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Sample records for advanced nonsmall cell

  1. Refining the treatment of advanced nonsmall cell lung cancer

    OpenAIRE

    Wozniak, Antoinette

    2010-01-01

    Shin Ogita, Antoinette J WozniakKarmanos Cancer Institute, Wayne State University, Detroit, MI, USAAbstract: Metastatic nonsmall cell lung cancer (NSCLC) is a debilitating and deadly disease with virtually no chance for long-term survival. Chemotherapy has improved both survival and quality of life for patients with advanced disease. Overall survival of patients with metastatic NSCLC has gradually increased from 8 to 12 months over the past three decades with the introduction of new chemother...

  2. Radio(chemotherapy in locally advanced nonsmall cell lung cancer

    Directory of Open Access Journals (Sweden)

    Markus Glatzer

    2016-03-01

    Full Text Available Definitive radiochemotherapy is the standard treatment for many patients with locally advanced nonsmall cell lung cancer (NSCLC. Treatment outcomes have improved over the last decades. Several treatment regimens have been shown effective and safe. This review summarises the results of significant studies between 1996 and 2015 on concomitant and sequential radiochemotherapy regimens and radiation dose per fraction. Beside therapy regimens, optimised radiotherapy planning is indispensable to improve outcome and minimise radiation-induced toxicity. An insight into the rationale of radiotherapy planning for stage III NSCLC is also provided.

  3. 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

  4. 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.

  5. 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

  6. Customising chemotherapy in advanced nonsmall cell lung cancer: daily practice and perspectives

    DEFF Research Database (Denmark)

    Vilmar, A C; Sorensen, J B

    2011-01-01

    Treating patients with advanced nonsmall cell lung cancer (NSCLC) is a daunting task but during recent years new options have emerged. By tailoring treatment using either information on histological subtypes of NSCLC or biomarkers it is now possible to improve outcome and maintain stable quality of...

  7. 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...

  8. 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...

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

    OpenAIRE

    2014-01-01

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

  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. 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. 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

  13. 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...

  14. Radio(chemo)therapy in locally advanced nonsmall cell lung cancer

    OpenAIRE

    Markus Glatzer; Olgun Elicin; Sara Ramella; Ursula Nestle; Paul Martin Putora

    2016-01-01

    Definitive radiochemotherapy is the standard treatment for many patients with locally advanced nonsmall cell lung cancer (NSCLC). Treatment outcomes have improved over the last decades. Several treatment regimens have been shown effective and safe. This review summarises the results of significant studies between 1996 and 2015 on concomitant and sequential radiochemotherapy regimens and radiation dose per fraction. Beside therapy regimens, optimised radiotherapy planning is indispensable to i...

  15. 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...

  16. 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...

  17. [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

  18. 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.

  19. 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

  20. 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.

  1. Radio(chemo)therapy in locally advanced nonsmall cell lung cancer.

    Science.gov (United States)

    Glatzer, Markus; Elicin, Olgun; Ramella, Sara; Nestle, Ursula; Putora, Paul Martin

    2016-03-01

    Definitive radiochemotherapy is the standard treatment for many patients with locally advanced nonsmall cell lung cancer (NSCLC). Treatment outcomes have improved over the last decades. Several treatment regimens have been shown effective and safe. This review summarises the results of significant studies between 1996 and 2015 on concomitant and sequential radiochemotherapy regimens and radiation dose per fraction. Beside therapy regimens, optimised radiotherapy planning is indispensable to improve outcome and minimise radiation-induced toxicity. An insight into the rationale of radiotherapy planning for stage III NSCLC is also provided. PMID:26929423

  2. 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 ...

  3. 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

  4. 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...

  5. 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.

  6. 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 ...

  7. 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

  8. 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.

  9. 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.)

  10. 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.

  11. 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.

  12. 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

  13. 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.

  14. Treatment Advances in Locally Advanced and Metastatic Non-Small Cell Lung Cancer

    OpenAIRE

    Surmont, Veerle

    2010-01-01

    textabstractLung cancer is the leading cause of cancer mortality in the United States and Europe. Approximately 85% of the patients with lung cancer have non–small cell lung cancer (NSCLC), which can be classified into squamous, adeno, large cell and not otherwise specified (NOS) histologies. The most common histologies are: adenocarcinoma ( 50%), squamous cell ( 20%), and large cell ( 10%). More than two third of the patients have locally advanced or metastatic disease at the time of diagnos...

  15. 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.

  16. 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.

  17. 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...

  18. 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.

  19. 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

  20. 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.)

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

    Directory of Open Access Journals (Sweden)

    Meina WU

    2011-03-01

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

  2. Prognostic Value of Fluoro-D-glucose Uptake of Primary Tumor and Metastatic Lesions in Advanced Nonsmall Cell Lung Cancer

    OpenAIRE

    Nguyen, Xuan Canh; Nguyen, Khoi; Tran, Minh Thong; Maurea, Simone; Salvatore, Marco

    2014-01-01

    To assess the prognostic value of maximum standardized uptake value (maxSUV) of the primary tumor (maxSUVpt), maxSUV of whole-body tumors (maxSUVwb) and sum of maximum standardized uptake value (sumaxSUV) measured by the sum of maxSUVs of the primary tumor, metastatic lymph nodes, and metastatic lesions per each organ on fluoro-D-glucose-positron emission tomography/computed tomography in advanced non-small cell lung cancer (NSCLC). Eighty-three patients (49 male, 34 female) with advanced NSC...

  3. 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.

  4. 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.

  5. 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...

  6. 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

  7. 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...

  8. 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

  9. 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

  10. The role of prophylactic cranial irradiation in regionally advanced non-small cell lung cancer. A Southwest Oncology Group Study

    Energy Technology Data Exchange (ETDEWEB)

    Rusch, V.W.; Griffin, B.R.; Livingston, R.B. (Univ. of Washington, Seattle (USA))

    1989-10-01

    Lung cancer is the most common malignant disease in the United States. Only the few tumors detected very early are curable, but there has been some progress in the management of more advanced non-small cell lung cancer, particularly in regionally inoperable disease. Prevention of central nervous system relapse is an important issue in this group of patients because brain metastases ultimately develop in 20% to 25% of them. Seventy-three patients with regionally advanced non-small cell lung cancer were entered into a Phase II trial of neutron chest radiotherapy sandwiched between four cycles of chemotherapy including cisplatin, vinblastine, and mitomycin C. Prophylactic cranial irradiation was administered concurrently with chest radiotherapy (3000 cGy in 10 fractions in 15 patients; 3600 cGy in 18 fractions in the remaining 50 patients). Patients underwent computed tomographic scan of the brain before treatment and every 3 months after treatment. The initial overall response rate was 79%, but 65 of the 73 patients have subsequently died of recurrent disease. Median follow-up is 9 months for all 73 patients and 26 months for eight long-term survivors. No patient who completed the prophylactic cranial irradiation program had clinical or radiologic brain metastases. Toxic reactions to prophylactic cranial irradiation included reversible alopecia in all patients, progressive dementia in one patient, and possible optic neuritis in one patient. Both of these patients received 300 cGy per fraction of irradiation. The use of prophylactic cranial irradiation has been controversial, but its safety and efficacy in this trial supports its application in a group of patients at high risk for central nervous system relapse. Further evaluation of prophylactic cranial irradiation in clinical trials for regionally advanced non-small cell lung cancer is warranted.

  11. The role of prophylactic cranial irradiation in regionally advanced non-small cell lung cancer. A Southwest Oncology Group Study

    International Nuclear Information System (INIS)

    Lung cancer is the most common malignant disease in the United States. Only the few tumors detected very early are curable, but there has been some progress in the management of more advanced non-small cell lung cancer, particularly in regionally inoperable disease. Prevention of central nervous system relapse is an important issue in this group of patients because brain metastases ultimately develop in 20% to 25% of them. Seventy-three patients with regionally advanced non-small cell lung cancer were entered into a Phase II trial of neutron chest radiotherapy sandwiched between four cycles of chemotherapy including cisplatin, vinblastine, and mitomycin C. Prophylactic cranial irradiation was administered concurrently with chest radiotherapy (3000 cGy in 10 fractions in 15 patients; 3600 cGy in 18 fractions in the remaining 50 patients). Patients underwent computed tomographic scan of the brain before treatment and every 3 months after treatment. The initial overall response rate was 79%, but 65 of the 73 patients have subsequently died of recurrent disease. Median follow-up is 9 months for all 73 patients and 26 months for eight long-term survivors. No patient who completed the prophylactic cranial irradiation program had clinical or radiologic brain metastases. Toxic reactions to prophylactic cranial irradiation included reversible alopecia in all patients, progressive dementia in one patient, and possible optic neuritis in one patient. Both of these patients received 300 cGy per fraction of irradiation. The use of prophylactic cranial irradiation has been controversial, but its safety and efficacy in this trial supports its application in a group of patients at high risk for central nervous system relapse. Further evaluation of prophylactic cranial irradiation in clinical trials for regionally advanced non-small cell lung cancer is warranted

  12. 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

  13. Randomized study of gefitinib versus pemetrexed as maintenance treatment in patients with advanced glandular non-small cell lung cancer

    OpenAIRE

    Xu, Yan-Hua; Mei, Jing-Song; Zhou, Juan

    2015-01-01

    Gefitinib was compared with pemetrexed as maintenance therapy in Patients with Advanced Glandular Non-small Cell Lung Cancer, mainly regarding clinical effect and side effect. A randomized trial of pemetrexed as study group (500 mg/m2, dl) versus gefitinib as the control group [250 mg on night 1, 250 mg on morning 2 (every day)] was conducted in 188 patients, 94 cases in each group with a therapy cycle of 21 days. In addition, the study group was also treated with folic acid, vitB12 and dexam...

  14. Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors for Elderly Patients with Advanced Non-Small Cell Lung Cancer

    OpenAIRE

    A. Zaniboni; Meriggi, F.

    2010-01-01

    Lung cancer is the leading cause of cancer-related mortality in both men and women and approximately 219,440 new cases of nonsmall cell lung cancer (NSCLC) were estimated to occur in the USA in 2009, which caused 159,390 NSCLC-related deaths. More than 50% of cases of advanced NSCLC are diagnosed in patients older than age 65, and recent Surveillance Epidemiology and End Results (SEERs) data suggest that the median age at diagnosis is 70 years. Until recently, the disease has been undertr...

  15. Clinical efficacy evaluation of Liujunzi decoction combined with EP chemotherapy regiment for advanced non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    Xin-Jun Xiong; Long-Jun Xiong

    2016-01-01

    Objective:To analyze the clinical efficacy of Liujunzi decoction combined with EP chemotherapy regiment for advanced non-small cell lung cancer.Methods:A total of 72 cases of patients with non-small cell lung cancer were included in the study, the range of patients’ treatment was from August 2012 to October 2014, and according to different treatment, they were divided into observation group 36 cases and control group 36 cases. Control group received EP chemotherapy, observation group received Liujunzi decoction combined with EP chemotherapy regiment, and then differences in serum tumor marker levels, tumor tissue-related protein levels, PDCD5, Nrf2, HIF-1α and GLUT1 levels, and levels of VEGF, GSTs, TSGF and so on were compared between two groups.Results:Serum CY211, SCC, NSE, CEA and CA199 levels of observation group after treatment were lower than those of control group; TUBB3, ERCC-1, MT and P53 expression levels of observation group after treatment were lower while Mcll and Fbw7 expression levels were higher; PDCD5 level of observation group after treatment was higher than that of control group while Nrf2, HIF-1α and GLUT1 levels were lower than those of control group; CD4+CD25+Foxp3+ Treg/CD4+ T, VEGF, GSTs and TSGF values of observation group after treatment were lower than those of control group. Conclusion:Liujunzi decoction combined with EP chemotherapy regiment for patients with advanced non-small cell lung cancer can effectively inhibit tumor cell proliferation as well as invasion and metastasis, is helpful for disease control and prognosis improvement, and has positive clinical significance.

  16. VINDESINE WITH CYCLOPHOSPHAMIDE-EPIRUBICIN-CISPLATIN IN THE TREATMENT LOCALLY ADVANCED NON-SMALL CELL LUNG CANCER

    Institute of Scientific and Technical Information of China (English)

    HU Yan-ping; KE Yu-hua; FU Xiao-yu

    1999-01-01

    Objective: To evaluate the addition of vindesine to a cyclophosphamide-epirubicin-cisplatin (CAP) regimen for treating the patients with locally advanced non-small cell lung cancer (NSCLC). Methods: From May 1994to August 1998, 59 previously untreated patients with stage Ⅲa and Ⅲb non-small cell lung cancer were enrolled into this trial. Patients characteristics were the following: the median age was 52 years; the median performance status was 1; there were 19 stage Ⅲa and 40 stage Ⅲb; there were 47 adenocarcinoma, 10squamous cell carcinoma and 2 large cell carcinoma. All patients were treated with vindesine (2 mg/m2, on day 1and day 8), cyclophosphamide (0.6/m2, on day 1),epirubicin (40 mg/m2, on day 1) and cisplatin (60 mg/m2,on day 1) every 3 or 4 weeks. Results: Four achieved a complete response (6.8%), 29 achieved a partial response (49.2%), 15 had stable disease, and 10 had progressive disease. A clinical improvement was in 45 of 59 patients (76.3%). The most frequent major toxic effects were myelosuppression, nausea and vomiting.Conclusion: The vindesine with CAP regimen was active combination chemotherapy in patients with locally advanced NSCLC accompanied by the limited side effects.

  17. 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.

  18. 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...

  19. [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

  20. 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

  1. Effect of nimotuzumab targeted therapy combined with conventional chemotherapy in treatment of advanced non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    Hai-Ping Xu; Hui-Juan Wu; Shang-Shuang Shi

    2016-01-01

    Objective:To study the clinical efficacy of nimotuzumab targeted therapy combined with conventional chemotherapy in treatment of advanced non-small cell lung cancer.Methods:Patients with non-small cell lung cancer were selected for study and randomly divided into targeted group and conventional group, efficacy of two groups after 2 and 4 treatment cycles was evaluated, tumor tissue was collected and activation of PI3K/AKT pathway, MAPK/ERK pathway and JAK2/STAT3 pathway was detected.Results:After 2 and 4 chemotherapy cycles, CR case number, PR case number and SD case number of targeted group were significantly more than those of conventional group (P<0.05); PD case number was significantly less than that of conventional group (P<0.05). Expression levels of PI3K, AKT, MAPK, ERK1, ERK2, JAK2 andSTAT3 in tumor tissue of targeted group were significantly lower than those of conventional group (P<0.05). Expression levels of FasL and Bim in tumor tissue of targeted group were significantly higher than those of conventional group (P<0.05), and expression levels ofBcl-2, Survivin, VEGF, HIF-1α andEPO were significantly lower than those of conventional group (P<0.05).Conclusions:Nimotuzumab targeted therapy combined with conventional chemotherapy can achieve more precise short-term efficacy and inhibit the activation of PI3K/AKT pathway, MAPK/ERK pathway and JAK2/STAT3 pathway, and it is a more ideal solution for treatment of advanced non-small cell lung cancer.

  2. EFFECT OF NEOADJUVANT CHEMOTHERAPY USING PACLITAXEL COMBINED WITH CARBOPLATIN ON ADVANCED NON-SMALL CELL LUNG CANCER

    Institute of Scientific and Technical Information of China (English)

    XIONG Hong-chao; CHEN Jin-feng; ZHANG Li-jian

    2006-01-01

    Objective: To assess the therapeutic effectiveness of preoperative neoadjuvant chemotherapy using a combination of paclitaxel and carboplatin on local advanced non-small cell lung cancer (NSCLC). Methods: Twenty-five patients with advanced NSCLC were treated with paclitaxel and carboplatin for 2 to 4 cycles before undergoing tumor resection and then postoperative chemotherapy/radiotherapy therapy for 2 to 4 cycles. Results: Following neoadjuvant chemotherapy, the most prominent side-effect was bone marrow restraint. The overall response rate of preoperative chemotherapy was 56%. The mean survival time was 26.5 months, with 1-, 2- and 5-year survival rates of 55%, 25%, and 16%, respectively. All NSCLC patients survived the perioperative period. Conclusion: Preoperative neoadjuvant chemotherapy combining paclitaxel and carboplatin produced minimal side-effect while increasing the probability that advanced NSCLC patients would be able to undergo surgery thus improving their prognosis.

  3. 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.

  4. Clinical Effects for Patients with Recurrent Advanced Non-small Cell Lung Cancer Treated with Icotinib Hydrochloride

    Directory of Open Access Journals (Sweden)

    Jingying NONG

    2013-05-01

    Full Text Available Background and objective Icotinib hydrochloride is the third single target EGFR-TKI used in clinical treatment of advanced non-small cell lung cancer (NSCLC. Clinical research reports on its efficacy and survival in patients with Recurrent Advanced NSCLC are still little.The aim of this study is to evaluate the efficacy and survival of Icotinib hydrochloride for patients with advanced non-small cell lung cancer who failed to previous chemotherapy and explore the association of clinical features with the efficacy and survival. Methods The clinical data of 60 NSCLC patients referred to the Beijing Chest Hospital, Capital Medical University from March 2009 to July 2012 were retrospectively analyzed. Results The overall response rate (ORR was 45.0% and the disease control rate (DCR was 80.0%. The median progression-free survival (PFS time was 6.7 months. RR and PFS in female were superior to male (P=0.014, 0.013, respectively. RR, DCR in 2nd-line subgroup were superior to ≥3rd-line subgroup (P=0.020, 0.024, respectively. RR, DCR and PFS in EGFR mutation carriers were significantly superior to wild-type patients (P=0.006, <0.001, 0.002, respectively . There was no statistical difference in RR and PFS between those age <65 and ≥65 or PS<2 and PS≥2. There was no statistical difference in RR and DCR between exon 19 deletion and exon 21 mutations, while the former had much longer PFS (P=0.020. EGFR mutation and exon 19 deletion are the independent prognostic factors to significantly improve the PFS (P=0.009, 0.012, respectively. The side effects were generally mild and consisted of rash and diarrhea. Conclusion Icotinib hydrochloride is effective especially in EGFR mutation carriers and well tolerated in patients with recurrent advanced non-small-cell lung cancer.

  5. 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

  6. 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.

  7. Effects of MICA expression on the prognosis of advanced non-small cell lung cancer and the efficacy of CIK therapy.

    Directory of Open Access Journals (Sweden)

    Yu Chen

    Full Text Available 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, stage, treatment history (including 38 patients who were given autologous CIK cell infusion, and overall survival (OS. MICA expression in lung cancer tissue was evaluated by immunohistochemical staining. Analyses of MICA expression, and CIK therapy association with survival outcomes were performed using Cox proportional models, Kaplan-Meier methods, and the log-rank test. RESULT: s MICA was expressed in both membrane and cytoplasm. MICA expression correlated with the stage of lung cancer, ECOG score, gender and age. Multivariate COX regression analysis showed that the expression of MICA was an independent prognostic factor of advanced non-small cell lung cancer (p = 0.002. In subgroup analysis, we divided the 222 patients into CIK and control groups. In the CIK group, the medium OS (mOS of patients with a high expression of MICA was longer than in those with low expression of MICA (27 months vs. 13 months. In the control group, the mOS in patients with a high expression of MICA was shorter than in patients with low MICA expression (9 months vs. 18 months. COX regression analysis showed that the MICA expression affects the effect of CIK therapy (p<0.0001. CONCLUSION: 1 The high expression of MICA is one of the indicators of a poor prognosis for advanced non-small cell lung cancer patients. 2 The high expression of MICA might be one of the predictive factors for successful CIK therapy.

  8. Third-generation inhibitors targeting EGFR T790M mutation in advanced non-small cell lung cancer.

    Science.gov (United States)

    Wang, Shuhang; Cang, Shundong; Liu, Delong

    2016-01-01

    The tyrosine kinase inhibitors (TKI) against epidermal growth factor receptor (EGFR) are widely used in patients with non-small cell lung cancer (NSCLC). However, EGFR T790M mutation leads to resistance to most clinically available EGFR TKIs. Third-generation EGFR TKIs against the T790M mutation have been in active clinical development. These agents include osimertinib, rociletinib, HM61713, ASP8273, EGF816, and PF-06747775. Osimertinib and rociletinib have shown clinical efficacy in phase I/II trials in patients who had acquired resistance to first- or second-generation TKIs. Osimertinib (AZD9291, TAGRISSO) was recently approved by FDA for metastatic EGFR T790M mutation-positive NSCLC. HM61713, ASP8237, EGF816, and PF-06747775 are still in early clinical development. This article reviews the emerging data regarding third-generation agents against EGFR T790M mutation in the treatment of patients with advanced NSCLC. PMID:27071706

  9. Clinical investigation of weekly carboplatin and paclitaxel with concurrent radiation therapy for locally advanced non-small cell lung cancer

    International Nuclear Information System (INIS)

    The aim of this study was to evaluate retrospectively chemotherapy of weekly carboplatin and paclitaxel with concurrent radiation therapy for patients with locally advanced non-small cell lung cancer (NSCLC). Between January 2000 and March 2008, 38 patients were treated by chemotherapy with carboplatin and paclitaxel once a week, repeated for 6 weeks, with thoracic radiation therapy of 1 or 2 times a day on weekdays. After concurrent chemoradiotherapy, we planned consolidation chemotherapy of carboplatin (area under the curve (AUC) 5-6) and weekly paclitaxel (70-80 mg/m2) on day 1, 8 and 15, when possible. The enrolled patients were 31 men and 7 women, with the median age of 59 years (39-76 years), stage IIIA/IIIB: 10/28, Ad/Sq/AdSq/Un: 17/17/2/2. The response rate of this chemoradiotherapy was 78.9%. The median survival time and time to progression were 24.7 months and 8.1 months, respectively. Grade 3 or 4 hematological toxicities during concomitant chemoradiotherapy were leukocytopenia (5.2%) and neutropenia (5.2%). Grade 3 or 4 non-hematological toxicities were esophagitis (2.6%) and pneumonitis (5.2%). There was a therapy-associated death by radiation pneumonitis. Carboplatin and paclitaxel with concurrent radiation therapy for a patient with stage III NSCLC showed a good response with relatively mild side effects. We reached the conclusion that concurrent chemoradiotherapy would be a useful choice for locally advanced non-small cell lung cancer on the practical clinic. (author)

  10. CLINICAL STUDY IN ACCELERATED HYPERFRACTIONATED IRRADIATION IN THE TREATMENT OF LOCAL ADVANCED NON-SMALL CELL LUNG CANCER

    Institute of Scientific and Technical Information of China (English)

    姚原; 吴国华; 陆冬青; 蒋马伟; 邬国琴; 翁霞

    2001-01-01

    Objective To evaluate the effect of accelerated hyperfractionated irradiation ( AHFI ) and conventional fractionated irradiation (CFI) for local advanced non-small cell lung cancer (NSCLC). Methods The patients of AHFI group were irradiated to large-field target volume by a daily fraction of 2Gy , and small-field target volume by a daily fraction of 1Gy with more than 6h interval. The total dose of largefield target volume was 50Gy /25Fx/5W and of small-field target volume was 75Gy /50Fx/5W. The patients in CFI group were irradiated by a daily fraction of 2Gy to the total dose of 66Gy /33Fx/6. 6W. After 3 months of radiotherapy, the tumor response rates of complete recovery ( CR ), partial recovery ( PR ), and no change ( NC ) and 1- and 2- year survival rate in the two groups were observed. Results The tumor response rates of CR, PR, NC in AHFI group and CFI group were 22.9% (8/35), 60.0% (21/35), 17.1% (6/35) and 11.4% (4/35), 51.4% (18/35), 37.2% (13/35) respectively (P>0.05). All patients were followed up 2 years or more. The 1- and 2- year survival rates in AHFI group and CFI group were 62.9% (22/35 ), 31.4 % ( 11/35) and 42.9% (15/35) , 17.1% (6/35) respectively (P0.05). Conclusion In comparison with CFI, AHFI may increase 1- and 2- year survival rate after treatment of local advanced non-small cell lung cancer, while the radio-reactions, either early or late, did not increase significantly.

  11. The Efficacy of Chinese Herbal Medicine as an Adjunctive Therapy for Advanced Non-small Cell Lung Cancer: A Systematic Review and Meta-analysis

    OpenAIRE

    Shi Guang Li; Hai Yong Chen; Chen Sheng Ou-Yang; Xi-Xin Wang; Zhen-Jiang Yang; Yao Tong; William C. S. Cho

    2013-01-01

    Many published studies reflect the growing application of complementary and alternative medicine, particularly Chinese herbal medicine (CHM) use in combination with conventional cancer therapy for advanced non-small cell lung cancer (NSCLC), but its efficacy remains largely unexplored. The purpose of this study is to evaluate the efficacy of CHM combined with conventional chemotherapy (CT) in the treatment of advanced NSCLC. Publications in 11 electronic databases were extensively searched, a...

  12. 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 ...

  13. Clinical Observation of Erlotinib in the Treatment of Advanced Non-small Cell Lung Cancer: A Report of 92 Eases

    Directory of Open Access Journals (Sweden)

    Baohui HAN

    2009-12-01

    Full Text Available Background and objective Erlotinib, a selective inhibitor of epidermal growth factor receptor tyrosine kinase, has been approved effective in local advanced or metastatic non-small cell lung cancer (NSCLC. The aim of this study was to evaluate the efficacy and safety of erlotinib for the treatment of advanced NSCLC. Methods Ninety-two patients with advanced NSCLC who had failed or not tolerated or refused chemotherapy received 150 mg oral doses of erlotinib once daily until the disease progression or intolerable toxicity. Results Among the 92 NSCLC patients, 2 patient got complete response (2.2%, 22 partial response (23.9%, 48 stable disease (52.2% and 20 progressive disease (21.7%. The overall response rate and the disease controlled rate of erlotinib was 26.1% (24/92 and 78.3% (72/92, respectively. The response rate of erlotinib were significantly higher in rash and ECOG 0-1 than no rash and ECOG ≥ 2. The disease controlled rate of erlotinib was significantly higher in female and non-smokers than male and smokers (P < 0.05. The response rate of erlotinib did not show significant differences within pathological type or previous treatment. The most common side effects were rash and diarrhea with 84.8% and 31.5%, respectively, but usually were mild. Conclusion Erlotinib is effective and safe in the treatment of advanced NSCLC patients.

  14. Risk factors associated with fatal pulmonary hemorrhage in locally advanced non-small cell lung cancer treated with chemoradiotherapy

    International Nuclear Information System (INIS)

    The purpose of this study was to identify the risk factors associated with fatal pulmonary hemorrhage (PH) in patients with locally advanced non-small cell lung cancer (NSCLC), treated with chemoradiotherapy. The medical records of 583 patients with locally advanced NSCLC, who were treated with chemoradiotherapy between July 1992 and December 2009 were reviewed. Fatal PH was defined as PH leading to death within 24 h of its onset. Tumor cavitation size was defined by the cavitation diameter/tumor diameter ratio and was classified as minimum (< 0.25), minor (≥ 0.25, but < 0.5), and major (≥ 0.5). Of the 583 patients, 2.1% suffered a fatal PH. The numbers of patients with minimum, minor, and major cavitations were 13, 11, and 14, respectively. Among the 38 patients with tumor cavitation, all 3 patients who developed fatal PH had major cavitations. On multivariate analysis, the presence of baseline major cavitation (odds ratio, 17.878), and a squamous cell histology (odds ratio, 5.491) proved to be independent significant risk factors for fatal PH. Interestingly, all patients with fatal PH and baseline major cavitation were found to have tumors with squamous cell histology, and the occurrence of fatal PH in patients having both risk factors was 33.3%. Patients at high risk of fatal PH could be identified using a combination of independent risk factors

  15. Targeted therapies for treatment of non-small cell lung cancer-Recent advances and future perspectives.

    Science.gov (United States)

    Minguet, Joan; Smith, Katherine H; Bramlage, Peter

    2016-06-01

    Non-small cell lung cancer (NSCLC) is one of the most deadly cancers worldwide, with poor prognosis once the disease has progressed past the point at which surgery is a viable option. Whilst chemotherapy has improved survival over recent decades, there is still great need for improvements in treatments for patients with advanced disease. Over the last decade, a variety of such drugs have received market approval for treating NSCLC, with a variety of others in the pipeline. Here, we review the development of targeted therapies for the treatment of advanced or metastatic NSCLC, including those already in clinical practice and those in early trials. The epidermal growth factor receptor (EGFR) inhibitors, gefitinib, erlotinib and afatinib; the anaplastic lymphoma kinase (ALK) inhibitor, crizotinib; and the anti-vascular endothelial growth factor receptor monoclonal antibody, bevacizumab, are already providing improved survival for patients with NSCLC. Moreover, the discovery of EGFR mutations and ALK rearrangements has enabled the identification of patients who are more likely to benefit from a specific drug. The recent approval of the immune checkpoint inhibitor nivolumab, along with the designation of alectinib and MPDL3280A as breakthrough therapies by the FDA, demonstrates how rapidly this area of research is expanding. Over the last decade there has been significant progress made in the treatment of advanced NSCLC, and the large and varied selection of drugs currently undergoing trials provide great promise for improving the prognosis of this highly prevalent and deadly form of cancer. PMID:26537995

  16. Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors for Elderly Patients with Advanced Non-Small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    A. Zaniboni

    2010-01-01

    Full Text Available Lung cancer is the leading cause of cancer-related mortality in both men and women and approximately 219,440 new cases of nonsmall cell lung cancer (NSCLC were estimated to occur in the USA in 2009, which caused 159,390 NSCLC-related deaths. More than 50% of cases of advanced NSCLC are diagnosed in patients older than age 65, and recent Surveillance Epidemiology and End Results (SEERs data suggest that the median age at diagnosis is 70 years. Until recently, the disease has been undertreated in this patient population, with a perception among many clinicians that elderly patients do not tolerate chemotherapy or radiotherapy. So, single agent chemotherapy is the recommended approach by the ASCO and International Expert Panels in unselected patients. The introduction of novel targeted therapies, such as Epidermal Growth Factor Receptor (EGFR Tyrosine Kinase Inhibitors (TKIs which improved survival versus placebo in patients who had previously failed on chemotherapy, gives clinicians new, effective, and better tolerated options to consider when treating NSCLC in elderly patients. This paper describes the advances of EGFR TKIs for elderly patients with advanced NSCLC.

  17. Risk factors for brain metastases after definitive chemoradiation for locally advanced non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Petrović Marina

    2009-01-01

    Full Text Available Background/Aim. As therapy for locally advanced nonsmall cell lung carcinoma (NSCLC improves, brain metastases (BM still remain a great problem. The aim of the study was to analyze risk factors for BM in patients with locally advanced NSCLC after chemoradiation therapy. Methods. Records for 150 patients with non-resectable stage IIIA/IIIB NSCLC treated with combined chemoradiation therapy were analyzed. All of them had negative brain metastases imaging result before the treatment. Incidence of BM was examined in relation to age, sex, histological type, stage, performance status scale of wellbeing of cancer patients, weight loss, chemotherapy regimen and chemotherapy timing. Results. One- and 2-year incidence rates of BM were 19 and 31%, respectively. Among pretreatment parameters, stage IIIB was associated with a higher risk of BM (p < 0.004 vs stage IIIA. Histologically, the patients with nonsquamous tumors had an exceptionally high 2-year BM risk rate of 32% (p < 0.02. Examining treatment-related parameters, 1-year and 2-year actuarial risk of BM were 27 and 39%, respectively, in the patients receiving chemotherapy before radiotherapy and 15 and 20%, respectively, when radiotherapy was not delayed (p < 0.03. On multivariate analysis, timing of chemotherapy (p < 0.05 and stage IIIA vs IIIB (p < 0.01 remained statistically significant. Conclusion. Patients with IIIB stage, nonsquamous NSCLC, particularly those receiving sequential chemotherapy, had significantly high BM rates.

  18. Strategies of dose escalation in the treatment of locally advanced non-small cell lung cancer: image guidance and beyond

    Directory of Open Access Journals (Sweden)

    Alexander eChi

    2014-06-01

    Full Text Available Radiation dose in the setting of chemo-radiation for locally advanced non-small cell lung cancer (NSCLC has been historically limited by the risk of normal tissue toxicity and this has been hypothesized to correlate with the poor results in regard to local tumor recurrences. Dose escalation, as a means to improve local control, with concurrent chemotherapy has been shown to be feasible with three-dimensional conformal radiotherapy in early phase studies with good clinical outcome. However, the potential superiority of moderate dose escalation to 74 Gy has not been shown in phase III randomized studies. In this review, the limitations in target volume definition in previous studies; and the factors that may be critical to safe dose escalation in the treatment of locally advanced NSCLC, such as respiratory motion management, image guidance, intensity modulation, FDG-PET incorporation in the treatment planning process, and adaptive radiotherapy, are discussed. These factors, along with novel treatment approaches that have emerged in recent years, are proposed to warrant further investigation in future trials in a more comprehensive and integrated fashion.

  19. Kanglaite injection combined with chemotherapy versus chemotherapy alone in the treatment of advanced non-small cell lung carcinoma

    Directory of Open Access Journals (Sweden)

    Xiaohong Liu

    2014-01-01

    Full Text Available Objective: To evaluate the clinical efficacy of Kanglaite (KLT injection combined with chemotherapy versus chemotherapy alone in the treatment of advanced non-small cell lung carcinoma (NSCLC by meta-analysis. Materials and Methods: Electronic search of PubMed, EMBASE, Chinese National Knowledge Infrastructure (CNKI and Wanfang databases was conducted to select studies about KLT injection combined with chemotherapy versus chemotherapy alone in the treatment of advanced NSCLC. The pooled risk ratio (RR and its 95% confidence interval (95% CI for objective response rate (ORR, Karnofsky (KPS score improvement and nausea and vomiting were calculated by Stata11.0 statistical software. Result: Finally, we included 34 clinical trials in this meta-analysis. The pooled results suggested that KLT injection combined with systematic chemotherapy can significantly increase the objective response rate (ORR [RR = 1.35, 95% CI: 1.23-1.48, (Z = 6.43, P = 0.000], the quality of patients′ life (KSP improvement [RR = 2.04, 95% CI: 1.79-2.33, (Z = 10.57, P = 0.000] and decrease the risk ratio of gastrointestinal reaction [RR = 0.53, 95% CI: 0.42-0.66, (Z = 5.53, P = 0.000] compared with chemotherapy alone. Conclusion: KLT injection combined with chemotherapy can improve the short-term efficacy, performance status and decrease the risk of gastrointestinal reaction compared with systematic chemotherapy alone.

  20. 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)

  1. Renal Salt Wasting in Patients Treated with High-Dose Cisplatin, Etoposide, and Mitomycin in Patients with Advanced Non-Small Cell Lung Cancer

    OpenAIRE

    Lee, Yong Koo; Shin, Dong Moon

    1992-01-01

    Cisplatin has many toxic effects; emesis, impairment of renal function, myelosuppression, peripheral neuropathy, ototoxicity and renal tubular wasting. We used MVP regimen (Mitomycin C, Vp-16, and Cisplatin) in advanced Non-Small Cell Lung Cancer (NSCLC). Using hydration and prophylactic supplementation of sodium and potassium before and during chemotherapy, we have observed the development of hyponatremia in 48 courses (43%), hypokalemia in 23 courses and hypomagnesemia in 11 courses. Some p...

  2. Shenqi fuzheng, an injection concocted from chinese medicinal herbs, combined with platinum-based chemotherapy for advanced non-small cell lung cancer: a systematic review

    OpenAIRE

    Wang Min-Yan; Su Shi-Yue; Dong Ju; Zhan Zhen

    2010-01-01

    Abstract Background Platinum-based chemotherapy has been a standard therapy for advanced non-small cell lung cancer (NSCLC), but it has high toxicity. In China, Shenqi Fuzheng, a newly developed injection concocted from Chinese medicinal herbs has been reported that may increase efficacy and reduce toxicity when combined with platinum-based chemotherapy, but little is known about it outside of China. The aim of this study was to systematically review the existing clinical evidence on Shenqi F...

  3. A clinical trial on docetaxel and carboplatin therapy with or without nimotuzumab for the treatment of advanced nonsmall cell lung cancer

    OpenAIRE

    Daliang Qi; Yan Cui; Qingsheng Wang; Chongbiao Huang; Jie Xu; Yanzhuo Yang; Liang Xin; Ye Tian; Xin Angelique Qi

    2015-01-01

    Background: To evaluate the role of nimotuzumab in combination with chemotherapy in patients with advanced nonsmall cell lung cancer (NSCLC) through progress-free survival, changes in tumor marker expression and adverse drug reactions. Materials and Methods: A total of 59 NSCLC patients were randomized into two groups. The treatment group (n = 30) received nimotuzumab (200 mg) with docetaxel (60 mg/m 2 ) and carboplatin (area under curve = 5), whereas the control group (n = 29) received c...

  4. Gene-guided Gefitinib switch maintenance therapy for patients with advanced EGFR mutation-positive Non-small cell lung cancer: an economic analysis

    OpenAIRE

    Zhu Jun; Li Te; Wang Xiaohui; Ye Ming; Cai Jian; Xu Yuejuan; Wu Bin

    2013-01-01

    Abstract Background Maintenance therapy with gefitinib notably improves survival in patients with advanced non-small cell lung cancer (NSCLC) and EGFR mutation-positive tumors, but the economic impact of this practice is unclear. Methods A decision-analytic model was developed to simulate 21-day patient transitions in a 10-year time horizon. The clinical data were primarily obtained from the results of a pivotal phase III trial that assessed gefitinib maintenance treatment in patients with ad...

  5. Prognostic implications of survivin and lung resistance protein in advanced non-small cell lung cancer treated with platinum-based chemotherapy

    OpenAIRE

    Huang, Wenfeng; Mao, Yan; ZHAN, YONGZI; Huang, Jianfeng; Wang, Xiangping; LUO, PENGHUI; Li LI; MO, DUNCHANG; Liu, Qiong; Xu, Huimin; Huang, Changjie

    2015-01-01

    Platinum-based chemotherapy is the first-line treatment for non-small cell lung cancer (NSCLC), but the chemotherapy often results in the development of chemoresistance. The present study aimed to explore the prognostic implications of survivin and lung resistance protein (LRP) in advanced NSCLC treated with platinum-based chemotherapy. Tumor samples were collected from 61 hospitalized patients with stage IIIB-IV NSCLC that underwent platinum-based chemotherapy. All patient samples were colle...

  6. Treatment outcome of locally advanced non-small cell lung cancer patients who received concurrent chemoradiotherapy with weekly paclitaxel

    International Nuclear Information System (INIS)

    To analyze the response, toxicity, patterns of failure and survival rate of patients with locally advanced non-small cell lung cancer who were treated with concurrent chemoradiotherapy with weekly paclitaxel. Twenty-three patients with locally advanced non-small cell lung cancer patients who received radical chemoradiotherapy from October 1999 to September 2004 were included in this retrospective study. Patients received total 55.4 ∼ 64.8 (median 64.8) Gy (daily 1.8 Gy per fraction, 5 days per weeks) over 7 ∼ 8 weeks. 50 or 60 mg/m2 of paclitaxel was administered on day 1, 8, 15, 22, 29 and 36 of radiotherapy. Four weeks after the concurrent chemoradiotherapy, three cycles of consolidation chemotherapy consisted of paclitaxel 135 mg/m2 and cisplatin 75 mg/m2 was administered every 3 weeks. Of the 23 patients, 3 patients refused to receive the treatment during the concurrent chemoradiotherapy. One patient died of bacterial pneumonia during the concurrent chemoradiotherapy. Grade 2 radiation esophagitis was observed in 4 patients (17%). Sixteen patients received consolidation chemotherapy. During the consolidation chemotherapy, 8 patients (50%) experienced grade 3 or 4 neutropenia and one of those patients died of neutropenic sepsis. Overall response rate for 20 evaluable patients was 90% including 4 complete responses (20%) and 14 partial responses (70%). Among 18 responders, 9 had local failure, 3 had local and distant failure and 2 had distant failure only. Median progression-free survival time was 9.5 months and 2-year progression-free survival rate was 19%. Eleven patients received second-line or third-line chemotherapy after the treatment failure. The median overall survival time was 21 months. 2-year and 5-year survival rate were 43% and 33%, respectively. Age, performance status, tumor size were significant prognostic factors for progression-free survival. Concurrent chemoradiotherapy with weekly paclitaxel revealed high response rate and low toxicity

  7. Treatment outcome of locally advanced non-small cell lung cancer patients who received concurrent chemoradiotherapy with weekly paclitaxel

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Su Zy; Kim, Sung Whan; Shim, Byoung Yong [The Catholic University of Korea College of Medicine, Seoul (Korea, Republic of)] (and others)

    2006-12-15

    To analyze the response, toxicity, patterns of failure and survival rate of patients with locally advanced non-small cell lung cancer who were treated with concurrent chemoradiotherapy with weekly paclitaxel. Twenty-three patients with locally advanced non-small cell lung cancer patients who received radical chemoradiotherapy from October 1999 to September 2004 were included in this retrospective study. Patients received total 55.4 {approx} 64.8 (median 64.8) Gy (daily 1.8 Gy per fraction, 5 days per weeks) over 7 {approx} 8 weeks. 50 or 60 mg/m{sup 2} of paclitaxel was administered on day 1, 8, 15, 22, 29 and 36 of radiotherapy. Four weeks after the concurrent chemoradiotherapy, three cycles of consolidation chemotherapy consisted of paclitaxel 135 mg/m{sup 2} and cisplatin 75 mg/m{sup 2} was administered every 3 weeks. Of the 23 patients, 3 patients refused to receive the treatment during the concurrent chemoradiotherapy. One patient died of bacterial pneumonia during the concurrent chemoradiotherapy. Grade 2 radiation esophagitis was observed in 4 patients (17%). Sixteen patients received consolidation chemotherapy. During the consolidation chemotherapy, 8 patients (50%) experienced grade 3 or 4 neutropenia and one of those patients died of neutropenic sepsis. Overall response rate for 20 evaluable patients was 90% including 4 complete responses (20%) and 14 partial responses (70%). Among 18 responders, 9 had local failure, 3 had local and distant failure and 2 had distant failure only. Median progression-free survival time was 9.5 months and 2-year progression-free survival rate was 19%. Eleven patients received second-line or third-line chemotherapy after the treatment failure. The median overall survival time was 21 months. 2-year and 5-year survival rate were 43% and 33%, respectively. Age, performance status, tumor size were significant prognostic factors for progression-free survival. Concurrent chemoradiotherapy with weekly paclitaxel revealed high

  8. Outcome of 289 locally advanced non-small cell lung cancer treated with radiotherapy alone and radiotherapy combined with chemotherapy

    International Nuclear Information System (INIS)

    Objective: To retrospectively analyze the outcome of locally advanced non-small cell lung cancer patients treated with radiotherapy and chemoradiotherapy. Methods: 289 patients who were treated either by radiotherapy alone (168 patients) or radiotherapy plus chemotherapy (121 patients) from Dec. 1999 to Dec. 2002 were entered into the database for analysis. Pathological types: squamous cancer (152), adenocarcinoma(74), squamoadenocarcinoma(2) and other types (2). 24 showed cancer unclassificable and 35 were diagnosed without pathological proof. Stages: 74 had III A and 215 III B stage disease. Among the 121 patients treated with combined modality, 24 were treated with concurrent chemoradiotherapy, 78 radiotherapy after chemotherapy(C + R), and 19 radiotherapy followed by chemotherapy(R + C). In patients treated by concurrent chemoradiotherapy or C + R, 38 received consolidation chemotherapy after induction treatment. Results: The 1-, 3-, 5-year overall survival, and the median survival were: 45% , 16% , 8%, and 16.2 months for all patients; 57%, 27%, 11%, and 21.7 months for stage IIIA; 41%, 12%, 7%, and 15.3 months for IIIB. By logrank test, clinical stage, KPS performance, tumor volume, hemoglobin level before treatment, consolidation chemotherapy, radiation dose, and response to treatment showed statistically dramatic impact on overall survival. The overall survival rate and median survival time were slightly higher in the combined group than in the radiotherapy alone group, but the difference is statistically insignificant. In Cox multivariable regression, stage and consolidation chemotherapy were independent prognostic factors; KPS performance, radiation dose, and response to treatment were at the margin of statistical significance. Esophagitis and pneumonitis of Grade II or higher were 24% and 8%, respectively. Failure sites included in the thorax(41%), outside of thorax(48%), and both in and outside the thorax(11%). There was no difference between the

  9. Daily etoposide and cisplatin during thoracic radiotherapy for patients with locally advanced non-small cell lung cancer

    International Nuclear Information System (INIS)

    Purpose: A phase I/II trial was performed to investigate the toxicity and potential efficacy of delivering two radiosensitizing chemotherapeutic agents (cisplatin and etoposide) on a daily basis during twice daily thoracic radiotherapy for patients with locally advanced non-small cell lung cancer. Methods: Patients were eligible for this trial if they had unresectable or incompletely resected biopsy-proven stage IIIA or IIIB non-small cell lung carcinoma. However, patients with contralateral hilar or supraclavicular disease were excluded. Patients were required to have an ECOG performance status of 0-2 and ≤10% weight loss during the preceding three months. Thoracic radiation treatment (TRT) was delivered as accelerated hyperfractionated TRT with 150 cGy given twice daily beginning on a Monday. Patients received a two-week break between two courses of 3000 cGy (total dose:6000cGy). Patients received etoposide (25 mg/m2 po) on days 1-12 and cisplatin (3 mg/m2 IV) on days 1-5 and 8-12 of each course of TRT. Two weeks following the completion of TRT patients began two cycles (q 28d) of etoposide (25 mg/m2, po, d1-21) and cisplatin (50 mg/m2 IV, d1). Patients were seen in followup at 2 months following the completion of therapy and subsequently at 3 month intervals for the first year. Results: Seventeen patients were entered on the trial and the median followup was 11 months. Of the 17 patients, 13 had evaluable disease and 4 had measurable disease; 16 were deemed unresectable and one had an incomplete resection; 6 had squamous cell carcinomas and 11 had non-squamous cell carcinomas; 5 had primary tumors greater than 6 cm, 9 were 3-6 cm and 3 were <3 cm; 14 had less than 5% weight loss and 3 had 5-10% weight loss; 9 had stage IIIA disease and 8 had IIIB disease. The most common hematologic toxicity was leukopenias: 4 patients had grade 3 and 1 had grade 4 toxicity. No grade 3 or greater thrombocytopenia was observed. There were 6 grade 3 nonhematologic toxicities

  10. 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

  11. Microwave Ablation in Combination with Chemotherapy for the Treatment of Advanced Non-Small Cell Lung Cancer

    International Nuclear Information System (INIS)

    PurposeTo verify whether microwave ablation (MWA) used as a local control treatment had an improved outcome regarding advanced non-small cell lung cancer (NSCLC) when combined with chemotherapy.MethodsThirty-nine patients with histologically verified advanced NSCLC and at least one measurable site other than the ablative sites were enrolled. Primary tumors underwent MWA followed by platinum-based doublet chemotherapy. Modified response evaluation criteria in solid tumors (mRECIST) and RECIST were used to evaluate therapeutic response. Complications were assessed using the National Cancer Institute Common Toxicity Criteria (version 3.0).ResultsMWA was administered to 39 tumors in 39 patients. The mean and median diameters of the primary tumor were 3.84 cm and 3.30 cm, respectively, with a range of 1.00–9.00 cm. Thirty-three (84.6 %) patients achieved a partial response. No correlation was found between MWA efficacy and clinicopathologic characteristics. For chemotherapy, 11 patients (28.2 %) achieved a partial response, 18 (46.2 %) showed stable disease, and 10 (25.6 %) had progressive disease. The overall objective response rate and disease control rate were 28.2 and 74.4 %, respectively. The median progression-free survival time was 8.7 months (95 % CI 5.5–11.9). The median overall survival time was 21.3 months (95 % CI 17.0–25.4). Complications were observed in 22 (56.4 %) patients, and grade 3 adverse events were observed in 3 (7.9 %) patients.ConclusionsPatients with advanced NSCLC could benefit from MWA in combination with chemotherapy. Complications associated with MWA were common but tolerable

  12. Phase II study. Concurrent chemotherapy and radiotherapy with nitroglycerin in locally advanced non-small cell lung cancer

    International Nuclear Information System (INIS)

    Background: Nitroglycerin, a nitric oxide donor agent, reduces the expression of hypoxia-inducible factor-1α (HIF-1α) and could be a normalizer of the tumor microenvironment. Both factors are associated with chemo-radio-resistance. The aim of this study was to determine the safety profile and efficacy of nitroglycerin administration with chemo-radiotherapy in patients with locally advanced non-small cell lung cancer (NSCLC). Methods: This is a phase II trial of locally advanced NSCLC patients treated with cisplatin and vinorelbine plus concurrent nitroglycerin with radiotherapy. A 25-mg NTG patch was administered to the patients for 5 days (1 day before and 4 days after chemotherapy induction and consolidation) and all day during chemo-radiotherapy. VEGF plasmatic level was determined before and after two cycles of chemotherapy. Results: Thirty-five patients were enrolled in this trial. Sixty-three percent of patients achieved an overall response after induction of chemotherapy, and 75% achieved an overall response after chemo-radiotherapy. The median progression-free survival was 13.5 months (95% CI, 8.8–18.2), and the median overall survival was 26.9 months (95% CI, 15.3–38.5). Reduction of VEGF level was associated with better OS. The toxicity profile related to nitroglycerin included headache (20%) and hypotension (2.9%). Conclusions: The addition of nitroglycerin to induction chemotherapy and concurrent chemoradiotherapy in patients with locally advanced NSCLC has an acceptable toxicity profile and supports the possibility to add nitroglycerin to chemotherapy and radiotherapy. A randomized trial is warranted to confirm these findings

  13. Clinical analysis of preoperative induction chemotherapy with gemcitabine combined with cisplatin for locally advanced non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    Qianping Li; Jianjun Wang; Jun Zhang; Chengyi Lin

    2012-01-01

    Objective: The purpose of this study was to assess the curative effect and adverse reaction of preoperative induction chemotherapy with gemcitabine combined with cisplatin for locally advanced non-small cell lung cancer (NSCLC). Methods: This prospective randomized controlled trial included 115 patients with locally advanced NSCLC were randomly divided into experimental and control groups and were treated from January 2007 to January 2010. The experimental group of 63 cases was treated with two cycles of induction chemotherapy before operation, radical surgery had been performed about three weeks after completion of chemotherapy, followed by received two cycles of chemotherapy. And the control group (52 cases) was treated at first with radical surgery, then treated with four cycles of chemotherapy. Two groups of the cases received routine thoracic radiotherapy with a total dose of 45 Gy. One cycle of gemcitabine combined with cisplatin regimen in-cluded gemcitabine 1000 mg/m2 on day 1 and day 8 and cisplatin 25 mg/m2 on day 1, day 2 and day 3 by intravenous infusion, with 21 days as one cycle. The tumor recurrence was evaluated by chest CT and abdominal B-ultrasound. Efficacy and toxicity results were compared by two groups. Results: All patients were followed up for three months to two years. The surgical stage of the experimental group reduced, two-years disease-free survival and postoperative recovery in the experimental group were better than in the control group, the difference was statistical significant. Toxicity and side effect after chemotherapy were mainly bone marrow suppression and gastrointestinal reactions, other complications included thrombocytopenia, leuko-penia, anemia, liver and kidney dysfunction were no significant difference in two groups. Conclusion: Preoperative induction chemotherapy with gemcitabine combined with cisplatin for locally advanced lung cancer can reduce the surgical staging and extend the postoperative disease-free survival.

  14. 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.

  15. Third-generation inhibitors targeting EGFR T790M mutation in advanced non-small cell lung cancer

    OpenAIRE

    Wang, Shuhang; Cang, Shundong; Liu, Delong

    2016-01-01

    The tyrosine kinase inhibitors (TKI) against epidermal growth factor receptor (EGFR) are widely used in patients with non-small cell lung cancer (NSCLC). However, EGFR T790M mutation leads to resistance to most clinically available EGFR TKIs. Third-generation EGFR TKIs against the T790M mutation have been in active clinical development. These agents include osimertinib, rociletinib, HM61713, ASP8273, EGF816, and PF-06747775. Osimertinib and rociletinib have shown clinical efficacy in phase I/...

  16. 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.

  17. 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...

  18. 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...

  19. A Clinical Study on Global TCM Therapy in Treating Senile Advanced Non-small Cell Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective:To assess the clinical efficacy of global traditional Chinese medicine(TCM)therapy in treating senile advanced non-small cell lung cancer(NSCLC),with the aim of seeking a standardized,rational and economical way to treat advanced NSCLC in old patients.Methods:A retrospective analysis and comparison was carried out in 86 patients with senile advanced NSCLC,44 treated by global TCM(TCM group)and 42 by chemotherapy(control group)through dynamical observation on related indexes including tumor size,quality of life and the survival time,as well as on the fee for medical service at various time points in the course of the treatment.Results:The changes of tumor size,score of clinical main symptoms and behavior condition(by ZPS scoring),as well as survival rates in the two groups at corresponding time points,were not different significantly(P>0.05).The mean survival time in the TCM group was 13.20±1.52 months and that in the chemotherapy group was 13.45±1.94 months,showing insignificant difference between them.However,the median survival time in the TCM group(12 months)was actually longer than that in the chemotherapy group (9 months,P<0.05).The mean daily expense and the mean expense(RMB yuan)for each patient in the TCM group were significantly lower than that in the control group,which was 180.73±93.21 vs 825.84±329.63 for the mean daily expense and 34 077.21±14 638.04 vs 58 516.59±45 429.76 for the mean expense for each patient(both P<0.01).Conclusion:Treatment of senile advanced NSCLC with TCM alone has its apparent superiority in stabilizing tumor focus,improving clinical symptoms,elevating quality of life and prolonging the survival time.TCM is also less expensive,making it a good alternative therapeutic approach for this specific group of people.

  20. Serum cytokine levels in patients with advanced non-small cell lung cancer: correlation with clinical outcome of erlotinib treatment

    Institute of Scientific and Technical Information of China (English)

    WANG Yong-sheng; MIAO Li-yun; LIU Lu; CAI Hou-rong; DING Jing-jing; REN Sheng-xiang; ZHOU Cai-cun

    2013-01-01

    Background Serum expression of cytokines may provide information about the clinical outcome of advanced non-small cell lung cancer (NSCLC) patients.This study aimed to investigate the relationship between serum cytokine levels and the clinical outcome of erlotinib treatment in a second or third line setting in patients with advanced NSCLC.Methods A total of 162 patients with advanced NSCLC who received erlotinib as either second or third line therapy were enrolled in this study.Blood samples were collected before the initiation of erlotinib treatment,and the levels of IL-1,IL-2R,IL-6,and tumor necrosis factor (TNF)-α were assessed by enzyme-linked immunosorbent assay (ELISA).Cutoff points were defined as the median levels of IL-1 (low (≤26.5 pg/ml) and high (>26.5 pg/ml)),IL-2R (low (≤115 pmol/L) and high (>15 pmol/L)),IL-6 (low (≤49.5 pg/ml) and high (>49.5 pg/ml)),and TNF-α (low (≤48.5 pg/ml) and high (>48.5 pg/ ml)).Kaplan-Meier analysis was used to estimate the survival time,and Cox regression analyses were used to correlate cytokines and baseline clinical characteristics with clinical outcomes,including time to progression (TTP) and overall survival (OS).Results Between January 2007 and May 2011,162 patients were enrolled.Their median age was 58 years.In this group,109 were males and 53 were females,74 were former or current smokers and 88 were non-smokers.A total of 122 patients had adenocarcinoma,27 had squamous cell carcinoma,and 13 had tumors with other types of histology.And 139 patients had an Eastern cooperative oncology group (ECOG) performance status of 0-1,while 23 scored at 2-3.Expression of IL-1,IL-2R,and IL-6 was not significantly associated with age,gender,ECOG performance status,smoking status,or histology and stage of tumor.Only TNF-α was associated with smoking status (P=0.045).Survival analysis showed that patients with low levels of either IL-6 or TNF-α had a statistically longer TTp and OS than patients with high

  1. Prognostic significance of total lesion glycolysis in patients with advanced non-small cell lung cancer receiving chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Zaizen, Yoshiaki [Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Kurume (Japan); Azuma, Koichi, E-mail: azuma@med.kurume-u.ac.jp [Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Kurume (Japan); Kurata, Seiji [Department of Radiology, Kurume University School of Medicine, Kurume (Japan); Sadashima, Eiji; Hattori, Satoshi [Biostatistics Center, Kurume University, Kurume (Japan); Sasada, Tetsuro [Department of Immunology and Immunotherapy, Kurume University School of Medicine, Kurume (Japan); Imamura, Yohei [Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Kurume (Japan); Kaida, Hayato [Department of Radiology, Kurume University School of Medicine, Kurume (Japan); Kawahara, Akihiko [Department of Pathology, Kurume University School of Medicine, Kurume (Japan); Kinoshita, Takashi [Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Kurume (Japan); Ishibashi, Masatoshi [Department of Radiology, Kurume University School of Medicine, Kurume (Japan); Hoshino, Tomoaki [Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Kurume (Japan)

    2012-12-15

    Background: [{sup 18}F]fluorodeoxyglucose positron emission tomography (FDG-PET) imaging has been employed as a non-invasive diagnostic tool for malignant tumors. Total lesion glycolysis (TLG) on FDG-PET is calculated by multiplying the mean standardized uptake value (SUVmean) by the tumor volume. Unlike the maximum standardized uptake value (SUVmax), which represents the point of greatest metabolic activity within tumors, TLG has been suggested to reflect global metabolic activity in whole tumors. Methods: We retrospectively examined whether or not FDG-PET measurements, including SUVmean, SUVmax, and TLG, could predict progression-free survival (PFS) or overall survival (OS) in patients with non-small cell lung cancer (NSCLC) receiving chemotherapy. Results: This study involved 81 consecutive patients with NSCLC who received chemotherapy. All of the patients underwent FDG-PET examination before treatment. SUVmean, SUVmax, and TLG on FDG-PET were significantly associated with gender, smoking status, and tumor histology. With adjustment for several other variables, Cox regression analysis showed that TLG was significantly prognostic for both PFS [hazard ratio = 2.34; 95% confidence interval, 1.18–4.64; P = 0.015] and OS (hazard ratio = 2.80; 95% confidence interval, 1.12–6.96; P = 0.003), whereas SUVmean and SUVmax had no significant association with PFS (P = 0.693 and P = 0.322, respectively) or OS (P = 0.587 and P = 0.214, respectively). Conclusions: Our findings suggest that TLG may be more useful than SUVmean and SUVmax for predicting PFS and OS in NSCLC patients receiving chemotherapy. The TLG measurement on FDG-PET imaging could be routinely recommended to advanced NSCLC patients.

  2. Prediction of response by FDG PET early during concurrent chemoradiotherapy for locally advanced non-small cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Su Zi; Oh, So Won; Kim, Jin Soo; Kim, Ki Hwan; Kim, Yu Kyeong [SMG-Seoul National University Boramae Medical Center, Seoul (Korea, Republic of)

    2014-12-15

    To evaluate the predictive value of the early response of 18F-flurodeoxyglucose positron emission tomography (FDG PET) during concurrent chemoradiotherapy (CCRT) for locally advanced non-small cell lung cancer (NSCLC). FDG PET was performed before and during CCRT for 13 NSCLC patients. Maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were measured and the changes were calculated. These early metabolic changes were compared with the standard tumor response by computed tomograms (CT) one month after CCRT.One month after the completion of CCRT, 9 patients had partial response (PR) of tumor and 4 patients had stable disease. The percent changes of SUVmax (%DeltaSUVmax) were larger in responder group than in non-responder group (55.7% +/- 15.6% vs. 23.1% +/- 19.0%, p = 0.01). The percent changes of SUVmean (%DeltaSUVmean) were also larger in responder group than in non-responder group (54.4% +/- 15.9% vs. 22.3% +/- 23.0%, p = 0.01). The percent changes of MTV (%DeltaMTV) or TLG (%DeltaTLG) had no correlation with the tumor response after treatment. All the 7 patients (100%) with %DeltaSUVmax > or = 50% had PR, but only 2 out of 6 patients (33%) with %DeltaSUVmax < 50% had PR after CCRT (p = 0.009). Likewise, all the 6 patients (100%) with %DeltaSUVmean > or = 50% had PR, but only 3 out of 7 patients (43%) with %DeltaSUVmean < 50% had PR after CCRT (p = 0.026). The degree of metabolic changes measured by PET-CT during CCRT was predictive for NSCLC tumor response after CCRT.

  3. Prophylactic cranial irradiation in locally advanced non-small cell lung cancer: outcome of recursive partitioning analysis group 1 patients

    Directory of Open Access Journals (Sweden)

    Onal Cem

    2008-12-01

    Full Text Available Abstract Background Prophylactic cranial irradiation (PCI has been demonstrated to reduce or delay the incidence of brain metastases (BM in locally advanced non-small cell lung carcinoma (LA-NSCLC patients with various prognostic groups. With this current cohort we planned to evaluate the potential usefulness of prophylactic cranial irradiation (PCI specifically in recursive partitioning analysis (RPA Group 1, which is the most favorable group of LA-NSCLC patients. Methods Between March 2007 and February 2008, 62 patients in RPA group 1 were treated with sequential chemoradiotherapy and PCI for stage IIIB NSCLC. The induction chemotherapy consisted of 3 courses of cisplatin (80 mg/m2 and docetaxel (80 mg/m2; each course was given every 21 days. Thoracic radiotherapy (TRT was given at a dose of 60 Gy using 3-D conformal planning. All patients received a total dose of 30 Gy PCI (2 Gy/fr, 5 days a week, beginning on the first day of the TRT. Then, all patients received 3 further courses of the same chemotherapy protocol. Results Six (9.7% patients developed brain metastases during their clinical course. Only one (2% patient developed brain metastasis as the site of first treatment failure. Median brain metastasis-free survival, overall survival, and progression free survival were 16.6, 16.7, and 13.0 months, respectively. By univariate analysis, rates of BM were significantly higher in patients younger than 60 years of age (p = 0.03. Multivariate analysis showed no significant difference in BM-free survival according to gender, age, histology, and initial T- and N-stage. Conclusion The current finding of almost equal bone metastasis free survival and overall survival in patients with LA-NSCLC in RPA group 1 suggests a longer survival for patients who receive PCI, and thereby have a reduced risk of BM.

  4. FDG PET for staging of advanced non-small cell lung cancer prior to neoadjuvant radio-chemotherapy

    International Nuclear Information System (INIS)

    The aim of this study was to evaluate positron emission tomography (PET) with fluorine-18 fluorodeoxyglucose (FDG) for the staging of non-small cell lung cancer (NSCLC) before combined neoadjuvant, i.e. preoperative, radio-chemotherapy (RCT). From November 1998 until September 2001, 101 patients with NSCLC were investigated prospectively. The inclusion criterion was a histologically proven NSCLC of stage IIIA or B according to conventional staging including biopsy. The results of PET were compared with those obtained by mediastinoscopy, computed tomography (CT), bone scan and abdominal ultrasonography. Validation of discrepant findings was achieved by biopsy or repeated CT. PET proved to be highly accurate for the detection of lymph node metastases (sensitivity 96%, specificity 73%, positive predictive value 88%, negative predictive value 89%, accuracy 88%) as well as distant metastases (in 25/101 patients, all previously unknown). PET findings changed further treatment in 29/101 patients (29%). Twenty-five were excluded from RCT due to the presence of previously unknown distant metastases. One patient was free of metastases and therefore was operated on without pre-treatment. Two patients did not receive any further treatment because a malignant tumour could be excluded after PET. In the final patient PET demonstrated a tumour pattern not typical for NSCLC which could be attributed to a seminoma after repeated biopsy. FDG PET is the most accurate non-invasive diagnostic procedure for the staging of advanced NSCLC. Therefore use of FDG PET is highly recommended in order to select patients for neoadjuvant or other stage-dependent treatment modalities. (orig.)

  5. Advances in the Molecular Mechanisms and Prognostic Significance of EMT 
in Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Qinchen CAO

    2014-07-01

    Full Text Available Epithelial to mesenchymal transition (EMT has an important role in the development of embryo, as well as that in the metastasis of non-small cell lung cancer (NSCLC. Recent researches have demonstrated that both morphological and phenotypic conversions emerge in cells undergoing EMT. As most of relevant studies were on other cancers, it is essential to uncover whether it is the similar mechanisms accounting for EMT in NSCLC. With the progress of the studies, EMT-related basic researches are gradually applied to predicting the prognosis of NSCLC. The aim of this article was to discuss the mechanisms related to EMT emerging in NSCLC.

  6. Risk Factors for Brain Metastases in Locally Advanced Non-Small Cell Lung Cancer With Definitive Chest Radiation

    International Nuclear Information System (INIS)

    Purpose: We intended to identify risk factors that affect brain metastases (BM) in patients with locally advanced non-small cell lung cancer (LA-NSCLC) receiving definitive radiation therapy, which may guide the choice of selective prevention strategies. Methods and Materials: The characteristics of 346 patients with stage III NSCLC treated with thoracic radiation therapy from January 2008 to December 2010 in our institution were retrospectively reviewed. BM rates were analyzed by the Kaplan-Meier method. Multivariate Cox regression analysis was performed to determine independent risk factors for BM. Results: The median follow-up time was 48.3 months in surviving patients. A total of 74 patients (21.4%) experienced BM at the time of analysis, and for 40 (11.7%) of them, the brain was the first site of failure. The 1-year and 3-year brain metastasis rates were 15% and 28.1%, respectively. In univariate analysis, female sex, age ≤60 years, non-squamous cell carcinoma, T3-4, N3, >3 areas of lymph node metastasis, high lactate dehydrogenase and serum levels of tumor markers (CEA, NSE, CA125) before treatment were significantly associated with BM (P<.05). In multivariate analysis, age ≤60 years (P=.004, hazard ratio [HR] = 0.491), non-squamous cell carcinoma (P=.000, HR=3.726), NSE >18 ng/mL (P=.008, HR=1.968) and CA125 ≥ 35 U/mL (P=.002, HR=2.129) were independent risk factors for BM. For patients with 0, 1, 2, and 3 to 4 risk factors, the 3-year BM rates were 7.3%, 18.9%, 35.8%, and 70.3%, respectively (P<.001). Conclusions: Age ≤60 years, non-squamous cell carcinoma, serum NSE >18 ng/mL, and CA125 ≥ 35 U/mL were independent risk factors for brain metastasis. The possibilities of selectively using prophylactic cranial irradiation in higher-risk patients with LA-NSCLC should be further explored in the future

  7. Risk Factors for Brain Metastases in Locally Advanced Non-Small Cell Lung Cancer With Definitive Chest Radiation

    Energy Technology Data Exchange (ETDEWEB)

    Ji, Zhe; Bi, Nan; Wang, Jingbo; Hui, Zhouguang; Xiao, Zefen; Feng, Qinfu; Zhou, Zongmei; Chen, Dongfu; Lv, Jima; Liang, Jun; Fan, Chengcheng; Liu, Lipin; Wang, Luhua, E-mail: wlhwq@yahoo.com

    2014-06-01

    Purpose: We intended to identify risk factors that affect brain metastases (BM) in patients with locally advanced non-small cell lung cancer (LA-NSCLC) receiving definitive radiation therapy, which may guide the choice of selective prevention strategies. Methods and Materials: The characteristics of 346 patients with stage III NSCLC treated with thoracic radiation therapy from January 2008 to December 2010 in our institution were retrospectively reviewed. BM rates were analyzed by the Kaplan-Meier method. Multivariate Cox regression analysis was performed to determine independent risk factors for BM. Results: The median follow-up time was 48.3 months in surviving patients. A total of 74 patients (21.4%) experienced BM at the time of analysis, and for 40 (11.7%) of them, the brain was the first site of failure. The 1-year and 3-year brain metastasis rates were 15% and 28.1%, respectively. In univariate analysis, female sex, age ≤60 years, non-squamous cell carcinoma, T3-4, N3, >3 areas of lymph node metastasis, high lactate dehydrogenase and serum levels of tumor markers (CEA, NSE, CA125) before treatment were significantly associated with BM (P<.05). In multivariate analysis, age ≤60 years (P=.004, hazard ratio [HR] = 0.491), non-squamous cell carcinoma (P=.000, HR=3.726), NSE >18 ng/mL (P=.008, HR=1.968) and CA125 ≥ 35 U/mL (P=.002, HR=2.129) were independent risk factors for BM. For patients with 0, 1, 2, and 3 to 4 risk factors, the 3-year BM rates were 7.3%, 18.9%, 35.8%, and 70.3%, respectively (P<.001). Conclusions: Age ≤60 years, non-squamous cell carcinoma, serum NSE >18 ng/mL, and CA125 ≥ 35 U/mL were independent risk factors for brain metastasis. The possibilities of selectively using prophylactic cranial irradiation in higher-risk patients with LA-NSCLC should be further explored in the future.

  8. Maintenance erlotinib in advanced nonsmall cell lung cancer: cost-effectiveness in EGFR wild-type across Europe

    Directory of Open Access Journals (Sweden)

    Walleser S

    2012-09-01

    Full Text Available Silke Walleser,1 Joshua Ray,2 Helge Bischoff,3 Alain Vergnenègre,4 Hubertus Rosery,5 Christos Chouaid,6 David Heigener,7 Javier de Castro Carpeño,8 Marcello Tiseo,9 Stefan Walzer21Health Economic Consultancy, Renens, Switzerland; 2F Hoffmann-La Roche Pharmaceuticals AG, Basel, Switzerland; 3Thoracic Hospital of Heidelberg, Heidelberg, Germany; 4Limoges University Hospital, Limoges, France; 5Assessment-in-Medicine GmbH, Loerrach, Germany; 6Hospital Saint Antoine, Paris, France; 7Hospital Grosshansdorf, Grosshansdorf, Germany; 8University Hospital La Paz, Madrid, Spain; 9University Hospital of Parma, Parma, ItalyBackground: First-line maintenance erlotinib in patients with locally advanced or metastatic nonsmall cell lung cancer (NSCLC has demonstrated significant overall survival and progression-free survival benefits compared with best supportive care plus placebo, irrespective of epidermal growth factor receptor (EGFR status (SATURN trial. The cost-effectiveness of first-line maintenance erlotinib in the overall SATURN population has been assessed and published recently, but analyses according to EGFR mutation status have not been performed yet, which was the rationale for assessing the cost-effectiveness of first-line maintenance erlotinib specifically in EGFR wild-type metastatic NSCLC.Methods: The incremental cost per life-year gained of first-line maintenance erlotinib compared with best supportive care in patients with EGFR wild-type stable metastatic NSCLC was assessed for five European countries (the United Kingdom, Germany, France, Spain, and Italy with an area-under-the-curve model consisting of three health states (progression-free survival, progressive disease, death. Log-logistic survival functions were fitted to Phase III patient-level data (SATURN to model progression-free survival and overall survival. The first-line maintenance erlotinib therapy cost (modeled for time to treatment cessation, medication cost in later lines, and

  9. Effects of EGFR Gene Polymorphisms on Efficacy and Prognosis 
in Advanced Non-small Cell Lung Cancer Treated with EGFR-TKIs

    Directory of Open Access Journals (Sweden)

    Liangshan DA

    2013-03-01

    Full Text Available An increasing number of patients with advanced non-small cell lung cancer (NSCLC have been treated with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs. However, significant differences in response to EGFR-TKIs have been shown among advanced NSCLC patients. Recently, selection of patients was mainly based on EGFR gene mutation detection. Nevertheless, mutation detection is often limited by tumour tissues derivation, technique complexity, high cost, and so on. It is urgent to seek other biological markers to predict efficacy of EGFR-TKIs. Many studies have founded that the EGFR gene polymorphisms are also associated with clinical outcome and prognosis in treatment of advanced NSCLC with EGFR-TKIs. Here, we presented a review discussing the correlation between EGFR gene polymorphisms and the efficacy of EGFR-TKIs in advanced NSCLC.

  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 Chemoradiotherapy with Biweekly Gemcitabine and Cisplatin in Patients with Locally Advanced Non-small Cell Lung Cancer

    International Nuclear Information System (INIS)

    In cases of locally advanced non-small cell lung cancer (NSCLC), concurrent chemoradiotherapy (CCRT) is the leading therapeutic modality. However, much controversy exists about the chemotherapeutic regimens and radiation methods. Materials and Methods: During concurrent chemoradiotherapy, three or four cycles of gemcitabine (500 mg/m2) and cisplatin (30 mg/m2) were administered every two weeks while 50.4 Gy of irradiation was administered in 28 fractions (once/day, 5 treatment days/week) to the tumor site, mediastinum, and the involved lymph node region. In addition, a booster irradiation dose of 18 Gy in 10 fractions was administered to the primary tumor site unless the disease progressed. Two or three cycles of consolidation chemotherapy were performed with gemcitabine (1,200 mg/m2, 1st and 8th day) and cisplatin (60 mg/m2) every three weeks. Results: A total of 29 patients were evaluable for modality response. Response and treatment toxicities were assessed after concurrent chemoradiotherapy and consolidation chemotherapy, respectively. One patient (4%) achieved a complete response; whereas 20 patients (69%) achieved a partial response after concurrent chemoradiotherapy. Following the consolidation chemotherapy, three patients (10.3%) achieved complete responses and 21 patients (72.4%) achieved partial responses. The median follow-up period was 20 months (range 3-39 months) and the median survival time was 16 months (95% CI; 2.4-39.2 months). The survival rates in one, two, and three years after the completion of treatment were 62.7%, 43.9%, and 20%, respectively. Complications associated to this treatment modality included grade 3 or 4 esophagitis, which occurred in 15 patients (51.7%). In addition, an incidence of 24% for grade 3 and 14% for grade 4 neutropenia. Lastly, grade 2 radiation pneumonitis occurred in 6 patients (22%). Conclusion: The response rate and survival time of concurrent chemoradiotherapy with biweekly gemcitabine (500 mg/m2) and cisplatin

  12. Thermo-chemotherapy of GP or TP for Advanced Non-small Cell Lung Cancer: 
A Systematic Review

    Directory of Open Access Journals (Sweden)

    Denghai MI

    2012-08-01

    Full Text Available Background and objective Advanced non-small cell lung cancer (NSCLC is characterized by poor treatment efficacy and short survival time. Clinical trials have shown that the combination of chemotherapy with thermotherapy exhibits strong efficacy. We performed this meta-analysis to evaluate the clinical efficacy and safety of gemcitabine plus cisplatin (GP and paclitaxel plus cisplatin (TP combined with thermotherapy in the treatment of NSCLC, as well as to provide reference for clinical practice and future research. Methods We searched international (Cochrane Library, PubMed, and EMBASE and Chinese (CBM, CNKI, VIP and Wanfang databases for relevant articles and imported other retrievable sources, such as tracing-related references. We also corresponded with other authors to obtain certain inaccessible information. Data from all relevant randomized controlled trials (RCT were collected to compare GP or TP thermochemotherapy with GP or TP chemotherapy alone. The quality of the included studies was assessed by adequate outcome-based standards and clinical circumstances. The meta-analysis was conducted using RevMan 5.1. Results Fifteen RCTs involving 952 patients were included in this meta-analysis. The results showed that the thermochemotherapy group had higher rates of improvement in quality of life (OR=3.84, 95%CI: 2.61-5.64, survival at 1 year (HR=1.94, 95%CI: 1.21-3.12, and survival at 2 years (HR=2.05, 95%CI: 1.18-3.58 compared with the chemotherapy group, with the differences between them being significant. However, these groups did not differ in other indicators of treatment effectiveness, such as myelosuppression, alimentary canal reactions, hepatic lesions, and diarrhea. Conclusion Compared with chemotherapy alone, thermochemotherapy can improve survival rates and curative effects, ameliorate symptoms, and enhance the quality of life of patients with advanced NSCLC, and it has an acceptable safety profile. The results of this meta

  13. Combining advanced radiotherapy technologies to maximize safety and tumor control probability in stage III non-small cell lung cancer

    International Nuclear Information System (INIS)

    Background: The goal of the current study was to investigate the tumor control probability (TCP) of advanced radiotherapy technologies for stage III non-small cell lung cancer (NSCLC) and to evaluate potential interplay effects between their applications. Materials and methods: Three-dimensional conformal radiotherapy (3D-CRT) with conventionally fractionated doses of 66 Gy served as reference for 13 patients with stage III NSCLC. Isotoxic dose escalation relative to the corresponding 3D-CRT plans was performed for three technologies and their combinations: intensity-modulated radiotherapy (IMRT), IMRT with a simultaneous integrated boost (IMRT-SIB) of 10% to the gross tumor volume (GTV), and adaptive re-planning twice during the treatment course (ART). All analyses were based on accumulated dose distributions using deformable image registration of CT images, which were acquired weekly during the treatment course. Results: IMRT reduced the mean lung dose (MLD) by 5.6% ± 3.8% compared to 3D-CRT. ART resulted in lung sparing of 7.9% ± 4.8% and 9.2% ± 3.9% in 3D-CRT and IMRT planning, respectively. IMRT and ART escalated the irradiation dose by 6.6% ± 3.2% and 8.8% ± 6.3%, respectively, which was not statistically different. For the 7 patients with the largest GTVs, IMRT-SIB was superior to IMRT and ART with dose escalation of 11.9% ± 3.7%. The combination of ART, IMRT, and SIB achieved maximum dose escalation in all 13 patients by 17.1% ± 5.4% on average, which increased TCP from 19.9% ± 7.0 to 37.1% ± 10.1%. Adaptive re-planning was required to continuously conform the escalated and hypofractionated SIB doses to the shrinking tumor. Conclusion: Combining advanced radiotherapy technologies is considered as a safe and effective strategy to maximize local tumor control probability in stage III NSCLC. (orig.)

  14. Efficacy and clinical/molecular predictors of erlotinib monotherapy for Chinese advanced non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    ZHU Yu-jia; XIA Ying; REN Guan-jun; WANG Meng-zhao; ZENG Xuan; ZHANG Li

    2010-01-01

    Background A retrospective analysis of clinical data were conducted reviewing patients who were given erlotinib at Peking Union Medical College (PUMC) Hospital from May 2005 to December 2009. Relationships between clinical factors, epidermal growth factor receptor (EGFR) mRNA expression, EGFR gene mutations, KRAS gene mutations and clinical outcomes were investigated in Chinese patients with advanced non-small cell lung cancer (NSCLC). Methods Patients with stage ⅢB/Ⅳ NSCLC who had not previously participated in erlotinib related clinical trials were enrolled into this study. All patients were given oral erlotinib 150 mg per day. Tumor samples of some patients were accessed with mutant-enriched polymerase chain reaction assay (EGFR, KRAS gene mutations) and multiplex branched DNA assay (EGFR mRNA expression).Results Seventy-nine patients were enrolled in this study, 23 patients had a partial response (PR), 36 patients had a stable disease (SD), 20 patients had a PD, with an objective response rate of 29.1%, and a disease control rate of 74.7%.Females (P=0.023), non-smokers (P=0.013), patients with a skin rash (P=0.047), and with highly differentiated tumors (P=0.037) were significantly correlated with the objective response rate. Patients with a lower ECOG PS (P=0.002),highly differentiated tumors (P=0.014), non-smokers (P=0.002), and patients with a skin rash (P <0.001) were significantly correlated with the disease control rate. The median progression-free survival was 35 weeks (95% CI: 13-57 weeks) and 1-year survival was 72.3%. Highly-differentiated tumors (P=0.027) and patients with a skin rash (P <0.001)were significantly correlated with PFS. Seventeen patients were tested for EGFR/KRAS gene mutations and EGFR mRNA expression. Progression-free survival (PFS) of patients with EGFR exon 19/21 mutations was 66 weeks, longer than patients with wild type EGFR exon 19/21 (P=0.018). No significant relationships were found between EGFR mRNA expression, EGFR

  15. Concurrent Chemoradiotherapy with Biweekly Gemcitabine and Cisplatin in Patients with Locally Advanced Non-small Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Oak, Chul Ho; Kim, Ja Kyung; Jang, Lee La; Moon, Dae Sung; Jang, Tae Won; Jung, Maan Hong; Cho, Sung Whan; Jeung, Tae Sig [Kosin University College of Medicine, Busan (Korea, Republic of)

    2008-09-15

    In cases of locally advanced non-small cell lung cancer (NSCLC), concurrent chemoradiotherapy (CCRT) is the leading therapeutic modality. However, much controversy exists about the chemotherapeutic regimens and radiation methods. Materials and Methods: During concurrent chemoradiotherapy, three or four cycles of gemcitabine (500 mg/m2) and cisplatin (30 mg/m2) were administered every two weeks while 50.4 Gy of irradiation was administered in 28 fractions (once/day, 5 treatment days/week) to the tumor site, mediastinum, and the involved lymph node region. In addition, a booster irradiation dose of 18 Gy in 10 fractions was administered to the primary tumor site unless the disease progressed. Two or three cycles of consolidation chemotherapy were performed with gemcitabine (1,200 mg/m2, 1st and 8th day) and cisplatin (60 mg/m2) every three weeks. Results: A total of 29 patients were evaluable for modality response. Response and treatment toxicities were assessed after concurrent chemoradiotherapy and consolidation chemotherapy, respectively. One patient (4%) achieved a complete response; whereas 20 patients (69%) achieved a partial response after concurrent chemoradiotherapy. Following the consolidation chemotherapy, three patients (10.3%) achieved complete responses and 21 patients (72.4%) achieved partial responses. The median follow-up period was 20 months (range 3-39 months) and the median survival time was 16 months (95% CI; 2.4-39.2 months). The survival rates in one, two, and three years after the completion of treatment were 62.7%, 43.9%, and 20%, respectively. Complications associated to this treatment modality included grade 3 or 4 esophagitis, which occurred in 15 patients (51.7%). In addition, an incidence of 24% for grade 3 and 14% for grade 4 neutropenia. Lastly, grade 2 radiation pneumonitis occurred in 6 patients (22%). Conclusion: The response rate and survival time of concurrent chemoradiotherapy with biweekly gemcitabine (500 mg/m2) and cisplatin

  16. Gefitinib Plus Interleukin-2 in Advanced Non-Small Cell Lung Cancer Patients Previously Treated with Chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Bersanelli, Melissa, E-mail: melissa.bersanelli@alice.it; Buti, Sebastiano; Camisa, Roberta [Oncology Unit, University Hospital of Parma, Via Gramsci, 14, 43126 Parma (Italy); Brighenti, Matteo; Lazzarelli, Silvia [Oncology Unit, Azienda Istituti Ospitalieri di Cremona, Largo Priori, 1, 26100 Cremona (Italy); Mazza, Giancarlo [Radiology Division, Spedali Civili di Brescia, P.le Spedali Civili,1, 25123 Brescia (Italy); Passalacqua, Rodolfo, E-mail: melissa.bersanelli@alice.it [1Oncology Unit, University Hospital of Parma, Via Gramsci, 14, 43126 Parma (Italy)

    2014-09-30

    The activation of lymphocytes by gefitinib treatment has been described. In this phase II pilot trial, we explored the possible synergism between IL-2 and gefitinib for non-small cell lung cancer (NSCLC) treatment. From September, 2003, to November, 2006, 70 consecutive patients with advanced, progressive NSCLC, previously treated with chemotherapy, received oral gefitinib 250 mg daily. The first 39 patients received gefitinib alone (G group). The other 31 also received subcutaneous IL-2 (GIL-2 group): 1 MIU/m{sup 2} (Million International Unit/m{sup 2})twice a day on Days 1 and 2, once a day on Days 3, 4, 5 every week for four consecutive weeks with a four-week rest period. Median follow-up was 25.2 months. Grade 3–4 toxicity of gefitinib was represented by skin rash (7%), asthenia/anorexia (6%) and diarrhea (7%); patients treated with IL-2 showed grade 2–3 fever (46%), fatigue (21%) and arthralgia (13%). In the GIL-2 group and G-group, we respectively observed: an overall response rate of 16.1% (6.4% complete response) and 5.1% (only partial response); a disease control rate of 41.9% and 41%; a median time to progression of 3.5 (CI 95% = 3.2–3.8) and 4.1 (CI 95% = 2.6–5.7) months; a median overall survival of 20.1 (CI 95% = 5.1–35.1) and 6.9 (CI 95% = 4.9–8.9) months (p = 0.002); and an actuarial one-year survival rate of 54% and 30%. Skin toxicity (p < 0.001; HR = 0.29; CI 95% = 0.16–0.54) and use of IL-2 (p < 0.001; HR = 0.33; CI 95% = 0.18–0.60) were independently associated with improvement of survival. In this consecutive, non-randomized, series of advanced NSCLC patients, the use of IL-2 increased the efficacy of gefitinib.

  17. Gefitinib Plus Interleukin-2 in Advanced Non-Small Cell Lung Cancer Patients Previously Treated with Chemotherapy

    Directory of Open Access Journals (Sweden)

    Melissa Bersanelli

    2014-09-01

    Full Text Available The activation of lymphocytes by gefitinib treatment has been described. In this phase II pilot trial, we explored the possible synergism between IL-2 and gefitinib for non-small cell lung cancer (NSCLC treatment. From September, 2003, to November, 2006, 70 consecutive patients with advanced, progressive NSCLC, previously treated with chemotherapy, received oral gefitinib 250 mg daily. The first 39 patients received gefitinib alone (G group. The other 31 also received subcutaneous IL-2 (GIL-2 group: 1 MIU/m2 (Million International Unit/m2twice a day on Days 1 and 2, once a day on Days 3, 4, 5 every week for four consecutive weeks with a four-week rest period. Median follow-up was 25.2 months. Grade 3–4 toxicity of gefitinib was represented by skin rash (7%, asthenia/anorexia (6% and diarrhea (7%; patients treated with IL-2 showed grade 2–3 fever (46%, fatigue (21% and arthralgia (13%. In the GIL-2 group and G-group, we respectively observed: an overall response rate of 16.1% (6.4% complete response and 5.1% (only partial response; a disease control rate of 41.9% and 41%; a median time to progression of 3.5 (CI 95% = 3.2–3.8 and 4.1 (CI 95% = 2.6–5.7 months; a median overall survival of 20.1 (CI 95% = 5.1–35.1 and 6.9 (CI 95% = 4.9–8.9 months (p = 0.002; and an actuarial one-year survival rate of 54% and 30%. Skin toxicity (p < 0.001; HR = 0.29; CI 95% = 0.16–0.54 and use of IL-2 (p < 0.001; HR = 0.33; CI 95% = 0.18–0.60 were independently associated with improvement of survival. In this consecutive, non-randomized, series of advanced NSCLC patients, the use of IL-2 increased the efficacy of gefitinib.

  18. CXCR4 expression on circulating pan-cytokeratin positive cells is associated with survival in patients with advanced non-small cell lung cancer

    International Nuclear Information System (INIS)

    The CXC chemokine, CXCL12, and its receptor, CXCR4 promote metastases of a variety of solid tumors, including non-small cell lung cancer (NSCLC). The expression of CXCR4 on tumor cells may represent a critical biomarker for their propensity to metastasize. This study was performed to evaluate the hypothesis that co-expression of pan-cytokeratin and CXCR4 may be a prognostic marker for patients with advanced NSCLC. We evaluated CXCR4 levels on circulating pan-cytokeratin positive cells from patients with NSCLC. NSCLC tumor and metastases were also assessed for the presence of CXCR4. Pan-cytokeratin positive cells were increased in the circulation of patients with NSCLC, as compared to normal control subjects. Patients with pan-cytokeratin +/CXCR4+ = 2,500 cells/ml had a significant improvement in median survival when compared with patients with pan-cytokeratin +/CXCR4+ >2,500 cells/ml (not achieved versus 14 weeks). CXCR4 expression was found on NSCLC tumors and at sites of tumor metastasis. This study suggests that CXCR4 may be a prognostic marker in NSCLC, and provides hypothesis-generating results, which may be important in determining metastatic potential. In future studies, we will prospectively evaluate the prognostic significance of pan-cytokeratin/CXCR4+ cells, and determine the mechanisms involved in the regulation of CXCR4 expression on tumor cells in a larger patient population

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

    DEFF Research Database (Denmark)

    von Plessen, Christian

    2011-01-01

    to incurable patients who spend a lot of their limited time at oncology outpatient clinics. Staffing, infrastructure and organisation of these units are often suboptimal to serve patients with palliative needs and reports of improvement projects can inspire and guide clinicians in improving their...... over time were effective tools in our project. The description of the experiences can serve as an example for the improvement of microsystems in settings with similar problems. Finally, in the registry study of Norwegian patients with lung cancer, we found significant geographical and temporal...... and patients with higher performance status have usually been under-represented in these trials and population studies of the effectiveness of chemotherapy are needed. OBJECTIVES: (i) To establish the optimal duration of platinum-based first line chemotherapy for advanced NSCLC; (ii) To improve the...

  20. Maintenance or non-maintenance therapy in the treatment of advanced non-small cell lung cancer: that is the question.

    Science.gov (United States)

    Galetta, D; Rossi, A; Pisconti, S; Millaku, A; Colucci, G

    2010-11-01

    Lung cancer is the most common cancer worldwide with non-small cell lung cancer (NSCLC), including squamous carcinoma, adenocarcinoma and large cell carcinoma, accounting for about 85% of all lung cancer types with most of the patients presenting with advanced disease at the time of diagnosis. In this setting first-line platinum-based chemotherapy for no more than 4-6 cycles are recommended. After these cycles of treatment, non-progressing patients enter in the so called "watch and wait" period in which no further therapy is administered until there is disease progression. In order to improve the advanced NSCLC outcomes, the efficacy of further treatment in the "watch and wait" period was investigated. This is the "maintenance therapy". Recently, the results coming from randomized phase III trials investigating two new agents, pemetrexed and erlotinib, in this setting led to their registration for maintenance therapy. Here, we report and discuss these results. PMID:21129607

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

    Directory of Open Access Journals (Sweden)

    Ali Murat Tatli

    2015-01-01

    Results: A total of 72 patients who had received third-line or higher chemotherapy were included in the analysis. The median age of patients was 49 years (range 41-76, and there were 13 (18.1% women and 59 (81.9% men. Estimated median survival was 26 months. Moreover, overall survival was significantly longer in patients for whom disease control was achieved after second-line chemotherapy compared to those with disease progression (34 vs. 17 months, respectively. Survival after third-line treatment was significantly longer in the group with Eastern Cooperative Oncology Group (ECOG performance status 0-1 at the beginning of third-line therapy compared to patients with a status of 2-3. Conclusions: In patients with advanced stage NSCLC, administration of third-line and higher systemic chemotherapy may be associated with increase in overall survival. Furthermore, greater increases in overall survival were also observed in patients for whom disease control was achieved after second-line therapy and in those with ECOG performance status of 0-1 before third-line treatment.

  2. Economic evaluation of first-line and maintenance treatments for advanced non-small cell lung cancer: a systematic review

    Directory of Open Access Journals (Sweden)

    Chouaïd C

    2014-12-01

    Full Text Available Christos Chouaïd,1 Perinne Crequit,2 Isabelle Borget,3 Alain Vergnenegre4 1Service de Pneumologie et de Pathologie Professionnelle, Centre Hospitalier Intercommunal Créteil et Université de Paris Est Créteil, Paris, France; 2Service de Pneumologie, Hôpital Tenon, Assistance Publique-Hôpitaux de Paris, Paris, France; 3Service de Biostatistique et d’Epidémiologie, Institut Gustave Roussy, Villejuif, France; 4Unité d’Oncologie Thoracique et Cutanée, Centre Hospitalier Universitaire Limoges, Limoges, France Abstract: During these last years, there have been an increased number of new drugs for non-small cell lung cancer (NSCLC, with a growing financial effect on patients and society. The purpose of this article was to review the economics of first-line and maintenance NSCLC treatments. We reviewed economic analyses of NSCLC therapies published between 2004 and 2014. In first-line settings, in unselected patients with advanced NSCLC, the cisplatin gemcitabine doublet appears to be cost-saving compared with other platinum doublets. In patients with nonsquamous NSCLC, the incremental cost-effectiveness ratios (ICERs per life-year gained (LYG were $83,537, $178,613, and more than $300,000 for cisplatin-pemetrexed compared with, respectively, cisplatin-gemcitabine, cisplatin-carboplatin-paclitaxel, and carboplatin-paclitaxel-bevacizumab. For all primary chemotherapy agents, use of carboplatin is associated with slightly higher costs than cisplatin. In all the analysis, bevacizumab had an ICER greater than $150,000 per quality-adjusted life-year (QALY. In epidermal growth factor receptor mutated advanced NSCLC, compared with carboplatin-paclitaxel doublet, targeted therapy based on testing available tissue yielded an ICER of $110,644 per QALY, and the rebiopsy strategy yielded an ICER of $122,219 per QALY. Compared with the triplet carboplatin-paclitaxel-bevacizumab, testing and rebiopsy strategies had ICERs of $25,547 and $44,036 per QALY

  3. Long-term Survival of Personalized Surgical Treatment of Locally Advanced Non-small Cell Lung Cancer Based on Molecular Staging

    Directory of Open Access Journals (Sweden)

    Qinghua ZHOU

    2011-02-01

    Full Text Available Background and objective Approximately 35%-40% of patients with newly diagnosed non-small cell Lung cancer have locally advanced disease. The average survival time of these patients only have 6-8 months with chemotherapy. The aim of this study is to explore and summarize the probability of detection of micrometastasis in peripheral blood for molecular staging, and for selection of indication of surgical treatment, and beneficiary of neoadjuvant chemotherapy and postoperative adjuvant therapy in locally advanced lung cancer; to summarize the long-time survival result of personalized surgical treatment of 516 patients with locally advanced non-small cell lung cancer based on molecular staging methods. Methods CK19 mRNA expression of peripheral blood samples was detected in 516 lung cancer patients by RT-PCR before operation for molecular diagnosis of micrometastasis, personalized molecular staging, and for selection of indication of surgical treatment and the beneficiary of neoadjuvant chemotherapy and postoperative adjuvant therapy in patients with locally advanced nonsmall cell lung cancer invaded heart, great vessels or both. The long-term survival result of personalized surgical treatment was retrospectively analyzed in 516 patients with locally advanced non-small cell lung cancer based on molecular staging methods. Results There were 322 patients with squamous cell carcinoma and 194 cases with adenocarcinoma in the series of 516 patients with locally advanced lung cancer involved heart, great vessels or both. There were 112 patients with IIIA disease and 404 cases with IIIB disease according to P-TNM staging. There were 97 patients with M-IIIA disease, 278 cases with M-IIIB disease and 141 cases with III disease according to our personalized molecular staging. Of the 516 patients, bronchoplastic procedures and pulmonary artery reconstruction was carried out in 256 cases; lobectomy combined with resection and reconstruction of partial left

  4. XPA A23G polymorphism is associated with the elevated response to platinum-based chemotherapy in advanced non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    Jifeng Feng; Xinchen Sun; Ning Sun; Shukui Qin; Fan Li; Hongyan Cheng; Baoan Chen; YuanDong Cao; Jun Ma; Lu Cheng; Zuhong Lu; Jiazhong Ji; Yingfeng Zhou

    2009-01-01

    DNA repair capacity(DRC)is correlated with sensi tivity of cancer cells toward platinum-based chemotherapy.We hypothesize that genetic polymorphisms in DNA repair gene XPA(xeroderma pigmentosum group A)and XPG(xeroderma pigmentosum group G)(ERCC5,excision repair cross-complementation group 5),which result in inter-individual differences in DNA repair efficiency,may predict clinical response to platinum agents in advanced non-small cell lung cancer (NSCLC)patients.In this study,we find that the A→G change of XPA A23G polymorphism significantly increased response to platinum-based chemotherapy.Polymorphism in XPG His46His was associated with a decreased treatment response,but was not statistically significant.

  5. Bronchial artery infusion of Gemcitabine and Cisplatin combined with systemic chemotherapy for advanced non-small cell lung cancer: its short-term efficacy

    International Nuclear Information System (INIS)

    Objective: To assess the short-term efficacy of bronchial artery infusion (BAI) of Gemcitabine (GEM) plus Cisplatin (DDP) combined with systemic chemotherapy of GEM for advanced non-small cell lung cancer (NSCLC). Methods: A total of 60 patients with pathologically proved primary NSCLC were randomly selected. BAI with GEM (1000 mg/m2) and DDP (DDP 50 mg/m2) was performed on the first day, and systemic chemotherapy of GEM (1000 mg/m2) was carried out on the eighth day. The clinical results were analyzed. Results: Of the 60 patients, CR, PR, SD and PD were obtained in 3, 35, 17 and 5, respectively, with an overall effective rate of 63%. Twenty-two patients had adenocarcinoma and the effective rate of them was 45%. Thirty-eight patients had squamous cell carcinoma and their effective rate was 74%. The difference in the effective rate between the above two pathologic types was significant (P<0.05). Central type lung cancer was seen in 37 cases, their effective rate was 73%. The peripheral type lung cancer was seen in the remaining 23 patients and the effective rate was 48%. The difference in the effective rate was statistically significant between the central type and the peripheral type (P<0.05). Conclusion: The combination of bronchial artery infusion with systemic chemotherapy by using GP plan is an effective, feasible approach in the treatment of advanced non-small cell lung cancer. The short-term efficacy of the treatment bears a close relationship to the anatomical location and pathological type of the cancer. (authors)

  6. Comparison of concurrent chemo-radiotherapy and sequential chemo-radiotherapy for locally advanced non-small cell lung cancer

    International Nuclear Information System (INIS)

    Objective: Prospective comparison was done on concurrent chemo-radiotherapy and sequential chemo-radiotherapy for unresectable stage III non-small cell lung cancer (NSCLC) and to evaluate three different regimens of concurrent chemo-radiotherapy. Methods: Ninety-six such patients were randomized into four groups: 1. sequential chemo-radiotherapy group received two cycles of induction chemotherapy with 40 mg/m2 of cisplatin on D 1-3, 29-31 and 100 mg/m2 of etoposide on D 1-3, 29-31 before conventional radiotherapy, 2. concurrent chemo-radiotherapy group 1 received 100 mg/m2 etoposide on D 1-3 and DDP 40 mg/m2 on D 1-3, D 29-31, iv. drip, 3. concurrent chemo-radiotherapy group 2 received concurrent chemotherapy with 40 mg/m2 of paclitaxel every Monday during conventional radiotherapy, 4. concurrent chemo-radiotherapy group 3 received concurrent chemotherapy with 40 mg/m2 of paclitaxel every Monday during three-dimensional conformal radiotherapy. All patients were irradiated with 2.0 Gy/fraction, 5 fractions/week, to a total dose of 60 -64 Gy. They all received two cycles of consolidation themotherapy with 40 mg/m2 of cisplatin on D 1-3 and 100 mg/m2 of etoposide on D 1-3. Results: The overall response rate was 67%, 71%, 71% and 79% for sequential chemo-radiotherapy group, concurrent chemo-radiotherapy group 1, 2 and 3, respectively. There was a significant difference between the concurrent chemo-radiotherapy and sequential chemo-radiotherapy(P0.05) also was the difference of toxicity (P>0.05), but the severe toxicity of concurrent chemo-radiotherapy groups 1 and 2 were higher than the sequential chemo-radio-therapy group and concurrent chemo-radiotherapy group 3. Conclusions: Better locoregional progression-free survival and overall survival of unresectable stage III non-small cell lung cancer could be achieved by concurrent chemo-radiotherapy as compared with sequential chemo-radiotherapy though at the expense of in- crease in toxicity. With the combination of

  7. Erlotinib Hydrochloride and Cetuximab in Treating Patients With Advanced Gastrointestinal Cancer, Head and Neck Cancer, Non-Small Cell Lung Cancer, or Colorectal Cancer

    Science.gov (United States)

    2015-09-28

    Adenocarcinoma of the Colon; Adenocarcinoma of the Rectum; Advanced Adult Primary Liver Cancer; Carcinoma of the Appendix; Gastrointestinal Stromal Tumor; Metastatic Gastrointestinal Carcinoid Tumor; Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Adenoid Cystic Carcinoma of the Oral Cavity; Recurrent Adult Primary Liver Cancer; Recurrent Anal Cancer; Recurrent Basal Cell Carcinoma of the Lip; Recurrent Colon Cancer; Recurrent Esophageal Cancer; Recurrent Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Recurrent Extrahepatic Bile Duct Cancer; Recurrent Gallbladder Cancer; Recurrent Gastric Cancer; Recurrent Gastrointestinal Carcinoid Tumor; Recurrent Inverted Papilloma of the Paranasal Sinus and Nasal Cavity; Recurrent Lymphoepithelioma of the Nasopharynx; Recurrent Lymphoepithelioma of the Oropharynx; Recurrent Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity; Recurrent Mucoepidermoid Carcinoma of the Oral Cavity; Recurrent Non-small Cell Lung Cancer; Recurrent Pancreatic Cancer; Recurrent Rectal Cancer; Recurrent Salivary Gland Cancer; Recurrent Small Intestine Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Small Intestine Adenocarcinoma; Small Intestine Leiomyosarcoma; Small Intestine Lymphoma; Stage IV Adenoid Cystic Carcinoma of the Oral Cavity; Stage IV Anal Cancer; Stage IV Basal Cell Carcinoma of the Lip; Stage IV Colon Cancer; Stage IV Esophageal Cancer; Stage IV Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Stage IV Gastric Cancer

  8. Influence of Methylenetetrahydrofolate Reductase C677T Polymorphism on the Risk of Lung Cancer and the Clinical Response to Platinum-Based Chemotherapy for Advanced Non-Small Cell Lung Cancer: An Updated Meta-Analysis

    OpenAIRE

    Zhu, Ning; Gong, Yi; He, Jian; Xia, Jingwen; Chen, Xiaodong

    2013-01-01

    Purpose Methylenetetrahydrofolate reductase (MTHFR) has been implicated in lung cancer risk and response to platinum-based chemotherapy in advanced non-small cell lung cancer (NSCLC). However, the results are controversial. We performed meta-analysis to investigate the effect of MTHFR C677T polymorphism on lung cancer risk and response to platinum-based chemotherapy in advanced NSCLC. Materials and Methods The databases of PubMed, Ovid, Wanfang and Chinese Biomedicine were searched for eligib...

  9. Advances in molecular biology of lung disease: aiming for precision therapy in non-small cell lung cancer.

    Science.gov (United States)

    Rooney, Claire; Sethi, Tariq

    2015-10-01

    Lung cancer is the principal cause of cancer-related mortality in the developed world, accounting for almost one-quarter of all cancer deaths. Traditional treatment algorithms have largely relied on histologic subtype and have comprised pragmatic chemotherapy regimens with limited efficacy. However, because our understanding of the molecular basis of disease in non-small cell lung cancer (NSCLC) has improved exponentially, it has become apparent that NSCLC can be radically subdivided, or molecularly characterized, based on recurrent driver mutations occurring in specific oncogenes. We know that the presence of such mutations leads to constitutive activation of aberrant signaling proteins that initiate, progress, and sustain tumorigenesis. This persistence of the malignant phenotype is referred to as "oncogene addiction." On this basis, a paradigm shift in treatment approach has occurred. Rational, targeted therapies have been developed, the first being tyrosine kinase inhibitors (TKIs), which entered the clinical arena > 10 years ago. These were tremendously successful, significantly affecting the natural history of NSCLC and improving patient outcomes. However, the benefits of these drugs are somewhat limited by the emergence of adaptive resistance mechanisms, and efforts to tackle this phenomenon are ongoing. A better understanding of all types of oncogene-driven NSCLC and the occurrence of TKI resistance will help us to further develop second- and third-generation small molecule inhibitors and will expand our range of precision therapies for this disease. PMID:26182407

  10. Pulmonary resection after chemoradiotherapy for advanced non-small cell lung cancer. The impact of presurgical radiation therapy

    International Nuclear Information System (INIS)

    Chemoradiation therapy (CRT) is recommended as standard care for stage III non-small cell lung cancer (NSCLC), but some patients experience local recurrence after the treatment. Surgical resection after CRT involves high surgical risk, but is expected to increase the curability. This study was performed to investigate the impact of presurgical CRT on the postoperative outcome, focusing especially on the effect of radiation therapy. Twenty-six patients with stage III (N2 or T3-4) NSCLC underwent pulmonary resection after CRT. A radiation dose up to 40-70 Gy was given with concurrent chemotherapy. The morbidity, mortality and survival after surgical resection were examined. Lung resection was performed as lobectomy (73%) or pneumonectomy (19%). Postoperative complications occurred in 12 patients (morbidity 46.1%). The overall 5-year survival of the entire cohort was 69.7%. The factors associated with favorable long-term survival included a pathological complete response (CR) and mediastinal node negative condition after CRT, and microscopic complete resection. Surgical resection for stage III patients after CRT may provide a survival benefit with acceptable morbidity. The surgical morbidity may be increased by prior radiation therapy, thus, surgeons should be familiar with the available countermeasures to reduce the surgical risk. (author)

  11. Pemetrexed Combined with Cisplatin or Carboplatin Regimen in the Treatment of Advanced Recurrent or Metastasis Non-small Cell Lung Cancer: Analysis of 63 Cases

    Directory of Open Access Journals (Sweden)

    Wei WANG

    2011-01-01

    Full Text Available Background and objective Since the poor outcome for advanced lung cancer with first-line chemotherapy, more efforts should be paid for treatment of advanced recurrent or metastasis non-small cell lung cancer (NSCLC patients. Pemetrexed, as a multi-target antifolate chemotherapeutic drug, was approved for the second-line treatment of advanced NSCLC. The aim of this study is to evaluate the efficacy and side effects of pemetrexed combined with cisplatin/carboplatin in the treatment of advanced recurrent or metastasis NSCLC. Methods Sixty-three advanced recurrent or metastasis NSCLC patients confirmed with pathology or cytology were enrolled in this study. Among them, 40 cases were male and 23 were female, with 62 years of median age. The combination regimen was patients received pemetrexed 500 mg/m2 on day 1 and cisplatin 30 mg/m2 on day 1, day 2 and day 3 or carboplatin 300 mg/m2 on day 1 by intravenous infusion, with 21 days as one cycle. All patients who received 2 or more cycles could be evaluated. Results Only 1 case got complete response, with 5 cases partial response, 36 stable and 21 cases progressive. The overal control rate was 66.7% (42/63. The median survival time was 9.0 months, while the median progression-free survival was 5.0 months (3.0 months in squamous cell carcinoma; 5.5 months in adenocarcinoma. There was a significant difference between squamous cell carcinoma and adenocarcinoma (P=0.017. The common adverse effects were leucopenia, anemia and gastrointestinal response. Conclusion Pemetrexed combined with cisplatin/carboplatin is effective and feasible for advanced recurrent or metastasis NSCLC.

  12. Treatment Choice for Advanced Non-small Cell Lung Cancer Patients Who Had Gradual Progression After EGFR-TKIs: 32 Cases Report

    Directory of Open Access Journals (Sweden)

    Lin LIN

    2013-10-01

    Full Text Available Background and objective The epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs have been widely used in the treatment of the advanced non-small cell lung cancer (NSCLC, especially in the adenocarcinoma patients with activating EGFR mutations. But there is no published overview of the following treatment. This report through observing the efficacy, toxicity and overall survival of different treatments to the advanced NSCLC patients who had gradual progression after EGFR-TKIs, evaluates the influence of the continued treatment and switching chemotherapy. Methods Retrospective review is conducted on 32 cases of advanced NSCLC patients who experienced treatment failure of EGFR-TKIs. One group accepted the continued treatment and the other group accepted the switching chemotherapy. Results The median overall survival of the continued treatment group is 36.0 months. The respose rate of the switching chemotherapy group is 43.75%, and clinical benefit rate (complete and partial response and stable disease is 87.5%. The median overall survival is 15.5 months. The main toxicities are nausea, vomiting and hematological toxicities. Conclusion For the advanced NSCLC patients who had gradual progression after EGFR-TKIs, the continued treatment is one of the acceptable choices.

  13. 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.

  14. The emerging role of histology in the choice of first-line treatment of advanced non-small cell lung cancer: implication in the clinical decision-making.

    Science.gov (United States)

    Rossi, Antonio; Maione, Paolo; Bareschino, Maria Anna; Schettino, Clorinda; Sacco, Paola Claudia; Ferrara, Marianna Luciana; Castaldo, Vincenzo; Gridelli, Cesare

    2010-01-01

    Lung cancer is the leading cause of cancer mortality worldwide. Non-small cell lung cancer (NSCLC), accounting for about 85% of all lung cancers, includes squamous carcinoma, adenocarcinoma and undifferentiated large cell carcinoma. The majority of patients have advanced disease at diagnosis, and medical treatment is the cornerstone of management. Several randomized trials comparing third-generation platinum-based doublets concluded that all such combinations are comparable in their clinical efficacy, failing to document a difference based on histology. However, recent evidences, arising from the availability of pemetrexed, have shown that histology represents an important variable in the decision making. The major progresses in the understanding cancer biology and mechanism of oncogenesis have allowed the development of several potential molecular targets for cancer treatment such as vascular growth factor and its receptors and epidermal growth factor receptor. Targeted drugs seem to be safer or more effective in a specific histology subtype. All of these data have led to choose the optimal first-line treatment of advanced NSCLC based on histologic diagnosis. However, this scenario raises a diagnostic issue: a specific diagnosis of NSCLC histologic subtype is mandatory. This review will discuss these new evidences in the first-line treatment of advanced NSCLC and their implication in the current clinical decision-making. PMID:20156162

  15. 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- ...

  16. 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- ...

  17. 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- ...

  18. 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- ...

  19. Consensus Statement on Proton Therapy in Early-Stage and Locally Advanced Non-Small Cell Lung Cancer.

    Science.gov (United States)

    Chang, Joe Y; Jabbour, Salma K; De Ruysscher, Dirk; Schild, Steven E; Simone, Charles B; Rengan, Ramesh; Feigenberg, Steven; Khan, Atif J; Choi, Noah C; Bradley, Jeffrey D; Zhu, Xiaorong R; Lomax, Antony J; Hoppe, Bradford S

    2016-05-01

    Radiation dose escalation has been shown to improve local control and survival in patients with non-small cell lung cancer in some studies, but randomized data have not supported this premise, possibly owing to adverse effects. Because of the physical characteristics of the Bragg peak, proton therapy (PT) delivers minimal exit dose distal to the target volume, resulting in better sparing of normal tissues in comparison to photon-based radiation therapy. This is particularly important for lung cancer given the proximity of the lung, heart, esophagus, major airways, large blood vessels, and spinal cord. However, PT is associated with more uncertainty because of the finite range of the proton beam and motion for thoracic cancers. PT is more costly than traditional photon therapy but may reduce side effects and toxicity-related hospitalization, which has its own associated cost. The cost of PT is decreasing over time because of reduced prices for the building, machine, maintenance, and overhead, as well as newer, shorter treatment programs. PT is improving rapidly as more research is performed particularly with the implementation of 4-dimensional computed tomography-based motion management and intensity modulated PT. Given these controversies, there is much debate in the oncology community about which patients with lung cancer benefit significantly from PT. The Particle Therapy Co-operative Group (PTCOG) Thoracic Subcommittee task group intends to address the issues of PT indications, advantages and limitations, cost-effectiveness, technology improvement, clinical trials, and future research directions. This consensus report can be used to guide clinical practice and indications for PT, insurance approval, and clinical or translational research directions. PMID:27084663

  20. Evaluation of Efficacy and Safety of Bevacizumab Combined with Chemotherapy 
for Chinese Patients with Advanced Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Xiao ZHAO

    2012-01-01

    Full Text Available Background and objective The current study reported the result of bevacizumab treatment administered to 25 Chinese patients with advanced non-small cell lung cancer (NSCLC who were treated at the Peking Union Medical College Hospital as a part of the SAiL (MO19390 trial. This trial is an open, international multicenter, single-arm clinical study that assesses the safety and efficacy of first-line bevacizumab-based therapy in advanced NSCLC. Methods Twenty-five Chinese patients with advanced non-squamous NSCLC received bevacizumab (15 mg/kg combined with chemotherapy (carboplatin plus paclitaxel treatment from August 2007 to February 2008. Adverse effects (AEs, objective response rate (ORR, median time to progression (TTP, and overall survival (OS were measured. Results AEs were generally mild and reversible. The most frequent AEs were alopecia, peripheral neuropathy, rash, proteinuria, nausea/vomitting, fatigue, myalgia, bleeding, and hypertension. The partial remission and stable disease rates were 68% and 28%, respectively. The median TTP and OS of all patients were 11.2 and 19.3 months, respectively. Conclusion Bevacizumab combined with carboplatin-based chemotherapy may be well tolerated and beneficial for Chinese patients with non-squamous NSCLC.

  1. Nedaplatin/Gemcitabine Versus Carboplatin/Gemcitabine in Treatment of Advanced Non-small Cell Lung Cancer: A Randomized Clinical Trial

    Institute of Scientific and Technical Information of China (English)

    Jin-ji Yang; Qing Zhou; Ri-qiang Liao; Yi-sheng Huang; Chong-rui Xu; Zhen Wang; Bin-chao Wang; Hua-jun Chen; Yi-long Wu

    2012-01-01

    Objective:To evaluate the efficacy and safety of nedaplatin/gemcitabine (NG) and carboplatin/gemcitabine (CG) in the management of untreated advanced non-small cell lung cancer (NSCLC).Methods:Sixty-two patients with previously untreated advanced NSCIC were recruited between June 2006 and November 2007.Subjects were randomly assigned to the NG arm (n=30) and the CG arm (n=32).Only patients (24 and 25 in the NG and CG arms,respectively) who completed ≥2 chemotherapy cycles were included in the data analysis.The primary outcome measure was the objective response rate (ORR).The secondary outcome measures included progression-free survival (PFS),overall survival (OS) and adverse events.Results:There were no statistically significant differences in the efficacy measures (ORR,P=0.305; median PFS,P=0.198; median OS,P=0.961) or in the major adverse events (grade 3/4 neutropenia,P=0.666; grade 3/4 anemia,P=0.263; grade 3/4 thrombocytopenia,P=0.212) between the two treatment arms.However,there was a trend towards higher ORR (37.5% vs.24.0%),longer PFS (6.0 vs.5.0 months),and less adverse events in the NG arm.Conclusion:NG regimen seems to be superior over CG regimen for advance NSCLS,but further investigation is needed to validate this superiority.

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

    Science.gov (United States)

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

    2016-01-01

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

  3. Concurrent three dimension conformal radiation therapy and chemotherapy followed by consolidation chemotherapy for locally advanced non-small cell lung cancer

    International Nuclear Information System (INIS)

    Objective: To investigate the comprehensive treatment of inoperable locally advanced non-small cell lung cancer (NSCLC), and to compare the efficacy and toxicity of concurrent chemoradiotherapy (CRT group) with those of concurrent chemoradiotherapy followed by consolidation chemotherapy (CCT group). Methods: Ninety patients with inoperable locally advanced NSCLC were randomized into CRT group or CCT group. CRT group was treated with weekly docetaxel and cisplatin based concurrent chemoradiotherapy. CCT group was treated with the same chemoradiotherapy followed by docetaxel and cisplatin based consolidation chemotherapy. For concurrent chemoradiotherapy, the total irradiation dose was 56-66 Gy given in 5-7 weeks, docetaxel 30 mg/m2 and cisplatin 20 mg/m2 were administrated on day 1, 8, 22 and 29 (≤2 hours before radiation fraction 1, 6, 16, and 21 ). For consolidation chemotherapy, docetaxel 75 mg/m2 and cisplatin 100 mg/m2 were given every three weeks to a total of two cycles. Results: For CRT group and CCT group, the response rates were 69% and 76% (P=0.480), respectively. The median progression-free survival time was 12.0 (95% CI 10.1-13.9) months and 14.5 (95% CI 11.8-17.2) months, respectively. The median survival time was 16.0 (95% CI 11.7-20.3)months and 16.0 (95% CI 13.5- 18.5 ) months, respectively. The 1-, 2- and 3-year progression-free survival rates were 56% and 62%, 12% and 24%, and 3% and 11% (P=0.044), respectively. The 1-, 2- and 3-year overall survival rates were 73% and 78%, 31% and 32%, and 20% and 21% (P=0.308), respectively. The difference of toxicity was not significant between the two group (P>0.05). Conclusions: For patients with locally advanced non-small cell lung cancer, concurrent conformal radiotherapy and chemotherapy followed by consolidation chemotherapy can improve the progression-free survival, but have few effects on overall survival and toxicity. Multicenter clinical trial with more patients should be carried out to confirm the

  4. Pemetrexed plus platinum as the first-line treatment option for advanced non-small cell lung cancer: a meta-analysis of randomized controlled trials.

    Directory of Open Access Journals (Sweden)

    Ming Li

    Full Text Available To compare the efficacy and toxicities of pemetrexed plus platinum with other platinum regimens in patients with previously untreated advanced non-small cell lung cancer (NSCLC.A meta-analysis was performed using trials identified through PubMed, EMBASE, and Cochrane databases. Two investigators independently assessed the quality of the trials and extracted data. The outcomes included overall survival (OS, progression-free survival (PFS, response rate (RR, and different types of toxicity. Hazard ratios (HRs, odds ratios (ORs and their 95% confidence intervals (CIs were pooled using RevMan software.Four trials involving 2,518 patients with previously untreated advanced NSCLC met the inclusion criteria. Pemetrexed plus platinum chemotherapy (PPC improved survival compared with other platinum-based regimens (PBR in patients with advanced NSCLC (HR = 0.91, 95% CI: 0.83-1.00, p = 0.04, especially in those with non-squamous histology (HR = 0.87, 95% CI: 0.77-0.98, p = 0.02. No statistically significant improvement in either PFS or RR was found in PPC group as compared with PBR group (HR = 1.03, 95% CI: 0.94-1.13, p = 0.57; OR = 1.15, 95% CI: 0.95-1.39, p = 0.15, respectively. Compared with PBR, PPC led to less grade 3-4 neutropenia and leukopenia but more grade 3-4 nausea. However, hematological toxicity analysis revealed significant heterogeneities.Our results suggest that PPC in the first-line setting leads to a significant survival advantage with acceptable toxicities for advanced NSCLC patients, especially those with non-squamous histology, as compared with other PRB. PPC could be considered as the first-line treatment option for advanced NSCLC patients, especially those with non-squamous histology.

  5. A phase II trial of accelerated hypofractionated three-dimensional conformal radiation therapy in locally advanced non-small cell lung cancer

    International Nuclear Information System (INIS)

    Purpose: The aim of this study is to evaluate the safety and efficacy of accelerated hypofractionated radiotherapy (HypoRT) combined with sequential chemotherapy in locally advanced non-small cell lung cancer (NSCLC). Materials and methods: A total of 34 patients with stage III NSCLC were enrolled. All patients received accelerated HypoRT (initially 50 Gy/20 fractions, then a fraction dose of 3 Gy) using three-dimensional conformal radiation therapy (3D-CRT), omitting elective nodal irradiation (ENI), to a total dose of 65-68 Gy. All patients received two cycles of induction chemotherapy; 1-2 cycles of consolidation chemotherapy were given to 31 patients. The primary outcome measure was a profile of radiation toxicity. The secondary endpoints included overall survival (OS), progression-free survival (PFS), locoregional PFS (LR-PFS) and the pattern of initial failure. Results: Radiation toxicity was minimal. The median and 3-year OS, PFS were 19.0 months, 32.1%; 10.0 months, 29.8%, respectively. The 1-, 2-, and 3-year LR-PFS were 69.6%, 60.9% and 60.9%, respectively. No patient experienced isolated elective nodal failure as the first site of failure. Conclusion: This study suggests that accelerated HypoRT using 3D-CRT omitting ENI can be used in combination with sequential chemotherapy in locally advanced NSCLC.

  6. Non-Cross Resistant Sequential Single Agent Chemotherapy in First-Line Advanced Non-Small Cell Lung Cancer Patients: Results of a Phase II Study

    Directory of Open Access Journals (Sweden)

    V. Surmont

    2009-01-01

    Full Text Available Background. sequential chemotherapy can maintain dose intensity and preclude cumulative toxicity by increasing drug diversity. Purpose. to investigate the toxicity and efficacy of the sequential regimen of gemcitabine followed by paclitaxel in first line advanced stage non-small cell lung cancer (NSCLC patients with good performance status (PS. Patients and methods. gemcitabine 1250 mg/m2 was administered on day 1 and 8 of course 1 and 2; Paclitaxel 150 mg/m2 on day 1 and 8 of course 3 and 4. Primary endpoint was response rate (RR, secondary endpoints toxicity and time to progression (TTP. Results. Of the 21 patients (median age 56, range 38–80 years; 62% males, 38% females 10% (2/21 had stage IIIB, 90% (19/21 stage IV, 15% PS 0, 85% PS 1. 20% of patients had a partial response, 30% stable disease, 50% progressive disease. Median TTP was 12 weeks (range 6–52 weeks, median overall survival (OS 8 months (range 1–27 months, 1-year survival was 33%. One patient had grade 3 hematological toxicity, 2 patients a grade 3 peripheral neuropathy. Conclusions. sequential administration of gemcitabine followed by paclitaxel in first line treatment of advanced NSCLC had a favourable toxicity profile, a median TTP and OS comparable with other sequential trials and might , therefore, be a treatment option for NSCLC patients with high ERCC1 expression.

  7. A systematic review of the clinical effectiveness of first-line chemotherapy for adult patients with locally advanced or metastatic non-small cell lung cancer.

    Science.gov (United States)

    Pilkington, Gerlinde; Boland, Angela; Brown, Tamara; Oyee, James; Bagust, Adrian; Dickson, Rumona

    2015-04-01

    Our aim was to evaluate the clinical effectiveness of chemotherapy treatments currently licensed in Europe and recommended by the National Institute for Health and Care Excellence (NICE) for the first-line treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC). A systematic search of MEDLINE, EMBASE and the Cochrane Library for randomised controlled trials (RCTs) published from 2001 to 2010 was carried out. Relative treatment effects for overall survival (OS) and progression-free survival (PFS) were estimated using standard meta-analysis and mixed treatment comparison methodology. A total of 23 RCTs were included: 18 trials compared platinum-based chemotherapy, two compared pemetrexed and three compared gefitinib. There are no statistically significant differences in OS between any of the four third-generation chemotherapy regimens. There is statistically significant evidence that pemetrexed+platinum increases OS compared with gemcitabine+platinum. There are no statistically significant differences in OS between gefitinib and docetaxel+platinum or between gefitinib and paclitaxel+platinum. There is a statistically significant improvement in PFS with gefitinib compared with docetaxel+platinum and gefitinib compared with paclitaxel+platinum. Due to reduced generic pricing, third-generation chemotherapy regimens (except vinorelbine) are still competitive options for most patients. This research provides a comprehensive evidence base, which clinicians and decision-makers can use when deciding on the optimal first-line chemotherapy treatment regimen for patients diagnosed with locally advanced or metastatic NSCLC. PMID:25661113

  8. Insulin-like growth factor receptor 1 mRNA expression as a prognostic marker in advanced non-small cell lung cancer

    DEFF Research Database (Denmark)

    Vilmar, Adam; Santoni-Rugiu, Eric; Cillas, Jesus Garcia-Fon;

    2014-01-01

    BACKGROUND: The insulin-like growth factor 1 receptor (IGF1R) has yet to be established as a biomarker in non-small cell lung cancer (NSCLC) but could prove useful in customized chemotherapy. We explored its prognostic value using both quantitative real-time reverse transcriptase polymerase chain...

  9. Quantitative study of lung perfusion SPECT scanning and pulmonary function testing for early radiation-induced lung injury in patients with locally advanced non-small cell lung cancer

    OpenAIRE

    Zhang, Wei; WANG, JIEZHONG; TANG, MINGDENG; Pan, Jianji; Bai, Penggang; LIN, DUANYU; QIAN, FEIYU; LIN, FENGJIE; YANG, XUEQIN; Zhang, Shengli

    2012-01-01

    Radiation lung injury is a common side-effect of pulmonary radiotherapy. The aim of this study was to quantitatively assess early changes in lung perfusion single photon emission computed tomography (SPECT) scanning and pulmonary function testing (PFT) prior to and after intensity modulated radiotherapy (IMRT) for patients suffering from locally advanced non-small cell lung cancer (LANSCLC). Twenty patients with LANSCLC received lung perfusion SPECT scanning and PFT prior to IMRT and immediat...

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

    International Nuclear Information System (INIS)

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

  11. Shenqi fuzheng, an injection concocted from chinese medicinal herbs, combined with platinum-based chemotherapy for advanced non-small cell lung cancer: a systematic review

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    Wang Min-Yan

    2010-10-01

    Full Text Available Abstract Background Platinum-based chemotherapy has been a standard therapy for advanced non-small cell lung cancer (NSCLC, but it has high toxicity. In China, Shenqi Fuzheng, a newly developed injection concocted from Chinese medicinal herbs has been reported that may increase efficacy and reduce toxicity when combined with platinum-based chemotherapy, but little is known about it outside of China. The aim of this study was to systematically review the existing clinical evidence on Shenqi Fuzheng Injection(SFI combined with platinum-based chemotherapy for advanced NSCLC. Methods Pubmed, Cochrane Library, EMBASE, CNKI, and CBM search were organized for all documents published, in English and Chinese, until April 2010. The randomized controlled clinical trials were selected based on specific criteria, in which a SFI plus platinum-based chemotherapy treatment group was compared with a platinum-based chemotherapy control group for patients with advanced NSCLC. The quality of studies was assessed by modified Jadad's scale, and Revman 4.2 software was used for data syntheses and analyses. Results Twenty nine studies were included in this review based on our selection criteria. Of them, ten studies were of high quality and the rest were of low quality, according to the modified Jadad scale. The meta-analysis showed there was a statistically significant higher tumor response (RR, 1.19; 95% CI, 1.07 to 1.32; P = 0.001 and performance status ((RR, 1.57; 95% CI, 1.45 to 1.70; P P = 0.016. Conclusions SFI intervention appears to be useful to increase efficacy and reduce toxicity when combined with platinum-based chemotherapy for advanced NSCLC, although this result needs to be further verified by more high-quality trials.

  12. Association between TYMS expression and efficacy of pemetrexed-based chemotherapy in advanced non-small cell lung cancer: a meta-analysis.

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    Ting Wang

    Full Text Available BACKGROUND: The predictive value of thymidylate synthase (TYMS to sensitivity to pemetrexed-based chemotherapy in advanced non-small cell lung cancer (NSCLC patients is controversial. We conducted a meta-analysis of all relevant published data to assess the association of TYMS expression with the clinical outcomes of pemetrexed-based regimen in advanced NSCLC. PATIENTS AND METHODS: We conducted an electronic search using using PubMed, Embase, OVID and Cochrane Library databases and manual search. Pooled odds ratio (OR for the response rate and hazard ratio (HR for the overall survival and progression free survival were calculated using the software Revman 5.0. RESULTS: There were 11 studies (n=798 met our criteria for evaluation. Response rate to pemetrexed-based regimen was significantly higher in patients with low/negative TYMS (OR=2.96, 95%CI [1.81, 4.86] P<0.0001. Patients with low/negative TYMS who were treated with pemetrexed-based regimen had longer progression free survival (HR 0.50, 95%CI [0.41, 0.61] P <0.00001 and overall survival (HR 0.41, 95%CI [0.22, 0.78] P=0.007 than those with high/positive TYMS. CONCLUSIONS: Low/negative TYMS expression was significantly associated with higher response rate, longer median survival and longer progression free survival for advanced NSCLC patients receiving pemtrexed-based chemotherapy. Hence, TYMS may be a potential predictor of sensitivity to pemtrexed-based chemotherapy in advanced NSCLC. Large scale prospective clinical trials are still warranted.

  13. Epidermal growth factor receptor genotype in plasma DNA and outcome of chemotherapy in the Chinese patients with advanced non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    ZHUO Ming-lei; DUAN Jian-chun; WANG Yu-yan; GUO Qing-zhi; LIU Xu-yi; LIU Ning-hong; WANG Jie; WU Mei-na; ZHAO Jun; Sonya Wei Song; BAI Hua; WANG Shu-hang; YANG Lu; AN Tong-tong; WANG Xin

    2011-01-01

    Background The genotype of epidermal growth factor receptor (EGFR) is associated with tyrosine kinase inhibitor and effectiveness of therapy,but its role in cytotoxic chemotherapy is still unknown.Previous studies indicated that certain EGFR mutations were associated with response and progression free survival following platinum based chemotherapy.Our recent studies have identified that EGFR genotypes in the tumour tissues were not associated with response to the first-line chemotherapy in Chinese patients with advanced non-small cell lung cancer (NSCLC).In this study,we investigated associations of EGFR genotypes from plasma of patients with advanced NSCLC and response to first-line chemotherapy and prognosis.Methods We enrolled 145 advanced NSCLC patients who had received first-line chemotherapy in our department.We examined plasma EGFR genotypes for these patients and associations of EGFR mutations with response to chemotherapy and clinical outcomes.Results There were 54 patients with known EGFR mutations and 91 cases of wild types.No significant difference was detected in the response rate to first-line chemotherapy between mutation carriers and wild-type patients (37.0% vs.31.9%).The median survival time and 1-,2-year survival rates were higher in mutation carriers than wild-types (24months vs.18 months,85.7% vs.65.7% and 43.7% vs.25.9%,P=0.047).Clinical stage (IV vs.Ⅲb),response to the first-line chemotherapy (partial vs.no) and EGFR genotype were independent prognostic factors.Conclusion Plasma EGFR mutations in the Chinese patients with advanced NSCLC is not a predictor for the response to first-line chemotherapy,but an independent prognostic factor indicating longer survival.

  14. Clinical impact of postprogression survival for overall survival in elderly patients (aged 75 years or older with advanced nonsmall cell lung cancer

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    Reiko Yoshino

    2015-01-01

    Full Text Available Introduction: The effects of first-line single-agent chemotherapy on overall survival (OS might be confounded by subsequent treatments in elderly patients with nonsmall cell lung cancer (NSCLC. We, therefore, aimed to evaluate whether progression-free survival (PFS, postprogression survival (PPS, or tumor response might be a valid surrogate endpoint for OS in this patient population. Patients and Methods: We retrospectively reviewed the clinical data of 58 elderly patients with advanced NSCLC, who received first-line single-agent cytotoxic chemotherapy at our institution between October 2003 and November 2013. The relationships of PFS, PPS, and tumor response with OS were individually analyzed. Results: The study cohort included 46 men and 12 women with a median age of 79 years (range: 75-87 years. There were 30 adenocarcinomas, 22 squamous cell carcinomas, and 6 other histologic types with 1 stage IIIA, 9 IIIB, and 48 IV cases. The performance status (PS scores were 0, 1, and 2 in 18, 35, and 5 patients, respectively. The median PFS and OS were 2.8 and 5.4 months, respectively. Our analyses revealed a strong correlation of PPS and PFS with OS, whereas that between tumor shrinkage and OS was weak. Tumor stage and PS after initial treatment were significantly associated with PPS. Individual analysis indicated that PPS might serve as a surrogate for OS in elderly patients with advanced NSCLC receiving first-line single-agent chemotherapy. Conclusion: Our findings suggested that the disease course after progression following first-line single-agent chemotherapy might influence the OS of elderly patients with advanced NSCLC.

  15. Relationship between the Genetic Polymorphisms of Phase I and II Drug-metabolizing Enzymes, as well as the Outcome of Chemotherapy in Advanced Non-small Cell Lung Cancer

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    Weiying LI

    2011-11-01

    Full Text Available Background and objective Currently available studies on the polymorphisms of drug-metabolizing enzymes and their chemotherapeutic effects in non-small cell lung cancer are not consistent. In the present study, the relationship of the gene polymorphisms of cytochrome P450 1A1 (CYP1A1, cytochrome P450 2E1 (CYP2E1, cytochrome P450 2D6 (CYP2D6, and glutathione S-transferase M1 (GSTM1 enzymes with chemotherapeutic effects were investigated. The effects of these relationships on the survival of advanced non-small cell lung cancer patients were also examined. Methods Four drug metabolism enzymes were genotyped in lung cancer patients by polymerase chain reaction (PCR and PCR-restriction fragment length polymorphism. These patients were followed for five years. Results The chemotherapeutic effect on patients carrying B-type CYP1A1 and null-type GSTM1 was better than on those carrying other types (P<0.001. The chemotherapeutic effect on patients carrying A-type CYP1A1 was better than on those carrying the B and C types when non-platinum drugs were administered (P=0.041. The chemotherapeutic effect on patients carrying null-type GSTM1 was better than on those carrying the functional type when platinum drugs were administered (P=0.011. The four enzymes did not affect the overall survival (OS of advanced non-small cell lung cancer patients (P>0.05. Conclusion The chemotherapeutic effect on patients carrying A-type CYP1A1 was better than on those carrying the B and C types when non-platinum drugs were administered. The chemotherapeutic effect on patients carrying null-type GSTM1 was better than on those carrying the functional type when platinum drugs were administered. The four enzymes did not affect the OS of advanced non-small cell lung cancer patients.

  16. Advances in the management of acquired resistance to EGFR-TKI in non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    Fei Zhou; Caicun Zhou

    2015-01-01

    Drugs that specifical y target the tyrosine kinase domain of epidermal growth factor receptor (EGFR), such as erlotinib or gefitinib, have exhibited striking ef icacy in non-smal cel lung cancer (NSCLC) patients har-boring activating EGFR mutations. However, acquired resistance inevitably develops and remains a serious barrier for the successful management of patients with this disease. Multiple mechanisms are reportedly involved in the process of acquired resistance, which provide new insights into the management of EGFR-tyrosine kinase inhibitor (EGFR-TKI) resistance. Here, we provide an overview of the emerging treatment approaches for patients with EGFR-TKI resistance.

  17. Comparison of dose distribution between simplified IMRT and different curative radiotherapy plans for locally advanced non-small cell lung cancer

    International Nuclear Information System (INIS)

    Objective: To evaluate the dose distribution of target volume and normal tissues with different treatment planning such as three dimensional conformal radiotherapy (3DCRT), Simplified intensity-modulated radiotherapy (sIMRT), and intensity-modulated radiotherapy (IMRT) for patients with locally advanced non-small cell lung carcinoma (NSCLC). Methods: Fourteen patients with stage III NSCLC who underwent concurrent radio chemotherapy were enrolled in this study. Five-field 3D-CRT, sIMRT and 5-field or 7-field IMRT plans were performed for each patient. The dose distributions of target volume and normal tissues, conformal index (CI), and heterogeneous index (HI) were analyzed using the dose-volume histogram for these techniques. The prescription dose was 60 Gy in 30 fractions. The total monitor units (MU) were also analyzed to compare the execution time indirectly. Results: The CI for planning target volume (PTV) was superior with IMRT, sIMRT to 3DCRT. Conversely, the HI for PTV was 3DCRT > sIMRT > IMRT. sIMRT and IMRT can protect the organs at risk better than 3DCRT. The mean of total MU for 3DCRT5f, sIMRT, IMRT5f and IMRT7f was 476±23, 523±29, 764±51 and 793±44, respectively. Conclusions: Comparing with 3DCRT and IMRT, sIMRT was optimal for clinical practice. sIMRT and IMRT radiotherapy techniques can protect the lung and spinal cord well. (authors)

  18. Genotypes and haplotypes of the VEGF gene and survival in locally advanced non-small cell lung cancer patients treated with chemoradiotherapy

    International Nuclear Information System (INIS)

    Vascular endothelial growth factor (VEGF) is a major mediator of angiogenesis involving in carcinogenesis, including lung cancer. We hypothesized that VEGF polymorphisms may affect survival outcomes among locally advanced non-small cell lung cancer (LA-NSCLC) patients. We genotyped three potentially functional VEGF variants [-460 T > C (rs833061), -634 G > C (rs2010963), and +936 C > T (rs3025039)] and estimated haplotypes in 124 Caucasian patients with LA-NSCLC treated with definitive radiotherapy. We used Kaplan-Meier log-rank tests, and Cox proportional hazard models to evaluate the association between VEGF variants and overall survival (OS). Gender, Karnofsky's performance scores (KPS) and clinical stage seemed to influence the OS. The variant C genotypes were independently associated with significantly improved OS (CT+CC vs. TT: adjusted hazard ratio [HR] = 0.58; 95% confidence interval [CI] = 0.37-0.92, P = 0.022), compared with the VEGF -460 TT genotype. Our study suggests that VEGF -460 C genotypes may be associated with a better survival of LA-NSCLC patients after chemoradiotherapy. Large studies are needed to confirm our findings

  19. Analysis of Differentially Expressed Proteins in Self-Paired Sera of Advanced Non-small Cell Lung Cancer Patients Responsive to Gefin

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    Ying HUANG

    2009-07-01

    Full Text Available Background and objective All the advanced NSCLC patients that received EGFR-TKI therapy will eventually relapse after a period of efficacy. The aim of this study is to investigate the serum biomarkers as potential predictive factors for the efficacy of epidermal growth factor receptor (EGFR tyrosine kinase inhibitor (TKI targeted therapy in advanced non-small cell lung cancer. Methods Twenty self-paired serum samples were collected from 9 advanced NSCLC patients that evaluated as disease control (SD or PR after gefinitib therapy, at the time points of before and after gefinitib treatment but 2 weeks before being evaluated as disease progress. All samples were pre-separated by WCX microbeads, and then detected on the MALDI-TOF-MS platform of Bruker AutoflexTM. ClinProTools (Version: 2.1 was used to analyze the differentially expressed proteins. Results There were 7 protein peaks (m/z, 3242.09, 8 690.36, 2 952.64, 3 224.04, 1 450.51, 1 887.8 and 3 935.73 found statistically differentially expressed between the self-paired samples. Three proteins (3 242.09, 2 952.64 and 3 224.04 were down-regulated and four proteins (8 690.36, 1 450.51, 1 887.8 and 3 935.73 up-regulated in gefinitib treated sera. Conclusion The data here suggest that several specific protein peaks might indicate gefinitib resistance, yet the identities of these proteins and the mechanisms underlying the responsiveness to gefinitib treatment need further investigation.

  20. Assessment on the Efficacy and Safety of Aidi Injection Combined with Vinorelbine and Cisplatin for Treatment of Advanced Nonsmall Cell Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    Hua-Ye Zhao; Hai-Yan Zhou; Yan-Ting Wang; Wei Chen; Shu-Ya Qi; Jun-Ling Cao; Guo-Hui Li

    2016-01-01

    Background:The aim of this study was to assess the efficacy and safety of vinorelbine and cisplatin (NP chemotherapy) alone or in combination with Aidi injection for the treatment of advanced nonsmall cell lung cancer (NSCLC).Methods:Pertinent publications were identified in PubMed,EMBASE,Cochrane Library,CNKI,CQVIP,and Wanfang databases,up to December 8,2015.After quality assessment of all included randomized controlled trials evaluating Aidi injection combined with NP chemotherapy for the treatment of advanced NSCLC,a meta-analysis was performed by Review Manager 5.2 and STATA 12.0 for statistical analyses.Results:Twelve studies including 509 and 503 cases in the experimental and control groups,respectively,were finally analyzed.The meta-analysis revealed that when cisplatin dose ranging from 20 to 40 mg/m2,combination of Aidi injection and NP chemotherapy was statistically different compared with NP chemotherapy alone in enhancing efficiency (relative risk [RR] =1.24,95% confidence interval [CI] [1.05-1.47],P =0.010) and reducing the incidence of Grade Ⅱ or above nausea and vomiting (RR =0.49,95% CI [0.30-0.80],P =0.005).Meanwhile,with cisplatin ranging from 80 to 120 mg/m2,no significant differences in efficiency (RR =1.11,95% CI [0.87-1.42],P =0.390) and Grade Ⅱ or above nausea and vomiting (RR =0.88,95% CI [0.71-1.10],P =0.260) were obtained.In addition,Aidi injection combined with NP chemotherapy was superior to NP chemotherapy alone in improving the quality of life,alleviating Grade Ⅱ or above leukopenia and thrombocytopenia.Conclusions:Aidi injection combined with NP chemotherapy can enhance efficiency,improve the quality of life,and decrease adverse effects in patients with advanced NSCLC.

  1. Gene-guided Gefitinib switch maintenance therapy for patients with advanced EGFR mutation-positive Non-small cell lung cancer: an economic analysis

    International Nuclear Information System (INIS)

    Maintenance therapy with gefitinib notably improves survival in patients with advanced non-small cell lung cancer (NSCLC) and EGFR mutation-positive tumors, but the economic impact of this practice is unclear. A decision-analytic model was developed to simulate 21-day patient transitions in a 10-year time horizon. The clinical data were primarily obtained from the results of a pivotal phase III trial that assessed gefitinib maintenance treatment in patients with advanced NSCLC. The cost data were derived from the perspective of the Chinese health care system. The primary outcome was the incremental cost-effectiveness ratio (ICER) at a willingness-to-pay (WTP) threshold of 3 times the per capita GDP of China. Sensitivity analyses were used to explore the impact of uncertainty regarding the results. The impact of the gefitinib patient assistance program (GPAP) was evaluated. After EGFR genotyping, gefitinib maintenance treatment for advanced NSCLC with EGFR mutations increased the life expectancy by 0.74 years and 0.46 QALYs compared with routine follow-up at an additional cost of $26,149.90 USD ($7,178.20 with the GPAP). The ICER for gefitinib maintenance was $57,066.40 and $15,664.80 per QALY gained (at a 3% discount rate) without and with the GPAP, respectively. The utility of progression free survival, the hazard ratio of progression-free survival for gefitinib treatment and the cost of gefitinib per dose were the three factors that had the greatest influence on the results. These results indicate that gene-guided maintenance therapy with gefitinib with the GPAP might be a cost-effective treatment option

  2. Translational Research on Epidermal Growth Factor Receptor Gene Mutations in Targeted Therapy for Patients with Advanced Non-Small Cell Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    WANG Xiao-yan; ZHOU Er-xi

    2015-01-01

    Objective:To explore the significance of epidermal growth factor receptor (EGFR) gene mutations in targeted therapy for patients with advanced non-small cell lung cancer (NSCLC). Methods:One hundred and seventeen patients with advanced NSCLC admitted in Maternal and Child Health Care Center of Zibo City from Jan., 2011 to Jan., 2014 were performed with EGFR gene detection and then divided into 3 groups according to the detecting results. Patients in group A and group B were given oral geiftinib, 250 mg/d while patients in Group C with docetaxel, 75 mg/m2. Chemotherapy for 3 groups was discontinued until severe adverse reactions or disease progression occurred, or continuous treatment was considered to be unfavorable by the doctors, or patients asked for withdrawal from the study. The relationship between clinicopathological features and EGFR mutations were analyzed. The short-term and long-term efifcacy and adverse reactions of 3 groups were observed. Results:Of the 31 cases with EGFR mutations, there were 16 cases (51.6%) of mutations in exon 19, 14 (45.2%) in exon 21 and 2 (6.45%) in exon 18. No EGFR mutation was found in exon 20. EGFR mutations were associated with histological types of tumors and whether patients were smoking. The median follow-up time was 26 months and 62 patients were dead. None of CR was in 3 groups. The disease control rate (DCR) in group A was obviously higher than that in group B (χ2=9.382,P=0.002), which was also higher in group C than that in group B (χ2=4.674,P=0.031). The 1-year survival rate in group A was obviously higher than that in group B and group C (P Conclusion:EGFR mutations are the main indicators for guiding the targeted therapy for patients with advanced NSCLC.

  3. Gene-guided Gefitinib switch maintenance therapy for patients with advanced EGFR mutation-positive Non-small cell lung cancer: an economic analysis

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    Zhu Jun

    2013-01-01

    Full Text Available Abstract Background Maintenance therapy with gefitinib notably improves survival in patients with advanced non-small cell lung cancer (NSCLC and EGFR mutation-positive tumors, but the economic impact of this practice is unclear. Methods A decision-analytic model was developed to simulate 21-day patient transitions in a 10-year time horizon. The clinical data were primarily obtained from the results of a pivotal phase III trial that assessed gefitinib maintenance treatment in patients with advanced NSCLC. The cost data were derived from the perspective of the Chinese health care system. The primary outcome was the incremental cost-effectiveness ratio (ICER at a willingness-to-pay (WTP threshold of 3 times the per capita GDP of China. Sensitivity analyses were used to explore the impact of uncertainty regarding the results. The impact of the gefitinib patient assistance program (GPAP was evaluated. Results After EGFR genotyping, gefitinib maintenance treatment for advanced NSCLC with EGFR mutations increased the life expectancy by 0.74 years and 0.46 QALYs compared with routine follow-up at an additional cost of $26,149.90 USD ($7,178.20 with the GPAP. The ICER for gefitinib maintenance was $57,066.40 and $15,664.80 per QALY gained (at a 3% discount rate without and with the GPAP, respectively. The utility of progression free survival, the hazard ratio of progression-free survival for gefitinib treatment and the cost of gefitinib per dose were the three factors that had the greatest influence on the results. Conclusions These results indicate that gene-guided maintenance therapy with gefitinib with the GPAP might be a cost-effective treatment option.

  4. Efficacy analysis of two drugs consisting platinum combined with first-line chemotherapeutics regimens on 117 elderly patients with advanced non-small cell lung carcinoma

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    Li-li ZHANG

    2013-09-01

    Full Text Available Objective To investigate the therapeutic effects of Gemcitabine(GEM, Vinorelbine(NVB,Paclitaxel(TAX and other first-line chemotherapeutics plus platinum containing drugs on the elderly patients with advanced non-small cell lung cancer(NSCLC who had undergone surgery, and analyze the clinicopathological factors influencing the prognosis. Methods One hundred and seventeen advanced NSCLC patients aged 60 or over were treated with GP(GEM+platinum, or NP(NVB+platinum, or TP(TAX+platinum, or other first-line chemotherapeutics plus platinum(OCP after surgery, and their clinical data were then retrospectively studied to look for the relationship of patients' prognosis to clinicopathological factors(gender, operation methods, pathologicaltypes, differentiation, clinical stages.The survival curve was plotted with Kaplan-Meier method, hypothesis test was performed by log-rank, and the independent prognostic factors were screened with Cox proportional hazards regression model. Results Theone-, three- and five-year survival rates of the 117 patients were 47.23%,17.52% and 8.05%, respectively. The progression free survival(PFS of GP, NP, TP and OCP groups were 6.0, 5.2, 6.1 and5.5 months(P>0.05, respectively. The median progression free survival was 5.7 months. Univariate and multivariate analysis showed that the differentiated degrees and clinical stages of elderly NSCLC patients were the independent prognostic factors. Conclusions Clinicopathological factors(differentiated degree andclinical stages are closely related to one-, three- and five-year survival rates of advanced NSCLC in elderly patients who received treatment of first-line chemotherapeutics plus platinum. However, the efficacy ofGP, NP, TP or OCP shows no significant difference.

  5. Treatment adherence in concurrent chemoradiation in patients with locally advanced non-small cell lung carcinoma: Results of daily intravenous prehydration

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    Purpose: To test the hypothesis that daily intravenous pre-hydration decreases renal toxicity and improves chemotherapy adherence in patients receiving daily cisplatin to concurrent radiotherapy for locally advanced non-small cell lung cancer (NSCLC). Patients and methods: Patients with locally advanced NSCLC were treated between 2008 and August 2012 with daily 6 mg/m2 cisplatin as a bolus injection in 10 ml; of saline and 66 Gy/24 fr radiotherapy in 32 days. Since January 2011, the administration of cisplatin was routinely preceded by intravenous pre-hydration with 1 L of natriumchloride 0.9%. Patients were divided in a pre-hydrated (PH) and non-pre-hydrated (NPH) cohort. Serum-creatinine and glomerular filtration rate (GFR) were assessed twice weekly during treatment. Retrospectively, baseline data, toxicity, treatment adherence and efficacy data were compared. Results: Of the 356 patients 232 NPH patients and 100 PH patients were eligible. Patient-and treatment characteristics compared equally. The median of the maximum decrease in GFR was 24% and 8% for NPH and PH (p < 0.01), respectively. Sixty-nine percent of the patients in the NPH group completed the 24 administrations of cisplatin, as compared to 83% of the PH group (p < 0.01). Nineteen percent vs. 2% of the patients in the NPH and PH group discontinued cisplatin treatment because of renal toxicity. Surprisingly, the incidence of acute esophageal toxicity grade ⩾2 decreased following prehydration: 62% vs. 34% (p < 0.001) for the NPH and PH groups, respectively. The one-year survival was comparable between groups (75% for NPH and 71% for PH). Conclusion: Daily pre-hydration was associated with a reduced rate of both renal and acute esophageal toxicity and an increased chemotherapy adherence in patients receiving daily dose of cisplatin and concurrent radiotherapy for locally advanced NSCLC

  6. Assessment on the Efficacy and Safety of Aidi Injection Combined with Vinorelbine and Cisplatin for Treatment of Advanced Nonsmall Cell Lung Cancer

    Science.gov (United States)

    Zhao, Hua-Ye; Zhou, Hai-Yan; Wang, Yan-Ting; Chen, Wei; Qi, Shu-Ya; Cao, Jun-Ling; Li, Guo-Hui

    2016-01-01

    Background: The aim of this study was to assess the efficacy and safety of vinorelbine and cisplatin (NP chemotherapy) alone or in combination with Aidi injection for the treatment of advanced nonsmall cell lung cancer (NSCLC). Methods: Pertinent publications were identified in PubMed, EMBASE, Cochrane Library, CNKI, CQVIP, and Wanfang databases, up to December 8, 2015. After quality assessment of all included randomized controlled trials evaluating Aidi injection combined with NP chemotherapy for the treatment of advanced NSCLC, a meta-analysis was performed by Review Manager 5.2 and STATA 12.0 for statistical analyses. Results: Twelve studies including 509 and 503 cases in the experimental and control groups, respectively, were finally analyzed. The meta-analysis revealed that when cisplatin dose ranging from 20 to 40 mg/m2, combination of Aidi injection and NP chemotherapy was statistically different compared with NP chemotherapy alone in enhancing efficiency (relative risk [RR] = 1.24, 95% confidence interval [CI] [1.05–1.47], P = 0.010) and reducing the incidence of Grade II or above nausea and vomiting (RR = 0.49, 95% CI [0.30–0.80], P = 0.005). Meanwhile, with cisplatin ranging from 80 to 120 mg/m2, no significant differences in efficiency (RR = 1.11, 95% CI [0.87–1.42], P = 0.390) and Grade II or above nausea and vomiting (RR = 0.88, 95% CI [0.71–1.10], P = 0.260) were obtained. In addition, Aidi injection combined with NP chemotherapy was superior to NP chemotherapy alone in improving the quality of life, alleviating Grade II or above leukopenia and thrombocytopenia. Conclusions: Aidi injection combined with NP chemotherapy can enhance efficiency, improve the quality of life, and decrease adverse effects in patients with advanced NSCLC. PMID:26960377

  7. Palliative chemotherapy followed by consolidation radiotherapy in patients with advanced and metastatic non-small cell lung cancer not suitable for radical treatment

    Institute of Scientific and Technical Information of China (English)

    Hany Eldeeb; Philip Gamileri; Ghoi Mak

    2012-01-01

    Objective: This is a retrospective study to assess the effectiveness of consolidation radiotherapy (CRT) following palliative chemotherapy in patients with metastatic or locally advanced non-small cell lung cancer (NSCLC) who are not suitable for radical treatment. Methods: This study involved retrospective analysis of a prospective database of Northampton Oncology Centre from January 2005 to December 2010,63 patients with advanced/metastatic NSCLC treated at the oncology centre were enrolled. Patients were either treated with high dose (39/36 Gy /13-12 fractions, group 1) or low dose (20 Gy / 5 fractions, group 2) CRT or those were not offered any CRT (group 3). Results: There was no significant difference between the three groups as regard age, sex, performance status, comorbidities or chemotherapy given. However there was a statistically significant difference as regard the stage P = 0.009 with more stage IV patients at group Ⅱ and Ⅲ compared to group l. The mean survival for the three groups was 27 months, 14 months &15 months, respectively. There was a statistically significant improvement of survival in patients treated with high dose palliative CRT compared to the other two groups (P = 0.006). In multivariate analysis only the radiotherapy dose remains as the only statistical significant factor affecting the survival with hazard ratio 0.372 and confidence interval (0.147-0.726). Conclusion: Despite the limitation of our retrospective study, it is worth considering CRT approach for patients with advanced and metastatic NSCLC - not suitable for radical treatment - who have not progressed on chemotherapy.

  8. Analysis of long-term survival in patients treated with three-dimensional conformal radiotherapy for locally advanced non-small cell lung cancer

    International Nuclear Information System (INIS)

    Objective: To evaluate the prognostic factors of locally advanced non-small cell lung cancer (LA-NSCLC) treated with three dimensional conformal radiation therapy (3D CRT). Methods: In 106 patients with stage IIIa/IIIb NSCLC treated with 3DCRT from Nov 2000 to Mar 2004, 46 of them were treated with radiotherapy alone, 41 by concurrent chemoradiation, and 19 by sequential chemoradiation. The influence of related prognostic factors on survival was evaluated by univariate and multivariate analysis. The treatment outcome was analyzed by prognostic index model. Results: The 1-, 3- and 5- year overall survival rate was 50.0%, 22.2% and 15.5%, respectively, and the median survival time was 12 months. The univariate analysis showed that the following factors were significantly associated with the longer survival: female, good kamofsky performance status (KPS), squamous cell carcinoma, absence of supraclavicular lymph nodes, no smoking history, hemoglobin ≥130 g/L before treatment, N stage, the maximum diameter of tumor ≤5 cm, the volume of tumor ≤90 cm3, GTV ≤150 cm3 and the radiotherapy efficacy. However, multivariate analysis revealed that no smoking history, hemoglobin ≥130 g/L and GTV ≤150 cm3 were the independent risk factors for predicting the survival. Conclusions: Three dimensional conformal radiation therapy could be effective in the treatment of locally advanced NSCLC. No smoking history, hemoglobin ≥130 g/L and GTV ≤150 cm3 might be the independent risk factors for predicting the survival. Prognostic index model could improve the potential of multivariate analysis in predicting the survival of patients treated with radiotherapy for NSCLC. (authors)

  9. Measurement of tumor volume by PET to evaluate prognosis in patients with advanced non-small cell lung cancer treated by non-surgical therapy

    International Nuclear Information System (INIS)

    Background: Patients with advanced non-small cell lung cancer (NSCLC) seem to have disparity in prognosis. Accurate prediction of prognosis could be useful in the future to predict individual risk and to develop more aggressive or alternative treatment strategies. Purpose: To evaluate the prognostic value of metabolic tumor volume (MTV) measured by 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) in patients with NSCLC. Material and Methods: We retrospectively reviewed 120 patients with pathologically proven NSCLC (61 squamous cell carcinomas and 59 adenocarcinomas) who underwent pretreatment 18F-FDG PET. MTV and maximum standardized uptake value (SUVmax) for the primary tumors were measured by 18F-FDG PET. Pretreatment variables (age, sex, American Joint Committee on Cancer [AJCC] stage, histological type, SUVmax, and MTV) were analyzed to identify their correlation with two-year survival. To further evaluate and compare the predictive value of PET parameters, MTV, and SUVmax, time-dependent receiver-operating characteristic curve (ROC) analysis was used. Results: In the univariate analysis, AJCC stage, histological type, MTV, and SUVmax of primary tumor were significant predictors of survival. On multivariate analysis, independent prognostic factors associated with decreased two-year survival were AJCC stage (hazard ratio [HR] 2.236, P 0.003), histological type (HR 2.038, P = 0. 004), and MTV (HR 1.016, P 0.001). SUVmax was not a significant factor (HR 0.96, P = 0.490). On time-dependent ROC analysis, MTV showed good predictive performance for two-year survival consistently better than SUVmax. Conclusion: MTV, a volumetric parameter of 18F-FDG PET, is an important independent prognostic factor for survival and a better predictor of survival than SUVmax for the primary tumor in patients with advanced NSCLC

  10. A Meta-analysis of Platinum Plus Taxanes Regimen on Treating Advanced Non-small Cell Lung Cancer

    OpenAIRE

    Zhu, Ning; He, Jian; Zhang, Siwei; Chen, Xiaodong

    2009-01-01

    Background and objective The platinum-based plus a third-generation agent doublet chemotherapy regimen has been recommended as the standard first-line chemotherapy for advanced NSCLC by ASCO and NCCN. This study was aimed to evaluate the clinical efficacy and side effects of the Platinum plus Taxanes or other novel agent. Methods The databases PubMed, CENTRAL, EMBASE and Chinese Biomedical Literature database were retrieved by using the key words “non small cell lung cancer” or “Carcinoma, No...

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

    International Nuclear Information System (INIS)

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

  12. Imaging of hypoxia with 18F-FAZA PET in patients with locally advanced non-small cell lung cancer treated with definitive chemoradiotherapy

    International Nuclear Information System (INIS)

    For many cancers, tumour hypoxia is an adverse prognostic factor, and increases chemoradiation resistance; its importance in non-small cell lung cancer (NSCLC) is unproven. This study evaluated tumoural hypoxia using fluoroazomycin arabinoside (18F-FAZA) positron emission tomography (PET) scans among patients with locoregionally advanced NSCLC treated with definitive chemoradiation. Patients with stage IIIA-IIIB NSCLC underwent 18F-FAZA PET scans and 18F-2-deoxyglucose (FDG)-PET scans within 4 weeks of commencing and 8 weeks following conventionally-fractionated concurrent platinum-based chemoradiation (60Gy). Intra-lesional hypoxic volumes of the primary and nodal masses were compared with FDG-PET metabolic volumes. Baseline tumoural hypoxia was correlated with disease free survival (DFS). Seventeen patients underwent pre-treatment 18F-FAZA PET and FDG-PET scans. Intra-lesional hypoxia was identified on 11 scans (65%). Baseline lesional hypoxic volumes were consistently smaller than FDG-PET volumes (P=0.012). There was no statistical difference between the mean FDG-PET volumes in patients with or without baseline hypoxia (P=0.38). Eight patients with baseline hypoxia had post treatment 18F-FAZA scans and 6 of these (75%) had resolution of imageable hypoxia following chemoradiation. The DFS was not significantly different between the hypoxic or non-hypoxic groups (median 0.8 years and 1.3 years respectively, P=0.42). Intra-lesional hypoxia, as detected by 18F-FAZA PET, was present in 65% of patients with locally-advanced NSCLC and resolved in the majority of patients following chemoradiation. Larger studies are required to evaluate the prognostic significance of the presence and resolution of hypoxia assessed by PET in NSCLC.

  13. Phase i study of 'dose-dense' pemetrexed plus carboplatin/radiotherapy for locally advanced non-small cell lung carcinoma

    International Nuclear Information System (INIS)

    This phase I study investigates the feasibility of carboplatin plus dose-dense (q2-week) pemetrexed given concurrently with radiotherapy (XRT) for locally advanced and oligometastatic non-small cell lung cancer (NSCLC). Eligible patients had Stage III or IV (oligometastatic) NSCLC. Patients received XRT to 63 Gy in standard fractionation. Patients received concurrent carboplatin (AUC = 6) during weeks 1 and 5 of XRT, and pemetrexed during weeks 1, 3, 5, and 7 of XRT. The starting dose level (level 1) of pemetrexed was 300 mg/m2. Following the finding of dose limiting toxicity (DLT) in dose level 1, an amended dose level (level 1A) continued pemetrexed at 300 mg/m2, but with involved field radiation instead of extended nodal irradiation. Consolidation consisted of carboplatin (AUC = 6) and pemetrexed (500 mg/m2) q3 weeks × 2 -3 cycles. Eighteen patients were enrolled. Fourteen patients are evaluable for toxicity analysis. Of the initial 6 patients treated on dose level 1, two experienced DLTs (one grade 4 sepsis, one prolonged grade 3 esophagitis). There was one DLT (grade 5 pneumonitis) in the 8 patients treated on dose level 1A. In 16 patients evaluable for response (4 with oligometastatic stage IV disease and 12 with stage III disease), the median follow-up time is 17.8 months. Thirteen of 16 patients had in field local regional response. The actuarial median survival time was 28.6 months in all patients and 34.7 months (estimated) in stage III patients. Concurrent carboplatin with dose-dense (q2week) pemetrexed at 300 mg/m2 with involved field XRT is feasible and encouraging in patients with locally advanced and oligometastatic NSCLC.

  14. Trial-Based Cost-Utility Analysis of Icotinib versus Gefitinib as Second-Line Therapy for Advanced Non-Small Cell Lung Cancer in China.

    Directory of Open Access Journals (Sweden)

    Chunxiang Zhang

    Full Text Available Our objective is to compare the cost-utility of icotinib and gefitinib for the second-line treatment of advanced non-small cell lung cancer (NSCLC from the perspective of the Chinese healthcare system.Model technology was applied to assess the data of randomized clinical trials and the direct medical costs from the perspective of the Chinese healthcare system. Five-year quality-adjusted life years (QALYs and incremental cost-utility ratios (ICURs were calculated. One-way and probabilistic sensitivity analyses (PSA were performed.Our model suggested that the median progression-free survival (PFS was 4.2 months in the icotinib group and 3.5 months in the gefitinib group while they were 4.6 months and 3.4 months, respectively, in the trials. The 5-year QALYs was 0.279 in the icotinib group and 0.269 in the gefitinib group, and the according medical costs were $10662.82 and $13127.57. The ICUR/QALY of icotinib versus gefitinib presented negative in this study. The most sensitive parameter to the ICUR was utility of PFS, ranging from $-1,259,991.25 to $-182,296.61; accordingly the icotinib treatment consistently represented a dominant cost-utility strategy.The icotinib strategy, as a second-line therapy for advanced NSCLC patients in China, is the preferred strategy relative to gefitinib because of the dominant cost-utility. In addition, icotinib shows a good curative effect and safety, resulting in a strong demand for the Chinese market.

  15. Gemcitabine concurrent with thoracic radiotherapy after induction chemotherapy with gemcitabine/vinorelbine in locally advanced non-small cell lung cancer. A phase I study

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    Gagel, B.; Piroth, M.; Pinkawa, M.; Fischedik, K.; Asadpour, B.; Schmachtenberg, A.; Eble, M.J. [Dept. of Radiotherapy, RWTH Aachen (Germany); Reinartz, P.; Zimny, M.; Buell, U. [Dept. of Nuclear Medicine, RWTH Aachen (Germany); Stanzel, S. [Inst. for Medical Statistics, RWTH Aachen (Germany); Breuer, C.; Skobel, E. [Dept. of Internal Medicine I, RWTH Aachen (Germany)

    2006-05-15

    Purpose: to determine the maximum tolerated dose (MTD) of gemcitabine every 2 weeks to a concurrent radiotherapy administered during an aggressive program of sequential and simultaneous radio-/chemotherapy for locally advanced, unresectable non-small cell lung cancer (NSCLC). Patients and methods: ten patients with histologically confirmed NSCLC were observed and treated in accordance with a combined radio-/chemotherapy protocol. This included two cycles of induction chemotherapy with gemcitabine (1,200 mg/m{sup 2}) and vinorelbine (30 mg/m{sup 2}) at days 1, 8 and 22, 29, followed by concurrent radiotherapy including [{sup 18}F] fluorodeoxyglucose positron emission tomography-(FDG-PET-) based target volume definition (2.0 Gy/d; total dose 66.0 Gy) and chemotherapy with gemcitabine every 2 weeks at days 43, 57, and 71. The initial dose was 300 mg/m{sup 2}. The dose of gemcitabine was increased by 100 mg/m{sup 2} until the MTD was realized. Three patients were enrolled for each dose level. Results: dose-limiting toxicity (DLT) was identified for the patient group receiving gemcitabine 500 mg/m{sup 2}, due to grade 2 esophagitis (next to grade 3) in all patients. 6 weeks after the completion of radio-/chemotherapy, most patients still presented treatment-induced esophagitis. In accordance with expected complications, such as esophagitis, dysphagia and odynophagia, the MTD was defined at this dose level, although no DLT grade 3 was reached. Conclusion: after induction chemotherapy, the MTD and frequency of gemcitabine in locally advanced NSCLC is 500 mg/m{sup 2} every 2 weeks during a maximum of 7 weeks of thoracic radiotherapy. (orig.)

  16. Efficacy and safety of extended use of platinum-based doublet chemotherapy plus endostatin in patients with advanced nonsmall cell lung cancer

    Science.gov (United States)

    Hu, Weiheng; Fang, Jian; Nie, Jun; Dai, Ling; Zhang, Jie; Chen, Xiaoling; Ma, Xiangjuan; Tian, Guangming; Wu, Di; Han, Sen; Han, Jindi; Wang, Yang; Long, Jieran

    2016-01-01

    Abstract The aim of this study was to investigate the efficacy and safety of the extended use of platinum-based doublet chemotherapy (PT-DC) plus endostatin in patients with advanced nonsmall cell lung cancer (NSCLC). We performed a retrospective analysis of 200 newly diagnosed advanced NSCLC patients who had received at least 1 cycle of endostatin plus PT-DC between September 2009 and November 2014. Of these patients, 155 received 4 or more cycles of therapy (the extended therapy group), while 45 received less than 4 cycles of therapy (the control group). Clinical tumor responses, progression-free survival (PFS), overall survival (OS), and toxicity profiles were recorded and retrospectively analyzed. In the extended therapy group, 67 patients (43.2%) achieved a best overall response rate of partial response (PR), while in the control group, 13 patients (28.9%) had a best overall response rate of PR. After a median follow-up of 15.9 months, the median PFS and OS were 8.0 and 23.1 months in the extended arm and 5.8 and 14.0 months in the control arm, respectively. There were statistically significant differences in median PFS and OS between these 2 arms. Hematologic and gastrointestinal toxicities occurred more frequently in the extended therapy group, but no statistically significant difference was detected in grade 3 to 4 toxicities overall between these 2 groups. In conclusion, extended treatment using endostatin combined with PT-DC can provide additional survival benefits and satisfactory toxicity profiles in previously untreated patients with NSCLC, which merits further evaluation in a larger prospective study. PMID:27428214

  17. Phase Ⅰ/Ⅱ study of gemcitabine and oxaliplatin chemotherapy in combination with concurrent 3-D conformal radiotherapy for locally advanced non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    XU Feng; WANG Jin; SHEN Yali; ZHANG Hong; ZHOU Qinghua

    2006-01-01

    Background and objective Recent studies have showed that combination of chemotherapy and radiotherapy might result in better outcome for locally advanced non-small cell lung cancer (NSCLC). The aim of this study is to determine the maximal tolerance dose (MTD) and efficacy of full-dose gemcitabine and oxaliplatin when given concurrently with 3-dimentional radiation therapy (3D-RT) for locally advanced NSCLC. Methods Oxaliplatin was administered at a fixed dose of 130 mg/m2, and gemcitabine was administered at a starting dose of 800 mg/m2 with an incremental dose gradient of 200 mg/m2 for 3 dose levels. MTD was defined as the immediate dose level lower than the dose at which dose-limiting toxicity (DLT) occurred in more than one-third of the patients. The chemotherapy was administered at 3-week cycle. The RT was given as 3-D conformal manner at a single daily dose of 2 Gy for 5 days per week. Results Twenty-two patients were evaluable and distributed to three different dose levels: 6 at level 1, 8 at level 2 and 8 at level 3. Pulmonary toxicity, esophageal and hematologic toxicity were the main DLT. Grade Ⅲ acute pulmonary toxicity occurred in one patient each at level 2 and level 3, both with V20>20%, and grade Ⅲ esophagitis in two patients at level 3. The MTD of gemcitabine in this study was 1000 mg/m2. The overall response rate was 75.0% (9/12). The 1- and 2-year survival rate was 70.0% and 30.5% respectively. The median time to progression was 8.7 months (range 5--11.8 months). Conclusion With reduced radiation volume, gemcitabine of 1000 mg/m2 in combination with oxaliplatin of 130 mg/m2 was effective and could be safely administered for NSCLC.

  18. Prognostic parameters for acute esophagus toxicity in Intensity Modulated Radiotherapy and concurrent chemotherapy for locally advanced non-small cell lung cancer

    International Nuclear Information System (INIS)

    Background and purpose: The aim of this study was to correlate clinical and dosimetric variables with acute esophageal toxicity (AET) following Intensity Modulated Radiotherapy (IMRT) with concurrent chemotherapy for locally advanced non-small cell lung cancer (NSCLC). In addition, timeline of AET was reported. Material and methods: 153 patients with locally advanced NSCLC treated with 66 Gy/2.75 Gy/24 fractions of radiotherapy and concurrent daily low dose cisplatin were selected. Medical records and treatments of these patients were retrospectively reviewed. Maximum AET grade ⩾2 and maximum grade 3 were the endpoints of this study. Dates for onset, maximum and recovery (to baseline) of AET were reported. Univariate and multivariate analysis were applied to correlate clinical, tumor, dosimetric and chemotherapy dose variables to AET grade ⩾2 and grade 3. Results: AET grade 2 occurred in 37% and grade 3 in 20% of the patients. The median onset of AET was around day 15 for all grades. The median onset of the maximum grade was day 30 for both grades 2 and 3. The median duration was 43 days for grade 1, 50 days for grade 2 and >80 days for grade 3. Of the grade 3 AET patients, 48% recovered within 3 months. Esophagus V50, ethnic background, and the number of cisplatin administrations were significantly correlated with grade 3 AET. Conclusions: For NSCLC patients treated with concurrent chemotherapy and IMRT A higher number of cisplatin administrations, non-Caucasian background and higher V50oes were associated with grade 3 AET. The median onset of AET grade 3 is 15 days after the start of treatment, maximized at day 30, with a median duration of >80 days

  19. Trial-Based Cost-Utility Analysis of Icotinib versus Gefitinib as Second-Line Therapy for Advanced Non-Small Cell Lung Cancer in China

    Science.gov (United States)

    Zhang, Chunxiang; Zhang, Hongmei; Shi, Jinning; Wang, Dong; Zhang, Xiuwei; Yang, Jian; Zhai, Qizhi; Ma, Aixia

    2016-01-01

    Background Our objective is to compare the cost-utility of icotinib and gefitinib for the second-line treatment of advanced non-small cell lung cancer (NSCLC) from the perspective of the Chinese healthcare system. Methods Model technology was applied to assess the data of randomized clinical trials and the direct medical costs from the perspective of the Chinese healthcare system. Five-year quality-adjusted life years (QALYs) and incremental cost-utility ratios (ICURs) were calculated. One-way and probabilistic sensitivity analyses (PSA) were performed. Results Our model suggested that the median progression-free survival (PFS) was 4.2 months in the icotinib group and 3.5 months in the gefitinib group while they were 4.6 months and 3.4 months, respectively, in the trials. The 5-year QALYs was 0.279 in the icotinib group and 0.269 in the gefitinib group, and the according medical costs were $10662.82 and $13127.57. The ICUR/QALY of icotinib versus gefitinib presented negative in this study. The most sensitive parameter to the ICUR was utility of PFS, ranging from $-1,259,991.25 to $-182,296.61; accordingly the icotinib treatment consistently represented a dominant cost-utility strategy. Conclusions The icotinib strategy, as a second-line therapy for advanced NSCLC patients in China, is the preferred strategy relative to gefitinib because of the dominant cost-utility. In addition, icotinib shows a good curative effect and safety, resulting in a strong demand for the Chinese market. PMID:27015267

  20. Effect of Brucea Javanica Oil Emulsion Combined with GP Regimen on the Immune Function of Patients with Advanced Non-Small Cell Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    Zhang Yu; Yu Like; Xia Ning

    2014-01-01

    Objective:To observe the effect of Brucea javanica oil emulsion combined with chemotherapy on the immune function of patients with advanced non-small cell lung cancer (NSCLC). Methods:One hundred and fifty-six patients with NSCLC were randomly divided into treatment group (n=82) treated with Brucea javanica oil emulsion combined with GP regimen chemotherapy and control group (n=74) only with GP regimen chemotherapy. The cellular immunity (CD3+, CD4+, CD8+, CD16+CD56+) and humoral immunity (IgG, IgA, IgM, C3, C4) before and after chemotherapy were tested by lfow cytometry (FCM) and biochemical method, respectively. The inlfuences of two treatment methods on the immune function were compared, and clinical efifcacy was evaluated. Results:The remission rates (RRs) were respectively 40.3% and 36.5% in treatment group and control group, without statistical difference (P>0.05). Compared with chemotherapy before, the cellular immune function after chemotherapy decreased in control group (P<0.05),whereas the levels of CD3+, CD4+, CD4+/CD8+ and CD16+CD56+increased signiifcantly in treatment group (P<0.05 orP<0.01). After chemotherapy, the cellular immune function in treatment group was obviously superior to that in control group, whereas there was no statistical signiifcance by comparison to humoral immune indexes between two groups. Conclusion:With similar efifcacy to control group, Brucea javanica oil emulsion combined with GP regimen chemotherapy can improve the cellular immune function of patients with advanced NSCLC and protect the chemotherapy-induced cellular immune function from damage to a certain extent.

  1. Gemcitabine concurrent with thoracic radiotherapy after induction chemotherapy with gemcitabine/vinorelbine in locally advanced non-small cell lung cancer. A phase I study

    International Nuclear Information System (INIS)

    Purpose: to determine the maximum tolerated dose (MTD) of gemcitabine every 2 weeks to a concurrent radiotherapy administered during an aggressive program of sequential and simultaneous radio-/chemotherapy for locally advanced, unresectable non-small cell lung cancer (NSCLC). Patients and methods: ten patients with histologically confirmed NSCLC were observed and treated in accordance with a combined radio-/chemotherapy protocol. This included two cycles of induction chemotherapy with gemcitabine (1,200 mg/m2) and vinorelbine (30 mg/m2) at days 1, 8 and 22, 29, followed by concurrent radiotherapy including [18F] fluorodeoxyglucose positron emission tomography-(FDG-PET-) based target volume definition (2.0 Gy/d; total dose 66.0 Gy) and chemotherapy with gemcitabine every 2 weeks at days 43, 57, and 71. The initial dose was 300 mg/m2. The dose of gemcitabine was increased by 100 mg/m2 until the MTD was realized. Three patients were enrolled for each dose level. Results: dose-limiting toxicity (DLT) was identified for the patient group receiving gemcitabine 500 mg/m2, due to grade 2 esophagitis (next to grade 3) in all patients. 6 weeks after the completion of radio-/chemotherapy, most patients still presented treatment-induced esophagitis. In accordance with expected complications, such as esophagitis, dysphagia and odynophagia, the MTD was defined at this dose level, although no DLT grade 3 was reached. Conclusion: after induction chemotherapy, the MTD and frequency of gemcitabine in locally advanced NSCLC is 500 mg/m2 every 2 weeks during a maximum of 7 weeks of thoracic radiotherapy. (orig.)

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

    OpenAIRE

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

    2012-01-01

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

  3. A Meta-analysis of Platinum Plus Taxanes Regimen on Treating Advanced Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Ning ZHU

    2009-08-01

    Full Text Available Background and objective The platinum-based plus a third-generation agent doublet chemotherapy regimen has been recommended as the standard first-line chemotherapy for advanced NSCLC by ASCO and NCCN. This study was aimed to evaluate the clinical efficacy and side effects of the Platinum plus Taxanes or other novel agent. Methods The databases PubMed, CENTRAL, EMBASE and Chinese Biomedical Literature database were retrieved by using the key words “non small cell lung cancer” or “Carcinoma, Non Small Cell Lung” so as to search the studies about the randomized controlled clinical trials, which compared Platinum plus Taxanes with Platinum plus other novel agents. A meta-analysis was conducted and the quality scores were evaluated according to the improved Jadad’s score. Results Nine randomized controlled clinical trials with 4 703 patients were included. The overall response rate and 1 year survival rate of the two groups were not significantly different (RR=1.00, 95%CI: 0.91-1.11, P=0.95; RR=0.98, 95%CI: 0.84-1.15, P=0.83. The incidence rate of grade 3-4 leukopenia, neutropenia, anemia, nausea and vomiting in TP is much lower than that in platinum plus other novel agent. Sub-group analysis showed that the overall response rate and 1 year survival rate of TP aren’t statistically different from NP or GP. The incidence rate of grade 3-4 leukopenia, neutropenia and anemia in TP is statistically lower than that in NP. The incidence rate of grade 3-4 anemia and thrombocytopenia in TP is statistically lower than that in GP. Conclusion The clinical efficacy of TP and platinum plus other novel agent is quite similar, but quite different from each other in side effects, which provides important evidence on selecting individual chemotherapy regimen.

  4. Non-small cell lung cancer: current status of chemoradiation for locally advanced disease and an update on susceptibility and prevention

    International Nuclear Information System (INIS)

    Locally advanced, inoperable non-small cell lung cancer (NSCLC) afflicts 40,000 patients yearly. The traditional treatment has been radiation therapy (RT) alone with 5 year survival rates averaging around 5%. Recent reports of randomized clinical trials using combined radiochemotherapy suggest significant improvement in survival compared to RT alone. These trials are difficult to evaluate because of differences in dose, timing and sequencing of both the chemotherapy (CT) and the RT. Dr. Byhardt will give an overview of the significant chemoradiation trials, especially with respect to the factors associated with reduction of local failure and distant metastasis. Dr. Tishler will review the biologic rationale of these regimens and make some prognostications about the potential role of new chemotherapy agents, new developments in RT dose-time-fractionation, and new RT technology in future radiochemotherapy trials. While progress continues to be made using the more traditional cancer treatment modalities, investigations in NSCLC epidemiology and prevention are providing new insights regarding susceptibility, etiology, failure risk stratification, and potential avenues of therapeutic intervention. Dr. Spitz will discuss NSCLC as a paradigm of an environmentally induced disease in which host susceptibility may be determined by genetically determined modulation of environmental exposures. A mutagen sensitivity assay can determine individuals at high risk for developing NSCLC if exposed to carcinogens such as those in cigarette smoke. This susceptibility may have prognostic implications that could influence choice of therapy. Highly susceptible individuals can also be selected for special counseling, smoking cessation, with consideration given to chemoprevention. Dr. Gritz will review major work done in this area

  5. Superiority of conventional intensity-modulated radiotherapy over helical tomotherapy in locally advanced non-small cell lung cancer. A comparative plan analysis

    Energy Technology Data Exchange (ETDEWEB)

    Song, C. [National Cancer Center, Research Institute and Hospital, Goyang (Korea, Republic of). Proton Therapy Center; Seoul National Univ. College of Medicine (Korea, Republic of). Dept. of Radiation Oncology; Pyo, H.; Kim, J. [Sungkyunkwan Univ. School of Medicine, Samsung Medical Center, Seoul (Korea, Republic of). Dept. of Radiation Oncology; Lim, Y.K.; Kim, D.W.; Cho, K.H. [National Cancer Center, Research Institute and Hospital, Goyang (Korea, Republic of). Proton Therapy Center; Kim, W.C. [Inha Univ. School of Medicine, Incheon (Korea, Republic of). Dept. of Radiation Oncology; Kim, H.J. [Seoul National Univ. College of Medicine (Korea, Republic of). Dept. of Radiation Oncology

    2012-10-15

    Purpose: To compare helical tomotherapy (HT) and conventional intensity-modulated radiotherapy (IMRT) using a variety of dosimetric and radiobiologic indexes in patients with locally advanced non-small cell lung cancer (LA-NSCLC). Patients and methods: A total of 20 patients with LA-NSCLC were enrolled. IMRT plans with 4-6 coplanar beams and HT plans were generated for each patient. Dose distributions and dosimetric indexes for the tumors and critical structures were computed for both plans and compared. Results: Both modalities created highly conformal plans. They did not differ in the volumes of lung exposed to > 20 Gy of radiation. The average mean lung dose, volume receiving {>=} 30 Gy, and volume receiving {>=} 10 Gy in HT planning were 18.3 Gy, 18.5%, and 57.1%, respectively, compared to 19.4 Gy, 25.4%, and 48.9%, respectively, with IMRT (p = 0.004, p < 0.001, and p < 0.001). The differences between HT and IMRT in lung volume receiving {>=} 10-20 Gy increased significantly as the planning target volume (PTV) increased. For 6 patients who had PTV greater than 700 cm{sup 3}, IMRT was superior to HT for 5 patients in terms of lung volume receiving {>=} 5-20 Gy. The integral dose to the entire thorax in HT plans was significantly higher than in IMRT plans. Conclusion: HT gave significantly better control of mean lung dose and volume receiving {>=} 30-40 Gy, whereas IMRT provided better control of the lung volume receiving {>=} 5-15 Gy and the integral dose to entire thorax. In most patients with PTV greater than 700 cm{sup 3}, IMRT was superior to HT in terms of lung volume receiving {>=} 5-20 Gy. It is therefore advised that caution should be exercised when planning LA-NSCLC using HT. (orig.)

  6. Treatment-Related Death during Concurrent Chemoradiotherapy for Locally Advanced Non-Small Cell Lung Cancer: A Meta-Analysis of Randomized Studies

    Science.gov (United States)

    Zhao, Jing; Xia, Yingfeng; Kaminski, Joseph; Hao, Zhonglin; Mott, Frank; Campbell, Jeff; Sadek, Ramses; Kong, Feng-Ming (Spring)

    2016-01-01

    Treatment related death (TRD) is the worst adverse event in chemotherapy and radiotherapy for patients with cancer, the reports for TRDs were sporadically. We aimed to study TRDs in non-small cell lung cancer (NSCLC) patients treated with concurrent chemoradiotherapy (CCRT), and determine whether high radiation dose and newer chemotherapy regimens were associated with the risk of TRD. Data from randomized clinical trials for locally advanced/unresectable NSCLC patients were analyzed. Eligible studies had to have at least one arm with CCRT. The primary endpoint was TRD. Pooled odds ratios (ORs) for TRDs were calculated. In this study, a total of fifty-three trials (8940 patients) were eligible. The pooled TRD rate (accounting for heterogeneity) was 1.44% for all patients. In 20 trials in which comparison of TRDs between CCRT and non-CCRT was possible, the OR (95% CI) of TRDs was 1.08 (0.70–1.66) (P = 0.71). Patients treated with third-generation chemotherapy and concurrent radiotherapy had an increase of TRDs compared to those with other regimens in CCRT (2.70% vs. 1.37%, OR = 1.50, 95% CI: 1.09–2.07, P = 0.008). No significant difference was found in TRDs between high (≥ 66 Gy) and low (< 66 Gy) radiation dose during CCRT (P = 0.605). Neither consolidation (P = 0.476) nor induction chemotherapy (P = 0.175) had significant effects with increased TRDs in this study. We concluded that CCRT is not significantly associated with the risk of TRD compared to non-CCRT. The third-generation chemotherapy regimens may be a risk factor with higher TRDs in CCRT, while high dose radiation is not significantly associated with more TRDs. This observation deserves further study. PMID:27300551

  7. Predictors of grade {>=}2 and grade {>=}3 radiation pneumonitis in patients with locally advanced non-small cell lung cancer treated with three-dimensional conformal radiotherapy

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    Dang, Jun; Li, Guang; Ma, Lianghua; Han, Chong; Zhang, Shuo; Yao, Lei [Dept. of Radiation Oncology, The First Hospital of China Medical Univ., Shenyang (China)], e-mail: gl1963516@yahoo.cn; Diao, Rao [Dept. of Experimental Technology Center, China Medical Univ., Shenyang (China); Zang, Shuang [Dept. of Nursing, China Medical Univ., Shenyang (China)

    2013-08-15

    Grade {>=}3 radiation pneumonitis (RP) is generally severe and life-threatening. Predictors of grade {>=}2 are usually used for grade {>=}3 RP prediction, but it is unclear whether these predictors are appropriate. In this study, predictors of grade {>=}2 and grade {>=}3 RP were investigated separately. The increased risk of severe RP in elderly patients compared with younger patients was also evaluated. Material and methods: A total of 176 consecutive patients with locally advanced non-small cell lung cancer were followed up prospectively after three-dimensional conformal radiotherapy. RP was graded according to Common Terminology Criteria for Adverse Events version 3.0. Results: Mean lung dose (MLD), mean heart dose, ratio of planning target volume to total lung volume (PTV/Lung), and dose-volume histogram comprehensive value of both heart and lung were associated with both grade {>=}2 and grade {>=}3 RP in univariate analysis. In multivariate logistic regression analysis, age and MLD were predictors of both grade {>=}2 RP and grade {>=}3 RP; receipt of chemotherapy predicted grade {>=}3 RP only; and sex and PTV/Lung predicted grade {>=}2 RP only. Among patients who developed high-grade RP, MLD and PTV/Lung were significantly lower in patients aged {>=}70 years than in younger patients (p<0.05 for both comparisons). Conclusions: The predictors were not completely consistent between grade {>=}2 RP and grade {>=}3 RP. Elderly patients had a higher risk of severe RP than younger patients did, possibly due to lower tolerance of radiation to the lung.

  8. Combination chemotherapy with intermittent erlotinib and pemetrexed for pretreated patients with advanced non-small cell lung cancer: a phase I dose-finding study

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    Minami Seigo

    2012-07-01

    Full Text Available Abstract Background Erlotinib and pemetrexed have been approved for the second-line treatment of non-small cell lung cancer (NSCLC. These two agents have different mechanisms of action. Combined treatment with erlotinib and pemetrexed could potentially augment the antitumor activity of either agent alone. In the present study, we investigated the safety profile of combined administration of the two agents in pretreated NSCLC patients. Methods A phase I dose-finding study (Trial registration: UMIN000002900 was performed in patients with stage III/IV nonsquamous NSCLC whose disease had progressed on or after receiving first-line chemotherapy. Patients received 500 mg/m2 of pemetrexed intravenously every 21 days and erlotinib (100 mg at Level 1 and 150 mg at Level 2 orally on days 2–16. Results Twelve patients, nine males and three females, were recruited. Patient characteristics included a median age of 66 years (range, 48–78 years, stage IV disease (nine cases, adenocarcinoma (seven cases and activating mutation-positives in the epidermal growth factor receptor gene (two cases. Treatment was well-tolerated, and the recommended dose of erlotinib was fixed at 150 mg. Dose-limiting toxicities were experienced in three patients and included: grade 3 elevation of serum alanine aminotransferase, repetitive grade 4 neutropenia that required reduction of the second dose of pemetrexed and grade 3 diarrhea. No patient experienced drug-induced interstitial lung disease. Three patients achieved a partial response and stable disease was maintained in five patients. Conclusions Combination chemotherapy of intermittent erlotinib with pemetrexed was well-tolerated, with promising efficacy against pretreated advanced nonsquamous NSCLC.

  9. Combination chemotherapy with intermittent erlotinib and pemetrexed for pretreated patients with advanced non-small cell lung cancer: a phase I dose-finding study

    International Nuclear Information System (INIS)

    Erlotinib and pemetrexed have been approved for the second-line treatment of non-small cell lung cancer (NSCLC). These two agents have different mechanisms of action. Combined treatment with erlotinib and pemetrexed could potentially augment the antitumor activity of either agent alone. In the present study, we investigated the safety profile of combined administration of the two agents in pretreated NSCLC patients. A phase I dose-finding study (Trial registration: UMIN000002900) was performed in patients with stage III/IV nonsquamous NSCLC whose disease had progressed on or after receiving first-line chemotherapy. Patients received 500 mg/m2 of pemetrexed intravenously every 21 days and erlotinib (100 mg at Level 1 and 150 mg at Level 2) orally on days 2–16. Twelve patients, nine males and three females, were recruited. Patient characteristics included a median age of 66 years (range, 48–78 years), stage IV disease (nine cases), adenocarcinoma (seven cases) and activating mutation-positives in the epidermal growth factor receptor gene (two cases). Treatment was well-tolerated, and the recommended dose of erlotinib was fixed at 150 mg. Dose-limiting toxicities were experienced in three patients and included: grade 3 elevation of serum alanine aminotransferase, repetitive grade 4 neutropenia that required reduction of the second dose of pemetrexed and grade 3 diarrhea. No patient experienced drug-induced interstitial lung disease. Three patients achieved a partial response and stable disease was maintained in five patients. Combination chemotherapy of intermittent erlotinib with pemetrexed was well-tolerated, with promising efficacy against pretreated advanced nonsquamous NSCLC

  10. Risk factors for radiation induced lung toxicity in locally advanced non-small cell lung cancer treated with three-dimensional radiotherapy

    International Nuclear Information System (INIS)

    Objective: To investigate the patient and treatment related predictors for the development of radiation induced lung toxicity (RILT) in patients with locally advanced non-small cell lung cancer (NSCLC) receiving definitive three-dimensional radiotherapy. Methods: Data were retrospectively collected from inoperable or unresectable 253 patients with stage III NSCLC treated with definitive three-dimensional radiotherapy between January 2001 and April 2007. National cancer institute common toxicity criteria version 3.0 was employed to evaluate the classification of RILT and grade ≥2 toxicity served as the endpoint. The correlation between RILT and aforementioned factors was analyzed. Results: The grade ≥ 2 RILT was 26.5%. Univariate analysis showed age, FEV1%, DLCO%, contralateral lung (CL) V5 -V15, ipsilateral lung (IL) V5 -V40, total lung (TL) V5 -V50, IL and TL mean lung dose (MLD) were significantly correlated with the development of RILT (χ2 =4.46 - 23.99, P = 0.000 - 0.035). Multivariate analysis showed TL MLD >17.5 Gy and FEV1% ≥72% were significantly correlated with the development of RILT (χ2 = 17.49, 9.30, P = 0.000, 0.002). Patients were stratified into four groups according to MLD and FEV1%, corresponding to the RILT incidence of 9.3%, 24.7%, 38.5% and 63.6%, respectively (χ2 =25.27, P = 0.000). Conclusions: TL MLD and baseline FEV1% are significant factors correlated with the development of RILT in NSCLC patients treated with three-dimensional radiation therapy. The combination of TL MLD and FEV1% may help classify NSCLC patients per risk of RILT and subsequently direct risk-adaptive radiation therapy. Poor baseline pulmonary function does not increase the risk of RILT and may even be associated with lower RILT probability, which has yet to be validated in larger patient cohorts. (authors)

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

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    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

  12. Surgery for nonsmall cell lung cancer

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    Loïc Lang-Lazdunski

    2013-09-01

    Full Text Available Surgery remains the best curative option in patients with early stage lung cancer (stage I and II. Developments in minimally invasive techniques now allow surgeons to perform lung resections on elderly patients, patients with poor pulmonary function or significant cardiopulmonary comorbidities. New techniques, such as stereotactic radiotherapy and ablative procedures, are being evaluated in early-stage lung cancer and may represent an alternative to surgery in patients unfit for lung resection. Perioperative mortality rates have dropped significantly at most institutions in the past two decades and complications are managed more efficiently. Progress in imaging and staging techniques have helped cut futile thoracotomy rates and offer patients the most adequate treatment options. Large randomised trials have helped clarify the role of neoadjuvant, induction and adjuvant chemotherapy, as well as radiotherapy. Surgery remains an essential step in the multimodality therapy of selected patients with advanced-stage lung cancer (stage III and IV. Interventional and endoscopic techniques have reduced the role of surgery in the diagnosis and staging of nonsmall cell lung cancer, but surgery remains an important tool in the palliation of advanced-stage lung cancer. Large national/international surgical databases have been developed and predictive risk-models for surgical mortality/morbidity published by learned surgical societies. Nonetheless, lung cancer overall survival rates remain deceptively low and it is hoped that early detection/screening, better understanding of tumour biology and development of biomarkers, and development of efficient targeted therapies will help improve the prognosis of lung cancer patients in the next decade.

  13. The efficacy of Chinese herbal medicine as an adjunctive therapy for advanced non-small cell lung cancer: a systematic review and meta-analysis.

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    Shi Guang Li

    Full Text Available Many published studies reflect the growing application of complementary and alternative medicine, particularly Chinese herbal medicine (CHM use in combination with conventional cancer therapy for advanced non-small cell lung cancer (NSCLC, but its efficacy remains largely unexplored. The purpose of this study is to evaluate the efficacy of CHM combined with conventional chemotherapy (CT in the treatment of advanced NSCLC. Publications in 11 electronic databases were extensively searched, and 24 trials were included for analysis. A sum of 2,109 patients was enrolled in these studies, at which 1,064 patients participated in CT combined CHM and 1,039 in CT (six patients dropped out and were not reported the group enrolled. Compared to using CT alone, CHM combined with CT significantly increase one-year survival rate (RR = 1.36, 95% CI = 1.15-1.60, p = 0.0003. Besides, the combined therapy significantly increased immediate tumor response (RR = 1.36, 95% CI = 1.19-1.56, p<1.0E-5 and improved Karnofsky performance score (KPS (RR = 2.90, 95% CI = 1.62-5.18, p = 0.0003. Combined therapy remarkably reduced the nausea and vomiting at toxicity grade of III-IV (RR = 0.24, 95% CI = 0.12-0.50, p = 0.0001 and prevented the decline of hemoglobin and platelet in patients under CT at toxicity grade of I-IV (RR = 0.64, 95% CI = 0.51-0.80, p<0.0001. Moreover, the herbs that are frequently used in NSCLC patients were identified. This systematic review suggests that CHM as an adjuvant therapy can reduce CT toxicity, prolong survival rate, enhance immediate tumor response, and improve KPS in advanced NSCLC patients. However, due to the lack of large-scale randomized clinical trials in the included studies, further larger scale trials are needed.

  14. Clinical benefit of gemcitabine plus cisplatin 3-week regimen for patients with advanced non-small cell lung cancer:a prospective observational study

    Institute of Scientific and Technical Information of China (English)

    王莉; 廖美琳; 李龙芸; 万欢英; 徐农; 刘基巍; 梁厚杰

    2004-01-01

    Background Platinum-based chemotherapy has been proved effective in patients with advanced non-small cell lung cancer (NSCLC). This study evaluated the effectiveness and safety of first-line chemotherapy with gemcitabine plus cisplatin (GEM-Cis) 3-week regimen in routine care of Chinese patients with advanced NSCLC.Methods Two hundred and twenty-one patients with NSCLC stage IIIb or IV were enrolled and 209 were eligible foreffectiveness and safety analysis. The median age was 58 (range 29 to 79) years. The percents of cases in stage Ⅳ and stage Ⅲb were 52.2% and 47.8%; of Karnofsky performance score (KPS) less than 80 and 80-100 were 37.3% and 62.7% and of adeno-cancer and non-adeno-cancer were 59.8% and 40.2%. The average number of completed chemotherapy cycles was three. Measures of effectiveness included clinical benefit, significant clinical response (SCR) and adverse effects of GEM-Cis in the treatment of NSCLC at stages Ⅲb/Ⅳ.Results KPS increased from 79±9 at baseline to 86±10 after chemotherapy (P<0.01). Lung cancer symptom scale (LCSS) score of pain, dyspnea and cough increased from 77±24, 74±22 and 63±19 to 92±15, 90±14 and 86±15, respectively (P<0.01). The clinical benefit rate was 85.2% [95% confidence interval (CI) 80.3%-90.0%]. The SCR was 89.5% (95% CI 85.3%-93.7%). Median survival time was 7.8 months (95% CI 7.1 months-9.1 months). Sixty-four patients (30.6%) experienced an adverse effect that was deemed clinically significant. Only one patient (0.5%) was hospitalized due to chemotherapy related adverse effects. Life-threatening toxicity was observed in two patients (1.0%).Conclusion First-line chemotherapy with GEM-Cis in the routine care of Chinese patients with advanced NSCLC is effective and safe.

  15. Comparing docetaxel with gemcitabine as second-line chemotherapy in patients with advanced non-small cell lung cancer: A single institute randomized phase II study

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    Khosravi A

    2015-01-01

    Full Text Available Background: Platinum-based doublet chemotherapy is the backbone of treatment in advanced non-small cell lung cancer (NSCLC however second-line treatment options are controversial particularly in patients with borderline performance status (PS of 2. The aim of this study was to compare efficacy and toxicity of weekly docetaxel versus gemcitabine in this clinical setting. Patients and methods: A total of 70 patients with advanced (stage IIIB, IV NSCLC entered this single institute study. Cases of this study had experienced disease progression after the first-line platinum-based doublet chemotherapy, with PS 0- 2 in “Eastern Cooperative Oncology Group” scale. They were randomly assigned by stratified blocks to receive docetaxel 35 mg/m2 (Arm A, n=34 or gemcitabine 1000 mg/m2 (Arm B, n=36 days 1, 8 and 15, every three weeks, for up to six cycles. Primary end point was progression free survival (PFS and secondary end points were objective response rate, disease control rate, median overall survival (OS and toxicity. Dose modification was permitted upon clinician’s discretion for each individual patient. Results: Median of PFS was 2.02 months in arm A and 2.63 months in arm B (HR= 1.279; 95% CI: 0.710-2.304, P= 0.551. Although median OS for arm A was numerically greater (9.2 months than arm B (8.3 months it was statistically non-significant (HR= 1.384; 95% CI: 0.632 to 2.809, P= 0.59. Objective response was higher in Arm B than that in Arm A (P= 0.20 but disease control rates were statistically different in both arms (P= 0.034. Statistically significant differences in term of leukopenia was seen in arm B (P= 0.013. Conclusion: This study, with limited number of cases, indicates that in advanced NSCLC, weekly docetaxel and gemcitabine are reasonable second-line treatment options with statistically similar effectiveness in terms of PFS and median OS with manageable toxicities in patients with PS 0-2.

  16. Translational Research on Epidermal Growth Factor Receptor Gene Mutations in Targeted Therapy for Patients with Advanced Non-Small Cell Lung Cancer

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    Xiao-yan WANG

    2015-12-01

    Full Text Available Abstract Objective: To explore the significance of epidermal growth factor receptor (EGFR gene mutations in targeted therapy for patients with advanced non-small cell lung cancer (NSCLC. Methods: One hundred and seventeen patients with advanced NSCLC admitted in Maternal and Child Health Care Center of Zibo City from Jan., 2011 to Jan., 2014 were performed with EGFR gene detection and then divided into 3 groups according to the detecting results. Patients in group A and group B were given oral gefitinib, 250 mg/d while patients in Group C with docetaxel, 75 mg/m2. Chemotherapy for 3 groups was discontinued until severe adverse reactions or disease progression occurred, or continuous treatment was considered to be unfavorable by the doctors, or patients asked for withdrawal from the study. The relationship between clinicopathological features and EGFR mutations were analyzed. The short-term and long-term efficacy and adverse drug reactions of 3 groups were observed. Results: Of the 31 cases with EGFR mutations, there were 16 cases (51.6% of mutations in exon 19, 14 (45.2% in exon 21 and 2 (6.45% in exon 18. No EGFR mutation was found in exon 20. EGFR mutations were associated with histological types of tumors and whether patients were smoking. The median follow-up time was 26 months and 62 patients were dead. None of CR was in 3 groups. The disease control rate (DCR in Group A was obviously higher than that in Group B ( χ 2 =9.382, P=0.002, which was also higher in Group C than that in Group B ( χ 2 =4.674, P=0.031. The 1-year survival rate in Group A was obviously higher than that in group B and group C ( P <0.05, or P<0.01 , which was prominently higher in Group C than that in Group B ( P <0.01 . The median progression-free survival (PFS and median overall survival (OS were the longest in Group A was and the shortest in Group B. The adverse reactions of two kinds of

  17. 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.

  18. Early Change in Metabolic Tumor Heterogeneity during Chemoradiotherapy and Its Prognostic Value for Patients with Locally Advanced Non-Small Cell Lung Cancer.

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    Xinzhe Dong

    Full Text Available To observe the early change of metabolic tumor heterogeneity during chemoradiotherapy and to determine its prognostic value for patients with locally advanced non-small cell lung cancer (NSCLC.From January 2007 to March 2010, 58 patients with NSCLC were included who were received 18F-fluorodeoxyglucose (18F-FDG PET/CT before and following 40 Gy radiotherapy with the concurrent cisplatin-based chemotherapy (CCRT. Primary tumor FDG uptake heterogeneity was determined using global and local scale textural features extracted from standardized uptake value (SUV histogram analysis (coefficient of variation [COV], skewness, kurtosis, area under the curve of the cumulative SUV histogram [AUC-CSH] and normalized gray-level co-occurrence matrix (contrast, dissimilarity, entropy, homogeneity. SUVmax and metabolic tumor volume (MTV were also evaluated. Correlations were analyzed between parameters on baseline or during treatments with tumor response, progression-free survival (PFS, and overall survival (OS.Compared with non-responders, responders showed significantly greater pre-treatment COV, contrast and MTV (AUC = 0.781, 0.804, 0.686, respectively. Receiver-operating-characteristic curve analysis showed that early change of tumor textural analysis serves as a response predictor with higher sensitivity (73.2%~92.1% and specificity (80.0%~83.6% than baseline parameters. Change in AUC-CSH and dissimilarity during CCRT could also predict response with optimal cut-off values (33.0% and 28.7%, respectively. The patients with greater changes in contrast and AUC-CSH had significantly higher 5-year OS (P = 0.008, P = 0.034 and PFS (P = 0.007, P = 0.039. In multivariate analysis, only change in contrast was found as the independent prognostic factor of PFS (HR 0.476, P = 0.021 and OS (HR 0.519, P = 0.015.The metabolic tumor heterogeneity change during CCRT characterized by global and local scale textural features may be valuable for predicting treatment response

  19. SU-E-T-572: Normal Lung Tissue Sparing in Radiation Therapy for Locally Advanced Non-Small Cell Lung Cancer

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    Hong, C; Ju, S; Ahn, Y [Samsung Medical Center, Seoul (Korea, Republic of)

    2015-06-15

    Purpose: To compare normal lung-sparing capabilities of three advanced radiation therapy techniques for locally advanced non-small cell lung cancer (LA-NSCLC). Methods: Four-dimensional computed tomography (4DCT) was performed in 10 patients with stage IIIb LA-NSCLC. The internal target volume (ITV); planning target volume (PTV); and organs at risks (OARs) such as spinal cord, total normal lung, heart, and esophagus were delineated for each CT data set. Intensity-modulated radiation therapy (IMRT), Tomohelical-IMRT (TH-IMRT), and TomoDirect-IMRT (TD-IMRT) plans were generated (total prescribed dose, 66 Gy in 33 fractions to the PTV) for each patient. To reduce the normal lung dose, complete and directional block function was applied outside the normal lung far from the target for both TH-IMRT and TD-IMRT, while pseudo- OAR was set in the same region for IMRT. Dosimetric characteristics of the three plans were compared in terms of target coverage, the sparing capability for the OAR, and the normal tissue complication probability (NTCP). Beam delivery efficiency was also compared. Results: TH-IMRT and TD-IMRT provided better target coverage than IMRT plans. Lung volume receiving ≥–30 Gy, mean dose, and NTCP were significant with TH-IMRT than with IMRT (p=0.006), and volume receiving ≥20–30 Gy was lower in TD-IMRT than in IMRT (p<0.05). Compared with IMRT, TH-IMRT had better sparing effect on the spinal cord (Dmax, NTCP) and heart (V45) (p<0.05). NTCP for the spinal cord, V45 and V60 for the heart, and Dmax for the esophagus were significantly lower in TD-IMRT than in IMRT. The monitor units per fraction were clearly smaller for IMRT than for TH-IMRT and TD-IMRT (p=0.006). Conclusion: In LA-NSCLC, TH-IMRT gave superior PTV coverage and OAR sparing compared to IMRT. TH-IMRT provided better control of the lung volume receiving ≥5–30 Gy. The delivery time and monitor units were lower in TD-IMRT than in TH-IMRT.

  20. Initial Progression-Free Survival after Non-First Line TKIs Therapy Potentially Guides Immediate Treatment after Its Failure in Advanced Non-Small Cell Lung Cancer

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    Fang Wang

    2012-03-01

    Full Text Available Objective: The standard therapy after failure of the initial non-first line epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI treatment in advanced non-small cell lung cancer (NSCLC has not yet been established. The aim of the current study was to identify whether the 2 TKI treatment or chemotherapy (paclitaxel-containing or non-paclitaxel regimen is the appropriate treatment for patients with NSCLC based on the efficacy of the initial TKIs. Methods: Seventy-two advanced NSCLC patients who had accepted 2nd TKIs or chemotherapy immediately after failure of the initial TKIs in non-first line setting from May 1, 2004 to January 31, 2010 at the Sun Yat-sen University Cancer Center were enrolled. The primary endpoint [2nd progression-free survival (PFS] and the second endpoint [overall survival (OS] were compared among the 2nd TKI and chemotherapy groups as well as their subgroups. Results: (1 Twenty-one patients were treated with 2nd TKIs, and 51 patients were administered chemotherapy after failure of the initial non-first line TKI treatment. There was nonsignificant difference in the responses (P=0.900 [2nd PFS (P=0.833 and OS (P=0.369] between the 2nd TKI and chemotherapy groups. (2 In the 2nd TKI group, 9 patients exhibited PFS≥7 months. The initial TKI treatment group exhibited a longer 2nd PFS than the other 12 patients with an initial PFS<7 months (7 months vs. 2 months, P=0.019. However, these groups had nonsignificantly different OS (P=0.369. (3 In the chemotherapy group, patients with PFS<5 months exhibited longer 2 PFS than those with PFS ≥ 5 months in the initial TKI treatment (3 months vs. 2 months, P=0.039. (4 In the chemotherapy group, patients treated with paclitaxel-containing regimen showed longer 2nd PFS than those treated with non-paclitaxel regimen (5 months vs. 2.3 months, P=0.043. Conclusions: Patients with PFS≥7 months or <5 months under the initial TKI treatment potentially benefit from the 2nd TKI

  1. A meta-analytic review of ERCC1/MDR1 polymorphism and chemosensitivity to platinum in patients with advanced non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    WEI Hai-bo; HU Jing; SHANG Li-hua; ZHANG Yun-yan; LU Fei-fei; WEI Min; YU Yan

    2012-01-01

    Background Platinum-based regimens are used as standard first-line chemotherapy in non-small cell lung cancer (NSCLC) patients.To study if pharmacogenetic approach may allow a tailored selection of platinum chemotherapy for advanced NSCLC,we performed a meta-analysis to compare chemosensitivity to platinum with different ERCC1 C118T/MDR1 C3435T single-nucleotide polymorphism (SNP).Methods Relevant studies were identified by searching the PubMed,Embase,Cochrane,OVID,Springer,EBSCO and CNKI databases.Inclusion criteria were patients with advanced NSCLC who received platinum-based chemotherapy,an evaluated polymorphism of ERCC/MDR1 and overall response rate.We excluded duplicate publications,letters and review articles.The RevMan 4.2 and STATA 11 package were used to do comprehensive quantitative assessment.Results A total of 11 studies were included in this meta-analysis.For studies evaluating ERCC1 C118T,test for heterogeneity was done (x2=13.41,P=0.1),and the odds ratio (OR) for the wild-type C/C genotype versus the heterozygous C/T and T/T genotypes was 1.50 (95% CI 1.09-2.06,P=-0.01).In four studies evaluating MDR1 polymorphism,test for heterogeneity was also done (x2=3.22,P=0.36),and the OR for the wild-type C/C genotype versus the heterozygous C/T and T/T genotypes was 2.30 (95% CI 1.44-3.68,P=0.0005).Conclusions The results indicated that platinum-based chemotherapy sensitivity was significantly associated with polymorphism of ERCC1 C118T and MDR1 C3435T SNP.In further perspective studies,the ERCC1/MDR1 SNPs might serve as simple and less invasive biomarkers for personalized chemotherapy with platinum-based anticancer drugs.

  2. SU-E-T-572: Normal Lung Tissue Sparing in Radiation Therapy for Locally Advanced Non-Small Cell Lung Cancer

    International Nuclear Information System (INIS)

    Purpose: To compare normal lung-sparing capabilities of three advanced radiation therapy techniques for locally advanced non-small cell lung cancer (LA-NSCLC). Methods: Four-dimensional computed tomography (4DCT) was performed in 10 patients with stage IIIb LA-NSCLC. The internal target volume (ITV); planning target volume (PTV); and organs at risks (OARs) such as spinal cord, total normal lung, heart, and esophagus were delineated for each CT data set. Intensity-modulated radiation therapy (IMRT), Tomohelical-IMRT (TH-IMRT), and TomoDirect-IMRT (TD-IMRT) plans were generated (total prescribed dose, 66 Gy in 33 fractions to the PTV) for each patient. To reduce the normal lung dose, complete and directional block function was applied outside the normal lung far from the target for both TH-IMRT and TD-IMRT, while pseudo- OAR was set in the same region for IMRT. Dosimetric characteristics of the three plans were compared in terms of target coverage, the sparing capability for the OAR, and the normal tissue complication probability (NTCP). Beam delivery efficiency was also compared. Results: TH-IMRT and TD-IMRT provided better target coverage than IMRT plans. Lung volume receiving ≥–30 Gy, mean dose, and NTCP were significant with TH-IMRT than with IMRT (p=0.006), and volume receiving ≥20–30 Gy was lower in TD-IMRT than in IMRT (p<0.05). Compared with IMRT, TH-IMRT had better sparing effect on the spinal cord (Dmax, NTCP) and heart (V45) (p<0.05). NTCP for the spinal cord, V45 and V60 for the heart, and Dmax for the esophagus were significantly lower in TD-IMRT than in IMRT. The monitor units per fraction were clearly smaller for IMRT than for TH-IMRT and TD-IMRT (p=0.006). Conclusion: In LA-NSCLC, TH-IMRT gave superior PTV coverage and OAR sparing compared to IMRT. TH-IMRT provided better control of the lung volume receiving ≥5–30 Gy. The delivery time and monitor units were lower in TD-IMRT than in TH-IMRT

  3. Classification and Regression Tree Analysis of Clinical Patterns to Predict the Survival of Patients with Advanced Non-small Cell Lung Cancer Treated with Erlotinib

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    Yutao LIU

    2011-10-01

    Full Text Available Background and objective Erlotinib is a targeted therapy drug for non-small cell lung cancer (NSCLC. It has been proven that, there was evidence of various survival benefits derived from erlotinib in patients with different clinical features, but the results are conflicting. The aim of this study is to identify novel predictive factors and explore the interactions between clinical variables as well as their impact on the survival of Chinese patients with advanced NSCLC heavily treated with erlotinib. Methods The clinical and follow-up data of 105 Chinese NSCLC patients referred to the Cancer Hospital and Institute, Chinese Academy of Medical Sciences from September 2006 to September 2009 were analyzed. Multivariate analysis of progressive-free survival (PFS was performed using recursive partitioning referred to as the classification and regression tree (CART analysis. Results The median PFS of 105 eligible consecutive Chinese NSCLC patients was 5.0 months (95%CI: 2.9-7.1. CART analysis was performed for the initial, second, and third split in the lymph node involvement, the time of erlotinib administration, and smoking history. Four terminal subgroups were formed. The longer values for the median PFS were 11.0 months (95%CI: 8.9-13.1 for the subgroup with no lymph node metastasis and 10.0 months (95%CI: 7.9-12.1 for the subgroup with lymph node involvement, but not over the second-line erlotinib treatment with a smoking history ≤35 packs per year. The shorter values for the median PFS were 2.3 months (95%CI: 1.6-3.0 for the subgroup with lymph node metastasis and over the second-line erlotinib treatment, and 1.3 months (95%CI: 0.5-2.1 for the subgroup with lymph node metastasis, but not over the second-line erlotinib treatment with a smoking history >35 packs per year. Conclusion Lymph node metastasis, the time of erlotinib administration, and smoking history are closely correlated with the survival of advanced NSCLC patients with first- to

  4. Relationship between Expression of β-tubulin-Ⅲ Plus Stathmin in Advanced Non-Small Cell Lung Cancer and its Sensitivity to Venorelbine Chemotherapy

    Directory of Open Access Journals (Sweden)

    Xiaolin PU

    2009-01-01

    Full Text Available Background and objective Vinorelbine plus cisplatin/carboplatin (NP is one of the standard combination chemotherapy regimen for advanced non-small cell lung cancer (NSCLC. The aim of this study is toinvestigate the relationship between expression of Stathmin and β-tubulin-Ⅲ in NSCLC biopsies and sensitivity to Vinorelbine, which would provide a basis of the proper medicine choice for the patients' tailored chemotherapy. Methods Western blot was used to investigate the expression of Stathmin and β-tubulin-Ⅲ protein in the biopsies from stage ⅢB-Ⅳ NSCLC patients. All the cases were divided into 4 groups according to the level of the two proteins, of which L represented both protein expressed lowly, B showed β-tubulin-Ⅲ lowly expressed group, while S showed Stathmin lowly, and H represented both protein highly expressed. At the same time, all the patients accepted NP chemotherapy for 2 or 4 cycles according to the responses to this regimen. The responses rate (RR, media survival time (MST, time to progress (TTP were observed. Results A total of 90 stage ⅢB-Ⅳ NSCLC patients were divided into 4 groups, 22 in L group, 23 in B and S group while 22 in H group respectively. The RR of the groups were 68.2%, 26.1%, 30.4% and 22.7% respectively.There were statistically significant differences between L group and other 3 groups (P <0.05. The MST were 377, 305, 321 and 271 days respectively, and the TTP were 240, 182, 190 and 166 days in the 4 groups. Statistically significant differences between L group and other 3 groups (P <0.05 can be seen in both MST and TTP. Conclusion The expression of β-tubulin-Ⅲ and Stathmin in advanced NSCLC biopsies had relationship with the sensitivity to NP chemotherapyregimen in the patients. Cases with high level of these two proteins would have poor responses to this cytotoxic drug.

  5. Insulin-like Growth Factor Receptor 1 mRNA Expression as a Prognostic Marker in Advanced Non-small Cell Lung Cancer

    DEFF Research Database (Denmark)

    Vilmar, Adam; Santoni-Rugiu, Eric; Cillas, Jesus Garcia-Fon;

    2014-01-01

    BACKGROUND: The insulin-like growth factor 1 receptor (IGF1R) has yet to be established as a biomarker in non-small cell lung cancer (NSCLC) but could prove useful in customized chemotherapy. We explored its prognostic value using both quantitative real-time reverse transcriptase polymerase chain......-points. RESULTS: Surgical tissue samples were available from 33 patients deemed inoperable. IGF1R status varied according to histopathology. Patients with tumors positive for IGF1R mRNA expression had a shorter progression-free and overall survival when compared to the negative sub-group (6.1 vs. 7.4 months, p=0...

  6. Tyrosine kinase inhibitors for epidermal growth factor receptor gene mutation-positive non-small cell lung cancers: an update for recent advances in therapeutics.

    Science.gov (United States)

    Chung, Clement

    2016-06-01

    The presence of activating gene mutations in the epidermal growth factor receptor of non-small cell lung cancer patients is predictive (improved progression-free survival and improved response rate) when treated with small molecule tyrosine kinase inhibitors such as gefitinib, erlotinib and afatinib. The two most common mutations that account for greater than 85% of all EGFR gene mutations are in-frame deletions in exon 19 (LREA deletions) and substitution in exon 21 (L858R). Exon 18 mutations occur much less frequently at about 4% of all EGFR gene mutations. Together, exon 19 deletion and exon 21 L858R gene substitution are present in about 10% of Caucasian patients and 20-40% of Asian patients with non-small cell lung cancer. T790M gene mutation at exon 20 is associated with acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors. Early studies showed that activating EGFR gene mutations are most common in patients with adenocarcinoma histology, women, never smokers and those of Asian ethnicity. A recent multi-center phase III trial suggested that frontline epidermal growth factor receptor tyrosine kinase inhibitor therapy with afatinib is associated with improved progression-free survival compared to chemotherapy regardless of race. Moreover, guidelines now suggest EGFR gene mutation testing should be conducted in all patients with lung adenocarcinoma or mixed lung cancers with an adenocarcinoma component, regardless of characteristics such as smoking status, gender or race. The success of targeted therapies in non-small cell lung cancer patients has changed the treatment paradigm in metastatic non-small cell lung cancer. However, despite a durable response of greater than a year, resistance to epidermal growth factor receptor tyrosine kinase inhibitors inevitably occurs. This mini-review describes the clinically relevant EGFR gene mutations and the efficacy/toxicity of small molecule epidermal growth factor receptor tyrosine kinase

  7. The role of circulating anti-p53 antibodies in patients with advanced non-small cell lung cancer and their correlation to clinical parameters and survival

    International Nuclear Information System (INIS)

    Lung cancer causes approximately one million deaths each year worldwide and protein p53 has been shown to be involved in the intricate processes regulating response to radiation and/or chemotherapeutic treatment. Consequently, since antibodies against p53 (anti-p53 antibodies) are associated with mutations within the p53 gene it seems likely that these antibodies could, hypothetically, be correlated with prognosis. Serum samples from patients with non-small cell lung cancer (NSCLC) admitted to the Department of Oncology, University Hospital, Uppsala, Sweden, during 1983–1996 were studied. Anti-p53 abs were measured using a sandwich ELISA (Dianova, Hamburg, Germany). The present study included 84 patients with stage IIIA-IV (advanced NSCLC). At least three serum samples from each patient were collected and altogether 529 serum samples were analysed for the presence of anti-p53 antibodies. The median value of anti-p53 antibodies was 0.06 (range 0 – 139.8). Seventeen percent of investigated NSCLC first serum samples (n = 84) expressed elevated levels of anti-p53 antibodies. Anti-p53 antibodies were not correlated to tumour volume or platelets. Survival analysis showed that anti-p53 antibodies were not associated with survival as revealed by univariate analysis (p = 0.29). However, patients with adenocarcinoma had a significantly poorer survival if they expressed anti-p53 antibodies (p = 0.01), whereas this was not found for patients with squamous cell carcinoma (p = 0.13). In patients where the blood samples were collected during radiation therapy, a statistically significant correlation towards poorer survival was found (p = 0.05) when elevated anti-p53 antibodies levels were present. No correlations to survival were found for serum samples collected prior to radiation therapy, during chemotherapy, or during follow-up. When anti-p53 antibodies were measured continuously, no increase in median anti-p53 values was observed the closer the individual patient come to

  8. 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)

  9. Predictive potential role of GSTs gene polymorphisms in the treatment outcome of advanced non-small cell lung cancer patients

    OpenAIRE

    Liu, Kaixiong; Lin, Qichang; Ding, Haibo; Jin, Yongxu; Chen, Gongping

    2015-01-01

    This study aimed to investigate the possible association between GSTP1, GSTM1, and GSTT1 polymorphisms and treatment outcome of advanced NSCLC. Between October 2009 and October 2011, a total of 308 patients of NSCLC on stage IIIA, IIIB or IV, treated with cisplatin-based chemotherapy were included. Polymerase chain reaction-restriction fragment length polymorphism was used to genotype the GSTP1 and GSTM1, and GSTT1 polymorphisms. We found that the IIe/Val and Val/Val genotypes of GSTP1 showed...

  10. Prediction of radiation-induced lung toxicity in locally advanced non-small cell lung cancer treated with chemoradiotherapy by functional lung dose-volume histogram

    International Nuclear Information System (INIS)

    Objective: To investigate the correlation between functional lung dose-volume histogram (f-DVH) parameters and radiation-induced lung toxicity (RILT) in patients of locally advanced non-small cell lung cancer (NSCLC) treated with late-course accelerated hyperfractionated radiotherapy and chemotherapy, and to identify the excellent predictors of f-DVH and their reference thresholds. Methods: A total of 51 patients of NSCLC at stage Ⅲ underwent PET/CT/SPECT coregistered image guided radiotherapy. Philips Pinnacle3 planning system was used for delineation of the target volume and organs at risk so as to establish the three dimensional conformal radiotherapy or intensity-modulated radiotherapy treatment plans. The version 3.0 of the NCI Common Terminology Criteria for Adverse Events was used to evaluate the grade of RILT, and analyze the correlation of the DVH parameters of the total lung (TL), ipsilateral lung (IL), and functional lung (FL) and RILT, and to identify the excellent predictors. The median follow-up was 15 months. Results: During the follow-up, 10 cases of RILT (19.6%) ≥grade 2 were observed. Single factor analysis showed that the V5-V40 of TL, V5-V20 of IL, and V5-V50 of FL were all related to the occurrence of RILT, and multiple factor analysis showed that TL-V15 and FL-V20 remained associated with RILT (P=0.005 and P=0.016). According to ROC analysis, the V10 (45.38%) of FL was the most sensitive predictor with a sensitivity rate of 90.0% and 1/25 (27.78%) of FL was the most specific predictor with a specificity rate of 90.24%. The sensitivity, specificity and accuracy of V20 of FL were 70.00%, 73.17%, and 74.90%, respectively. Conclusions: The occurrence of RILT is closely associated with multiple f-DVH parameters of FL, and f-DVH has good sensitivity and specificity for prediction. (authors)

  11. SU-E-J-244: Development and Validation of a Knowledge Based Planning Model for External Beam Radiation Therapy of Locally Advanced Non-Small Cell Lung Cancer

    International Nuclear Information System (INIS)

    Purpose: The study aims to develop and validate a knowledge based planning (KBP) model for external beam radiation therapy of locally advanced non-small cell lung cancer (LA-NSCLC). Methods: RapidPlan™ technology was used to develop a lung KBP model. Plans from 65 patients with LA-NSCLC were used to train the model. 25 patients were treated with VMAT, and the other patients were treated with IMRT. Organs-at-risk (OARs) included right lung, left lung, heart, esophagus, and spinal cord. DVH and geometric distribution DVH were extracted from the treated plans. The model was trained using principal component analysis and step-wise multiple regression. Box plot and regression plot tools were used to identify geometric outliers and dosimetry outliers and help fine-tune the model. The validation was performed by (a) comparing predicted DVH boundaries to actual DVHs of 63 patients and (b) using an independent set of treatment planning data. Results: 63 out of 65 plans were included in the final KBP model with PTV volume ranging from 102.5cc to 1450.2cc. Total treatment dose prescription varied from 50Gy to 70Gy based on institutional guidelines. One patient was excluded due to geometric outlier where 2.18cc of spinal cord was included in PTV. The other patient was excluded due to dosimetric outlier where the dose sparing to spinal cord was heavily enforced in the clinical plan. Target volume, OAR volume, OAR overlap volume percentage to target, and OAR out-of-field volume were included in the trained model. Lungs and heart had two principal component scores of GEDVH, whereas spinal cord and esophagus had three in the final model. Predicted DVH band (mean ±1 standard deviation) represented 66.2±3.6% of all DVHs. Conclusion: A KBP model was developed and validated for radiotherapy of LA-NSCLC in a commercial treatment planning system. The clinical implementation may improve the consistency of IMRT/VMAT planning

  12. Adaptive/Nonadaptive Proton Radiation Planning and Outcomes in a Phase II Trial for Locally Advanced Non-small Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Koay, Eugene J.; Lege, David [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Mohan, Radhe [Department of Radiation Physics, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Komaki, Ritsuko; Cox, James D. [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Chang, Joe Y., E-mail: jychang@mdanderson.org [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2012-12-01

    Purpose: To analyze dosimetric variables and outcomes after adaptive replanning of radiation therapy during concurrent high-dose protons and chemotherapy for locally advanced non-small cell lung cancer (NSCLC). Methods and Materials: Nine of 44 patients with stage III NSCLC in a prospective phase II trial of concurrent paclitaxel/carboplatin with proton radiation [74 Gy(RBE) in 37 fractions] had modifications to their original treatment plans after re-evaluation revealed changes that would compromise coverage of the target volume or violate dose constraints; plans for the other 35 patients were not changed. We compared patients with adaptive plans with those with nonadaptive plans in terms of dosimetry and outcomes. Results: At a median follow-up of 21.2 months (median overall survival, 29.6 months), no differences were found in local, regional, or distant failure or overall survival between groups. Adaptive planning was used more often for large tumors that shrank to a greater extent (median, 107.1 cm{sup 3} adaptive and 86.4 cm{sup 3} nonadaptive; median changes in volume, 25.3% adaptive and 1.2% nonadaptive; P<.01). The median number of fractions delivered using adaptive planning was 13 (range, 4-22). Adaptive planning generally improved sparing of the esophagus (median absolute decrease in V{sub 70}, 1.8%; range, 0%-22.9%) and spinal cord (median absolute change in maximum dose, 3.7 Gy; range, 0-13.8 Gy). Without adaptive replanning, target coverage would have been compromised in 2 cases (57% and 82% coverage without adaptation vs 100% for both with adaptation); neither patient experienced local failure. Radiation-related grade 3 toxicity rates were similar between groups. Conclusions: Adaptive planning can reduce normal tissue doses and prevent target misses, particularly for patients with large tumors that shrink substantially during therapy. Adaptive plans seem to have acceptable toxicity and achieve similar local, regional, and distant control and overall

  13. SU-E-J-244: Development and Validation of a Knowledge Based Planning Model for External Beam Radiation Therapy of Locally Advanced Non-Small Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Z; Kennedy, A [Sarah Cannon, Nashville, TN (United States); Larsen, E; Hayes, C; Grow, A [North Florida Cancer Center, Gainesville, FL (United States); Bahamondes, S.; Zheng, Y; Wu, X [JFK Comprehensive Cancer Institute, Lake Worth, FL (United States); Choi, M; Pai, S [Good Samaritan Hospital, Los Gatos, CA (United States); Li, J [Doctors Hospital of Augusta, Augusta, GA (United States); Cranford, K [Trident Medical Center, Charleston, SC (United States)

    2015-06-15

    Purpose: The study aims to develop and validate a knowledge based planning (KBP) model for external beam radiation therapy of locally advanced non-small cell lung cancer (LA-NSCLC). Methods: RapidPlan™ technology was used to develop a lung KBP model. Plans from 65 patients with LA-NSCLC were used to train the model. 25 patients were treated with VMAT, and the other patients were treated with IMRT. Organs-at-risk (OARs) included right lung, left lung, heart, esophagus, and spinal cord. DVH and geometric distribution DVH were extracted from the treated plans. The model was trained using principal component analysis and step-wise multiple regression. Box plot and regression plot tools were used to identify geometric outliers and dosimetry outliers and help fine-tune the model. The validation was performed by (a) comparing predicted DVH boundaries to actual DVHs of 63 patients and (b) using an independent set of treatment planning data. Results: 63 out of 65 plans were included in the final KBP model with PTV volume ranging from 102.5cc to 1450.2cc. Total treatment dose prescription varied from 50Gy to 70Gy based on institutional guidelines. One patient was excluded due to geometric outlier where 2.18cc of spinal cord was included in PTV. The other patient was excluded due to dosimetric outlier where the dose sparing to spinal cord was heavily enforced in the clinical plan. Target volume, OAR volume, OAR overlap volume percentage to target, and OAR out-of-field volume were included in the trained model. Lungs and heart had two principal component scores of GEDVH, whereas spinal cord and esophagus had three in the final model. Predicted DVH band (mean ±1 standard deviation) represented 66.2±3.6% of all DVHs. Conclusion: A KBP model was developed and validated for radiotherapy of LA-NSCLC in a commercial treatment planning system. The clinical implementation may improve the consistency of IMRT/VMAT planning.

  14. 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

  15. Pemetrexed single agent chemotherapy in previously treated patients with locally advanced or metastatic non-small cell lung cancer

    International Nuclear Information System (INIS)

    The main objective of this study was to evaluate the safety of second-line pemetrexed in Stage IIIB or IV NSCLC. Overall, 95 patients received pemetrexed 500 mg/m2 i.v. over Day 1 of a 21-day cycle. Patients also received oral dexamethasone, oral folic acid and i.m. vitamin B12 supplementation to reduce toxicity. NCI CTC 2.0 was used to rate toxicity. All the adverse events were graded in terms of severity and relation to study treatment. Dose was reduced in case of toxicity and treatment was delayed for up to 42 days from Day 1 of any cycle to allow recovering from study drug-related toxicities. Tumor response was measured using the RECIST criteria. Patients received a median number of 4 cycles and 97.8% of the planned dose. Overall, 75 patients (78.9% of treated) reported at least one adverse event: 34 (35.8%) had grade 3 as worst grade and only 5 (5.2%) had grade 4. Drug-related events occurred in 57.9% of patients. Neutropenia (8.4%) and leukopenia (6.3 %) were the most common grade 3/4 hematological toxicities. Grade 3 anemia and thrombocytopenia were reported in 3.2% and 2.1% of patients, respectively. Diarrhea (6.3%), fatigue (3.2%) and dyspnea (3.2%) were the most common grade 3/4 non-hematological toxicities. The most common drug-related toxicities (any grade) were pyrexia (11.6%), vomiting, nausea, diarrhea and asthenia (9.5%) and fatigue (8.4%). Tumor Response Rate (CR/PR) in treated patients was 9.2%. The survival at 4.5 months (median follow-up) was 79% and the median PFS was 3.1 months. Twenty patients (21.1%) died mainly because of disease progression. Patients with locally advanced or metastatic NSCLC could benefit from second-line pemetrexed, with a low incidence of hematological and non-hematological toxicities

  16. 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

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

    DEFF Research Database (Denmark)

    Sorensen, Boe S; Wu, Lin; Wei, Wen; Tsai, Julie; Weber, Britta; Nexo, Ebba; Meldgaard, Peter

    2014-01-01

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

  18. A prospective study of the efficacy of a combination of autologous dendritic cells, cytokine-induced killer cells, and chemotherapy in advanced non-small cell lung cancer patients.

    Science.gov (United States)

    Zhong, Runbo; Han, Baohui; Zhong, Hua

    2014-02-01

    Dendritic cells (DC) play a crucial role in the induction of an effective antitumor immune response. Cytokine-induced killer (CIK) cells, a subset of T lymphocytes, have the capacity to eliminate cancer cells. This study was to evaluate the correlation between the frequency of DC/CIK immunotherapies following regular chemotherapy, the time-to-progression (TTP), and overall survival (OS) of advanced non-small lung cancer patients. Sixty patients with IIIB-IV non-small-cell lung carcinoma (NSCLC) were enrolled from August 2007 to December 2009 and were randomized into two groups. All 60 patients received four courses of navelbine-platinum (NP) chemotherapy. In one group, 30 patients were treated with adoptive autologous DC/CIK cell transfusion twice every 30 days. In the other group, the patients received immunotherapies more than twice every 30 days. The adverse effects, TTP, and OS were evaluated between the two groups. Median survival time of all 60 patients was 13.80 months. The 1-, 2-, and 3-year overall survival rates were 60.0, 21.7, and 15.0 %, respectively. The 1-, 2-, and 3-year overall survival rates of patients receiving more than two immunotherapies were 63.3, 30.0, and 23.3 %, and the rates of those receiving two immunotherapies were 56.7, 13.3, and 6.7 %, respectively. The difference between the two groups was statistically significant (P = 0.037). Compared with patients in the fewer immunotherapies group, TTP in the group receiving more immunotherapies significantly prolonged, with the median improving from 6.2 months (95 % CI, 5.35-9.24) to 7.3 months (95 % CI, 5.45-6.95; P = 0.034). The adverse effects of chemoimmunotherapy were tolerable. Advanced NSCLC patients can benefit from the combination of DC/CIK immunotherapies following conventional chemotherapy. More than two immunotherapies improved TTP and OS of those patients in this study. PMID:24006222

  19. Meta-analysis of EGFR tyrosine kinase inhibitors compared with chemotherapy as second-line treatment in pretreated advanced non-small cell lung cancer.

    Directory of Open Access Journals (Sweden)

    Ning Li

    Full Text Available Since efficacy and safety of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs versus chemotherapy in the treatment of patients with pretreated advanced non-small cell lung cancer (NSCLC remain controversial, we performed a meta-analysis to compare them.An internet search of several databases was performed, including PubMed, Embase, and the Cochrane database. Randomized trials that compared an EGFR-TKI with chemotherapy in the second-line setting were included. The outcomes were progression-free survival (PFS, overall survival (OS, objective response rate (ORR, and grade 3-4 toxicities. The PFS, OS for the EGFR mutation-positive (EGFR M+ and EGFR mutation-negative (EGFR M- subgroups were pooled. The pooled hazard ratios (HRs and odds ratios (ORs with their corresponding confidence intervals (CIs were calculated on the STATA software.Our meta-analysis combined 3,825 patients from 10 randomized trials. Overall, EGFR-TKIs and second-line chemotherapy have equivalent efficacy in terms of PFS (HR, 1.03; 95%CI, 0.87-1.21; P = 0.73; I2 = 78.7%, Pheterogeneity<0.001, OS (HR, 1.00; 95%CI, 0.92-1.08; P = 0.90; I2 = 0.0%, Pheterogeneity = 0.88, and ORR (OR, 1.34; 95%CI, 0.86-2.08; P = 0.20; I2 = 73.1%, Pheterogeneity<0.001. However, subgroup analysis based on EGFR mutation status showed that second-line chemotherapy significantly improved PFS (HR, 1.35; 95%CI, 1.09-1.66; P = 0.01; I2 = 55.7%, Pheterogeneity = 0.046 for EGFR M- patients, whereas OS was equal (HR, 0.96; 95%CI, 0.77-1.19; P = 0.69; I2 = 0.0%, Pheterogeneity = 0.43; EGFR-TKIs significantly improved PFS (HR, 0.28; 95%CI, 0.15-0.53; P<0.001; I2 = 4.1%, Pheterogeneity = 0.35 for EGFR M+ patients, whereas OS was equal (HR, 0.86; 95%CI, 0.44-1.68; P = 0.65; I2 = 0.0%, Pheterogeneity = 0.77. Compared with chemotherapy, EGFR-TKIs led to more grade 3-4 rash, but less fatigue/asthenia disorder, leukopenia and

  20. 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

  1. Clinical and Immunological Effects in Patients with Advanced Non-Small Cell Lung-Cancer after Vaccination with Dendritic Cells Exposed to an Allogeneic Tumor Cell Lysate

    OpenAIRE

    Mogens H. Claesson; Ayako W. Pedersen; Pia Kvistborg; Mai-Britt Zocca; Lotte Engell-Noerregaard; Anders Mellemgaard

    2013-01-01

    Background: We evaluated the clinical and immunological effects of dendritic cell (DC) vaccination of patients with NSCLC. Autologous DCs were pulsed with a MAGE containing allogeneic melanoma cell lysate (MelCancerVac&174, Dandrit Biotech,Copenhagen,Denmark). Imiquimod cream, proleukin and celecoxib were used as adjuvants to the vaccines. The objective of the study was to evaluate specific T cell response in vitro by IFNg EliSpot. Secondary objectives were overall survival, response and qua...

  2. 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

  3. Clinical and Immunological Effects in Patients with Advanced Non-Small Cell Lung-Cancer after Vaccination with Dendritic Cells Exposed to an Allogeneic Tumor Cell Lysate*

    DEFF Research Database (Denmark)

    Engell-Noerregaard, Lotte; Kvistborg, Pia; Zocca, Mai-Britt;

    2013-01-01

    Background: We evaluated the clinical and immunological effects of dendritic cell (DC) vaccination of patients with NSCLC. Autologous DCs were pulsed with a MAGE containing allogeneic melanoma cell lysate (MelCancerVac®, Dandrit Biotech, Copenhagen, Denmark). Imiquimod cream, proleukin and......-layed effect of DC vaccination after completion of the treatment. A prospective randomized phase-IIb or -III is needed to further evaluate the use of MelCancerVac® vaccine treatment in patients with progressive NSCLC....

  4. Advances in Treatment of Brain Metastases from Primary Non-small Cell Lung Cancer%非小细胞肺癌脑转移治疗进展

    Institute of Scientific and Technical Information of China (English)

    林根; 徐海鹏; 黄诚

    2014-01-01

    脑是非小细胞肺癌常见的转移部位,手术和放疗是以往脑转移治疗的基石,但近年来随着对肿瘤发生发展机制的认识深化,靶向治疗在脑转移治疗中开始崭露头角。本文主要针对一些相关热点问题如脑转移治疗手段等(手术、放疗、化疗、靶向治疗)进行简要述评。%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. hTis review mainly summarizes the current applications of these data to surgery, radiation therapy, chemotherapy and targeted therapy.

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

    Institute of Scientific and Technical Information of China (English)

    郏博

    2014-01-01

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

  6. 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).

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

    Directory of Open Access Journals (Sweden)

    Shengye WANG

    2012-09-01

    Full Text Available Background and objective Controversy exists on whether amifostine can reduce the efficacy and decrease the side effects of non-small cell lung cancer (NSCLC treated by radiotherapy. The aim of this meta-analysis is to evaluate the efficacy and side effects of amifostine in NSCLC patients treated with radiotherapy. Methods Open published randomized controlled trials on the efficacy and side effects of amifostine in NSCLC patients treated with radiotherapy were collected from Medline, Cochrane Central Register of Controlled Trials, EMBSE, CBM, CNKI, WANFANG, American Society of Clinical Oncology, and European Society of Medical Oncology databases. The pooled efficacy and side effects of amifostine in these patients were calculated using the statistics software Stata 11.0. Results Nine trials that included 769 (381 and 388 in each arm patients were analyzed. The pooled relative risk of complete, partial, and objective responses were 1.16 (95%CI: 0.90-1.50, Z=1.07, P=0.29, 1.02 (95%CI: 0.87-1.19, Z=0.21, P=0.83 and 1.06 (95%CI: 0.97-1.17, Z=1.31, P=0.20, respectively. The side effects in seven trials including 738 (367 and 371 in each arm patients were analyzed. The pooled relative risk of developing grades 3 to 4 esophagitis and pneumonitis were 0.51 (95%CI: 0.37-0.72, Z=3.88, P<0.001 and 0.51 (95%CI: 0.26-0.99, Z=1.98, P=0.04, respectively. Conclusion Amifostine can significantly decrease the risk of developing serious esophagitis and pneumonitis without reducing the response rate in NSCLC patients treated by radiotherapy.

  8. Circulating Endothelial-Derived Activated Microparticle: A Useful Biomarker for Predicting One-Year Mortality in Patients with Advanced Non-Small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Chin-Chou Wang

    2014-01-01

    Full Text Available Background. This study tested the hypothesis that circulating microparticles (MPs are useful biomarkers for predicting one-year mortality in patients with end-stage non-small cell lung cancer (ES-NSCLC. Methods and Results. One hundred seven patients were prospectively enrolled into the study between April 2011 and February 2012, and each patient received regular follow-up after enrollment. Levels of four MPs in circulation, (1 platelet-derived activated MPs (PDAc-MPs, (2 platelet-derived apoptotic MPs (PDAp-MPs, (3 endothelial-derived activated MPs (EDAc-MPs, and (4 endothelial-derived apoptotic MPs (EDAp-MPs, were measured just after the patient was enrolled into the study using flow cytometry. Patients who survived for more than one year were categorized into group 1 (n=56 (one-year survivors and patients who survived less than one year were categorized into group 2 (n=51 (one-year nonsurvivors. Male gender, incidence of liver metastasis, progression of disease after first-line treatment, poor performance status, and the Charlson comorbidity index were significantly higher in group 2 than in group 1 (all P<0.05. Additionally, as measured by flow cytometry, only the circulating level of EDAc-MPs was found to be significantly higher in group 2 than in group 1 (P=0.006. Multivariate analysis demonstrated that circulating level of EDAc-MPs along with brain metastasis and male gender significantly and independently predictive of one-year mortality (all P<0.035. Conclusion. Circulating EDAc-MPs may be a useful biomarker predictive of one-year morality in ES-NSCLC patients.

  9. Phase I study of celecoxib with concurrent irinotecan, cisplatin, and radiation therapy for patients with unresectable locally advanced non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Ritsuko eKomaki

    2011-12-01

    Full Text Available Purpose: Preclinical findings suggest that adding targeted therapies to combination radiation-chemotherapy can enhance treatment efficacy; however, this approach may enhance normal tissue toxicity. We investigated the maximum tolerated dose, dose-limiting toxicities, and response rate when the selective cyclo-oxygenase-2 inhibitor celecoxib is added to concurrent irinotecan, cisplatin, and radiation therapy for patients with inoperable stage II-III non-small cell lung cancer. Methods and materials: Eighteen patients were analyzed in a phase I clinical dose-escalation trial. Celecoxib was given daily beginning 5 days before radiation followed by maintenance doses for 12 weeks. Toxicity was graded with the Common Terminology Criteria for Adverse Events V3.0 and response with the World Health Organization system. Primary endpoints were maximum tolerated dose of celecoxib and treatment toxicity; secondary endpoints were response and survival rates. Results: The maximum tolerated dose of celecoxib was not reached, in part owing to discontinuation of the drug supply. At doses of 200 or 400 mg/day, no patients experienced any dose-limiting toxicity (acute grade ≥4 esophagitis or pneumonitis, neutropenic fever or thrombocytopenia requiring transfusion, or acute grade ≥3 diarrhea. Grade 3 toxicities were leukopenia (5 patients, fatigue (3, pneumonitis (2, dyspnea (1, pain (1, and esophageal stricture (1. Interestingly, pulmonary fibrosis (a late toxicity was no more severe in the higher-dose (400-mg group and may have been less common than in the lower-dose group. The clinical response rate was 100% (8 complete, 10 partial. Two-year rates were: overall survival 65%; local-regional control 69%; distant metastasis-free survival 71%; and disease-free survival 64%. Conclusions: Although preliminary, our results suggest that adding celecoxib to concurrent chemoradiation for inoperable NSCLC is safe and can improve outcome without increasing normal tissue

  10. Concurrent chemoradiotherapy with tomotherapy in locally advanced non-small cell lung cancer: a phase i, docetaxel dose-escalation study, with hypofractionated radiation regimen

    OpenAIRE

    Bearz, Alessandra; Minatel, Emilio; Rumeileh, Imad Abu; Borsatti, Eugenio; Talamini, Renato; Franchin, Giovanni; Gobitti, Carlo; Del Conte, Alessandro; Trovò, Marco; Baresic, Tanja

    2013-01-01

    Background Concurrent chemo-radiotherapy is demonstrately superior to sequential chemo-radiotherapy in the treatment of advanced Non-Small-Cell Lung Cancer not suitable for surgery. Docetaxel is considered to enhance the cytotoxic effect of radiotherapy on the tumour cells. Tomotherapy (HT) is a novel radiotherapeutic technique, which allows the delivery of Image Guided-IMRT (IG-IMRT), with a highly conformal radiation dose distribution. The goal of the study was to estimate tolerability of D...

  11. GP方案引起NSCLC患者糖耐量异常的临床研究%Clinical Study of Glucose Levels in Patients with Advanced Non-small Cell Lung Cancer Treated by GP Regimen

    Institute of Scientific and Technical Information of China (English)

    姚兰; 蒋成霞; 徐勇; 叶序卷; 贾钰铭; 雷开键; 唐元英

    2015-01-01

    Objective To evaluate blood glucose differences before and after three cycles of chemotherapy in patients with advanced non-small cell lung cancer. Methods 44 patients with advanced non-small cell lung cancer conducted blood routine,bi-ochemical,and C-reactive protein test;Normal blood glucose group treated chemotherapy with GP 3 cycles,high blood sugar groups measured blood glucose by oral glucose tolerance test,then were on diets,exercised or injected insulin. After GP regimen of 3 cy-cles,blood analysis,biochemical,C-reactive protein,oral glucose tolerance test,c-peptide and insulin release test were measured. Results After 3 cycles of GP,25%(8/32) of patients with normal glucose appears abnormal,and half of patients with abnormal glucose tolerance turn into diabetic. After chemotherapy,aspartate aminotransferase and C-reactive protein were significantly differ-ent from the patients with increased blood glucose and normal blodd glucose,the difference was statistically significant(P<0. 05). Conclusion GP regimen could cause glucose metabolism disorders in some patients with advanced non-small cell lung cancer and even induce diabetes. Patients with abnormal aspartate aminotransferase and C-reactive protein are susceptible to elevate blood glu-cose.%目的:分析非小细胞肺癌晚期患者GP方案化疗3周期前后血糖的差异。方法将44名非小细胞肺癌晚期患者根据血糖情况分为血糖正常组和血糖升高组:血糖正常组32例患者直接用GP方案化疗3周期,血糖升高组12例患者予以饮食、运动及胰岛素干预后,再进行GP方案化疗3周期,化疗前后行口服葡萄糖耐量试验、C肽及胰岛素释放试验。结果化疗前血糖正常者经GP方案化疗3周期后25%(8/32)的患者出现血糖升高,而糖调节受损患者化疗后出现一半的患者转变为糖尿病患者。化疗后血糖升高者与血糖正常者比较谷草转氨酶及C反应蛋白差异有统计学意义(P<0.05)

  12. 艾迪注射液对晚期非小细胞肺癌NP方案化疗的影响%Effects of Aidi injection on vinorelbine plus cisplatin chemotherapy for advanced non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    Ximing Xu; Wei Ge; Guangjin Yuan

    2008-01-01

    Objective: To evaluate the effects of Aidi injection on vinorelbine plus cisplatin (NP) chemotherapy for advanced non-small cell lung cancer (NSCLC). Methods: Ninety eight patients with advanced NSCLC were randomized to receive either NP alone or NP plus Aidi injection every 3 weeks. The primary endpoint was overall survival; secondary endpoints included overall response rate, time to progression, and safety. Results: The median overall survival time was 11.6 months in NP plus Aidi-treated patients and 10.1 months in NP alone-treated ones, and 1- and 2-year survival rates were higher in the former (47% and 22%) than the latter (42% and 15%). The overall response rates in Aidi injection plus NP-treated patients tended to be higher but not statistically significant compared with NP alone-treated ones. The occurrence rates of grades 3 or 4 toxicities, e.g. fatigue, nausea, vomiting, appetite loss, leucopenia, thrombocytopenia and anemia, were lower in Aidi injection plus NP-treated patients than NP alone-treated ones, although not significantly different between them. Conclusion: Aidi injection promotes NP chemotherapeutic effects, reduces the toxicities, and improves the patients' tolerance to chemotherapy as well. It may be an effective adjunct to chemotherapy in patients with NSCLC.

  13. Epidermal growth factor receptor tyrosine kinase (EGFR-TK) mutation testing in adults with locally advanced or metastatic non-small cell lung cancer : a systematic review and cost-effectiveness analysis

    NARCIS (Netherlands)

    Westwood, Marie; Joore, Manuela; Whiting, Penny; van Asselt, Thea; Ramaekers, Bram; Armstrong, Nigel; Misso, Kate; Severens, Johan; Kleijnen, Jos

    2014-01-01

    BACKGROUND: Non-small cell lung cancer (NSCLC) is the most common form of lung cancer. Some epidermal growth factor receptor tyrosine kinase (EGFR-TK) mutations make tumours responsive to treatment with EGFR-TK inhibitors (EGFR-TKIs) but less responsive to treatment with standard chemotherapy. Patie

  14. The emerging role of epidermal growth factor receptor (EGFR) inhibitors in first-line treatment for patients with advanced non-small cell lung cancer positive for EGFR mutations

    OpenAIRE

    Okamoto, Isamu; Mitsudomi, Tetsuya; Nakagawa, Kazuhiko; Fukuoka, Masahiro

    2010-01-01

    Gefitinib and erlotinib, small-molecule tyrosine kinase inhibitors (TKIs) of the epidermal growth factor receptor (EGFR), were the first molecularly targeted agents to become clinically available for the treatment of non-small cell lung cancer (NSCLC). During the course of their clinical development, it has become clear that the substantial clinical benefit associated with EGFR-TKIs is limited ...

  15. Epidermal growth factor receptor tyrosine kinase (EGFR-TK) mutation testing in adults with locally advanced or metastatic non-small cell lung cancer: A systematic review and cost-effectiveness analysis

    NARCIS (Netherlands)

    M. Westwood (Marie); M.A. Joore (Manuela); P. Whiting (Penny); T. van Asselt (Thea); B.L.T. Ramaekers (Bram); N. Armstrong (Nigel); K. Misso (Kate); J.L. Severens (Hans); J. Kleijnen (Jos)

    2014-01-01

    markdownabstract__Abstract__ Background: Non-small cell lung cancer (NSCLC) is the most common form of lung cancer. Some epidermal growth factor receptor tyrosine kinase (EGFR-TK) mutations make tumours responsive to treatment with EGFR-TK inhibitors (EGFR-TKIs) but less responsive to treatment wit

  16. Effect of EGFR-TKI retreatment following chemotherapy for advanced non-small cell lung cancer patients who underwent EGFR-TKI

    International Nuclear Information System (INIS)

    Non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR)-activating mutations have higher response rate and more prolonged survival following treatment with single-agent EGFR tyrosine kinase inhibitor (EGFR-TKI) compared with patients with wild-type EGFR. However, all patients treated with reversible inhibitors develop acquired resistance over time. The mechanisms of resistance are complicated. The lack of established therapeutic options for patients after a failed EGFR-TKI treatment poses a great challenge to physicians in managing this group of lung cancer patients. This study evaluates the influence of EGFR-TKI retreatment following chemotherapy after failure of initial EGFR-TKI within at least 6 months on NSCLC patients. The data of 27 patients who experienced treatment failure from their initial use of EGFR-TKI within at least 6 months were analyzed. After chemotherapy, the patients were retreated with EGFR-TKI (gefitinib 250 mg qd or erlotinib 150 mg qd), and the tumor progression was observed. The patients were assessed for adverse events and response to therapy. Targeted tumor lesions were assessed with CT scan. Of the 27 patients who received EGFR-TKI retreatment, 1 (3.7%) patient was observed in complete response (CR), 8 (29.6%) patients in partial response (PR), 14 (51.9%) patients in stable disease (SD), and 4 (14.8%) patients in progressive disease (PD). The disease control rate (DCR) was 85.2% (95% CI: 62%-94%). The median progression-free survival (mPFS) was 6 months (95% CI: 1-29). Of the 13 patients who received the same EGFR-TKI, 1 patient in CR, 3 patients in PR, 8 patients in SD, and 2 patients in PD were observed. The DCR was 84.6%, and the mPFS was 5 months. Of the 14 patients who received another EGFR-TKI, no patient in CR, 6 patients in PR, 6 patients in SD, and 2 patients in PD were observed. The DCR was 85.7%, and the mPFS was 9.5 months. Significant difference was found between the two groups in PFS but not

  17. Influence of oral glutamine supplementation on survival outcomes of patients treated with concurrent chemoradiotherapy for locally advanced non-small cell lung cancer

    International Nuclear Information System (INIS)

    Glutamine (Gln) supplementation during concurrent chemoradiotherapy (C-CRT) effectively reduces the incidence and severity of acute radiation-induced esophagitis (RIE). However, there are concerns that Gln might stimulate tumor growth, and therefore negatively impact the outcomes of anticancer treatment. We retrospectively investigated the effect of co-administration of oral Gln during C-CRT on survival outcomes of patients with stage IIIB non-small cell lung carcinoma (NSCLC). We additionally evaluated role of oral Gln in preventing C-CRT-induced weight change, acute and late toxicities. The study included 104 patients: 56 (53.8%) received prophylactic powdered Gln (Gln+) orally at a dose of 10 g/8 h and 48 (46.2%) did not receive Gln (Gln-) and served as controls. The prescribed radiation dose to the planning target volume was 66 Gy in 2-Gy fractions. Primary endpoints of progression-free survival (PFS), local/regional progression-free survival (LRPFS), and overall survival (OS) were correlated with status of Gln supplementation. Oral Gln was well tolerated except for mild nausea/vomiting in 14 (25.0%) patients. There was no C-CRT-related acute or late grade 4–5 toxicity. Administration of Gln was associated with a decrease in the incidence of grade 3 acute radiation-induced esophagitis (RIE) (7.2% vs. 16.7% for Gln+ vs. Gln-; p=0.02) and late-RIE (0% vs. 6.3%; p=0.06), a reduced need for unplanned treatment breaks (7.1% vs. 20.8%; p=0.04), and reduced incidence of weight loss (44.6% vs. 72.9%; p=0.002). At a median follow-up of 24.2 months (range 9.2-34.4) the median OS, LRPFS, and PFS for Gln+ vs. Gln- cohorts were 21.4 vs. 20.4 (p=0.35), 14.2 vs.11.3 (p=0.16), and 10.2 vs. 9.0 months (p=0.11), respectively. In our study, supplementation with Gln during C-CRT had no detectable negative impact on tumor control and survival outcomes in patients with Stage IIIB NSCLC. Furthermore, Gln appeared to have a beneficial effect with respect to prevention of weight loss

  18. Phase I-II trial of concomitant continuous carboplatin (CBDCA) infusion and radiotherapy in advanced nonsmall cell lung cancer with evaluation for surgery: final report

    International Nuclear Information System (INIS)

    Purpose: The goal of this trial was to determine the maximum tolerable dose when carboplatin (CBDCA) was administered in continuous infusion concurrently with radiotherapy in patients with nonsmall cell lung cancer. Methods and Materials: From October 1989 to July 1993, 54 patients were studied (male/female ratio: 44 to 10), median age was 62 years. Two patients had Stage II cancer, 22 had Stage IIIA, 24 had Stage IIIB, and 6 had Stage IV. Carboplatin was given for 96 h, starting at a dose of 30 mg/m2/day: 13 patients received 30 mg/m2/day (group A), 12 patients received 50 mg/m2/day (group B), 12 patients received 70 mg/m2/day (group C), 10 patients received 90 mg/m2/day (group D), and 7 patients 110 mg/m2/day (group E). The radiation dose was 50.40 Gy delivered to the target volume in 5.3 weeks. Results: Fifty-three of 54 patients were evaluable for toxicity and 52 out of 54 for response. Toxicity (Miller score): Myelotoxicity: in groups A and B it was almost absent; in groups C and D it was moderate (leukopenia G1-2: 45.4% patients; trombocytopenia G1-2: 22.7%, G3: 9%; anemia G1-2: 9%); only in group E was it severe (leukopenia G1 and G3 16.6% respectively; trombocytopenia G3: 33.3%, G4: 16.6%; anemia G1-2: 50%). Nephrotoxicity was present only in one patient of group E and was Grade 3. Nausea and vomiting were related to CBDCA dose. One patient in Group E died of intractable toxicity 3 days after the end of infusion; then the study was closed. The limiting toxicity dose was shown to be 110 mg/m2/day given for 96 h. Clinical response rate: Twenty-six of 52 patients had major response, 24 had minor response, and only 2 patients had progression of disease. Surgery: Twenty-one of 52 tumors were judged resectable: 18 patients had complete tumor resection, 1 had exploratory thoracotomy, and 2 patients refused surgery. Pathological response rate: Five patients had pathologic state T0 or Tis. Conclusions: These results indicate that the maximum tolerable dose of CBDCA

  19. A Study Of Oral PF-02341066, A c-Met/Hepatocyte Growth Factor Tyrosine Kinase Inhibitor, In Patients With Advanced Cancer

    Science.gov (United States)

    2016-06-03

    Non-Small Cell Lung Cancer (ALK-positive); Non-Small Cell Lung Cancer (c-Met Dependent); Non-Small Cell Lung Cancer (ROS Marker Positive); Systemic Anaplastic Large-Cell Lymphoma; Advanced Malignancies (Except Leukemia)

  20. A Randomized study on the Effects of Paclitaxel Liposme and Cisplatin Induction Chemotherapy Followed Concurrent Chemoradiotherapy and Sequential Radiotherapy on Locally Advanced Non-small Cell Lung Cancer Patients

    Directory of Open Access Journals (Sweden)

    Youyi DAI

    2011-02-01

    Full Text Available Background and objective Sequential and concurrent chemoradiotherapy were widely studied in locally advanced non-small cell lung cancer (NSCLC, but the reports of induction chemotherapy followed concurrent chemoradiotherapy are rare so far. The little side effects of paclitaxel liposme may be convenient to carry out induction chemotherapy followed concurrent chemoradiotherapy. The aim of this study is to compare the effects and side effects of TP regimen (Paclitaxel liposme and cisplatin induction chemotherapy followed concurrent chemoradiotherapy with sequential radiotherapy on locally advanced NSCLC. Methods Sixty locally advanced NSCLC patients were randomly divided into group A, induction chemotherapy followed concurrent chemoradiotherapy and group B, sequential radiotherapy group. The patients in group A received 2-3 cycles of induced chemotherapy included of Paclitaxel liposme 135 mg/m2-175 mg/m2, d1 and cisplatin 70 mg/m2-80 mg/m2, d2, 3 weeks repeat and after 2-3 cycles followed by concurrent chemoradiotherapy. The patients in group B received chemotherapy, (as described above in group A 4-6 cycles of chemotherapy followed one cycle of radiotherapy. The three-dimensional conformal radiotherapy at the total dose of 56 Gy-70 Gy was applied in all patients. Results The response rate in group A and group B were 80.3% and 60%, respectively (P=0.042. 1-year survival rates were 71.4% and 53.2%, respectively (P=0.18. And there were no significant difference of myelosuppression, radiation esophagitis and pulmonary fibrosis between the two groups (P=0.09, P=0.147, P=0.276, respectively. Conclusion The recent effects of induction chemotherapy followed by concurrent chemoradiotherapy group were better than sequential radiotherapy group on locally advanced NSCLC and there was no significant difference in side effects between the two groups.

  1. Acquired EGFR C797S mediates resistance to AZD9291 in advanced non-small cell lung cancer harboring EGFR T790M

    OpenAIRE

    Thress, Kenneth S.; Paweletz, Cloud P.; Felip, Enriqueta; Cho, Byoung Chul; Stetson, Daniel; Dougherty, Brian; Lai, Zhongwu; Markovets, Aleksandra; Vivancos, Ana; Kuang, Yanan; Ercan, Dalia; Matthews, Sarah; Cantarini, Mireille; Barrett, J. Carl; Jänne, Pasi A.

    2015-01-01

    Here we studied cell-free plasma DNA (cfDNA) collected from subjects with advanced lung cancer whose tumors had developed resistance to the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) AZD9291. We first performed next-generation sequencing of cfDNA from seven subjects and detected an acquired EGFR C797S mutation in one; expression of this mutant EGFR construct in a cell line rendered it resistant to AZD9291. We then performed droplet digital PCR on serial cfDNA spec...

  2. 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...

  3. 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

  4. 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...

  5. 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

  6. Induction gemcitabine in standard dose or prolonged low-dose with cisplatin followed by concurrent radiochemotherapy in locally advanced non-small cell lung cancer: a randomized phase II clinical trial

    International Nuclear Information System (INIS)

    The optimal combination of chemotherapy with radiation therapy for treatment locally advanced non-small cell lung cancer (NSCLC) remains an open issue. This randomized phase II study compared gemcitabine in two different schedules and cisplatin - as induction chemotherapy, followed by radiation therapy concurrent with cisplatin and etoposid. Eligible patients had microscopically confirmed inoperable non-metastatic non-small cell lung cancer; fulfilled the standard criteria for platin-based chemotherapy; and signed informed consent. Patients were treated with 3 cycles of induction chemotherapy with gemcitabine and cisplatin. Two different aplications of gemcitabine were compared: patients in arm A received gemcitabine at 1250 mg/m2 in a standard half hour i.v. infusion on days 1 and 8; patients in arm B received gemcitabine at 250 mg/m2 in prolonged 6-hours i.v. infusion on days 1 and 8. In both arms, cisplatin 75 mg/m2 on day 2 was administered. All patients continued treatment with radiation therapy with 60–66 Gy concurrent with cisplatin 50 mg/m2 on days 1, 8, 29 and 36 and etoposid 50 mg/m2 on days 1–5 and 29–33. The primary endpoint was response rate (RR) after induction chemotherapy; secondary endpoints were toxicity, progression-free survival (PFS) and overall survival (OS). From September 2005 to November 2010, 106 patients were recruited to this study. No statistically signifficant differences were found in RR after induction chemotherapy between the two arms (48.1% and 57.4%, p = 0.34). Toxicity profile was comparable and mild with grade 3/4 neutropenia as primary toxicity in both arms. One patient in arm B suffered from acute peripheral ischemia grade 4 and an amputation of lower limb was needed. With a median follow-up of 69.3 months, progression-free survival and median survival in arm A were 15.7 and 24.8 months compared to 18.9 and 28.6 months in arm B. The figures for 1- and 3-year overall survival were 73.1% and 30.8% in arm A, and 81.5 % and

  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. 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

  9. 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.

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

    Institute of Scientific and Technical Information of China (English)

    王杰; 胡学宁; 陈大兴

    2014-01-01

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

  11. The superiority of hybrid-volumetric arc therapy (VMAT) technique over double arcs VMAT and 3D-conformal technique in the treatment of locally advanced non-small cell lung cancer – A planning study

    International Nuclear Information System (INIS)

    Purpose: To compare the dosimetric performance of three different treatment techniques – conformal radiotherapy (CRT), double arcs volumetric modulated arc therapy (RapidArc, RA) and Hybrid-RapidArc (H-RA) for locally-advanced non-small cell lung cancer (NSCLC). Material and methods: CRT, RA and H-RA plans were optimized for 24 stage III NSCLC patients. The target prescription dose was 60 Gy. CRT consisted of 5–7 coplanar fields, while RA comprised of two 204o arcs. H-RA referred to two 204o arcs plus 2 static fields, which accounted for approximately half of the total dose. The plans were optimized to fulfill the departmental plan acceptance criteria. Results: RA and H-RA yielded a 20% better conformity compared with CRT. Lung volume receiving >20 Gy (V20) and mean lung dose (MLD) were the lowest in H-RA (V20 1.7% and 2.1% lower, MLD 0.59 Gy and 0.41 Gy lower than CRT and RA respectively) without jeopardizing the low-dose lung volume (V5). H-RA plans gave the lowest mean maximum spinal cord dose (34.4 Gy, 3.9 Gy < CRT and 2.2 Gy < RA plans) and NTCP of lung. Higher average MU per fraction (addition 52.4 MU) was observed with a reduced treatment time compared with CRT plans. Conclusion: The H-RA technique was superior in dosimetric outcomes for treating locally-advanced NSCLC compared to CRT and RA.

  12. Can EGFR-TKIs be used in first line treatment for advanced non-small cell lung cancer based on selection according to clinical factors ? -- A literature-based meta-analysis

    Directory of Open Access Journals (Sweden)

    Xu Chongrui

    2012-10-01

    Full Text Available Abstract Background In the first line treatment of non-small cell lung cancer (NSCLC, several clinical trials have shown that not all NSCLC patients can benefit from treatment with tyrosine kinase inhibitors (TKIs than receiving chemotherapy. Some trials treated patients with TKI according to their clinical characteristics. A few studies only chose patients with an epidermal grouth factor receptor (EGFR mutation for TKI therapy. We aimed to determine whether patients could be treated with TKIs based on clinical factors in the first-line setting. Methods We performed a meta-analysis of randomized trials involving patients with advanced NSCLC treated with chemotherapy or TKIs by different selections. Efficacy outcomes of interest were the objective response rate (ORR, progression-free survival (PFS and the overall survival (OS of each treatment arm. Results Four trials enrolled unselected patients, and two trials selected East Asian patients using the clinical factors of gender and smoking history. Five trials chose patients with an EGFR mutation who were randomized for treatment with TKI or chemotherapy. For unselected patients, the risk ratio (RR of the ORR was 3.52, the hazard ratio (HR of the PFS was 1.29 and the HR of the OS was 1.35. For the clinically selected patients, the RR of the ORR was 0.64. The HRs of the PFS and OS were 0.83 and 0.92, respectively. The ORR and PFS were better for TKIs than for chemotherapy in patients with an EGFR mutation. The ORR was 0.47, and the HRs of the PFS and OS were 0.36 and 1.00, respectively. Conclusions Advanced NSCLC patients with an EGFR mutation benefit most from TKIs. EGFR-TKI treatment is justified for patients with unknown EGFR status,and those who cannot tolerate chemotherapy owing to age, poor performance status (PS or other medical conditions, when selected according to clinical factors in the first-line setting.

  13. Classification and Regression Tree Analysis of Clinical Patterns that Predict Survival in 127 Chinese Patients with Advanced Non-small Cell Lung Cancer Treated by Gefitinib Who Failed to Previous Chemotherapy

    OpenAIRE

    Wang, Ziping; Guo, Jihong; Wang, Yan; Yutao LIU; Juan YANG

    2011-01-01

    Background and objective It has been proven that gefitinib produces only 10%-20% tumor regression in heavily pretreated, unselected non-small cell lung cancer (NSCLC) patients as the second- and third-line setting. Asian, female, nonsmokers and adenocarcinoma are favorable factors; however, it is difficult to find a patient satisfying all the above clinical characteristics. The aim of this study is to identify novel predicting factors, and to explore the interactions between clinical variable...

  14. 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

  15. 77 FR 24717 - Scientific Information Request on Local Therapies for the Treatment of Stage I Non-Small Cell...

    Science.gov (United States)

    2012-04-25

    ... Therapies for the Treatment of Stage I Non-Small Cell Lung Cancer and Endobronchial Obstruction Due to Advanced Lung Tumors AGENCY: Agency for Healthcare Research and Quality (AHRQ), HHS. ACTION: Request for... therapy (IMRT), Stereotactic body radiation therapy (SBRT), Proton beam radiotherapy (PBR),...

  16. Astragalus polysaccharide injection integrated with vinorelbine and cisplatin for patients with advanced non-small cell lung cancer: effects on quality of life and survival.

    Science.gov (United States)

    Guo, Li; Bai, Shu-Ping; Zhao, Ling; Wang, Xiao-Hong

    2012-09-01

    A platinum-based two-drug regimen is currently the standard of care for patients with advanced non-small-cell lung cancer (NSCLC). However, chemotherapy-induced side effects still remain a significant clinical problem. Astragalus polysaccharide (APS) is a polysaccharide isolated from the radix of astragalus membranaceus, a commonly used herbal compound in traditional Chinese medicine. APS was reported to increase tumor response, stabilize and improve performance status, and reduce chemotherapy toxicity. We designed this trial to determine whether APS injection integrated with vinorelbine and cisplatin (VC) offered an improved QOL over VC for patients with advanced NSCLC. Secondary objectives were tumor response, toxicity, and survival results. One hundred thirty-six patients with histologically or cytologically confirmed NSCLC were enrolled in this study from May 2008 to March 2010. Patients were randomized to receive either VC (VC arm) or VC combined with APS (VC-APS arm). The objective response rate of was 42.64% in the VC-APS arm and 36.76% in the VC arm. The difference was not statistically significant (P = 0.483). Median survival time was 10.7 and 10.2 months (P = 0.76) in VC-APS arm and VC arm, with 1-year survival rates of 35.3 and 32.4% (P = 0.717), respectively. After 3 cycles of treatment, there were significant differences in the overall patient QOL (P = 0.003), physical function (P = 0.01), fatigue (P pain (P = 0.007), and loss of appetite (P = 0.023) between the two study groups. In summary, we have proved that the treatment of APS integrated with VC had significantly improved QOL in patients with advanced NSCLC compared with VC alone. PMID:21928106

  17. Severe haemoptysis in patients with nonsmall cell lung carcinoma.

    Science.gov (United States)

    Razazi, Keyvan; Parrot, Antoine; Khalil, Antoine; Djibre, Michel; Gounant, Valerie; Assouad, Jalal; Carette, Marie France; Fartoukh, Muriel; Cadranel, Jacques

    2015-03-01

    Severe haemoptysis due to nonsmall cell lung cancer (NSCLC) is considered a grim condition, and there is still scarce data on its characteristics and outcome, despite new imaging and treatment modalities. This retrospective study sought to describe the clinical characteristics, pathophysiology and outcome of NSCLC-related haemoptysis. We included 125 consecutive patients with severe haemoptysis (>100 mL) at admission, 65 (52%) exhibiting squamous cell carcinoma. Tumour cavitation/necrosis was reported in 26 (21%) patients. 52 patients had received anticancer treatment, but none had received anti-angiogenic agents. Severe haemoptysis was related mainly to the bronchial artery (82%), and major pulmonary artery involvement was rare (6.4%). Interventional radiology was performed in 102 patients. Bleeding cessation was achieved in 108 (87%) out of 125 patients. The overall in-hospital and 1-year survival rates were 69% and 30%, respectively. Performance status (PS) ≥ 2 (OR 3.6, 95% CI 1.3-9.6), advanced stage (OR 8.6, 95% CI 2-37) and mechanical ventilation (OR 13, 95% CI 4.5-36) were independent predictors of in-hospital mortality. Performance status ≥ 2 (hazard ratio (HR) 2.4, 95% CI 1.5-3.7), advanced stage (HR 4, 95% CI 2.1-7.7), cancer progression (HR 2, 95% CI 1.01-2.7) and cavitation/necrosis (HR 1.7, 95% CI 1.21-3.2) were independently associated with 1-year mortality. Management of severe haemoptysis related to NSCLC should be improved, given our observed survival rates after hospital discharge. PMID:25359349

  18. Acquired EGFR C797S mediates resistance to AZD9291 in advanced non-small cell lung cancer harboring EGFR T790M

    Science.gov (United States)

    Thress, Kenneth S.; Paweletz, Cloud P.; Felip, Enriqueta; Cho, Byoung Chul; Stetson, Daniel; Dougherty, Brian; Lai, Zhongwu; Markovets, Aleksandra; Vivancos, Ana; Kuang, Yanan; Ercan, Dalia; Matthews, Sarah; Cantarini, Mireille; Barrett, J. Carl; Jänne, Pasi A.; Oxnard, Geoffrey R.

    2015-01-01

    Here we studied cell-free plasma DNA (cfDNA) collected from subjects with advanced lung cancer whose tumors had developed resistance to the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) AZD9291. We first performed next-generation sequencing of cfDNA from seven subjects and detected an acquired EGFR C797S mutation in one; expression of this mutant EGFR construct in a cell line rendered it resistant to AZD9291. We then performed droplet digital PCR on serial cfDNA specimens collected from 15 AZD9291-treated subjects. All were positive for T790M prior to treatment, but at resistance three molecular subtypes emerged: 6 cases acquired the C797S mutation, 5 cases maintained the T790M mutation but did not acquire the C797S mutation, and 4 cases lost the T790M mutation despite detecting of the underlying EGFR activating mutation. Our findings provide insight into the diversity of mechanisms through which tumors acquire resistance to AZD9291 and highlight the need for therapies able to overcome resistance mediated by EGFR C797S. PMID:25939061

  19. 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...

  20. 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

  1. Classification and Regression Tree Analysis of Clinical Patterns that Predict Survival in 127 Chinese Patients with Advanced Non-small Cell Lung Cancer Treated by Gefitinib Who Failed to Previous Chemotherapy

    Directory of Open Access Journals (Sweden)

    Ziping WANG

    2011-09-01

    Full Text Available Background and objective It has been proven that gefitinib produces only 10%-20% tumor regression in heavily pretreated, unselected non-small cell lung cancer (NSCLC patients as the second- and third-line setting. Asian, female, nonsmokers and adenocarcinoma are favorable factors; however, it is difficult to find a patient satisfying all the above clinical characteristics. The aim of this study is to identify novel predicting factors, and to explore the interactions between clinical variables and their impact on the survival of Chinese patients with advanced NSCLC who were heavily treated with gefitinib in the second- or third-line setting. Methods The clinical and follow-up data of 127 advanced NSCLC patients referred to the Cancer Hospital & Institute, Chinese Academy of Medical Sciences from March 2005 to March 2010 were analyzed. Multivariate analysis of progression-free survival (PFS was performed using recursive partitioning, which is referred to as the classification and regression tree (CART analysis. Results The median PFS of 127 eligible consecutive advanced NSCLC patients was 8.0 months (95%CI: 5.8-10.2. CART was performed with an initial split on first-line chemotherapy outcomes and a second split on patients’ age. Three terminal subgroups were formed. The median PFS of the three subsets ranged from 1.0 month (95%CI: 0.8-1.2 for those with progressive disease outcome after the first-line chemotherapy subgroup, 10 months (95%CI: 7.0-13.0 in patients with a partial response or stable disease in first-line chemotherapy and age <70, and 22.0 months for patients obtaining a partial response or stable disease in first-line chemotherapy at age 70-81 (95%CI: 3.8-40.1. Conclusion Partial response, stable disease in first-line chemotherapy and age ≥ 70 are closely correlated with long-term survival treated by gefitinib as a second- or third-line setting in advanced NSCLC. CART can be used to identify previously unappreciated patient

  2. A phase II study of cisplatin with intravenous and oral vinorelbine as induction chemotherapy followed by concomitant chemoradiotherapy with oral vinorelbine and cisplatin for locally advanced non-small cell lung cancer

    International Nuclear Information System (INIS)

    Concomitant platinum-based chemotherapy and radiotherapy (CT-RT) is the recommended treatment for unresectable locally advanced stage III non-small cell lung cancer (NSCLC). We conducted a phase II study to evaluate the efficacy and safety of fractionated oral vinorelbine with cisplatin as induction CT followed by CT-RT. Patients with stage III NSCLC received 2 induction cycles of intravenous vinorelbine 25 mg/m2 and cisplatin 80 mg/m2 on day 1 and oral vinorelbine 60 mg/m2 on day 8. Responding patients received 2 more cycles of cisplatin 80 mg/m2 on day 1 and oral vinorelbine 20 mg on days 1, 3 and 5 concomitantly with radiotherapy 2 Gy daily, 5 days/week for a total of 66 Gy. Seventy patients, median age 61 years, were enrolled. Overall response rate (ORR) was 50.0%; Disease Control Rate was 81.42%. Median PFS was 14.58 months [95% CI, 10.97-18.75]. Median OS was 17.08 months [95% CI, 13.57-29.57]. One-year and 2-year survival rates were 68.6% [95% CI, 57.7-79.4] and 37%. One patient had a grade 3 pulmonary radiation injury and 26.5% had graded 1/2 esophagitis. In non-operable IIIA-IIIB NSCLC, the combination oral vinorelbine (fractionated fixed dose) plus cisplatin, during concomitant CT-RT, could offer a well-tolerated option, with comparable activity to I.V. vinorelbine-based chemoradiotherapy regimens. ClinicalTrials.gov, http://clinicaltrials.gov/ct2/show/NCT01839032

  3. Phase 2 Study of Concurrent Cetuximab Plus Definitive Thoracic Radiation Therapy Followed by Consolidation Docetaxel Plus Cetuximab in Poor Prognosis or Elderly Patients With Locally Advanced Non-Small Cell Lung Cancer

    International Nuclear Information System (INIS)

    Background: Recursive partitioning analysis has shown that Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ≥2, male sex, and age ≥70 years are prognostic of poor outcome in locally advanced non-small cell lung cancer (LA-NSCLC) patients. Concurrent chemoradiation therapy (CRT) improves survival, but toxicity is a concern in this frail patient cohort. We therefore opened this trial of concurrent definitive thoracic radiation therapy (XRT) and cetuximab, followed by consolidation docetaxel plus cetuximab. Methods and Materials: Eligible patients had pathologically proven, unresectable LA-NSCLC (stage IIA-“dry” IIIB). They had ECOG PS 2 or weight loss ≥5% in 3 months or were aged ≥70 years. The primary objective was progression-free survival (PFS). Secondary objectives included overall survival (OS) and overall response rate (ORR). Results: From May 2008 to November 2010, a total of 32 patients were evaluated in our single-institution, institutional review board–approved prospective clinical trial. Three patients were screen failures and 2 more withdrew consent before treatment, leaving 27 evaluable patients. One was removed because of poor therapy compliance, and 2 were taken off trial because of grade 3 cetuximab-related toxicities but were followed up under intent-to-treat analysis. The median follow-up and OS were 10.5 months. The median PFS was 7.5 months. The ORR was 59.3%. Eight early/sudden deaths were reported. Upon review, 6 patients developed severe pulmonary complications. Conclusions: Patients enrolled in this trial had improved OS compared with poor-PS historical controls (10.5 vs 6.4 months) and comparable OS to good-PS historical controls (10.5 vs 11.9 months) treated with XRT alone. However, pulmonary toxicity is a concern. Consolidative cetuximab/docetaxel, in conjunction with high-dose radiation therapy, is a putative cause

  4. Phase 2 Study of Concurrent Cetuximab Plus Definitive Thoracic Radiation Therapy Followed by Consolidation Docetaxel Plus Cetuximab in Poor Prognosis or Elderly Patients With Locally Advanced Non-Small Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Dilling, Thomas J. [Department of Radiation Oncology, Moffitt Cancer Center, Tampa, Florida (United States); Extermann, Martine [Department of Senior Adult Oncology, Moffitt Cancer Center, Tampa, Florida (United States); Kim, Jongphil [Department of Biostatistics and Bioinformatics, Moffitt Cancer Center, Tampa, Florida (United States); Thompson, Lora M. [Department of Supportive Care Medicine, Moffitt Cancer Center, Tampa, Florida (United States); Yue, Binglin [Department of Biostatistics and Bioinformatics, Moffitt Cancer Center, Tampa, Florida (United States); Stevens, Craig W. [Department of Radiation Oncology, Moffitt Cancer Center, Tampa, Florida (United States); Antonia, Scott; Gray, Jhanelle; Williams, Charles; Haura, Eric; Pinder-Schenck, Mary; Tanvetyanon, Tawee [Department of Thoracic Oncology, Moffitt Cancer Center, Tampa, Florida (United States); Kim, Sungjune [Department of Radiation Oncology, Moffitt Cancer Center, Tampa, Florida (United States); Chiappori, Alberto, E-mail: alberto.chiappori@moffitt.org [Department of Thoracic Oncology, Moffitt Cancer Center, Tampa, Florida (United States)

    2014-11-15

    Background: Recursive partitioning analysis has shown that Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ≥2, male sex, and age ≥70 years are prognostic of poor outcome in locally advanced non-small cell lung cancer (LA-NSCLC) patients. Concurrent chemoradiation therapy (CRT) improves survival, but toxicity is a concern in this frail patient cohort. We therefore opened this trial of concurrent definitive thoracic radiation therapy (XRT) and cetuximab, followed by consolidation docetaxel plus cetuximab. Methods and Materials: Eligible patients had pathologically proven, unresectable LA-NSCLC (stage IIA-“dry” IIIB). They had ECOG PS 2 or weight loss ≥5% in 3 months or were aged ≥70 years. The primary objective was progression-free survival (PFS). Secondary objectives included overall survival (OS) and overall response rate (ORR). Results: From May 2008 to November 2010, a total of 32 patients were evaluated in our single-institution, institutional review board–approved prospective clinical trial. Three patients were screen failures and 2 more withdrew consent before treatment, leaving 27 evaluable patients. One was removed because of poor therapy compliance, and 2 were taken off trial because of grade 3 cetuximab-related toxicities but were followed up under intent-to-treat analysis. The median follow-up and OS were 10.5 months. The median PFS was 7.5 months. The ORR was 59.3%. Eight early/sudden deaths were reported. Upon review, 6 patients developed severe pulmonary complications. Conclusions: Patients enrolled in this trial had improved OS compared with poor-PS historical controls (10.5 vs 6.4 months) and comparable OS to good-PS historical controls (10.5 vs 11.9 months) treated with XRT alone. However, pulmonary toxicity is a concern. Consolidative cetuximab/docetaxel, in conjunction with high-dose radiation therapy, is a putative cause.

  5. A teaching intervention in a contouring dummy run improved target volume delineation in locally advanced non-small cell lung cancer. Reducing the interobserver variability in multicentre clinical studies

    International Nuclear Information System (INIS)

    Interobserver variability in the definition of target volumes (TVs) is a well-known confounding factor in (multicentre) clinical studies employing radiotherapy. Therefore, detailed contouring guidelines are provided in the prospective randomised multicentre PET-Plan (NCT00697333) clinical trial protocol. This trial compares strictly FDG-PET-based TV delineation with conventional TV delineation in patients with locally advanced non-small cell lung cancer (NSCLC). Despite detailed contouring guidelines, their interpretation by different radiation oncologists can vary considerably, leading to undesirable discrepancies in TV delineation. Considering this, as part of the PET-Plan study quality assurance (QA), a contouring dummy run (DR) consisting of two phases was performed to analyse the interobserver variability before and after teaching. In the first phase of the DR (DR1), radiation oncologists from 14 study centres were asked to delineate TVs as defined by the study protocol (gross TV, GTV; and two clinical TVs, CTV-A and CTV-B) in a test patient. A teaching session was held at a study group meeting, including a discussion of the results focussing on discordances in comparison to the per-protocol solution. Subsequently, the second phase of the DR (DR2) was performed in order to evaluate the impact of teaching. Teaching after DR1 resulted in a reduction of absolute TVs in DR2, as well as in better concordance of TVs. The Overall Kappa(κ) indices increased from 0.63 to 0.71 (GTV), 0.60 to 0.65 (CTV-A) and from 0.59 to 0.63 (CTV-B), demonstrating improvements in overall interobserver agreement. Contouring DRs and study group meetings as part of QA in multicentre clinical trials help to identify misinterpretations of per-protocol TV delineation. Teaching the correct interpretation of protocol contouring guidelines leads to a reduction in interobserver variability and to more consistent contouring, which should consequently improve the validity of the overall study

  6. Analysis of clinical and dosimetric factors associated with severe acute radiation pneumonitis in patients with locally advanced non-small cell lung cancer treated with concurrent chemotherapy and intensity-modulated radiotherapy

    Directory of Open Access Journals (Sweden)

    Xu Bo

    2010-05-01

    Full Text Available Abstract Background To evaluate the association between the clinical, dosimetric factors and severe acute radiation pneumonitis (SARP in patients with locally advanced non-small cell lung cancer (LANSCLC treated with concurrent chemotherapy and intensity-modulated radiotherapy (IMRT. Methods We analyzed 94 LANSCLC patients treated with concurrent chemotherapy and IMRT between May 2005 and September 2006. SARP was defined as greater than or equal 3 side effects and graded according to Common Terminology Criteria for Adverse Events (CTCAE version 3.0. The clinical and dosimetric factors were analyzed. Univariate and multivariate logistic regression analyses were performed to evaluate the relationship between clinical, dosimetric factors and SARP. Results Median follow-up was 10.5 months (range 6.5-24. Of 94 patients, 11 (11.7% developed SARP. Univariate analyses showed that the normal tissue complication probability (NTCP, mean lung dose (MLD, relative volumes of lung receiving more than a threshold dose of 5-60 Gy at increments of 5 Gy (V5-V60, chronic obstructive pulmonary disease (COPD and Forced Expiratory Volume in the first second (FEV1 were associated with SARP (p p = 0.001 and V10 (p = 0.015 were the most significant factors associated with SARP. The incidences of SARP in the group with NTCP > 4.2% and NTCP ≤4.2% were 43.5% and 1.4%, respectively (p 50% were 5.7% and 29.2%, respectively (p Conclusions NTCP value and V10 are the useful indicators for predicting SARP in NSCLC patients treated with concurrent chemotherapy and IMRT.

  7. Analysis of clinical and dosimetric factors associated with severe acute radiation pneumonitis in patients with locally advanced non-small cell lung cancer treated with concurrent chemotherapy and intensity-modulated radiotherapy

    International Nuclear Information System (INIS)

    To evaluate the association between the clinical, dosimetric factors and severe acute radiation pneumonitis (SARP) in patients with locally advanced non-small cell lung cancer (LANSCLC) treated with concurrent chemotherapy and intensity-modulated radiotherapy (IMRT). We analyzed 94 LANSCLC patients treated with concurrent chemotherapy and IMRT between May 2005 and September 2006. SARP was defined as greater than or equal 3 side effects and graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. The clinical and dosimetric factors were analyzed. Univariate and multivariate logistic regression analyses were performed to evaluate the relationship between clinical, dosimetric factors and SARP. Median follow-up was 10.5 months (range 6.5-24). Of 94 patients, 11 (11.7%) developed SARP. Univariate analyses showed that the normal tissue complication probability (NTCP), mean lung dose (MLD), relative volumes of lung receiving more than a threshold dose of 5-60 Gy at increments of 5 Gy (V5-V60), chronic obstructive pulmonary disease (COPD) and Forced Expiratory Volume in the first second (FEV1) were associated with SARP (p < 0.05). In multivariate analysis, NTCP value (p = 0.001) and V10 (p = 0.015) were the most significant factors associated with SARP. The incidences of SARP in the group with NTCP > 4.2% and NTCP ≤4.2% were 43.5% and 1.4%, respectively (p < 0.01). The incidences of SARP in the group with V10 ≤50% and V10 >50% were 5.7% and 29.2%, respectively (p < 0.01). NTCP value and V10 are the useful indicators for predicting SARP in NSCLC patients treated with concurrent chemotherapy and IMRT

  8. 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...

  9. An IMRT/VMAT Technique for Nonsmall Cell Lung Cancer

    OpenAIRE

    Nan Zhao; Ruijie Yang; Junjie Wang; Xile Zhang; Jinna Li

    2015-01-01

    The study is to investigate a Hybrid IMRT/VMAT technique which combines intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) for the treatment of nonsmall cell lung cancer (NSCLC). Two partial arcs VMAT, 5-field IMRT, and hybrid plans were created for 15 patients with NSCLC. The hybrid plans were combination of 2 partial arcs VMAT and 5-field IMRT. The dose distribution of planning target volume (PTV) and organs at risk (OARs) for hybrid technique was compa...

  10. The early predictive value of a decrease of metabolic tumor volume in repeated {sup 18}F-FDG PET/CT for recurrence of locally advanced non-small cell lung cancer with concurrent radiochemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Wei, E-mail: weihuang@mcw.com [Department of Radiation Oncology (Chest Section), Shandong' s Key Laboratory of Radiation Oncology, Shandong Cancer Hospital, Shandong Academy of Medical Sciences, 440 Jiyan Road, Jinan 250117 (China); Liu, Bo; Fan, Min [Department of Internal Medicine Oncology, Shandong Cancer Hospital, Shandong Academy of Medical Sciences, Jinan (China); Zhou, Tao [Department of Radiation Oncology (Chest Section), Shandong' s Key Laboratory of Radiation Oncology, Shandong Cancer Hospital, Shandong Academy of Medical Sciences, 440 Jiyan Road, Jinan 250117 (China); Fu, Zheng [PET/CT center, Shandong Cancer Hospital, Shandong Academy of Medical Sciences, Jinan (China); Zhang, Zicheng; Li, Hongsheng [Department of Radiation Oncology (Chest Section), Shandong' s Key Laboratory of Radiation Oncology, Shandong Cancer Hospital, Shandong Academy of Medical Sciences, 440 Jiyan Road, Jinan 250117 (China); Li, Baosheng, E-mail: alvinbird@163.com [Department of Radiation Oncology (Chest Section), Shandong' s Key Laboratory of Radiation Oncology, Shandong Cancer Hospital, Shandong Academy of Medical Sciences, 440 Jiyan Road, Jinan 250117 (China)

    2015-03-15

    Highlights: •The patients underwent the second FDG PET during the early stage of concurrent chemoradiotherapy (CCRT). •To our knowledge, this could be the first study showing that the repeated FDG PET during the early stage of CCRT has added value by being a prognostic factor for recurrence of the locally advanced NSCLC patients. •This is a result of continuous research. •The decrease of MTV was the only significant risk factor for recurrence. -- Abstract: Purpose: The aim of this study is to investigate the value of [{sup 18}F] fluorodeoxyglucose positron emission tomography/computed tomography ({sup 18}F FDG PET/CT) to predict recurrence of patients with locally advanced non-small cell lung cancer (NSCLC) during the early stage of concurrent chemoradiotherapy (CCRT). Methods: A total of 53 stage III NSCLC patients without diabetics or undergoing surgery were enrolled in the prospective study. Those patients were evaluated by FDG PET before and following 40 Gy radiotherapy (RT) with a concurrent cisplatin-based heterogeneous chemotherapy regimen. Semiquantitative assessment was used to determine maximum and mean SUVs (SUVmax/SUVmean) and metabolic tumor volume (MTV) of the primary tumor. The prognostic significance of PET/CT parameters and other clinical variables was assessed using Cox regression analyses. The cutoffs of PET/CT parameters which have been determined by the previous study were used to separate the groups with Kaplan–Meier curves. Results: Recurrence rates at 1- and 2-years were 18.9% (10/53) and 50.9% (27/53) for all patients, respectively. Cox regression analysis showed that the only prognostic factor for recurrence was a decrease of MTV. Using the cutoff of 29.7%, a decrease of MTV can separate the patients into 2 groups with Kaplan–Meier curve successfully. Conclusion: The prospective study has reinforced the early predictive value of MTV in repeated {sup 18}F-FDG PET/CT for recurrence in a subgroup of locally advanced NSCLC who

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

    Institute of Scientific and Technical Information of China (English)

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

    2013-01-01

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

  12. A Phase II Clinical Trial of Celecoxib Combined with Platinum-Based Regimen as First-Line Chemotherapy for Advanced Non-Small Cell Lung Cancer Patients with Cyclooxygenase-2 Positive Expression

    Institute of Scientific and Technical Information of China (English)

    Jun Zhao; Mei-na Wu; Xu-yi Liu; Jie Wang; Zhi-jie Wang; Jian-chun Duan; Qing-zhi Guo; Hua Bai; Lu Yang; Tong-tong An; Xin Wang; Yu-yan Wang

    2009-01-01

    Objective: To evaluate the efficacy and safety of celecoxib plus platinum-doublet as first-line chemotherapy in treatment of advanced non-small cell lung cancer (NSCLC), and to determine the subgroup benefiting from celecoxib combined therapy by molecular analysis. Methods: A total of 44 treatment-naive patients of advanced NSCLC with positive cyclooxygenase-2 (COX-2) expression confirmed by immunohistochemical (IHC) staining were designed to receive celecoxib plus platinum-doublet chemotherapy (cisplatin plus gemcitabine, novelbine or docetaxol) from February 2005 to May 2007. On 5(7 day before chemotherapy, 400 mg celecoxib was administered twice a day orally until obvious evidence of disease progression or intolerable toxicity was found. Adverse events were recorded according to NCI-CTC criteria. The primary endpoint was overall survival (OS). The secondary endpoints included progression-free survival (PFS), 1-year survival rate, response rate (RR) and safety. Additionally, we detected epithelial growth factor receptor (EGFR) status including EGFR gene amplification by real-time PCR and gene mutations by DHPLC followed by sequencing. Results: The response rate was 45% (20/44), and the disease control rate (DCR) was 59% (26/44). The median progression-free survival time and median survival time were 6 m and 18 m, respectively. The 1-year survival rate was 68%. Chemotherapy cycle numbers and best response were found to be the predictive factors for PFS by COX model analysis (P=0.023 and P=0.000, respectively). No factor was found to affect OS. The most common toxicities included neutropenia and nausea/vomit. EGFR gene amplification was an independent prognostic factor influencing OS (P=0.0002). Patients with EGFR mutations (exon 21) had a tendency of disease progression (P=0.041). Conclusion: Encouraging activities of celecoxib combined with platinum-doublet chemotherapy were demonstrated in treatment-naive patients with advanced NSCLC, with good tolerances. For

  13. 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.

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

    OpenAIRE

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

    2016-01-01

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

  15. 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

  16. HDAC6-mediated EGFR stabilization and activation restrict cell response to sorafenib in non-small cell lung cancer cells.

    Science.gov (United States)

    Wang, Zhihao; Hu, Pengchao; Tang, Fang; Xie, Conghua

    2016-05-01

    Sorafenib is a multi-targeted kinase inhibitor and has been the subject of extensive clinical research in advanced non-small cell lung cancer (NSCLC). However, sorafenib fails to improve overall survival of patients with advanced NSCLC. The molecular mechanisms that account for this phenomenon are unclear. Here we show that sorafenib treatment stabilizes epidermal growth factor receptor (EGFR) and activates EGFR pathway. Moreover, this is partly mediated by stabilization of histone deacetylase 6 (HDAC6), which has been shown to regulate EGFR endocytic trafficking and degradation. Overexpression of HDAC6 confers resistance to sorafenib in NSCLC cells. Inhibition of HDAC6 with selective inhibitors synergizes with sorafenib to kill NSCLC cells via inhibition of sorafenib-mediated EGFR pathway activation. Taken together, our findings might partly explain the failure of Phase III trial of sorafenib in improving overall survival of advanced NSCLC patients and bear possible implications for the improvement on the efficacy of sorafenib in treatment of NSCLC. PMID:27090797

  17. 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

  18. XRCC1 Arg399Gln and clinical outcome of platinum-based treatment for advanced non-small cell lung cancer:a meta-analysis in 17 studies

    Institute of Scientific and Technical Information of China (English)

    Jian CHEN; Qing-wei ZHAO; Gen-ming SHI; Lin-run WANG

    2012-01-01

    Objective:XRCC1 polymorphism is a research hotpot in individual treatment for non-small cell lung cancer (NSCLC).To obtain the association between XRCC1 polymorphism and clinical outcome of platinum-based treatment for NSCLC,a meta-analysis was conducted.Methods:Databases including PubMed,Embase,Cochrane,and Chinese National Knowledge Infrastructure (CNKI) were searched for publications that met the inclusion criteria.A fixed effect model was used to estimate pooled odds ratio (OR) and hazard ratio (HR) with 95% confidence interval (CI) for the association between XRCC1 Arg399Gln and response or survival of platinum-based treatment for advanced NSCLC.A chi-squared-based Q-test was used to test the heterogeneity hypothesis.Egger's test was used to check publication bias.Results:Seventeen published case-control studies that focus on the association between XRCC1 Arg399GIn and response or survival of platinum-based treatment for advanced NSCLC in 2 256 subjects were included in this meta-analysis,of whom 522 were AA genotypes (23.2% frequency),916 AG genotypes (40.6% frequency),and 818 GG genotypes (36.2% frequency).The overall response rate (ORR) was 45.2% (110/243) for AA genotype patients,29.9% for AG genotype (73/244),and 30.7% for GG genotype (124/403).The heterogeneity test did not show any heterogeneity and the Egger's test did not reveal an obvious publication bias among the included studies.The meta-analysis indicated that AA genotype patients presented higher response rates toward platinum drug treatment compared with G model (GG+GA) patients (GG vs.AA model:OR=0.489,95% CI 0.266-0.900,P=0.021;AG vs.AA model:OR=0.608,95% CI 0.392-0.941,P=0.026; GA+AA vs.GG model:OR=1.259,95% CI 0.931-1.701,P=0.135; GG+GA vs.AA model:OR=0.455,95% CI 0.313-0.663,P=0.0001).However,no evidence validates XRCC1 associates with the survival following platinum drug therapy.Conclusions:Our meta-analysis suggested that XRCC1 Arg399GIn is related with the

  19. 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....

  20. 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

  1. Association of GSTs gene polymorphisms with treatment outcome of advanced non-small cell lung cancer patients with cisplatin-based chemotherapy

    OpenAIRE

    Wu, Gun; Jiang, Bin; Liu, Xiaoqin; Shen, Yi; Yang, Shujuan

    2015-01-01

    We evaluated the association of GSTM1 null/present, GSTT1 null/present, and GSTP1 IIe105Val polymorphisms with the clinical response to chemotherapy and treatment outcome of NSCLC. Between October 2009 and October 2012, a total of 282 patients with advanced NSCLC were enrolled into our study, and they were followed up until October 2014. The genotypes of GSTM1, GSTT1, and GSTP1 IIe105Val were performed by polymerase chain reaction (PCR) coupled with restriction fragment length polymorphism (R...

  2. 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).

  3. 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

  4. Maintenance therapy in advanced non-small cell lung cancer%晚期非小细胞肺癌维持治疗的研究进展

    Institute of Scientific and Technical Information of China (English)

    程婷婷; 杨谨

    2011-01-01

    目的:总结维持治疗在晚期非小细胞肺癌中的研究进展,探讨维持治疗的意义.方法:应用PubMed和CNKI期刊全文数据库检索系统,以“NSCLC maintenance therapy及非小细胞肺癌,维持治疗”为关键词,共检索到2001-2011年相关文献284篇,纳入分析25篇.结果:维持治疗是近年来为延长晚期NSCLC患者生存期并提高其生存质量而出现的新的治疗观点,目前已有多项临床试验证实标准一线化疗结束使疾病获得控制后,继续给予维持治疗可以显著延长患者的无疾病进展生存期(progression-free survival,PFS),部分药物可以显著延长总生存(overall survival,OS),患者耐受良好.结论:维持治疗可以使晚期NSCLC患者获益,但是其最终疗效和患者的病理类型、EGFR突变状况、体力状况和对药物的耐受情况密切相关,结合患者的实际情况,进行个体化治疗,是NSCLC患者未来治疗的方向.%OBJECTIVE; To summarize the advances of maintenance therapy in NSCLC, and discuss the significance of this therapeutic method. METHODS; The full text database of PubMed and CNKI were searched, and the words " NSCLC ( maintenance therapy" were used as key words. Totally 284 related articles were retrieved between the year of 2001 and 2011 in all, then 25 were analyzed. RESULTS; Maintenance therapy emerged as a new viewpoint in these years in order to prolong the overall survival and to improve quality of life for patients with advanced NSCLC. At present,many clinical trials have demonstrated that the patients with advanced NSCLC who achieved CR.PR and SD after the first-line chemotherapy could be significantly prolonged Progression-free survivaKPFS) and overall survivalCOS) if they received continued maintenance therapy. The tolerance was well. CONCLUSIONS: Patients with advanced NSCLC can benefit from the maintenance therapy. However, the final therapeutic effect is closely related to the pathological type,EGFR mutation, physical

  5. Sequential (gemcitabine/vinorelbine) and concurrent (gemcitabine) radiochemotherapy with FDG-PET-based target volume definition in locally advanced non-small cell lung cancer: first results of a phase I/II study

    International Nuclear Information System (INIS)

    The aim of the study was to determine the maximal tolerated dose (MTD) of gemcitabine every two weeks concurrent to radiotherapy, administered during an aggressive program of sequential and simultaneous radiochemotherapy for locally advanced, unresectable non-small cell lung cancer (NSCLC) and to evaluate the efficacy of this regime in a phase II study. 33 patients with histologically confirmed NSCLC were enrolled in a combined radiochemotherapy protocol. 29 patients were assessable for evaluation of toxicity and tumor response. Treatment included two cycles of induction chemotherapy with gemcitabine (1200 mg/m2) and vinorelbine (30 mg/m2) at day 1, 8 and 22, 29 followed by concurrent radiotherapy (2.0 Gy/d; total dose 66.0 Gy) and chemotherapy with gemcitabine every two weeks at day 43, 57 and 71. Radiotherapy planning included [18F] fluorodeoxyglucose positron emission tomography (FDG PET) based target volume definition. 10 patients were included in the phase I study with an initial gemcitabine dose of 300 mg/m2. The dose of gemcitabine was increased in steps of 100 mg/m2 until the MTD was realized. MTD was defined for the patient group receiving gemcitabine 500 mg/m2 due to grade 2 (next to grade 3) esophagitis in all patients resulting in a mean body weight loss of 5 kg (SD = 1.4 kg), representing 8% of the initial weight. These patients showed persisting dysphagia 3 to 4 weeks after completing radiotherapy. In accordance with expected complications as esophagitis, dysphagia and odynophagia, we defined the MTD at this dose level, although no dose limiting toxicity (DLT) grade 3 was reached. In the phase I/II median follow-up was 15.7 months (4.1 to 42.6 months). The overall response rate after completion of therapy was 64%. The median overall survival was 19.9 (95% CI: [10.1; 29.7]) months for all eligible patients. The median disease-free survival for all patients was 8.7 (95% CI: [2.7; 14.6]) months. After induction chemotherapy, the maximum tolerated dose

  6. Sequential (gemcitabine/vinorelbine and concurrent (gemcitabine radiochemotherapy with FDG-PET-based target volume definition in locally advanced non-small cell lung cancer: first results of a phase I/II study

    Directory of Open Access Journals (Sweden)

    Stanzel Sven

    2007-06-01

    Full Text Available Abstract Background The aim of the study was to determine the maximal tolerated dose (MTD of gemcitabine every two weeks concurrent to radiotherapy, administered during an aggressive program of sequential and simultaneous radiochemotherapy for locally advanced, unresectable non-small cell lung cancer (NSCLC and to evaluate the efficacy of this regime in a phase II study. Methods 33 patients with histologically confirmed NSCLC were enrolled in a combined radiochemotherapy protocol. 29 patients were assessable for evaluation of toxicity and tumor response. Treatment included two cycles of induction chemotherapy with gemcitabine (1200 mg/m2 and vinorelbine (30 mg/m2 at day 1, 8 and 22, 29 followed by concurrent radiotherapy (2.0 Gy/d; total dose 66.0 Gy and chemotherapy with gemcitabine every two weeks at day 43, 57 and 71. Radiotherapy planning included [18F] fluorodeoxyglucose positron emission tomography (FDG PET based target volume definition. 10 patients were included in the phase I study with an initial gemcitabine dose of 300 mg/m2. The dose of gemcitabine was increased in steps of 100 mg/m2 until the MTD was realized. Results MTD was defined for the patient group receiving gemcitabine 500 mg/m2 due to grade 2 (next to grade 3 esophagitis in all patients resulting in a mean body weight loss of 5 kg (SD = 1.4 kg, representing 8% of the initial weight. These patients showed persisting dysphagia 3 to 4 weeks after completing radiotherapy. In accordance with expected complications as esophagitis, dysphagia and odynophagia, we defined the MTD at this dose level, although no dose limiting toxicity (DLT grade 3 was reached. In the phase I/II median follow-up was 15.7 months (4.1 to 42.6 months. The overall response rate after completion of therapy was 64%. The median overall survival was 19.9 (95% CI: [10.1; 29.7] months for all eligible patients. The median disease-free survival for all patients was 8.7 (95% CI: [2.7; 14.6] months. Conclusion

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

    Institute of Scientific and Technical Information of China (English)

    徐成伟; 陈威龙

    2014-01-01

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

  9. 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...

  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. Correlation of F-18 FDG PET with morphometric tumor response after neoadjuvant chemoradiation in locally advanced (stage III) non-small cell lung cancer (NSCLC)

    International Nuclear Information System (INIS)

    Aim: To determine the role of 2-[(18)F] fluoro-2- deoxy-D-glucose (FDG) positron emission tomography (PET) in morphometric tumor response after neoadjuvant chemoradiation, findings in 32 patients were analyzed prospectively in an ongoing multicenter trial (LUCAS-MD, Germany). Material and Methods: Inclusion criteria was histologically confirmed NSCLC stage IIIA/IIIB. For staging all patients received a PET scan in addition to a spiral CT and/or MRI before therapy. Neoadjuvant treatment consisted of 2-3 cycles of chemotherapy with paclitaxel (225 mg/m2) and carboplatin (AUC 6), each d1 q22 and a block of chemoradiation (45Gy, 1.5Gy b.i.d., concomitant with paclitaxel (50 mg/m2) and carboplatin (AUC = 2), each d1, d8, d15) followed by surgery. All patients received a second PET after completion of neoadjuvant therapy prior to surgery. Whole-body PET (ECAT Exact 47) studies (attenuation corrected, iteratively reconstructed) were obtained 60 min. after injection of 6 MBq/kg body weight F-18 FDG. For semi-quantitative analysis, the tumor standardized uptake values (SUV), the tumor to background SUV ratio (T/B ratio), the metabolic tumor diameter (MTD) and the metabolic tumor index (MTI = SUV x MTD) were assessed in all primary tumors and in metastatic lymph nodes. Additionally, image fusion of PET with CT data was applied (using a HERMES Computer, Nuclear Diagnostics, Sweden). Results: So far, all patients (7/32) with complete metabolic response in lymph node metastases detected by PET, had no vital tumor cells (morphometric regression grade III). In primary tumors showing complete metabolic response, the regression grade was IIB (less than 10% vital tumor cells) or III. Conclusion: Morphometric tumor response after neoadjuvant therapy correlates strongly with metabolic remission by FDG-PET. PET precedes the tumor response as measured by CT after neoadjuvant treatment and may predict the long term therapeutic outcome in stage III NSCLC

  12. 中晚期非小细胞肺癌患者外周血Treg、Th17细胞化疗前后的变化及临床意义%Changes of Th17 and Treg Cells in the Peripheral Blood of Patients with Advanced Non-small Cell Lung Cancer Before and After Chemotherapy

    Institute of Scientific and Technical Information of China (English)

    赵丽丽; 张良明

    2015-01-01

    目的:分析中晚期非小细胞肺癌患者化疗前后外周血中 Treg 细胞和 Th17细胞比例变化及临床意义。方法收集51例中晚期非小细胞肺癌患者(观察组)化疗前后及47例健康对照组外周血标本,应用流式细胞术检测 Treg 细胞和 Th17细胞所占 CD4+ T 细胞的比例,观察 Treg 和 Th17细胞比例在化疗前后的变化及其相关性。结果化疗后缓解组外周血中 Th17及 Treg 细胞比例较化疗前降低(P 0.05)。非缓解组2种细胞的比例较化疗前增高(P 0. 05), but the proportion of Treg cells of the remission group was higher significantly(P < 0. 05). The proportion of Th17 and Treg cells of the non-remission group after chemotherapy were all significantly higher than before chemotherapy (P < 0. 05),and were higher than those of the control group(P < 0. 05). The proportion of Th17 cells were posi-tively related to the proportion of Treg cells in the peripheral blood of patients with advanced non-small cell lung cancer before and after chemotherapy(r = 0. 589,0. 657;P < 0. 05). Conclusion Chemotherapy can reduce the proportion of Th17 cells and Treg cells in the peripheral blood of patients with advanced non-small cell lung cancer, and has the positive significance for tumor immune function.

  13. Phase 2 trial of the use of neo adjuvant carboplatin, mitomcyn C and etoposide plus radiotherapy in the treatment of locally advanced non-small cell carcinoma of the lung; Estudo de fase 2 do uso de quimioterapia neo-adjuvante combinado carboplatina, mitomicina C e etoposido a radioterapia no tratamento do carcinoma broncogenico de celulas nao-pequenas localmente avancado

    Energy Technology Data Exchange (ETDEWEB)

    Murad, Andre M.; Saldanha, T.M.; Pereira, S.P. [Minas Gerais Univ., Belo Horizonte, MG (Brazil). Hospital das Clinicas; Moura, J.E. [Hospital Belo Horizonte, MG (Brazil); Xavier, O.G. [Instituto Joao Resende Alves, Belo Horizonte, MG (Brazil)

    1995-01-01

    Twenty-three patients (22 male and 1 female) with stage III non-small carcinoma of the lung without pleural effusion, age less than 70, adequate cardiac, renal, hematological and pulmonary functions, with Karnofsky performance status {>=} 60 were treated with 3 cycles 28-32 day cycles of carboplatin - 300 mg/m{sup 2} day 1, mitomycin C- 6 mg/m{sup 2} day 1 e etoposide-120 mg/m{sup 2} days 1,2,3. By the end of chemotherapy the patients were submitted to radiation (total dose of 54 Gy in 5 weeks). Median age was 60 (range 38-70). Median Karnofsky performance status was 70. Pathology: 16 squanous, 6 adenocarcinoma, and 1 large cell. Fifteen (65%) patients attained objective responses, including 3 (13%) complete responders. One patient had the complete response pathologically documented by thoracotomy. The median overall survival was 12 months (range 3-24). The 12 month overall survival was 50%. The toxicity was considered acceptable and manageable. The median nadir of thrombocytopenia was 79 x 10{sup 9}. There was no death due to treatment. This regimen seems to be effective in inducing some complete and prolonged tumor responses, with acceptable toxicity profile in patients with locally advanced non-small cell lung cancer. However, the results are still modest and needed to be improved. (author) 14 refs., 2 figs., 1 tab.

  14. 树突状细胞共培养因子诱导的杀伤细胞联合化疗治疗中晚期非小细胞肺癌的临床疗效%Clinical Efficacy of Dendritic Cells Co-cultured with Cytokine Induced Killer Cells Com-bined with Chemotherapy for Middle and Advanced Non-small Cell Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    罗敏; 张娟; 薛军

    2015-01-01

    Objective To investigate the effect of co-culture of dendritic cells and cytokine-induced killer cells on cyto-kine-induced killer cells,and the 2 co-cultured cells combined with oxaliplatin for advanced non-small cell lung cancer.Methods Patients with non-small cell lung cancer and malignant pleural effusions take density gradient centrifugation dendritic cells in vitro to obtain mature dendritic cells;from healthy patients monocytes in vitro obtained killer cells;2 cells were identified by flow cy-tometry after co-culture phenotypes,in vitro cytotoxicity was analyzed by MTT assay in advanced non-small cell lung cancer.Re-sults Malignant pleural effusion dendritic precursor cells were obtained after in vitro maturation of dendritic cells,dendritic cells cultured 9 days and showed markers CD83,CD80,CD86 and MHC-II related HLA-DR molecules than former culture were signifi-cantly higher ( P<0.05);after 2 weeks in dendritic cells co-cultured with killer cells and killer cells cultured alone,CD3 +, CD4 +,CD8 +number increased significantly,there had statistically significant difference (P<0.05) between groups.Dendrit-ic cells-killer cells in patients with advanced non-small cell lung cancer had inhibited the use of lethal than simply killer cells, there had statistical difference (P<0.05).Dendritic cells co-cultured with killer cells in combination with oxaliplatin for ad-vanced non-small cell lung cancer has the effect of killing in vitro,there had statistically difference (P<0.05).Conclusion Malignant pleural effusion derived dendritic cell precursors can induce mature dendritic cells cultured,mature dendritic cells com-bined with killer cells can promote the proliferation and lethal of killer cells,combined with oxaliplatin can enhancement killing effect of advanced non-small cell lung cancer.%目的 探讨树突状细胞与细胞因子诱导的杀伤细胞共培养对细胞因子诱导的杀伤细胞的作用及两者共培养后联合化疗药物奥沙利铂对

  15. 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.

  16. A teaching intervention in a contouring dummy run improved target volume delineation in locally advanced non-small cell lung cancer. Reducing the interobserver variability in multicentre clinical studies

    Energy Technology Data Exchange (ETDEWEB)

    Schimek-Jasch, Tanja; Prokic, Vesna; Doll, Christian; Grosu, Anca-Ligia; Nestle, Ursula [University Medical Center Freiburg, Department of Radiation Oncology, Freiburg (Germany); German Cancer Research Center (DKFZ), Heidelberg (Germany); German Cancer Consortium (DKTK) partner site: Freiburg, Heidelberg (Germany); Troost, Esther G.C. [Maastricht University Medical Centre, Department of Radiation Oncology (MAASTRO), GROW School for Oncology and Developmental Biology, Maastricht (Netherlands); Ruecker, Gerta [University Medical Center Freiburg, Institute for Medical Biometry and Statistics, Centre for Medical Biometry and Medical Informatics, Freiburg (Germany); Avlar, Melanie [German Cancer Research Center (DKFZ), Heidelberg (Germany); Duncker-Rohr, Viola [Ortenau-Klinikum Offenburg-Gengenbach, Department of Radiation Oncology, Gengenbach (Germany); Mix, Michael [University Medical Center Freiburg, Department of Nuclear Medicine, Freiburg (Germany); German Cancer Research Center (DKFZ), Heidelberg (Germany); German Cancer Consortium (DKTK) partner site: Freiburg, Heidelberg (Germany)

    2015-02-10

    Interobserver variability in the definition of target volumes (TVs) is a well-known confounding factor in (multicentre) clinical studies employing radiotherapy. Therefore, detailed contouring guidelines are provided in the prospective randomised multicentre PET-Plan (NCT00697333) clinical trial protocol. This trial compares strictly FDG-PET-based TV delineation with conventional TV delineation in patients with locally advanced non-small cell lung cancer (NSCLC). Despite detailed contouring guidelines, their interpretation by different radiation oncologists can vary considerably, leading to undesirable discrepancies in TV delineation. Considering this, as part of the PET-Plan study quality assurance (QA), a contouring dummy run (DR) consisting of two phases was performed to analyse the interobserver variability before and after teaching. In the first phase of the DR (DR1), radiation oncologists from 14 study centres were asked to delineate TVs as defined by the study protocol (gross TV, GTV; and two clinical TVs, CTV-A and CTV-B) in a test patient. A teaching session was held at a study group meeting, including a discussion of the results focussing on discordances in comparison to the per-protocol solution. Subsequently, the second phase of the DR (DR2) was performed in order to evaluate the impact of teaching. Teaching after DR1 resulted in a reduction of absolute TVs in DR2, as well as in better concordance of TVs. The Overall Kappa(κ) indices increased from 0.63 to 0.71 (GTV), 0.60 to 0.65 (CTV-A) and from 0.59 to 0.63 (CTV-B), demonstrating improvements in overall interobserver agreement. Contouring DRs and study group meetings as part of QA in multicentre clinical trials help to identify misinterpretations of per-protocol TV delineation. Teaching the correct interpretation of protocol contouring guidelines leads to a reduction in interobserver variability and to more consistent contouring, which should consequently improve the validity of the overall study

  17. 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.

  18. 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

  19. 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.

  20. Surgical results and long-term follow-up of T4-non-small cell lung cancer invading the left atrium or the intrapericardial base of the pulmonary veins

    OpenAIRE

    Stella, Franco; Dell'Amore, Andrea; Caroli, Guido; Dolci, Giampiero; Cassanelli, Nicola; Luciano, Giulia; Davoli, Fabio; Bini, Alessandro

    2012-01-01

    Patients with locally advanced non-small cell lung cancer infiltrating the left atrium (LA) or the intrapericardial base of the pulmonary veins (PVs) are generally not considered good candidates for surgery because of the poor long-term survival. In the last 10 years, 31 consecutive patients with non-small cell lung cancer directly invading the LA or the intrapericardial base of the PVs underwent surgery. Pneumonectomy was the operation performed most frequently. In-hospital mortality was 9.7...

  1. Radical radiotherapy for early nonsmall cell lung cancer

    International Nuclear Information System (INIS)

    Purpose: To evaluate the results of a departmental treatment policy in a consecutive series of patients with nonsmall cell carcinoma of the lung. A second purpose was to estimate the survival of patients treated with radical intent. A third purpose was to estimate the impact of comorbidity on the selection of patients for treatment and on its outcome. Methods and Materials: The records of 720 consecutive patients referred to a single Department of Radiation Oncology between 1979 and 1985 were reviewed. One hundred fifty patients with early stage (Stage I and II disease) were studied in detail and the results are presented for the outcome of 103 patients treated by radical radiotherapy. All patients were followed for a minimum period of five years or until death. Results: Patients referred for radiation therapy were elderly and usually had squamous cell carcinoma of the lung. Comorbidity was significant as was weight loss which occurred in a third of patients. The overall survival of patients treated with radical intent was 13%. In a small subgroup of patients with T1 tumors without weight loss and aged under 70 survival reached 50% at 5 years with no treatment-related mortality and with insignificant treatment-related morbidity. Conclusion: Highly selected subsets of patients suitable for treatment with radiotherapy can be defined equally as well as highly selected subsets of patients can be selected for surgery. Treatment outcome can be surprisingly good in these subsets indicating that the treatment of nonsmall cell lung cancer, particularly in older patients without comorbidity should not automatically be by a surgical approach

  2. 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...

  3. 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

  4. Traditional Chinese medicinal herbs combined with epidermal growth factor receptor tyrosine kinase inhibitor for advanced non-small cell lung cancer:a systematic review and meta-analysis

    Institute of Scientific and Technical Information of China (English)

    Zhong-liang Liu; Wei-rong Zhu; Wen-chao Zhou; Hai-feng Ying; Lan Zheng; Yuan-biao Guo; Jing-xian Chen; Xiao-heng Shen

    2014-01-01

    BACKGROUND: Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) targeted treatment has been a standard therapy for advanced non-small cell lung cancer (NSCLC), but it is not tolerated well by all patients. In China, some studies have reported that traditional Chinese medicinal herbs (TCMHs) may increase efifcacy and reduce toxicity when combined with EGFR-TKI, but outside of China few studies of this kind have been attempted. OBJECTIVE:This study is intended to systematically review the existing clinical evidence on TCMHs combined with EGFR-TKI for treatment of advanced NSCLC. SEARCH STRATEGY:PubMed, the Cochrane Library, the Excerpta Medica Database (EMBASE), the China BioMedical Literature (CBM), and the China National Knowledge Infrastructure (CNKI) and web site of the American Society of Clinical Oncology (ASCO), the European Society for Medical Oncology (ESMO), the World Conference of Lung Cancer (WCLC) were searched; the search included all documents published in English or Chinese before October 2013. INCLUSION CRITERIA:We selected randomized controlled trials based on speciifc criteria, the most important of which was that a TCMH plus EGFR-TKI treatment group was compared with an EGFR-TKI control group in patients with advanced NSCLC. DATA EXTRACTION AND ANALYSIS: The modiifed Jadad scale was used to assess the quality of studies. For each included study, patient characteristics, treatment details, therapeutic approach and clinical outcomes were collected on a standardized form. When disagreements on study inclusion or data extracted from a study emerged, the consensus of all coauthors provided the resolution. The clinical outcome metrics consisted of objective response rate (ORR; complete response + partial response divided by the total number of patients), disease control rate (DCR; complete response + partial response + no change divided by the total number of patients), survival rate, improved or stabilized Karnofsky performance status

  5. 541例女性晚期非小细胞肺癌患者的预后因素分析%Analysis of Prognostic Factors in 541 Female Patients with Advanced Non-small Cell Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    吴梅娜; 刘叙仪; 王洁; 王玉艳; 安彤同; 赵军; 杨鹭; 段建春; 王志杰; 卓明磊; 白桦

    2011-01-01

    背景与目的 随着女性肺癌发病率的攀升,其独特的临床和流行病学特征及良好预后引起了学界的关注.本研究通过回顾性分析女性晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)患者的临床资料,探讨其预后相关因素.方法 收集541例女性晚期NSCLC患者的临床资料,并随访至死亡.主要观察指标为总生存(overallsurvival,OS).采用SPSS 11.0统计软件进行生存分析.结果 全组腺癌占80.2% (434/541),总体中位OS为15个月(95%CI:13.87-16.13),1年、2年、5年生存率分别为58.8%,23.7%和3.20%.单因素分析显示,临床分期、ECOG评分、体重下降、临床症状、血行转移和一线治疗后化疗方案数>1、一线化疗有效、曾接受靶向治疗或放疗均与中位OS明显相关(P值均<0.05).治疗前体重下降、ECOG评分、靶向治疗及一线化疗有效为生存的独立预后因素(P值均<0.05).结论 女性晚期NSCLC患者的病理类型以腺癌为主,体重下降、ECOG评分、接受靶向治疗及一线化疗有效可能成为女性晚期NSCLC患者生存的独立预后指标.%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% (434/54 1).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

  6. 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

  7. 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

  8. 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)

  9. 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

  10. 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)

  11. Consensus for EGFR mutation testing in non-small cell lung cancer: results from a European workshop

    DEFF Research Database (Denmark)

    Pirker, Robert; Herth, Felix J F; Kerr, Keith M; Filipits, Martin; Taron, Miquel; Gandara, David; Hirsch, Fred R; Grunenwald, Dominique; Popper, Helmut; Smit, Egbert; Dietel, Manfred; Marchetti, Antonio; Manegold, Christian; Schirmacher, Peter; Thomas, Michael; Rosell, Rafael; Cappuzzo, Federico; Stahel, Rolf; de Stricker, Karin

    2010-01-01

    Activating somatic mutations of the tyrosine kinase domain of epidermal growth factor receptor (EGFR) have recently been characterized in a subset of patients with advanced non-small cell lung cancer (NSCLC). Patients harboring these mutations in their tumors show excellent response to EGFR...... tyrosine kinase inhibitors (EGFR-TKIs). The EGFR-TKI gefitinib has been approved in Europe for the treatment of adult patients with locally advanced or metastatic NSCLC with activating mutations of the EGFR TK. Because EGFR mutation testing is not yet well established across Europe, biomarker...

  12. Fluosol and oxygen breathing as an adjuvant to radiation therapy in the treatment of locally advanced non-small cell carcinoma of the lung: Results of a phase I/II study

    International Nuclear Information System (INIS)

    Fluosol, a perflourcarbon emulsion, has the ability to carry oxygen in solution. In conjunction with oxygen breathing and radiation, fluosol has been shown in animal models to enhance local tumor control. In September 1985, a Phase I/II Study was instituted to evaluate the effect of this adjuvant therapy with radiation in non-small cell carcinomas of the lung. Of the 49 patients administered Fluosol, 34 mild moderate adverse reactions were noted in 22 patients to either the test dose/infusion or post infusion. Flushing, dyspnea and hypertension and chills and/or fever were the typical symptoms. Transient elevation of blood chemistries were noted in some patients. Six patients had transient depression of WBC counts and two patients had transient depression of platelets. None of these altered treatment. Forty-five patients received Fluosol of which 34 completed the planned therapy. Six patients were diagnosed with metastatic disease during therapy and three patients died of their disease during treatment. Radiation therapy was administered at a daily fraction of 165 to 200 cGy per fraction to a total dose of 5940 to 6800 cGy

  13. The EGFR mutation status affects the relative biological effectiveness of carbon-ion beams in non-small cell lung carcinoma cells

    OpenAIRE

    Amornwichet, Napapat; Oike, Takahiro; Shibata, Atsushi; Nirodi, Chaitanya S.; Ogiwara, Hideaki; Makino, Haruhiko; Kimura, Yuka; HIROTA, YUKA; Isono, Mayu; Yoshida, Yukari; Ohno, Tatsuya; Kohno, Takashi; Nakano, Takashi

    2015-01-01

    Carbon-ion radiotherapy (CIRT) holds promise to treat inoperable locally-advanced non-small cell lung carcinoma (NSCLC), a disease poorly controlled by standard chemoradiotherapy using X-rays. Since CIRT is an extremely limited medical resource, selection of NSCLC patients likely to benefit from it is important; however, biological predictors of response to CIRT are ill-defined. The present study investigated the association between the mutational status of EGFR and KRAS, driver genes frequen...

  14. TP53 Mutations in Nonsmall Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Akira Mogi

    2011-01-01

    Full Text Available The tumor suppressor gene TP53 is frequently mutated in human cancers. Abnormality of the TP53 gene is one of the most significant events in lung cancers and plays an important role in the tumorigenesis of lung epithelial cells. Human lung cancers are classified into two major types, small cell lung cancer (SCLC and nonsmall cell lung cancer (NSCLC. The latter accounts for approximately 80% of all primary lung cancers, and the incidence of NSCLC is increasing yearly. Most clinical studies suggest that NSCLC with TP53 alterations carries a worse prognosis and may be relatively more resistant to chemotherapy and radiation. A deep understanding of the role of TP53 in lung carcinogenesis may lead to a more reasonably targeted clinical approach, which should be exploited to enhance the survival rates of patients with lung cancer. This paper will focus on the role of TP53 in the molecular pathogenesis, epidemiology, and therapeutic strategies of TP53 mutation in NSCLC.

  15. The treatment Results of Radiotherapy for nonsmall Cell Lung Cancer

    International Nuclear Information System (INIS)

    From Nov. 1983 through Jan. 1986, 43 patients with nonsmall cell lung cancer were treated by radiation therapy at Inje Medical College Paik Hospital. 38 patients were available for the analysis of this study. 33 patients received definite irradiation with curative intent, while 5 patients received postoperative irradiation. Chemotherapy was added in 12 patients before, during and after radio-therapy. 28 patients were squamous cell carcinoma and 10 patients were adenocarcinoma. There were 29 men and 9 women (median age, 58 years; range 34 to 74 years). Stage I was 1 patient, Stage 11, 7 patient, and Stage 111, 30 patients. Among 33 patients who received radiotherapy with curative intent, follow up radiological study revealed complete response in 12 patients (36%), partial response, in 9 patients (27%), and minimal response, in 5 patients (15%), while 7 patients (21%) were nonresponders. Median survival for all patients was 6.9 months; squamous cell carcinoma, 7.3 months, adenocarcinoma, 5.9 months. Responders survived median 7 months, while nonresponders survived median 1.9 months. Improved complete response rate and survival were shown in high radiation dose group. As prognostic factors, age, initial performance status, sex, histology and tumor location were evaluated

  16. Roles of noncoding RNAs in metastasis of nonsmall cell lung cancer: A mini review

    Directory of Open Access Journals (Sweden)

    Tao Wu

    2015-01-01

    Full Text Available Recent advances in genome-wide sequencing and gene expression profiling technologies has facilitated the discovery of a huge amount of long noncoding RNA (lncRNA transcripts. In general, these lncRNAs have been reported to participate in multiple biological processes and human diseases through transcriptional, posttranscriptional and epigenetic pathway. Furthermore, emerging evidence has suggested that dysregulation of lncRNA contributes to the development and progression of human malignancies, notably lung cancer, which is one of the leading causes of cancer-related death. In this review, we will summarize the functions of lncRNAs from recent reports in human nonsmall cell lung cancer (NSCLC research, especially in the metastasis of NSCLC, and highlight the future opportunities and challenges in diagnostics and therapy of NSCLC patients.

  17. 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...

  18. Effects of gemcitabine and cisplatin chemotherapy in advanced non-small cell lung cancer patients with RRM1 low protein expression%GP方案治疗RRMl蛋白低表达的晚期非小细胞肺癌的疗效观察

    Institute of Scientific and Technical Information of China (English)

    Meiling Zhao; Haihong Yang; Jun liu; Yubao Guan; Mingchong Mo; Enyun Lin; Jianxing He

    2011-01-01

    Objective: The aim of this study was to observe the efficacy of gemcitabine combined with cisplatin (GP) in advanced non-small cell lung cancer (NSCLC) patients with low expression of ribonucleotide reductase 1 (RRM1) protein using immunohistochemistry. Methods: RRM1 protein expression in tumor tissue was detected by streptavidin-peroxidase (SP) method of immunohistochemistry. GP regimen (gemcitabine 1000-1250 mg d1, d8, cisplatin 75 mg/m2) was given to advanced NSCLC patients with low expression of RRM1 protein. Results: In the total of 40 patients, these patients with RRM1 low expression performing GP chemotherapy had a good response rate, the objective response rate (ORR) was 47.5% (95%CI, 32.02%- 62.98%), and the disease control rate (DCR) was 72.5% (95 % CI, 65.44%-79.56%). ORR is 45.45% (5/11) in the squamous cell carcinoma patients while 48.15% (13/27) in the adenocarcinoma patients. Conclusion: Superior ORR and DCR were found in advanced NSCLC patients with low expression of RRM1 protein expression performing GP regimen.

  19. UFT plus cisplatin with concurrent radiotherapy in unresectable stage III non-small cell lung cancer. Its application to outpatient practice

    International Nuclear Information System (INIS)

    Combination chemotherapy with tegafur-uracil (UFT) and cisplatin is active and less toxic for advanced non-small cell lung cancer. This treatment is likely to be applied to concurrent chemoradiotherapy for locally advanced non-small cell lung cancer, especially in the outpatient setting. Ten patients with unresectable stage III non-small cell lung cancer received the UFT plus cisplatin treatment combined with concurrent radiotherapy. The chemotherapeutic regimen consisted of oral administration of UFT 400 mg/m2 daily and venous infusion of cisplatin 20-25 mg/m2 on days 8-10. The administration of cisplatin was repeated every 3-4 weeks. Thoracic radiation started on day 8, and was completed to a total dose of 60-70 Gy. Adverse events (grade 3 or 4) occurred in 2 patients (esophagitis 2, leukopenia/neutropenia 1) with no treatment-related death. There were 7 partial responses (response rate 70.0%; 95% confidence interval (C.I.), 41.6-98.4%). The median survival time was 18.7 months with a 1-year survival rate of 77.8%. Two patients uneventfully received the treatment in an outpatient setting. With regard to the quality of life of patients, UFT plus cisplatin with concurrent radiotherapy might be the treatment of choice for unresectable stage III non-small cell lung cancer. (author)

  20. 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

  1. Clinical study on concurrent and sequential therapy of intensity modulated radiation therapy (IMRT) combined with NP regimen chemotherapy in the treatment of middle and advanced non-small cell lung cancer%调强放疗联合NP方案同步与序贯治疗中晚期非小细胞肺癌的疗效观察

    Institute of Scientific and Technical Information of China (English)

    Xiaodong Jiang; Da'an Song; Weiming Zhang; Jin Wu

    2007-01-01

    Objective: To evaluate the clinical effects of concurrent and sequential therapy for middle and advanced stage non-small cell lung cancer (NSCLC) useing IMRT combined with NP regimen chemotherapy.Methods: Eighty patients with middle and advanced stage NSCLC were randomized into two groups. Forty patients were underwent sequential therapy and other 40 patients were underwent concurrent therapy. IMRT was used in radiotherapy and NP regimen of vinorelbine+cispatin(NP) was used in chemotherapy. Results: (1) The overall response (CR+PR) rate was 75% in concurrent group and 45% in sequential group (P<0.05); (2) The treatment courses were 84 days and 140 days for concurrent group and sequential group respectively (P<0.05); (3) One-year survival rate in concurrent group was 72.4% and 52.3% in sequential group respectively;(4) The toxic effects can be tolerable by all of patients. Conclusion: The concurrent chemo-radiotherapy has better overall response, one-year survival rate and shorter treatment course than the sequential chemo-radiotherapy, so it is a better method for the treatment of middle and advanced stage NSCLC, but the long term survival rate will be studied.

  2. An IMRT/VMAT Technique for Nonsmall Cell Lung Cancer.

    Science.gov (United States)

    Zhao, Nan; Yang, Ruijie; Wang, Junjie; Zhang, Xile; Li, Jinna

    2015-01-01

    The study is to investigate a Hybrid IMRT/VMAT technique which combines intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) for the treatment of nonsmall cell lung cancer (NSCLC). Two partial arcs VMAT, 5-field IMRT, and hybrid plans were created for 15 patients with NSCLC. The hybrid plans were combination of 2 partial arcs VMAT and 5-field IMRT. The dose distribution of planning target volume (PTV) and organs at risk (OARs) for hybrid technique was compared with IMRT and VMAT. The monitor units (MUs) and treatment delivery time were also evaluated. Hybrid technique significantly improved the target conformity and homogeneity compared with IMRT and VMAT. The mean delivery time of IMRT, VMAT, and hybrid plans was 280 s, 114 s, and 327 s, respectively. The mean MUs needed for IMRT, VMAT, and hybrid plans were 933, 512, and 737, respectively. Hybrid technique reduced V5, V10, V30, and MLD of normal lung compared with VMAT and spared the OARs better with fewer MUs with the cost of a little higher V5, V10, and mean lung dose (MLD) of normal lung compared with IMRT. Hybrid IMRT/VMAT can be a viable radiotherapy technique with better plan quality. PMID:26539515

  3. An IMRT/VMAT Technique for Nonsmall Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Nan Zhao

    2015-01-01

    Full Text Available The study is to investigate a Hybrid IMRT/VMAT technique which combines intensity modulated radiation therapy (IMRT and volumetric modulated arc therapy (VMAT for the treatment of nonsmall cell lung cancer (NSCLC. Two partial arcs VMAT, 5-field IMRT, and hybrid plans were created for 15 patients with NSCLC. The hybrid plans were combination of 2 partial arcs VMAT and 5-field IMRT. The dose distribution of planning target volume (PTV and organs at risk (OARs for hybrid technique was compared with IMRT and VMAT. The monitor units (MUs and treatment delivery time were also evaluated. Hybrid technique significantly improved the target conformity and homogeneity compared with IMRT and VMAT. The mean delivery time of IMRT, VMAT, and hybrid plans was 280 s, 114 s, and 327 s, respectively. The mean MUs needed for IMRT, VMAT, and hybrid plans were 933, 512, and 737, respectively. Hybrid technique reduced V5, V10, V30, and MLD of normal lung compared with VMAT and spared the OARs better with fewer MUs with the cost of a little higher V5, V10, and mean lung dose (MLD of normal lung compared with IMRT. Hybrid IMRT/VMAT can be a viable radiotherapy technique with better plan quality.

  4. 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....

  5. 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.

  6. 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

  7. 吉西他滨与三维适形放疗同步治疗局部晚期非小细胞肺癌的临床观察%Clinical observation of gemcitabine and concomitant three-dimensional conformal radiotherapy in the treatment of locally advanced non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    Jing Cheng; Gang Wu; Hongge Wu; Jun Xue

    2008-01-01

    Objective:To evaluate lhe clinical effect of gemcitabine and concurrent three-dimensional conformal radiation therapy(3D-CRT)for locally advanced non-small cell lung cancer(NSCLC).Methods:From April 2002 to June 2005,38 patients with inoperable stage Ⅲ NSCLC were treated with gemcitabine and 3D-CRT simultaneously.Chemotherapy consisted of intravenously gemcitabine 350 mg/m2 on days 1,8,15,22,29,36.3D-CRT was delivered up to a total dose of 60-64 Gy with a 2.0 Gy dose fraction per day,5 days per week.Results:The overall response rates of primary tumor and mediastinum metastatic node were 86.8%(33/38)and 90.6%(29/32)respectively,and 91.7%(22/24)and 78.6%(11/14)for squamous cell carcinoma and adenocarcinoma respectively.The acute side effects of patients were mostly myelosuppression,nausea,vomiting,radiation-induced esophagitis and pneumonitis(RTOG Ⅰ/Ⅱ),however,all of them were cured.Conclusion:Concurrent application of gemcitabine and 3D-CRT can improve the overall response rate for locally advanced NSCLC without aggravating the side effects.

  8. Clinical activity of the mutant-selective EGFR inhibitor AZD9291 in patients with EGFR inhibitor—resistant non-small cell lung cancer

    OpenAIRE

    Tao JIANG; Caicun ZHOU

    2014-01-01

    The first generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are effective in advanced non-small cell lung cancer (NSCLC) with EGFR mutations. Unfortunately, disease progression generally occurs after 9 to 14 months of targeted therapy. The substitution of threonine with methionine at amino acid position 790 (T790M), as the second mutation in EGFR, is the most common resistance mechanism and is detected in tumor cells from more than 50-60% of patients after dis...

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

    OpenAIRE

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

    2015-01-01

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

  10. Brief versions of the FACIT-fatigue and FAACT subscales for patients with non-small cell lung cancer cachexia

    OpenAIRE

    Salsman, John M.; Beaumont, Jennifer L.; WORTMAN, KATY; Yan, Ying; Friend, John; Cella, David

    2014-01-01

    Purpose Cancer anorexia-cachexia syndrome (CACS) is common in advanced cancer patients and associated with weight loss, fatigue, impaired quality of life (QoL), and poor prognosis. The goal of this project was to identify the most responsive items from two QoL measures in the ROMANA 2 (NCT01387282) phase III global study evaluating anamorelin HCl in the treatment of non-small cell lung cancer (NSCLC) cachexia: the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) and the Func...

  11. 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

  12. Observation of Efficacy and Side Effects of Gefitinib for Advanced Non-small Cell Lung Cancer%吉非替尼治疗晚期非小细胞肺癌的疗效和毒副作用观察

    Institute of Scientific and Technical Information of China (English)

    隋东江; 王蓉美; 李伟生; 赵海霞; 李海燕

    2014-01-01

    目的:观察吉非替尼治疗晚期非小细胞肺癌( NSCLC)的疗效和毒副作用。方法对化疗失败的68例晚期非小细胞肺癌患者进行口服吉非替尼治疗,每日口服250 mg/次,每日1次,1个月之后观察疗效。结果 CR 3例,PR 21例,SD 27例,PD 17例。治疗有效率为35.29%,疾病控制率为75.00%。女性患者的疗效明显优于男性患者,腺癌患者疗效明显优于鳞癌患者的疗效,差异均有统计学意义,P<0.05;疗效与是否采取化疗和有无吸烟史无关(P>0.05);不良反应:皮疹40例,腹泻23例,恶心18例,皮肤干燥11例,经对症处理,均可缓解。结论吉非替尼对晚期非小细胞肺癌疗效较好,其中对于女性以及腺癌的患者治疗效果更好,值得在临床进行深入研究。%Objective To evaluate the efficacy and side effects of gefitinib for advanced non-small cell lung cancer (NSCLC).Methods 68 cases of advanced non-small cell lung cancer patients who failed chemotherapy were treated with ge-fitinib,oral administration of 250 mg/times a day,efficacy was observed after a month .Results CR 3 cases,PR 21 cases,SD 27 cases,PD 17 cases.The effective rate was 35.29%,disease control rate was 75.00%.Efficacy of female patients was significantly better than that of male patients ,the efficacy of cancer patients were significantly better than patients with squamous cell carcino -ma,the differences were statistically significant ,P0.05);adverse reactions:skin rash in 40 cases,23 cases of diarrhea,nausea in 18 cases,11 cases of dry skin,they can be allevia-ted with symptomatic treatment .Conclusion Gefitinib for advanced non-small cell lung cancer is effective , and it has better effect for women and adenocarcinoma ,it is worthy of further study in clinical practice .

  13. The association between PD-L1 and EGFR status and the prognostic value of PD-L1 in advanced non-small cell lung cancer patients treated with EGFR-TKIs

    OpenAIRE

    Tang, Yanna; Fang, Wenfeng; Zhang, Yaxiong; Hong, Shaodong; Kang, Shiyang; Yan, Yue; Chen, Nan; Zhan, Jianhua; He, Xiaobo; Qin, Tao; Li, Ge; Tang, Wenyi; Peng, Peijian; Zhang, Li

    2015-01-01

    Backgrounds Recent clinical trials have shown that immune-checkpoint blockade yields remarkable response in a subset of non–small cell lung cancer (NSCLC) patients. However, few studies directly focus on the association between epidermal growth factor receptor (EGFR) mutational status and programmed cell death-ligand 1 (PD-L1) expression. We examined whether PD-L1 is related to clinicopathologic factors and prognosis in patients with advanced NSCLC treated with EGFR-tyrosine kinase inhibitors...

  14. 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.

  15. 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

  16. 局部晚期非小细胞肺癌患者同步放化疗医院感染的病原学分析及预防%Etiology of nosocomial infections in locally advanced non-small cell lung cancer patients undergoing chemoradiotherapy and the prevention

    Institute of Scientific and Technical Information of China (English)

    林白桦; 贾勇士; 毕爱红; 吴树强

    2012-01-01

    目的 探讨局部晚期非小细胞肺癌患者同步放(化)疗医院感染的病原学情况及预防对策.方法 选取2007年1月-2010年1月84例进行同步放(化)疗的局部晚期非小细胞肺癌并发医院感染的患者为研究对象,将其医院感染的发生率、病原菌分布、危险因素及临床对策进行研究.结果 84例患者中以肺部感染所占比例最高,达46.43%,其次为口咽部、胃肠道及泌尿道,分别占19.05%、15.48%及13.09%;而病原菌以革兰阴性菌为主,占47.67%,其次依次为革兰阳性菌占37.21%、真菌占15.12%;患者年龄、营养状况、合并其他基础疾病种类、有侵入性操作、住院时间≥14d、应用抗菌药物≥3种为医院感染的危险因素(P<0.05);所有患者经针对性的治疗后感染得到有效控制.结论 局部晚期非小细胞肺癌同步放(化)疗医院感染患者的感染部位及病原菌分布均有其特殊性,给予针对性的治疗可改善预后.%OBJECTIVE To investigate the etiology of nosocomial infections in locally advanced non-small cell lung cancer patients who underwent chemoradiotherapy and propose prevention countermeasures. METHODS A total of 84 patients with nosocomial infections who underwent synchronous chemoradiotherapy for locally advanced non-small cell lung cancer from Jan 2007 to Jan 2010 were chosen as the research objects. The incidence of nosocomial infections, distribution of the pathogens , risk factors and clinical strategies were studied. RESULTS In the 84 patients, the rate of lung infections was the highest (46. 43%) , followed by the oropharynx infections (19. 05%) , gastrointestinal tract infections (15. 48%) and urinary tract infections (13. 09%); and gram-negative bacteria were dominated in the pathogens, accounting for 47. 67%, followed by gram-positive bacteria (37. 21%) and fungi (15. 12%); the age , nutrition status, combination with other underlying diseases, invasive operation, hospital

  17. Early palliative care and metastatic non-small cell lung cancer: potential mechanisms of prolonged survival.

    Science.gov (United States)

    Irwin, Kelly E; Greer, Joseph A; Khatib, Jude; Temel, Jennifer S; Pirl, William F

    2013-02-01

    Patients with advanced cancer experience a significant burden of physical symptoms and psychological distress at the end of life, and many elect to receive aggressive cancer-directed therapy. The goal of palliative care is to relieve suffering and promote quality of life (QOL) for patients and families. Traditionally, both the public and medical community have conceptualized the need for patients to make a choice between pursuing curative therapy or receiving palliative care. However, practice guidelines from the World Health Organization and leadership from the oncology and palliative care communities advocate a different model of palliative care that is introduced from the point of diagnosis of life-threatening illness. Early palliative care has been shown to provide benefits in QOL, mood, and health care utilization. Additionally, preliminary research has suggested that in contrast to fears about palliative care hastening death, referral to palliative care earlier in the course of illness may have the potential to lengthen survival, particularly in patients with advanced nonsmall-cell lung cancer. This review summarizes the literature on potential survival benefits of palliative care and presents a model of how early integrated palliative care could potentially influence survival in patients with advanced cancer. PMID:23355404

  18. [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

  19. The challenge of targeting EGFR: experience with gefitinib in nonsmall cell lung cancer

    Directory of Open Access Journals (Sweden)

    C.L. Watkins

    2010-09-01

    Full Text Available As the first approved epidermal growth factor receptor (EGFR-targeted therapy for nonsmall cell lung cancer (NSCLC, the clinical development of gefitinib was complex. Advances in scientific understanding of the target biology during its clinical development enabled the identification of a biomarker to define patients most likely to derive benefit from gefitinib. Initial phase II trials showed clinically meaningful anti-tumour activity in 12–18% of unselected pretreated patients with advanced NSCLC at the optimum biological dose (250 mg. Subgroup analyses of these and subsequent phase III trials in unselected patients suggested that EGFR mutation and some clinical characteristics associated with a higher incidence of EGFR mutation (Asian ethnicity, adenocarcinoma histology, never-smoking and female sex were linked with increased response to gefitinib. Consequently, the IRESSA Pan-Asia Study (IPASS was conducted in never-smokers or former light-smokers in East Asia who had adenocarcinoma of the lung. IPASS showed that EGFR mutation was the strongest predictor of improved progression-free survival (mutation-positive subgroup hazard ratio (HR 0.48, 95% CI 0.36–0.64 (p<0.001, n = 261; mutation-negative subgroup HR 2.85, 95% CI 2.05–3.98 (p<0.001, n = 176; interaction test p<0.001 with gefitinib versus carboplatin/paclitaxel as first-line therapy for advanced NSCLC. Important lessons for the development of future personalised medicines are discussed.

  20. 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

  1. Clinical study of docetaxel-vinorelbine as second-line chemotherapy in advanced non-small cell lung cancer%多西紫杉醇联合长春瑞滨二线治疗晚期非小细胞肺癌的临床研究

    Institute of Scientific and Technical Information of China (English)

    Jun Guo; Weiping Li; Degang Song; Zhehai Wang; Jie Liu; Changzheng Li; Zhen Chen; Huan Shi

    2008-01-01

    Objective:To evaluate the efficacy and toxicity of docetaxel and vinorelbine as second-line chemotherapy in the treatment of advanced non-small cell lung cancer (NSCLC).Methods:48 histologically or cytologically confirmed NSCLC patients with progressive or recurrent disease after first-line treatment were treated with docetaxel and vinorelbine.The chemotherapy included vinorelbine (25 mg/m2) on days 1,5 and docetaxel (60 mg/m2) on day 1.The treatment was repeated every 3 weeks.Patients receiving at least two cycles were evaluated for efficacy and toxicity.Results:Of 48 patients,1 patient achieved complete response and 16 achieved partial response.Overall response rate for all 48 patients was 35.4% (17/48).Main hematologic toxicities included neutropenia (60.4%) and febrile neutropenia (29.2%) and non-hematologic toxicities were mild.Conclusion:The combination of docetaxel-vinorelbine as second-line chemotherapy is an effective regimen with manageable toxicity for the treatment of advanced NSCLC.Further studies may confirm these results.

  2. The impact of induction chemotherapy on the dosimetric parameters of subsequent radiotherapy: an investigation of 30 consecutive patients with locally-advanced non-small cell lung cancer and modern radiation planning techniques

    International Nuclear Information System (INIS)

    To investigate the influence of induction chemotherapy (ICT) on dosimetric outcomes in patients with inoperable non-small cell lung cancer (NSCLC) treated with definitive chemoradiation (CRT). 30 patients with inoperable stage II-III NSCLC treated with 2–4 cycles of ICT followed by definitive CRT to ≥ 60 Gy were selected. Tumor response to chemotherapy was scored by RECIST criteria. Treatment plans based on tumor extent prior to chemotherapy were generated based on equivalent planning constraints and techniques as the original post-chemotherapy plans. Dosimetric parameters predictive of toxicity for lung, esophagus, heart, and spinal cord were compared amongst the pre- and post-ICT plans. The majority of patients (70%) experienced an overall reduction in GTV size between the pre-ICT imaging and the time of simulation. Comparing pre-and post-ICT diagnostic imaging, 5 patients met the RECIST criteria for response, 23 were classified as stable, and 2 experienced disease progression on diagnostic imaging. Despite a significantly reduced GTV size in the post-ICT group, no systematic improvements in normal tissue doses were seen amongst the entire cohort. This result persisted amongst the subgroup of patients with larger pre-ICT GTV tumor volumes (>100 cc3). Among patients with RECIST-defined response, a significant reduction in lung mean dose (1.9 Gy absolute, median 18.2 Gy to 16.4 Gy, p = 0.04) and V20, the percentage of lung receiving 20 Gy (3.1% absolute, median 29.3% to 26.3%, p = 0.04) was observed. In the non-responding group of patients, an increased esophageal V50 was found post-chemotherapy (median 28.9% vs 30.1%, p = 0.02). For patients classified as having a response by RECIST to ICT, modest improvements in V20 and mean lung dose were found. However, these benefits were not realized for the cohort as a whole or for patients with larger tumors upfront. Given the variability of tumor response to ICT, the a priori impact of induction chemotherapy to reduce

  3. 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

  4. 低剂量脾照射对局部晚期非小细胞肺癌放疗患者免疫系统的影响%The effects of low-dose splenic irradiation and radiotherapy on immune system of patients with locally advanced non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    Jun Liu; Hongsheng Yu; Qingjun Shang; Chao Yan; Peng Jiang; Xiang Wang

    2013-01-01

    Objective:The aim of the research was to study the effects of low-dose splenic irradiation and radiotherapy on immune system of patients with locally advanced non-small cell lung cancer (NSCLC). Methods:Twelve cases of stage III NSCLC in Tumor Radiotherapy Center of our hospital (the Affiliated Hospital of Medical College Qingdao University, China) were collected from July 2011 to July 2012; all patients were under 75 years old with clear pathology, measurable lesions and good personal statement. They were randomly divided into combined treatment group (D1 + D2) and control group (D1). The control group (D1) only received radiotherapy to the chest; combined treatment group (D1 + D2) received low-dose splenic irradiation plus conventional dose irradiation. Flow cytometry was used to detect the peripheral blood T lymphocyte immune indexes of patients before, during and after the treatment, classification by five blood cell analyzer was used to determine white blood cells, neutrophils, hemoglobin and platelet count. The radiation induced toxicity including esophagitis, pneumonia and gastrointestinal reaction was observed, as well as the dose when it happened. Results:There was no significant difference in the ratio between two groups in cells CD4+, CD8+ and CD4+/CD8+ after radiotherapy (P > 0.05). There was no change in these indicators in combined treatment group after treatment (P > 0.05), but it decreased in control group (P 0.05), but the patients in combined treatment group seemed to tolerate high dose well (P < 0.05). Conclusion:Low-dose splenic irradiation combined with radiotherapy to the chest can alleviate the injury degree of acute radiation induced the toxicity of locally advanced NSCLC patients, through affect the patient's immune function.

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

    Institute of Scientific and Technical Information of China (English)

    朱方; 徐瀚峰; 郑勤; 张全安

    2014-01-01

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

  6. Randomize Trial of Cisplatin plus Gemcitabine with either Sorafenib or Placebo as First-line Therapy for Non-small Cell Lung Cancer

    OpenAIRE

    Yan WANG; Wang, Lin; Liu, Yutao; Shufei YU; Xiangru ZHANG; Shi, Yuankai; Sun, Yan

    2011-01-01

    Background and objective Platinum-based chemotherapy doublets reached an efficacy plateau in nonsmall-cell lung cancer (NSCLC). This randomized controlled study prospectively assessed the efficacy and safety of cisplatin plus gemcitabine with either Sorafenib or placebo as first-line therapy for NSCLC. Methods Thirty patients, which were confirmed advanced NSCLC histologically or cytologically, were randomly assigned to receive up to six cycles of cisplatin plus gemcitabine with sorafenib or ...

  7. 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 ...

  8. Downregulated TIPE2 is associated with poor prognosis and promotes cell proliferation in non-small cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Li, Yuexia [Intensive Care Unit, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052 (China); Li, Xiaohui [Department of Cardiovascular Surgery, Henan Provincial People’s Hospital, Zhengzhou, Henan 450003 (China); Liu, Gang; Sun, Rongqing; Wang, Lirui [Intensive Care Unit, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052 (China); Wang, Jing, E-mail: jing_wang1980@163.com [Department of Respiratory Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052 (China); Wang, Hongmin, E-mail: hmwangzz@126.com [Department of Respiratory Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052 (China)

    2015-01-30

    Highlights: • TIPE2 is down-regulated in NSCLC tissues. • TIPE2 inhibits NSCLC cell proliferation, colony formation and invasion. • TIPE2 reduces the anti-apoptotic Bcl-XL protein and mesenchymal marker N-cadherin expression. - Abstract: The present study aims to investigate the expression pattern of TIPE2 protein and its clinical significance in human non-small cell lung cancer (NSCLC). We investigated the expression levels of TIPE2 in 96 NSCLC tumor samples by immunohistochemistry and then analyzed its clinical significance. Furthermore, the role of TIPE2 on the biological properties of the NSCLC cell line H1299 and A549 was experimentally tested in vitro and in vivo. We found that the expression level of TIPE2 was significantly higher in normal lung tissues compared with NSCLC tissues (P < 0.001), and TIPE2 downregulation was significantly correlated with advanced TNM stage (P = 0.006). TIPE2 expression was lower in lung cancer cell lines than normal bronchial cell line HBE. Transfection of TIPE2 plasmid was performed in H1299 and A549 cells. TIPE2 overexpression inhibited lung cancer cell proliferation, colony formation and cell invasive in vitro, and prevented lung tumor growth in vivo. In addition, TIPE2 transfection reduced the anti-apoptotic Bcl-XL protein and mesenchymal marker N-cadherin expression. Taken together, our results demonstrate that TIPE2 might serve as a tumor suppressor in NSCLC progression.

  9. Downregulated TIPE2 is associated with poor prognosis and promotes cell proliferation in non-small cell lung cancer

    International Nuclear Information System (INIS)

    Highlights: • TIPE2 is down-regulated in NSCLC tissues. • TIPE2 inhibits NSCLC cell proliferation, colony formation and invasion. • TIPE2 reduces the anti-apoptotic Bcl-XL protein and mesenchymal marker N-cadherin expression. - Abstract: The present study aims to investigate the expression pattern of TIPE2 protein and its clinical significance in human non-small cell lung cancer (NSCLC). We investigated the expression levels of TIPE2 in 96 NSCLC tumor samples by immunohistochemistry and then analyzed its clinical significance. Furthermore, the role of TIPE2 on the biological properties of the NSCLC cell line H1299 and A549 was experimentally tested in vitro and in vivo. We found that the expression level of TIPE2 was significantly higher in normal lung tissues compared with NSCLC tissues (P < 0.001), and TIPE2 downregulation was significantly correlated with advanced TNM stage (P = 0.006). TIPE2 expression was lower in lung cancer cell lines than normal bronchial cell line HBE. Transfection of TIPE2 plasmid was performed in H1299 and A549 cells. TIPE2 overexpression inhibited lung cancer cell proliferation, colony formation and cell invasive in vitro, and prevented lung tumor growth in vivo. In addition, TIPE2 transfection reduced the anti-apoptotic Bcl-XL protein and mesenchymal marker N-cadherin expression. Taken together, our results demonstrate that TIPE2 might serve as a tumor suppressor in NSCLC progression

  10. 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.

  11. 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...

  12. The Evolution of Therapies in Non-Small Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Boolell, Vishal, E-mail: vishal.boolell@monashhealth.org.au; Alamgeer, Muhammad [Department of Medical Oncology, Monash Medical Centre, 823-865 Centre Road, East Bentleigh VIC 3165 (Australia); Hudson Institute of Medical Research, Monash University, 27-31 Wright Street, Clayton VIC 3168 (Australia); Watkins, David N. [Hudson Institute of Medical Research, Monash University, 27-31 Wright Street, Clayton VIC 3168 (Australia); Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, Sydney NSW 2010 (Australia); UNSW Faculty of Medicine, St Vincent’s Clinical School, 390 Victoria Street, Darlinghurst, Sydney NSW 2010 (Australia); Department of Thoracic Medicine, St Vincent’s Hospital, 390 Victoria Street, Darlinghurst, Sydney NSW 2010 (Australia); Ganju, Vinod [Department of Medical Oncology, Monash Medical Centre, 823-865 Centre Road, East Bentleigh VIC 3165 (Australia); Hudson Institute of Medical Research, Monash University, 27-31 Wright Street, Clayton VIC 3168 (Australia)

    2015-09-09

    The landscape of advanced non-small lung cancer (NSCLC) therapies has rapidly been evolving beyond chemotherapy over the last few years. The discovery of oncogenic driver mutations has led to new ways in classifying NSCLC as well as offered novel therapeutic targets for anticancer therapy. Targets such as epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) gene rearrangements have successfully been targeted with appropriate tyrosine kinase inhibitors (TKIs). Other driver mutations such as ROS, MET, RET, BRAF have also been investigated with targeted agents with some success in the early phase clinical setting. Novel strategies in the field of immune-oncology have also led to the development of inhibitors of cytotoxic T lymphocyte antigen-4 (CTLA-4) and programmed death-1 receptor (PD-1), which are important pathways in allowing cancer cells to escape detection by the immune system. These inhibitors have been successfully tried in NSCLC and also now bring the exciting possibility of long term responses in advanced NSCLC. In this review recent data on novel targets and therapeutic strategies and their future prospects are discussed.

  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. The Evolution of Therapies in Non-Small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Vishal Boolell

    2015-09-01

    Full Text Available The landscape of advanced non-small lung cancer (NSCLC therapies has rapidly been evolving beyond chemotherapy over the last few years. The discovery of oncogenic driver mutations has led to new ways in classifying NSCLC as well as offered novel therapeutic targets for anticancer therapy. Targets such as epidermal growth factor receptor (EGFR mutations and anaplastic lymphoma kinase (ALK gene rearrangements have successfully been targeted with appropriate tyrosine kinase inhibitors (TKIs. Other driver mutations such as ROS, MET, RET, BRAF have also been investigated with targeted agents with some success in the early phase clinical setting. Novel strategies in the field of immune-oncology have also led to the development of inhibitors of cytotoxic T lymphocyte antigen-4 (CTLA-4 and programmed death-1 receptor (PD-1, which are important pathways in allowing cancer cells to escape detection by the immune system. These inhibitors have been successfully tried in NSCLC and also now bring the exciting possibility of long term responses in advanced NSCLC. In this review recent data on novel targets and therapeutic strategies and their future prospects are discussed.

  15. The Evolution of Therapies in Non-Small Cell Lung Cancer

    International Nuclear Information System (INIS)

    The landscape of advanced non-small lung cancer (NSCLC) therapies has rapidly been evolving beyond chemotherapy over the last few years. The discovery of oncogenic driver mutations has led to new ways in classifying NSCLC as well as offered novel therapeutic targets for anticancer therapy. Targets such as epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) gene rearrangements have successfully been targeted with appropriate tyrosine kinase inhibitors (TKIs). Other driver mutations such as ROS, MET, RET, BRAF have also been investigated with targeted agents with some success in the early phase clinical setting. Novel strategies in the field of immune-oncology have also led to the development of inhibitors of cytotoxic T lymphocyte antigen-4 (CTLA-4) and programmed death-1 receptor (PD-1), which are important pathways in allowing cancer cells to escape detection by the immune system. These inhibitors have been successfully tried in NSCLC and also now bring the exciting possibility of long term responses in advanced NSCLC. In this review recent data on novel targets and therapeutic strategies and their future prospects are discussed

  16. 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

  17. 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.

  18. 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.

  19. 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...

  20. Computed tomography to assess pulmonary injury associated with concurrent chemo-radiotherapy for inoperable non-small cell lung cancer

    International Nuclear Information System (INIS)

    To characterize serial computed tomography (CT) findings of pulmonary injury after a uniform regimen of concurrent chemo-radiotherapy in inoperable non-small cell lung cancer, and to compare the radiation-induced lung toxicity with other concurrent chemo-radiation regimens. Twenty-four patients with advanced non-small cell lung cancer received 2 induction cycles of cisplatin and vinblastine, followed by 2 further cycles of cisplatin and vinblastine, concurrent with 60 Gy radiation at 2 Gy per fraction. Radiation-induced lung injury in the acute and chronic phases was assessed by serial CT scans and compared with preradiation baseline scans. Acute radiation pneumonitis was evaluated using the Common Toxicity Criteria, and chronic radiation fibrosis was graded according to the European Organisation for Research and Treatment of Cancer - Radiation Therapy Oncology Group Scale. Seventeen (81%) patients had characteristic CT findings of radiation induced pulmonary damage, which were confined to the radiation ports. Although patchy nonhomogeneous and air-space opacities characterized acute radiation pneumonitis, and homogeneous opacities with loss of volume were typical for chronic fibrosis, ground-glass opacities were found frequently in both phases. Acute radiation pneumonitis grade 1 was seen in 29% and grade 2 in 9.5%. Chronic radiation fibrosis grades 1, 2 and 3 were found in 14%, 33% and 19% of the patients respectively. Median survival time was 13 months. CT enables detailed evaluation of radiation-induced pulmonary injury after concurrent chemo-radiation for inoperable non-small cell lung cancer. Although survival time with the present regimen is comparable to other concurrent chemo-radiation regimens, a high incidence of radiation injury was found, though the severity was not life threatening. (author)

  1. 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...

  2. 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

  3. 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

  4. 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.

  5. 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

  6. 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

  7. 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...

  8. 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...

  9. The number and microlocalization of tumor-associated immune cells are associated with patient's survival time in non-small cell lung cancer

    OpenAIRE

    Zhang Shangfu; Ma Junliang; Pu Qiang; Yu Nanbin; Che Guowei; Liu Lunxu; Dai Fuqiang; Ma Lin; You Zongbing

    2010-01-01

    Abstract Background Tumor microenvironment is composed of tumor cells, fibroblasts, endothelial cells, and infiltrating immune cells. Tumor-associated immune cells may inhibit or promote tumor growth and progression. This study was conducted to determine whether the number and microlocalization of macrophages, mature dendritic cells and cytotoxic T cells in non-small cell lung cancer are associated with patient's survival time. Methods Ninety-nine patients with non-small cell lung cancer (NSC...

  10. 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

  11. XCR1 promotes cell growth and migration and is correlated with bone metastasis in non-small cell lung cancer

    International Nuclear Information System (INIS)

    Bone metastasis occurs in approximately 30–40% patients with advanced non-small cell lung cancer (NSCLC), but the mechanism underlying this bone metastasis remains poorly understood. The chemokine super family is believed to play an important role in tumor metastasis in lung cancer. The chemokine receptor XCR1 has been identified to promote cell proliferation and migration in oral cancer and ovarian carcinoma, but the role of XCR1 in lung cancer has not been reported. In this study, we demonstrated for the first time that XCR1 was overexpressed in lung cancer bone metastasis as compared with that in patients with primary lung cancer. In addition, the XCR1 ligand XCL1 promoted the proliferation and migration of lung cancer cells markedly, and knockdown of XCR1 by siRNA abolished the effect of XCL1 in cell proliferation and migration. Furthermore, we identified JAK2/STAT3 as a novel downstream pathway of XCR1, while XCL1/XCR1 increased the mRNA level of the downstream of JAK2/STAT3 including PIM1, JunB, TTP, MMP2 and MMP9. These results indicate that XCR1 is a new potential therapeutic target for the treatment of lung cancer bone metastasis. - Highlights: • XCR1 is overexpressed in bone metastasis compared with primary NSCLC. • XCR1 activation by XCL1 promotes lung cancer cell proliferation and migration. • JAK2/STAT3 is a novel potential downstream pathway of XCR1

  12. XCR1 promotes cell growth and migration and is correlated with bone metastasis in non-small cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Ting; Han, Shuai; Wu, Zhipeng; Han, Zhitao; Yan, Wangjun; Liu, Tielong; Wei, Haifeng; Song, Dianwen; Zhou, Wang, E-mail: brilliant212@163.com; Yang, Xinghai, E-mail: cnspineyang@163.com; Xiao, Jianru, E-mail: jianruxiao83@163.com

    2015-08-21

    Bone metastasis occurs in approximately 30–40% patients with advanced non-small cell lung cancer (NSCLC), but the mechanism underlying this bone metastasis remains poorly understood. The chemokine super family is believed to play an important role in tumor metastasis in lung cancer. The chemokine receptor XCR1 has been identified to promote cell proliferation and migration in oral cancer and ovarian carcinoma, but the role of XCR1 in lung cancer has not been reported. In this study, we demonstrated for the first time that XCR1 was overexpressed in lung cancer bone metastasis as compared with that in patients with primary lung cancer. In addition, the XCR1 ligand XCL1 promoted the proliferation and migration of lung cancer cells markedly, and knockdown of XCR1 by siRNA abolished the effect of XCL1 in cell proliferation and migration. Furthermore, we identified JAK2/STAT3 as a novel downstream pathway of XCR1, while XCL1/XCR1 increased the mRNA level of the downstream of JAK2/STAT3 including PIM1, JunB, TTP, MMP2 and MMP9. These results indicate that XCR1 is a new potential therapeutic target for the treatment of lung cancer bone metastasis. - Highlights: • XCR1 is overexpressed in bone metastasis compared with primary NSCLC. • XCR1 activation by XCL1 promotes lung cancer cell proliferation and migration. • JAK2/STAT3 is a novel potential downstream pathway of XCR1.

  13. 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.

  14. 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.

  15. Dihydroartemisinin inhibits glucose uptake and cooperates with glycolysis inhibitor to induce apoptosis in non-small cell lung carcinoma cells.

    Directory of Open Access Journals (Sweden)

    Yan-jun Mi

    Full Text Available Despite recent advances in the therapy of non-small cell lung cancer (NSCLC, the chemotherapy efficacy against NSCLC is still unsatisfactory. Previous studies show the herbal antimalarial drug dihydroartemisinin (DHA displays cytotoxic to multiple human tumors. Here, we showed that DHA decreased cell viability and colony formation, induced apoptosis in A549 and PC-9 cells. Additionally, we first revealed DHA inhibited glucose uptake in NSCLC cells. Moreover, glycolytic metabolism was attenuated by DHA, including inhibition of ATP and lactate production. Consequently, we demonstrated that the phosphorylated forms of both S6 ribosomal protein and mechanistic target of rapamycin (mTOR, and GLUT1 levels were abrogated by DHA treatment in NSCLC cells. Furthermore, the upregulation of mTOR activation by high expressed Rheb increased the level of glycolytic metabolism and cell viability inhibited by DHA. These results suggested that DHA-suppressed glycolytic metabolism might be associated with mTOR activation and GLUT1 expression. Besides, we showed GLUT1 overexpression significantly attenuated DHA-triggered NSCLC cells apoptosis. Notably, DHA synergized with 2-Deoxy-D-glucose (2DG, a glycolysis inhibitor to reduce cell viability and increase cell apoptosis in A549 and PC-9 cells. However, the combination of the two compounds displayed minimal toxicity to WI-38 cells, a normal lung fibroblast cell line. More importantly, 2DG synergistically potentiated DHA-induced activation of caspase-9, -8 and -3, as well as the levels of both cytochrome c and AIF of cytoplasm. However, 2DG failed to increase the reactive oxygen species (ROS levels elicited by DHA. Overall, the data shown above indicated DHA plus 2DG induced apoptosis was involved in both extrinsic and intrinsic apoptosis pathways in NSCLC cells.

  16. 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...

  17. 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.

  18. 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...

  19. Influence of comorbidity on the choice of treatment and survival of elderly patients with advanced non-small cell lung cancer%合并症对老年晚期NSCLC患者治疗和生存期的影响

    Institute of Scientific and Technical Information of China (English)

    Aiwu Li; Caicun Zhou; Jianfang Xu; Ren Zhu; Jie Luo; Shanhao Chen

    2008-01-01

    Objective:To identify the influence of comorbidity on the choice of treatment and survival of elderly patients (≥70 years) with advanced non-small cell lung cancer (NSCLC).Methods:The clinical characteristics and the choices of treatment of 177 elderly patients,who had a good performance status (PS<1) were retrospectively analyzed in Oncology Department,Shanghai Pulmonary Hospital,between January 2005 to December 2005.Survival data were only analyzed in those whose had received chemotherapy.All patients were stratified by number of comorbidity as none (0),mild (1-2) and severe (≥3) groups.Results:The proportion of patients,who received chemotherapy,with none,mild and severe comorbidity was significantly different (79.3%,76.2% and 57.4%,P=0.038),and there was also significantly different about palliative radiotherapy rate among the three groups (21 1%,11.7% and 37.0%,P=0.014).The median survival and 1-year survival rate in none,mild and severe comorbidity groups,were 13.6 vs.10.2 vs.7.6 months and 53.5% vs.41.3% vs.20.8% respectively (Log-rank,P=0.071).In univadate and multivariate Cox models analysis,only severe comorbidity was a independent hazard factor of survival of elderly patients with NSCLC.Relative ratio (RR,95% Cl):(2.09,1.06-4.15),P=0.034.Conclusion:Comorbidity may affect the choice of treatment of elderly patients with advanced NSCLC slightly,but only severe comorbidity is a independent prognostic factor of survival.

  20. Docetaxel as salvage chemotherapy in patients with advanced non-small cell lung cancer after failure of cytotoxic agents and gefitinib treatment%晚期非小细胞肺癌化疗和靶向治疗失败后的挽救性化疗

    Institute of Scientific and Technical Information of China (English)

    Yilong Wu; Jinji Yang; Yujuan Huang; Qin Zhou; Yisheng Huang; Chongrui Xu

    2008-01-01

    Objective:We conducted a prospective phase Ⅱ trial of single-agent salvage chemotherapy with docetaxel in patients with advanced non-small cell lung cancer (NSCLC) after failure of chemotherapy and gefitinib to assess the efficacy and toxicity of docetaxel in this setting.Methods:Patients with histologically confirmed NSCLC who were failure of chemotherapy and gefitinib were given docetaxel 75 mg/m2 intravenously for 30 min every 3 weeks until the toxicity was unacceptable or disease progressed.The response evaluation criteria in solid tumors (RECIST) guidelines were used for the evaluation of antitumor activity.Toxicity was graded according to the National Cancer Institute Common Toxicity Criteria version 2.0.Results:In total,31 patients were enrolled in this phase Ⅱ trial between February 2004 and December 2006,and 84 cycles (average 2.7 cycles) were given.We observed 4 partial responses (PRs) and 10 stable disease (SD) states in 31 eligible patients.The objective response rate was 12.9%,and the disease control rate was 45.2%.The median survival time (MST) was 10 months (95% Cl,5.05-15.08 months).The 1-year survival rate was 40.6%.The most common toxicities were neutropenia,anemia,and peripheral neuropathy that occurred as follows:45% of the patients experienced grade 3 or 4 neutropenia,29% experienced grade 3 anemia,and 25.8% had grade 3 peripheral neuropathy.No patient terminated docetaxel chemotherapy due to toxicity.Conclusion:Docetaxei is beneficial as salvage chemotherapy in patients with advanced NSCLC after failure of cytotoxic agents and gefitinib.

  1. 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.

  2. 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...

  3. 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...

  4. Efficacy and Toxicity of Maintenance Pemetrexed Following Induction Treatment with Pemetrexed Plus Cisplatin for Advanced Non-small-cell Non-squamous Carcinoma of the Lung

    Directory of Open Access Journals (Sweden)

    Kim D. H.

    2015-06-01

    Full Text Available INTRODUCTION: The aim of this study is to assess the efficacy and toxicity of maintenance pemetrexed following induction treatment with cisplatin and pemetrexed for patients with advanced non-small cell lung cancer.

  5. Preoperative concurrent chemoradiotherapy for unresectable stage III nonsmall cell lung cancer

    International Nuclear Information System (INIS)

    Purpose: We carried out a Phase II trial in an attempt to improve resectability and survivability of inoperable Stage III A and III B nonsmall cell lung cancer (NSCLC) patients by implementing a neoadjuvant chemoradiotherapy treatment program. Methods and Materials: Thirty-six patients with locally advanced Stage III NSCLC received neoadjuvant therapy consisting of 50.4 Gy in 5.5 weeks concurrent with two cycles of chemotherapy, using cisplatin and etoposide. No postsurgical consolidation therapy was given. Results: Assessment at 3 to 6 weeks after treatment suggested that 26 (72%) patients had been rendered resectable. Toxicities were common but usually tolerable; however, one toxic death occurred. Of 24 patients who proceeded to thoracotomy, complete resection was achieved in 20 (56%). There were two surgically related deaths. Surgical-pathological staging showed downstaging in 18 patients, including complete sterilization of the tumor in 3 (8%). The median survival for all 36 patients is 15 months, but at the time of analysis, median survival of resectable patients had not been reached. The actuarial 2-year survival is 39% for all study groups, 57% for resectable patients, and 16% for the remaining (p < 0.005). Conclusions: While this preoperative neoadjuvant appears to improve survival of patients with Stage III NSCLC, comparison with previous reports of other similar trials indicate a superior survival advantage in association with higher doses of radiotherapy

  6. [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

  7. 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.

  8. Second-line combination therapies in nonsmall cell lung cancer without known driver mutations

    Directory of Open Access Journals (Sweden)

    Maria-Virginia Bluthgen

    2015-12-01

    Full Text Available In advanced nonsmall cell lung cancer (NSCLC patients, platinum-based combination chemotherapy is standard treatment in the first-line setting; however, the large majority of patients ultimately progress. For more than a decade, single-agent therapy with docetaxel, pemetrexed or erlotinib has been the standard of care after failure with platinum salts, showing some benefit over best supportive care. Nonetheless, prognosis remains poor and new second-line strategies are urgently needed. Combinations of cytotoxic agents, including rechallenge with platinum salts, do not offer clear benefit over single-agent therapy for the majority of patients. In patients without a known tumoural oncogenic driver mutation, regimens based on combinations of targeted agents have shown promising results; however, a clear role in therapeutic management is yet to be established. Some success has been reported in recent research combining a cytotoxic agent with targeted therapies. In this review, we summarise published data for the various strategies evaluated over the past decade in second-line treatment of NSCLC patients without a known driver mutation. We focus on combination treatments and consider future perspectives, including the need to identify predictive markers to support personalised therapeutic strategies.

  9. 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

  10. 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

  11. 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.

  12. 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

  13. 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

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

    Directory of Open Access Journals (Sweden)

    Xueying Zhao

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

  15. Cyclosporine A sensitizes human non-small cell lung cancer cells to gefitinib through inhibition of STAT3.

    Science.gov (United States)

    Shou, Jiawei; You, Liangkun; Yao, Junlin; Xie, Jiansheng; Jing, Jing; Jing, Zhao; Jiang, Liming; Sui, Xinbing; Pan, Hongming; Han, Weidong

    2016-08-28

    The epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have dramatically prolonged the overall survival of non-small cell lung cancer (NSCLC) patients with EGFR-activating mutation, but the presence of primary or acquired resistance eventually leads to therapeutic failure. Thus, how to improve the efficacy and reverse the resistance to EGFR-TKIs remains a significant challenge. In this study, we found that CsA significantly augmented the anti-cancer effect of gefitinib in EGFR-TKI-sensitive and -resistant NSCLC cells. Mechanistically, CsA promoted gefitinib-induced apoptosis through inhibition of the STAT3 pathway. Similar with the function of CsA, siRNAs against STAT3 also enhanced gefitinib-induced apoptosis in multiple lung cancer cells. Xenograft studies further demonstrated that CsA promoted the anti-cancer activity of gefitinib on lung cancer cells through inhibition of STAT3. Moreover, NSCLC patients with high levels of phosphorylated STAT3 (Y705) showed a significantly poorer therapeutic response to EGFR-TKIs. This study provides preclinical evidence that the combination of CsA or a STAT3 inhibitor with EGFR-TKIs is a promising approach to improve the efficacy of EGFR-TKIs for the treatment of patients with advanced NSCLC. PMID:27264264

  16. FDG PET in monitoring response to neoadjuvant chemoradiotherapy in patients with locally advanced non-small lung carcinoma

    International Nuclear Information System (INIS)

    Full text:Aim: The aim of our study was to correlate 18F-FDG PET response to neoadjuvant chemoradiotherapy with histopathology in patients with locally advanced non-small cell lung carcinoma. Methods: All patients with stage III NSCLC planned for surgery following induction chemotherpay and/or radiotherapy who underwent pre- and post-treatment FDG-PET between 2004 and 2007 were retrospectively reviewed. The PET scans were performed according to standard protocol. The clinical FDG-PET TNM stage was correlated with the histopathology of the surgical specimens. Results: There were 9 patients (6M:3F), median age 59.7 years (range 49 to 73 years). Post-treatment FDG-PET correctly predicted mediastinal pathological N stage in 8/9 patients, with one patient having microsopic disease in two nodes. The post-treatment FDG-PET correctly predicted pathological T stage in 7/9 patients, with 2 patients having small volume T4 disease not detected by PET. Post-treatment FDG-PET correctly downstaged 4 patients. Of the 5 patients, incorrectly staged on the post-treatment FDG-PET, one patient had microscopic pN2 disease, 2 had pN1 disease, and 2 had pT4 disease. Conclusion: Post-treatment FDG-PET is predictive of pathological nodal stage within the mediastinum in patients with locally advanced NSCLC treated with neoadjuvant chemoradiotherapy. FDG-PET does not detect microscopic or small volume disease, nor is it able to define the boundaries of mediastinal tissue invasion.

  17. The impact of three-dimensional radiation on the treatment of non-small cell lung cancer

    International Nuclear Information System (INIS)

    Non-small cell lung cancer (NSCLC) patients with locally advanced unresectable disease have a grim prognosis. Radiotherapeutic strategies are necessary to improve the permanent eradication of thoracic disease. The poor results achieved with conventional external beam radiation therapy reflect in part, the inadequacy of such therapy in achieving its primary objective of achieving local control. The impact of three-dimensional conformal radiation therapy (3-DCRT) on local disease eradication and its potential role in improving survival is assessed. This review addresses aspects of the software and hardware technology of 3-DCRT, the clinical and technical aspects of target volume definition, the use of 3-DCRT to predict radiation pneumonitis, strategies for dose escalation in NSCLC, and analyses the clinical results to date. Initially investigators compared the best treatment techniques devised with conventional planning techniques to those devised with 3-DCRT. These analyses showed that 3-DCRT had the potential to deliver high dose radiation (>70 Gy) with minimal underdosing and with a concomitant relative sparing of normal tissues. This technical demonstration of enhanced therapeutic ratio is the basis for the evolving clinical utilization of 3-DCRT for NSCLC. Software and hardware developments continue to develop and have the potential to solve evolving clinical issues. Dose-volume-histograms have been used to accurately quantify lung dose and derived parameters have the potential to predict the risk of pneumonitis for individual patients before treatment. Initial clinical results have been promising and strategies for further dose escalation are emerging. Preliminary experience has resulted in promising survival following three-dimensional conformal radiation therapy alone for locally advanced NSCLC. More follow-up and experience will determine late toxicity, maximum dose, and efficacy of dose escalation with three-dimensional conformal radiation therapy

  18. 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.

  19. 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

  20. 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

  1. 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

  2. Maintenance pemetrexed in nonsmall cell lung carcinoma: Outcome analysis from a tertiary care center

    Directory of Open Access Journals (Sweden)

    Avinash Vijaykumar Pandey

    2015-01-01

    Full Text Available Background: Maintenance pemetrexed is a standard treatment option for selected non squamous nonsmall cell lung carcinoma patients having a response to platin based doublet. We conducted a clinical audit of such selected patients and report the outcome among the Indian population. Aim: To evaluate the outcomes with maintenance pemetrexed in the patients with locally advanced and metastatic adenocarcinoma lung. Objectives: To calculate the progression free survival (PFS, overall survival (OS, and factors affecting the outcome. Materials and Methods: Data of patients with locally advanced and metastatic adenocarcinoma lung were retrieved from prospectively maintained lung cancer database registered between June 2011 and March 2014. The patients who achieved partial response (n = 87 or stable disease (n = 101 after 6 cycles of pemetrexed platin based doublet and received the maintenance pemetrexed were selected for final analysis (n = 188. Kaplan-Meir survival analysis was used for PFS and OS. Log rank test was used to evaluate the factors affecting the outcome. Results: Median follow-up is 14 months. The median number of maintenance pemetrexed cycles received is 6 (1-38. Common reason for the discontinuation are disease progression (n = 127, renal toxicity (n = 4, and social/financial (n = 7. Median PFS and OS are 8 months and 20 months, respectively. The patients with baseline pleural effusion had better PFS (9 months vs. 7 months, P = 0.02 and OS (26 months vs. 18 months, P = 0.05. The patients receiving more than 6 cycles of maintenance had improved PFS (12 vs. 7 months, P = 0.002 and OS (26 vs. 16 months, P = 0.05. Conclusion: Maintenance pemetrexed is feasible and well tolerated by the majority of Indian patients who achieved the response after platin based doublet. The patients with baseline pleural effusion benefit more with maintenance pemetrexed.

  3. 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...

  4. 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...

  5. 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.

  6. 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)....

  7. 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...

  8. 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...

  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. 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...

  12. 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...

  13. 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\\

  14. 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...

  15. 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...

  16. 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...

  17. 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...

  18. 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-...

  19. 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 ...

  20. 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 ...

  1. 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....

  2. 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 ...

  3. The proteasomal and apoptotic phenotype determine bortezomib sensitivity of non-small cell lung cancer cells

    Directory of Open Access Journals (Sweden)

    Chęcińska Agnieszka

    2007-11-01

    Full Text Available Abstract Bortezomib is a novel anti-cancer agent which has shown promising activity in non-small lung cancer (NSCLC patients. However, only a subset of patients respond to this treatment. We show that NSCLC cell lines are differentially sensitive to bortezomib, IC50 values ranging from 5 to 83 nM. The apoptosis-inducing potential of bortezomib in NSCLC cells was found to be dependent not only on the apoptotic phenotype but also on the proteasomal phenotype of individual cell lines. Upon effective proteasome inhibition, H460 cells were more susceptible to apoptosis induction by bortezomib than SW1573 cells, indicating a different apoptotic phenotype. However, exposure to a low dose of bortezomib did only result in SW1573 cells, and not in H460 cells, in inhibition of proteasome activity and subsequent apoptosis. This suggests a different proteasomal phenotype as well. Additionally, overexpression of anti-apoptotic protein Bcl-2 in H460 cells did not affect the proteasomal phenotype of H460 cells but did result in decreased bortezomib-induced apoptosis. In conclusion, successful proteasome-inhibitor based treatment strategies in NSCLC face the challenge of having to overcome apoptosis resistance as well as proteasomal resistance of individual lung cancer cells. Further studies in NSCLC are warranted to elucidate underlying mechanisms.

  4. 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.

  5. 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

  6. 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

  7. 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)

  8. 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.

  9. 紫龙金片治疗晚期非小细胞肺癌患者化疗后感染的临床观察%Clinical effect of Zilongjin tablets on treatment of advanced non-small cell lung cancer complicated with infections after chemotherapy

    Institute of Scientific and Technical Information of China (English)

    孙彩萍; 陈遐林; 朱晓灵; 叶万立; 刘秋霞; 王建芳

    2014-01-01

    目的:探讨紫龙金片治疗晚期非小细胞肺癌化疗后合并感染的临床效果,为合理使用抗菌药物提供依据。方法回顾性分析晚期非小细胞肺癌患者化疗后发生医院感染的72例患者的临床资料,并观察采用紫龙金片治疗的临床效果。结果273例治疗患者中发生感染72例,感染率为26.4%;单部位感染68例占94.4%,多部位感染4例占5.6%;感染高发部位以呼吸系统及消化系统为主,分别占72.0%和19.5%;72例感染患者中化疗1次占15.3%、2次占34.7%、≥3次占50.0%;共检出病原菌68株,其中革兰阳性菌22株占32.3%,革兰阴性菌38株占55.9%,真菌8株占11.8%;感染控制65例,占90.3%,死亡3例,病死率4.1%,自动出院4例。结论晚期非小细胞肺癌化疗后感染时,应在药敏结果的指导下合理使用抗菌药物药物治疗,同时防止真菌感染的发生,合理使用粒细胞集落刺激因子,并加强营养支持治疗。%OBJECTIVE To explore the clinical effect of Zilongjin tablets on treatment of advanced non-small cell lung caner complicated with infections after chemotherapy so as to provide guidance for reasonable use of antibiot-ics .METHODS The clinical data of 72 patients with advanced non-small cell lung cancer complicated with nosoco-mial infections were retrospectively analyzed ,then the clinical therapeutic effect of Zilongjin tablets was observed . RESULTS The infections occurred in 72 of 273 patients with the infection rate of 26 .4% ,including 68 (94 .4% ) cases of single site infections and 4 (5 .6% ) cases of multiple sites infections ;the patients with respiratory system infections accounted for 72 .0% ,the patients with digestive system infections 19 .5% .Of the 72 patients with in-fections ,15 .3% underwent the chemotherapy for once ,34 .7% for twice ,50 .0% for no less than three times .A total of 68 strains of pathogens have

  10. Change of serum tumor markers and short-term efficacy after radiotherapy in advanced non-small cell lung cancer patients%晚期非小细胞肺癌患者放疗前后肿瘤标志物变化与近期疗效的临床分析

    Institute of Scientific and Technical Information of China (English)

    张天; 苑惠敏; 毛凯; 任晔; 任既晨; 刘德志; 王斌; 王宗烨

    2013-01-01

    Objective To investigate the change of the serum levels of CEA,CYFAR21-1,SCC,CA125 in advanced non-small cell lung cancer.patients before and after radiotherapy retrospectively and to explore the relationship between the change of serum tumor markers and the short-term efficacy of radiotherapy.Methods The serum levels of CEA,CYFAR21-1,SCC,CA125 in 205 cases with advanced non-small cell lung cancer were detected (by electro-chemiluminescence immunoassay method)before and after radiotherapy,and the short-term efficacy of radiotherapy was assessed (RECIST 1.1 edition) at the same time.The changes in tumor markers and the short-term efficacy were analyzed.Results Totally 113 patients achieved response of short-term efficacy after radiotherapy,and the effective rate of the short-term efficacy was 55.1%.Among these 113 patients,the serum levels of tumor markers decreased significantly after radiotherapy(t =3.224,2.896,3.137,3.219,P < 0.05).The serum levels of tumor markers in patients with stage Ⅲ and Ⅳ decreased after radiotherapy (t =2.484,2.445,2.148,2.109,P < 0.05 ;t =2.072,2.857,2.277,2.436,P < 0.05).Among 92 patients who did not achieve response of short-term efficacy,the serum level of tumor markers increased significantly after radiotherapy(t=2.224,2.005,2.261,2.545,P < 0.05).For the patient who achieved response of radiotherapy with tumor markers decreased,the short-term efficacy was significantly better than the group of which tumor maker increased (x2 =80.001,P < 0.01).Conclusions The serum levels of CEA,CYFAR21-1,SCC,CA125 can be used for assessment of short-term efficacy after radiotherapy in advanced non-small cell lung cancer patients.%目的 回顾性研究晚期非小细胞肺癌患者放疗前后血清CEA、CYFAR21-1、SCC、CA125的水平变化,探讨血清肿瘤标志物的改变及与放疗近期疗效的关系.方法 常规检查205例经确诊的晚期非小细胞肺癌患者放疗前、后血清CEA、CYFAR21-1、SCC、CA125等肿

  11. 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

  12. IARS2 silencing induces non-small cell lung cancer cells proliferation inhibition, cell cycle arrest and promotes cell apoptosis.

    Science.gov (United States)

    Yin, J; Liu, W; Li, R; Liu, J; Zhang, Y; Tang, W; Wang, K

    2016-01-01

    The purpose of this study was to investigate the potential role of Ileucyl-tRNA synthetase (IARS2) silencing in non-small cell lung cancer (NSCLC). The silencing of IARS2 in H1299 cells and A549 cells were performed by lentivirus encoding shRNAs. The efficiency of IARS2 silencing was detected by quantitative real time PCR and western blot. The effects of IARS2 silencing on cell growth, cell apoptosis, cell cycle and cell colony formation ability were assessed by cells counting, MTT assay, flow cytometer analysis and soft agar colony formation assay, respectively. Compared with negative control group, IARS2 was significantly knockdown by transfection with lentivirus encoding shRNA of IARS2. The IARS2 silencing significantly inhibited the cells proliferation and cells colony formation ability, induced cell cycle arrest at G1/S phase and promoted cell apoptosis. IARS2 silencing induced NSCLC cells growth inhibition, cell cycle arrest and promoted cell apoptosis. These results suggest that IARS2 may be a novel target for the treatment of NSCLC. PMID:26639235

  13. 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

  14. Fibroblast growth factor signaling and inhibition in non-small cell lung cancer and their role in squamous cell tumors

    International Nuclear Information System (INIS)

    With the introduction of targeted agents primarily applicable to non-small cell lung cancer (NSCLC) of adenocarcinoma histology, there is a heightened unmet need in the squamous cell carcinoma population. Targeting the angiogenic fibroblast growth factor (FGF)/FGF receptor (FGFR) signaling pathway is among the strategies being explored in squamous NSCLC; these efforts are supported by growth-promoting effects of FGF signaling in preclinical studies (including interactions with other pathways) and observations suggesting that FGF/FGFR-related aberrations may be more common in squamous versus adenocarcinoma and other histologies. A number of different anti-FGF/FGFR approaches have shown promise in preclinical studies. Clinical trials of two multitargeted tyrosine kinase inhibitors are restricting enrollment to patients with squamous NSCLC: a phase I/II trial of nintedanib added to first-line gemcitabine/cisplatin and a phase II trial of ponatinib for previously treated advanced disease, with the latter requiring not only squamous disease but also a confirmed FGFR kinase amplification or mutation. There are several ongoing clinical trials of multitargeted agents in general NSCLC populations, including but not limited to patients with squamous disease. Other FGF/FGFR-targeted agents are in earlier clinical development. While results are awaited from these clinical investigations in squamous NSCLC and other disease settings, additional research is needed to elucidate the role of FGF/FGFR signaling in the biology of NSCLC of different histologies

  15. A Systemic Review of Resistance Mechanisms and Ongoing Clinical Trials in ALK-rearranged Non-Small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    VictorCohen

    2014-07-01

    Full Text Available The identification of oncogenic driver driver mutations in non-small cell lung cancer has led to a paradigm shift and the development of specific molecular treatments. Tumors harboring a rearranged EML4-ALK fusion oncogene are highly sensitive to therapy with ALK-targeted inhibitors. Crizotinib is the first approved treatment for advanced lung tumors containing this genetic abnormality. In this mini review, we discuss the existing data on crizotinib as well as ongoing trials involving this medication. A brief overview of the known resistance mechanisms to criztotinib will also be presented followed by a summary of the ongoing trials involving next-generation ALK inhibitors or other targeted therapies in patients with ALK+ NSCLC.

  16. 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

  17. S1415CD, Prophylactic Colony Stimulating Factor Management in Patients With Breast, Colorectal or Non-Small Cell Lung Cancer Receiving Chemotherapy and With Risk of Developing Febrile Neutropenia

    Science.gov (United States)

    2016-04-08

    Febrile Neutropenia; Stage 0 Breast Cancer; Stage 0 Colorectal Cancer; Stage 0 Non-Small Cell Lung Cancer; Stage I Colorectal Cancer; Stage IA Breast Cancer; Stage IA Non-Small Cell Lung Carcinoma; Stage IB Breast Cancer; Stage IB Non-Small Cell Lung Carcinoma; Stage IIA Breast Cancer; Stage IIA Colorectal Cancer; Stage IIA Non-Small Cell Lung Carcinoma; Stage IIB Breast Cancer; Stage IIB Colorectal Cancer; Stage IIB Non-Small Cell Lung Carcinoma; Stage IIC Colorectal Cancer; Stage IIIA Breast Cancer; Stage IIIA Colorectal Cancer; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Breast Cancer; Stage IIIB Colorectal Cancer; Stage IIIB Non-Small Cell Lung Cancer; Stage IIIC Breast Cancer; Stage IIIC Colorectal Cancer; Stage IV Breast Cancer; Stage IV Non-Small Cell Lung Cancer; Stage IVA Colorectal Cancer; Stage IVB Colorectal Cancer

  18. 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.

  19. 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.

  20. Treatment rationale and study design for a phase III, double-blind, placebo-controlled study of maintenance pemetrexed plus best supportive care versus best supportive care immediately following induction treatment with pemetrexed plus cisplatin for advanced nonsquamous non-small cell lung cancer

    International Nuclear Information System (INIS)

    To improve the efficacy of first-line therapy for advanced non-small cell lung cancer (NSCLC), additional maintenance chemotherapy may be given after initial induction chemotherapy in patients who did not progress during the initial treatment, rather than waiting for disease progression to administer second-line treatment. Maintenance therapy may consist of an agent that either was or was not present in the induction regimen. The antifolate pemetrexed is efficacious in combination with cisplatin for first-line treatment of advanced NSCLC and has shown efficacy as a maintenance agent in studies in which it was not included in the induction regimen. We designed a phase III study to determine if pemetrexed maintenance therapy improves progression-free survival (PFS) and overall survival (OS) after cisplatin/pemetrexed induction therapy in patients with advanced nonsquamous NSCLC. Furthermore, since evidence suggests expression levels of thymidylate synthase, the primary target of pemetrexed, may be associated with responsiveness to pemetrexed, translational research will address whether thymidylate synthase expression correlates with efficacy outcomes of pemetrexed. Approximately 900 patients will receive four cycles of induction chemotherapy consisting of pemetrexed (500 mg/m2) and cisplatin (75 mg/m2) on day 1 of a 21-day cycle. Patients with an Eastern Cooperative Oncology Group performance status of 0 or 1 who have not progressed during induction therapy will randomly receive (in a 2:1 ratio) one of two double-blind maintenance regimens: pemetrexed (500 mg/m2 on day 1 of a 21-day cycle) plus best supportive care (BSC) or placebo plus BSC. The primary objective is to compare PFS between treatment arms. Secondary objectives include a fully powered analysis of OS, objective tumor response rate, patient-reported outcomes, resource utilization, and toxicity. Tumor specimens for translational research will be obtained from consenting patients before induction treatment

  1. Elevated serum level of VEGF in advanced non-small cell lung cancer and its clinical significance%晚期非小细胞肺癌外周血血管内皮生长因子检测及其临床意义

    Institute of Scientific and Technical Information of China (English)

    郭沁香; 宋霞

    2007-01-01

    Objective To study the level of serum vascular endothelial growth factor(sVEGF)in advanced non-small cell lung cancer(NSCLC) and its clinical significance.Methods Serum level of VEGF was detected by ELISA method in 96 patients with advanced NSCLC.sVEGF level was analyzed after giving 2-4 cycles of cisplatin-based chemotherapy.At the same time,serum level of VEGF in 50 healthy controls was detected.Results The level of sVEGF was significantly higher in patient with lung cancer than in control group (P<0.01).No statistical significant defference was observed between sVEGF level of stage Ⅲ and Ⅳ NSCLC patients,the patients with squamocellular lung cancer and adenocarcinoma(P>0.05);Descended sVEGF level was found in the patients with response to chemotherapy(P<0.05).Conclusion sVEGF can be used to evaluate chemotherapy response and diagnoses in the patients with advanced NSCLC.%目的 探讨晚期非小细胞肺癌(NSCLC)患者血清中血管内皮生长因子(sVEGF)水平及评价其临床意义.方法 应用酶联免疫吸附法(ELISA)测定sVEGF在96例晚期NSCLC患者血清中的表达,分别给含顺铂的联合化疗方案2~4个周期后再测定其sVEGF水平;同时检测50例健康体检者的sVEGF水平.结果 肺癌患者sVEGF含量明显高于健康对照组(P<0.01);腺癌sVEGF水平与鳞癌相比差异无统计学意义(P>0.05);Ⅲ、Ⅳ期患者sVEGF水平相比差异无统计学意义(P>0.05);所有缓解病例化疗后sVEGF水平均显著下降(P<0.05).结论 晚期NSCLC患者sVEGF水平与其诊断及治疗效果密切相关.

  2. The benefit of treatment intensification is age and histology-dependent in patients with locally advanced non-small cell lung cancer (NSCLC): a quality-adjusted survival analysis of radiation therapy oncology group (RTOG) chemoradiation studies

    International Nuclear Information System (INIS)

    Purpose: Currently, chemoradiation treatment strategies in locally advanced NSCLC are essentially the same irrespective of tumor histology or patient age. The purpose of this study is to analyze the impact of age, histology, Karnofsky performance status (KPS), and specific toxicities on the median survival time (MST) and quality-adjusted survival (QTime) for each treatment strategy. Methods and Materials: Nine hundred seventy-nine patients with Stage II-IIIB inoperable NSCLC were enrolled on 6 prospective Phase II and III studies from 1983 to 1995. Treatment regimens ranged from standard RT (SRT) to 60 Gy, hyperfractionated RT (HRT) to 69.6 Gy, induction chemotherapy (ICT) of cisplatin (CIS) and vinblastine (VBL) followed by SRT, ICT + concurrent CT (CCT) + SRT, and CCT + HRT; CCT consisted of etoposide or VBL + CIS. Toxicities assessed were skin, mucous membrane, lung, esophagus, neurologic, hematologic, and upper GI. QTime was calculated by weighting the time spent with a specific toxicity, as well as local or distant tumor progression. Each toxicity was weighted with increasing severity as the toxicity increased in grade. Results: As expected, patients with the worst KPS (50-70) had the lowest MST (7.8 months) and QTime (6.7 months). Patients 70 years achieved the best QTime with standard RT (SRT) alone. In patients with squamous cell carcinoma, those treated with ICT + CCT + SRT had dramatically improved MST (25.7 months) and QTime (21.8 months) compared to the other treatment regimens (11.7-12.8 and 10.7-12 months, respectively). Patients with adenocarcinoma, however, generally manifested incrementally better MST and QTime as the therapies intensified. Within the concurrent chemoradiation arms, the upper GI and lung toxicities had the greatest impact on QTime. Conclusion: This quality-adjusted survival analysis suggests that there is a critical relationship between the type of histology and its optimal treatment, age and the ability to tolerate intensive

  3. 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.

  4. Characteristics and overall survival of EGFR mutation-positive non-small cell lung cancer treated with EGFR tyrosine kinase inhibitors: a retrospective analysis for 1660 Japanese patients

    Science.gov (United States)

    Inoue, Akira; Yoshida, Kazushi; Morita, Satoshi; Imamura, Fumio; Seto, Takashi; Okamoto, Isamu; Nakagawa, Kazuhiko; Yamamoto, Nobuyuki; Muto, Satoshi; Fukuoka, Masahiro

    2016-01-01

    Background The Japan Guidelines of Lung Cancer Therapy recommend epidermal growth factor receptor-tyrosine kinase inhibitors as a first-line therapy for advanced/recurrent non-small cell lung cancer patients with epidermal growth factor receptor mutation. Although survival periods in recent reports of epidermal growth factor receptor-tyrosine kinase inhibitor treatment have been getting longer, the reasons why are unclear. We investigated the survival, prognostic factors and real-world treatment of non-small cell lung cancer patients with epidermal growth factor receptor mutation in clinical practice. Methods Non-small cell lung cancer patients (n = 1660) who started first-line treatment from January 2008 to December 2012 were enrolled. Patients were diagnosed with epidermal growth factor receptor mutation-positive advanced/recurrent non-small cell lung cancer by histology or cytology samples. The primary objective was to estimate overall survival. The secondary objectives were to determine prognostic factors, real-world treatment patterns and efficacy of gefitinib treatment. We calculated the treatment exposure rate for each treatment category using the following formula: exposure rate = person-years for the treatment category/total person-years × 100. Results The median overall survival was 30.8 months. Sex, age, histology, epidermal growth factor receptor mutation type, clinical stage and performance status affected overall survival. The exposure rates for all epidermal growth factor receptor-tyrosine kinase inhibitors, gefitinib and platinum-doublet chemotherapy were 62.1, 46.4 and 8.5% respectively. Overall 56.1% of patients were administered gefitinib as first-line therapy, and 39.0% were treated with ≥2 epidermal growth factor receptor-tyrosine kinase inhibitor regimens. The median progression-free survival in the first-line gefitinib group was 11.4 months. Factors affecting prognosis were sex, histology, clinical stage and performance status. Conclusion

  5. Noncoding RNA small nucleolar RNA host gene 1 promote cell proliferation in nonsmall cell lung cancer

    Directory of Open Access Journals (Sweden)

    J You

    2014-01-01

    Full Text Available Background: Nonsmall cell lung cancer (NSCLC is the major cause of cancer death worldwide. Increasing evidence shows that noncoding RNAs (ncRNAs are widely involved in the development and progression of NSCLC. ncRNA small nucleolar RNA host gene 1 (SNHG1 has not been studied in cancer, especially its role in lung cancer remains unknown. Our studies were designed to investigate the expression and biological significance of SNHG1 in lung cancer. SNHG1 may be a novel ncRNA in early diagnosis in lung cancer. Methods: Noncoding RNA SNHG1 expression in 7 lung cancer cell lines was measured by quantitative real-time polymerase chain reaction. RNA interference approaches were used to find the biological functions of SNHG1. The effect of SNHG1 on proliferation was evaluated by cell count and crystal violet stains. Results: Noncoding RNA SNHG1 expression was significantly upregulated in lung cancer cells when compared with normal bronchial epithelial cells. In addition, in vitro assays our results indicated that knockdown of SNHG1 inhibited cell proliferation. Conclusions: Our data indicated that ncRNA SNHG1 is significantly upregulated in NSCLC cell lines and may represent a new biomarker and a potential therapeutic target for NSCLC intervention.

  6. THE EXPRESSION OF DNA REPAIR GENE XPA IN ADVANCED NON-SMALL CELL LUNG CANCER AND ITS CLINICAL SIGNIFICANCE%DNA修复基因XPA在非小细胞肺癌中的表达及其临床意义

    Institute of Scientific and Technical Information of China (English)

    覃芳卉; 刘志辉; 谢伟敏; 廖小莉; 姚铠涛; 王洪学; 房亮; 陆永奎; 周文献; 胡晓桦

    2012-01-01

    目的:分析非小细胞肺癌(NSCLC)组织中DNA修复基因Xeroderma Pigmentosum Group A(XPA)的表达状况及其与临床病理特征的关系.方法:采用免疫组织化学方法(IHC)检测初治中晚期NSCLC患者癌组织中XPA的表达状况,采用χ2检验比较各亚组之间的XPA表达状况的差异.结果:109例NSCLC组织中XPA的阳性表达率为55.0%(60/109),其表达与性别、吸烟史有密切关系,在男性组中的阳性率(61.0%)显著高于女性组(37.0%)(P=0.030);吸烟组的XPA阳性率显著高于不吸烟组(分别为68.1%和45.2%,P=0.017);但在吸烟人群中,吸烟量不同的亚组间XPA的表达率未见明显差异.XPA阳性率在不同年龄、临床TNM分期、组织学类型或分化程度、淋巴结转移和远处转移亚组中的差异均无统计学意义(均P>0.05).结论:XPA在NSCLC组织中的表达状况与性别、吸烟状况密切相关,并可能与NSCLC的发生有关.%Objective: To investigate the association between the expression of DNA repair gene XPA with the clinicopathology characteristics in patients with advanced non-small cell lung cancer (NSCLC) and its clinical significance. Methods: The expression of XPA -was examined -with immunohistochemistry (IHC) , the positive expression rate of XPA in different clinicopathology characteristic groups -was analyzed. Re-sultS: In 109 patients with NSCLC, the positive rate of XPA was 55. 0% (60/109) , and the expression rate in males was significantly higher than that in females (61. 0% vs. 37. 0%, P = 0. 030). The expression rate -was also higher in smokers than in non-smokers (68. 1 % vs. 45. 2% , P =0. 017). There -were no significant differences in the expression of XPA among different ages, TNM stages, and pathological classification ( P >0. 05 for all). Conclusion: In NSCLC cases, the expression status of XPA is markedly associated with gender and smoking status. Thus, XPA may play a potential role in non-small cell lung cancer occur process.

  7. Analysis of the clinical factors in the treatment of advanced non-small cell lung cancer%影响晚期非小细胞肺癌治疗效果的临床因素分析

    Institute of Scientific and Technical Information of China (English)

    周秀开; 孙秀华; 赵金波; 李曼; 吴涛; 张阳

    2011-01-01

    Objective To investigate the clinical factors related to the treatment efficacy of advanced non -small cell lung cancer ( NSCLC) hy analyzing the clinical data of 157 patients with NSCLC. Methods The patients with advanced NSCLC visiting 2nd Affiliated Hospital of Dalian Medical Oncology in Jan . 2006-Jan. 2008 were included in this retrospective analysis . All relevant factors which have effected on the short -and long-term treatment efficacy were analyzed. The procedures are :1. Statistics analysis of time to progression ( TTP) after first-line treatment ( chemotherapy and targeted therapy ) to investigate the effect of gender , age, Kamofsky score and pathological type on the short-term treatment efficacy of advanced NSCLC. 2. Patients were divided into three groups according to survival time , A: less than 12 months; B: more than 12 months and less than 24 months; C: more than 24 months.Stratified analysis were done to analyze the effect of gender , age, Kamofsky score , clinical stage , histological type, malignant pleural effusion, number of metastasis and the combined therapy on the long-term treatment efficacy of NSCLC. Results 157 patients , female 53 (33. 8% ) and male 104 ( 66. 2% ) ; squamous cell carcinoma 46 cases ( 29. 3% ) , adenocarcinoma 99 ( 63. 1% ) . and others 12 (7. 6% ) ; stage Ⅲb 60( 38. 2% ) and stage Ⅳ 97 ( 61. 8% ) ; median TTP is 4 months after first-line chemotherapy and first -line targeted therapy ;the overall median survival is 13 months; 12-month survival rate is 58. 0%, and 24-month survival rate is 25. 5% ;Kamofsky score has impact on the TTP after first -line chemotherapy , the patients having a Kamofsky score ≥70 had longer TTP. Sex .age , and pathological type failed to affect TTP . First-Iine targeted therapy has similar short -term efficacy as first -line chemotherapy.Age and Kamofskv score were influencing factors on the long -term efficacy of advanced NSCLC. Both 12-and 24-month survival rate were

  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. 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

  10. 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.

  11. 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

  12. 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...

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

    Directory of Open Access Journals (Sweden)

    Antonino Bruno

    2013-02-01

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

  14. 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.

  15. 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...

  16. 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...

  17. Antiangiogenic agents combined with chemotherapy in non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    Shanshan Chen; Shun Lu 

    2015-01-01

    As a targeted therapy, antiangiogenic treatment has been increasingly studied for advanced non-smal cel lung cancer (NSCLC) and has proven ef ective for the treatment of advanced NSCLC. Bevacizumab, a monoclonal antibody targeting angiogenesis, is the only antiangiogenic agent approved for use in com-bination with first-line chemotherapy for non-squamous NSCLC. Smal-molecule inhibitors targeting the tyrosine kinase receptor have also shown promise when combined with standard chemotherapeutic agents in patients with advanced NSCLC. However, unlike bevacizumab, not al other antiangiogenic agents show significant benefits when combined with chemotherapy. As for the failures of most other combinations, the combination schedule may be an important reason that has so far been overlooked in clinical trials. This article reviews the combination of angiogenic agents with chemotherapy in the treatment of NSCLC.

  18. 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

  19. Association of nutritional status and serum albumin levels with development of toxicity in patients with advanced non-small cell lung cancer treated with paclitaxel-cisplatin chemotherapy: a prospective study

    OpenAIRE

    Martínez Luis; Rodríguez Cindy M; Diaz-Romero Consuelo; Flores-Estrada Diana; Serna-Thomé Maria G; Villanueva-Rodríguez Geraldine; Michel Ortega Rosa M; Arrieta Oscar; Sánchez-Lara Karla

    2010-01-01

    Abstract Background A frequent manifestation of advanced NSCLC is malnutrition, even though there are many studies which relate it with a poor survival, its relation with toxicity has not yet been consistently reported. The aim of this study was to associate malnutrition and albumin serum levels with the occurrence of chemotherapy-induced toxicity in cisplatin plus paclitaxel chemotherapy-treated NSCLC. Methods We prospectively evaluated 100 stage IV NSCLC patients treated with paclitaxel (17...

  20. Survival Model Established by Combined Serum Tumor Markers in Predicating the Effect of Erlotinib on Patients with Recurrent Non-small Cell Lung Cancer

    OpenAIRE

    Lan Shao; Wei Hong; Yiping Zhang

    2013-01-01

    Objective: To investigate the relationship of serum pulmonary surfactant-associated pretein (SP-D), transforming growth factor-α (TGF-α), matrix metalloproteinases-9 (MMP-9), tissue polypeptide specific antigen (TPS) and lung adenocarcinoma-related antigen (KL-6) with the effect and survival of treating advanced recurrent non-small cell lung cancer (NSCLC), and to establish a survival predication model. Methods: ELISA was applied to detect peripheral serum SP-D, TGF-α, MMP-9, TPS and KL-6 lev...

  1. Research Progress of Epidermal Growth Factor Receptor and Molecular-Targeted Therapy in Treatment of Non-Small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Xiaoyou Li

    2014-03-01

    Full Text Available Molecular target therapy has become a new approach in the treatment of advanced non-small cell lung cancer (NSCLC. The sensitivity of lung cancer to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs has been found to be associated with gene mutationss in the tyrosine kinase domain of RGFR. However, not all EGFR gene mutationss are sensitive to EGFR-TKIs. The review was conducted to study the research progress of EGFR mutations and the sensitivity to EGFR-TKIs and the mechanism of resistance of molecular target therapy in NSCLC.

  2. Research Progress of Epidermal Growth Factor Receptor and Molecular-Targeted Therapy in Treatment of Non-Small Cell Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    Li Xiaoyou; Feng Jifeng

    2014-01-01

    Molecular target therapy has become a new approach in the treatment of advanced non-small cell lung cancer (NSCLC). The sensitivity of lung cancer to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) has been found to be associated with gene mutationss in the tyrosine kinase domain of RGFR. However, not all EGFR gene mutationss are sensitive to EGFR-TKIs. The review was conducted to study the research progress of EGFR mutations and the sensitivity to EGFR-TKIs and the mechanism of resistance of molecular target therapy in NSCLC.

  3. 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

  4. [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

  5. 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)

  6. Application of CT-guided percutaneous lung biopsy in detecting epidermal growth factor receptor gene mutations in patients with advanced non-small cell lung cancer%CT引导经皮肺穿刺活检检测晚期非小细胞肺癌表皮生长因子受体基因突变

    Institute of Scientific and Technical Information of China (English)

    侯晓玮; 庄兴俊; 宋谦; 李露嘉; 王宁宁

    2013-01-01

    Objective To investigate the feasibility of CT-guided percutaneous lung biopsy for the detection of epidermal growth factor receptor (EGFR) gene mutations in patients with advanced non-small cell lung cancer (NSCLC). Methods Forty patients with inoperable advanced or locally - advanced NSCLC were enrolled in this study. By using an 18-gauge core biopsy instrument, CT - guided lung biopsy was performed in all patients to get tumor tissue for the determination of EGFR gene mutations. Postoperative complications and histological results were analyzed. Results Sufficient amount of tumor tissue used for the histological examination and the determination of EGFR gene mutations was successfully obtained by puncturing biopsy in all the forty patients. EGFR mutations occurred in 37.5% of all NSCLC cases (15/40). The mutation rate in adenocarcinoma was 50% (12/24), while the mutation rate in non-adenocarcinoma was only 18.8% (12/24), the difference in the mutation rate between the two pathologic types was statistically significant (P = 0.046). Three patients developed pneumothorax. Hemoptysis occurred in three patients. No hemothorax, mediastinal emphysema, infection or needle tract seeding occurred. The patients with EGFR gene mutations tended to respond well to gefitinib. Conclusion CT-guided lung biopsy is a simple and safe technique, which can be reliably used for the detection of EGFR gene mutations in patients with advanced NSCLC. Besides, this method is also very helpful in predicting the clinic efficacy of targeted therapy for advanced NSCLC.%目的 研究CT引导经皮肺穿刺活检获得组织检测非小细胞肺癌(NSCLC)表皮生长因子受体(EGFR)基因突变的可行性.方法 入组40例晚期或局部晚期无法手术的NSCLC患者,采用18G自动活检枪,经CT引导行肺穿刺活检获取肿瘤组织,行EGFR基因检测,观察术后并发症,分析检测结果.结果 40例病例均经穿刺活检获得足够的病变组织进行组织学诊断和基

  7. Activation of the IGF1R pathway potentially mediates acquired resistance to mutant-selective 3rd-generation EGF receptor tyrosine kinase inhibitors in advanced non-small cell lung cancer.

    Science.gov (United States)

    Park, Ji Hyun; Choi, Yun Jung; Kim, Seon Ye; Lee, Jung-Eun; Sung, Ki Jung; Park, Sojung; Kim, Woo Sung; Song, Joon Seon; Choi, Chang-Min; Sung, Young Hoon; Rho, Jin Kyung; Lee, Jae Cheol

    2016-04-19

    Mutant-selective, 3rd-generation EGFR-TKIs were recently developed to control lung cancer cells harboring T790M-mediated resistance. However, the development of resistance to these novel drugs seems inevitable. Thus, we investigated the mechanism of acquired resistance to the mutant-selective EGFR-TKI WZ4002. We established five WZ4002-resistant cells, derived from cells harboring both EGFR and T790M mutations by long-term exposure to increasing doses of WZ4002. Compared with the parental cells, all resistant cells showed 10-100-folds higher resistance to WZ4002, as well as cross-resistance to other mutant-selective inhibitors. Among them, three resistant cells (HCC827/WR, PC-9/WR and H1975/WR) showed dependency on EGFR signaling, but two other cells (PC-9/GR/WR and PC-9/ER/WR) were not. Notably, insulin-like growth factor-1 receptor (IGF1R) was aberrantly activated in PC-9/GR/WR cells in phospho-receptor tyrosine kinase array, consistently accompanied by loss of IGF binding protein-3 (IGFBP3). Down-regulation of IGF1R by shRNA, as well as inhibition of IGF1R activity either by AG-1024 (a small molecule IGF1R inhibitor) or BI 836845 (a monoclonal anti-IGF1/2 blocking antibody), restored the sensitivity to WZ4002 both in vitro and xenograft. Taken together, these results suggest that activation of the IGF1R pathway associated with IGFBP3 loss can induce an acquired resistance to the mutant-selective EGFR-TKI, WZ4002. Therefore, a combined therapy of IGF1R inhibitors and mutant-selective EGFR-TKIs might be a viable treatment strategy for overcoming acquired resistance. PMID:26980747

  8. Activation of the IGF1R pathway potentially mediates acquired resistance to mutant-selective 3rd-generation EGF receptor tyrosine kinase inhibitors in advanced non-small cell lung cancer

    Science.gov (United States)

    Park, Ji Hyun; Choi, Yun Jung; Kim, Seon Ye; Lee, Jung-Eun; Sung, Ki Jung; Park, Sojung; Kim, Woo Sung; Song, Joon Seon; Choi, Chang-Min; Sung, Young Hoon; Rho, Jin Kyung; Lee, Jae Cheol

    2016-01-01

    Mutant-selective, 3rd-generation EGFR-TKIs were recently developed to control lung cancer cells harboring T790M-mediated resistance. However, the development of resistance to these novel drugs seems inevitable. Thus, we investigated the mechanism of acquired resistance to the mutant-selective EGFR-TKI WZ4002. We established five WZ4002-resistant cells, derived from cells harboring both EGFR and T790M mutations by long-term exposure to increasing doses of WZ4002. Compared with the parental cells, all resistant cells showed 10–100-folds higher resistance to WZ4002, as well as cross-resistance to other mutant-selective inhibitors. Among them, three resistant cells (HCC827/WR, PC-9/WR and H1975/WR) showed dependency on EGFR signaling, but two other cells (PC-9/GR/WR and PC-9/ER/WR) were not. Notably, insulin-like growth factor-1 receptor (IGF1R) was aberrantly activated in PC-9/GR/WR cells in phospho-receptor tyrosine kinase array, consistently accompanied by loss of IGF binding protein-3 (IGFBP3). Down-regulation of IGF1R by shRNA, as well as inhibition of IGF1R activity either by AG-1024 (a small molecule IGF1R inhibitor) or BI 836845 (a monoclonal anti-IGF1/2 blocking antibody), restored the sensitivity to WZ4002 both in vitro and xenograft. Taken together, these results suggest that activation of the IGF1R pathway associated with IGFBP3 loss can induce an acquired resistance to the mutant-selective EGFR-TKI, WZ4002. Therefore, a combined therapy of IGF1R inhibitors and mutant-selective EGFR-TKIs might be a viable treatment strategy for overcoming acquired resistance. PMID:26980747

  9. Analysis of complications and outcomes after pulmonary resection in patients aged 80 years or over with non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Wen-bing LI

    2014-10-01

    Full Text Available Objective To explore the therapeutic effect and degree of safety in patients aged 80 years or over with nonsmall cell lung cancer undergoing radical resection. Methods A retrospective survey of 97 elder patients aged 80 years or over, in whom non-small cell lung cancer was pathologically confirmed after partial resection of the lung in Chinese PLA General Hospital from Jan. 2003 to Dec. 2012. The peri-operative features were evaluated, including gender, age, history of smoking, pulmonary function, surgical procedure, histopathologic type, pathologic stage, etc. The relation of the postoperative complications and mortality with the factors mentioned above was analyzed. Results Among all patients, the surgical procedure comprised 36 lobectomies, 31 segmentectomies, and 30 wedge resections. The histopathologic diagnosis showed there were adenocarcinoma in 51 patients, squamous cell carcinoma in 29, large cell carcinoma in 9, adenosquamous cell carcinoma in 6 and neuro-endocrine cell carcinomas in 2. The disease stage was determined as ⅠA in 55 cases, ⅠB in 33, ⅡA in 7, ⅢA in 2. The post-operative complications (POC occurred in 14 of 97 patients (14.4%, and the most common complication was cardiovascular complication (9 cases, followed by pulmonary complication (5 cases. Only two patients died to the complications, one of them was post-operative pneumonia and respiratory failure, and the other one was acute myocardial infarction. The survival rate of the 97 patients was 91.7%, 70.2% and 52.8% at 1, 3 and 5 years, respectively, and in the patients with stage I disease, the survival rate was 93.9%, 73.6% and 54.1%, respectively. Conclusion Advanced age is not a contraindication to radical pulmonary resection in patients over 80 years old suffering from early stage non-small cell lung cancer. DOI: 10.11855/j.issn.0577-7402.2014.10.13

  10. 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

  11. High dose combination chemotherapy with ifosfamide, cyclophosphamide or cisplatin, mitomycin C and mustine with autologous bone marrow support in advanced non-small cell lung cancer. A phase I/II study.

    OpenAIRE

    Gomm, S. A.; Thatcher, N; Cuthbert, A.; Chang, J.; Burmester, H.; Hall, P.; Carroll, K. B.

    1991-01-01

    Twenty-three patients with advanced NSCLC were treated with high dose chemotherapy using four agents and autologous bone marrow reinfusion. Ten patients received two bolus doses of cyclophosphamide (maximum tolerated total dose 10 G m-2), ifosfamide as a 24 h infusion (11 G m-2) followed by mitomycin C (70 mg m-2) as a subsequent 24 h infusion and mustine as two boluses (total dose 30 mg m-2). Another 13 patients received the same agents except cisplatin was substituted for cyclophosphamide, ...

  12. Additional weekly Cetuximab to concurrent chemoradiotherapy in locally advanced non-small cell lung carcinoma: Efficacy and safety outcomes of a randomized, multi-center phase II study investigating

    International Nuclear Information System (INIS)

    Background: Modest benefits from concurrent chemoradiotherapy in patients with locally advanced NSCLC warrant further clinical investigations to identify more effective treatment regimens. Cetuximab, a monoclonal antibody against the epidermal growth factor receptor has shown activity in NSCLC. We report on the safety and efficacy of the combination of daily dose Cisplatin and concurrent radiotherapy with or without weekly Cetuximab. Patients and methods: Patients received high dose accelerated radiotherapy (66 Gy in 24 fractions) and concurrent daily Cisplatin (6 mg/m2) without (Arm A) or with (Arm B) weekly Cetuximab (400 mg/m2 loading dose one week prior to radiotherapy followed by weekly 250 mg/m2). The primary endpoint of the trial was objective local control rate (OLCR) determined at 6–8 weeks after treatment. Toxicity was reported as well. Results: Between February 2009 and May 2011, 102 patients were randomized. Median follow up was 29 months. The OLCR was 84% in Arm A and 92% in Arm B (p = 0.36). The one-year local progression free interval (LPFI) and overall survival (OS) were 69% and 82% for Arm A and 73% and 71% for Arm B, respectively (LPFI p = 0.39; OS p = 0.99). Toxicity compared equally between both groups. Conclusion: The addition of Cetuximab to radiotherapy and concurrent Cisplatin did not improve disease control in patients with locally advanced NSCLC but increased treatment related toxicity

  13. Clinical Study on Human Recombinant Endostatin Injection Combined With Chemotherapy in Treatment of Middle-advanced Non-small Cell Lung Cancer%重组人血管内皮抑制素注射液联合化疗治疗中晚期非小细胞肺癌的临床研究

    Institute of Scientific and Technical Information of China (English)

    刘辉霞

    2016-01-01

    目的:研究重组人血管内皮抑制素注射液(恩度)联合化疗治疗中晚期非小细胞肺癌的临床效果。方法研究年度2015年1月~2015年12月,纳入中晚期非小细胞肺癌共47例,抽签法分组。接受化疗者有23例,入对照组;接受恩度联合化疗者有24例,入实验组。组间比较。结果2组中实验组临床有效率更高,KPS改善率更高,有统计学意义(P<0.05)。结论恩度联合化疗治疗中晚期非小细胞肺癌效果佳,临床有效率高。%Objective Clinical effect of human recombinant endostatin injection(endostar)combined with chemotherapy in treatment of middle-advanced non-smal cel lung cancer is to be studied. Methods Chose 47 patients of middle-advanced non-smal cel lung cancer who were treated in hospital from January 2015 to December 2015 and separated them into two groups by drawing lottery,23 patients in control group were given chemotherapy treatment,while another 24 patients in study group were given endostar combined with chemotherapy treatment,and then compared patients’treatment effects between two groups. Results Patients'clinical treatment efficiency was much higher and their KPS improvements were much better in study group compared to counterparts in control group. there was a differential between two groups and such a differential had statistic value(P < 0.05). Conclusion Endostar combined with chemotherapy is much more clinical y effective in treatment of middle-Advanced non-smal cel lung cancer.

  14. 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.

  15. 血清 CEA、CYFAR21-1、SCC、CA125水平对晚期非小细胞肺癌放疗疗效的评估价值%Assessment Value of Serum CEA,CYFAR21-1,SCC,CA125 Levels in Efficacy of Radiotherapy for Advanced Non-small Cell Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    阿合力·那斯肉拉; 巴尔夏古丽·扎比胡拉; 穆朝东

    2014-01-01

    目的:探讨血清肿瘤标志物水平对晚期非小细胞肺癌患者放疗疗效的评估价值。方法将晚期非小细胞肺癌患者共176例,分为观察组(近期放疗有效)和对照组(近期放疗无效),采用电化学发光法检测放疗前、后血清肿瘤CEA、CYFAR21-1、SCC、CA125水平。结果176例患者放疗有效率为58.0%,观察组放疗前血清CEA、CYFAR21-1、SCC、CA125水平分别为(33.65±5.41)ng/ml、(19.44±3.14)ng/ml、(16.87±2.74)ng/ml、(46.81±5.49)U/ml,放疗后各项标志物水平分别为(25.13±4.65)ng/ml、(12.35±4.18)ng/ml、(11.77±3.04)ng/ml、(39.67±4.63)U/ml,均明显低于放疗前,差异均有统计学意义(P<0.05);对照组放疗前血清肿瘤标志物CEA、CYFAR21-1、SCC、CA125水平分别为(46.87±5.93)ng/ml、(28.63±10.82)ng/ml、(26.46±8.68)ng/ml、(68.16±7.38)U/ml,放疗后各项标志物水平分别为(52.17±5.49)ng/ml、(46.72±11.75)ng/ml、(38.74±63.48)ng/ml、(87.34±8.16)U/ml,均明显高于放疗前,差异均有统计学意义(P<0.05);观察组放疗前各项标志物水平均低于对照组,差异显著(P<0.05);对照组放疗后标志物水平降低患者的近期疗效明显好于放疗后血清肿瘤标志物水平升高者,差异有统计学意义(χ2=76.45,P<0.05)。结论肿瘤血清肿瘤标志物CEA、CYFAR21-1、SCC、CA125的水平对晚期非小细胞肺癌患者放疗疗效具有评估价值。%Objective To explore the assessment value of serum level of tumor markers in efficacy of radiotherapy for advanced non-small cell lung cancer .Methods 176 cases of advanced non-small cell lung cancer were divided into 2 groups:the observation group ( recent radiotherapy effective ) and the control group ( recent radiotherapy invalid ) , tumor

  16. 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

  17. 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...

  18. 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...

  19. 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

  20. 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.

  1. 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)

  2. 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...

  3. Pulmonary Artery Agenesis Associated With Emphysema and Multiple Invasive Non-Small Cell