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Sample records for advanced-stage non-small-cell lung

  1. Circulating tumor DNA identified by targeted sequencing in advanced-stage non-small cell lung cancer patients.

    Science.gov (United States)

    Xu, Song; Lou, Feng; Wu, Yi; Sun, Da-Qiang; Zhang, Jing-Bo; Chen, Wei; Ye, Hua; Liu, Jing-Hao; Wei, Sen; Zhao, Ming-Yu; Wu, Wen-Jun; Su, Xue-Xia; Shi, Rong; Jones, Lindsey; Huang, Xue F; Chen, Si-Yi; Chen, Jun

    2016-01-28

    Non-small cell lung cancers (NSCLC) have unique mutation patterns, and some of these mutations may be used to predict prognosis or guide patient treatment. Mutation profiling before and during treatment often requires repeated tumor biopsies, which is not always possible. Recently, cell-free, circulating tumor DNA (ctDNA) isolated from blood plasma has been shown to contain genetic mutations representative of those found in the primary tumor tissue DNA (tDNA), and these samples can readily be obtained using non-invasive techniques. However, there are still no standardized methods to identify mutations in ctDNA. In the current study, we used a targeted sequencing approach with a semi-conductor based next-generation sequencing (NGS) platform to identify gene mutations in matched tDNA and ctDNA samples from 42 advanced-stage NSCLC patients from China. We identified driver mutations in matched tDNA and ctDNA in EGFR, KRAS, PIK3CA, and TP53, with an overall concordance of 76%. In conclusion, targeted sequencing of plasma ctDNA may be a feasible option for clinical monitoring of NSCLC in the near future. PMID:26582655

  2. 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

  3. A voice that wraps around the body--communication problems in the advanced stages of non-small cell lung cancer.

    OpenAIRE

    Moore, R. J.; Chamberlain, R. M.; Khuri, F R

    2001-01-01

    INTRODUCTION: Significant problems in clinician-patient communication have been described in the oncology literatures. Advanced stage non-small lung cancer a devastating disease, can cause the communication between survivors, significant others, and clinicians to falter. To date, however, no studies have used qualitative methods to examine experiential aspects of living with non-small cell lung cancer. Nor have any studies evaluated the tools survivors might use to repair some of the damage c...

  4. The correlation between clinical factors and radiation pneumonitis in advanced stage non-small-cell lung cancer treated with concurrent radiochemotherapy

    International Nuclear Information System (INIS)

    Objective: To evaluate clinical factors as predictors of radiation pneumonitis (RP)in advanced stage non-small cell lung cancer (NSCLC) patients treated with concurrent radio chemotherapy when gross tumor volume is 70 Gy. Methods: Data of 84 patients with histologically proved NSCLC treated with 3DCRT or IMRT were collected. To evaluate the correlation between clinical parameters and radiation pneumonitis (RP). The clinical parameters were considered: pathological type, therapy agents, age,gender, stage, karnofsky performance status (KPS), smoking status, diabetes, chronic obstructive pulmonary disease (COPD). Results: The occurrence of grade 1, 2 RP was 63%, 33%, respectively. In univariate analysis, diabetes was significantly associated with RP of ≥ grade 1(χ2 =4.03, P = 0.045)and ≥grade 2(χ2 = 15.59, P =0.000). KPS was significantly associated with RP of ≥grade 1(χ2 =3.98, P = 0.046)and ≥grade 2(χ2 = 5.21, P = 0.023). In logistic multivariate analysis, diabetes was significantly associated with RP of ≥grade 1(χ2 =5.50, P =0.019)and ≥grade 2(χ2 = 12.92, P =0.000). KPS was significantly associated with RP of ≥ grade 1(χ2 = 6.29, P = 0.012)and ≥ grade 2(χ2 = 6.61, P =0.010). Conclusion: The definite statistical significant risk factors of RP are diabetes and KPS. (authors)

  5. Anaplastic lymphoma kinase gene rearrangements in patients with advanced-stage non-small-cell lung cancer: CT characteristics and response to chemotherapy

    International Nuclear Information System (INIS)

    Few articles have been published on the imaging findings of anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC). To investigate the radiological findings of ALK-positive NSCLC in the advanced stage, CT scans were examined. In addition, the response to chemotherapy was evaluated. Of the 36 patients with ALK-rearranged NSCLC, a mass and a nodule were identified in 17 (47.2%) and 16 (44.4%), respectively, indicating that more than 40% had a small-sized tumor. Overall, 31 (86.1%) patients had lymphadenopathy, seven (19.4%) had extranodal lymph node invasion, and three (8.3%) had lymphangitis. A pleural effusion was seen in 15 patients (41.7%). All but one patient had no ground-glass opacity (GGO) lesions, indicating that most ALK-positive tumors showed a solid growth pattern without GGO on CT. Twenty were evaluable for response to chemotherapy; 10 (50.0%) had a partial response (PR), nine (45.0%) had stable disease (SD), and one (5.0%) had progressive disease (PD) with first-line chemotherapy. With second-line chemotherapy, five (26.3%) had PR, 11 (57.9%) had SD, and three (15.8%) had PD. The five patients with PR were all treated by using crizotinib. Time to progression was 8.2 months with first-line chemotherapy, and 6.0 months with second-line chemotherapy. Advanced-stage ALK-positive tumors have a relatively aggressive phenotype, which cannot be inferred from the size of the tumor alone. ALK-positive patients have a good response to first-line cytotoxic drugs and to crizotinib as second-line therapy, but a relatively poor response to cytotoxic drugs as second-line therapy

  6. Lung cancer - non-small cell

    Science.gov (United States)

    Cancer - lung - non-small cell; Non-small cell lung cancer; NSCLC; Adenocarcinoma - lung; Squamous cell carcinoma - lung ... Horn L, Eisenberg R, Gius D, et al. Cancer of the lung. In: Niederhuber JE, Armitage JO, Doroshow JH, Kastan ...

  7. A Case Series of Survival Outcomes in Patients with Advanced-stage IIIb/IV Non-small-cell Lung Cancer Treated with HangAm-Plus

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    Bang Sun-Hwi

    2012-06-01

    Full Text Available Background and Objectives: Non-small-cell lung cancer (NSCLC represents approximately 80% of all lung cancers. Unfortunately, at their time of diagnosis, most patients have advanced to unresectable disease with a very poor prognosis. The oriental herbal medicine HangAm-Plus (HAP has been developed for antitumor purposes, and several previous studies have reported its therapeutic effects. In this study, the efficacy of HAP was evaluated as a third-line treatment for advanced-stage IIIb/IV NSCLC. Methods: The study involved six patients treated at the East- West Cancer Center (EWCC from April 2010 to October 2011. Inoperable advanced-stage IIIb/IV NSCLC patients received 3,000 or 6,000 mg of HAP on a daily basis over a 12-week period. Computed tomography (CT scans were obtained from the patients at the time of the initial administration and after 12 weeks of treatment. We observed and analyzed the patients overall survival (OS and progression-free survival (PFS. Results: Of the six patients, three expired during the study, and the three remaining patients were alive as of October 31, 2011. The OS ranged from 234 to 512 days, with a median survival of 397 days and a one-year survival rate of 66.7%. In the 12-week-interval chest CT assessment, three patients showed stable disease (SD, and the other three showed progressive disease (PD. The PFS of patients ranged from 88 to 512 days, the median PFS being 96 days. Longer OS and PFS were correlated with SD. Although not directly comparable, the OS and the PFS of this study were greater than those of the docetaxel or the best supportive care group in other studies. Conclusion: HAP may prolong the OS and the PFS of inoperable stage IIIb/IV NSCLC patients without significant adverse effects. In the future, more controlled clinical trials with larger samples from multi-centers should be conducted to evaluate the efficacy and the safety of HAP.

  8. Results of paclitaxel (day 1 and 8 and carboplatin given on every three weeks in advanced (stage III-IV non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Salepci Taflan

    2005-01-01

    Full Text Available Abstract Background Both paclitaxel (P and carboplatin (C have significant activity in non-small cell lung cancer (NSCLC. The weekly administration of P is active, dose intense, and has a favorable toxicity profile. We retrospectively reviewed the data of 51 consecutive patients receiving C and day 1 and 8 P chemotherapy (CT regimen in advanced stage NSCLC to evaluate the efficacy and toxicity. Methods Patients treated in our institutions having pathologically proven NSCLC, no CNS metastases, adequate organ function and performance status (PS ECOG 0–2 were given P 112.5 mg/m2 intravenously (IV over 1 hour on day 1 and 8, followed by C AUC 5 IV over 1 hour, repeated in every three weeks. PC was given for maximum of 6 cycles. Results Median age was 58 (age range 39–77 and 41 patients (80% were male. PS was 0/1/2 in 29/17/5 patients and stage was IIIA/IIIB/IV in 3/14/34 patients respectively. The median number of cycles administered was 3 (1–6. Seven patients (14% did not complete the first 3 cycles either due to death, progression, grade 3 hypersensitivity reactions to P or lost to follow up. Best evaluable response was partial response (PR in 45% and stable disease (SD in 18%. Twelve patients (24% received local RT. Thirteen patients (25% received 2nd line CT at progression. At a median follow-up of 7 months (range, 1–20, 25 (49% patients died and 35 patients (69% progressed. Median overall survival (OS was 11 ± 2 months (95% CI; 6 to 16, 1-year OS ratio was 44%. Median time to progression (TTP was 6 ± 1 months (95% CI; 4 to 8, 1-year progression free survival (PFS ratio was 20%. We observed following grade 3 toxicities: asthenia (10%, neuropathy (4%, anorexia (4%, anemia (4%, hypersensitivity to P (2%, nausea/vomiting (2%, diarrhea (2% and neutropenia (2%. Two patients (4% died of febrile neutropenia. Doses of CT were reduced or delayed in 12 patients (24%. Conclusions P on day 1 and 8 and C every three weeks is practical and fairly

  9. 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 common. Conclusion In advanced NSCLC, cisplatin/pemetrexed provides similar efficacy with better tolerability and more convenient administration than cisplatin....../gemcitabine. This is the first prospective phase III study in NSCLC to show survival differences based on histologic type Udgivelsesdato: 2008/7/20...

  10. Lung cancer - non-small cell

    Science.gov (United States)

    Cancer - lung - non-small cell; Non-small cell lung cancer; NSCLC; Adenocarcinoma - lung; Squamous cell carcinoma - lung ... Smoking causes most cases (around 90%) of lung cancer. The risk ... day and for how long you have smoked. Being around the smoke ...

  11. Concurrent Hyperfractionated Radiation Therapy and Chemotherapy in Locally Advanced (Stage III) Non-Small-Cell Lung Cancer: Single Institution Experience With 600 Patients

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    Jeremic, Branislav, E-mail: nebareje@gmail.com [Department of Oncology, University Hospital, Kragujevac (Serbia); Milicic, Biljana; Milisavljevic, Slobodan [Department of Oncology, University Hospital, Kragujevac (Serbia)

    2012-03-01

    Purpose: Our institutional experience with the use of hyperfractionated radiation therapy (RT) alone or concurrently with chemotherapy (RT-CHT) in Stage III non-small-cell lung cancer was reviewed. Methods and Materials: Three phase III and two phase II studies included a total of 600 patients. Hyperfractionated RT alone was given to 127 patients, and hyperfractionated RT-CHT was given to 473 patients. RT doses were 64.8 Gy and 69.6 Gy (using 1.2 Gy twice daily) and 67.6 Gy (using 1.3 Gy twice daily). CHT consisted of concurrent administration of carboplatin and etoposide to 409 patients and concurrent administration of carboplatin and paclitaxel to 64 patients. Results: The median survival times were 19 months, 21 months, and 12 months for all, RT-CHT, and RT-only patients, respectively. The survival difference between the RT-CHT and RT group was significant (p < 0.0001). Four-year rates of local progression-free survival (LPFS) and distant metastasis-free survival (DMFS) were 29% and 35%, respectively, for the entire group. The RT-CHT group had significantly better LPFS rates than the RT group (31% for the RT-CHT group vs. 16% for the RT group; p = 0.0015) but not DMFS rates (36% for the RT-CHT group vs. 36% for the RT group, p = 0.0571). Acute high-grade esophagitis, pneumonitis, and hematological toxicities were seen most frequently and in 11%, 9%, and 12% of patients, respectively. Late high-grade esophageal and bronchopulmonary toxicity were each seen in 6% of patients. Conclusions: Compared to the majority of existing phase II and III studies, this study reconfirmed the excellent results achieved with concurrent RT-CHT, including low toxicity. Concurrent RT-CHT results in survival benefit primarily by increasing LPFS, not DMFS.

  12. Concurrent Hyperfractionated Radiation Therapy and Chemotherapy in Locally Advanced (Stage III) Non-Small-Cell Lung Cancer: Single Institution Experience With 600 Patients

    International Nuclear Information System (INIS)

    Purpose: Our institutional experience with the use of hyperfractionated radiation therapy (RT) alone or concurrently with chemotherapy (RT-CHT) in Stage III non-small-cell lung cancer was reviewed. Methods and Materials: Three phase III and two phase II studies included a total of 600 patients. Hyperfractionated RT alone was given to 127 patients, and hyperfractionated RT-CHT was given to 473 patients. RT doses were 64.8 Gy and 69.6 Gy (using 1.2 Gy twice daily) and 67.6 Gy (using 1.3 Gy twice daily). CHT consisted of concurrent administration of carboplatin and etoposide to 409 patients and concurrent administration of carboplatin and paclitaxel to 64 patients. Results: The median survival times were 19 months, 21 months, and 12 months for all, RT-CHT, and RT-only patients, respectively. The survival difference between the RT-CHT and RT group was significant (p < 0.0001). Four-year rates of local progression-free survival (LPFS) and distant metastasis-free survival (DMFS) were 29% and 35%, respectively, for the entire group. The RT-CHT group had significantly better LPFS rates than the RT group (31% for the RT-CHT group vs. 16% for the RT group; p = 0.0015) but not DMFS rates (36% for the RT-CHT group vs. 36% for the RT group, p = 0.0571). Acute high-grade esophagitis, pneumonitis, and hematological toxicities were seen most frequently and in 11%, 9%, and 12% of patients, respectively. Late high-grade esophageal and bronchopulmonary toxicity were each seen in 6% of patients. Conclusions: Compared to the majority of existing phase II and III studies, this study reconfirmed the excellent results achieved with concurrent RT-CHT, including low toxicity. Concurrent RT-CHT results in survival benefit primarily by increasing LPFS, not DMFS.

  13. Treatment Option Overview (Non-Small Cell Lung Cancer)

    Science.gov (United States)

    ... Prevention Lung Cancer Screening Research Non-Small Cell Lung Cancer Treatment (PDQ®)–Patient Version General Information About Non-Small Cell Lung Cancer Go to Health Professional Version Key Points Non- ...

  14. Stages of Non-Small Cell Lung Cancer

    Science.gov (United States)

    ... Prevention Lung Cancer Screening Research Non-Small Cell Lung Cancer Treatment (PDQ®)–Patient Version General Information About Non-Small Cell Lung Cancer Go to Health Professional Version Key Points Non- ...

  15. General Information about Non-Small Cell Lung Cancer

    Science.gov (United States)

    ... Prevention Lung Cancer Screening Research Non-Small Cell Lung Cancer Treatment (PDQ®)–Patient Version General Information About Non-Small Cell Lung Cancer Go to Health Professional Version Key Points Non- ...

  16. Treatment Options by Stage (Non-Small Cell Lung Cancer)

    Science.gov (United States)

    ... Prevention Lung Cancer Screening Research Non-Small Cell Lung Cancer Treatment (PDQ®)–Patient Version General Information About Non-Small Cell Lung Cancer Go to Health Professional Version Key Points Non- ...

  17. An Open-Label, Multicenter, Randomized, Phase II Study of Pazopanib in Combination with Pemetrexed in First-Line Treatment of Patients with Advanced-Stage Non-Small-Cell Lung Cancer

    DEFF Research Database (Denmark)

    Scagliotti, Giorgio V; Felip, Enriqueta; Besse, Benjamin; von Pawel, Joachim; Mellemgaard, Anders; Reck, Martin; Bosquee, Lionel; Chouaid, Christos; Lianes-Barrag�n, Pilar; Paul, Elaine M; Ruiz-Soto, Rodrigo; Sigal, Entisar; Ottesen, Lone H; Lechevalier, Thierry

    2013-01-01

    This randomized open-label phase II study evaluated the efficacy, safety, and tolerability of pazopanib in combination with pemetrexed compared with the standard cisplatin/pemetrexed doublet in patients with previously untreated, advanced, nonsquamous non-small-cell lung cancer....

  18. Neoadjuvant Therapy in Non-Small Cell Lung Cancer.

    Science.gov (United States)

    Zheng, Yifan; Jaklitsch, Michael T; Bueno, Raphael

    2016-07-01

    Locally advanced (stage IIIA) non-small cell lung cancer (NSCLC) is confined to the chest, but requires more than surgery to maximize cure. Therapy given preoperatively is termed neoadjuvant, whereas postoperative therapy is termed adjuvant. Trimodality therapy (chemotherapy, radiation, and surgery) has become the standard treatment regimen for resectable, locally advanced NSCLC. During the past 2 decades, several prospective, randomized, and nonrandomized studies have explored various regimens for preoperative treatment of NSCLC. The evaluation of potential candidates with NSCLC for neoadjuvant therapy as well as the currently available therapeutic regimens are reviewed. PMID:27261916

  19. Gefitinib in Non Small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Raffaele Costanzo

    2011-01-01

    Full Text Available Gefitinib is an oral, reversible, tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR that plays a key role in the biology of non small cell lung cancer (NSCLC. Phase I studies indicated that the recommended dose of gefitinib was 250 mg/day. Rash, diarrhea, and nausea were the most common adverse events. The positive results obtained in early phase 2 clinical trials with gefitinib were not confirmed in large phase 3 trials in unselected patients with advanced NSCLC. The subsequent discovery that the presence of somatic mutations in the kinase domain of EGFR strongly correlates with increased responsiveness to EGFR tyrosine kinase inhibitors prompted phase 2 and 3 trials with gefitinib in the first line-treatment of EGFR-mutated NSCLC. The results of these trials have demonstrated the efficacy of gefitinib that can be now considered as the standard first-line treatment of patients with advanced NSCLC harbouring activating EGFR mutations.

  20. Personalized Therapy of Non-small Cell Lung Cancer (NSCLC).

    Science.gov (United States)

    Gadgeel, Shirish M

    2016-01-01

    Lung cancer remains the most common cause of cancer related deaths in both men and women in the United States and non-small cell lung cancer (NSCLC) accounts for over 85 % of all lung cancers. Survival of these patients has not significantly altered in over 30 years. This chapter initially discusses the clinical presentation of lung cancer patients. Most patients diagnosed with lung cancer due to symptoms have advanced stage cancer. Once diagnosed, lung cancer patients need imaging studies to assess the stage of the disease before decisions regarding therapy are finalized. The most important prognostic factors are stage of the disease and performance status and these factors also determine therapy. The chapter subsequently discusses management of each stage of the disease and the impact of several pathologic, clinical factors in personalizing therapy for each individual patient. Transition from chemotherapy for every patient to a more personalized approach based on histology and molecular markers has occurred in the management of advanced stage NSCLC. It is expected that such a personalized approach will extend to all stages of NSCLC and will likely improve the outcomes of all NSCLC patients. PMID:26703806

  1. A phase I study of concurrent chemotherapy and thoracic radiotherapy with oral epigallocatechin-3-gallate protection in patients with locally advanced stage III non-small-cell lung cancer

    International Nuclear Information System (INIS)

    Background and purpose: Patients with unresectable stage III non-small-cell lung cancer receiving concurrent chemoradiotherapy often develop esophagitis that may lead to unplanned treatment interruptions, which may severely reduce rates of locoregional tumor control and survival. No effective treatment that would reduce the incidence and severity of this complication has been identified up to now. Although acceleration of normal tissue protection using epigallocatechin-3-gallate (EGCG) has been reported, its actual clinical practicability remains obscure. Methods and materials: This is a phase I study of EGCG in combination with standard chemoradiation in surgically unresectable stage III non-small-cell lung cancer. Chemotherapy (cisplatin and etoposide) was given concurrently with radiation. EGCG solution was swallowed three times a day after the occurrence of grade 2 esophagitis at six concentration levels and dose escalation followed a standard phase I design. Esophageal toxicity and patient-reported pain was recorded weekly. Results: Twenty-four patients with AJCC stage IIIA (six) and IIIB (eighteen) completed the course of therapy. Twelve had squamous histology, ten adenocarcinoma, and two not specified. Patients were treated in six cohorts at six dose levels of EGCG. RT was not interrupted with a median dose of 64 Gy. There were no dose-limiting toxicities reported in all EGCG dosing tiers. Dramatic regression of esophagitis to grade 0/1 was observed in 22 of 24 patients, whereas grade 2 esophagitis persisted in 2 of 24 patients at the end of radiotherapy. The pain score was also reduced from a mean of 4.58 (N = 24), 1.29 (N = 24), 1.42 (N = 24), 0.96 (N = 23) to 1.13 (N = 16) every week in turn. Conclusion: We conclude that the oral administration of EGCG is feasible, safe and effective. The phase II recommended concentration is 440 μmol/L

  2. Pulmonary Rehabilitation in Improving Lung Function in Patients With Locally Advanced Non-Small Cell Lung Cancer Undergoing Chemoradiation

    Science.gov (United States)

    2015-03-17

    Cachexia; Fatigue; Pulmonary Complications; Radiation Toxicity; Recurrent Non-small Cell Lung Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer

  3. Non-Small Cell Lung Cancer: Screening, Diagnosis, and Staging

    OpenAIRE

    Ferreira, J; Magalhães, M; Rocha, E; Marques, F

    2012-01-01

    Lung cancer is the leading cause of cancer deaths worldwide. Tobacco consumption is the primary cause of lung cancer, accounting for more than 85% 90% of all lung cancer deaths. Non-small cell lung cancer accounts for about 85% of all lung cancers. Several studies have shown that low-dose helical CT of the lung detects more nodules and lung cancers, including early-stage cancers, than does chest radiography. The National Lung Cancer Screening Trial results show that three annual roun...

  4. Update in non small- cell lung cancer staging

    OpenAIRE

    Salgado, RA; Snoeckx, A.; Spinhoven, M; Beeck, B Op de; Corthouts, B; Parizel, PM

    2013-01-01

    Significant progress has been made with the introduction of the TNM-7 staging system for non-small cell lung cancer (NSCLC). Constituting the first major revision in 12 years, the seventh edition of NSCLC TNM (TNM-7) is based on the recommendations from the International Association for the Study of Lung Cancer (IASLC) Lung Cancer Staging Project of 2007. This new TNM iteration includes a subset analysis on SCLC and carcinoid tumors.A thorough understanding of its principles by the radiologis...

  5. New targeted treatments for non-small-cell lung cancer – role of nivolumab

    OpenAIRE

    Baas, Paul; Muller,Mirte; van den Heuvel,Michel; Zago,Giulia

    2016-01-01

    Giulia Zago,1,2,* Mirte Muller,1,* Michel van den Heuvel,1 Paul Baas1 1Department of Thoracic Oncology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek (NKI-AvL), Amsterdam, the Netherlands; 2Medical Oncology 2, Istituto Oncologico Veneto (IOV), Padova, Italy *These authors contributed equally to this work Abstract: Non-small-cell lung cancer (NSCLC) is often diagnosed at an advanced stage of disease, where it is no longer amenable to curative treatment. During the last decades, the ...

  6. 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...

  7. Integrated molecular portrait of non-small cell lung cancers

    OpenAIRE

    Lazar, Vladimir; Suo, Chen; Orear, Cedric; van den Oord, Joost; Balogh, Zsofia; Guegan, Justine; Job, Bastien; Meurice, Guillaume; Ripoche, Hugues; Calza, Stefano; Hasmats, Johanna; Lundeberg, Joakim; Lacroix, Ludovic; Vielh, Philippe; Dufour, Fabienne

    2013-01-01

    Background Non-small cell lung cancer (NSCLC), a leading cause of cancer deaths, represents a heterogeneous group of neoplasms, mostly comprising squamous cell carcinoma (SCC), adenocarcinoma (AC) and large-cell carcinoma (LCC). The objectives of this study were to utilize integrated genomic data including copy-number alteration, mRNA, microRNA expression and candidate-gene full sequencing data to characterize the molecular distinctions between AC and SCC. Methods Comparative genomic hybridiz...

  8. 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...

  9. Hedgehog Pathway Inhibition Radiosensitizes Non-Small Cell Lung Cancers

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    Zeng, Jing; Aziz, Khaled; Chettiar, Sivarajan T. [Department of Radiation Oncology and Molecular Radiation Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Aftab, Blake T. [Department of Medical Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Armour, Michael; Gajula, Rajendra; Gandhi, Nishant; Salih, Tarek; Herman, Joseph M.; Wong, John [Department of Radiation Oncology and Molecular Radiation Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Rudin, Charles M. [Department of Medical Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Tran, Phuoc T. [Department of Radiation Oncology and Molecular Radiation Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Department of Medical Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Hales, Russell K., E-mail: rhales1@jhmi.edu [Department of Radiation Oncology and Molecular Radiation Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland (United States)

    2013-05-01

    Purpose: Despite improvements in chemoradiation, local control remains a major clinical problem in locally advanced non-small cell lung cancer. The Hedgehog pathway has been implicated in tumor recurrence by promoting survival of tumorigenic precursors and through effects on tumor-associated stroma. Whether Hedgehog inhibition can affect radiation efficacy in vivo has not been reported. Methods and Materials: We evaluated the effects of a targeted Hedgehog inhibitor (HhAntag) and radiation on clonogenic survival of human non-small cell lung cancer lines in vitro. Using an A549 cell line xenograft model, we examined tumor growth, proliferation, apoptosis, and gene expression changes after concomitant HhAntag and radiation. In a transgenic mouse model of Kras{sup G12D}-induced and Twist1-induced lung adenocarcinoma, we assessed tumor response to radiation and HhAntag by serial micro-computed tomography (CT) scanning. Results: In 4 human lung cancer lines in vitro, HhAntag showed little or no effect on radiosensitivity. By contrast, in both the human tumor xenograft and murine inducible transgenic models, HhAntag enhanced radiation efficacy and delayed tumor growth. By use of the human xenograft model to differentiate tumor and stromal effects, mouse stromal cells, but not human tumor cells, showed significant and consistent downregulation of Hedgehog pathway gene expression. This was associated with increased tumor cell apoptosis. Conclusions: Targeted Hedgehog pathway inhibition can increase in vivo radiation efficacy in lung cancer preclinical models. This effect is associated with pathway suppression in tumor-associated stroma. These data support clinical testing of Hedgehog inhibitors as a component of multimodality therapy for locally advanced non-small cell lung cancer.

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

    Directory of Open Access Journals (Sweden)

    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.

  11. 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

  12. FR901228 in Treating Patients With Refractory or Progressive Small Cell Lung Cancer or Non-small Cell Lung Cancer

    Science.gov (United States)

    2013-08-14

    Extensive Stage Small Cell Lung Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer; Recurrent Small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Recurrent Non-small Cell Lung Cancer

  13. Genes and pathology of non-small cell lung carcinoma.

    Science.gov (United States)

    Sakashita, Shingo; Sakashita, Mai; Sound Tsao, Ming

    2014-02-01

    While histopathology has traditionally been the cornerstone of treatment decisions in the management of lung cancer patients, the complexity and heterogeneity of histological classification has had a limited impact in the routine practice of oncology. This has changed dramatically in the last few years, owing to discoveries of genomic aberrations and results of clinical trials of novel and targeted therapies. These discoveries have resulted in a new way of classifying non-small cell lung cancer (NSCLC), based on the occurrence of putative or proven driver and targetable genomic changes. The rapidity by which the landscape of mutation and genomic changes is being identified also has led to a new paradigm and approaches to pathological diagnosis of NSCLC. In this context, international consortia have proposed new classifications of lung adenocarcinoma and guidelines for molecular testing in lung cancer and have provided concrete recommendations on new ways to practice lung cancer pathology. PMID:24565579

  14. Targeted therapy in non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    Shou-Ching Tang

    2004-01-01

    @@ 1 Introduction Recent progress in molecular biology has enabled us to better understand the molecular mechanism underlying pathogenesis of human malignancy including lung cancer. Sequencing of human genome has identified many oncogenes and tumor suppressor genes,giving us a better understanding of the molecular events leading to the formation, progression, metastasis, and the development of drug resistance in human lung cancer. In addition, many signal transduction pathways have been discovered that play important roles in lung cancer. Novel strategy of anti-cancer drug development now involves the identification and development of targeted therapy that interrupts one or more than one pathways or cross-talk among different signal transduction pathways. In addition, efforts are underway that combine the traditional cytotoxic (non-targeted) agents with the biological (targeted) therapy to increase the response rate and survival in patients with lung cancer, especially advanced non-small cell lung cancer (NSCLC).

  15. Effect of Fuzheng mistura combined with chemotherapy on patients with non-small cell lung cancer in senile advanced stage%扶正合剂联合化疗治疗老年晚期非小细胞肺癌疗效观察

    Institute of Scientific and Technical Information of China (English)

    张莹; 贾英杰; 陈军; 孙一予; 李小江

    2012-01-01

    [目的]观察扶正合剂联合GP方案化疗治疗老年晚期非小细胞肺癌患者的临床疗效和毒副反应.[方法]选择50例经明确诊断的老年晚期非小细胞肺癌患者,随机分为两组,A组给予吉西他滨加卡铂方案(GP方案)静脉化疗,B组加用扶正合剂口服,28 d为1个周期,连续观察2个化疗周期.[结果]在缩小瘤体方面,B组临床受益率优于A组,差异有统计学意义(P<0.05);在降低血清肿瘤标志物方面,两组治疗前后癌胚抗原(CEA)水平变化差异有统计学意义(P<0.05),细胞角质素19片段(CYFRA-21)水平变化差异无统计学意义(P>0.05);两组患者在免疫功能、卡氏评分、临床症状改善方面,差异有统计性意义(P<0.05);在毒副反应方面,恶心呕吐、白细胞减少的B组发生率较A组低,两组差异均有统计学意义(P<0.05).[结论]扶正合剂对老年晚期非小细胞肺癌化疗具有增效减毒的治疗作用.%[Objective] To observe the effect and side reaction of Fuzheng mistura combined with GP scheme chemotherapy on patients with non-small cell lung cancer in senile advanced stage. [Methods] Fifty patients with confirmed diagnosis of advanced non-small cell lung cancer were enrolled. They were randomly divided into two groups. Group A was given with gemcitabine plus carboplatin solution chemotherapy intravenously, and group B with Fuzheng mistura orally. Twenty-eight days was a course and the treatment was continuously used for two chemotherapy courses. [Results] Fuzheng mistura in chemotherapy of older patients with advanced non small cell lung cancer had a therapeutic effect. In decreasing the cancer size the clinical benefit rate of group B was better than that of group A with significant difference (P0.05). There was significant difference (P< 0.05) between two groups of patients in the improvement of immune function, casparian score, clinical symptoms. A significant differences were also found in side reactions

  16. Treatment outcome and toxicity of intensity-modulated (chemo) radiotherapy in stage III non-small cell lung cancer patients

    NARCIS (Netherlands)

    Govaert, S.L.; Troost, E.G.C.; Schuurbiers, O.C.J.; Geus-Oei, L.F. de; Termeer, A.; Span, P.N.; Bussink, J.

    2012-01-01

    ABSTRACT: PURPOSE: The aim of this retrospective cohort study was to assess treatment outcome, and acute pulmonary and esophageal toxicity using intensity modulated (sequential/concurrent chemo)radiotherapy (IMRT) in locally advanced stage III non-small cell lung cancer (NSCLC). METHODS AND MATERIAL

  17. Application of proteomics in non-small-cell lung cancer.

    Science.gov (United States)

    Cho, William C S

    2016-01-01

    Non-small-cell lung cancer (NSCLC) is a heterogeneous disease with diverse pathological features. Clinical proteomics allows the discovery of molecular markers and new therapeutic targets for this most prevalent type of lung cancer. Some of them may be used to detect early lung cancer, while others may serve as predictive markers of resistance to different therapies. Therapeutic targets and prognostic markers in NSCLC have also been discovered. These proteomics biomarkers may help to pair the individual NSCLC patient with the best treatment option. Despite the fact that implementation of these biomarkers in the clinic appears to be scarce, the recently launched Precision Medicine Initiative may encourage their translation into clinical practice. PMID:26577456

  18. Cetuximab in non-small-cell lung cancer.

    Science.gov (United States)

    Carillio, Guido; Montanino, Agnese; Costanzo, Raffaele; Sandomenico, Claudia; Piccirillo, Maria Carmela; Di Maio, Massimo; Daniele, Gennaro; Giordano, Pasqualina; Bryce, Jane; Normanno, Nicola; Rocco, Gaetano; Perrone, Francesco; Morabito, Alessandro

    2012-02-01

    Cetuximab is a chimeric human-mouse anti-EGF receptor monoclonal antibody. In Phase I studies, no dose-limiting toxicities were observed with cetuximab as a single agent or combined with chemotherapy; pharmacokinetic and pharmacodynamic analyses supported 250 mg/m(2) weekly administration. Skin toxicity, diarrhea and fatigue were the most common toxicities. The positive results obtained in Phase II trials in patients with advanced non-small-cell lung cancer prompted two randomized Phase III trials evaluating cetuximab in addition to first-line chemotherapy. Both trials showed a small benefit in overall survival for the experimental treatment, which was considered insufficient by the EMA for marketing approval. However, a subgroup analysis of the FLEX Phase III trial recently demonstrated a larger survival benefit from the experimental treatment in patients with high immunohistochemical EGF receptor expression. This finding, if confirmed prospectively, could represent a new opportunity for positioning cetuximab into the standard treatment of advanced non-small-cell lung carcinoma. PMID:22316364

  19. Non-small cell lung cancer in never smokers: a clinical entity to be identified

    Directory of Open Access Journals (Sweden)

    Ilka Lopes Santoro

    2011-01-01

    Full Text Available OBJECTIVES: It has been recognized that patients with non-small cell lung cancer who are lifelong never-smokers constitute a distinct clinical entity. The aim of this study was to assess clinical risk factors for survival among neversmokers with non-small cell lung cancer. METHODS: All consecutive non-small cell lung cancer patients diagnosed (n = 285 between May 2005 and May 2009 were included. The clinical characteristics of never-smokers and ever-smokers (former and current were compared using chi-squared or Student's t tests. Survival curves were calculated using the Kaplan-Meier method, and log-rank tests were used for survival comparisons. A Cox proportional hazards regression analysis was evaluated by adjusting for age (continuous variable, gender (female vs. male, smoking status (never- vs. ever-smoker, the Karnofsky Performance Status Scale (continuous variable, histological type (adenocarcinoma vs. non-adenocarcinoma, AJCC staging (early vs. advanced staging, and treatment (chemotherapy and/or radiotherapy vs. the best treatment support. RESULTS: Of the 285 non-small cell lung cancer patients, 56 patients were never-smokers. Univariate analyses indicated that the never-smoker patients were more likely to be female (68% vs. 32% and have adenocarcinoma (70% vs. 51%. Overall median survival was 15.7 months (95% CI: 13.2 to 18.2. The never-smoker patients had a better survival rate than their counterpart, the ever-smokers. Never-smoker status, higher Karnofsky Performance Status, early staging, and treatment were independent and favorable prognostic factors for survival after adjusting for age, gender, and adenocarcinoma in multivariate analysis. CONCLUSIONS: Epidemiological differences exist between never- and ever-smokers with lung cancer. Overall survival among never-smokers was found to be higher and independent of gender and histological type.

  20. Advances in Immunotherapies for Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Yuan HE

    2014-03-01

    Full Text Available Globally, Lung cancer is the leading cause of cancer-related death of high morbidity and mortality with poor prognosis, which needs some more effective and less toxic therapies. The immunotherapies offer a novel approach for the treatment of patients with non-small cell lung cancer (NSCLC in both the adjuvant and palliative disease settings. A number of promising immunotherapies based on different mechanism have now been evaluated showing an increasing response rate. Moreover, further phase II/III clinical trials will be indicated to explore its value. These include checkpoint inhibitors (anti-CTLA4 antibody, anti-PD-1 antibody, anti-PD-L1 antibody, active vaccination (L-BLP25 liposome vaccine, Belagenpumatucel-L vaccine, MAGE-A3 protein vaccine and adoptive vaccination (CIK cells. The purpose of this paper will draw a summary on the theory, clinical trials, toxicity and problems to be solved of the immunotherapies in NSCLC.

  1. Profile of nivolumab in the treatment of metastatic squamous non-small-cell lung cancer

    Science.gov (United States)

    Ang, Yvonne LE; Lim, Joline SJ; Soo, Ross A

    2016-01-01

    Until recently, the prognosis and treatment of patients with advanced-stage squamous cell lung cancers have been limited. An improvement in the understanding of the role of the immune system in tumor immunosurveillance has led to the development of the programmed death-1 (PD-1) immune checkpoint inhibitor nivolumab (Opdivo). Nivolumab is the first PD-1 inhibitor approved for the treatment of advanced-stage squamous cell non-small-cell lung cancer following platinum-based chemotherapy. In the key Phase III trial CHECKMATE 017, a better overall survival and progression-free survival were seen in patients treated with second-line nivolumab compared with docetaxel. Programmed death ligand-1 (PD-L1) expression did not predict for outcome. In addition, nivolumab had better safety and tolerability, and led to better patient reported outcomes. Further research on the role of PD-L1 expression as a predictive biomarker should be performed, and other biomarkers that can predict the efficacy of PD-1/PD-L1 inhibitors should also be pursued. Further studies on the combination treatment are ongoing to determine the optimal role of nivolumab as monotherapy or nivolumab with other agents in non-small-cell lung cancer.

  2. Advances in immunotherapy for non-small cell lung cancer.

    Science.gov (United States)

    Reckamp, Karen L

    2015-12-01

    In most patients, lung cancer presents as advanced disease with metastases to lymph nodes and/or distant organs, and survival is poor. Lung cancer is also a highly immune-suppressing malignancy with numerous methods to evade antitumor immune responses, including deficiencies in antigen processing and presentation, release of immunomodulatory cytokines, and inhibition of T-cell activation. Advances in understanding the complex interactions of the immune system and cancer have led to novel therapies that promote T-cell activation at the tumor site, resulting in prolonged clinical benefit. Immune checkpoint inhibitors, specifically programmed death receptor 1 pathway antibodies, have demonstrated impressively durable responses and improved survival in patients with non-small cell lung cancer. This article will review the recent progress made in immunotherapy for lung cancer with data from trials evaluating programmed death receptor 1 and cytotoxic T-lymphocyte-associated protein 4 monoclonal antibodies in addition to cancer vaccines. The review will focus on studies that have been published and the latest randomized trials exploring immune therapy in lung cancer. These results form the framework for a new direction in the treatment of lung cancer toward immunotherapy. PMID:27058851

  3. [Maintenance therapy for advanced non-small-cell lung cancer].

    Science.gov (United States)

    Saruwatari, Koichi; Yoh, Kiyotaka

    2014-08-01

    Maintenance therapy is a new treatment strategy for advanced non-small-cell lung cancer(NSCLC), and it consists of switch maintenance and continuation maintenance.Switch maintenance is the introduction of a different drug, not included as part of the induction therapy, immediately after completion of 4 cycles of first-line platinum-based chemotherapy.Continuation maintenance is a continuation of at least one of the drugs used in the induction therapy in the absence of disease progression.Several phase III trials have reported survival benefits with continuation maintenance of pemetrexed and switch maintenance of pemetrexed or erlotinib.Therefore, maintenance therapy has become a part of the standard first-line treatment for advanced NSCLC.However, further research is needed to elucidate the selection criteria of patients who may benefit the most from maintenance therapy. PMID:25132023

  4. Postoperative radiotherapy for non-small cell lung cancer

    International Nuclear Information System (INIS)

    To evaluate effect of postoperative radiotherapy on survival and local control for patients with non-small cell lung cancer (NSCLC). Ninety two NSCLC patients with N1 or N2 involvement who were treated with postoperative radiotherapy following surgery with curative intent from May 1987 to October 1999 were retrospectively analyzed. Age of the patients was ranged from 32 to 78 years. According to TNM Stage, 35 patients had Stage II and 57 had Stage III disease. There were 49 patients with N1 involvement and 43 patients with N2 involvement. Fifty six patients were noted to have T1-2 tumors and 36 patients to have T3-4 tumors. Delivered total dose was ranged from 40 to 60 Gy. Majority of patients received 50 Gy or 50.4 Gy. Follow-up period was ranged from 9 month to 7 years with median follow-up of 26 months. Overall survival rates at 3 and 5 years for entire group of patients were 46% and 38%, respectively. Corresponding disease free survival rates were 44% and 36%. There was significant difference in survival between patients with Stage II and Stage III disease (50% vs 28% at 5-year). Five year survival rates for N1 and N2 patients were 52% and 20%, respectively (p<0.05). These were 40% and 34% for patients with T1-2 tumors and T3-4 tumors. There were documented local relapses in 13% of the patients. For patients with N1 and N2 Stage, local relapse rates were 8% and 18%, respectively. Our study confirms that postoperative radiotherapy for patients with non-small cell lung cancer improves local control. However, influence of postoperative radiotherapy on long-term survival is less clear. More effective systemic treatment to prevent distant metastasis should be investigated in future study to improve long-term survival

  5. Sirolimus and Gold Sodium Thiomalate in Treating Patients With Advanced Squamous Non-Small Cell Lung Cancer

    Science.gov (United States)

    2012-12-13

    Recurrent Non-small Cell Lung Cancer; Squamous Cell Lung Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer; Unspecified Adult Solid Tumor, Protocol Specific

  6. Bukangling combined with chemotherapy improves quality of life in patients with middle-advanced stage non-small cell lung cancer%补康灵对非小细胞肺癌化疗患者生存质量的影响

    Institute of Scientific and Technical Information of China (English)

    张锦林; 杨磊; 谭清和; 张一心

    2012-01-01

    Objective To evaluate the effect of Bukangling combined with chemotherapy on quality of life in patients with middle-advanced stage non-small cell lung cancer. Methods Ninety patients with middle-advanced non-small cell lung cancer were randomly divided into chemotherapy group ( Group A) , Bukangling combined with chemotherapy group ( Group B) and Kanglaite combined with chemotherapy group ( Group C) with 30 patients in each group. The TP regimen was given to all patients, which consisted of paclitaxel 135 ~ 175 mg/m dl and cisplatin 25 mg/m dl - d3 with every 21 d as 1 cycle. Patients in Group B also received Bukangling 50 mL, bid, from 1 week before till 1 week after chemotherapy; Patients in Group C also received Kanglaite injection 100 mL,bid,dl - 10. After 2 courses of chemotherapy,the quality of life of patients was assessed with Karnofsky performance score (KPS) and Quality of Life Questionnaire ( QLQ-LC43 ). Results The KPS in Group B was increased by 73. 3% , which was significantly different from that of Group A (P 0. 05). After treatment the scores of physical function, social function, overall health, difficulty breathing and other indicators of sub-module were decreased and the scores of fatigue, loss of appetite and other indicators increase in Group A compared to those before treatment ( P < 0. 05 ) . In Group B the scores of physical function, role function, emotional function, cognitive function, social function and overall health were increased; the scores of fatigue, loss of appetite, difficulty breathing, pain, insomnia were decreased after treatment compared with those before treatment ( P < 0. 05 or P < 0. 01 ). Conclusion Bukangling combined with chemotherapy can improve the quality of life in patients with middle-advanced stage non-small cell lung cancer.%目的 探讨补康灵对非小细胞肺癌化疗患者生存质量的影响.方法 将90例中晚期非小细胞肺癌患者随机分为化疗组、补康灵加化疗

  7. The increasing role of amphiregulin in non-small cell lung cancer.

    OpenAIRE

    Busser, Benoît; Coll, Jean-Luc; Hurbin, Amandine

    2009-01-01

    International audience Non-small cell lung cancers present a 5-year survival rate below 12%. Such a poor prognosis may be explained by non small cell lung cancer cells evasion to apoptosis and resistance to treatments. Amphiregulin, an epidermal growth factor-related growth factor is secreted by non-small cell lung cancer cells in an autocrine/paracrine manner to promote autonomous growth of tumor cells and to provide resistance to apoptosis. Furthermore, amphiregulin is involved in non-sm...

  8. Surgical Treatment for Non-small Cell Lung Cancer Patients with Synchronous Solitary Brain Metastasis

    OpenAIRE

    Bai, Hao; Han, Baohui

    2013-01-01

    Background and objective Brain metastases are common in non-small cell lung cancer. Usual treatments include radiotherapy and chemotherapy. However, these methods result in poor patient prognosis. The aim of this study is to assess the effectiveness of surgical resection in the multimodality management of non-small cell lung cancer patients with synchronous solitary brain metastasis. Methods The clinical data of 46 non-small cell lung cancer patients with synchronous solitary brain metastasis...

  9. Cetuximab and biomarkers in non-small-cell lung carcinoma

    Directory of Open Access Journals (Sweden)

    Patil N

    2012-07-01

    Full Text Available Nitin Patil, Mohammed Abba, Heike AllgayerDepartment of Experimental Surgery, Medical Faculty Mannheim, University of Heidelberg and Molecular Oncology of Solid Tumors Unit, German Cancer Research Center (DKFZ, Heidelberg, GermanyAbstract: Cancer progression is a highly complex process that is driven by a constellation of deregulated signaling pathways and key molecular events. In non-small-cell lung cancer (NSCLC, as in several other cancer types, the epidermal growth factor receptor (EGFR and its downstream signaling components represent a key axis that has been found not only to trigger cancer progression but also to support advanced disease leading to metastasis. Two major therapeutic approaches comprising monoclonal antibodies and small molecule tyrosine kinase inhibitors have so far been used to target this pathway, with a combination of positive, negative, and inconsequential results, as judged by patient survival indices. Since these drugs are expensive and not all patients derive benefits from taking them, it has become both pertinent and paramount to identify biomarkers that can predict not only beneficial response but also resistance. This review focuses on the chimeric monoclonal antibody, cetuximab, its application in the treatment of NSCLC, and the biomarkers that may guide its use in the clinical setting. A special emphasis is placed on the EGFR, including its structural and mechanistic attributes.Keywords: NSCLC, cetuximab, biomarker, cancer progression

  10. Genetically Modified T Cells in Treating Patients With Stage III-IV Non-small Cell Lung Cancer or Mesothelioma

    Science.gov (United States)

    2016-05-02

    Advanced Pleural Malignant Mesothelioma; HLA-A*0201 Positive Cells Present; Recurrent Non-Small Cell Lung Carcinoma; Recurrent Pleural Malignant Mesothelioma; Stage III Pleural Mesothelioma; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Non-Small Cell Lung Cancer; Stage IV Non-Small Cell Lung Cancer; Stage IV Pleural Mesothelioma

  11. Radiation Therapy, Chemotherapy, and Soy Isoflavones in Treating Patients With Stage IIIA-IIIB Non-Small Cell Lung Cancer

    Science.gov (United States)

    2016-02-08

    Adenocarcinoma of the Lung; Adenosquamous Cell Lung Cancer; Bronchoalveolar Cell Lung Cancer; Large Cell Lung Cancer; Recurrent Non-small Cell Lung Cancer; Squamous Cell Lung Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer

  12. Palliative Care Intervention in Improving Symptom Control and Quality of Life in Patients With Stage II-IV Non-small Cell Lung Cancer and Their Family Caregivers

    Science.gov (United States)

    2016-04-06

    Caregiver; Psychological Impact of Cancer and Its Treatment; Recurrent Non-small Cell Lung Cancer; Stage IIA Non-small Cell Lung Cancer; Stage IIB Non-small Cell Lung Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer

  13. Profile of nivolumab in the treatment of metastatic squamous non-small-cell lung cancer

    Directory of Open Access Journals (Sweden)

    Ang YLE

    2016-05-01

    Full Text Available Yvonne LE Ang,1 Joline SJ Lim,1,2 Ross A Soo1–3 1Department of Haematology-Oncology, National University Cancer Institute, National University Health System, 2Cancer Science Institute of Singapore, National University of Singapore, Singapore; 3Department of Surgery, University of Western Australia, Perth, WA, Australia Abstract: Until recently, the prognosis and treatment of patients with advanced-stage squamous cell lung cancers have been limited. An improvement in the understanding of the role of the immune system in tumor immunosurveillance has led to the development of the programmed death-1 (PD-1 immune checkpoint inhibitor nivolumab (Opdivo. Nivolumab is the first PD-1 inhibitor approved for the treatment of advanced-stage squamous cell non-small-cell lung cancer following platinum-based chemotherapy. In the key Phase III trial CHECKMATE 017, a better overall survival and progression-free survival were seen in patients treated with second-line nivolumab compared with docetaxel. Programmed death ligand-1 (PD-L1 expression did not predict for outcome. In addition, nivolumab had better safety and tolerability, and led to better patient reported outcomes. Further research on the role of PD-L1 expression as a predictive biomarker should be performed, and other biomarkers that can predict the efficacy of PD-1/PD-L1 inhibitors should also be pursued. Further studies on the combination treatment are ongoing to determine the optimal role of nivolumab as monotherapy or nivolumab with other agents in non-small-cell lung cancer. Keywords: immunotherapy, programmed death-1, PD-1, NSCLC, squamous cell, nivolumab

  14. Wnt signaling pathway in non-small cell lung cancer.

    Science.gov (United States)

    Stewart, David J

    2014-01-01

    Wnt/β-catenin alterations are prominent in human malignancies. In non-small cell lung cancer (NSCLC), β-catenin and APC mutations are uncommon, but Wnt signaling is important in NSCLC cell lines, and Wnt inhibition reduces proliferation. Overexpression of Wnt-1, -2, -3, and -5a and of Wnt-pathway components Frizzled-8, Dishevelled, Porcupine, and TCF-4 is common in resected NSCLC and is associated with poor prognosis. Conversely, noncanonical Wnt-7a suppresses NSCLC development and is often downregulated. Although β-catenin is often expressed in NSCLCs, it was paradoxically associated with improved prognosis in some series, possibly because of E-cadherin interactions. Downregulation of Wnt inhibitors (eg, by hypermethylation) is common in NSCLC tumor cell lines and resected samples; may be associated with high stage, dedifferentiation, and poor prognosis; and has been reported for AXIN, sFRPs 1-5, WIF-1, Dkk-1, Dkk-3, HDPR1, RUNX3, APC, CDX2, DACT2, TMEM88, Chibby, NKD1, EMX2, ING4, and miR-487b. AXIN is also destabilized by tankyrases, and GSK3β may be inactivated through phosphorylation by EGFR. Preclinically, restoration of Wnt inhibitor function is associated with reduced Wnt signaling, decreased cell proliferation, and increased apoptosis. Wnt signaling may also augment resistance to cisplatin, docetaxel, and radiotherapy, and Wnt inhibitors may restore sensitivity. Overall, available data indicate that Wnt signaling substantially impacts NSCLC tumorigenesis, prognosis, and resistance to therapy, with loss of Wnt signaling inhibitors by promoter hypermethylation or other mechanisms appearing to be particularly important. Wnt pathway antagonists warrant exploration clinically in NSCLC. Agents blocking selected specific β-catenin interactions and approaches to increase expression of downregulated Wnt inhibitors may be of particular interest. PMID:24309006

  15. Therapeutic vaccines in non-small cell lung cancer

    Science.gov (United States)

    Socola, Francisco; Scherfenberg, Naomi; Raez, Luis E

    2013-01-01

    Non-small cell lung cancer (NSCLC) unfortunately carries a very poor prognosis. Patients usually do not become symptomatic, and therefore do not seek treatment, until the cancer is advanced and it is too late to employ curative treatment options. New therapeutic options are urgently needed for NSCLC, because even current targeted therapies cure very few patients. Active immunotherapy is an option that is gaining more attention. A delicate and complex interplay exists between the tumor and the immune system. Solid tumors utilize a variety of mechanisms to evade immune detection. However, if the immune system can be stimulated to recognize the tumor as foreign, tumor cells can be specifically eliminated with little systemic toxicity. A number of vaccines designed to boost immunity against NSCLC are currently undergoing investigation in phase III clinical trials. Belagenpumatucel-L, an allogeneic cell vaccine that decreases transforming growth factor (TGF-β) in the tumor microenvironment, releases the immune suppression caused by the tumor and it has shown efficacy in a wide array of patients with advanced NSCLC. Melanoma-associated antigen A3 (MAGE-A3), an antigen-based vaccine, has shown promising results in MAGE-A3+ NSCLC patients who have undergone complete surgical resection. L-BLP25 and TG4010 are both antigenic vaccines that target the Mucin-1 protein (MUC-1), a proto-oncogene that is commonly mutated in solid tumors. CIMAVax is a recombinant human epidermal growth factor (EGF) vaccine that induces anti-EGF antibody production and prevents EGF from binding to its receptor. These vaccines may significantly improve survival and quality of life for patients with an otherwise dismal NSCLC prognosis. This review is intended to give an overview of the current data and the most promising studies of active immunotherapy for NSCLC.

  16. Interpretation of NCCN Guidelines: General Therapies on Non-small Cell Lung Cancer (Version 6. 2015

    Directory of Open Access Journals (Sweden)

    Xin-en HUANG

    2015-06-01

    Full Text Available Lung cancer is one of the most common malignant tumors in China and ranks the first of cancer-related death. The major etiological agent of lung cancer is an industry-made and promoted addictive product, so lung cancer is considered to be a unique disease in all cancers. Effective policies for public health are required to prevent the smoking initiation so as to reduce the mortality of lung cancer, so Food and Drug Administration (FDA has introduced a series of measures to monitor the tobacco products. As to patients with strong suspicion of lung cancer in stage Ⅰ-Ⅱ, a preoperative biopsy is needed and intra-operative diagnosis is necessary before pneumonectomy, bilobectomy or lobectomy if the preoperative tissue diagnosis is not obtained. However, lung cancer still cannot be easily diagnosed and cured, so the annual improvement and update of new therapeutic protocols and the development of new agents is of great significance. Non-small cell lung cancer (NSCLC accounts for about 80% of all lung cancer, and above 75% NSCLC patients are in middle-advanced stage when diagnosed, so they have lost the optimal therapeutic opportunity and the 5-year survival rate is relatively low. Therefore, this study mainly interpreted the National Comprehensive Cancer Network (NCCN guidelines on the general therapies on NSCLC, hoping to provide references for the treatment of NSCLC patients and prolong their long-term survival.

  17. 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; Danø, Keld; Pappot, Helle; Dienemann, Hendrik; Muley, Thomas

    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....

  18. Micrometastasis in non-small-cell lung cancer: Detection and staging

    Directory of Open Access Journals (Sweden)

    Gholamreza Mohajeri

    2012-01-01

    Full Text Available Background: The clinical relevance of bone marrow micrometastasis (BMM in non-small-cell lung cancer is undetermined, and the value of such analyses in advanced stage patients has not been clearly assessed previously. This study was conducted to estimate the accuracy of both polymerase chain reaction (PCR and immunohistochemistry (IHC in micrometastases detection and determine the best site for bone marrow biopsy in order to find micrometastasis. Methods: This prospective cross-sectional study was performed in the Department of Thoracic Surgery, Alzahra University Hospital from September 2008 to June 2009. To evaluate the bone marrow, a 3-cm rib segment and an aspirated specimen from the iliac bone prior to tumor resection were taken. PCR and IHC were performed for each specimen to find micrometastasis. Results: Of 41 patients, 14 (34% were positive for BMM by PCR compared with two positive IHC (4.8%. All BMMs were diagnosed in rib segments, and iliac specimens were all free from metastatic lesion. Our data showed no significant association between variables such as age, sex, histology, tumor location, side of tumor, involved lobe, smoking, or weight loss and presence of BMM. Conclusion: PCR could use as a promising method for BMM detection. BMM in a sanctuary site (rib is not associated with advanced stages of lung cancer. In addition, when predictor variables such as age, sex, histology, tumor location, smoking, or weight loss are analyzed, no correlation can be found between micrometastasis prevalence and any of those variables.

  19. Cost and effectiveness studies in non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Pinar Yalcin-Balcik

    2015-02-01

    Full Text Available Lung cancer disease diagnosis and treatment is costly. As the numbers of inflicted rise so does the economic burden assumed for this cancer type. When the treatment expenditures are considered for all types of cancer, the lung cancer is thought to occupy a 20% share. The disease examined in two basic groups as small-cell lung cancer and non-small cell lung cancer (NSCLC is the most frequently encountered type of its kind nationally and in the World. This study considers the cost, effectiveness and cost effectiveness of platinum based chemotherapy medications with active ingredients pemetrexed and gemcitabine used for NSCLC. A review of studies relevant to the advanced stage NSCLC where majority of patients are positioned is foreseen to be useful to the decision makers since policy makers, regulating authorities and physicians require more information due to increased overall finance and costs, as well as treatment cost effectiveness. Furthermore, due to the entry attempt of pemetrexed active ingredient to the list of reimbursed medications for the first stage lung cancer treatment, it is assumed that a review of studies containing pemetrexed and gemcitabine will draw the attention of decision makers at the Social Security Instutition. [TAF Prev Med Bull 2015; 14(1.000: 55-64

  20. Non-Small-Cell Lung Cancer Molecular Signatures Recapitulate Lung Developmental Pathways

    OpenAIRE

    Borczuk, Alain C.; Gorenstein, Lyall; Walter, Kristin L.; Assaad, Adel A.; Wang, Liqun; Powell, Charles A.

    2003-01-01

    Current paradigms hold that lung carcinomas arise from pleuripotent stem cells capable of differentiation into one or several histological types. These paradigms suggest lung tumor cell ontogeny is determined by consequences of gene expression that recapitulate events important in embryonic lung development. Using oligonucleotide microarrays, we acquired gene profiles from 32 microdissected non-small-cell lung tumors. We determined the 100 top-ranked marker genes for adenocarcinoma, squamous ...

  1. Epigenetics in non-small cell lung cancer: from basics to therapeutics

    Science.gov (United States)

    Ansari, Junaid; El-Osta, Hazem

    2016-01-01

    Lung cancer remains the number one cause of cancer-related deaths worldwide with 221,200 estimated new cases and 158,040 estimated deaths in 2015. Approximately 80% of cases are non-small cell lung cancer (NSCLC). The diagnosis is usually made at an advanced stage where the prognosis is poor and therapeutic options are limited. The evolution of lung cancer is a multistep process involving genetic, epigenetic, and environmental factor interactions that result in the dysregulation of key oncogenes and tumor suppressor genes, culminating in activation of cancer-related signaling pathways. The past decade has witnessed the discovery of multiple molecular aberrations that drive lung cancer growth, among which are epidermal growth factor receptor (EGFR) mutations and translocations involving the anaplastic lymphoma kinase (ALK) gene. This has translated into therapeutic agent developments that target these molecular alterations. The absence of targetable mutations in 50% of NSCLC cases and targeted therapy resistance development underscores the importance for developing alternative therapeutic strategies for treating lung cancer. Among these strategies, pharmacologic modulation of the epigenome has been used to treat lung cancer. Epigenetics approaches may circumvent the problem of tumor heterogeneity by affecting the expression of multiple tumor suppression genes (TSGs), halting tumor growth and survival. Moreover, it may be effective for tumors that are not driven by currently recognized druggable mutations. This review summarizes the molecular pathology of lung cancer epigenetic aberrations and discusses current efforts to target the epigenome with different pharmacological approaches. Our main focus will be on hypomethylating agents, histone deacetylase (HDAC) inhibitors, microRNA modulations, and the role of novel epigenetic biomarkers. Last, we will address the challenges that face this old-new strategy in treating lung cancer.

  2. Epigenetics in non-small cell lung cancer: from basics to therapeutics.

    Science.gov (United States)

    Ansari, Junaid; Shackelford, Rodney E; El-Osta, Hazem

    2016-04-01

    Lung cancer remains the number one cause of cancer-related deaths worldwide with 221,200 estimated new cases and 158,040 estimated deaths in 2015. Approximately 80% of cases are non-small cell lung cancer (NSCLC). The diagnosis is usually made at an advanced stage where the prognosis is poor and therapeutic options are limited. The evolution of lung cancer is a multistep process involving genetic, epigenetic, and environmental factor interactions that result in the dysregulation of key oncogenes and tumor suppressor genes, culminating in activation of cancer-related signaling pathways. The past decade has witnessed the discovery of multiple molecular aberrations that drive lung cancer growth, among which are epidermal growth factor receptor (EGFR) mutations and translocations involving the anaplastic lymphoma kinase (ALK) gene. This has translated into therapeutic agent developments that target these molecular alterations. The absence of targetable mutations in 50% of NSCLC cases and targeted therapy resistance development underscores the importance for developing alternative therapeutic strategies for treating lung cancer. Among these strategies, pharmacologic modulation of the epigenome has been used to treat lung cancer. Epigenetics approaches may circumvent the problem of tumor heterogeneity by affecting the expression of multiple tumor suppression genes (TSGs), halting tumor growth and survival. Moreover, it may be effective for tumors that are not driven by currently recognized druggable mutations. This review summarizes the molecular pathology of lung cancer epigenetic aberrations and discusses current efforts to target the epigenome with different pharmacological approaches. Our main focus will be on hypomethylating agents, histone deacetylase (HDAC) inhibitors, microRNA modulations, and the role of novel epigenetic biomarkers. Last, we will address the challenges that face this old-new strategy in treating lung cancer. PMID:27186511

  3. Immunotherapy for non-small cell lung cancer: current concepts and clinical trials.

    Science.gov (United States)

    Mayor, Marissa; Yang, Neng; Sterman, Daniel; Jones, David R; Adusumilli, Prasad S

    2016-05-01

    Recent successes in immunotherapeutic strategies are being investigated to combat cancers that have less than ideal responses to standard of care treatment, such as non-small-cell lung cancer. In this paper, we summarize concepts and the current status of immunotherapy for non-small cell lung cancer, including salient features of the major categories of immunotherapy-monoclonal antibody therapy, immune checkpoint blockade, immunotoxins, anticancer vaccines, and adoptive cell therapy. PMID:26516195

  4. Treatment Algorithms for Patients with Metastatic Non-Small Cell, Non-Squamous Lung Cancer

    OpenAIRE

    Melosky, Barbara

    2014-01-01

    A number of developments have altered the treatment paradigm for metastatic non-small cell, non-squamous lung cancer. These include increasing knowledge of molecular signal pathways, as well as the outcomes of several large-scale trials. As a result, treatments are becoming more efficacious and more personalized, and are changing the management and prognosis of non-small cell lung cancer patients. This is resulting in increased survival in select patient groups. In this paper, a simplified al...

  5. Chemotherapy for advanced non-small-cell lung cancer: Role of paclitaxel and gemcitabine

    OpenAIRE

    Lam, WK; Tsang, KWT; Ip, MSM

    1999-01-01

    Objective. To review the role of chemotherapy in advanced non-small-cell lung cancer, focusing on cisplatin-based regimens and two new drugs: paclitaxel and gemcitabine. Data sources. Medline search of the relevant English literature. Study selection. Open and randomised comparative (phases II and III) studies, and meta-analyses of cytotoxic drugs/regimens used to treat advanced non-small-cell lung cancer. Data extraction. The following factors were studied and compared: symptomatic response ...

  6. Comparison of Two Therapeutic Strategies in Patients With Non-squamous Non-small Cell Lung Cancer (NSCLC) With Asymptomatic Brain Metastases

    Science.gov (United States)

    2015-11-29

    Non-small Cell Lung Cancer Metastatic; Non Epidermoid; Non-small Cell Lung Cancer; Adenocarcinoma of Lung Metastatic to Brain; Cerebral Metastases; Cerebral Radiotherapy; Brain Radiotherapy; Bevacizumab

  7. New targeted treatments for non-small-cell lung cancer - role of nivolumab.

    Science.gov (United States)

    Zago, Giulia; Muller, Mirte; van den Heuvel, Michel; Baas, Paul

    2016-01-01

    Non-small-cell lung cancer (NSCLC) is often diagnosed at an advanced stage of disease, where it is no longer amenable to curative treatment. During the last decades, the survival has only improved significantly for lung cancer patients who have tumors harboring a driver mutation. Therefore, there is a clear unmet need for effective therapies for patients with no mutation. Immunotherapy has emerged as an effective treatment for different cancer types. Nivolumab, a monoclonal inhibitory antibody against PD-1 receptor, can prolong survival of NSCLC patients, with a manageable toxicity profile. In two Phase III trials, nivolumab was compared to docetaxel in patients with, respectively, squamous (CheckMate 017) and non-squamous NSCLC (CheckMate 057). In both trials, nivolumab significantly reduced the risk of death compared to docetaxel (41% and 27% lower risk of death for squamous and non-squamous NSCLC, respectively). Therefore, nivolumab has been approved in the US and in Europe as second-line treatment for advanced NSCLC. Unfortunately, accurate predictive factors for patient selection are lacking, making it difficult to decide who will benefit and who will not. Currently, there are many ongoing trials that evaluate the efficacy of nivolumab in different settings and in combination with other agents. This paper reviews the present literature about the role of nivolumab in the treatment of NSCLC. Particular attention has been given to efficacy studies, toxicity profile, and current and emerging predictive factors. PMID:27536062

  8. A Predictive Model for Personalized Therapeutic Interventions in Non-small Cell Lung Cancer.

    Science.gov (United States)

    Kureshi, Nelofar; Abidi, Syed Sibte Raza; Blouin, Christian

    2016-01-01

    Non-small cell lung cancer (NSCLC) constitutes the most common type of lung cancer and is frequently diagnosed at advanced stages. Clinical studies have shown that molecular targeted therapies increase survival and improve quality of life in patients. Nevertheless, the realization of personalized therapies for NSCLC faces a number of challenges including the integration of clinical and genetic data and a lack of clinical decision support tools to assist physicians with patient selection. To address this problem, we used frequent pattern mining to establish the relationships of patient characteristics and tumor response in advanced NSCLC. Univariate analysis determined that smoking status, histology, epidermal growth factor receptor (EGFR) mutation, and targeted drug were significantly associated with response to targeted therapy. We applied four classifiers to predict treatment outcome from EGFR tyrosine kinase inhibitors. Overall, the highest classification accuracy was 76.56% and the area under the curve was 0.76. The decision tree used a combination of EGFR mutations, histology, and smoking status to predict tumor response and the output was both easily understandable and in keeping with current knowledge. Our findings suggest that support vector machines and decision trees are a promising approach for clinical decision support in the patient selection for targeted therapy in advanced NSCLC. PMID:25494516

  9. Chemotherapy and Radiation Therapy With or Without Metformin Hydrochloride in Treating Patients With Stage III Non-small Cell Lung Cancer

    Science.gov (United States)

    2016-01-29

    Adenosquamous Lung Carcinoma; Bronchioloalveolar Carcinoma; Large Cell Lung Carcinoma; Lung Adenocarcinoma; Non-Small Cell Lung Carcinoma; Recurrent Non-Small Cell Lung Carcinoma; Squamous Cell Lung Carcinoma; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Non-Small Cell Lung Cancer

  10. Accelerated repopulation as a cause of radiation treatment failure in non-small cell lung cancer: review of current data and future clinical strategies.

    Science.gov (United States)

    Yom, Sue S

    2015-04-01

    Despite convincing evidence that the principles of accelerated repopulation would open up additional therapeutic opportunities in the treatment of advanced-stage non-small cell lung cancer, this strategy has been generally underexplored. The implementation of accelerated radiotherapy schedules has been hampered by logistical barriers, concerns about acute toxicity, and the prioritization of integrating concurrent chemotherapy into the standard treatment platform. At present, it is unclear to what extent accelerated fractionation will influence future treatment paradigms in non-small cell lung cancer, although technical advances in radiotherapy, allowing higher dose delivery with reduced toxicity, could permit the development of more convenient and tolerable forms of accelerated schedules. PMID:25771413

  11. Topographical Distributions of Allelic Loss in Individual Non-Small-Cell Lung Cancers

    OpenAIRE

    Yatabe, Yasushi; Konishi, Hiroyuki; Mitsudomi, Tetsuya; Nakamura, Shigeo; Takahashi, Takashi

    2000-01-01

    Non-small-cell carcinomas of the lung, especially adenocarcinomas, are characterized by a high degree of morphological heterogeneity. As carcinogenesis has been suggested to be a multistep process involving sequential accumulation of multiple genetic alterations, morphological heterogeneity may represent a cross-sectional view of genetic alterations within individual tumors. We therefore examined the topographical distribution of loss of heterozygosity (LOH) events within 10 non-small-cell lu...

  12. Surgical management of non-small-cell lung cancer

    Directory of Open Access Journals (Sweden)

    Bamousa Ahmed

    2008-10-01

    Full Text Available Surgery plays a major role in the management of patients with lung cancer. Surgery is not only the main curative treatment modality in patients with early-stage lung cancer but it also has a significant role in the initial workup for the diagnosis and staging of lung cancer. This article describes the surgical management of patients with lung cancer. Surgical resection for lung cancer is still regarded as the most effective method for controlling the primary tumor, provided it is resectable for cure and the risks of the procedure are low. The 5-year survival rare following complete resection (R0 of a lung cancer is stage dependent [Table 1]. [1-3] Incomplete resection (R1, R2 rarely, if ever, cures the patient.

  13. Mediastinal Staging in Non-Small Cell Lung Cancer.

    Science.gov (United States)

    Gamliel, Ziv

    2016-07-01

    In the absence of distant metastases, lung cancer treatment is determined by the results of mediastinal lymph node staging. Occult mediastinal lymph node metastases can be missed by radiologic and needle-based staging methods. Aggressive staging of mediastinal lymph nodes improves staging accuracy. Improved accuracy of mediastinal lymph node staging results in more appropriate lung cancer treatment. Improved accuracy of mediastinal lymph node staging can improve stage-specific survival from lung cancer. PMID:27261911

  14. Current status of immunotherapy for non-small-cell lung cancer.

    Science.gov (United States)

    Imbimbo, Martina; Lo Russo, Giuseppe; Blackhall, Fiona

    2016-08-01

    In the last few years, the introduction of novel immunotherapeutic agents has represented a treatment shift for a subset of patients with non-small-cell lung cancer (NSCLC). Checkpoint inhibitors have been demonstrated to improve survival in advanced stage disease with very good tolerability. This success follows many years of scientific effort to manipulate the human immune system to attack cancer cells. With a variety of approaches ranging from vaccines to administration of interleukin or interferon-γ, the results in NSCLC were unsuccessful, with the view that it is a scarcely immunogenic cancer, unlike melanoma or renal cell carcinoma. The step change has come from understanding of immune checkpoints-cell surface molecules that regulate immune system activation and mediate coinhibitory signaling pathways that physiologically protect the body from autoimmunity. These pathways play an important role in tumors, including NSCLC, and are a mechanism of escape from immune surveillance. Several monoclonal antibodies have been developed in order to inhibit these molecules and unleash the brakes of the immune system. Currently in NSCLC, 7 different checkpoint inhibitors are under investigation: 2 anti-cytotoxic T-lymphocyte-associated antigen 4, 2 anti-programmed death (PD)-1, and 3 anti-PD-ligand 1 antibodies. Here we review the progress to date in developing immunotherapy for NSCLC, summarize results from published trials, highlight ongoing trials, and discuss progress in the question of how best to select patients for this treatment. PMID:27443896

  15. Combined modality therapy for locally advanced non-small cell lung carcinoma

    International Nuclear Information System (INIS)

    Multi-modality treatment consisting of cisplatin, VP-16, and 5-fluorouracil chemotherapy given concomitantly with external beam radiation was used to treat 64 patients with locally advanced Stage III non-small cell lung carcinoma. This regimen was used in a preoperative fashion for four cycles in patients considered surgically resectable and with curative intent for six cycles in the remainder of patients. The clinical response rate for the entire group was 84% and the overall local control rate was 74%. The median survival was 13 months with a median follow-up for live patients of 19 months. The actuarial 3-year survival and disease-free survival rates were 30% and 23%, respectively. Histologic complete response was 39% and appeared to predict for survival. The 3-year actuarial survival and disease-free survival rates for 23 resected patients were 69% and 45%, respectively, with the complete histologic responders having a disease-free survival of 78%. The pattern of first recurrence did not appear to differ by histology or presence of lymph nodes in this subset of patients. The actuarial 3-year survival and disease-free survival rates for inoperable patients receiving six cycles of treatment were 18% and 23%, respectively. The local control was 67% with the majority of these patients having Stage IIIB disease. The Mountain International staging system appeared to predict for operability, local recurrence, and survival. This concomitant treatment regimen is feasible, with the major toxicities being leukopenia, nausea, and vomiting

  16. Metastatic non-small cell lung cancer Current treatment based on evidence (ONCOL Group)

    International Nuclear Information System (INIS)

    to perform a review of evidence about the treatment of non-small cell lung cancer (NSCLC). Source of data: the information was obtained from searches conducted in Medline, CCTR, Biosis, Embase, Lilacs and CINHAL. We also collected the most representative references presented during the last five years at Asco, ESMO and IASLC. Data extraction: data were extracted by associate members to the ONCOL Group. The collection of information did not follow a uniform strategy. Results of data synthesis: therapy for NSCLC can prolong survival and improve quality of life, but the majority of advanced stage patients dies due to disease progression within 2 years, meaning that there is room for improvement. The standard chemotherapy for NSCLC involves one of a number of platinum-based doublets that have been shown to improve survival when compared with single agents or best supportive care. These doublets are generally comparable in terms of efficacy, differing primarily in their toxicity profiles. However, encouraging new options may be approaching, including therapies targeted to specific patient subpopulations, and the use of combinations of current and new drugs to produce synergistic effects. This review present a detailed analysis of current evidence regarding the treatment of NSCLC based on a representative case series. This review didn't conduct a systematic evaluation of the evidence. Conclusion: medical therapy for NSCLC produces positive changes in main outcomes, including quality of life

  17. Crizotinib for Advanced Non-Small Cell Lung Cancer

    Science.gov (United States)

    A summary of results from an international phase III clinical trial that compared crizotinib versus chemotherapy in previously treated patients with advanced lung cancer whose tumors have an EML4-ALK fusion gene.

  18. PET/CT in the Staging of the Non-Small-Cell Lung Cancer

    OpenAIRE

    Fangfang Chao; Hong Zhang

    2012-01-01

    Lung cancer is a common disease and the leading cause of cancer-related death in many countries. Precise staging of patients with non-small-cell lung cancer plays an important role in determining treatment strategy and prognosis. Positron emission tomography/computed tomography (PET/CT), combining anatomic information of CT and metabolic information of PET, is emerging as a potential diagnosis and staging test in patients with non-small-cell lung cancer (NSCLC). The purpose of this paper is t...

  19. Non small-cell lung cancer with metastasis to thigh muscle and mandible: two case reports

    OpenAIRE

    Giugliano, Francesca Maria; Alberti, Domingo; Guida, Giovanna; Palma, Giampaolo De; Iadanza, Luciano; Mormile, Maria; Cammarota, Fabrizio; Montanino, Agnese; Fulciniti, Franco; Ravo, Vincenzo; Muto, Paolo

    2013-01-01

    Introduction Lung cancer is the leading cause of cancer-related death in Europe and the US. Isolated metastases to skeletal muscle and the mandible are very uncommon. Case presentation This report presents two cases. Case 1 concerns a 45-year-old Caucasian woman affected by muscle metastasis of the right thigh from non-small-cell lung cancer. Case 2 concerns a 61-year-old Caucasian man affected by mandible metastasis from non-small-cell lung cancer. Both metastases were detected by diagnostic...

  20. Treatment outcome and toxicity of intensity-modulated (chemo radiotherapy in stage III non-small cell lung cancer patients

    Directory of Open Access Journals (Sweden)

    Govaert Stephanie LA

    2012-09-01

    Full Text Available Abstract Purpose The aim of this retrospective cohort study was to assess treatment outcome, and acute pulmonary and esophageal toxicity using intensity modulated (sequential/concurrent chemoradiotherapy (IMRT in locally advanced stage III non-small cell lung cancer (NSCLC. Methods and materials Eighty-six patients with advanced stage NSCLC, treated with either IMRT only (66 Gy or combined with (sequential or concurrent chemotherapy were retrospectively included in this study. Overall survival and metastasis-free survival were assessed as well as acute pulmonary and esophageal toxicity using the RTOG Acute Radiation Morbidity Scoring Criteria. Results Irrespective of the treatment modality, the overall survival rate for patients receiving 66 Gy was 71% (±11%; 95% CI after one year and 56% (±14% after two years resulting in a median overall survival of 29.7 months. Metastasis-free survival was 73% (±11% after both one and two years. There were no statistically significant differences between the treatment groups. Treatment related esophageal toxicity was significantly more pronounced in the concurrent chemoradiotherapy group (p = 0.013 with no differences in pulmonary toxicity. Conclusions This retrospective cohort study in advanced non-small cell lung cancer patients shows that IMRT is an effective technique with acceptable acute toxicity, also when (sequentially or concomitantly combined with chemotherapy.

  1. Treatment outcome and toxicity of intensity-modulated (chemo) radiotherapy in stage III non-small cell lung cancer patients

    International Nuclear Information System (INIS)

    The aim of this retrospective cohort study was to assess treatment outcome, and acute pulmonary and esophageal toxicity using intensity modulated (sequential/concurrent chemo)radiotherapy (IMRT) in locally advanced stage III non-small cell lung cancer (NSCLC). Eighty-six patients with advanced stage NSCLC, treated with either IMRT only (66 Gy) or combined with (sequential or concurrent) chemotherapy were retrospectively included in this study. Overall survival and metastasis-free survival were assessed as well as acute pulmonary and esophageal toxicity using the RTOG Acute Radiation Morbidity Scoring Criteria. Irrespective of the treatment modality, the overall survival rate for patients receiving 66 Gy was 71% (±11%; 95% CI) after one year and 56% (±14%) after two years resulting in a median overall survival of 29.7 months. Metastasis-free survival was 73% (±11%) after both one and two years. There were no statistically significant differences between the treatment groups. Treatment related esophageal toxicity was significantly more pronounced in the concurrent chemoradiotherapy group (p = 0.013) with no differences in pulmonary toxicity. This retrospective cohort study in advanced non-small cell lung cancer patients shows that IMRT is an effective technique with acceptable acute toxicity, also when (sequentially or concomitantly) combined with chemotherapy

  2. EXPRESSION OF P120ctn IN NON-SMALL-CELL LUNG CANCER: A CLINICOPATHOLOGICAL STUDY

    Institute of Scientific and Technical Information of China (English)

    张志坤; 林东; 王恩华; 关奕

    2002-01-01

    Objective: To investigate the expression of p120ctn in non-small-cell lungcancer (NSCLC) and its relationship with clinicopathological factors and prognosis. Methods: p120ctn expression was tested by immunohistochemistry for 80 tumors from patients with non-small-cell lung cancer. Correlations were investigated between p120ctn immunostaining in primary tumors and clinicopathological characteristics and survival. Results: Abnormal expression of p120ctn was found in 68/80(85%) tumors in which 43 cases had cytoplasmic staining. Abnormal staining of p120ctn was related with high TNM stage (P=0.003) and nodal metastasis (P=0.024).However, there was no correlation between altered expression with poor differentiation and histological type. According to Kaplan-Meier survival estimate, the expression of p120ctn was related to the poor survival (P=0.015) of patients. A Cox regression analysis revealed that p120ctn expression was a significant independent factor in the prediction of survival for patients with non-small-cell lung cancer (P=0.008). Conclusion: altered expression of p120ctn was found in non-small-cell lung cancers and was correlated with lymph node metastasis and prognosis. From a practical point of view, the expression of p120ctn can be of prognostic value for patients with non-small-cell lung cancer.

  3. Staging of non-small cell lung cancer (NSCLC)

    OpenAIRE

    Rankin, S. C.

    2006-01-01

    Staging of non-small lung cancer (NSCLC) uses the TNM classification and is undertaken to identify those patients who are surgical candidates, either initially or after chemo-radiotherapy, and to differentiate patients who will be treated radically from those requiring palliation and to plan radiotherapy fields. Computed tomography and magnetic resonance imaging (MRI) are used in staging and provide anatomical information but have well known limitations in differentiating reactive from malign...

  4. Maintenance Therapies for Non-Small Cell Lung Cancer

    OpenAIRE

    NormandBlais

    2014-01-01

    Treatment of lung cancer had evolved during the last decade with the introduction of new chemotherapeutic regimens and targeted therapies. However, the maximum benefit reached after first-line therapy is limited by the cumulative toxicity of platinum drugs and the subsequent deterioration in performance status in a high percentage of patients who end up receiving not more than one line of treatment. Maintenance therapy had been introduced and evaluated in many large randomized trials showing ...

  5. 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

  6. GENETIC ALTERRATIONS OF MICROSATELLITE MARKERS AT CHROMOSOME 17 IN NON-SMALL CELL LUNG CANCER

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective: To analyse the microsatellite instability (MI) and loss of heterozygosity (LOH) in non-small cell lung cancer (NSCLC). Methods: MI and LOH at chromosome 17 were checked in 35 cases of NSCLC tumor-normal paired tissues using four microsatellite markers TP53 (17p13.1), THRA1 (17q11.2-12), D17S579 (17q12-21) and D17S855 (17q21) by PCR based analysis. Mutations of P53 exons 5-8 were also tested using PCR-single strand conformation polymorphism (PCR-SSCP) and PCR-denaturing gradient gel electrophoresis (PCR-DGGE) analysis. Results: 22 of 35 tumors (62.8%) displayed MI or LOH. 14 tumors (40.0%) exhibited MI, 11 tumors (31.4%) exhibited LOH, while 3 tumors (8.6%) exhibited MI and LOH concurrently. 23 tumors (65.7%) exhibited P53 gene mutations. The frequency of MI or LOH was obviously higher in the early-stage (stages I and II, 78.9%) than in the advanced-stage (stage III, 43.8%). However, the frequency of MI or LOH had no difference either between high-grade (75.0%) and low-grade (52.6%) differentiated NSCLC or between the tumors with P53 mutations (59.1%) and those without P53 mutations (69.2%). No relationship was observed between the presence of MI or LOH and the histologic subtype of NSCLC. Conclusion: The results suggest that MI and LOH at chromosome 17 may play a alterations on chromosome 17 in tumors of non-small cell lung cancer (NSCLC). In addition, studies reported contradictory results concerning the incidence of these alterations and the relationship between these genetic alterations and the clinical behavior of NSCLC. The aim of this study was to investigate the incidence of MI and LOH at chromosome 17 in tumors of patients with NSCLC and its association with clinical and histologic features of NSCLC.

  7. Radiotherapy for ''non-small-cell'' cancer of the lung

    International Nuclear Information System (INIS)

    Radiotherapy serves a very important role in the palliation of distressing symptoms caused by an intrathoracic tumor or its distant manifestations. When the tumor is confined to the thorax, irradiation can eradicate or control the cranial-regional disease, prolonging survival and offering the possibility of cure. In addition, there is a role for radiotherapy as an adjuvant to surgery in a subset the patients with resectable cancinoma of the lung. The following review sill put us on radiotherapy as a surgical adjuvant; the use of radiotherapy in the palliative treatment, life prolongation, and cure of patients with unresectable tumors; the characteristics of patient who live 3 or more years after irradiation; the special problems of superior sulcus tumors and malignant superoir vena cranial obstruction. The treatment of patients with brain metastases from carcinoma of the lung and the potential for prophylactic cranial irradiation is explored. Prognostic factors are noted for patients with unresectable tumors. Finally, the status of current investigations and prospects for future studies are surveyed

  8. Protein signature for non-small cell lung cancer prognosis

    Science.gov (United States)

    Liu, Wei; Wu, Yong; Wang, Libo; Gao, Ling; Wang, Yingping; Liu, Xiaoliang; Zhang, Kai; Song, Jena; Wang, Hongxia; Bayer, Thomas A; Glaser, Laurel; Sun, Yezhou; Zhang, Weijia; Cutaia, Michael; Zhang, David Y; Ye, Fei

    2014-01-01

    Background: Current histopathological classification and TNM staging have limited accuracy in predicting survival and stratifying patients for appropriate treatment. The goal of the study is to determine whether the expression pattern of functionally important regulatory proteins can add additional values for more accurate classification and prognostication of non-small lung cancer (NSCLC). Methods: The expression of 108 proteins and phosphoproteins in 30 paired NSCLC samples were assessed using Protein Pathway Array (PPA). The differentially expressed proteins were further confirmed using a tissue microarray (TMA) containing 94 NSCLC samples and were correlated with clinical data and survival. Results: Twelve of 108 proteins (p-CREB(Ser133), p-ERK1/2(Thr202/Tyr204), Cyclin B1, p-PDK1(Ser241), CDK4, CDK2, HSP90, CDC2p34, β-catenin, EGFR, XIAP and PCNA) were selected to build the predictor to classify normal and tumor samples with 97% accuracy. Five proteins (CDC2p34, HSP90, XIAP, CDK4 and CREB) were confirmed to be differentially expressed between NSCLC (n=94) and benign lung tumor (n=19). Over-expression of CDK4 and HSP90 in tumors correlated with a favorable overall survival in all NSCLC patients and the over-expression of p-CREB(Ser133) and CREB in NSCLC correlated with a favorable survival in smokers and those with squamous cell carcinoma, respectively. Finally, the four proteins (CDK4, HSP90, p-CREB and CREB) were used to calculate the risk score of each individual patient with NSCLC to predict survival. Conclusion: In summary, our data demonstrated a broad disturbance of functionally important regulatory proteins in NSCLC and some of these can be selected as clinically useful biomarkers for diagnosis, classification and prognosis. PMID:24959380

  9. Non-small cell lung cancer staging: proposed revisions to the TNM system

    OpenAIRE

    Schneider, Bryan J.

    2008-01-01

    Abstract Patients with non-small cell lung cancer (NSCLC) require careful staging at the time of diagnosis to determine prognosis and guide treatment recommendations. The seventh edition of the TNM Classification of Malignant Tumors is scheduled to be published in 2009 and the International Association for the Study of Lung Cancer (IASLC) created the Lung Cancer Staging Project (LCSP) to guide revisions to the current lung cancer staging system. These recommendations will be submitted to the ...

  10. GENETIC ALTERRATIONS OF MICROSATELLITE MARKERS AT CHROMOSOME 17 IN NON-SMALL CELL LUNG CANCER

    Institute of Scientific and Technical Information of China (English)

    GUO; Xue-jun

    2001-01-01

    [1]Froudarakis ME, Bouros D, Spandidos DA, et al. Microsatellite instability and loss of heterozygosity at chromosomes 17 in non-small cell lung cancer [J]. Chest 1998; 113:1091.[2]Fong KM, Zimmerman PV, Smith PJ. Microsatellite instability and other molecular abnormalities in non-small cell lung cancer [J]. Cancer Res 1994; 54:2098.[3]Mountain CF. A new international staging system for lung cancer [J]. Chest 1986; 89(suppl):225.[4]Shridhar V, Siegfried J, Hunt J, et al. Genetic instability of microsatellite sequences in many non-small cell lung carcinomas [J]. Cancer Res 1994; 54:2084.[5]Loeb LA. Microsatellite instability: Marker of a mutator phenotype in cancer [J]. Cancer Res 1994; 54:5059.[6]Sanchez CM, Monzo M, Rosell R, et al. Detection of chromosome 3p alterations in serum DNA of non-small cell lung cancer patients [J]. Ann Oncol 1989; 113.

  11. Molecular biologic study about the non-small cell lung carcinoma (2) : p53 gene alteration in non-small cell lung carcinoma

    International Nuclear Information System (INIS)

    The main purpose of this research was to identify of the p53 and 3p gene alteration in non-small cell lung cancer patients residing in Korea. Furthermore, we analyzed the relationship between the p53 and 3p gene alterations and the clinicopathologic results of lung cancer patients. And we have investigated the role of PCR-LOH in analyzing tumor samples for LOH of defined chromosomal loci. We have used the 40 samples obtained from the lung cancer patients who were diagnosed and operated curatively at Korea Cancer Center Hospital. We have isolated the high molecular weight. DNA from the tumors and normal tissues. And we have amplified the DNA with PCR method and used the microsatellite assay method to detect the altered p53 and 3p gene. The conclusions were as follow: 1) The 3p gene alteration was observed in 9/39 (23.1%) and p53 gene alteration was observed in 15/40 (37.5%) of resected non-small cell lung cancer. 2) There was no correlations between the 3p or p53 gene alterations and prognosis of patients, but further study is necessary. 3) PCR-LOH is a very useful tool for analyzing small amount of tumor samples for loss of heterozygosity of defined chromosomal loci. (author). 10 refs

  12. Significances of RET Fusion Gene in Non-small Cell Lung Cancer

    OpenAIRE

    Liu, Jingjing; Minghong BI

    2013-01-01

    Lung cancer is the leading cause of cancer-related death worldwide, molecular target therapy has become a hot research direction of non-small cell lung cancer (NSCLC) treatment. RET fusion gene with an identifiable clinical pathological features, is present in some subsets of lung cancer, and its treatment is effective by RET inhibitor, suggesting that RET fusion gene may be a new target for individualized treatment to the subgroup of NSCLC. This article reviews the structural characteristics...

  13. Roles of Mir-144-ZFX Pathway in Growth Regulation of Non-Small-Cell Lung Cancer

    OpenAIRE

    Zha, Wangjian; Cao, Liu; Shen, Ying; Mao HUANG

    2013-01-01

    Background Lung cancer is the leading cause of cancer-related death worldwide. Non-small cell lung carcinoma (NSCLC) accounts for most of the lung cancer cases and the prognosis of this disease remains poor despite decades of intensive investigation. Thus new insights into underlying mechanisms by which NSCLC develops are avidly needed as the basis for development of new lines of therapeutic strategies. The past decade has witnessed a growing interest on the regulatory roles of micro RNAs on ...

  14. Functional image-based radiotherapy planning for non-small cell lung cancer: a simulation study

    OpenAIRE

    Bates, E.L.; Bragg, C.M.; Wild, J. M.; Hatton, M.Q.F.; Ireland, R.H.

    2009-01-01

    Background and purpose: To investigate the incorporation of data from single-photon emission computed tomography (SPECT) or hyperpolarized helium-3 magnetic resonance imaging (He-3-MRI) into intensity-modulated radiotherapy (IMRT) planning for non-small cell lung cancer (NSCLC). Material and methods: Seven scenarios were simulated that represent cases of NSCLC with significant functional lung defects. Two independent IMRT plans were produced for each scenario; one to minimise total lung vo...

  15. HOXA11 hypermethylation is associated with progression of non-small cell lung cancer

    OpenAIRE

    Hwang, Jung-Ah; Lee, Bo Bin; Kim, Yujin; Park, Seong-Eun; Heo, Kyun; Hong, Seung-Hyun; Kim, Young-Ho; Han, Joungho; Shim, Young Mog; Lee, Yeon-Su; Kim, Duk-Hwan

    2013-01-01

    This study was aimed at understanding the functional significance of HOXA11 hypermethylation in non-small cell lung cancer (NSCLC). HOXA11 hypermethylation was characterized in six lung cancer cell lines, and its clinical significance was analyzed using formalin-fixed paraffin-embedded tissues from 317 NSCLC patients, and Ki-67 expression was analyzed using immunohistochemistry. The promoter region of HOXA11 was highly methylated in six lung cancer cell lines, but not in normal bronchial epit...

  16. Rational use of cetuximab in the treatment of advanced non-small cell lung cancer

    OpenAIRE

    Borghaei, Hossein

    2009-01-01

    Charu Aggarwal, Hossein BorghaeiDepartment of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA, USAAbstract: Lung cancer is the leading cause of mortality in the United States. Non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancers. Most NSCLC patients present with loco-regionally advanced or metastatic disease where response rates are low and median overall survival approximates 8 to 10 months. Chemotherapy is the mainstay of treatment for NSCLC pati...

  17. Safety and Efficacy of Vinorelbine in the Treatment of Non-Small Cell Lung Cancer

    OpenAIRE

    Faller, Bryan A; Pandit, Trailokya N.

    2011-01-01

    Lung cancer remains the most frequently diagnosed cancer in the United States, excluding non-melanoma skin cancer. Non-small cell lung cancer (NSCLC) constitutes the majority (more than 80%) of lung cancer diagnoses. Systemic therapy, with either cytotoxic chemotherapy and/or targeted therapies, has been established to provide benefit to patients with NSCLC in both the adjuvant and advanced disease settings. Vinorelbine, a semi-synthetic vinca-alkaloid has been extensively tested alone and in...

  18. Genome-wide DNA methylation profiling of non-small cell lung carcinomas

    NARCIS (Netherlands)

    R.H. Carvalho (Rejane Hughes); V. Haberle (Vanja); J. Hou (Jun); T. van Gent (Teus); S. Thongjuea (Supat); W.F.J. van IJcken (Wilfred); C. Kockx (Christel); R.W.W. Brouwer; E.J. Rijkers; A.M. Sieuwerts (Anieta); J.A. Foekens (John); M. van Vroonhoven (Mirjam); J.G.J.V. Aerts (Joachim); F.G. Grosveld (Frank); B. Lenhard (Boris); J.N.J. Philipsen (Sjaak)

    2012-01-01

    textabstractBackground: Non-small cell lung carcinoma (NSCLC) is a complex malignancy that owing to its heterogeneity and poor prognosis poses many challenges to diagnosis, prognosis and patient treatment. DNA methylation is an important mechanism of epigenetic regulation involved in normal developm

  19. Diagnosis, staging and treatment of patients with non-small cell lung cancer for the surgeon

    OpenAIRE

    Bryant, Ayesha S.; Cerfolio, Robert J.

    2009-01-01

    This article covers the risk factors, diagnostic tools, staging methods/modalities and treatment for patients with non-small cell lung cancer (NSCLC). Also presented is the new 7th edition American Joint Cancer Committee (AJCC) TNM classification for staging of NSCLC and a recommended treatment algorithm.

  20. PET/CT for staging and monitoring non small cell lung cancer

    OpenAIRE

    Rankin, Sheila

    2008-01-01

    Abstract Correct staging of non small cell lung cancer (NSCLC) is vital for appropriate management. Initial staging is usually performed with computerised tomography (CT), but increasingly functional imaging using integrated positron emission tomography and CT (PET/CT) is being used to provide more accurate staging, guide biopsies, assess response to therapy and identify recurrent disease.

  1. Multidisciplinary management of the locally advanced unresectable non-small cell lung cancer

    International Nuclear Information System (INIS)

    Locally advanced (Stage III) non-small cell lung cancer (NSCLC) accounts for approximately one third of all cases of NSCLC. Few patients with locally advanced NSCLC present with disease amenable to curative surgical resection. Historically, these patients were treated with primary thoracic radiation therapy (RT) and had poor long term survival rates, due to both progression of local disease and development of distant metastases. Over the last two decades, the use of multidisciplinary approach has improved the outcome for patients with locally advanced NSCLC. Combined chemoradiotherapy is the most favored approach for treatment of locally advanced unresectable NSCLC. There are two basic treatment protocols for administering combined chemotherapy and radiation, sequential versus concurrent. The rationale for using chemotherapy is to eliminate subclinical metastatic disease while improving local control. Sequential use of chemotherapy followed by radiotherapy has improved median and long term survival compared to radiation therapy alone. This approach appears to decrease the risk of distant metastases, but local failure rates remain the same as radiation alone. Concurrent chemoradiotherapy has been studied extensively. The potential advantages of this approach may include sensitization of tumor cells to radiation by the administration of chemotherapy, and reduced overall treatment time compared to sequential therapy; which is known to be important for improving local control in radiation biology. This approach improves survival primarily as a result of improved local control. However, it doesn't seem to decrease the risk of distant metastases probably because concurrent chemoradiation requires dose reductions in chemotherapy due to increased risks of acute morbidity such as acute esophageal toxicity. Although multidisciplinary therapy has led to improved survival rates compared to radiation therapy alone and has become the new standard of care, the optimal therapy of

  2. PHASE II STUDY OF GEMCITABINE AND CISPLATIN IN ADVANCED NON-SMALL CELL LUNG CANCER

    Directory of Open Access Journals (Sweden)

    M. Hoseinzadeh Mollayosefy

    2006-06-01

    Full Text Available Cisplatin-based chemotherapy is the standard treatment for advanced non-small cell lung cancer (NSCLC. Many novel drugs have been used in combination with cisplatin in this setting. Of these drugs, gemcitabine is reported to have a high response rate and acceptable toxicity. The aim of this study was to evaluate the efficacy and safety of gemcitabine and cisplatin combination. Twentythree patients with NSCLC were enrolled from January 2001 till September 2003. All of them were confirmed by histology and were in advanced stage, i.e. stage IIIB or stage IV. Cisplatin with the dose of 70 mg/m2 was given every 21 days, in combination with gemcitabine at a dose of 1250 mg/m2 administered on days 1, 8 of a 21-day cycle. Of the 23 patients, 1 showed complete remission, 5 achieved partial remission and 7 had stable disease and 2 patients showed progressive disease, 8 patients were not evaluable for response. The overall response in 15 evaluable patients was 40% (95% CI., median survival was 13.5 months (95% CI, 3.5-27.4 months, and median progression free survival was 11 months (95% CI, 1.04-20.9 months. Hematological toxicity’s included anemia, neutropenia and thrombocytopenia. Non-hematological toxicities included nausea/vomiting, peripheral neuropathy, skin rashes, mild renal impairment and one case of acute respiratory distress syndrome;another case developed transient acute psychosis. The regimen of combined gemcitabine with cisplatin is safe and effective and well tolerated in patients. In this combination, a lower dose of cisplatin seems to have an efficacy similar to that seen in previous reports.

  3. Methoxyamine, Pemetrexed Disodium, Cisplatin, and Radiation Therapy in Treating Patients With Stage IIIA-IV Non-small Cell Lung Cancer

    Science.gov (United States)

    2016-04-05

    Metastatic Malignant Neoplasm in the Brain; Stage IIIA Large Cell Lung Carcinoma; Stage IIIA Lung Adenocarcinoma; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Large Cell Lung Carcinoma; Stage IIIB Lung Adenocarcinoma; Stage IIIB Non-Small Cell Lung Cancer; Stage IV Large Cell Lung Carcinoma; Stage IV Lung Adenocarcinoma; Stage IV Non-Small Cell Lung Cancer

  4. Current situation of interventional treatment for non-small cell lung cancer

    International Nuclear Information System (INIS)

    Primary bronchogenic carcinoma, which referred to as lung cancer, is one of the most common malignant tumors in china. The 2010 China Health Statistical Yearbook indicates that in 2005 the mortality of lung cancer was at the first place of all cancers. Non-small-cell lung cancer (NSCLC) accounts for 8.5% of all the lung cancers, most of the patents are diagnosed in their late stages and have lost the chance of operation resection, and the 5-year survival rate is only about 15%. Being of technical simplicity, mild side reaction, satisfactory local effect and reliable reproducibility, interventional therapy has become an important and non-surgical method for advanced NSCLC, and has been widely applied in clinical practice. This paper aims to make a review about the current situation of interventional treatment for non-small cell lung cancer. (authors)

  5. Association of sarcopenia and observed physical performance with attainment of multidisciplinary team planned treatment in non-small cell lung cancer: an observational study protocol

    OpenAIRE

    Collins, Jemima T.; Noble, Simon; Chester, John; Davies, Helen E; Evans, William D.; Lester, Jason; Parry, Diane; Pettit, Rebecca J.; Byrne, Anthony

    2015-01-01

    Background Non-small cell lung cancer (NSCLC) frequently presents in advanced stages. A significant proportion of those with reportedly good ECOG performance status (PS) fail to receive planned multidisciplinary team (MDT) treatment, often for functional reasons, but an objective decline in physical performance is not well described. Sarcopenia, or loss of muscle mass, is an integral part of cancer cachexia. However, changes in both muscle mass and physical performance may predate clinically ...

  6. Medical treatment of advanced non-small cell lung cancer: progress in 2014

    Directory of Open Access Journals (Sweden)

    Yong SONG

    2015-04-01

    Full Text Available Non-small cell lung cancer is the most common pathological type of lung cancer. Along with the rising incidence in recent years, lung cancer has been the leading cause of death due to malignancies both in our country and worldwide. Due to simplistic therapeutic approach for lung cancer decades ago, those patients suffering from advanced lung cancer had short lifetime, and it was difficult to ensure their life quality. In recent years, many molecular targeted drugs, such as Gefitinib, Erlotinib and Crizotinib etc., have been successively applied in clinical use, and they bring about a substantial prolongation of survival life and improvement in life quality of those patients with advanced lung cancer. In 2014, there was a number of important reports concerning the diagnosis and treatment of non-small cell lung cancer in the annual meetings of either American Society of Clinical Oncology or European Society for Medical Oncology. On the basis of the relevant reports delivered in the conferences, it is our attempt to summarize the recent advances in regard to chemotherapy, molecular targeted therapy, measures to treat TKI therapy resistant cases, and immune therapy, followed by a comment regarding recent advances in the treatment of non-small cell lung cancer in 2014. DOI: 10.11855/j.issn.0577-7402.2015.01.03

  7. Targeted therapies and radiation therapy in non-small cell lung cancer; Therapies ciblees et radiotherapie dans les cancers bronchiques non a petites cellules

    Energy Technology Data Exchange (ETDEWEB)

    Rivera, S.; Quero, L.; Wong Hee Kam, S.; Maylin, C.; Hennequin, C. [Service de cancerologie radiotherapie, hopital Saint-Louis, AP-HP, 1, avenue Claude-Vellefaux, 75010 Paris (France); Deutsch, E. [UMR 1030 ' radiosensibilite des tumeurs et tissus sains ' , Inserm, 114, rue edouard-Vaillant, 94805 Villejuif (France); Departement de radiotherapie, institut de cancerologie Gustave-Roussy, 114, rue edouard-Vaillant, 94805 Villejuif (France)

    2011-10-15

    Lung cancer is the leading cause of cancer-related death. Between 80-85% of lung cancers are non-small cell lung carcinomas. One third of the patients are diagnosed with locally advanced stage. In this condition, concomitant radio-chemotherapy is the standard treatment for patients with good performance status. Despite important improvements in the last years, non-small cell lung carcinoma prognosis remains poor, with high rates of both local recurrences and metastases. The heterogeneity of molecular characteristics of non-small cell lung carcinoma cells and a better knowledge of potential targets offer promising developments for new pharmacologic agents. Hereafter we will review the currently most studied pathways and the most promising ones for the treatment of locally advanced unresectable non-small cell lung carcinoma. Two of the most attractive pathways where new agents have been developed and assessed in combination with thoracic radiotherapy or radio-chemotherapy are the EGFR pathway (either with the use of monoclonal antibodies or tyrosine kinase inhibitors) and the angiogenesis inhibition. The development of targeted agents could lead to individualized therapeutic combinations taking into account the intrinsic characteristics of tumor cells. Pharmacological modulation of tumour cells radiosensitivity by targeted therapies is only starting, but yet offers promising perspectives. (authors)

  8. Expression of TMPRSS4 in non-small cell lung cancer and its modulation by hypoxia

    OpenAIRE

    NGUYEN, TRI-HUNG; WEBER, WILLIAM; HAVARI, EVIS; CONNORS, TIMOTHY; BAGLEY, REBECCA G.; McLAREN, RAJASHREE; Nambiar, Prashant R; Madden, Stephen L.; Teicher, Beverly A.; Roberts, Bruce; Kaplan, Johanne; SHANKARA, SRINIVAS

    2012-01-01

    Overexpression of TMPRSS4, a cell surface-associated transmembrane serine protease, has been reported in pancreatic, colorectal and thyroid cancers, and has been implicated in tumor cell migration and metastasis. Few reports have investigated both TMPRSS4 gene expression levels and the protein products. In this study, quantitative RT-PCR and protein staining were used to assess TMPRSS4 expression in primary non-small cell lung carcinoma (NSCLC) tissues and in lung tumor cell lines. At the tra...

  9. 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...

  10. 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)...

  11. Clinical evaluation of serum tumour marker CA 242 in non-small cell lung cancer.

    OpenAIRE

    Pujol, J L; Cooper, E H; Lehmann, M.; Purves, D. A.; Dan-Aouta, M.; Midander, J.; Godard, P.; Michel, F B

    1993-01-01

    CA 242, a novel tumour carbohydrate antigen present in serum (upper limit of normal values: 20.0 U ml-1), has been measured in a group of 102 pathologically confirmed non-small cell lung cancer patients. The aim of the present prospective study was to identify any relationship between pre-treatment serum CA 242 level and different features of lung cancer including prognosis. Serum CA 242 was measured using the delayed europium lanthanide fluoroimmunometric assay. Sensitivity and specificity w...

  12. Recent advances in the treatment of non-small cell and small cell lung cancer

    OpenAIRE

    Stinchcombe, Thomas E.

    2014-01-01

    Recent presentations at the American Society of Clinical Oncology (ASCO) meeting from 30 May to 3 June, 2014, will impact routine clinical care and the development of clinical trials in non-small cell lung cancer (NSCLC) and extensive stage small cell lung cancer (ES-SCLC). Patients with activating epidermal growth factor receptor (EGFR) mutations, defined as exon 19 and exon 21 L858R point mutations, experience a high objective response rate and prolonged progression-free survival with EGFR ...

  13. A multi-analyte serum test for the detection of non-small cell lung cancer

    OpenAIRE

    Farlow, E C; Vercillo, M S; Coon, J. S.; S. Basu; Kim, A.W.; Faber, L P; Warren, W H; Bonomi, P; Liptay, M. J.; Borgia, J A

    2010-01-01

    Background: In this study, we appraised a wide assortment of biomarkers previously shown to have diagnostic or prognostic value for non-small cell lung cancer (NSCLC) with the intent of establishing a multi-analyte serum test capable of identifying patients with lung cancer. Methods: Circulating levels of 47 biomarkers were evaluated against patient cohorts consisting of 90 NSCLC and 43 non-cancer controls using commercial immunoassays. Multivariate statistical methods were used on all biomar...

  14. Challenges in optimizing chemoradiation in locally advanced non small-cell lung cancers in India

    OpenAIRE

    Sushma Agrawal

    2013-01-01

    Data supporting use of concurrent chemoradiation in locally advanced lung cancers comes from clinical trials from developed countries. Applicability and outcomes of such schedules in developing countries is not widely reported. There are various challenges in delivering chemoradiation in locally advanced non small cell lung cancer in developing countries which is highlighted by an audit of patients treated with chemoradiation in our center. This article deals with the challenges in the contex...

  15. Clinical and surgical-pathological staging in early non-small cell lung cancer

    OpenAIRE

    Ioannis Koukis; Ioannis Gkiozos; Ioannis Ntanos; Elias Kainis; Konstantinos N. Syrigos

    2013-01-01

    Staging is of the utmost importance in the evaluation of a patient with non-small cell lung cancer (NSCLC) because it defines the actual extent of the disease. Accurate staging allows multidisciplinary oncology teams to plan the best surgical or medical treatment and to predict patient prognosis. Based on the recommendation of the International Association for the Study of Lung Cancer (IASLC), a tumor, node, and metastases (TNM) staging system is currently used for NSCLC. Clinical staging (c-...

  16. Prognostic implication of PTPRH hypomethylation in non-small cell lung cancer

    OpenAIRE

    Sato, Takashi; Soejima, Kenzo; Arai, Eri; HAMAMOTO, JUNKO; Yasuda, Hiroyuki; Arai, Daisuke; Ishioka, Kota; Ohgino, Keiko; Naoki, Katsuhiko; Kohno, Takashi; Tsuta, Koji; Watanabe, Shun-ichi; Kanai, Yae; Betsuyaku, Tomoko

    2015-01-01

    PTPRH is a receptor-type protein tyrosine phosphatase thought to be a potential regulator of tumorigenesis. The aim of the present study was to clarify the significance of PTPRH expression and its regulation by DNA methylation in non-small cell lung cancer (NSCLC), especially in lung adenocarcinoma (LADC). PTPRH mRNA expression was examined in 89 NSCLC and corresponding non-cancerous tissues. The correlation between DNA methylation and PTPRH gene expression was investigated in another cohort ...

  17. 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...

  18. Determination of Carboplatin Dose by Area Under the Curve in Combination Chemotherapy for Senile Non-small Cell Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    YIN Tiejun; LIU Qingqing; HU Changyao; LIU Mengtao

    2007-01-01

    To preliminarily determine the appropriate dosage of carboplatin (CBP) at AUC of 5 mg·Ml-1·min-1 in the combination chemotherapy for Chinese senile patients with non-small cell lung cancer (NSCLC). Thirty-five Chinese senile patients with NSCLC in advanced stage (Ⅲ/Ⅳ) were given 96 cycles of combination chemotherapy. Chemotherapy schedules included Taxol+CBE Gemzar+CBP and NVB+CBP. The dose of CBP was at 5 mg·mL-1·min-1 of area under the concen- tration-time curve (AUC). Side effects and quality of life were observed before and after the chemo- therapy. Myelosuppression was severe and commonly observed. Grade 3/4 of granuiocytopenia was found in 47.9% (46/96) of the patients and grade 3/4 of thrombocytopenia was noted in 28.1% (27/96) of the subjects. However, other side effects were slight. The mean score of quality of life (QOL), ac- cording to the criteria of QOL for Chinese cancer patients had reduced 6.8. At 5 mg·mL-1·min-1 by AUC, the hematological toxicity of CBP was severe and it had some negative effects on the QOL. The administration of CBP at 5 mg·mL-1·min-1 by AUC may be too high for Chinese senile patients with non-small cell lung cancer.

  19. Interpretation of NCCN Guidelines:General Therapies on Non-small Cell Lung Cancer (Version 6. 2015)

    Institute of Scientific and Technical Information of China (English)

    HUANG Xin-en

    2015-01-01

    Lung cancer is one of the most common malignant tumors in China and ranks the ifrst of cancer-related death. The major etiological agent of lung cancer is an industry-made and promoted addictive product, so lung cancer is considered to be a unique disease in all cancers. Effective policies for public health are required to prevent the smoking initiation so as to reduce the mortality of lung cancer, so Food and Drug Administration (FDA) has introduced a series of measures to monitor the tobacco products. As to patients with strong suspicion of lung cancer in stageⅠ-Ⅱ, a preoperative biopsy is needed and intra-operative diagnosis is necessary before pneumonectomy, bilobectomy or lobectomy if the preoperative tissue diagnosis is not obtained. However, lung cancer still cannot be easily diagnosed and cured, so the annual improvement and update of new therapeutic protocols and the development of new agents is of great significance. Non-small cell lung cancer (NSCLC) accounts for about 80% of all lung cancer, and above 75% NSCLC patients are in middle-advanced stage when diagnosed, so they have lost the optimal therapeutic opportunity and the 5-year survival rate is relatively low. Therefore, this study mainly interpreted the National Comprehensive Cancer Network (NCCN) guidelines on the general therapies on NSCLC, hoping to provide references for the treatment of NSCLC patients and prolong their long-term survival.

  20. The effect of comorbidity on stage-specific survival in resected non-small cell lung cancer patients

    DEFF Research Database (Denmark)

    Lüchtenborg, Margreet; Jakobsen, Erik; Krasnik, Mark; Linklater, Karen M; Mellemgaard, Anders; Møller, Henrik

    2012-01-01

    To quantify the effect of comorbidity on stage-specific survival in resected non-small cell lung cancer (NSCLC) patients.......To quantify the effect of comorbidity on stage-specific survival in resected non-small cell lung cancer (NSCLC) patients....

  1. Profile of ceritinib in the treatment of ALK+ metastatic non-small-cell lung cancer

    OpenAIRE

    Kim, Eric

    2015-01-01

    Mark W Burns, Eric S Kim Wilmot Cancer Center, University of Rochester, Rochester, NY, USA Abstract: Lung cancer has become one of the leading causes of death in both men and women in the United States, with approximately 230,000 new cases and 160,000 deaths each year. Approximately 80% of lung cancer patients are diagnosed with non-small-cell lung cancer (NSCLC), a subset of epithelial lung cancers that are generally insensitive to chemotherapy. An estimated 3%–7% of NSCLC patient...

  2. Profile of ceritinib in the treatment of ALK+ metastatic non-small-cell lung cancer

    OpenAIRE

    Burns MW; Kim ES

    2015-01-01

    Mark W Burns, Eric S Kim Wilmot Cancer Center, University of Rochester, Rochester, NY, USA Abstract: Lung cancer has become one of the leading causes of death in both men and women in the United States, with approximately 230,000 new cases and 160,000 deaths each year. Approximately 80% of lung cancer patients are diagnosed with non-small-cell lung cancer (NSCLC), a subset of epithelial lung cancers that are generally insensitive to chemotherapy. An estimated 3%–7% of NSCLC patients ha...

  3. Chemotherapy related toxicity in locally advanced non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Bahl Amit

    2006-01-01

    Full Text Available Background: For inoperable non-small cell lung cancer combined chemotherapy and radiotherapy plays an important role as a therapeutic modality. The aim of the present study was to analyze neoadjuvant chemotherapy related acute toxicity in locally advanced lung cancer (stage IIIA and IIIB in Indian patients using Cisplatin and Etoposide combination chemotherapy. Material and methods: Forty patients of locally advanced Non small cell lung cancer received three cycles neoadjuvant chemotherapy using Injection Cisplatin and Etoposide. The patients were taken for Radical radiotherapy to a dose of 60 Gray over 30 fractions in conventional fractionation after completing chemotherapy. Chemotherapy associated toxicity was assessed using common toxicity criteria (CTC v2.0 Results: Forty patients were available for final evaluation. Median age of presentation of patients was fifty-six years. Thirteen patients had Non small cell lung cancer stage IIIA while twenty-seven patients had Stage IIIB disease. Anemia was the most common hematological toxicity observed (seen in 81% of patients. Nausea and vomiting were the most common non -hematological toxicity seen. Sensory neuropathy was seen in 38%of patients. 88% patients developed alopecia. Seven patients developed febrile neutropenias. Conclusion: Neo-adjuvant chemotherapy using Cisplatin and Etoposide continues to be a basic regimen in the Indian set up despite availability of higher molecules, since it is cost effective, well tolerated and therapeutically effective. Blood transfusions, growth factors and supportive care can be used effectively to over come toxicity associated with this regimen.

  4. A rare case of non-small cell carcinoma of lung presenting as miliary mottling.

    Science.gov (United States)

    Jayaram Subhashchandra, Ballaekere; Ismailkhan, Mohammed; Chikkaveeraiah Shashidhar, Kuppegala; Gopalakrishna Narahari, Moda

    2013-03-01

    Miliary mottling on chest radiography is seen in miliary tuberculosis, certain fungal infections, sarcoidosis, coal miner's pneumoconiosis, silicosis, hemosiderosis, fibrosing alveolitis, acute extrinsic allergic alveolitis, pulmonary eosinophilic syndrome, pulmonary alveolar proteinosis, and rarely in hematogenous metastases from the primary cancers of the thyroid, kidney, trophoblasts, and some sarcomas. Although very infrequent, miliary mottling can be seen in primary lung cancers. Herein, we report the case of a 28-year-old female with chest X-ray showing miliary mottling. Thoracic computed tomography (CT) features were suggestive of tuberculoma with miliary tuberculosis. CT-guided fine needle aspiration cytology confirmed the diagnosis as lower-lobe, left lung non-small cell carcinoma (adenocarcinoma). It is rare for the non-small cell carcinoma of the lung to present as miliary mottling. The rarity of our case lies in the fact that a young, non-smoking female with miliary mottling was diagnosed with non-small cell carcinoma of the lung. PMID:23645961

  5. A Rare Case of Non-Small Cell Carcinoma of Lung Presenting as Miliary Mottling

    Directory of Open Access Journals (Sweden)

    Ballaekere Jayaram Subhashchandra

    2013-03-01

    Full Text Available Miliary mottling on chest radiography is seen in miliary tuberculosis, certain fungal infections, sarcoidosis, coal miner’s pneumoconiosis, silicosis, hemosiderosis, fibrosing alveolitis, acute extrinsic allergic alveolitis, pulmonary eosinophilic syndrome, pulmonary alveolar proteinosis, and rarely in hematogenous metastases from the primary cancers of the thyroid, kidney, trophoblasts, and some sarcomas. Although very infrequent, miliary mottling can be seen in primary lung cancers. Herein, we report the case of a 28-year-old female with chest X-ray showing miliary mottling. Thoracic computed tomography (CT features were suggestive of tuberculoma with miliary tuberculosis. CT-guided fine needle aspiration cytology confirmed the diagnosis as lower-lobe, left lung non-small cell carcinoma (adenocarcinoma. It is rare for the non-small cell carcinoma of the lung to present as miliary mottling. The rarity of our case lies in the fact that a young, non-smoking female with miliary mottling was diagnosed with non-small cell carcinoma of the lung.

  6. Secondary osteosarcoma developing 10 years after chemoradiotherapy for non-small-cell lung cancer.

    Science.gov (United States)

    Yagishita, Shigehiro; Horinouchi, Hidehito; Yorozu, Takashi; Kitazono, Satoru; Mizugaki, Hidenori; Kanda, Shintaro; Fujiwara, Yutaka; Nokihara, Hiroshi; Yamamoto, Noboru; Mori, Taisuke; Tsuta, Koji; Sumi, Minako; Tamura, Tomohide

    2014-02-01

    A 53-year-old female patient was admitted with pain and a progressively enlarging mass in the right upper chest. Chest computed tomography revealed a mass lesion in the region of the right upper ribs. Ten years prior to this admission, the patient had undergone right lobectomy for lung adenocarcinoma. One year after the surgery, follow-up computed tomography had revealed tumor recurrence in the mediastinal and supraclavicular lymph nodes, and the patient had been treated by chemoradiotherapy. Thereafter, regular follow-up had revealed no evidence of recurrence of the non-small-cell lung cancer. Histopathological findings revealed proliferation of spindle-shaped malignant tumor cells in a background of osteoid, consistent with the diagnosis of osteosarcoma. The location of the tumor was consistent with the radiation field. Based on the clinicopathological findings, the patient was diagnosed as having secondary osteosarcoma occurring as a result of the chemoradiotherapy administered previously for the recurrent non-small-cell lung cancer. Unfortunately, the patient died of rapid progression of the osteosarcoma within a week of admission to the hospital. The autopsy revealed contiguous invasion by the tumor of the heart, with massive thrombus formation. The peripheral pulmonary arteries were diffusely occluded by metastatic tumors. Our case serves to highlight the risk of development of secondary sarcoma as a life-threatening late complication after chemoradiotherapy for locally advanced non-small-cell lung cancer, even after complete cure of the primary tumor. PMID:24338556

  7. Image-Guided Hypofractionated Radiation Therapy With Stereotactic Body Radiation Therapy Boost and Combination Chemotherapy in Treating Patients With Stage II-III Non-Small Cell Lung Cancer That Cannot Be Removed By Surgery

    Science.gov (United States)

    2016-09-07

    Adenocarcinoma of the Lung; Adenosquamous Cell Lung Cancer; Large Cell Lung Cancer; Recurrent Non-small Cell Lung Cancer; Squamous Cell Lung Cancer; Stage IIA Non-small Cell Lung Cancer; Stage IIB Non-small Cell Lung Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer

  8. Nonsurgical combined modality therapies in non-small cell lung cancer

    International Nuclear Information System (INIS)

    Nonsurgical combined approaches of non-small cell lung cancer represent a concept that has only been investigated so far with chemotherapy and radiation therapy. Thoracic irradiation of locoregional disease is associated with a high rate of local control and a 5-10% long-term (5-year) survival; however, distant metastases remain the main cause of failure. This observation suggests that the tumor is often microscopically disseminated at the time of diagnosis. Systemic therapy therefore must be associated to radiation therapy to try to control both the undetectable metastases and the local disease. However, the results reported so far have been disappointing, probably because of the modest activity of the available chemotherapy. Further progress with the combined approach requires new developments in the chemotherapy of non-small cell lung cancer, particularly the introduction of new active drugs.67 references

  9. Expressions and Significance of TIMP-3 and mtp53 in Non-small Cell Lung Cancer

    OpenAIRE

    Zhang, Shangfu; Jie LI; Guo, Jia; Yang, Hong

    2012-01-01

    Background and objective Tissue inhibitor of metalloproteinase-3 (TIMP-3) can regulate tumor infiltration and metastasis through multiple channels and is likely associated with mutant-type p53 (mtp53). This study detected the expressions of TIMP-3 and mtp53 in non-small cell lung cancer (NSCLC) and lymph node metastasis using tissue microarray and evaluated their significance. Methods TIMP-3 and mtp53 expressions were detected in 288 cases of NSCLC (NSCLC group), 106 cases of metastatic carci...

  10. ABCC3 as a marker for multidrug resistance in non-small cell lung cancer

    OpenAIRE

    Yanbin Zhao; Hailing Lu; An Yan; Yanmei Yang; Qingwei Meng; Lichun Sun; Hui Pang; Chunhong Li; Xiaoqun Dong; Li Cai

    2013-01-01

    Multidrug resistance (MDR) contributes to the failure of chemotherapy and high mortality in non-small cell lung cancer (NSCLC). We aim to identify MDR genes that predict tumor response to chemotherapy. 199 NSCLC fresh tissue samples were tested for chemosensitivity by MTT assay. cDNA microarray was done with 5 samples with highest resistance and 6 samples with highest sensitivity. Expression of ABCC3 mRNA and protein was detected by real-time PCR and immunohistochemisty, respectively. The ass...

  11. Effect of cryoablation sequential chemotherapy on patients with advanced non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    Shu-Hui Yao

    2016-01-01

    Objective:To evaluate the effect of cryoablation sequential chemotherapy on patients with advanced non-small cell lung cancer.Methods:A total of 39 cases with advanced non-small cell lung cancer who received cryoablation sequential chemotherapy and 39 cases with advanced non-small cell lung cancer who received chemotherapy alone were selected and enrolled in sequential group and control group, disease progression and survival of two groups were followed up, and contents of tumor markers and angiogenesis molecules in serum as well as contents of T-lymphocyte subsets in peripheral blood were detected.Results:Progression-free survival and median overall survival (mOS) of sequential group were longer than those of control group, and cumulative cases of tumor progression at various points in time were significantly less than those of control group (P<0.05); 1 month after treatment, serum tumor markers CEA, CYFRA21-1 and NSE contents, serum angiogenesis molecules PCDGF, VEGF and HDGF contents as well as CD3+CD4-CD8+CD28-T cell content in peripheral blood of sequential group were significantly lower than those of control group (P<0.05), and contents of CD3+CD4+CD8-T cell and CD3+CD4-CD8+CD28+T cell in peripheral blood were higher than those of control group (P<0.05).Conclusions:Cryoablation sequential chemotherapy can improve the prognosis of patients with advanced non-small cell lung cancer, delay disease progression, prolong survival time, inhibit angiogenesis and improve immune function.

  12. 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...

  13. Optimal Therapeutic Strategy for Non-small Cell Lung Cancer with Mutated Epidermal Growth Factor Receptor

    Directory of Open Access Journals (Sweden)

    Zhong SHI

    2015-02-01

    Full Text Available Although epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs have been widely used in non-small cell lung cancer (NSCLC patients, it is still controversial about how to combine EGFR-TKI with chemotherapy and other targeted drugs. We have made a summary on the current therapeutic models of EGFR-TKI combined with chemotherapy/bevacizumab in this review and aimed to find the optimal therapeutic strategy for NSCLC patients with EGFR mutation.

  14. The ALK inhibitor ceritinib overcomes crizotinib resistance in non-small cell lung cancer

    OpenAIRE

    Friboulet, Luc; Li, Nanxin; Katayama, Ryohei; Lee, Christian C.; Gainor, Justin F.; Crystal, Adam S.; Michellys, Pierre-Yves; Awad, Mark M.; Yanagitani, Noriko; Kim, Sungjoon; Pferdekamper, AnneMarie C.; Li, Jie; Kasibhatla, Shailaja; Sun, Frank; Sun, Xiuying

    2014-01-01

    Non-small cell lung cancers (NSCLC) harboring anaplastic lymphoma kinase (ALK) gene rearrangements invariably develop resistance to the ALK tyrosine kinase inhibitor (TKI) crizotinib. Herein, we report the first preclinical evaluation of the next-generation ALK TKI, ceritinib (LDK378) in the setting of crizotinib resistance. Interrogation of in vitro and in vivo models of acquired resistance to crizotinib, including cell lines established from biopsies of crizotinib-resistant NSCLC patients r...

  15. Intratumour variation of biomarker expression by immunohistochemistry in resectable non-small cell lung cancer

    DEFF Research Database (Denmark)

    Jakobsen, Jan Nyrop; Santoni-Rugiu, Eric; Ravn, Jesper;

    2013-01-01

    truly reflect the pattern of biomarker expression. It may also be an important factor in chemo resistance, as tumours with heterogeneous biomarker expression may potentially harbour chemo resistant tumour clones. MATERIALS AND METHODS: Immunohistochemical evaluation of the expression of excision repair...... intratumour heterogeneity in 33-87% of tumours examined. This heterogeneity may influence results in studies investigating the therapeutic impact of predictive biomarkers in non-small cell lung cancer (NSCLC)....

  16. Vinorelbine in Advanced Non-Small Cell Lung Cancer: A Pharmacoeconomic Review

    OpenAIRE

    Allan J. Coukell; Stuart Noble; Diana Faulds

    1999-01-01

    Vinorelbine is a semisynthetic vinca alkaloid that is effective against advanced non-small cell lung cancer (NSCLC). Myelosuppression is the primary dose-limiting toxicity; vinorelbine is otherwise relatively well tolerated. Two studies assessed the cost effectiveness of vinorelbine with or without cisplatin based primarily on data from a phase III comparison with vindesine plus cisplatin. Survival and cost data from this study were supplemented with those from other sources. One model simula...

  17. Maintaining clarity: Review of maintenance therapy in non-small cell lung cancer

    OpenAIRE

    Dearing, Kristen R; Sangal, Ashish; Weiss, Glen J

    2014-01-01

    The purpose of this article is to review the role of maintenance therapy in the treatment of advanced non-small cell lung cancer (NSCLC). A brief overview about induction chemotherapy and its primary function in NSCLC is provided to address the basis of maintenance therapies foundation. The development of how maintenance therapy is utilized in this population is discussed and current guidelines for maintenance therapy are reviewed. Benefits and potential pitfalls of maintenance therapy are ad...

  18. Association between MGMT Promoter Methylation and Non-Small Cell Lung Cancer: A Meta-Analysis

    OpenAIRE

    Changmei Gu; Jiachun Lu; Tianpen Cui; Cheng Lu; Hao Shi; Wenmao Xu; Xueli Yuan; Xiaobo Yang; Yangxin Huang; Meixia Lu

    2013-01-01

    BACKGROUND: O(6)-methylguanine-DNA methyltransferase (MGMT) is one of most important DNA repair enzyme against common carcinogens such as alkylate and tobacco. Aberrant promoter methylation of the gene is frequently observed in non-small cell lung cancer (NSCLC). However, the importance of epigenetic inactivation of the gene in NSCLC published in the literature showed inconsistence. We quantified the association between MGMT promoter methylation and NSCLC using a meta-analysis method. METHODS...

  19. Role of Chemokines in Non-Small Cell Lung Cancer: Angiogenesis and Inflammation

    OpenAIRE

    Rivas-Fuentes, Selma; Salgado-Aguayo, Alfonso; Pertuz Belloso, Silvana; Gorocica Rosete, Patricia; Alvarado-Vásquez, Noé; Aquino-Jarquin, Guillermo

    2015-01-01

    Non-small cell lung cancer (NSCLC) is one of the most common types of aggressive cancer. The tumor tissue, which shows an active angiogenesis, is composed of neoplastic and stromal cells, and an abundant inflammatory infiltrate. Angiogenesis is important to support tumor growth, while infiltrating cells contribute to the tumor microenvironment through the secretion of growth factors, cytokines and chemokines, important molecules in the progression of the disease. Chemokines are important in d...

  20. New treatment options for ALK+ advanced non-small-cell lung cancer: critical appraisal of ceritinib

    OpenAIRE

    Rothschild SI

    2016-01-01

    Sacha I Rothschild Department of Internal Medicine, Medical Oncology, University Hospital Basel, Basel, Switzerland Abstract: Rearrangements in ALK gene and EML4 gene were first described in 2007. This genomic aberration is found in about 2%–8% of non-small-cell lung cancer (NSCLC) patients. Crizotinib was the first ALK tyrosine kinase inhibitor licensed for the treatment of metastatic ALK-positive NSCLC based on a randomized Phase III trial. Despite the initial treatment response of ...

  1. 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...

  2. 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\\

  3. Personalizing Therapy with Targeted Agents in Non-Small Cell Lung Cancer

    OpenAIRE

    DIENSTMANN, RODRIGO; Martinez, Pablo; Felip, Enriqueta

    2011-01-01

    In the last 6 years, since the first reports of an association between somatic mutations in epidermal growth factor receptor (EGFR) exons 19 and 21 and response to EGFR tyrosine kinase inhibitors (TKIs), treatment of non-small cell lung cancer (NSCLC) has changed dramatically. Based on laboratory and clinical observations, investigators have anticipated that these mutations could be predictive of response to EGFR TKIs and numerous studies have confirmed that the presence of mutation was assoc...

  4. Osteopontin is a prognostic biomarker in non-small cell lung cancer

    OpenAIRE

    Rud, Ane Kristine Kongsgaard; Pedersen, Kjetil Boye; Øijordsbakken, Miriam; Lund-Iversen, Marius; Halvorsen, Ann Rita; Solberg, Steinar; Berge, Gisle; Helland, Åslaug; Brustugun, Odd Terje; Mælandsmo, Gunhild

    2013-01-01

    Background: In a previously published report we characterized the expression of the metastasis-associated proteins S100A4, osteopontin (OPN) and ephrin-A1 in a prospectively collected panel of non-small cell lung cancer (NSCLC) tumors. The aim of the present follow-up study was to investigate the prognostic impact of these potential biomarkers in the same patient cohort. In addition, circulating serum levels of OPN were measured and single nucleotide polymorphisms (SNP) in the −44...

  5. Review of the current targeted therapies for non-small-cell lung cancer

    OpenAIRE

    Nguyen, Kim-Son H.; Neal, Joel W.; Wakelee, Heather

    2014-01-01

    The last decade has witnessed the development of oncogene-directed targeted therapies that have significantly changed the treatment of non-small-cell lung cancer (NSCLC). In this paper we review the data demonstrating efficacy of gefitinib, erlotinib, and afatinib, which target the epidermal growth factor receptor (EGFR), and crizotinib which targets anaplastic lymphoma kinase (ALK). We discuss the challenge of acquired resistance to these small-molecular tyrosine kinase inhibitors and review...

  6. Advances in Treatment of Brain Metastases 
from Primary Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Gen LIN

    2014-12-01

    Full Text Available Metastatic tumors involving the brain are an important complication in the overall management of non-small cell lung cancers. Surgery and radiation remain the cornerstones of the therapy, however, the burgeoning knowledge of tumor biology has facilitated the entry of systemically administered therapies into the clinic. This review mainly summarizes the current applications of these data to surgery, radiation therapy, chemotherapy and targeted therapy.

  7. Natural History of Non-Small-Cell Lung Cancer with Bone Metastases

    OpenAIRE

    Santini Daniele; Barni Sandro; Intagliata Salvatore; Falcone Alfredo; Ferraù Francesco; Galetta Domenico; Moscetti Luca; La Verde Nicla; Ibrahim Toni; Petrelli Fausto; Vasile Enrico; Ginocchi Laura; Ottaviani Davide; Longo Flavia; Ortega Cinzia

    2015-01-01

    We conducted a large, multicenter, retrospective survey aimed to explore the impact of tumor bone involvement in Non-Small Cell Lung Cancer.Data on clinical-pathology, skeletal outcomes and bone-directed therapies for 661 deceased patients with evidence of bone metastasis were collected and statistically analyzed. Bone metastases were evident at diagnosis in 57.5% of patients. In the remaining cases median time to bone metastases appearance was 9 months. Biphosphonates were administered in 59...

  8. Clinical utility of Circulating Tumor Cells in ALK-Positive Non-Small-Cell Lung Cancer

    OpenAIRE

    Vincent eFaugeroux; Emma ePailler; Nathalie eAuger; Meilissa eTaylor; Françoise eFarace

    2014-01-01

    The advent of rationally targeted therapies such as small-molecule tyrosine kinase inhibitors (TKIs) has considerably transformed the therapeutic management of a subset of patients with non-small cell lung cancer (NSCLC) harboring defined molecular abnormalities. When such genetic molecular alterations are detected the use of specific TKI has demonstrated better results (overall response rate (ORR), progression free survival (PFS)) compared to systemic therapy. However the detection of such m...

  9. Clinical Utility of Circulating Tumor Cells in ALK-Positive Non-Small-Cell Lung Cancer

    OpenAIRE

    Faugeroux, Vincent; Pailler, Emma; Auger, Nathalie; Taylor, Melissa; Farace, Françoise

    2014-01-01

    The advent of rationally targeted therapies such as small-molecule tyrosine kinase inhibitors (TKIs) has considerably transformed the therapeutic management of a subset of patients with non-small-cell lung cancer (NSCLC) harboring defined molecular abnormalities. When such genetic molecular alterations are detected the use of specific TKI has demonstrated better results (overall response rate, progression free survival) compared to systemic therapy. However, the detection of such molecular ab...

  10. Advances in radiological staging of non-small cell lung cancer (NSCLC)

    OpenAIRE

    Rankin, S. C.

    2004-01-01

    Imaging plays a vital role in the management of non-small cell lung cancer including diagnosis, staging and follow-up. CT and magnetic resonance imaging (MRI) are used in staging and provide anatomical information but have well known limitations in differentiating reactive from malignant nodes, and fibrosis from active disease and in defining the extent of invasion. MRI with its superior soft tissue contrast provides optimal information on brachial plexus and central nervous system involvemen...

  11. The practice of cardiothoracic surgeons in the perioperative staging of non-small cell lung cancer.

    OpenAIRE

    Tsang, G M; Watson, D C

    1992-01-01

    BACKGROUND: The treatment and prognosis of non-small cell lung cancer, and assessment of the results of treatment, depend on accurate perioperative staging. The extent to which this is carried out in the United Kingdom is unknown. METHODS: A postal questionnaire survey was undertaken in 1990 to determine the perioperative staging practices of cardiothoracic surgeons in the United Kingdom. RESULTS: Replies from 77 surgeons, who between them performed about 4833 pulmonary resections a year for ...

  12. Progress of Treatments in Non-small Cell Lung Cancer with Brain Metastases

    OpenAIRE

    MA, CHUNHUA; Jiang, Rong

    2012-01-01

    Brain metastases is one of the most common complications of non-small cell lung cancer, whole brain radiotherapy (WBRT), stereotactic radiosurgery (SRS), surgery and chemotherapy are standard methods in the treatment of brain metastases. But the effect of those treatments are still sad. Comprehensive treatment can prolong the survival and improve the quality of life. Recently, the improvement of technology, targeted therapy, survival time and the quality of life are in increasingly concerned....

  13. 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...

  14. 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...

  15. 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

  16. RET-rearranged non-small-cell lung carcinoma: a clinicopathological and molecular analysis

    OpenAIRE

    Tsuta, K; Kohno, T.; Yoshida, A.; Shimada, Y.; Asamura, H.; Furuta, K; Kushima, R

    2014-01-01

    Background: To elucidate clinicopathological characteristics of non-small-cell lung carcinoma (NSCLC) cases carrying RET rearrangements causing oncogenic fusions to identify responders to therapy with RET tyrosine kinase inhibitors. Methods: We investigated 1874 patients with carcinomas, including 1620 adenocarcinomas (ADCs), 203 squamous cell carcinomas (SCCs), 8 large cell carcinomas, and 43 sarcomatoid carcinomas (SACs). Fluorescence in situ hybridisation (FISH) and/or reverse transcriptio...

  17. Prospective randomized clinical trial of non-small cell lung cancer for intraoperative radiotherapy

    International Nuclear Information System (INIS)

    Objective: To analyse the long-term effect of non-small cell lung cancer treated with either postoperative irradiation(group A) or intraoperative radiotherapy(IORT) followed by postoperative irradiation( group B). Methods: 154 patients with non-small cell lung carcinoma were randomized into two groups(groups A and B) with 77 patients in each. There were 134 squamous, 17 adenocarcinoma and 3 adeno-squamous carcinoma. Seventeen patients had stage I, 76 stage II and 61 stage III lesions. The dose of postoperative irradiation in both groups was DT40-60 Gy. In group B, the IORT dose was 15-25 Gy, delivered by 9-16 MeV electrons. Results: The local control rate was 49% and 62% in groups A and B, respectively (P0.05). Sixteen patients died of radiotherapy-induced complication: 2 in group A and 14 in group B. Conclusions: Intraoperative radiotherapy followed by postoperative irradiation can enhance the local control rate of non-small cell lung cancer but can not improve the long term survival, The high complication mortality rate of IORT (18%) in contrast to that (3%) of postoperative radiotherapy is worth noticing. (authors)

  18. B7-H6 expression in non-small cell lung cancers

    OpenAIRE

    Zhang, Xiuqin; Zhang, Guangbo; Qin, Yan; Bai, Ruizhen; Huang, Jianan

    2014-01-01

    B7 family has been known to be a negative regulator of immunity response in patients with lung cancer. B7-H6 as a novel identified member of B7 family is found to trigger natural killer (NK) cell cytotoxicity and cytokine secretion by binding natural cytotoxicity receptor NKp30. Up until now, no investigations have been made about B7-H6 expression in lung cancer. We present the result of the B7-H6 prognostic value in 65 non-small cell lung cancer (NSCLC) tissues and 65 matched adjacent non-tu...

  19. Wif1 Hypermethylation as Unfavorable Prognosis of Non-Small Cell Lung Cancers with EGFR Mutation

    OpenAIRE

    Lee, Su Man; Park, Jae Yong; Kim, Dong Sun

    2013-01-01

    Lung cancer is a leading cause of cancer-related mortality across the world and tobacco smoking is the major risk factor. The Wnt signaling pathway is known to be involved in smoke-induced tumorigenesis in the lung. Promoter hypermethylation of Wnt inhibitory factor 1 (Wif1) has become a common event in a number of human tumors. Using a methylation-specific PCR, hypermethylation of the Wif1 gene promoter was evaluated in 139 primary non-small cell lung cancers (NSCLCs) and its correlation wit...

  20. ANALYSIS OF IMMUNOREGULATORY BIOMARKERS IN NON-SMALL CELL LUNG CANCER

    OpenAIRE

    USÓ MARCO, MARTA

    2015-01-01

    [EN] Lung cancer is the leading cause of cancer-related death worldwide, and is the third most common cancer type; it can be classified into two subgroups based on histology: non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC). The 5-year survival still remains poor and despite the existence of several distinct tumour phenotypes, therapeutic decisions are mainly based on clinical features such as stage or performance status. This highlights the need for new diagnostic and pro...

  1. Advances of Driver Gene and Targeted Therapy of Non-small Cell Lung Cancer

    OpenAIRE

    Zhang, Dan; Huang, Yan; Wang, Hongyang

    2014-01-01

    Lung cancer is the leading cause of cancer-related mortality in the worldwide. The discovery of drive gene makes tumor treatment is no longer "one-size-fits-all". Targeted therapy to change the present situation of cancer drugs become "bullet" with eyes, the effect is visible and bring a revolution in the treatment of lung cancer. The diver gene and targeted therapy have became the new cedule of non-small cell lung cancer (NSCLC). Society of Clinical Oncology (ASCO) has showed 11 kinds of div...

  2. [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

  3. Non-small-cell lung cancer resectability: diagnostic value of PET/MR.

    OpenAIRE

    Fraioli, F.; Screaton, N J; Janes, S. M.; Win, T; Menezes, L.; Kayani, I.; Syed, R; Zaccagna, F.; O'Meara, C.; Barnes, A.; Bomanji, J B; Punwani, S.; Groves, A. M.

    2014-01-01

    Purpose To assess the diagnostic performance of PET/MR in patients with non-small-cell lung cancer. Methods Fifty consecutive consenting patients who underwent routine 18F-FDG PET/CT for potentially radically treatable lung cancer following a staging CT scan were recruited for PET/MR imaging on the same day. Two experienced readers, unaware of the results with the other modalities, interpreted the PET/MR images independently. Discordances were resolved in consensus. PET/MR TNM staging was com...

  4. [Targeted Therapy and Immunotherapy for Non-small Cell Lung Cancer 
with Brain Metastasis].

    Science.gov (United States)

    Song, Qi; Jiao, Shunchang; Li, Fang

    2016-08-20

    Brain metastasis, a common complication of non-small cell lung cancer (NSCLC) with an incidence rate of 30%-50%, significantly affects the patients' quality of life. The prognosis of patients of NSCLC with brain metastasis is extremely poor, the average median survival is only 1 m-2 m without treatment. The targeted therapy based on lung cancer driven gene is a new treatment. Besides, the immunotherapy which can enhance the effect of anti-cancer by simulating the immune system is a new approach. The combination of targeted therapy and immunotherapy can greatly benefit patients in clinical work. PMID:27561803

  5. [Stereotactic radiotherapy is established treatment in localized non-small cell lung cancer].

    Science.gov (United States)

    Sailas, Liisa; Virsunen, Heli

    2016-01-01

    Surgery has been the standard treatment in localized non-small cell lung cancer. Some of the early stage lung cancer patients are not suitable for surgery owing to associated diseases or refusing surgery. Ninety percent of untreated patients die within five years. Stereotactic ablative radiotherapy is a technique in which highly focused radiation treatment is given at a couple of high single doses to the tumor region. The treatment results in an average of 90% local control of the cancer, and the adverse effects are minor. Treatment outcome is equivalent to those of surgical therapy and is better than obtained with conventional external radiation therapy. PMID:27132296

  6. Mitochondrial Variations in Non-Small Cell Lung Cancer (NSCLC) Survival

    OpenAIRE

    Zhaoxi Wang; Sojung Choi; Jinseon Lee; Yen-Tsung Huang; Feng Chen; Yang Zhao; Xihong Lin; Donna Neuberg; Jhingook Kim; Christiani, David C.

    2015-01-01

    Mutations in the mtDNA genome have long been suspected to play an important role in cancer. Although most cancer cells harbor mtDNA mutations, the question of whether such mutations are associated with clinical prognosis of lung cancer remains unclear. We resequenced the entire mitochondrial genomes of tumor tissue from a population of 250 Korean patients with non-small cell lung cancer (NSCLC). Our analysis revealed that the haplogroup (D/D4) was associated with worse overall survival (OS) o...

  7. Proton Beam Therapy for Non-Small Cell Lung Cancer: Current Clinical Evidence and Future Directions

    Energy Technology Data Exchange (ETDEWEB)

    Berman, Abigail T., E-mail: abigail.berman@uphs.upenn.edu [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA 19104 (United States); James, Sara St.; Rengan, Ramesh [Department of Radiation Oncology, University of Washington Medical Center, Seattle, WA 98195 (United States)

    2015-07-02

    Lung cancer is the leading cancer cause of death in the United States. Radiotherapy is an essential component of the definitive treatment of early-stage and locally-advanced lung cancer, and the palliative treatment of metastatic lung cancer. Proton beam therapy (PBT), through its characteristic Bragg peak, has the potential to decrease the toxicity of radiotherapy, and, subsequently improve the therapeutic ratio. Herein, we provide a primer on the physics of proton beam therapy for lung cancer, present the existing data in early-stage and locally-advanced non-small cell lung cancer (NSCLC), as well as in special situations such as re-irradiation and post-operative radiation therapy. We then present the technical challenges, such as anatomic changes and motion management, and future directions for PBT in lung cancer, including pencil beam scanning.

  8. Proton Beam Therapy for Non-Small Cell Lung Cancer: Current Clinical Evidence and Future Directions

    International Nuclear Information System (INIS)

    Lung cancer is the leading cancer cause of death in the United States. Radiotherapy is an essential component of the definitive treatment of early-stage and locally-advanced lung cancer, and the palliative treatment of metastatic lung cancer. Proton beam therapy (PBT), through its characteristic Bragg peak, has the potential to decrease the toxicity of radiotherapy, and, subsequently improve the therapeutic ratio. Herein, we provide a primer on the physics of proton beam therapy for lung cancer, present the existing data in early-stage and locally-advanced non-small cell lung cancer (NSCLC), as well as in special situations such as re-irradiation and post-operative radiation therapy. We then present the technical challenges, such as anatomic changes and motion management, and future directions for PBT in lung cancer, including pencil beam scanning

  9. Proton Beam Therapy for Non-Small Cell Lung Cancer: Current Clinical Evidence and Future Directions

    Directory of Open Access Journals (Sweden)

    Abigail T. Berman

    2015-07-01

    Full Text Available Lung cancer is the leading cancer cause of death in the United States. Radiotherapy is an essential component of the definitive treatment of early-stage and locally-advanced lung cancer, and the palliative treatment of metastatic lung cancer. Proton beam therapy (PBT, through its characteristic Bragg peak, has the potential to decrease the toxicity of radiotherapy, and, subsequently improve the therapeutic ratio. Herein, we provide a primer on the physics of proton beam therapy for lung cancer, present the existing data in early-stage and locally-advanced non-small cell lung cancer (NSCLC, as well as in special situations such as re-irradiation and post-operative radiation therapy. We then present the technical challenges, such as anatomic changes and motion management, and future directions for PBT in lung cancer, including pencil beam scanning.

  10. Veliparib, Cisplatin, and Gemcitabine Hydrochloride in Treating Patients With Advanced Biliary, Pancreatic, Urothelial, or Non-Small Cell Lung Cancer

    Science.gov (United States)

    2013-07-01

    Advanced Adult Primary Liver Cancer; Localized Unresectable Adult Primary Liver Cancer; Metastatic Transitional Cell Cancer of the Renal Pelvis and Ureter; Regional Transitional Cell Cancer of the Renal Pelvis and Ureter; Stage III Bladder Cancer; Stage III Pancreatic Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Bladder Cancer; Stage IV Non-small Cell Lung Cancer; Stage IV Pancreatic Cancer; Transitional Cell Carcinoma of the Bladder; Unresectable Extrahepatic Bile Duct Cancer; Unresectable Gallbladder Cancer

  11. What are we able to achieve in the treatment of metastatic non-small cell lung cancer today?

    International Nuclear Information System (INIS)

    Several meta analyses published in the beginning of the 1990s confirmed effectivity of chemotherapy in comparison with best supportive care in advanced/metastatic non-small cell lung cancer: the median survival time was prolonged by 6 weeks - 2 months, and the number of patients surviving one year increased by about 10%. Influence of these meta analyses on perception of non-small cell lung cancer chemotherapy as an indicated but less effective treatment continues until today in some extend. Image of the advanced non-small cell lung cancer treatment has improved during the last years markedly, mainly due to new treatment possibilities discussed in this case report. (author)

  12. Prognostic impact of serum albumin levels on the recurrence of stage I non-small cell lung cancer

    OpenAIRE

    Ying Jin; Li Zhao; Fang Peng

    2013-01-01

    Objective: Patients with stage I non-small cell lung cancer who have undergone complete surgical resection harbor a 30% risk for tumor recurrence. Thus, the identification of factors that are predictive for tumor recurrence is urgently needed. The aim of this study was to test the prognostic value of serum albumin levels on tumor recurrence in patients with stage I non-small cell lung cancer. Methods: Stage I non-small cell lung cancer patients who underwent complete surgical resection of the...

  13. Therapeutic effects of gensenoside-Rg3 combined with radiotherapy on advanced non-small cell lung cancer

    International Nuclear Information System (INIS)

    Objective: To study the efficacy and toxicity of gensenoside-Rg3 (Rg3) combined with radiotherapy on non-small cell lung cancer (NSCLC) at advanced stages (Ⅲ and Ⅴ). Methods: Sixty-three patients with stage Ⅲ or Ⅳ NSCLC were divided randomly into two groups:treatment group (n=35) treated with Rg3 combined with radiotherapy and control group (n=28) treated with radiotherapy alone. The efficacy and side effects were compared after the treatment. Results: The response rate (CR + PR) of the treatment group was 57.14%, significantly higher than that of the control group (32.14%, χ2 =3.91, P<0.05). The median survival time of the treatment group was 14.2 months, significantly longer than that of the control group (11.2 months, χ2=2.07, P<0.05). The one-year survival rate of the treatment group was 62.86%, significantly higher than that of the control group (39.29%, χ2=4.40, P<0.05). The incidence rates of side effects of the treatment group were all lower than those of the control group, but there were not significant difference. Conclusions: Gensenoside-Rg3 combined with radiotherapy is effective for advanced stage NSCLC, with attenuation and synergistic effects. (authors)

  14. Genomic profiling toward precision medicine in non-small cell lung cancer: getting beyond EGFR

    Directory of Open Access Journals (Sweden)

    Richer AL

    2015-02-01

    Full Text Available Amanda L Richer,1 Jacqueline M Friel,1 Vashti M Carson,2 Landon J Inge,1 Timothy G Whitsett2 1Norton Thoracic Institute, St Joseph’s Hospital and Medical Center, 2Cancer and Cell Biology Division, Translational Genomics Research Institute, Phoenix, AZ, USA Abstract: Lung cancer remains the leading cause of cancer-related mortality worldwide. The application of next-generation genomic technologies has offered a more comprehensive look at the mutational landscape across the different subtypes of non-small cell lung cancer (NSCLC. A number of recurrent mutations such as TP53, KRAS, and epidermal growth factor receptor (EGFR have been identified in NSCLC. While targeted therapeutic successes have been demonstrated in the therapeutic targeting of EGFR and ALK, the majority of NSCLC tumors do not harbor these genomic events. This review looks at the current treatment paradigms for lung adenocarcinomas and squamous cell carcinomas, examining genomic aberrations that dictate therapy selection, as well as novel therapeutic strategies for tumors harboring mutations in KRAS, TP53, and LKB1 which, to date, have been considered “undruggable”. A more thorough understanding of the molecular alterations that govern NSCLC tumorigenesis, aided by next-generation sequencing, will lead to targeted therapeutic options expected to dramatically reduce the high mortality rate observed in lung cancer. Keywords: non-small cell lung cancer, precision medicine, epidermal growth factor receptor, Kirsten rat sarcoma viral oncogene homolog, serine/threonine kinase 11, tumor protein p53

  15. A Preliminary Analysis of Non-small Cell Lung Cancer Biomarkers in Serum

    Institute of Scientific and Technical Information of China (English)

    XUE-YUAN XIAO; YING TANG; XIU-PING WEI; DA-CHENG HE

    2003-01-01

    Objective To identify potential serum biomarkers that could be used to discriminate lungcancers from normal. Methods Proteomic spectra of twenty-eight serum samples from patientswith non-small cell lung cancer and twelve from normal individuals were generated by SELDI(Surfaced Enhanced Laser Desorption/Ionization) Mass Spectrometry. Anion-exchange columns wereused to fractionate the sera into 6 designated pH groups. Two different types of protein chip arrays,IMAC-Cu and WCX2, were employed. Samples were examined in PBSII Protein Chip Reader(Ciphergen Biosystem Inc) and the discriminatory profiling between cancer and normal samples wasanalyzed with Biomarker Pattern software. Results Five distinct potential lung cancer biomarkerswith higher sensitivity and specificity were found, with four common biomarkers in both IMAC-Cuand WCX2 chip; the remaining biomarker occurred only in WCX2 chip. Two biomarkers wereup-regulated while three biomarkers were down-regulated in the serum samples from patients withnon-small cell lung cancer. The sensitivities provided by the individual biomarkers were 75%-96.43%and specificities were 75%-100%. Conclusions The preliminary results suggest that serum is acapable resource for detecting specific non-small cell lung cancer biomarkers. SELDI massspectrometry is a useful tool for the detection and identification of new potential biomarker ofnon-small cell lung cancer in serum.

  16. Role of positron emission tomography-computed tomography in non-small cell lung cancer.

    Science.gov (United States)

    Garg, Pankaj Kumar; Singh, Saurabh Kumar; Prakash, Gaurav; Jakhetiya, Ashish; Pandey, Durgatosh

    2016-03-26

    Lung cancer is the leading cause of cancer-related mortality worldwide. Non-small cell carcinoma and small cell carcinoma are the main histological subtypes and constitutes around 85% and 15% of all lung cancer respectively. Multimodality treatment plays a key role in the successful management of lung cancer depending upon the histological subtype, stage of disease, and performance status. Imaging modalities play an important role in the diagnosis and accurate staging of the disease, in assessing the response to neoadjuvant therapy, and in the follow-up of the patients. Last decade has witnessed voluminous upsurge in the use of positron emission tomography-computed tomography (PET-CT); role of PET-CT has widened exponentially in the management of lung cancer. The present article reviews the role of 18-fluoro-deoxyglucose PET-CT in the management of non small cell lung cancer with emphasis on staging of the disease and the assessment of response to neoadjuvant therapy based on available literature. PMID:27018223

  17. Downregulation of the TGFβ Pseudoreceptor BAMBI in Non-Small Cell Lung Cancer Enhances TGFβ Signaling and Invasion.

    Science.gov (United States)

    Marwitz, Sebastian; Depner, Sofia; Dvornikov, Dmytro; Merkle, Ruth; Szczygieł, Magdalena; Müller-Decker, Karin; Lucarelli, Philippe; Wäsch, Marvin; Mairbäurl, Heimo; Rabe, Klaus F; Kugler, Christian; Vollmer, Ekkehard; Reck, Martin; Scheufele, Swetlana; Kröger, Maren; Ammerpohl, Ole; Siebert, Reiner; Goldmann, Torsten; Klingmüller, Ursula

    2016-07-01

    Non-small cell lung cancer (NSCLC) is characterized by early metastasis and has the highest mortality rate among all solid tumors, with the majority of patients diagnosed at an advanced stage where curative therapeutic options are lacking. In this study, we identify a targetable mechanism involving TGFβ elevation that orchestrates tumor progression in this disease. Substantial activation of this pathway was detected in human lung cancer tissues with concomitant downregulation of BAMBI, a negative regulator of the TGFβ signaling pathway. Alterations of epithelial-to-mesenchymal transition (EMT) marker expression were observed in lung cancer samples compared with tumor-free tissues. Distinct alterations in the DNA methylation of the gene regions encoding TGFβ pathway components were detected in NSCLC samples compared with tumor-free lung tissues. In particular, epigenetic silencing of BAMBI was identified as a hallmark of NSCLC. Reconstitution of BAMBI expression in NSCLC cells resulted in a marked reduction of TGFβ-induced EMT, migration, and invasion in vitro, along with reduced tumor burden and tumor growth in vivo In conclusion, our results demonstrate how BAMBI downregulation drives the invasiveness of NSCLC, highlighting TGFβ signaling as a candidate therapeutic target in this setting. Cancer Res; 76(13); 3785-801. ©2016 AACR. PMID:27197161

  18. CXCR4/CXCL12 in Non-Small-Cell Lung Cancer Metastasis to the Brain

    Directory of Open Access Journals (Sweden)

    Sebastiano Cavallaro

    2013-01-01

    Full Text Available Lung cancer represents the leading cause of cancer-related mortality throughout the world. Patients die of local progression, disseminated disease, or both. At least one third of the people with lung cancer develop brain metastases at some point during their disease, even often before the diagnosis of lung cancer is made. The high rate of brain metastasis makes lung cancer the most common type of tumor to spread to the brain. It is critical to understand the biologic basis of brain metastases to develop novel diagnostic and therapeutic approaches. This review will focus on the emerging data supporting the involvement of the chemokine CXCL12 and its receptor CXCR4 in the brain metastatic evolution of non-small-cell lung cancer (NSCLC and the pharmacological tools that may be used to interfere with this signaling axis.

  19. Proton Beam Therapy of Stage II and III Non-Small-Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Nakayama, Hidetsugu, E-mail: hnakayam@tokyo-med.ac.jp [Proton Medical Research Center, University of Tsukuba Graduate School of Comprehensive Human Sciences, Tsukuba, Ibaraki (Japan); Department of Radiation Oncology, Tokyo Medical University, Shinjuku, Tokyo (Japan); Satoh, Hiroaki [Department of Respiratory Medicine, University of Tsukuba Graduate School of Comprehensive Human Sciences, Tsukuba, Ibaraki (Japan); Sugahara, Shinji [Proton Medical Research Center, University of Tsukuba Graduate School of Comprehensive Human Sciences, Tsukuba, Ibaraki (Japan); Department of Radiation Oncology, Tokyo Medical University, Shinjuku, Tokyo (Japan); Kurishima, Koichi [Department of Respiratory Medicine, University of Tsukuba Graduate School of Comprehensive Human Sciences, Tsukuba, Ibaraki (Japan); Tsuboi, Koji; Sakurai, Hideyuki [Proton Medical Research Center, University of Tsukuba Graduate School of Comprehensive Human Sciences, Tsukuba, Ibaraki (Japan); Ishikawa, Shigemi [Department of Thoracic Surgery, University of Tsukuba Graduate School of Comprehensive Human Sciences, Tsukuba, Ibaraki (Japan); Tokuuye, Koichi [Proton Medical Research Center, University of Tsukuba Graduate School of Comprehensive Human Sciences, Tsukuba, Ibaraki (Japan); Department of Radiation Oncology, Tokyo Medical University, Shinjuku, Tokyo (Japan)

    2011-11-15

    Purpose: The present retrospective study assessed the role of proton beam therapy (PBT) in the treatment of patients with Stage II or III non-small-cell lung cancer who were inoperable or ineligible for chemotherapy because of co-existing disease or refusal. Patients and Methods: Between November 2001 and July 2008, PBT was given to 35 patients (5 patients with Stage II, 12 with Stage IIIA, and 18 with Stage IIIB) whose median age was 70.3 years (range, 47.4-85.4). The median proton dose given was 78.3 Gy (range, 67.1-91.3) (relative biologic effectiveness). Results: Local progression-free survival for Stage II-III patients was 93.3% at 1 year and 65.9% at 2 years during a median observation period of 16.9 months. Four patients (11.4%) developed local recurrence, 13 (37.1%) developed regional recurrence, and 7 (20.0%) developed distant metastases. The progression-free survival rate for Stage II-III patients was 59.6% at 1 year and 29.2% at 2 years. The overall survival rate of Stage II-III patients was 81.8% at 1 year and 58.9% at 2 years. Grade 3 or greater toxicity was not observed. A total of 15 patients (42.9%) developed Grade 1 and 6 (17.1%) Grade 2 toxicity. Conclusion: PBT for Stage II-III non-small-cell lung cancer without chemotherapy resulted in good local control and low toxicity. PBT has a definite role in the treatment of patients with Stage II-III non-small-cell lung cancer who are unsuitable for surgery or chemotherapy.

  20. Gefitinib for Non-small Cell Lung Cancer: A meta Analysis

    Directory of Open Access Journals (Sweden)

    Jiwu GUO

    2011-04-01

    Full Text Available Background and objective Malignant grade and death rate are very high for non-small cell lung cancer, and gefitinib is a new molecule target anticancer drug. The aim of this meta analysis is to evaluate the clinical efficacy and safety of gefitinib for non-small cell lung cancer. Methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL (The Cochrane Library, Issue 8, 2010, PubMed (1966-2010.8, EMBASE (1974-2010.8, CNKI (1994-2010.8, VIP (1989-2010.8, and CMD Digital Periodicals (1998-2010.8. Two reviewers independently evaluated the quality of the included studies and extracted the data. Meta-analyses were performed by RevMan 5.0 software. Results Thirteen randomized controlled trials (RCTs involving 6,207 patients were included. The results of meta-analyses showed that: gefitinib showed no remarkable advantage in media survival time, 1 year survival rate, complete response rate (CRR, partial response rate (PRR, stable disease (SD when compared to Placebo, Docetaxel, Cisplatin+Docetaxel, Pemetrexed. Gifitinib could increase overall survival rate compared to Docetaxel, Cisplatin+Docetaxel (RR=1.41, 95%CI: 1.10-1.80; RR=1.93, 95%: 1.26-2.94. When compared to Placebo, Docetaxel, gifitinib could improve life quality of Total-FACT-L improve rate (RR=1.42, 95%CI: 1.16-1.74; RR=1.66, 95%CI: 1.39-1.97. The major adverse event for gifitinib were rash/acne, dry skin, diarrhea. While gifitinib showed lower hematology toxicity. Conclusion Gifitinib shows more superiority for non-small cell lung cancer, and its clinical application is worthy to be advocated.

  1. Pulmonary Artery Agenesis Associated With Emphysema and Multiple Invasive Non-Small Cell Lung Cancers.

    Science.gov (United States)

    Makdisi, George; Edell, Eric S; Maleszewski, Joseph J; Molina, Julian R; Deschamps, Claude

    2015-06-01

    Pulmonary artery (PA) agenesis in the absence of associated cardiac abnormalities is a rare congenital abnormality. It may remain undiagnosed until adulthood when patients present with respiratory symptoms such as hemoptysis, dyspnea, repeated respiratory infections, or pulmonary hypertension. Herein we present a case of a 50-year-old woman who was found to have multiple, morphologically distinct non-small cell lung cancers in association with agenesis of the PA. This instance represents the fourth reported case of such association in the English literature. PMID:26046873

  2. 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...

  3. Chemoradiation treatment of non-small-cell lung cancer oriented to apoptosis induction

    International Nuclear Information System (INIS)

    A comparative analysis of the radiotherapy results in different modes of fractionation with etoposide modification on gamma-therapeutic apparatus and linear accelerator in patients with non-small cell lung cancer. Objective effect and one year survival rates were significantly higher in the cases of accelerated fractionation regimes, while the frequency of radiation pneumonitis and esophagitis was reduced in cases of the treatment on a linear accelerator compared to gamma radiation. Modes of accelerated hyperfractionated combined with etoposide modification are aimed at the induction of ceramide apoptosis pathway, as evidenced by the dynamics of sphingomyelinase activity in serum of patients with NSCLC

  4. Current trends of the external radiotherapy in treatment of non small cell lung cancer

    International Nuclear Information System (INIS)

    Non-small cell lung cancer belongs to the most frequent malign cancer on the world. Local and loco-regional methods of therapy are for this form of cancer highly important. Dominant position has radiation therapy, which is treating 60 % of all patients. Author provides an overview about the conventional and non-conventional sources of radiation, mainly about linear accelerator, which is used in therapy of NSCLC. This article offers basic information about conventional radiotherapy; it evaluates the fractional modes and doses used for curative and palliative radiation therapy. (author)

  5. Cyclooxygenase-2 Expression in Non-Small Cell Lung Cancer Correlates With Hypertrophic Osteoarthropathy.

    Science.gov (United States)

    Rotas, Ioannis; Cito, Giovanni; Letovanec, Igor; Christodoulou, Michel; Perentes, Jean Y

    2016-02-01

    Hypertrophic osteoarthrpathy (HO) is a rare paraneoplasic syndrome associated with non-small cell lung cancer (NSCLC). The pathophysiology of HO is unknown but was recently related to enhanced levels of urine prostaglandin E2 (PGE2). Here, we report the case of a patient that presented HO in association with a resectable left upper lobe NSCLC. Following surgery and adjuvant chemotherapy, HO resolved and did not recur with development of a brain metastasis 1 year later. Interestingly, tumor cyclooxygenase-2, an enzyme responsible the synthesis of PGE2, was expressed in the primary tumor but not in the resected metastasis. PMID:26777972

  6. Advances of Drug Resistance Marker of Gemcitabine for Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Baorui LIU

    2011-05-01

    Full Text Available With the development of pharmacogenomics and pharmacogenetics, personal therapy based on genes has become one of the most effective ways to enhance chemotherapeutic effect on non-small cell lung cancer (NSCLC patients. Much attention has been paid to validate the predictive biomarkers of chemotherapy in order to guide chemotherapy and enhance effect in general. Gemcitabine is one of the common agents treating NSCLC recently. This review is mainly about the recent reports on potential biomarkers of Gemcitabine in tailored therapy of NSCLC.

  7. 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.)

  8. AZD9291 in epidermal growth factor receptor inhibitor—resistant non-small-cell lung cancer

    OpenAIRE

    Stinchcombe, Thomas E.

    2016-01-01

    Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in advanced EGFR mutant non-small cell lung cancer have an objective response rate (ORR) of approximately 60–70% and a median progression free-survival (PFS) of approximately 10-13 months. Studies of tumor biopsies performed after progression on EGFR TKI revealed that 50-60% of EGFR mutant NSCLC developed an EGFR exon 20 T790M mutation as a mechanism of acquired resistance. AZD9291 is a third generation irreversible EGF...

  9. Overcoming toxicity-challenges in chemoradiation for non-small cell lung cancer

    Science.gov (United States)

    2016-01-01

    Concurrent chemoradiation (CCRT) is the treatment of choice for locally advanced non-small cell lung cancer (NSCLC) with a modest survival benefit over sequential chemoradiation or radiotherapy (SCRT) alone. However, this benefit is at the cost of increasing acute toxicity such as esophagitis. Previous analysis revealed several predictive parameters in dose-volume and patient characteristics which helped us to identify those patients at risk for severe esophagus toxicity. As a result, supportive care interventions including individualized patient information, dietary guidance, adequate medication, hydration and tubefeeding could be initiated. This paper discusses the challenges in overcoming chemoradiation induced acute esophageal toxicity (AET).

  10. SSX2-4 expression in early-stage non-small cell lung cancer

    DEFF Research Database (Denmark)

    Greve, K B V; Pøhl, M; Olsen, K E; Nielsen, O; Ditzel, H J; Gjerstorff, M F

    2014-01-01

    The expression of cancer/testis antigens SSX2, SSX3, and SSX4 in non-small cell lung cancers (NSCLC) was examined, since they are considered promising targets for cancer immunotherapy due to their immunogenicity and testis-restricted normal tissue expression. We characterized three SSX antibodies......-4 expression was only detected in 5 of 143 early-stage NSCLCs, which is rare compared to other cancer/testis antigens (e.g. MAGE-A and GAGE). However, further studies are needed to determine whether SSX can be used as a prognostic or predictive biomarker in NSCLC....

  11. Bronchoscopy: Diagnostic and Therapeutic for Non-Small Cell Lung Cancer.

    Science.gov (United States)

    Bauer, Thomas L; Berkheim, David B

    2016-07-01

    The bronchoscope has gone through much advancement from its origin as a thin metal tube. It has become a highly sophisticated tool for clinicians. Both rigid and the flexible bronchoscopes are invaluable in the diagnosis and treatment of non-small cell lung cancer. Treatment of this disease process hinges on accurate diagnosis and lymph node staging. Technologies, such as endobronchial ultrasound, navigational bronchoscopy, and autofluorescence, have improved efficacy of endobronchial diagnosis and sample collection. If a patient is not a candidate for surgery and has a complication from a centrally located mass, the bronchoscope has been used to deliver palliative therapies. PMID:27261910

  12. Targeted therapy for localized non-small-cell lung cancer: a review

    OpenAIRE

    Chouaid, Christos

    2016-01-01

    Nicolas Paleiron,1 Olivier Bylicki,2 Michel André,1 Emilie Rivière,1 Frederic Grassin,1 Gilles Robinet,3 Christos Chouaïd4 On behalf of the GFPC Group 1Chest Department, HIA Clermont Tonnerre, Brest, 2Chest Department, HIA Percy, Clamart, 3Chest Department, CHU de Brest, Brest, 4GRC OncoEst, Université Paris XII, Paris, France Abstract: Targeted therapies have markedly improved the management of patients with advanced non-small-cell lung cancer (NS...

  13. Effect of image-guided hypofractionated stereotactic radiotherapy on peripheral non-small-cell lung cancer

    OpenAIRE

    Ren, Juan; Wang, Shuwen; Yan, Yanli; Xue, Chaofan; Tan, Li; Ma, Xiaowei

    2016-01-01

    Shu-wen Wang,1 Juan Ren,1 Yan-li Yan,2 Chao-fan Xue,2 Li Tan,2 Xiao-wei Ma2 1Department of Radiotherapy, First Affiliated Hospital of Xian Jiaotong University, 2Medical School of Xian Jiaotong University, Xi’an, Shaanxi, People’s Republic of China Abstract: The objective of this study was to compare the effects of image-guided hypofractionated radiotherapy and conventional fractionated radiotherapy on non-small-cell lung cancer (NSCLC). Fifty stage- and age-matched cases...

  14. Detection of MTAP Protein and Gene Expression in Non-small Cell Lung Cancer

    OpenAIRE

    Li, Shasha; Zhang, Yijun; LI, HONGLI; Ding, Baoqing

    2011-01-01

    Background and objective The abnormal expression of MTAP, a tumor suppressor gene, is found in a variety of tumor tissues. The aim of this study is to detect the expression of MTAP mRNA protein and the clinical significance for the therapy of non-small cell lung cancer tissue (NSCLC). Methods The expression of MTAP protein was detected by immunohistochemistry in 52 cases of NSCLC patients. The relative expression MTAP mRNA was detected by real-time quantitative PCR. Results The expression of ...

  15. Optimizing the management of advanced non-small-cell lung cancer: a personal view

    OpenAIRE

    Vincent, M. D.

    2009-01-01

    The management of advanced non-small-cell lung cancer (a-nsclc) is currently undergoing one of its rare paradigm shifts. Just as the nihilism of the 1970s gave way to the empiricism of the 1980s and 1990s, so the current decade has seen the first truly rational therapies based on informed design. In addition, molecular markers and traditional parameters can now be combined to provide a framework of knowledge that will guide the application of not just the new therapies, but also the older one...

  16. Molecular imaging of hypoxia in non-small-cell lung cancer

    International Nuclear Information System (INIS)

    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.)

  17. Myc Is a Metastasis Gene for Non-Small-Cell Lung Cancer

    OpenAIRE

    Rapp, U R; Korn, C.; Ceteci, F.; Karreman, C; Luetkenhaus, K.; Serafin, V; Zanucco, E.; Castro, I.; Potapenko, T.

    2009-01-01

    Background Metastasis is a process by which cancer cells learn to form satellite tumors in distant organs and represents the principle cause of death of patients with solid tumors. NSCLC is the most lethal human cancer due to its high rate of metastasis. Methodology/Principal Findings Lack of a suitable animal model has so far hampered analysis of metastatic progression. We have examined c-MYC for its ability to induce metastasis in a C-RAF-driven mouse model for non-small-cell lung cancer. c...

  18. GENOMIC LANDSCAPE OF NON-SMALL CELL LUNG CANCER IN SMOKERS AND NEVER SMOKERS

    OpenAIRE

    Govindan, Ramaswamy; Ding, Li; Griffith, Malachi; Subramanian, Janakiraman; Nathan D Dees; Kanchi, Krishna L.; Maher, Christopher A.; Fulton, Robert; Fulton, Lucinda; Wallis, John; Chen, Ken; Walker, Jason; McDonald, Sandra; Bose, Ron; Ornitz, David

    2012-01-01

    We report the results of whole genome and transcriptome sequencing of tumor and adjacent normal tissue samples from 17 patients with non-small cell lung carcinoma (NSCLC). We identified 3,726 point mutations and over 90 indels in the coding sequence, with an average mutation frequency more than 10-fold higher in smokers than in never-smokers. Novel alterations in genes involved in chromatic modification and DNA repair pathways were identified along with DACH1, CFTR, RELN, ABCB5, and HGF. Deep...

  19. Interaction between fragile histamine triad and protein kinase C alpha in human non-small cell lung cancer tissues

    Institute of Scientific and Technical Information of China (English)

    Peng-hui Zhuang; Zhao-hui Liu; Xiao-gang Jiang; Cheng-en Pan

    2009-01-01

    Objective To investigate the interaction between fragile histamine triad (FHIT) and protein kinase C alpha (PKCα) in human non-small cell lung cancer tissues. Methods FHIT and PKC伪 double positive samples were screened by immunohistochemical staining from 13 human non-small cell lung cancer tissues. Co-immunoprecipitation was performed by using anti-FHIT and anti-PKCα. The immune precipitate was analyzed by SDS-PAGE and Western blot. Results Immune precipitate staining detection showed that 3 samples out of the 13 cases were double positive for FHIT and PKCα. FHIT protein was present in the immune precipitate of anti-PKCα while there was PKCα in the immune precipitate of anti-FHITmAb. Conclusion FHIT and PKCα exist as a complex in human non-small cell lung cancer tissues, which will provide a new route for studying the pathogenesis and immunotherapy of human non-small cell lung cancer.

  20. Accuracy of transbronchial needle aspiration for mediastinal staging of non-small cell lung cancer: a meta-analysis

    OpenAIRE

    Holty, J; Kuschner, W; Gould, M

    2005-01-01

    Background: The reported accuracy of transbronchial needle aspiration (TBNA) for mediastinal staging in non-small cell lung cancer (NSCLC) varies widely. We performed a meta-analysis to estimate the accuracy of TBNA for mediastinal staging in NSCLC.

  1. Recombinant Interleukin-15 in Treating Patients With Advanced Melanoma, Kidney Cancer, Non-small Cell Lung Cancer, or Squamous Cell Head and Neck Cancer

    Science.gov (United States)

    2016-05-05

    Head and Neck Squamous Cell Carcinoma; Recurrent Head and Neck Carcinoma; Recurrent Non-Small Cell Lung Carcinoma; Recurrent Renal Cell Carcinoma; Recurrent Skin Carcinoma; Stage III Renal Cell Cancer; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIA Skin Melanoma; Stage IIIB Non-Small Cell Lung Cancer; Stage IIIB Skin Melanoma; Stage IIIC Skin Melanoma; Stage IV Non-Small Cell Lung Cancer; Stage IV Renal Cell Cancer; Stage IV Skin Melanoma

  2. Toward precision medicine with next-generation EGFR inhibitors in non-small-cell lung cancer

    Directory of Open Access Journals (Sweden)

    Yap TA

    2014-09-01

    Full Text Available Timothy A Yap,1,2 Sanjay Popat1,3 1Lung Cancer Unit, Department of Medicine, The Royal Marsden National Health Service Foundation Trust, London, United Kingdom; 2The Institute of Cancer Research, London, United Kingdom; 3National Heart and Lung Institute, London, United Kingdom Abstract: The use of genomics to discover novel targets and biomarkers has placed the field of oncology at the forefront of precision medicine. First-generation epidermal growth factor receptor (EGFR inhibitors have transformed the therapeutic landscape of EGFR mutant non-small-cell lung carcinoma through the genetic stratification of tumors from patients with this disease. Somatic EGFR mutations in lung adenocarcinoma are now well established as predictive biomarkers of response and resistance to small-molecule EGFR inhibitors. Despite early patient benefit, primary resistance and subsequent tumor progression to first-generation EGFR inhibitors are seen in 10%–30% of patients with EGFR mutant non-small-cell lung carcinoma. Acquired drug resistance is also inevitable, with patients developing disease progression after only 10–13 months of antitumor therapy. This review details strategies pursued in circumventing T790M-mediated drug resistance to EGFR inhibitors, which is the most common mechanism of acquired resistance, and focuses on the clinical development of second-generation EGFR inhibitors, exemplified by afatinib (BIBW2992. We discuss the rationale, mechanism of action, clinical efficacy, and toxicity profile of afatinib, including the LUX-Lung studies. We also discuss the emergence of third-generation irreversible mutant-selective inhibitors of EGFR and envision the future management of EGFR mutant lung adenocarcinoma. Keywords: afatinib, EGFR, erlotinib, gefitinib, LUX-Lung, NSCLC 

  3. Identification of Serum Peptidome Signatures of Non-Small Cell Lung Cancer.

    Science.gov (United States)

    Klupczynska, Agnieszka; Swiatly, Agata; Hajduk, Joanna; Matysiak, Jan; Dyszkiewicz, Wojciech; Pawlak, Krystian; Kokot, Zenon J

    2016-01-01

    Due to high mortality rates of lung cancer, there is a need for identification of new, clinically useful markers, which improve detection of this tumor in early stage of disease. In the current study, serum peptide profiling was evaluated as a diagnostic tool for non-small cell lung cancer patients. The combination of the ZipTip technology with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) for the analysis of peptide pattern of cancer patients (n = 153) and control subjects (n = 63) was presented for the first time. Based on the observed significant differences between cancer patients and control subjects, the classification model was created, which allowed for accurate group discrimination. The model turned out to be robust enough to discriminate a new validation set of samples with satisfactory sensitivity and specificity. Two peptides from the diagnostic pattern for non-small cell lung cancer (NSCLC) were identified as fragments of C3 and fibrinogen α chain. Since ELISA test did not confirm significant differences in the expression of complement component C3, further study will involve a quantitative approach to prove clinical utility of the other proteins from the proposed multi-peptide cancer signature. PMID:27043541

  4. Chemotherapy in elderly patients with advanced non-small cell lung cancer.

    Science.gov (United States)

    Quoix, Elisabeth; Westeel, Virginie; Zalcman, Gérard; Milleron, Bernard

    2011-12-01

    Because of increasing life expectancy and of higher risk of cancer with ageing, lung cancer in elderly is a frequent disease. For a long time nihilism influenced treatment decisions in elderly patients with advanced non-small cell lung cancer. Since the beginning of the last decade single agent chemotherapy has been accepted as standard of care, vinorelbine and gemcitabine being the most frequently used drugs in Europe and US, docetaxel in Japan. Platinum-based doublets have been shown to be superior to monotherapy in young and fit patients with advanced non-small cell lung cancer. Although there were some indications from subgroup analyses of clinical trials not specifically dedicated to elderly patients that a platinum-based doublet might also benefit to older patients, there was no definitive proof of concept until ASCO meeting 2010. At this meeting results of a phase 3 trial showed that PS 0-2 patients, aged 70-89 years drove a significant benefit from a treatment with carboplatin associated to weekly paclitaxel compared to a monotherapy. Thus, the paradigm of treatment in elderly patients should perhaps be modified from a single agent to doublet chemotherapy. Whether other platinum-based doublets would provide the same benefit as the specific one studied remains to be evaluated. PMID:21893363

  5. Radiation therapy for non-small cell lung cancer with postoperative intrathoracic recurrence

    International Nuclear Information System (INIS)

    We reviewed patients with intrathoracic recurrence of non-small cell lung cancer after surgery, with reference to the feasibility of radiotherapy. The series consisted of 46 patients (39 males and 7 females) treated by radiotherapy from 1982 to 1995. Histology included squamous cell carcinoma (28 patients), adenocarcinoma (17), and large cell carcinoma (1). Clinical stage by UICC classification (1987) was as follows: stage I (2 patients), stage II (1), stage IIIa (13), stage IIIb (23), and stage IV (7). Recurrences were noted in bronchial stump (18 patients) and surgical scar (4). Metastases occurred in hilar-mediastinal lymphnodes (15), lung fields (7), and pleuropericardium (2). The mean interval from surgery to recurrence was 27 months. Delivered dose ranged from 45 to 80 Gy, and 19 patients received combined chemotherapy. Therapeutic results were as follows: complete response in 16 patients, partial response in 27, no response in 12 and progressive disease in 1. Overall 2- and 5-year survival rates were 17% and 11%, respectively, and 10 months in MST. On univariate analysis, significant prognostic factors were sex, stage at recurrence, recurrence pattern, performance status and initial response to radiotherapy, while multivariate analysis showed sex and initial response. From these data, we are encouraged by effective radiotherapy for postoperative intrathoracic recurrence of non-small cell lung cancer, especially in patients with stump or lymphnode recurrence. (author)

  6. Palliation of symptoms in non-small cell lung cancer: a study by the Yorkshire Regional Cancer Organisation Thoracic Group.

    OpenAIRE

    Muers, M. F.; Round, C. E.

    1993-01-01

    BACKGROUND--Although most treatment for non-small cell lung cancer is palliative, data on the adequacy of symptom control are scanty and there has been little discussion about the appropriate indices. METHODS--Two hundred and eighty nine unselected patients presenting sequentially to six specialists were studied; 242 cases were confirmed histologically and all were managed as non-small cell lung cancer. At presentation and two monthly for one year or until death each of 12 symptoms was graded...

  7. Evaluation of Irinotecan as a Third- or Fourth-line Treatment for Advanced Non-small Cell Lung Cancer

    OpenAIRE

    Keener, James

    2013-01-01

    Lung cancer is the leading cause of cancer-related deaths in the United States. There are two major types of lung cancer: non-small cell lung cancer (NSCLC), which comprises approximately 85% of all lung cancers, and small cell lung cancer. Currently, the most prevalent third- and fourth- line treatment for non-small cell lung cancer is cisplatin-based therapy. This form of therapy has been long established as the chief treatment for advanced NSCLC; however, cisplatin-based therapy also impai...

  8. Advances on Mechanisms of Coagulation with Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Yanhua LI

    2013-12-01

    Full Text Available Recently, researchers have been increasingly finding coagulation disorders are commonly the first sign of malignancy. It has now been established that cancer development leads to an increased risk of thrombosis, and conversely, excessive activation of blood coagulation profoundly influences cancer progression. In patients with lung cancer, a sustained stimulation of blood coagulation takes place. Cancer cells trigger coagulation through expression of tissue factor, and affect coagulation through expression of thrombin, release of microparticles that augment coagulation and so on. Coagulation also facilitates tumour progression through release of platelet granule contents, inhibition of natural killer cells and recruitment of macrophages. Non-small cell lung cancer (NSCLC accounts for about 80%-85% of all lung malignancies. In the present review, we summarized the newly updated data about the physiopathological mechanisms of various components of the clotting system in different stages of carcinogenesis in NSCLC.

  9. Clinicopathological Characteristics and Prognosis of Non-Small Cell Lung Cancer Patients Associated with a Family History of Lung Cancer

    OpenAIRE

    Shuji Haraguchi, Kiyoshi Koizumi, Iwao Mikami, Okamoto Junichi, Yoshihito Iijima, Takayuki Ibi, Kazuo Shimizu

    2012-01-01

    Introduction: Clinicopathological characteristics and prognosis of non-small cell lung cancer (NSCLC) patients with a family history of lung cancer (FHLC) have not been well established.Methods: Clinical records of patients with NSCLC treated at our institute from 1982 to 2010 were reviewed with special reference to family history of lung cancer and clinicopathological factors including patient's outcome. Univariate analyses of the factors between the groups of FHLC and non-FHLC were performe...

  10. Clinicopathological Characteristics and Prognosis of Non-Small Cell Lung Cancer Patients Associated with a Family History of Lung Cancer

    OpenAIRE

    Haraguchi, Shuji; Koizumi, Kiyoshi; Mikami, Iwao; Junichi, Okamoto; Iijima, Yoshihito; Ibi, Takayuki; Shimizu, Kazuo

    2011-01-01

    Introduction: Clinicopathological characteristics and prognosis of non-small cell lung cancer (NSCLC) patients with a family history of lung cancer (FHLC) have not been well established. Methods: Clinical records of patients with NSCLC treated at our institute from 1982 to 2010 were reviewed with special reference to family history of lung cancer and clinicopathological factors including patient's outcome. Univariate analyses of the factors between the groups of FHLC and non-FHLC were perform...

  11. Primary non-small cell lung cancer in a transplanted lung treated with stereotactic body radiation therapy. A case study

    International Nuclear Information System (INIS)

    The first case of primary lung cancer in a transplanted lung was described in 2001. Since then, only 5 cases of lung cancer in donated lung have been reported. We present one more patient with non-small cell cancer in the transplanted lung treated with stereotactic body radiation therapy. In most cases of primary lung cancer in transplanted lung, rapid progression of the cancer was reported. Occurrence of the locoregional failure in our case could be explained by factors related to the treatment protocol and also to underlying immunosuppression.

  12. Overexpression of SAMD9 suppresses tumorigenesis and progression during non small cell lung cancer

    International Nuclear Information System (INIS)

    Highlights: • SAMD9 is down-regulated in human non-small cell lung cancer (NSCLC). • Knockdown of SAMD9 expression is increased the invasion, migration and proliferation in H1299 cells in vitro. • Overexpression of SAMD9 suppressed proliferation and invasion in A549 cells in vitro. • Depletion of SAMD9 increases tumor formation in vivo. - Abstract: The Sterile Alpha Motif Domain-containing 9 (SAMD9) gene has been recently emphasized during the discovery that it is expressed at a lower level in aggressive fibromatosis and some cases of breast and colon cancer, however, the underlying mechanisms are poorly understood. Here, we found that SAMD9 is down-regulated in human non-small cell lung cancer (NSCLC). Furthermore, knockdown of SAMD9 expression is increased the invasion, migration and proliferation in H1299 cells in vitro and overexpression of SAMD9 suppressed proliferation and invasion in A549 cells. Finally, depletion of SAMD9 increases tumor formation in vivo. Our results may provide a strategy for blocking NSCLC tumorigenesis and progression

  13. Concurrent chemoradiation for stage III non small cell lung cancer: present results and future prospects

    International Nuclear Information System (INIS)

    The prognosis of stage III non small cell lung cancer is reportedly poor, particularly in patients with mediastinal lymph node involvement. These patients may be either good surgical candidates, marginally resectable, or inoperable for technical or medical reasons, but, in any case, surgery and/or radiotherapy are curative in only a minority of them. The high incidence of early distant failures underscores the need for early and effective systemic therapy in association with local treatment, since occult metastatic disease is present in most patients at the time of diagnosis. Recent phase III trials have demonstrated significant benefit to induction chemotherapy prior to irradiation or surgery in reducing the distant metastasis rate. However, poor local control remains a major issue in these locally advanced tumors. In patients with inoperable disease, the concomitant use of chemotherapy along with radiotherapy substantially improves local control. For operable patients, induction chemotherapy with concomitant moderate-dose radiotherapy improves local control as well, and may facilitate surgical resection in marginally operable cases. Currently, a number of phase II clinical trials report encouraging results with concomitant chemoradiotherapy used either prior to surgery or with curative intent in locally advanced non small cell lung cancer. (authors). 27 refs

  14. Outcome following radiotherapy for loco-regionally recurrent non-small cell lung cancer

    International Nuclear Information System (INIS)

    Local and regional recurrence of non-small cell lung cancer is reported to occur in 13-20% of treatment failures after resection. Reported post-recurrent median survival following radiotherapy ranges from 9 to 14 months. This study examines survival following radiotherapy alone for patients with loco-regionally recurring non-small cell lung cancer after initial surgery. Fifty-five patients, receiving radiotherapy at Westmead Hospital between 1979 and 1997, were eligible for study. Data were collected retrospectively by reviewing patient records. The end-point was overall survival. Symptom control was also recorded. Prognostic factors for analysis included age, sex, original presenting stage, disease-free interval (DFI), performance status, site of recurrence, treatment intent and dose. The median overall survival was 11.5 months (95% confidence interval: 8.1-13.0). Survival following treatment with radical intent was 26 months compared to 10.5 months for patients treated with palliative intent (P = 0.025). There was no significant difference in survival for short (<2 years) or long DFI, performance status, radiation dose, age, sex, site of recurrence or stage. Most patients (55%) had partial or complete resolution of symptoms. Radiotherapy results in overall post-recurrence median survival of nearly 1 year, consistent with previous published data. Radical treatment intent predicts better prognosis as a result of patient selection and higher dose. Radiotherapy is effective at palliating symptoms of this disease Copyright (2005) Blackwell Publishing Asia Pty Ltd

  15. The plasma lncRNA acting as fingerprint in non-small-cell lung cancer.

    Science.gov (United States)

    Hu, Xiaodong; Bao, Jitao; Wang, Zhen; Zhang, Zigang; Gu, Peijie; Tao, Feng; Cui, Di; Jiang, Weilong

    2016-03-01

    Recent studies have indicated that long non-coding RNAs (lncRNAs) could act as non-invasive tumor markers in both diagnosis and predicting the prognosis. In this study, we focused to determine the expression of circulating lncRNAs in patients suffering from non-small-cell lung cancer (NSCLC), aiming to found the potential lncRNA as predictor. Twenty-one lncRNAs which previously identified were selected as candidate targets for subsequent circulating lncRNA assay. The candidate lncRNAs were validated by qRT-PCR arranged in the training and validation sets. Circulating SPRY4-IT1, ANRIL, and NEAT1 were significantly increased in plasma samples of NSCLC patients during training set and validation set. Receiver operating characteristic curve (ROC) analysis revealed that plasma ANRIL provided the highest diagnostic performance with an area under ROC curve value (AUC) of 0.798. Further combination with the three factors indicated a higher power (AUC, 0.876; sensitivity, 82.8 %; specificity, 92.3 %). The stableness detection of the three factors indicated that circulating SPRY4-IT1, ANRIL, and NEAT might serve as a predictor for the early warning of non-small-cell lung cancer. PMID:26453113

  16. Natural History of Non-Small-Cell Lung Cancer with Bone Metastases

    Science.gov (United States)

    Daniele, Santini; Sandro, Barni; Salvatore, Intagliata; Alfredo, Falcone; Francesco, Ferraù; Domenico, Galetta; Luca, Moscetti; Nicla, La Verde; Toni, Ibrahim; Fausto, Petrelli; Enrico, Vasile; Laura, Ginocchi; Davide, Ottaviani; Flavia, Longo; Cinzia, Ortega; Antonio, Russo; Giuseppe, Badalamenti; Elena, Collovà; Gaetano, Lanzetta; Giovanni, Mansueto; Vincenzo, Adamo; Filippo, De Marinis; Satolli, Maria Antonietta; Flavia, Cantile; Andrea, Mancuso; Tanca, Francesca Maria; Raffaele, Addeo; Marco, Russano; Sterpi, M; Francesco, Pantano; Bruno, Vincenzi; Giuseppe, Tonini

    2015-01-01

    We conducted a large, multicenter, retrospective survey aimed to explore the impact of tumor bone involvement in Non-Small Cell Lung Cancer.Data on clinical-pathology, skeletal outcomes and bone-directed therapies for 661 deceased patients with evidence of bone metastasis were collected and statistically analyzed. Bone metastases were evident at diagnosis in 57.5% of patients. In the remaining cases median time to bone metastases appearance was 9 months. Biphosphonates were administered in 59.6% of patients. Skeletal-related events were experienced by 57.7% of patients; the most common was the need for radiotherapy. Median time to first skeletal-related event was 6 months. Median survival after bone metastases diagnosis was 9.5 months and after the first skeletal-related event was 7 months. We created a score based on four factors used to predict the overall survival from the diagnosis of bone metastases: age >65 years, non-adenocarcinoma histology, ECOG Performance Status >2, concomitant presence of visceral metastases at the bone metastases diagnosis. The presence of more than two of these factors is associated with a worse prognosis.This study demonstrates that patients affected by Non-Small Cell Lung Cancer with bone metastases represent a heterogeneous population in terms of risk of skeletal events and survival. PMID:26690845

  17. Radiotherapy alone for elderly patients with stage III non-small cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Nakano, Kikuo; Hiramoto, Takehiko; Kanehara, Masasi; Doi, Mihoko; Furonaka, Osamu; Miyazu, Yuka; Hada, Yosihiro [National Hospital of Kure, Hiroshima (Japan)

    1999-04-01

    We undertook a retrospective study of elderly patients with stage III non-small cell lung cancer who had been treated solely with radiotherapy during the period 1986 to 1995. Our study was designed to assess the influence of age on survival and malnutrition in patients aged 75 years or older (elderly group) and patients aged 74 years or younger (younger group). Radiotherapy alone resulted in a median survival period of 11.5 months in the younger group and 6.3 months in the elderly group (p=0.0043). With the Cox multivariate model, good performance status, age less than 75 years, and good response were significant favorable independent predictors. Furthermore, the elderly group patients more frequently died of respiratory infections and had lower prognostic nutritional indexes than the younger group patients before and after radiotherapy. These findings suggested elderly patients with stage III non-small cell lung cancer who had been treated with radiotherapy alone had a poor prognosis and that malnutrition caused by radiotherapy was a factor contributing to the risk of death from respiratory infection in such patients. (author)

  18. Overexpression of SAMD9 suppresses tumorigenesis and progression during non small cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Ma, Qing; Yu, Tao; Ren, Yao-Yao; Gong, Ting; Zhong, Dian-Sheng, E-mail: zhongdsyx@126.com

    2014-11-07

    Highlights: • SAMD9 is down-regulated in human non-small cell lung cancer (NSCLC). • Knockdown of SAMD9 expression is increased the invasion, migration and proliferation in H1299 cells in vitro. • Overexpression of SAMD9 suppressed proliferation and invasion in A549 cells in vitro. • Depletion of SAMD9 increases tumor formation in vivo. - Abstract: The Sterile Alpha Motif Domain-containing 9 (SAMD9) gene has been recently emphasized during the discovery that it is expressed at a lower level in aggressive fibromatosis and some cases of breast and colon cancer, however, the underlying mechanisms are poorly understood. Here, we found that SAMD9 is down-regulated in human non-small cell lung cancer (NSCLC). Furthermore, knockdown of SAMD9 expression is increased the invasion, migration and proliferation in H1299 cells in vitro and overexpression of SAMD9 suppressed proliferation and invasion in A549 cells. Finally, depletion of SAMD9 increases tumor formation in vivo. Our results may provide a strategy for blocking NSCLC tumorigenesis and progression.

  19. Radiotherapy alone for elderly patients with stage III non-small cell lung cancer

    International Nuclear Information System (INIS)

    We undertook a retrospective study of elderly patients with stage III non-small cell lung cancer who had been treated solely with radiotherapy during the period 1986 to 1995. Our study was designed to assess the influence of age on survival and malnutrition in patients aged 75 years or older (elderly group) and patients aged 74 years or younger (younger group). Radiotherapy alone resulted in a median survival period of 11.5 months in the younger group and 6.3 months in the elderly group (p=0.0043). With the Cox multivariate model, good performance status, age less than 75 years, and good response were significant favorable independent predictors. Furthermore, the elderly group patients more frequently died of respiratory infections and had lower prognostic nutritional indexes than the younger group patients before and after radiotherapy. These findings suggested elderly patients with stage III non-small cell lung cancer who had been treated with radiotherapy alone had a poor prognosis and that malnutrition caused by radiotherapy was a factor contributing to the risk of death from respiratory infection in such patients. (author)

  20. Concurrent chemo-radiotherapy for stage III non-small cell lung cancer

    International Nuclear Information System (INIS)

    In patients with unresectable stage III non-small cell lung cancer, we performed chemotherapy and concurrent thoracic radiotherapy. Thirty-five registered patients were intravenously treated with cisplatin (80mg/m2) on day 1 and vindesine (3mg/m2) on days 1, 3 and were irradiated from days 1 to 10 with single doses of 2.5 Gy up to a total dosage of 20 Gy. Each course lasted 28 days. Patients received 3 courses, and a total dosage of 60 Gy was delivered. Response to this treatment was evaluable in terms of results in 35 patients. Twenty-two patients showed partial response (response rate 62.9%), 10 had no change, and 3 cases had progressive disease. In 7.5 to 37.8 months observation, three PR patients are alive for more than 24 months without recurrence, but eight PR patients died of local relapse, and the median survival time was 15.7 months. Throughout this treatment course, grade 4 leukopenia was noted in 66% and grade 3 thrombocytopenia was observed in 3%. However all were reversible condition and no treatment-related death was observed. However, two cases died due to complications of pulmonary abscess, which occurred in the area of radiation pulmonary fibrosis about one year later after treatment. Although this concurrent chemo-radiotherapy is a tolerable treatment for non-small cell lung cancer and obtained a good response rate, it did not improve the survival rate. (author)

  1. Non-small-cell lung cancer: unusual presentation in the gluteal muscle.

    LENUS (Irish Health Repository)

    Al-Alao, Bassel Suffian

    2011-05-01

    Lung cancer is one of the most commonly diagnosed cancers in both men and women worldwide. It is also one of the most common forms of cancer in Ireland, accounting for about 20% of all deaths from cancer each year. Early detection of lung cancer is infrequent, and most cases are not diagnosed and treated until they are at an advanced stage. Distant metastases in lung cancer commonly involve the adrenal glands, liver, bones, and central nervous system; they are only rarely seen in the skeletal system. We report a rare case of metastasis to the gluteal muscle as the initial presentation of lung cancer.

  2. INTEGRATED PET-CT SCAN IN THE STAGING OF NON SMALL CELL LUNG CANCER

    Directory of Open Access Journals (Sweden)

    I Made Ngurah Agus Surya Negara S

    2013-09-01

    Full Text Available Normal 0 false false false EN-US X-NONE X-NONE Lung cancer is a common disease and is a leading cause of death in many countries. The most kind of lung cancer was Non Small Cell Lung Cancer. The management of lung cancer is directed by an optimal staging of the tumour. On 1998, integrated positron emission tomography (PET-computed tomography (CT was published. PET-CT is an anatomo-metabolic imaging modality that has recently been introduced to clinical practice and combines two different techniques: CT, which provides very detailed anatomic information; and PET, which provides metabolic information. One of the advantages of PET/CT is the improved image interpretation. There wasbetter results for PET/CT in the staging of non small cell lung cancer in comparison with CT nor PET alone. /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin-top:0in; mso-para-margin-right:0in; mso-para-margin-bottom:10.0pt; mso-para-margin-left:0in; line-height:115%; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:"Times New Roman"; mso-bidi-theme-font:minor-bidi;}

  3. Assessment of metal contaminants in non-small cell lung cancer by EDX microanalysis

    Directory of Open Access Journals (Sweden)

    M. Scimeca

    2014-09-01

    Full Text Available Human cardio-respiratory diseases are strongly correlated to concentrations of atmospheric elements. Bioaccumulation of heavy metals is strictly monitored, because of its possible toxic effects. In this work, we utilized the EDX microanalysis in order to identify the potential heavy metal accumulation in the lung tissue.  To this aim, we enrolled 45 human lung biopsies: 15 non-small cell lung cancers, 15 lung benign lesions and 15 control biopsies. Lung samples were both paraffin embedded for light microscopy study and eponepoxid embedded for transmission electron microscopy. EDX microanalysis was performed on 100 nm thick unstained ultrathin-sections placed on specific copper grids. Our results demonstrated that the EDX technology was particularly efficient in the study of elemental composition of lung tissues, where we found heavy metals, such as Cobalt (Co, Chromium (Cr, Manganese (Mn and Lead (Pb. Furthermore, in malignant lesions we demonstrated the presence of multiple bio-accumulated elements. In fact, a high rate of lung cancers was associated with the presence of 3 or more bio-accumulated elements compared to benign lesions and control tissue (91.7%, 0%, 8.3%, respectively. The environmental impact on pulmonary carcinogenesis could be better clarified by demonstrating the presence of polluting agents in lung tissues. The application of EDX microanalysis on biological tissuescould shed new light in the study of the possible bioaccumulation of polluting agents in different human organs and systems.

  4. Epidermal Growth Factor Receptor Mutations and Radiotherapy 
in Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Xing ZHONG

    2013-03-01

    Full Text Available Radiotherapy plays a pivotal role in the treatment for lung cancer. Epidermal growth factor receptor (EGFR mutation in non-small cell lung cancer (NSCLC which predicts tyrosine kinase inhibitor (TKI treatment response may also has effect on radiation response. NSCLC harboring kinase-domain mutations in EGFR exhibits enhanced radio-sensitivity due to dramatically diminished capacity to resolve radiation-induced DSBs (DNA double-strand breaks associating with the inefficiency of EGFR nuclear translocation. Recently, several preliminary clinical studies show certain efficacy of concurrent EGFR tyrosine kinase inhibitors and radiotherapy. However its further response in EGFR-mutated NSCLC is unclear. The correlation between EGFR mutation genotype and the radiotherapy response and clinical outcome is worthy of further study.

  5. Targeting PD-L1 for non-small-cell lung cancer.

    Science.gov (United States)

    Feld, Emily; Horn, Leora

    2016-06-01

    Lung cancer is the leading cause of cancer-related death worldwide. For decades, cytotoxic chemotherapy has been the mainstay of treatment for the majority of patients, yet median survival remains poor and side effects from chemotherapy are not trivial. Immune checkpoint inhibitors, which exert antitumor effects by inhibiting negative T-cell regulators, are changing the landscape of treatment options for patients with non-small-cell lung cancer (NSCLC). The anti-PD-1 antibodies nivolumab and pembrolizumab are approved by the US FDA for treatment of patients with NSCLC and other tumor types. Additional agents are in clinical development. This review provides an update on the PD-1 and PD-L1 immune checkpoint inhibitors currently being evaluated in NSCLC patients. PMID:27197542

  6. Tissue Microarrays in Non-Small Cell Lung Cancer: Reliability of Immunohistochemically-Determined Biomarkers

    DEFF Research Database (Denmark)

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

    2014-01-01

    BACKGROUND: The reliability of immunohistochemically-determined biomarkers using tissue microarrays (TMAs) of clinical specimens has long been open to question. Heterogeneity related to tumor biology might compromise determination of accurate biomarker expression in tumors, especially in small core...... biopsies. We evaluated the reliability of immunohistochemical staining scoring in small core biopsies using 11 biomarkers in non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: Four 1-mm tumor cores from 178 NSCLCs, 2 representing peripheral areas close to the border of normal lung tissue and 2...... representing central areas, were examined. The biomarkers analyzed included p63, p40, cytokeratin 1/5/10/14, cytokeratin 7, thyroid transcription factor-1, napsin A, cyclin-D1, p53, Ki-67, integrin beta-1, and thymidylate synthase. RESULTS: Using a random intercept logistic regression model...

  7. BLOOD TELOMERASE ACTIVITY AND ITS CORRELATIVITY WITH NON-SMALL CELL LUNG CARCINOMA

    Institute of Scientific and Technical Information of China (English)

    胡坚; 李任远; 孙骊; 倪一鸣

    2004-01-01

    Objective: To study the correlativity between blood telomerase activity and Non-small cell lung carcinoma (NSCLC) through relative quantitative analysis of telomerase activity. Methods: Thirty-eight NSCLC and 25 inpatients with benign lung disease were selected. Telomerase repeat amplification protocol was adopted. PCR products were assayed with ELISA. Results: (a) Blood telomerase activity during operation was higher than that before or after operation (P0.05). (c) Blood telomerase activity of adenocarcinoma during and after operation was higher than that before operation (P0.05). Conclusion: The qualitative assay of blood telomerase activity can be adopted as an assistant index for diagnosis of NSCLC. Postoperative blood telomerase activity of adenocarcinoma is higher than that of squamous carcinoma. It may be an evidence for the likelihood of adenocarcinoma to metastase through blood. Blood telomerase activity increases significantly during operation, suggesting that operation may cause more cancer cells entering into circulation.

  8. Gender-related disparities in non-small cell lung cancer.

    Science.gov (United States)

    Paggi, Marco G; Vona, Rosa; Abbruzzese, Claudia; Malorni, Walter

    2010-12-01

    Epidemiological studies clearly outline some disparities in cancer onset, progression as well as prognosis and therapeutic response between sexes. In particular, in lung cancer, the leading cause of cancer death, at least in Western countries, a gender disparity appears now to emerge, especially for non-small cell lung cancer (NSCLC). Such a disparity is apparently due to a variety of mechanisms, ranging from genetic and epigenetic differences to gender-specific lifestyle as well as to behavioral causes and, clearly, to sex hormones activity. Here we briefly recapitulate gender differences in terms of risk factors, histopathological features and pathogenetic mechanisms in NSCLC, and hypothesize that a gender-oriented pharmacology could beneficially impact on innovative therapeutic strategies. PMID:20826048

  9. Pattern of loco-regional failure after definitive radiotherapy for non-small cell lung cancer

    DEFF Research Database (Denmark)

    Schytte, Tine; Nielsen, Tine Bjørn; Brink, Carsten; Hansen, Olfred

    2014-01-01

    Non-small cell lung cancer (NSCLC) is associated with poor survival even though patients are treated with curatively intended radiotherapy. Survival is affected negatively by lack of loco-regional tumour control, but survival is also influenced by comorbidity caused by age and smoking, and...... had loco-regional failure only. Of these patients, 68 had intrapulmonary failure only, one patient had failure in mediastinum only, and 24 patients had intrapulmonary failure as well as mediastinal failure. Of the patients which had lung failure only, 78% had mediastinal involvement at treatment start....... The only covariate with significant impact on developing intrapulmonary failure only was gross tumour volume. Median survival for the total group of 331 patients was 19 months. The median survival for patients with intrapulmonary failure only was 19 months, and it was 20 months for the patients with...

  10. Socioeconomic position and surgery for early-stage non-small-cell lung cancer

    DEFF Research Database (Denmark)

    Starr, Laila Kærgaard; Osler, Merete; Steding-Jessen, Marianne;

    2012-01-01

    explain the association with income or living alone for early-stage NSCLC patients. CONCLUSION: Early-stage NSCLC patients with low income or who live alone are less likely to undergo surgery than those with a high income or who live with a partner, even after control for possible explanatory factors......AIM: To examine possible associations between socioeconomic position and surgical treatment of patients with early-stage non-small-cell lung cancer (NSCLC). METHODS: In a register-based clinical cohort study, patients with early-stage (stages I-IIIa) NSCLC were identified in the Danish Lung Cancer...... and separately for stages I, II and IIIa. RESULTS: Of the 5538 eligible patients with stages I-IIIa NSCLC diagnosed 2001-2008, 53% underwent surgery. Higher stage, older age, being female and diagnosis early in the study period were associated with higher odds for not receiving surgery. Low disposable...

  11. GENOMIC LANDSCAPE OF NON-SMALL CELL LUNG CANCER IN SMOKERS AND NEVER SMOKERS

    Science.gov (United States)

    Govindan, Ramaswamy; Ding, Li; Griffith, Malachi; Subramanian, Janakiraman; Dees, Nathan D.; Kanchi, Krishna L.; Maher, Christopher A.; Fulton, Robert; Fulton, Lucinda; Wallis, John; Chen, Ken; Walker, Jason; McDonald, Sandra; Bose, Ron; Ornitz, David; Xiong, Donghai; You, Ming; Dooling, David J.; Watson, Mark; Mardis, Elaine R.

    2013-01-01

    Summary We report the results of whole genome and transcriptome sequencing of tumor and adjacent normal tissue samples from 17 patients with non-small cell lung carcinoma (NSCLC). We identified 3,726 point mutations and over 90 indels in the coding sequence, with an average mutation frequency more than 10-fold higher in smokers than in never-smokers. Novel alterations in genes involved in chromatic modification and DNA repair pathways were identified along with DACH1, CFTR, RELN, ABCB5, and HGF. Deep digital sequencing revealed diverse clonality patterns in both never smokers and smokers. All validated EFGR and KRAS mutations were present in the founder clones, suggesting possible roles in cancer initiation. Analysis revealed 14 fusions including ROS1 and ALK as well as novel metabolic enzymes. Cell cycle and JAK-STAT pathways are significantly altered in lung cancer along with perturbations in 54 genes that are potentially targetable with currently available drugs. PMID:22980976

  12. Aberrant DNA methylation in non-small cell lung cancer-associated fibroblasts

    Science.gov (United States)

    Vizoso, Miguel; Puig, Marta; Carmona, F.Javier; Maqueda, María; Velásquez, Adriana; Gómez, Antonio; Labernadie, Anna; Lugo, Roberto; Gabasa, Marta; Rigat-Brugarolas, Luis G.; Trepat, Xavier; Ramírez, Josep; Moran, Sebastian; Vidal, Enrique; Reguart, Noemí; Perera, Alexandre; Esteller, Manel; Alcaraz, Jordi

    2015-01-01

    Epigenetic changes through altered DNA methylation have been implicated in critical aspects of tumor progression, and have been extensively studied in a variety of cancer types. In contrast, our current knowledge of the aberrant genomic DNA methylation in tumor-associated fibroblasts (TAFs) or other stromal cells that act as critical coconspirators of tumor progression is very scarce. To address this gap of knowledge, we conducted genome-wide DNA methylation profiling on lung TAFs and paired control fibroblasts (CFs) from non-small cell lung cancer patients using the HumanMethylation450 microarray. We found widespread DNA hypomethylation concomitant with focal gain of DNA methylation in TAFs compared to CFs. The aberrant DNA methylation landscape of TAFs had a global impact on gene expression and a selective impact on the TGF-β pathway. The latter included promoter hypermethylation-associated SMAD3 silencing, which was associated with hyperresponsiveness to exogenous TGF-β1 in terms of contractility and extracellular matrix deposition. In turn, activation of CFs with exogenous TGF-β1 partially mimicked the epigenetic alterations observed in TAFs, suggesting that TGF-β1 may be necessary but not sufficient to elicit such alterations. Moreover, integrated pathway-enrichment analyses of the DNA methylation alterations revealed that a fraction of TAFs may be bone marrow-derived fibrocytes. Finally, survival analyses using DNA methylation and gene expression datasets identified aberrant DNA methylation on the EDARADD promoter sequence as a prognostic factor in non-small cell lung cancer patients. Our findings shed light on the unique origin and molecular alterations underlying the aberrant phenotype of lung TAFs, and identify a stromal biomarker with potential clinical relevance. PMID:26449251

  13. Radiofrequency ablation in primary non-small cell lung cancer: What a radiologist needs to know

    Directory of Open Access Journals (Sweden)

    Shivank Bhatia

    2016-01-01

    Full Text Available Lung cancer continues to be one of the leading causes of death worldwide. In advanced cases of lung cancer, a multimodality approach is often applied, however with poor local control rates. In early non-small cell lung cancer (NSCLC, surgery is the standard of care. Only 15-30% of patients are eligible for surgical resection. Improvements in imaging and treatment delivery systems have provided new tools to better target these tumors. Stereotactic body radiation therapy (SBRT has evolved as the next best option. The role of radiofrequency ablation (RFA is also growing. Currently, it is a third-line option in stage 1 NSCLC, when SBRT cannot be performed. More recent studies have demonstrated usefulness in recurrent tumors and some authors have also suggested combination of RFA with other modalities in larger tumors. Following the National Lung Screening Trial (NLST, screening by low-dose computed tomography (CT has demonstrated high rates of early-stage lung cancer detection in high-risk populations. Hence, even considering the current role of RFA as a third-line option, in view of increasing numbers of occurrences detected, the number of potential RFA candidates may see a steep uptrend. In view of all this, it is imperative that interventional radiologists be familiar with the techniques of lung ablation. The aim of this article is to discuss the procedural technique of RFA in the lung and review the current evidence regarding RFA for NSCLC.

  14. AKAP4 is a circulating biomarker for non-small cell lung cancer

    Science.gov (United States)

    Gumireddy, Kiranmai; Li, Anping; Chang, David H.; Liu, Qin; Kossenkov, Andrew V.; Yan, Jinchun; Korst, Robert J.; Nam, Brian T.; Xu, Hua; Zhang, Lin; Ganepola, Ganepola A.P.; Showe, Louise C.; Huang, Qihong

    2015-01-01

    Cancer testis antigens (CTAs) are widely expressed in tumor tissues, circulating tumor cells (CTCs) and in cancer derived exosomes that are frequently engulfed by lymphoid cells. To determine whether tumor derived CTA mRNAs could be detected in RNA from purified peripheral blood mononuclear cells (PBMC) of non-small cell lung cancer (NSCLC) patients, we assayed for the expression of 116 CTAs in PBMC RNA in a discovery set and identified AKAP4 as a potential NSCLC biomarker. We validated AKAP4 as a highly accurate biomarker in a cohort of 264 NSCLCs and 135 controls from 2 different sites including a subset of controls with high risk lung nodules. When all (264) lung cancers were compared with all (135) controls the area under the ROC curve (AUC) was 0.9714. When 136 stage I NSCLC lung cancers are compared with all controls the AUC is 0.9795 and when all lung cancer patients were compared to 27 controls with histologically confirmed benign lung nodules, a comparison of significant clinical importance, the AUC was 0.9825. AKAP4 expression increases significantly with tumor stage, but independent of age, gender, smoking history or cancer subtype. Follow-up studies in a small number of resected NSCLC patients revealed a decrease of AKAP4 expression post-surgical resection that remained low in patients in remission and increased with tumor recurrence. AKAP4 is a highly accurate biomarker for the detection of early stage lung cancer. PMID:26160834

  15. EF5 and Motexafin Lutetium in Detecting Tumor Cells in Patients With Abdominal or Non-Small Cell Lung Cancer

    Science.gov (United States)

    2013-01-15

    Advanced Adult Primary Liver Cancer; Carcinoma of the Appendix; Fallopian Tube Cancer; Gastrointestinal Stromal Tumor; Localized Extrahepatic Bile Duct Cancer; Localized Gallbladder Cancer; Localized Gastrointestinal Carcinoid Tumor; Localized Resectable Adult Primary Liver Cancer; Localized Unresectable Adult Primary Liver Cancer; Metastatic Gastrointestinal Carcinoid Tumor; Ovarian Sarcoma; Ovarian Stromal Cancer; Primary Peritoneal Cavity Cancer; Recurrent Adult Primary Liver Cancer; Recurrent Adult Soft Tissue Sarcoma; Recurrent Colon Cancer; Recurrent Extrahepatic Bile Duct Cancer; Recurrent Gallbladder Cancer; Recurrent Gastric Cancer; Recurrent Gastrointestinal Carcinoid Tumor; Recurrent Non-small Cell Lung Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Ovarian Germ Cell Tumor; Recurrent Pancreatic Cancer; Recurrent Rectal Cancer; Recurrent Small Intestine Cancer; Recurrent Uterine Sarcoma; Regional Gastrointestinal Carcinoid Tumor; Small Intestine Adenocarcinoma; Small Intestine Leiomyosarcoma; Small Intestine Lymphoma; Stage 0 Non-small Cell Lung Cancer; Stage I Adult Soft Tissue Sarcoma; Stage I Colon Cancer; Stage I Gastric Cancer; Stage I Non-small Cell Lung Cancer; Stage I Ovarian Epithelial Cancer; Stage I Ovarian Germ Cell Tumor; Stage I Pancreatic Cancer; Stage I Rectal Cancer; Stage I Uterine Sarcoma; Stage II Adult Soft Tissue Sarcoma; Stage II Colon Cancer; Stage II Gastric Cancer; Stage II Non-small Cell Lung Cancer; Stage II Ovarian Epithelial Cancer; Stage II Ovarian Germ Cell Tumor; Stage II Pancreatic Cancer; Stage II Rectal Cancer; Stage II Uterine Sarcoma; Stage III Adult Soft Tissue Sarcoma; Stage III Colon Cancer; Stage III Gastric Cancer; Stage III Ovarian Epithelial Cancer; Stage III Ovarian Germ Cell Tumor; Stage III Pancreatic Cancer; Stage III Rectal Cancer; Stage III Uterine Sarcoma; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Adult Soft Tissue Sarcoma; Stage IV Colon Cancer; Stage

  16. Advanced Research of Fibroblast Growth Factor Receptor 
in Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Dan PU

    2013-11-01

    Full Text Available Lung cancer is severely threatening human health. In recent years, the treatment for lung adenocarcinoma has made a great progress, targeted therapy has been widely applied in clinic, and benefits amount of patients. However, in squamous cell lung cancer, the incidence of epidermal growth factor receptor (EGFR gene mutant and ALK fusion gene are low,and targeted therapy like Tarceva and crizotinib, can hardly work. Since the fibroblast growth factors (fibroblast growth factor, FGF pathway is considered to be related to tumor cell proliferation, metastasis and angiogenesis, more and more researches proved the amplification of fibroblast growth factor receptor (FGFR in squamous cell lung cancer. Experiments in vivo and in vitro found that blocking FGF pathway could reduce the proliferation of tumor cells and inhibit metastasis. The FGF pathway might be a new target for treatment of squamous cell lung cancer. This article reviews the effect of FGFR in tumorigenesis,as well as the prospect as a therapeutic target in non-small cell lung cancer.

  17. Expression of Syk in non-small cell lung cancer and its relationship with clinicopathological parameters

    Institute of Scientific and Technical Information of China (English)

    Fen LAN; Shengdao XIONG; Weining XIONG; Guopeng XU; Xiaoxia LU

    2009-01-01

    This study aims to research the expression of spleen tyrosine kinase (Syk) in non-small cell lung cancer (NSCLC) and the relationship between Syk and clinico-pathologic factors and p53. Immunohistochemistry was applied to detect the expression of Syk and p53 protein in 39 cases of NSCLC (23 cases of lung squamous cell can-cer, 16 cases of lung adenocarcinoma) and tumor-sur-rounding normal lung tissues. The positive rate of Syk was 46.15% (18/39) and 100% (39/39) in NSCLC and tumor-surrounding normal lung tissues, respectively. The expres-sion level of Syk in NSCLC was significantly lower than that in tumor-surrounding normal lung tissues (P = 0.000). The Syk expression was positively correlated with the p53 expression in NSCLC specimens (P = 0.025). There was no significant association between Syk expression and lymph node metastasis, differentiation degree, tumor size and tumor node metastasis (TNM). The present study demonstrated that Syk was aberrantly expressed in the NSCLC and might have a significant impact on tumor growth and progression.

  18. Curative radiotherapy in non-small cell carcinoma of the lung

    International Nuclear Information System (INIS)

    Recent reports suggest radiotherapy administered to the 5000-6000 cGy level can result in significant long-term survival in non-small cell carcinoma of the lung. This is particularly true for many cases that are technically operable but for medical or other reasons thoracotomy cannot be performed. Such patients drawn from Southern Appalachia where the principal industry is coal mining are the subject of this report. In this region coal miners pneumoconiosis (black lung) is common as well as other chronic respiratory disorders resulting in poor tolerance for surgery. Three hundred and eleven cases of non-small cell carcinoma were irradiated during the 4 years of 1980 through 1983. This group consisted of 77 patients with clinical Stage T1, T2, T3 all N0, M0 tumors, the majority of which were technically operable but upon whom no thoracotomy was performed because of medical reasons or patient refusal. All are available for 5-year study. Each of these patients was uniformly irradiated to 6000 cGy target dose in 30 fractions over 6 weeks using standard techniques.Comparison with reported surgical series treated for cure show little difference in survival up to 2 years. Thereafter, the survival curves diverge with radiotherapy patients dying at a somewhat higher rate although by 4 years both survival curves slope similarly. A possible explanation for this difference is the advantage thoracotomy offers in early case selection allowing exclusion of advance cases from surgical reports whereas radiotherapy must include patients with occult local metastasis not identifiable on clinical grounds. This experience, among other reports include evidence that radiotherapy can result in long-term survival or cure with minimal morbidity in lung cancer patients in whom surgery carries excessive risk

  19. Wedge resection and segmentectomy in patients with stage I non-small cell lung carcinoma

    Directory of Open Access Journals (Sweden)

    Konstantinos Reveliotis

    2014-09-01

    Full Text Available The use of sublobar resections as definitive management in stage I non-small cell lung carcinoma is a controversial topic in the medical community. We intend to report the latest developments and trends in relative indications for each of the above-mentioned surgical approaches for the treatment of stage I non-small cell lung carcinoma as well as the results of studies regarding local recurrence, disease-free survival and five-year survival rates. We reviewed 45 prospective and retrospective studies conducted over the last 25 years listed in the Pubmed and Scopus electronic databases. Trials were identified through bibliographies and a manual search in journals. Authors, citations, objectives and results were extracted. No meta-analysis was performed. Validation of results was discussed. Segmentectomies are superior to wedge resections in terms of local recurrences and cancer-related mortality rates. Sublobar resections are superior to lobectomy in preserving the pulmonary parenchyma. High-risk patients should undergo segmentectomy, whereas lobectomies are superior to segmentectomies only for tumors >2 cm (T2bN0M0 in terms of disease-free and overall 5-year survival. In most studies no significant differences were found in tumors <2 cm. Disease-free surgical margins are crucial to prevent local recurrences. Systematic lymphadenectomy is mandatory regardless of the type of resection used. In sublobar resections with less thorough nodal dissections, adjuvant radiotherapy can be used. This approach is preferable in case of prior resection. In pure bronchoalveolar carcinoma, segmentectomy is recommended. Sublobar resections are associated with a shorter hospital stay. The selection of the type of resection in T1aN0M0 tumors should depend on characteristic of the patient and the tumor. Patient age, cardiopulmonary reserve and tumor size are the most important factors to be considered. However further prospective randomized trials are needed to

  20. THROMBOCYTOSIS AS PROGNOSTIC FACTOR FOR SURVIVAL IN PATIENTS WITH ADVANCED NON SMALL CELL LUNG CANCER TREATED WITH FIRST- LINE CHEMOTHERAPY.

    Directory of Open Access Journals (Sweden)

    Deyan Davidov

    2014-12-01

    Full Text Available Objective: The aim of this study was to evaluate elevated platelet count as a prognostic factor for survival in patients with advanced (stage IIIB/ IV non- small cell lung cancer (NSCLC receiving first- line chemotherapy. Methods: From 2005 to 2009 three hundreds forty seven consecutive patients with stage IIIB or IV NSCLC, treated in Department of Medical Oncology, UMHAT "Dr Georgi Stranski" entered the study. The therapeutic regimens included intravenous administration of platinum- based doublets. Survival analysis was evaluated by Kaplan- Meier test. The influence of pretreatment thrombocytosis as prognostic factor for survival was analyzed using multivariate stepwise Cox regression analyses. Results: Elevated platelet counts were found in 78 patients. The overall survival for patients without elevated platelet counts was 9,6 months versus 6,9 months for these with thrombocytosis. In multivariate analysis as independent poor prognostic factors were identified: stage, performance status and elevated platelet counts. Conclusions: These results indicated that platelet counts as well as some clinical pathologic characteristics could be useful prognostic factors in patients with unresectable NSCLC.

  1. The effects on surgery and preoperative patients with non-small cell lung cancer by preoperative bronchial artery infusion chemotherapy

    Institute of Scientific and Technical Information of China (English)

    Shuhong Tang; Jilai Bian; Mingwu Li

    2008-01-01

    Objective: To study the efficiency, safety and feasibility of preoperative bronchial artery infusion (BAI) chemotherapy on operation in patients with locally advanced (stage Ⅲ) non-small cell lung cancer (NSCLC).Methods: 92 cases with locally advanced NSCLC patients were randomly divided into two groups: (1) BAI chemotherapy group: 39 cases were received BAI chemotherapy for 2 courses and followed surgery; (2) surgery alone group: 51 cases were treated by operation alone.The complete resection rate and preoperative complications were compared between these two groups.Results: In BAI chemotherapy group, the rate of clinical efficiency was 68.3% with slight toxicity.In BAI chemotherapy group the surgery complete resection rate was 89.7%, which was significantly higher than that in surgery alone group (72.5%, P<0.05).No significant differences of blood loss, operative complications and mortality were observed between these two groups.Conclusion: BAI neoadjuvant chemotherapy was safe and effective, which can increase the complete resection rate of the tumor and did not increase the operative complications and mortality.

  2. Assessment of quality of life in patients with advanced non-small cell lung carcinoma treated with a combination of carboplatin and paclitaxel

    Directory of Open Access Journals (Sweden)

    Camila Uanne Resende Avelino

    2015-04-01

    Full Text Available OBJECTIVE: Non-small cell lung carcinoma (NSCLC is the most common type of lung cancer. Most patients are diagnosed at an advanced stage, palliative chemotherapy therefore being the only treatment option. This study was aimed at evaluating the health-related quality of life (HRQoL of advanced-stage NSCLC patients receiving palliative chemotherapy with carboplatin and paclitaxel. METHODS: This was a multiple case study of advanced-stage NSCLC outpatients receiving chemotherapy at a public hospital in Rio de Janeiro, Brazil. The European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire was used in conjunction with its supplemental lung cancer-specific module in order to assess HRQoL. RESULTS: Physical and cognitive functioning scale scores differed significantly among chemotherapy cycles, indicating improved and worsened HRQoL, respectively. The differences regarding the scores for pain, loss of appetite, chest pain, and arm/shoulder pain indicated improved HRQoL. CONCLUSIONS: Chemotherapy was found to improve certain aspects of HRQoL in patients with advanced-stage NSCLC.

  3. Autophagy Accompanied with Bisdemethoxycurcumin-induced Apoptosis in Non-small Cell Lung Cancer Cells

    Institute of Scientific and Technical Information of China (English)

    XU Jin Hong; YANG He Ping; ZHOU Xiang Dong; WANG Hai Jing; GONG Liang; TANG Chun Lan

    2015-01-01

    Objective To investigate the effects of bisdemethoxycurcumin (BDMC) on non-small cell lung cancer (NSCLC) cell line, A549, and the highly metastatic lung cancer 95D cells. Methods CCK-8 assay was used to assess the effect of BDMC on cytotoxicity. Flow cytometry was used to evaluate apoptosis. Western blot analysis, electron microscopy, and quantification of GFP-LC3 punctuates were used to test the effect of BDMC on autophagy and apoptosis of lung cancer cells. Results BDMC inhibited the viability of NSCLC cells, but had no cytotoxic effects on lung small airway epithelial cells (SAECs). The apoptotic cell death induced by BDMC was accompanied with the induction of autophagy in NSCLC cells. Blockage of autophagy by the autophagy inhibitor 3-methyladenine (3-MA) repressed the growth inhibitory effects and induction of apoptosis by BDMC. In addition, BDMC treatment significantly decreased smoothened (SMO) and the transcription factor glioma-associated oncogene 1 (Gli1) expression. Furthermore, depletion of Gli1 by siRNA and cyclopamine (a specific SMO inhibitor) induced autophagy. Conclusion Aberrant activation of Hedgehog (Hh) signaling has been implicated in several human cancers, including lung cancers. The present findings provide direct evidence that BDMC-induced autophagy plays a pro-death role in NSCLC, in part, by inhibiting Hedgehog signaling.

  4. Expression of SKP2 Protein in Non-small Cell Lung Carcinoma

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective: To study the expressive characteristics of SKP2 protein in non-small cell lung carcinoma and it is affection to NSCLC patients' prognosis. Methods: The expression of SKP2 protein was detected in 89 NSCLC, 5 benign lung neoplasmas, 5 normal bronchus and lung tissues by Tissue Chip and immunohistochemistry technology.Results: The positive rate of SKP2 protein staining was (23.52±13.57)% in NSCLC tissues, significantly higher than that in benign lung neoplasmas, normal brochus and lung tissues (2.91±1.27)% (P=0.0000<0.001). The expressive level of SKP2 protein in NSCLC tissues was closely related to cell differentiation (P1=0.000<0.001),but not to age, sex, smoking history, pathological type, site, size, lymph node metastasis and TNM stage (each P1>0.05). The survival analysis displayed that the NSCLC patients' 5 years survival rate was lower in positive expression group than that in negative expression group (P1=0.042/0.031<0.05; r=-0.186, P2=0.000<0.001).Conclusion: The positive expression of SKP2 protein may play an enhancement role in the occurrence and development of NSCLC. Moreover, it may be a bad indicator to NSCLC patients' prognosis.

  5. Loss of aquaporin-4 expression and putative function in non-small cell lung cancer

    International Nuclear Information System (INIS)

    Aquaporins (AQPs) have been recognized to promote tumor progression, invasion, and metastasis and are therefore recognized as promising targets for novel anti-cancer therapies. Potentially relevant AQPs in distinct cancer entities can be determined by a comprehensive expression analysis of the 13 human AQPs. We analyzed the presence of all AQP transcripts in 576 different normal lung and non-small cell lung cancer (NSCLC) samples using microarray data and validated our findings by qRT-PCR and immunohistochemistry. Variable expression of several AQPs (AQP1, -3, -4, and -5) was found in NSCLC and normal lung tissues. Furthermore, we identified remarkable differences between NSCLC subtypes in regard to AQP1, -3 and -4 expression. Higher transcript and protein levels of AQP4 in well-differentiated lung adenocarcinomas suggested an association with a more favourable prognosis. Beyond water transport, data mining of co-expressed genes indicated an involvement of AQP4 in cell-cell signalling, cellular movement and lipid metabolism, and underlined the association of AQP4 to important physiological functions in benign lung tissue. Our findings accentuate the need to identify functional differences and redundancies of active AQPs in normal and tumor cells in order to assess their value as promising drug targets

  6. Raman spectroscopy identifies radiation response in human non-small cell lung cancer xenografts

    Science.gov (United States)

    Harder, Samantha J.; Isabelle, Martin; Devorkin, Lindsay; Smazynski, Julian; Beckham, Wayne; Brolo, Alexandre G.; Lum, Julian J.; Jirasek, Andrew

    2016-02-01

    External beam radiation therapy is a standard form of treatment for numerous cancers. Despite this, there are no approved methods to account for patient specific radiation sensitivity. In this report, Raman spectroscopy (RS) was used to identify radiation-induced biochemical changes in human non-small cell lung cancer xenografts. Chemometric analysis revealed unique radiation-related Raman signatures that were specific to nucleic acid, lipid, protein and carbohydrate spectral features. Among these changes was a dramatic shift in the accumulation of glycogen spectral bands for doses of 5 or 15 Gy when compared to unirradiated tumours. When spatial mapping was applied in this analysis there was considerable variability as we found substantial intra- and inter-tumour heterogeneity in the distribution of glycogen and other RS spectral features. Collectively, these data provide unique insight into the biochemical response of tumours, irradiated in vivo, and demonstrate the utility of RS for detecting distinct radiobiological responses in human tumour xenografts.

  7. Pharmacogenomics of Cisplatin Sensitivity in Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Maimon C. Rose

    2014-10-01

    Full Text Available Cisplatin, a platinum-based chemotherapeutic drug, has been used for over 30 years in a wide variety of cancers with varying degrees of success. In particular, cisplatin has been used to treat late stage non-small cell lung cancer (NSCLC as the standard of care. However, therapeutic outcomes vary from patient to patient. Considerable efforts have been invested to identify biomarkers that can be used to predict cisplatin sensitivity in NSCLC. Here we reviewed current evidence for cisplatin sensitivity biomarkers in NSCLC. We focused on several key pathways, including nucleotide excision repair, drug transport and metabolism. Both expression and germline DNA variation were evaluated in these key pathways. Current evidence suggests that cisplatin-based treatment could be improved by the use of these biomarkers.

  8. Pharmacogenomics of Cisplatin Sensitivity in Non-small Cell Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    Maimon C Rose; Elina Kostyanovskaya; R Stephanie Huang

    2014-01-01

    Cisplatin, a platinum-based chemotherapeutic drug, has been used for over 30 years in a wide variety of cancers with varying degrees of success. In particular, cisplatin has been used to treat late stage non-small cell lung cancer (NSCLC) as the standard of care. However, therapeutic outcomes vary from patient to patient. Considerable efforts have been invested to identify biomark-ers that can be used to predict cisplatin sensitivity in NSCLC. Here we reviewed current evidence for cisplatin sensitivity biomarkers in NSCLC. We focused on several key pathways, including nucleotide excision repair, drug transport and metabolism. Both expression and germline DNA variation were evaluated in these key pathways. Current evidence suggests that cisplatin-based treatment could be improved by the use of these biomarkers.

  9. The potential diagnostic power of circulating tumor cell analysis for non-small-cell lung cancer.

    Science.gov (United States)

    Ross, Kirsty; Pailler, Emma; Faugeroux, Vincent; Taylor, Melissa; Oulhen, Marianne; Auger, Nathalie; Planchard, David; Soria, Jean-Charles; Lindsay, Colin R; Besse, Benjamin; Vielh, Philippe; Farace, Françoise

    2015-01-01

    In non-small-cell lung cancer (NSCLC), genotyping tumor biopsies for targetable somatic alterations has become routine practice. However, serial biopsies have limitations: they may be technically difficult or impossible and could incur serious risks to patients. Circulating tumor cells (CTCs) offer an alternative source for tumor analysis that is easily accessible and presents the potential to identify predictive biomarkers to tailor therapies on a personalized basis. Examined here is our current knowledge of CTC detection and characterization in NSCLC and their potential role in EGFR-mutant, ALK-rearranged and ROS1-rearranged patients. This is followed by discussion of the ongoing issues such as the question of CTC partnership as diagnostic tools in NSCLC. PMID:26564313

  10. Chemotherapy and cyclic radiation therapy in locally advanced non-small cell lung carcinoma

    International Nuclear Information System (INIS)

    Nine patients with non-small cell lung carcinoma (4 squamous, 4 adenocarcinoma, 1 large cell) were treated with a combination of radiation therapy and cyclic chemotherapy with 5-fluorouracil, methotrexate and platinum. Four previously untreated patients had stage III, 2 having distant metastases, 5 previously treated patients were restaged as stage III with distant metastasis in one. Moderate hematologic toxicity was noted. Objective responses occurred in 67 per cent, regardless of previous treatment or performance status. Responders survived for a median of 11 months with one complete response patient surviving at 14 months while 5 partial response patients survived for a median of 10 months. This regimen is feasible and its utility as the initial treatment of locally advanced disease should be further investigated. (Auth.)

  11. Longitudinal assessment of TUBB3 expression in non-small cell lung cancer patients

    DEFF Research Database (Denmark)

    Jakobsen, Jan Nyrop; Santoni-Rugiu, Eric; Sørensen, Jens Benn

    2014-01-01

    NSCLC patients stage T1-4N0-1 was treated with surgery alone without preceding chemotherapy (OP-group). Paired repeated samples were compared in order to evaluate for changes in TUBB3 expression. RESULTS: No statistically significant change in TUBB3 expression was observed between initial diagnostic......INTRODUCTION: Class-III-beta-tubulin (TUBB3) expression may be a potential predictive factor for treatment with microtubule interfering cytotoxic drugs in non-small cell lung cancer (NSCLC). Potential changes in TUBB3 expression during chemotherapy may be of interest if future choice of...... chemotherapy is to be based on TUBB3 expression. If the biomarker expression changes during chemotherapy, biopsies before initiation of chemotherapy beyond first line may be needed if treatment decision is to be based on TUBB3 expression. Thus, the aim was to explore TUBB3 expression heterogeneity and changes...

  12. A case of spontaneous pneumothorax following radiation therapy for non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Himanshu Bhardwaj

    2013-01-01

    Full Text Available Spontaneous pneumothorax (SPTX is a potentially devastating rare complication of the thoracic radiation therapy. Most of the cases in the medical literature, have been described in lymphoma patients receiving radiation therapy. The pathogenesis of this adverse event remains undefined although different mechanisms have been proposed. We present a case of post-radiation therapy SPTX in a non-small cell lung cancer (NSCLC, following intensity modulated radiation therapy (IMRT, which to our knowledge is the first such reported case related to this newer mode of radiation therapy. This report highlights the importance of keeping a close eye for this complication as timely treatment with chest tube insertion and drainage of the pneumothorax can be a lifesaving in these patients.

  13. Review of the current targeted therapies for non-small-cell lung cancer.

    Science.gov (United States)

    Nguyen, Kim-Son H; Neal, Joel W; Wakelee, Heather

    2014-10-10

    The last decade has witnessed the development of oncogene-directed targeted therapies that have significantly changed the treatment of non-small-cell lung cancer (NSCLC). In this paper we review the data demonstrating efficacy of gefitinib, erlotinib, and afatinib, which target the epidermal growth factor receptor (EGFR), and crizotinib which targets anaplastic lymphoma kinase (ALK). We discuss the challenge of acquired resistance to these small-molecular tyrosine kinase inhibitors and review promising agents which may overcome resistance, including the EGFR T790M-targeted agents CO-1686 and AZD9291, and the ALK-targeted agents ceritinib (LDK378), AP26113, alectinib (CH/RO5424802), and others. Emerging therapies directed against other driver oncogenes in NSCLC including ROS1, HER2, and BRAF are covered as well. The identification of specific molecular targets in a significant fraction of NSCLC has led to the personalized deployment of many effective targeted therapies, with more to come. PMID:25302162

  14. 17 cases of advanced non-small cell lung cancer treated with paclitaxel liposome plus nedaplatin

    Institute of Scientific and Technical Information of China (English)

    Tao Suo; Wei Ge; Jinzhong Zhang; Yongfa Zheng; Shunxiang Luo

    2012-01-01

    Objective: The aim of this study was to evaluate the recent efficacy and adverse reactions of paclitaxel liposome plus nedaplatin in the treatment of advanced non-small cell lung cancer (NSCLC).Methods: Seventeen cases of NSCLC treated with paclitaxel liposome and nedaplatin for 2 to 6 cycles, by infusing paclitaxel liposome 135 mg/m2 for 3 h on d1 and nedaplatin 80 mg/m2 as infusion on d2.Results: Among 17 patients being evaluated for response to treatment, 1 achieved complete response (CR), 4 achieved partial response (PR), 3 achieved stable disease (SD), 9 achieved progress disease (PD).The main adverse reaction was haematological toxicities, especially leukopenia and thrombocytopenia.The non-haematological toxicities included nausea, vomiting, mild hepatic dysfunction, alopecia and so on.Conclusion: Paclitaxel liposome plus nedaplatin was effective and well tolerated for treating patients with advanced NSCLC.

  15. Adoptive immunotherapy combined chemoradiotherapy for non-small-cell lung cancer: a meta-analysis.

    Science.gov (United States)

    Qian, Haili; Wang, Haijuan; Guan, Xiuwen; Yi, Zongbi; Ma, Fei

    2016-06-01

    The aim of this study was to compare the efficacies between adoptive immunotherapy combined chemoradiotherapy and chemoradiotherapy alone in patients with non-small-cell lung cancer (NSCLC). The databases PubMed, EMBASE, and Cochrane database were searched to identify eligible clinical trials. Data analyses were carried out using a comprehensive meta-analysis program, version 2 software. A total of seven articles were finally included in the analysis. Meta-analyses showed that compared with chemoradiotherapy alone, adoptive immunotherapy combined with chemoradiotherapy could improve the 2-year overall survival [odds ratio (OR)=2.45, 95% confidence interval (CI): 1.60-3.75, Pshiver, nausea, fatigue, etc. and severe toxicities were not observed. Adoptive immunotherapy combined with chemoradiotherapy can delay the recurrence of NSCLC and improve survival in patients, where the benefits are even more significant in patients with early-stage NSCLC. PMID:26872311

  16. Changes in epidermal growth factor receptor expression during chemotherapy in non-small cell lung cancer

    DEFF Research Database (Denmark)

    Jakobsen, Jan Nyrop; Santoni-Rugiu, Eric; Sørensen, Jens Benn

    2014-01-01

    BACKGROUND: Antibodies targeting epidermal growth factor receptor (EGFR), such as cetuximab, may potentially improve outcome in non-small cell lung cancer (NSCLC) patients with high EGFR expression. The EGFR expression may be heterogeneously distributed within tumors, and small biopsies may thus...... not accurately reveal the EGFR expression. In addition, EGFR expression may also change during chemotherapy. The current study investigates the magnitude of these two issues. MATERIALS AND METHODS: EGFR expression in diagnostic biopsies and resection specimen was compared in 53 NSCLC patients stage T1......-4N0-1M0 treated with surgery without preceding chemotherapy (OP group), and 65 NSCLC patients stage T1-3N0-2M0 (NAC group) treated with preoperative carboplatin and paclitaxel in order to evaluate the discordance of EGFR expression between samples. RESULTS: Discordance between tumors dichotomized...

  17. Unlocking Pandora's box: personalising cancer cell death in non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Fennell Dean A

    2012-06-01

    Full Text Available Abstract Evasion of apoptosis is a hallmark of tumorigenesis and a recognised cause of multidrug resistance. Over the last decade, insights into how apoptosis might be exploited in non-small cell lung cancer (NSCLC and how cancer therapeutics might be used to engage apoptotic signalling in a personalised manner have changed markedly. We are now in the wake of a paradigm shift in stratified therapeutic approaches related to NSCLC. At the heart of this shift in thinking is the emerging knowledge that even the most drug-resistant cancers exhibit a functional death pathway and, critically, that this pathway can be efficiently engaged, leading to clinical benefit. This review will summarise current knowledge of mitochondrial apoptotic pathway dysfunction in NSCLC and how the next generation of targeted therapeutics might be used to exploit deficiencies in apoptotic signalling in a personalised manner to improve clinical outcome and predict therapeutic benefit.

  18. Pharmacokinetics of gemcitabine in Chinese patients with non-small-cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    WANG Lin-run; HUANG Ming-zhu; XU Nong; SHENTU Jian-zhong; LIU Jian; CAI Jie

    2005-01-01

    To determine the pharmacokinetics of gemcitabine (2',2'-difluorodeoxycytidine) in Chinese non-small-cell lung cancer (NSCLC) patients. Six study subjects were administered gemcitabine at a fixed dose rate of 10 mg/m2 per min (1200 mg/m2,two hours infusion) and carboplatin, and plasma gemcitabine concentrations were measured by ion-pair reversed-phase high-performance liquid chromatography (HPLC). 3P97 Pharmaceutical Kinetics Software was used for the calculation of pharmacokinetic parameters. The obtained mean parameters, elimnation half life (t1/2) (10.67±3.38 min), area under the curve hematologic toxicology result showed that the regimen was effective on and tolerated by the patients.

  19. The Conceptual Oligometastatic Non-small Cell Lung Cancer and Therapeutic Strategies

    Directory of Open Access Journals (Sweden)

    Xiaozheng KANG

    2012-04-01

    Full Text Available Non-small cell lung cancer (NSCLC ranks among the most prevalent malignancies and is the major cause of cancer-related deaths worldwide. Nearly 20%-50% will accompany by metastatic disease and the most common extrapulmonary sites of distant metastases are the brain, bone, liver and adrenal gland. The oligometastatic state is a biologically mild tumor stage and a intermediate state in which spread may be limited to specific organs and metastases might be present in limited numbers. Oligometastases are thought to arise from micrometastases, which have been dormant for a period of time. Local control may be an crucial component of a curative therapeutic strategy in the following four clinical schemes: to prohibit metastases; to cure occult metastatic disease; to remedy oligometastases; and to deracinate any residual lesion after systemic therapy. This review aims to outline the concept of the oligometastatic NSCLC and its strategies of treatment.

  20. Profile of ramucirumab in the treatment of metastatic non-small-cell lung cancer.

    Science.gov (United States)

    Cooper, Maryann R; Binkowski, Chelsea; Hartung, Jessica; Towle, Jennifer

    2016-01-01

    The interaction between vascular endothelial growth factor and its receptor is an important therapeutic target due to the importance of this pathway in carcinogenesis. In particular, this pathway promotes and regulates angiogenesis as well as increases endothelial cell proliferation, permeability, and survival. Ramucirumab is a fully human monoclonal antibody that specifically targets the vascular endothelial growth factor receptor-2, the key receptor implicated in angiogenesis. Currently, ramucirumab is approved for the second-line treatment of metastatic non-small-cell lung cancer (NSCLC) in combination with docetaxel. In a Phase III clinical trial, ramucirumab was shown to improve the overall survival in patients with disease progression, despite platinum-based chemotherapy for advanced NSCLC. This review describes the pharmacology, pharmacokinetics and dynamics, adverse event profile, and the clinical activity of ramucirumab observed in Phase II and III trials in NSCLC. PMID:27110124

  1. Difficulties encountered and solutions found when implementing stereotactic radiotherapy of non-small cell lung cancer

    International Nuclear Information System (INIS)

    The aim of this paper is to describe the difficulties encountered when implementing stereotactic radiotherapy of non-small cell lung cancer (T1-T2, N0, M0) using a voluntary breath-hold technique. From 25/03/2010 to 22/02/2011, eight patients with a non-small cell lung cancer were selected for treatment. CT images were obtained with the patient maintaining breath-hold using a spirometer. Treatment was delivered when the patient maintains this level of breath-hold. Treatment was performed with a 4 MV and 10 MV photon beams from a linear accelerator Varian 2100CS, equipped with a 120 leaves collimator. 60 Gy or 48 Gy were delivered, in four sessions, to the 80% isodose. The planning target volume (PTV) was defined by adding a 5 mm margin to the internal target volume (ITV), the ITV corresponding to the gross tumour volume (GTV) plus a 3 mm margin. CTV is considered equal to GTV. The non-understanding of the gating technique, the great number of beams and the limited breath-hold times led to the failure of some treatments. It can be explained by some patients insufficient respiratory abilities and the low dose rate of one of the beams used for treatment, thus forcing some radiation fields to be delivered in two or three times. Implementing such a technique can be limited by the patients' physical abilities and the materials used. Some solutions were found: a training phase more intense with a coaching of the breath-hold technique more precise, or the use of an abdominal compression device. (authors)

  2. Nintedanib plus docetaxel as second-line therapy in patients with non-small-cell lung cancer

    DEFF Research Database (Denmark)

    Popat, Sanjay; Mellemgaard, Anders; Fahrbach, Kyle;

    2015-01-01

    BACKGROUND: Nintedanib plus docetaxel has proven an overall survival benefit over docetaxel monotherapy in second-line treatment of non-small-cell lung cancer of adenocarcinoma histology in the LUME-Lung 1 pivotal trial. No published trials have previously compared nintedanib plus docetaxel with...... agents – other than docetaxel – that are approved second-line treatments for non-small-cell lung cancer. METHODS: The relative efficacy of nintedanib plus docetaxel versus second-line agents was evaluated by conducting a network meta-analysis of progression-free survival and overall survival. RESULTS...... with advanced non-small-cell lung cancer of adenocarcinoma histology, results suggest that nintedanib plus docetaxel offers clinical benefit compared with docetaxel alone, when used as second-line treatment, and suggests that this combination may also add clinical benefit compared with erlotinib in...

  3. Surgery Versus Stereotactic Radiosurgery for Single Synchronous Brain Metastasis from Non-Small Cell Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    Hui LI; Sheng-cai HOU; Bin HU; Tong LI; Yang Wang; Jin-bai Miao; Bin You; Yi-li Fu

    2009-01-01

    Objective: The aim of this study is to compare the effectiveness of surgery with stereotactic radiosurgery (SRS) for patients with a single synchronous brain metastasis from successfully treated non-small cell lung cancer.Methods: Between 1995 and 2002, 53 patients underwent resection of both primary non-small cell lung cancer and the associated single brain metastasis. There were 33 men and 20 women with a mean age of 57 years (range, 32(85 years). At the time of diagnosis, 42 patients experienced lung cancer related symptoms, whereas 11 patients experienced brain metastases-related symptoms. 42 patients had received thoracic surgery first, and 11 patients had undergone neurosurgery or radiosurgery first. Pneumonectomy was performed in 9 out of 42 patients (21.4%), lobectomies in 30 (71.4%), and wedge resection in 3 (7.2%). 48 patients (90.5%) underwent complete lymphadenectomy. 35 patients underwent brain metastasectomy. 18 underwent SRS.Results: There was no postoperative mortality and severe complications after either lung or brain surgery. Histology showed 34 adenocarcinomas, 16 squamous cell carcinomas, and 3 large cell lung cancers. 15 patients (28.3%) had no evidence of lymph node metastases (N0), 20 patients (37.7%) had hilar metastases (N1), and 18 patients (34%) had mediastinal metastases (N2). The 1-, 2-, 3- and 5-year overall survival rates were 49%, 19%, 10%, and 5%, respectively. The corresponding data for neurosurgery group were 55%, 17%, 11%, and 6%, respectively. The median survival time was 13 months. For SRS group the corresponding data were 44.8%, 20.9% 10.5%, and 2%, respectively. The median survival time was 14 months. The differences between the two groups were not significant (P>0.05). In lymph node negative patients (N0), the overall 5-year survival rate was 10%, as compared with a 1% survival rate in patients with lymph node metastases (N1(2). The difference was significant (P0.05).Conclusion: Although the overall survival rate for

  4. Human leukocyte antigen (HLA)-G gene polymorphism in patients with non-small cell lung cancer

    OpenAIRE

    Kowal, Aneta; Wiśniewski, Andrzej; Kuśnierczyk, Piotr; Jankowska, Renata

    2015-01-01

    Background Lung cancer represents the highest morbidity and mortality caused by neoplasms in the world; therefore researchers continue to search for new tools to diagnose and treat the disease. The aim of the study was to establish the role of single nucleotide polymorphisms (SNP) in the promoter region of the human leukocyte antigen (HLA)-G gene in patients with non-small cell lung cancer. Methods We enrolled 143 patients with a mean age of 63 years, diagnosed with non-small cell lung cancer...

  5. Cross-talk between AMPK and EGFR dependent Signaling in Non-Small Cell Lung Cancer

    Science.gov (United States)

    Praveen, Paurush; Hülsmann, Helen; Sültmann, Holger; Kuner, Ruprecht; Fröhlich, Holger

    2016-06-01

    Lung cancers globally account for 12% of new cancer cases, 85% of these being Non Small Cell Lung Cancer (NSCLC). Therapies like erlotinib target the key player EGFR, which is mutated in about 10% of lung adenocarcinoma. However, drug insensitivity and resistance caused by second mutations in the EGFR or aberrant bypass signaling have evolved as a major challenge in controlling these tumors. Recently, AMPK activation was proposed to sensitize NSCLC cells against erlotinib treatment. However, the underlying mechanism is largely unknown. In this work we aim to unravel the interplay between 20 proteins that were previously associated with EGFR signaling and erlotinib drug sensitivity. The inferred network shows a high level of agreement with protein-protein interactions reported in STRING and HIPPIE databases. It is further experimentally validated with protein measurements. Moreover, predictions derived from our network model fairly agree with somatic mutations and gene expression data from primary lung adenocarcinoma. Altogether our results support the role of AMPK in EGFR signaling and drug sensitivity.

  6. Teroxirone inhibited growth of human non-small cell lung cancer cells by activating p53

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Jing-Ping; Lin, Kai-Han; Liu, Chun-Yen; Yu, Ya-Chu; Wu, Pei-Tsun [Department of Life Science, National Taiwan Normal University, Taipei, Taiwan (China); Chiu, Chien-Chih [Department of Biotechnology, Kaohsiung Medical University, Kaohsiung, Taiwan (China); Su, Chun-Li [Department of Human Development and Family Studies, National Taiwan Normal University, Taipei, Taiwan (China); Chen, Kwun-Min [Department of Chemistry, National Taiwan Normal University, Taipei, Taiwan (China); Fang, Kang, E-mail: kangfang@ntnu.edu.tw [Department of Life Science, National Taiwan Normal University, Taipei, Taiwan (China)

    2013-11-15

    In this work, we demonstrated that the growth of human non-small-cell-lung-cancer cells H460 and A549 cells can be inhibited by low concentrations of an epoxide derivative, teroxirone, in both in vitro and in vivo models. The cytotoxicity was mediated by apoptotic cell death through DNA damage. The onset of ultimate apoptosis is dependent on the status of p53. Teroxirone caused transient elevation of p53 that activates downstream p21 and procaspase-3 cleavage. The presence of caspase-3 inhibitor reverted apoptotic phenotype. Furthermore, we showed the cytotoxicity of teroxirone in H1299 cells with stable ectopic expression of p53, but not those of mutant p53. A siRNA-mediated knockdown of p53 expression attenuated drug sensitivity. The in vivo experiments demonstrated that teroxirone suppressed growth of xenograft tumors in nude mice. Being a potential therapeutic agent by restraining cell growth through apoptotic death at low concentrations, teroxirone provides a feasible perspective in reversing tumorigenic phenotype of human lung cancer cells. - Highlights: • Teroxirone repressed tumor cell growth in nude mice of human lung cancer cells. • The apoptotic cell death reverted by caspase-3 inhibitor is related to p53 status. • Teroxirone provides a good candidate for lung cancer treatment.

  7. Takotsubo cardiomyopathy associated with pulmonary resections after induction chemoradiotherapy for non-small cell lung cancer

    International Nuclear Information System (INIS)

    Takotsubo cardiomyopathy (TTC), also known as transient left ventricular (LV) apical ballooning syndrome, is characterized by transient LV dysfunction. We present the case of a 72-year-old man who was diagnosed as having TTC after surgery for two lung tumors. The patient was treated with induction chemoradiotherapy (CRT) followed by pulmonary resections for double primary non-small cell lung cancers (NSCLC): cT4N1M0 disease in the right lung and cT2N0M0 in the left lung. Induction CRT was performed. A right upper lobectomy was initially performed, and a left upper divisionectomy was subsequently performed. At 3 days after the second surgery, he developed dyspnea and general fatigue accompanied by a T-wave inversion on electrocardiography (ECG). An echocardiogram revealed akinesis at the apex with a 30% ejection fraction. He was diagnosed as having TTC and recovered with supportive care. This case is the first report of TTC occurring after tri-modality therapy for NSCLC. (author)

  8. Effects of Monoclonal Antibody Cetuximab on Proliferation of Non-small Cell Lung Cancer Cell lines

    Directory of Open Access Journals (Sweden)

    Zhen CHEN

    2010-08-01

    Full Text Available Background and objective The epidermal growth factor receptor (EGFR monoclonal antibody cetuximab has been used widely in non-small cell lung cancer patients. The aim of this study is to explore the effect of lung cancer cells (A549, H460, H1299, SPC-A-1 which were treated by cetuximab in vitro. Methods We studied the effects of increasing concentrations of cetuximab (1 nmol/L-625 nmol/L in four human lung cancer cell lines (A549, SPC-A-1, H460, H1229. CCK8 measured the inhibition of cell proliferation in each group. A549, SPC-A-1 were marked by PI and the statuses of apoptosis were observed. Western blot were used to detect the proliferation-related signaling protein and apoptosis-related protein in A549. Results The treatment with cetuximab resulted in the effect on cell proliferation and apoptosis in a time- and dosedependent manner. The expression of activated key enzymes (p-AKT, p-EGFR, p-MAPK in EGFR signaling transduction pathway were down-regulated more obviously. Conclusion Cetuximab is an effective targeted drug in the treatment of lung cancer cell lines, tissues, most likely to contribute to the inhibition of key enzymes in EGFR signaling transduction pathway.

  9. The expression of GST isoenzymes and p53 in non-small cell lung cancer.

    Directory of Open Access Journals (Sweden)

    MĂźzeyyen Ozhavzali

    2010-06-01

    Full Text Available This study investigated the immunohistochemical staining characteristics of glutathione-S-transferase alpha, pi, mu, theta and p53 in non-small cell lung carcinoma and normal lung tissue from 50 patients. The relationships between expressions of the Glutathione-S-transferase isoenzymes and some clinicopathological features were also examined. Expression of glutathione-S-transferase pi, mu, alpha, theta and p53 was assessed by immunohistochemistry for primary lung carcinomas of 50 patients from the Sanitarium Education and Research Hospital, Ankara lung cancer collection. The relationships between expression of the glutathione-S-transferase isoenzymes, p53 in normal and tumor tissue by Student T test and the clinicopathological data were also examined by Spearman Rank tests. When the normal and tumor tissue of these cases were compared according to their staining intensity and percentage of positive staining, glutathione-S-transferase alpha, pi, mu, theta expressions in tumor cells was significantly higher than normal cells (p<0.05. There was no significant difference in the expression of p53 between normal and tumor cells (p>0.05. When the immunohistochemical results of glutathione-S-transferase isoenzymes and p53 were correlated with the clinical parameters, there were no significant associations between glutathione-S-transferases and p53 expressions and tumor stage, tumor grade and smoking status (p>0.05.

  10. Teroxirone inhibited growth of human non-small cell lung cancer cells by activating p53

    International Nuclear Information System (INIS)

    In this work, we demonstrated that the growth of human non-small-cell-lung-cancer cells H460 and A549 cells can be inhibited by low concentrations of an epoxide derivative, teroxirone, in both in vitro and in vivo models. The cytotoxicity was mediated by apoptotic cell death through DNA damage. The onset of ultimate apoptosis is dependent on the status of p53. Teroxirone caused transient elevation of p53 that activates downstream p21 and procaspase-3 cleavage. The presence of caspase-3 inhibitor reverted apoptotic phenotype. Furthermore, we showed the cytotoxicity of teroxirone in H1299 cells with stable ectopic expression of p53, but not those of mutant p53. A siRNA-mediated knockdown of p53 expression attenuated drug sensitivity. The in vivo experiments demonstrated that teroxirone suppressed growth of xenograft tumors in nude mice. Being a potential therapeutic agent by restraining cell growth through apoptotic death at low concentrations, teroxirone provides a feasible perspective in reversing tumorigenic phenotype of human lung cancer cells. - Highlights: • Teroxirone repressed tumor cell growth in nude mice of human lung cancer cells. • The apoptotic cell death reverted by caspase-3 inhibitor is related to p53 status. • Teroxirone provides a good candidate for lung cancer treatment

  11. Overexpression of Cathepsin L is associated with gefitinib resistance in non-small cell lung cancer.

    Science.gov (United States)

    Cui, F; Wang, W; Wu, D; He, X; Wu, J; Wang, M

    2016-07-01

    Lung cancer, the most common malignancy, is still the leading cause of cancer-related death worldwide. Non-small-cell lung cancer (NSCLC) accounts for 80 % of all lung cancers. Recent studies showed Cathepsin L (CTSL) is overexpressed in various cancerous tissues; however, the association between CTSL expression and EGFR-TKI resistance remains unknown. In this study, we investigated the expression of CTSL in lung cancer specimens and matched normal tissues by quantitative real-time PCR and IHC. The functional role of CTSL in resistant PC-9/GR cell line was investigated by proliferation and apoptosis analysis compared with control PC-9 cells. Our results found that the level of CTSL expression was higher in NSCLC tissues compared with matched normal adjacent tissue samples, and CTSL was more highly expressed in PC-9/GR cells compared to PC-9 cells. Knocking-down of CTSL in PC-9/GR cells could decrease cell proliferation and potentiate apoptosis induced by gefitinib, suggesting CTSL may contribute to gefitinib resistance in NSCLC. CTSL might be explored as a candidate of therapeutic target for modulating EGFR-TKI sensitivity in NSCLC. PMID:26474873

  12. Clinicopathological and immunohistochemical profile of non-small cell lung carcinoma in a tertiary care medical centre in South India

    OpenAIRE

    Shanmugapriya Shankar; Vijayalakshmi Thanasekaran; Dhanasekar, T.; Prathiba Duvooru

    2014-01-01

    Background: Lung cancer is a highly aggressive malignancy causing high morbidity and mortality. An increasing incidence of lung cancer has been observed in India. Currently, the classification of lung carcinoma has gone beyond small cell lung carcinoma and non-small cell lung carcinoma (NSCLC). Precise subtyping of poorly differentiated NSCLC into adenocarcinoma and squamous cell carcinoma has a direct impact on patient management and prognosis. With this background, many molecules are under ...

  13. Serum levels of HMGB1, survivin, and VEGF in patients with advanced non-small cell lung cancer during chemotherapy.

    Directory of Open Access Journals (Sweden)

    Wiesława Nilklińska

    2010-05-01

    Full Text Available Recently, several reports have suggested that HMGB1 (the high-mobility group box-1 plays a key role in tumor angiogenesis through multiple mechanisms, including up-regulation of proangiogenic factors. This study was conducted to investigate the prognostic role and the effects of chemotherapy on serum (ELISA angiogenic factors: HMGB1, survivin and VEGF (Vascular Endothelial Growth Factor in patients with advanced stage non-small cell lung cancer (NSCLC. The study entered 40 patients (31 man and 15 healthy volunteers (control group. Peripheral blood samples were taken before and after four cycles of chemotherapy. The mean serum HMGB1 and VEGF levels were significantly higher in patients with advanced NSCLC than in controls (p=0.024, p=0.028, respectively. The levels of survivin in NSCLC patients were comparable to controls. No correlation was found between HMGB1, survivin and VEGF concentrations and the histological type and staging of lung cancer. Similarly, no correlation was revealed between the concentrations of HMGB1, survivin and VEGF and the effect of chemotherapy. However, in patients with NSCLC, HMGB1 positevely correlated with survivin (R=0.814, p=0.007 before chemotherapy, and negatively with VEGF (R=-0.841, p=0.035 after chemotherapy. When the cut-off values of serum HMGB1, survivin and VEGF (2.38 ng/ml, 81.92 pg/ml, 443.26 pg/ml, respectively were used, the prognoses of high and low groups were not different. Concluding, patients with NSCLC have a higher serum concentration of HMGB1 and VEGF, while survivin levels are comparable to healthy individuals. In our opinion, determination of HMGB1, survivin and VEGF concentrations has no clinical significance in the prognosis of the survival time in lung cancer.

  14. Impact of chronic obstructive pulmonary disease on postoperative recurrence in patients with resected non-small-cell lung cancer

    Directory of Open Access Journals (Sweden)

    Qiang GL

    2015-12-01

    Full Text Available Guangliang Qiang, Chaoyang Liang, Fei Xiao, Qiduo Yu, Huanshun Wen, Zhiyi Song, Yanchu Tian, Bin Shi, Yongqing Guo, Deruo Liu Department of Thoracic Surgery, China–Japan Friendship Hospital, Beijing, People’s Republic of China Purpose: This study aimed to determine whether the severity of chronic obstructive pulmonary disease (COPD affects recurrence-free survival in non-small-cell lung cancer (NSCLC patients after surgical resection.Patients and methods: A retrospective study was performed on 421 consecutive patients who had undergone lobectomy for NSCLC from January 2008 to June 2011. Classification of COPD severity was based on guidelines of the Global Initiative for Chronic Obstructive Lung Disease (GOLD. Characteristics among the three subgroups were compared and recurrence-free survivals were analyzed.Results: A total of 172 patients were diagnosed with COPD (124 as GOLD-1, 46 as GOLD-2, and two as GOLD-3. The frequencies of recurrence were significantly higher in patients with higher COPD grades (P<0.001. Recurrence-free survival at 5 years was 78.1%, 70.4%, and 46.4% in non-COPD, mild COPD, and moderate/severe COPD groups, respectively (P<0.001. By univariate analysis, the age, sex, smoking history, COPD severity, tumor size, histology, and pathological stage were associated with recurrence-free survival. Multivariate analysis showed that older age, male, moderate/severe COPD, and advanced stage were independent risk factors associated with recurrence-free survival.Conclusion: NSCLC patients with COPD are at high risk for postoperative recurrence, and moderate/severe COPD is an independent unfavorable prognostic factor. Keywords: lung neoplasms, surgery, pulmonary function test, prognosis

  15. Overexpression of TRPV3 Correlates with Tumor Progression in Non-Small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Xiaolei Li

    2016-03-01

    Full Text Available (1 Background: Transient receptor potential vanilloid 3 (TRPV3 is a member of the TRP channels family of Ca2+-permeant channels. The proteins of some TRP channels are highly expressed in cancer cells. This study aimed to assess the clinical significance and biological functions of TRPV3 in non-small cell lung cancer (NSCLC; (2 Methods: Immunohistochemistry was used to detect the expression of TRPV3 in NSCLC tissues and adjacent noncancerous lung tissues. Western blot was used to detect the protein expressions of TRPV3, CaMKII, p-CaMKII, CyclinA, CyclinD, CyclinE1, CDK2, CDK4, and P27. Small interfering RNA was used to deplete TRPV3 expression. A laser scanning confocal microscope was used to measure intracellular calcium concentration ([Ca2+]i. Flow cytometry was used to analyze cell cycle; (3 Results: TRPV3 was overexpressed in 65 of 96 (67.7% human lung cancer cases and correlated with differentiation (p = 0.001 and TNM stage (p = 0.004. Importantly, TRPV3 expression was associated with short overall survival. In addition, blocking or knockdown of TRPV3 could inhibit lung cancer cell proliferation. Moreover, TRPV3 inhibition could decrease [Ca2+]i of lung cancer cells and arrest cell cycle at the G1/S boundary. Further results revealed that TRPV3 inhibition decreased expressions of p-CaMKII, CyclinA, CyclinD1, CyclinE, and increased P27 level; (4 Conclusions: Our findings demonstrate that TRPV3 was overexpressed in NSCLC and correlated with lung cancer progression. TRPV3 activation could promote proliferation of lung cancer cells. TRPV3 might serve as a potential companion drug target in NSCLC.

  16. Transcription factor FOXA2-centered transcriptional regulation network in non-small cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Jang, Sang-Min; An, Joo-Hee; Kim, Chul-Hong; Kim, Jung-Woong, E-mail: jungkim@cau.ac.kr; Choi, Kyung-Hee, E-mail: khchoi@cau.ac.kr

    2015-08-07

    Lung cancer is the leading cause of cancer-mediated death. Although various therapeutic approaches are used for lung cancer treatment, these mainly target the tumor suppressor p53 transcription factor, which is involved in apoptosis and cell cycle arrest. However, p53-targeted therapies have limited application in lung cancer, since p53 is found to be mutated in more than half of lung cancers. In this study, we propose tumor suppressor FOXA2 as an alternative target protein for therapies against lung cancer and reveal a possible FOXA2-centered transcriptional regulation network by identifying new target genes and binding partners of FOXA2 by using various screening techniques. The genes encoding Glu/Asp-rich carboxy-terminal domain 2 (CITED2), nuclear receptor subfamily 0, group B, member 2 (NR0B2), cell adhesion molecule 1 (CADM1) and BCL2-associated X protein (BAX) were identified as putative target genes of FOXA2. Additionally, the proteins including highly similar to heat shock protein HSP 90-beta (HSP90A), heat shock 70 kDa protein 1A variant (HSPA1A), histone deacetylase 1 (HDAC1) and HDAC3 were identified as novel interacting partners of FOXA2. Moreover, we showed that FOXA2-dependent promoter activation of BAX and p21 genes is significantly reduced via physical interactions between the identified binding partners and FOXA2. These results provide opportunities to understand the FOXA2-centered transcriptional regulation network and novel therapeutic targets to modulate this network in p53-deficient lung cancer. - Highlights: • Identification of new target genes of FOXA2. • Identifications of novel interaction proteins of FOXA2. • Construction of FOXA2-centered transcriptional regulatory network in non-small cell lung cancer.

  17. Transcription factor FOXA2-centered transcriptional regulation network in non-small cell lung cancer

    International Nuclear Information System (INIS)

    Lung cancer is the leading cause of cancer-mediated death. Although various therapeutic approaches are used for lung cancer treatment, these mainly target the tumor suppressor p53 transcription factor, which is involved in apoptosis and cell cycle arrest. However, p53-targeted therapies have limited application in lung cancer, since p53 is found to be mutated in more than half of lung cancers. In this study, we propose tumor suppressor FOXA2 as an alternative target protein for therapies against lung cancer and reveal a possible FOXA2-centered transcriptional regulation network by identifying new target genes and binding partners of FOXA2 by using various screening techniques. The genes encoding Glu/Asp-rich carboxy-terminal domain 2 (CITED2), nuclear receptor subfamily 0, group B, member 2 (NR0B2), cell adhesion molecule 1 (CADM1) and BCL2-associated X protein (BAX) were identified as putative target genes of FOXA2. Additionally, the proteins including highly similar to heat shock protein HSP 90-beta (HSP90A), heat shock 70 kDa protein 1A variant (HSPA1A), histone deacetylase 1 (HDAC1) and HDAC3 were identified as novel interacting partners of FOXA2. Moreover, we showed that FOXA2-dependent promoter activation of BAX and p21 genes is significantly reduced via physical interactions between the identified binding partners and FOXA2. These results provide opportunities to understand the FOXA2-centered transcriptional regulation network and novel therapeutic targets to modulate this network in p53-deficient lung cancer. - Highlights: • Identification of new target genes of FOXA2. • Identifications of novel interaction proteins of FOXA2. • Construction of FOXA2-centered transcriptional regulatory network in non-small cell lung cancer

  18. [Whole Brain Irradiation and Hypo-fractionation Radiotherapy for the Metastases in Non-small Cell Lung Cancer].

    Science.gov (United States)

    Gu, Xingting; Zhao, Yaqin; Xu, Feng

    2016-04-20

    Up to 40% non-small cell lung cancer patients developed brain metastasis during progression. Multiple brain metastases are common in non-small cell lung cancer. The prognosis of brain metastasis is poor with median survival of less than 1 year. Radio therapy for brain metastases has gradually developed from whole brain radiotherapy (WBRT) to various radiation strategies. WBRT, surgery+WBRT, stereotactic radiotherapy+WBRT or WBRT with simultaneous integrated boost (SIB), etc. have better overall survival than those untreated patients. The damage of the cognitive function from WBRT has been realized recently, however, options of radiation strategies for long expected survival patients remain controversial. This paper will discuss different WBRT strategies and treatment side effects of non-small cell lung cancer with brain metastases. PMID:27118651

  19. Combined chemoradiotherapy with daily low-dose cisplatin in stage III non-small cell lung cancer. An interim report

    International Nuclear Information System (INIS)

    To improve the local control of stage III non-small cell lung cancer, we tried concurrent chemoradiotherapy with daily low-dose cisplatin during the first 5 weeks conventional radiotherapy. Ten consecutive patients with stage III non-small cell lung cancer were treated with chemoradiotherapy with 66 Gy in conventional fractionation and concurrent daily low-dose cisplatin (4 mg/m2), which was given 5 days per week (from Monday to Friday) for the first 5 weeks. There was no case with ≥grade 3 toxicity. The median survival was 14.6 months, and the 2-year local progression-free survival rate was 35%. Daily low-dose cisplatin combined with conventional radiotherapy was considered to be feasible and to have the possibility to offer better local control than radiotherapy alone in the treatment of stage III non-small cell lung cancer. (author)

  20. Osteopontin knockdown suppresses non-small cell lung cancer cell invasion and metastasis

    Institute of Scientific and Technical Information of China (English)

    SUN Bing-sheng; YOU Jian; LI Yue; ZHANG Zhen-fa; WANG Chang-li

    2013-01-01

    Background Osteopontin (OPN) was identified as one of the leading genes that promote the metastasis of malignant tumor.However,the mechanism by which OPN mediates metastasis in non-small cell lung cancer (NSCLC) remains unknown.The aim of the study is to investigate the biological significance and the related molecular mechanism of OPN expression in lung cancer cell line.Methods Lentiviral-mediated RNA interference was applied to inhibit OPN expression in metastatic human NSCLC cell line (A549).The invasion,proliferation,and metastasis were evaluated OPN-silenced in A549 cells in vitro and in vivo.The related mechanism was further investigated.Results Interestingly,OPN knockdown significantly suppressed the invasiveness of A549 cells,but had only a minor effect on the cellular migration and proliferation.Moreover,we demonstrated that OPN knockdown significantly reduced the levels of matrix metalloproteinase (MMP)-2 and urokinase plasminogen activator (uPA),and led to an obviousinhibition of both in vitro invasion and in vivo lung metastasis of A549 cells (P <0.001).Conclusions Our data demonstrate that OPN contributes to A549 cell metastasis by stimulating cell invasion,independent of cellular migration and proliferation.OPN could be a new treatment target of NSCLC.

  1. [Photodynamic therapy in combined treatment of stage III non-small cell lung carcinoma].

    Science.gov (United States)

    Akopov, A L; Rusanov, A A; Molodtsova, V P; Chistiakov, I V; Kazakov, N V; Urtenova, M A; Rait, Makhmud; Papaian, G V

    2013-01-01

    The aim of the study was to evaluate the effectiveness of combined treatment of locally advanced lung cancer with the use of neoadjuvant chemotherapy and surgery with the use of pre- and intraoperative photodynamic therapy. 20 patients with IIIa (n=7) and IIIb (n=13) stage of non-small cell lung carcinoma were included. At the time of diagnosis the surgical treatment was decided to abstain because of the trachea invasion in 9 patients, wide mediastinal invasion in 2 patients and contralateral mediastinal lymph nodes metastases in 2 patients; pneumonectomy was not possible due to the poor respiratory function in 7 patients. Neoadjuvant therapy included 3 courses of chemotherapy and endobronchial photodynamic therapy. During the operation, along with the lung resection (pneumonectomy - 15, lobectomy - 5), photodynamic therapy of the resection margins were carried out. No adjuvant treatment was done. Preoperative treatment led to partial regress of the disease in all cases; the goal of surgery was the complete tumor removal. No complications of the photodynamic therapy were observed. 18 surgical interventions were radical and two non-complete microscopically (R1). Postoperative morbidity was 20%, one patient died due to massive gastrointestinal bleeding. The average follow-up period was 18 months: 19 patients were alive, of them 18 with no signs of the disease recurrence. The first experience of the combined use of neoadjuvant chemotherapy and surgery with pre- and intraoperative photodynamic therapy demonstrates safety and efficacy of the suggested treatment tactics. PMID:23612332

  2. [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

  3. Safety of Racotumomab in the treatment of patients with non-small cell lung cancer

    International Nuclear Information System (INIS)

    In Cuba, lung cancer ranks second in incidence and first in mortality. Therefore, it is necessary to identify new therapeutical options. Immunological approaches are interesting because of the potential activity without the toxicities of conventional chemotherapy. The Center of Molecular Immunology developed a vaccine called Racotumomab; it acts on the lung carcinoma inducing an increase in tumor apoptosis and a decrease in the number of tumor vessels. A expanded access, multicenter, open study was conducted in 86 patients with non-small cell lung cancer in order to assess its safety. The administered dose was 1 mg/mL intradermically. The first 5 doses were administered every 14 days and the remaining 10 every 28 days until completing the treatment. The follow-up re immunizations were every 28 days. The occurrence of adverse events (AE) was analyzed and they were classified according to CTC v4.02 criteria. Adverse events were reported by 58 patients (67.4%), making a total of 215 events. burning at the injection site was the most frequently reported event, 32 (14.9%). The use of the vaccine in the patients under study showed good safety and tolerance

  4. Pyruvate carboxylase is critical for non-small-cell lung cancer proliferation.

    Science.gov (United States)

    Sellers, Katherine; Fox, Matthew P; Bousamra, Michael; Slone, Stephen P; Higashi, Richard M; Miller, Donald M; Wang, Yali; Yan, Jun; Yuneva, Mariia O; Deshpande, Rahul; Lane, Andrew N; Fan, Teresa W-M

    2015-02-01

    Anabolic biosynthesis requires precursors supplied by the Krebs cycle, which in turn requires anaplerosis to replenish precursor intermediates. The major anaplerotic sources are pyruvate and glutamine, which require the activity of pyruvate carboxylase (PC) and glutaminase 1 (GLS1), respectively. Due to their rapid proliferation, cancer cells have increased anabolic and energy demands; however, different cancer cell types exhibit differential requirements for PC- and GLS-mediated pathways for anaplerosis and cell proliferation. Here, we infused patients with early-stage non-small-cell lung cancer (NSCLC) with uniformly 13C-labeled glucose before tissue resection and determined that the cancerous tissues in these patients had enhanced PC activity. Freshly resected paired lung tissue slices cultured in 13C6-glucose or 13C5,15N2-glutamine tracers confirmed selective activation of PC over GLS in NSCLC. Compared with noncancerous tissues, PC expression was greatly enhanced in cancerous tissues, whereas GLS1 expression showed no trend. Moreover, immunohistochemical analysis of paired lung tissues showed PC overexpression in cancer cells rather than in stromal cells of tumor tissues. PC knockdown induced multinucleation, decreased cell proliferation and colony formation in human NSCLC cells, and reduced tumor growth in a mouse xenograft model. Growth inhibition was accompanied by perturbed Krebs cycle activity, inhibition of lipid and nucleotide biosynthesis, and altered glutathione homeostasis. These findings indicate that PC-mediated anaplerosis in early-stage NSCLC is required for tumor survival and proliferation. PMID:25607840

  5. Detecting the epidermal growth factor receptors status in non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    MENG Xue; YU Jin-ming

    2011-01-01

    Non-small cell lung cancer is one of the leading causes of all cancer deaths,but despite years of research,it is still difficult to predict the response and clinical outcome of the disease.In recent years,new treatment strategies targeting the epidermal growth factor receptors (EGFR) have been developed.EGFR is one of the most frequently over expressed proteins in various cancers,including lung cancer,and signaling through this receptor has been known to cause tumor progression as well as resistance to different treatments.Therefore,EGFR has become an attractive target for various treatment strategies.However,it is important to note that not all patients with lung cancer are suitable for targeted treatment,and that patients should be selected for this treatment.Several studies have proven that the status of the EGFR can be both an indicator of suitability for treatment with,and predict the likelihood of response to EGFR targeted therapy.There are many standard techniques to be used for the detection of EGFR.This overview summarizes the ongoing and future investigations to determine the status of the EGFR.

  6. Prognostic implication of PTPRH hypomethylation in non-small cell lung cancer.

    Science.gov (United States)

    Sato, Takashi; Soejima, Kenzo; Arai, Eri; Hamamoto, Junko; Yasuda, Hiroyuki; Arai, Daisuke; Ishioka, Kota; Ohgino, Keiko; Naoki, Katsuhiko; Kohno, Takashi; Tsuta, Koji; Watanabe, Shun-Ichi; Kanai, Yae; Betsuyaku, Tomoko

    2015-09-01

    PTPRH is a receptor-type protein tyrosine phosphatase thought to be a potential regulator of tumorigenesis. The aim of the present study was to clarify the significance of PTPRH expression and its regulation by DNA methylation in non-small cell lung cancer (NSCLC), especially in lung adenocarcinoma (LADC). PTPRH mRNA expression was examined in 89 NSCLC and corresponding non-cancerous tissues. The correlation between DNA methylation and PTPRH gene expression was investigated in another cohort that consisted of 145 patients with LADC, a major NSCLC subtype. Gene regulation by DNA methylation was assessed using a DNA methylation inhibitor. PTPRH mRNA expression was significantly upregulated in NSCLC. PTPRH DNA methylation was reduced in LADC samples and inversely correlated with mRNA expression. 5-Aza-2'-deoxycytidine treatment of lung cancer cell lines with low PTPRH expression, restored mRNA PTPRH expression levels. Furthermore, low PTPRH methylation was associated with shorter recurrence-free survival (P=1.64x10(-4)) and overall survival (P=5.54x10(-5)). Multivariate analysis revealed that PTPRH DNA methylation was an independent prognostic factor (P=6.88x10(-3)). It was confirmed that PTPRH is overexpressed in NSCLC. Furthermore, we determined that PTPRH is epigenetically regulated by DNA hypomethylation, with prognostic implications for LADC. PMID:26134684

  7. Spanish patterns of care for 3D radiotherapy in non-small-cell lung cancer

    International Nuclear Information System (INIS)

    Purpose: Curative radiotherapy for non-small-cell lung cancer is a difficult challenge, despite the use of conformal radiotherapy. Optimal three-dimensional delineation of treatment volumes is essential for improvement of local control and for limiting of tissue toxicity. Material and Methods: A planning course on clinical practice of lung cancer was held in Barcelona. A questionnaire was given concerning (1) patient positioning, (2) planning-computed tomography scan, (3) accounting for tumor mobility, (4) investigative-procedure respiration-gated radiotherapy and breath-holding maneuvers, (5) generation of target volumes, (6) treatment planning, and (7) treatment delivery. This questionnaire was made to determine the Spanish application of European recommendations. Results: On the negative side, 1 hospital did not use three-dimensional tools, less than 50% used immobilization devices, and 55.6% used computed tomography slices of greater than 5 mm. On the positive side, 70.4% did not use standard margins for gross target volume derived from a computed tomography scan, 92.6% agreed with the inclusion of Naruke anatomic criteria of 1 cm or more in gross target volume planning, and 75% used V20 to estimate the risk of pneumonitis. Conclusions: This study is the first validation of European recommendations for treatment planning and execution of radiotherapy in lung cancer. The main conclusion is the need to improve the negative aspects determined

  8. Radiotherapy alone for medically inoperable Stage I non-small-cell lung cancer: The Duke experience

    International Nuclear Information System (INIS)

    Purpose: To review our experience treating clinical Stage I non-small-cell lung carcinoma with radiotherapy alone using modern techniques and staging. The effect of dose and volume on outcome is to be analyzed. Methods: Between January 1980 and December 1995, 156 patients with Stage I medically inoperable non-small-cell lung cancer were irradiated at Duke University Medical Center and the Durham Veterans Administration Medical Center. Fifteen patients were excluded from analysis (7 treated with palliative intent, and 8 lost to follow-up immediately following radiation). Characteristics of the 141 evaluable patients were as follows: Median age 70 years (range 46-95); gender: male 83%, female 17%; institution: DUMC 65%, DVAMC 35%; T1N0 54%, T2N0 46%; median size 3 cm (range 0.5 to 8); pathology: squamous cell carcinoma 52%, adenocarcinoma 18%, large cell carcinoma 19%, not otherwise specified 11%; presenting symptoms: weight loss 26%, cough 23%, none (incidental diagnosis) 57%. All patients underwent simulation prior to radiotherapy using linear accelerators of ≥4 MV. No patients received surgery or chemotherapy as part of their initial treatment. The median dose of radiotherapy (not reflecting lung inhomogeneity corrections) was 64 Gy (50 to 80 Gy) given in 1.2 bid to 3 Gy qid fractionation. The majority of cases included some prophylactic nodal regions (73%). Results: Of the 141 patients, 108 have died; 33% of intercurrent death, 35% of cancer, and 7% of unknown causes. At last follow-up, 33 patients were alive (median 24 months, range 7-132 months). The 2- and 5-year overall survival was 39% and 13%, respectively (median 18 months). The corresponding cause-specific survival was 60%, and 32% (median 30 months). On multivariate analysis, significant factors influencing overall and/or cause-specific survival were age, squamous cell histology, incidental diagnosis, and pack-years of smoking. There was a nonsignificant trend towards improved cause-specific survival

  9. 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.

  10. 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

  11. Interaction between fragile histamine triad and protein kinase C alpha in human non-small cell lung cancer tissues

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Objective To investigate the interaction between fragile histamine triad (FHIT) and protein kinase C alpha (PKCα) in human non-small cell lung cancer tissues. Methods FHIT and PKCα double positive samples were screened by immunohistochemical staining from 13 human non-small cell lung cancer tissues. Co-immunoprecipitation was performed by using anti-FHIT and anti-PKCα. The immune precipitate was analyzed by SDS-PAGE and Western blot. Results Immune precipitate staining detection showed that 3 samples out of...

  12. Comparison of efficiency and toxicity of two chemotherapy protocols in treatment of advanced non-small cell lung cancer

    OpenAIRE

    Mekić-Abazović Alma; Šišić Ibrahim; Kovčin Vladimir; Bečulić Hakija; Dervišević Senad; Musić Miralem

    2011-01-01

    Introduction. This study was aimed at comparing the efficiency and tolerability of two reference protocols Cisplatin and Etoposide and Cisplatin and Vinorelbine in advanced Non-Small Cell Lung Cancer. Material and Methods. A total of 60 patients (two groups consisting of 30 patients) were treated for advanced Non-Small Cell Lung Cancer during the period from January to December 2005 according to the reference protocols (Cisplatin 100mg/m2 D1; Vinorelbine 30 mg/m2 D1, D8 on 4 weeks) and ...

  13. Video-assisted thoracoscopic surgery for non-small-cell lung cancer is beneficial to elderly patients

    OpenAIRE

    Wang, Yan

    2015-01-01

    The aim of this study was to explore whether video-assisted thoracoscopic surgery (VATS) has short or long-term benefits in elderly patients with non-small-cell lung cancer compared with open surgery. Between June 2007 and December 2014, 579 patients older than 70 years underwent radical pulmonary resection for non-small-cell lung cancer, including 138 who received VATS and 441 who received open surgery. A retrospective pair-matched study was performed to compare 194 patients (97 pairs) who u...

  14. Survival Analysis of 1,742 Patients with Stage IV Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Hong PENG

    2011-04-01

    Full Text Available Background and objective At present non-small cell lung cancer (NSCLC is still the leading cause of death induced by cancer. The aim of this study is to investigate the prognostic factors of advanced NSCLC. Methods Total 1,742 cases of stage IV NSCLC data from Jan 4, 2000 to Dec 25, 2008 in Shanghai Chest Hospital were collected, confirmed by pathological examinations. Analysis was made to observe the impact of treatment on prognosis in gender, age, smoking history, pathology, classification, clinical TNM stage. Survival rate, survival difference were evaluated by Kaplan-Meire method and Logrank test respectively. The prognosis were analyzed by Cox multivariate regression. Results The median survival time of 1,742 patients was 10.0 months (9.5 months-10.5 months. One, two, three, four, and five-year survival rates were 44%, 22%, 13%, 9%, 6% respectively. The median survivals of single or multiple metastasis were 11 months vs 7 months (P < 0.001. Survival time were different in metastasic organs, with the median survival time as follows: lung for about 12 months (11.0 months-12.9 months, bone for 9 months (8.3 months-9.6 months, brain for 8 months (6.8 months-9.1 months, liver, adrenal gland, distannt lymph node metastasis for 5 months (3.8 months-6.1 months, and subcutaneous for 3 months (1.7 months-4.3 months. The median survival times of adenocarcinoma (n=1,086, 62% and squamous cell carcinoma cases (n=305, 17.5% were 12 months vs 8 months (P < 0.001. The median survival time of chemotherapy and best supportive care were 11 months vs 6 months (P < 0.001; the median survival times of with and without radiotherapy were 11 months vs 9 months (P=0.017. Conclusion Gender, age, gross type, pathological type, clinical T stage, N stage, numbers of metastatic organ, smoking history, treatment of advanced non-small cell lung cancer were independent prognostic factors.

  15. Targeting DNA Damage Response in the Radio(Chemo)therapy of Non-Small Cell Lung Cancer

    OpenAIRE

    Ling Li; Tao Zhu; Yuan-Feng Gao; Wei Zheng; Chen-Jing Wang; Ling Xiao; Ma-Sha Huang; Ji-Ye Yin; Hong-Hao Zhou; Zhao-Qian Liu

    2016-01-01

    Lung cancer is the leading cause of cancer death worldwide due to its high incidence and mortality. As the most common lung cancer, non-small cell lung cancer (NSCLC) is a terrible threat to human health. Despite improvements in diagnosis and combined treatments including surgical resection, radiotherapy and chemotherapy, the overall survival for NSCLC patients still remains poor. DNA damage is considered to be the primary cause of lung cancer development and is normally recognized and repair...

  16. Non-small cell lung cancer cell survival crucially depends on functional insulin receptors.

    Science.gov (United States)

    Frisch, Carolin Maria; Zimmermann, Katrin; Zilleßen, Pia; Pfeifer, Alexander; Racké, Kurt; Mayer, Peter

    2015-08-01

    Insulin plays an important role as a growth factor and its contribution to tumor proliferation is intensely discussed. It acts via the cognate insulin receptor (IR) but can also activate the IGF1 receptor (IGF1R). Apart from increasing proliferation, insulin might have additional effects in lung cancer. Therefore, we investigated insulin action and effects of IR knockdown (KD) in three (NCI-H292, NCI-H226 and NCI-H460) independent non-small cell lung cancer (NSCLC) cell lines. All lung cancer lines studied were found to express IR, albeit with marked differences in the ratio of the two variants IR-A and IR-B. Insulin activated the classical signaling pathway with IR autophosphorylation and Akt phosphorylation. Moreover, activation of MAPK was observed in H292 cells, accompanied by enhanced proliferation. Lentiviral shRNA IR KD caused strong decrease in survival of all three lines, indicating that the effects of insulin in lung cancer go beyond enhancing proliferation. Unspecific effects were ruled out by employing further shRNAs and different insulin-responsive cells (human pre-adipocytes) for comparison. Caspase assays demonstrated that IR KD strongly induced apoptosis in these lung cancer cells, providing the physiological basis of the rapid cell loss. In search for the underlying mechanism, we analyzed alterations in the gene expression profile in response to IR KD. A strong induction of certain cytokines (e.g. IL20 and tumour necrosis factor) became obvious and it turned out that these cytokines trigger apoptosis in the NSCLC cells tested. This indicates a novel role of IR in tumor cell survival via suppression of pro-apoptotic cytokines. PMID:26113601

  17. Role of ATG10 expression quantitative trait loci in non-small cell lung cancer survival.

    Science.gov (United States)

    Xie, Kaipeng; Liang, Cheng; Li, Qin; Yan, Caiwang; Wang, Cheng; Gu, Yayun; Zhu, Meng; Du, Fangzhi; Wang, Hui; Dai, Juncheng; Liu, Xiao'an; Jin, Guangfu; Shen, Hongbing; Ma, Hongxia; Hu, Zhibin

    2016-10-01

    The aim of this article was to evaluate whether genetic variants in autophagy-related genes affect the overall survival (OS) of non-small cell lung cancer (NSCLC) patients. We analyzed 14 single nucleotide polymorphisms (SNPs) in core autophagy-related genes for OS in 1,001 NSCLC patients. Three promising SNPs in ATG10 were subsequently annotated by the expression quantitative trait loci (eQTL) and methylation quantitative trait loci (meQTL) analyses based on Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) datasets. We observed that the variants of rs10514231, rs1864182 and rs1864183 were associated with poor lung cancer survival (HR = 1.33, 95% CI = 1.07-1.65; HR = 1.43, 95% CI = 1.13-1.81; HR = 1.38, 95% CI = 1.14-1.68, respectively) and positively correlated with ATG10 expression (all p lung cancer patients in TCGA dataset (HR = 2.10, 95% CI = 1.33-3.29). Moreover, the variants of rs10514231 and rs1864182 were associated with the increased methylation levels of cg17942617 (meQTL), which in turn contributed to the elevated ATG10 expression and decreased survival time. Further functional assays revealed that ATG10 facilitated lung cancer cell proliferation and migration. Our findings suggest that eQTL/meQTL variations of ATG10 could influence lung cancer survival through regulating ATG10 expression. PMID:27225307

  18. REV3L modulates cisplatin sensitivity of non-small cell lung cancer H1299 cells.

    Science.gov (United States)

    Wang, Wenjie; Sheng, Wenjiong; Yu, Chenxiao; Cao, Jianping; Zhou, Jundong; Wu, Jinchang; Zhang, Huojun; Zhang, Shuyu

    2015-09-01

    Lung cancer remains the leading cause of cancer-related mortality worldwide and non-small cell lung cancer (NSCLC) accounts for approximately 80-85% of all cases of lung cancer. Cisplatin plays a significant role in the management of human lung cancer. Translesion DNA synthesis (TLS) is involved in DNA damage repair. DNA polymerase ζ (Pol ζ) is able to mediate the DNA replication bypass of DNA damage, which is suggested to be involved in chemoresistance. REV3L is the catalytic subunit of Pol ζ. Due to its critical role in translesion DNA synthesis, whether REV3L modulates cisplatin response in NSCLC cells remains unknown. In this study, REV3L overexpression and silencing H1299 cell lines were established. The reports showed that cisplatin induced the expression of REV3L by recruiting Sp1 to its promoter. Similar results were obtained when the ability of the cells to express luciferase from a platinated plasmid was measured. Co-transfection of the reporter with the REV3L overexpression vector or REV3L plus REV7L significantly enhanced the reporter activity. Nuclear condensation and fragmentation of shRNA-REV3L H1299 cells were more pronounced than shRNA-NC H1299 cells after cisplatin exposure, indicating that REV3L overexpression abolished cisplatin-induced DNA damage. Moreover, a forced expression of REV3L conferred the resistance of H1299 cells to cisplatin, whereas the knockdown of REV3L sensitized cisplatin efficacy in H1299 cells. Taken together, we demonstrated that inhibition of REV3L sensitized lung cancer H1299 cells to cisplatin treatment. Thus, REV3L may be a novel target for the chemotherapy of NSCLC. PMID:26165320

  19. Carbon Ion Therapy for Early-Stage Non-Small-Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Yusuke Demizu

    2014-01-01

    Full Text Available Carbon ion therapy is a type of radiotherapies that can deliver high-dose radiation to a tumor while minimizing the dose delivered to the organs at risk; this profile differs from that of photon radiotherapy. Moreover, carbon ions are classified as high-linear energy transfer radiation and are expected to be effective for even photon-resistant tumors. Recently, high-precision radiotherapy modalities such as stereotactic body radiotherapy (SBRT, proton therapy, and carbon ion therapy have been used for patients with early-stage non-small-cell lung cancer, and the results are promising, as, for carbon ion therapy, local control and overall survival rates at 5 years are 80–90% and 40–50%, respectively. Carbon ion therapy may be theoretically superior to SBRT and proton therapy, but the literature that is currently available does not show a statistically significant difference among these treatments. Carbon ion therapy demonstrates a better dose distribution than both SBRT and proton therapy in most cases of early-stage lung cancer. Therefore, carbon ion therapy may be safer for treating patients with adverse conditions such as large tumors, central tumors, and poor pulmonary function. Furthermore, carbon ion therapy may also be suitable for dose escalation and hypofractionation.

  20. Prospective study on stereotactic radiotherapy of limited-stage non-small-cell lung cancer

    DEFF Research Database (Denmark)

    Høyer, Morten; Roed, Henrik; Hansen, Anders Traberg;

    2006-01-01

    Purpose: To test the effect of stereotactic body radiotherapy (SBRT) in       the treatment of medically inoperable patients with limited-stage       non-small-cell lung cancer (NSCLC) in a Phase II trial. Methods and       Materials: Forty patients with Stage I NSCLC were treated with SBRT with a...... 2       years, 54% were without local or distant progression, and overall survival       was 47%. Within 6 months after treatment, one or more Grade >/=2 reactions       were observed in 48% of the patients. Conclusions: Stereotactic body       radiotherapy in patients with limited-stage NSCLC...... resulted in a high       probability of local control and a promising survival rate. The toxicity       after SBRT of lung tumors was moderate. However, deterioration in       performance status, respiratory insufficiency, and other side effects were       observed...

  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. Correlation of diffusion MRI with the Ki-67 index in non-small cell lung cancer

    International Nuclear Information System (INIS)

    The primary objective of the study was to evaluate the association between the minimum apparent diffusion coefficient (ADCmin) and Ki-67, an index for cellular proliferation, in non-small cell lung cancers. Also, we aimed to assess whether ADCmin values differ between tumour subtypes and tissue sampling method. The patients who had diffusion weighted magnetic resonance imaging (DW-MRI) were enrolled retrospectively. The correlation between ADCmin and the Ki-67 index was evaluated. Ninety three patients, with a mean age 65 ± 11 years, with histopathologically proven adenocarcinoma and squamous cell carcinoma of the lungs and had technically successful DW-MRI were included in the study. The numbers of tumour subtypes were 47 for adenocarcinoma and 46 for squamous cell carcinoma. There was a good negative correlation between ADCmin values and the Ki-67 proliferation index (r = −0.837, p < 0.001). The mean ADCmin value was higher and the mean Ki-67 index was lower in adenocarcinomas compared to squamous cell carcinoma (p < 0.0001). There was no statistical difference between tissue sampling methods. Because ADCmin shows a good but negative correlation with Ki-67 index, it provides an opportunity to evaluate tumours and their aggressiveness and may be helpful in the differentiation of subtypes non-invasively

  3. New antiangiogenics in non-small cell lung cancer treatment: Vargatef™ (BIBF 1120 and beyond

    Directory of Open Access Journals (Sweden)

    Gori B

    2011-11-01

    Full Text Available Bruno Gori1, Serena Ricciardi1, Alberto Fulvi1, Salvatore Intagliata2, Ester Del Signore1, Filippo de Marinis11Oncological-Pulmonary Unit 1st, San Camillo Hospital, Rome, Italy; 2Department of Medical Oncology, University Campus Bio-Medico, Rome, ItalyAbstract: Lung cancer is the leading cause of mortality worldwide. Non-small cell lung cancer (NSCLC is a particularly aggressive cancer, the optimum management of which is still being determined. In the metastatic disease, the standard therapy is a platinum-based combination chemotherapy; however, in spite of available treatment options for patients who progress beyond first-line therapy, prognosis remains poor. Angiogenesis is a tightly regulated process which comprises a complex, complementary, and overlapping network. Inhibition of tumor-related angiogenesis has become an attractive target for anticancer therapy. Antiangiogenic strategy includes: monoclonal antibodies against vascular endothelial growth factor (VEGF and VEGF receptor (VEGFR, small molecule inhibitors of VEGF tyrosine kinase activity, VEGF Trap, and a new class named “vascular disrupting agents,” tested in ongoing clinical trials which will further define their role in the management of NSCLC. BIBF 1120 is an investigational orally administered receptor tyrosine kinase inhibitor that has shown antiangiogenic and antineoplastic activity, inhibiting VEGFR, platelet-derived growth factor receptor, and fibroblast growth factor receptor tyrosine kinases, preventing tumor growth and interfering with the angiogenesis-signaling cascade and overcoming drug resistances.Keywords: NSCLC, angiogenesis, oral antiangiogenic agents, VEGF, PDGF, FGF

  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

    BACKGROUND: Lung cancer is one of the most common malignant diseases worldwide and associated with considerable morbidity and mortality. New agents targeting the epidermal growth factor system are emerging, but only a subgroup of the patients will benefit from the therapy. Cell free DNA (cf......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......-KRAS mutation had a significantly shorter OS and PFS compared to the wild type (WT) patients (median OS 4.8 months versus 9.5 months, HR 1.87, 95% CI 1.23-2.84, p=0.0002 and median PFS 3.0 months versus 5.6 months, HR 1.60, 95% CI 1.09-2.37, p=0.0043). A multivariate Cox regression analysis confirmed...

  5. Clinical and surgical-pathological staging in early non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Ioannis Koukis

    2013-12-01

    Full Text Available Staging is of the utmost importance in the evaluation of a patient with non-small cell lung cancer (NSCLC because it defines the actual extent of the disease. Accurate staging allows multidisciplinary oncology teams to plan the best surgical or medical treatment and to predict patient prognosis. Based on the recommendation of the International Association for the Study of Lung Cancer (IASLC, a tumor, node, and metastases (TNM staging system is currently used for NSCLC. Clinical staging (c-TNM is achieved via non-invasive modalities such as examination of case history, clinical assessment and radiological tests. Pathological staging (p-TNM is based on histological examination of tissue specimens obtained with the aid of invasive techniques, either non-surgical or during the intervention. This review is a critical evaluation of the roles of current pre-operative staging modalities, both invasive and non-invasive. In particular, it focuses on new techniques and their role in providing accurate confirmation of patient TNM status. It also evaluates the surgical-pathological staging modalities used to obtain the true-pathological staging for NSCLC.

  6. Spontaneous pneumothorax after stereotactic radiotherapy for non-small-cell lung cancer

    International Nuclear Information System (INIS)

    The report presented here describes a case of spontaneous pneumothorax observed after stereotactic radiotherapy (SRT) for non-small-cell lung cancer (NSCLC). An 84-year-old man with a Stage IIB, T3N0M0 NSCLC in the right upper lobe and a Stage IA NSCLC in the right lower lobe of the lung was treated with SRT for both tumors. He received SRT with a total dose of 60.0 Gy in 10 fractions delivered to the right upper lobe, and 48.0 Gy in 4 fractions delivered to the right lower lobe. Two months after completion of the treatment, he developed spontaneous pneumothorax. He was asymptomatic and recovered with conservative management. Spontaneous pneumothorax has occasionally been reported to occur following thoracic radiotherapy for malignancy. Almost all of the reported cases are patients who had received mantle irradiation for Hodgkin's disease. We have been unable to find any reports of spontaneous pneumothorax after SRT, which has recently been used for treating patients with early-stage NSCLC. Because a case of spontaneous pneumothorax after SRT was observed in our institution, its clinical course is described here along with a discussion of possible causes of spontaneous pneumothorax. (author)

  7. Optimal radiotherapy for non-small-cell lung cancer. Current progress and future challenges

    International Nuclear Information System (INIS)

    Radiotherapy has a key role in treating lung cancer. Advances in physics and computer technology have improved radiation delivery systems. With innovations in the radiation therapy of non-small-cell lung cancer (NSCLC), new strategies have emerged, such as intensity-modulated radiation therapy, stereotactic body radiation therapy, and particle therapy. Compared with previous methods, these newer technologies can deliver even higher doses precisely to the tumor while minimizing doses to normal tissues, which should lead to better tumor control with less toxicity. In patients with stage I NSCLC, stereotactic body radiation therapy is highly effective and may achieve local control and survival equivalent to that achieved with surgery. In patients with stage III NSCLC, dose escalation has been investigated using three-dimensional conformal radiation therapy, intensity-modulated radiation therapy, and particle therapy. The results from ongoing randomized trials on both patient populations are awaited. It is important to generate new hypotheses and to explore newer radiotherapy approaches to overcome NSCLC. (author)

  8. Lymphatic drainage, CTV and molecular imaging in non-small cell lung cancer.

    Science.gov (United States)

    Trodella, Lucio; Ciresa, Marzia; D'Angelillo, Rolando; Ramella, Sara

    2003-01-01

    Prognosis for non-small cell lung cancer (NSCLC) patients who have locally advanced unresectable disease is poor for persistent thoracic disease and development of distant metastasis. In view of the poor rate of local control following conventional radiation therapy, there is a great need for methods to improve its efficacy. Three-dimensional conformal radiation therapy (3DCRT) is a high precision radiotherapy able to deliver higher doses with smaller doses to the surrounding normal tissues. However, the real problem is: "what do I want to treat?" This question is addressed based on the clinical and biological target volume definition. Selection of the CTV is therefore basically the clinical compromise between the most radical possible CTV and the critical normal tissue tolerance. The clinical target volume includes the GTV plus a margin to encompass subclinical or microscopic malignant disease immediately adjacent to it. Standard radiation therapy consists of a dose of 40 Gy to the entire mediastinum, supraclavicular fossa, and ipsilateral hilum, even if there is no evidence of disease in these areas. Despite the high risk of nodal spread in lung cancer, the benefit of additional elective nodal irradiation (ENI) is not proven while it seems to significantly increase the rate of radiation morbidity. Several studies have been published where ENI was systematically omitted. The main arguments for omitting ENI and the principal clinical experiences, are discussed. PMID:15018317

  9. Recent advances in immunotherapy for non-small-cell lung cancer.

    Science.gov (United States)

    Suzuki, Hiroyuki; Owada, Yuki; Watanabe, Yuzuru; Inoue, Takuya; Fukuharav, Mitsuro; Yamaura, Takumi; Mutoh, Satoshi; Okabe, Naoyuki; Yaginuma, Hiroshi; Hasegawa, Takeo; Yonechi, Atsushi; Ohsugi, Jun; Hoshino, Mika; Higuchi, Mitsunori; Shio, Yutaka; Gotoh, Mitsukazu

    2014-01-01

    Despite of recent development in the field of molecular targeted therapies, lung cancer is a leading cause of cancer death in the world. Remarkable progress has been made recently in immunotherapy for patients with non-small-cell lung cancer (NSCLC), with several modalities, concepts, and treatment settings being investigated. In vaccine development, large-scale clinical trials such as those with L-BLP25, belagenpumatucel-L, TG4010, and talactoferrin are already ongoing and some results have been reported. A trial of a vaccine as adjuvant therapy for patients with completely resected NSCLC is also ongoing with one of the major cancer-testis antigens, melanoma-associated antigen (MAGE)-A3. More recently, the effectiveness of multiple peptide vaccines has also been shown. Recently developed unique treatment modalities are the immune checkpoint inhibitors, such as antibodies against PD-1 and PD-L1, which also show promise. However, although therapeutic cancer vaccines are generally thought to be safe, severe adverse events should be monitored carefully when using immune checkpoint inhibitors. Here, we discuss recent advances and future perspectives of immunotherapy for patients with NSCLC. PMID:24196313

  10. Detection of MTAP Protein and Gene Expression in Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Shasha LI

    2011-02-01

    Full Text Available Background and objective The abnormal expression of MTAP, a tumor suppressor gene, is found in a variety of tumor tissues. The aim of this study is to detect the expression of MTAP mRNA protein and the clinical significance for the therapy of non-small cell lung cancer tissue (NSCLC. Methods The expression of MTAP protein was detected by immunohistochemistry in 52 cases of NSCLC patients. The relative expression MTAP mRNA was detected by real-time quantitative PCR. Results The expression of MTAP protein in NSCLC tissue was significantly lower than that in paracarcinomous tissue and borderline lung tissue respectively (t=10.283, 10.940, P < 0.001. There was no significant difference among gender, age, smoking history, histology except differentiation (t=2.310, P=0.025. The MTAP mRNA relative expression in NSCLC tissue was significantly lower than that in paracarcinomous tissue (t=9.902, P < 0.001. Conclusion Downregulation of MTAP protein and gene expression is correlated to the oncogenesis and progression of NSCLC.

  11. MYC is a metastasis gene for non-small-cell lung cancer.

    Directory of Open Access Journals (Sweden)

    Ulf R Rapp

    Full Text Available BACKGROUND: Metastasis is a process by which cancer cells learn to form satellite tumors in distant organs and represents the principle cause of death of patients with solid tumors. NSCLC is the most lethal human cancer due to its high rate of metastasis. METHODOLOGY/PRINCIPAL FINDINGS: Lack of a suitable animal model has so far hampered analysis of metastatic progression. We have examined c-MYC for its ability to induce metastasis in a C-RAF-driven mouse model for non-small-cell lung cancer. c-MYC alone induced frank tumor growth only after long latency at which time secondary mutations in K-Ras or LKB1 were detected reminiscent of human NSCLC. Combination with C-RAF led to immediate acceleration of tumor growth, conversion to papillary epithelial cells and angiogenic switch induction. Moreover, addition of c-MYC was sufficient to induce macrometastasis in liver and lymph nodes with short latency associated with lineage switch events. Thus we have generated the first conditional model for metastasis of NSCLC and identified a gene, c-MYC that is able to orchestrate all steps of this process. CONCLUSIONS/SIGNIFICANCE: Potential markers for detection of metastasis were identified and validated for diagnosis of human biopsies. These markers may represent targets for future therapeutic intervention as they include genes such as Gata4 that are exclusively expressed during lung development.

  12. Radiosensitization on non-small cell lung cancer induced by celecoxib

    International Nuclear Information System (INIS)

    Objective: To establish the nude mice model of non-small cell lung cancer (NSCLC) H460 cell to investigate the combined effects of radiotherapy and celecoxib. Methods: Athymic mice bearing H460 were randomly divided into 4 groups: control, radiotherapy, celecoxib and radiotherapy plus celecoxib group. The administration dose of celecoxib was 16 mg·kg-1·d-1. The mice were treated with radiotherapy 2 hours after administration and the fractionated dose was 5 Gy, 2 fractions per week. Mice were killed to detect tumor weight 4 weeks after treatment. The expression levels of ataxia telangiectasis mutated (ATM) and epidermal growth factor receptor (EGFR) in tumor tissues were detected by immune-histochemical method. Results: The tumor weight in control,radiotherapy, celecoxib and radiotherapy plus celecoxib group were (133.62±12.37), (130.37 ±12.59), (81.17 ±8.29) and (35.51 ±4.23) mg respectively. There was significant difference between the radiotherapy plus celecoxib group and the radiotherapy group (t=5.41, P<0.01). The expression levels of ATM and EGFR in the radiotherapy plus celecoxib group were significantly lower than that in radiotherapy group (t=4.23 and 3.17, both P<0.01). Conclusions: Celecoxib promotes radiotherapeutic sensitivity of H460 by down-regulating the expression levels of ATM and EGFR.Celecoxib may presents potency in curing human lung cancer. (authors)

  13. Pre-operative concurrent chemoradiotherapy for stage IIIA (N2) Non-Small cell lung cancer

    International Nuclear Information System (INIS)

    This is to evaluate the acute complication, resection rate, and tumor down-staging after pre-operative concurrent chemoradiotherapy for stage IIIA (N2) non-small cell lung cancer. Fifteen patients with non-small cell lung cancer were enrolled in this study from May 1997 to June 1998 in Samsung Medical Center. The median age of the patients was 61 (range, 45-67) years and male to female ratio was 12:3. Pathologic types were squamous cell carcinoma (11) and adenocarcinoma (4). Pre-operative clinical tumor stages were cT1 in 2 patients, cT2 in 12, and cT3 in 1 and all were N2. Ten patients were proved to be N2 with mediastinoscopic biopsy and five had clinically evident mediastinal lymph node metastases on the chest CT scans. Pre-operative radiation therapy field included the primary tumor, the ipsilateral hilum, and the mediastinum. Total radiation dose was 45 Gy over 5 weeks with daily dose of 1.8 Gy. Pre-operative concurrent chemotherapy consisted of two cycles of intraventous cis-Platin (100 mg/m2) on day 1 and oral Etoposide (50 mg/m2/day) on days 1 through 14 with 4 weeks' interval. Surgery was followed after the pre-operative re-evaluation including chest CT scan in 3 weeks of the completion of the concurrent chemoradiotherapy if there was no evidence of disease progression. Full dose radiation therapy was administered to all the 15 patients. Planned two cycles of chemotherapy was completed in 11 patients and one cycle was given to four. One treatment related death of acute respiratory distress syndrome occurred in 15 days of surgery. Hospital admission was required in three patients including one with radiation pneumonitis and two with neutropenic fever. Hematologic complications and other acute complications including esophagitis were tolerable. Resection rate was 92.3% (12/13) in 13 patients excluding two patients who refused surgery. Pleural seeding was found in one patient after thoracotomy and tumor resection was not feasible. Post-operative tumor

  14. Pre-operative concurrent chemoradiotherapy for stage IIIA (N2) Non-Small cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Kyu Chan; Ahn, Yong Chan; Park, Keun Chil [College of Medicine, Sungkyunkwan Univ., Seoul (Korea, Republic of)] [and others

    1999-06-01

    This is to evaluate the acute complication, resection rate, and tumor down-staging after pre-operative concurrent chemoradiotherapy for stage IIIA (N2) non-small cell lung cancer. Fifteen patients with non-small cell lung cancer were enrolled in this study from May 1997 to June 1998 in Samsung Medical Center. The median age of the patients was 61 (range, 45-67) years and male to female ratio was 12:3. Pathologic types were squamous cell carcinoma (11) and adenocarcinoma (4). Pre-operative clinical tumor stages were cT1 in 2 patients, cT2 in 12, and cT3 in 1 and all were N2. Ten patients were proved to be N2 with mediastinoscopic biopsy and five had clinically evident mediastinal lymph node metastases on the chest CT scans. Pre-operative radiation therapy field included the primary tumor, the ipsilateral hilum, and the mediastinum. Total radiation dose was 45 Gy over 5 weeks with daily dose of 1.8 Gy. Pre-operative concurrent chemotherapy consisted of two cycles of intraventous cis-Platin (100 mg/m{sup 2}) on day 1 and oral Etoposide (50 mg/m{sup 2}/day) on days 1 through 14 with 4 weeks' interval. Surgery was followed after the pre-operative re-evaluation including chest CT scan in 3 weeks of the completion of the concurrent chemoradiotherapy if there was no evidence of disease progression. Full dose radiation therapy was administered to all the 15 patients. Planned two cycles of chemotherapy was completed in 11 patients and one cycle was given to four. One treatment related death of acute respiratory distress syndrome occurred in 15 days of surgery. Hospital admission was required in three patients including one with radiation pneumonitis and two with neutropenic fever. Hematologic complications and other acute complications including esophagitis were tolerable. Resection rate was 92.3% (12/13) in 13 patients excluding two patients who refused surgery. Pleural seeding was found in one patient after thoracotomy and tumor resection was not feasible. Post

  15. EXPRESSION OF VASCULAR ENDOTHELIAL GROWTH FACTOR IN PRIMARY NON-SMALL CELL LUNG CARCINOMA

    Institute of Scientific and Technical Information of China (English)

    ZHANG Lijian; YANG Guoli; XIE Yuquan; XU Weiguo

    1999-01-01

    Objective: Tumor growth depends on angiogenesis.The aim of this paper is to clarify the relationship between the expression of vascular endothelial growth factor (VEGF)/vascular permeability factor (VPF) and the angiogenesis, or growth, or invasion and prognostic value in Non-Small Cell Lung Cancer (NSCLC).Methods: Microvessei quantification and expression of VEGF was performed immunohistochemically, using multiclonal antibodies against endothelial protein factor Ⅷ-related antigen (F-Ⅷ antigen, or factor Ⅷ) for evaluating the angiogenesis; against VEGF antigen for the expression of VEGF. Results: A total of 53 patients with NSCLC after the radical resection were evaluated.The patients with high and low expression of VEGF were 33 and 20, respectively. A significant higher microvessel density (MVD) was observed in the tumors with high expression of VEGF compared with the tumors with low expression of it (12.17±2.57/mm2 vs 6.01±1.161/mm2, rank sum test, P<0.01). There were 29patients with lymphonodes metastasis in the high expression VEGF/VPF (29/33, 87.88%) group, and 9patients in the low (9/20, 45%) group. There was good correlation between MVD and expression of VEGF (chisquare tests, P<0.001). The overall 5 years survival for 53 patients was 20.75±5.78%; that of the high expression of the VEGF group was 3.03±2.98%; that of the low group was 36.36±13.94%, by Log rank test, P=0.0001.The difference between them had a high significance.There was good correlation between the survival and the expression of VEGF. By the COX's proportional hazard model analysis, the expression of VEGF and MVD was considered to be an independent marker of the prognosis in non-small cell lung cancer. Conclusion: the expression of VEGF has a significant correlation with MVD, growth, invasion, and lymph node metastasis. The increasing of the node metastasis and the size of tumor accompanied the increasing of VEGF/VPF. The cancer patient with higher VEGF and MVD expression might

  16. Expression of transcription factor Pokemon in non-small cell lung cancer and its clinical significance

    Institute of Scientific and Technical Information of China (English)

    ZHAO Zhi-hong; WANG Sheng-fa; YU Liang; WANG Ju; CHANG Hao; YAN Wei-li; FU Kai; ZHANG Jian

    2008-01-01

    Background Transcription factor Pokemon,a central regulation gene of the important tumor suppressor ARF gene,exerted its activity by acting upstream of many tumor-suppressing genes and proto-oncogenes.Its expression in non-small cell lung cancer (NSCLC)and its clinical significance remains unclear.The aim of this study was to investigate the expression of Pokemon in NSCLC and to explore its correlation with the clinical pathological characteristics and its influence on patients'prognosis.Methods Fifty-five cases of NSCLC were involved in this study.The expression of Pokemon in the tumor tissue,the corresponding tumor adjacent tissue and the surrounding tissue was detected via reverse transcription-polymerase chain reaction(RT-PCR)and Western blotting,with the aim of investigating the correlation between the expression of Pokemon in tumor tissue of NSCLC and its clinicaI pathological characteristics.Moreover,a prognostic analysis was carried out based upon the immunohistochemical(IHC)detection of the expression of Pokemon gene in archival tumor specimens (5 years ago) of 62 cases of NSCLC.Results Statistical significance of the expression of Pokemon mRNA and protein was determined in the tumor tissue,the tumor adjacent tissue and the surrounding tissue (P<0.05).The expression of Pokemon was determined not to be associated with the patients'sex,age,smoking condition,tumor differentiation degree,histology and lymph node metastasis condition.However,its relationship with TNM staging was established(P<0.05).Furthermore,it was shown that the suwival rate of patients with negative Pokemon expression was significantly higher than that of those with positive Pokemon expression(P=0.004),therefore,the expression of Pokemon is believed to be an independent factor affectinq prognosis (P=0.034).Concluaion Pokemon was over-expressed in NSCLC tissue and the expression of Pokemon might be of clinical significance in non-small cell lung cancer prognostic evaluation.

  17. Thermoradiotherapy in the Treatment of Locally Advanced Non small Cell Lung Cancer

    International Nuclear Information System (INIS)

    Purpose : To improve the treatment results of locally advanced non small cell lung cancer (NSCLC) patient, we treated those patients with regional hyperthermia combined with radiotherapy. And we conducted a retrospective analysis of the results.Methods and Materials : Thirty two non small cell lung cancer patients treated at the Department of Radiation Oncology, St. Mary's hospital. Catholic University Medical College were the base of this analysis. Fourteen patients of above them were treated with hyperthermia and radiotherapy of more than 3000 cGy in radiation dose. Radiofrequency capacitive hyperthermia was administered twice weekly, immediately after radiotherapy. Total sessions of hyperthermia ranged from 3 to 13 times (mean 7,8). Eighteen patient received an external radiation therapy alone. Median radiation dose was 5580 cGy (range, 3000-7000 cGy) in fraction of 180-300 cGy, 5 fractions per week.Results : The results of thermoradiotherapy group (HTRT group) were compared with radiation alone group (RT group). There were no complete response (CR) and 12 partial responses (PR) (CR rate 0%, response rate 85.7%) in HTRT group, whereas there were 2 CRs, 8 PRs and 8 no responses (CR rate 11.1%, response rate 55.6%) in RT group. There was significant difference in local response rate of the tumors between RT group and HTRT group (p<0.05). Overall 2 year survival rate and mean survival were 7.1% and 10.5 months for HTRT group, and 0% 8.1 months for RT group. However, by the number of hyperthermia, in cases with more than or equal to 10 sessions of hyperthermia, there were significant improvement in 2 year survival rate and mean survival (40.0% and 18.2 months) compared with those in cases with less than 10 sessions of hyperthermia (7.4% and 7.4 months) (p<0.05).Conclusion : Thermoradiotherapy in locally advanced NSCLC patients increased their response rate but not 2 year survival and mean survival, therefore thermoradiotherapy with enough number of hyperthermia is

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

    Science.gov (United States)

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

    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 expression profiles of different NSCLC subtypes. A moderated two-sample t-test was used to identify differentially expressed genes between all tumor samples and cancer-free control tissue, between SCC samples and AC/BC samples and between stage I tumor samples and all other tumor samples. Gene expression microarray measurements were validated using qRT-PCR. Bayesian regression analysis and Kaplan-Meier survival analysis were performed to determine metagenes associated with survival. We identified 599 genes which were down-regulated and 402 genes which were up-regulated in NSCLC compared to the normal lung tissue and 112 genes which were up-regulated and 101 genes which were down-regulated in AC/BC compared to the SCC. Further, for stage Ib patients the metagenes potentially associated with survival were identified. Genes that expressed differently between normal lung tissue and cancer showed enrichment in gene ontology terms which were associated with mitosis and proliferation. Bayesian regression and Kaplan-Meier analysis showed that gene-expression patterns and metagene profiles can be applied to predict the probability of different survival outcomes in NSCLC patients. PMID:21695068

  19. Lentivirus-mediated gene silencing of NOB1 suppresses non-small cell lung cancer cell proliferation.

    Science.gov (United States)

    Huang, Weiyi; Zhong, Weiqing; Xu, Jun; Su, Benhua; Huang, Guanghui; Du, Jiajun; Liu, Qi

    2015-09-01

    NIN/RPN12 binding protein 1 (NOB1p) encoded by NOB1 has been found to be an essential factor in 26S proteasome biogenesis which participates in protein degradation. However, the functions of NOB1 in non-small cell lung cancer cells are largely unknown. In the present study, lentivirus-mediated NOB1 shRNA transfection in two non-small cell lung cancer cell lines (A549 and H1299) was accomplished, as determined by fluorescence imaging. Downregulation of NOB1 expression was confirmed by real-time PCR and western blotting. NOB1 silencing resulted in a significant decline in the proliferation and colony formation capability of non-small cell lung cancer cells. Moreover, flow cytometry showed that A549 cells were arrested in the G0/G1 phase of the cell cycle after NOB1 suppression. Furthermore, depletion of NOB1 resulted in a significant decrease in CDK4 and cyclin D1 expression. These results suggest that NOB1 may act as an important regulator in non-small cell lung cancer growth and could be a therapeutic target of non‑small cell lung cancer. PMID:26178254

  20. ABCC4 is required for cell proliferation and tumorigenesis in non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Zhao X

    2014-02-01

    Full Text Available Xiaoting Zhao, Yinan Guo, Wentao Yue, Lina Zhang, Meng Gu, Yue Wang Department of Cellular and Molecular Biology, Beijing TB and Thoracic Tumor Research Institute/Beijing Chest Hospital, Capital Medical University, Beijing, People's Republic of China Background: Multidrug resistance protein 4 (MRP4, also known as ATP-cassette binding protein 4 (ABCC4, is a member of the MRP/ABCC subfamily of ATP-binding cassette transporters, which are capable of pumping a wide variety of drugs out of the cell. However, little is known about the function of ABCC4 in the proliferation of lung cancer cells. Methods: ABCC4 mRNA and protein levels in lung cancer cell lines were measured by real-time polymerase chain reaction and Western blot, respectively. A lentivirus-mediated RNA interference technique was used to inhibit ABCC4 mRNA expression in A549 and 801D cells. The function of ABCC4 in cell growth was investigated by MTS and colony formation assays. The role of ABCC4 in cell cycle progression was evaluated by flow cytometry and Western blot analysis. ABCC4 mRNA levels in 30 pairs of tumors and corresponding matched adjacent normal tissues from non-small cell lung cancer patients were detected by real-time polymerase chain reaction. Results: ABCC4 was highly expressed in lung cancer cell lines. ABCC4 expression was markedly downregulated in A549 and 801D cells using the RNA interference technique. Suppression of ABCC4 expression inhibited cell growth. The percentage of cells in G1 phase was increased when ABCC4 expression was suppressed. Phosphorylation of retinoblastoma protein was weakened, originating in the downregulation of ABCC4. ABCC4 mRNA was highly expressed in lung cancer tissue and lung cancer cell lines. Conclusion: ABCC4 may play an important role in the control of A549 and 801D cell growth. ABCC4 is a potential target for lung cancer therapy. Keywords: ABCC4, cell proliferation, lung cancer, cell cycle

  1. Effects of MICA Expression on the Prognosis of Advanced Non-Small Cell Lung Cancer and the Efficacy of CIK Therapy

    OpenAIRE

    Yu Chen; Gen Lin; Zeng-qing Guo; Zhi-feng Zhou; Zhi-yong He; Yun-bin Ye

    2013-01-01

    OBJECTIVE: To investigate the clinical significance of the expression of MHC class I chain-related gene A (MICA) in patients with advanced non-small cell lung cancer and explore the relationship between MICA expression and the efficacy of cytokine-induced killer cell (CIK) therapy for treating advanced non-small cell lung cancer. METHODS: We obtained data on 222 patients with advanced non-small cell lung cancer, including data on MICA expression, age, gender, ECOG score, pathological type, st...

  2. Overexpression of cyclin Y in non-small cell lung cancer is associated with cancer cell proliferation

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Cyclin Y (CCNY) is a key cell cycle regulator that acts as a growth factor sensor to integrate extracellular signals with the cell cycle machinery. The expression status of CCNY in lung cancer and its clinical significance remain unknown. The data indicates that CCNY may be deregulated in non-small cell lung cancer, where it may act to promote cell proliferation. These studies suggest that CCNY may be a candidate biomarker of NSCLC and a possible therapeutic target for lung cancer treatment.

  3. Combination of Circulating Tumor Cells with Serum Carcinoembryonic Antigen Enhances Clinical Prediction of Non-Small Cell Lung Cancer

    OpenAIRE

    Xi Chen; Xu Wang; Hua He; Ziling Liu; Ji-Fan Hu; Wei Li

    2015-01-01

    Circulating tumor cells (CTCs) have emerged as a potential biomarker in the diagnosis, prognosis, treatment, and surveillance of lung cancer. However, CTC detection is not only costly, but its sensitivity is also low, thus limiting its usage and the collection of robust data regarding the significance of CTCs in lung cancer. We aimed to seek clinical variables that enhance the prediction of CTCs in patients with non-small cell lung cancer (NSCLC). Clinical samples and pathological data were c...

  4. Survival and treatment patterns in elderly patients with advanced non-small-cell lung cancer in Manitoba

    OpenAIRE

    Baunemann Ott, C.L.; Ratna, N.; Prayag, R.; Nugent, Z; Badiani, K.; Navaratnam, S.

    2011-01-01

    Lung cancer is the leading cause of cancer death worldwide. Non-small-cell lung cancer (nsclc) is the most common form of lung cancer, with a median age at diagnosis of 70 years. These elderly patients are often underrepresented in the randomized clinical trials upon which chemotherapy plans are based. The objective of the present study was to determine the patterns of treatment and survival in elderly patients with advanced nsclc in Manitoba.

  5. Over-Expression of LSD1 Promotes Proliferation, Migration and Invasion in Non-Small Cell Lung Cancer

    OpenAIRE

    Lv, Tangfeng; Yuan, Dongmei; Xiaohui MIAO; Lv, Yanling; Zhan, Ping; Shen, Xiaokun; Song, Yong

    2012-01-01

    Background Lysine specific demethylase 1 (LSD1) has been identified and biochemically characterized in epigenetics, but the pathological roles of its dysfunction in lung cancer remain to be elucidated. The aim of this study was to evaluate the prognostic significance of LSD1 expression in patients with non-small cell lung cancer (NSCLC) and to define its exact role in lung cancer proliferation, migration and invasion. Methods The protein levels of LSD1 in surgically resected samples from NSCL...

  6. First line treatment of advanced non-small-cell lung cancer – specific focus on albumin bound paclitaxel

    OpenAIRE

    Gupta N; Hatoum H; Dy GK

    2013-01-01

    Neha Gupta, Hassan Hatoum, Grace K DyDepartment of Medicine, Roswell Park Cancer Institute, Buffalo, NY, USAAbstract: Lung cancer is the leading cause of cancer mortality worldwide in both men and women. Non-small-cell lung cancer (NSCLC) is the most common type of lung cancer, accounting for more than 80% of cases. Paclitaxel has a broad spectrum of activity against various malignancies, including NSCLC. Paclitaxel is poorly soluble in water and thus, until recently, its commercially availab...

  7. Computational discovery of pathway-level genetic vulnerabilities in non-small-cell lung cancer | Office of Cancer Genomics

    Science.gov (United States)

    Novel approaches are needed for discovery of targeted therapies for non-small-cell lung cancer (NSCLC) that are specific to certain patients. Whole genome RNAi screening of lung cancer cell lines provides an ideal source for determining candidate drug targets. Unsupervised learning algorithms uncovered patterns of differential vulnerability across lung cancer cell lines to loss of functionally related genes. Such genetic vulnerabilities represent candidate targets for therapy and are found to be involved in splicing, translation and protein folding.

  8. PD-1/PD-L1 blockades in non-small-cell lung cancer therapy

    Directory of Open Access Journals (Sweden)

    Jing W

    2016-01-01

    Full Text Available Wang Jing,1,2,* Miaomiao Li,3,* Yan Zhang,2 Feifei Teng,2 Anqin Han,2 Li Kong,2 Hui Zhu2 1Weifang Medical University, Weifang, Shandong Province, People’s Republic of China; 2Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Jinan, Shandong Province, People’s Republic of China; 3Shandong Medical College, Jinan, Shandong Province, People’s Republic of China *Both these authors contributed equally to the work Abstract: Lung cancer is the leading cause of cancer death in males and the second leading cause of death in females worldwide. Non-small-cell lung cancer (NSCLC is the main pathological type of lung cancer, and most newly diagnosed NSCLC patients cannot undergo surgery because the disease is already locally advanced or metastatic. Despite chemoradiotherapy and targeted therapy improving clinical outcomes, overall survival remains poor. Immune checkpoint blockade, especially blockade of programmed death-1 (PD-1 receptor and its ligand PD-L1, achieved robust responses and improved survival for patients with locally advanced/metastatic NSCLC in preclinical and clinical studies. However, with regard to PD-1/PD-L1 checkpoint blockade as monotherapy or in combination with other antitumor therapies, such as chemotherapy, radiotherapy (including conventional irradiation and stereotactic body radiotherapy, and target therapy, there are still many unknowns in treating patients with NSCLC. Despite this limited understanding, checkpoint blockade as a novel therapeutic approach may change the treatment paradigm of NSCLC in the future. Here we review the main results from completed and ongoing studies to investigate the feasibility of PD-1/PD-L1 inhibitors, as monotherapy or combinatorial agents in patients with locally advanced and metastatic NSCLC, and explore optimal strategy in such patients. Keywords: immunotherapy, checkpoint, PD-1, PD-L1, NSCLC

  9. EXPRESSION OF FRAGILE HISTIDINE TRIAD AND P53 IN NON-SMALL CELL LUNG CANCER

    Institute of Scientific and Technical Information of China (English)

    HOU Xing-hua; ZHANG Dao-rong

    2006-01-01

    Objective: To investigate the expression of fragile histidine triad (FHIT) and p53 protein in non-small cell lung cancer (NSCLC) and explore the relationship between their expressions and the clinicopathological features. Methods: FHIT protein and p53 protein were detected by immunohistochemistry in 76 cases of NSCLCs and matched normal lung tissues. Results:Fifty-one cases (67.1%) showed negative expression of FHIT (apparent reduction or loss) and thirty-seven cases (48.7%)showed p53 positive expression (overexpression). The difference was significant (P=0.04). However, there was no significant difference in FHIT expression between the p53-positive group and the p53-negative group (64.9% versus 69.2%, P=0.686).The negative rate of FHIT protein expression was higher in squamous cell carcinoma than in adenocarcinoma, in moderately and poorly differentiated carcinoma than in well-differentiated carcinoma, and in cases with smoking history than in cases without smoking history (P<0.05). There was no relationship between FHIT expression and clinical stage or lymph node metastasis. The negative FHIT expression was not an independent predictor of overall survival (P=0.338). Conclusion: The frequency of negative expression of FHIT protein is higher than that of positive expression of p53 in NSCLCs. The negative expression of FHIT is independent of the expression of p53. The change of expression of FHIT may play a role in the smoking related lung tumorigenesis while it may have no relationship with the progress of NSCLC or prognosis of the patients.

  10. Roles of Mir-144-ZFX pathway in growth regulation of non-small-cell lung cancer.

    Directory of Open Access Journals (Sweden)

    Wangjian Zha

    Full Text Available BACKGROUND: Lung cancer is the leading cause of cancer-related death worldwide. Non-small cell lung carcinoma (NSCLC accounts for most of the lung cancer cases and the prognosis of this disease remains poor despite decades of intensive investigation. Thus new insights into underlying mechanisms by which NSCLC develops are avidly needed as the basis for development of new lines of therapeutic strategies. The past decade has witnessed a growing interest on the regulatory roles of micro RNAs on various categories of malignancies. Related data has been well documented in carcinogenesis and pathophysiology of a variety of malignancies. Even so, there is a relative lack of data on roles of mir-144 in tumor biology and there has been no report showing the involvement of mir-144 in NSCLC development. METHODS/PRINCIPAL FINDING: From human NSCLC tumor tissue samples and cell culture samples, we found that the expression of mir-144 is associated with malignant phenotype of NSCLC. Further investigations showed that ectopic mir-144 expression dramatically inhibits NSCLC tumor cell growth and induces apoptosis as manifested by elevated apoptotic protein markers and flowcytometry change. Moreover, we also found that ZFX protein expression is also associated with malignant phenotype of NSCLC and knockdown of ZFX protein results in a similar effect as of ectopic mir-144 expression. Finally, we found that ZFX expression is highly adjustable upon presence of mir-144 and ectopic expression of ZFX dramatically dampens mir-144 action of tumor inhibition. CONCLUSIONS: Our results for the first time showed mir-144-ZFX pathway is involved in the development of NSCLC, which sheds a light for further investigations on underlying mechanisms toward better understanding and management of NSCLC.

  11. Dose escalation for non-small cell lung cancer: Analysis and modelling of published literature

    International Nuclear Information System (INIS)

    Purpose: To review the published clinical data on non-small cell lung cancer treated with radical radiotherapy to confirm a dose-response relationship as a basis for further dose-escalation trials. Methods: Twenty-four published clinical trials were identified, 16 of which - with 29 different standard, hyper- and hypofractionated treatment schedules - were analysed. Prescription doses were converted to biologically-equivalent dose (BED), with a correction for repopulation. Disease-free survival data were corrected for the stage profile of each cohort to allow better comparison of results. We also analysed moderate (grade II and III) lung and oesophageal acute toxicity related to the corrected BED delivered to the tumour. Results: The clinical data analysed showed good agreement between the observed and modelled disease-free survival at 2 years when compared to the published models of Fenwick (correlation coefficient 0.525, p = 0.003) and Martel (correlation coefficient 0.492, p = 0.007), indicating a clear tumour dose-response. In the normally fractionated treatments (∼2 Gy per fraction), improved disease-free survival was generally observed in the shorter schedules (maximum around 6 weeks). However, the best outcomes were obtained for the hypofractionated schedules. No systematic relationship was seen between prescribed dose and lung or oesophageal acute toxicity, possibly due to dose selection depending on V20 or MLD in some studies and the diversity of the patients analysed. Conclusions: We have demonstrated a dose-response relationship for NSCLC based on clinical data. The clinical data provide a rational basis for selection of dose escalation schedules to be tested in future randomised trials.

  12. Recent advances in the treatment of non-small cell and small cell lung cancer.

    Science.gov (United States)

    Stinchcombe, Thomas E

    2014-01-01

    Recent presentations at the American Society of Clinical Oncology (ASCO) meeting from 30 May to 3 June, 2014, will impact routine clinical care and the development of clinical trials in non-small cell lung cancer (NSCLC) and extensive stage small cell lung cancer (ES-SCLC). Patients with activating epidermal growth factor receptor (EGFR) mutations, defined as exon 19 and exon 21 L858R point mutations, experience a high objective response rate and prolonged progression-free survival with EGFR tyrosine kinase inhibitors. However, inevitably, patients experience disease progression and the most common mechanism of acquired resistance is an EGFR exon 20 T790M mutation. Several agents (AZD9291, CO-1686 and HM61713) have demonstrated impressive activity in patients with T790M resistance mutations. Additional data on the efficacy of first-line therapy with afatinib and the combination of erlotinib and bevacizumab for patients with EGFR mutant NSCLC were presented. The results of a phase III trial of crizotinib compared to platinum-pemetrexed in the first-line setting, and a phase I trial and expansion cohort of ceritinib, provided additional efficacy and toxicity data for patients with anaplastic lymphoma kinase rearranged NSCLC. A phase III trial of cisplatin and gemcitabine, with and without necitumumab, revealed an improvement in overall survival with the addition of necitumumab in patients with squamous NSCLC. In the second-line setting, a phase III trial of docetaxel with ramucirumab or placebo revealed an improvement in overall survival with the addition of ramucirumab. In extensive stage small cell lung cancer phase III trials of consolidative thoracic radiation therapy and prophylactic cranial radiation failed to reveal an improvement in overall survival. PMID:25580271

  13. Quality of Life After Stereotactic Radiotherapy for Stage I Non-Small-Cell Lung Cancer

    International Nuclear Information System (INIS)

    Purpose: To determine the impact of stereotactic radiotherapy on the quality of life of patients with inoperable early-stage non-small-cell lung cancer (NSCLC). Overall survival, local tumor control, and toxicity were also evaluated in this prospective study. Methods and Materials: From January 2006 to February 2008, quality of life, overall survival, and local tumor control were assessed in 39 patients with pathologically confirmed T1 to 2N0M0 NSCLC. These patients were treated with stereotactic radiotherapy. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ) C30 and the QLQ LC13 lung cancer-specific questionnaire were used to investigate changes in quality of life. Assessments were done before treatment, at 3 weeks, and at 2, 4, 6, 9, and 12 months after treatment, until death or progressive disease. Toxicity was evaluated using common terminology criteria for adverse events version 3.0. Results: Emotional functioning improved significantly after treatment. Other function scores and QLQ C30 and QLQ LC13 lung symptoms (such as dyspnea and coughing) showed no significant changes. The overall 2-year survival rate was 62%. After a median follow-up of 17 months, 1 patient had a local recurrence (3%). No grade 4 or 5 treatment-related toxicity occurred. Grade 3 toxicity consisted of thoracic pain, which occurred in 1 patient within 4 months of treatment, while it occurred thereafter in 2 patients. Conclusions: Quality of life was maintained, and emotional functioning improved significantly after stereotactic radiotherapy for stage I NSCLC, while survival was acceptable, local tumor control was high, and toxicity was low.

  14. 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.

  15. Non-small-cell lung cancer resectability: diagnostic value of PET/MR

    Energy Technology Data Exchange (ETDEWEB)

    Fraioli, Francesco; Menezes, Leon; Kayani, Irfan; Syed, Rizwan; O' Meara, Celia; Barnes, Anna; Bomanji, Jamshed B.; Punwani, Shonit; Groves, Ashley M. [University College London Hospitals NHS Foundation Trust, Department of Nuclear Medicine and Radiology, London (United Kingdom); Screaton, Nicholas J. [Papworth Hospital NHS Foundation Trust, Department of Radiology, Cambridge (United Kingdom); Janes, Samuel M. [University College London, Lungs for Living Research Centre, UCL Respiratory Division of Medicine, London (United Kingdom); Win, Thida [Lister Hospital, Respiratory Medicine, Stevenage (United Kingdom); Zaccagna, Fulvio [University of Rome ' ' Sapienza' ' , Department of Radiological Sciences, Rome (Italy)

    2015-01-15

    To assess the diagnostic performance of PET/MR in patients with non-small-cell lung cancer. Fifty consecutive consenting patients who underwent routine {sup 18}F-FDG PET/CT for potentially radically treatable lung cancer following a staging CT scan were recruited for PET/MR imaging on the same day. Two experienced readers, unaware of the results with the other modalities, interpreted the PET/MR images independently. Discordances were resolved in consensus. PET/MR TNM staging was compared to surgical staging from thoracotomy as the reference standard in 33 patients. In the remaining 17 nonsurgical patients, TNM was determined based on histology from biopsy, imaging results (CT and PET/CT) and follow-up. ROC curve analysis was used to assess accuracy, sensitivity and specificity of the PET/MR in assessing the surgical resectability of primary tumour. The kappa statistic was used to assess interobserver agreement in the PET/MR TNM staging. Two different readers, without knowledge of the PET/MR findings, subsequently separately reviewed the PET/CT images for TNM staging. The generalized kappa statistic was used to determine intermodality agreement between PET/CT and PET/MR for TNM staging. ROC curve analysis showed that PET/MR had a specificity of 92.3 % and a sensitivity of 97.3 % in the determination of resectability with an AUC of 0.95. Interobserver agreement in PET/MR reading ranged from substantial to perfect between the two readers (Cohen's kappa 0.646 - 1) for T stage, N stage and M stage. Intermodality agreement between PET/CT and PET/MR ranged from substantial to almost perfect for T stage, N stage and M stage (Cohen's kappa 0.627 - 0.823). In lung cancer patients PET/MR appears to be a robust technique for preoperative staging. (orig.)

  16. Erlotinib treatment for persistent spontaneous pneumothorax in non-small cell lung cancer: a case report

    Institute of Scientific and Technical Information of China (English)

    REN Sheng-xiang; ZHOU Song-wen; ZHANG Ling; ZHOU Cai-cun

    2010-01-01

    @@ Spontaneous pneumothorax (SP) develops secondary to primary lung cancer. It has a very low incidence and accounts for less than 1% of all cases.1 Once SP develops, the prognosis is usually very poor, and majority of patients live no longer than 3 months.1,2Most patients with advanced stage can not undergo resection due to the poor general condition. Thus, chest tube drainage remains among the treatments of choice although it is not always completely effective in preventing recurrence. In refractory SP, patients would bear the chest tube for their whole life.3 Here we report a case of SP following chemotherapy in adenocarcinoma of the lung with multiple organs metastases. In this case, chest tube drainage was not effective in preventing recurrence of SP.However, the treatment was successful with oral erlotinib,an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI).

  17. Radiochemotherapy in non-small cell lung cancer. A report of experiences

    International Nuclear Information System (INIS)

    60 inoperable patients (42 M0- and 18 M1-stage) with non-small cell lung cancer who had received combined radiochemotherapy (RT+CT) were examined retrospectively. Different drugs or drug-combinations were used. The sequence of radiotherapy and chemotherapy also differed. The survival was compared to that of another group of patients who had received at least 50 Gy with definitive radiotherapy at the same period of time (RT: N=135). The Karnofsky-performance-index (KPI) was on an average of 80% in both groups. The primary of patients with systemic disease was treated by radiation when it became symptomatic or when it showed an evident progression. The two investigated treatment groups were comparable regarding KPI, histology, stage, tumor dose and age. The survival was significantly better when chemotherapy was added to radiotherapy. The median survival times in months were as follows: M0: RT 10.6/RT+CT 14.7; M1: RT 6.0/RT+CT 9.3. Lokal tumor control was the major problem with or without chemotherapy (local progression of about 70% in both groups). The toxicity of radiochemotherapy was acceptable (bonemarrow toxicity WHO-grade 4: 10.5%; nausea WHO-grade 4: 3%). (orig.)

  18. Polymeric Nanoparticles Containing Taxanes Enhance Chemoradiotherapeutic Efficacy in Non-small Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Jung, Joohee [Institute for Innovative Cancer Research, ASAN Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); College of Pharmacy, Duksung Women' s University, Seoul (Korea, Republic of); Park, Sung-Jin [Institute for Innovative Cancer Research, ASAN Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Laboratory of Bioimaging Probe Development, Singapore Bioimaging Consortium (Singapore); Chung, Hye Kyung [Center for Development and Commercialization of Anti-cancer Therapeutics, ASAN Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Kang, Hye-Won; Lee, Sa-Won; Seo, Min Hyo [Department of Parenteral Delivery Program, Samyang Pharmaceuticals R and D, Daejeon (Korea, Republic of); Park, Heon Joo [Department of Microbiology, College of Medicine, Inha University, Inchon (Korea, Republic of); Song, Si Yeol [Institute for Innovative Cancer Research, ASAN Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Department of Radiation Oncology, ASAN Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Jeong, Seong-Yun, E-mail: syj@amc.seoul.kr [Institute for Innovative Cancer Research, ASAN Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Choi, Eun Kyung, E-mail: ekchoi@amc.seoul.kr [Institute for Innovative Cancer Research, ASAN Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Department of Radiation Oncology, ASAN Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); College of Pharmacy, Duksung Women' s University, Seoul (Korea, Republic of)

    2012-09-01

    Purpose: To reduce the side effects and improve the efficacy of chemoradiation therapy, taxanes were incorporated into polymeric nanoparticles (PNP), and their synergic effect on radiation therapy in non-small cell lung cancer was evaluated. Methods and Materials: The properties of PNP-taxanes were characterized by transmission electron microscopy and dynamic light scattering. The chemoradiotherapeutic efficacy of PNP-taxanes was determined by clonogenic assay, cellular morphology, and flow cytometry in A549 cells. In mice bearing A549-derived tumors, the tumor growth delay was examined after the treatment of PNP-taxanes and/or ionizing radiation (IR). Results: The PNP-taxanes were found to be approximately 45 nm in average diameter and to have high solubility in water. They showed the properties of active internalization into cells and preserved the anticancer effect of free taxanes. The survival fraction of A549 cells by clonogenic assay was significantly reduced in the group receiving combined treatment of PNP-taxanes and IR. In addition, in vivo radiotherapeutic efficacy was markedly enhanced by the intravenous injection of PNP-taxanes into the xenograft mice. Conclusions: We have demonstrated the feasibility of PNP-taxanes to enhance the efficacy of chemoradiation therapy. These results suggest PNP-taxanes can hold an invaluable and promising position in treating human cancers as a novel and effective chemoradiation therapy agent.

  19. Neoadjuvant therapy affects tumor growth markers in early stage non-small-cell lung cancer

    Directory of Open Access Journals (Sweden)

    Chorostowska-Wynimko J

    2009-12-01

    Full Text Available Abstract Introduction While adjuvant therapy of early-stage non-small-cell lung cancer (NSCLC is widely accepted, literature data concerning neoadjuvant treatment provide contradictory results with both improved and unaffected survival rates. Also, data concerning potential effects of neo-adjuvant therapy on cellular level are scarce. Objective The aim of present study was to analyze the effect of chemotherapy followed by surgical resection on several key biological markers of tumor growth (TGF-β, VEGF, apoptosis (sAPO-1/Fas/CD95 and invasiveness (TIMP-1 assessed in the sera of NSCLC early-stage patients (IB-IIIA. Materials and methods Measurements were performed by ELISA method in blood serum from 24 NSCLC patients (I-IIIA collected prior therapy, one day before surgery and 3 days after. Results TGF-β serum concentrations were significantly lower after both chemotherapy (P Conclusion Neoadjuvant treatment of early-stage NSCLC affects mostly mechanisms responsible for tumor growth and vascularization. Its effect on cancer cells apoptotic activity needs further evaluation.

  20. Progress of Platelet Derived Grow Factor Family in Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Yijun TIAN

    2014-01-01

    Full Text Available Non-small cell lung cancer (NSCLC is a malignant tumour with quite high cancer specific mortality, and it still lacks stable and reliable markers for NSCLC's prognosis. Platelet derived grow factor (PDGF and PDGFR has been considered to be involved in the process of cell proliferation, migration, metastasis and epithelial mesenchymal transition of cancer cell through various intracellular signal pathways. Pathology analysis showed that PDGF pathway mainly stimulates the proliferation of NSCLC tumour stroma through paracrine pattern, and some reaseach found that PDGF pathway directly promotes some NSCLC cell's proliferation. The expression of PDGF and PDGFR within NSCLC tissue correlates with status of lymphatic metastasis and patients’ prognosis. In clinical treatment of NSCLC, the great effect of PDGF pathway in angiogenesis and promoting distribution of chemotherapy by inhibition of PDGF should not be neglected. As an important pro-angiogenesis pathway, functions of PDGF in radiotherapy is dicovered by more and more fundamental research. This review focuses on the progress of PDGF pathway in NSCLC and aims to provide some new ideas for clinical and fundamental researchers.

  1. Treating advanced non-small-cell lung cancer in Chinese patients: focus on icotinib

    Directory of Open Access Journals (Sweden)

    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

  2. PIAS1-FAK Interaction Promotes the Survival and Progression of Non-Small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Jerfiz D. Constanzo

    2016-05-01

    Full Text Available The sequence of genomic alterations acquired by cancer cells during tumor progression and metastasis is poorly understood. Focal adhesion kinase (FAK is a non-receptor tyrosine kinase that integrates cytoskeleton remodeling, mitogenic signaling and cell survival. FAK has previously been reported to undergo nuclear localization during cell migration, cell differentiation and apoptosis. However, the mechanism behind FAK nuclear accumulation and its contribution to tumor progression has remained elusive. We report that amplification of FAK and the SUMO E3 ligase PIAS1 gene loci frequently co-occur in non-small cell lung cancer (NSCLC cells, and that both gene products are enriched in a subset of primary NSCLCs. We demonstrate that endogenous FAK and PIAS1 proteins interact in the cytoplasm and the cell nucleus of NSCLC cells. Ectopic expression of PIAS1 promotes proteolytic cleavage of the FAK C-terminus, focal adhesion maturation and FAK nuclear localization. Silencing of PIAS1 deregulates focal adhesion turnover, increases susceptibility to apoptosis in vitro and impairs tumor xenograft formation in vivo. Nuclear FAK in turn stimulates gene transcription favoring DNA repair, cell metabolism and cytoskeleton regulation. Consistently, ablation of FAK by CRISPR/Cas9 editing, results in basal DNA damage, susceptibility to ionizing radiation and impaired oxidative phosphorylation. Our findings provide insight into a mechanism regulating FAK cytoplasm-nuclear distribution and demonstrate that FAK activity in the nucleus promotes NSCLC survival and progression by increasing cell-ECM interaction and DNA repair regulation.

  3. Stereotactic radiotherapy for early stage non-small cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Ricardi, Umberto; Badellino, Serena; Filippi, Andrea Riccardo [Dept. of Oncology, Radiation Oncology, University of Torino, Torino (Italy)

    2015-06-15

    Stereotactic body radiotherapy (SBRT) represents a consolidated treatment option for patients with medically inoperable early stage non-small cell lung cancer (NSCLC). The clinical evidence accumulated in the past decade supports its use as an alternative to surgery with comparable survival outcomes. Due to its limited toxicity, SBRT is also applicable to elderly patients with very poor baseline pulmonary function or other severe comorbidities. Recent comparative studies in operable patients raised the issue of the possible use of SBRT also for this subgroup, with quite promising results that still should be fully confirmed by prospective trials with long-term follow-up. Aim of this review is to summarize and discuss the major studies conducted over the years on SBRT and to provide data on the efficacy and toxicity of this radiotherapy technique for stage I NSCLC. Technical aspects and quality of life related issues are also discussed, with the goal to provide information on the current role and limitations of SBRT in clinical practice.

  4. Surgical Outcomes of Synchronous Multiple Primary Non-Small Cell Lung Cancers.

    Science.gov (United States)

    Zhang, Zhirong; Gao, Shugeng; Mao, Yousheng; Mu, Juwei; Xue, Qi; Feng, Xiaoli; He, Jie

    2016-01-01

    The prognostic indicators for synchronous multiple primary non-small cell lung cancer (NSCLC) vary across reports. In present study, the prognostic factors for the patients with synchronous multiple primary NSCLC were analyzed in a large cohort. A total of 285 patients with synchronous multiple primary NSCLC who underwent radical surgical resection and with complete follow-up information were included in this study. The Kaplan-Meier method were used for survival analysis, Cox proportional hazards regression models were used for risk factors evaluation. Among them, 94 (33.0%) patients had bilateral tumors and 51 (17.9%) had multiple (≥3) tumors. The 5-year disease-free survival (DFS) and overall survival (OS) rate was 58.7% and 77.6%, respectively. Univariate analysis identified parameters conferring shorter OS including male gender, symptomatic disease, negative family history, large maximal tumor size, not all adenocarcinomas, advanced highest T stage, and lymph node involvement. Multivariate analysis showed that male gender (p = 0.020), symptomatic disease (p = 0.017), and lymph node involvement (p involvement (p = 0.002) were the independent unfavorable prognosticators. In conclusion, we identified independent prognosticators which will provide the valuable clues for postoperative management of patients with synchronous multiple primary NSCLC. PMID:27254665

  5. Potential clinical predictors of outcome after postoperative radiotherapy of non-small cell lung cancer

    International Nuclear Information System (INIS)

    The aim of this analysis was to investigate the impact of tumour-, treatment- and patient-related cofactors on local control and survival after postoperative adjuvant radiotherapy in patients with non-small cell lung cancer (NSCLC), with special focus on waiting and overall treatment times. For 100 NSCLC patients who had received postoperative radiotherapy, overall, relapse-free and metastases-free survival was retrospectively analysed using Kaplan-Meier methods. The impact of tumour-, treatment- and patient-related cofactors on treatment outcome was evaluated in uni- and multivariate Cox regression analysis. No statistically significant difference between the survival curves of the groups with a short versus a long time interval between surgery and radiotherapy could be shown in uni- or multivariate analysis. Multivariate analysis revealed a significant decrease in overall survival times for patients with prolonged overall radiotherapy treatment times exceeding 42 days (16 vs. 36 months) and for patients with radiation-induced pneumonitis (8 vs. 29 months). Radiation-induced pneumonitis and prolonged radiation treatment times significantly reduced overall survival after adjuvant radiotherapy in NSCLC patients. The negative impact of a longer radiotherapy treatment time could be shown for the first time in an adjuvant setting. The hypothesis of a negative impact of longer waiting times prior to commencement of adjuvant radiotherapy could not be confirmed. (orig.)

  6. Simulating non-small cell lung cancer with a multiscale agent-based model

    Directory of Open Access Journals (Sweden)

    Deisboeck Thomas S

    2007-12-01

    Full Text Available Abstract Background The epidermal growth factor receptor (EGFR is frequently overexpressed in many cancers, including non-small cell lung cancer (NSCLC. In silico modeling is considered to be an increasingly promising tool to add useful insights into the dynamics of the EGFR signal transduction pathway. However, most of the previous modeling work focused on the molecular or the cellular level only, neglecting the crucial feedback between these scales as well as the interaction with the heterogeneous biochemical microenvironment. Results We developed a multiscale model for investigating expansion dynamics of NSCLC within a two-dimensional in silico microenvironment. At the molecular level, a specific EGFR-ERK intracellular signal transduction pathway was implemented. Dynamical alterations of these molecules were used to trigger phenotypic changes at the cellular level. Examining the relationship between extrinsic ligand concentrations, intrinsic molecular profiles and microscopic patterns, the results confirmed that increasing the amount of available growth factor leads to a spatially more aggressive cancer system. Moreover, for the cell closest to nutrient abundance, a phase-transition emerges where a minimal increase in extrinsic ligand abolishes the proliferative phenotype altogether. Conclusion Our in silico results indicate that in NSCLC, in the presence of a strong extrinsic chemotactic stimulus (and depending on the cell's location downstream EGFR-ERK signaling may be processed more efficiently, thereby yielding a migration-dominant cell phenotype and overall, an accelerated spatio-temporal expansion rate.

  7. Efifcacy of Icotinib Hydrochloride in the Treatment of Advanced Non-small Cell Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    Ma Xianglei; Tang Yiqun; Kou Yingying; Shi Meiqi

    2013-01-01

    Objective:To observe and evaluate the efifcacy and adverse responses of icotinib hydrochloride in the treatment of advanced non-small cell lung cancer (NSCLC), and analyze the relative factors impacting its efifcacy and prognosis. Methods: The clinical data of 260 patients with advanced NSCLC treated with icotinib hydrochloride in Jiangsu Cancer Hospital was retrospectively analyzed. Results:Four weeks after initial administration, 256 patients were evaluable for efifcacy except 4 who withdrew the drug due to intolerable adverse responses. Among the 256 patients, there were 0 complete response (CR), 96 partial response (PR, 37.5%), 97 stable disease (SD, 37.9%) and 63 progression disease (PD, 24.6%), with the objective remission rate (ORR) and disease control rate (DCR) being 37.6%and 75.4%respectively. However, in all patients, the median progression-free survival (PFS) was 7 (0.4~16.3) months, and were 11 (1~16.3), 6 (0.4~11.3) and 5 (1~13.5) months in those treated with ifrst-line, second-line, and≥third-line treatments, respectively. Conclusion: Icotinib hydrochloride has significant efficiency and better safety for treating advanced NSCLC.

  8. Clinical Utility of Circulating Tumor Cells in ALK-Positive Non-Small-Cell Lung Cancer.

    Science.gov (United States)

    Faugeroux, Vincent; Pailler, Emma; Auger, Nathalie; Taylor, Melissa; Farace, Françoise

    2014-01-01

    The advent of rationally targeted therapies such as small-molecule tyrosine kinase inhibitors (TKIs) has considerably transformed the therapeutic management of a subset of patients with non-small-cell lung cancer (NSCLC) harboring defined molecular abnormalities. When such genetic molecular alterations are detected the use of specific TKI has demonstrated better results (overall response rate, progression free survival) compared to systemic therapy. However, the detection of such molecular abnormalities is complicated by the difficulty in obtaining sufficient tumor material, in terms of quantity and quality, from a biopsy. Here, we described how circulating tumor cells (CTCs) can have a clinical utility in anaplastic lymphoma kinase (ALK) positive NSCLC patients to diagnose ALK-EML4 gene rearrangement and to guide therapeutic management of these patients. The ability to detect genetic abnormalities such ALK rearrangement in CTCs shows that these cells could offer new perspectives both for the diagnosis and the monitoring of ALK-positive patients eligible for treatment with ALK inhibitors. PMID:25414829

  9. Clinical Utility of Circulating Tumor Cells in ALK-Positive Non-Small-Cell Lung Cancer

    Science.gov (United States)

    Faugeroux, Vincent; Pailler, Emma; Auger, Nathalie; Taylor, Melissa; Farace, Françoise

    2014-01-01

    The advent of rationally targeted therapies such as small-molecule tyrosine kinase inhibitors (TKIs) has considerably transformed the therapeutic management of a subset of patients with non-small-cell lung cancer (NSCLC) harboring defined molecular abnormalities. When such genetic molecular alterations are detected the use of specific TKI has demonstrated better results (overall response rate, progression free survival) compared to systemic therapy. However, the detection of such molecular abnormalities is complicated by the difficulty in obtaining sufficient tumor material, in terms of quantity and quality, from a biopsy. Here, we described how circulating tumor cells (CTCs) can have a clinical utility in anaplastic lymphoma kinase (ALK) positive NSCLC patients to diagnose ALK-EML4 gene rearrangement and to guide therapeutic management of these patients. The ability to detect genetic abnormalities such ALK rearrangement in CTCs shows that these cells could offer new perspectives both for the diagnosis and the monitoring of ALK-positive patients eligible for treatment with ALK inhibitors. PMID:25414829

  10. Acute phase response before treatment predicts radiation esophagitis in non-small cell lung cancer

    International Nuclear Information System (INIS)

    Background and purpose: Radiation esophagitis (RE) represents an inflammatory reaction to radiation therapy (RT). We hypothesized that aspects of the physiologic acute phase response (APR) predicts RE. Material and methods: We retrospectively analyzed 285 patients with non-small cell lung cancer (NSCLC) treated with definitive radiation. The primary analysis was the association of pretreatment lab values reflective of the APR with symptomatic (grade ⩾2) RE. Univariate and multivariate odds ratios (ORs) were calculated to test associations of clinical and pretreatment lab values with RE. Optimal cutpoints and multivariable risk stratification groupings were determined via recursive partitioning analysis. Results: Pretreatment platelet counts were higher and hemoglobin levels lower in patients who developed RE (P < 0.05). Based on these two pre-treatment risk factors, an APR score was defined as 0 (no risk factors), 1 (either risk factor), or 2 (both risk factors). APR score was significantly associated with RE in both univariate (OR = 2.3 for each point, 95% confidence interval [CI] 1.5–3.4, P = 0.001) and multivariate (OR = 2.1, 95% CI 1.3–3.4, P = 0.002) analyses. Conclusions: The APR score may represent a novel metric to predict RE. However, pending validation in an independent dataset, caution is advised when interpreting these results given their retrospective and thus exploratory nature

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

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    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.

  12. TELOMERASE ACTIVITY OF FIBROBRONCHOSCOPIC BRUSHING CELLS IN NON-SMALL CELL LUNG CANCER

    Institute of Scientific and Technical Information of China (English)

    吴晓红; 应可净; 张行

    2003-01-01

    Objective: To evaluate the clinical significance of telomerase activity particularly in terms of prognostic impact in non-small cell lung cancer (NSCLC). Methods: The exfoliated cells from fibrobronchoscopic brushing were studied using polymerase chain reaction based on a telomerase repeat amplification protocal assay. Samples were taken from 60 NSCLC and 20 pulmonary infection cases. Results: Telomerase activity was detected in 53 of 60(88.3%) NSCLC specimens from the lesion side and in 5 of 25(20.0%) from the contralateral side but only in 2 of 20 pulmonary infection samples (P<0.05). The telomerase activity levels in NSCLC (medium 0.109) were significantly higher than those in pulmonary infection (medium 0.018, U=4.95, P<0.05). The telomerase activity levels in tumor staged IIIb-IV (medium 0.173) were higher than those in staged I-IIIa (medium 0.132, U=1.899, P<0.05). Conclusion: Telomerase activity is one of the most important marker in patients with NSCLC. Telomerase activity increases with the advance of tumor stage and can be used as a prognostic indicator of advanced NSCLC.

  13. Current Status of Targeted Therapy for Anaplastic Lymphoma Kinase in Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Li MA

    2014-12-01

    Full Text Available The rate of the anaplastic lymphoma kinase (ALK gene rearrangements in non-small cell lung cancer (NSCLC tissues is 3%-5%. The first-in-class ALK tyrosine kinase inhibitor, crizotinib, can effectively target these tumors represent a significant advance in the evolution of personalized medicine for NSCLC. A randomized phase III clinical trial in which superiority of crizotinib over chemotherapy was seen in previously treated ALK-positive NSCLC patients demonstrated durable responses and well tolerance in the majority of ALK-positive NSCLC patients treated with crizotinib. However, despite the initial responses, most patients develop acquired resistance to crizotinib. Several novel therapeutic approaches targeting ALK-positive NSCLC are currently under evaluation in clinical trials, including second-generation ALK inhibitors, such as LDK378, CH5424802 (RO5424802, and AP26113, and new agents shock protein 90 inhibitors. This review aims to present the current knowledge on this fusion gene, the treatment advances, and novel drug clinical trials in ALK rearranged NSCLC.

  14. Monitoring drug induced apoptosis and treatment sensitivity in non-small cell lung carcinoma using dielectrophoresis.

    Science.gov (United States)

    Taruvai Kalyana Kumar, Rajeshwari; Liu, Shanshan; Minna, John D; Prasad, Shalini

    2016-09-01

    Non-invasive real time methods for characterizing biomolecular events that contribute towards apoptotic kinetics would be of significant importance in the field of cancer biology. Effective drug-induced apoptosis is an important factor for establishing the relationship between cancer genetics and treatment sensitivity. The objective of this study was to develop a non-invasive technique to characterize cancer cells that are undergoing drug-induced apoptosis. We used dielectrophoresis to determine apoptotic cells as early as 2h post drug treatment as compared to 24h with standard flow cytometry method using non-small cell lung cancer (NSCLC) adenocarcinoma cell line (HCC1833) as a study model. Our studies have shown significant differences in apoptotic cells by chromatin condensation, formation of apoptotic bodies and exposure of phosphatidylserine (PS) on the extracellular surface when the cells where treated with a potent Bcl-2 family inhibitor drug (ABT-263). Time lapse dielectrophoretic studies were performed over 24h period after exposure to ABT-263 at clinically relevant concentrations. The dielectrophoretic studies were compared to Annexin-V FITC flow assay for the detection of PS in mid-stage apoptosis using flow cytometry. As a result of physical and biochemical changes, inherent dielectric properties of cells undergoing varying stages of apoptosis showed amplified changes in their cytoplasmic and membrane capacitance. In addition, zeta potential of these fixed isolated cells was measured to obtain direct correlation to biomolecular events. PMID:27262539

  15. Molecular targeted therapy to improve radiotherapeutic outcomes for non-small cell lung carcinoma

    Science.gov (United States)

    Bhardwaj, Bhaskar; Bhardwaj, Himanshu; Balusu, Sree; Shwaiki, Ali

    2016-01-01

    Effective treatments for non-small cell lung carcinoma (NSCLC) remain elusive. The use of concurrent chemotherapy with radiotherapy (RT) has improved outcomes, but a significant proportion of NSCLC patients are too frail to be able to tolerate an intense course of concurrent chemoradiotherapy. The development of targeted therapies ignited new hope in enhancing radiotherapeutic outcomes. The use of targeted therapies against the epidermal growth factor receptor (EGFR) has offered slight but significant benefits in concurrent use with RT for certain patients in certain situations. However, despite theoretical promise, the use of anti-angiogenics, such as bevacizumab and endostatin, has not proven clinically safe or useful in combination with RT. However, many new targeted agents against new targets are being experimented for combined use with RT. It is hoped that these agents may provide a significant breakthrough in the radiotherapeutic management of NSCLC. The current review provides a brief discussion about the targets, the targeted therapies, the rationale for the use of targeted therapies in combination with RT, and a brief review of the existing data on the subject. PMID:26904572

  16. 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.

  17. Neoadjuvant intratumoral immuno-gene therapy for non-small cell lung cancer.

    Science.gov (United States)

    Predina, Jarrod D; Keating, Jane; Venegas, Ollin; Nims, Sarah; Singhal, Sunil

    2016-04-01

    Non-small Cell Lung Cancer (NSCLC) remains a deadly disease despite aggressive treatment protocols which incorporate chemotherapy, radiation and surgery. These traditional approaches have reached a plateau in therapeutic benefit. There is emerging evidence suggesting that immunotherapy can serve as an alternative treatment modality for NSCLC. Our group has nearly two decades of experience involving immuno-gene therapy with Ad.hIFN-α and Ad.hIFN-β in human mesothelioma trials, and has observed both safety and efficacy in treatment of Thoracic malignancies. We have expanded the scope of our work and have obtained encouraging pre-clinical evidence suggesting a role for immunotherapy as a surgical adjuvant for NSCLC cancers. By combining immunotherapy with surgery, synergistic results have been observed. Based on these observations, we have prepared a Phase I Clinical Trial that pairs Ad.hIFN-α with surgery for patients with resectable NSCLC. Patient enrollment is likely to begin in the Summer of 2016. We hope that this trial will serve as a platform for future trials aimed at pairing immunotherapy with surgery for patients diagnosed with NSCLC. PMID:27232513

  18. Anti-PD-1 Inhibitor-Related Pneumonitis in Non-Small Cell Lung Cancer.

    Science.gov (United States)

    Nishino, Mizuki; Chambers, Emily S; Chong, Curtis R; Ramaiya, Nikhil H; Gray, Stacy W; Marcoux, J Paul; Hatabu, Hiroto; Jänne, Pasi A; Hodi, F Stephen; Awad, Mark M

    2016-04-01

    The recent approval of two PD-1 inhibitors for the treatment of non-small cell lung cancer (NSCLC) has rapidly led to the widespread use of these agents in oncology practices. Pneumonitis has been recognized as a potentially life-threatening adverse event among NSCLC patients treated with PD-1 inhibitors; however, the detailed clinical and radiographic manifestations of this entity remain to be described. We report on two cases of anti-PD-1 pneumonitis in advanced NSCLC patients treated with nivolumab after its FDA approval. Both patients presented with ground-glass and reticular opacities and consolidations in a peripheral distribution on CT, demonstrating a radiographic pattern of cryptogenic organizing pneumonia. Consolidations were extensive and rapidly developed within 8 weeks of therapy in both cases. Both patients were treated with corticosteroids with subsequent improvement of respiratory symptoms and radiographic findings. One patient experienced recurrent pneumonitis after completing corticosteroid taper, or a "pneumonitis flare," in the absence of nivolumab retreatment, with subsequent improvement upon corticosteroid readministration. With the increasing use of immune checkpoint inhibitors in a growing number of tumor types, awareness of the radiographic and clinical manifestations of PD-1 inhibitor-related pneumonitis will be critical for the prompt diagnosis and management of this potentially serious adverse event.Cancer Immunol Res; 4(4); 289-93. ©2016 AACR. PMID:26865455

  19. Epigenetic Regulation of Glucose Transporters in Non-Small Cell Lung Cancer

    International Nuclear Information System (INIS)

    Due to their inherently hypoxic environment, cancer cells often resort to glycolysis, or the anaerobic breakdown of glucose to form ATP to provide for their energy needs, known as the Warburg effect. At the same time, overexpression of the insulin receptor in non-small cell lung cancer (NSCLC) is associated with an increased risk of metastasis and decreased survival. The uptake of glucose into cells is carried out via glucose transporters or GLUTs. Of these, GLUT-4 is essential for insulin-stimulated glucose uptake. Following treatment with the epigenetic targeting agents histone deacetylase inhibitors (HDACi), GLUT-3 and GLUT-4 expression were found to be induced in NSCLC cell lines, with minimal responses in transformed normal human bronchial epithelial cells (HBECs). Similar results for GLUT-4 were observed in cells derived from liver, muscle, kidney and pre-adipocytes. Bioinformatic analysis of the promoter for GLUT-4 indicates that it may also be regulated by several chromatin binding factors or complexes including CTCF, SP1 and SMYD3. Chromatin immunoprecipitation studies demonstrate that the promoter for GLUT-4 is dynamically remodeled in response to HDACi. Overall, these results may have value within the clinical setting as (a) it may be possible to use this to enhance fluorodeoxyglucose (18F) positron emission tomography (FDG-PET) imaging sensitivity; (b) it may be possible to target NSCLC through the use of HDACi and insulin mediated uptake of the metabolic targeting drugs such as 2-deoxyglucose (2-DG); or (c) enhance or sensitize NSCLC to chemotherapy

  20. Molecularly targeted approaches herald a new era of non-small-cell lung cancer treatment

    International Nuclear Information System (INIS)

    The discovery of activating mutations in the epidermal growth-factor receptor (EGFR) gene in 2004 opened a new era of personalized treatment for non-small-cell lung cancer (NSCLC). EGFR mutations are associated with a high sensitivity to EGFR tyrosine kinase inhibitors, such as gefitinib and erlotinib. Treatment with these agents in EGFR-mutant NSCLC patients results in dramatically high response rates and prolonged progression-free survival compared with conventional standard chemotherapy. Subsequently, echinoderm microtubule-associated protein-like 4 (EML4)–anaplastic lymphoma kinase (ALK), a novel driver oncogene, has been found in 2007. Crizotinib, the first clinically available ALK tyrosine kinase inhibitor, appeared more effective compared with standard chemotherapy in NSCLC patients harboring EML4-ALK. The identification of EGFR mutations and ALK rearrangement in NSCLC has further accelerated the shift to personalized treatment based on the appropriate patient selection according to detailed molecular genetic characterization. This review summarizes these genetic biomarker-based approaches to NSCLC, which allow the instigation of individualized therapy to provide the desired clinical outcome

  1. Polymeric Nanoparticles Containing Taxanes Enhance Chemoradiotherapeutic Efficacy in Non-small Cell Lung Cancer

    International Nuclear Information System (INIS)

    Purpose: To reduce the side effects and improve the efficacy of chemoradiation therapy, taxanes were incorporated into polymeric nanoparticles (PNP), and their synergic effect on radiation therapy in non-small cell lung cancer was evaluated. Methods and Materials: The properties of PNP-taxanes were characterized by transmission electron microscopy and dynamic light scattering. The chemoradiotherapeutic efficacy of PNP-taxanes was determined by clonogenic assay, cellular morphology, and flow cytometry in A549 cells. In mice bearing A549-derived tumors, the tumor growth delay was examined after the treatment of PNP-taxanes and/or ionizing radiation (IR). Results: The PNP-taxanes were found to be approximately 45 nm in average diameter and to have high solubility in water. They showed the properties of active internalization into cells and preserved the anticancer effect of free taxanes. The survival fraction of A549 cells by clonogenic assay was significantly reduced in the group receiving combined treatment of PNP-taxanes and IR. In addition, in vivo radiotherapeutic efficacy was markedly enhanced by the intravenous injection of PNP-taxanes into the xenograft mice. Conclusions: We have demonstrated the feasibility of PNP-taxanes to enhance the efficacy of chemoradiation therapy. These results suggest PNP-taxanes can hold an invaluable and promising position in treating human cancers as a novel and effective chemoradiation therapy agent.

  2. Selenium-containing thioredoxin reductase inhibitor ethaselen sensitizes non-small cell lung cancer to radiotherapy.

    Science.gov (United States)

    Wang, Lei; Fu, Jia-Ning; Wang, Jing-Yu; Jin, Cun-Jing; Ren, Xiao-Yuan; Tan, Qiang; Li, Jing; Yin, Han-Wei; Xiong, Kun; Wang, Tian-Yu; Liu, Xin-Min; Zeng, Hui-Hui

    2011-09-01

    It has been proposed that thioredoxin reductase (TR) is a mediator that allows non-small cell lung cancer (NSCLC) to develop resistance to irradiation; however, little is known regarding the detailed mechanisms of action. Thus, ethaselen {1, 2-[bis (1,2-benzisoselenazolone-3 (2H)-ketone)] ethane, BBSKE}, a novel organoselenium TR inhibitor, is currently being investigated in a phase I clinical trial in China. However, its radiosensitizing effect remains unexplored. In this study, we found that the activity of TR increased dramatically in both A549 and H1299 cells after radiation, and moreover, could be inhibited by pretreatment with BBSKE (5 μmol/l). As a TR inhibitor, BBSKE enhanced the efficacy of radiation therapy both in vivo and in vitro without observable toxicity. BBSKE was found to suppress irradiation-induced NF-κB activation dramatically when using A549 cells stably transfected with NF-κB luciferase reporter. These results show the critical role of TR in the radioresistance of NSCLC and suggest that BBSKE is a potentially promising agent for the treatment of patients with NSCLC clinically. PMID:21562407

  3. Detection of lymphangiogenesis in non-small cell lung cancer and its prognostic value

    Directory of Open Access Journals (Sweden)

    Liao Rong-xia

    2009-02-01

    Full Text Available Abstract Background Our aim was to detect lymphatic endothelial marker podoplanin, lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1 and vascular endothelial growth factor receptor-3 (VEGFR-3 and study the prognostic relevance of lymphangiogenesis in non-small cell lung cancer (NSCLC. Materials 82 paraffin-embedded tissues and 40 fresh frozen tissues from patients with NSCLC were studied. Tumor samples were immunostained for the lymphatic endothelial markers. Lymphangiogenesis was assessed by immunohistochemical double stains for Podoplanin and Ki-67. The prognostic relevance of lymphangiogenesis-related clinicopathological parameters in NSCLC was evaluated. Results We found that the number of podoplanin positive vessels was correlated positively with the number of LYVE-1 positive vessels. Most of VEGFR-3 positive, few of LYVE-1 positive and none of podoplanin positive vessels were blood vessels. Peritumoral lymphatic vessel density (ptLVD, pathologic stage, lymph node status, lymphatic vessel invasion (LVI, vascular endothelial growth factor-C (VEGF-C expression and Ki-67 index of the endothelium cells of the micro lymphatic vessels (Ki67% were associated significantly with a higher risk of tumor progress. ptLVD, pathologic stage, lymph-node metastasis and Ki67% were independent prognostic parameters for overall survival. Conclusion Podoplanin positive ptLVD might play important roles in the lymphangiogenesis and progression of NSCLC. Patients with high podoplanin+ ptLVD have a poor prognosis.

  4. Impact of tumor local factors on radiotherapy in non-small cell lung cancer

    International Nuclear Information System (INIS)

    Objective: To evaluate the impact of tumor local factors on radiotherapy in non-small cell lung cancer (NSCLC). Methods: From Jan. 2000 to Jun. 2002, 75 stage I- IIIb NSCLC patients who received definitive radiotherapy were analyzed retrospectively. Thirty-nine patients treated by conventional radiotherapy and 36 by three dimensional radiotherapy with 60-70 Gy/30-35F/6-7w. The tumor diameter and volume were measured on CT scans. The impact of related prognostic factors on survival was evaluated by univariate and multivariate analysis. The treatment outcome was analyzed by prognostic index model. Results: The complete response (CR) was 33.3%(25/75), partial response was 52.0%(39/75) and median survival time was 13.8 months. The 1.02, 1.52 year survival rates were 54.7% and 27.5%, respectively. Smaller tumor diameter and volume, earlier T stage, shorter overall treatment time and milder acute radiation pneumonitis were favorable factors for survival when analyzed by univariate and multivariate. Prognostic index was higher sensitivity for predicting treatment outcome. Conclusions: Tumor diameter, tumor volume, T stage, overall treatment time, milder acute radiation-induced pneumonitis are likely to be independent prognostic factors. Prognostic index model may well raise the predictive value of multivariate analysis for NSCLC treated by radiotherapy. (authors)

  5. Treatment approaches for EGFR-inhibitor-resistant patients with non-small-cell lung cancer.

    Science.gov (United States)

    Tan, Chee-Seng; Gilligan, David; Pacey, Simon

    2015-09-01

    Discovery of activating mutations in EGFR and their use as predictive biomarkers to tailor patient therapy with EGFR tyrosine kinase inhibitors (TKIs) has revolutionised treatment of patients with advanced EGFR-mutant non-small-cell lung cancer (NSCLC). At present, first-line treatment with EGFR TKIs (gefitinib, erlotinib, and afatinib) has been approved for patients harbouring exon 19 deletions or exon 21 (Leu858Arg) substitution EGFR mutations. These agents improve response rates, time to progression, and overall survival. Unfortunately, patients develop resistance, limiting patient benefit and posing a challenge to oncologists. Optimum treatment after progression is not clearly defined. A more detailed understanding of the biology of EGFR-mutant NSCLC and the mechanisms of resistance to targeted therapy mean that an era of treatment approaches based on rationally developed drugs or therapeutic strategies has begun. Combination approaches-eg, dual EGFR blockade-to overcome resistance have been trialled and seem to be promising but are potentially limited by toxicity. Third-generation EGFR-mutant-selective TKIs, such as AZD9291 or rociletininb, which target Thr790Met-mutant tumours, the most common mechanism of EGFR TKI resistance, have entered clinical trials, and exciting, albeit preliminary, efficacy data have been reported. In this Review, we summarise the scientific literature and evidence on therapy options after EGFR TKI treatment for patients with NSCLC, aiming to provide a guide to oncologists, and consider how to maximise therapeutic advances in outcomes in this rapidly advancing area. PMID:26370354

  6. AZD9291 in EGFR-mutant advanced non-small-cell lung cancer patients.

    Science.gov (United States)

    Remon, Jordi; Planchard, David

    2015-11-01

    Non-small-cell lung cancer (NSCLC) patients whose tumors have an EGFR-activating mutation develop acquired resistance after a median of 9-11 months from the beginning of treatment with erlotinib, gefitinib and afatinib. T790M mutation is the cause of this resistance in approximately 60% of cases. AZD9291 is an oral, irreversible, mutant-selective EGF receptor (EGFR) tyrosine kinase inhibitor (TKI) developed to have potency against EGFR mutations, including T790M mutation, while sparing wild-type EGFR. A Phase I trial of AZD9291 in EGFR-mutant NSCLC patients, demonstrated high activity, essentially among T790M-mutant tumors, with a manageable tolerability profile. Ongoing Phase III trials are evaluating AZD9291 in EGFR-mutant patients as first-line treatment compared with erlotinib and gefitinib; and as second-line treatment compared with chemotherapy after progression on EGFR TKI in T790M-mutant tumors. Better identification of T790M-mutant tumors post EGFR TKI relapse and mechanisms of resistance to AZD9291 are the future challenges. This article reviews the emerging data regarding AZD9291 in the treatment of patients with advanced NSCLC. PMID:26450446

  7. CT findings in non-small-cell lung cancer patients treated with gefitinib or erlotinib

    Directory of Open Access Journals (Sweden)

    Im Il Na

    2012-01-01

    Full Text Available Purpose: We performed this study to explore the association of computed tomography (CT findings with outcomes of patients with non-small-cell lung cancer (NSCLC treated with tyrosin kinase inhibitor (TKI such as gefitinib or erlotinib. Materials and Methods: We analyzed outcomes for 240 patients according to primary tumor (T, regional nodal (N staging and diffuse small pulmonary metastases (DSPM at the initial presentation. Tests for epidermal growth factor receptor (EGFR mutation were performed in 92 patients. Results: On multivariate analysis for tumor response, the N3 stage was predictive of a poor response (P < 0.001, whereas DSPM was a favorable factor (P = 0.007. Multivariate analysis for progression-free survival showed that the T3-4 stage (hazard ratio [HR]: 2.5, P < 0.001, in addition to the N3 stage (HR: 2.1, P < 0.001, was predictive of a poor outcome, whereas DSPM (HR: 0.6, P = 0.006 was a favorable factor. Notably, the multivariate model that included the EGFR mutational status revealed that the T3-4 stage predicted poor progression-free survival (HR: 2.2, P = 0.017 and poor overall survival (HR: 4.1, P < 0.001. Conclusion: Our data suggest that, in addition to EGFR mutational status, T-stage based on CT is predictive of outcomes of TKI-treated NSCLC patients.

  8. Cetuximab Combination with Chemotherapy in Advanced Non-Small Cell Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    Jian-chun Duan; Lu Yang; Jie Wang; Jun Zhao; Mei-na Wu; Tong-tong An

    2009-01-01

    Objective: To observe the efficacy and safety of cetuximab combined with chemotherapy in advanced non-small-cell lung cancer (NSCLC), and to investigate the association of status of K-RAS gene mutation and epidermal growth factor receptor (EGFR) genotype with clinical outcome.Methods: Between Jan. 2006 and Sep. 2009, nineteen patients with advanced NSCLC received cetuximab (≥4 weeks) combined with chemotherapy in Department of Thoracic Oncology at Beijing Cancer Hospital. Response, survival and toxicity were retrospectively assessed, epidermal growth factor receptor (EGFR) protein expression was evaluated by ELISA Kit. The status of K-RAS gene mutation was tested by PCR-RFLP and EGFR gene amplification was measured by EGFR fluorescence in situ hybridization (FISH).Results: Partial response(PR) was observed in 26.3%(5/19) of the patients and stable disease(SD) in 52.6%(10/19). Median progression free survival(PFS) was 6 months (95% CI: 3.6-8.4). Median overall survival (MST) and 1-year survival rate(SR) were 10.6 months (95% CI: 6.6-14.6) and 47.6%, respectively. Mild or moderate skin rash was the most common toxicity related with cetuximab. K-RAS gene mutation, EGFR protein level and amplification have little correlation with prognosis.Conclusion: Cetuximab combined with chemotherapy was tolerable and the skin rash related with cetuximab was mild to moderate. Cetuximab may prolong survival of the patients who failed to previous chemotherapy.

  9. The estimation of chemotherapeutic pathomorphosis of non-small cell lung cancer.

    Directory of Open Access Journals (Sweden)

    Sukhoversha O.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 device the method of its estimation. 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. After ICT in NSCLC noticed the effective ThP (2-3 st. in 48% with better response rate in low-differentiation tumor. Being influenced by ICT, the part of viable tumors’ parenchyma and its proliferating activity has significantly decreased. According to our results the ICT is an effective method of multimodality treatment of NSCLC. To achieve more objective estimation of therapeutic pathomorphosis and more prognostic value, it is recommended to imply our method (№u2006 13104, which includes the definition the secondary tumor changes, its proliferation activity, apoptisis, inflammation reaction.

  10. Drug Repositioning Discovery for Early- and Late-Stage Non-Small-Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Chien-Hung Huang

    2014-01-01

    Full Text Available Drug repositioning is a popular approach in the pharmaceutical industry for identifying potential new uses for existing drugs and accelerating the development time. Non-small-cell lung cancer (NSCLC is one of the leading causes of death worldwide. To reduce the biological heterogeneity effects among different individuals, both normal and cancer tissues were taken from the same patient, hence allowing pairwise testing. By comparing early- and late-stage cancer patients, we can identify stage-specific NSCLC genes. Differentially expressed genes are clustered separately to form up- and downregulated communities that are used as queries to perform enrichment analysis. The results suggest that pathways for early- and late-stage cancers are different. Sets of up- and downregulated genes were submitted to the cMap web resource to identify potential drugs. To achieve high confidence drug prediction, multiple microarray experimental results were merged by performing meta-analysis. The results of a few drug findings are supported by MTT assay or clonogenic assay data. In conclusion, we have been able to assess the potential existing drugs to identify novel anticancer drugs, which may be helpful in drug repositioning discovery for NSCLC.

  11. Targeted therapy using novel agents in the treatment of non-small-cell lung cancer.

    Science.gov (United States)

    Herbst, Roy S

    2002-03-01

    Patients with advanced non-small-cell lung cancer (NSCLC) have a poor prognosis and high mortality. The therapeutic improvement caused by the new generation of cytotoxic agents seems to have reached a plateau. The main categories of targeted therapeutics applicable for NSCLC include receptor-targeted therapy, signal transduction or cell-cycle inhibition, angiogenesis inhibitors, gene therapy, and vaccines. Several major classes of agents directed at specific cellular mechanisms exist for the treatment of NSCLC. The anti-epidermal growth factor receptor (EGFR) group contains trastuzumab and IMC-C225, monoclonal antibodies against EGFRs that are overexpressed in many cancers. OSI-774 and ZD1839 are inhibitors of EGFR tyrosine kinase, a key enzyme of the signaling pathway. Farnesyl transferase inhibitors, such as SCH66336, and protein kinase C inhibitors, such as ISIS 3521, have also shown antitumor activity. Antiangiogenesis agents that have shown promise include TNP-470, recombinant endostatin, and angiostatin. Antibodies to vascular endothelial growth factor (VEGF) also seem to control tumor progression and may prolong survival. LY317615, an inhibitor of protein kinase Cb, augmented the tumor growth delay produced by cytotoxic drugs. All of these agents are in different phases of clinical testing and have shown encouraging activity as single agents or in combination with chemotherapy drugs. These new agents are more target specific, less toxic, easier to administer, and may lead to enhanced safety and survival for patients with advanced NSCLC. PMID:14720353

  12. Regression of brain metastases of non-small cell lung cancer after radiotherapy

    International Nuclear Information System (INIS)

    Regression of metastatic brain tumors after irradiation was studied. Twenty-three patients with 80 metastatic tumors were irradiated by conventional fractionation (8-9 Gy/5 Fx/week, 17 patients with 54 tumors) or a hypofractionation (10 Gy/1 Fx/week, 6 patients with 26 tumors). TDF (Time Dose Fractionation Factor) calculated from radiation doses was between 60 and 106 in the former fractionation, and 80 and 89 in the latter. The tumor regression curves were obtained from the volume of each tumor measured on contrast enhanced CT. The tumor regression correlated well with the initial tumor volume. Smaller volume tumors showed greater regression. This trend was more remarkable in patients treated by hypofractionation than in those by conventional fractionation 4 and 6 weeks after starting the radiotherapy. Response rates (PR+CR) after 4, 6, 12 and 26 weeks were 56% (45/80), 83% (40/48), 89% (24/27) and 90% (17/19). Complete response was observed in 6%, 15%, 59% and 74%, respectively. Eighty seven percent (14/16) of the tumors smaller than 103 mm3 showed CR after 12 weeks. All the 14 CR tumors had been treated by the conventional fractionation. Based on our results the brain metastases of non-small cell lung cancer were controled well by radiotherapy with doses below the brain tolerance dose level, especially in tumors smaller than 103 mm3. (author)

  13. FDG uptake as a factor for recurrence of non-small cell lung cancer

    International Nuclear Information System (INIS)

    The purpose of this study is to examine the prognostic significance for recurrence of FDG uptake in comparison with different biomarkers (DNA ploidy pattern, Proliferating cell nuclear antigen labeling index (PCNA-LI), pathologic differentiation and histologic type) in patients with non-small cell lung cancer (NSCLC). We analyzed the follow-up findings of 57 surgically resected NSCLC patients. Before surgery, FDG PET was performed 40 min after injection. Tumor FDG uptake was quantitated with the standardized uptake value (SUV). Tumor FDG uptake (SUV), ploidy estimated by DNA flow cytometry, PCNA-LI determined by immunohistochemistry, pathologic stage, pathologic differentiation and historogic type were analyzed for any possible association with disease-free survival. Treatment was complete resection in all 57 cases. In a univariate analysis SUV greater than 5 (p<0.0001), pathologic stage (p<0.0001) and pathologic differentiation were correlated with disease-free survival, whereas ploidy and PCNA-LI were not correlated. A multivariate Cox analysis identified SUV as most important for the disease-free survival (0.042). Patients with pathologic stage I had an expected 5-year disease-free survival of 88%, if the SUV was below 5, and 17%, if above 5. We conclude that the FDG uptake in primary NSCLC PET is of important post-operative prognostic value for recurrence, especially in patients with pathologic stage I NSCLC. FDG uptake could supplant other well-known biomarkers in determining individual patients' treatments. (author)

  14. [Advance of second-line chemotherapy in advanced non-small cell lung cancer.].

    Science.gov (United States)

    Zhang, Li

    2008-02-20

    There is a temporal disease-free period after 1st line chemotherapy in advanced non-small cell lung cancer (NSCLC), most of patients need 2nd line chemotherapy. The recommended drugs in the 2nd line were docetaxel, pemetrexed and epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Single docetaxel is the established therapy for second-line treatment of NSCLC.Pemetexem was validated its indication in the 2nd line in advanced NSCLC through a phase III randomised clinical trial which was compared with docetaxel. Although there were little toxicity, the further research can't find the survival benefit in high dose pemetrexed. EGFR-TKIs target therapy is a hot spot now. Gefitinib and erlotinib monotherapy have a good efficacy in the 2nd line. The research of gefitinib versus traditional chemotherapy manifested that its efficacy was no less than docetaxel, and was less toxicitity . The comparison of erlotinib with chemotherapy is going on. There are more and more other drugs proved their effect in the 2nd line, such as the efficacy of oral toptecan and vinflunine were similar to docetaxel. PMID:20727256

  15. Advance of second-line chemotherapy in advanced non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Li ZHANG

    2008-02-01

    Full Text Available There is a temporal disease-free period after 1st line chemotherapy in advanced non-small cell lung cancer (NSCLC, most of patients need 2nd line chemotherapy. The recommended drugs in the 2nd line were docetaxel, pemetrexed and epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs. Single docetaxel is the established therapy for second-line treatment of NSCLC.Pemetexem was validated its indication in the 2nd line in advanced NSCLC through a phase III randomised clinical trial which was compared with docetaxel. Althoughthere were little toxicity, the further research can't find the survival benefit in high dose pemetrexed. EGFR-TKIs target therapy is a hot spot now. Gefitinib and erlotinib monotherapy have a good efficacy in the 2nd line. The research of gefitinib versus traditional chemotherapy manifested that its efficacy was no less than docetaxel, and was less toxicitity . The comparison of erlotinib with chemotherapy is going on. There are more and more other drugs proved their effect in the 2nd line, such as the efficacy of oral toptecan and vinflunine were similar to docetaxel.

  16. Perspectives in Surgery of Oligometastatic Non-Small-Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Fabio Villa

    2015-03-01

    Full Text Available 20-50% of patients with newly diagnosed non-small-cell lung cancer (NSCLC have synchronous metastases. This dramatically affects survival and traditionally excludes patients from the spectrum of curative therapies. Nonetheless, studies have been performed to assess the role of surgery in Stage 4 NSCLC with metastases circumscribed to a single or limited number of organs, proposing the definition of oligometastatic NSCLC to enlarge the possibility of curative resection. Aggressive treatments have shown promising results; however, the great heterogeneity of survival outcomes implies the bias of selection of patients who can benefit from surgery. The new molecular-targeted systemic therapies, cytotoxic regimens, and radiant treatments can complement surgery in metastatic NSCLC, leading to optimal control of the disease. Retrospective series can help us to design prospective trials, selecting patients with positive prognostic determinants to undergo intensive resective and pharmacologic treatments. Molecular and gene profiling will probably be the most accurate method to elect candidates to sanative therapy in Stage 4 NSCLC.

  17. The value of positron emission tomography in patients with non-small cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kee, Frank [Centre for Public Health, Queen' s University Belfast, Mulhouse Building, Royal Victoria Hospital Site, Grosvenor Road, Belfast BT12 6BJ, Northern Ireland (United Kingdom)], E-mail: f.kee@qub.ac.uk; Erridge, Sara [Edinburgh Cancer Centre, University of Edinburgh, Crewe Road South, Edinburgh EH4 2XU, Scotland (United Kingdom); Bradbury, Ian [Frontier Science (Scotland) Ltd., Grampian View, Kincraig, Inverness-shire PH21 1NA, Scotland (United Kingdom); Cairns, Karen [School of Maths and Physics, Queen' s University Belfast, David Bates Building, University Road, Belfast BT7 1NN, Northern Ireland (United Kingdom)

    2010-01-15

    Background: Pre-operative assessment of non-small cell lung cancer (NSCLC) is a major application of positron emission tomography (FDG-PET). Despite substantial evidence of diagnostic accuracy, relatively little attention has been paid to its effects on patient outcomes. This paper addresses this by extending an existing decision model to include patient-elicited utilities. Patients and methods: A decision-tree model of the effect of FDG-PET on pre-operative staging was converted to a Markov model. Utilities for futile and appropriate thoracotomy were elicited from 75 patients undergoing staging investigation for NSCLC. The decision model was then used to estimate the expected value of perfect information (EVPI) associated with three sources of uncertainty-the accuracy of PET, the accuracy of CT and the patient related utility of a futile thoracotomy. Results: The model confirmed the apparent cost-effectiveness of FDG-PET and indicated that the EVPI associated with the utility of futile thoracotomy considerably exceeds that associated with measures of accuracy. Conclusion: The study highlights the importance of patient related utilities in assessing the cost-effectiveness of diagnostic technologies. In the specific case of PET for pre-operative staging of NSCLC, future research effort should focus on such elicitation, rather than further refinement of accuracy estimates.

  18. Induction chemoradiotherapy followed by surgery for stage III non-small cell lung cancer

    International Nuclear Information System (INIS)

    Twenty-five patients with stage III, non-small cell lung cancer were treated with cisplatin-based chemotherapy and thoracic radiation therapy followed by surgery. Thirteen patients had stage IIIA disease and 12, stage IIIB disease. The chemotherapy and radiotherapy were intensively combined with only a few days' interval between them. Radiation therapy delivering a total dose of 50-70 Gy was started 10 days after the beginning of chemotherapy. A few additional courses of chemotherapy were repeated until a thoracotomy was performed. All but two surgically-treated patients underwent tumor resection, with 19 lobectomies and four pneumonectomies. Eighteen patients underwent curative and five, non-curative resections. Pathological examination of the resected specimen provided accurate intrathoracic information. Six patients (24%) showed a pathologically complete response, with no cancer cells detected in the resected specimens. Severe postoperative complications occurred in five patients (20%), with one death. The disease recurred in five of the 18 patients who underwent a curative resection. A second primary tumor developed in two other patients. Seventeen patients (68%) are alive, with a median follow-up of 37 months after thoracotomy. The estimated three-year survival was 67% for all patients. (author)

  19. Radiation therapy after non-curative resection or exploration in non-small cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Saito, Yoshihiro; Hayakawa, Kazushige; Mitomo, Osamu; Nakayama, Yuko; Katano, Susumu; Furuta, Masaya; Mitsuhashi, Norio; Niibe, Hideo (Gunma Univ., Maebashi (Japan). School of Medicine)

    1994-08-01

    Thirty eight patients with non-small cell lung cancer have been treated with radiation therapy after non-curative resection or exploratory thoracotomy during the past 20 years. Tumors were surgically staged; Three patients were Stage I, 6 Stage II, and 29 Stage III. Twenty four patients had epidermoid carcinoma, 11 adenocarcinoma and 3 large cell carcinoma. Fifteen patients underwent incomplete mediastinal lymph node resections, 19 had macroscopic or microscopic residual tumors and 4 underwent only biopsies. The dose of radiation to microscopic or macroscopic residual tumors was more than 60 Gy. Chemotherapy was not used as part of the initial therapy in any patient. The overall 5-year survival rate was 44%. The actuarial 5-year survivals for the patients with Stage II and those with Stage III were 44% and 39% respectively. 5-year survivals for those with a relatively non-curative resection and those with an absolutely non-curative resection were 48% and 43% respectively. Of the 8 patients who are alive more than 5 years, 4 had epidermoid carcinoma and 4 had adenocarcinoma. Two patients had recurrences within the irradiated area. No radiation injuries were observed. Radiation therapy after non-curative resection appears to be effective for local control and survival. (author).

  20. The value of positron emission tomography in patients with non-small cell lung cancer

    International Nuclear Information System (INIS)

    Background: Pre-operative assessment of non-small cell lung cancer (NSCLC) is a major application of positron emission tomography (FDG-PET). Despite substantial evidence of diagnostic accuracy, relatively little attention has been paid to its effects on patient outcomes. This paper addresses this by extending an existing decision model to include patient-elicited utilities. Patients and methods: A decision-tree model of the effect of FDG-PET on pre-operative staging was converted to a Markov model. Utilities for futile and appropriate thoracotomy were elicited from 75 patients undergoing staging investigation for NSCLC. The decision model was then used to estimate the expected value of perfect information (EVPI) associated with three sources of uncertainty-the accuracy of PET, the accuracy of CT and the patient related utility of a futile thoracotomy. Results: The model confirmed the apparent cost-effectiveness of FDG-PET and indicated that the EVPI associated with the utility of futile thoracotomy considerably exceeds that associated with measures of accuracy. Conclusion: The study highlights the importance of patient related utilities in assessing the cost-effectiveness of diagnostic technologies. In the specific case of PET for pre-operative staging of NSCLC, future research effort should focus on such elicitation, rather than further refinement of accuracy estimates.

  1. 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.

  2. 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.

  3. 125I brachytherapy combined with chemotherapy of advanced non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    林元强; 孙昱; 王任婕; 高识; 陈滨; 孙步彤; 马庆杰; 纪铁凤; 张海山

    2015-01-01

    This study was to evaluate effect of 125I brachytherapy combined with chemotherapy on advanced non-small cell lung cancer (NSCLC). Patients with NSCLC in stages III to IV were divided into two groups: Group A (n = 27) received 125I brachytherapy combined with gemcitabine and cisplatin (GP) chemotherapy, and Group B (n = 27) received GP chemotherapy only. The results showed that the overall response rate and median progression-free survival time were 78%and 11.5 months in Group A, 41%and 8 months in Group B, respectively (P 0.05). The interventional complications in Group A included 5 patients with postoperative pneumothorax and 4 patients with hemoptysis. No patients had radiation pneumonia, radiation esophagitis or esophagotracheal fistula. Chemotherapy treatment-related toxicities were not significantly different between the two groups. The relief of tumor-associated symptoms including cough, hemoptysis, chest pain, and short breath was found in both groups, without statistical difference in remission rates between Groups A and B (P >0.05). In conclusion, 125I brachytherapy combined with chemotherapy proved to be safe and effective for treating advanced NSCLC with few complications. It improves local control rate and prolongs the progression-free survival time.

  4. Intraoperative radioisotope sentinel lymph node mapping in non-small cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Sugi, Kazuro; Sudou, Manabu [National Sanyo Hospital, Ube, Yamaguchi (Japan); Kaneda, Yoshikazu; Hamano, Kimikazu [Yamaguchi Univ., Ube (Japan). School of Medicine

    2003-05-01

    We performed intraoperative Technetium (Tc) 99m sentinel lymph node (SN) mapping in patients with clinical T1N0M0 non-small cell lung cancer (NSCLC). Twenty patients with clinical T1N0M0 NSCLC were enrolled. Before thoracotomy, the primary tumor was injected with 2 mCi Tc-99m. After dissection, scintigraphic readings of lymph nodes were obtained ex vivo with a handheld gamma counter. The migration of the Tc solution was considered successful if any node registered five times or more count comared with background values. If lymph nodes were found to have the highest or more than 50% of the highest counts and measurements were greater than five times the intrathoracic background, those nodes were classified as sentinel nodes. Four of the 20 patients did not have NSCLC and were excluded. Eleven patients (68.8%) had SNs identified. No inaccurately identified SNs were encountered. Intraoperative SN mapping with Tc-99m is an accurate way to identify the first site of potential nodal metastases of NSCLC. Several technical problems still remain unresolved in this method, however. (author)

  5. Prophylactic cranial irradiation for non-small cell lung cancer: a systematic review

    International Nuclear Information System (INIS)

    Objective: To determine whether prophylactic cranial irradiation (PCI) has a role in the management of patients with non-small cell lung carcinoma (NSCLC) treated with radical intent. Methods: We searched the Cochrane Library, MEDLINE, EMbase, CBM, CNKI and VIP. The quality of the included studies was critically evaluated. Data analyses were performed using the Cochrane Collaboration's RevMan 5.1 software. Results: Four randomized controlled trials involving 905 patients met the inclusion criteria. The results meta-analyses showed the incidence of brain metastases was lower in PCI group compared with the observation group (χ2=1.98, P=0.000); but there is no evidence of 1-year overall survival (OS) benefit (χ2=1.12, P=0.880). Only RTOG 2009 provides prospective data: There were no significant differences in global cognitive function (P=0.600) or ADL (P=0.880) after PCI, but there was a significant decline in immediate recall (P=0.030) and delayed recall (P=0.008) at 1 year. At 1 year, there was no significant differences in QOL after PCI (P=0.050). Conclusions: This systematic review show significantly decreases the risk of BM without improving 1-year OS in NSCLC patient receiving prophylactic cranial irradiation. There is insufficient evidence to support the use of PCI in clinical practice. Where possible, patients should be offered entry into a clinical trial. (authors)

  6. Palliative radiotherapy in asymptomatic patients with locally advanced, unresectable, non-small cell lung cancer

    International Nuclear Information System (INIS)

    Between 1983 and 1990, 332 patients with non-small cell lung cancer (NSCLC) were referred to short-time, split-course palliative thoracic radiotherapy. The group consisted of patients with locally advanced (IIIo), unresectable cancer, not suitable for curative radiotherapy, asymptomatic or having only minimal symptoms related to intrathoracic tumor. The therapeutic plan involved two series of irradiation. Tumor dose delivered in each series was 20 Gy given in five daily fractions over five treatment days. There were four weeks interval between series. Of 332 patients initially qualified to thoracic radiotherapy only 170 patients received the treatment; the other 162 patients were not irradiated because of treatment refusal or logistic problems concerning therapy. They made the control group of the study, receiving the best possible symptomatic care. Twelve-month survivals in the radiotherapy and control groups were 32.4% and 9.3%, respectively; 24-month survivals 11.2% and 0%, respectively. Improvement of survival after palliative thoracic radiotherapy was observed only in patients with clinical stage IIIA and Karnofsky's performance status (KPS) ≥ 70. (orig.)

  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. Profile of ramucirumab in the treatment of metastatic non-small-cell lung cancer

    Directory of Open Access Journals (Sweden)

    Cooper MR

    2016-04-01

    Full Text Available Maryann R Cooper,1 Chelsea Binkowski,2,3 Jessica Hartung,2,4 Jennifer Towle1 1Department of Pharmacy Practice, School of Pharmacy – Worcester/Manchester, MCPHS University, Manchester, NH, 2School of Pharmacy – Boston, MCPHS University, Boston, MA, 3North America Medical Affairs, 4Global Medical Affairs, Sanofi Oncology, Cambridge, MA, USA Abstract: The interaction between vascular endothelial growth factor and its receptor is an important therapeutic target due to the importance of this pathway in carcinogenesis. In particular, this pathway promotes and regulates angiogenesis as well as increases endothelial cell proliferation, permeability, and survival. Ramucirumab is a fully human monoclonal antibody that specifically targets the vascular endothelial growth factor receptor-2, the key receptor implicated in angiogenesis. Currently, ramucirumab is approved for the second-line treatment of metastatic non-small-cell lung cancer (NSCLC in combination with docetaxel. In a Phase III clinical trial, ramucirumab was shown to improve the overall survival in patients with disease progression, despite platinum-based chemotherapy for advanced NSCLC. This review describes the pharmacology, pharmacokinetics and dynamics, adverse event profile, and the clinical activity of ramucirumab observed in Phase II and III trials in NSCLC. Keywords: NSCLC, antiangiogenesis, VEGF-targeted therapy

  9. Concurrent versus Sequential Chemoradiotherapy with Cisplatin and Vinorelbine in Locally Advanced Non-Small Cell Lung Cancer: A Randomized Study

    Czech Academy of Sciences Publication Activity Database

    Zatloukal, P.; Petruželka, L.; Zemanová, M.; Havel, L.; Janků, F.; Judas, L.; Kubík, A.; Křepela, E.; Fiala, P.; Pecen, Ladislav

    2004-01-01

    Roč. 46, - (2004), s. 87-98. ISSN 0169-5002 Institutional research plan: CEZ:AV0Z1030915 Keywords : concurrent chemoradiotherapy * sequential chemoradiotherapy * locally advanced non-small cell lung cancer * cisplatin * vinorelbine Subject RIV: BB - Applied Statistics, Operational Research Impact factor: 2.914, year: 2004

  10. 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

  11. Approval Summary: Pemetrexed Maintenance Therapy of Advanced/Metastatic Nonsquamous, Non-Small Cell Lung Cancer (NSCLC)

    OpenAIRE

    Cohen, Martin H.; Cortazar, Patricia; Justice, Robert; Pazdur, Richard

    2010-01-01

    The study that led to U.S. Food and Drug Administration approval of pemetrexed injection for maintenance treatment of patients with locally advanced or metastatic nonsquamous non-small cell lung cancer whose disease has not progressed after four cycles of platinum-based doublet induction chemotherapy is reviewed.

  12. Cediranib Maleate and Whole Brain Radiation Therapy in Patients With Brain Metastases From Non-Small Cell Lung Cancer

    Science.gov (United States)

    2013-03-07

    Male Breast Cancer; Stage IV Breast Cancer; Stage IV Melanoma; Stage IV Non-small Cell Lung Cancer; Stage IV Renal Cell Cancer; Stage IVA Colon Cancer; Stage IVA Rectal Cancer; Stage IVB Colon Cancer; Stage IVB Rectal Cancer; Tumors Metastatic to Brain

  13. SINGLE AGENT DOCETAXEL AS SECOND- LINE CHEMOTHERAPY FOR PRETREATED PATIENTS WITH RECURRENT NON- SMALL CELL LUNG CANCER

    Directory of Open Access Journals (Sweden)

    Deyan N. Davidov

    2013-04-01

    Full Text Available Objective: Single agent Docetaxel is a standard therapy for patients with non- small cell lung cancer after the failure of platinum- containing regimens. The aim of this study was to explore the efficacy and safety of Docetaxel monotherapy as second- line chemotherapy in pretreated patient with inoperable non- small cell lung cancer. Methods: From January 2005 to May 2008 thirty- six consecutive patients with locally advanced or metastatic morphologically proven stage IIIB/ IV non- small cell lung cancer entered the study after failure of previous platinum- based regimens. Treatment schedule consist of Docetaxel 75 mg/m2 administered every three weeks with repetition after 21 days with Dexamethasone premedication. Results: Overall response rate, median time to progression and median survival was 16,6 %, 4,5 months and 5,6 months respectively. The main hematological toxicity was neutropenia. Conclusions: That data suggest that single agent Docetaxel remain reasonable choices for the chemotherapy in pretreated patients with non- small cell lung cancer.

  14. Pemetrexed in maintenance treatment of advanced non-squamous non-small-cell lung cancer

    Directory of Open Access Journals (Sweden)

    Minami S

    2015-01-01

    Full Text Available Seigo Minami,1 Takashi Kijima2 1Department of Respiratory Medicine, Osaka Police Hospital, 2Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Osaka University Graduate School of Medicine, Osaka, Japan Abstract: Pemetrexed, a multitargeting antifolate cytotoxic drug, plays a leading role in front-line chemotherapy for patients with advanced non-squamous non-small-cell lung cancer (NSCLC. Following its approval as second-line monotherapy for locally advanced or metastatic non-squamous NSCLC, pemetrexed has established itself as the first-line regimen in combination with cisplatin, and its powerful antitumor effects and less cumulative toxicities were then taken advantage of in the JMEN and PARAMOUNT trials, respectively, to pioneer a new treatment strategy of switch and continuation maintenance monotherapy. These developments have brought about a marked paradigm shift, and made pemetrexed indispensable in the treatment for non-squamous NSCLC. So far, only three drugs have been approved for maintenance therapy; pemetrexed both by switch and continuation maintenance, erlotinib by switch maintenance, and bevacizumab by continuation maintenance. Compared with observation alone after defined cycles of the first-line chemotherapy, subsequent pemetrexed maintenance therapy has provided significantly longer survival and infrequent severe adverse events. The cost-effectiveness of pemetrexed maintenance therapy is controversial, as well as the other two maintenance drugs, bevacizumab and erlotinib. The latest attractive attention is a combination maintenance therapy. We may have to consider epidermal growth factor receptor (EGFR mutation status for selection of a combination pattern. A combination maintenance therapy of pemetrexed plus bevacizumab is potential for patients with wild-type EGFR status, while a EGFR tyrosine kinase inhibitor-containing combination is promising for patients with active EGFR mutation status. Pemetrexed will be

  15. Galectin-3 and cyclin D1 expression in non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Gołecki Marcin

    2011-10-01

    Full Text Available Abstract Introduction Lung cancer is a major cause of mortality and morbidity worldwide. Galectin-3 is multifunctional protein, which is involved in regulation of cell growth, cell adhesion, cell proliferation, angiogenesis and apoptosis. Cyclin D1 together with other cyclin plays an important role in cell cycle control. Cyclin D1 regulates the G1-to-S phase transition. The aim of this study was the evaluation of correlations between clinicopathological findings and cyclin D1 and galectin-3 expression in non-small cell lung cancer (NSCLC. We wanted also to analyze the prognostic value of cyclin D1 and galectin-3 expression. Moreover we tried to evaluate the correlations between galectin-3 and cyclin D1 expression in tumor tissue. Materials and methods We used the immunochemistry method to investigate the expression of galectin-3 and cyclin D1 in the paraffin-embedded tumor tissue of 47 patients (32 men and 15 women; mean age 59.34 ± 8.90. years. We used monoclonal antibodies to cyclin D1 (NCL-L-cyclin D1-GM clone P2D11F11 NOVO CASTRA and to galectin-3 (mouse monoclonal antibody NCL-GAL3 NOVO CASTRA. Results Galectin-3 expression was positive in 18 cases (38.29% and cyclin D1 in 39 (82.97%. We showed only weak trend, that galectin-3 expression was lower in patients without lymph node involvement (p = 0.07 and cyclin D1 expression was higher in this group (p = 0.080. We didn't reveal differences in cyclin D1 and galectin-3 expression in SCC and adenocarcinoma patients. We didn't demonstrated also differences in galectin-3 and cyclin D1 expression depending on disease stage. Moreover we analyzed the prognostic value of cyclin D1 expression and galectin-3 in all examinated patients and separately in SCC and in adenocarcinoma and in all stages, but we didn't find any statistical differences. We demonstrated that in galectin-3 positive tumors cyclin D1 expression was higher (96.55% vs 61.11%, Chi2 Yatesa 7.53, p = 0.0061 and we revealed negative

  16. Prognostic impact of serum albumin levels on the recurrence of stage I non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Ying Jin

    2013-05-01

    Full Text Available Objective: Patients with stage I non-small cell lung cancer who have undergone complete surgical resection harbor a 30% risk for tumor recurrence. Thus, the identification of factors that are predictive for tumor recurrence is urgently needed. The aim of this study was to test the prognostic value of serum albumin levels on tumor recurrence in patients with stage I non-small cell lung cancer. Methods: Stage I non-small cell lung cancer patients who underwent complete surgical resection of the primary tumor at Zhejiang Hospital were analyzed in this study. Serum albumin levels were measured before surgery and once again after surgery in 101 histologically diagnosed non-small cell lung cancer patients. Correlations between the pre- and post-operative serum albumin levels and various clinical demographics and recurrence-free survival rates were analyzed. Results: Patients with pre-operative hypoalbuminemia (<3.5 g/dl had a significantly worse survival rate than patients with normal pre-operative serum albumin levels (≥3.5 g/dl (p=0.008. Patients with post-operative hypoalbuminemia had a worse survival rate when compared with patients with normal post-operative serum albumin levels (p=0.001. Cox multivariate analysis identified pre-operative hypoalbuminemia, post-operative hypoalbuminemia and tumor size over 3 cm as independent negative prognostic factors for recurrence. Conclusion: Serum albumin levels appear to be a significant independent prognostic factor for tumor recurrence in patients with stage I non-small cell lung cancer who have undergone complete resection. Patient pre-treatment and post-treatment serum albumin levels provide an easy and early means of discrimination between patients with a higher risk for recurrence and patients with a low risk of recurrence.

  17. Afatinib for the treatment of metastatic non-small cell lung cancer

    International Nuclear Information System (INIS)

    Targeting the epidermal growth factor receptor (EGFR) in patients with non-small cell lung cancer (NSCLC) harboring sensitizing mutations in the tyrosine kinase (TKI) domain has led to a significant change in the management of this disease. The classic or sensitizing mutations are G719X mutation in exon 18, in-frame deletions or insertion of exon 19, L858R or L861Q mutation in exon 21. Approximately 90% of these mutations are exon 19 deletion or exon 21 L858R point mutation. Gefitinib and erlotinib are reversible first-generation inhibitors of mutant EGFR, and treatment with these agents in the first-line setting has demonstrated a progression-free survival of 9.5–13.7 months. However, the majority of these patients ultimately develop resistance to these drugs. Afatinib is an irreversible pan-ErbB inhibitor that was developed to circumvent the problem of resistance to first-generation TKIs. The LUX-Lung studies have evaluated the efficacy and toxicities of afatinib in treatment-naïve and refractory NSCLC patients. The promising results of some of these trials led to approval of afatinib by the US Food and Drug Administration for patients with advanced NSCLC and EGFR exon 19 deletions or exon 21 (L858R) substitution mutations. Afatinib causes toxicities similar to those of the first-generation EGFR TKIs, such as diarrhea, rash, acne, and stomatitis, and overall is well tolerated. This article focuses on the clinical studies of afatinib in patients with NSCLC

  18. Correlation of Aquaporin 3 Expression with the Clinicopathologic Characteristics of Non-small Cell Lung Cancer

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    Bailing LI

    2012-07-01

    Full Text Available Background and objective Lung cancer is a major health problem worldwide. The aim of this study is to investigate aquaporin 3 (AQP3 expression and its relationship with the clinicopathologic characteristics of non-small cell lung cancer (NSCLC. Methods AQP3 expression and the microvascular density (MVD of tissue samples from 180 cases with NSCLC were detected by immunohistochemistry. Results AQP3 expression was negative in 25 (13.9%, positive in 67 (37.2%, and strongly positive in 88 (48.9% of the 180 cases, which was significantly higher than that in the normal tissue (P<0.01. A significant correlation was found between AQP3 expression and MVD (P<0.01, whereas a high MVD was found among patients with strongly positive AQP3 expression. Male patients with positive or strongly positive AQP3 expression had significantly higher expression than female patients did (P=0.003. AQP3 expression was more significantly enhanced in adenocarcinoma than that in squamous cell carcinoma (P<0.001. Statistical analysis indicated that the positive rate of AQP3 expression in well-differentiated carcinoma was significantly higher than that in poorly differentiated tumors (P<0.001. Lymph node metastasis was positively correlated with high AQP3 expression (P=0.026. Conclusion AQP3 expression was closely correlated with MVD in NSCLC, whereas high MVD was frequently found in tumors with high AQP3 expression. AQP3, as a therapeutic target for inhibiting high AQP3 expression in NSCLC tissues, may weaken cancer cell proliferation, invasion, and metastasis.

  19. Estimation of preoperative induction chemoradiotherapy effectiveness for non small-cell lung cancer

    International Nuclear Information System (INIS)

    We have performed the clinical evaluations of preoperative induction chemoradiotherapy (CRTx) for 25 patients with non small-cell lung cancer (male: 19, female: 6, mean age: 66.4-year-old). The clinical stages of these patients were IIA: 1, IIB: 7, IIIA: 14, and IIIB: 3, respectively. In the histological type of lung cancer, there were 12 patients of adenocarcinoma, 7 of squamous cell carcinoma, 1 of adenosquamousl carcinoma, 1 of anaplastic carcinoma, and 4 of large cell carcinoma. We applied two courses of regimen as the pre-operative chemotherapy (cisplatin (CDDP)+docetaxel (DOC) or carboplatin (CBDCA)+paclitaxel (PTX)). Twenty-four patients received radiotherapy as the concurrent radiotherapy (44 Gy: 22 patients, 60 Gy: 2 patients). Among the 25 patients, 16 patients accomplished both chemotherapies, and the effects of the treatment were as follows: complete response (CR); none, partial response (PR); 15, stable disease (SD); 9, respectively. And the other patient was not an evaluable case due to atelectasis. Histopathological effects (Ef) were Ef-3: 3, Ef-2: 11, Ef-1: 7, Ef-0: 1 and Ef was not evaluable in 3 cases. Post operative pathological findings showed that 14 patients were down staged. There were no operative mortality associated with the operation, and no serious morbidity case was observed. Eighteen patients were survived and 1 patient was survived with tumor metastases. Only one patient died of recurrence in the upper mediastinal lymph nodes, 3 patients died of the brain metastases, one died of hepatic metastasis, and one died of cryptogenic sudden death. As a result, there was no serious operative morbidity observed in the course of this CRTx. We therefore recommend that induction chemoradiotherapy as a beneficial pre-operative treatment. (author)

  20. Prognostic implications of ezrin and phosphorylated ezrin expression in non-small cell lung cancer

    International Nuclear Information System (INIS)

    The cytoskeletal organizer ezrin is a member of the ezrin-radixin-moesin (ERM) family and plays important roles in not only cell motility, cell adhesion, and apoptosis, but also in various cell signaling pathways. Phosphorylation at Thr-567 and Tyr-353 are key regulatory events in the transition of the dormant to active form of ezrin. This study investigated the prognostic implications of ezrin and phosphorylated ezrin (p-ezrin) expression in non-small cell lung carcinoma (NSCLC). Ezrin and p-ezrin protein expressions were examined by immunohistochemistry in 150 NSCLC and adjacent non-tumor tissues and 14 normal lung tissues. qRT-PCR was used to determine ezrin mRNA expression levels in fresh tissues. The correlations between overexpression of ezrin and p-ezrin and the clinicopathological features of NSCLC were analyzed. The survival rates were calculated by the Kaplan-Meier method for 108 NSCLC cases. Ezrin and ezrinThr-567 proteins showed cytosolic and membranous staining patterns; however, ezrinTyr-353 protein only showed cytosolic staining. Ezrin and p-ezrin were significantly upregulated in NSCLC compared with the normal counterparts. Increased ezrin, ezrinThr-567, and ezrinTyr-353 levels were correlated with the late stage and poor differentiation of NSCLC. However, only ezrinThr-567 was correlated with the presence of lymph node metastasis. In regard to survival, only ezrinThr-567 was related with the overall survival time of patients with NSCLC, and both ezrin and ezrinThr-567 were associated with shortened survival time for patients with early stage NSCLC. Ezrin and p-ezrin, especially ezrinThr-567, may prove to be useful as a novel prognostic biomarker of NSCLC

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

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    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.

  2. Consensus conference: multimodality management of early- and intermediate-stage non-small cell lung cancer.

    Science.gov (United States)

    Bordoni, Rodolfo

    2008-09-01

    Surgery is the mainstay of treatment in early- and intermediate-stage non-small cell lung cancer (NSCLC), yet recurrences are frequent. Studies have documented the benefits of chemotherapy administered after resection, but a number of questions remain regarding how overall outcomes can be further improved. To provide the oncology community with direction on these issues, a consensus conference of leading experts in the NSCLC field was held at the Fifth Annual Atlanta Lung Cancer Symposium on October 25-27, 2007. The available scientific literature is presented and when such literature is lacking, clinical experience is provided to support the following conclusions. Preoperative staging should be done in accordance with the National Comprehensive Cancer Network guidelines, but endoscopic fine needle aspiration of enlarged mediastinal nodes can be used, and if histology is positive for malignancy, mediastinoscopy can be avoided. Neoadjuvant systemic therapy is not generally recommended but can be considered to downstage an unresectable patient. There is currently no role for preoperative radiation or chemoradiation. Adjuvant systemic therapy is not recommended for stage IA and IB patients; however, adverse prognostic factors are acceptable reasons to consider adjuvant systemic therapy in the latter. Adjuvant systemic therapy is recommended for stage IIA, IIB, and IIIA patients, consistent with recent American Society of Clinical Oncology guidelines. A cisplatin-based regimen should be started within 60 days after surgery, but if relatively contraindicated, carboplatin is an acceptable alternative. Adjuvant radiation therapy is not recommended for N0 and N1 patients, but is used in N2 patients to decrease local recurrence. PMID:18779538

  3. Expression of Rab25 in non-small cell lung cancer and its clinical significance

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    Pu ZHOU

    2014-03-01

    Full Text Available Objective To assess the expression of Rab25 protein in non-small cell lung cancer (NSCLC, and explore the correlation of its expression with tumor proliferation and metastasis. Methods Sixty-one cases of NSCLC specimens (31 cases of squamous cell carcinoma, 26 cases of adenocarcinoma, and 4 cases of adenosquamous carcinoma undergone surgical treatment, and 40 specimens of adjacent normal lung tissues were obtained from Jan. 2009 to Jun. 2010 at Xingqiao Hospital of Third Military Medical University. Immunochemistry method of MaxVision was used to detect the expression of Rab25 in the specimens, and then the correlation of the expression with the clinicopathological parameters (patients' sex, age, smoking history, tumor type, differentiation, volume, TNM stage, lymph metastasis, etc. was analyzed using statistical software SPSS 21.0. Results  Rab25 protein was mainly expressed in cytoplasm and cell membrane. The positive rate of Rab25 in NSCLC was 93.4%, which was significantly higher than that in adjacent normal tissues (27.5%, P<0.01. The expression of Rab25 protein was significantly associated with the TNM stage and tumor size (P<0.05. Conclusions The expression of Rab25 is obviously higher in NSCLC than in the adjacent normal tissues, and the expression is associated with TNM stage and tumor size. Moreover, the later of the NSCLC stage, the larger of tumor size, and the higher of Rab25 expression will be in the NSCLC tissue. DOI: 10.11855/j.issn.0577-7402.2014.02.16

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

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    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.

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

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    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.

  6. Prognostic factors for long term survival in patients with advanced non-small cell lung cancer

    Science.gov (United States)

    Moumtzi, Despoina; Lampaki, Sofia; Porpodis, Konstantinos; Lagoudi, Kalliopi; Hohenforst-Schmidt, Wolfgang; Pataka, Athanasia; Tsiouda, Theodora; Zissimopoulos, Athanasios; Lazaridis, George; Karavasilis, Vasilis; Timotheadou, Helen; Barbetakis, Nikolaos; Pavlidis, Pavlos; Kontakiotis, Theodoros; Zarogoulidis, Konstantinos

    2016-01-01

    Background Non-small cell lung cancer (NSCLC) represents 85% of all lung cancers. It is estimated that 60% of patients with NSCLC at time of diagnosis have advanced disease. The aim of this study was to investigate clinical and demographic prognostic factors of long term survival in patients with unresectable NSCLC. Methods We retrospectively reviewed data of 1,156 patients with NSCLC stage IIIB or IV who survived more than 60 days from the time of diagnosis and treated from August 1987 until March 2013 in the Oncology Department of Pulmonary Clinic of the General Hospital Papanikolaou. Initially univariate analysis using the log-rank test was conducted and then multivariate analysis using the proportional hazards model of Cox. Also Kaplan Meier curves were used to describe the distribution of survival times of patients. The level of significance was set at 0.05. Results The mean age at diagnosis was 62 years. About 11.9% of patients were women and 88.1% were male. The majority of cases were adenocarcinomas (42.2%), followed squamous (33%) and finally the large cell (6%). Unlike men, most common histological type among women was adenocarcinoma rather than squamous (63% vs. 10.9%). In univariate analysis statistically significant factors in the progression free survival (PFS) and overall survival (OS) were: weight loss ≥5%, histological type, line 1 drugs, line 1 combination, line 1 cycles and radio lung. Specifically radio lung gives clear survival benefit in the PFS and OS in stage IIIB (P=0.002) and IV (Pcell carcinoma recorded the shortest OS and PFS compared with adenocarcinoma (P=0.043 and P=0.016 respectively) and squamous cell carcinoma (P=0.021 and P=0.004 respectively). In multivariate analysis the same predictors were statistically significant except for line 1 drugs. Conclusions This study confirms the increased incidence of adenocarcinoma in women than in men and the aggressiveness of large cell carcinoma. It also underlines the vitality of factors

  7. 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

  8. TRIM31 is downregulated in non-small cell lung cancer and serves as a potential tumor suppressor.

    Science.gov (United States)

    Li, Hui; Zhang, Yi; Zhang, Yue; Bai, Xue; Peng, Yang; He, Ping

    2014-06-01

    The present study aims to investigate expression pattern and biological roles of TRIM31 in human non-small cell lung cancer (NSCLC). We examined TRIM31 expression in 116 NSCLC tissues and 20 corresponding normal lung tissues by immumohistochemistry. We found TRIM31 downregulation in 47 out of 116 (40.5 %) cancer samples, which correlated with tumor status (p=0.0132), advanced p-TNM stage (p=0.001), and nodal metastasis (p=0.0382). TRIM31 expression was lower in lung cancer cell lines than normal bronchial cell line HBE. Transfection of TRIM31 plasmid was performed in H157 and H1299 cells. TRIM31 overexpression inhibited cell growth rate and colony formation ability in both cell lines. In addition, expression of cell cycle regulator cyclin D1 and cyclin E were decreased after TRIM31 transfection. In conclusion, TRIM31 might serve as a tumor suppressor in non-small cell lung cancer. PMID:24566900

  9. Using the theory of coevolution to predict protein-protein interactions in non-small cell lung cancer

    OpenAIRE

    Meng Zhang; Man-Him Chan; Wen-Jian Tu; Li-Ran He; Chak-Man Lee; Miao He

    2013-01-01

    Systems biology has become an effective approach for understanding the molecular mechanisms underlying the development of lung cancer. In this study, sequences of 100 non-small cell lung cancer (NSCLC)-related proteins were downloaded from the National Center for Biotechnology Information (NCBI) databases. The Theory of Coevolution was then used to build a protein-protein interaction (PPI) network of NSCLC. Adopting the reverse thinking approach, we analyzed the NSCLC proteins one at a time. ...

  10. Analysis of Differentially Expressed Proteome in Urine 
from Non-small Cell Lung Cancer Patients

    OpenAIRE

    Chen, Zhengang; Liu, Jinbo; Lin, Ling; Xie, Hui; Zhang, Wencheng; Zhang, Hongbo; Wang, Guangshun

    2015-01-01

    Background and objective Screen differentially expressed proteins in patients with non-small cell lung cancer (NSCLC), and aim to identify biomarkers for early screening, monitoring prognosis and evaluating therapy of NSCLC. Methods Urinary samples were collected from 40 newly diagnosed NSCLC patients, 8 patients with lung benign disorders and 22 healthy people. 0.9% sodium dodecylsulfate- polyacrylamide gel electrophoresis (1D SDS-PAGE) and MS-Thermo-Orbitrap-Velos were applied to separate, ...

  11. A Meta-analysis of Association between MGMT Gene 
Promoter Methylation and Non-small Cell Lung Cancer

    OpenAIRE

    Fang, Nianzhen; Gu, Jundong; Wei, Huijun; Jiacong YOU; Zhou, Qinghua

    2014-01-01

    Backgroud and objective DNA promoter methylation of the tumor suppressor genes was one of the key mechanism for gene silence. The aim of this study is to investigate the difference of MGMT gene promoter methylation rate in tumor tissue and autologous controls (serum, normal lung tissue and bronchial lavage fluid) in patients with non-small cell lung cancer (NSCLC). Methods The databases of Medline, EMBSE, CNKI and Wanfang were searched for selection of published articles of MGMT gene promoter...

  12. Non-small cell lung cancer stem/progenitor cells are enriched in multiple distinct phenotypic subpopulations and exhibit plasticity

    OpenAIRE

    Akunuru, S; James Zhai, Q; Zheng, Y.

    2012-01-01

    Cancer stem cells (CSCs) represent a population of cancer cells that possess unique self-renewal and differentiation characteristics required for tumorigenesis and are resistant to chemotherapy-induced apoptosis. Lung CSCs can be enriched by several markers including drug-resistant side population (SP), CD133pos and ALDHhigh. Using human non-small cell lung adenocarcinoma cell lines and patient-derived primary tumor cells, we demonstrate that SP cells represent a subpopulation distinct from o...

  13. Effect of comorbidity on the treatment and prognosis of elderly patients with non-small cell lung cancer

    OpenAIRE

    Janssen-Heijnen, M; Smulders, S.; Lemmens, V; Smeenk, F; van Geffen, H J A A; Coebergh, J

    2004-01-01

    Background: With the rising mean age, more patients will be diagnosed with one or more other serious diseases at the time of lung cancer diagnosis. Little is known about the best way to treat elderly patients with comorbidity or the outcome of treatment. This study was undertaken to evaluate the independent effects of age and comorbidity on treatment and prognosis in patients with non-small cell lung cancer (NSCLC).

  14. Impact of Brachyury on epithelial-mesenchymal transitions and chemosensitivity in non-small cell lung cancer

    OpenAIRE

    Xu, Ke; Liu, Bin; Liu, Yongyu

    2015-01-01

    The objective of the current study was to investigate the impact of Brachyury on epithelial-mesenchymal transitions and chemosensitivity in non-small cell lung cancer (NSCLC). In 115 archived NSCLC tissue samples, the expression of Brachyury was observed to be significantly higher than that in adjacent normal lung tissues. In addition, the current study demonstrated that the expression of Brachyury is closely associated with TNM staging, lymph node metastasis and the prognosis of NSCLC, altho...

  15. Mer receptor tyrosine kinase is frequently overexpressed in human non-small cell lung cancer, confirming resistance to erlotinib

    OpenAIRE

    Xie, Shengzhi; Li, Yongwu; Li, Xiaoyan; WANG, LINXIONG; Yang, Na; Wang, Yadi; Wei, Huafeng

    2015-01-01

    Mer is a receptor tyrosine kinase (RTK) with oncogenic properties that is often overexpressed or activated in various malignancies. Using both immunohistochemistry and microarray analyses, we demonstrated that Mer was overexpressed in both tumoral and stromal compartments of about 70% of non-small cell lung cancer (NSCLC) samples relative to surrounding normal lung tissue. This was validated in freshly harvested NSCLC samples; however, no associations were found between Mer expression and pat...

  16. Has the practice of radiation oncology for locally advanced and metastatic non-small-cell lung cancer changed in Canada?

    OpenAIRE

    Han, K.; Bezjak, A.; Xu, W.; Kane, G.

    2010-01-01

    Aim Previous surveys have revealed wide variations in the management by radiation oncologists of non-small-cell lung cancer (nsclc) in Canada. The aim of the present study was to determine the current patterns of practice for locally advanced and metastatic nsclc among Canadian radiation oncologists. Materials and Methods An online survey was distributed electronically to all members of the Canadian Association of Radiation Oncologists. Those who treat lung cancer were invited to participate....

  17. Genes suppressed by DNA methylation in non-small cell lung cancer reveal the epigenetics of epithelial-mesenchymal transition.

    OpenAIRE

    Lin, Steven; Wang, Jing; Saintigny, Pierre; Wu, Chia-Chin; Giri, Uma; Jing ZHANG; Menju, Toshi; Diao, Lixia; Byers, Lauren; Weinstein, John ,; Coombes, Kevin; Girard, Luc; Komaki, Ritsuko; Wistuba, Ignacio; Date, Hiroshi

    2013-01-01

    Background DNA methylation is associated with aberrant gene expression in cancer, and has been shown to correlate with therapeutic response and disease prognosis in some types of cancer. We sought to investigate the biological significance of DNA methylation in lung cancer. Results We integrated the gene expression profiles and data of gene promoter methylation for a large panel of non-small cell lung cancer cell lines, and identified 578 candidate genes with expression levels that were inver...

  18. Analysis of the molecular expression profile of non small cell lung carcinoma associated to chronic obstructive pulmonary disease

    OpenAIRE

    Garcia-Lujan, Ricardo; Conde-Gallego, Esther; Lopez-Ríos, Fernando; Martin de Nicolas, Jose Luis; Sanchez-Céspedes, Montserrat; García-Quero, Cristina; Echave-Sustaeta, José María; Lopez-Encuentra, Angel

    2009-01-01

    Chronic obstructive pulmonary disease (COPD) is an independent risk factor to develop lung cancer but there are no different functional clusters of biomarkers between patients with non-small cell lung cancer (NSCLC) with or without COPD. To analyse protein expression, in order to find out whether samples of resected NSCLC from patients with COPD present a different molecular expression. Observational, cohort, concurrent study with sampling since treatment of disease...

  19. Regulation of Mitochondria-dependent Apoptosis in Non-Small Cell Lung Cancer: Implications for Cancer Therapy

    OpenAIRE

    Checinska, A.

    2007-01-01

    Summary The work described in this thesis focuses on the characterization of the mechanism(s) underlying the deregulated activation of the intrinsic or mitochondrial apoptotic pathway in non-small cell lung cancer (NSCLC) cells. Apoptosis suppression might contribute to the chemoresistance often observed in NSCLC patients, and elucidation of the molecular causes of this resistance may provide clues for the development of targeted apoptosis-based therapies. In this introduction, lung cancer an...

  20. Secretion of beta-human chorionic gonadotropin by non-small cell lung cancer: a case report

    OpenAIRE

    Varma Seema; Vivekanandarajah Abhirami; Khattri Saakshi; Kong Frank

    2011-01-01

    Abstract Introduction We describe a case of non-small cell lung cancer that was found to stain positive for beta-human chorionic gonadotropin on immunohistochemistry. Only a few case reports have described lung cancers that secrete beta-human chorionic gonadotropin. Case presentation A 68-year-old Caucasian man presented with symptoms of weakness, fatigue and weight loss for the past two months. On examination, he was found to have generalized lymphadenopathy, and radiologic workup revealed n...

  1. Wnt signaling pathway pharmacogenetics in non-small cell lung cancer.

    Science.gov (United States)

    Stewart, D J; Chang, D W; Ye, Y; Spitz, M; Lu, C; Shu, X; Wampfler, J A; Marks, R S; Garces, Y I; Yang, P; Wu, X

    2014-12-01

    Wingless-type protein (Wnt)/β-catenin pathway alterations in non-small cell lung cancer (NSCLC) are associated with poor prognosis and resistance. In 598 stage III-IV NSCLC patients receiving platinum-based chemotherapy at the MD Anderson Cancer Center (MDACC), we correlated survival with 441 host single-nucleotide polymorphisms (SNPs) in 50 Wnt pathway genes. We then assessed the most significant SNPs in 240 Mayo Clinic patients receiving platinum-based chemotherapy for advanced NSCLC, 127 MDACC patients receiving platinum-based adjuvant chemotherapy and 340 early stage MDACC patients undergoing surgery alone (cohorts 2-4). In multivariate analysis, survival correlates with SNPs for AXIN2 (rs11868547 and rs4541111, of which rs11868547 was assessed in cohorts 2-4), Wnt-5B (rs12819505), CXXC4 (rs4413407) and WIF-1 (rs10878232). Median survival was 19.7, 15.6 and 10.7 months for patients with 1, 2 and 3-5 unfavorable genotypes, respectively (P=3.8 × 10(-9)). Survival tree analysis classified patients into two groups (median survival time 11.3 vs 17.3 months, P=4.7 × 10(-8)). None of the SNPs achieved significance in cohorts 2-4; however, there was a trend in the same direction as cohort 1 for 3 of the SNPs. Using online databases, we found rs10878232 displayed expression quantitative trait loci correlation with the expression of LEMD3, a neighboring gene previously associated with NSCLC survival. In conclusion, results from cohort 1 provide further evidence for an important role for Wnt in NSCLC. Investigation of Wnt inhibitors in advanced NSCLC would be reasonable. Lack of an SNP association with outcome in cohorts 2-4 could be due to low statistical power, impact of patient heterogeneity or false-positive observations in cohort 1. PMID:24980784

  2. A laboratory prognostic index model for patients with advanced non-small cell lung cancer.

    Directory of Open Access Journals (Sweden)

    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.

  3. Observer variation in FDG PET-CT for staging of non-small-cell lung carcinoma

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    Hofman, Michael S. [St Thomas' Hospital, PET Imaging Centre, London (United Kingdom)]|[Southern Health, Nuclear Medicine, Melbourne (Australia); Smeeton, Nigel C. [King' s College London, Division of Health and Social Care Research, London (United Kingdom); Rankin, Sheila C.; Nunan, Tom; O' Doherty, Michael J. [St Thomas' Hospital, PET Imaging Centre, London (United Kingdom)

    2009-02-15

    Error and variation in reporting remains one of the weakest features of clinical imaging despite enormous technological advances in nuclear medicine and radiology. The aim of this study was to evaluate agreement amongst experienced readers in staging non-small-cell lung cancer (NSCLC) with PET-CT. A series of {sup 18}F-FDG PET-CT scans from 100 consecutive patients were reviewed independently by three experienced readers, with two readers reviewing each scan series a second time. Individual mediastinal lymph node stations were assessed as benign/inflammatory, equivocal or malignant, and AJCC N and M stage were also assigned. Kappa ({kappa}) was used to compare ratings from two categories and weighted kappa ({kappa}{sub w}) for three or more categories, and kappa values were interpreted according to the Landis-Koch benchmarks. Both intra- and interobserver agreement for N and M staging were high. For M staging there was almost perfect intra- and interobserver agreement ({kappa} = 0.90-0.93). For N staging, agreement was either almost perfect or substantial (intraobserver {kappa}{sub w} = 0.79, 0.91; interobserver {kappa}{sub w} = 0.75-0.81). Importantly, there was almost perfect agreement for N0/1 vs N2/3 disease ({kappa} = 0.80-0.97). Agreement for inferior and superior mediastinal nodes (stations 1, 2, 3, 7, 8, 9) was either almost perfect or substantial ({kappa}{sub w} = 0.71-0.88), but lower for hilar nodes (10; {kappa}{sub w} = 0.56-0.71). Interreporter variability was greatest for aortopulmonary nodes (5, 6; {kappa}{sub w} = 0.48-0.55). Amongst experienced reporters in a single centre, there was a very high level of agreement for both mediastinal nodal stage and detection of distant metastases with PET-CT. This supports the use of PET-CT as a robust imaging modality for staging NSCLC. (orig.)

  4. Expression of Bim, Noxa, and Puma in non-small cell lung cancer

    International Nuclear Information System (INIS)

    The BH3-only members of the Bcl-2 protein family have been proposed to play a key role in the control of apoptosis and in the initiation of the apoptotic pathways. In this study, we evaluated the expression of Bim, Noxa, and Puma in non-small cell lung cancer (NSCLC). A total of 135 surgically resected NSCLCs were immunohistochemically assessed for Bim, Noxa, and Puma expression. The immunoscores were determined, and then its correlation with either the clinicopathological variables or the survival outcomes were analyzed. Immunohistochemical reactivity for Bim, Noxa, and Puma was detected in the cytoplasm of the tumor cells. Bim expression was associated with several clinicopathological factors, including sex (p < 0.001), smoking habit (p = 0.03), pathological histology (p = 0.001), pathological T stage (p = 0.03), pathological disease stage (p = 0.02), and differentiation of tumor (p < 0.001). Multivariate logistic regression analysis showed a significant correlation between low Bim expression and squamous cell carcinoma (p = 0.04), in addition to a correlation between high Bim expression and well differentiated tumors (p = 0.02). Analysis of cellular biological expression demonstrated a link between low Bim expression and high Ki67. While Noxa expression was also shown to be correlated with both smoking habit (p = 0.02) and the pathological histology (p = 0.03), there was no strong association observed between the expression and the clinical features when they were examined by a multivariate logistic regression analysis. No correlations were noted between Puma expression and any of the variables. Our analyses also indicated that the expression levels of the BH3-only proteins were not pertinent to the survival outcome. The current analyses demonstrated that Bim expression in the NSCLCs was associated with both squamous cell carcinoma histology and tumor proliferation

  5. Targeting SHP2 for EGFR inhibitor resistant non-small cell lung carcinoma

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    Xu, Jie; Zeng, Li-Fan; Shen, Weihua [Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis (United States); Turchi, John J. [Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis (United States); Department of Medicine, Indiana University School of Medicine, Indianapolis (United States); Zhang, Zhong-Yin, E-mail: zyzhang@iu.edu [Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis (United States)

    2013-10-04

    Highlights: •SHP2 is required for EGFR inhibitor resistant NSCLC H1975 cell proliferation. •SHP2 inhibitor blocks EGF-stimulated ERK1/2 activation and proliferation. •SHP2 inhibitor exhibits marked anti-tumor activity in H1975 xenograft mice. •SHP2 inhibitor synergizes with PI3K inhibitor in suppressing cell growth. •Targeting SHP2 represents a novel strategy for EGFR inhibitor resistant NSCLCs. -- Abstract: Targeted therapy with inhibitors of epidermal growth factor receptor (EGFR) has produced a noticeable benefit to non-small cell lung cancer (NSCLC) patients whose tumors carry activating mutations (e.g. L858R) in EGFR. Unfortunately, these patients develop drug resistance after treatment, due to acquired secondary gatekeeper mutations in EGFR (e.g. T790M). Given the critical role of SHP2 in growth factor receptor signaling, we sought to determine whether targeting SHP2 could have therapeutic value for EGFR inhibitor resistant NSCLC. We show that SHP2 is required for EGF-stimulated ERK1/2 phosphorylation and proliferation in EGFR inhibitor resistant NSCLC cell line H1975, which harbors the EGFR T790M/L858R double-mutant. We demonstrate that treatment of H1975 cells with II-B08, a specific SHP2 inhibitor, phenocopies the observed growth inhibition and reduced ERK1/2 activation seen in cells treated with SHP2 siRNA. Importantly, we also find that II-B08 exhibits marked anti-tumor activity in H1975 xenograft mice. Finally, we observe that combined inhibition of SHP2 and PI3K impairs both the ERK1/2 and PI3K/AKT signaling axes and produces significantly greater effects on repressing H1975 cell growth than inhibition of either protein individually. Collectively, these results suggest that targeting SHP2 may represent an effective strategy for treatment of EGFR inhibitor resistant NSCLCs.

  6. Prognostic significance of CD44s expression in resected non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Ko Yoon

    2011-08-01

    Full Text Available Abstract Background CD44s is a cell adhesion molecule known to mediate cellular adhesion to the extracellular matrix, a prerequisite for tumor cell migration. CD44s plays an important role in invasion and metastasis of various cancers. In the present study, we sought to determine whether CD44s is involved in clinical outcomes of patients with resected non-small cell lung cancer (NSCLC. Methods Using immunohistochemical staining, we investigated CD44s protein expression using tissue array specimens from 159 patients with resected NSCLC (adenocarcinoma (AC; n = 82 and squamous cell carcinoma (SCC; n = 77. Additionally, the immunoreactivity of cyclooxygenase (COX-2 was also studied. The clinicopathological implications of these molecules were analyzed statistically. Results High CD44s expression was detected more frequently in NSCLC patients with SCC (66/72; 91.7% than in those with AC histology (P 0.001. Additionally, high CD44s expression was significant correlated with more advanced regional lymph node metastasis (P = 0.021. In multivariate analysis of survival in NSCLC patients with AC histology, significant predictors were lymph node metastasis status (P P = 0.046, and high CD44s expression (P = 0.014. For NSCLC patients with SCC histology, the significant predictor was a more advanced tumor stage (P = 0.015. No significant association was found between CD44s and clinical outcome (P = 0.311. Conclusions High CD44s expression was a negative prognostic marker with significance in patients with resected NSCLC, particularly those with AC histology, and was independent of tumor stage.

  7. The Radiotherapeutic Significance of Serum NSE Level in Non-Small Cell Lung Cancers (NSCLC)

    International Nuclear Information System (INIS)

    From December 1989 to February 1993, 108 patients with Non-Small Cell Lung Cancers(NSCLC) were studied retrospectively to evaluate radiotherapeutic significance of serum levels of NSE. We considered elevated serum neuron specific pathologic evaluation revealed 86 squamous cell carcinomas, 11 adenocarcinomas, 3 large cell carcinomas, 3 mucoepidermoid carcinomas, and 5 unknown pathology. Eight patients had stage I, 40 stage IIIA, and 60 stage IIIB. S-NSE level greater than 15 ng/ml was considered as elevated, and below this considered as normal. All patients received radiotherapy as primary treatment modality. The responders to radiotherapy had significantly higher mean S-NSE level than on-responders (28.5 ng/ml vs 20 ng/ml, p=0.01). Overall 2-year survival rate (YSR) was 23.6%. According to radiotherapy response, 2 YSR for patients with CR, PR, and NR were 39.2%, 28.6%, and 6.2% respectively (p=0.001). 2 YSR for patients with elevated and normal S-NSE were 14.6% and 31.7%(p=0.02). The patients with NR showed no difference in survival according to S-NSE level. When we considered all patients, S-NSE level showed no significant impact on response. But for squamous cell cardinomas alone, patients with elevated S-NSE had more patients with higher nodal stage. Based on our and other data, NSCLSC with neuroendocrine features have different response to treatment and clinical behavior compared to other NSCLSC. Thus, this subgroup may need different treatment modality, and S-NSE level may have prognostic significance

  8. Quality of life after palliative radiotherapy in non-small cell lung cancer: a prospective study

    International Nuclear Information System (INIS)

    Purpose: The purpose of this study was to investigate changes in respiratory symptoms and quality of life (QoL) in patients with locally advanced and metastatic non-small cell lung cancer (NSCLC) receiving thoracic radiotherapy. Additionally, the correlation between the level of symptom relief and objective tumor response was investigated. Methods and Materials: Sixty-five patients were entered in this prospective study. The EORTC QLQ-C30 and EORTC QLQ-LC13 were used to investigate changes in QoL. Assessments were performed before radiotherapy and 2 weeks, 6 weeks, and 3 months after radiotherapy. Results: The QoL response rates were excellent for hemoptysis (79%); good for arm/shoulder pain (56%), chest wall pain (53%), and cough (49%); moderate for dyspnea (39%); and minimal for the general symptoms fatigue (22%) and appetite loss (11%). The QoL response rates for the five functioning scales of the QLQ-C30 varied from 35% for role functioning to 57% for emotional functioning. Global QoL improved in 37% of the cases. In general, there was a tendency for better palliation of symptoms and improvement of QoL among patients with an objective tumor response than among those without objective tumor response, which was statistically significant for dyspnea (p = 0.02) and social functioning (p = 0.04). Conclusions: This study confirms that conventional thoracic radiotherapy offers palliation of respiratory symptoms and improved QoL in a substantial proportion of patients with locally advanced and metastatic NSCLC. Tumor reduction is only one of the mechanisms by which palliation of symptoms and improvement of QoL is achieved

  9. ADJUVANT CHEMOTHERAPY FOLLOWING RADICAL SURGERY FOR NON-SMALL CELL LUNG CANCER:A RANDOMIZED STUDY

    Institute of Scientific and Technical Information of China (English)

    XU Guang-chuan; RONG Tie-hua; LIN Peng

    1999-01-01

    Objective: To evaluate the efficacy of adjuvant chemotherapy after radical surgery for non-small cell lung cancer (NSCLC). Methods: Seventy patients with NSCLC (stage Ⅰ-Ⅲ) undergone radical surgery were randomized into two groups: 35 patients received adjuvant chemotherapy with cyclophosphamide (CTX)300 mg/m2, vincristine (VCR) 1.4% mg/m2, adriamycin (ADM) 50 mg/m2, lomustine (CCNU) 50 mg/m2 d1,cisplatin (DDP) 20 mg/m2, d1-5, for 4 cycles, and followed by oral Ftorafur (FT-207) 600-900 mg/d for 1year (adjuvant chemotherapy group). The other 35patients received surgical treatment only (surgery group). Results: The overall 5-year survival rate was 48.6% in the adjuvant chemotherapy group, and 31.4%in the surgery group, respectively. The difference between the two groups was not statistically significant (P>0.05). The 5-year survival rate of patients in stage Ⅲwas 44.0% and 20.8% received surgery with and without adjuvant chemotherapy, respectively. The difference between the two groups was statistically significant (P<0.025). The 5-year survival rate of patients in stage Ⅰ-Ⅱ in the two groups was 60.0% and 54.5%, respectively (P>0.75). Conclusion: Postoperative adjuvant chemotherapy in NSCLC can improve survival, for those patients in stage Ⅲ, it suggests significantly 5-year survival rate in the adjuvant chemotherapy group was higher than that in the surgery alone group.

  10. Gene Polymorphisms and Chemotherapy in Non-small Cell Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    Kayo OSAWA

    2009-01-01

    The phamacogenetics is being used to predict whether the selected chemotherapy will be really effective and tolerable to the patient. Irinotecan, oxidized by CYP3A4 to produce inactive compounds, is used for treatment of various cancers including advanced non small cell lung cancer (NSCLC) patients. CYP3A4*16B polymorphism was associated with decreased metabolism ofirrinotecan. Irinotecan is also metabolized by carboxylesterase to its principal active metabolite, SN-38, which is subsequently glucuronidated by UGT1As to form the inactive compound SN-38G. UGT1A1*28 and UGT1A1*6 polymorphisms were useful for predicting severe toxicity with NSCLC patients treated with irinotecan-based chemotherapy. Platinum-based compounds (cisplatin, carboplatin) are being used in combination with new cytotoxic drugs such as gemcitabine, paclitaxel, docetaxel, or vinorelbine in the treatment of advanced NSCLC. Cisplatin activity is mediated through the formation of cisplatin-DNA adducts. Gene polymorphisms of DNA repair factors are therefore obvious candidates for determinants of repair capacity and chemotherapy efficacy. ERCC1, XRCC1 and XRCC3 gene polymorphisms were a useful marker for predicting better survival in advanced NSCLC patients treated with platinum-based chemotherapy. XPA and XPD polymorphisms significantly increased response to platinum-based chemotherapy. These DNA repair gene polymorphisms were useful as a predictor of clinical outcome to the platinum-based chemotherapy. EGFR kinase inhibitors induce dramatic clinical responses in NSCLC patients with advanced disease. EGFR gene polymorphism in intron 1 contains a polymorphic single sequence dinudeotide repeat (CA-SSR) showed a statistically significant correlation with the gefitinib response and was appeared to be a useful predictive marker of the development of clinical outcome containing skin rashes with gefitinib treatment. The other polymorphisms of EGFR were also associated with increased EGFR promoter activity

  11. Targeting SHP2 for EGFR inhibitor resistant non-small cell lung carcinoma

    International Nuclear Information System (INIS)

    Highlights: •SHP2 is required for EGFR inhibitor resistant NSCLC H1975 cell proliferation. •SHP2 inhibitor blocks EGF-stimulated ERK1/2 activation and proliferation. •SHP2 inhibitor exhibits marked anti-tumor activity in H1975 xenograft mice. •SHP2 inhibitor synergizes with PI3K inhibitor in suppressing cell growth. •Targeting SHP2 represents a novel strategy for EGFR inhibitor resistant NSCLCs. -- Abstract: Targeted therapy with inhibitors of epidermal growth factor receptor (EGFR) has produced a noticeable benefit to non-small cell lung cancer (NSCLC) patients whose tumors carry activating mutations (e.g. L858R) in EGFR. Unfortunately, these patients develop drug resistance after treatment, due to acquired secondary gatekeeper mutations in EGFR (e.g. T790M). Given the critical role of SHP2 in growth factor receptor signaling, we sought to determine whether targeting SHP2 could have therapeutic value for EGFR inhibitor resistant NSCLC. We show that SHP2 is required for EGF-stimulated ERK1/2 phosphorylation and proliferation in EGFR inhibitor resistant NSCLC cell line H1975, which harbors the EGFR T790M/L858R double-mutant. We demonstrate that treatment of H1975 cells with II-B08, a specific SHP2 inhibitor, phenocopies the observed growth inhibition and reduced ERK1/2 activation seen in cells treated with SHP2 siRNA. Importantly, we also find that II-B08 exhibits marked anti-tumor activity in H1975 xenograft mice. Finally, we observe that combined inhibition of SHP2 and PI3K impairs both the ERK1/2 and PI3K/AKT signaling axes and produces significantly greater effects on repressing H1975 cell growth than inhibition of either protein individually. Collectively, these results suggest that targeting SHP2 may represent an effective strategy for treatment of EGFR inhibitor resistant NSCLCs

  12. Prognostic Factors in Stereotactic Body Radiotherapy for Non-Small-Cell Lung Cancer

    International Nuclear Information System (INIS)

    Purpose: To investigate the factors that influence clinical outcomes after stereotactic body radiotherapy (SBRT) for non-small-cell lung cancer (NSCLC). Methods and Materials: A total of 101 consecutive patients who underwent SBRT with 48 Gy in 4 fractions for histologically confirmed Stage I NSCLC were enrolled in this study. Factors including age, maximal tumor diameter, sex, performance status, operability, histology, and overall treatment time were evaluated with regard to local progression (LP), disease progression (DP), and overall survival (OS) using the Cox proportional hazards model. Prognostic models were built with recursive partitioning analysis. Results: Three-year OS was 58.6% with a median follow-up of 31.4 months. Cumulative incidence rates of LP and DP were 13.2% and 40.8% at 3 years, respectively. Multivariate analysis demonstrated that tumor diameter was a significant factor in all endpoints of LP, DP, and OS. Other significant factors were age in DP and sex in OS. Recursive partitioning analysis indicated a condition for good prognosis (Class I) as follows: female or T1a (tumor diameter ≤20 mm). When the remaining male patients with T1b-2a (>20 mm) were defined as Class II, 3-year LP, DP, and OS were 6.8%, 23.6%, and 69.9% in recursive partitioning analysis Class I, respectively, whereas these values were 19.9%, 58.3%, and 47.1% in Class II. The differences between the classes were statistically significant. Conclusions: Tumor diameter and sex were the most significant factors in SBRT for NSCLC. T1a or female patients had good prognosis.

  13. Primary therapeutic decision-making in inoperable non-small cell lung cancer

    International Nuclear Information System (INIS)

    Purpose: To test the accuracy of our treatment decisions for patients with inoperable non-small cell lung cancer (NSCLC) using a prototype decision-support system (DSS) and a prognostic index (PI). Methods and Materials: To predict patient outcome and select optimal treatment, the systems protocol was tested retrospectively in 242 patients with Stage I-IV disease. The PI was determined in 184 patients with Stage I-IIIa,b disease. Survival was the final determinant of the accuracy of our treatment decisions. Results: Until 1996 it was our treatment policy to treat all Stage III patients with radical intent unless they had symptoms requiring palliation. In 1997, after the palliation concept of the DSS and the PI were changed to include all Stage III disease, there was considerable discordance between the rates of palliative treatment indicated by the DSS and the PI (69% and 99%, respectively) as well as that observed in our practice (30% in the DSS group and 20% in the PI group, respectively). There was also a significant difference in survival between the patients in the low- and high-risk categories defined by the PI (median survival of 12 versus 6 months, respectively; p = 0.0001). In the group that received radical radiotherapy, there was also a significant difference in the duration of survival between the low- and high-risk groups (median survival of 12 versus 8 months, respectively; p = 0.01). In addition, the risk categories proved to be the most important predictor of survival in the patients receiving radiotherapy longer than 2 weeks (median survival of 12 versus 7 months, respectively; p = 0.0001). In high-risk patients, however, the duration of radiotherapy did not have a significant impact on survival (p = 0.25). Conclusion: Our data indicate that the PI is a useful method for selecting radical or palliative treatment modalities as well as for determining treatment duration

  14. AZD9291 in epidermal growth factor receptor inhibitor—resistant non-small-cell lung cancer

    Science.gov (United States)

    2016-01-01

    Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in advanced EGFR mutant non-small cell lung cancer have an objective response rate (ORR) of approximately 60–70% and a median progression free-survival (PFS) of approximately 10-13 months. Studies of tumor biopsies performed after progression on EGFR TKI revealed that 50-60% of EGFR mutant NSCLC developed an EGFR exon 20 T790M mutation as a mechanism of acquired resistance. AZD9291 is a third generation irreversible EGFR TKI with activity against the activating EGFR mutation, the T790M acquired resistance mutation, and relative sparing of the wild-type EGFR. AZD9291 was investigated in a phase I trial with expansion cohorts in patients with disease progression after EGFR TKI. Patients with and without detectable T790M mutations were enrolled in the trial. The ORR in patients with centrally confirmed and without detectable T790M mutations was 61% (95% CI, 52–70%) and 21% (95% CI, 12–34%), respectively. The PFS observed in patients with centrally confirmed and without detectable T790M mutations was 9.6 months (95% CI, 8.3 to not reached) and 2.8 months (95% CI, 2.1–4.3 months), respectively. At the dose for further investigation, 80 mg daily, the rate of all grade 3-5 drug related adverse events was 11%, and the rates of grade 3 diarrhea and rash were 1% and 0%, respectively. The identification of the T790M resistance mutation and the subsequent development of an agent against the mechanism of resistance provide a template for future drug development for acquired resistance to targeted therapy. PMID:26958499

  15. AZD9291 in epidermal growth factor receptor inhibitor-resistant non-small-cell lung cancer.

    Science.gov (United States)

    Stinchcombe, Thomas E

    2016-02-01

    Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in advanced EGFR mutant non-small cell lung cancer have an objective response rate (ORR) of approximately 60-70% and a median progression free-survival (PFS) of approximately 10-13 months. Studies of tumor biopsies performed after progression on EGFR TKI revealed that 50-60% of EGFR mutant NSCLC developed an EGFR exon 20 T790M mutation as a mechanism of acquired resistance. AZD9291 is a third generation irreversible EGFR TKI with activity against the activating EGFR mutation, the T790M acquired resistance mutation, and relative sparing of the wild-type EGFR. AZD9291 was investigated in a phase I trial with expansion cohorts in patients with disease progression after EGFR TKI. Patients with and without detectable T790M mutations were enrolled in the trial. The ORR in patients with centrally confirmed and without detectable T790M mutations was 61% (95% CI, 52-70%) and 21% (95% CI, 12-34%), respectively. The PFS observed in patients with centrally confirmed and without detectable T790M mutations was 9.6 months (95% CI, 8.3 to not reached) and 2.8 months (95% CI, 2.1-4.3 months), respectively. At the dose for further investigation, 80 mg daily, the rate of all grade 3-5 drug related adverse events was 11%, and the rates of grade 3 diarrhea and rash were 1% and 0%, respectively. The identification of the T790M resistance mutation and the subsequent development of an agent against the mechanism of resistance provide a template for future drug development for acquired resistance to targeted therapy. PMID:26958499

  16. 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

  17. Use of Palliative Radiotherapy Among Patients With Metastatic Non-Small-Cell Lung Cancer

    International Nuclear Information System (INIS)

    Purpose: Radiotherapy (RT) is known to effectively palliate many symptoms of patients with metastatic non-small-cell lung cancer (NSCLC). Anecdotally, RT is believed to be commonly used in this setting, but limited population-based data are available. The objective of this study was to examine the utilization patterns of palliative RT among elderly patients with Stage IV NSCLC and, in particular, to identify factors associated with its use. Methods and Materials: A retrospective population-based cohort study was performed using linked Surveillance, Epidemiology and End Results (SEER)-Medicare data to identify 11,084 Medicare beneficiaries aged ≥65 years who presented with Stage IV NSCLC in the 11 SEER regions between 1991 and 1996. The primary outcome was receipt of RT. Logistic regression analysis was used to identify factors associated with receipt of RT. Results: A total of 58% of these patients received RT, with its use decreasing over time (p = 0.01). Increasing age was negatively associated with receipt of treatment (p <0.001), as was increasing comorbidities (p <0.001). Factors positively associated with the receipt of RT included income (p = 0.001), hospitalization (p <0.001), and treatment with chemotherapy (p <0.001). Although the use varied across the SEER regions (p = 0.001), gender, race/ethnicity, and distance to the nearest RT facility were not associated with treatment. Conclusions: Elderly patients with metastatic NSCLC frequently receive palliative RT, but its use varies, especially with age and receipt of chemotherapy. Additional research is needed to determine whether this variability reflects good quality care

  18. Accelerated hypofractionation for early-stage non-small-cell lung cancer

    International Nuclear Information System (INIS)

    Purpose: To describe the outcome of treating early-stage non-small-cell lung cancer (NSCLC) with an accelerated hypofractionated course of radiotherapy. Methods and Materials: A policy of treating early-stage NSCLC with a dose of 48 Gy in 12 once-daily fractions without elective irradiation of radiologically uninvolved regional nodes was adopted in 1996. We describe the outcome in 33 patients with NSCLC treated with this dose-fractionation schedule. Results: The median patient age was 72.0 years. Most patients (75.8%) were not surgical candidates because of medical comorbidities or old age. For staging, 97.0% underwent CT of the thorax, and mediastinoscopy was performed in 6.1%. All patients had Stage T1-T2N0, except for 4 patients with positive nodes based on pathologically involved or clinically enlarged lymph nodes adjacent to the primary tumor. The overall survival rate was 80.1% at 1 year and 46.0% at 2 years. The median survival was 22.6 months. The cause-specific survival rate was 89.8% at 1 year and 54.1% at 2 years. The recurrence-free survival rate was 66.4% at 1 year and 40.0% at 2 years. Lateral radiotherapy field margins of <2 cm predicted for inferior overall survival, cause-specific survival, and recurrence-free survival on univariate and multivariate analyses (p<0.05). The most commonly reported toxicities were acute dermatitis (30.3%) and late cutaneous/subcutaneous fibrosis (24.2%). Conclusion: Accelerated hypofractionation for early-stage NSCLC appears to be safe and produces promising early results. Very small radiotherapy field margins may lead to an inferior outcome. Prospective studies are needed to determine the optimal dose-fractionation schedule

  19. FDG uptake in PET imaging correlates with DNA ploidy in non small cell lung carcinoma

    International Nuclear Information System (INIS)

    Objective: DNA ploidy analysis of resected tumor tissue to grade the malignancy is of prognostic value for patients with non-small cell lung cancer (NSCLC). 18F-fluorodeoxyglucose (FDG) imaging has been proven useful for tumor staging. In this study, the authors evaluated whether 18F-FDG uptake within the primary lesion correlates with DNA ploidy of tumors in patients with NSCLC. Methods: Forty-nine patients with histologically proven NSCLC underwent whole-body FDG PET 45-90 min after i.v. injection of 6 MBq/kg body weight of 18F-FDG prior to surgery, and the primary tumor FDG uptake on PET images was quantified with the standardized uptake value (SUV) and metabolic tumor diameter (MTD). The DNA content and DNA-malignancy grading (DNA-MG) of Schiff-stained nuclei obtained from fresh tumor fragments taken from these patients during the surgery were evaluated by means of image cytometry. The correlation between SUV and MTD and between SUV and 2c deviation index (2cDI) or between SUV and DNA-MG were analyzed using linear fit. Results: The primary tumors as well as metastatic lymph nodes of the total 49 patients were well present on PET images, so that the result data of SUV and MTD were demonstrated satisfactorily. Of the DNA histograms of these 49 patients, 46(93.88%) were aneuploid and only 3(6.12%) were tetraploid. A linear correlation of the SUV versus the MTD (r = 0.632, P 18F-FDG PET as a non-invasive metabolic imaging technique, may also provide correlated information between SUV and DNA contents, 2cDI or DNA-MG, which may be valuable in malignancy differentiation and prognostic predication

  20. FDG uptake at the bronchial stump after curative lobectomy for non-small cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Keyzer, Caroline; Corbusier, Florence; Kyratzi, Eirini; Gevenois, Pierre Alain [Universite libre de Bruxelles, Department of Radiology, Hopital Erasme, Brussels (Belgium); Sokolow, Youri [Universite libre de Bruxelles, Department of Thoracic Surgery, Hopital Erasme, Brussels (Belgium); Goldman, Serge [Universite libre de Bruxelles, Department of Nuclear Medicine, Hopital Erasme, Brussels (Belgium)

    2016-05-15

    Focal areas of FDG uptake may occur at the bronchial stump following curative lobectomy for non-small-cell lung carcinoma (NSCLC), even in the absence of suspicious CT changes. The purpose of our study was to investigate the significance of such PET/CT findings. FDG-PET/CT scans performed in 54 patients after lobectomy for NSCLC were reviewed. The presence of focal areas of FDG uptake at the bronchial stump, associated CT abnormalities, SUVmax, and normalized SUV (SUVnorm = SUVmax/mean liver SUV) were recorded. Final diagnosis was based on biopsy or imaging follow-up. Focal areas of FDG uptake at the bronchial stump were detected in 30 patients (56 %). Mean SUVmax was 4.0 ± 1.9 (range; 2.2-12.1) and mean SUVnorm was 1.8 ± 0.8 (range; 0.9-4.5). Biopsy showed recurrence in two patients. In these patients, SUVnorm was respectively 4.4 and 4.5 (with SUVmax of 8.8 and 12.1), whereas SUVnorm was lower than 4.0 in those without recurrence, with mean SUVnorm of 1.6 ± 0.5 (range; 0.9-3.4) and mean SUVmax of 3.6 ± 0.9 (range; 2.2-5.8). The CT component of the PET/CT revealed ill-defined peribronchial soft tissue opacity only in both patients with recurrence. FDG uptake at the bronchial stump is a frequent finding after pulmonary lobectomy. Moderate levels of FDG uptake (i.e., SUVnorm < 4.0) without corresponding abnormal CT findings might be a dual criterion for diagnosing benign post-surgical changes. (orig.)

  1. Definitive Primary Therapy in Patients Presenting With Oligometastatic Non-Small Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Parikh, Ravi B. [Harvard Medical School, Boston, Massachusetts (United States); Cronin, Angel M. [Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Kozono, David E.; Oxnard, Geoffrey R.; Mak, Raymond H.; Jackman, David M. [Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Brigham and Women' s Hospital, Boston, Massachusetts (United States); Lo, Peter C. [Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Baldini, Elizabeth H.; Johnson, Bruce E. [Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Brigham and Women' s Hospital, Boston, Massachusetts (United States); Chen, Aileen B., E-mail: achen@lroc.harvard.edu [Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Brigham and Women' s Hospital, Boston, Massachusetts (United States)

    2014-07-15

    Purpose: Although palliative chemotherapy is the standard of care for patients with diagnoses of stage IV non-small cell lung cancer (NSCLC), patients with a small metastatic burden, “oligometastatic” disease, may benefit from more aggressive local therapy. Methods and Materials: We identified 186 patients (26% of stage IV patients) prospectively enrolled in our institutional database from 2002 to 2012 with oligometastatic disease, which we defined as 5 or fewer distant metastatic lesions at diagnosis. Univariate and multivariable Cox proportional hazards models were used to identify patient and disease factors associated with improved survival. Using propensity score methods, we investigated the effect of definitive local therapy to the primary tumor on overall survival. Results: Median age at diagnosis was 61 years of age; 51% of patients were female; 12% had squamous histology; and 33% had N0-1 disease. On multivariable analysis, Eastern Cooperate Oncology Group performance status ≥2 (hazard ratio [HR], 2.43), nodal status, N2-3 (HR, 2.16), squamous pathology, and metastases to multiple organs (HR, 2.11) were associated with a greater hazard of death (all P<.01). The number of metastatic lesions and radiologic size of the primary tumor were not significantly associated with overall survival. Definitive local therapy to the primary tumor was associated with prolonged survival (HR, 0.65, P=.043). Conclusions: Definitive local therapy to the primary tumor appears to be associated with improved survival in patients with oligometastatic NSCLC. Select patient and tumor characteristics, including good performance status, nonsquamous histology, and limited nodal disease, may predict for improved survival in these patients.

  2. Non-small-cell lung carcinoma: role of the Notch signaling pathway

    Directory of Open Access Journals (Sweden)

    Barse L

    2015-06-01

    Full Text Available Levi Barse, Maurizio Bocchetta Department of Pathology, Oncology Institute, Loyola University Chicago, Maywood, IL, USA Abstract: Notch signaling plays a pivotal role during embryogenesis. It regulates three fundamental processes: lateral inhibition, boundary formation, and lineage specification. During post-natal life, Notch receptors and ligands control critical cell fate decisions both in compartments that are undergoing differentiation and in pluripotent progenitor cells. First recognized as a potent oncogene in certain lymphoblastic leukemias and mesothelium-derived tissue, the role of Notch signaling in epithelial, solid tumors has been far more controversial. The overall consequence of Notch signaling and which form of the Notch receptor drives malignancy in humans is deeply debated. Most likely, this is due to the high degree of context-dependent effects of Notch signaling. More recently, it has been discovered that Notch (especially Notch-1 can exert different, even opposite effects in the same tissue under differing microenvironmental conditions. Further complicating the understanding of Notch receptors is the recently discovered role for non-canonical Notch signaling. Additionally, the most frequent Notch signaling antagonists used in biological systems have been inhibitors of the transmembrane protease complex γ-secretase, which itself processes a plethora of class one transmembrane proteins and thus cannot be considered a Notch-specific upstream regulator. Here we review the available empirical evidence gathered in recent years concerning Notch receptors and ligands in non-small-cell lung carcinoma (NSCLC. Although an overview of the field reveals seemingly contradicting results, we propose that Notch signaling can be exploited as a therapeutic target in NSCLC and represents a promising complement to the current arsenal utilized to combat this malignancy, particularly in targeting NSCLC tissues under specific environmental

  3. SHP1-mediated cell cycle redistribution inhibits radiosensitivity of non-small cell lung cancer

    International Nuclear Information System (INIS)

    Radioresistance is the common cause for radiotherapy failure in non-small cell lung cancer (NSCLC), and the degree of radiosensitivity of tumor cells is different during different cell cycle phases. The objective of the present study was to investigate the effects of cell cycle redistribution in the establishment of radioresistance in NSCLC, as well as the signaling pathway of SH2 containing Tyrosine Phosphatase (SHP1). A NSCLC subtype cell line, radioresistant A549 (A549S1), was induced by high-dose hypofractionated ionizing radiations. Radiosensitivity-related parameters, cell cycle distribution and expression of cell cycle-related proteins and SHP1 were investigated. siRNA was designed to down-regulate SHP1expression. Compared with native A549 cells, the proportion of cells in the S phase was increased, and cells in the G0/G1 phase were consequently decreased, however, the proportion of cells in the G2/M phase did not change in A549S1 cells. Moreover, the expression of SHP1, CDK4 and CylinD1 were significantly increased, while p16 was significantly down-regulated in A549S1 cells compared with native A549 cells. Furthermore, inhibition of SHP1 by siRNA increased the radiosensitivity of A549S1 cells, induced a G0/G1 phase arrest, down-regulated CDK4 and CylinD1expressions, and up-regulated p16 expression. SHP1 decreases the radiosensitivity of NSCLC cells through affecting cell cycle distribution. This finding could unravel the molecular mechanism involved in NSCLC radioresistance

  4. Silence of fibronectin 1 increases cisplatin sensitivity of non-small cell lung cancer cell line.

    Science.gov (United States)

    Gao, Weiwei; Liu, Ying; Qin, Ruiling; Liu, Daijian; Feng, Qingqing

    2016-07-15

    Fibronectin 1 (FN1) is a member of the glycoprotein family which is widely expressed by multiple cell types and involved in cellular adhesion and migration processes. Recent studies have reported that FN1 might have a role in regulating chemoresistance in tumors. However, the regulation of FN1 on cisplatin resistance in non-small cell lung cancer (NSCLC) has not been investigated. The present study aims to illustrate the effect of FN1 on cisplatin resistance in NSCLC and explore potential mechanisms. In the present study, the mRNA and protein expression levels of FN1 were investigated by RT-PCR and Western blot analysis, respectively, and the 50% inhibitory concentration (IC50) value of cisplatin was measured by MTT assay. Apoptotic ratio and migration were determined using an annexin V-FITC/PI detection kit and a Transwell assay, respectively. The interaction between FN1 and integrin-β1 was evaluated by co-immunoprecipitation assay. The protein expression of β-catenin, cyclin D1 and c-myc were tested using Western blot analysis. The results showed that FN1 was more highly expressed in A549/DDP than in A549 cells, and significantly upregulated by cisplatin treatment in H1299 cells. Knockdown of FN1 reduced the IC50 value of cisplatin, inhibited cell migration and promoted apoptosis. FN1 and integrin-β1 protein directly interacted with each other both in A549 and A549/DDP cells. FN1 silencing suppressed the Wnt/β-catenin signaling pathway, and this effect was dampened by integrin-β1-blocking antibody. Taken together, our findings first suggest that FN1 plays a role in the development of cisplatin resistance in NSCLC, possibly by modulation of β-catenin signaling through interaction with integrin-β1 in NSCLC. PMID:27207836

  5. Impact of Neoadjuvant Radiation on Survival in Stage III Non-Small-Cell Lung Cancer

    International Nuclear Information System (INIS)

    Purpose: The role of surgery in Stage III non-small-cell lung cancer (NSCLC) is controversial. This study was undertaken to assess the impact of neoadjuvant radiation therapy for Stage III NSCLC. Methods and Materials: This was a retrospective study from the Surveillance, Epidemiology, and End Results (SEER) database that included patients who were 18 years and older with NSCLC classified as Stage III and who underwent definitive therapy from 1988 to 2004. Patients were characterized by type of treatment received. Survival functions were estimated by the Kaplan-Meier method, and Cox regression model was used to analyze trends in overall (OS) and cause-specific survival (CSS). Results: A total of 48,131 patients were selected, with a median follow-up of 10 months (range, 0-203 months). By type of treatment, the 3-year OS was 10% with radiation therapy (RT), 37% with surgery (S), 34% with surgery and postoperative radiation (S-RT), and 45% with neoadjuvant radiation followed by surgery (Neo-RT) (p = 0.0001). Multivariable Cox model identified sex, race, laterality, T stage, N stage, and type of treatment as factors affecting survival. Estimated hazard ratios (HR) adjusted for other variables in regression model showed the types of treatment: S (HR, 1.3; 95% confidence interval [CI], 1.2-1.4), S-RT (HR, 1.2; 95% CI, 1.1-1.3), and RT (HR, 2.3; 95% CI, 2.15-2.53) were associated with significantly worse overall survival when compared with Neo-RT (p = 0.0001). Conclusion: This population based study demonstrates that patients with Stage III NSCLC receiving Neo-RT had significantly improved overall survival when compared with other treatment groups.

  6. Prognostic significance of CD44s expression in resected non-small cell lung cancer

    International Nuclear Information System (INIS)

    CD44s is a cell adhesion molecule known to mediate cellular adhesion to the extracellular matrix, a prerequisite for tumor cell migration. CD44s plays an important role in invasion and metastasis of various cancers. In the present study, we sought to determine whether CD44s is involved in clinical outcomes of patients with resected non-small cell lung cancer (NSCLC). Using immunohistochemical staining, we investigated CD44s protein expression using tissue array specimens from 159 patients with resected NSCLC (adenocarcinoma (AC; n = 82) and squamous cell carcinoma (SCC; n = 77). Additionally, the immunoreactivity of cyclooxygenase (COX)-2 was also studied. The clinicopathological implications of these molecules were analyzed statistically. High CD44s expression was detected more frequently in NSCLC patients with SCC (66/72; 91.7%) than in those with AC histology (P <0.001). Additionally, high CD44s expression was significant correlated with more advanced regional lymph node metastasis (P = 0.021). In multivariate analysis of survival in NSCLC patients with AC histology, significant predictors were lymph node metastasis status (P < 0.001), high-grade tumor differentiation (P = 0.046), and high CD44s expression (P = 0.014). For NSCLC patients with SCC histology, the significant predictor was a more advanced tumor stage (P = 0.015). No significant association was found between CD44s and clinical outcome (P = 0.311). High CD44s expression was a negative prognostic marker with significance in patients with resected NSCLC, particularly those with AC histology, and was independent of tumor stage

  7. Respiration-averaged CT for attenuation correction in non-small-cell lung cancer

    International Nuclear Information System (INIS)

    Breathing causes artefacts on PET/CT images. Cine CT has been used to reduce respiratory artefacts by acquiring multiple images during a single breathing cycle. The aim of this prospective study in non-small-cell lung cancer (NSCLC) patients was twofold. Firstly, we sought to compare the motion artefacts in PET/CT images attenuation-corrected with helical CT (HCT) and with averaged CT (ACT), which provides an average of cine CT images. Secondly, we wanted to evaluate the differences in maximum standardized uptake values (SUVmax) between HCT and ACT. Enrolled in the study were 80 patients with NSCLC. PET images attenuation-corrected with HCT (PET/HCT) and with ACT (PET/ACT) were obtained in all patients. Misregistration was evaluated by measurement of the curved photopenic area in the lower thorax of the PET images for all patients and direct measurement of misregistration for selected lesions. SUVmax was measured separately at the primary tumours, regional lymph nodes, and background. A total of 80 patients with NSCLC were included. Significantly lower misregistrations were observed in PET/ACT images than in PET/HCT images (below-thoracic misregistration 0.25±0.58 cm vs. 1.17±1.17 cm, pmax were noted in PET/ACT images than in PET/HCT images in the primary tumour (pmax in PET/ACT images was higher by 0.35 for the main tumours and 0.34 for lymph nodes. Due to its significantly reduced misregistration, PET/ACT provided more reliable SUVmax and may be useful in treatment planning and monitoring the therapeutic response in patients with NSCLC. (orig.)

  8. Dose escalation with stereotactic body radiation therapy boost for locally advanced non small cell lung cancer

    International Nuclear Information System (INIS)

    Low survival outcomes have been reported for the treatment of locally advanced non small cell lung cancer (LA-NSCLC) with the standard of care treatment of concurrent chemoradiation (cCRT). We present our experience of dose escalation using stereotactic body radiosurgery (SBRT) following conventional cCRT for patients with LA-NSCLC. Sixteen patients with a median age of 67.5 treated with fractionated SBRT from 2010 to 2012 were retrospectively analyzed. Nine (56%) of the patients had stage IIIB, 6 (38%) has stage IIIA, and 1 (6%) had recurrent disease. Majority of the patients (63%) presented with N2 disease. All patients had a PET CT for treatment planning. Patients received conventional cCRT to a median dose of 50.40 Gy (range 45–60) followed by an SBRT boost with an average dose of 25 Gy (range 20–30) given over 5 fractions. With a median follow-up of 14 months (range, 1–14 months), 1-year overall survival (OS), progression free survival (PFS), local control (LC), regional control (RC), and distant control (DC) rates were, 78%, 42%, 76%, 79%, and 71%, respectively. Median times to disease progression and regional failure were 10 months and 18 months, respectively. On univariate analysis, advanced age and nodal status were worse prognostic factors of PFS (p < 0.05). Four patients developed radiation pneumonitis and one developed hemoptysis. Treatment was interrupted in one patient who required hospitalization due to arrhythmias and pneumonia. Risk adaptive dose escalation with SBRT following external beam radiotherapy is possible and generally tolerated treatment option for patients with LA-NSCLC

  9. Definitive Primary Therapy in Patients Presenting With Oligometastatic Non-Small Cell Lung Cancer

    International Nuclear Information System (INIS)

    Purpose: Although palliative chemotherapy is the standard of care for patients with diagnoses of stage IV non-small cell lung cancer (NSCLC), patients with a small metastatic burden, “oligometastatic” disease, may benefit from more aggressive local therapy. Methods and Materials: We identified 186 patients (26% of stage IV patients) prospectively enrolled in our institutional database from 2002 to 2012 with oligometastatic disease, which we defined as 5 or fewer distant metastatic lesions at diagnosis. Univariate and multivariable Cox proportional hazards models were used to identify patient and disease factors associated with improved survival. Using propensity score methods, we investigated the effect of definitive local therapy to the primary tumor on overall survival. Results: Median age at diagnosis was 61 years of age; 51% of patients were female; 12% had squamous histology; and 33% had N0-1 disease. On multivariable analysis, Eastern Cooperate Oncology Group performance status ≥2 (hazard ratio [HR], 2.43), nodal status, N2-3 (HR, 2.16), squamous pathology, and metastases to multiple organs (HR, 2.11) were associated with a greater hazard of death (all P<.01). The number of metastatic lesions and radiologic size of the primary tumor were not significantly associated with overall survival. Definitive local therapy to the primary tumor was associated with prolonged survival (HR, 0.65, P=.043). Conclusions: Definitive local therapy to the primary tumor appears to be associated with improved survival in patients with oligometastatic NSCLC. Select patient and tumor characteristics, including good performance status, nonsquamous histology, and limited nodal disease, may predict for improved survival in these patients

  10. Response to gefitinib and erlotinib in Non-small cell lung cancer: a retrospective study

    International Nuclear Information System (INIS)

    In Non-small cell lung cancer (NSCLC), an overactive epidermal growth factor receptor (EGFR) pathway is a component of the malignant phenotype. Two tyrosine kinase inhibitors (TKIs) of EGFR, gefinitib and erlotinib, have been used with variable benefit. We have analyzed outcome data of a population of NSCLC patients that received these TKIs to determine the benefit derived and to define the clinical and molecular parameters that correlate with response. Tumor tissue from a subgroup of these patients was analyzed by immunohistochemistry to measure the expression level of EGFR and four activated (phosphorylated) members of the pathway, pEGFR, pERK, pAKT, and pSTAT3. Erlotinib was slightly superior to gefitinib in all measures of response, although the differences were not statistically significant. The most robust clinical predictors of time to progression (TTP) were best response and rash (p < 0.0001). A higher level of pEGFR was associated with longer TTP, while the total EGFR level was not associated with response. Higher levels of pAKT and pSTAT3 were also associated with longer TTP. In contrast, a higher level of pERK1/2 was associated with shorter TTP. These observations suggest the hypothesis that tumor cells that have activated EGFR pathways, presumably being utilized for survival, are clinically relevant targets for pathway inhibition. An accurate molecular predictive model of TKI response should include activated members of the EGFR pathway. TKIs may be best reserved for tumors expressing pEGFR and pAKT or pSTAT, and little pERK. In the absence of molecular predictors of response, the appearance of a rash and a positive first scan are good clinical indicators of response

  11. Exosomal proteins as potential diagnostic markers in advanced non-small cell lung carcinoma

    DEFF Research Database (Denmark)

    Jakobsen, Kristine Raaby; Paulsen, Birgitte Sandfeld; Bæk, Rikke;

    2015-01-01

    Background: Lung cancer is one of the leading causes of cancer-related death. At the time of diagnosis, more than half of the patients will have disseminated disease and, yet, diagnosing can be challenging. New methods are desired to improve the diagnostic work-up. Exosomes are cell-derived vesic......Background: Lung cancer is one of the leading causes of cancer-related death. At the time of diagnosis, more than half of the patients will have disseminated disease and, yet, diagnosing can be challenging. New methods are desired to improve the diagnostic work-up. Exosomes are cell...... control subjects based on the differential display of exosomal protein markers. Methods: Plasma was isolated from 109 NSCLC patients with advanced stage (IIIa–IV) disease and 110 matched control subjects initially suspected of having cancer, but diagnosed to be cancer free. The Extracellular Vesicle Array...... (EV Array) was used to phenotype exosomes directly from the plasma samples. The array contained 37 antibodies targeting lung cancer-related proteins and was used to capture exosomes, which were visualised with a cocktail of biotin-conjugated CD9, CD63 and CD81 antibodies. Results: The EV Array...

  12. Exosomal proteins as potential diagnostic markers in advanced non-small cell lung carcinoma

    DEFF Research Database (Denmark)

    Jakobsen, Kristine R; Paulsen, Birgitte S; Bæk, Rikke;

    2015-01-01

    BACKGROUND: Lung cancer is one of the leading causes of cancer-related death. At the time of diagnosis, more than half of the patients will have disseminated disease and, yet, diagnosing can be challenging. New methods are desired to improve the diagnostic work-up. Exosomes are cell-derived vesic......BACKGROUND: Lung cancer is one of the leading causes of cancer-related death. At the time of diagnosis, more than half of the patients will have disseminated disease and, yet, diagnosing can be challenging. New methods are desired to improve the diagnostic work-up. Exosomes are cell...... control subjects based on the differential display of exosomal protein markers. METHODS: Plasma was isolated from 109 NSCLC patients with advanced stage (IIIa-IV) disease and 110 matched control subjects initially suspected of having cancer, but diagnosed to be cancer free. The Extracellular Vesicle Array...... (EV Array) was used to phenotype exosomes directly from the plasma samples. The array contained 37 antibodies targeting lung cancer-related proteins and was used to capture exosomes, which were visualised with a cocktail of biotin-conjugated CD9, CD63 and CD81 antibodies. RESULTS: The EV Array...

  13. Quality of life in patients receiving curative radiation therapy for non-small cell lung cancer

    International Nuclear Information System (INIS)

    Purpose/Objective: The purpose of this study was to determine if perceptions of quality of life (QOL) change in patients with non-small cell lung cancer (NSCLC) receiving curative radiation therapy (XRT) alone or in combination with other treatment modalities. Materials and Methods: The Functional Assessment of Cancer Therapy-Lung (FACT-L) (Cella, 1994), a 37-item Likert-type questionnaire that measures QOL in lung cancer patients, was used to assess QOL in NSCLC patients receiving curative XRT. A descriptive, longitudinal design with repeated measures was utilized for this study, and subjects were selected using a consecutive sampling technique. Subjects completed the FACT-L prior to beginning XRT, during the fourth week of XRT, and one and four months after completion of XRT. Results: The sample included 23 patients with Stage IIIA (n=8, 35%) or IIIB (n=15, 65%) NSCLC. Treatment regimens included XRT alone (n=1, 4%), postoperative XRT (n=9, 39%), postoperative XRT with concurrent chemotherapy (n=1, 4%), induction chemotherapy followed by XRT with concurrent chemotherapy (n=4, 17%), and XRT with concurrent chemotherapy (n=8, 35%). Internal consistency reliability was adequate for the FACT-L (r=.85-.96) over the four measures. The research question, do perceptions of QOL change in NSCLC patients receiving XRT, was examined using a multivariate approach to analysis of variance (ANOVA) for repeated measures. QOL was significantly less during XRT than prior to XRT (p=.006, power=.83) and was significantly greater one month after XRT than prior to XRT (p=.01, power=.77) or during XRT (p≤.0005, power=.99). There was no significant difference between QOL at one and four months after completion of XRT. No correlation was found between QOL and treatment regimen. Conclusions: These preliminary findings suggest that there is a significant decrease in QOL in NSCLC patients during treatment with XRT, but QOL is significantly greater following XRT than it was prior to or

  14. Carbon ion radiotherapy in a hypofraction regimen for stage I non-small cell lung cancer

    International Nuclear Information System (INIS)

    From 1994 to 1999, we conducted a phase I/II clinical trial for patients with stage I non-small cell lung cancer (NSCLC) using carbon ion beams alone, demonstrating optimal doses of 90.0 GyE in 18 fractions over 6 weeks (Protocol no.9303) and 72.0 GyE in 9 fractions over 3 weeks (Protocol no.9701), which led to more than 95% local control with minimal pulmonary damage. In the present study, the total dose was fixed at 72.0 GyE in 9 fractions over 3 weeks (Protocol no.9802), and at 52.8 GyE for stage IA and 60.0 GyE for stage IB in 4 fractions in 1 week (Protocol no.0001). Following this schedule, we conducted a phase II clinical trial for stage I NSCLC from 1999 to 2003. We also conducted a phase I/II single fractionation clinical trial (Protocol no.0201) as a dose escalation study. The total dose was initially 28.0 GyE in 2003, and it was increased to 46.0 GyE in 2008. This article describes the intermediate steps. Most targets were irradiated from four oblique directions. A respiratory-gated irradiation system was used for all sessions. Local control and survival were assessed by the Kaplan-Meier method. For statistical testing, the Log-rank test was used. The local control rate for all patients (no.9802 and no.0001) was 91.5%, and for those with T1 and T2 tumors was 96.3% and 84.7%, respectively. While there was a significant difference (p=0.0156) in the tumor control rate between patients with T1 and T2 tumors, there was no significant difference (P=0.1516) between squamous cell carcinomas and non-squamous cell carcinomas. The 5-year cause-specific survival rate was 67.0% (IA: 84.4, IB: 43.7), and overall survival was 45.3% (IA: 53.9, IB: 34.2). No adverse effects greater than grade 2 occurred in the lungs. In a single fractionation trial, the 3-year local control rate for 117 patients was 81.9%, and the control rates for patients with T1 and T2 tumors were 84.7% and 78.0%, respectively. No adverse effects greater than grade 2 occurred in the lungs. Carbon beam

  15. Carbon ion radiotherapy in a hypofraction regimen for stage I non-small cell lung cancer

    International Nuclear Information System (INIS)

    From 1994 to 1999, we conducted a phase I/II clinical trial for patients with stage I non-small cell lung cancer (NSCLC) by using carbon ion beams alone, demonstrating optimal doses of 90.0 GyE in 18 fractions over 6 weeks (Protocol no.9303) and 72.0 GyE in 9 fractions over 3 weeks (Protocol no.9701), which achieved a more than 95% local control rate with minimal pulmonary damage. In the present study, the total dose was fixed at 72.0 GyE in 9 fractions over 3 weeks (Protocol no.9802), and at 52.8 GyE for stage IA and 60.0 GyE for stage IB in 4 fractions in 1 week (Protocol no.0001). Following this schedule, we conducted a phase II clinical trial for stage I NSCLC from 1999 to 2003. We also conducted a phase I/II single fractionation clinical trial (Protocol no.0201) as a dose escalation study. The total dose was initially 28.0 GyE in 2003, and it was increased to 50.0 GyE in 2011. This article describes the intermediate steps. Most targets were irradiated from four oblique directions. A respiratory-gated irradiation system was used for all sessions. Local control and survival were assessed by the Kaplan-Meier method. For statistical testing, the Log-rank test was used. The local control rate for all patients (no.9802 and no.0001) was 91.5%, and those for T1 and T2 tumors were 96.3% and 84.7%, respectively. While there was a significant difference (p=0.0156) in the tumor control rates between T1 and T2 tumors, there was no significant difference (P=0.1516) between squamous cell carcinomas and non-squamous cell carcinomas. The 5-year cause-specific survival rate was 67.0% (IA: 84.4, IB: 43.7), and the overall survival was 45.3% (IA: 53.9, IB: 34.2). No adverse effects greater than grade 2 occurred in the lungs. In a single fractionation trial, the 5-year local control rate for 131 patients was 80.5%, and the control rates for T1 and T2 tumors were 82.8% and 78.4%, respectively. No adverse effects greater than grade 2 occurred in the lungs. Carbon beam radiotherapy

  16. Carbon ion radiotherapy in hypofraction regimen for stage I non-small cell lung cancer

    International Nuclear Information System (INIS)

    From 1994 to 1999, we conducted a phase I/II clinical trial for stage I non-small cell lung cancer (NSCLC) by using carbon ion beams alone, demonstrating optimal doses of 90.0 GyE in 18 fractions over 6 weeks (Protocol no.9303) and 72.0 GyE in 9 fractions over 3 weeks (Protocol no.9701) for achieving more than 95% local control with minimal pulmonary damage. In the present study, the total dose was fixed at 72.0 GyE in 9 fractions over 3 weeks (Protocol no.9802), and at 52.8 GyE for stage IA and 60.0 GyE for stage IB in 4 fractions in 1 week (Protocol no.0001). Following this schedule, we conducted a phase II clinical trial for stage I NSCLC from 1999 to 2003. We also conducted a phase I/II single fractionation clinical trial (Protocol no.0201), a dose escalation study. The total dose was initially 28.0 GyE in 2003, and it was raised to 44.0 GyE in 2007. This article describes the intermediate steps. Most targets were irradiated from four oblique directions. A respiratory-gated irradiation system was used for all sessions. Local control and survival were assessed by Kaplan-Meier method. For statistical testing, the Log-rank test was used. The local control rate for all patients (no.9802 and no.0001) was 91.5%, and those for T1 and T2 tumors were 96.3% and 84.7%, respectively. While there was a significant difference (p=0.0156) in tumor control rate between T1 and T2, there was no significant difference (P=0.1516) between squamous cell carcinomas and non-squamous cell carcinomas. The 5-year cause-specific survival rate was 67.0% (IA: 84.4, IB: 43.7), and overall survival was 45.3% (IA: 53.9, IB: 34.2). No adverse effects greater than grade 2 occurred in the lung. In a single fractionation trial, the local control rate for all 72 patients was 89.3%, and the control rates for T1 and T2 tumors were 94.6% and 78.7%, respectively. No adverse effects greater than grade 2 occurred in the lung. Carbon beam radiotherapy, an excellent new modality in terms of high quality of

  17. FoxM1 mediated resistance to gefitinib in non-small-cell lung cancer cells

    Institute of Scientific and Technical Information of China (English)

    Nuo XU; Xin ZHANG; Xun WANG; Hai-yan GE; Xiao-ying WANG; David GARFIELD; Ping YANG; Yuan-lin SONG; Chun-xue BAI

    2012-01-01

    Gefitinib is effective in only approximately 20% of patients with non-small-cell lung cancer (NSCLC),and the underlying mechanism remains unclear.FoxM1 is upregulated in NSCLC and associated with a poor prognosis in NSCLC patients.In this study,we examined the possible role of FoxM1 in gefitinib resistance and the related mechanisms.Methods:Gefitinib resistant human lung adenocarcinoma cell line SPC-A-1 and gefitinib-sensitive human lung mucoepidermoid carcinoma cell line NCI-H292 were used.mRNA and protein expression of FoxM1 and other factors were tested with quantitative RT PCR and Western blot analysis.RNA interference was performed to suppress FoxM1 expression in SPC-A-1 cells,and lentiviral infection was used to overexpress FoxM1 in H292 cells.MTT assay and flow cytometry were used to examine the proliferation and apoptosis of the cells.Results:Treatment of SPC-A-1 cells with gefitinib (1 and 10 μmol/L) upregulated the expression of FoxM1 in time- and concentrationdependent manners,while gefrtinib (1 μmol/L) downregulated in H292 cells.In SPC-A-1 cells treated with gefitinib (1 μmol/L),the expression of several downstream targets of FoxM1,including survivin,cyclin B1,SKP2,PLK1,Aurora B kinase and CDC25B,were significantly upregulated.Overexpression of FoxM1 increased the resistance in H292 cells,while attenuated FoxM1 expression restored the sensitivity to gefitinib in SPC-A-1 cells by inhibiting proliferation and inducing apoptosis.Conclusion:The results suggest that FoxM1 plays an important role in the resistance of NSCLC cells to gefitinib in vitro.FoxM1 could be used as a therapeutic target to overcome the resistance to gefitinib.

  18. Clinical application of radiofrequency ablation combined with bronchial artery infusion of docetaxel in treating non-small cell lung cancer

    International Nuclear Information System (INIS)

    Objective: To discuss the clinical application of radiofrequency ablation combined with bronchial artery infusion of docetaxel in treating non-small cell lung cancer and to summarize the experience of using this therapy in clinical practice. Methods: Radiofrequency ablation was performed in twenty-one patients with lung cancer. The diagnosis was confirmed by CT-guided percutaneous needle biopsy or bronchoscopic biopsy in all patients. One week after radiofrequency ablation treatment, bronchial artery infusion of docetaxel was conducted. The therapeutic results were observed and evaluated. Results: After the treatment, the lesion's size was markedly reduced and the clinical symptoms were dramatically improved in all patients. Conclusion: Radiofrequency ablation combined with bronchial artery infusion of docetaxel is a safe, effective and simple technique with excellent therapeutic results for the treatment of non-small cell lung cancer. It is really worth popularizing this technique in clinical practice. (authors)

  19. [3rd generation's TKI in lung cancer non-small cell EGFR-mutated having acquired a secondary T790M resistance].

    Science.gov (United States)

    Brosseau, Solenn; Viala, Marie; Varga, Andréa; Planchard, David; Besse, Benjamin; Soria, Jean-Charles

    2015-09-01

    Activating EGFR mutations discovery and efficacy of 1st generation tyrosine kinase inhibitors (TKI), such as erlotinib or gefitinib, inaugurated the beginning of personalized medicine in the treatment of EGFR-mutated non-small cell lung cancer (NSCLC). However, all patients showed a tumor progression of 10 to 16 months after the onset of TKI therapy related to molecular resistance mechanisms as T790M mutation. Till now, patients suffering from EGFR-mutated NSCLC with acquired resistance have conventional treatment options. Two new 3rd generations' TKI, AZD9291 and rociletinib, are currently being studied in phases 1-3 studies. Preliminary results show relevant therapeutic properties in patients with T790M mutated-EGFR NSCLC. This review aims to highlight these new molecules, their effectiveness and their clinical toxicities in the treatment of advanced stages of NSCLC expressing the T790M mutation. PMID:26235419

  20. Deletion and Mutation of WWOX Exons 6-8 in Human Non-small Cell Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    To examine the deletion and point mutation of WWOX (WW domain containing oxidoreductase) exons 6-8 in human non-small cell lung cancer and their possible relationship with pathological stages, tumor tissues and the corresponding normal tissues were obtained from 44 Chinese patients who had undergone surgery for non-small cell lung cancer. RNA was extracted from each sample and deletion and mutation of WWOX exons 6-8 were analyzed by RT-PCR and DNA sequencing. Our results showed that 28 of 44 (63.6 %) lung cancer samples showed loss of WWOX exons 6-8 transcript and the deletion was detected in only 3 of 44 (6.8 %) corresponding adjacent normal tissues (P<0.05). The transcript sequencing analyses of the 16 lung cancer samples without transcript loss of WWOX exons 6-8 revealed no difference from the sequence of GenBank. Moreover, the deletion of WWOX exons 6-8 was significantly higher in the smokers when compared with the non-smokers. It is also higher in the men and squamous carcinomas than in women and adenocarcinomas (P<0.05). The deletion, however, was not found to be associated with pathological stages of the tumors. Our study documented a high incidence of deletion of WWOX exons 6-8 in non-small cell lung cancer in Chinese patients and suggested that the frequent loss of WWOX exons 6-8 might play an important role in the tumorigenesis of non-small cell lung cancer in Chinese. WWOX exons 6-8 may serves as a candidate molecular target of smoking carcinogenesis, and point mutation is not a predominant way of alteration of WWOX exons 6-8.

  1. The Role of MET Receptor Tyrosine Kinase in Non-Small Cell Lung Cancer and Clinical Development of Targeted Anti-MET Agents

    OpenAIRE

    Robinson, Kyle W.; Sandler, Alan B.

    2013-01-01

    The role of MET in the pathophysiology of non-small cell lung cancer and in acquired resistance to epidermal growth factor receptor inhibitors is summarized. An update on progress in the clinical development of inhibitors of MET for treatment of non-small cell lung cancer is provided.

  2. Influence of clinical characteristics on radiation therapy effect in patients with stage III non-small-cell lung cancer at non-standard fractionation modes

    International Nuclear Information System (INIS)

    A comparative analysis of different modes of radiotherapy fractionation with modification using etoposide and cisplatin in patients with non-small-cell lung cancer is given. The general condition of the patient, the form of the macroscopic tumor growth, the degree of tumor regression are prognostically significant for stage III non-small-cell lung cancer

  3. 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

  4. 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

  5. Expression of T cell factor-4 in non-small-cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    LI Chun-yan; WANG Yan; CUI Ze-shi; WANG En-hua

    2005-01-01

    Background T cell factor- 4 (TCF- 4) plays an important role in development and carcinogenesis. Recently, the role of TCF- 4 has been described in colon cancer and other cancers. However, whether TCF- 4 plays a similar role in lung cancer is unknown. To answer this question, we studied the expression of TCF- 4 protein and mRNA in non-small-cell lung cancer (NSCLC) and the relation of TCF- 4 expression pattern to histological type and cell differentiation. Methods Tissue samples from sixty cases of pathologically diagnosed NSCLC and eight normal tissue samples were obtained between September 2001 and March 2003. Immunohistochemistry was used to investigate the distribution of TCF- 4 protein. The staining patterns of the tumors were divided into 4 categories: nuclear staining alone or nuclear staining greater than cytoplasmic staining; cytoplasmic staining or cytoplasmic staining greater than nuclear staining; equal nuclear and cytoplasmic staining; no nuclear staining or cytoplasmic staining. The integrated optical density (OD) values of all sections were analyzed by UIC MetaMorph image analysis software. The expression of TCF- 4 mRNA was detected by one-step reverse transcription-polymerase chain reaction (RT-PCR). The integrated density values of the PCR products were analyzed semi-quantitatively.Results Immunohistochemistry showed that there was no expression of TCF- 4 in normal tissue. However, TCF- 4 was expressed in 86.7% (52/60) of NSCLC samples, mainly in the nuclei of tumor cells. Furthermore, there was a significant difference in TCF- 4 localization patterns between squamous cell carcinomas and adenocarcinomas (P<0.05). The integrated OD values of TCF- 4 expression was significantly higher in tumors with moderate-poor cell differentiation than in well differentiated tumors (51.63±6.67 vs 46.13±12.31, P<0.01). There was no TCF- 4 mRNA expression in normal tissue. However, 63.9% (23/36) of carcinoma samples expressed TCF- 4 mRNA. TCF- 4 mRNA expression was

  6. Role of Metallothionein1H in Cisplatin Resistance of Non-Small Cell Lung Cancer Cells

    Institute of Scientific and Technical Information of China (English)

    Xin-fang Hou; Qing-xia Fan; Liu-xing Wang; Shi-xin Lu

    2009-01-01

    Objective: Despite platinum-based adjuvant chemotherapy has improved greatly patients' outcomes, drug resistance poses a major impediment to the successful use of such an effective agent. Metallothioneins(MTs) are known to play putative roles in cancer cell proliferation, apoptosis, differentiation, drug resistance and prognosis. The present studiy was to investigte the role of metallethioein1H(MT1H) in cisplatin resistance of human non-small cell lung cancer(NSCLC) cell lines in vitro or its possible molecular mechanisms. Methods: MT1H mRNA expression in A549 and A549/DDP cells was detected by RT-PCR. A recombinant eukaryotic expression plasmid pcDNA3.1(-)-MT1H was constructed and transfected into A549 cells which express no MT1H. MT1H siRNA was transfected into A549/DDP cells which express MT1H highly. MT1H expression was detected by RT-PCR and Immunoblot. The chemosensitivity to cisplatin was assessed by MTT assay. Apoptosis rate was determined by Tunel and FCM. Bcl-2 and Bax were determined by immunohistochemistry. Results: MT1H mRNA was expressed in A549/DDP but not in A549. After transfection of MT1H, MT1H expression was enhanced and the chemosensitivity to cisplatin was decreased in A549 cells. Inversely, after transfection of MT1H siRNA, MT1H expression was decreased and the chemosensitivity to cisplatin was increased in A549/DDP. The apoptosis rate induced by cisplatin was increased and Bcl-2 was down-regulated but Bax showed little change in A549/DDP cells interferred with MT1H siRNA. Conclusion: MT1H overexpression can promote drug resistance in A549 cells . Down-regulation of MT1H interfered with siRNA can effectively reverses the drug resistance in A549/DDP cells by down-regulating the expression of Bcl-2 and increasing cisplatin induced apoptosis. SiRNA targeting MT1H combined with chemotherapy may be a very promising strategy for treatment of lung cancer.

  7. Increased expression of the lncRNA PVT1 promotes tumorigenesis in non-small cell lung cancer

    OpenAIRE

    Yang, Yan-Rong; Zang, Shu-Zhi; Zhong, Chun-Lei; Li, Yun-Xia; Zhao, Sha-Sha; Feng, Xian-Jun

    2014-01-01

    Introduction: Non-small cell lung cancer (NSCLC) is the major cause of cancer death worldwide. Increasing evidence shows that long non coding RNAs (lncRNAs) are widely involved in the development and progression of NSCLC. lncRNA PVT1 in several cancers has been studied, its role in lung cancer remains unknown. Our studies were designed to investigate the expression, biological role and clinical significance of PVT1 in lung cancer. Methods: lncRNA PVT1 expression in 82 NSCLC tissues and 3 lung...

  8. DNA methylation-based biomarkers for early detection of non-small cell lung cancer: an update

    OpenAIRE

    Laird-Offringa Ite A; Alonzo Todd A; Anglim Paul P

    2008-01-01

    Abstract Lung cancer is the number one cancer killer in the United States. This disease is clinically divided into two sub-types, small cell lung cancer, (10–15% of lung cancer cases), and non-small cell lung cancer (NSCLC; 85–90% of cases). Early detection of NSCLC, which is the more common and less aggressive of the two sub-types, has the highest potential for saving lives. As yet, no routine screening method that enables early detection exists, and this is a key factor in the high mortalit...

  9. Hyperfractionated Radiotherapy and Concurrent Chemotherapy for Stage III Unascertainable Non Small Cell Lung Cancer : Preliminary Report for Response and Toxicity

    International Nuclear Information System (INIS)

    Lung cancer study group at Asan Medical Center has conducted the second prospective study to determine the efficacy and feasibility of MVP chemotherapy with concurrent hyperfractionated radiotherapy for patients with stage III unresectable non-small cell lung cancer(NSCLC). All eligible patients with stage III unresectable NSCLC were treated with hyperfractionated radiotherapy( 120 cGy/fx BID, 6480 cGY/54fx) and concurrent 2 cycles of MVP(Motomycin C 6 mg/m2 , d2 and d29, Vinblastin 6 mg/m2 , d2 and d29, Cisplatin 6 mg/m2 , d1 and d28) chemotherapy. Between Aug. 1993 and Nov. 1994, 62 patients entered this study ; 6(10%) had advanced stage IIIa and 56(90%) had IIIb disease including 1 with pleural effusion and 10 with supraclavicular metastases. Among 62 Patients, 48(77%) completed planned therapy. Fourteen patients refused further treatment during chemoradiotherapy. Of 46 patients evaluable for response, 34(74%) showed major response including 10(22%) with complete and 24(52%) with partial responses. Of 48 patients evaluable for toxicity, 13(27%) showed grade IV hematologic toxicity but treatment delay did not exceed 5 days. Two patients died of sepsis during chemoradiotherapy. Server weight(more than 10%) occurred in 9 patients(19%) during treatment. Nine patients(19%) developed radiation pneumonitis. Six of these patients had grad I(mild) pneumonitis with radiographic changes within the treatment fields. Three other patients had grade II pneumonitis, but none of theses patients had continuous symptoms after steroid treatment. Concurrent chemoradiotherapy for patients with advanced NSCLC was well tolerated with acceptable toxicity and achieved higher response rates than the first study, but rather low compliance rate(7%) in this study is worrisome. We need to improve nutritional support during treatment and to use G-CSF to improve leukopenia and if necessary, supportive care will given as in patients. Longer follow-up and larger sample size is needed to observe

  10. Validation of an elastic registration technique to estimate anatomical lung modification in Non-Small-Cell Lung Cancer Tomotherapy

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    Persano Diego

    2011-04-01

    Full Text Available Abstract Background The study of lung parenchyma anatomical modification is useful to estimate dose discrepancies during the radiation treatment of Non-Small-Cell Lung Cancer (NSCLC patients. We propose and validate a method, based on free-form deformation and mutual information, to elastically register planning kVCT with daily MVCT images, to estimate lung parenchyma modification during Tomotherapy. Methods We analyzed 15 registrations between the planning kVCT and 3 MVCT images for each of the 5 NSCLC patients. Image registration accuracy was evaluated by visual inspection and, quantitatively, by Correlation Coefficients (CC and Target Registration Errors (TRE. Finally, a lung volume correspondence analysis was performed to specifically evaluate registration accuracy in lungs. Results Results showed that elastic registration was always satisfactory, both qualitatively and quantitatively: TRE after elastic registration (average value of 3.6 mm remained comparable and often smaller than voxel resolution. Lung volume variations were well estimated by elastic registration (average volume and centroid errors of 1.78% and 0.87 mm, respectively. Conclusions Our results demonstrate that this method is able to estimate lung deformations in thorax MVCT, with an accuracy within 3.6 mm comparable or smaller than the voxel dimension of the kVCT and MVCT images. It could be used to estimate lung parenchyma dose variations in thoracic Tomotherapy.

  11. Validation of an elastic registration technique to estimate anatomical lung modification in Non-Small-Cell Lung Cancer Tomotherapy

    International Nuclear Information System (INIS)

    The study of lung parenchyma anatomical modification is useful to estimate dose discrepancies during the radiation treatment of Non-Small-Cell Lung Cancer (NSCLC) patients. We propose and validate a method, based on free-form deformation and mutual information, to elastically register planning kVCT with daily MVCT images, to estimate lung parenchyma modification during Tomotherapy. We analyzed 15 registrations between the planning kVCT and 3 MVCT images for each of the 5 NSCLC patients. Image registration accuracy was evaluated by visual inspection and, quantitatively, by Correlation Coefficients (CC) and Target Registration Errors (TRE). Finally, a lung volume correspondence analysis was performed to specifically evaluate registration accuracy in lungs. Results showed that elastic registration was always satisfactory, both qualitatively and quantitatively: TRE after elastic registration (average value of 3.6 mm) remained comparable and often smaller than voxel resolution. Lung volume variations were well estimated by elastic registration (average volume and centroid errors of 1.78% and 0.87 mm, respectively). Our results demonstrate that this method is able to estimate lung deformations in thorax MVCT, with an accuracy within 3.6 mm comparable or smaller than the voxel dimension of the kVCT and MVCT images. It could be used to estimate lung parenchyma dose variations in thoracic Tomotherapy

  12. Evaluation of safety and efficacy of tivantinib in the treatment of inoperable or recurrent non-small-cell lung cancer

    International Nuclear Information System (INIS)

    Tivantinib is a selective, oral, non-ATP-competitive, small molecule inhibitor of the c-Met receptor, tyrosine kinase, which is implicated at different levels of tumor cell migration, invasion, proliferation, and metastasis. Tivantinib has shown antitumor activity in various human tumor cell lines and in xenograft models of human cancers, including non-small-cell lung cancer. Few therapeutic options are available at present for advanced non-small-cell lung cancer, so there is a pressing need for new therapeutic strategies to improve response and survival. Amplification of Met has been reported in more than 20% of lung tumors that have acquired resistance to epidermal growth factor receptor inhibitors, implying that treatment of these tumors with a c-Met inhibitor should overcome resistance. Tivantinib has shown interesting and promising results in advanced non-small-cell lung cancer and appears to be well tolerated, either alone or in combination with other drugs. An interesting additional feature is the ability of the drug to delay development of new metastasis, in agreement with the proposed role of Met in this particular setting

  13. Prognostic significance of MCM2, Ki-67 and gelsolin in non-small cell lung cancer

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    Huberman Joel

    2006-08-01

    Full Text Available Abstract Background Uncontrolled proliferation and increased motility are hallmarks of neoplastic cells, therefore markers of proliferation and motility may be valuable in assessing tumor progression and prognosis. MCM2 is a member of the minichromosome maintenance (MCM protein family. It plays critical roles in the initiation of DNA replication and in replication fork movement, and is intimately related to cell proliferation. Ki-67 is a proliferation antigen that is expressed during all but G0 phases of the cell cycle. Gelsolin is an actin-binding protein that regulates the integrity of the actin cytoskeletal structure and facilitates cell motility. In this study, we assessed the prognostic significance of MCM2 and Ki-67, two markers of proliferation, and gelsolin, a marker of motility, in non-small cell lung cancer (NSCLC. Methods 128 patients with pathologically confirmed, resectable NSCLC (stage I-IIIA were included. Immunohistochemistry was utilized to measure the expressions of these markers in formalin-fixed, paraffin-embedded tumor tissues. Staining and scoring of MCM2, Ki-67 and gelsolin was independently performed. Analyses were performed to evaluate the prognostic significance of single expression of each marker, as well as the prognostic significance of composite expressions of MCM2 and gelsolin. Cox regression and Kaplan-Meier survival analysis were used for statistical analysis. Results Of the three markers, higher levels of gelsolin were significantly associated with an increased risk of death (adjusted RR = 1.89, 95% CI = 1.17–3.05, p = 0.01, and higher levels of MCM2 were associated with a non-significant increased risk of death (adjusted RR = 1.36, 95% CI = 0.84–2.20, p = 0.22. Combined, adjusted analyses revealed a significantly poor prognostic effect for higher expression of MCM2 and gelsolin compared to low expression of both biomarkers (RR = 2.32, 95% CI = 1.21–4.45, p = 0.01. Ki-67 did not display apparent prognostic

  14. Prognostic significance of thymidylate synthase in postoperative non-small cell lung cancer patients

    Directory of Open Access Journals (Sweden)

    Zhao HY

    2014-07-01

    Full Text Available Hong-Yun Zhao,1,* Guo-Wei Ma,1,* Ben-Yan Zou,1,* Mei Li,1 Su-Xia Lin,1 Li-Ping Zhao,2 Ying Guo,1 Yan Huang,1 Ying Tian,1 Dan Xie,1 Li Zhang1 1Sun 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 Medical Oncology, Zhongshan Hospital of Sun Yat-Sen University, Zhongshan People’s City Hospital, Zhongshan, People’s Republic of China *The first three authors contributed equally to this work Abstract: The aim of the present study was to investigate the clinicopathologic/prognostic significance of thymidylate synthase (TS, orotate phosphoribosyltransferase (OPRT, and thymidine phosphorylase (TP proteins in postoperative non-small cell lung cancer (NSCLC patients. Microarray slides from a set of 178 NSCLC patients were used for the detection of TS, OPRT, and TP expression by immunohistochemistry. The correlation between clinicopathologic factors and protein expression of three proteins was analyzed. Ninety seven carcinomas (57.4% were TS-positive, 90 carcinomas (53.9% were OPRT-positive, and 102 carcinomas (69.4% were TP-positive. Compared with the TS-positive patients, the overall survival (OS was significantly lower in the TS-negative patients (hazard ratio [HR] =1.766, 95% confidence interval [CI] =1.212–2.573, P=0.003. Significant differences between TS-positive and TS-negative patients was also observed in the following stratified analyses: 1 adenocarcinoma subgroup (HR =2.079, 95% CI =1.235–3.500, P=0.006; 2 less than 60-year-old subgroup (HR =1.890, 95% CI =1.061–3.366, P=0.031; 3 stage II/III subgroup (HR =1.594, 95% CI =1.036–2.453, P=0.034; and 4 surgery plus adjuvant therapy subgroup (HR =1.976, 95% CI =1.226–3.185, P=0.005. However, the OS was not significantly correlated with OPRT or TP protein expression. This study demonstrates that the TS level in tumor tissues may be a useful marker

  15. Quality of life after curative radiotherapy in Stage I non-small-cell lung cancer

    International Nuclear Information System (INIS)

    Purpose: The aim of this study was to investigate changes in quality of life (QOL) among medically inoperable Stage I non-small-cell lung cancer (NSCLC) patients treated with curative radiotherapy. Patients and Methods: The study sample was composed of 46 patients irradiated for Stage I NSCLC. Quality of life was assessed before, during, and after radiotherapy using the European Organization for the Research and Treatment of Cancer QLQ-C30 and QLQ-LC13. Changes in symptom and QOL scores over time were evaluated with a repeated measurement analysis of variance using the mixed effect modeling procedure, SAS Proc Mixed. Twenty-seven patients were treated only at the primary site, whereas for 19 patients, the regional lymph nodes were included in the target volume as well. Results: The median follow-up time of patients alive was 34 months. The median survival was 19.0 months. None of the locally treated patients developed regional recurrence. A significant, gradual increase over time was observed for dyspnea, fatigue, and appetite loss. A significant, gradual deterioration was observed also for role functioning. No significant changes were noted for the other symptoms or the functioning scales. Significantly higher levels of dysphagia, which persisted up to 12 months, were observed in those in which the regional lymph nodes were treated, as compared to the locally treated patients. Radiation-induced pulmonary changes assessed with chest radiograph were more pronounced in the group treated with locoregional radiotherapy. Conclusions: After curative radiotherapy for Stage I medically inoperable NSCLC, a gradual increase in dyspnea, fatigue, and appetite loss, together with a significant deterioration of role functioning, was observed, possibly because of pre-existing, slowly progressive chronic obstructive pulmonary disease and radiation-induced pulmonary changes. Taking into account the low incidence of regional recurrences after local irradiation, the higher incidence

  16. Potential clinical predictors of outcome after postoperative radiotherapy of non-small cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Buetof, R. [Medical Faculty and University Hospital Carl Gustav Carus, Technische Universitaet Dresden, Department of Radiation Oncology, Dresden (Germany); Medical Faculty and University Hospital Carl Gustav Carus, Technische Universitaet Dresden, OncoRay National Center for Radiation Research in Oncology, Dresden (Germany); Kirchner, K.; Appold, S. [Medical Faculty and University Hospital Carl Gustav Carus, Technische Universitaet Dresden, Department of Radiation Oncology, Dresden (Germany); Loeck, S. [Medical Faculty and University Hospital Carl Gustav Carus, Technische Universitaet Dresden, OncoRay National Center for Radiation Research in Oncology, Dresden (Germany); Rolle, A. [Lungenfachklinik Coswig, Department of Thoracic and Vascular Surgery, Coswig (Germany); Hoeffken, G. [Lungenfachklinik Coswig, Department of Pneumology, Coswig (Germany); Krause, M.; Baumann, M. [Medical Faculty and University Hospital Carl Gustav Carus, Technische Universitaet Dresden, Department of Radiation Oncology, Dresden (Germany); Medical Faculty and University Hospital Carl Gustav Carus, Technische Universitaet Dresden, OncoRay National Center for Radiation Research in Oncology, Dresden (Germany); German Cancer Consortium (DKTK), Dresden (Germany); German Cancer Research Center (DKFZ), Heidelberg (Germany); Helmholtz-Zentrum Dresden-Rossendorf, Dresden (Germany)

    2014-03-15

    The aim of this analysis was to investigate the impact of tumour-, treatment- and patient-related cofactors on local control and survival after postoperative adjuvant radiotherapy in patients with non-small cell lung cancer (NSCLC), with special focus on waiting and overall treatment times. For 100 NSCLC patients who had received postoperative radiotherapy, overall, relapse-free and metastases-free survival was retrospectively analysed using Kaplan-Meier methods. The impact of tumour-, treatment- and patient-related cofactors on treatment outcome was evaluated in uni- and multivariate Cox regression analysis. No statistically significant difference between the survival curves of the groups with a short versus a long time interval between surgery and radiotherapy could be shown in uni- or multivariate analysis. Multivariate analysis revealed a significant decrease in overall survival times for patients with prolonged overall radiotherapy treatment times exceeding 42 days (16 vs. 36 months) and for patients with radiation-induced pneumonitis (8 vs. 29 months). Radiation-induced pneumonitis and prolonged radiation treatment times significantly reduced overall survival after adjuvant radiotherapy in NSCLC patients. The negative impact of a longer radiotherapy treatment time could be shown for the first time in an adjuvant setting. The hypothesis of a negative impact of longer waiting times prior to commencement of adjuvant radiotherapy could not be confirmed. (orig.) [German] Das Ziel der vorliegenden Analyse war, den Einfluss von tumor-, patienten- und therapieabhaengigen Kofaktoren auf die lokoregionale Tumorkontrolle und das Ueberleben nach postoperativer adjuvanter Strahlentherapie bei Patienten mit einem nicht-kleinzelligen Bronchialkarzinom (NSCLC) zu untersuchen. Ein spezieller Fokus lag dabei auf der Wartezeit zwischen Operation und Beginn der Strahlentherapie sowie der Gesamtbehandlungszeit der Strahlentherapie. Fuer 100 Patienten, die eine postoperative

  17. Prognostic indices in stereotactic radiotherapy of brain metastases of non-small cell lung cancer

    International Nuclear Information System (INIS)

    Our purpose was to analyze the long-term clinical outcome and to identify prognostic factors after Linac-based stereotactic radiosurgery (SRS) or fractionated stereotactic radiotherapy (FSRT) on patients with brain metastases (BM) from non-small cell lung cancer (NSCLC). We performed a retrospective analysis of survival on 90 patients who underwent SRS or FSRT of intracranial NSCLC metastases between 04/2004 and 05/2014 that had not undergone prior surgery or whole brain radiotherapy (WBRT) for BM. Follow-up data was analyzed until May 2015. Potential prognostic factors were examined in univariable and multivariable analyses. The Golden Grading System (GGS), the disease-specific graded prognostic assessment (DS-GPA), the RADES II prognostic index as well as the NSCLC-specific index proposed by Rades et al. in 2013 (NSCLC-RADES) were calculated and their predictive values were tested in univariable analysis. The median follow-up time of the surviving patients was 14 months. The overall survival (OS) rate was 51 % after 6 months and 29.9 % after 12 months. Statistically significant factors of better OS after univariable analysis were lower International Union Against Cancer (UICC) stage at first diagnosis, histology of adenocarcinoma, prior surgery of the primary tumor and lower total BM volume. After multivariable analysis adenocarcinoma histology remained a significant factor; higher Karnofsky Performance Score (KPS) and the presence of extracranial metastases (ECM) were also significant. The RADES II and the NSCLC-RADES indices were significant predictors of OS. However, the NSCLC-RADES failed to differentiate between intermediate- and low-risk patients. The DS-GPA and GGS were not statistically significant predictors of survival in univariable analysis. The ideal prognostic index has not been defined yet. We believe that more specific indices will be developed in the future. Our results indicate that the histologic subtype of NSCLC could add to the prognostic

  18. 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

  19. A Systematic Overview of Radiation Therapy Effects in Non-Small Cell Lung Cancer

    International Nuclear Information System (INIS)

    A systematic review of radiation therapy trials in several tumour types was performed by The Swedish Council of Technology Assessment in Health Care (SBU). The procedures for evaluation of the scientific literature are described separately. This synthesis of the literature on radiation therapy for non-small cell lung cancer (NSCLC) is based on data from 4 meta-analyses and 31 randomized trials. Moreover, data from 12 prospective studies, 12 retrospective studies and 6 other articles were used. In total, 65 scientific articles are included, involving 18,310 patients. The results were compared with those of a similar overview from 1996 including 28,172 patients. The conclusions reached can be summarized as follows: Extensive clinical experience indicates that radiotherapy for medically inoperable patients or patients refusing surgery with NSCLC stage I/II prolongs survival, 15-20% of these patients reaching long-term (5-year) survival. However, no randomized trials have addressed this issue. There is strong evidence that postoperative radiotherapy in radically resected stage I/II NSCLC does not prolong survival compared with observation alone. There is some evidence that continuous hyperfractionated accelerated radiotherapy (CHART) is associated with increased survival compared to conventional radiotherapy in locally advanced NSCLC and also in medically unfit patients with stage I/II NSCLC. However, the benefit is limited to squamous cell histology. There is strong evidence that combined modality treatment with platinum-based chemotherapy and radiotherapy, either neoadjuvant or concomitant, is superior to radiotherapy alone in terms of survival in locally advanced unresectable NSCLC and should be the standard of care in patients with good performance status. There is some evidence that concomitant chemo-radiotherapy is associated with increased survival compared with sequential chemo-radiotherapy, albeit at the price of increased toxicity. Comment: Combined chemo

  20. Non-small cell lung cancer. The role of chemoimmunoradiotherapy after surgery

    International Nuclear Information System (INIS)

    The aim of this study was to determine expediency of adjuvant chemoimmunoradiotherapy for radically operated non-small cell lung cancer patients (LCP) with pathologic stage II-III (T1-4N0-2M0G1-3). In retrospective trial (1985-1998) a 5-year survival of 54 consecutive radically operated LCP after radical procedures (group C) and with therapy (group A) was compared with 5-year survival of 264 LCP, after radical procedures (group C) and with 5-year survival of 86 radically operated LCP after postoperative radiotherapy (group B) (45-50 Gy). 1 cycle of chemoimmunotherapy was given on day 10-14 after complete resections. Radiotherapy (45-50 Gy) was administered since day 7 after 1 cycle. After irradiation 3-4 courses of CAVT were repeated every 21-28 day. Variables selected for 5-year survival and life span study were sex, age, TNMG, cell type, tumor size. Survival curves were estimated by the Kaplan-Meier method. Differences in curves between groups of LCP were evaluated using a logrank test. Multivariate proportional hazard Cox regression, multi-factor clustering, structural equation modeling and Monte Carlo simulation were used to determine any significant overall regularity. 5-year survival was superior in group A (64.8%: 35 out of 54 LCP with N0-2: life span=1998.2±156.9 days) compared with group B (45.3%: 39 out of 86 LCP with N0-2; life span=1296.4±109.5 days) (P0.05 for group A and P<0.001 for group B). For LCP with N1-2 5-year survival was significantly superior for group A (63.6%: 21 from 33; life span=1934.0±189.9 days) compared with group C (28.1%: 25 out of 89; life span=1056.9±91.1 days) (P<0.001) and with group B (35.6%: 21 out of 59; life span=1051.7±119.6 days) (P<0.001). Structural equation modeling and Monte Carlo simulation confirmed significant overall differences between 5-year survival (P<0.05) and life span (P<0.001) of LCP with N1-2 in group A with respect to group C or B; however, 5-year survival of LCP for N0 in groups A, B and C were not

  1. Involved-field radiotherapy alone for early-stage non-small-cell lung cancer

    International Nuclear Information System (INIS)

    Purpose: To describe the outcome of involved-field radiotherapy in patients with early-stage non-small-cell lung cancer (NSCLC). Methods and Materials: A written policy for the radical treatment of early-stage NSCLC with involved-field radiotherapy was adopted at our center in 1986. The sites of known disease were treated to a dose of 52.5 Gy in 20 daily fractions over 4 weeks without elective irradiation of radiologically uninvolved regional nodes. We have reviewed the outcome of this policy in 102 patients treated with radiotherapy alone between 1986 and 1995. Results: The patients' median age was 71.5 years. The stage distribution was as follows: T1, 33.3%; T2, 56.9%; T3, 8.8%; and T4, 1.0%. Only 5 cases were N1; the remainder were N0. Most patients (76.5%) were not surgical candidates because of co-morbidity. Ninety-three percent had a CT of the thorax as part of their initial staging, while mediastinoscopy was performed in only 16.7%. Overall survival was 35% at 3 years and 16% at 5 years. Recurrence free survival was 23.9% at 3 years and 13.9% at 5 years. Cause-specific survival was 43.5% at 3 years and 26.8% at 5 years. Of those who recurred, 68.9% had a local component of failure at initial relapse, and 49.2% failed locally without evidence of regional or distant metastases. Isolated regional nodal relapse at initial failure occurred in only 6.6% of recurrences. There were no treatment interruptions due to acute toxicity and no treatment-related deaths. Conclusion: Involved-field radiotherapy alone cures a small but significant number of patients with early-stage NSCLC. This approach is recommended in patients who are unfit for surgery and who have severely compromised pulmonary function that would preclude the use of wide-field radiotherapy. The dose used in this study was well tolerated, but produced suboptimal local control rates

  2. Dose, volume, and tumor control prediction in primary radiotherapy of non-small-cell lung cancer

    International Nuclear Information System (INIS)

    Background: To evaluate the influence of total dose and tumor volume on local control and survival in primary radiotherapy of non-small-cell lung cancer (NSCLC). Methods and Materials: We retrospectively analyzed the clinical course and CT-derived pre- and post-therapeutic tumor volume data of 135 patients with NSCLC undergoing primary radiotherapy at our department between 1989 and 1996. Among these, a total of 192 spatially separated tumor volumes (135 primary tumors, 1 additional intrapulmonary tumor, and 56 involved lymph nodes) were available for analysis. In all patients, treatment was planned using CT-based three-dimensional treatment planning. The dose to each tumor volume was derived from the individual dose plans. Mean total dose was 59.9 Gy (range: 30-80 Gy). All but 3 patients were followed until death. For local control analysis, each tumor was analyzed separately, and its remission status was determined in serial follow-up CT scans. A total of 784 CT scans were analyzed. Actuarial local control analysis was performed for the 192 separated tumor volumes, and survival analysis was performed for the 135 patients. Tumor control probability was calculated using a Poisson statistical model. Results: Overall 1- and 2-year local control rate was 50% and 37%, respectively. The 2-year local control rate for tumors 200 ccm was 51%, 22%, and 10%, respectively (p=0.02). The 2-year local control rate for dose levels ≤60 Gy and >60 Gy was 28% and 43% (p100 ccm were controlled more than 2 years. Multivariate analysis revealed tumor volume, total dose, histopathologic type, and grading as significant and independent prognostic factors for local control. The number of delay days by split course (if used) and application of chemotherapy was not found to influence local control. Overall 1- and 2-year survival rate was 42% and 13%. Total radiation dose, chemotherapy, and T and N stage--but not tumor volume--were found to be independent and significant prognostic factors

  3. Prognostic factors of tumor recurrence in completely resected non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Tantraworasin A

    2013-06-01

    Full Text Available Apichat Tantraworasin,1 Somcharean Seateang,1 Nirush Lertprasertsuke,2 Nuttapon Arreyakajohn,3 Choosak Kasemsarn,4 Jayanton Patumanond5 1General Thoracic Unit, Department of Surgery, Faculty of Medicine, Chiang Mai University Hospital, Chiang Mai, Thailand; 2Department of Pathology, Faculty of Medicine, Chiang Mai University Hospital, Chiang Mai, Thailand; 3Cardiovascular Thoracic Unit, Department of Surgery, Lampang Hospital, Lampang, Thailand; 4Cardiovascular Thoracic Unit, Department of Surgery, Chest Institute, Nonthaburi, Thailand; 5Department of Community Medicine, Faculty of Medicine, Chiang Mai University Hospital, Chiang Mai, Thailand Background: Patients with completely resected non-small cell lung cancer (NSCLC have an excellent outcome; however tumor recurs in 30%-77% of patients. This study retrospectively analyzed the clinicopathologic features of patients with any operable stage of NSCLC to identify the prognostic factors that influence tumor recurrence, including intratumoral blood vessel invasion (IVI, tumor size, tumor necrosis, and nodal involvement. Methods: From January 2002 to December 2011, 227 consecutive patients were enrolled in this study. They were divided into two groups: the “no recurrence” group and the “recurrence” group. Recurrence-free survival was analyzed by multivariable Cox regression analysis, stratified by tumor staging, chemotherapy, and lymphatic invasion. Results: IVI, tumor necrosis, tumor diameter more than 5 cm, and nodal involvement were identified as independent prognostic factors of tumor recurrence. The hazard ratio (HR of patients with IVI was 2.1 times higher than that of patients without IVI (95% confident interval [CI]: 1.4–3.2 (P = 0.001.The HR of patients with tumor necrosis was 2.1 times higher than that of patients without tumor necrosis (95% CI: 1.3–3.4 (P = 0.001. Patients who had a maximum tumor diameter greater than 5 cm had significantly higher risk of recurrence than

  4. Erlotinib for the treatment of relapsed non-small cell lung cancer.

    Science.gov (United States)

    McLeod, C; Bagust, A; Boland, A; Hockenhull, J; Dundar, Y; Proudlove, C; Davis, H; Green, J; Macbeth, F; Stevenson, J; Walley, T; Dickson, R

    2009-06-01

    This paper presents a summary of the evidence review group (ERG) report into the clinical and cost-effectiveness of erlotinib for the treatment of relapsed non-small cell lung cancer (NSCLC), according to its licensed indication, based upon the evidence submission from Roche Products to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal (STA) process. The submitted clinical evidence includes one randomised controlled trial (RCT) (BR21) investigating the effect of erlotinib versus placebo, which demonstrates that erlotinib significantly increases median overall survival, progression-free survival and response rate compared with placebo. The majority of patients in the trial experienced non-haematological drug-related adverse effects. Currently there are no trials that directly compare erlotinib with any other second-line chemotherapy agent. For the purposes of indirect comparison, the manufacturer's submission provides a narrative discussion of data from 11 RCTs investigating the use of docetaxel. From these data the manufacturer concludes that erlotinib has similar clinical efficacy levels to docetaxel but results in fewer serious haematological adverse events; however, it is difficult to compare the results of BR21 with those of the docetaxel trials or with current UK clinical practice because, for example, the BR21 patient population is younger than that expected to present in UK clinical practice and almost half of the BR21 participants received erlotinib as third-line chemotherapy, with third-line chemotherapy being rare in the UK. The manufacturer's submission included a three-state model comparing erlotinib with docetaxel, reporting an incremental cost-effectiveness ratio (ICER) of 1764 pounds per quality-adjusted life-year (QALY) gained for erlotinib compared with docetaxel. Rerunning the manufacturer's economic model with varied parameters and assumptions increases the ICER to in excess of 52

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

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    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

  6. Targeted therapies in development for non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Thanyanan Reungwetwattana

    2013-01-01

    Full Text Available The iterative discovery in various malignancies during the past decades that a number of aberrant tumorigenic processes and signal transduction pathways are mediated by "druggable" protein kinases has led to a revolutionary change in drug development. In non-small cell lung cancer (NSCLC, the ErbB family of receptors (e.g., EGFR [epidermal growth factor receptor], HER2 [human epidermal growth factor receptor 2], RAS (rat sarcoma gene, BRAF (v-raf murine sarcoma viral oncogene homolog B1, MAPK (mitogen-activated protein kinase c-MET (c-mesenchymal-epithelial transition, FGFR (fibroblast growth factor receptor, DDR2 (discoidin domain receptor 2, PIK3CA (phosphatidylinositol-4,5-bisphosphate3-kinase, catalytic subunit alpha, PTEN (phosphatase and tensin homolog, AKT (protein kinase B, ALK (anaplastic lym phoma kinase, RET (rearranged during transfection, ROS1 (reactive oxygen species 1 and EPH (erythropoietin-producing hepatoma are key targets of various agents currently in clinical development. These oncogenic targets exert their selective growth advantage through various intercommunicating pathways, such as through RAS/RAF/MEK, phosphoinositide 3-kinase/AKT/mammalian target of rapamycin and SRC-signal transduction and transcription signaling. The recent clinical studies, EGFR tyrosine kinase inhibitors and crizotinib were considered as strongly effective targeted therapies in metastatic NSCLC. Currently, five molecular targeted agents were approved for treatment of advanced NSCLC: Gefitinib, erlotinib and afatinib for positive EGFR mutation, crizotinib for positive echinoderm microtubule-associated protein-like 4 (EML4-ALK translocation and bevacizumab. Moreover, oncogenic mutant proteins are subject to regulation by protein trafficking pathways, specifically through the heat shock protein 90 system. Drug combinations affecting various nodes in these signaling and intracellular processes are predicted and demonstrated to be synergistic and

  7. Changes in volume of stage I non-small-cell lung cancer during stereotactic body radiotherapy

    International Nuclear Information System (INIS)

    The overall treatment time of stereotactic body radiotherapy (SBRT) for non-small-cell lung cancer is usually 3 to over 10 days. If it is longer than 7 days, tumor volume expansion during SBRT may jeopardize the target dose coverage. In this study, volume change of stage I NSCLC during SBRT was investigated. Fifty patients undergoing 4-fraction SBRT with a total dose of 48 Gy (n = 36) or 52 Gy (n = 14) were analyzed. CT was taken for registration at the first and third SBRT sessions with an interval of 7 days in all patients. Patient age was 29–87 years (median, 77), and 39 were men. Histology was adenocarcinoma in 28, squamous cell carcinoma in 17, and others in 5. According to the UICC 7th classification, T-stage was T1a in 9 patients, T1b in 27, and T2a in 14. Tumor volumes on the first and 8th days were determined on CT images taken during the exhalation phase, by importing the data into the Dr. View/LINAX image analysis system. After determining the optimal threshold for distinguishing tumor from pulmonary parenchyma, the region above -250 HU was automatically extracted and the tumor volumes were calculated. The median tumor volume was 7.3 ml (range, 0.5-35.7) on day 1 and 7.5 ml (range, 0.5-35.7) on day 8. Volume increase of over 10% was observed in 16 cases (32%); increases by >10 to ≤20%, >20 to ≤30%, and >30% were observed in 9, 5, and 2 cases, respectively. The increase in the estimated tumor diameter was over 2 mm in 3 cases and 1–2 mm in 6. A decrease of 10% or more was seen in 3 cases. Among the 16 tumors showing a volume increase of over 10%, T-stage was T1a in 2 patients, T1b in 9, and T2a in 5. Histology was adenocarcinoma in 10 patients, squamous cell carcinoma in 5, and others in 1. Volume expansion >10% was observed in 32% of the tumors during the first week of SBRT, possibly due to edema or sustained tumor progression. When planning SBRT, this phenomenon should be taken into account

  8. Association between MGMT Promoter Methylation and Non-Small Cell Lung Cancer: A Meta-Analysis

    Science.gov (United States)

    Gu, Changmei; Lu, Jiachun; Cui, Tianpen; Lu, Cheng; Shi, Hao; Xu, Wenmao; Yuan, Xueli; Yang, Xiaobo; Huang, Yangxin; Lu, Meixia

    2013-01-01

    Background O6-methylguanine-DNA methyltransferase (MGMT) is one of most important DNA repair enzyme against common carcinogens such as alkylate and tobacco. Aberrant promoter methylation of the gene is frequently observed in non-small cell lung cancer (NSCLC). However, the importance of epigenetic inactivation of the gene in NSCLC published in the literature showed inconsistence. We quantified the association between MGMT promoter methylation and NSCLC using a meta-analysis method. Methods We systematically reviewed studies of MGMT promoter methylation and NSCLC in PubMed, EMBASE, Ovid, ISI Web of Science, Elsevier and CNKI databases and quantified the association between MGMT promoter methylation and NSCLC using meta-analysis method. Odds ratio (OR) and corresponding 95% confidence interval (CI) were calculated to evaluate the strength of association. Potential sources of heterogeneity were assessed by subgroup analysis and meta-regression. Results A total of 18 studies from 2001 to 2011, with 1, 160 tumor tissues and 970 controls, were involved in the meta-analysis. The frequencies of MGMT promote methylation ranged from 1.5% to 70.0% (median, 26.1%) in NSCLC tissue and 0.0% to 55.0% (median, 2.4%) in non-cancerous control, respectively. The summary of OR was 4.43 (95% CI: 2.85, 6.89) in the random-effects model. With stratification by potential source of heterogeneity, the OR was 20.45 (95% CI: 5.83, 71.73) in heterogeneous control subgroup, while it was 4.16 (95% CI: 3.02, 5.72) in the autologous control subgroup. The OR was 5.31 (95% CI: 3.00, 9.41) in MSP subgroup and 3.06 (95% CI: 1.75, 5.33) in Q-MSP subgroup. Conclusion This meta-analysis identified a strong association between methylation of MGMT gene and NSCLC. Prospective studies should be required to confirm the results in the future. PMID:24086261

  9. Association between MGMT promoter methylation and non-small cell lung cancer: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Changmei Gu

    Full Text Available BACKGROUND: O(6-methylguanine-DNA methyltransferase (MGMT is one of most important DNA repair enzyme against common carcinogens such as alkylate and tobacco. Aberrant promoter methylation of the gene is frequently observed in non-small cell lung cancer (NSCLC. However, the importance of epigenetic inactivation of the gene in NSCLC published in the literature showed inconsistence. We quantified the association between MGMT promoter methylation and NSCLC using a meta-analysis method. METHODS: We systematically reviewed studies of MGMT promoter methylation and NSCLC in PubMed, EMBASE, Ovid, ISI Web of Science, Elsevier and CNKI databases and quantified the association between MGMT promoter methylation and NSCLC using meta-analysis method. Odds ratio (OR and corresponding 95% confidence interval (CI were calculated to evaluate the strength of association. Potential sources of heterogeneity were assessed by subgroup analysis and meta-regression. RESULTS: A total of 18 studies from 2001 to 2011, with 1, 160 tumor tissues and 970 controls, were involved in the meta-analysis. The frequencies of MGMT promote methylation ranged from 1.5% to 70.0% (median, 26.1% in NSCLC tissue and 0.0% to 55.0% (median, 2.4% in non-cancerous control, respectively. The summary of OR was 4.43 (95% CI: 2.85, 6.89 in the random-effects model. With stratification by potential source of heterogeneity, the OR was 20.45 (95% CI: 5.83, 71.73 in heterogeneous control subgroup, while it was 4.16 (95% CI: 3.02, 5.72 in the autologous control subgroup. The OR was 5.31 (95% CI: 3.00, 9.41 in MSP subgroup and 3.06 (95% CI: 1.75, 5.33 in Q-MSP subgroup. CONCLUSION: This meta-analysis identified a strong association between methylation of MGMT gene and NSCLC. Prospective studies should be required to confirm the results in the future.

  10. Prognostic biomarker study in pathologically staged N1 non-small cell lung cancer

    International Nuclear Information System (INIS)

    Purpose: The prognostic influence of 6 biomarkers correlated to histologic subtypes of non-small cell lung cancer (NSCLC) on loco-regional control, overall survival, disease-free survival (DFS), and distant disease control (DDC) rates, all measured at 5 years, were examined. Materials and Methods: Cell blocks from the primary tumors of 137 patients with pathologically staged N1 NSCLC at MDACC were analyzed by 6-biomarker status correlated to histological subtypes and their outcomes. Results: The ranges of biomarker values were as follows: apoptotic index, 0.2-2.8%; mitotic index, 0-1.8%; the proportion of cells in S+G2M, 3-36%; p53 status, 0-100%; Ki-67, 0-9.3%; DNA index, 1.0-2.74. Subtypes of 137 cases from the postoperative pathology specimen showed that 74 patients had squamous carcinoma and 63 patients had adenocarcinoma. Mean and median lengths of follow-up were 4.21 years and 2.43 years, respectively. Patients with squamous cell carcinoma (SCC) had a better 5-year survival (p = 0.006), DFS (pp = 0.002) than patients with adenocarcinoma (AC). Among patients with AC, the DNA index was a significant predictor of 5-year DFS (p = 0.02), DDC rate (p = 0.04), and local-regional control (p < 0.05). Higher apoptosis (p 0.03) and mitosis indices (p = 0.03) were also univariate predictors of increased distant disease among patients with AC. Multivariate analysis of patients with AC revealed that the DNA index and Ki-67 were the only significant independent predictors of distant metastasis (p < 0.04 and p < 0.02, respectively) and DFS (p < 0.04 for both). Among patients with SCC, univariate analysis showed that S+G2M proportion (p < 0.05) and Ki-67 levels (p < 0.02) were significant predictors for local-regional control; for SC, multivariate analysis showed that only mitosis was a significant predictor in this case for overall survival (p < 0.04). Conclusion: Spontaneous apoptotic index and Ki-67 were significantly higher in SC than in AC. Patients with SC had less

  11. Respiration-averaged CT for attenuation correction in non-small-cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, Nai-Ming; Ho, Kung-Chu; Yen, Tzu-Chen [Chang Gung Memorial Hospital Linkou Medical Center, Department of Nuclear Medicine, Taoyuan (China); Yu, Chih-Teng [Chang Gung Memorial Hospital and Chang Gung University, Department of Chest Medicine, Taoyuan (China); Wu, Yi-Cheng [Chang Gung Memorial Hospital and Chang Gung University, Department of Chest Surgery, Taoyuan (China); Liu, Yuan-Chang [Chang Gung Memorial Hospital and Chang Gung University, Department of Diagnostic Radiology, Taoyuan (China); Wang, Chih-Wei [Chang Gung Memorial Hospital and Chang Gung University, Department of Pathology, Taoyuan (China)

    2009-04-15

    Breathing causes artefacts on PET/CT images. Cine CT has been used to reduce respiratory artefacts by acquiring multiple images during a single breathing cycle. The aim of this prospective study in non-small-cell lung cancer (NSCLC) patients was twofold. Firstly, we sought to compare the motion artefacts in PET/CT images attenuation-corrected with helical CT (HCT) and with averaged CT (ACT), which provides an average of cine CT images. Secondly, we wanted to evaluate the differences in maximum standardized uptake values (SUV{sub max}) between HCT and ACT. Enrolled in the study were 80 patients with NSCLC. PET images attenuation-corrected with HCT (PET/HCT) and with ACT (PET/ACT) were obtained in all patients. Misregistration was evaluated by measurement of the curved photopenic area in the lower thorax of the PET images for all patients and direct measurement of misregistration for selected lesions. SUV{sub max} was measured separately at the primary tumours, regional lymph nodes, and background. A total of 80 patients with NSCLC were included. Significantly lower misregistrations were observed in PET/ACT images than in PET/HCT images (below-thoracic misregistration 0.25{+-}0.58 cm vs. 1.17{+-}1.17 cm, p<0.001; lesion misregistration 1.38{+-}2.10 vs. 3.10{+-}4.09, p=0.013). Significantly higher SUV{sub max} were noted in PET/ACT images than in PET/HCT images in the primary tumour (p<0.001) and regional lymph nodes (p<0.001). Compared with PET/HCT images, the magnitude of SUV{sub max} in PET/ACT images was higher by 0.35 for the main tumours and 0.34 for lymph nodes. Due to its significantly reduced misregistration, PET/ACT provided more reliable SUV{sub max} and may be useful in treatment planning and monitoring the therapeutic response in patients with NSCLC. (orig.)

  12. Prognostic significance of MCM2, Ki-67 and gelsolin in non-small cell lung cancer

    International Nuclear Information System (INIS)

    Uncontrolled proliferation and increased motility are hallmarks of neoplastic cells, therefore markers of proliferation and motility may be valuable in assessing tumor progression and prognosis. MCM2 is a member of the minichromosome maintenance (MCM) protein family. It plays critical roles in the initiation of DNA replication and in replication fork movement, and is intimately related to cell proliferation. Ki-67 is a proliferation antigen that is expressed during all but G0 phases of the cell cycle. Gelsolin is an actin-binding protein that regulates the integrity of the actin cytoskeletal structure and facilitates cell motility. In this study, we assessed the prognostic significance of MCM2 and Ki-67, two markers of proliferation, and gelsolin, a marker of motility, in non-small cell lung cancer (NSCLC). 128 patients with pathologically confirmed, resectable NSCLC (stage I-IIIA) were included. Immunohistochemistry was utilized to measure the expressions of these markers in formalin-fixed, paraffin-embedded tumor tissues. Staining and scoring of MCM2, Ki-67 and gelsolin was independently performed. Analyses were performed to evaluate the prognostic significance of single expression of each marker, as well as the prognostic significance of composite expressions of MCM2 and gelsolin. Cox regression and Kaplan-Meier survival analysis were used for statistical analysis. Of the three markers, higher levels of gelsolin were significantly associated with an increased risk of death (adjusted RR = 1.89, 95% CI = 1.17–3.05, p = 0.01), and higher levels of MCM2 were associated with a non-significant increased risk of death (adjusted RR = 1.36, 95% CI = 0.84–2.20, p = 0.22). Combined, adjusted analyses revealed a significantly poor prognostic effect for higher expression of MCM2 and gelsolin compared to low expression of both biomarkers (RR = 2.32, 95% CI = 1.21–4.45, p = 0.01). Ki-67 did not display apparent prognostic effect in this study sample. The results suggest

  13. Molecular predictors of response to tyrosine kinase inhibitors in patients with Non-Small-Cell Lung Cancer

    OpenAIRE

    Murray Samuel; Karavasilis Vasilios; Bobos Mattheos; Razis Evangelia; Papadopoulos Savvas; Christodoulou Christos; Kosmidis Paris; Fountzilas George

    2012-01-01

    Abstract Introduction Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have become a treatment option in non-small-cell lung cancer (NSCLC) patients. However, despite their use in this disease, a significant number of patients will eventually develop resistance and relapse. In this study, we aimed to characterize several molecular events involved in potential resistance mechanisms to anti-EGFR treatment and correlate our findings with clinical outcome. Material and me...

  14. P-glycoprotein Mediates Ceritinib Resistance in Anaplastic Lymphoma Kinase-rearranged Non-small Cell Lung Cancer

    OpenAIRE

    Ryohei Katayama; Takuya Sakashita; Noriko Yanagitani; Hironori Ninomiya; Atsushi Horiike; Luc Friboulet; Gainor, Justin F.; Noriko Motoi; Akito Dobashi; Seiji Sakata; Yuichi Tambo; Satoru Kitazono; Shigeo Sato; Sumie Koike; John Iafrate, A.

    2015-01-01

    The anaplastic lymphoma kinase (ALK) fusion oncogene is observed in 3%–5% of non-small cell lung cancer (NSCLC). Crizotinib and ceritinib, a next-generation ALK tyrosine kinase inhibitor (TKI) active against crizotinib-refractory patients, are clinically available for the treatment of ALK-rearranged NSCLC patients, and multiple next-generation ALK-TKIs are currently under clinical evaluation. These ALK-TKIs exhibit robust clinical activity in ALK-rearranged NSCLC patients; however, the emerge...

  15. Current Status and Development of Traditional Chemotherapy in Non-small Cell Lung Cancer under the Background of Targeted Therapy

    OpenAIRE

    Zhang, Guowei; Wang, Huijuan; Mina ZHANG; Li, Peng; Ma, ZhiYong

    2015-01-01

    In recent years, along with rapid development of targeted therapy in non-small cell lung cancer, traditional chemotherapy get less and less attention. Yet it still can not be ignored in the current that how to locate and use traditional chemotherapy so patients could derive maximum benefit. For this purpose, through the literature review and analysis, we point out there are still many traditional chemotherapy irreplaceable places whatever patients’ driver gene status. And there are some new t...

  16. Stereotactic body radiation therapy versus conventional radiation therapy in patients with early stage non-small cell lung cancer

    DEFF Research Database (Denmark)

    Jeppesen, Stefan S; 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...... 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....

  17. A Case of Stage IV Non-Small Cell Lung Cancer Treated with Korean Medicine Therapy Alone

    OpenAIRE

    Lee, Dong-Hyun; Seong, Shin; Kim, Sung-Su; Han, Jae-Bok

    2013-01-01

    This report presents a case that shows a significant anticancer effect of Korean medicine therapy (KMT). A 79-year-old man, who was diagnosed as stage IV non-small cell lung cancer (NSCLC) in December 2012, was treated with KMT including intravenous pharmacopunctures and oral herbal medicine from February 22, 2013, until September 2013 without any surgical intervention, chemotherapy or radiotherapy. The intravenous pharmacopunctures were the wild ginseng pharmacopuncture, Cordyceps sinensis p...

  18. Efficacy and safety of metronomic administration of paclitaxel for advanced recurrent non-small-cell lung cancer

    OpenAIRE

    V Noronha; Patil, V M; Joshi, A; K Prabhash

    2013-01-01

    Context: There are limited effective therapeutic options in the relapsed setting for non-small cell lung cancer (NSCLC) or in the first line for platinum-ineligible patients. Aim: To evaluate the safety and efficacy of a metronomic schedule of paclitaxel administered weekly in relapsed refractory NSCLC or upfront in patients not eligible for platinum-based chemotherapy. Settings and Design: Retrospective analysis of a prospectively collected database from the medical oncology department at Ta...

  19. 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 ...

  20. Expression and clinical significance of aminopeptidase N/CD13 in non-small cell lung cancer

    OpenAIRE

    Quan Zhang; Jinghui Wang; Haiqing Zhang; Dan Zhao; Zongde Zhang; Shucai Zhang

    2015-01-01

    Background: The objective of this study was to analyze the expression of aminopeptidase N/CD13 (APN/CD13) in non-small cell lung cancer (NSCLC) and investigate its correlation with various clinical factors, including prognosis and efficacy of adjuvant chemotherapy. Materials and Methods: Using immunohistochemistry analysis, we analyzed the expression of CD13 in clinicopathologically characterized 127 NSCLC cases. The relationship between the expression levels of CD13 and clinical features ...