples.

  12. Immune-modulating effects of bevacizumab in metastatic non-small-cell lung cancer patients

    Science.gov (United States)

    Martino, EC; Misso, G; Pastina, P; Costantini, S; Vanni, F; Gandolfo, C; Botta, C; Capone, F; Lombardi, A; Pirtoli, L; Tassone, P; Ulivieri, C; Tagliaferri, P; Cusi, MG; Caraglia, M; Correale, P

    2016-01-01

    The mPEBev is an anticancer regimen which combines a chemotherapy doublet, based on cisplatin and oral etoposide (mPE), with bevacizumab (mPEBev), a mAb targeting the vasculo-endothelial growth factor (VEGF). In previous studies, this regimen showed powerful anti-angiogenetic effects and significant antitumor activity in metastatic non-small-cell lung cancer (mNSCLC) patients. We also recorded the best benefit in patients exhibiting low-systemic inflammatory profile at baseline. On these bases, we hypothesized that mPEBev antitumor activity could be partially related to bevacizumab-associated immunological effects. For this reason, we performed an immunological monitoring in 59 out of 120 stage IIIb-IV NSCLC patients enrolled in the BEVA2007 phase II trial, who received fractioned cisplatin (30 mg/sqm days 1-3q21) and oral etoposide (50 mg, days 1-15q21) (mPE doublet) ±bevacizumab. In this group of patients, 12 received the mPE doublet alone and 47 the doublet in combination with bevacizumab (5 mg/kg on the day 3q21; mPEBev regimen). Blood cell counts, serum analysis, multiplex cytokine assay and immunocytofluorimetric analysis, performed on baseline and post-treatment on blood samples from these patients, revealed that bevacizumab addition to the doublet decreased levels of pro-angiogenic (VEGF, Angiostatin-1 and Follistatin) and inflammatory cytokines (interferon (IFN)γ, IL4 and IL17), improved in vivo and in vitro cytotoxic T-lymphocytes (CTL) response and promoted dendritic cell activation. These results suggest that the mPEBev regimen improve the micro-environmental conditions for an efficient antigen-specific CTL response, making it a feasible candidate regimen to be assessed in combination with immune-checkpoint inhibitors in NSCLC patients.

  13. [Weight loss in cancer patients].

    Science.gov (United States)

    Lordick, Florian; Hacker, Ulrich

    2016-02-01

    Cancer patients are regularly affected by malnutrition which often leads to a worsened quality of life and activity in daily living, more side effects and complications during anticancer treatment and shorter survival times. The early diagnosis and treatment of malnutrition are therefore relevant components of oncological treatment. The assessment of the nutritional status and determination of the body-mass-index should be done in every patient with cancer. The clinical examination delivers important findings and indications for malnutrition. Bioimpedance analysis can deliver additional objective information. The treatment of malnutrition should start early and follows a step-wise escalation reaching from nutritional counseling to enteral nutritional support to parenteral nutrition.

  14. [The quality of life after chemotherapy in advanced non-small cell lung cancer patients].

    Science.gov (United States)

    Słowik-Gabryelska, A; Szczepanik, A; Kalicka, A

    1999-01-01

    The intensity of complains, short survival and great number of patients makes many oncologists to apply chemotherapy in advanced non-small cell lung cancer/NSCLC/. The achieved median duration of life after chemotherapy was 6 to 12 month. From the other hand non small cell lung cancer chemotherapy is a big burden even to healthy persons. It can worsen the quality of life. That was the reason we evaluated the quality of life after chemotherapy in advanced non small cell lung cancer patients. Taking into account, that the evaluation of quality of life, used in most diseases is useless in advanced NSCLC patients, for appreciation the quality of life in these cases the lung cancer symptoms scale/LCSS/was adopted. In 110 non small cell lung cancer patients in stage IIIB and IV, who received combined chemotherapy by Le Chevalier/Vindesine, Cisplatin, Cyclophosphamide, Lomustin/or by Rosell/Mitomycin, Cyclophosphamide, Cisplatin/the quality of life was evaluated. In 20-persons control group all patients received the symptomatic treatment. In observed group of 110 patients, tumor regressions after 4 courses of chemotherapy allowed to resect cancer in 14 cases, to apply radiotherapy in 42 and to continue chemiotherapy in 23 persons. In every person from above mentioned group the quality of life was evaluated on the basis of intensity of cancer symptoms, accordingly to LCSS. The intensity of cancer symptoms was compared before and after treatment. There were compared; the innensity of complains, weakness, appetite, malnutrition, and hematological, neurological, performans state as well as respiratory sufficiency, infections, cardiac disorders and pain. Apart it, the side effects of applied therapy were assessed in 5 degree scale. The level of hemoglobin, the number of leucocytes, thrombocytes, bilirubine and transaminases in peripheral blood, hematurie, proteinurie, bleedings, appetite, nausea, vomitings, diarrhea, mucosal lesions, infections, skin lesions, cardiac lesions

  15. 肿瘤标志物指数用于术前非小细胞肺癌的预后评估%Prognostic evaluation of tumor marker index for preoperative NSCLC patients

    Institute of Scientific and Technical Information of China (English)

    王火强; 郑金旭; 刘丽; 李梅

    2012-01-01

    目的 评价基于癌胚抗原(CEA)和细胞角蛋白片段19(Cyfra21-1)的肿瘤标志物指数(TMI)对临床Ⅰ期非小细胞肺癌(NSCLC)预后评估的意义.方法 对351例术前为临床Ⅰ期、病理类型均为腺癌或鳞癌的NSCLC病例进行回顾性分析,随访时间≥5年.比较血清CEA和Cyfra 21-1水平以及TMI与患者生存率的关系,并用单因素和多因素分析其风险比(95%可信区间)[ OR(95% CI)].结果 血清CEA水平正常组[(5.14±1.65) ng/mL,n=266]和升高组[(45.88±27.78) ng/mL,n=85]5年生存率分别为89.85%和8.24% (x2=299.30,P<0.01);血清Cyfra21-1水平升高组[(4.85±1.41) ng/mL,n=95]和正常组[(2.23±0.68) ng/mL,n=256]5年生存率分别为15.96%和90.27%(x2=255.70,P<0.01).TMI≤1.0组的5年生存率为96.81%,TMI>1.0组的5年生存率仅为3.02% (x2=461.13,P<0.01).单因素分析OR (95% CI)为104.15(48.600,223.218),P<O.01,多因素分析为107.435 (49.722,232.138),P<0.01,均显示TMI作为预后判断的独立影响因素意义显著.结论 TMI可用于NSCLC的预后评估和治疗参考.%Objective To clarify the prognostic evaluation of carcinoembryonic antigen (CEA) , Cyfra21-1 levels and tumor marker index (TMI) in the sera of preoperative clinical stage I non-small-cell lung carcinoma (NSCLC) patients. Methods A total of 351 patients with clinical stage I NSCLC who had undergone complete resection were reviewed retrospectively. Any patients with follow-up periods less than 5 years were excluded. The univariate and multivariate analysis were used to estimate OR (95% CI). Results The 5-year survival rates of patients with different CEA level showed significant statistical difference (% =299. 30, P <0. 01). The survival rate of the patients (n = 266) whose CEA level were in normal range [(5.14±1.65) ng/mL ] was 89. 85 % , but the patients (n = 85) whose CEA were high [ (45. 88 ±27. 78) ng/mL] was only 8.24%. The 5-year survival rates of patients with different Cyfra21

  16. 18F-FDG uptake as a biologic factor predicting outcome in patients with resected non-small-cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    ZHANG Zhen-jiang; CHEN Jing-han; MENG Long; DU Jia-jun; ZHANG Lin; LIU Ying; DAI Hong-hai

    2007-01-01

    Background The outcome of surgical treatment of non-small-cell lung cancer (NSCLC) remains poor. In many patients the biological behavior of NSCLC does not follow a definite pattern, and can not be accurately predicted before treatment. 18F-fluoro-2-deoxy-glucose (18F-FDG) uptake on positron-emission tomography (PET) is associated with the aggressiveness of NSCLC. The present study focused on the role of 18F-FDG uptake in predicting the outcome of surgically treated patients with NSCLC.Methods A retrospective analysis was made of 82 patients who underwent complete resection and preoperative FDG PET. The maximum standardized uptake value (SUVmax), in addition to five clinicopathological factors and three biomolecular factors, which could possibly influence survival, was compared for possible association with patients' recurrence and survival, by the Log-rank test in univariate analysis and the Cox proportional hazards model in multivariate analysis. The association between SUVmax and other factors was also analyzed. Results Patients with SUVmax more than 11 had a disease-free survival and overall survival shorter than patients with SUVmax less than 11 in univariate analyses (P<0.001, P=0.002). In the multivariate analysis, SUVmax (dichotomized by 11) was the only significant predictor for tumor recurrence. TNM stage and SUVmax (dichotomized by 11) were independent predictors for the overall survival. Associations of SUVmax with p53 overexpression, proliferating cell nuclear antigen (PCNA) labeling index and microvascular density of the tumor were significant in the entire group. Conclusions 18F-FDG uptake on PET may be used to noninvasively assess biological aggressiveness of NSCLC in vivo, identifying the surgically-treated patients with poor prognosis who could benefit from additional therapy.

  17. A Validated Prediction Model for Overall Survival From Stage III Non-Small Cell Lung Cancer: Toward Survival Prediction for Individual Patients

    International Nuclear Information System (INIS)

    Purpose: Although patients with stage III non-small cell lung cancer (NSCLC) are homogeneous according to the TNM staging system, they form a heterogeneous group, which is reflected in the survival outcome. The increasing amount of information for an individual patient and the growing number of treatment options facilitate personalized treatment, but they also complicate treatment decision making. Decision support systems (DSS), which provide individualized prognostic information, can overcome this but are currently lacking. A DSS for stage III NSCLC requires the development and integration of multiple models. The current study takes the first step in this process by developing and validating a model that can provide physicians with a survival probability for an individual NSCLC patient. Methods and Materials: Data from 548 patients with stage III NSCLC were available to enable the development of a prediction model, using stratified Cox regression. Variables were selected by using a bootstrap procedure. Performance of the model was expressed as the c statistic, assessed internally and on 2 external data sets (n=174 and n=130). Results: The final multivariate model, stratified for treatment, consisted of age, gender, World Health Organization performance status, overall treatment time, equivalent radiation dose, number of positive lymph node stations, and gross tumor volume. The bootstrapped c statistic was 0.62. The model could identify risk groups in external data sets. Nomograms were constructed to predict an individual patient's survival probability ( (www.predictcancer.org)). The data set can be downloaded at (https://www.cancerdata.org/10.1016/j.ijrobp.2015.02.048). Conclusions: The prediction model for overall survival of patients with stage III NSCLC highlights the importance of combining patient, clinical, and treatment variables. Nomograms were developed and validated. This tool could be used as a first building block for a decision support system

  18. A Validated Prediction Model for Overall Survival From Stage III Non-Small Cell Lung Cancer: Toward Survival Prediction for Individual Patients

    Energy Technology Data Exchange (ETDEWEB)

    Oberije, Cary, E-mail: cary.oberije@maastro.nl [Radiation Oncology, Research Institute GROW of Oncology, Maastricht University Medical Center, Maastricht (Netherlands); De Ruysscher, Dirk [Radiation Oncology, Research Institute GROW of Oncology, Maastricht University Medical Center, Maastricht (Netherlands); Universitaire Ziekenhuizen Leuven, KU Leuven (Belgium); Houben, Ruud [Radiation Oncology, Research Institute GROW of Oncology, Maastricht University Medical Center, Maastricht (Netherlands); Heuvel, Michel van de; Uyterlinde, Wilma [Department of Thoracic Oncology, Netherlands Cancer Institute, Amsterdam (Netherlands); Deasy, Joseph O. [Memorial Sloan Kettering Cancer Center, New York (United States); Belderbos, Jose [Department of Radiation Oncology, Netherlands Cancer Institute, Amsterdam (Netherlands); Dingemans, Anne-Marie C. [Department of Pulmonology, University Hospital Maastricht, Research Institute GROW of Oncology, Maastricht (Netherlands); Rimner, Andreas; Din, Shaun [Memorial Sloan Kettering Cancer Center, New York (United States); Lambin, Philippe [Radiation Oncology, Research Institute GROW of Oncology, Maastricht University Medical Center, Maastricht (Netherlands)

    2015-07-15

    Purpose: Although patients with stage III non-small cell lung cancer (NSCLC) are homogeneous according to the TNM staging system, they form a heterogeneous group, which is reflected in the survival outcome. The increasing amount of information for an individual patient and the growing number of treatment options facilitate personalized treatment, but they also complicate treatment decision making. Decision support systems (DSS), which provide individualized prognostic information, can overcome this but are currently lacking. A DSS for stage III NSCLC requires the development and integration of multiple models. The current study takes the first step in this process by developing and validating a model that can provide physicians with a survival probability for an individual NSCLC patient. Methods and Materials: Data from 548 patients with stage III NSCLC were available to enable the development of a prediction model, using stratified Cox regression. Variables were selected by using a bootstrap procedure. Performance of the model was expressed as the c statistic, assessed internally and on 2 external data sets (n=174 and n=130). Results: The final multivariate model, stratified for treatment, consisted of age, gender, World Health Organization performance status, overall treatment time, equivalent radiation dose, number of positive lymph node stations, and gross tumor volume. The bootstrapped c statistic was 0.62. The model could identify risk groups in external data sets. Nomograms were constructed to predict an individual patient's survival probability ( (www.predictcancer.org)). The data set can be downloaded at (https://www.cancerdata.org/10.1016/j.ijrobp.2015.02.048). Conclusions: The prediction model for overall survival of patients with stage III NSCLC highlights the importance of combining patient, clinical, and treatment variables. Nomograms were developed and validated. This tool could be used as a first building block for a decision support system.

  19. 数字PCR检测非小细胞肺癌患者血浆EGFR基因T790M突变平台的建立%Establishment of a digital PCR platform for detection of EGFR T790M mutation in plasma circulating DNA from NSCLC patients

    Institute of Scientific and Technical Information of China (English)

    黄斐; 虞倩; 吴炯; 邬升超; 王蓓丽; 张春燕; 郭玮; 潘柏申

    2016-01-01

    Objective Digital PCR ( dPCR ) was established to detect plasma epidermal growth factor receptor (EGFR) T790M mutation of non-small cell lung cancer (NSCLC) patients and was evaluated in terms of analytical performance and clinical application significance.Methods The specific primers and probes for EGFR T790M mutation and wildtype were designed to establish dPCR platform.Limit of blank, sensitivity and linearity of dPCR were evaluated by the detection of plasmids with different concentrations to set up optimal reporting system and reanalyzing process.The mutation of EGFR T790M in plasma and tissue samples from 10 patients with advanced NSCLC resistant to EGFR-TKI therapy who were enrolled in Zhongshan Hospital Fudan University from January 2014 to October 2015 were analyzed by dPCR and amplification refractory ( ARMS) , respectively.The consistency was evaluated between dPCR and ARMS by Chi-square test.The correlation of T790M abundance detected by dPCR between plasma and tissue samples was also analyzed by Peasrson correlation analysis.Results Limit of blank and sensitivity of dPCR was 10 copies and 0.01%, respectively.dPCR was evaluated as linear in the range of 0.01%-100%( Y=1.226X-3.984,R2 =0.999 ).The consistency between dPCR and ARMS of tissue samples was good ( kappa=0.80), while the positive rates of plasma T790M detected by dPCR was significantly higher than ARMS (50%vs 20%,P<0.05).It was found that T790M abundance detected by dPCR was highly correlated between lung cancer tissue and plasma ( R =0.923, P <0.05 ) using Pearson correlation analysis. Conclusions A new method of dPCR with high sensitivity and absolute quantification is established for the detection of EGFR T790M mutation in plasma from advanced NSCLC patients, which brings tumor liquid biopsy into real.It has the ability to provide the most direct and valuable guidance for clinicians to make decision on EGFR tyrosine kinase inhibitors therapy in patients with advanced NSCLC resistant to EGFR

  20. The lung cancer exercise training study: a randomized trial of aerobic training, resistance training, or both in postsurgical lung cancer patients: rationale and design

    Directory of Open Access Journals (Sweden)

    Crawford Jeffrey

    2010-04-01

    Full Text Available Abstract Background The Lung Cancer Exercise Training Study (LUNGEVITY is a randomized trial to investigate the efficacy of different types of exercise training on cardiorespiratory fitness (VO2peak, patient-reported outcomes, and the organ components that govern VO2peak in post-operative non-small cell lung cancer (NSCLC patients. Methods/Design Using a single-center, randomized design, 160 subjects (40 patients/study arm with histologically confirmed stage I-IIIA NSCLC following curative-intent complete surgical resection at Duke University Medical Center (DUMC will be potentially eligible for this trial. Following baseline assessments, eligible participants will be randomly assigned to one of four conditions: (1 aerobic training alone, (2 resistance training alone, (3 the combination of aerobic and resistance training, or (4 attention-control (progressive stretching. The ultimate goal for all exercise training groups will be 3 supervised exercise sessions per week an intensity above 70% of the individually determined VO2peak for aerobic training and an intensity between 60 and 80% of one-repetition maximum for resistance training, for 30-45 minutes/session. Progressive stretching will be matched to the exercise groups in terms of program length (i.e., 16 weeks, social interaction (participants will receive one-on-one instruction, and duration (30-45 mins/session. The primary study endpoint is VO2peak. Secondary endpoints include: patient-reported outcomes (PROs (e.g., quality of life, fatigue, depression, etc. and organ components of the oxygen cascade (i.e., pulmonary function, cardiac function, skeletal muscle function. All endpoints will be assessed at baseline and postintervention (16 weeks. Substudies will include genetic studies regarding individual responses to an exercise stimulus, theoretical determinants of exercise adherence, examination of the psychological mediators of the exercise - PRO relationship, and exercise-induced changes

  1. [Jinlong capsule combined with chemoradiotherapy for NSCLC: a Meta-analysis].

    Science.gov (United States)

    Lu, Qiang; Luo, Jing-bin; Feng, Yi-fan; She, Qin; Shi, Zhong-feng

    2015-11-01

    The purpose of this study was to evaluate the effect and safety of Jinlong capsule combined with chemotherapy or radio-therapy for non-small cell lung cancer (NSCLS) using Meta-analysis. PubMed, Embase, CNKI and Wanfang databases were all searched without language restriction, and searching time was from January 1990 to July 2015. All eligible published studies were included in this study for quality assessment and data extraction. All the data were analyzed using Revman 5.3. A total of ten studies including 736 subjects (370 in Jinlong capsule plus chemoradiotherapy and 366 in chemoradiotherapy only) were finally included in this Meta-analysis. The result of Meta analysis showed that compared with pure chemoradiotherapy group, Jinlong capsule combined with chemoradiotherapy for NSCLC could improve the patients' curative effect (OR = 1.77, 95% CI: 1.29-2.43, P benefit rate (OR = 1.89, 95% CI: 1.22-2.91, P < 0.05), life quality improvement rate (OR = 2. 56, 95% CI: 1.61-4.05, P < 0.05), and decrease leucopenia incidence rate (OR = 0.35, 95% CI: 0. 22-0.56, P < 0.05) and gastrointestinal reaction rate (OR = 0.67, 95% CI: 0.40-1.11, P < 0.05). The pooled results showed that Jinlong capsule combined with chemoradiotherapy for NSCLC could improve the curative effect and life quality, and decrease the adverse reaction of patients. PMID:27097429

  2. Features of fatigue in patients with early-stage non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Xianping Huang

    2015-01-01

    Full Text Available Background: The objective of this study was to investigate the fatigue status and related factors in patients with early-stage non-small cell lung cancer (NSCLC 1-5 years after surgery. Materials and Methods: This cross-sectional study included 254 patients with stage IA or IB NSCLC, who had undergone surgery. They completed several surveys, including the Brief Fatigue Inventory, Karnofsky Performance Scale, Physical Activity Questionnaire, Baseline Dyspnea Index, Hospital Anxiety and Depression Scale. The association between fatigue and functional status was assessed using Chi-square analysis. Spearman rank correlation and multivariate logistic regression analysis were used to assess the correlation between fatigue and various other factors. Results: The overall incidence of postoperative fatigue was 59.8%. Among patients with moderate to severe fatigue, 21.1% had obvious dysfunction, whereas only 9.6% of patients with mild or no fatigue (χ2 = 5.369; P = 0.02 showed obvious dysfunction. Multivariate logistic regression analysis showed that functional status (odds ratio [OR]: 3.57; 95% confidence interval [CI]: 1.17-6.19, concurrent lung disease (OR: 2.34; 95% CI: 1.08-4.99, depression (OR: 6.39; 95% CI: 2.42-17.35, and anxiety (OR: 2.45; 95% CI: 1.13-4.87 were independent risk factors for fatigue, whereas physical activity (OR: 0.27; 95% CI: 0.11-0.73 could prevent fatigue. Conclusion: More than half of the patients with early-stage NSCLC experienced fatigue 1-5 years after surgery, and moderate to severe fatigue was often associated with obvious dysfunction. The strong association of fatigue with anxiety, depression, and lung complications suggests that fatigue and other symptoms constitute a symptom cluster. Therefore, comprehensive treatment methods may achieve better therapeutic results.

  3. In vivo synergistic cytogenetic effects of aminophylline on lymphocyte cultures from patients with lung cancer undergoing chemotherapy

    International Nuclear Information System (INIS)

    Highlights: ► SCEs in vivo, a possible predictor of tumor chemoresponse. ► In vivo exposure to combined treatment, applying the SCE assay. ► Aminophylline enhances DNA instability induced by chemotherapy in vivo. ► In vivo synergistic effect of Aminophylline with the chemotherapeutic agents. - Abstract: Background: The anti-cancer and cytogenetic effects of aminophylline (AM) have been demonstrated in several clinical trials. The aim of the present study was to investigate the in vivo cytogenetic effects of AM in newly diagnosed patients with small cell (SCLC) and non-small cell lung cancer (NSCLC), receiving chemotherapy for the first time. Methods: Sister chromatid exchanges (SCEs) and proliferation rate index (PRI) were evaluated in peripheral blood lymphocyte cultures from six patients with SCLC and six patients with NSCLC after the in vitro addition of AM and after the in vivo administration of AM in patients receiving chemotherapy. Results: The in vitro addition of AM significantly increased SCEs only in SCLC patients (p 0.05). Conclusions: These observations suggest that AM enhances the results of concurrently administered chemotherapy by synergistically increasing its cytogenetic effects in patients with lung cancer

  4. Detection and Evaluation of EGFR Mutation Status in Serum of Patients with Advanced Non-small Cell Lung Cancer Treated with EGFR-TKIs

    Directory of Open Access Journals (Sweden)

    Ling MA

    2013-06-01

    Full Text Available Background and objective Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs has shown a high response rate in the treatment of lung cancer in patients with (EGFR mutation. The aim of this study is to evaluate the relationship between EGFR mutation status in serum and predicting benefit from EGFR-TKIs therapy in patients with advanced non-small cell lung cancer (NSCLC. Methods We examined EGFR mutation status in serum of 80 patients with advanced, EGFR-TKIs given as first-line therapy NSCLC. All patients were received long-term follow-up, and the drug efficacy were observed and evaluated. Results The EGFR mutation in serum was detected in 33.8% (27/80 of NSCLC patients examined, in which exon 19 deletion mutation was present at a frequency of 44.4% (12/27 and exon 21 point mutation was 55.6% (15/27; The response rate to EGFR-TKI in patients with EGFR mutation in serum was (55.6%, 15/27, which was remarkably higher than that in EGFR wild-type patients (17.0%, 9/53, the difference was statistically significant (χ2=0.370, P<0.001; The median progression free survival (PFS of patients with EGFR mutation in serum was remarkably better than that of EGFR wild-type patients (9.8 months vs 5.7 months, P=0.014. Conclusion In patients with advanced, EGFR-positive in serum NSCLC, EGFR-TKIs given as first-line therapy is associated with improved drug efficacy. The results suggest that it is feasible to use serum to detect EGFR mutation, which can predict a benefit from EGFR-TKIs given as first-line therapy.

  5. Prognostic predictors for non-small cell lung cancer patients with brain metastasis after radiotherapy

    Directory of Open Access Journals (Sweden)

    Qiuhong FAN

    2008-06-01

    Full Text Available Background and objective Brain metastasis (BM is often found in the patients with lung cancer. Radiotherapy is regular and effective means of therapy and it aims at palliating symptoms and prolonging survival time. However, now there are different viewpoints on protocols of radiotherapy and prognostic factors. A retrospective analysis is used to evaluate the results of treatment for 82 cases with brain metastasis from non-small cell lung cancer (NSCLC and explore the prognostic factors to establish a prognostic index (PI model. Methods From Feb.1995 to Oct. 2006, 82 patients irradiated for BM from NSCLC, with both complete medical charts and follow-up data available, were eligible for this retrospective analysis. A number of potential factors which might affect prognosis after irradiation were evaluated. The significance of prognostic variables in the survival resulted from both univariate analysis by Kaplan-Meier combining with log-rank test and multivariate Cox regression model. The prognostic index (PI was established based on Cox regression analysis and subgrouping values. Results The follow-up time was 1-120 months. For the entire cohort, the median survival from the start of radiation for BM was 10.5 months, and the actuarial overall survival rate was 50.8%, 23.7% and 5.1% at 0.5, 1 and 2 years respectively. Univariate analysis showed KPS, control of primary tumor, interval from the beginning of diagnostic to BM, extracranial systemic metastasis, counts of lymphocyte and solitary BM were predictors of prognosis. However, in the Cox multivariate analysis, only KPS, control of primary tumor, interval from the beginning of diagnostic to BM and solitary BM were significant prognostic factors. The prognostic index was established based on Cox regression analysis and 82 patients were stratified good, intermediate and poor prognostic sub-groups. The difference of survival rate among 3 subgroups is significant (P<0.001. Conclusion Radiotherapy is

  6. PD-L1 Expression and Survival among Patients with Advanced Non–Small Cell Lung Cancer Treated with Chemotherapy

    Directory of Open Access Journals (Sweden)

    Steffen Filskov Sorensen

    2016-02-01

    Full Text Available BACKGROUND: Recent clinical trial results have suggested that programmed cell death ligand 1 (PD-L1 expression measured by immunohistochemistry may predict response to anti–programmed cell death 1 (PD-1 therapy. Results on the association between PD-L1 expression and survival among patients with advanced non–small cell lung cancer (NSCLC treated with chemotherapy are inconsistent. MATERIAL AND METHODS: We evaluated the relationship between PD-L1 expression and overall survival (OS among 204 patients with advanced NSCLC treated at Aarhus University Hospital, Aarhus, Denmark, from 2007 to 2012. PD-L1 expression was measured using a prototype immunohistochemistry assay with the anti–PD-L1 22C3 antibody (Merck. PD-L1 strong positivity and weak positivity were defined to be traceable to the clinical trial version of the assay. RESULTS: Twenty-five percent of patients had PD-L1 strong-positive tumors, and 50% had PD-L1 weak-positive tumors. No statistically significant association was found between PD-L1 expression and survival; adjusted hazard ratio of 1.34 (95% confidence interval, 0.88-2.03; median OS, 9.0 months for the PD-L1 strong-positive group and 1.07 (0.74-1.55; median OS, 9.8 months for the PD-L1 weak-positive group compared with the PD-L1–negative group (median OS, 7.5 months. No association was seen between PD-L1 expression and OS when PD-L1 expression levels were stratified by median or tertiles. CONCLUSIONS: In concordance with previous studies, we found PD-L1 measured by immunohistochemistry to be frequently expressed in patients with advanced NSCLC. However, PD-L1 expression is not a strong prognostic marker in patients with advanced NSCLC treated with chemotherapy.

  7. Prognostic significance of total lesion glycolysis in patients with advanced non-small cell lung cancer receiving chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Zaizen, Yoshiaki [Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Kurume (Japan); Azuma, Koichi, E-mail: azuma@med.kurume-u.ac.jp [Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Kurume (Japan); Kurata, Seiji [Department of Radiology, Kurume University School of Medicine, Kurume (Japan); Sadashima, Eiji; Hattori, Satoshi [Biostatistics Center, Kurume University, Kurume (Japan); Sasada, Tetsuro [Department of Immunology and Immunotherapy, Kurume University School of Medicine, Kurume (Japan); Imamura, Yohei [Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Kurume (Japan); Kaida, Hayato [Department of Radiology, Kurume University School of Medicine, Kurume (Japan); Kawahara, Akihiko [Department of Pathology, Kurume University School of Medicine, Kurume (Japan); Kinoshita, Takashi [Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Kurume (Japan); Ishibashi, Masatoshi [Department of Radiology, Kurume University School of Medicine, Kurume (Japan); Hoshino, Tomoaki [Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Kurume (Japan)

    2012-12-15

    Background: [{sup 18}F]fluorodeoxyglucose positron emission tomography (FDG-PET) imaging has been employed as a non-invasive diagnostic tool for malignant tumors. Total lesion glycolysis (TLG) on FDG-PET is calculated by multiplying the mean standardized uptake value (SUVmean) by the tumor volume. Unlike the maximum standardized uptake value (SUVmax), which represents the point of greatest metabolic activity within tumors, TLG has been suggested to reflect global metabolic activity in whole tumors. Methods: We retrospectively examined whether or not FDG-PET measurements, including SUVmean, SUVmax, and TLG, could predict progression-free survival (PFS) or overall survival (OS) in patients with non-small cell lung cancer (NSCLC) receiving chemotherapy. Results: This study involved 81 consecutive patients with NSCLC who received chemotherapy. All of the patients underwent FDG-PET examination before treatment. SUVmean, SUVmax, and TLG on FDG-PET were significantly associated with gender, smoking status, and tumor histology. With adjustment for several other variables, Cox regression analysis showed that TLG was significantly prognostic for both PFS [hazard ratio = 2.34; 95% confidence interval, 1.18–4.64; P = 0.015] and OS (hazard ratio = 2.80; 95% confidence interval, 1.12–6.96; P = 0.003), whereas SUVmean and SUVmax had no significant association with PFS (P = 0.693 and P = 0.322, respectively) or OS (P = 0.587 and P = 0.214, respectively). Conclusions: Our findings suggest that TLG may be more useful than SUVmean and SUVmax for predicting PFS and OS in NSCLC patients receiving chemotherapy. The TLG measurement on FDG-PET imaging could be routinely recommended to advanced NSCLC patients.

  8. What Do Prostate Cancer Patients Die Of?

    OpenAIRE

    Riihimäki, Matias; Thomsen, Hauke; Brandt, Andreas; Sundquist, Jan; Hemminki, Kari

    2011-01-01

    The cause of death in prostate cancer patients is examined using the Swedish Family-Cancer Database. Prostate cancer patients were found to have a higher risk for dying from various causes other than prostate cancer, including external causes and heart failure.

  9. Epilepsy in the cancer patient

    OpenAIRE

    Kargiotis, Odysseas; Markoula, Sofia; Kyritsis, Athanasios P.

    2011-01-01

    Abstract Purpose Epileptic seizures in patients with malignancies usually occur as a consequence of brain metastases from systemic cancer or the presence of a primary brain tumor. Other less-frequent causes include metabolic disorders such as electrolyte abnormalities, hypoglycemia, hypoxia and liver failure, paraneoplastic encephalitis, leptomeningeal carcinomatosis, side effects of certain chemotherapeutic agents, central nervous system infections, and ...

  10. Swallowing dysfunction in cancer patients

    NARCIS (Netherlands)

    J.E. Raber-Durlacher; M.T. Brennan; I.M. Verdonck- de Leeuw; R.J. Gibson; J.G. Eilers; T. Waltimo; C.P. Bots; M. Michelet; T.P. Sollecito; T.S. Rouleau; A. Sewnaik; R.J. Bensadoun; M.C. Fliedner; S. Silverman; F.K.L. Spijkervet

    2012-01-01

    Purpose Dysphagia (swallowing dysfunction) is a debilitating, depressing, and potentially life-threatening complication in cancer patients that is likely underreported. The present paper is aimed to review relevant dysphagia literature between 1990 and 2010 with a focus on assessment tools, prevalen

  11. Pegfilgrastim in pediatric cancer patients

    NARCIS (Netherlands)

    te Poele, EM; Kamps, WA; Tamminga, RYJ; Leew, JA; Postma, A; de Bont, ESJM

    2005-01-01

    Chemotherapy-induced neutropenia is a major dose-limiting side effect of intensive chemotherapy in cancer patients. Recently, pegfilgrastim (a product with a long half-life, resulting in once-per-cycle dosage) was introduced to prevent neutropenia in adults. The authors report 32 episodes of pegfilg

  12. Circulating tumour DNA profiling reveals heterogeneity of EGFR inhibitor resistance mechanisms in lung cancer patients

    Science.gov (United States)

    Chabon, Jacob J.; Simmons, Andrew D.; Lovejoy, Alexander F.; Esfahani, Mohammad S.; Newman, Aaron M.; Haringsma, Henry J.; Kurtz, David M.; Stehr, Henning; Scherer, Florian; Karlovich, Chris A.; Harding, Thomas C.; Durkin, Kathleen A.; Otterson, Gregory A.; Purcell, W. Thomas; Camidge, D. Ross; Goldman, Jonathan W.; Sequist, Lecia V.; Piotrowska, Zofia; Wakelee, Heather A.; Neal, Joel W.; Alizadeh, Ash A.; Diehn, Maximilian

    2016-01-01

    Circulating tumour DNA (ctDNA) analysis facilitates studies of tumour heterogeneity. Here we employ CAPP-Seq ctDNA analysis to study resistance mechanisms in 43 non-small cell lung cancer (NSCLC) patients treated with the third-generation epidermal growth factor receptor (EGFR) inhibitor rociletinib. We observe multiple resistance mechanisms in 46% of patients after treatment with first-line inhibitors, indicating frequent intra-patient heterogeneity. Rociletinib resistance recurrently involves MET, EGFR, PIK3CA, ERRB2, KRAS and RB1. We describe a novel EGFR L798I mutation and find that EGFR C797S, which arises in ∼33% of patients after osimertinib treatment, occurs in <3% after rociletinib. Increased MET copy number is the most frequent rociletinib resistance mechanism in this cohort and patients with multiple pre-existing mechanisms (T790M and MET) experience inferior responses. Similarly, rociletinib-resistant xenografts develop MET amplification that can be overcome with the MET inhibitor crizotinib. These results underscore the importance of tumour heterogeneity in NSCLC and the utility of ctDNA-based resistance mechanism assessment. PMID:27283993

  13. Circulating tumour DNA profiling reveals heterogeneity of EGFR inhibitor resistance mechanisms in lung cancer patients.

    Science.gov (United States)

    Chabon, Jacob J; Simmons, Andrew D; Lovejoy, Alexander F; Esfahani, Mohammad S; Newman, Aaron M; Haringsma, Henry J; Kurtz, David M; Stehr, Henning; Scherer, Florian; Karlovich, Chris A; Harding, Thomas C; Durkin, Kathleen A; Otterson, Gregory A; Purcell, W Thomas; Camidge, D Ross; Goldman, Jonathan W; Sequist, Lecia V; Piotrowska, Zofia; Wakelee, Heather A; Neal, Joel W; Alizadeh, Ash A; Diehn, Maximilian

    2016-01-01

    Circulating tumour DNA (ctDNA) analysis facilitates studies of tumour heterogeneity. Here we employ CAPP-Seq ctDNA analysis to study resistance mechanisms in 43 non-small cell lung cancer (NSCLC) patients treated with the third-generation epidermal growth factor receptor (EGFR) inhibitor rociletinib. We observe multiple resistance mechanisms in 46% of patients after treatment with first-line inhibitors, indicating frequent intra-patient heterogeneity. Rociletinib resistance recurrently involves MET, EGFR, PIK3CA, ERRB2, KRAS and RB1. We describe a novel EGFR L798I mutation and find that EGFR C797S, which arises in ∼33% of patients after osimertinib treatment, occurs in <3% after rociletinib. Increased MET copy number is the most frequent rociletinib resistance mechanism in this cohort and patients with multiple pre-existing mechanisms (T790M and MET) experience inferior responses. Similarly, rociletinib-resistant xenografts develop MET amplification that can be overcome with the MET inhibitor crizotinib. These results underscore the importance of tumour heterogeneity in NSCLC and the utility of ctDNA-based resistance mechanism assessment. PMID:27283993

  14. Predictive and prognostic effect of CD133 and cancer-testis antigens in stage Ib-IIIA non-small cell lung cancer

    OpenAIRE

    SU, CHUNXIA; Xu, Ying; Xuefei LI; Ren, Shengxiang; Zhao, Chao; Hou, Likun; Ye, Zhiwei; Zhou, Caicun

    2015-01-01

    CD133 and cancer-testis antigens (CTAs) may be potential predicted markers of adjuvant chemotherapy or immune therapy, and they may be the independent prognostic factor of NSCLC. Nowadays, there is still no predictive biomarker identified for the use of adjuvant chemotherapy in non-small cell lung cancer (NSCLC) patients. To clarify the role of CD133 and CTAs as a predictive marker for adjuvant chemotherapy or prognostic factors of overall survival, we performed a retrospective study in 159 s...

  15. Optimal pharmacotherapeutic strategies for elderly patients with advanced non-small cell lung cancer.

    Science.gov (United States)

    Quoix, Elisabeth

    2011-11-01

    Increases in both life expectancy and cancer incidence with age result in a significant rise in lung cancer rates among elderly patients, with a median age at diagnosis of between 63 and 70 years. However, elderly patients are under-represented in clinical trials and generally receive suboptimal treatment, mainly because of fears about increased toxicity of chemotherapy. Indeed, physiological modification of renal and haematopoietic functions with age together with co-morbidity and associated polypharmacy may alter the metabolism of chemotherapy drugs, resulting in greater toxicity. Moreover, performance status (PS), the main prognostic factor in younger patients, does not correlate well with geriatric indexes such as activities of daily living, cognition and physical performance, and comprehensive geriatric assessment is important in elderly patients. Until 2010, based on the small number of clinical trials designed for elderly patients, monotherapy was the recommended treatment for those with advanced non-small cell lung cancer (NSCLC), whereas for fit younger patients, a platinum-based doublet was and continues to be the recommended first-line therapy. However, at the plenary session of the 2010 Annual Meeting of the American Society of Clinical Oncology, results were presented from a randomized controlled trial conducted by the French Intergroup of Thoracic Oncology that demonstrated that in PS 0-2 patients aged≥70 years with advanced NSCLC, monthly carboplatin with weekly paclitaxel resulted in significantly longer survival than single-agent therapy (vinorelbine or gemcitabine). It should be noted that even in a priori unfavourable prognostic subgroups (patients with a PS score of 2, those aged>80 years or those with an activities of daily living scale score of nihilism in the treatment of elderly patients with advanced NSCLC. Such patients should be evaluated carefully by geriatric indexes and, if they have a PS score of 0-2, may be treated with platinum

  16. Association of CT perfusion imaging to plasma levels of pigment epithelial-derived factor (PEDF) and vas-cular endothelial growth (VEGF) in patients with NSCLC%非小细胞肺癌CT灌注成像与血浆PEDF及VEGF水平的相关性研究

    Institute of Scientific and Technical Information of China (English)

    魏英

    2015-01-01

    目的:探讨非小细胞肺癌CT灌注成像参数与患者血浆色素上皮衍生因子( pigment epithelial-derived factor, PEDF)及血管内皮生长因子( vascular endothelial growth, VEGF)水平的相关性。方法92例非小细胞肺癌患者和80例肺部良性病变患者均行CT灌注扫描,灌注软件分析获得病灶感兴趣区域( region of interest, ROI)的灌注参数血流量( blood flow, BF)、血容量( blood volume, BV)、平均通过时间( mean transit time, MTT)、达峰值时间(time to peal, TTP)及表面通透性(permeability surface, PS)5个灌注参数数值。采用酶联免疫吸附法( ELISA法)检测两组血浆PEDF与VEGF水平。 Pearson相关分析血浆PEDF及VEGF水平与CT灌注扫描各参数的关系。结果非小细胞肺癌患者CT灌注成像BF、BV、MTT、TTP、PS及血浆VEGF水平较肺部良性病变者均明显增高(P均<0.05),而PEDF水平则显著降低(P<0.01);同时CT灌注成像各参数及PEDF、VEGF水平在非小细胞肺癌不同分期亦存在明显差异性。 Pearson相关分析结果显示:血浆PEDF水平与CT灌注成像参数BF、BV及MTT呈负相关,与TTP呈正相关(P均<0.05),与PS无明显相关性;血浆VEGF水平与CT灌注成像参数BF、BV及MTT呈正相关,与TTP呈负相关( P均<0.05),仍与PS无明显相关性。结论非小细胞肺癌肺癌CT灌注成像与患者血浆PEDF、VEGF及其生物学特性密切相关,是定量检测肿瘤血流灌注方便、有效的检查手段。%Objective To observe the association of CT perfusion parameters to plasma levels of pigment ep-ithelial-derived factor ( PEDF) and vascular endothelial growth ( VEGF) in patients with non-small-cell lung cancer ( NSCLC) . Methods 92 patients with NSCLC and 80 patients with benign lesion were given CT perfusion imaging to obtain blood flow ( BF) , blood volume ( BV) , mean transit time ( MTT) , time to peal ( TTP) and permeability sur-face ( PS) through CT perfusion software. The plasma

  17. Lung Cancer Surgery Worthwhile for Older Patients

    Science.gov (United States)

    ... nlm.nih.gov/medlineplus/news/fullstory_158689.html Lung Cancer Surgery Worthwhile for Older Patients Study found those ... 2016 THURSDAY, May 5, 2016 (HealthDay News) -- Older lung cancer patients are surviving longer when they have lung ...

  18. Lung Cancer Surgery Worthwhile for Older Patients

    Science.gov (United States)

    ... page: https://medlineplus.gov/news/fullstory_158689.html Lung Cancer Surgery Worthwhile for Older Patients Study found ... 2016 THURSDAY, May 5, 2016 (HealthDay News) -- Older lung cancer patients are surviving longer when they have ...

  19. Survival Analysis of 121 Stage N2-IIIa Non-small Cell Lung Cancer Patients 
Treated with Surgery

    Directory of Open Access Journals (Sweden)

    Heli YANG

    2015-08-01

    Full Text Available Background and objective It has still been controversial to treat N2-IIIa non-small cell lung cancer (NSCLC patients by surgery or non-surgery. We retrospectively analysed the survival of 121 stage N2-IIIa NSCLC patients treated with surgery and explored their postoperatively long-term prognostic factors. Methods All of 1,290 patients in Beijing Cancer Hospital underwent resection by single-surgeon-team, among which 121 cases with stage N2-IIIa were enrolled in the study. We retrospectively analysed the impact of gender, age, smoking, perioperative chemotherapy, incision, histological type, vascular tumor emboli, pTstage and tumor size on survival of stage N2-IIIa patients, and compared the survival between patients with single-and multi-station N2 metastasis, and between intraoperatively or postoperatively pathological N2 (IIIa1/a2 and preoperative N2 (IIIa3/a4. Univariate analysis was conducted by Kaplan-Meier curve, and significance test was performed by Log-rank test and Cox regression factor analysis was applicated for multivariate analysis. Results The 5-yr of all the 121 cases was 43.6%, with a median survival time being 50.3 mo. Univariate analysis showed the 5-year survival rate in patients with single- and multi- station N2 metastasis were 58.3% and 25.5%, respectively (P=0.001, 5-year survival rate in patients with stage IIIa1/a2 and stag IIIa3/a4 were 52.7% and 38.4%, respectively (P=0.020. Multivariate analysis demonstrated that only single station N2 (HR=0.326, 95%CI: 0.186-0.572, P<0.001 and IIIa1/a2 (HR=0.494, 95%CI: 0.259-0.941, P=0.032 were independent prognostic factors for stage N2-IIIa lung cancer patients. Conclusion The prognosis of stage N2-IIIa NSCLC patients with single-station N2 metastasis were better than those with multi-station N2 metastasis. Besides, IIIa1/a2 patients had a better survival compared with stage IIIa3/a4 patients. A multi-disciplinary comprehensive treatment based on surgery may allow patients with

  20. Determination of EGFR and KRAS mutational status in Greek non-small-cell lung cancer patients

    Science.gov (United States)

    PAPADOPOULOU, EIRINI; TSOULOS, NIKOLAOS; TSIRIGOTI, ANGELIKI; APESSOS, ANGELA; AGIANNITOPOULOS, KONSTANTINOS; METAXA-MARIATOU, VASILIKI; ZAROGOULIDIS, KONSTANTINOS; ZAROGOULIDIS, PAVLOS; KASARAKIS, DIMITRIOS; KAKOLYRIS, STYLIANOS; DAHABREH, JUBRAIL; VLASTOS, FOTIS; ZOUBLIOS, CHARALAMPOS; RAPTI, AGGELIKI; PAPAGEORGIOU, NIKI GEORGATOU; VELDEKIS, DIMITRIOS; GAGA, MINA; ARAVANTINOS, GERASIMOS; KARAVASILIS, VASILEIOS; KARAGIANNIDIS, NAPOLEON; NASIOULAS, GEORGE

    2015-01-01

    It has been reported that certain patients with non-small-cell lung cancer (NSCLC) that harbor activating somatic mutations within the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) gene may be effectively treated using targeted therapy. The use of EGFR inhibitors in patient therapy has been demonstrated to improve response and survival rates; therefore, it was suggested that clinical screening for EGFR mutations should be performed for all patients. Numerous clinicopathological factors have been associated with EGFR and Kirsten-rat sarcoma oncogene homolog (KRAS) mutational status including gender, smoking history and histology. In addition, it was reported that EGFR mutation frequency in NSCLC patients was ethnicity-dependent, with an incidence rate of ~30% in Asian populations and ~15% in Caucasian populations. However, limited data has been reported on intra-ethnic differences throughout Europe. The present study aimed to investigate the frequency and spectrum of EGFR mutations in 1,472 Greek NSCLC patients. In addition, KRAS mutation analysis was performed in patients with known smoking history in order to determine the correlation of type and mutation frequency with smoking. High-resolution melting curve (HRM) analysis followed by Sanger sequencing was used to identify mutations in exons 18–21 of the EGFR gene and in exon 2 of the KRAS gene. A sensitive next-generation sequencing (NGS) technology was also employed to classify samples with equivocal results. The use of sensitive mutation detection techniques in a large study population of Greek NSCLC patients in routine diagnostic practice revealed an overall EGFR mutation frequency of 15.83%. This mutation frequency was comparable to that previously reported in other European populations. Of note, there was a 99.8% concordance between the HRM method and Sanger sequencing. NGS was found to be the most sensitive method. In addition, female non-smokers demonstrated a high prevalence of

  1. Treatment Advances in Locally Advanced and Metastatic Non-Small Cell Lung Cancer

    NARCIS (Netherlands)

    V.M.F. Surmont (Veerle)

    2010-01-01

    textabstractLung cancer is the leading cause of cancer mortality in the United States and Europe. Approximately 85% of the patients with lung cancer have non–small cell lung cancer (NSCLC), which can be classified into squamous, adeno, large cell and not otherwise specified (NOS) histologies. The mo

  2. Prognostic value of p53 and Ki67 expression in fiberoptic bronchial biopsies of patients with non small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Ciancio Nicola

    2012-09-01

    Full Text Available Abstract Background Overexpression of the tumor suppressor gene p53 and the marker for cellular proliferation Ki67 in open lung biopsies are indicated as predictor factors of survival of patients with lung cancer. However, the prognostic value of p53 and Ki67 in fiberoptic bronchial biopsies (FBB has not been fully investigated. We evaluated p53 and Ki67 immunostaining in FBB from 19 with Non Small-Cell Lung Cancer (NSCLC: 12 adenocarcinomas, 5 squamous cell carcinomas and 2 NSCLC-NOS. Methods FBB specimens were fixed in formalin, embedded in paraffin, and immunostained using anti-p53 and anti-Ki67 antibodies. Slides were reviewed by two independent observers and classified as positive (+ve when the number of cells with stained nuclei exceeded 15% for p53 or when >25% positive cells were observed throughout each section for Ki67. Results Positive (+ve immunostaining was found in 9 patients for p53 (47.37% and 8 patients for Ki67 (42.10%. We examined overall survival curves of the patients with Mantel's logrank test, both p53 -ve and Ki67 -ve patients had significantly higher survival rates than p53 + ve (p  Conclusion This study suggests that negative immunostaining of fiberoptic bronchial biopsies for p53 and Ki67 could represent a better prognostic factor for patients with NSCLC.

  3. Incidence and clinical implication of tumor cavitation in patients with advanced non-small cell lung cancer induced by Endostar, an angiogenesis inhibitor

    Science.gov (United States)

    Huang, Chun; Wang, Xuan; Wang, Jing; Lin, Li; Liu, Zhujun; Xu, Wenjing; Wang, Liuchun; Xiao, Jianyu; Li, Kai

    2014-01-01

    Background Antiangiogenesis plays a key role in the treatment of non-small lung cancer (NSCLC). We observed the cavitation of lesions in patients with stage IIIB/IV NSCLC treated with Endostar and vinorelbine-cisplatin (NP) chemotherapy, and evaluated the imaging characteristics and clinical outcome of patients who developed tumor cavitation. Methods Our study included 105 untreated NSCLC patients who received Endostar in combination with NP chemotherapy at the Tianjin Lung Cancer Center. Chest computed tomography (CT) was performed to evaluate the efficacy every two cycles. The number of activated circulating endothelial cells (aCECs) was measured by flow cytometry. Rates of tumor cavitation were documented and their clinical CT imaging data were analyzed. Results Tumor cavitation occurred in 11 of the 105 (10.5%) patients treated with Endostar and NP. The response rates were 37.2% (35/94) in patients without cavitation, 27.3% (3/11) evaluated by Response Evaluation Criteria in Solid Tumors, and 100.0% (11/11) if evaluated by an alternate method in patients who developed cavitation. Three of the 11 cases with cavitation had a centrally located tumor. No patients had hemoptysis or any other severe side effects. Compared with patients not developing cavitation, cavity formation resulted in a longer median survival time (13.6 vs. 11.8 months, P = 0.011) and an increase in the number of aCECs (244.4/105 vs. 23.3/105, P = 0.000). Conclusions Intratumoral cavitation induced by Endostar is common in NSCLC patients, and is not correlated with squamous histology, tumor location or pulmonary hemorrhage. Cavitation might have a significant effect on the number of aCECs and overall prognosis. PMID:26767036

  4. Genetic polymorphism in the epidermal growth factor receptor gene predicts outcome in advanced non-small cell lung cancer patients treated with erlotinib

    DEFF Research Database (Denmark)

    Winther-Larsen, Anne; Nissen, Peter H.; Jakobsen, Kristine Raaby;

    2015-01-01

    OBJECTIVES: Epidermal growth factor receptor (EGFR) mutations are important predictors of treatment response to tyrosine kinase inhibitors (TKIs) in patients with non-small cell lung cancer (NSCLC). However, some patients with mutations do not respond and some patients without mutations show...... with advanced NSCLC. Genotypes were correlated with clinical characteristics, toxicity and outcome. A multivariate analysis was performed using Cox proportional hazards model while adjusting for clinically relevant factors including EGFR mutation status. RESULTS: 181946CT or TT genotypes showed an association...... response. We therefore need additional biomarkers to improve the selection of these patients for treatment. A promising candidate could be germline genetic variations in the EGFR gene that can alter protein expression or function and may influence the response to TKIs. Thus, the aim of this study...

  5. Gene expression profiles of ERCC1, TYMS, RRM1, TUBB3 and EGFR in tumor tissue from non-small cell lung cancer patients

    Institute of Scientific and Technical Information of China (English)

    Yu Daping; Li Jie; Han Yi; Liu Shuku; Xiao Ning; Li Yunsong; Sun Xiaojun

    2014-01-01

    Background Personalized medicine becomes essential in lung cancer treatment,however lung-cancer-related gene expression profiles in Chinese patients remain unknown.In this study,the correlation of gene expression profiles and clinical characteristics in non-small-cell lung cancer (NSCLC) was investigated.Methods Seventy-six Chinese patients with NSCLC were enrolled in the study to investigate mRNA expression profiles of excision repair cross complement group 1 (ERCC1),thymidylate synthetase (TYMS),ribonucleotide reductase (RRM1),class Ⅲ β-tubulin (TUBB3),and epidermal growth factor receptor (EGFR) genes and their correlation with patient clinical characteristics.A novel liquidchip technology was used to detect mRNA expression levels in formalin fixed paraffin embedded tumor pathology samples.The relationships between gene expression and clinical characteristics were assessed using the Mann-Whitney test.Results ERCC1 mRNA levels were higher in tumors from patients with metastatic disease than patients with nonmetastatic disease (P=0.021),and higher in adenocarcinomas than squamous cell carcinomas (P=0.006).Increased TUBB3 mRNA expression levels were found in patients with performance status (PS) 1 in comparison with PS 0 (P=0.049),with poorly differentiated tumors in comparison with tumors that were moderately and well differentiated (P ≤0.000 1),and with advanced stage in comparison with early stage disease (P≤0.000 1).Conclusions ERCC1 mRNA levels were higher in metastatic adenocarcinoma NSCLC; TUBB3 mRNA levels were significantly higher in poody differentiated tumors and in advanced stage NSCLC,which indicates the poor prognosis.

  6. Detection of epidermal growth factor receptor mutations in formalin fixed paraffin embedded biopsies in Malaysian non-small cell lung cancer patients

    OpenAIRE

    Shi Yeen, Tiffany Ng; Pathmanathan, Rajadurai; Shiran, Mohd Sidik; Ahmad Zaid, Fattah Azman; Cheah, Yoke Kqueen

    2013-01-01

    Background Somatic mutations of the epidermal growth factor receptor (EGFR) are reportedly associated with various responses in non-small cell lung cancer (NSCLC) patients receiving the anti-EGFR agents. Detection of the mutation therefore plays an important role in therapeutic decision making. The aim of this study was to detect EGFR mutations in formalin fixed paraffin embedded (FFPE) samples using both Scorpion ARMS and high resolution melt (HRM) assay, and to compare the sensitivity of th...

  7. A new scoring system for predicting survival in patients with non-small cell lung cancer

    International Nuclear Information System (INIS)

    This analysis was performed to create a scoring system to estimate the survival of patients with non-small cell lung cancer (NSCLC). Data from 1274 NSCLC patients were analyzed to create and validate a scoring system. Univariate (UV) and multivariate (MV) Cox models were used to evaluate the prognostic importance of each baseline factor. Prognostic factors that were significant on both UV and MV analyses were used to develop the score. These included quality of life, age, performance status, primary tumor diameter, nodal status, distant metastases, and smoking cessation. The score for each factor was determined by dividing the 5-year survival rate (%) by 10 and summing these scores to form a total score. MV models and the score were validated using bootstrapping with 1000 iterations from the original samples. The score for each prognostic factor ranged from 1 to 7 points with higher scores reflective of better survival. Total scores (sum of the scores from each independent prognostic factor) of 32–37 correlated with a 5-year survival of 8.3% (95% CI = 0–17.1%), 38–43 correlated with a 5-year survival of 20% (95% CI = 13–27%), 44–47 correlated with a 5-year survival of 48.3% (95% CI = 41.5–55.2%), 48–49 correlated to a 5-year survival of 72.1% (95% CI = 65.6–78.6%), and 50–52 correlated to a 5-year survival of 84.7% (95% CI = 79.6–89.8%). The bootstrap method confirmed the reliability of the score. Prognostic factors significantly associated with survival on both UV and MV analyses were used to construct a valid scoring system that can be used to predict survival of NSCLC patients. Optimally, this score could be used when counseling patients, and designing future trials

  8. Circulating tumor DNA detection in lung cancer patients before and after surgery

    Science.gov (United States)

    Guo, Nannan; Lou, Feng; Ma, Yongfu; Li, Jie; Yang, Bo; Chen, Wei; Ye, Hua; Zhang, Jing-Bo; Zhao, Ming-Yu; Wu, Wen-Jun; Shi, Rong; Jones, Lindsey; Chen, Katherine S.; Huang, Xue F.; Chen, Si-Yi; Liu, Yang

    2016-01-01

    Circulating tumor DNA (ctDNA) in peripheral blood is a “liquid biopsy” that contains representative tumor information including gene mutations. Additionally, repeated ctDNA samples can be easily obtained to monitor response to treatment and disease progression, which may be especially valuable to lung cancer patients with tumors that cannot be easily biopsied or removed. To investigate the changes in ctDNA after surgical tumor resection, tumor and blood samples obtained before and after surgery were collected prospectively from 41 non-small lung cancer (NSCLC) patients. Somatic driver mutations in tumor DNA (tDNA) and pre- and post-op plasma ctDNA sample pairs were identified by targeted sequencing in several genes including EGFR, KRAS, and TP53 with an overall study concordance of 78.1% and sensitivity and specificity of 69.2% and 93.3%, respectively. Importantly, the frequency of 91.7% of ctDNA mutations decreased after surgery and these changes were observed as little as 2 days post-op. Moreover, the presence of ctDNA had a higher positive predictive value than that of six tumor biomarkers in current clinical use. This study demonstrates the use of targeted sequencing to reliably identify ctDNA changes in response to treatment, indicating a potential utility of this approach in the clinical management of NSCLC. PMID:27641744

  9. Limb edemas in cancer patients

    International Nuclear Information System (INIS)

    Diagnostic radiology in cancer patients suffering from limb edemas serves two main purposes: to detect or to rule out lymph node metastases, recurrent cancer, or secondary malignancies, and to differentiate venous edema from lymphedema. The authors suggest an algorithmic pathway where the non-invasive imaging modalities, real-time ultrasonography and computed tomography are recommended as the initial diagnostic step. Both techniques are equally well suited to detect enlarged lymph nodes with high accuracy. In addition, computed tomography allows to a certain degree to separate venous from lymphedema. Phlebography is rarely needed in these patients. Lymphography should only be considered in patients undergoing microsurgical reconstructive operations of the lymphatics (e.g. lymphovenous anastomoses) because this invasive study carries the risk of deteriorating the edematous limb. (orig.)

  10. Chronic diseases among older cancer patients.

    NARCIS (Netherlands)

    Deckx, L.D.; Akker, M.A. van der; Metsemakers, J.M.; Knottnerus, A.K.; Schellevis, F.G.; Buntinx, F.B.

    2011-01-01

    Introduction: With the growing number of older cancer patients, the burden of chronic diseases among older cancer patients will become increasingly important. Chronic diseases often interfere with treatment decisions and prognosis for cancer patients. However, little is known about the occurrence of

  11. Pain and Distress in Cancer Patients

    Directory of Open Access Journals (Sweden)

    Anna Burger-Szabo

    2015-09-01

    Full Text Available Background: A significant number of patients with cancer suffer from anxiety and depressive disorder. Perceived emotional distress, anxiety and depressive symptoms are significantly more frequent in cancer patients with pain than in patients without pain. Despite their high prevalence cancer pain and distress are frequently undertreated.

  12. Genetic association between polymorphism of mdm2 gene and symptoms and pathological types of NSCLC

    International Nuclear Information System (INIS)

    Objective: To investigate the genetic association between polymorphism of mdm2 gene and symptoms and pathological types of non-small cell lung cancer (NSCLC). Methods: Polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) was used to identify mdm2 genotypes. The Pearson Chi square test and Woolf statistic method were used to analyze the relative risk and 95% confidence interval (CI) in order to find the genetic association between polymorphism of mdm2 gene and symptoms and pathological types of NSCLC. Results: In the SNP rs1196337 (a G to A base change) AA genotype showed association with cough of NSCLC (P<0.05). Conclusion: The polymorphism of mdm2 gene may be associated with symptom as cough of NSCLC. (authors)

  13. The disparity of health facilities in an urban area discourages proposed treatment application in inoperable lung cancer patients

    International Nuclear Information System (INIS)

    Patients with a newly diagnosed non-small cell lung cancer (NSCLC) stage IIIB are offered chemoradiotherapy, as proposed by the current guidelines. This combination treatment is facilitated by the coexistence of corresponding departments in the same establishment. The geographical disparity of these health facilities influences patients’ willingness to be treated and may influence their survival. This is an observational study that compares the survival of two groups of patients with NSCLC stage IIIB: those treated with chemoradiotherapy versus those treated only with chemotherapy. These two comparable groups were formed exclusively by patients’ and/or their families’ decisions. One hundred fifteen consecutive NSCLC stage IIIB patients were included in the study. All were hospitalized in the biggest Chest Disease Hospital in Athens and were offered sequential chemoradiotherapy. Only 54 patients opted for the proposed treatment, while 61 decided to be treated with chemotherapy only, denying continuing their treatment in another health care unit (radiotherapy). Their survival and related factors were analyzed. Mean overall survival was estimated 10 months (95% confidence interval [CI]: 7.96–12.04). Patients treated with chemoradiotherapy had almost double overall survival compared to those under chemotherapy (P = 0.001): 13.6 months (95% CI: 12.3–14.9) versus 7.5 (95% CI: 6.1–8.9). Patients aged ≤ 65 years (P < 0.001), smokers (P < 0.001), and those without a cancer history (P < 0.001) survived longer. The lack of a radiotherapy department in a hospital providing chemotherapy impedes the application of current guidelines advocating combined radiochemotherapy. When recommended radiotherapy after six chemo cycles, half of the patients are unwilling to be displaced and do not follow the recommendations. This has an impact on patient survival

  14. Stereotactic body radiation therapy versus conventional radiation therapy in patients with early stage non-small cell lung cancer

    DEFF Research Database (Denmark)

    Jeppesen, Stefan Starup; Schytte, Tine; Jensen, Henrik R;

    2013-01-01

    Abstract Introduction. Stereotactic body radiation therapy (SBRT) for early stage non-small cell lung cancer (NSCLC) is now an accepted and patient friendly treatment, but still controversy exists about its comparability to conventional radiation therapy (RT). The purpose of this single...... and SBRT predicted improved prognosis. However, staging procedure, confirmation procedure of recurrence and technical improvements of radiation treatment is likely to influence outcomes. However, SBRT seems to be as efficient as conventional RT and is a more convenient treatment for the patients....

  15. Correlation of Hsp70 Serum Levels with Gross Tumor Volume and Composition of Lymphocyte Subpopulations in Patients with Squamous Cell and Adeno Non-Small Cell Lung Cancer.

    Science.gov (United States)

    Gunther, Sophie; Ostheimer, Christian; Stangl, Stefan; Specht, Hanno M; Mozes, Petra; Jesinghaus, Moritz; Vordermark, Dirk; Combs, Stephanie E; Peltz, Friedhelm; Jung, Max P; Multhoff, Gabriele

    2015-01-01

    Heat-shock protein 70 (Hsp70) is frequently found on the plasma membrane of a large number of malignant tumors including non-small cell lung cancer (NSCLC) and gets released into the blood circulation in lipid vesicles. On the one hand, a membrane (m)Hsp70-positive phenotype correlates with a high aggressiveness of the tumor; on the other hand, mHsp70 serves as a target for natural killer (NK) cells that had been pre-stimulated with Hsp70-peptide TKD plus low-dose interleukin-2 (TKD/IL-2). Following activation, NK cells show an up-regulated expression of activatory C-type lectin receptors, such as CD94/NKG2C, NKG2D, and natural cytotoxicity receptors (NCRs; NKp44, NKp46, and NKp30) and thereby gain the capacity to kill mHsp70-positive tumor cells. With respect to these results, the efficacy of ex vivo TKD/IL-2 stimulated, autologous NK cells is currently tested in a proof-of-concept phase II clinical trial in patients with squamous cell NSCLC after radiochemotherapy (RCT) at the TUM. Inclusion criteria are histological proven, non-resectable NSCLC in stage IIIA/IIIB, clinical responses to RCT and a mHsp70-positive tumor phenotype. The mHsp70 status is determined in the serum of patients using the lipHsp70 ELISA test, which enables the quantification of liposomal and free Hsp70. Squamous cell and adeno NSCLC patients had significantly higher serum Hsp70 levels than healthy controls. A significant correlation of serum Hsp70 levels with the gross tumor volume was shown for adeno and squamous cell NSCLC. However, significantly elevated ratios of activated CD69(+)/CD94(+) NK cells that are associated with low serum Hsp70 levels were observed only in patients with squamous cell lung cancer. These data might provide a first hint that squamous cell NSCLC is more immunogenic than adeno NSCLC. PMID:26579130

  16. Phase III trial comparing vinflunine with docetaxel in second-line advanced non-small-cell lung cancer previously treated with platinum-containing chemotherapy

    DEFF Research Database (Denmark)

    Krzakowski, Maciej; Ramlau, Rodryg; Jassem, Jacek;

    2010-01-01

    To compare vinflunine (VFL) to docetaxel in patients with stage IIIB/IV non-small-cell lung cancer (NSCLC) who have experienced treatment failure with first-line platinum-based chemotherapy.......To compare vinflunine (VFL) to docetaxel in patients with stage IIIB/IV non-small-cell lung cancer (NSCLC) who have experienced treatment failure with first-line platinum-based chemotherapy....

  17. Integrin and gene network analysis reveals that ITGA5 and ITGB1 are prognostic in non-small-cell lung cancer

    OpenAIRE

    Zheng WQ; Jiang CH; Li RF

    2016-01-01

    Weiqi Zheng, Caihui Jiang, Ruifeng Li Department of Radiation Oncology, Guangqian Hospital, Quanzhou, Fujian, People’s Republic of China Background: Integrin expression has been identified as a prognostic factor in non-small-cell lung cancer (NSCLC). This study was aimed at determining the predictive ability of integrins and associated genes identified within the molecular network.Patients and methods: A total of 959 patients with NSCLC from The Cancer Genome Atlas cohorts were en...

  18. Clinical Application of Adjuvant Treatment after Operation in Patients with Stage IIIa Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Yajie GAO

    2010-04-01

    Full Text Available Background and objective The efficacy of complete resection of the cancer for patients with stage IIIa non-small cell lung cancer (NSCLC is limited. Synthetic therapy is taken the lead in advocating at present. However, the value of post-operative radiotherapy is not still clear. The aim of this study is to evaluate the survival time and side effects of postoperative chemotherapy or chemoradiotherapy in the treatment of stage IIIa NSCLC. Methods Between December 2003 and June 2007, 52 cases that have completed followed-up data with stage IIIa of NSCLC received in the First Affiliated Hospital of Dalian Medical University. Twenty-three patients received postoperative chemoradiotherapy (group A and 29 patients received postoperative chemotherapy combined with radiotherapy (group B. Group A adopted platinum-based combination chemotherapy for 4-6 cycles. The chemotherapeutics included gemcitabine, vinorelbine and docetaxel. Group B used chemotherapy for 2-4 cycles and then received 3-dimensional conformal radiotherapy (3D-CRT. The prescribe dose of target volume was 50 Gy. The chemotherapy was same as for group A and needed 4 cycles in all. The impact of postoperative adjuvant treatment on survival and toxicity was observed in patients with stage IIIa NSCLC and the reason of disease progression was analyzed. Results The median survival was 32.5 months in group A and 31.9 months in group B (P=0.371. Progression-free survival extended about 6 months (P=0.044. The survival rate was 87% at 1 year, 0.1% at 2 year, 33% at 3 year for group A compared with 93%, 69%, 45% for group B. The major side effects were hematological and gastrointestinal toxicities, including nausea, vomiting and neutropenia. There was no significant difference in these toxicities between the two groups (P>0.05. Radioactiv esophageal infection occurred in 17.2% of the patients. Acute and late radioactive lung infection occurred in 13.8% and 27.6% of the patients. All these toxicities

  19. Stereotactic body radiotherapy for centrally located stage I NSCLC. A multicenter analysis

    Energy Technology Data Exchange (ETDEWEB)

    Schanne, Daniel H.; Nestle, Ursula; Grosu, Anca L. [Universitaetsklinik Freiburg, Klinik fuer Strahlenheilkunde, Freiburg (Germany); Allgaeuer, Michael [Barmherzige Brueder, Klinik fuer Strahlentherapie, Regensburg (Germany); Andratschke, Nicolaus; Molls, Michael [TU Muenchen, Klinik und Poliklinik fuer Strahlentherapie und Radiologische Onkologie, Muenchen (Germany); Appold, Steffen [Universitaetsklinikum Dresden, Klinik und Poliklinik fuer Strahlentherapie und Radioonkologie, Dresden (Germany); Dieckmann, Ute [Allgemeines Krankenhaus Wien, Univ. Klinik fuer Strahlentherapie, Wien (Austria); Ernst, Iris [Universitaetsklinikum Muenster, Klinik fuer Strahlentherapie, Muenster (Germany); Ganswindt, Ute [LMU Muenchen, Klinik und Poliklinik fuer Strahlentherapie und Radioonkologie, Muenchen (Germany); Holy, Richard [Universitaetsklinikum Aachen, Klinik fuer Strahlentherapie, Aachen (Germany); Nevinny-Stickel, Meinhard [Medizinischen Universitaet Innsbruck, Univ. Klinik fuer Strahlentherapie und Radioonkologie, Innsbruck (Austria); Semrau, Sabine [Universitaetsklinikum Erlangen, Strahlenklinik Erlangen, Erlangen (Germany); Sterzing, Florian [Universitaetsklinikum Heidelberg, Klinik fuer Radioonkologie und Strahlentherapie, Heidelberg (Germany); Wittig, Andrea [Philipps-Universitaet Marburg, Klinik fuer Strahlentherapie und Radioonkologie, Marburg (Germany); Guckenberger, Matthias [Universitaet Wuerzburg, Klinik und Poliklinik fuer Strahlentherapie, Wuerzburg (Germany)

    2014-08-27

    The purpose of this work is to analyze patterns of care and outcome after stereotactic body radiotherapy (SBRT) for centrally located, early-stage, non-small cell lung cancer (NSCLC) and to address the question of potential risk for increased toxicity in this entity. A total of 90 patients with centrally located NSCLC were identified among 613 cases in a database of 13 German and Austrian academic radiotherapy centers. The outcome of centrally located NSCLC was compared to that of cases with peripheral tumor location from the same database. Patients with central tumors most commonly presented with UICC stage IB (50 %), while the majority of peripheral lesions were stage IA (56 %). Average tumor diameters were 3.3 cm (central) and 2.8 cm (peripheral). Staging PET/CT was available for 73 and 74 % of peripheral and central tumors, respectively. Biopsy was performed in 84 % (peripheral) and 88 % (central) of cases. Doses varied significantly between central and peripheral lesions with a median BED{sub 10} of 72 Gy and 84 Gy, respectively (p < 0.001). Fractionation differed as well with medians of 5 (central) and 3 (peripheral) fractions (p < 0.001). In the Kaplan-Meier analysis, 3-year actuarial overall survival was 29 % (central) and 51 % (peripheral; p = 0.004) and freedom from local progression was 52 % (central) and 84 % (peripheral; p < 0.001). Toxicity after treatment of central tumors was low with no grade III/IV and one grade V event. Mortality rates were 0 and 1 % after 30 and 60 days, respectively. Local tumor control in patients treated with SBRT for centrally located, early-stage NSCLC was favorable, provided ablative radiation doses were prescribed. This was, however, not the case in the majority of patients, possibly due to concerns about treatment-related toxicity. Reported toxicity was low, but prospective trials are needed to resolve the existing uncertainties and to establish safe high-dose regimens for this cohort of patients. (orig.) [German] Ziel

  20. Randomized cross-over study of patient preference for oral or intravenous vinorelbine in combination with carboplatin in the treatment of advanced NSCLC

    DEFF Research Database (Denmark)

    Jensen, Lars Henrik; Osterlind, Kell; Rytter, Carsten

    2008-01-01

    BACKGROUND: Most chemotherapeutics are administrated intravenously (iv), but some are also available in an oral (po) formulation. This study was designed with the primary objective to estimate the patients' preference for po or iv vinorelbine in combination with carboplatin for the palliative.......001). The response rate was 23% and median survival 11.4 months. Patients with preference for po treatment stated that side effects were less with capsules and that daily life was less affected by capsules. CONCLUSION: Three out of four patients preferred oral vinorelbine. Clinical outcomes were comparable to other...

  1. Relationship between radiation dose and lung function in patients with lung cancer receiving radiotherapy

    International Nuclear Information System (INIS)

    In patients with inoperable non-small cell lung cancer (NSCLC), radical radiotherapy is the treatment of choice. The dose is limited by consequential pneumonitis and lung fibrosis. Hence, a better understanding of the relationship between the dose-volume distributions and normal tissue side effects is needed. CT is a non-invasive method to monitor the development of fibrosis and pneumonitis, and spirometry is an established tool to measure lung function. NSCLC patients were included in a multicenter trial and treated with megavoltage conformal radiotherapy. In a subgroup comprising 16 patients, a total dose of 59-63 Gy with 1.8-1.9 Gy per fraction was given. Dose-volume histograms were calculated and corrected according to the linear-quadratic formula using alpha/beta=3 Gy. The patients underwent repetitive CT examinations (mean follow-up, 133 days) following radiotherapy, and pre and post treatment spirometry (mean follow-up, 240 days). A significant correlation was demonstrated between local lung dose and changes in CT numbers >30 days after treatment (p40 Gy Gy there was a sudden increase in CT numbers at 70-90 days. Somewhat unexpectedly, the highest mean lung doses were found in patients with the least reductions in lung function (peak expiratory flow; p<0.001). The correlation between CT numbers, radiation dose and time after treatment show that CT may be used to monitor development of lung fibrosis/pneumonitis after radiotherapy for lung cancer. Paradoxically, the patients with the highest mean lung doses experienced the minimum deterioration of lung function. This may be explained by reduction in the volume of existing tumour masses obstructing the airways, leading to relief of symptoms. This finding stresses the role of radiotherapy for lung cancer, especially where the treatment aim is palliative

  2. Clinical Effects for Patients with Recurrent Advanced Non-small Cell Lung Cancer Treated with Icotinib Hydrochloride

    Directory of Open Access Journals (Sweden)

    Jingying NONG

    2013-05-01

    Full Text Available Background and objective Icotinib hydrochloride is the third single target EGFR-TKI used in clinical treatment of advanced non-small cell lung cancer (NSCLC. Clinical research reports on its efficacy and survival in patients with Recurrent Advanced NSCLC are still little.The aim of this study is to evaluate the efficacy and survival of Icotinib hydrochloride for patients with advanced non-small cell lung cancer who failed to previous chemotherapy and explore the association of clinical features with the efficacy and survival. Methods The clinical data of 60 NSCLC patients referred to the Beijing Chest Hospital, Capital Medical University from March 2009 to July 2012 were retrospectively analyzed. Results The overall response rate (ORR was 45.0% and the disease control rate (DCR was 80.0%. The median progression-free survival (PFS time was 6.7 months. RR and PFS in female were superior to male (P=0.014, 0.013, respectively. RR, DCR in 2nd-line subgroup were superior to ≥3rd-line subgroup (P=0.020, 0.024, respectively. RR, DCR and PFS in EGFR mutation carriers were significantly superior to wild-type patients (P=0.006, <0.001, 0.002, respectively . There was no statistical difference in RR and PFS between those age <65 and ≥65 or PS<2 and PS≥2. There was no statistical difference in RR and DCR between exon 19 deletion and exon 21 mutations, while the former had much longer PFS (P=0.020. EGFR mutation and exon 19 deletion are the independent prognostic factors to significantly improve the PFS (P=0.009, 0.012, respectively. The side effects were generally mild and consisted of rash and diarrhea. Conclusion Icotinib hydrochloride is effective especially in EGFR mutation carriers and well tolerated in patients with recurrent advanced non-small-cell lung cancer.

  3. Fever of unknown origin in cancer patients.

    Science.gov (United States)

    Loizidou, A; Aoun, M; Klastersky, J

    2016-05-01

    Fever of unknown origin (FUO) remains a challenging clinical problem, namely in patients with cancer. In cancer patients, FUO may be due to the cancer itself, as it is the case of hematological malignancies; digestive tumors (colon cancer, liver metastases) are significantly associated with FUO and infection can be demonstrated in some cases. Prevention with G-CSF and empirical antimicrobial therapy are essential approaches for the management of FUO in cancer patients. New diagnostic approaches, such as PET imaging, should be further evaluated in cancer patients with FUO. PMID:26995082

  4. Consensus for EGFR mutation testing in non-small cell lung cancer: results from a European workshop

    DEFF Research Database (Denmark)

    Pirker, Robert; Herth, Felix J F; Kerr, Keith M;

    2010-01-01

    Activating somatic mutations of the tyrosine kinase domain of epidermal growth factor receptor (EGFR) have recently been characterized in a subset of patients with advanced non-small cell lung cancer (NSCLC). Patients harboring these mutations in their tumors show excellent response to EGFR...... tyrosine kinase inhibitors (EGFR-TKIs). The EGFR-TKI gefitinib has been approved in Europe for the treatment of adult patients with locally advanced or metastatic NSCLC with activating mutations of the EGFR TK. Because EGFR mutation testing is not yet well established across Europe, biomarker......-directed therapy only slowly emerges for the subset of NSCLC patients most likely to benefit: those with EGFR mutations....

  5. Fluid biopsy for circulating tumor cell identification in patients with early-and late-stage non-small cell lung cancer: a glimpse into lung cancer biology

    Science.gov (United States)

    Wendel, Marco; Bazhenova, Lyudmila; Boshuizen, Rogier; Kolatkar, Anand; Honnatti, Meghana; Cho, Edward H.; Marrinucci, Dena; Sandhu, Ajay; Perricone, Anthony; Thistlethwaite, Patricia; Bethel, Kelly; Nieva, Jorge; van den Heuvel, Michel; Kuhn, Peter

    2012-02-01

    Circulating tumor cell (CTC) counts are an established prognostic marker in metastatic prostate, breast and colorectal cancer, and recent data suggest a similar role in late stage non-small cell lung cancer (NSCLC). However, due to sensitivity constraints in current enrichment-based CTC detection technologies, there are few published data about CTC prevalence rates and morphologic heterogeneity in early-stage NSCLC, or the correlation of CTCs with disease progression and their usability for clinical staging. We investigated CTC counts, morphology and aggregation in early stage, locally advanced and metastatic NSCLC patients by using a fluid-phase biopsy approach that identifies CTCs without relying on surface-receptor-based enrichment and presents them in sufficiently high definition (HD) to satisfy diagnostic pathology image quality requirements. HD-CTCs were analyzed in blood samples from 78 chemotherapy-naïve NSCLC patients. 73% of the total population had a positive HD-CTC count (>0 CTC in 1 mL of blood) with a median of 4.4 HD-CTCs mL-1 (range 0-515.6) and a mean of 44.7 (±95.2) HD-CTCs mL-1. No significant difference in the medians of HD-CTC counts was detected between stage IV (n = 31, range 0-178.2), stage III (n = 34, range 0-515.6) and stages I/II (n = 13, range 0-442.3). Furthermore, HD-CTCs exhibited a uniformity in terms of molecular and physical characteristics such as fluorescent cytokeratin intensity, nuclear size, frequency of apoptosis and aggregate formation across the spectrum of staging. Our results demonstrate that despite stringent morphologic inclusion criteria for the definition of HD-CTCs, the HD-CTC assay shows high sensitivity in the detection and characterization of both early- and late-stage lung cancer CTCs. Extensive studies are warranted to investigate the prognostic value of CTC profiling in early-stage lung cancer. This finding has implications for the design of extensive studies examining screening, therapy and surveillance in

  6. Fluid biopsy for circulating tumor cell identification in patients with early-and late-stage non-small cell lung cancer: a glimpse into lung cancer biology

    International Nuclear Information System (INIS)

    Circulating tumor cell (CTC) counts are an established prognostic marker in metastatic prostate, breast and colorectal cancer, and recent data suggest a similar role in late stage non-small cell lung cancer (NSCLC). However, due to sensitivity constraints in current enrichment-based CTC detection technologies, there are few published data about CTC prevalence rates and morphologic heterogeneity in early-stage NSCLC, or the correlation of CTCs with disease progression and their usability for clinical staging. We investigated CTC counts, morphology and aggregation in early stage, locally advanced and metastatic NSCLC patients by using a fluid-phase biopsy approach that identifies CTCs without relying on surface-receptor-based enrichment and presents them in sufficiently high definition (HD) to satisfy diagnostic pathology image quality requirements. HD-CTCs were analyzed in blood samples from 78 chemotherapy-naïve NSCLC patients. 73% of the total population had a positive HD-CTC count (>0 CTC in 1 mL of blood) with a median of 4.4 HD-CTCs mL−1 (range 0–515.6) and a mean of 44.7 (±95.2) HD-CTCs mL−1. No significant difference in the medians of HD-CTC counts was detected between stage IV (n = 31, range 0–178.2), stage III (n = 34, range 0–515.6) and stages I/II (n = 13, range 0–442.3). Furthermore, HD-CTCs exhibited a uniformity in terms of molecular and physical characteristics such as fluorescent cytokeratin intensity, nuclear size, frequency of apoptosis and aggregate formation across the spectrum of staging. Our results demonstrate that despite stringent morphologic inclusion criteria for the definition of HD-CTCs, the HD-CTC assay shows high sensitivity in the detection and characterization of both early- and late-stage lung cancer CTCs. Extensive studies are warranted to investigate the prognostic value of CTC profiling in early-stage lung cancer. This finding has implications for the design of extensive studies examining screening, therapy and

  7. High EMT Signature Score of Invasive Non-Small Cell Lung Cancer (NSCLC Cells Correlates with NFκB Driven Colony-Stimulating Factor 2 (CSF2/GM-CSF Secretion by Neighboring Stromal Fibroblasts.

    Directory of Open Access Journals (Sweden)

    Albin Rudisch

    Full Text Available We established co-cultures of invasive or non-invasive NSCLC cell lines and various types of fibroblasts (FBs to more precisely characterize the molecular mechanism of tumor-stroma crosstalk in lung cancer. The HGF-MET-ERK1/2-CREB-axis was shown to contribute to the onset of the invasive phenotype of Calu-1 with HGF being secreted by FBs. Differential expression analysis of the respective mono- and co-cultures revealed an upregulation of NFκB-related genes exclusively in co-cultures with Calu-1. Cytokine Array- and ELISA-based characterization of the "cytokine fingerprints" identified CSF2 (GM-CSF, CXCL1, CXCL6, VEGF, IL6, RANTES and IL8 as being specifically upregulated in various co-cultures. Whilst CXCL6 exhibited a strictly FB-type-specific induction profile regardless of the invasiveness of the tumor cell line, CSF2 was only induced in co-cultures of invasive cell lines regardless of the partnered FB type. These cultures revealed a clear link between the induction of CSF2 and the EMT signature of the cancer cell line. The canonical NFκB signaling in FBs, but not in tumor cells, was shown to be responsible for the induced and constitutive CSF2 expression. In addition to CSF2, cytokine IL6, IL8 and IL1B, and chemokine CXCL1 and CXCL6 transcripts were also shown to be increased in co-cultured FBs. In contrast, their induction was not strictly dependent on the invasiveness of the co-cultured tumor cell. In a multi-reporter assay, additional signaling pathways (AP-1, HIF1-α, KLF4, SP-1 and ELK-1 were found to be induced in FBs co-cultured with Calu-1. Most importantly, no difference was observed in the level of inducibility of these six signaling pathways with regard to the type of FBs used. Finally, upon tumor fibroblast interaction the massive induction of chemokines such as CXCL1 and CXCL6 in FBs might be responsible for increased recruitment of a monocytic cell line (THP-1 in a transwell assay.

  8. 阿米福汀在局部晚期非小细胞肺癌放疗中的作用研究%Short-term Effect of Amifostine on Locally Advanced NSCLC Patients Treated with Radiotherapy

    Institute of Scientific and Technical Information of China (English)

    林展; 严浩林; 朱海生; 梁雷锋

    2013-01-01

    目的 探讨阿米福汀在局部晚期非小细胞肺癌(NSCLC)放疗中对近期疗效的影响及降低放射性食管炎和放射性肺炎的作用.方法 2008年1月-2010年2月我院放疗科收治62例局部晚期NSCLC患者,采用随机数字表法分为单纯三维适形放疗组(对照组)和阿米福汀+三维适形放疗组(试验组).试验组每次放疗前15~30 min给予阿米福汀300 mg/m2,静脉滴注.每周放疗5次,持续6周.放疗结束后6周评价两组患者的近期疗效.放疗期间每周记录1次放射性食管炎、放射性肺炎的发生率.结果 两组共44例患者完成了预定试验,对照组23例,试验组21例.对照组完全缓解(CR)1例,部分缓解(PR)11例,客观有效率为52%;试验组CR 2例,PR 12例,客观有效率为67%,两组客观有效率比较差异无统计学意义(χ2=0.95,P>0.05).对照组累计发生放射性食管炎15例(65%),放射性肺炎16例(70%);试验组累计发生放射性食管炎和放射性肺炎各5例(24%),两组放射性食管炎和放射性肺炎累计发生率比较,差异均有统计学意义(P值分别为0.017和0.003).结论 阿米福汀可以降低 NSCLC放疗中放射性食管炎和放射性肺炎的发生率,但不降低放疗的近期疗效.%Objective To evaluate the short - term effect of locally advanced NSCLC patients treated with radiotherapy and to understand its effect on alleviating radiation esophagitis and radiation pneumonitis. Methods 62 patients with locally advanced NSCLC admitted to radiotherapy department of our hospital from January 2008 to February 2010 were randomly divided into pure 3D conformal radiotherapy group ( control group ) and amifostine combined with 3D conformal radiotherapy group ( experiment group ). The experiment group was given 15 to 30 min intravenous drip of 300 mg/m amifostine. Six weeks after radiotherapy , the short - term effect of the two groups was assessed. During radiotherapy, the incidences of radiation esophagitis and radiation

  9. Gender difference in treatment outcomes in patients with stage III non-small cell lung cancer receiving concurrent chemoradiotherapy

    International Nuclear Information System (INIS)

    The objective of this study was to identify any gender differences in the outcomes of concurrent platinum-based chemotherapy and thoracic radiotherapy for unresectable stage III non-small cell lung cancer (NSCLC). A comparative retrospective review of the clinical characteristics and treatment outcomes between female and male NSCLC patients receiving chemoradiotherapy. Of a total of 204 patients, 44 (22%) were females and 160 (78%) were males. There was no difference in age, body weight loss, performance status or disease stage between the sexes, whereas never-smokers and adenocarcinoma were more common in female patients (55% vs. 3%, P80% of the patients, respectively, of both sexes. Grade 3-4 neutropenia was observed in 64% of the female patients and 63% of the male patients. Severe esophagitis was encountered in <10% of the patients, irrespective of the sex. The response rate was higher in the female than in the male patients (93% vs. 79%, P=0.028), but the median progression-free survival did not differ between the sexes. The median survival time in the female and male patients was 22.3 and 24.3 months, respectively (P=0.64). This study failed to show any gender differences in the survival or toxicity among patients treated by concurrent chemoradiotherapy. These results contrast with the better survival in female patients undergoing surgery for localized disease or chemotherapy for metastatic disease. (author)

  10. The Role of Epigenetics in Resistance to Cisplatin Chemotherapy in Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    O' Byrne, Kenneth J.; Barr, Martin P.; Gray, Steven G., E-mail: sgray@stjames.ie [Trinity College Dublin, Department of Clinical Medicine, Trinity Centre for Health Sciences, St James Hospital, James Street, Dublin 8 (Ireland)

    2011-03-17

    Non-small cell lung cancer (NSCLC) is the most common cause of cancer related death in the world. Cisplatin and carboplatin are the most commonly used cytotoxic chemotherapeutic agents to treat the disease. These agents, usually combined with drugs such as gemcitabine or pemetrexed, induce objective tumor responses in only 20–30% of patients. Aberrant epigenetic regulation of gene expression is a frequent event in NSCLC. In this article we review the emerging evidence that epigenetics and the cellular machinery involved with this type of regulation may be key elements in the development of cisplatin resistance in NSCLC.

  11. Molecular imaging of hypoxia in non-small-cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yip, Connie [King' s College London, St Thomas' Hospital, Department of Cancer Imaging, Division of Imaging Sciences and Biomedical Engineering, London (United Kingdom); National Cancer Centre, Department of Radiation Oncology, Singapore (Singapore); St Thomas' Hospital, Imaging 2, London (United Kingdom); Blower, Philip J. [King' s College London, St Thomas' Hospital, Department of Imaging Chemistry and Biology, Division of Imaging Sciences and Biomedical Engineering, London (United Kingdom); Goh, Vicky [King' s College London, St Thomas' Hospital, Department of Cancer Imaging, Division of Imaging Sciences and Biomedical Engineering, London (United Kingdom); St Thomas' Hospital, Department of Radiology, Guy' s and St Thomas' NHS Foundation Trust, London (United Kingdom); Landau, David B. [King' s College London, St Thomas' Hospital, Department of Cancer Imaging, Division of Imaging Sciences and Biomedical Engineering, London (United Kingdom); St Thomas' Hospital, Department of Clinical Oncology, Guy' s and St Thomas' NHS Foundation Trust, London (United Kingdom); Cook, Gary J.R. [King' s College London, St Thomas' Hospital, Department of Cancer Imaging, Division of Imaging Sciences and Biomedical Engineering, London (United Kingdom); St Thomas' Hospital, Clinical PET Imaging Centre, Guy' s and St Thomas' NHS Foundation Trust, London (United Kingdom)

    2015-05-01

    Non-small-cell lung cancer (NSCLC) is the commonest cancer worldwide but survival remains poor with a high risk of relapse, particularly after nonsurgical treatment. Hypoxia is present in a variety of solid tumours, including NSCLC. It is associated with treatment resistance and a poor prognosis, although when recognised may be amenable to different treatment strategies. Thus, noninvasive assessment of intratumoral hypoxia could be used to stratify patients for modification of subsequent treatment to improve tumour control. Molecular imaging approaches targeting hypoxic cells have shown some early success in the clinical setting. This review evaluates the evidence for hypoxia imaging using PET in NSCLC and explores its potential clinical utility. (orig.)

  12. TFIIB-Related Factor 2 Is Associated with Poor Prognosis of Nonsmall Cell Lung Cancer Patients through Promoting Tumor Epithelial-Mesenchymal Transition

    OpenAIRE

    Yu Tian; Ming Lu; Weiming Yue; Lin Li; Shuhai Li; Cun Gao; Libo Si; Lei Qi; Wensi Hu; Hui Tian

    2014-01-01

    In this study, we found that increased BRF2 protein expression was prevalent in NSCLC. Overexpression of BRF2 correlated with abnormal expression of E-cadherin, N-cadherin, and snail. Additionally, expression of BRF2 was found to be an independent prognostic factor in NSCLC patients. Furthermore, we showed that targeted knockdown of BRF2 expression could inhibit the migratory and invasive abilities of NSCLC cells and induced loss of the epithelial-mesenchymal transition of NSCLC cells. These ...

  13. Efficacy and safety of icotinib in Chinese patients with advanced non-small cell lung cancer after failure of chemotherapy

    Institute of Scientific and Technical Information of China (English)

    Shao Lan; Zhang Beibei; He Chunxiao; Lin Baochai; Song Zhengbo; Lou Guangyuan; Yu Xinmin

    2014-01-01

    Background The preclinical experiments and several clinical studies showed icotinib,an oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor,in Chinese patients with advanced non-small cell lung cancer (NSCLC) who failed previous chemotherapy.We performed a retrospective study of the efficacy and safety of icotinib monotherapy in a different and more recent sample of Chinese patients.Methods The clinical data of 149 patients with advanced NSCLC who were admitted to Zhejiang Cancer Hospital from August 1,2011 to July 31,2012 were retrospectively analyzed.All patients were given icotinib treatment after the failure of previous chemotherapy.Univariate and multivariate analyses were conducted based on the Kaplan Meier method and Cox proportional hazards model.Results The objective response rate was 33/149 and disease control rate was 105/149.No complete response occurred.Median progression free survival (PFS) with icotinib treatment was 5.03 months (95% CI:3.51 to 6.55).Median overall survival was 12.3 months (95% CI:10.68 to 13.92).Multivariate analysis showed that the mutation of EGFR and one regimen of prior chemotherapy were significantly associated with longer PFS.At least one drug related adverse event was observed in 65.8% (98/149) of patients,but mostly grade 1 or 2 and reversible and none grade 4 toxicity.Conclusions lcotinib monotherapy is an effective and well tolerated regimen for Chinese patients with NSCLC after the failure of chemotherapy.It is a promising agent and further study with icotinib in properly conducted trials with larger patient samples and other ethnic groups is warranted.

  14. [Metastatic non-small cell lung cancer: Systemic treatment of patients aged 70 and over].

    Science.gov (United States)

    Quoix, Elisabeth; Ducoloné, Alain; Mennecier, Bertrand; Fraisse, Philippe

    2011-04-01

    Patients aged 70 and over represent the third of the population of patients with lung cancer. There has been for a long time a certain nihilism regarding the treatment of elderly patients with advanced lung cancer as well from medical doctors but also from families and patients themselves with the false belief of an indolent course of the disease in elderly patients. As a result, clinical trials devoted to elderly patients were quite scarce until the end of the last decade. Nevertheless, an important trial was published in 1999 with the comparison of vinorelbine as a single agent versus best supportive care only in patients aged 70 and over with an advanced non-small cell lung cancer. The survival benefit with vinorelbine was important. Then two trials were published comparing monotherapy with either vinorelbine or gemcitabine to the doublet vinorelbine and gemcitabine without convincing results. As a consequence, the ASCO 2004 recommendations were to treat elderly patients with a monotherapy (gemcitabine or vinorelbine). Recently an IFCT trial was presented at the plenary session of the ASCO 2010. A carboplatin (every 4weeks)+weekly paclitaxel doublet was compared to a vinorelbine or gemcitabine (choice of the center). The survival benefit was of such magnitude that the paradigm of treatment of elderly patients PS 0-2 with advanced NSCLC should be modified in favor of the tested doublet. There should be a reappraisal of the geriatric indexes recommended by the oncogeriatricians regarding their exact prognostic or predictive role. PMID:21388776

  15. Significance of tumor markers in lung cancer

    OpenAIRE

    Mumbarkar, P. P.; Raste, A. S.; Ghadge, M. S.

    2006-01-01

    The objective was to test the utility of the cytokeratins CYFRA 21-1, tissue polypeptide specific antigen (TPS), Neuron specific enolase (NSE) and Carcino Embryonic antigen (CEA) in patients with lung cancer and in the pleural fluid of the patients with lung cancer and also the predicting ability of these tumor markers with respect to the histological types [including non small cell lung cancer (NSCLC) and small cell lung cancer (SCLC)] and pathological stages. 40 normal subjects and 222 case...

  16. Patient-tailored modulation of the immune system may revolutionize future lung cancer treatment

    International Nuclear Information System (INIS)

    Cancer research has devoted most of its energy over the past decades on unraveling the control mechanisms within tumor cells that govern its behavior. From this we know that the onset of cancer is the result of cumulative genetic mutations and epigenetic alterations in tumor cells leading to an unregulated cell cycle, unlimited replicative potential and the possibility for tissue invasion and metastasis. Until recently it was often thought that tumors are more or less undetected or tolerated by the patient’s immune system causing the neoplastic cells to divide and spread without resistance. However, it is without any doubt that the tumor environment contains a wide variety of recruited host immune cells. These tumor infiltrating immune cells influence anti-tumor responses in opposing ways and emerges as a critical regulator of tumor growth. Here we provide a summary of the relevant immunological cell types and their complex and dynamic roles within an established tumor microenvironment. For this, we focus on both the systemic compartment as well as the local presence within the tumor microenvironment of late-stage non-small cell lung cancer (NSCLC), admitting that this multifaceted cellular composition will be different from earlier stages of the disease, between NSCLC patients. Understanding the paradoxical role that the immune system plays in cancer and increasing options for their modulation may alter the odds in favor of a more effective anti-tumor immune response. We predict that the future standard of care of lung cancer will involve patient-tailor-made combination therapies that associate (traditional) chemotherapeutic drugs and biologicals with immune modulating agents and in this way complement the therapeutic armamentarium for this disease

  17. Epigenetic alterations leading to TMPRSS4 promoter hypomethylation and protein overexpression predict poor prognosis in squamous lung cancer patients

    Science.gov (United States)

    Villalba, Maria; Diaz-Lagares, Angel; Redrado, Miriam; de Aberasturi, Arrate L.; Segura, Victor; Bodegas, Maria Elena; Pajares, Maria J.; Pio, Ruben; Freire, Javier; Gomez-Roman, Javier; Montuenga, Luis M.; Esteller, Manel; Sandoval, Juan; Calvo, Alfonso

    2016-01-01

    Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide, which highlights the need of innovative therapeutic options. Although targeted therapies can be successfully used in a subset of patients with lung adenocarcinomas (ADC), they are not appropriate for patients with squamous cell carcinomas (SCC). In addition, there is an unmet need for the identification of prognostic biomarkers that can select patients at risk of relapse in early stages. Here, we have used several cohorts of NSCLC patients to analyze the prognostic value of both protein expression and DNA promoter methylation status of the prometastatic serine protease TMPRSS4. Moreover, expression and promoter methylation was evaluated in a panel of 46 lung cancer cell lines. We have demonstrated that a high TMPRSS4 expression is an independent prognostic factor in SCC. Similarly, aberrant hypomethylation in tumors, which correlates with high TMPRSS4 expression, is an independent prognostic predictor in SCC. The inverse correlation between expression and methylation status was also observed in cell lines. In vitro studies showed that treatment of cells lacking TMPRSS4 expression with a demethylating agent significantly increased TMPRSS4 levels. In conclusion, TMPRSS4 is a novel independent prognostic biomarker regulated by epigenetic changes in SCC and a potential therapeutic target in this tumor type, where targeted therapy is still underdeveloped. PMID:26989022

  18. Randomized cross-over study of patient preference for oral or intravenous vinorelbine in combination with carboplatin in the treatment of advanced NSCLC

    DEFF Research Database (Denmark)

    Jensen, Lisa Helene Toft; Østerlind, Kell Erik; Rytter, C.

    2008-01-01

    BACKGROUND: Most chemotherapeutics are administrated intravenously (iv), but some are also available in an oral (po) formulation. This study was designed with the primary objective to estimate the patients' preference for po or iv vinorelbine in combination with carboplatin for the palliative tre...

  19. Evaluation of setup accuracy for NSCLC patients; studying the impact of different types of cone-beam CT matches based on whole thorax, columna vertebralis, and GTV

    DEFF Research Database (Denmark)

    Ottosson, W.; Baker, M.; Hedman, Mattias;

    2010-01-01

    Purpose. The aim of this study is to evaluate the patient setup accuracy by investigating the impact of different types of CBCT matches, performed with 3 (translations only) or 6 (including rotations) degrees-of-freedom (DOF). The purpose is also to calculate and compare CTV to PTV margins based...

  20. Effect of Recombinant Human Endostatin on Radiosensitivity in Patients With Non–Small-Cell Lung Cancer

    International Nuclear Information System (INIS)

    Purpose: To observe the effects of recombinant human endostatin (RHES) on the radiosensitivity of non-small cell lung cancer (NSCLC). Methods and Materials: First, 10 hypoxia-positive cases of pathology-diagnosed NSCLC selected from 15 patients were used to determine the normalization window, a period during which RHES improves NSCLC hypoxia. Second, 50 hypoxia-positive cases of pathology-diagnosed NSCLC (Stages I–III) were randomly divided into a RHES plus radiotherapy group (25 cases) and a radiotherapy-alone group (25 cases). Intensity = modulated radiotherapy with a total dose of 60 Gy in 30 fractions for 6 weeks was adopted in the two groups. The target area included primary foci and metastatic lymph nodes. In the RHES plus radiotherapy group, RHES (15 mg/day) was intravenously given during the normalization window. Results: After RHES administration, the tumor-to=normal tissue radioactivity ratio and capillary permeability surface were first decreased and then increased, with their lowest points on the fifth day compared with the first day (all p < 0.01). Blood flow was first increased and then decreased, with the highest point on the fifth day, compared with the first and tenth day (all p < 0.01). In the RHES plus radiotherapy group and the radiotherapy-alone group, the total effective rates (complete response plus partial response) were 80% and 44% (p = 0.009), respectively. The median survival times were 21.1 ± 0.97 months and 16.5 ± 0.95 months (p = 0.004), respectively. The 1-year and 2-year local control rates were 78.9 ± 8.4% and 68.1 ± 7.8% (p = 0.027) and 63.6 ± 7.2% and 43.4 ± 5.7% (p = 0.022), respectively. The 1-year and 2-year overall survival rates were 83.3 ± 7.2% and 76.6 ± 9.3% (p = 0.247) and 46.3 ± 2.4% and 37.6 ± 9.1% (p = 0.218), respectively. Conclusion: The RHES normalization window is within about 1 week after administration. RHES combined with radiotherapy within the normalization window has better short-term therapeutic

  1. Oral complications in cancer patients

    International Nuclear Information System (INIS)

    Ionizing radiation used in treating the head and neck area produces oral side effects such as mucositis, salivary changes, trismus and radiation caries. Sequelae of cancer chemotherapy often include oral stomatitis, myelosuppression and immunosuppression. Infections of dental origin in compromised patients are potentially lethal. Specific programs to eliminate dental pathology before radiation and chemotherapy, and to maintain oral hygiene during and after therapy, will minimize these complications

  2. In Silico Oncology: Quantification of the In Vivo Antitumor Efficacy of Cisplatin-Based Doublet Therapy in Non-Small Cell Lung Cancer (NSCLC) through a Multiscale Mechanistic Model

    Science.gov (United States)

    Kolokotroni, Eleni; Dionysiou, Dimitra; Veith, Christian; Kim, Yoo-Jin; Franz, Astrid; Grgic, Aleksandar; Bohle, Rainer M.; Stamatakos, Georgios

    2016-01-01

    The 5-year survival of non-small cell lung cancer patients can be as low as 1% in advanced stages. For patients with resectable disease, the successful choice of preoperative chemotherapy is critical to eliminate micrometastasis and improve operability. In silico experimentations can suggest the optimal treatment protocol for each patient based on their own multiscale data. A determinant for reliable predictions is the a priori estimation of the drugs’ cytotoxic efficacy on cancer cells for a given treatment. In the present work a mechanistic model of cancer response to treatment is applied for the estimation of a plausible value range of the cell killing efficacy of various cisplatin-based doublet regimens. Among others, the model incorporates the cancer related mechanism of uncontrolled proliferation, population heterogeneity, hypoxia and treatment resistance. The methodology is based on the provision of tumor volumetric data at two time points, before and after or during treatment. It takes into account the effect of tumor microenvironment and cell repopulation on treatment outcome. A thorough sensitivity analysis based on one-factor-at-a-time and latin hypercube sampling/partial rank correlation coefficient approaches has established the volume growth rate and the growth fraction at diagnosis as key features for more accurate estimates. The methodology is applied on the retrospective data of thirteen patients with non-small cell lung cancer who received cisplatin in combination with gemcitabine, vinorelbine or docetaxel in the neoadjuvant context. The selection of model input values has been guided by a comprehensive literature survey on cancer-specific proliferation kinetics. The latin hypercube sampling has been recruited to compensate for patient-specific uncertainties. Concluding, the present work provides a quantitative framework for the estimation of the in-vivo cell-killing ability of various chemotherapies. Correlation studies of such estimates with

  3. Inhibitory effect of Disulfiram/copper complex on non-small cell lung cancer cells.

    Science.gov (United States)

    Duan, Lincan; Shen, Hongmei; Zhao, Guangqiang; Yang, Runxiang; Cai, Xinyi; Zhang, Lijuan; Jin, Congguo; Huang, Yunchao

    2014-04-18

    Non-small cell lung cancer (NSCLC) is the most common cause of cancer-related death in both men and women worldwide. Recently, Disulfiram has been reported to be able to inhibit glioblastoma, prostate, or breast cancer cell proliferation. In this study, the synergistic effect of Disulfiram and copper on NSCLC cell growth was investigated. Inhibition of cancer cell proliferation was detected by 1-(4,5-Dimethylthiazol-2-yl)-3,5-diphenylformazan (MTT) assay and cell cycle analysis. Liquid colony formation and tumor spheroid formation assays were used to evaluate their effect on cancer cell clonogenicity. Real-time PCR was performed to test the mRNA level of cancer stem cell related genes. We found that Disulfiram or copper alone did not potently inhibit NSCLC cell proliferation in vitro. However, the presence of copper significantly enhanced inhibitory effect of Disulfiram on NSCLC cell growth, indicating a synergistic effect between Disulfiram and copper. Cell cycle analysis showed that Disulfiram/copper complex caused NSCLC cell cycle arrest in G2/M phase. Furthermore, Disulfiram/copper significantly increased the sensitivity of cisplatin in NSCLC cells tested by MTT assay. Liquid colony formation assay revealed that copper dramatically increased the inhibitory effect of Disulfiram on NSCLC cell colony forming ability. Disulfiram combined with copper significantly attenuated NSCLC cell spheroid formation and recuded the mRNA expression of lung cancer stem cell related genes. Our data suggest that Disulfiram/copper complex alone or combined with other chemotherapy is a potential therapeutic strategy for NSCLC patients.

  4. Validation of an Ion Torrent Sequencing Platform for the Detection of Gene Mutations in Biopsy Specimens from Patients with Non-Small-Cell Lung Cancer.

    Directory of Open Access Journals (Sweden)

    Shiro Fujita

    Full Text Available Treatment for patients with advanced non-small cell lung cancer (NSCLC is often determined by the presence of biomarkers that predict the response to agents targeting specific molecular pathways. Demands for multiplex analysis of the genes involved in the pathogenesis of NSCLC are increasing.We validated the Ion Torrent Personal Genome Machine (PGM system using the Ion AmpliSeq Cancer Hotspot Panel and compared the results with those obtained using the gold standard methods, conventional PCR and Sanger sequencing. The cycleave PCR method was used to verify the results.The Ion Torrent PGM resulted in a similar level of accuracy in identifying multiple genetic mutations in parallel, compared with conventional PCR and Sanger sequencing; however, the Ion Torrent PGM was superior to the other sequencing methods in terms of increased ease of use, even when taking into account the small amount of DNA that was obtained from formalin-fixed paraffin embedded (FFPE biopsy specimens.

  5. Efficacy and safety of gefitinib as monotherapy for Chinese patients with advanced non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    @@ Platinum-based chemotherapy can improve the survival and quality of life of patients with locally advanced and metastatic lung cancer. Second-line docetaxel monotherapy can improve overall survival following the failure of first line chemotherapy. However, many limiting factors such as poor performance status, advanced age, adverse effects of chemotherapy and reluctance to receive cytotoxic chemotherapeutic agents render patients unable to accept chemotherapy. Furthermore, for patients who have failed second-line chemotherapy treatment options are often limited to best support care or palliative radiotherapy. 1 Gefitinib (Iressa) is a HER1/EGFR (epidermal growth factor receptor)- tyrosine kinase inhibitor approved in a number of countries including the US, Japan and recently China for the treatment of patients with non-small cell lung cancer (NSCLC), who have failed platinum/docetaxel-based first line and second line chemotherapy. 2,3 Current data show heterogeneity in response to gefitinib among people of different ethnic origin, but there is very little data concerning the safety and efficacy of gefitinib in Chinese patients. This paper aims to summarize the safety and efficacy data for gefitinib 250 mg treatment in Chinese NSCLC patients at Peking Union Medical College Hospital who received gefitinib as part of an Expanded Access Programme.