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Sample records for cancer patients non-small-cell-lung-cancer

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

    DEFF Research Database (Denmark)

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

    2011-01-01

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

  2. Low-Dose Acetylsalicylic Acid in Treating Patients With Stage I-III Non-Small Cell Lung Cancer

    Science.gov (United States)

    2016-06-28

    Adenocarcinoma of the Lung; Recurrent Non-small Cell Lung Cancer; Stage IA Non-small Cell Lung Cancer; Stage IB 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

  3. Molecular-targeted therapy for elderly patients with advanced non-small cell lung cancer

    OpenAIRE

    Antonelli,Giovanna; Libra, Massimo; PANEBIANCO, VINCENZO; Russo,Alessia Erika; Vitale, Felice Vito; COLINA, PAOLO; D'Angelo,Alessandro; ROSSELLO, ROSALBA; Ferraù, Francesco

    2015-01-01

    Lung cancer is the most common cause of cancer-related mortality in men and women. Non-small cell lung cancer (NSCLC) represents close to 90% of all lung cancers. When diagnosed, >50% of patients are >65 years old. Through an improved understanding of the molecular mechanisms involved in lung oncogenesis, molecular-targeted approaches have become an essential element for the treatment of patients with NSCLC. As the toxicity profiles of the techniques are definitely more favorable compared wit...

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

    LENUS (Irish Health Repository)

    McCarthy, Ita

    2012-01-31

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

  5. 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

  6. 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.

  7. [The quality of life after chemotherapy in advanced non-small cell lung cancer patients].

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    Słowik-Gabryelska, A; Szczepanik, A; Kalicka, A

    1999-01-01

    The intensity of complains, short survival and great number of patients makes many oncologists to apply chemotherapy in advanced non-small cell lung cancer/NSCLC/. The achieved median duration of life after chemotherapy was 6 to 12 month. From the other hand non small cell lung cancer chemotherapy is a big burden even to healthy persons. It can worsen the quality of life. That was the reason we evaluated the quality of life after chemotherapy in advanced non small cell lung cancer patients. Taking into account, that the evaluation of quality of life, used in most diseases is useless in advanced NSCLC patients, for appreciation the quality of life in these cases the lung cancer symptoms scale/LCSS/was adopted. In 110 non small cell lung cancer patients in stage IIIB and IV, who received combined chemotherapy by Le Chevalier/Vindesine, Cisplatin, Cyclophosphamide, Lomustin/or by Rosell/Mitomycin, Cyclophosphamide, Cisplatin/the quality of life was evaluated. In 20-persons control group all patients received the symptomatic treatment. In observed group of 110 patients, tumor regressions after 4 courses of chemotherapy allowed to resect cancer in 14 cases, to apply radiotherapy in 42 and to continue chemiotherapy in 23 persons. In every person from above mentioned group the quality of life was evaluated on the basis of intensity of cancer symptoms, accordingly to LCSS. The intensity of cancer symptoms was compared before and after treatment. There were compared; the innensity of complains, weakness, appetite, malnutrition, and hematological, neurological, performans state as well as respiratory sufficiency, infections, cardiac disorders and pain. Apart it, the side effects of applied therapy were assessed in 5 degree scale. The level of hemoglobin, the number of leucocytes, thrombocytes, bilirubine and transaminases in peripheral blood, hematurie, proteinurie, bleedings, appetite, nausea, vomitings, diarrhea, mucosal lesions, infections, skin lesions, cardiac lesions

  8. 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)

    2016-10-13

    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

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

    Science.gov (United States)

    Ellis, P M

    2012-06-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2005-01-01

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

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

    Science.gov (United States)

    ... Cancer Screening Research Non-Small Cell Lung Cancer Treatment (PDQ®)–Patient Version General Information About Non-Small ... Certain factors affect prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery ) and treatment ...

  12. Chemotherapy response evaluation with 18F-FDG PET in patients with non-small cell lung cancer

    NARCIS (Netherlands)

    de Geus-Oei, Lioe-Fee; van der Heijden, Henricus F. M.; Visser, Eric P.; Hermsen, Rick; van Hoorn, Bas A.; Timmer-Bonte, Johanna N. H.; Willemsen, Antoon T.; Pruim, Jan; Corstens, Frans H. M.; Krabbe, Paul F. M.; Oyen, Wim J. G.

    2007-01-01

    The aim of this prospective study was to evaluate the value of F-18-FDG PET for the assessment of chemotherapy response in patients with non-small cell lung cancer. Furthermore, part of the objective of this study was to compare 2 methods to quantify changes in glucose metabolism. Methods: In 51 pat

  13. SINGLE AGENT DOCETAXEL AS SECOND- LINE CHEMOTHERAPY FOR PRETREATED PATIENTS WITH RECURRENT NON- SMALL CELL LUNG CANCER

    Directory of Open Access Journals (Sweden)

    Deyan N. Davidov

    2013-04-01

    Full Text Available Objective: Single agent Docetaxel is a standard therapy for patients with non- small cell lung cancer after the failure of platinum- containing regimens. The aim of this study was to explore the efficacy and safety of Docetaxel monotherapy as second- line chemotherapy in pretreated patient with inoperable non- small cell lung cancer. Methods: From January 2005 to May 2008 thirty- six consecutive patients with locally advanced or metastatic morphologically proven stage IIIB/ IV non- small cell lung cancer entered the study after failure of previous platinum- based regimens. Treatment schedule consist of Docetaxel 75 mg/m2 administered every three weeks with repetition after 21 days with Dexamethasone premedication. Results: Overall response rate, median time to progression and median survival was 16,6 %, 4,5 months and 5,6 months respectively. The main hematological toxicity was neutropenia. Conclusions: That data suggest that single agent Docetaxel remain reasonable choices for the chemotherapy in pretreated patients with non- small cell lung cancer.

  14. Comparison of survival of chronic obstructive pulmonary disease patients with or without a localized non-small cell lung cancer

    DEFF Research Database (Denmark)

    Jeppesen, Stefan Starup; Gerner Hansen, Niels-Christian; Schytte, Tine

    2016-01-01

    OBJECTIVES: Chronic obstructive pulmonary disease (COPD) and non-small cell lung cancer (NSCLC) are often co-existing diseases with poor prognosis. The aim of this study was to compare survival in COPD patients with localized NSCLC treated with stereotactic body radiotherapy (NSCLC group) with COPD...

  15. Molecular-targeted therapy for elderly patients with advanced non-small cell lung cancer.

    Science.gov (United States)

    Antonelli, Giovanna; Libra, Massimo; Panebianco, Vincenzo; Russo, Alessia Erika; Vitale, Felice Vito; Colina, Paolo; D'Angelo, Alessandro; Rossello, Rosalba; Ferraù, Francesco

    2016-01-01

    Lung cancer is the most common cause of cancer-related mortality in men and women. Non-small cell lung cancer (NSCLC) represents close to 90% of all lung cancers. When diagnosed, >50% of patients are >65 years old. Through an improved understanding of the molecular mechanisms involved in lung oncogenesis, molecular-targeted approaches have become an essential element for the treatment of patients with NSCLC. As the toxicity profiles of the techniques are definitely more favorable compared with chemotherapy, they are particularly attractive for use in elderly patients, who are potentially more susceptible to the toxicity of systemic oncological therapies. However, studies on the activity of molecular-targeted agents in this aged patient setting are much more limited compared with those in their younger counterparts. In the present review, the literature on molecular-targeted therapy for elderly patients with advanced NSCLC is discussed. It is concluded that bevacizumab should be reserved only for highly select elderly patients with advanced NSCLC when the clinician deems it useful in the face of acceptable toxicities. In elderly patients with advanced epidermal growth factor receptor mutation-positive NSCLC, erlotinib and gefitinib appear to repeat the same favorable performance as that documented on a larger scale in the overall population of patients with activating mutations. A good toxicity profile is also confirmed for active molecules on different pathways, such as crizotinib.

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

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    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.

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

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    Viola Sacchi

    2011-06-01

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

  18. 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.

  19. Prognostic significance of Notch ligands in patients with non-small cell lung cancer.

    Science.gov (United States)

    Pancewicz-Wojtkiewicz, Joanna; Eljaszewicz, Andrzej; Kowalczuk, Oksana; Niklinska, Wieslawa; Charkiewicz, Radoslaw; Kozłowski, Miroslaw; Miasko, Agnieszka; Moniuszko, Marcin

    2017-01-01

    The Notch signaling pathway is deregulated in numerous solid types of cancer including non-small cell lung cancer (NSCLC). However, the profile of Notch ligand expression remains unclear. Therefore, the present study aimed to determine the profile of Notch ligands in NSCLC patients and to investigate whether quantitative assessment of Notch ligand expression may have prognostic significance in NSCLC patients. The study was performed in 61 pairs of tumor and matched unaffected lung tissue specimens obtained from patients with various stages of NSCLC, which were analyzed by reverse transcription-polymerase chain reaction. The marked expression levels of certain analyzed genes were detected in NSCLC samples and in noncancerous lung samples. Of the five Notch ligands, jagged 1 (Jag1), jagged 2, delta-like protein 1 and delta-like protein 4 were expressed in the majority of tissues, but their expression levels were reduced in NSCLC when compared with noncancerous lung tissue (PNotch ligands are expressed in NSCLC. However, the expression level is reduced when compared to noncancerous tissue. Furthermore, the present study revealed that quantitative assessment of Jag1 expression in NSCLC may improve prognostication of patient survival.

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

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    Asmita Anilkumar Mehta

    2013-01-01

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

  1. The value of positron emission tomography in patients with non-small cell lung cancer

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    Kee, Frank [Centre for Public Health, Queen' s University Belfast, Mulhouse Building, Royal Victoria Hospital Site, Grosvenor Road, Belfast BT12 6BJ, Northern Ireland (United Kingdom)], E-mail: f.kee@qub.ac.uk; Erridge, Sara [Edinburgh Cancer Centre, University of Edinburgh, Crewe Road South, Edinburgh EH4 2XU, Scotland (United Kingdom); Bradbury, Ian [Frontier Science (Scotland) Ltd., Grampian View, Kincraig, Inverness-shire PH21 1NA, Scotland (United Kingdom); Cairns, Karen [School of Maths and Physics, Queen' s University Belfast, David Bates Building, University Road, Belfast BT7 1NN, Northern Ireland (United Kingdom)

    2010-01-15

    Background: Pre-operative assessment of non-small cell lung cancer (NSCLC) is a major application of positron emission tomography (FDG-PET). Despite substantial evidence of diagnostic accuracy, relatively little attention has been paid to its effects on patient outcomes. This paper addresses this by extending an existing decision model to include patient-elicited utilities. Patients and methods: A decision-tree model of the effect of FDG-PET on pre-operative staging was converted to a Markov model. Utilities for futile and appropriate thoracotomy were elicited from 75 patients undergoing staging investigation for NSCLC. The decision model was then used to estimate the expected value of perfect information (EVPI) associated with three sources of uncertainty-the accuracy of PET, the accuracy of CT and the patient related utility of a futile thoracotomy. Results: The model confirmed the apparent cost-effectiveness of FDG-PET and indicated that the EVPI associated with the utility of futile thoracotomy considerably exceeds that associated with measures of accuracy. Conclusion: The study highlights the importance of patient related utilities in assessing the cost-effectiveness of diagnostic technologies. In the specific case of PET for pre-operative staging of NSCLC, future research effort should focus on such elicitation, rather than further refinement of accuracy estimates.

  2. 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.

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

    Directory of Open Access Journals (Sweden)

    Liang JL

    2014-05-01

    Full Text Available Jun-Li Liang,1 Xiao-Cang Ren,2 Qiang Lin2 1Department of Radiation Oncology, Hebei Medical University Fourth Hospital, Shijiazhuang, People’s Republic of China; 2Department of Oncology, North China Petroleum Bureau General Hospital of Hebei Medical University, Renqiu, Hebei Province, People’s Republic of China Abstract: Icotinib hydrochloride is an orally administered small-molecule reversible tyrosine kinase inhibitor that has been independently researched and developed and has independent intellectual property rights in the People’s Republic of China. Clinical trials have demonstrated that the response to icotinib among advanced non-small-cell lung cancer (NSCLC patients who received at least one platinum-based chemotherapy regimen was not inferior to gefitinib. Since being launched August 2011 in the People’s Republic of China, icotinib has been widely used in clinics, and has become an important treatment option for Chinese patients with advanced NSCLC. The present study presents the Phase I, II, and III clinical trials of icotinib and discusses current clinical applications in the People’s Republic of China and future research directions. Keywords: targeted therapy, EGFR-TKI, NSCLC

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

    DEFF Research Database (Denmark)

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

    2014-01-01

    Class-III-beta-tubulin (TUBB3) expression may be a potential predictive factor for treatment with microtubule interfering cytotoxic drugs in non-small cell lung cancer (NSCLC). Potential changes in TUBB3 expression during chemotherapy may be of interest if future choice of chemotherapy...... is to be based on TUBB3 expression. If the biomarker expression changes during chemotherapy, biopsies before initiation of chemotherapy beyond first line may be needed if treatment decision is to be based on TUBB3 expression. Thus, the aim was to explore TUBB3 expression heterogeneity and changes during...

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

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    Jiankun SUN

    2008-04-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

  7. Definitive Primary Therapy in Patients Presenting With Oligometastatic Non-Small Cell Lung Cancer

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    Parikh, Ravi B. [Harvard Medical School, Boston, Massachusetts (United States); Cronin, Angel M. [Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Kozono, David E.; Oxnard, Geoffrey R.; Mak, Raymond H.; Jackman, David M. [Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Brigham and Women' s Hospital, Boston, Massachusetts (United States); Lo, Peter C. [Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Baldini, Elizabeth H.; Johnson, Bruce E. [Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Brigham and Women' s Hospital, Boston, Massachusetts (United States); Chen, Aileen B., E-mail: achen@lroc.harvard.edu [Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Brigham and Women' s Hospital, Boston, Massachusetts (United States)

    2014-07-15

    Purpose: Although palliative chemotherapy is the standard of care for patients with diagnoses of stage IV non-small cell lung cancer (NSCLC), patients with a small metastatic burden, “oligometastatic” disease, may benefit from more aggressive local therapy. Methods and Materials: We identified 186 patients (26% of stage IV patients) prospectively enrolled in our institutional database from 2002 to 2012 with oligometastatic disease, which we defined as 5 or fewer distant metastatic lesions at diagnosis. Univariate and multivariable Cox proportional hazards models were used to identify patient and disease factors associated with improved survival. Using propensity score methods, we investigated the effect of definitive local therapy to the primary tumor on overall survival. Results: Median age at diagnosis was 61 years of age; 51% of patients were female; 12% had squamous histology; and 33% had N0-1 disease. On multivariable analysis, Eastern Cooperate Oncology Group performance status ≥2 (hazard ratio [HR], 2.43), nodal status, N2-3 (HR, 2.16), squamous pathology, and metastases to multiple organs (HR, 2.11) were associated with a greater hazard of death (all P<.01). The number of metastatic lesions and radiologic size of the primary tumor were not significantly associated with overall survival. Definitive local therapy to the primary tumor was associated with prolonged survival (HR, 0.65, P=.043). Conclusions: Definitive local therapy to the primary tumor appears to be associated with improved survival in patients with oligometastatic NSCLC. Select patient and tumor characteristics, including good performance status, nonsquamous histology, and limited nodal disease, may predict for improved survival in these patients.

  8. CIMAvax-EGF: A New Therapeutic Vaccine for Advanced Non-Small Cell Lung Cancer Patients

    Science.gov (United States)

    Saavedra, Danay; Crombet, Tania

    2017-01-01

    Lung cancer is the common fatal illness with the highest incidence and mortality globally. Epidermal growth factor receptor overexpression by tumor cells is associated with uncontrolled proliferation, angiogenesis, anti-apoptotic signals, metastization, and invasiveness. CIMAvax-EGF vaccine consists of a chemical conjugate of the EGF with the P64 protein derived from the Meningitis B bacteria and Montanide ISA 51, as adjuvant. The vaccine is projected to induce antibodies against EGF that results in EGF withdrawal. CIMAvax-EGF demonstrated to be safe and immunogenic in advanced non-small cell lung cancer (NSCLC) patients. The efficacy study was an open-label, multicentric Phase III clinical trial, which enrolled 405 advanced NSCLC patients. Patients with proven stage IIIB/IV NSCLC, who had completed four to six cycles of chemotherapy (CTP) were randomized to receive CIMAvax-EGF or best supportive care. CIMAvax-EGF resulted in a significantly larger overall survival in patients receiving at least four doses. High EGF concentration at baseline was a good predictive biomarker of the vaccine activity and a poor prognostic biomarker for the non-treated population. The proportion of CD8+CD28− cells, CD4 cells, and the CD4/CD8 ratio after first-line CTP was also associated with CIMAvax-EGF clinical benefit. After completing the Phase III, a Phase IV trial was done where the vaccine was administered in primary care units. Administering the vaccine at primary care institutions granted better access and treatment compliance. Safety was confirmed. Several clinical trials are currently ongoing to validate EGF as a predictive biomarker of CIMAvax-EGF efficacy.

  9. Disturbed Th17/Treg Balance in Patients with Non-small Cell Lung Cancer.

    Science.gov (United States)

    Duan, Min-Chao; Han, Wei; Jin, Pei-Wen; Wei, Yu-Ping; Wei, Qiu; Zhang, Liang-Ming; Li, Jun-Chen

    2015-12-01

    The fine balance of T help-17 (Th17)/regulatory T(Treg) cells is crucial for maintenance of immune homeostasis. However, there is little information concerning the role played in non-small cell lung cancer (NSCLC) by Th17/Treg cells. The objective of this study was to investigate the variation of Th17 and Treg cells in the peripheral blood of patients with NSCLC. Blood samples were collected from 19 patients with NSCLC and 19 healthy donors. Samples were processed to detect CD4(+)IL-17(+) Th17 cells and CD4(+)CD25(+)Foxp3(+) Treg cells by flow cytometry, and related gene expressions were assessed by real-time quantitative polymerase chain reaction. The concentrations of interleukin (IL)-1β, IL-6, IL-10, IL-17, IL-23, and transforming growth factor-beta (TGF-β1) were also measured by enzyme-linked immunosorbent assay analysis (ELISA). The frequency of circulating Th17 cells and Treg cells was increased in samples derived from patients with NSCLC, accompanied by the upregulation of Foxp3 and RORγt. However, a negative correlation between Treg cells and Th17 cells was found in patients with NSCLC. Additionally, the Th17/Treg ratio and the related cytokines were also significantly higher in patients with NSCLC than in healthy controls. Furthermore, the frequency of Th17 cells was positively correlated with IL-1β, IL-6, and IL-23 in patients with NSCLC, and the frequency of Treg cells was positively correlated with TGF-β1 and IL-10. More importantly, the Th17/Treg ratio was positively correlated with the CEA concentrations in patients with NSCLC. Our data indicated that Th17 and Treg subset are involved in the immunopathology of NSCLC. Distinct cytokine environment might play a key role in the differentiation of the Th17 and Treg cells in NSCLC. Reconstituting an adequate balance between Th17 and Treg may be beneficial in the treatment of NSCLC.

  10. Immune-modulating effects of bevacizumab in metastatic non-small-cell lung cancer patients

    Science.gov (United States)

    Martino, EC; Misso, G; Pastina, P; Costantini, S; Vanni, F; Gandolfo, C; Botta, C; Capone, F; Lombardi, A; Pirtoli, L; Tassone, P; Ulivieri, C; Tagliaferri, P; Cusi, MG; Caraglia, M; Correale, P

    2016-01-01

    The mPEBev is an anticancer regimen which combines a chemotherapy doublet, based on cisplatin and oral etoposide (mPE), with bevacizumab (mPEBev), a mAb targeting the vasculo-endothelial growth factor (VEGF). In previous studies, this regimen showed powerful anti-angiogenetic effects and significant antitumor activity in metastatic non-small-cell lung cancer (mNSCLC) patients. We also recorded the best benefit in patients exhibiting low-systemic inflammatory profile at baseline. On these bases, we hypothesized that mPEBev antitumor activity could be partially related to bevacizumab-associated immunological effects. For this reason, we performed an immunological monitoring in 59 out of 120 stage IIIb-IV NSCLC patients enrolled in the BEVA2007 phase II trial, who received fractioned cisplatin (30 mg/sqm days 1-3q21) and oral etoposide (50 mg, days 1-15q21) (mPE doublet) ±bevacizumab. In this group of patients, 12 received the mPE doublet alone and 47 the doublet in combination with bevacizumab (5 mg/kg on the day 3q21; mPEBev regimen). Blood cell counts, serum analysis, multiplex cytokine assay and immunocytofluorimetric analysis, performed on baseline and post-treatment on blood samples from these patients, revealed that bevacizumab addition to the doublet decreased levels of pro-angiogenic (VEGF, Angiostatin-1 and Follistatin) and inflammatory cytokines (interferon (IFN)γ, IL4 and IL17), improved in vivo and in vitro cytotoxic T-lymphocytes (CTL) response and promoted dendritic cell activation. These results suggest that the mPEBev regimen improve the micro-environmental conditions for an efficient antigen-specific CTL response, making it a feasible candidate regimen to be assessed in combination with immune-checkpoint inhibitors in NSCLC patients.

  11. 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.

  12. Dietary Flaxseed in Non-Small Cell Lung Cancer Patients Receiving Chemoradiation

    Science.gov (United States)

    Berman, Abigail T; Turowski, Jason; Mick, Rosemarie; Cengel, Keith; Farnese, Nicole; Basel-Brown, Lisa; Mesaros, Clementina; Blair, Ian; Lawson, James; Christofidou-Solomidou, Melpo; Lee, James; Rengan, Ramesh

    2013-01-01

    Purpose The standard of care in Locally-Advanced Non-Small Cell Lung Cancer (LA-NSCLC) is chemotherapy and radiation; however, Radiation-Induced Lung Injury (RILI), which may be prevented by the anti-inflammatory and anti-oxidant properties of Flaxseed (FS), impedes its maximum benefit. Materials and Methods Patients with LA-NSCLC requiring definitive RT were randomized to one FS or control muffin daily from start to 2 weeks after RT. Blood and urine were collected to quantify plasma FS metabolites, Enterodione (ED) and Enterolactone (EL), and urinary oxidative stress biomarkers, 8, 12-iso-iPF2a-VI (isoprostane) and 8-oxo-7,8-dihydro-2′deoxyguanosine (8-oxo-dGuo). Tolerability was defined as consuming ≥ 75% of the intended muffins and no ≥ grade 3 gastrointestinal toxicities. Results Fourteen patients (control,7; FS,7) were enrolled. The tolerability rates were 42.9 versus 71.4% (p=0.59) for FS and control, respectively. Mean percentages of intended number of muffins consumed were 37% versus 73% (p=0.12). ED and EL increased at onset of FS and decreased with discontinuation, confirming bioavailability. Isoprostane and 8-oxo-dGuo were detectable. There was a trend towards decreased rates of pneumonitis in FS. Conclusions This is the first study to report FS bioavailability and quantify oxidative stress markers in NSCLC patients. FS in the administered muffin formulation did not meet tolerability criteria. Given the promising mechanism of FS as a radioprotectant, further investigations should focus on the optimal method for administration of FS. PMID:24575360

  13. A Retrospective Study of Erlotinib in the Treatment of 70 Patients with Non-small Cell Lung Cancer

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    Mingzhi LI

    2009-12-01

    Full Text Available Background and objective Erlotinib is a small molecular inhibitor of tyrosine kinase. Multiple foreign and demestic studies have confirmed that it can prolong the median progression-free survival time (PFS and the overall survival (OS, which could be more significant in the selected population. In this study we retrospectively oberserved the response, the survival and adverse reaction of erlotinib in non-selected non-small cell lung cancer. Methods The retrospective study included seventy non-small-cell lung cancer patients, who were treated with erlotinib from July 2005 to July 2009. Erlotinib was prescribed at a dose of 150 mg daily. Results Sixty-eight patients were evaluated response. Among these patients, CR 0 case, PR 26 cases, RR (CR+PR 38.2% and SD 24 cases as their best response, disease control rate (DCR=CR+PR+SD 73.5%, PD 18 cases (26.5%. Sixty-three patients were evaluated PFS. The median PFS was 3.0 months. The median PFS of adenocarcinoma and non-adenocarcinoma was 3.0 months vs 2.6 months. The drug-related adverse reactions were skin rash , diarrhea and interstitial lung disease (ILD(4.3%. Conclusion Erlotinib is active in non-small cell lung cancer, and it is much more effective in adenocarcinoma and non-smoking patients. There is no difference in response or suvival concerning the sexuality. It is well tolerated in most patients.

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

    Institute of Scientific and Technical Information of China (English)

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

    2011-01-01

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

  15. Pembrolizumab in the treatment of metastatic non-small-cell lung cancer: patient selection and perspectives

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    Somasundaram A

    2017-01-01

    Full Text Available Ashwin Somasundaram, Timothy F Burns Division of Hematology/Oncology, Department of Medicine, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA Abstract: Lung cancer is the leading killer of both men and women in the US, and the 5-year survival remains poor. However, the approval of checkpoint blockade immunotherapy has shifted the treatment paradigm and provides hope for improved survival. The ability of non-small-cell lung cancer (NSCLC to evade the host immune system can be overcome by agents such as pembrolizumab (MK-3475/lambrolizumab, which is a monoclonal antibody targeting the programmed death 1 (PD-1 receptor. In early studies, treatment with pembrolizumab led to dramatic and durable responses in select patients (PD-L1+ tumors. This remarkable efficacy lead to approval of pembrolizumab in the second-line setting as response rates were almost doubled compared to standard of care (SOC chemotherapy. Most recently, data in the first-line setting from the KEYNOTE-024 study have redefined the SOC therapy for a selected subset of patients. In patients with ≥50% PD-L1+ tumors, pembrolizumab had a clear progression-free survival and overall survival benefit. Toxicity was mostly immune related and similar to checkpoint blockade toxicities observed in previous studies. The initial approval and subsequent studies of pembrolizumab required and utilized a companion diagnostic test, Dako’s IHC 22C3, to assess PD-L1 status of patients. The evaluation and scoring system of this assay has been used by other companies as a reference to develop their own assays, which may complicate selection of patients. Finally, the impact of pembrolizumab in NSCLC is growing as evidenced by the numerous, ongoing trials open for combinations with chemotherapy, chemoradiation, other immunotherapeutics, immunomodulators, tyrosine kinase inhibitors, PI3K inhibitors, MEK inhibitors, hypomethylating agents, and histone deacetylase inhibitors. Further studies

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

    Directory of Open Access Journals (Sweden)

    Baohui HAN

    2009-12-01

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

  17. Prognostic predictors for non-small cell lung cancer patients with brain metastasis after radiotherapy

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    Qiuhong FAN

    2008-06-01

    Full Text Available Background and objective Brain metastasis (BM is often found in the patients with lung cancer. Radiotherapy is regular and effective means of therapy and it aims at palliating symptoms and prolonging survival time. However, now there are different viewpoints on protocols of radiotherapy and prognostic factors. A retrospective analysis is used to evaluate the results of treatment for 82 cases with brain metastasis from non-small cell lung cancer (NSCLC and explore the prognostic factors to establish a prognostic index (PI model. Methods From Feb.1995 to Oct. 2006, 82 patients irradiated for BM from NSCLC, with both complete medical charts and follow-up data available, were eligible for this retrospective analysis. A number of potential factors which might affect prognosis after irradiation were evaluated. The significance of prognostic variables in the survival resulted from both univariate analysis by Kaplan-Meier combining with log-rank test and multivariate Cox regression model. The prognostic index (PI was established based on Cox regression analysis and subgrouping values. Results The follow-up time was 1-120 months. For the entire cohort, the median survival from the start of radiation for BM was 10.5 months, and the actuarial overall survival rate was 50.8%, 23.7% and 5.1% at 0.5, 1 and 2 years respectively. Univariate analysis showed KPS, control of primary tumor, interval from the beginning of diagnostic to BM, extracranial systemic metastasis, counts of lymphocyte and solitary BM were predictors of prognosis. However, in the Cox multivariate analysis, only KPS, control of primary tumor, interval from the beginning of diagnostic to BM and solitary BM were significant prognostic factors. The prognostic index was established based on Cox regression analysis and 82 patients were stratified good, intermediate and poor prognostic sub-groups. The difference of survival rate among 3 subgroups is significant (P<0.001. Conclusion Radiotherapy is

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

    Science.gov (United States)

    PAPADOPOULOU, EIRINI; TSOULOS, NIKOLAOS; TSIRIGOTI, ANGELIKI; APESSOS, ANGELA; AGIANNITOPOULOS, KONSTANTINOS; METAXA-MARIATOU, VASILIKI; ZAROGOULIDIS, KONSTANTINOS; ZAROGOULIDIS, PAVLOS; KASARAKIS, DIMITRIOS; KAKOLYRIS, STYLIANOS; DAHABREH, JUBRAIL; VLASTOS, FOTIS; ZOUBLIOS, CHARALAMPOS; RAPTI, AGGELIKI; PAPAGEORGIOU, NIKI GEORGATOU; VELDEKIS, DIMITRIOS; GAGA, MINA; ARAVANTINOS, GERASIMOS; KARAVASILIS, VASILEIOS; KARAGIANNIDIS, NAPOLEON; NASIOULAS, GEORGE

    2015-01-01

    It has been reported that certain patients with non-small-cell lung cancer (NSCLC) that harbor activating somatic mutations within the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) gene may be effectively treated using targeted therapy. The use of EGFR inhibitors in patient therapy has been demonstrated to improve response and survival rates; therefore, it was suggested that clinical screening for EGFR mutations should be performed for all patients. Numerous clinicopathological factors have been associated with EGFR and Kirsten-rat sarcoma oncogene homolog (KRAS) mutational status including gender, smoking history and histology. In addition, it was reported that EGFR mutation frequency in NSCLC patients was ethnicity-dependent, with an incidence rate of ~30% in Asian populations and ~15% in Caucasian populations. However, limited data has been reported on intra-ethnic differences throughout Europe. The present study aimed to investigate the frequency and spectrum of EGFR mutations in 1,472 Greek NSCLC patients. In addition, KRAS mutation analysis was performed in patients with known smoking history in order to determine the correlation of type and mutation frequency with smoking. High-resolution melting curve (HRM) analysis followed by Sanger sequencing was used to identify mutations in exons 18–21 of the EGFR gene and in exon 2 of the KRAS gene. A sensitive next-generation sequencing (NGS) technology was also employed to classify samples with equivocal results. The use of sensitive mutation detection techniques in a large study population of Greek NSCLC patients in routine diagnostic practice revealed an overall EGFR mutation frequency of 15.83%. This mutation frequency was comparable to that previously reported in other European populations. Of note, there was a 99.8% concordance between the HRM method and Sanger sequencing. NGS was found to be the most sensitive method. In addition, female non-smokers demonstrated a high prevalence of

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

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    Ling XL

    2015-06-01

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

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

    Institute of Scientific and Technical Information of China (English)

    李琳

    2013-01-01

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

  1. 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

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

    DEFF Research Database (Denmark)

    Pan, Yi; Brink, Carsten; Knap, Marianne

    2016-01-01

    PURPOSE: Esophagitis is common in patients treated with definitive radiotherapy for local-regional advanced non small cell lung cancer (NSCLC). The purpose of this study was to estimate the dose-effect relationship using clinical and dosimetric parameters in patients receiving intensity modulated...... radiotherapy (IMRT) and concomitant chemotherapy (CCT). METHODS: Between 2009 and 2013, 117 patients with stages IIB-IIIB NSCLC were treated in a multicenter randomized phase II trial with 2 cycles of induction chemotherapy followed by IMRT and CCT. The esophagitis was prospectively scored using the Common...

  3. Stereotactic body radiation therapy versus conventional radiation therapy in patients with early stage non-small cell lung cancer

    DEFF Research Database (Denmark)

    Jeppesen, Stefan Starup; Schytte, Tine; Jensen, Henrik R;

    2013-01-01

    Abstract Introduction. Stereotactic body radiation therapy (SBRT) for early stage non-small cell lung cancer (NSCLC) is now an accepted and patient friendly treatment, but still controversy exists about its comparability to conventional radiation therapy (RT). The purpose of this single...... and SBRT predicted improved prognosis. However, staging procedure, confirmation procedure of recurrence and technical improvements of radiation treatment is likely to influence outcomes. However, SBRT seems to be as efficient as conventional RT and is a more convenient treatment for the patients....

  4. Sirolimus and Auranofin in Treating Patients With Advanced or Recurrent Non-Small Cell Lung Cancer or Small Cell Lung Cancer

    Science.gov (United States)

    2016-08-25

    Extensive Stage Small Cell Lung Carcinoma; Lung Adenocarcinoma; Recurrent Non-Small Cell Lung Carcinoma; Recurrent Small Cell Lung Carcinoma; Squamous Cell Lung Carcinoma; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Non-Small Cell Lung Cancer; Stage IV Non-Small Cell Lung Cancer

  5. Assessment of Treg and Th17 contents in peripheral blood of patients with non-small cell lung cancer and analysis of their correlation with clinicopathologic characteristics

    Institute of Scientific and Technical Information of China (English)

    Jin Pu; Yuan-Yuan Zhou; Wen-Shu Ge; Hui-Lan Hong; Jing-Feng Zhang; Chong Bai

    2016-01-01

    Objective:To analyze Treg and Th17 contents in peripheral blood of patients with non-small cell lung cancer and their correlation with clinicopathologic characteristics.Methods:Peripheral blood and serum specimens were collected from patients with non-small cell lung cancer and healthy volunteers to detect Treg and Th17 contents in peripheral blood as well as CEA, TSGF, CYFRA21-1, PTX3 and HE4 contents in serum; tumor tissue and paracancer tissue were collected from lung cancer patients to detect mRNA expression of TRIM25, PKM2, Endoglin, Pin1, Stahmin and HMGA2.Results:Treg cell content and Treg/Th17 ratio in peripheral blood of patients with non-small cell lung cancer were significantly higher than those of healthy volunteers, and Th17 cell content was significantly lower than that of healthy volunteers; the higher the TNM stage and the lower the degree of differentiation, the higher the Treg cell content and Treg/Th17 ratio and the lower the Th17 cell content in peripheral blood; 1 week and 1 month after operation, Treg cell content and Treg/Th17 ratio in peripheral blood of patients with non-small cell lung cancer were lower than those before operation, and Th17 cell content was higher than that before treatment; serum CEA, TSGF, CYFRA21-1, PTX3 and HE4 contents of patients with non-small cell lung cancer were significantly higher than those of healthy volunteers and positively correlated with Treg/Th17 ratio; mRNA contents of TRIM25, PKM2, Endoglin, Pin1, Stahmin and HMGA2 in non-small cell lung cancer tissue were significantly higher than those in paracancer tissue and positively correlated with Treg/Th17 ratio.Conclusion:Increased Treg content and decreased Th17 content are related to the occurrence and development of non-small cell lung cancer.

  6. Therapy for non-small-cell lung cancer patients with brain metastasis Therapy for non-small-cell lung cancer patients with brain metastasis

    Institute of Scientific and Technical Information of China (English)

    Bing Li; Yuchen Bao Co-first author; Bin Chen; Songwen Zhou

    2014-01-01

    Brain metastasis is a major cause of poor prognosis and high mortality for non-smal celllung cancer patients. The prognosis of non-smal-celllung cancer (NSCLC) patients with brain metastasis is generaly poor and more efective treatment is required to improve their prognosis. Whole-brain radiotherapy, surgery, stereotactic radiosurgery, chemotherapy and targeted therapy are the main treatment for brain metastasis. This review focuses on the five therapeutic strategy and in particular, on targeted therapy.

  7. PET-Adjusted Intensity Modulated Radiation Therapy and Combination Chemotherapy in Treating Patients With Stage II-IV Non-small Cell Lung Cancer

    Science.gov (United States)

    2017-01-23

    Metastatic Malignant Neoplasm in the Brain; Recurrent Non-Small Cell Lung Carcinoma; Stage IIA Non-Small Cell Lung Carcinoma; Stage IIB Non-Small Cell Lung Carcinoma; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Non-Small Cell Lung Cancer; Stage IV Non-Small Cell Lung Cancer

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

    Science.gov (United States)

    2016-10-05

    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

  9. Leptomeningeal carcinomatosis in non-small cell lung cancer patients: A continuing challenge in the personalized treatment era.

    Science.gov (United States)

    Remon, J; Le Rhun, E; Besse, B

    2017-02-01

    Leptomeningeal metastasis is a fatal manifestation seen in advanced cancer patients. Its incidence is increasing, reaching 3.8% in molecularly unselected non-small cell lung cancer patients and up to 5% and 9% in ALK-rearranged and EGFR-mutant lung cancer patients, respectively. The prognosis remains poor despite systemic treatment, intrathecal chemotherapy, radiation therapy and personalized treatments in molecularly selected patients. However, new therapies with improved cerebral-spinal fluid penetration have been developed for subgroups of molecular selected patients indicating they could be promising therapeutic options for managing leptomeningeal disease. Systemic chemotherapy, which may be combined with intrathecal chemotherapy, remains standard treatment for lung cancer patients with leptomeningeal disease and a good-risk profile. We summarize evidence reported in the literature for managing this complication in lung cancer patients. Based on this, we have selected potential therapeutic strategies that could be used in daily clinical practice.

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

    DEFF Research Database (Denmark)

    Popat, Sanjay; Mellemgaard, Anders; Fahrbach, Kyle

    2015-01-01

    BACKGROUND: Nintedanib plus docetaxel has proven an overall survival benefit over docetaxel monotherapy in second-line treatment of non-small-cell lung cancer of adenocarcinoma histology in the LUME-Lung 1 pivotal trial. No published trials have previously compared nintedanib plus docetaxel with ...

  11. Circulating Tumor Cells Identify Early Recurrence in Patients with Non-Small Cell Lung Cancer Undergoing Radical Resection

    Science.gov (United States)

    Cueto Ladrón de Guevara, Antonio; Puche, Jose L.; Ruiz Zafra, Javier; de Miguel-Pérez, Diego; Ramos, Abel Sánchez-Palencia; Giraldo-Ospina, Carlos Fernando; Navajas Gómez, Juan A.; Delgado-Rodriguez, Miguel; Lorente, Jose A.; Serrano, María Jose

    2016-01-01

    Background Surgery is the treatment of choice for patients with non-small cell lung cancer (NSCLC) stages I-IIIA. However, more than 20% of these patients develop recurrence and die due to their disease. The release of tumor cells into peripheral blood (CTCs) is one of the main causes of recurrence of cancer. The objectives of this study are to identify the prognostic value of the presence and characterization of CTCs in peripheral blood in patients undergoing radical resection for NSCLC. Patients and Methods 56 patients who underwent radical surgery for previously untreated NSCLC were enrolled in this prospective study. Peripheral blood samples for CTC analysis were obtained before and one month after surgery. In addition CTCs were phenotypically characterized by epidermal growth factor receptor (EGFR) expression. Results 51.8% of the patients evaluated were positive with the presence of CTCs at baseline. A decrease in the detection rate of CTCs was observed in these patients one month after surgery (32.1%) (p = 0.035). The mean number of CTCs was 3.16 per 10 ml (range 0–84) preoperatively and 0.66 (range 0–3) in postoperative determination. EGFR expression was found in 89.7% of the patients at baseline and in 38.9% patients one month after surgery. The presence of CTCs after surgery was significantly associated with early recurrence (p = 0.018) and a shorter disease free survival (DFS) (p = .008). In multivariate analysis CTC presence after surgery (HR = 5.750, 95% CI: 1.50–21.946, p = 0.010) and N status (HR = 0.296, 95% CI: 0.091–0.961, p = 0.043) were independent prognostic factors for DFS. Conclusion CTCs can be detected and characterized in patients undergoing radical resection for non-small cell lung cancer. Their presence might be used to identify patients with increased risk of early recurrence. PMID:26913536

  12. Circulating Tumor Cells Identify Early Recurrence in Patients with Non-Small Cell Lung Cancer Undergoing Radical Resection.

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    Clara Bayarri-Lara

    Full Text Available Surgery is the treatment of choice for patients with non-small cell lung cancer (NSCLC stages I-IIIA. However, more than 20% of these patients develop recurrence and die due to their disease. The release of tumor cells into peripheral blood (CTCs is one of the main causes of recurrence of cancer. The objectives of this study are to identify the prognostic value of the presence and characterization of CTCs in peripheral blood in patients undergoing radical resection for NSCLC.56 patients who underwent radical surgery for previously untreated NSCLC were enrolled in this prospective study. Peripheral blood samples for CTC analysis were obtained before and one month after surgery. In addition CTCs were phenotypically characterized by epidermal growth factor receptor (EGFR expression.51.8% of the patients evaluated were positive with the presence of CTCs at baseline. A decrease in the detection rate of CTCs was observed in these patients one month after surgery (32.1% (p = 0.035. The mean number of CTCs was 3.16 per 10 ml (range 0-84 preoperatively and 0.66 (range 0-3 in postoperative determination. EGFR expression was found in 89.7% of the patients at baseline and in 38.9% patients one month after surgery. The presence of CTCs after surgery was significantly associated with early recurrence (p = 0.018 and a shorter disease free survival (DFS (p = .008. In multivariate analysis CTC presence after surgery (HR = 5.750, 95% CI: 1.50-21.946, p = 0.010 and N status (HR = 0.296, 95% CI: 0.091-0.961, p = 0.043 were independent prognostic factors for DFS.CTCs can be detected and characterized in patients undergoing radical resection for non-small cell lung cancer. Their presence might be used to identify patients with increased risk of early recurrence.

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

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    Shu Yong-Qian

    2010-09-01

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

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

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    Mikiko Ishihara

    2014-06-01

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

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

    Institute of Scientific and Technical Information of China (English)

    Runbo Zhong; Baohui Han; Bo Jin

    2008-01-01

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

  16. Personalized treatment strategies for non-small-cell lung cancer in Chinese patients: the role of crizotinib

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    Niu FY

    2015-05-01

    Full Text Available Fei-Yu Niu,1,2 Yi-Long Wu2 1Graduate School, Southern Medical University, Guangzhou, People’s Republic of China; 2Guangdong Lung Cancer Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, People’s Republic of China Abstract: Anaplastic lymphoma kinase (ALK rearrangement is an oncogene targeted with approved drugs second to epidermal growth factor receptor (EGFR in lung cancer. Crizotinib was developed and introduced into clinical practice rapidly and successfully after the discovery of ALK rearrangement in non-small-cell lung cancer. Chinese and other Asian patients treated with crizotinib seem to have lower toxicity and higher efficacy compared with other ethnicities. Crizotinib showed potent antitumor activity and manageable toxicity in mesenchymal–epithelial transition factor (c-Met/ROS1-positive non-small-cell lung cancer patients, but prospective clinical trials are still needed to confirm its efficacy and safety. Crizotinib appears to be effective against tumors originating from various organs that harbor ALK abnormalities. In the near future, we would classify the tumors by their genetic information beyond organs, such as ALKoma, EGFRoma, and RAFoma, and a single compound could be used for many different types of cancer in different organs. The major challenge of the widespread use of crizotinib in clinical practice is establishing convenient diagnostic techniques for the detection of ALK/c-Met/ROS1. In the present study, we reviewed the application of crizotinib in Chinese patients. Keywords: NSCLC, crizotinib, ALK, c-Met, ROS1

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

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    Li MJ

    2016-03-01

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

  18. [Clinical application value of prognostic nutritional index for predicting survival in patients with advanced non-small cell lung cancer].

    Science.gov (United States)

    Xu, W J; Kang, Y M; Zhou, L; Chen, F F; Song, Y H; Zhang, C Q

    2017-02-23

    Objective: To explore the clinical application value of prognostic nutritional index(PNI) for predicting overall survival(OS) in patients with advanced non-small cell lung cancer (NSCLC). Methods: 123 patients with histologically confirmed non-small cell lung cancer were enrolled in this study, and their clinical and laboratory data were reviewed. The PNI was calculated as 10×serum albumin value+ 5×total lymphocyte countin peripheral blood.Univariate and multivariate analyses were used to identify the potential prognostic factors for advanced NSCLC. Results: PNI of the 123 NSCLC patients was 46.24±6.56. PNI was significantly associated with age, weight loss and pleural effusion (P0.05). The median OS of the 123 patients was 19.5 months. The median OS in the higher PNI group (PNI≥46.24) and lower PNI group(PNI<46.24) were 25.2 months and 16.4 months, respectively.The 1-year survival rates were 80.6% and 63.9%, and 2-year survival rates were 54.8% and 19.6%, respectively (P<0.01). Univariate analysis showed that PNI, age, dyspnea, and weight loss were related to the OS of the advanced NSCLC patients (P<0.05). Multivariate analysis identified PNI as an independent prognostic factor for OS of advanced NSCLC (P<0.001). Conclusion: PNI can be easily calculated, and may be used as a relatively new prognostic indicator for advanced NSCLC in clinical practice.

  19. Mutation of the BRAF Genes in Non-small Cell Lung Cancer

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    Zhimin HUANG

    2012-03-01

    Full Text Available BRAF mutations have been found to be a driver mutation and maybe a therapy target in patients with non-small cell lung cancer. This article reviews the current understanding of BRAF gene, its structure, expression, the signal pathway, as well as its relationship with cancer especially the targeted therapies for non-small cell lung cancer.

  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. Impact of Introducing Stereotactic Lung Radiotherapy for Elderly Patients With Stage I Non-Small-Cell Lung Cancer : A Population-Based Time-Trend Analysis

    NARCIS (Netherlands)

    Palma, David; Visser, Otto; Lagerwaard, Frank J.; Belderbos, Jose; Slotman, Ben J.; Senan, Suresh

    2010-01-01

    Purpose Stereotactic body radiotherapy (SBRT) for stage I non-small-cell lung cancer (NSCLC) is associated with high local control rates. The impact of introducing SBRT in patients 75 years of age or older was studied using a population-based cancer registry. Methods The Amsterdam Cancer Registry wa

  2. OLC1 protein levels in plasma of patients with non-small cell lung cancer and its clinical application

    Institute of Scientific and Technical Information of China (English)

    杨龙海

    2014-01-01

    Objective To detect the plasma concentration of OLC1(overexpressed in lung cancer 1)protein as a potential cancer biomarker,and evaluating its clinical application value in the diagnosis of non-small cell lung cancer(NSCLC).Methods We prepared OLC1 antibody with OLC1 full length protein,in 5-6-week old Bal B/c mice.Each mouse was immunized four times at a dose of

  3. Treatment and survival of patients with EGFR-mutated non-small cell lung cancer and leptomeningeal metastasis : A retrospective cohort analysis

    NARCIS (Netherlands)

    Kuiper, Justine L.; Hendriks, Lizza E.; Wekken, van der Anthonie J.; de Langen, Adrianus J.; Bahce, Idris; Thunnissen, Erik; Heideman, Danielle A. M.; Berk, Yvonne; Buijs, Ed J. M.; Speel, Ernst-Jan M.; Krouwels, Frans H.; Smit, Hans J. M.; Groen, Harry J. M.; Dingemans, Anne-Marie C.; Smit, Egbert F.

    2015-01-01

    Objectives: Development of leptomeningeal metastasis (LM) in non-small cell lung cancer (NSCLC)patients is associated with a poor prognosis. It has been suggested that LM-patients with epidermal growth factor receptor mutated (EGER+) NSCLC have a superior prognosis compared to EGFR-wild type NSCLC.

  4. Randomized Phase II and Pharmacogenetic Study of Pemetrexed Compared With Pemetrexed Plus Carboplatin in Pretreated Patients With Advanced Non-Small-Cell Lung Cancer

    NARCIS (Netherlands)

    Smit, Egbert F.; Burgers, Sjaak A.; Biesma, Bonne; Eppinga, Pier; Dingemans, Anne-Marie C.; Joerger, Markus; Schellens, Jan H.; Vincent, Andrew; van Zandwijk, Nico; Groen, Harry J. M.

    2009-01-01

    Purpose We performed a randomized phase II trial comparing pemetrexed with pemetrexed plus carboplatin (PC) in patients experiencing relapse after platinum-based chemotherapy. Patients and Methods Main eligibility criteria were histologic or cytologic proof of advanced non-small-cell lung cancer (NS

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

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    Ying ZHANG

    2010-12-01

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

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

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    Xi LI

    2015-12-01

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

  7. ERCC1 and the efficacy of cisplatin in patients with resected non-small cell lung cancer.

    Science.gov (United States)

    Li, Chunhong; Liu, Meiyan; Yan, An; Liu, Wei; Hou, Junjun; Cai, Li; Dong, Xiaoqun

    2014-12-01

    Excision repair cross-complementing gene 1 (ERCC1) protein is proposed as a predictor for cisplatin efficacy in patients with non-small cell lung cancer (NSCLC). However, recent studies declare that ERCC1 is not associated with the response of platinum-based chemotherapy or clinical outcomes. The purpose of this study is to assess whether ERCC1 expression level is linked to cisplatin sensitivity and clinical outcomes in resected NSCLC patients. Paraffin-embedded cancer samples from 112 patients were used for immunohistochemical staining. Cancer cells isolated from fresh tumor tissues were used to determine the sensitivity to cisplatin by MTT assay. The association between ERCC1 expression and cisplatin sensitivity was tested by Spearman's rho test. The correlation of ERCC1 expression with clinicopathologic parameters was evaluated by the chi-square tests. The relationship between variables and survival was assessed by log-rank test. Overall survival (OS) and disease-free survival (DFS) curves were plotted by the Kaplan-Meier method. Cox proportional hazards model was used for multivariate analysis of survival. ERCC1 expression was significantly correlated with the sensitivity of cisplatin in vitro (p < 0.01, r = 0.37). ERCC1 was not associated with OS (p = 0.17) or DFS (p = 0.13) in patients with resected NSCLC. ERCC1 is not a sensible marker for the choice of treatment in clinical patients with resected NSCLC.

  8. Decreased IL-27 Negatively Correlated with Th17 Cells in Non-Small-Cell Lung Cancer Patients.

    Science.gov (United States)

    Duan, Minchao; Ning, Zhengqing; Fu, Zhijun; Zhang, Jianquan; Liu, Guangnan; Wei, Qiu; Zheng, Xiaoyu

    2015-01-01

    The presence of Th17 cells and IL-27 is observed in a variety of inflammatory associated cancers. However, there are some data on the role of Th17 cells and IL-27 in the regulation of immune reactions in non-small-cell lung cancer (NSCLC). The aim of this study is to assess the variation of Th17 cells and IL-27 in the peripheral blood (PB) of patients with NSCLC. The proportion of Th17 cells in peripheral blood mononuclear cells (PBMCs) was evaluated by flow cytometry. The serum concentrations of IL-27 and IL-17 were measured by enzyme-linked immunosorbent assay (ELISA). The mRNA expression of RORγt and IL-27 in the peripheral blood was examined by real-time quantitative polymerase chain reaction (QPCR). Expression of IL-27 was lower in NSCLC patients compared with normal controls. The frequency of Th17 cells was increased in NSCLC patients, accompanied by the upregulation of IL-17 and RORγt. IL-27 negatively correlated with the number of Th17 cells and the RORγt mRNA. Our results indicate that IL-27 might inhibit Th17 differentiation in NSCLC patients and better understanding of the regulatory effects of IL-27 on Th17 cells may shed light on potential new targets in cancer prevention and therapy.

  9. Efficacy and safety of gefitinib as monotherapy for Chinese patients with advanced non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    @@ Platinum-based chemotherapy can improve the survival and quality of life of patients with locally advanced and metastatic lung cancer. Second-line docetaxel monotherapy can improve overall survival following the failure of first line chemotherapy. However, many limiting factors such as poor performance status, advanced age, adverse effects of chemotherapy and reluctance to receive cytotoxic chemotherapeutic agents render patients unable to accept chemotherapy. Furthermore, for patients who have failed second-line chemotherapy treatment options are often limited to best support care or palliative radiotherapy. 1 Gefitinib (Iressa) is a HER1/EGFR (epidermal growth factor receptor)- tyrosine kinase inhibitor approved in a number of countries including the US, Japan and recently China for the treatment of patients with non-small cell lung cancer (NSCLC), who have failed platinum/docetaxel-based first line and second line chemotherapy. 2,3 Current data show heterogeneity in response to gefitinib among people of different ethnic origin, but there is very little data concerning the safety and efficacy of gefitinib in Chinese patients. This paper aims to summarize the safety and efficacy data for gefitinib 250 mg treatment in Chinese NSCLC patients at Peking Union Medical College Hospital who received gefitinib as part of an Expanded Access Programme.

  10. Alectinib for choroidal metastasis in a patient with crizotinib-resistant ALK rearranged positive non-small cell lung cancer.

    Science.gov (United States)

    Okuma, Yusuke; Tanaka, Yuichiro; Kamei, Tina; Hosomi, Yukio; Okamura, Tatsuru

    2015-01-01

    Choroidal metastasis is rare in cancer patients. Small molecules of molecular targeted agents for lung cancer with actionable mutations were reported to be palliated for symptoms caused by choroidal metastasis. Visual disturbance by choroidal metastasis significantly decreases quality of life during the patient's remaining lifespan; therefore, radiotherapy or laser photocoagulation is proposed with consensus. However, improvement in survival with matched molecular targeted agents for oncogenic driver mutations reminds us to also be concerned with late treatment toxicities. A 30-year-old female patient previously treated with crizotinib harboring ALK rearranged non-small cell lung cancer complained of visual disturbance, fever, and bone pains undergoing anti-PD-1 antibody treatment. A decreased proportion of ALK fusion was demonstrated by fluorescence in situ hybridization in liver metastasis compared to the primary site in a chemo-naïve state. She was diagnosed with low vision, choroidal metastasis and retinal detachment. Therefore, she started alectinib treatment and both her ocular and systemic symptoms were palliated in a week. Later, she temporarily discontinued alectinib because of skin rash although the choroidal metastasis and retinal detachment resolved and she regained low vision completely at 2 weeks. She obtained partial response with alectinib for more than 5 months after recovering from skin rash.

  11. Treatment of Unfit Patients With Advanced Non-Small-Cell Lung Cancer: Definition Criteria According an Expert Panel.

    Science.gov (United States)

    De Marinis, Filippo; Bria, Emilio; Baas, Paul; Tiseo, Marcello; Camerini, Andrea; Favaretto, Adolfo Gino; Gridelli, Cesare

    2015-11-01

    The assessment of special categories of non-small-cell lung cancer (NSCLC) patients requires a comprehensive analysis of all factors potentially influencing the daily quality of life and the relative contribution of tumor-related symptoms on the overall patient health status. While for elderly patients prospective evidence and recommendations allow clinicians to better address their patients to a shared treatment, a paucity of reliable data refers to treatment opportunities for these patients, termed frail or unfit, who are not considered eligible for chemotherapy usually administered to adult patients. This consensus was inspired by the absence of clear criteria to define the category of unfit patients in the context of advanced NSCLC in order to share all the available tools for their classification and evaluation and to support decisions for clinical practice on a daily basis. After review of the literature and panelist consensus, a series of items was identified as relevant: age, performance status, renal function, heart failure, previous cerebrovascular events, uncontrolled hypertension, neuropathy, hearing loss, symptomatic brain metastases, severe psychiatric disorders, and absence of caregiver support. On the basis of these factors, a treatment algorithm for clinical practice to categorize unfit NSCLC patient into 3 major clinical scenarios was defined: (1) unfit for cisplatin-based chemotherapy, (2) unfit for carboplatin-based chemotherapy, and (3) unfit for single-agent chemotherapy.

  12. Circulating Thrombospondin-2 and FGF-2 in Patients with Advanced Non-small Cell Lung Cancer: Correlation with Survival.

    Science.gov (United States)

    Naumnik, W; Ossolińska, M; Płońska, I; Chyczewska, E; Nikliński, J

    2015-01-01

    Thrombospondin-2 (TSP-2) is an endogenous negative regulator of vascularization in human cancer. TSP-2 regulates angiogenesis through binding and sequestration of the proangiogenic fibroblast growth factor-2 (FGF-2). However, it is unclear whether TSP-2 and FGF-2 are related to prognosis in non-small cell lung cancer (NSCLC). To study this issue, we measured serum (Elisa) levels of TSP-2 and FGF-2 in 40 NSCLC patients (before chemotherapy) and 22 healthy subjects. Both TSP-2 and FGF-2 concentrations were elevated in the NSCLC group compared with control (TSP-2: 26.72±8.00 vs. 18.64±5.50 ng/ml, p=0.002; FGF-2: 11.90±5.80 vs. 7.26±3.90 pg/ml, p=0.01). Receiver-operating characteristic (ROC) curves were applied to find the cut-off serum levels of TSP-2 and FGF-2 (NSCLC vs. healthy: TSP-2=15.09 ng/ml, FGF-2=2.23 pg/ml). Patients before treatment with the TSP-2 level24.15 ng/ml had only 9 months' median survival (p=0.007). Patients with FGF-2 level>11.21 pg/ml had significantly shorter survival than patients with FGF-2FGF-2 than healthy people. High levels of TSP-2 and FGF-2 may predict worse survival.

  13. Telomere length of tumor tissues and survival in patients with early stage non-small cell lung cancer.

    Science.gov (United States)

    Jeon, Hyo-Sung; Choi, Yi Young; Choi, Jin Eun; Lee, Won Kee; Lee, Eungbae; Yoo, Seung Soo; Lee, Shin Yup; Lee, Jaehee; Cha, Seung Ick; Kim, Chang Ho; Park, Jae Yong

    2014-04-01

    Telomere shortening leads to genomic instability that drives oncogenesis through the activation of telomerase and the generation of other mutations necessary for tumor progression. This study was conducted to determine the impact of telomere shortening on the survival of patients with early stage non-small cell lung cancer (NSCLC). Relative telomere length in tumor tissues was measured by quantitative polymerase chain reaction in 164 patients with surgically resected NSCLC. The association between telomere length and overall survival (OS) and disease-free survival (DFS) was analyzed. When the patients were categorized into quartiles based on telomere length, those patients with the 1st quartile (shortest) of telomere length had a significantly worse OS and DFS compared to patients with the 2nd to the 4th quartiles of telomere length (adjusted hazard ratio for OS = 2.67, 95% confidence interval = 1.50-4.75, P = 0.001; and adjusted hazard ratio for DFS = 1.92, 95% confidence interval = 1.17-3.14, P = 0.01). An association between telomere length and survival outcome was more pronounced in squamous cell carcinomas than adenocarcinomas (P-value of test for homogeneity for OS and DFS = 0.05 and 0.02, respectively). Telomere length of tumor tissues is an independent prognostic factor in patients with surgically resected early stage NSCLC.

  14. Predictive molecular markers for EGFR-TKI in non-small cell lung cancer patients: new insights and critical aspects

    Directory of Open Access Journals (Sweden)

    Paola Ulivi

    2010-07-01

    Full Text Available In recent years, a number of novel agents have been investigated that target specific molecular pathways in non-small cell lung cancer (NSCLC. A great deal of effort has been focused on identifying specific markers that predict treatment response, given that a tailored approach would maximize both the therapeutic index and the cost-effectiveness. The epidermal growth factor receptor (EGFR pathway has emerged as a key regulator of cancer cell proliferation and invasion, and several specific EGFR inhibitors have been examined. Gefitinib and erlotinib are selective EGFR tyrosine kinase inhibitors (EGFR-TKIs, demonstrating good results in selected cases both in terms of objective response rate and of overall survival. At present, EGFR gene mutations are the best positive predictive factors for TKI therapy, and a number of other potential biomarkers are being investigated as additional positive or negative predictors of response. The correct selection of patients that could benefit from these innovative therapies, based on an accurate molecular characterization, is mandatory to provide the best clinical management. Currently, the main factor limiting the characterization of metastatic NSCLC patients is the small quantity of tumor cells available for molecular analysis. In this paper we provide an overview of the most important molecular predictive markers for EGFR-TKIs therapy in NSCLC patients, and focus attention on biological samples suitable for analysis and alternative sampling approaches such as plasma- or serum-derived DNA.

  15. Survival Analysis of Advanced Non-Small Cell Lung Cancer Patients Treated by Using Wheel Balance Cancer Therapy.

    Science.gov (United States)

    Kim, Jongmin; Cho, Chong-Kwan; Yoo, Hwa-Seung

    2016-12-01

    Objective To investigate the clinical effect and the overall survival (OS) rate of patients with advanced non-small cell lung cancer (NSCLC) who have undergone Wheel Balance Cancer Therapy (WBCT). Methods The cases of 33 patients with advanced NSCLC who were treated with WBCT at the East West Cancer Center (EWCC) between October 4, 2004, and October 3, 2013, without undergoing concurrent conventional treatment were analyzed. The Kaplan-Meier method was used to estimate the OS of the cases, and the median OS was calculated according to age, Eastern Cooperative Oncology Group Performance Status (ECOG PS), conventional-treatment history, WBCT treatment duration, and histological tumor type. Results The median OS of all patients was 31.1 (95% confidence interval [CI] = 3.5-58.7) months; the OS rates were 63.6% and 24.2% at years 1 and 2, respectively. The median OS rates of patients under and over 65 years were 45.2 (95% CI = 13.5-76.9) and 19.5 (95% CI = 7.1-31.8) months, respectively (P = .189). The median OS rates of patients who received WBCT for >14 days but treatment and those who had not were 45.2 (95% CI = 9.1-81.3) and 3.9 (95% CI = unable to calculate) months, respectively (P = .000). The median OS rates of patients with squamous cell carcinoma (SCC) and non-SCC lung cancer were 5.6 (95% CI = unable to calculate) and 45.2 (95% CI = 9.1-81.3) months, respectively (P = .262). The median OS rate of patients with ECOG PS ≥3 was 14.3 (95% CI = 8.8-19.8) months; that of patients ECOG PS treatment and have an ECOG PS <3.

  16. Is the Glut expression related to FDG uptake in PET/CT of non-small cell lung cancer patients?

    Science.gov (United States)

    Choi, Woo Hee; Yoo, Ie Ryung; O, Joo Hyun; Kim, Tae Jung; Lee, Kyo Young; Kim, Young Kyoon

    2015-01-01

    Though 18F-FDG PET/CT scans are widely used in non-small cell lung cancer (NSCLC), the mechanism of FDG uptake by lung cancer cells has not yet been fully elucidated. This study evaluated the relationship between FDG uptake and the expression of glucose transporters in NSCLC. Sixty-four NSCLC patients who underwent both preoperative 18F-FDG PET/CT scanning and thoracotomy were included. The maximum standardized uptake value (SUVmax) of the primary lung cancer was compared to the immunohistochemistry results for Glut expression and tumor size. In all the NSCLC cases, degree of FDG uptake significantly correlated with both Glut-1 and Glut-3 expression. When stratified by the histology, squamous cell carcinomas showed higher mean SUVmax, Glut-1 expression intensity, and percentage of area positive for Glut-1 expression than adenocarcinomas. Glut-1 and Glut-3 expressions correlated with SUVmax in adenocarcinomas, but there was no significant correlation in squamous cell carcinomas. No significant correlation was observed between tumor size and FDG uptake or Glut expression. These results show that Glut expression was significantly correlated with SUVmax in NSCLC, especially in adenocarcinomas, and that neither FDG uptake nor the expression of Glut was associated with tumor size.

  17. Gene-expression signature predicts postoperative recurrence in stage I non-small cell lung cancer patients.

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    Yan Lu

    Full Text Available About 30% stage I non-small cell lung cancer (NSCLC patients undergoing resection will recur. Robust prognostic markers are required to better manage therapy options. The purpose of this study is to develop and validate a novel gene-expression signature that can predict tumor recurrence of stage I NSCLC patients. Cox proportional hazards regression analysis was performed to identify recurrence-related genes and a partial Cox regression model was used to generate a gene signature of recurrence in the training dataset -142 stage I lung adenocarcinomas without adjunctive therapy from the Director's Challenge Consortium. Four independent validation datasets, including GSE5843, GSE8894, and two other datasets provided by Mayo Clinic and Washington University, were used to assess the prediction accuracy by calculating the correlation between risk score estimated from gene expression and real recurrence-free survival time and AUC of time-dependent ROC analysis. Pathway-based survival analyses were also performed. 104 probesets correlated with recurrence in the training dataset. They are enriched in cell adhesion, apoptosis and regulation of cell proliferation. A 51-gene expression signature was identified to distinguish patients likely to develop tumor recurrence (Dxy = -0.83, P85%. Multiple pathways including leukocyte transendothelial migration and cell adhesion were highly correlated with recurrence-free survival. The gene signature is highly predictive of recurrence in stage I NSCLC patients, which has important prognostic and therapeutic implications for the future management of these patients.

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

    Directory of Open Access Journals (Sweden)

    Deyan Davidov

    2014-12-01

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

  19. KRAS mutations in the circulating free DNA (cfDNA) of non-small cell lung cancer (NSCLC) patients

    Science.gov (United States)

    Villatoro, Sergi; Teixidó, Cristina; Mayo, Clara; Martínez, Alejandro; de los Llanos Gil, Maria; Viteri, Santiago; Morales-Espinosa, Daniela; Rosell, Rafael

    2016-01-01

    Circulating free DNA (cfDNA) is obtained from serum or plasma by non-invasive methods such as a simple blood draw, a technique known as “liquid biopsy”. Genetic analyses of driver alterations in cfDNA have proved very effective to predict survival and treatment response of cancer patients according to tumoral cfDNA burden in blood. Non-small cell lung cancer (NSCLC) patients with higher concentration of tumoral cfDNA in blood have, on average, shorter progression-free survival (PFS) and overall survival (OS). Regarding specific genetic alterations, KRAS proto-oncogene, GTPase (KRAS) is one of the main genes involved in NSCLC and several studies have been performed to determine its value as a predictive and prognostic biomarker in liquid biopsy. Unfortunately, to date no strong conclusions can be drawn since they have yielded contradictory results. Therefore, further investigations are necessary to establish the value of KRAS testing in liquid biopsy as prognostic or predictive factor in NSCLC. Herein, we review the current knowledge on the importance of KRAS as prognostic and predictive biomarker using non-invasive approaches and the scientific data available regarding its application in clinical practice for treatment of NSCLC. PMID:27826532

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

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    Dong Chen

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

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

    Science.gov (United States)

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

    2013-09-01

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

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

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    Shuhong Tang; Jilai Bian; Mingwu Li

    2008-01-01

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

  3. Oligometastatic non-small-cell lung cancer: current treatment strategies

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    Richard PJ

    2016-11-01

    Full Text Available Patrick J Richard, Ramesh Rengan Department of Radiation Oncology, University of Washington, Seattle, WA, USA Abstract: The oligometastatic disease theory was initially described in 1995 by Hellman and Weichselbaum. Since then, much work has been performed to investigate its existence in many solid tumors. This has led to subclassifications of stage IV cancer, which could redefine our treatment approaches and the therapeutic outcomes for this historically “incurable” entity. With a high incidence of stage IV disease, non-small-cell lung cancer (NSCLC remains a difficult cancer to treat and cure. Recent work has proven the existence of an oligometastatic state in NSCLC in terms of properly selecting patients who may benefit from aggressive therapy and experience long-term overall survival. This review discusses the current treatment approaches used in oligometastatic NSCLC and provides the evidence and rationale for each approach. The prognostic factors of many trials are discussed, which can be used to properly select patients for aggressive treatment regimens. Future advances in both molecular profiling of NSCLC to find targetable mutations and investigating patient selection may increase the number of patients diagnosed with oligometastatic NSCLC. As this disease entity increases, it is of utmost importance for oncologists treating NSCLC to be aware of the current treatment strategies that exist and the potential advantages/disadvantages of each. Keywords: oligometastatic, non-small-cell lung cancer, oligoprogressive, treatment

  4. The Effect of Different Comorbidities on Survival of Non-small Cells Lung Cancer Patients

    DEFF Research Database (Denmark)

    Iachina, Maria; Jakobsen, Erik; Møller, Henrik

    2015-01-01

    of each comorbid disease groups on survival. METHODS: The analysis is based on all patients with NSCLC who were registered in 2009-2011, in total 10,378 patients. To estimate the effect of each comorbidity group on the survival, we fitted a Cox regression model for each comorbidity group adjusting for age......PURPOSE: Primary lung cancer is one of the most common types of cancers. Comorbidity has been shown to be a negative prognostic factor in the overall lung cancer population. The significance of the individual comorbidities is less well known. The purpose of this paper is to investigate the effect...... have a significant impact on survival of NSCLC patients....

  5. Exercise intervention for patients diagnosed with operable non-small cell lung cancer

    DEFF Research Database (Denmark)

    Missel, Malene; Pedersen, Jesper Holst; Hendriksen, Carsten

    2015-01-01

    PURPOSE: The purpose was to explore operable lung cancer patient experiences with an exercise intervention from a longitudinal perspective according to patient motivation and patient perceived benefits and barriers of exercise. METHODS: Nineteen patients enrolled in an exercise intervention 2 weeks...... patients' expectations of physical benefits and the security of having professionals present. Patients experienced physical and emotional benefits and affirmed their social identity. Barriers were primarily related to side effects of chemotherapy. CONCLUSION: The exercise intervention was undertaken safely...... post-surgery participated in qualitative interviews at three time points. A criteria sampling strategy was applied. Ricoeur's phenomenological hermeneutical philosophy inspired the analysis. RESULTS: Patients initiated exercising median 15 days postoperative. Eight patients included in the interview...

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

    DEFF Research Database (Denmark)

    Madsen, Kirsten Riis; Bødtger, Uffe

    , tobacco pack years, or FEV1. Former malignancy was significantly more prevalent among asymptomatic than symptomatic subjects (33 % vs. 11%), with insignificant differences in prevalence of other co-morbidities or in post-surgical TNM (82% vs 85% in stages IA-IIB). 12-months mortality was insignificantly...... higher in asymptomatic than symptomatic subjects (23% vs. 12%), and in patients with former malignancy compared to patients with no former cancer (17% vs. 16%). Discussion: Symptoms at diagnosis per se appear unrelated to mortality in patients with NSCLC referred for surgery. Asymptomatic patients were...

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

    Science.gov (United States)

    2016-06-17

    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

  8. Combination Therapy of Gefitinib and Korean Herbal Medicines Could be a Beneficial Option for Patients with Non-Small-Cell Lung Cancer

    OpenAIRE

    2016-01-01

    Abstract Abstract Lung cancer has a high mortality rate and is often diagnosed at the metastatic stage. Gefitinib is a targeted molecular therapeutic drug used to treat patients with non-small-cell lung cancer (NSCLC). Korean herbal medicines may also have therapeutic efficacy against lung cancer, reduce the side effects associated with chemotherapy, and improve patient quality of life (QOL). This case report describes the effects of a Korean herbal medicine regimen combined with gefitinib in...

  9. Echocardiography and cardiac biomarkers in patients with non-small cell lung cancer treated with platinum-based chemotherapy

    Science.gov (United States)

    Omersa, Daniel; Cufer, Tanja; Marcun, Robert

    2017-01-01

    Abstract Background Non-small cell lung cancer (NSCLC) is the most common type of lung cancer and remains an important cause of cancer death worldwide. Platinum-based chemotherapy (PBC) for NSCLC can modify outcome while the risk of cardiotoxicity remains poorly researched. We aimed to evaluate the incidence and severity of cardiac injury during PBC in patients with NSCLC and to identify patients at risk. Methods This was a single-centre, prospective, observational study of patients with early and advanced stage NSCLC referred for PBC. In addition to standard care, patients were examined and evaluated for cardiotoxicity before the first dose (visit 1), at the last dose (visit 2) and 6 months after the last dose of PBC (visit 3). Cardiotoxicity (at visit 2 and 3) was defined as increase in the ultrasensitive troponin T, N-terminal pro-B type natriuretic peptide or decrease in left ventricular ejection fraction (LVEF). Results Overall, 41 patients (mean age 61 ± 9; 54% men; 68% advanced lung cancer) were included. The median number of PBC cycles was 4. During the study period, there were no incidents of heart failure, and 3 deaths caused by tumour progression were recorded. The mean values of biomarkers and LVEF did not change significantly (p > 0.20). However, 10 (25%) had cardiotoxicity which was independently associated with a history of ischemic heart disease (p = 0.026). Conclusions In NSCLC, cardiac assessment and lifestyle modifications may be pursued in patients with a history of cardiac disease and in patients with longer life expectancy.

  10. Successful afatinib treatment of advanced non-small-cell lung cancer patients undergoing hemodialysis.

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    Imai, Hisao; Kaira, Kyoichi; Naruse, Ichiro; Hayashi, Hideki; Iihara, Hirotoshi; Kita, Yutaro; Mizusaki, Naoki; Asao, Takayuki; Itoh, Yoshinori; Sugiyama, Tadashi; Minato, Koichi; Yamada, Masanobu

    2017-01-01

    The treatment for patients with lung cancer undergoing hemodialysis, who are frequently elderly and have poor performance status, becomes a more important subject. However, the feasibility of afatinib in patients with chronic renal failure undergoing hemodialysis has not, so far, been reported. Here, afatinib was administered to three patients with NSCLC harboring EGFR mutation and chronic renal failure undergoing hemodialysis. Pharmacokinetic (PK) data of afatinib supported the safety of afatinib treatment. After receiving their written informed consent from all patients, they were administered 30 mg afatinib daily with HD three times a week. We performed PK analyses of afatinib on days 1, 2, 10, and 11 after initial administration of afatinib. All three patients exhibited a partial response without any serious adverse events during the administration of afatinib. These PK data were similar to those of patients with normal organ function, which were previously reported. Our findings may be particularly useful given the current opportunity to use afatinib as a first-line treatment for EGFR-mutated NSCLC patients, providing an additional option for patients with impaired renal function.

  11. Alectinib for choroidal metastasis in a patient with crizotinib-resistant ALK rearranged positive non-small cell lung cancer

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    Okuma Y

    2015-06-01

    Full Text Available Yusuke Okuma,1,2 Yuichiro Tanaka,3 Tina Kamei,1 Yukio Hosomi,1 Tatsuru Okamura1 1Department of Thoracic Oncology and Respiratory Medicine, Tokyo Metropolitan Cancer and Infectious diseases Center Komagome Hospital, 2Division of Oncology, Research Center for Medical Sciences, The Jikei University School of Medicine, 3Department of Ophthalmology, Tokyo Metropolitan Cancer and Infectious diseases Center Komagome Hospital, Tokyo, Japan Abstract: Choroidal metastasis is rare in cancer patients. Small molecules of molecular targeted agents for lung cancer with actionable mutations were reported to be palliated for symptoms caused by choroidal metastasis. Visual disturbance by choroidal metastasis significantly decreases quality of life during the patient’s remaining lifespan; therefore, radiotherapy or laser photocoagulation is proposed with consensus. However, improvement in survival with matched molecular targeted agents for oncogenic driver mutations reminds us to also be concerned with late treatment toxicities. A 30-year-old female patient previously treated with crizotinib harboring ALK rearranged non-small cell lung cancer complained of visual disturbance, fever, and bone pains undergoing anti-PD-1 antibody treatment. A decreased proportion of ALK fusion was demonstrated by fluorescence in situ hybridization in liver metastasis compared to the primary site in a chemo-naïve state. She was diagnosed with low vision, choroidal metastasis and retinal detachment. Therefore, she started alectinib treatment and both her ocular and systemic symptoms were palliated in a week. Later, she temporarily discontinued alectinib because of skin rash although the choroidal metastasis and retinal detachment resolved and she regained low vision completely at 2 weeks. She obtained partial response with alectinib for more than 5 months after recovering from skin rash. Keywords: lung cancer, ALK rearrangement, alectinib, choroidal metastasis, molecular targeted

  12. Use of PET/CT for staging and radiation therapy planning in patients with non-small cell lung cancer.

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    Mac Manus, M P

    2010-10-01

    Positron emission tomography (PET) and more recently PET/computed tomography (CT) scanning represent major advances in the imaging of lung cancer and have an especially high impact on the management of patients who are candidates for potentially curative or "radical" radiotherapy (RT). This article reviews the current status of PET and PET/CT for staging patients before RT and considers the use of PET and PET/CT images for target volume definition. The relevant literature on the use of PET for staging lung cancer is reviewed and placed in the context of patients who are candidates for RT. Research that specifically considers the use of PET for RT planning is considered critically and some promising areas for future research are discussed. The available literature is almost exclusively devoted to non small cell lung cancer (NSCLC) with few relevant studies of small cell lung cancer (SCLC). The primary PET radiopharmaceutical shown to have value for staging and RT planning is 18F-fluorodeoxyglucose (FDG). In prospective studies where PET imaging was used to stage radical RT candidates, 25-30% of patients were excluded from radical therapy because of PET detected advanced disease. In all studies where "PET-assisted" and conventional target or treatment volumes were compared, there were major differences between PET and conventional volumes. Because PET-assisted staging is proven to be significantly more accurate than conventional staging and because all studies show major differences between PET-assisted and conventional treatment volumes in NSCLC, routine use of PET/CT for RT planning is recommended.

  13. Patient-Derived Xenograft Models of Non-Small Cell Lung Cancer and Their Potential Utility in Personalized Medicine

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    Morgan, Katherine M.; Riedlinger, Gregory M.; Rosenfeld, Jeffrey; Ganesan, Shridar; Pine, Sharon R.

    2017-01-01

    Traditional preclinical studies of cancer therapeutics have relied on the use of established human cell lines that have been adapted to grow in the laboratory and, therefore, may deviate from the cancer they were meant to represent. With the emphasis of cancer drug development shifting from non-specific cytotoxic agents to rationally designed molecularly targeted therapies or immunotherapy comes the need for better models with predictive value regarding therapeutic activity and response in clinical trials. Recently, the diversity and accessibility of immunodeficient mouse strains has greatly enhanced the production and utility of patient-derived xenograft (PDX) models for many tumor types, including non-small cell lung cancer (NSCLC). Combined with next-generation sequencing, NSCLC PDX mouse models offer an exciting tool for drug development and for studying targeted therapies while utilizing patient samples with the hope of eventually aiding in clinical decision-making. Here, we describe NSCLC PDX mouse models generated by us and others, their ability to reflect the parental tumors’ histomorphological characteristics, as well as the effect of clonal selection and evolution on maintaining genomic integrity in low-passage PDXs compared to the donor tissue. We also raise vital questions regarding the practical utility of PDX and humanized PDX models in predicting patient response to therapy and make recommendations for addressing those questions. Once collaborations and standardized xenotransplantation and data management methods are established, NSCLC PDX mouse models have the potential to be universal and invaluable as a preclinical tool that guides clinical trials and standard therapeutic decisions. PMID:28154808

  14. Afatinib beyond progression in patients with non-small-cell lung cancer following chemotherapy, erlotinib/gefitinib and afatinib: phase III randomized LUX-Lung 5 trial

    OpenAIRE

    Schuler, M.; Yang, J. C.-H.; Park, K.; Kim, J. -H.; Bennouna, J; Chen, Y.-M.; Chouaid, C.; de Marinis, F.; Feng, J. -F.; Grossi, F; Kim, D.-W.; Liu, X.; Lu, S.; Strausz, J.; Vinnyk, Y.

    2015-01-01

    Background Afatinib has demonstrated clinical benefit in patients with non-small-cell lung cancer progressing after treatment with erlotinib/gefitinib. This phase III trial prospectively assessed whether continued irreversible ErbB-family blockade with afatinib plus paclitaxel has superior outcomes versus switching to chemotherapy alone in patients acquiring resistance to erlotinib/gefitinib and afatinib monotherapy. Patients and methods Patients with relapsed/refractory disease following ≥1 ...

  15. Clinical retrospective analysis of erlotinib in the treatment of elderly patients with advanced non-small cell lung cancer.

    Science.gov (United States)

    Platania, Marco; Agustoni, Francesco; Formisano, Barbara; Vitali, Milena; Ducceschi, Monika; Pietrantonio, Filippo; Zilembo, Nicoletta; Gelsomino, Francesco; Pusceddu, Sara; Buzzoni, Roberto

    2011-09-01

    In order to evaluate the clinical efficacy and the safety profile of molecularly targeted therapies as a palliative approach in elderly populations affected by advanced thoracic neoplasms, we retrospectively studied, in terms of effectiveness and toxicities, a group of pretreated elderly metastatic non-small cell lung cancer (NSCLC) patients admitted to our institution and treated with erlotinib at standard daily/dose. Forty-three patients aged 70 years or older who had previously failed on chemotherapy or radiotherapy were treated with oral Eerlotinib (150 mg/d) until disease progression or unacceptable toxicity. Clinical data, pathological types, potential prognostic factors, efficacy and toxicity of erlotinib were included in this analysis. In our series we observed: objective responses in six patients (14%) and stable disease in 15 (35%). Skin rash was the most common side effect (67%). Grade 3-4 adverse events were observed in 16 cases (37%). The median overall survival and the median progression-free survival were 8.4 months (CI 95%: 0.7-43.6) and 3 months (CI 95%: 0.4-28.4), respectively. Patients with adenocarcinoma achieved the best disease control rate (p = 0.027), while not/former smokers showed a better response (p = 0.069). In our experience the use of erlotinib after chemotherapy failure in an unselected elderly population affected by NSCLC showed moderate efficacy and a moderate safety profile. However, erlotinib represents a valid option in this setting, but other factors such as biological information, comorbidities and concomitant medications need to be carefully take into consideration in this particular subset of cancer patients.

  16. Pulmonary Artery Invasion, High-Dose Radiation, and Overall Survival in Patients With Non-Small Cell Lung Cancer

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    Han, Cheng-Bo [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Department of Oncology, Shengjing Hospital of China Medical University, Shenyang (China); Wang, Wei-Li [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Department of Radiation Oncology, Fourth Hospital of China Medical University, Shenyang (China); Quint, Leslie [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Xue, Jian-Xin [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Department of Thoracic Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu (China); Matuszak, Martha; Ten Haken, Randall [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Kong, Feng-Ming, E-mail: fkong@gru.edu [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States)

    2014-06-01

    Purpose: To investigate whether high-dose radiation to the pulmonary artery (PA) affects overall survival (OS) in patients with non-small cell lung cancer (NSCLC). Methods and Materials: Patients with medically inoperable/unresectable NSCLC treated with definitive radiation therapy in prospective studies were eligible for this study. Pulmonary artery involvement was defined on the basis of pretreatment chest CT and positron emission tomography/CT fusion. Pulmonary artery was contoured according to the Radiation Therapy Oncology Group protocol 1106 atlas, and dose-volume histograms were generated. Results: A total of 100 patients with a minimum follow-up of 1 year for surviving patients were enrolled: 82.0% underwent concurrent chemoradiation therapy. Radiation dose ranged from 60 to 85.5 Gy in 30-37 fractions. Patients with PA invasion of grade ≤2, 3, 4, and 5 had 1-year OS and median survival of 67% and 25.4 months (95% confidence interval [CI] 15.7-35.1), 62% and 22.2 months (95% CI 5.8-38.6), 90% and 35.8 months (95% CI 28.4-43.2), and 50% and 7.0 months, respectively (P=.601). Two of the 4 patients with grade 5 PA invasion died suddenly from massive hemorrhage at 3 and 4.5 months after completion of radiation therapy. Maximum and mean doses to PA were not significantly associated with OS. The V45, V50, V55, and V60 of PA were correlated significantly with a worse OS (P<.05). Patients with V45 >70% or V60 >37% had significantly worse OS (13.3 vs 37.9 months, P<.001, and 13.8 vs 37.9 months, P=.04, respectively). Conclusions: Grade 5 PA invasion and PA volume receiving more than 45-60 Gy may be associated with inferior OS in patients with advanced NSCLC treated with concurrent chemoradiation.

  17. Clinical significance of preoperative carcinoembryonic antigen level in patients with clinical stage IA non-small cell lung cancer

    Science.gov (United States)

    Suda, Takashi; Hachimaru, Ayumi; Tochii, Daisuke; Tochii, Sachiko; Takagi, Yasushi

    2017-01-01

    Background The objective of this study was to assess the preoperative serum carcinoembryonic antigen (CEA) level in patients with clinical stage IA non-small cell lung cancer (NSCLC) and to evaluate its clinical significance. Methods Between January 2005 and December 2014, a total of 378 patients with clinical stage IA NSCLC underwent complete resection with systematic node dissection. The survival rate was estimated starting from the date of surgery to the date of either death or the last follow-up by the Kaplan-Meier method. Univariate analyses by log-rank tests were used to determine prognostic factors. Cox proportional hazards ratios were used to identify independent predictors of poor prognosis. Clinicopathological predictors of lymph node metastases were evaluated by logistic regression analyses. Results The 5-year survival rate of patients with an elevated preoperative serum CEA level was significantly lower than that of patients with a normal CEA level (75.5% vs. 87.7%; P=0.02). However, multivariate analysis did not show the preoperative serum CEA level to be an independent predictor of poor prognosis. Postoperative pathological factors, including lymphatic permeation, visceral pleural invasion, and lymph node metastases, tended to be positive in patients with an elevated preoperative serum CEA level. In addition, the CEA level was a statistically significant independent clinical predictor of lymph node metastases. Conclusions The preoperative serum CEA level was not an independent predictor of poor prognosis in patients with pathological stage IA NSCLC but was an important clinical predictor of tumor invasiveness and lymph node metastases in patients with clinical stage IA NSCLC. Therefore, measurement of the preoperative serum CEA level should be considered even for patients with early-stage NSCLC.

  18. Topoisomerase II alpha expression and the benefit of adjuvant chemotherapy for postoperative patients with non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Jie Li

    2010-11-01

    Full Text Available Abstract Background Adjuvant chemotherapy has been shown to improve survival rates of postoperative patients with non-small cell lung cancer (NSCLC. Biomarkers could help select an appropriate chemotherapy for NSCLC patients or predict the efficacy of chemotherapy. The objective of this study was to explore the possible prognostic and predictive role of topoisomerase II alpha (TopIIα expression level in postoperative NSCLC patients who received adjuvant chemotherapy. Methods Patients with stage I-III NSCLC, who underwent surgery in our hospital from January 2004 to December 2007 and who also received adjuvant chemotherapy after surgery, were analyzed in this study. Expression of TopIIα and Ki67 in paraffin-embedded tissues was detected by immunohistochemistry (IHC. The relationships between clinicopathological characteristics, chemotherapy regimens, the expression of biomarkers and disease free survival (DFS were analyzed. Results TopIIα and Ki67 were highly expressed in 22.5% and 36.4% of the 151 patients, respectively. Univariate survival analysis showed that male sex (P = 0.036, non-adenocarcinoma (P = 0.004, earlier pathological TNM stage (P = 0.001 or pathological N stage (P Conclusions High TopIIα expression was discovered to be correlated with better DFS for postoperative NSCLC patients who received adjuvant chemotherapy. The NVB-containing chemotherapy regimen was more effective than the TXT-containing regimen in improving DFS in patients with low TopIIα expression. TopIIα could be considered to be an independent prognostic biomarker of DFS in postoperative NSCLC patients who received adjuvant chemotherapy.

  19. High-definition imaging of circulating tumor cells and associated cellular events in non-small cell lung cancer patients: a longitudinal analysis

    Science.gov (United States)

    Nieva, Jorge; Wendel, Marco; Luttgen, Madelyn S.; Marrinucci, Dena; Bazhenova, Lyudmila; Kolatkar, Anand; Santala, Roger; Whittenberger, Brock; Burke, James; Torrey, Melissa; Bethel, Kelly; Kuhn, Peter

    2012-02-01

    Sampling circulating tumor cells (CTCs) from peripheral blood is ideally accomplished using assays that detect high numbers of cells and preserve them for downstream characterization. We sought to evaluate a method using enrichment free fluorescent labeling of CTCs followed by automated digital microscopy in patients with non-small cell lung cancer. Twenty-eight patients with non-small cell lung cancer and hematogenously seeded metastasis were analyzed with multiple blood draws. We detected CTCs in 68% of analyzed samples and found a propensity for increased CTC detection as the disease progressed in individual patients. CTCs were present at a median concentration of 1.6 CTCs ml-1 of analyzed blood in the patient population. Higher numbers of detected CTCs were associated with an unfavorable prognosis.

  20. Phase I study of docetaxel and irinotecan in patients with advanced non-small-cell lung cancer.

    Science.gov (United States)

    Nogami, Naoyuki; Harita, Shingo; Ueoka, Hiroshi; Yonei, Toshiro; Kiura, Katsuyuki; Kamei, Haruhito; Tabata, Masahiro; Segawa, Yoshihiko; Gemba, Kenichi; Tanimoto, Mitsune

    2004-07-01

    The role of non-platinum combination chemotherapy in the treatment of advanced non-small-cell lung cancer (NSCLC) has not yet been clarified. In this phase I study, the dose-limiting toxicity (DLT), the maximum tolerable dose (MTD) and the antitumor activity of a two-drug combination of docetaxel (DCT) and irinotecan (CPT) in patients with advanced NSCLC were evaluated. Previously untreated patients with NSCLC in stage IIIB with malignant pleural effusion or stage IV were eligible. Both drugs were administered by 1-h intravenous infusion on day 1, and repeated every 3 weeks. DCT was given before CPT administration. Five escalating dose levels of DCT/CPT (40/135, 50/135, 50/150, 60/150, and 60/165 mg/m2) were studied. Eighteen patients received 44 courses. The DLT was considered to be neutropenia, because grade 4 neutropenia lasting for 3 days or more was observed in three patients, which was accompanied with three episodes of febrile neutropenia. As a non-hematological toxicity, grade 3 diarrhea occurred in three patients. Since all the three patients treated at the fifth dose level (DCT at 60 mg/m2 and CPT at 165 mg/m2) experienced DLT (grade 4 neutropenia in two patients and grade 3 hepatic toxicity in one), this dose level was determined to be the MTD. The objective response rate was 33.3%, and the median survival time was 13.6 months. To confirm the effectiveness of this combination for advanced NSCLC which was suggested in the present study, a phase II study with the recommended doses (150 mg/m2 for CPT and 50-60 mg/m2 for DCT) is warranted.

  1. A phase II study of STEALTH cisplatin (SPI-77) in patients with advanced non-small cell lung cancer.

    Science.gov (United States)

    Kim, E S; Lu, C; Khuri, F R; Tonda, M; Glisson, B S; Liu, D; Jung, M; Hong, W K; Herbst, R S

    2001-12-01

    Cisplatin-based chemotherapy improves survival in appropriately selected patients with stage IV non-small cell lung cancer (NSCLC). However, cisplatin-based regimens have well-known dose-related toxicities, particularly renal insufficiency and neurotoxicity. On the basis of prior preclinical and phase I studies, we initiated a phase II study of SPI-77 (STEALTH) Liposomal Cisplatin) in patients with stage IIIB and IV NSCLC who failed previous treatment with platinum. Disease in all subjects had progressed during therapy, failed to respond, or progressed within 3 months after discontinuing the platinum-based chemotherapy. Between January and June 1999, 13 patients were enrolled at our institution. Patient characteristics included: seven women, six men; median age, 61 years; median Karnofsky performance status, 80%; median number of prior chemotherapy regimens, two (range, 1-3). All patients had adequate hepatic and renal function. SPI-77 was administered at a dose of 260 mg/m(2) IV every 3 weeks. A median of two cycles (range 1-6) were given; the total number of cycles was 35. Among the 12 patients evaluable for response, two had (17%) stable disease and ten (83%) had progressive disease. The median survival was 24.3 weeks, and the median follow-up was 43.9 weeks. Toxicity could be evaluated in all subjects. Moderate anemia (46% of cycles, or=grade 3) with minimal granulocytopenia and thrombocytopenia (26% of cycles grade 1; 0% of cycles, >or=grade 2) were the most notable manifestations of myelosuppression. Grade 3 nonhematological toxicities included dyspnea (8%), fatigue (8%), and pain (8%). There were no grade 4 toxicities. These data suggest that this liposomal cisplatin formulation does not have appreciable activity in this population of patients with NSCLC who had received prior platinum-based chemotherapy. The lack of encouraging results from SPI-77 use in other phase I and II studies resulted in early closure of this trial by the manufacturer.

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

    Directory of Open Access Journals (Sweden)

    Qiang GL

    2015-12-01

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

  3. Overexpression of stathmin is resistant to paclitaxel treatment in patients with non-small cell lung cancer.

    Science.gov (United States)

    Sun, Ruifang; Liu, Zhigang; Wang, Lumin; Lv, Weidong; Liu, Jia; Ding, Caixia; Yuan, Yong; Lei, Guangyan; Xu, Changfu

    2015-09-01

    Paclitaxel can exert therapeutic effects by interacting with microtubules. Stathmin and β-III-tubulin, which have impact on microtubule activity, are believed to be involved in the chemotherapy. The purpose of the present study was to evaluate the associations between stathmin and β-III-tubulin expression and treatment response and survivals in patients with non-small cell lung cancer (NSCLC). Two hundred thirty-eight patients who were treated by platinum-based chemotherapy were enrolled in this study, among them, 111 patients also received paclitaxel treatment. Formalin-fixed and paraffin-embedded tumor tissues were collected for messenger RNA (mRNA) and protein detection. We assessed the associations of the two molecules with treatment response and survival outcome. High level of stathmin exhibited poor response to chemotherapy (for mRNA, P = 0.041; for protein, P = 0.017). Overexpression of stathmin was associated with shorter overall survival (for mRNA, P = 0.012; for protein, P = 0.014) and progression-free survival (for mRNA, P = 0.039; for protein, P = 0.022). Of note, this association was only observed in patients who were treated by both platinum and paclitaxel. Similar effects were not observed for β-III-tubulin. The findings demonstrated that paclitaxel effect may be interfered with stathmin; overexpression of stathmin is a predictive marker for a worse prognosis in patients with NSCLC who were treated by both platinum and paclitaxel chemotherapy.

  4. 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.

  5. Lived experiences of everyday life during curative radiotherapy in patients with non-small-cell lung cancer: A phenomenological study

    Directory of Open Access Journals (Sweden)

    Suzanne Petri

    2015-11-01

    Full Text Available Aim: To explore and describe the essential meaning of lived experiences of the phenomenon: Everyday life during curative radiotherapy in patients with non-small-cell lung cancer (NSCLC. Background: Radiotherapy treatment in patients with NSCLC is associated with severe side effects such as fatigue, anxiety, and reduced quality of life. However, little is known about the patients’ experience of everyday life during the care trajectory. Design: This study takes a reflective lifeworld approach using an empirical application of phenomenological philosophy described by Dahlberg and colleagues. Method: A sample of three patients treated with curative radiotherapy for NSCLC was interviewed 3 weeks after the end of radiotherapy treatment about their experiences of everyday life during their treatment. Data were collected in 2014 and interviews and analysis were conducted within the descriptive phenomenological framework. Findings: The essential meaning structure of the phenomenon studied was described as “Hope for recovery serving as a compass in a changed everyday life,” which was a guide for the patients through the radiotherapy treatment to support their efforts in coping with side effects. The constituents of the structure were: Radiotherapy as a life priority, A struggle for acceptance of an altered everyday life, Interpersonal relationships for better or worse, and Meeting the health care system. Conclusion: The meaning of hope was essential during radiotherapy treatment and our results suggest that interpersonal relationships can be a prerequisite to the experience of hope. “Hope for recovery serving as a compass in a changed everyday life,” furthermore identifies the essentials in the patients’ assertive approach to believing in recovery and thereby enabling hope in a serious situation.

  6. Investigation of simple IMRT delivery techniques for non-small cell lung cancer patients with respiratory motion using 4DCT.

    Science.gov (United States)

    Reitz, Bodo; Parda, David S; Colonias, Athanasios; Lee, Vincent; Miften, Moyed

    2009-01-01

    Techniques for generating simplified IMRT treatment plans for treating non-small cell lung cancer (NSCLC) patients with respiratory motion were investigated. To estimate and account for respiratory motion, 4-dimensional computed tomography (4DCT) datasets from 5 patients were used to design 5-field 6-MV ungated step-and-shoot intensity modulated radiotherapy (IMRT) plans delivering a dose of 66 Gy to the planning target volume (PTV). For each patient, 2 plans were generated using the mean intensity and the maximum intensity of 10 CT datasets from different breathing phases. The plans also utilized different margins around the clinical target volume/internal target volume (CTV/ITV) to account for tumor motion. To reduce the treatment time and ensure accurate dose delivery to moving targets, the number of intensity levels was minimized while maintaining dose coverage to PTV and minimizing dose to organs at risk (OARs). Dose-volume histograms (DVHs), dosimetric metrics, and outcome probabilities were evaluated for all plans. Plans using the averaged CT image dataset were inferior, requiring larger margins around the PTV, with a maximum of 1.5 cm, to ensure coverage of the tumor, and therefore increased the dose to OARs located in proximity of the tumor. The plans based on superimposed CT image datasets achieved full coverage of the tumor, while allowing tight margins around the PTV and minimizing the dose to OARs. A small number of intensity-levels (3 to 5), resulting in IMRT plans with a total of 13 to 30 segments, were sufficient for homogeneous PTV coverage, without affecting the sparing of OARs. In conclusion, a technique involving treatment planning with the superimposed CT scans of all respiratory phases, and the application of IMRT with only a small number of segments was feasible despite significant tumor motion; however, greater patient numbers are needed to support the statistical significance of the results presented in this work.

  7. Phase II Trial of Improved Regimen with Gemcitabine in Patients 
with Advanced Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Lulu MIAO

    2012-01-01

    Full Text Available Background and objective Gemcitabine-platinum-combined with chemotherapy is the most common treatment for advanced non-small cell lung cancer (NSCLC. Gemcitabine is administered once a week in a general three-week schedule. In the present study, gemcitabine is administered on d1 and d5 to improve compliance, and the efficacy and safety of the improved regimen is evaluated in untreated patients with advanced NSCLC. Methods A total of 83 patients were enrolled between October 2007 and October 2009. In each cycle, gemcitabine was administered at a dose of 1,000 mg/m2-1,250 mg/m2 via a 30 min intravenous infusion on d1 and d5 followed by cisplatin at a dose of 75 mg/m2 or carboplatin (AUC=5 on d1 every three weeks. At least two cycles of chemotherapy were completed in each case, and clinical response and toxicity of the regimen were observed. Results The objective response rate was 37.3%. The median progression free survival and overall survival time were 6.1 months and 15.0 months, respectively. The one-year and two-year survival rates were 57.8% and 16.2%, respectively. Myelosuppression and gastrointestinal responses were the main toxicities. The incidence of grade 3/4 of leucopenia, hypohemia, and thrombocytopenia were 26.5%, 10.8% and 7.2%, respectively. A total of 27.5% of the patients in the cisplatin group had grade 3/4 gastrointestinal responses. Treatment related deaths were not observed in this study. Conclusion The regimen is active and well-tolerated in untreated patients with advanced NSCLC. Further randomized controlled studies are necessary.

  8. Docetaxel-carboplatin in combination with erlotinib and/or bevacizumab in patients with non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Boutsikou E

    2013-03-01

    Full Text Available Eftimia Boutsikou,1 Theodoros Kontakiotis,1 Paul Zarogoulidis,1 Kaid Darwiche,2 Ellada Eleptheriadou,1 Konstantinos Porpodis,1 Grammati Galaktidou,3 Leonidas Sakkas,4 Wolfgang Hohenforst-Schmidt,5 Kosmas Tsakiridis,6 Theodoros Karaiskos,7 Konstantinos Zarogoulidis11Pulmonary Department-Oncology Unit, G Papanikolaou General Hospital, Aristotle University of Thessaloniki, Greece; 2University Pulmonary Department-Interventional Unit, Ruhrland Klinic, University of Duisburg-Essen, Essen, Germany; 3Theagenio Anticancer Institute Research Laboratory, 4Department of Pathology, G Papanikolaou Hospital, Thessaloniki, Greece; 5II Medical Clinic, Hospital Coburg, University of Wuerzburg, Coburg, Germany; 6Cardiothoracic Surgery Department, Saint Luke Private Hospital, Panorama, 7Cardiothoracic Surgery Department, G Papanikolaou General Hospital, Aristotle University of Thessaloniki, Thessaloniki, GreeceBackground: Bevacizumab and erlotinib have been demonstrated to prolong overall survival in patients with non-squamous non-small cell lung cancer (NSCLC. We designed a four-arm Phase III trial to evaluate the efficacy and toxicity of the combination of docetaxel, carboplatin, bevacizumab, and erlotinib in the first-line treatment of patients with NSCLC.Methods: A total of 229 patients with stage IIIb/IV non-squamous NSCLC were treated with two cycles of carboplatin (area under the concentration-time curve 5.5 and docetaxel 100 mg/m2 as chemotherapy. After completion of two treatment cycles, patients were evaluated for response and divided into four groups: 61/229 continued with four more cycles of chemotherapy (control group, 52/229 received chemotherapy plus erlotinib 150 mg daily, 56/229 received chemotherapy plus bevacizumab 7.5 mg/kg, and 60/229 were treated with the combination of chemotherapy, erlotinib, and bevacizumab until disease progression. The primary endpoint was overall survival.Results: Over 4 years of follow-up, there was no statistically

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

    Institute of Scientific and Technical Information of China (English)

    刘苓霜

    2014-01-01

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

  10. Effectiveness of third-generation chemotherapy on the survival of patients with advanced non-small cell lung cancer in Norway

    DEFF Research Database (Denmark)

    von Plessen, C; Strand, T-E; Wentzel-Larsen, T;

    2008-01-01

    BACKGROUND: To investigate whether the introduction of modern third-generation chemotherapy was associated with survival benefits in a national population of patients with advanced non-small cell lung cancer (ANSCLC) and to explore geographical and temporary variations in the utilisation of chemo......BACKGROUND: To investigate whether the introduction of modern third-generation chemotherapy was associated with survival benefits in a national population of patients with advanced non-small cell lung cancer (ANSCLC) and to explore geographical and temporary variations in the utilisation...... of death (HR 0.84, 95% CI 0.73 to 0.98). County of residence predicted chemotherapy utilisation with odds ratios in the range 0.13 (95% CI 0.1 to 0.19) to 1.04 (95% CI 0.64 to 1.69), a county with traditionally high utilisation as reference. CONCLUSION: Utilisation of third-generation chemotherapy...

  11. ATM Polymorphisms Predict Severe Radiation Pneumonitis in Patients With Non-Small Cell Lung Cancer Treated With Definitive Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Xiong, Huihua [Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan (China); Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Liao, Zhongxing, E-mail: zliao@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Liu, Zhensheng [Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Xu, Ting [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Wang, Qiming; Liu, Hongliang [Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Komaki, Ritsuko; Gomez, Daniel [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Wang, Li-E [Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Wei, Qingyi, E-mail: qwei@mdanderson.org [Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2013-03-15

    Purpose: The ataxia telangiectasia mutated (ATM) gene mediates detection and repair of DNA damage. We investigated associations between ATM polymorphisms and severe radiation-induced pneumonitis (RP). Methods and Materials: We genotyped 3 potentially functional single nucleotide polymorphisms (SNPs) of ATM (rs1801516 [D1853N/5557G>A], rs189037 [-111G>A] and rs228590) in 362 patients with non-small cell lung cancer (NSCLC), who received definitive (chemo)radiation therapy. The cumulative severe RP probabilities by genotypes were evaluated using the Kaplan-Meier analysis. The associations between severe RP risk and genotypes were assessed by both logistic regression analysis and Cox proportional hazard model with time to event considered. Results: Of 362 patients (72.4% of non-Hispanic whites), 56 (15.5%) experienced grade ≥3 RP. Patients carrying ATM rs189037 AG/GG or rs228590 TT/CT genotypes or rs189037G/rs228590T/rs1801516G (G-T-G) haplotype had a lower risk of severe RP (rs189037: GG/AG vs AA, adjusted hazard ratio [HR] = 0.49, 95% confidence interval [CI], 0.29-0.83, P=.009; rs228590: TT/CT vs CC, HR=0.57, 95% CI, 0.33-0.97, P=.036; haplotype: G-T-G vs A-C-G, HR=0.52, 95% CI, 0.35-0.79, P=.002). Such positive findings remained in non-Hispanic whites. Conclusions: ATM polymorphisms may serve as biomarkers for susceptibility to severe RP in non-Hispanic whites. Large prospective studies are required to confirm our findings.

  12. Comparison of concurrent chemoradiotherapy versus sequential radiochemotherapy in patients with completely resected non-small cell lung cancer

    Science.gov (United States)

    Kim, Hwan-Ik; Noh, O Kyu; Oh, Young-Taek; Chun, Mison; Kim, Sang-Won; Cho, Oyeon; Heo, Jaesung

    2016-01-01

    Purpose Our institution has implemented two different adjuvant protocols in treating patients with non-small cell lung cancer (NSCLC): chemotherapy followed by concurrent chemoradiotherapy (CT-CCRT) and sequential postoperative radiotherapy (PORT) followed by postoperative chemotherapy (POCT). We aimed to compare the clinical outcomes between the two adjuvant protocols. Materials and Methods From March 1997 to October 2012, 68 patients were treated with CT-CCRT (n = 25) and sequential PORT followed by POCT (RT-CT; n = 43). The CT-CCRT protocol consisted of 2 cycles of cisplatin-based POCT followed by PORT concurrently with 2 cycles of POCT. The RT-CT protocol consisted of PORT followed by 4 cycles of cisplatin-based POCT. PORT was administered using conventional fractionation with a dose of 50.4–60 Gy. We compared the outcomes between the two adjuvant protocols and analyzed the clinical factors affecting survivals. Results Median follow-up time was 43.9 months (range, 3.2 to 74.0 months), and the 5-year overall survival (OS), locoregional recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) were 53.9%, 68.2%, and 51.0%, respectively. There were no significant differences in OS (p = 0.074), LRFS (p = 0.094), and DMFS (p = 0.490) between the two protocols. In multivariable analyses, adjuvant protocol remained as a significant prognostic factor for LRFS, favouring CT-CCRT (hazard ratio [HR] = 3.506, p = 0.046) over RT-CT, not for OS (HR = 0.647, p = 0.229). Conclusion CT-CCRT protocol increased LRFS more than RT-CT protocol in patients with completely resected NSCLC, but not in OS. Further studies are warranted to evaluate the benefit of CCRT strategy compared with sequential strategy. PMID:27730801

  13. Comparison of concurrent chemoradiotherapy versus sequential radiochemotherapy in patients with completely resected non-small cell lung cancer

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    Kim, Hwan Ik; Noh, O Kyu; Oh, Young Taek; Chun, Mi Son; Kim, Sang Won; Cho, O Yeon; Heo, Jae Sung [Ajou University School of Medicine, Suwon (Korea, Republic of)

    2016-09-15

    Our institution has implemented two different adjuvant protocols in treating patients with non-small cell lung cancer (NSCLC): chemotherapy followed by concurrent chemoradiotherapy (CT-CCRT) and sequential postoperative radiotherapy (PORT) followed by postoperative chemotherapy (POCT). We aimed to compare the clinical outcomes between the two adjuvant protocols. From March 1997 to October 2012, 68 patients were treated with CT-CCRT (n = 25) and sequential PORT followed by POCT (RT-CT; n = 43). The CT-CCRT protocol consisted of 2 cycles of cisplatin-based POCT followed by PORT concurrently with 2 cycles of POCT. The RT-CT protocol consisted of PORT followed by 4 cycles of cisplatin-based POCT. PORT was administered using conventional fractionation with a dose of 50.4–60 Gy. We compared the outcomes between the two adjuvant protocols and analyzed the clinical factors affecting survivals. Median follow-up time was 43.9 months (range, 3.2 to 74.0 months), and the 5-year overall survival (OS), locoregional recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) were 53.9%, 68.2%, and 51.0%, respectively. There were no significant differences in OS (p = 0.074), LRFS (p = 0.094), and DMFS (p = 0.490) between the two protocols. In multivariable analyses, adjuvant protocol remained as a significant prognostic factor for LRFS, favouring CT-CCRT (hazard ratio [HR] = 3.506, p = 0.046) over RT-CT, not for OS (HR = 0.647, p = 0.229). CT-CCRT protocol increased LRFS more than RT-CT protocol in patients with completely resected NSCLC, but not in OS. Further studies are warranted to evaluate the benefit of CCRT strategy compared with sequential strategy.

  14. Polymorphisms of homologous recombination genes and clinical outcomes of non-small cell lung cancer patients treated with definitive radiotherapy.

    Directory of Open Access Journals (Sweden)

    Ming Yin

    Full Text Available The repair of DNA double-strand breaks (DSBs is the major mechanism to maintain genomic stability in response to irradiation. We hypothesized that genetic polymorphisms in DSB repair genes may affect clinical outcomes among non-small cell lung cancer (NSCLC patients treated with definitive radio(chemotherapy. We genotyped six potentially functional single nucleotide polymorphisms (SNPs (i.e., RAD51 -135G>C/rs1801320 and -172G>T/rs1801321, XRCC2 4234G>C/rs3218384 and R188H/rs3218536 G>A, XRCC3 T241M/rs861539 and NBN E185Q/rs1805794 and estimated their associations with overall survival (OS and radiation pneumonitis (RP in 228 NSCLC patients. We found a predictive role of RAD51 -135G>C SNP in RP development (adjusted hazard ratio [HR] = 0.52, 95% confidence interval [CI], 0.31-0.86, P = 0.010 for CG/CC vs. GG. We also found that RAD51 -135G>C and XRCC2 R188H SNPs were independent prognostic factors for overall survival (adjusted HR = 1.70, 95% CI, 1.14-2.62, P = 0.009 for CG/CC vs. GG; and adjusted HR = 1.70; 95% CI, 1.02-2.85, P = 0.043 for AG vs. GG, respectively and that the SNP-survival association was most pronounced in the presence of RP. Our study suggests that HR genetic polymorphisms, particularly RAD51 -135G>C, may influence overall survival and radiation pneumonitis in NSCLC patients treated with definitive radio(chemotherapy. Large studies are needed to confirm our findings.

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

    DEFF Research Database (Denmark)

    von Plessen, Christian

    2011-01-01

    treatment option is palliative chemotherapy. Given the palliative intention of the chemotherapy, it is clinically highly relevant to establish the optimal treatment duration. While chemotherapy prolongs survival and improves quality of life (QoL), it also has side effects and only a minority of patients...... achieve an objective treatment response. Clinicians need guidance on treatment duration from controlled trials to balance these aspects. Improvements of the conditions under which chemotherapy is given can increase patient and staff satisfaction and increase system performance. This is especially relevant...... of care. Clinicians, health care administrators and the public need knowledge about the outcomes of palliative chemotherapy in unselected patient populations. The efficacy of palliative chemotherapy for advanced NSCLC has been amply documented in controlled clinical trials. Meanwhile, the elderly...

  16. Bioinformatics Analyses of the Role of Vascular Endothelial Growth Factor in Patients with Non-Small Cell Lung Cancer.

    Directory of Open Access Journals (Sweden)

    Ying Wang

    Full Text Available This study was aimed to identify the expression pattern of vascular endothelial growth factor (VEGF in non-small cell lung cancer (NSCLC and to explore its potential correlation with the progression of NSCLC.Gene expression profile GSE39345 was downloaded from the Gene Expression Omnibus database. Twenty healthy controls and 32 NSCLC samples before chemotherapy were analyzed to identify the differentially expressed genes (DEGs. Then pathway enrichment analysis of the DEGs was performed and protein-protein interaction networks were constructed. Particularly, VEGF genes and the VEGF signaling pathway were analyzed. The sub-network was constructed followed by functional enrichment analysis.Total 1666 up-regulated and 1542 down-regulated DEGs were identified. The down-regulated DEGs were mainly enriched in the pathways associated with cancer. VEGFA and VEGFB were found to be the initiating factor of VEGF signaling pathway. In addition, in the epidermal growth factor receptor (EGFR, VEGFA and VEGFB associated sub-network, kinase insert domain receptor (KDR, fibronectin 1 (FN1, transforming growth factor beta induced (TGFBI and proliferating cell nuclear antigen (PCNA were found to interact with at least two of the three hub genes. The DEGs in this sub-network were mainly enriched in Gene Ontology terms related to cell proliferation.EGFR, KDR, FN1, TGFBI and PCNA may interact with VEGFA to play important roles in NSCLC tumorigenesis. These genes and corresponding proteins may have the potential to be used as the targets for either diagnosis or treatment of patients with NSCLC.

  17. Perioperative considerations in patients with non small cell lung cancer and metastases in mediastinal lymph nodes

    Institute of Scientific and Technical Information of China (English)

    Dragan SUBOTIC

    2008-01-01

    Since the latest revision of the TNM system reclassified T3N0 tumours into the ⅡB stage, N2 lesions became the major determinant of the ⅢA stage. Concerning the minority of patients with T3N1 tumours in this stage,

  18. Pemetrexed in Previously Treated Non-small Cell Lung Cancer Patients with Poor Performance Status

    Institute of Scientific and Technical Information of China (English)

    Sun YoungJUNG; Su JinYOO; Ji Young SHIN; Ji Won PARK; Jeong Eun LEE; Hee Sun PARK; Ju Ock KIM; Sun Young KIM

    2011-01-01

    Background and objective Pemetrexed have been approved for the treatment of patients affected by advanced non-small cell lung cancner (NSCLC) in progression after first-line chemotherapy. We evaluated the activity and feasibility of pemetrexed in previously treated NSCLC.Methods Patients with histologically or cytologically confirmed NSCLC were evaluated from April 2007 to March 2009. The patients had relapsed or progressed after prior chemotherapy treatment. Pemetrexed (500 mg/m2) was administered intravenously once every 3 weeks after progression to prior chemotherapy. The tumor response was evaluated according to RECIST criteria by chest CT at every 2 cycles of chemotherapy.Results A total 61 patients were eligible for analysis. Performance status of them (100%) was over 2. The response rate and disease control rate were 14.7% and 37.7% respectively. Non-squamous cell carcinoma histology was significantly associated with a superior response rate (P=0.045) and disease control rate (P=0.008). The median survival time and the median progression free survival (PFS) time were 6.11 months and 2.17 months, respectively. Comparing the efficacy of pemetrexed in these two settings [second-line versus (12/61) more than third (49/61)], there was no significant difference in regard to median survival (11.18 months vs 11.46 months, P=0.922,S), but PFS was more longer in third- or further-line groups than second-line group (1.39 months vs 2.25 months, P=0.015,3).Conclusion Pemetrexed is a feasible regimen in previously treated NSCLC with poor performance status.

  19. Third-space fluid distribution of pemetrexed in non-small cell lung cancer patients

    DEFF Research Database (Denmark)

    Honoré, Per Gustaf Hartvig; Joensen, Sigrid Jóhansdóttir; Olsen, Michelle;

    2014-01-01

    with perchloric acid. Pharmacokinetic analysis was performed using a non-compartment method as well a two-compartment model. RESULTS: The results were calculated from 10 samples taken from eight patients, where data from one patient point were excluded as the patient had impaired renal function, and three samples...... were reported as below limit of quantification. The plasma PEM pharmacokinetics calculated showed an elimination half-life (t ½ elimination) of 3.2 h and distribution half-life (t ½-distribution) of 6 min. Clearance (CL) was 5.1 L/h, central volume of distribution (V central) 23.2 L and peripheral...... volume distribution (V peripheral) 10.6 L, and the area under the curve was 186 μg h/mL. Using non-compartment methods, an elimination half-life of 3.1 h and an apparent CL of 3.2 L/h were measured, whereas an apparent steady-state volume became 14.2 L. The pleura concentrations were only half...

  20. 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).

  1. Gefitinib in Treating Patients With Metastatic or Unresectable Head and Neck Cancer or Non-Small Cell Lung Cancer

    Science.gov (United States)

    2013-01-11

    Anaplastic Thyroid Cancer; Insular Thyroid Cancer; Metastatic Parathyroid Cancer; Recurrent Adenoid Cystic Carcinoma of the Oral Cavity; Recurrent Basal Cell Carcinoma of the Lip; Recurrent Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; 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 Parathyroid Cancer; Recurrent Salivary Gland 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 Thyroid Cancer; Recurrent Verrucous Carcinoma of the Larynx; Stage III Follicular Thyroid Cancer; Stage III Papillary Thyroid Cancer; Stage III Salivary Gland Cancer; Stage III Squamous Cell Carcinoma of the Hypopharynx; Stage III Squamous Cell Carcinoma of the Larynx; Stage III Verrucous Carcinoma of the Larynx; Stage IIIB Non-small Cell Lung Cancer; Stage IV Lymphoepithelioma of the Nasopharynx; Stage IV Non-small Cell Lung Cancer; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IVA Adenoid Cystic Carcinoma of the Oral Cavity; Stage IVA Basal Cell Carcinoma of the Lip; Stage IVA Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Stage IVA Follicular Thyroid Cancer; Stage IVA Inverted Papilloma of the Paranasal Sinus and Nasal Cavity; Stage IVA Lymphoepithelioma of the Oropharynx; Stage IVA Midline Lethal Granuloma of the Paranasal Sinus

  2. 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.

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

    Directory of Open Access Journals (Sweden)

    Yanhua LI

    2014-11-01

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

  4. Precision Hypofractionated Radiation Therapy in Poor Performing Patients With Non-Small Cell Lung Cancer: Phase 1 Dose Escalation Trial

    Energy Technology Data Exchange (ETDEWEB)

    Westover, Kenneth D. [Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Loo, Billy W. [Department of Radiation Oncology, Stanford University, Stanford, California (United States); Gerber, David E. [Division of Hematology-Oncology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Iyengar, Puneeth; Choy, Hak [Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Diehn, Maximilian [Department of Radiation Oncology, Stanford University, Stanford, California (United States); Hughes, Randy; Schiller, Joan; Dowell, Jonathan [Division of Hematology-Oncology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Wardak, Zabi [Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Sher, David [Department of Radiation Oncology, Rush University Medical Center, Chicago, Illinois (United States); Christie, Alana; Xie, Xian-Jin [Department of Clinical Science, Southwestern Medical Center, Dallas, Texas (United States); Corona, Irma [Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Sharma, Akanksha [School of Medicine, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Wadsworth, Margaret E. [Radiation Oncology of Mississippi, Jackson, Mississippi (United States); Timmerman, Robert, E-mail: Robert.Timmerman@utsouthwestern.edu [Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas (United States)

    2015-09-01

    Purpose: Treatment regimens for locally advanced non-small cell lung cancer (NSCLC) give suboptimal clinical outcomes. Technological advancements such as radiation therapy, the backbone of most treatment regimens, may enable more potent and effective therapies. The objective of this study was to escalate radiation therapy to a tumoricidal hypofractionated dose without exceeding the maximally tolerated dose (MTD) in patients with locally advanced NSCLC. Methods and Materials: Patients with stage II to IV or recurrent NSCLC and Eastern Cooperative Oncology Group performance status of 2 or greater and not candidates for surgical resection, stereotactic radiation, or concurrent chemoradiation were eligible. Highly conformal radiation therapy was given to treat intrathoracic disease in 15 fractions to a total of 50, 55, or 60 Gy. Results: Fifty-five patients were enrolled: 15 at the 50-Gy, 21 at the 55-Gy, and 19 at the 60-Gy dose levels. A 90-day follow-up was completed in each group without exceeding the MTD. With a median follow-up of 12.5 months, there were 93 grade ≥3 adverse events (AEs), including 39 deaths, although most AEs were considered related to factors other than radiation therapy. One patient from the 55- and 60-Gy dose groups developed grade ≥3 esophagitis, and 5, 4, and 4 patients in the respective dose groups experienced grade ≥3 dyspnea, but only 2 of these AEs were considered likely related to therapy. There was no association between fraction size and toxicity (P=.24). The median overall survival was 6 months with no significant differences between dose levels (P=.59). Conclusions: Precision hypofractionated radiation therapy consisting of 60 Gy in 15 fractions for locally advanced NSCLC is generally well tolerated. This treatment regimen could provide patients with poor performance status a potent alternative to chemoradiation. This study has implications for the cost effectiveness of lung cancer therapy. Additional studies of long

  5. Prognosis of R1-resection at the bronchial stump in patients with non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    Lyu Jima; Hao Xuezhi; Hui Zhouguang; Liang Jun; Zhou Zongmei; Feng Qinfu; Xiao Zefen

    2014-01-01

    Background The prognosis of R1-resection at the bronchial stump in patients with non-small cell lung cancer (NSCLC) remains unclear.This study intends to identify the prognostic factors and to optimize treatments for these patients under update conditions.Methods The data of 124 NSCLC patients who underwent R1-resection at the bronchial stump was reviewed.There were 41 patients in the surgery group (S),21 in the postoperative radiotherapy (PORT) group (S+R),30 in the postoperative chemotherapy (POCT) group (S+C),and 32 in the PORT plus POCT group (S+R+C).The constitute proportion in different groups was tested using the X2 method,univariate analysis was performed using the Kaplan-Meier and log-rank method,and multivariate analysis was done using the Cox hazard regression with entry factors including age,sex,pathological type and stage,classification of the residual disease,and treatment procedure.The process was performed stepwise backward with a maximum iteration of 20 and an entry possibility of 0.05 as well as an excluded possibility of 0.10 at each step.Results In univariate analysis,survival was more favorable for patients with squamous cell carcinoma,early pathological T or N stage,and chemotherapy or radiotherapy.There was no significant difference in the survival for patients with different types of the residual disease,except for the difference between patients with carcinoma in situ and lymphangiosis carcinomatosa (P=0.030).The survival for patients receiving chemoradiotherapy was superior to that for those undergoing surgery alone (P=0.016).In multivariate analysis,the pathological type (HR 2.51,95% CI 1.59 to 3.96,P=0.000),pathological T (HR 1.29,95% CI 1.04 to 1.60,P=-0.021) or N stage (HR 2.04,95% CI 1.40 to 2.98,P=0.000),and chemotherapy (HR 0.24,95% CI 0.13 to 0.43,P=0.000) were independent prognostic factors.Conclusion Patients with squamous cell carcinoma,early pathological T or N stage,or receiving chemotherapy had a more favorable

  6. Predicting Esophagitis After Chemoradiation Therapy for Non-Small Cell Lung Cancer: An Individual Patient Data Meta-Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Palma, David A., E-mail: david.palma@uwo.ca [Department of Radiation Oncology, London Regional Cancer Program, London, Ontario (Canada); Senan, Suresh [Department of Radiation Oncology, VU University Medical Center, Amsterdam (Netherlands); Oberije, Cary [Department of Radiation Oncology (MAASTRO Clinic), GROW – School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht (Netherlands); Belderbos, Jose [Department of Radiation Oncology, The Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Dios, Núria Rodríguez de [Department of Radiation Oncology, Parc de Salut Mar, Barcelona, Universidad Pompeu Fabra, Barcelona (Spain); Bradley, Jeffrey D. [Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri (United States); Barriger, R. Bryan [Department of Radiation Oncology, Indiana University School of Medicine, Indianapolis, Indiana (United States); Moreno-Jiménez, Marta [Department of Oncology, Radiation Oncology Division, Clínica Universidad de Navarra, University of Navarra, Pamplona (Spain); Kim, Tae Hyun [Center for Proton Therapy, Research Institute and Hospital, National Cancer Center, Goyang, Gyeonggi (Korea, Republic of); Ramella, Sara [Division of Radiation Oncology, Campus Bio-Medico University, Rome (Italy); Everitt, Sarah [Radiation Therapy Services, Peter MacCallum Cancer Centre, Melbourne, Australia and Department of Medical Imaging and Radiation Sciences, Faculty of Medicine, Nursing and Health Sciences, Monash University (Australia); Rengan, Ramesh [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Marks, Lawrence B. [Department of Radiation Oncology, University of North Carolina, Chapel Hill, North Carolina (United States); De Ruyck, Kim [Department of Basic Medical Sciences, Ghent University, Ghent (Belgium); and others

    2013-11-15

    Purpose: Concurrent chemoradiation therapy (CCRT) improves survival compared with sequential treatment for locally advanced non-small cell lung cancer, but it increases toxicity, particularly radiation esophagitis (RE). Validated predictors of RE for clinical use are lacking. We performed an individual-patient-data meta-analysis to determine factors predictive of clinically significant RE. Methods and Materials: After a systematic review of the literature, data were obtained on 1082 patients who underwent CCRT, including patients from Europe, North America, Asia, and Australia. Patients were randomly divided into training and validation sets (2/3 vs 1/3 of patients). Factors predictive of RE (grade ≥2 and grade ≥3) were assessed using logistic modeling, with the concordance statistic (c statistic) used to evaluate the performance of each model. Results: The median radiation therapy dose delivered was 65 Gy, and the median follow-up time was 2.1 years. Most patients (91%) received platinum-containing CCRT regimens. The development of RE was common, scored as grade 2 in 348 patients (32.2%), grade 3 in 185 (17.1%), and grade 4 in 10 (0.9%). There were no RE-related deaths. On univariable analysis using the training set, several baseline factors were statistically predictive of RE (P<.05), but only dosimetric factors had good discrimination scores (c > .60). On multivariable analysis, the esophageal volume receiving ≥60 Gy (V60) alone emerged as the best predictor of grade ≥2 and grade ≥3 RE, with good calibration and discrimination. Recursive partitioning identified 3 risk groups: low (V60 <0.07%), intermediate (V60 0.07% to 16.99%), and high (V60 ≥17%). With use of the validation set, the predictive model performed inferiorly for the grade ≥2 endpoint (c = .58) but performed well for the grade ≥3 endpoint (c = .66). Conclusions: Clinically significant RE is common, but life-threatening complications occur in <1% of patients. Although several factors

  7. 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

  8. FGFR4 genetic polymorphisms determine the chemotherapy response of Chinese patients with non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    Hong-mei FANG; Gang TIAN; Li-juan ZHOU; Han-ying ZHOU; Ying-zhi FANG

    2013-01-01

    Aim:To investigate the relationship of fibroblast growth factor receptor 4 (FGFR4) gene polymorphisms with the response of Chinese patients with non-small cell lung cancer (NSCLC) to chemotherapy.Methods:A total of 629 patients with Stage Ⅲ (A+B) or Ⅳ NSCLC,as well as 729 age-and gender-matched healthy controls were recruited.All the patients received platinum-based chemotherapy,and the therapeutic effects were evaluated.Three polymorphisms in the FGFR4 gene (rs351855G/A,rs145302848C/G,and rs147603016G/A) were genotyped,and the association between the 3 polymorphisms and the chemotherapy effect was analyzed using SPSS software,version 16.0.Results:The genotype frequencies of rs145302848C/G and rs147603016G/A were not significantly different between NSCLC patients and healthy controls on one hand,and between the responders and non-responders to the chemotherapy on the other hand.The distribution of AA genotype and A-allele of rs351855G/A was significantly lower in NSCLC patients than in healthy controls.Using patients with the GG genotype as a reference,the AA carrier had a significantly reduced risk for the development of NSCLC after normalizing to age,sex and smoking habits.In NSCLC patients,this genotype occurred more frequently in the responders to the chemotherapy than in non-responders.The chance of being a responder was significantly increased with the AA genotype as compared to G genotype.The AA genotype of rs351855G/A had a better prognosis compared with GA and GG genotype carriers:the over all survival of patients with the AA genotype of rs351855G/A was significantly longer than those with the GG+GA genotype (21.1 vs 16.5 months).Conclusion:The rs351855G/A polymorphisms of FGFR4 gene can be used to predict the occurrence,chemotherapy response and prognosis of NSCLC.

  9. 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

  10. Molecular predictors of response to tyrosine kinase inhibitors in patients with Non-Small-Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Murray Samuel

    2012-09-01

    Full Text Available Abstract Introduction Epidermal growth factor receptor (EGFR tyrosine kinase inhibitors (TKIs have become a treatment option in non-small-cell lung cancer (NSCLC patients. However, despite their use in this disease, a significant number of patients will eventually develop resistance and relapse. In this study, we aimed to characterize several molecular events involved in potential resistance mechanisms to anti-EGFR treatment and correlate our findings with clinical outcome. Material and methods The medical records of patients with NSCLC who received anti-EGFR TKIs in any line within the participating centers were reviewed and available paraffin embedded tissue was retrieved. Mutational analysis for EGFR, KRAS, BRAF and intron-exon 14 deletions of MET; FISH analysis for chromosomal gain or amplification for EGFR, MET and the deletion marker D7S486 were performed. Furthermore, the expression of EGFR and MET were analysed by immunohistochemistry. All results were correlated with treatment outcomes. Results Between 10/2001 and 12/2009 from an initial cohort of 72 treated patients, 59 cases (28 gefitinib/ 31 erlotinib were included in the analysis. The majority had adenocarcinoma histology (68%, and received treatment in the second line setting (56%. Disease control rate (DCR was 25.4% for all patients. EGFR and RAS mutational rates were 33% and 10% respectively, no other mutations were identified. High EGFR expressing tumors were found in 7 of 45 cases and pEGFR positivity (IHC was found in 56% of the cases; MET expression was found in 48% of tumors. EGFR gene amplification was found in 4 cases, two cases showed high polysomy; overall, 13% cases were FISH positive for EGFR. High polysomy of MET gene was detected in 1/43 cases tested. D7S486 locus deletion was detected in 15/37 (40% of cases. EGFR mutational status and gene gain were both associated with more favorable DCR. No other associations between examined biomarkers and DCR or survival were

  11. 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.

  12. Effect analysis of chemoradiotherapy after operation in patients with stage栿A non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    Sheng Chen; Yu-Ling Cheng; Shi-Ting Li; Yao-Jun Ni; Biao Gu

    2012-01-01

    Objective: To investigate the effect of chemoradiotherapy after surgery onⅢA stage non-small cell lung cancer (NSCLC). Methods: A total of 156 NSCLC patients undergoing total pneumonectomy or pulmonary lobectomy were included in this study. The chemotherapy group (n=75) received the protocol of cisplatin (DDP)+gemcitabine (GEM)/docetaxel (DOC)/vinorelbine (NVB);the radiotherapy +chemotherapy group (n=81) received sequential chemoradiotherapy. The response rate, local control rate in 1 to 2 years, overall survival (OS), progression-free survival (PFS) and adverse reactions were evaluated. Results: The overall response rate was obviously higher in radiotherapy+chemotherapy group (79.4%) than in chemotherapy group (56.8%) (P<0.01). The 1 year local control rates for chemotherapy group and radiotherapy+chemotherapy group were (69.1±7.9)%and (77.8±8.2)%respectively and the difference reached statistical significance (P<0.001). The 2 year local control rates were (42.1±6.1)%and (61.5±6.9)%respectively (P<0.001). The difference in median follow-up time between the two groups did not reach statistical meaning (P<0.05), while the median PFS of two groups were 10.8 months and 16.9 months respectively (P<0.001). 1-year and 3-year survival rates were obviously higher in radiotherapy+ chemotherapy group than in chemotherapy group, and the difference reached statistical significance (P<0.05 or P<0.01). The adverse reactions manifested as hematological toxicity and digestive tract reaction in the two groups. In the radiotherapy+chemotherapy group, incidences of radiation-induced esophagus injury and lung injury were 24.7%and 34.6%respectively, all occurring within 2 to 6 weeks after the start of radiation and both below grade 2. Conclusions:Chemoradiotherapy after surgery can improve local control rate and reduce or prevent distant metastasis, but there are still many controversies. In clinical work, we should carefully evaluate each patient’s age, lung function, basic

  13. Changes of activated circulating endothelial cells and survivin in patients with non-small cell lung cancer after antiangiogenesis therapy

    Institute of Scientific and Technical Information of China (English)

    WANG Jing; HUANG Chun; WEI Xi-yin; QI Da-liang; GONG Li-qun; MU Hai-yu; YAO Qiang; LI Kai

    2008-01-01

    Background Although antiangiogenesis therapy plays an important role in anti-neoplastic treatment with its recognized efficacy and slight adverse effect,there is no prospective clinical trial to define ideal markers for predicting efficacy of antiangiogenic therapy.This study was undertaken to investigate the changes of activated circulating endothelial cells (aCECs) and survMn after anti-angiogenesis therapy and their significance in predicting the efficacy of the therapy.Methods Patients of non-small cell lung cancer (NSCLC) treated with chemotherapy with or without Endostar were observed.The amount of activated CECs was detected by flow cytometry,and the expression of survivin mRNA was determined by real-time polymerase chain reaction (PCR).Results After treatment,the amount of activated CECs decreased significantly in clinical benefit cases (P=-0.021 in chemotherapy alone,P=0.001 in chemotherapy plus Endostar),increased in disease progressive cases (P=-0.015 in chemotherapy alone,but P=0.293 in chemotherapy with Endotatar).After therapy,the expression of survivin mRNA decreased in clinical benefit cases (P=0.001) and increased in disease progressive cases (P=0.018).A positive correlation was found between activated CECs and survivin in the chemotherapy group pre- and post-therapy (P=0.001 and 0.021,respectively),but only in the chemotherapy with Endostar group pre-therapy (P=0.030) rather than post-therapy.A positive correlation was found between the decreased activated CECs after therapy and time to progression (TTP) (r=0.322,P=0.012);a negative correlation was found between the amount of survivin mRNA in serum post-therapy and TTP(r= -0.291,P=0.048).Conclusions Activated CECs and survMn may be ideal markers forecasting efficacy and prognosis of NSCLC.The former can reflect more sensitively antiangiogenic efficacy and the latter is more sensitive to shrinkage or swelling of tumors.Their combination can evaluate more accurately the efficacy of antiangiogenic

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

    DEFF Research Database (Denmark)

    Scagliotti, Giorgio V; Felip, Enriqueta; Besse, Benjamin;

    2013-01-01

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

  15. Survival of patients with non-small cell lung cancer without treatment: a systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Wao Hesborn

    2013-02-01

    Full Text Available Abstract Background Lung cancer is considered a terminal illness with a five-year survival rate of about 16%. Informed decision-making related to the management of a disease requires accurate prognosis of the disease with or without treatment. Despite the significance of disease prognosis in clinical decision-making, systematic assessment of prognosis in patients with lung cancer without treatment has not been performed. We conducted a systematic review and meta-analysis of the natural history of patients with confirmed diagnosis of lung cancer without active treatment, to provide evidence-based recommendations for practitioners on management decisions related to the disease. Specifically, we estimated overall survival when no anticancer therapy is provided. Methods Relevant studies were identified by search of electronic databases and abstract proceedings, review of bibliographies of included articles, and contacting experts in the field. All prospective or retrospective studies assessing prognosis of lung cancer patients without treatment were eligible for inclusion. Data on mortality was extracted from all included studies. Pooled proportion of mortality was calculated as a back-transform of the weighted mean of the transformed proportions using the random-effects model. To perform meta-analysis of median survival, published methods were used to pool the estimates as mean and standard error under the random-effects model. Methodological quality of the studies was examined. Results Seven cohort studies (4,418 patients and 15 randomized controlled trials (1,031 patients were included in the meta-analysis. All studies assessed mortality without treatment in patients with non-small cell lung cancer (NSCLC. The pooled proportion of mortality without treatment in cohort studies was 0.97 (95% CI: 0.96 to 0.99 and 0.96 in randomized controlled trials (95% CI: 0.94 to 0.98 over median study periods of eight and three years, respectively. When data

  16. Gefitinib versus docetaxel in previously treated non-small-cell lung cancer (INTEREST): a randomised phase III trial

    DEFF Research Database (Denmark)

    Kim, E.S.; Hirsh, V.; Mok, T.;

    2008-01-01

    BACKGROUND: Two phase II trials in patients with previously-treated advanced non-small-cell lung cancer suggested that gefitinib was efficacious and less toxic than was chemotherapy. We compared gefitinib with docetaxel in patients with locally advanced or metastatic non-small-cell lung cancer wh...

  17. Older patients with inoperable non-small cell lung cancer. Long-term survival after concurrent chemoradiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Semrau, Sabine; Fietkau, Rainer [Friedrich-Alexander-University Erlangen-Nuernberg, Department of Radiation Oncology, Erlangen (Germany); Zettl, Heike [Rostock Cancer Registry University of Rostock, Rostock (Germany); Hildebrandt, Guido [University of Rostock, Department of Radiation Therapy, Rostock (Germany); Klautke, Gunther [Klinikum Chemnitz, Department of Radiation Therapy, Chemnitz (Germany)

    2014-12-15

    Considering the various comorbidities associated with aging, the feasibility and usefulness of concurrent chemoradiotherapy (CRT) in older patients with inoperable non-small cell lung cancer (NSCLC) is a controversial issue. Here, we compared the feasibility of CRT and the effects of various comorbidities on the prognosis of a minimally selected population of inoperable NSCLC patients aged 60-77 years. The study comprised 161 patients with inoperable NSCLC who received CRT with a target radiation dose greater than 60 Gy and platinum-based chemotherapy from 1998 to 2007. The total population included 69 patients aged 60-69 years and 53 aged 70-77 years. These two age cohorts were included in the study with a follow-up of a median 14.5 months. The two groups showed no differences in long-term survival, as reflected by the 5-year survival rates of 13.0 ± 4.1 % (60- to 69-year-olds) and 14.4 ± 4.9 % (70- to 77-year-olds). During the treatment phase, the groups were comparable in terms of toxicity and the feasibility of chemotherapy. Compared to patients in their 60s, the septuagenarians had more pulmonary comorbidities (p = 0.02), diabetes mellitus (p = 0.04), cardiac comorbidities (p = 0.08), and previous cancer disease (p = 0.08) that exerted a negative effect on survival. In patients without comorbidities, there were no differences between the age groups. Age is not a contraindication for concurrent CRT per se, because elderly patients do not have a worse long-term prognosis than younger seniors. However, ''elderly patients'' (≥ 70-77 years) have more concomitant diseases associated with shorter survival than ''moderately aged patients'' (≥ 60-69 years). (orig.) [German] Hinsichtlich der verschiedenen altersbedingten Komorbiditaeten werden die Durchfuehrbarkeit und der Nutzen einer simultanen Chemoradiotherapie (''concurrent chemoradiotherapy'', CRT) bei alten Patienten mit einem inoperablen nicht

  18. Analysis of EML4-ALK Gene Fusion Mutation in Patients 
with Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Xuzhou WANG

    2015-02-01

    Full Text Available Background and objective Non-small cell lung cancer (NSCLC is the main type of lung cancer, and the related locus mutation detection research has become a hot direction of molecular targeted therapy, studying on gene mutation status of echinodem microtubule associated protein like 4-Anaplastic lymphoma kinase (EML4-ALK and epidermal growth factor receptor (EGFR, detecting the sensitivity of EML4-ALK gene fusion and gene mutation of EGFR. Methods EML4-ALK gene fusion in 85 cases of paraffin embedded tumor tissue and adjacent lung tissue was detected with the application of immunohistochemistry (IHC, Scorpions amplification refractory mutation system (Scorpions ARMS fluorescence quantitative PCR and fluorescence in situ hybridization (FISH technology, and EGFR gene in 18, 19, 20 and 21 exon mutation status was detected with the application of ARMS method. Results In 115 cases of NSCLC, IHC showed 32 cases with ALK (D5F3 expression, the expression rate was 27.8%; ARMS showed 27 cases with EML4-ALK fusion gene mutation, the mutation detection rate was 23.5%; 53 cases were detected with EGFR mutation, the mutation rate was 46%. While FISH showed 23 cases with EML4-ALK fusion gene mutation, the detection rate was 20%, slightly lower than the ARMS detection results, suggesting that ARMS more sensitive. Conclusion The application of IHC, ARMS fluorescence quantitative PCR and FISH technology can make a rapid and accurate evaluation of EML4-ALK gene fusion.

  19. RH-ENDOSTATIN PLUS GEMCITABINE/NAVELBINE AND CISPLATIN AS FIRST-LINE TREATMENT PROTOCOL FOR NON-SMALL CELL LUNG CANCER PATIENTS:A SINGLE CENTRE STUDY

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    Objective To assess the efficacy of Rh-endostatin plus the combination of gemcitabine/navelbine and cisplatin in patients with non-small cell lung cancer (NSCLC).Methods NSCLC patients,not receiving chemotherapy,were divided into two groups.Then they were given the combination of gemcitabine/navelbine and cisplatin with or without Rh-endostatin at 2-week intervals for 4 treatment cycles.Results Forty patients were enrolled and all of them were assessable for response and toxicity.None had complete response ...

  20. Comparison of therapeutic effects between EGFR-TKI in first-line and second-line therapy in non-small cell lung cancer (NSCLC) patients

    OpenAIRE

    CHEN, LIANG-AN

    2011-01-01

    Platinum-based chemotherapy is still the standard first-line treatment for patients with advanced non-small cell lung cancer(NSCLC).Molecular targeted agents provide a new option for NSCLC patients.Clinical trial had shown that survival rate with epidermal growth factor receptor tyrosine kinase inhibitor(EGFR-TKI) treatment was not inferior compared with platinum-based chemotherapy in second line NSCLC therapy.However,for the patients with EGFR gene mutation,a better outcome has been achieved...

  1. Therapeutic vaccines in non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Socola F

    2013-09-01

    Full Text Available Francisco Socola,1 Naomi Scherfenberg,2 Luis E Raez3 1Division of Hematology/Oncology, Sylvester Comprehensive Cancer Center, University of Miami Leonard M Miller School of Medicine, Miami, Florida, USA; 2University of Miami Leonard M Miller School of Medicine, Miami, Florida, USA; 3Thoracic Oncology Program, Memorial Cancer Institute, Memorial Health Care System, Pembroke Pines, Florida, USA Abstract: 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

  2. Radiobiological modeling analysis of the optimal fraction scheme in patients with peripheral non-small cell lung cancer undergoing stereotactic body radiotherapy

    OpenAIRE

    Bao-Tian Huang; Jia-Yang Lu; Pei-Xian Lin; Jian-Zhou Chen; De-Rui Li; Chuang-Zhen Chen

    2015-01-01

    This study aimed to determine the optimal fraction scheme (FS) in patients with small peripheral non-small cell lung cancer (NSCLC) undergoing stereotactic body radiotherapy (SBRT) with the 4 × 12 Gy scheme as the reference. CT simulation data for sixteen patients diagnosed with primary NSCLC or metastatic tumor with a single peripheral lesion ≤3 cm were used in this study. Volumetric modulated arc therapy (VMAT) plans were designed based on ten different FS of 1 × 25 Gy, 1 × 30 Gy, 1 × 34 Gy...

  3. Chronic myelomonocytic leukemia blast crisis in a patient with advanced non-small cell lung cancer treated with EGFR tyrosine kinase inhibitors.

    Science.gov (United States)

    Ogata, Hiroaki; Okamoto, Isamu; Yoshimoto, Goichi; Obara, Teppei; Ijichi, Kayo; Iwama, Eiji; Harada, Taishi; Akashi, Koichi; Nakanishi, Yoichi

    2017-03-01

    A 59-year-old woman with epidermal growth factor receptor gene (EGFR) mutation-positive advanced lung adenocarcinoma was treated with afatinib after a diagnosis of chronic myelomonocytic leukemia (CMML). Twenty-one weeks later, she developed agranulocytosis, and CMML subsequently progressed to blast crisis. After complete remission of CMML, gefitinib was initiated; however, agranulocytosis recurred. This is the first reported case of both EGFR mutation-positive advanced non-small cell lung cancer with CMML, and of CMML blast crisis. Physicians should be aware of such risks and monitor EGFR-TKI-treated patients with myeloid neoplasms accordingly.

  4. Photodynamic therapy for the treatment of non-small cell lung cancer.

    Science.gov (United States)

    Simone, Charles B; Friedberg, Joseph S; Glatstein, Eli; Stevenson, James P; Sterman, Daniel H; Hahn, Stephen M; Cengel, Keith A

    2012-02-01

    Photodynamic therapy is increasingly being utilized to treat thoracic malignancies. For patients with early-stage non-small cell lung cancer, photodynamic therapy is primarily employed as an endobronchial therapy to definitely treat endobronchial, roentgenographically occult, or synchronous primary carcinomas. As definitive monotherapy, photodynamic therapy is most effective in treating bronchoscopically visible lung cancers ≤1 cm with no extracartilaginous invasion. For patients with advanced-stage non-small cell lung cancer, photodynamic therapy can be used to palliate obstructing endobronchial lesions, as a component of definitive multi-modality therapy, or to increase operability or reduce the extent of operation required. A review of the available medical literature detailing all published studies utilizing photodynamic therapy to treat at least 10 patients with non-small cell lung cancer is performed, and treatment recommendations and summaries for photodynamic therapy applications are described.

  5. Bilateral Choroidal Metastasis from Non-Small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Tariq Namad

    2014-01-01

    Full Text Available Breast and lung cancers are the most common primary neoplasms to manifest with choroidal metastases. The incidence of choroidal metastases from metastatic lung cancer was reported to be 2–6.7%. We report a case of bilateral choroidal metastasis from non-small cell lung cancer. A 59-year-old Caucasian female patient, never a smoker, was diagnosed with stage IV lung adenocarcinoma metastatic to the pleura, bones, and the brain. Her initial scan of the chest showed innumerable soft tissue nodules and mediastinal adenopathy compatible with metastatic disease. Her initial brain MRI showed numerous small enhancing lesions consistent with extensive disease. Unfortunately, during her follow-up visits, she presented with bulge on her left eye. Simultaneously, her follow-up chest scan showed increase in the size of the lung nodules. She continued to have a reasonable performance status at that time, except for mild increase in her dyspnea. The choroidal metastases require a multidisciplinary care and should be among the differential patients with malignancy who present with ocular symptoms.

  6. Combination of afatinib with cetuximab in patients with EGFR-mutant non-small-cell lung cancer resistant to EGFR inhibitors

    Directory of Open Access Journals (Sweden)

    Ribeiro Gomes J

    2015-05-01

    Full Text Available Jéssica Ribeiro Gomes, Marcelo Rocha S Cruz Antonio Ermirio de Moraes Oncology Center, São Paulo-Brazil Abstract: Tyrosine kinase inhibitors (TKIs targeting the epidermal growth factor receptor (EGFR have shown effectiveness for advanced non-small-cell lung cancer (NSCLC with activating mutations in the EGFR gene. However, resistance to the EGFR TKIs develops mostly secondary to T790M mutation in exon 20. The use of afatinib associated with cetuximab represents a new possibility of therapy following progression on gefitinib or erlotinib. We present two patients who acquired resistance to first-generation TKI and who underwent combination treatment with afatinib plus cetuximab as third-line therapy. Both patients presented partial response, and the time duration of disease control was 8 months and 10 months. The combined use of afatinibplus cetuximab emerges as a new possibility for the treatment of patients with advanced NSCLC harboring mutated EGFR after progression on first-generation EGFR TKIs with consequently acquired resistance to TKIs. Further studies are necessary to consolidate the data. Keywords: lung cancer, non-small-cell lung cancer, EGFR, afatinib, cetuximab, case report 

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

    Science.gov (United States)

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

    2012-02-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  9. Afatinib treatment in advanced non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Hurwitz JL

    2011-10-01

    Full Text Available Jane L Hurwitz, Paula Scullin, Lynn CampbellDepartment of Medical Oncology, Northern Ireland Cancer Centre, Belfast, UKAbstract: Despite some recent advances in the management of advanced non-small cell lung cancer (NSCLC, prognosis for these patients remains poor. Small molecule epidermal growth factor receptor (EGFR tyrosine kinase inhibitors (TKIs have however provided a new therapeutic option in this disease setting and EGFR mutation testing is now routine practice for newly diagnosed NSCLC patients. A proportion of patients will not respond to first-generation EGFR-TKIs however, and those who do will ultimately develop resistance and disease relapse. Next-generation EGFR-TKIs which inhibit multiple members of the EGFR family are being developed in order to increase sensitivity and overcome resistance to existing agents. Afatinib (BIBW 2992 is an oral, irreversible inhibitor of EGFR and HER2 tyrosine kinases and is the most advanced of these agents in clinical development. Pre-clinical and early-phase clinical trials have demonstrated a favorable safety profile as a single agent and in combination with other anti-cancer agents, and provide evidence of clinical activity in advanced NSCLC. The LUX-Lung trials suggest that for selected patients, afatinib offers symptomatic improvement and prolonged progression-free survival, although this has not yet translated into improved overall survival. This article aims to review the use of EGFR-TKIs in the management of advanced NSCLC and the mechanisms underlying resistance to these agents. We will discuss the current pre-clinical and clinical data regarding afatinib, its potential to overcome resistance to first-generation TKIs, and its emerging role in advanced NSCLC treatment.Keywords: EGFR, tyrosine kinase inhibitor, mutation, LUX-lung

  10. The association of race with timeliness of care and survival among Veterans Affairs health care system patients with late-stage non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Zullig LL

    2013-07-01

    Full Text Available Leah L Zullig,1,2 William R Carpenter,2 Dawn T Provenzale,1,3 Morris Weinberger,1,2 Bryce B Reeve,2 Christina D Williams,1 George L Jackson1,4 1Center of Excellence for Health Services Research in Primary Care, Durham Veterans Affairs Medical Center, Durham, NC, USA; 2Department of Health Policy and Management, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; 3Division of Gastroenterology, Duke University, Durham, NC, USA; 4Division of General Internal Medicine, Duke University, Durham, NC, USA Background: Non-small cell lung cancer is the leading cause of cancer-related mortality in the United States. Patients with late-stage disease (stage 3/4 have five-year survival rates of 2%–15%. Care quality may be measured as time to receiving recommended care and, ultimately, survival. This study examined the association between race and receipt of timely non-small cell lung cancer care and survival among Veterans Affairs health care system patients. Methods: Data were from the External Peer Review Program, a nationwide Veterans Affairs quality-monitoring program. We included Caucasian or African American patients with pathologically confirmed late-stage non-small cell lung cancer in 2006 and 2007. We examined three quality measures: time from diagnosis to (1 treatment initiation, (2 palliative care or hospice referral, and (3 death. Unadjusted analyses used log-rank and Wilcoxon tests. Adjusted analyses used Cox proportional hazard models. Results: After controlling for patient and disease characteristics using Cox regression, there were no racial differences in time to initiation of treatment (72 days for African American versus 65 days for Caucasian patients, hazard ratio 1.04, P = 0.80 or palliative care or hospice referral (129 days versus 116 days, hazard ratio 1.10, P = 0.34. However, the adjusted model found longer survival for African American patients than for Caucasian patients (133 days versus 117 days, hazard ratio 0

  11. Epidemiology, diagnostics and long-term overall survival of patients with non-small cell lung cancer in the Brest Region

    Directory of Open Access Journals (Sweden)

    Siarhei Panko

    2013-10-01

    Full Text Available Introduction: Lung cancer has been the most common cancer in the world and in Belarus. Aim of the research: To evaluate the epidemiology of non-small cell lung cancer and improvements in diagnostics and treatment for the past 11 years in the Brest Region of Belarus. Material and methods: We conducted a retrospective analysis of statistical data (incidence rate, mortality in the regional cancer registry of the Brest oncological clinic since 2000 and assessed survival for 652 adult patients with different stages of non-small-cell lung cancer (NSCLC who underwent surgery in the Thoracic Surgery Department of Brest Regional Hospital in 2002–2010. Results: Lung cancer continues to have the highest incidence rate among malignant neoplasms and because of its high fatality rate is a leading cause of cancer-related mortality in the Brest Region and Belarus. The chest radiography screening programme of lung cancer since 2000 and the implementation of computed tomography (CT- and ultrasonography (USG-guided needle biopsy and VATS LigaSure pulmonary wedge resection for the evaluation of solitary pulmonary nodules has allowed an increase of diagnostic rates and improved the histological confirmation rate of lung cancer in the Brest Region. Multivariate analysis indicates that male sex, age older than seventy and incomplete surgical resection are independent predictors of poor prognosis for postoperative long-term overall survival. Conclusions : Today it is necessary to carry out low-dose spiral computerized diagnostics in the Brest Region, which would detect a greater proportion of asymptomatic lung cancers. Surgical resection remains the only consistent and successful option of a cure for patients with lung cancer.

  12. Two Cases of Non-Small Cell Lung Cancer Treated with Intravenous Cultivated Wild Ginseng Pharmacopuncture

    Directory of Open Access Journals (Sweden)

    Sun-Hwi Bang

    2008-06-01

    Full Text Available Objectives : To investigate the therapeutic effects of intravenous cultivated wild ginseng(Panax ginseng C.A. Meyer pharmacopuncture(CWGP in treating patients with non-small cell lung cancer(NSCLC. Design : Prospective case series. Setting : This study was conducted at the East-West Cancer Center of Dunsan Oriental Hospital, Daejeon University. Patients : Two non-small cell lung cancer patients. Intervention : Two non-small cell lung cancer patients were injected CWGP(20mL/day mixed with 0.9% normal saline(100mL intravenously. Each patient received a total of 16 and 9 cycles, respectively. One cycle is composed of 14 days. Outcome Measures : The effect of intravenous CWGP was measured by scanning with computed tomography(CT after every 2 cycle and Positron emission tomography- computed tomography(PET/CT after every 6 cycles. Response and progression was evaluated using the Response Evaluation Criteria in Solid Tumors(RECIST Committee classification of complete response(CR, partial response(PR, progressive disease(PD and stable disease(SD. Results : They were treated with intravenous CWGP for 8 and 5 months respectively. time later, each tumor remains stable disease(SD Conclusion : These cases may give us a possibility that intravenous CWGP offers potential benefits for non-small cell lung cancer patients.

  13. Carcinomatous meningitis in non-small cell lung cancer: Palliation with intrathecal treatment

    Directory of Open Access Journals (Sweden)

    D. Santhosh Kumar

    2014-01-01

    Full Text Available Carcinomatous meningitis or meningeal carcinomatosis is seen in up to 5% of patients of metastatic non-small cell lung cancer. However, isolated carcinomatous meningitis without brain parenchymal metastasis is less common. Patients with carcinomatous meningitis have limited treatment options. However, intrathecal therapy if used optimally along with targeted therapy when indicated result in good palliation with improvement in survival.

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

    DEFF Research Database (Denmark)

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

    2010-01-01

    AIM OF THE STUDY: To investigate whether patients with severe comorbidity receiving platinum-based chemotherapy for advanced non-small-cell lung cancer (NSCLC) have a shorter overall survival, experience more toxicity or more deterioration of health-related quality of life (HRQoL) than other....... Comorbidity was assessed from hospital medical records using the Cumulative Illness Rating Scale for Geriatrics (CIRS-G). Toxicity was graded using the CTCAE v3.0 and the patients reported HRQoL on the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30...... neutropenic fevers (12% versus 5%; p=.012) and deaths from neutropenic infections (3% versus 0%; p=.027). They had more thrombocytopenia (46% versus 36%; p=.03), but not more thrombocytopenic bleedings (3% versus 4%; p=.65). In general, the patients with severe comorbidity reported poorer HRQoL...

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

    Institute of Scientific and Technical Information of China (English)

    张志坤; 林东; 王恩华; 关奕

    2002-01-01

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

  16. Exosomal proteins as prognostic biomarkers in non-small cell lung cancer

    DEFF Research Database (Denmark)

    Paulsen, Birgitte Sandfeld; Aggerholm-Pedersen, N; Bæk, R

    2016-01-01

    BACKGROUND: Use of exosomes as biomarkers in non-small cell lung cancer (NSCLC) is an intriguing approach in the liquid-biopsy era. Exosomes are nano-sized vesicles with membrane-bound proteins that reflect their originating cell. Prognostic biomarkers are needed to improve patient selection...

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

    DEFF Research Database (Denmark)

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

    2014-01-01

    BACKGROUND: Antibodies targeting epidermal growth factor receptor (EGFR), such as cetuximab, may potentially improve outcome in non-small cell lung cancer (NSCLC) patients with high EGFR expression. The EGFR expression may be heterogeneously distributed within tumors, and small biopsies may thus...

  18. Detection of EGFR mutations in plasma and biopsies from non-small cell lung cancer patients by allele-specific PCR assays

    DEFF Research Database (Denmark)

    Weber, Britta; Meldgaard, Peter; Hager, Henrik

    2014-01-01

    BACKGROUND: Lung cancer patients with mutations in the epidermal growth factor receptor (EGFR) are primary candidates for EGFR-targeted therapy. Reliable analyses of such mutations have previously been possible only in tumour tissue. Here, we demonstrate that mutations can be detected in plasma...... samples with allele-specific PCR assays. METHODS: Pairs of the diagnostic biopsy and plasma obtained just prior to start of erlotinib treatment were collected from 199 patients with adenocarcinoma of non-small-cell lung cancer. DNA from both sample types was isolated and examined for the presence...... identified in 24/199 (12%) plasma samples and 28/196 (14%) biopsy samples, and 17/196 (9%) matched pairs contained the same mutation. Six EGFR mutations were present only in plasma samples but not in the biopsy samples. The overall concordance of the EGFR gene mutations detected in plasma and biopsy tissue...

  19. Usefulness of circulating free DNA for monitoring epidermal growth factor receptor mutations in advanced non-small cell lung cancer patients: a case report

    Science.gov (United States)

    Gonzalez-Cao, Maria; Ramirez, Santiago Viteri; Ariza, Nuria Jordana; Balada, Ariadna; Garzón, Mónica; Teixidó, Cristina; Karachaliou, Niki; Morales-Espinosa, Daniela; Molina-Vila, Miguel Ángel; Rosell, Rafael

    2016-01-01

    Genomic analysis of circulating tumor DNA (ctDNA) released from cancer cells into the bloodstream has been proposed as a useful method to capture dynamic changes during the course of the disease. In particular, the ability to monitor epidermal growth factor receptor (EGFR) mutation status in cell-free circulating DNA (cfDNA) isolated from advanced non-small cell lung cancer (NSCLC) patients EGFR can help to the correct management of the disease and overcome the challenges associated with tumor heterogeneity and insufficient biopsied material to perform key molecular diagnosis. Here, we report a case of long term monitorization of EGFR mutation status in cfDNA from peripheral blood in an NSCLC patient in, with excellent correlation with clinical evolution. PMID:27826535

  20. 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

  1. Genetic polymorphism in the epidermal growth factor receptor gene predicts outcome in advanced non-small cell lung cancer patients treated with erlotinib

    DEFF Research Database (Denmark)

    Winther-Larsen, Anne; Nissen, Peter H.; Jakobsen, Kristine Raaby;

    2015-01-01

    OBJECTIVES: Epidermal growth factor receptor (EGFR) mutations are important predictors of treatment response to tyrosine kinase inhibitors (TKIs) in patients with non-small cell lung cancer (NSCLC). However, some patients with mutations do not respond and some patients without mutations show...... with advanced NSCLC. Genotypes were correlated with clinical characteristics, toxicity and outcome. A multivariate analysis was performed using Cox proportional hazards model while adjusting for clinically relevant factors including EGFR mutation status. RESULTS: 181946CT or TT genotypes showed an association...... response. We therefore need additional biomarkers to improve the selection of these patients for treatment. A promising candidate could be germline genetic variations in the EGFR gene that can alter protein expression or function and may influence the response to TKIs. Thus, the aim of this study...

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

    DEFF Research Database (Denmark)

    Reck, Martin; Kaiser, Rolf; Mellemgaard, Anders

    2014-01-01

    a median follow-up of 31·7 months (IQR 27·8-36·1), overall survival was significantly improved for patients with adenocarcinoma histology who progressed within 9 months after start of first-line treatment in the docetaxel plus nintedanib group (206 patients) compared with those in the docetaxel plus......BACKGROUND: The phase 3 LUME-Lung 1 study assessed the efficacy and safety of docetaxel plus nintedanib as second-line therapy for non-small-cell lung cancer (NSCLC). METHODS: Patients from 211 centres in 27 countries with stage IIIB/IV recurrent NSCLC progressing after first-line chemotherapy...... 200 mg orally twice daily or matching placebo on days 2-21, every 3 weeks until unacceptable adverse events or disease progression. Investigators and patients were masked to assignment. The primary endpoint was progression-free survival (PFS) by independent central review, analysed by intention...

  3. Comparison of therapeutic effects between EGFR-TKI in first-line and second-line therapy in non-small cell lung cancer (NSCLC patients

    Directory of Open Access Journals (Sweden)

    Liang-an CHEN

    2011-08-01

    Full Text Available Platinum-based chemotherapy is still the standard first-line treatment for patients with advanced non-small cell lung cancer(NSCLC.Molecular targeted agents provide a new option for NSCLC patients.Clinical trial had shown that survival rate with epidermal growth factor receptor tyrosine kinase inhibitor(EGFR-TKI treatment was not inferior compared with platinum-based chemotherapy in second line NSCLC therapy.However,for the patients with EGFR gene mutation,a better outcome has been achieved with the use of EGFR-TKI as first-line treatment.Currently,controversy still exists in the use of EGFR-TKI for treatment of NSCLC as first-line or second-line therapy.In present paper,the optimal time to use EGFR-TKI for treatment of NSCLC has been discussed based on the analysis of a series of clinical trials.

  4. Effect of OK-432 combined UFT in patients with stage III non-small cell lung cancer treated by radiotherapy. A randomized prospective study

    Energy Technology Data Exchange (ETDEWEB)

    Jingu, Kenichi [Fukuoka Univ. (Japan). School of Medicine; Ohmagari, Junichi; Masuda, Kouji [and others

    1997-06-01

    Distant metastasis and local recurrence are the causes of poor treatment results of unresectable non-small cell lung cancer patients. Inhibition of repair from radiation damage in tumors and distant metastases may improve the survival rate. Some authors of this paper previously reported that tegafur combined with OK-432 significantly improved the survival rate in these patients. We conducted a prospective randomized trial using UFT (mixed preparation of tegafur and uracil) with or without OK-432, after radiotherapy in these patients, to assess the effect of OK-432 on survival rate, the duration of continued response by previous treatment, and the effect on leucopenia due to UFT. However, unexpected results were obtained. OK-432 did not prolong response duration, did not improve the survival rate, and did not inhibit the leucopenia due to UFT. (author)

  5. Post-study therapy as a source of confounding in survival analysis of first-line studies in patients with advanced non-small-cell lung cancer.

    Science.gov (United States)

    Zietemann, Vera D; Schuster, Tibor; Duell, Thomas Hg

    2011-06-01

    Clinical trials exploring the long-term effects of first-line therapy in patients with advanced non-small-cell lung cancer generally disregard subsequent treatment although most patients receive second and third-line therapies. The choice of further therapy depends on critical intermediate events such as disease progression and it is usually left at the physician's discretion. Time-dependent confounding may then arise with standard survival analyses producing biased effect estimates, even in randomized trials. Herein we describe the concept of time-dependent confounding in detail and discuss whether the response to first-line treatment may be a potential time-dependent confounding factor for survival in the context of subsequent therapy. A prospective observational study of 406 patients with advanced non-small-cell lung cancer served as an example base. There is evidence that time-dependent confounding may occur in multivariate survival analysis after first-line therapy when disregarding subsequent treatment. In the light of this important but underestimated aspect some of the large and meaningful recent clinical first-line lung cancer studies are discussed, focussing on subsequent treatment and its potential impact on the survival of the study patients. No recently performed lung cancer trial applied adequate statistical analyses despite the frequent use of subsequent therapies. In conclusion, effect estimates from standard survival analysis may be biased even in randomized controlled trials because of time-dependent confounding. To adequately assess treatment effects on long-term outcomes appropriate statistical analyses need to take subsequent treatment into account.

  6. Validation of an Ion Torrent Sequencing Platform for the Detection of Gene Mutations in Biopsy Specimens from Patients with Non-Small-Cell Lung Cancer.

    Directory of Open Access Journals (Sweden)

    Shiro Fujita

    Full Text Available Treatment for patients with advanced non-small cell lung cancer (NSCLC is often determined by the presence of biomarkers that predict the response to agents targeting specific molecular pathways. Demands for multiplex analysis of the genes involved in the pathogenesis of NSCLC are increasing.We validated the Ion Torrent Personal Genome Machine (PGM system using the Ion AmpliSeq Cancer Hotspot Panel and compared the results with those obtained using the gold standard methods, conventional PCR and Sanger sequencing. The cycleave PCR method was used to verify the results.The Ion Torrent PGM resulted in a similar level of accuracy in identifying multiple genetic mutations in parallel, compared with conventional PCR and Sanger sequencing; however, the Ion Torrent PGM was superior to the other sequencing methods in terms of increased ease of use, even when taking into account the small amount of DNA that was obtained from formalin-fixed paraffin embedded (FFPE biopsy specimens.

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    BACKGROUND AND PURPOSE: This study investigates the ability of pre-treatment factors and response markers extracted from standard cone-beam computed tomography (CBCT) images to predict the lung density changes induced by radiotherapy for non-small cell lung cancer (NSCLC) patients. METHODS...... AND MATERIALS: Density changes in follow-up computed tomography scans were evaluated for 135 NSCLC patients treated with radiotherapy. Early response markers were obtained by analysing changes in lung density in CBCT images acquired during the treatment course. The ability of pre-treatment factors and CBCT...... markers to predict lung density changes induced by radiotherapy was investigated. RESULTS: Age and CBCT markers extracted at 10th, 20th, and 30th treatment fraction significantly predicted lung density changes in a multivariable analysis, and a set of response models based on these parameters were...

  8. Prognostic significance of urokinase plasminogen activator receptor and its cleaved forms in blood from patients with non-small cell lung cancer

    DEFF Research Database (Denmark)

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

    2009-01-01

    in lung tumour extracts. Here we analyse uPAR forms in blood from patients with non-small cell lung cancer (NSCLC). Preoperatively sampled plasma/serum from 32 patients with NSCLC was analysed. Three time-resolved fluoroimmunoassays (TR-FIAs) measuring intact uPAR(I-III) (TR-FIA 1), uPAR(I-III) + u...... survival. Adjusted for histological subtype high plasma uPAR(I-III) and uPAR(I) levels as well as serum uPAR(I) levels were significantly associated with shorter OS (hazards ratios = 4.3, 2.8 and 3.8 respectively). High blood levels of intact uPAR and its cleaved forms are associated with poor prognosis...

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

    Directory of Open Access Journals (Sweden)

    Lin Zhu

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

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

    DEFF Research Database (Denmark)

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

    2008-01-01

    Purpose Cisplatin plus gemcitabine is a standard regimen for first-line treatment of advanced non-small-cell lung cancer (NSCLC). Phase II studies of pemetrexed plus platinum compounds have also shown activity in this setting. Patients and Methods This noninferiority, phase III, randomized study...... compared the overall survival between treatment arms using a fixed margin method (hazard ratio [HR] cisplatin 75 mg/m(2) on day 1...... and gemcitabine 1,250 mg/m(2) on days 1 and 8 (n = 863) or cisplatin 75 mg/m(2) and pemetrexed 500 mg/m(2) on day 1 (n = 862) every 3 weeks for up to six cycles. Results Overall survival for cisplatin/pemetrexed was noninferior to cisplatin/ gemcitabine (median survival, 10.3 v 10.3 months, respectively; HR = 0...

  11. Long-term Survival of A Patient with Advanced Non-small Cell Lung Cancer 
on Bevacizumab Therapy: Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Wei WU

    2013-06-01

    Full Text Available We report an advanced stage Chinese female lung adenocarcinoma patient who was negative for epidermal growth factor receptor (EGFR, V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS gene mutations, also negative for chinodem microtubule-associated protein-like 4/anaplastic lymphoma kinase (EML4-ALK gene rearrangement and treated with bevacizumab (15 mg/kg in combination with 6 cycles of conventional doses of paclitaxel and carboplatin chemotherapy. She was then treated with maintenance bevacizumab for a total of 42 cycles, the total dose of bevacizumab is 44,730 mg. The progression-free survival was 39 months. Our findings suggest that maintenance bevacizumab for the treatment of non-small cell lung cancer (NSCLC is safe and its benefit for long-term survival overwhelms its side effects.

  12. Circulating Tumor DNA in Predicting Outcomes in Patients With Stage IV Head and Neck Cancer or Stage III-IV Non-small Cell Lung Cancer

    Science.gov (United States)

    2016-10-19

    Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma; Salivary Gland Squamous Cell Carcinoma; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IVA Salivary Gland Cancer; Stage IVA Squamous Cell Carcinoma of the Larynx; Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Oropharynx; Stage IVA Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVA Verrucous Carcinoma of the Larynx; Stage IVA Verrucous Carcinoma of the Oral Cavity; Stage IVB Salivary Gland Cancer; Stage IVB Squamous Cell Carcinoma of the Larynx; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Oropharynx; Stage IVB Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVB Verrucous Carcinoma of the Larynx; Stage IVB Verrucous Carcinoma of the Oral Cavity; Stage IVC Salivary Gland Cancer; Stage IVC Squamous Cell Carcinoma of the Larynx; Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVC Squamous Cell Carcinoma of the Oropharynx; Stage IVC Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVC Verrucous Carcinoma of the Larynx; Stage IVC Verrucous Carcinoma of the Oral Cavity; Tongue Cancer; Untreated Metastatic Squamous Neck Cancer With Occult Primary

  13. Detection of EMI4-ALK fusion gene in non-small cell lung cancer and its clinicopathologic correlation

    Institute of Scientific and Technical Information of China (English)

    钟山

    2013-01-01

    Objective To investigate the frequency of EML4-ALK fusion gene in non small-cell lung cancer NSCLC patients,and its correlation with clinicopathologic features.Methods Real-time PCR was used to detect

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

    NARCIS (Netherlands)

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

    2012-01-01

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

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

    NARCIS (Netherlands)

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

    2012-01-01

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

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

    NARCIS (Netherlands)

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

    2012-01-01

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

  17. [Analysis of the factors associated with abnormal coagulation and prognosis
 in patients with non-small cell lung cancer].

    Science.gov (United States)

    Li, Yanhua; Wei, Suju; Wang, Junyan; Hong, Lei; Cui, Lige; Wang, Cai

    2014-11-01

    背景与目的 凝血及纤溶系统激活在肺癌患者中较为常见,与肺癌侵袭、转移的高风险和预后差相关。非小细胞肺癌(non-small cell lung cancer, NSCLC)占肺癌的80%-85%,本研究旨在回顾性分析凝血功能指标对NSCLC的预后价值,为目前NSCLC患者高凝状态的预防及治疗提供参考。方法 回顾性分析2009年1月-2012年12月首次就诊于河北医科大学第四医院的604例经病理学证实的NSCLC患者的临床资料。资料内容包括患者治疗前凝血功能相关指标[血浆凝血酶原时间(prothrombin time, PT)、凝血酶原活动度(prothrombin time activity, PTA)、国际标准化比率(international normalized ratio, INR)、活化部分凝血活酶时间(activated partial thromboplastin time, APTT)、纤维蛋白原(fibrinogen, Fib)、D二聚体(D-dimer, D-D)、血小板计数(platelet count, PLT)]、性别、年龄、病理分型、TNM分期、淋巴结状态等。本研究选择了50例同期就诊于河北医科大学第四医院的非癌症患者作为对照组。采用SPSS 13.0统计软件进行分析。结果 NSCLC组与对照组之间所有的凝血功能指标(包括PT、PTA、INR、APTT、Fib、D-D、血小板计数)的血浆水平显示均有统计学差异[除了Fib(P=0.001,5)、Plt(P=0.004,5),其余指标(P<0.001)]。纤维蛋白原水平与NSCLC的组织学亚型之间相关,鳞癌比腺癌的Fib水平明显升高(P<0.001)。III期、IV期期比I期-II期患者的Fib、PLT水平升高(P<0.001, P=0.014),APTT缩短(P<0.001)。与N0患者相比,N1-N3患者的APTT,明显缩短(P<0.001),Fib、D-D水平升高(P<0.001, P=0.048)。对生存率的比较研究显示,PT、INR延长(P=0.032, P=0.001),Fib升高(P<0.001),PTA下降(P=0.005),在统计学上对总生存有明显的不利影响。多因素生存分析显示,在凝血功能指标中INR是唯

  18. Epidemiology, diagnostics and long-term overall survival of patients with non-small cell lung cancer in the Brest Region

    OpenAIRE

    2013-01-01

    Introduction: Lung cancer has been the most common cancer in the world and in Belarus. Aim of the research: To evaluate the epidemiology of non-small cell lung cancer and improvements in diagnostics and treatment for the past 11 years in the Brest Region of Belarus. Material and methods: We conducted a retrospective analysis of statistical data (incidence rate, mortality) in the regional cancer registry of the Brest oncological clinic since 2000 and assessed survival for 652 adul...

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

    Institute of Scientific and Technical Information of China (English)

    高洁

    2012-01-01

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

  20. Different impact of excision repair cross-complementation group 1 on survival in male and female patients with inoperable non-small-cell lung cancer treated with carboplatin and gemcitabine

    DEFF Research Database (Denmark)

    Holm, Bente; Mellemgaard, Anders; Skov, Torsten;

    2009-01-01

    PURPOSE: The excision repair cross-complementation group 1 (ERCC1) status was assessed in patients receiving carboplatin and gemcitabine for inoperable non-small-cell lung cancer (NSCLC). We analyzed the association between the ERCC1 status and the overall survival after the chemotherapy. PATIENTS...

  1. Progesterone and estrogen receptor expression and activity in human non-small cell lung cancer

    OpenAIRE

    2011-01-01

    Lung cancer is the most common cause of cancer mortality in male and female patients in the US. Although it is clear that tobacco smoking is a major cause of lung cancer, about half of all women with lung cancer worldwide are never-smokers. Despite a declining smoking population, the incidence of non-small cell lung cancer (NSCLC), the predominant form of lung cancer, has reached epidemic proportions particularly in women. Emerging data suggest that factors other than tobacco, namely endogeno...

  2. Safety and Efficacy of First-Line Bevacizumab Plus Chemotherapy in Elderly Patients with Advanced or Recurrent Nonsquamous Non-small Cell Lung Cancer Safety of Avastin in Lung trial (MO19390)

    NARCIS (Netherlands)

    Laskin, Janessa; Crino, Lucio; Felip, Enriqueta; Franke, Fabio; Gorbunova, Vera; Groen, Harry; Jiang, Guo-liang; Reck, Martin; Schneider, Claus-Peter

    2012-01-01

    Introduction: Safety of Avastin in Lung (MO19390) was an international, open-label, single-arm study, which assessed the safety and efficacy of first-line bevacizumab (Avastin (R)) in combination with standard chemotherapy in patients (n = 2212) with advanced or recurrent non-small cell lung cancer

  3. Multicenter Phase II Study of Whole-Body and Intracranial Activity With Ceritinib in Patients With ALK-Rearranged Non-Small-Cell Lung Cancer Previously Treated With Chemotherapy and Crizotinib : Results From ASCEND-2

    NARCIS (Netherlands)

    Crino, Lucio; Ahn, Myung-Ju; De Marinis, Filippo; Groen, Harry J. M.; Wakelee, Heather; Hida, Toyoaki; Mok, Tony; Spigel, David; Felip, Enriqueta; Nishio, Makoto; Scagliotti, Giorgio; Branle, Fabrice; Emeremni, Chetachi; Quadrigli, Massimiliano; Zhang, Jie; Shaw, Alice T.

    2016-01-01

    Purpose Phase I data (ASCEND-1) showed ceritinib efficacy in patients with ALK-rearranged non-small-cell lung cancer (NSCLC), regardless of brain metastases status and with or without prior therapy with an inhibitor of the ALK protein. Data are presented from a phase II trial (ASCEND-2) in which cer

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

    NARCIS (Netherlands)

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

    2015-01-01

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

  5. 根治性治疗后非小细胞肺癌的预防性脑照射%Prophylactic Cranial Irradiation for Preventing Brain Metastases in Patients Undergoing Radical Treatment for Non-Small Cell Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    李伟雄; 黄玉娟

    2008-01-01

    @@ 1 文献来源 Lester JF,Coles B,Macbeth FR.Prophylactic cranial irradiation for preventing brain metastases in patients undergoing radical treatment for non-small cell lung cancer[DB/CD].The Cochrane Library 2007,Issue 3.

  6. Carboplatin and paclitaxol (Taxol) as an induction regimen for patients with biopsy-proven stage IIIA N2 non-small cell lung cancer. an EORTC phase II study (EORTC 08958).

    NARCIS (Netherlands)

    O'Brien, ME; Splinter, T; Smit, E.F.; Biesma, B.; Krzakowski, M; Tjan-Heijnen, VC; Bochove, A Van; Stigt, J; Smid-Geirnaerdt, MJ; Debruyne, C.; Legrand, C; Giaccone, G.

    2003-01-01

    The aim of this study was to document the activity and toxicity of paclitaxel (Taxol)/carboplatin when used as induction chemotherapy in patients with stage IIIA N2 non-small cell lung cancer (NSCLC) prior to definitive local treatment within a large, ongoing comparative study (EORTC 08941). 52 elig

  7. Safety and efficacy of gefitinib treatment in elderly patients with non-small-cell lung cancer: Okayama Lung Cancer Study Group experience.

    Science.gov (United States)

    Hotta, Katsuyuki; Ueoka, Hiroshi; Kiura, Katsuyuki; Tabata, Masahiro; Ogino, Atsuko; Umemura, Shigeki; Harita, Shingo; Gemba, Kenichi; Yonei, Toshiro; Bessho, Akihiro; Maeda, Tadashi; Tanimoto, Mitsune

    2005-01-01

    We evaluated the safety and efficacy of gefitinib treatment in elderly patients with non-small-cell lung cancer (NSCLC). We retrospectively compared toxicity, response and survival outcomes for gefitinib in patients aged 75 years or older (elderly group) with the same outcomes in patients aged younger than 75 years. In total, 350 patients were eligible for this analysis, of whom 92 were in the elderly group and 258 in the non-elderly group. In the elderly group, adverse events were generally mild to moderate and grade 3-4 adverse events were observed in 8 (9%) patients. The objective response rate (17 vs. 21% for elderly vs. non-elderly, respectively) and median survival time (7.6 vs. 9.3 months) were also similar in the two groups. Multivariate analysis revealed elderly patients with lower Brinkman index tended to be more sensitive to gefitinib (odds ratio: 4.57, 95% confidence interval: 0.91-22.72, p = 0.0642). In this study, treatment with gefitinib appeared to be as safe and effective in elderly patients (aged 75 or older) with NSCLC as in non-elderly patients.

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

    DEFF Research Database (Denmark)

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

    2012-01-01

    AIM: To examine possible associations between socioeconomic position and surgical treatment of patients with early-stage non-small-cell lung cancer (NSCLC). METHODS: In a register-based clinical cohort study, patients with early-stage (stages I-IIIa) NSCLC were identified in the Danish Lung Cancer...... in a health care system with free, equal access to health services, disadvantaged groups are less likely to receive surgery for lung cancer....

  9. Relationship between serum carcinoembryonic antigen level and epidermal growth factor receptor mutations with the influence on the prognosis of non-small-cell lung cancer patients

    Directory of Open Access Journals (Sweden)

    Cai ZX

    2016-06-01

    Full Text Available Zuxun Cai Department of Thoracic Surgery, Henan Provincial Chest Hospital, Zhengzhou City, People’s Republic of China Objective: To investigate the relationship between serum carcinoembryonic antigen (CEA level and epidermal growth factor receptor (EGFR gene mutations in non-small-cell lung cancer (NSCLC patients and to analyze the influence of CEA level on postoperative survival time in lung cancer patients. Methods: A total of 296 patients who were treated in Thoracic Surgery Department of Henan Provincial Chest Hospital from September 2011 to September 2013 were recruited. The level of tumor markers, such as CEA, was determined before the surgery, and EGFR gene mutations were detected after surgery. Thereby, the relationship between tumor makers, including CEA, and EGFR mutation and its influence on prognosis could be investigated. Results: Among 296 patients, the positive rate of EGFR gene mutation was 37.84% (112/296; the mutation occurred more frequently in nonsmokers, adenocarcinoma patients, women, and patients aged <60 years (P<0.05. Both tumor markers and chemosensitivity indicators were related to the profile of EGFR mutations. Elevated squamous cell carcinoma and Cyfra21-1 as well as positively expressed ERCC1 were more common in patients with wild-type EGFR (P<0.05, whereas increased CEA level was observed more frequently in patients with EGFR gene mutation (P=0.012. The positive rate of EGFR gene mutations was higher as the serum CEA level increased, that is, the positive rate in patients with serum CEA level <5, 5–20, and >20 µg/L was 39.81%, 45.32%, and 65.47%, respectively (P=0.004. Logistic regression analysis showed that CEA level was an independent factor in predicting EGFR gene mutations, and serum CEA level was also an independent factor in affecting the prognosis of NSCLC patients, as the overall 2-year survival rate was 73.86% in elevated CEA group and 86.43% in normal group (P<0.01. Conclusion: The prognosis of

  10. Survival and prognostic factors in non-small cell lung cancer patients with spinal bone metastases. A retrospective analysis of 303 patients

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    Rief, H.; Welzel, T.; Rieken, S.; Bischof, M.; Lindel, K.; Combs, S.E.; Debus, J. [University Hospital of Heidelberg, Department of Radiation Oncology, Heidelberg (Germany); Muley, T. [University Hospital of Heidelberg, Thorax Clinic, Department of Thoracic Oncology, Heidelberg (Germany); Bruckner, T. [University Hospital of Heidelberg, Department of Medical Biometry, Heidelberg (Germany)

    2014-01-15

    For palliative care of spinal bone metastases, stability assessment is of crucial importance. Pathological fractures, instability-related patient immobility and the extent of bone metastasis have been reported to affect patient outcome and these parameters have therefore been used for treatment stratification. We report on stability-dependent fracture and survival rates in over 300 non-small cell lung cancer (NSCLC) patients. Data from 303 patients with 868 osteolytic metastases treated with radiotherapy (RT) between 2000 and 2012 were evaluated retrospectively. In NSCLC patients with bone metastases only, the retrospective 6- and 12-month overall survival (OS) rates were 76.7 and 47.2%, respectively. In patients with additional non-bone distant metastases, these values were 60.0 and 34.0%, respectively. Survival rates were significantly lower in patients with multiple bone metastases and in those suffering pathological fractures (p=0.017). No significant impact of histological type, location of spinal lesions or treatment regime was detected. Furthermore, stability assessment revealed no influence of vertebral column stability on patient outcome (p=0.739). Our analysis demonstrated a correlation between the pathological fractures of bone lesions, the number of bone metastases, additional distant metastases and survival. The results offer a rationale for future prospective investigations. (orig.)

  11. Cross-market cost-effectiveness analysis of erlotinib as first-line maintenance treatment for patients with stable non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Vergnenègre A

    2012-01-01

    Full Text Available Alain Vergnenègre1, Joshua A Ray2, Christos Chouaid3, Francesco Grossi4, Helge G Bischoff5, David F Heigener6, Stefan Walzer21Department of Pneumology, Hôpital du Cluzeau, Limoges, France; 2Global Health Economics and Strategic Pricing, F Hoffmann-La Roche Ltd, Basel, Switzerland; 3Respiratory Service, Hôpital Saint Antoine, Paris, France; 4Lung Cancer Unit, National Institute for Cancer Research, Genoa, Italy; 5Thoracic Oncology, Onkologie Thoraxklinik Heidelberg, Heidelberg, Germany; 6Department of Thoracic Oncology, Krankenhaus Großhansdorf, Großhansdorf, GermanyBackground: Platinum-doublet, first-line treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC is limited to 4–6 cycles. An alternative strategy used to prolong the duration of first-line treatment and extend survival in metastatic NSCLC is first-line maintenance therapy. Erlotinib was approved for first-line maintenance in a stable disease population following results from a randomized, controlled Phase III trial comparing erlotinib with best supportive care. We aimed to estimate the incremental cost-effectiveness of erlotinib 150 mg/day versus best supportive care when used as first-line maintenance therapy for patients with locally advanced or metastatic NSCLC and stable disease.Methods: An economic decision model was developed using patient-level data for progression-free survival and overall survival from the SATURN (SequentiAl Tarceva in UnResectable NSCLC study. An area under the curve model was developed; all patients entered the model in the progression-free survival health state and, after each month, moved to progression or death. A time horizon of 5 years was used. The model was conducted from the perspective of national health care payers in France, Germany, and Italy. Probabilistic sensitivity analyses were performed.Results: Treatment with erlotinib in first-line maintenance resulted in a mean life expectancy of 1.39 years in all countries

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

    Directory of Open Access Journals (Sweden)

    Chien-Chou Pan

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

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

    Directory of Open Access Journals (Sweden)

    Sushma Agrawal

    2013-01-01

    Full Text Available Data supporting use of concurrent chemoradiation in locally advanced lung cancers comes from clinical trials from developed countries. Applicability and outcomes of such schedules in developing countries is not widely reported. There are various challenges in delivering chemoradiation in locally advanced non small cell lung cancer in developing countries which is highlighted by an audit of patients treated with chemoradiation in our center. This article deals with the challenges in the context of a developing country. We conclude that sequential chemoradiotherapy is better tolerated than concurrent chemoradiation in Indian patients with locally advanced non-small cell lung cancers. Patients with stage IIIa, normal weight or overweight, and adequate baseline pulmonary function should be offered concurrent chemoradiation.

  14. Accelerated high-dose radiotherapy alone or combined with either concomitant or sequential chemotherapy; treatments of choice in patients with Non-Small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Pieters Bradley R

    2007-07-01

    Full Text Available Abstract Background Results of high-dose chemo-radiotherapy (CRT, using the treatment schedules of EORTC study 08972/22973 or radiotherapy (RT alone were analyzed among all patients (pts with Non Small Cell Lung Cancer (NSCLC treated with curative intent in our department from 1995–2004. Material Included are 131 pts with medically inoperable or with irresectable NSCLC (TNM stage I:15 pts, IIB:15 pts, IIIA:57 pts, IIIB:43 pts, X:1 pt. Treatment Group I: Concomitant CRT: 66 Gy/2.75 Gy/24 fractions (fx/33 days combined with daily administration of cisplatin 6 mg/m2: 56 pts (standard. Group II: Sequential CRT: two courses of a 21-day schedule of chemotherapy (gemcitabin 1250 mg/m2 d1, cisplatin 75 mg/m2 d2 followed by 66 Gy/2.75 Gy/24 fx/33 days without daily cisplatin: 26 pts. Group III: RT: 66 Gy/2.75 Gy/24 fx/33 days or 60 Gy/3 Gy/20 fx/26 days: 49 pts. Results The 1, 2, and 5 year actuarial overall survival (OS were 46%, 24%, and 15%, respectively. At multivariate analysis the only factor with a significantly positive influence on OS was treatment with chemo-radiation (P = 0.024 (1-, 2-, and 5-yr OS 56%, 30% and 22% respectively. The incidence of local recurrence was 36%, the incidence of distant metastases 46%. Late complications grade 3 were seen in 21 pts and grade 4 in 4 patients. One patient had a lethal complication (oesophageal. For 32 patients insufficient data were available to assess late complications. Conclusion In this study we were able to reproduce the results of EORTC trial 08972/22973 in a non-selected patient population outside of the setting of a randomised trial. Radiotherapy (66 Gy/24 fx/33 days combined with either concomitant daily low dose cisplatin or with two neo-adjuvant courses of gemcitabin and cisplatin are effective treatments for patients with locally advanced Non-Small Cell Lung Cancer. The concomitant schedule is also suitable for elderly people with co-morbidity.

  15. Expression of KISS1 and KISS1R (GPR54) may be used as favorable prognostic markers for patients with non-small cell lung cancer.

    Science.gov (United States)

    Sun, Yan-Bin; Xu, Shun

    2013-08-01

    Lung cancer is the most commonly diagnosed cancer worldwide. Loss of KISS1 expression has been associated with progression and poor prognosis of various cancers, however, the precise role of KISS1 expression in non-small cell lung cancer (NSCLC) is not well defined. KISS1 receptor (KISS1R, also named GPR54) coupled to KISS1, has been shown to play a pivotal role in suppressing cancer metastasis. In this study, 56 NSCLC specimens were divided into stage IIIB (locally advanced) and stage IV (metastatic). The mRNA and protein levels of KISS1 and KISS1R in cancer tissues were found to be lower compared to that in normal tissues using RT-PCR and western blot analysis, respectively. In addition, the expression of both KISS1 and KISS1R in stage IV NSCLC was lower compared to that in stage IIIB stage NSCLC. The cumulative survival rate of the patients with KISS1 or KISS1R expression was significantly higher compared to that without expression. KISS1 or KISS1R expression in NSCLC can be used to indicate favorable prognosis for disease outcome. Metastin, the product of the KISS1 gene, was lower in the serum of patients with stage IV NSCLC compared to that in stage IIIB NSCLC.

  16. Treatment paradigms for patients with metastatic non small cell lung cancer (NSCLC, squamous lung cancer: first, second and third-line

    Directory of Open Access Journals (Sweden)

    Abdulaziz eAl Farsi

    2014-06-01

    Full Text Available Historically, the treatment algorithm applied to non small cell lung cancer (NSCLC was the same for all histologic subtypes. However, recent advances in our understanding of the molecular profiles of squamous and non-squamous NSCLC have changed this perspective. Histologic subtype and the presence of specific molecular abnormalities have predictive value for response to and toxicity from therapy, as well as overall survival. For patients with squamous NSCLC, a platinum agent plus gemcitabine, or paclitaxel is recommended as first-line therapy. The role of EGFR monoclonal antibodies is uncertain. Maintenance therapy is not widely recommended, although data exist for the use of erlotinib. The standard recommendation for second-line therapy is docetaxel and erlotinib should be considered as second or third-line therapy. There is ongoing research identifying molecular targets in squamous NSCLC and many agents are in early phase clinical trials. Immunotherapeutic approaches targeting programmed death 1 receptor (PD-1 and its ligand (PD-L1 appear promising.

  17. Expression levels of some antioxidant and epidermal growth factor receptor genes in patients with early-stage non-small cell lung cancer.

    Science.gov (United States)

    De Palma, Giuseppe; Mozzoni, Paola; Acampa, Olga; Internullo, Eveline; Carbognani, Paolo; Rusca, Michele; Goldoni, Matteo; Corradi, Massimo; Tiseo, Marcello; Apostoli, Pietro; Mutti, Antonio

    2010-01-01

    THIS STUDY WAS AIMED AT: (i) investigating the expression profiles of some antioxidant and epidermal growth factor receptor genes in cancerous and unaffected tissues of patients undergoing lung resection for non-small cell lung cancer (NSCLC) (cross-sectional phase), (ii) evaluating if gene expression levels at the time of surgery may be associated to patients' survival (prospective phase). Antioxidant genes included heme oxygenase 1 (HO-1), superoxide dismutase-1 (SOD-1), and -2 (SOD-2), whereas epidermal growth factor receptor genes consisted of epidermal growth factor receptor (EGFR) and v-erb-b2 erythroblastic leukaemia viral oncogene homolog 2 (HER-2). Twenty-eight couples of lung biopsies were obtained and gene transcripts were quantified by Real Time RT-PCR. The average follow-up of patients lasted about 60 months. In the cancerous tissues, antioxidant genes were significantly hypo-expressed than in unaffected tissues. The HER-2 transcript levels prevailed in adenocarcinomas, whereas EGFR in squamocellular carcinomas. Patients overexpressing HER-2 in the cancerous tissues showed significantly lower 5-year survival than the others.

  18. Expression Levels of Some Antioxidant and Epidermal Growth Factor Receptor Genes in Patients with Early-Stage Non-Small Cell Lung Cancer

    Science.gov (United States)

    De Palma, Giuseppe; Mozzoni, Paola; Acampa, Olga; Internullo, Eveline; Carbognani, Paolo; Rusca, Michele; Goldoni, Matteo; Corradi, Massimo; Tiseo, Marcello; Apostoli, Pietro; Mutti, Antonio

    2010-01-01

    This study was aimed at: (i) investigating the expression profiles of some antioxidant and epidermal growth factor receptor genes in cancerous and unaffected tissues of patients undergoing lung resection for non-small cell lung cancer (NSCLC) (cross-sectional phase), (ii) evaluating if gene expression levels at the time of surgery may be associated to patients' survival (prospective phase). Antioxidant genes included heme oxygenase 1 (HO-1), superoxide dismutase-1 (SOD-1), and -2 (SOD-2), whereas epidermal growth factor receptor genes consisted of epidermal growth factor receptor (EGFR) and v-erb-b2 erythroblastic leukaemia viral oncogene homolog 2 (HER-2). Twenty-eight couples of lung biopsies were obtained and gene transcripts were quantified by Real Time RT-PCR. The average follow-up of patients lasted about 60 months. In the cancerous tissues, antioxidant genes were significantly hypo-expressed than in unaffected tissues. The HER-2 transcript levels prevailed in adenocarcinomas, whereas EGFR in squamocellular carcinomas. Patients overexpressing HER-2 in the cancerous tissues showed significantly lower 5-year survival than the others. PMID:20700416

  19. Economic analysis of combined endoscopic and endobronchial ultrasound in the evaluation of patients with suspected non-small cell lung cancer.

    LENUS (Irish Health Repository)

    Harewood, Gavin C

    2010-03-01

    Lung cancer remains the most common cause of cancer-related death in the United States. This study evaluated the costs of alternative diagnostic evaluations for patients with suspected non-small cell lung cancer (NSCLC). Researchers used a cost-minimization model to compare various diagnostic approaches in the evaluation of patients with NSCLC. It was less expensive to use an initial endoscopic ultrasound (EUS) with fine needle aspiration (FNA) to detect a mediastinal lymph node metastasis ($18,603 per patient), compared with combined EUS FNA and endobronchial ultrasound (EBUS) with FNA ($18,753). The results were sensitive to the prevalence of malignant mediastinal lymph nodes; EUS FNA remained least costly, if the probability of nodal metastases was <32.9%, as would occur in a patient without abnormal lymph nodes on computed tomography (CT). While EUS FNA combined with EBUS FNA was the most economical approach, if the rate of nodal metastases was higher, as would be the case in patients with abnormal lymph nodes on CT. Both of these strategies were less costly than bronchoscopy or mediastinoscopy. The pre-test probability of nodal metastases can determine the most cost-effective testing strategy for evaluation of a patient with NSCLC. Pre-procedure CT may be helpful in assessing probability of mediastinal nodal metastases.

  20. 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

  1. 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.

  2. Genetic variants of CHRNA5-A3 and CHRNB3-A6 predict survival of patients with advanced non-small cell lung cancer.

    Science.gov (United States)

    Wang, Yang; Peng, Xiaonu; Zhu, Lijun; Hu, Likuan; Song, Yipeng

    2016-05-03

    Nicotinic acetylcholine receptors (nAChRs) play a key role in carcinogenesis and progression of lung cancer; and polymorphisms in CHRNA5-A3 and CHRNB3-A6, two gene clusters encoding nAChR subunits, have been associated with lung cancer risk. In this study, we investigated whether variants in the two gene clusters were associated with prognosis of advanced non-small cell lung cancer (NSCLC). A total of 165 stage IIIB-IV NSCLC patients were enrolled in this study. Three polymorphisms (rs667282 and rs3743073 in CHRNA5-A3 and rs13280604 in CHRNB3-A6) were genotyped using the TaqMan method. Overall survival (OS) was estimated using the log-rank test and the Cox models. Our results showed that patients with CHRNA5-A3 rs667282 TT or TC genotypes had a significantly shorter OS than those carrying the CC genotype (Log-rank, P = 0.043). Furthermore, multivariate Cox regression analysis showed that rs667282 TT/TC genotypes are significantly associated with increased risk of overall deaths (adjusted hazard ratio, 1.7; 95% CI, 1.1-2.7). However, the similar results were not observed for other two polymorphisms. Furthermore, no evident association was found between these variants and clinicopathologic features of advanced NSCLC. Our present study suggested that rs667282 in CHRNA5-A3 may modify the prognosis of patients with advanced NSCLC.

  3. 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.

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

    Science.gov (United States)

    Grossi, Francesco; Dal Bello, Maria Giovanna; Salvi, Sandra; Puzone, Roberto; Pfeffer, Ulrich; Fontana, Vincenzo; Alama, Angela; Rijavec, Erika; Barletta, Giulia; Genova, Carlo; Sini, Claudio; Ratto, Giovanni Battista; Taviani, Mario; Truini, Mauro; Merlo, Domenico Franco

    2015-01-01

    Biomarkers can help to identify patients with early-stages or locally advanced non-small cell lung cancer (NSCLC) who have high risk of relapse and poor prognosis. To correlate the expression of seven biomarkers involved in DNA synthesis and repair and in cell division with clinical outcome, we consecutively collected 82 tumour tissues from radically resected NSCLC patients. The following biomarkers were investigated using IHC and qRT-PCR: excision repair cross-complementation group 1 (ERCC1), breast cancer 1 (BRCA1), ribonucleotide reductase subunits M1 and M2 (RRM1 and RRM2), subunit p53R2, thymidylate synthase (TS), and class III beta-tubulin (TUBB3). Gene expression levels were also validated in an available NSCLC microarray dataset. Multivariate analysis identified the protein overexpression of RRM2 and TS as independent prognostic factors of shorter overall survival (OS). Kaplan-Meier analysis showed a trend in shorter OS for patients with RRM2, TS, and ERCC1, BRCA1 overexpressed tumours. For all of the biomarkers except TUBB3, the OS trends relative to the gene expression levels were in agreement with those relative to the protein expression levels. The NSCLC microarray dataset showed RRM2 and TS as biomarkers significantly associated with OS. This study suggests that high expression levels of RRM2 and TS might be negative prognostic factors for resected NSCLC patients. PMID:26663950

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

    Directory of Open Access Journals (Sweden)

    Francesco Grossi

    2015-01-01

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

  6. Prognostic Impact of Radiation Therapy to the Primary Tumor in Patients With Non-small Cell Lung Cancer and Oligometastasis at Diagnosis

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    Lopez Guerra, Jose Luis [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Department of Radiation Oncology, Instituto Madrileno de Oncologia/Grupo IMO, Madrid (Spain); Gomez, Daniel, E-mail: dgomez@mdanderson.org [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Zhuang, Yan; Hong, David S. [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Heymach, John V. [Department of Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Swisher, Stephen G. [Department of Thoracic Surgery, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Lin, Steven H.; Komaki, Ritsuko; Cox, James D.; Liao Zhongxing [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2012-09-01

    Purpose: We investigated prognostic factors associated with survival in patients with non-small cell lung cancer (NSCLC) and oligometastatic disease at diagnosis, particularly the influence of local treatment to the primary site on prognosis. Methods and Materials: From January 2000 through June 2011, 78 consecutive patients with oligometastatic NSCLC (<5 metastases) at diagnosis underwent definitive chemoradiation therapy ({>=}45 Gy) to the primary site. Forty-four of these patients also received definitive local treatment for the oligometastases. Survival outcomes were estimated using the Kaplan-Meier method, and risk factors were identified by univariate and multivariate analyses. Results: Univariate Cox proportional hazard analysis revealed better overall survival (OS) for those patients who received at least 63 Gy of radiation to the primary site (P=.002), received definitive local treatment for oligometastasis (P=.041), had a Karnofsky performance status (KPS) score >80 (P=.007), had a gross tumor volume {<=}124 cm{sup 3} (P=.002), had adenocarcinoma histology (P=.002), or had no history of respiratory disease (P=.016). On multivariate analysis, radiation dose, performance status, and tumor volume retained significance (P=.004, P=.006, and P<.001, respectively). The radiation dose also maintained significance when patients with and without brain metastases were analyzed separately. Conclusions: Tumor volume, KPS, and receipt of at least 63 Gy to the primary tumor are associated with improved OS in patients with oligometastatic NSCLC at diagnosis. Our results suggest that a subset of such patients may benefit from definitive local therapy.

  7. Effect of Neoadjuvant Chemotherapy on Improvement of Surgical Resectibility and Survival of Patients with Stage ⅢA Non Small Cell Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    LIJian; YULichao; 等

    2002-01-01

    Ojbective To assess the effect of neoadjuvant chemotherapy on surgical resectibility and survival in patients with stage ⅢA non small cell lung cancer(NSCLC).Methods 42 patients with stage ⅢA NSCLC were randomized to receive either two cycles chemotherapy followed by surgery(neoadjuvant chemotherapy group)or surgery alone(surgery alone group).All patients received four cycles chemotherapy after surgery.Results The overall response to chemotherapy was 42.9%(38.1% partial response and 4.8% complete response).Toxicity of chemotherapy was minor and consisted mainly of gastroenterological side effects and myelosuppression.Patients treated with neoadjuvant chemotherapy had estimated surgical resection rate of 95.2%(n=20)and a complete resection rate in 52.4%(n=11) compared to 66.7%(n=14)and 28.6%(n=6)respectively,for patients with surgery alone(P<0.05).None of the patients died from the operation.The median survival was 24.6 months in the neoadjuvant chemotherapy group as compared to only 10.8 months in the surgery alone group(P<0.05).The 2-year survival rate was 57.1% in the chemotherapy group as compared to 28.6% in the surgery alone group(P<0.05).Conclusion Neoadjuvant chemotherapy improves the surgical resectibility and increases the median survival and 2-year survival rate of patients with stage ⅢA NSCLC.

  8. [Prognostic relevance of body mass index and rash for patients with metastatic non-small-cell lung cancer under therapy with erlotinib].

    Science.gov (United States)

    Böker, B; Lüders, H; Grohé, C

    2012-02-01

    Tyrosine kinase inhibition (TKI) such as erlotinib is a well established treatment option in the palliative care of patients with non small cell lung cancer (NSCLC). Histology and sex have been associated with different prognostic outcome measures in patients treated with erlotinib. Furthermore, the degree of rash, developed during treatment might be a relevant marker in respect to tumor response. To dissect these clinical relevant features we analysed a cohort of 275 patients treated with erlotinib in different lines of chemotherapy in our hospital. Nutrition status plays an important role in the prognosis of patients in a palliative chemotherapeutic setting, we therefore included body mass index measurements (BMI) in our analysis. We found that BMI and smoking status influence different survival patterns. Male patients have a poorer survival based on low BMI, rash development and smoking status. We therefore conclude that both nutritional and smoking status should be taken into account in the surveillance of patients with NSCLC in a palliative therapeutic setting under TKI treatment.

  9. Oral nutritional supplements containing (n-3) polyunsaturated fatty acids affect the nutritional status of patients with stage III non-small cell lung cancer during multimodality treatment.

    Science.gov (United States)

    van der Meij, Barbara S; Langius, Jacqueline A E; Smit, Egbert F; Spreeuwenberg, Marieke D; von Blomberg, B Mary E; Heijboer, Annemieke C; Paul, Marinus A; van Leeuwen, Paul A M

    2010-10-01

    Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), (n-3) fatty acids from fish oil, have immune-modulating effects and may improve nutritional status in cancer. The objective of this study was to investigate the effects of an oral nutritional supplement containing (n-3) fatty acids on nutritional status and inflammatory markers in patients with non-small cell lung cancer (NSCLC) undergoing multimodality treatment. In a double-blind experiment, 40 patients with stage III NSCLC were randomly assigned to receive 2 cans/d of a protein- and energy-dense oral nutritional supplement containing (n-3) fatty acids (2.0 g EPA + 0.9 g DHA/d) or an isocaloric control supplement. EPA in plasma phospholipids, energy intake, resting energy expenditure (REE), body weight, fat free mass (FFM), mid-upper arm circumference (MUAC), and inflammatory markers were assessed. Effects of intervention were analyzed by generalized estimating equations and expressed as regression coefficients (B). The intervention group (I) had a better weight maintenance than the control (C) group after 2 and 4 wk (B = 1.3 and 1.7 kg, respectively; P nutritional supplement containing (n-3) fatty acids beneficially affects nutritional status during multimodality treatment in patients with NSCLC.

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

    Science.gov (United States)

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

    2014-02-01

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

  11. Definitive surgery and intraoperative photodynamic therapy: a prospective study of local control and survival for patients with pleural dissemination of non-small cell lung cancer.

    Science.gov (United States)

    Simone, Charles B; Cengel, Keith A

    2014-02-01

    Patients with non-small cell lung cancer (NSCLC) with pleural dissemination have very limited survivals often of just 6-9 months. Prior reports of aggressive surgical resection of pleural metastases have shown no consistent improvements in overall survival and very high rates of local recurrences. Based on this and the generally very diffuse pleural dissemination seen in patients, chemotherapy and palliative interventions are standard of care. By attempting to sterile microscopic residual disease after surgical resection, intraoperative photodynamic therapy (PDT) could improve local pleural control and overall survival compared with surgery alone for patients with NSCLC with pleural metastasis. Prior attempts to demonstrate an improvement in clinical outcomes with PDT as an intraoperative adjuvant combined with definitive surgery to treat pleural malignancies have not been successful, perhaps due, in part, to limited ability to perform real-time dosimetry and ensure adequate and even light distribution throughout the chest cavity. A stratified phase II trial assessed the efficacy of definitive surgery and intraoperative PDT with real-time dosimetry in patients with NSCLC with pleural dissemination demonstrated prolonged local control and a higher than expected 21.7-month median survival from the time of surgery and PDT among 22 enrolled patients. This is the first ever report describing optimal methods, techniques, and dosimetry that could be used to safely and reproducibly deliver intraoperative PDT to the chest cavity as part of multimodality therapy for NSCLC with pleural metastasis.

  12. Survival prognostic value of morphological and metabolic variables in patients with stage I and II non-small cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Domachevsky, L. [Rabin Medical Center, Department of Nuclear Medicine, Petah Tikva (Israel); Beilinson Hospital, Petah Tikva (Israel); Groshar, D.; Bernstine, H. [Rabin Medical Center, Department of Nuclear Medicine, Petah Tikva (Israel); Tel Aviv University, Sackler Faculty of Medicine, Tel Aviv (Israel); Galili, R. [Lady Davis-Carmel Medical Center, Department of Cardiothoracic Surgery, Haifa (Israel); Saute, M. [Rabin Medical Center, Department of Cardiothoracic Surgery, Petah Tiqva (Israel)

    2015-11-15

    The prognosis of patients with non-small cell lung cancer (NSCLC) is important, as patients with resectable disease and poor prognostic variables might benefit from neoadjuvant therapy. The goal of this study is to evaluate SUVmax, SUVmax ratio, CT volume (CTvol), metabolic tumour volume (MTV) and total lesion glycolisis (TLG) as survival prognostic markers. In addition, we defined two variables; MTV x SUVmax (MTVmax) and CTvol x SUVmax (CTvolmax) and assessed whether they can be used as prognostic markers. Patients with stage I-II NSCLC who underwent 18 F FDG PET/CT and surgery were evaluated. Cox proportional-hazard model was used to determine the association between variables and survival. Similar analysis was performed in cases with no lymph node (LN) involvement. One hundred and eighty-one patients were included (at the end of the study, 140 patients were alive). SUVmax with a cut-off value of 8.2 was significant survival prognostic factor regardless of LN involvement (P = 0.012). In cases with no LN involvement, SUVmax and CTvol (≥7.1 ml) were significant survival prognostic factors with P = 0.004 and 0.03, respectively. SUVmax may be a useful prognostic variable in stage I-II NSCLC while morphologic tumour volume might be useful in cases with no lymph node involvement. (orig.)

  13. A phase I study of S-1 with concurrent thoracic radiotherapy in elderly patients with localized advanced non-small cell lung cancer.

    Science.gov (United States)

    Takigawa, Nagio; Kiura, Katsuyuki; Hotta, Katsuyuki; Hosokawa, Shinobu; Nogami, Naoyuki; Aoe, Keisuke; Gemba, Kenichi; Fujiwara, Keiichi; Harita, Shingo; Takemoto, Mitsuhiro; Himei, Kengo; Shinkai, Tetsu; Fujiwara, Yoshirou; Takata, Saburo; Tabata, Masahiro; Kanazawa, Susumu; Tanimoto, Mitsune

    2011-01-01

    S-1, an oral 5-fluorouracil derivative, is effective against advanced non-small cell lung cancer (NSCLC) with mild toxicity and synergistic effects with radiation in preclinical trials. In this phase I study, we evaluated the dose-limiting toxicity and recommended dose of S-1 for a future phase II study when administered concurrently with thoracic radiation (total dose of 60 Gy at 2 Gy per daily fraction) in elderly patients (>75 years old) with localized advanced NSCLC. S-1 was administered on days 1-14 and 29-42 at the following dosages: 60, 70, and 80 mg/m(2)/day. Twenty-two previously untreated patients were enrolled in this study. Dose-limiting toxicity included febrile neutropenia, thrombocytopenia, stomatitis, and pneumonitis. One patient had grade 5 radiation pneumonitis. No other patient experienced radiation pneumonitis or esophagitis exceeding grade 2. The recommended dose for S-1 was determined to be 80 mg/m(2)/day, which produced an overall response rate of 75% (n=12). The median progression-free survival time was 11.5 months (95% confidence interval: 7.1-15.8 months) with a median follow-up time of 27.9 months. These results indicate that concurrent treatment with S-1 and thoracic radiation is a feasible option for NSCLC in the elderly. A phase II study is currently under way.

  14. 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.

  15. Increase in soluble PD-1 is associated with prolonged survival in patients with advanced EGFR-mutated non-small cell lung cancer treated with erlotinib

    DEFF Research Database (Denmark)

    Sorensen, Steffen Filskov; Demuth, Christina; Weber, Britta;

    2016-01-01

    OBJECTIVES: The central immune co-inhibitory programmed cell death receptor/ligand 1 (PD-1/PD-L1) pathway plays a key role in tumor immune evasion in non-small cell lung cancer (NSCLC). Soluble PD-1 (sPD-1) can be detected in the blood, and preclinical evidence suggests that sPD-1 blocks PD-1/-L1...... interaction and improves anti-tumor immunity. The present study compares the concentration of sPD-1 in the serum of advanced NSCLC patients with Epidermal Growth Factor Receptor (EGFR) mutation prior to erlotinib treatment and at the time of progression and correlates these results to patient outcome....... MATERIALS AND METHODS: Blood samples from 38 patients with EGFR-mutated advanced NSCLC treated with erlotinib were analyzed for sPD-1 by sandwich ELISA. EGFR mutational status was assessed in circulating tumor DNA (ctDNA) and tumor biopsies. RESULTS: sPD-1 could be detected in 21% of patients prior...

  16. 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.

  17. Severe acute interstitial lung disease in a patient with anaplastic lymphoma kinase rearrangement-positive non-small cell lung cancer treated with alectinib.

    Science.gov (United States)

    Yamamoto, Yuzo; Okamoto, Isamu; Otsubo, Kohei; Iwama, Eiji; Hamada, Naoki; Harada, Taishi; Takayama, Koichi; Nakanishi, Yoichi

    2015-10-01

    Alectinib, the second generation anaplastic lymphoma kinase (ALK) inhibitor, has significant potency in patients with ALK rearrangement positive non-small cell lung cancer (NSCLC), and its toxicity is generally well tolerable. We report a patient who developed severe acute interstitial lung disease after alectinib treatment. An 86-year-old woman with stage IV lung adenocarcinoma positive for rearrangement of ALK gene was treated with alectinib. On the 215th day after initiation of alectinib administration, she was admitted to our hospital with the symptom of progressive dyspnea. Computed tomography (CT) revealed diffuse ground glass opacities and consolidations in both lungs, and analysis of bronchoalveolar lavage fluid revealed pronounced lymphocytosis. There was no evidence of infection or other specific causes of her condition, and she was therefore diagnosed with interstitial lung disease induced by alectinib. Her CT findings and respiratory condition improved after steroid pulse therapy. As far as we are aware, this is the first reported case of alectinib-induced severe interstitial lung disease (ILD). We should be aware of the possibility of such a severe adverse event and should therefore carefully monitor patients treated with this drug.

  18. 老年非小细胞肺癌的靶向治疗%Targeted therapy for elderly patients with non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    方红明; 马胜林

    2009-01-01

    With the development of tumor cell biology,many targeted therapy drugs that aim specifically to inhibit tumor growth have been developed. Application of targeted drugs as first-line and second-line therapy in patients with advanced non-small cell lung cancer (NSCLC) have acquired exciting curative effect. Molecular targeted therapy for old patients have important clinical values,because old patients have weak toleration to chemotherapy as a result of physical and pharmacological features.%随着肿瘤细胞生物学的进展,已研制出许多针对特异性分子靶向的治疗药物,而且在晚期非细胞肺癌患者的一线和二线治疗中均已显示出较好的疗效,由于老年患者有着生理学、药理学等各方面的特点,对化疗耐受性差,而针对此类患者的分子靶向治疗具有重要临床价值.

  19. Concurrent pemetrexed and radiation therapy in the treatment of patients with inoperable stage III non-small cell lung cancer: a systematic review of completed and ongoing studies.

    Science.gov (United States)

    Choy, Hak; Gerber, David E; Bradley, Jeffrey D; Iyengar, Puneeth; Monberg, Matthew; Treat, Joseph; Govindan, Ramaswamy; Koustensis, Andrew; Barker, Scott; Obasaju, Coleman

    2015-03-01

    Current standard for locally advanced non-small cell lung cancer (NSCLC) is combined concurrent therapy with a platinum-based regimen. Preclinical synergistic activity of pemetrexed with radiation therapy (RT) and favorable toxicity profile has led to clinical trials evaluating pemetrexed in chemoradiation regimens. This literature search of concurrent pemetrexed and RT treatment of patients with stage III NSCLC included MEDLINE database, meeting abstracts, and the clinical trial registry database. Nineteen unique studies were represented across all databases including 11 phase I studies and eight phase II studies. Of the six phase II trials with mature data available, median overall survival ranged from 18.7 to 34 months. Esophagitis and pneumonitis occurred in 0-16% and 0-23% of patients, respectively. Of the ongoing trials, there is one phase III and four phase II trials with pemetrexed in locally advanced NSCLC. Pemetrexed can be administered safely at full systemic doses with either cisplatin or carboplatin concomitantly with radical doses of thoracic radiation therapy. While results from the ongoing phase III PROCLAIM trial are needed to address definitively the efficacy of pemetrexed-cisplatin plus RT in stage III NSCLC, available results from phase II trials suggest that this regimen has promising activity with an acceptable toxicity profile.

  20. Erlotinib Induced Fatal Interstitial Lung Disease in a Patient with Metastatic Non-Small Cell Lung Cancer: Case Report and Review of Literature.

    Science.gov (United States)

    Mangla, Ankit; Agarwal, Nikki; Carmel, Chou; Lad, Thomas

    2016-09-05

    Erlotinib is one of the most widely used tyrosine kinase inhibitor targeting human epidermal growth factor receptor. Since its introduction, it has revolutionized the treatment of advanced non-small cell lung cancer. Skin rashes and diarrhea are the most often reported side effects of erlotinib however it is also associated with interstitial pneumonitis or interstitial lung disease, which often turns out to be fatal complication of using this medicine. Though reported scarcely in the western world, the association of interstitial lung disease with epidermal growth factor receptor has attracted a lot of attention in the recent times. Various researches working with murine models of bleomycin-induced pulmonary fibrosis have found a pro and con role of the receptor in development of the interstitial lung disease. We present the case of a patient diagnosed with stage IV adenocarcinoma of the lung with metastasis to brain. He was found to be positive for the human epidermal growth factor mutation and was hence started on erlotinib. Within a few weeks of starting the medicine the patient was admitted with diarrhea. During the course of this admission he developed acute shortness of breath diagnosed as interstitial pneumonitis. The purpose of this case report is to review the literature associated with erlotinib induced interstitial pneumonitis and make the practicing oncologists aware of this rare yet fatal complication of erlotinib. Here we will also review literature, pertaining to the role of epidermal growth factor receptor in development of interstitial lung disease.

  1. From Cisplatin-Containing Sequential Radiochemotherapy towards Concurrent Treatment for Patients with Inoperable Locoregional Non-Small Cell Lung Cancer: Still Unanswered Questions

    Directory of Open Access Journals (Sweden)

    C. C. E. Koning

    2010-01-01

    Full Text Available Radiotherapy has been the mainstay of the treatment of stage III non-small cell lung cancer (NSCLC patients. In the early nineties, combined treatment with chemotherapy was introduced. In 1995, a meta-analysis showed improved treatment outcome of the sequential use of radiochemotherapy (RCT compared to radiotherapy alone, provided cisplatin was part of the chemotherapy course. Concurrent RCT compared to radiotherapy only yielded the same improvements of 4% in the 2-year and 2% in the 5-year overall survival rates. Just recently, two meta-analyses demonstrated that concurrent RCT is definitely superior to sequential RCT in terms of local control and 2-, 3-, and 5-year survival. However, several unanswered questions remain concerning the optimal chemotherapy regimen and radiotherapy doses and techniques in terms of treatment outcome and toxicity profile. Arguments supporting a daily low-dose cisplatin scheme are presented because of comparable radiosensitizing characteristics and favourable side effects. Increasing radiotherapy doses applied according to up-to-date techniques and combinations with new biologicals might lead to further treatment improvements.

  2. High expression of MAGE-A9 in tumor and stromal cells of non-small cell lung cancer was correlated with patient poor survival.

    Science.gov (United States)

    Zhang, Siya; Zhai, Xiaolu; Wang, Gui; Feng, Jian; Zhu, Huijun; Xu, Liqin; Mao, Guoxin; Huang, Jianfei

    2015-01-01

    Melanoma associated antigen-A (MAGE-A) is an oncogene and correlated with tumor initiation and development. However the roles of MAGE-A9 in non-small cell lung cancer (NSCLC) are still unknown. We investigated MAGE-A9 mRNA expression in 18 tumor tissues of NSCLC by qRT-PCR and MAGE-A9 protein expression in 213 NSCLC samples of tissue arrays by immunohistochemical staining. We assessed the relationship between MAGE-A9 expression and clinical parameters. The results showed that the high expression of MAGE-A9 protein in NSCLC tumor cells were commonly present in squamous cell carcinomas (P = 0.030). It was also related to larger tumor diameter, lymph node metastasis and later stage grouping with TNM classification (all P cells was higher in squamous cell carcinomas as well. Cox regression univariate and multivariable analysis revealed that MAGE-A9 expression in tumor cells of NSCLC (P < 0.001) is an independent prognostic factor in five-year overall survival rate. We concluded that the molecular assessment of MAGEA9 could be considered to improve prognostic evaluation and to identify eligible patients for potential target therapy.

  3. Chemotherapy with or without gefitinib in patients with advanced non-small-cell lung cancer: a meta-analysis of 6844 patients

    Institute of Scientific and Technical Information of China (English)

    ZHOU Hang; ZENG Chao; WANG Li-yang; XIE Hua; ZHOU Jin; DIAO Peng; YAO Wen-xiu

    2013-01-01

    Background Gefitinib is widely used in patients with advanced non-small-cell lung cancer (NSCLC),in whom chemotherapy had failed.Previous trials reported inconsistent findings regarding the efficacy of gefitinib on overall survival (OS) and progression free survival (PFS).This study was to evaluate the effects of chemotherapy plus gefitinib versus chemotherapy alone on survival of patients with NSCLC.Methods We systematically searched Medline,EmBase,the Cochrane Central Register of Controlled Trials,reference lists of articles,and proceedings of major meetings for relevant literature.Randomized controlled trials (RCTs) comparing chemotherapy with and without gefitinib in the treatment of patients with advanced NSCLC were included in our analysis.The primary endpoints were OS and PFS.Results Of 182 relevant studies,12 were included in the final analysis,which consisted of 6844 patients with NSCLC.Overall,we noted that gefitinib therapy had an 8% improvement in the OS as compared to the gefltinib-free therapy,but this difference was not statistically significant (HR,0.92; 95% C/:0.85-1.00; P=0.051).Furthermore,gefltinib therapy had significantly longer PFS compared to gefitinib-free therapy (HR,0.72; 95% C/ 0.60-0.87,P=0.001).Patients receiving gefitinib therapy also had a more frequent objective response rate (ORR) than the control arm (OR,2.51; 95% C/,1.67-3.78,P <0.001).Rashes,diarrhea,dry skin,pruritus,paronychia,and abnormal hepatic function were more frequent in the gefitinib therapy group.Conclusions Treatment with gefitinib had a clear effect on PFS and ORR,and it might contribute considerably to the OS.Furthermore,there was some evidence of benefit for gefitinib therapy among patients with adenocarcinoma.

  4. Clinical implications of cytosine deletion of exon 5 of P53 gene in non small cell lung cancer patients

    Directory of Open Access Journals (Sweden)

    Rashid Mir

    2016-01-01

    Full Text Available Aim: Lung cancer is considered to be the most common cancer in the world. In humans, about 50% or more cancers have a mutated tumor suppressor p53 gene thereby resulting in accumulation of p53 protein and losing its function to activate the target genes that regulate the cell cycle and apoptosis. Extensive research conducted in murine cancer models with activated p53, loss of p53, or p53 missense mutations have facilitated researchers to understand the role of this key protein. Our study was aimed to evaluate the frequency of cytosine deletion in nonsmall cell lung cancer (NSCLC patients. Methods: One hundred NSCLC patients were genotyped for P53 (exon5, codon168 cytosine deletion leading to loss of its function and activate the target genes by allele-specific polymerase chain reaction. The P53 cytosine deletion was correlated with all the clinicopathological parameters of the patients. Results and Analysis: 59% cases were carrying P53 cytosine deletion. Similarly, the significantly higher incidence of cytosine deletion was reported in current smokers (75% in comparison to exsmoker and nonsmoker. Significantly higher frequency of cytosine deletion was reported in adenocarcinoma (68.08% than squamous cell carcinoma (52.83%. Also, a significant difference was reported between p53 cytosine deletion and metastasis (64.28%. Further, the majority of the cases assessed for response carrying P53 cytosine deletion were found to show faster disease progression. Conclusion: The data suggests that there is a significant association of the P53 exon 5 deletion of cytosine in codon 168 with metastasis and staging of the disease.

  5. Experience of segmentectomy from 36 Chinese patients with non-small cell lung cancer at stage Ⅰ

    Institute of Scientific and Technical Information of China (English)

    QIAN Li-qiang; ZHAO Xiao-jing; LUO Qing-quan; HUANG Jia

    2013-01-01

    Background Although video-assisted radical operation for lung cancer has been widely accepted for treatment of nonsmall cell lung cancer (NSCLC),the debate over video-assisted thoracic surgery (VATS) segmentectomy still remains.This study analyzed the clinical outcomes using VATS segmentectomy for stage Ⅰ NSCLC patients to explore the safety and efficacy of VATS segmentectomy for la NSCLC.Methods Retrospective review was conducted of patients who underwent VATS segmentectomy for clinical stage Ⅰ NSCLC at Shanghai Chest Hospital between November 2009 and May 2012.VATS segmentectomy was performed on 36 patients.Analyses of the patient group were performed on patient demographics and clinical characteristics,intraoperative parameters,complications,and postoperative survival.Results Thirty-five of thirty-six patients underwent VATS segmentectomy with only one conversion to open thoracic surgery.There was one peri-operative mortality from the segmentectomy group and all other patients are alive with a median follow up of 327 days.The mean volume of chest tube drainage after operation for segmentectomy was 1021.4 ml.Among other parameters,the mean blood loss was 162.5 ml (50.0-1600.0 ml),the mean operation time 124.8 minutes (75.0-271.0 minutes),chest tube duration 4.1 days (2-8 days),and the mean length of hospital stay 6.2 days (4-11 days).There was one (2.8%) locoregional recurrence after segmentectomy.Two patients successfully underwent bilateral segmentectomies and are still disease free.Conclusion For patients with stage Ⅰ NSCLC,VATS segmentectomy offers a safe and equally effective option and can be applied to complicated operations such as bilateral segmentectomy.

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

    Institute of Scientific and Technical Information of China (English)

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

    2013-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Acampa Olga

    2005-07-01

    Full Text Available Abstract Background Non-invasive diagnostic strategies aimed at identifying biomarkers of lung cancer are of great interest for early cancer detection. The aim of this study was to set up a new method for identifying and quantifying volatile organic compounds (VOCs in exhaled air of patients with non-small cells lung cancer (NSCLC, by comparing the levels with those obtained from healthy smokers and non-smokers, and patients with chronic obstructive pulmonary disease. The VOC collection and analyses were repeated three weeks after the NSCLC patients underwent lung surgery. Methods The subjects' breath was collected in a Teflon® bulb that traps the last portion of single slow vital capacity. The 13 VOCs selected for this study were concentrated using a solid phase microextraction technique and subsequently analysed by means of gas cromatography/mass spectrometry. Results The levels of the selected VOCs ranged from 10-12 M for styrene to 10-9 M for isoprene. None of VOCs alone discriminated the study groups, and so it was not possible to identify one single chemical compound as a specific lung cancer biomarker. However, multinomial logistic regression analysis showed that VOC profile can correctly classify about 80 % of cases. Only isoprene and decane levels significantly decreased after surgery. Conclusion As the combination of the 13 VOCs allowed the correct classification of the cases into groups, together with conventional diagnostic approaches, VOC analysis could be used as a complementary test for the early diagnosis of lung cancer. Its possible use in the follow-up of operated patients cannot be recommended on the basis of the results of our short-term nested study.

  8. Practical recommendation for rash and diarrhea management in Indian patients treated with tyrosine kinase inhibitors for the treatment of non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    P Parikh

    2016-01-01

    Full Text Available Tyrosine kinase inhibitors (TKIs are a pharmaceutical class of small molecules, orally available with manageable safety profile, approved worldwide for the treatment of several neoplasms, including lung, breast, kidney and pancreatic cancer as well as gastro-intestinal stromal tumours and chronic myeloid leukaemia. In recent years, management of lung cancer has been moving towards molecular-guided treatment, and the best example of this new approach is the use of the tyrosine kinase inhibitors (TKIs in patients with mutations in the epidermal growth factor receptor (EGFR. The identification of molecular predictors of response can allow the selection of patients who will be the most likely to respond to these tyrosine kinase inhibitors (TKIs. Gastrointestinal (GI adverse events (AEs are frequently observed in patients receiving EGFR tyrosine kinase inhibitor therapy and are most impactful on the patient's quality of life. Dermatologic side effects are also relatively common among patients treated with EGFR inhibitors. Evidence has emerged in recent years to suggest that the incidence and severity of rash, positively correlated with response to treatment.These skin disorders are generally mild or moderate in severity and can be managed by appropriate interventions or by reducing or interrupting the dose. Appropriate and timely management make it possible to continue a patient's quality of life and maintain compliance; however if these adverse events (AEs are not managed appropriately, and become more severe, treatment cessation may be warranted compromising clinical outcome. Strategies to improve the assessment and management of TKI related skin AEs are therefore essential to ensure compliance with TKI therapy, thereby enabling patients to achieve optimal benefits. This article provides a consensus on practical recommendation for the prevention and management of diarrhoea and rash in Non-Small Cell Lung Cancer (NSCLC patients receiving TKIs.

  9. The Clinical Significance of β-arrestin 2 Expression in the Serum of 
Non-small Cell Lung Cancer Patients

    Directory of Open Access Journals (Sweden)

    Zhengqing WU

    2011-06-01

    Full Text Available Background and objective Non-small cell lung cancer (NSCLC with high morbidity and mortality is the most common types of lung cancer. beta-arrestin 2 is a kind of soluble protein regulating signal transduction mediated by G protein coupling receptor. The aim of this research is to evaluate the clinical significance of β-arrestin 2 expression in the serum of NSCLC patients. Methods The clinical and follow-up data of 20 healthy candidates and 67 patients diagnosed with NSCLC in Sun Yat-sen University Cancer Center from January 2005 to December 2006 was retrospectively analyzed. ELISA was applied to detect the expression of beta-arrestin 2. Results The serum level of β-arrestin 2 in NSCLC patients were all significally lower than those in healthy controls (P<0.001, P<0.001, P<0.001. The serum level of β-arrestin 2 in stage I NSCLC patients were higher than those in stage III as well as in stage IV (P<0.001, P<0.001. No statistical difference of β-arrestin 2’ serum level was found between with stage III and stage IV patients (P=0.273. Univariate prognostic factor analyzed by Kaplan-Meier method indicated patients’ prognosis with high serum level of β-arrestin 2 was better than patients with low and middle (P<0.001, P<0.001. The serum level of β-arrestin 2 and the stage of NSCLC signally affected prognosis in COX regression model (P=0.003, P=0.004. Conclusion The serum level of β-arrestin 2 had significant difffrence between NSCLC patients and healthy controls, likewise between the early and advanced NSCLC patients. The serum level of β-arrestin 2 affected NSCLC patients’ prognosis.

  10. Genetic polymorphisms and non-small-cell lung cancer: future paradigms

    Energy Technology Data Exchange (ETDEWEB)

    Mello, Ramon Andrade Bezerra de [Serviço de Oncologia Médica, Instituto Português de Oncologia Francisco Gentil, Porto (Portugal); Departamento de Ciências Biomédicas e Medicina, Universidade do Algarve, Faro (Portugal)

    2014-07-01

    This article addresses some current issues about genetic polymorphisms studied in the non-small-cell lung cancer translational field. Furthermore, it discusses about new potential biomarkers regarding lung cancer risk and prognosis.

  11. 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

  12. N2 disease in non-small cell lung cancer patients, diagnosis and evaluation: a Turkish chest surgeon's perspective

    Institute of Scientific and Technical Information of China (English)

    Alper TOKER

    2008-01-01

    Mediastinal or N2 disease is the most important factor in selecting the optimal treatment strategy in patients without distant metastasis. A direct surgical resection has not generally been accepted as a treatment modality in whom media.stinal nodal involvement is demonstrated. Patients with lung cancer can be diagnosed as clinical N2 disease based on CT and PET-CT characteristics of the mediastinum and the clinical presentation. Invasive diagnostic modalities used in the detection of N2 disease are: mediastinoscopy, endoesophageal ultrasound guided biopsy (EUS), transbronchial needle aspiration (TBNA), endobronehial ultrasound guided biopsy (EBUS), video-assisted thoracoscopic surgery (VATS),and mediastinotomy/extended mediastinoacopy. In this article, the author discusses about invasive and noninvasive techniques on the evaluation of mediastinal disease and presents his experience on this topic.

  13. Detection and Evaluation of EGFR Mutation Status in Serum of Patients with Advanced Non-small Cell Lung Cancer Treated with EGFR-TKIs

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    Ling MA

    2013-06-01

    Full Text Available Background and objective Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs has shown a high response rate in the treatment of lung cancer in patients with (EGFR mutation. The aim of this study is to evaluate the relationship between EGFR mutation status in serum and predicting benefit from EGFR-TKIs therapy in patients with advanced non-small cell lung cancer (NSCLC. Methods We examined EGFR mutation status in serum of 80 patients with advanced, EGFR-TKIs given as first-line therapy NSCLC. All patients were received long-term follow-up, and the drug efficacy were observed and evaluated. Results The EGFR mutation in serum was detected in 33.8% (27/80 of NSCLC patients examined, in which exon 19 deletion mutation was present at a frequency of 44.4% (12/27 and exon 21 point mutation was 55.6% (15/27; The response rate to EGFR-TKI in patients with EGFR mutation in serum was (55.6%, 15/27, which was remarkably higher than that in EGFR wild-type patients (17.0%, 9/53, the difference was statistically significant (χ2=0.370, P<0.001; The median progression free survival (PFS of patients with EGFR mutation in serum was remarkably better than that of EGFR wild-type patients (9.8 months vs 5.7 months, P=0.014. Conclusion In patients with advanced, EGFR-positive in serum NSCLC, EGFR-TKIs given as first-line therapy is associated with improved drug efficacy. The results suggest that it is feasible to use serum to detect EGFR mutation, which can predict a benefit from EGFR-TKIs given as first-line therapy.

  14. Optimizing Treatment Risk and Benefit for Elderly Patients With Advanced Non-Small-Cell Lung Cancer: The Right Treatment for the Right Patient.

    Science.gov (United States)

    Presley, Carolyn J; Gross, Cary P; Lilenbaum, Rogerio C

    2016-05-01

    The Oncology Grand Rounds series is designed to place original reports published in theJournal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published inJournal of Clinical Oncology, to patients seen in their own clinical practice.A 78-year-old woman with a 40-pack-year smoking history has been referred for treatment of advanced non-small-cell lung cancer. She presented with a persistent cough and worsening dyspnea on exertion. A chest x-ray followed by a chest computed tomography scan revealed a 3-cm right upper lobe mass along with a moderate-size pleural effusion. Pleural fluid cytology was positive for adenocarcinoma. A brain magnetic resonance imaging scan was negative. A reflex molecular profile, includingKRAS,EGFR,ALK,BRAF,HER2,RET,MET, andROS, did not reveal an actionable abnormality. Her past medical history includes diabetes, hypertension, and osteopenia. Her medications include a β-blocker, angiotensin-converting enzyme inhibitor, oral antidiabetic agent, calcium, and vitamin D. The laboratory evaluation is notable for a hemoglobin of 10.8 g/dL and a creatinine clearance of 36 mL/min. The other laboratories are within normal limits. She is somewhat limited by the shortness of breath but maintains an Eastern Cooperative Oncology Group performance status of 1. She is independent in all of her instrumental and basic activities of daily living and denies falls. She has been referred to discuss treatment options.

  15. Curative Treatment of Stage I Non-Small-Cell Lung Cancer in Patients With Severe COPD: Stereotactic Radiotherapy Outcomes and Systematic Review

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    Palma, David, E-mail: david.palma@uwo.ca [VU University Medical Center, Amsterdam (Netherlands); Division of Radiation Oncology, London Regional Cancer Program, London, Ontario (Canada); Lagerwaard, Frank [VU University Medical Center, Amsterdam (Netherlands); Rodrigues, George [Division of Radiation Oncology, London Regional Cancer Program, London, Ontario (Canada); Haasbeek, Cornelis; Senan, Suresh [VU University Medical Center, Amsterdam (Netherlands)

    2012-03-01

    Objectives: Patients with severe chronic obstructive pulmonary disease (COPD) have a high risk of lung cancer and of postsurgical complications. We studied outcomes after stereotactic body radiotherapy (SBRT) in patients with severe COPD, as defined by Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria, and performed a systematic review of the literature on outcomes after SBRT or surgery in these patients. Methods: A single-institution cohort of 176 patients with COPD GOLD III-IV and Stage I non-small-cell lung cancer (NSCLC) treated with SBRT was evaluated. A systematic review identified studies reporting outcomes after SBRT or surgery for Stage I NSCLC in patients with GOLD III-IV or a predicted postoperative forced expiratory volume in 1 second (FEV1) of {<=}40%. Results: In the single-institution cohort, median follow-up was 21 months and median overall survival (OS) was 32 months. Actuarial 3-year local control was 89%, and 1- and 3-year OS were 79% and 47%, respectively. COPD severity correlated with OS (p = 0.01). The systematic review identified four other studies (two surgical, two SBRT, n = 196 patients). SBRT studies were published more recently and included older patients than surgical studies. Mean 30-day mortality was 0% post-SBRT and 10% after surgery. Local or locoregional control was high ({>=}89%) after both treatments. Post-SBRT, actuarial OS was 79-95% at 1 year and 43-70% at 3 years. Postsurgical actuarial OS was 45-86% at 1 year and 31-66% at 3 years. Conclusions: SBRT and surgery differ in risk of 30-day mortality in patients with severe COPD. Despite the negative selection of SBRT patients, survival at 1 and 3 years is comparable between the two treatments.

  16. [Safety and effectiveness of pemetrexed in patients with non-small cell lung cancer in Japan - analysis of post-marketing surveillance].

    Science.gov (United States)

    Okubo, Sumiko; Kobayashi, Noriko; Taketsuna, Masanori; Kaneko, Naoya; Enatsu, Sotaro; Nishiuma, Shinichi

    2014-04-01

    The safety and effectiveness of pemetrexed(PEM)in patients with non-small cell lung cancer(NSCLC)were reviewed using data from post-marketing surveillance. Among 699 patients registered from June 2009 to May 2010, 683 patients were analyzed(343, first-line therapy: 340, second-line therapy or beyond). Patient backgrounds were as follows: median age=65 years(16.1%B75 years old); 64.7% male; 91.9% performance status 0-1; 83.2% Stage IV; 99.0% non-squamous cell cancer. Also, 86% of the first-line and 20% of the second-line cohort were receiving a concomitant anti-cancer drug(mostly platinum agents). The incidence rate of adverse drug reactions(ADR)was 76.7%, including serious cases(18.0%). The most common ADRs were decreased white blood cell count(26.8%), decreased neutrophil count(25.3%), anemia(19.2%), decreased platelet count(17.0%), and nausea(23.0%). The incidence of interstitial lung disease, which is a concern during chemotherapy, was 2.6%. Peripheral neuropathy and alopecia, events influencing a patient's quality of life, were less than 1%. The estimated median survival time was 23.2 months[95%CI: 19.8 months-not calculable]in the first-line cohort, and 11.8 months[95% CI: 10.5-13.7 months]in the B second-line cohort. The surveillance results showed no apparent difference in total ADRs in this current study compared to the safety profile established in clinical trials previously conducted in Japan and overseas. These results demonstrate the safety and effectiveness of PEM treatment for NSCLC patients in daily clinical settings.

  17. Gene expression profiles of ERCC1, TYMS, RRM1, TUBB3 and EGFR in tumor tissue from non-small cell lung cancer patients

    Institute of Scientific and Technical Information of China (English)

    Yu Daping; Li Jie; Han Yi; Liu Shuku; Xiao Ning; Li Yunsong; Sun Xiaojun

    2014-01-01

    Background Personalized medicine becomes essential in lung cancer treatment,however lung-cancer-related gene expression profiles in Chinese patients remain unknown.In this study,the correlation of gene expression profiles and clinical characteristics in non-small-cell lung cancer (NSCLC) was investigated.Methods Seventy-six Chinese patients with NSCLC were enrolled in the study to investigate mRNA expression profiles of excision repair cross complement group 1 (ERCC1),thymidylate synthetase (TYMS),ribonucleotide reductase (RRM1),class Ⅲ β-tubulin (TUBB3),and epidermal growth factor receptor (EGFR) genes and their correlation with patient clinical characteristics.A novel liquidchip technology was used to detect mRNA expression levels in formalin fixed paraffin embedded tumor pathology samples.The relationships between gene expression and clinical characteristics were assessed using the Mann-Whitney test.Results ERCC1 mRNA levels were higher in tumors from patients with metastatic disease than patients with nonmetastatic disease (P=0.021),and higher in adenocarcinomas than squamous cell carcinomas (P=0.006).Increased TUBB3 mRNA expression levels were found in patients with performance status (PS) 1 in comparison with PS 0 (P=0.049),with poorly differentiated tumors in comparison with tumors that were moderately and well differentiated (P ≤0.000 1),and with advanced stage in comparison with early stage disease (P≤0.000 1).Conclusions ERCC1 mRNA levels were higher in metastatic adenocarcinoma NSCLC; TUBB3 mRNA levels were significantly higher in poody differentiated tumors and in advanced stage NSCLC,which indicates the poor prognosis.

  18. The relationship between tyrosine kinase inhibitor therapy and overall survival in patients with non-small cell lung cancer carrying EGFR mutations

    Institute of Scientific and Technical Information of China (English)

    Hidekazu Suzuki; Tomonori Hirashima; Norio Okamoto; Tadahiro Yamadori; Motohiro Tamiya; Naoko Morishita; Takayuki Shiroyama

    2013-01-01

    For patients with epidermal growth factor receptor (EGFR) mutation-positive lung cancer,the relationship between the dose or duration of treatment with tyrosine kinase inhibitor (TKI) and overall survival remains unclear.Here,we analyzed clinical data of 39 patients who were diagnosed with EGFR mutation-positive non-small cell lung cancer and treated with TKI,but subsequently died.Several parameters were measured in this study:overall survival; first,second,and overall TKI therapy durations;first TKI intensity (actual dose/normal dose); and TKI rate (overall TKI therapy duration/overall survival).The response rate to TKI therapy was 50%,and the median survival was 553 days.After TKI therapy failed,38.5% patients were re-challenged with TKI.We observed a moderate relationship [r =0.534,95%confidential interval (CI) =0.263 to 0.727,P < 0.001] between overall TKI therapy duration and overall survival.However,we found no relationship between overall survival and first TKI intensity (r =0.073,95%CI =-0.380 to 0.247,P =0.657) or TKI rate (r =0.0345,95% CI =-0.284 to 0.346,P =0.835).Nonsmall cell lung cancer patients with mutation-positive tumors remained on TKI therapy for,on average,33% of the overall survival time.These findings suggest that patients with EGFR mutation-positive tumors should not stick to using TKIs.

  19. A Panel of Genetic Polymorphism for the Prediction of Prognosis in Patients with Early Stage Non-Small Cell Lung Cancer after Surgical Resection.

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    Shin Yup Lee

    Full Text Available This study was conducted to investigate whether a panel of eight genetic polymorphisms can predict the prognosis of patients with early stage non-small cell lung cancer (NSCLC after surgical resection.We selected eight single nucleotide polymorphisms (SNPs which have been associated with the prognosis of lung cancer patients after surgery in our previous studies. A total of 814 patients with early stage NSCLC who underwent curative surgical resection were enrolled. The association of the eight SNPs with overall survival (OS and disease-free survival (DFS was analyzed.The eight SNPs (CD3EAP rs967591, TNFRSF10B rs1047266, AKT1 rs3803300, C3 rs2287845, HOMER2 rs1256428, GNB2L1 rs3756585, ADAMTSL3 rs11259927, and CD3D rs3181259 were significantly associated with OS and/or DFS. Combining those eight SNPs, we designed a prognostic index to predict the prognosis of patients. According to relative risk of death, a score value was assigned to each genotype of the SNPs. A worse prognosis corresponded to a higher score value, and the sum of score values of eight SNPs defined the prognostic index of a patient. When we categorized the patients into two groups based on the prognostic index, high risk group was significantly associated with worse OS and DFS compared to low risk group (aHR for OS = 2.21, 95% CI = 1.69-2.88, P = 8.0 x 10-9, and aHR for DFS = 1.58, 95% CI = 1.29-1.94, P = 1.0 x 10-5.Prognostic index using eight genetic polymorphisms may be useful for the prognostication of patients with surgically resected NSCLC.

  20. Neuromuscular electrical stimulation of the quadriceps in patients with non-small cell lung cancer receiving palliative chemotherapy: a randomized phase II study.

    Directory of Open Access Journals (Sweden)

    Matthew Maddocks

    Full Text Available A reduced exercise capacity is associated with increased morbidity and mortality in patients with advanced non-small cell lung cancer (NSCLC. Therapeutic exercise can be beneficial and neuromuscular electrical stimulation (NMES of the quadriceps muscles may represent a practical approach. The primary aim of this study was to determine the acceptability of NMES of the quadriceps to patients with NSCLC used alongside palliative chemotherapy. Secondary aims explored aspects of safety and efficacy of NMES in this setting.Patients with advanced NSCLC due to receive first-line palliative chemotherapy were randomized to usual care with or without NMES. They were asked to undertake 30 minute sessions of NMES, ideally daily, but as a minimum, three times weekly. For NMES to be considered acceptable, it was predetermined that ≥80% of patients should achieve this minimum level of adherence. Qualitative interviews were held with a subset of patients to explore factors influencing adherence. Safety was assessed according to the Common Terminology Criteria for Adverse Events. Quadriceps muscle strength, thigh lean mass, and physical activity level were assessed at baseline and after three cycles of chemotherapy.49 patients (28 male, median (IQR age 69 (64-75 years participated. Of 30 randomized to NMES, 18 were eligible for the primary endpoint, of whom 9 (50% [90% CI, 29 to 71] met the minimum level of adherence. Adherence was enhanced by incorporating sessions into a daily routine and hindered by undesirable effects of chemotherapy. There were no serious adverse events related to NMES, nor significant differences in quadriceps muscle strength, thigh lean mass or physical activity level between groups.NMES is not acceptable in this setting, nor was there a suggestion of benefit. The need remains to explore NMES in patients with cancer in other settings.Current Controlled Trials ISRCTN 42944026 www.controlled-trials.com/ISRCTN42944026.

  1. Overview of KRAS-Driven Genetically Engineered Mouse Models of Non-Small Cell Lung Cancer.

    Science.gov (United States)

    Sheridan, Clare; Downward, Julian

    2015-01-01

    KRAS, the most frequently mutated oncogene in non-small cell lung cancer, has been utilized extensively to model human lung adenocarcinomas. The results from such studies have enhanced considerably an understanding of the relationship between KRAS and the development of lung cancer. Detailed in this overview are the features of various KRAS-driven genetically engineered mouse models (GEMMs) of non-small cell lung cancer, their utilization, and the potential of these models for the study of lung cancer biology.

  2. Distribution Atlas of Proliferating Bone Marrow in Non-Small Cell Lung Cancer Patients Measured by FLT-PET/CT Imaging, With Potential Applicability in Radiation Therapy Planning

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    Campbell, Belinda A., E-mail: Belinda.Campbell@petermac.org [Department of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, East Melbourne (Australia); Callahan, Jason [Centre for Molecular Imaging, Peter MacCallum Cancer Centre, East Melbourne (Australia); Bressel, Mathias [Centre for Biostatistics and Clinical Trials, Peter MacCallum Cancer Centre, East Melbourne (Australia); Simoens, Nathalie [Centre for Molecular Imaging, Peter MacCallum Cancer Centre, East Melbourne (Australia); Everitt, Sarah [Radiotherapy Services, Peter MacCallum Cancer Centre, East Melbourne (Australia); Hofman, Michael S.; Hicks, Rodney J. [Centre for Molecular Imaging, Peter MacCallum Cancer Centre, East Melbourne (Australia); Burbury, Kate [Department of Haematology, Peter MacCallum Cancer Centre, East Melbourne (Australia); MacManus, Michael [Department of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, East Melbourne (Australia)

    2015-08-01

    Purpose: Proliferating bone marrow is exquisitely sensitive to ionizing radiation. Knowledge of its distribution could improve radiation therapy planning to minimize unnecessary marrow exposure and avoid consequential prolonged myelosuppression. [18F]-Fluoro-3-deoxy-3-L-fluorothymidine (FLT)–positron emission tomography (PET) is a novel imaging modality that provides detailed quantitative images of proliferating tissues, including bone marrow. We used FLT-PET imaging in cancer patients to produce an atlas of marrow distribution with potential clinical utility. Methods and Materials: The FLT-PET and fused CT scans of eligible patients with non-small cell lung cancer (no distant metastases, no prior cytotoxic exposure, no hematologic disorders) were reviewed. The proportions of skeletal FLT activity in 10 predefined bony regions were determined and compared according to age, sex, and recent smoking status. Results: Fifty-one patients were studied: 67% male; median age 68 (range, 31-87) years; 8% never smokers; 70% no smoking in the preceding 3 months. Significant differences in marrow distribution occurred between sex and age groups. No effect was detected from smoking in the preceding 3 months. Using the mean percentages of FLT uptake per body region, we created an atlas of the distribution of functional bone marrow in 4 subgroups defined by sex and age. Conclusions: This atlas has potential utility for estimating the distribution of active marrow in adult cancer patients to guide radiation therapy planning. However, because of interindividual variation it should be used with caution when radiation therapy risks ablating large proportions of active marrow; in such cases, individual FLT-PET scans may be required.

  3. Interstitial lung disease in gefitinib-treated Japanese patients with non-small cell lung cancer – a retrospective analysis: JMTO LC03-02

    Directory of Open Access Journals (Sweden)

    Tada Harue

    2009-08-01

    Full Text Available Abstract Background In Japan, high incidences of interstitial lung disease (ILD and ILD-related deaths have been reported among gefitinib-treated patients with non-small cell lung cancer (NSCLC. We investigated the efficacy of gefitinib, the incidence of ILD and risk factors for ILD in these patients. Findings We obtained patient data retrospectively using questionnaires sent to 22 institutions. We asked for demographic and clinical data on NSCLC patients for whom gefitinib treatment had begun between July 2002 and February 2003. Data from a total of 526 patients were analyzed. The patient characteristics were as follows: 64% male, 69% with adenocarcinoma, 61% with a performance score of 0–1, and 5% with concurrent interstitial pneumonitis. The objective response proportion was 80/439 (18.2%; 95% CI: 14.7–22.0. ILD developed in 17 patients (3.2%; 95% CI 1.9–5.1%, of whom 7 died. According to multivariate analysis, female sex, history of prior chemotherapy, low absolute neutrophil count before gefitinib treatment, and adenocarcinoma histology were associated with response to gefitinib treatment. None of the factors we evaluated were associated with the development of ILD. Conclusion The results of this study are consistent with previously published values for treatment response proportions and incidence of ILD during gefitinib treatment in Japanese patients. Future studies should be aimed at identifying factors indicating that a patient has a high probability of receiving benefit from gefitinib and a low risk of developing ILD.

  4. Vorinostat and bortezomib as third-line therapy in patients with advanced non-small cell lung cancer: a Wisconsin Oncology Network Phase II study

    Science.gov (United States)

    Campbell, Toby C.; Zhang, Chong; Kim, KyungMann; Kolesar, Jill M.; Oettel, Kurt R.; Blank, Jules H.; Robinson, Emily G.; Ahuja, Harish G.; Kirschling, Ron J.; Johnson, Peter H.; Huie, Michael S.; Wims, Mary E.; Larson, Martha M.; Hernan, Hilary R.; Traynor, Anne M.

    2014-01-01

    Summary Introduction The primary objective of this phase II trial was to evaluate the efficacy and tolerability of vorinostat and bortezomib as third-line therapy in advanced non-small cell lung cancer (NSCLC) patients. Methods Eligibility criteria included recurrent/metastatic NSCLC, having received 2 prior systemic regimens, and performance status 0–2. Patients took vorinostat 400 mg PO daily days 1–14 and bortezomib 1.3 mg/m2 IV day 1, 4, 8 and 11 in a 21-day cycle. Primary endpoint was 3-month progression free survival (3m-PFS), with a goal of at least 40 % of patients being free of progression at that time point. This study followed a two-stage minimax design. Results Eighteen patients were enrolled in the first stage. All patients had two prior lines of treatment. Patients received a median of two treatment cycles (range: 1–6) on study. There were no anti-tumor responses; stable disease was observed in 5 patients (27.8 %). Median PFS was 1.5 months, 3m-PFS rate 11.1 %, and median overall survival 4.7 months. The most common grade 3/4 toxicities were thrombocytopenia and fatigue. Two patients who had baseline taxane-related grade 1 peripheral neuropathy developed grade 3 neuropathy. The study was closed at its first interim analysis for lack of efficacy. Conclusions Bortezomib and vorinostat displayed minimal anti-tumor activity as third-line therapy in NSCLC. We do not recommend this regimen for further investigation in unselected patients. PMID:23728919

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

    Directory of Open Access Journals (Sweden)

    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.

  6. Analysis of Expression of Vascular Endothelial Growth Factor A and Hypoxia Inducible Factor-1alpha in Patients Operated on Stage I Non-Small-Cell Lung Cancer

    Science.gov (United States)

    Honguero Martínez, Antonio Francisco; Arnau Obrer, Antonio; Figueroa Almánzar, Santiago; León Atance, Pablo; Guijarro Jorge, Ricardo

    2014-01-01

    Objectives. Recent studies show that expression of hypoxia inducible factor-1alpha (HIF-1α) favours expression of vascular endothelial growth factor A (VEGF-A), and these biomarkers are linked to cellular proliferation, angiogenesis, and metastasis in different cancers. We analyze expression of HIF-1α and VEGF-A to clinicopathologic features and survival of patients operated on stage I non-small-cell lung cancer. Methodology. Prospective study of 52 patients operated on with stage I. Expression of VEGF-A and HIF-1α was performed through real-time quantitative polymerase chain reaction (qRT-PCR). Results. Mean age was 64.7 and 86.5% of patients were male. Stage IA represented 23.1% and stage IB 76.9%. Histology classification was 42.3% adenocarcinoma, 34.6% squamous cell carcinoma, and 23.1% others. Median survival was 81.0 months and 5-year survival 67.2%. There was correlation between HIF-1α and VEGF-A (P = 0.016). Patients with overexpression of HIF-1α had a tendency to better survival with marginal statistical significance (P = 0.062). Patients with overexpression of VEGF-A had worse survival, but not statistically significant (P = 0.133). Conclusion. The present study revealed that VEGF-A showed correlation with HIF-1α. HIF-1α had a tendency to protective effect with a P value close to statistical significance. VEGF-A showed a contrary effect but without statistical significance. PMID:26316946

  7. Percutaneous Lung Thermal Ablation of Non-surgical Clinical N0 Non-small Cell Lung Cancer: Results of Eight Years’ Experience in 87 Patients from Two Centers

    Energy Technology Data Exchange (ETDEWEB)

    Palussiere, Jean, E-mail: J.Palussiere@bordeaux.unicancer.fr [Institut Bergonié, Comprehensive Cancer Centre, Department of Interventional Radiology (France); Lagarde, Philippe, E-mail: P.Lagarde@bordeaux.unicancer.fr [Institut Bergonié, Comprehensive Cancer Center, Radiation Oncology Department (France); Aupérin, Anne, E-mail: auperin@igr.fr [Institut Gustave-Roussy, Unit of Biostatistics and Epidemiology (France); Deschamps, Frédéric, E-mail: frederic.deschamps@igr.fr [Institut Gustave-Roussy, Department of Interventional Radiology (France); Chomy, François, E-mail: F.Chomy@bordeaux.unicancer.fr [Institut Bergonié, Comprehensive Cancer Center, Department of medical oncology (France); Baere, Thierry de, E-mail: debaere@igr.fr [Institut Gustave-Roussy, Department of Interventional Radiology (France)

    2015-02-15

    PurposeTo evaluate the survival outcomes of percutaneous thermal ablation (RFA + microwaves) for patients presenting N0 non-small-cell lung cancer (NSCLC) ineligible for surgery.Materials and MethodsEighty-seven patients from two comprehensive cancer centers were included. Eighty-two patients were treated with RFA electrodes and five with microwave antenna. Overall survival (OS) and disease-free survival (DFS) were estimated and predictive factors of local tumor progression, OS and DFS identified and compared by univariate and multivariate analysesResultsMedian follow-up was 30.5 months (interquartile range 16.7–51) and tumor size was 21 mm (range 10–54 mm). Treatment was incomplete for 14 patients with a local tumor progression of 11.5, 18.3, and 21.1 % at 1, 2, and 3 years, respectively. Two patients presented with neurological (grade III or IV) complications, and one died of respiratory and multivisceral failure as a result of the procedure at 29 days. In univariate analysis, increasing tumor size (P = 0.003) was the only predictive factor related to risk of local tumor progression. 5-year OS and DFS were 58.1 and 27.9 %, respectively. Sex (P = 0.044), pathology (P = 0.032), and tumor size >2 cm (P = 0.046) were prognostic factors for DFS. In multivariate analysis, pathology (P = 0.033) and tumor size >2 cm (P = 0.032) were independent prognostic factors for DFS.ConclusionsOversized and overlapping ablation of N0 NSCLC was well tolerated, effective, with few local tumor progressions, even over long-term follow-up. Increasing tumor size was the main prognostic factor linked to OS, DFS, and local tumor progression.

  8. Using machine learning to predict radiation pneumonitis in patients with stage I non-small cell lung cancer treated with stereotactic body radiation therapy

    Science.gov (United States)

    Valdes, Gilmer; Solberg, Timothy D.; Heskel, Marina; Ungar, Lyle; Simone, Charles B., II

    2016-08-01

    To develop a patient-specific ‘big data’ clinical decision tool to predict pneumonitis in stage I non-small cell lung cancer (NSCLC) patients after stereotactic body radiation therapy (SBRT). 61 features were recorded for 201 consecutive patients with stage I NSCLC treated with SBRT, in whom 8 (4.0%) developed radiation pneumonitis. Pneumonitis thresholds were found for each feature individually using decision stumps. The performance of three different algorithms (Decision Trees, Random Forests, RUSBoost) was evaluated. Learning curves were developed and the training error analyzed and compared to the testing error in order to evaluate the factors needed to obtain a cross-validated error smaller than 0.1. These included the addition of new features, increasing the complexity of the algorithm and enlarging the sample size and number of events. In the univariate analysis, the most important feature selected was the diffusion capacity of the lung for carbon monoxide (DLCO adj%). On multivariate analysis, the three most important features selected were the dose to 15 cc of the heart, dose to 4 cc of the trachea or bronchus, and race. Higher accuracy could be achieved if the RUSBoost algorithm was used with regularization. To predict radiation pneumonitis within an error smaller than 10%, we estimate that a sample size of 800 patients is required. Clinically relevant thresholds that put patients at risk of developing radiation pneumonitis were determined in a cohort of 201 stage I NSCLC patients treated with SBRT. The consistency of these thresholds can provide radiation oncologists with an estimate of their reliability and may inform treatment planning and patient counseling. The accuracy of the classification is limited by the number of patients in the study and not by the features gathered or the complexity of the algorithm.

  9. 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.

  10. Effectiveness and safety of post-induction phase bevacizumab treatment for patients with non-small-cell lung cancer: results from the ARIES observational cohort study.

    Science.gov (United States)

    Kosty, Michael P; Wozniak, Antoinette J; Jahanzeb, Mohammad; Leon, Larry; Fish, Susan; Hazard, Sebastien J; Lynch, Thomas J

    2015-12-01

    Data from randomized, controlled trials suggest that post-induction phase (IP) treatment with bevacizumab may benefit patients with advanced non-small-cell lung cancer (NSCLC). Real-world clinical practice, however, can involve variable use and patterns of treatment in broader patient populations. To assess the effect of bevacizumab on post-IP overall survival (OS) following IP chemotherapy + bevacizumab, analyses were conducted in patients enrolled in the Avastin(®) Registry--Investigation of Effectiveness and Safety (ARIES) observational cohort study (OCS) who received post-IP bevacizumab. ARIES was a large, prospective OCS of patients who received chemotherapy in combination with bevacizumab for the first-line treatment of NSCLC. This unplanned, post hoc analysis included patients who received chemotherapy and bevacizumab and who did not have progressive disease through the completion of IP treatment. A dichotomous analysis compared outcomes in patients who did and did not receive bevacizumab before a landmark date of day 30 post IP. A cumulative exposure analysis used a time-dependent Cox regression model to assess the effect of cumulative post-IP bevacizumab exposure on post-IP OS. In the dichotomous analysis, the duration of post-IP OS was significantly longer in patients who received post-IP bevacizumab; median post-IP OS was 15.6 vs. 11.3 months, respectively (hazard ratio [HR] = 0.80; 95 % confidence interval 0.71-0.91; P post-IP OS by 2.7 %, on average. In conclusion, post-IP bevacizumab exposure was associated with improved post-IP OS in patients with advanced NSCLC who were enrolled in the ARIES OCS.

  11. 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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  12. Weekly gemcitabine as a radiosensitiser for the treatment of brain metastases in patients with non-small cell lung cancer:phase I trial

    Institute of Scientific and Technical Information of China (English)

    HUANG Yu-juan; WU Yi-long; XIE Song-xi; YANG Jing-ji; HUANG Yi-sheng; LIAO Ri-qiang

    2007-01-01

    Background Conventional treatment for non-small cell lung cancer (NSCLC) brain metastases (BM) is whole-brain radiotherapy (WBRT). The efficacy is limited. It might be increased by a Potent radiosensitizer such as gemcitabine,which is believed to cross the disrupted blood-brain barrier. The primary objective of this study was to determine the maximum tolerated dose (MTD) of weekly gemcitabine given concurrently with WBRT.Methods Patients with BM from NSCLC were included. The dose of WBRT was 3750 cGy (total 15 times, 3 weeks).Gemcitabine was given concurrently with WBRT on days 1, 8 and 15. The starting dose was 400 mg/m2, escalated by100 mg/m2 increments. At least three patients were included per level. Dose limiting toxicity (DLT) was defined as grade 4hematological or grade 2 neurological toxicity. When two or more patients experience DLT, the MTD was reached.Results A total of 16 patients were included; 69% had a performance status (PS) 1 (Eastern Cooperative Oncology Group, ECOG). A total of 69% had concurrent active extra cranial diseases. All had more than 3 BM. Up to 600 mg/m2(Ievel 3) no neurology toxicity was observed. At 600 mg/m2 two out of 9 patients developed grade 4 thrombocytopenia.One of the two patients' thrombocytopenia was confused with disseminated intravascular coagulation (DIC). At 700mg/m2 two out of 4 patients developed neurotoxicities. One developed grade 3 seizure and cognitive disorder. Another patient developed suspected grade 2 muscle weakness.Conclusions The MTD was reached at a dose of 700 mg/m2. The dose of 600 mg/m2 would be considered for further study.

  13. The impact of both platinum-based chemotherapy and EGFR-TKIs on overall survival of patients with advanced non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    Jian-Wei Zhang; Wen-Feng Fang; Yu-Xiang Ma; Li Zhang; Yuan-Yuan Zhao; Ying Guo; Cong Xue; Zhi-Huang Hu; Yan Huang; Hong-Yun Zhao; Jing Zhang; Xuan Wu

    2014-01-01

    Both platinum-based doublet chemotherapy (PBC) and epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) prolong the survival of patients with advanced non-small cell lung cancer (NSCLC). In early studies, most patients underwent PBC as first-line treatment, but not all patients could afford EGFR-TKIs as second-line treatment. To understand the impact of PBC and EGFR-TKIs on NSCLC prognosis, we evaluated the association between the receipt of both regimens and overall survival (OS). Using MEDLINE and EMBASE, we identified prospective, randomized, controlled phase III clinical trials in advanced NSCLC that met the inclusion criteria: in general population with advanced NSCLC, the percentage of patients treated with both PBC and EGFR-TKIs was available in the trial and OS was reported. After collecting data from the selected trials, we correlated the percentage of patients treated with both PBC and EGFR-TKIs with the reported OS, using a weighted analysis. Fifteen phase III clinical trials-involving 11,456 adult patients in 32 arms-were included in the analysis, including 6 trials in Asian populations and 9 in non-Asian (predominantly Caucasian) populations. The OS was positively correlated with the percentage of patients treated with both PBC and EGFR-TKIs (r = 0.797,P < 0.001). The correlation was obvious in the trials in Asian populations (r = 0.936,P < 0.001) but was not statisticaly significant in the trials in predominantly Caucasian populations (r = 0.116,P = 0.588). These results suggest that treatment with PBC and EGFR-TKIs may provide a survival benefit to patients with advanced NSCLC, highlighting the importance of having both modalities available for therapy.

  14. EGFR Mutations in Surgically Resected Fresh Specimens from 697 Consecutive Chinese Patients with Non-Small Cell Lung Cancer and Their Relationships with Clinical Features

    Directory of Open Access Journals (Sweden)

    Yuanyang Lai

    2013-12-01

    Full Text Available We aimed to reveal the true status of epidermal growth factor receptor (EGFR mutations in Chinese patients with non-small cell lung cancer (NSCLC after lung resections. EGFR mutations of surgically resected fresh tumor samples from 697 Chinese NSCLC patients were analyzed by Amplification Refractory Mutation System (ARMS. Correlations between EGFR mutation hotspots and clinical features were also explored. Of the 697 NSCLC patients, 235 (33.7% patients had tyrosine kinase inhibitor (TKIs sensitive EGFR mutations in 41 (14.5% of the 282 squamous carcinomas, 155 (52.9% of the 293 adenocarcinomas, 34 (39.5% of the 86 adenosquamous carcinomas, one (9.1% of the 11 large-cell carcinomas, 2 (11.1% of the 18 sarcomatoid carcinomas, and 2 (28.6% of the 7 mucoepidermoid carcinomas. TKIs sensitive EGFR mutations were more frequently found in female patients (p < 0.001, non-smokers (p = 0.047 and adenocarcinomas (p < 0.001. The rates of exon 19 deletion mutation (19-del, exon 21 L858R point mutation (L858R, exon 21 L861Q point mutation (L861Q, exon 18 G719X point mutations (G719X, including G719C, G719S, G719A were 43.4%, 48.1%, 1.7% and 6.8%, respectively. Exon 20 T790M point mutation (T790M was detected in 3 squamous carcinomas and 3 adenocarcinomas and exon 20 insertion mutation (20-ins was detected in 2 patients with adenocarcinoma. Our results show the rates of EGFR mutations are higher in all types of NSCLC in Chinese patients. 19-del and L858R are two of the more frequent mutations. EGFR mutation detection should be performed as a routine postoperative examination in Chinese NSCLC patients.

  15. Can radiomics features be reproducibly measured from CBCT images for patients with non-small cell lung cancer?

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    Fave, Xenia, E-mail: xjfave@mdanderson.org; Fried, David [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030 and The University of Texas Graduate School of Biomedical Sciences at Houston, 6767 Bertner Avenue, Houston, Texas 77030 (United States); Mackin, Dennis; Yang, Jinzhong; Zhang, Joy; Balter, Peter; Followill, David [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030 (United States); Gomez, Daniel [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030 (United States); Kyle Jones, A. [Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030 (United States); Stingo, Francesco [Department of Biostatistics, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030 (United States); Fontenot, Jonas [Mary Bird Perkins Cancer Center, 4950 Essen Lane, Baton Rouge, Louisiana 70809 (United States); Court, Laurence [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030 and Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030 (United States)

    2015-12-15

    Purpose: Increasing evidence suggests radiomics features extracted from computed tomography (CT) images may be useful in prognostic models for patients with nonsmall cell lung cancer (NSCLC). This study was designed to determine whether such features can be reproducibly obtained from cone-beam CT (CBCT) images taken using medical Linac onboard-imaging systems in order to track them through treatment. Methods: Test-retest CBCT images of ten patients previously enrolled in a clinical trial were retrospectively obtained and used to determine the concordance correlation coefficient (CCC) for 68 different texture features. The volume dependence of each feature was also measured using the Spearman rank correlation coefficient. Features with a high reproducibility (CCC > 0.9) that were not due to volume dependence in the patient test-retest set were further examined for their sensitivity to differences in imaging protocol, level of scatter, and amount of motion by using two phantoms. The first phantom was a texture phantom composed of rectangular cartridges to represent different textures. Features were measured from two cartridges, shredded rubber and dense cork, in this study. The texture phantom was scanned with 19 different CBCT imagers to establish the features’ interscanner variability. The effect of scatter on these features was studied by surrounding the same texture phantom with scattering material (rice and solid water). The effect of respiratory motion on these features was studied using a dynamic-motion thoracic phantom and a specially designed tumor texture insert of the shredded rubber material. The differences between scans acquired with different Linacs and protocols, varying amounts of scatter, and with different levels of motion were compared to the mean intrapatient difference from the test-retest image set. Results: Of the original 68 features, 37 had a CCC >0.9 that was not due to volume dependence. When the Linac manufacturer and imaging protocol

  16. A planning study of radiotherapy dose escalation of PET-active tumour volumes in non-small cell lung cancer patients

    Energy Technology Data Exchange (ETDEWEB)

    Sloth Moeller, Ditte; Hoffmann, Lone (Dept. of Medical Physics, Aarhus Univ. Hospital, Aarhus (Denmark)), e-mail: dittmoel@rm.dk; Khalil, Azza Ahmed; Marquard Knap, Marianne (Dept. of Oncology, Aarhus Univ. Hospital, Aarhus (Denmark)); Muren, Ludvig Paul (Dept. of Medical Physics, Aarhus Univ. Hospital, Aarhus (Denmark); Dept. of Oncology, Aarhus Univ. Hospital, Aarhus (Denmark))

    2011-08-15

    Background. Patients with non-small cell lung cancer (NSCLC) have poor prognosis partly because of high local failure rates. Escalating the dose to the tumour may decrease the local failure rates and thereby, improve overall survival, but the risk of complications will limit the possibility to dose-escalate a broad range of patients. Escalating only PET-active areas of the tumour may increase the potential for reaching high doses for a variety of tumour sizes and locations. Material and methods. Ten patients were randomly chosen for a dose escalation planning study. A planning target volume (PTV) was defined on the mid-ventilation scan of a four-dimensional computed tomography (4D-CT) scan and a boost planning target volume (PTV-boost) was defined based on a positron emission tomography computed tomography (PET-CT) scan. Treatment plans were created aiming to reach the highest achievable of 74 Gy, 78 Gy or 82 Gy in 2 Gy per fraction prescribed to the PTV-boost without compromising normal tissue constraints and with the PTV prescribed in all cases a biological equivalent dose in 2 Gy fractions of 66 Gy. Results. Nine of ten patients could be escalated to the highest dose level (82 Gy), while one patient was limited by the oesophagus dose constraint and could only reach 74 Gy. Four patients could be dose-escalated above 82 Gy without compromising normal tissue constraints. Conclusion. Dose-escalating only the PET-active areas of lung tumours to doses of 82 Gy while respecting normal tissue constraints is feasible, also in a series of unselected patients including cases with relatively large tumours

  17. 18F-FDG uptake as a biologic factor predicting outcome in patients with resected non-small-cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    ZHANG Zhen-jiang; CHEN Jing-han; MENG Long; DU Jia-jun; ZHANG Lin; LIU Ying; DAI Hong-hai

    2007-01-01

    Background The outcome of surgical treatment of non-small-cell lung cancer (NSCLC) remains poor. In many patients the biological behavior of NSCLC does not follow a definite pattern, and can not be accurately predicted before treatment. 18F-fluoro-2-deoxy-glucose (18F-FDG) uptake on positron-emission tomography (PET) is associated with the aggressiveness of NSCLC. The present study focused on the role of 18F-FDG uptake in predicting the outcome of surgically treated patients with NSCLC.Methods A retrospective analysis was made of 82 patients who underwent complete resection and preoperative FDG PET. The maximum standardized uptake value (SUVmax), in addition to five clinicopathological factors and three biomolecular factors, which could possibly influence survival, was compared for possible association with patients' recurrence and survival, by the Log-rank test in univariate analysis and the Cox proportional hazards model in multivariate analysis. The association between SUVmax and other factors was also analyzed. Results Patients with SUVmax more than 11 had a disease-free survival and overall survival shorter than patients with SUVmax less than 11 in univariate analyses (P<0.001, P=0.002). In the multivariate analysis, SUVmax (dichotomized by 11) was the only significant predictor for tumor recurrence. TNM stage and SUVmax (dichotomized by 11) were independent predictors for the overall survival. Associations of SUVmax with p53 overexpression, proliferating cell nuclear antigen (PCNA) labeling index and microvascular density of the tumor were significant in the entire group. Conclusions 18F-FDG uptake on PET may be used to noninvasively assess biological aggressiveness of NSCLC in vivo, identifying the surgically-treated patients with poor prognosis who could benefit from additional therapy.

  18. 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.

  19. 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.

  20. A Validated Prediction Model for Overall Survival From Stage III Non-Small Cell Lung Cancer: Toward Survival Prediction for Individual Patients

    Energy Technology Data Exchange (ETDEWEB)

    Oberije, Cary, E-mail: cary.oberije@maastro.nl [Radiation Oncology, Research Institute GROW of Oncology, Maastricht University Medical Center, Maastricht (Netherlands); De Ruysscher, Dirk [Radiation Oncology, Research Institute GROW of Oncology, Maastricht University Medical Center, Maastricht (Netherlands); Universitaire Ziekenhuizen Leuven, KU Leuven (Belgium); Houben, Ruud [Radiation Oncology, Research Institute GROW of Oncology, Maastricht University Medical Center, Maastricht (Netherlands); Heuvel, Michel van de; Uyterlinde, Wilma [Department of Thoracic Oncology, Netherlands Cancer Institute, Amsterdam (Netherlands); Deasy, Joseph O. [Memorial Sloan Kettering Cancer Center, New York (United States); Belderbos, Jose [Department of Radiation Oncology, Netherlands Cancer Institute, Amsterdam (Netherlands); Dingemans, Anne-Marie C. [Department of Pulmonology, University Hospital Maastricht, Research Institute GROW of Oncology, Maastricht (Netherlands); Rimner, Andreas; Din, Shaun [Memorial Sloan Kettering Cancer Center, New York (United States); Lambin, Philippe [Radiation Oncology, Research Institute GROW of Oncology, Maastricht University Medical Center, Maastricht (Netherlands)

    2015-07-15

    Purpose: Although patients with stage III non-small cell lung cancer (NSCLC) are homogeneous according to the TNM staging system, they form a heterogeneous group, which is reflected in the survival outcome. The increasing amount of information for an individual patient and the growing number of treatment options facilitate personalized treatment, but they also complicate treatment decision making. Decision support systems (DSS), which provide individualized prognostic information, can overcome this but are currently lacking. A DSS for stage III NSCLC requires the development and integration of multiple models. The current study takes the first step in this process by developing and validating a model that can provide physicians with a survival probability for an individual NSCLC patient. Methods and Materials: Data from 548 patients with stage III NSCLC were available to enable the development of a prediction model, using stratified Cox regression. Variables were selected by using a bootstrap procedure. Performance of the model was expressed as the c statistic, assessed internally and on 2 external data sets (n=174 and n=130). Results: The final multivariate model, stratified for treatment, consisted of age, gender, World Health Organization performance status, overall treatment time, equivalent radiation dose, number of positive lymph node stations, and gross tumor volume. The bootstrapped c statistic was 0.62. The model could identify risk groups in external data sets. Nomograms were constructed to predict an individual patient's survival probability ( (www.predictcancer.org)). The data set can be downloaded at (https://www.cancerdata.org/10.1016/j.ijrobp.2015.02.048). Conclusions: The prediction model for overall survival of patients with stage III NSCLC highlights the importance of combining patient, clinical, and treatment variables. Nomograms were developed and validated. This tool could be used as a first building block for a decision support system.

  1. The Response, Outcome and Toxicity of Aggressive Palliative Thoracic Radiotherapy for Metastatic Non-Small Cell Lung Cancer Patients with Controlled Extrathoracic Diseases.

    Directory of Open Access Journals (Sweden)

    Yun Chiang

    Full Text Available For metastatic non-small cell lung cancer (NSCLC patients with controlled extrathoracic disease after systemic treatment, stable or progressive primary lung lesions may cause respiratory symptoms and increase comorbidities. In the present study, we sought to investigate whether aggressive palliative thoracic radiotherapy (RT can enhance local control and improve the survival for this subgroup of patients.Between March 2006 and December 2014, 56 patients with metastatic NSCLC who had responsive or stable extrathoracic diseases after chemotherapy and/or molecular targets, and received thoracic RT for stable and progressive primary lung lesions were included. RT with a median dose of 55 Gy (range, 40-62 Gy was administered in 1.8-2.5 Gy fractions to primary lung tumor and regional mediastinal lymph nodes using modern RT technique. Overall survival (OS from diagnosis, and locoregional progression-free survival (LRPFS, and survival calculated from radiotherapy (OS-RT were estimated using the Kaplan-Meier method.There were 37 men and 19 women with a median age of 60 years at diagnosis. The median interval from the diagnosis of metastatic disease to thoracic RT was 8 months. Following thoracic RT, 26 patients (46% achieved complete or partial response (overall response rate, ORR. Patients with squamous cell carcinoma or poorly-differentiated carcinoma had a higher ORR than those with adenocarcinoma (63% vs. 34%, P = 0.034. EGFR mutations was closely associated with a better ORR (45% vs. 29%, P = 0.284. At a median follow-up time of 44 months, the median OS, LRPFS after RT, and OS-RT were 50 months, 15 months, and 18 months.Radical palliative throractic RT is safe and might be beneficial for primary lung lesions of metastatic NSCLC patients with controlled extrathoracic diseases.

  2. Relationship between epidermal growth factor receptor gene mutation and copy number in Chinese patients with non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    Lan-Jun Zhang; Ling Cai; Zhe Li; Wu-Ping Wang; Kang Guo; Jian-Yong Shao; Jun-Ye Wang; Hui Yu; Tie-Hua Rong

    2012-01-01

    Epidermal growth factor receptor (EGFP) gene mutation and copy number are useful predictive markers that guide the selection of non-small cell lung cancer (NSCLC) patients for EGFR-targeting therapy.This study aimed to investigate the correlation between EGFR gene mutation and copy number and clinicopathologic characteristics of Chinese patients with NSCLC.NSCLC specimens collected from 205 patients between November 2009 and January 2011 were selected to detect EGFR gene mutations with real-time polymerase chain reaction (RT-PCR) and to detect EGFR gene copy number with fluorescence in situ hybridization (FISH).EGFR mutations primarily occurred in females,non-smokers,and patients with adenocarinomas (all P < 0.001).Tissues from 128 (62%) patients were FISH-positive for EGFR,including 37 (18%) with gene amplification and 91 (44%) with high polysomy.EGFR gene mutation was correlated with FISH-positive status (R =0.340,P < 0.001).Multivariate analysis showed that not smoking (OR =5.910,95% CI =2.363-14.779,P < 0.001) and having adenocarcinoma (OR =0.122,95% CI =0.026-0.581,P =0.008) were favorable factors for EGFR gene mutation.These results show a high frequency of EGFR FISH positivity in NSCLC tissues from Chinese patients and a significant relevance between EGFR gene mutations and FISH-positive status.Among the FISH-positive samples,EGFR gene mutation occurred more frequently in samples with gene amplification compared to those with high polysomy,suggesting that EGFR mutation and gene amplification should be used as clinical decision parameters to predict response to EGFR-targeting therapy.

  3. HSPB1 Gene Polymorphisms Predict Risk of Mortality for US Patients After Radio(chemo)therapy for Non-Small Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Xu Ting [Institute of Clinical Pharmacology, Central South University, Changsha, Hunan (China); Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Wei Qingyi [Department of Epidemiology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Lopez Guerra, Jose Luis [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Department of Radiation Oncology, Instituto Madrileno de Oncologia/Grupo IMO, Madrid (Spain); Wang Lie; Liu Zhensheng [Department of Epidemiology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Gomez, Daniel; O' Reilly, Michael; Lin, Steven Hsesheng [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Zhuang Yan [Department of Radiation Physics, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Levy, Lawrence B. [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); Zhou Honghao [Institute of Clinical Pharmacology, Central South University, Changsha, Hunan (China); Liao Zhongxing, E-mail: zliao@mdanderson.org [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2012-10-01

    Purpose: We investigated potential associations between single-nucleotide polymorphisms (SNPs) in the heat shock protein beta-1 (HSPB1) gene and overall survival in US patients with non-small cell lung cancer (NSCLC). Methods and Materials: Using available genomic DNA samples from 224 patients with NSCLC treated with definitive radio(chemo)therapy, we genotyped 2 SNPs of HSPB1 (NCBI SNP nos. rs2868370 and rs2868371). We used both Kaplan-Meier cumulative probability and Cox proportional hazards analyses to evaluate the effect of HSPB1 genotypes on survival. Results: Our cohort consisted of 117 men and 107 women, mostly white (79.5%), with a median age of 70 years. The median radiation dose was 66 Gy (range, 63-87.5 Gy), and 183 patients (82%) received concurrent platinum-based chemotherapy. The most common genotype of the rs2868371 SNP was CC (61%). Univariate and multivariate analyses showed that this genotype was associated with poorer survival than CG and GG genotypes (univariate hazard ratio [HR] = 1.39, 95% confidence interval [CI], 1.02-1.90; P=.037; multivariate HR = 1.39; 95% CI, 1.01-1.92; P=.045). Conclusions: Our results showed that the CC genotype of HSPB1 rs2868371 was associated with poorer overall survival in patients with NSCLC after radio(chemo)therapy, findings that contradict those of a previous study of Chinese patients. Validation of our findings with larger numbers of similar patients is needed, as are mechanical and clinical studies to determine the mechanism underlying these associations.

  4. A phase I study of STEALTH cisplatin (SPI-77) and vinorelbine in patients with advanced non small-cell lung cancer.

    Science.gov (United States)

    Vokes, E E; Gordon, G S; Mauer, A M; Rudin, C M; Krauss, S A; Szeto, L; Golomb, H M; Hoffman, P C

    2000-11-01

    STEALTH cisplatin (SPI-77) is a liposomal formulation of cisplatin that has activity in animal models of non small-cell lung cancer (NSCLC). Vinorelbine has documented clinical activity in NSCLC. The purpose of this study was to determine the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of SPI-77 when administered in combination with a fixed dose of vinorelbine to patients with stage IIIB or IV NSCLC refractory to or recurrent following previous chemotherapy. SPI-77 was given on day 1 in combination with vinorelbine at a fixed dose of 25 mg/m2 on days 1 and 8 of a 3-week treatment cycle. Dose escalation of SPI-77 progressed as follows: 20, 40, 80, 100, 120, and 140 mg/m2. Twenty patients were entered (11 men and nine women; median age, 63 years). Sixty-four complete cycles of therapy were administered, and 19 of 20 patients completed at least 1 cycle of combination chemotherapy. Neutropenia was dose limiting at a SPI-77 dose of 140 mg/m2. Neuropathy and nephrotoxicity were minimal and not dose related. A partial response was observed in three of 17 patients eligible for a response evaluation and response duration ranged from 6 weeks to 5 months. In conclusion, treatment with combination SPI-77 and vinorelbine was well tolerated, and our recommended phase II dose is 120 mg/m2 of SPI-77 in combination with vinorelbine at 25 mg/m2. Activity was observed in this patient population, and additional phase II testing of this regimen in a less extensively pretreated cohort of patients with NSCLC is indicated.

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

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    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.

  6. Improvement of internal tumor volumes of non-small cell lung cancer patients for radiation treatment planning using interpolated average CT in PET/CT.

    Directory of Open Access Journals (Sweden)

    Yao-Ching Wang

    Full Text Available Respiratory motion causes uncertainties in tumor edges on either computed tomography (CT or positron emission tomography (PET images and causes misalignment when registering PET and CT images. This phenomenon may cause radiation oncologists to delineate tumor volume inaccurately in radiotherapy treatment planning. The purpose of this study was to analyze radiology applications using interpolated average CT (IACT as attenuation correction (AC to diminish the occurrence of this scenario. Thirteen non-small cell lung cancer patients were recruited for the present comparison study. Each patient had full-inspiration, full-expiration CT images and free breathing PET images by an integrated PET/CT scan. IACT for AC in PET(IACT was used to reduce the PET/CT misalignment. The standardized uptake value (SUV correction with a low radiation dose was applied, and its tumor volume delineation was compared to those from HCT/PET(HCT. The misalignment between the PET(IACT and IACT was reduced when compared to the difference between PET(HCT and HCT. The range of tumor motion was from 4 to 17 mm in the patient cohort. For HCT and PET(HCT, correction was from 72% to 91%, while for IACT and PET(IACT, correction was from 73% to 93% (*p<0.0001. The maximum and minimum differences in SUVmax were 0.18% and 27.27% for PET(HCT and PET(IACT, respectively. The largest percentage differences in the tumor volumes between HCT/PET and IACT/PET were observed in tumors located in the lowest lobe of the lung. Internal tumor volume defined by functional information using IACT/PET(IACT fusion images for lung cancer would reduce the inaccuracy of tumor delineation in radiation therapy planning.

  7. Multiparametric imaging of patient and tumour heterogeneity in non-small-cell lung cancer: quantification of tumour hypoxia, metabolism and perfusion

    Energy Technology Data Exchange (ETDEWEB)

    Elmpt, Wouter van; Zegers, Catharina M.L.; Reymen, Bart; Even, Aniek J.G.; Oellers, Michel; Troost, Esther G.C.; Lambin, Philippe [Maastricht University Medical Centre, Department of Radiation Oncology (MAASTRO), GROW - School for Oncology and Developmental Biology, Maastricht (Netherlands); Dingemans, Anne-Marie C. [Maastricht University Medical Centre, Department of Pulmonology, GROW - School for Oncology and Developmental Biology, Maastricht (Netherlands); Wildberger, Joachim E.; Das, Marco [Maastricht University Medical Centre, Department of Radiology, GROW - School for Oncology and Developmental Biology, Maastricht (Netherlands); Mottaghy, Felix M. [Maastricht University Medical Centre, Department of Nuclear Medicine, GROW - School for Oncology and Developmental Biology, Maastricht (Netherlands); University Hospital RWTH Aachen University, Department of Nuclear Medicine, Aachen (Germany)

    2016-02-15

    Multiple imaging techniques are nowadays available for clinical in-vivo visualization of tumour biology. FDG PET/CT identifies increased tumour metabolism, hypoxia PET visualizes tumour oxygenation and dynamic contrast-enhanced (DCE) CT characterizes vasculature and morphology. We explored the relationships among these biological features in patients with non-small-cell lung cancer (NSCLC) at both the patient level and the tumour subvolume level. A group of 14 NSCLC patients from two ongoing clinical trials (NCT01024829 and NCT01210378) were scanned using FDG PET/CT, HX4 PET/CT and DCE CT prior to chemoradiotherapy. Standardized uptake values (SUV) in the primary tumour were calculated for the FDG and hypoxia HX4 PET/CT scans. For hypoxia imaging, the hypoxic volume, fraction and tumour-to-blood ratio (TBR) were also defined. Blood flow and blood volume were obtained from DCE CT imaging. A tumour subvolume analysis was used to quantify the spatial overlap between subvolumes. At the patient level, negative correlations were observed between blood flow and the hypoxia parameters (TBR >1.2): hypoxic volume (-0.65, p = 0.014), hypoxic fraction (-0.60, p = 0.025) and TBR (-0.56, p = 0.042). At the tumour subvolume level, hypoxic and metabolically active subvolumes showed an overlap of 53 ± 36 %. Overlap between hypoxic sub-volumes and those with high blood flow and blood volume was smaller: 15 ± 17 % and 28 ± 28 %, respectively. Half of the patients showed a spatial mismatch (overlap <5 %) between increased blood flow and hypoxia. The biological imaging features defined in NSCLC tumours showed large interpatient and intratumour variability. There was overlap between hypoxic and metabolically active subvolumes in the majority of tumours, there was spatial mismatch between regions with high blood flow and those with increased hypoxia. (orig.)

  8. Fluorescence in situ hybridization analysis of the ALK gene in 2,045 non-small cell lung cancer patients from North-Western Spain (Galicia).

    Science.gov (United States)

    Sánchez-Ares, María; Cameselle-Teijeiro, José M; Vázquez-Estévez, Sergio; Lázaro-Quintela, Martín; Vázquez-Boquete, Ángel; Afonso-Afonso, Francisco J; Casal-Rubio, Joaquín; González-Piñeiro, Ana L; Rico-Rodríguez, Yolanda; Fírvida-Pérez, José L; Ruíz-Bañobre, Juan; Couso, Elena; Santomé, Lucía; Pérez-Becerra, Raquel; García-Campelo, Rosario; Amenedo, Margarita; Azpitarte-Raposeiras, Cristina; Antúnez, José; Abdulkader, Ihab

    2016-08-01

    Identification of anaplastic lymphoma receptor tyrosine kinase (ALK) gene rearrangements is a standard diagnostic test in patients with advanced non-small cell lung cancer (NSCLC). The current study describes the experience of ALK rearrangement detection of a referral center in the public health care system of Galicia in North-Western Spain. The fluorescence in situ hybridization (FISH) patterns of the ALK gene and the clinical and pathological features of these patients are reported. This study is also of interest for comparative purposes due to the relative geographical isolation of the area, which could have contributed to particular genetic features. A total of 2,045 tissue samples from NSCLC patients were collected between October 2010 and July 2015 and tested for ALK rearrangements by FISH. Examination of 1,686 paraffin-embedded tissue specimens and 395 cytological samples (306 cell block preparations and 53 cytological smears) was conducted, and any associations between the FISH results and clinicopathological features were assessed. The rate of successful evaluation was marginally higher in tissue samples than in cytological samples (92.9% vs. 84.1%); this difference was not significant. ALK rearrangements were identified in 82 patients(4%): 65 (79.3%) in tissue specimens, 15 (18.3%) in cell block samples and 2 (2.4%) in cytological smears. This genetic translocation appeared to be associated with a non-smoking history, younger age, female gender, stage IV and adenocarcinoma histological type. The findings demonstrate that ALK evaluation by FISH is feasible in tissue and cytological samples. The clinical and pathological features of the ALK-positive series of patients are similar to those previously reported in the literature.

  9. Pemetrexed combined with paclitaxel in patients with advanced or metastatic non-small-cell lung cancer: a phase I-II trial.

    Science.gov (United States)

    Stathopoulos, George P; Dimitroulis, John; Toubis, Michael; Katis, Costas; Karaindros, Dimitris; Stathopoulos, John; Koutandos, John

    2007-07-01

    Pemetrexed, a novel multi-targeted agent established for the treatment of mesothelioma, has been under investigation for other malignancies, and in recent years particularly for non-small-cell lung cancer (NSCLC). In the present trial we investigated pemetrexed in combination with paclitaxel as front-line treatment in advanced or metastatic NSCLC. Our objectives were to determine the response rate, median and overall survival and toxicity. From April 2005 until May 2006, 51 patients with advanced or metastatic NSCLC were enrolled and 48 were considered evaluable. There were 39 males and nine females, median age 62 years (range 37-81 years), one patient stage IIIA N(2), 23 patients, IIIB and 24, stage IV. All patients had a cytologically- or histologically-confirmed diagnosis. Pemetrexed was administered at a standard dose of 500mg/m(2) and paclitaxel at an escalating dose starting at 135mg/m(2), then 150mg/m(2) and ending at a dose of 175mg/m(2); the level was increased every three patients. Both agents were administered on day 1, repeated every 3 weeks for six courses. A 39.6% partial response rate was observed with a median survival of 14 months. Toxicity was mild with 8.3% grade 3 and 4 neutropenia and other very mild hematologic and non-hematologic adverse reactions. The combination of pemetrexed and paclitaxel at doses of 500mg/m(2) and 175mg/m(2), respectively, has been shown to be an effective combination with very limited toxicity.

  10. Fibroblast Growth Factor 2-A Predictor of Outcome for Patients Irradiated for Stage II-III Non-Small-Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Rades, Dirk, E-mail: Rades.Dirk@gmx.net [Department of Radiation Oncology, University of Lubeck, Lubeck (Germany); Setter, Cornelia [Department of Radiation Oncology, University of Lubeck, Lubeck (Germany); Dahl, Olav [Section of Oncology, Institute of Medicine, University of Bergen, Bergen (Norway); Department of Oncology, Haukeland University Hospital, Bergen (Norway); Schild, Steven E. [Department of Radiation Oncology, Mayo Clinic Scottsdale, Scottsdale, Arizona (United States); Noack, Frank [Institute of Pathology, University of Lubeck, Lubeck (Germany)

    2012-01-01

    Purpose: The prognostic value of the tumor cell expression of the fibroblast growth factor 2 (FGF-2) in patients with non-small-cell lung cancer (NSCLC) is unclear. The present study investigated the effect of tumor cell expression of FGF-2 on the outcome of 60 patients irradiated for Stage II-III NSCLC. Methods and Materials: The effect of FGF-2 expression and 13 additional factors on locoregional control (LRC), metastasis-free survival (MFS), and overall survival (OS) were retrospectively evaluated. These additional factors included age, gender, Karnofsky performance status, histologic type, histologic grade, T and N category, American Joint Committee on Cancer stage, surgery, chemotherapy, pack-years, smoking during radiotherapy, and hemoglobin during radiotherapy. Locoregional failure was identified by endoscopy or computed tomography. Univariate analyses were performed with the Kaplan-Meier method and the Wilcoxon test and multivariate analyses with the Cox proportional hazard model. Results: On univariate analysis, improved LRC was associated with surgery (p = .017), greater hemoglobin levels (p = .036), and FGF-2 negativity (p <.001). On multivariate analysis of LRC, surgery (relative risk [RR], 2.44; p = .037), and FGF-2 expression (RR, 5.06; p <.001) maintained significance. On univariate analysis, improved MFS was associated with squamous cell carcinoma (p = .020), greater hemoglobin levels (p = .007), and FGF-2 negativity (p = .001). On multivariate analysis of MFS, the hemoglobin levels (RR, 2.65; p = .019) and FGF-2 expression (RR, 3.05; p = .004) were significant. On univariate analysis, improved OS was associated with a lower N category (p = .048), greater hemoglobin levels (p <.001), and FGF-2 negativity (p <.001). On multivariate analysis of OS, greater hemoglobin levels (RR, 4.62; p = .002) and FGF-2 expression (RR, 3.25; p = .002) maintained significance. Conclusions: Tumor cell expression of FGF-2 appeared to be an independent negative predictor

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

    Directory of Open Access Journals (Sweden)

    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.

  12. EGFR mutations are associated with favorable intracranial response and progression-free survival following brain irradiation in non-small cell lung cancer patients with brain metastases

    Science.gov (United States)

    2012-01-01

    Background The presence of epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) is associated with increased radiosensitivity in vitro. However, the results from clinical studies regarding the radiosensitivity in NSCLC with mutant EGFR are inconclusive. We retrospectively analyzed our NSCLC patients who had been regularly followed up by imaging studies after irradiation for brain metastases, and investigated the impact of EGFR mutations on radiotherapy (RT). Methods Forty-three patients with brain metastases treated with RT, together with EGFR mutation status, demographics, smoking history, performance status, recursive partitioning analysis (RPA) class, tumor characteristics, and treatment modalities, were included. Radiological images were taken at 1 to 3 months after RT, and 3 to 6 months thereafter. Radiographic response was evaluated by RECIST criteria version 1.1 according to the intracranial images before and after RT. Log-rank test and Cox regression model were used to correlate EGFR mutation status and other clinical features with intracranial radiological progression-free survival (RPFS) and overall survival (OS). Results The median follow-up duration was 15 months. Patients with mutant EGFR had higher response rates to brain RT than those with wild-type EGFR (80% vs. 46%; p = 0.037). Logistic regression analysis showed that EGFR mutation status is the only predictor for treatment response (p = 0.032). The median intracranial RPFS was 18 months (95% CI = 8.33-27.68 months). In Cox regression analysis, mutant EGFR (p = 0.025) and lower RPA class (p = 0.026) were associated with longer intracranial RPFS. EGFR mutation status (p = 0.061) and performance status (p = 0.076) had a trend to predict OS. Conclusions Mutant EGFR in NSCLC patients is an independent prognostic factor for better treatment response and longer intracranial RPFS following RT for brain metastases. PMID:23110940

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

    Science.gov (United States)

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

    2015-12-01

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

  14. Dynamic contrast-enhanced CT in patients treated with sorafenib and erlotinib for non-small cell lung cancer: a new method of monitoring treatment?

    Energy Technology Data Exchange (ETDEWEB)

    Lind, Joline S.W.; Postmus, Pieter E.; Smit, Egbert F. [VU University Medical Center, Department of Pulmonary Diseases, Amsterdam (Netherlands); Meijerink, Martijn R.; Kuijk, Cornelis van [VU University Medical Center, Department of Radiology, De Boelelaan 1117, P.O. Box 7075, Amsterdam (Netherlands); Dingemans, Anne-Marie C. [Maastricht University, Medical Centre, Department of Pulmonary Diseases, Maastricht (Netherlands); Oellers, Michel C.; Ruysscher, Dirk de [Maastricht University, Medical Centre, Department of Radiation Oncology (MAASTRO Clinic), GROW - School for Oncology and Developmental Biology, Maastricht (Netherlands)

    2010-12-15

    We investigated the feasibility of serial dynamic contrast-enhanced computed tomography (DCE-CT) in patients with advanced/metastatic non-small cell lung cancer (NSCLC) receiving anti-angiogenic (sorafenib) and anti-EGFR (erlotinib) treatment, and correlated tumour blood flow (BF) with treatment outcome. DCE-CTs were performed at baseline and 3 and 6 weeks after starting treatment. Tumour BF, calculated with the maximum slope method, and percentage change were measured in 23 patients (14 male; median age 59 years). Tumour BF was compared at baseline and weeks 3 and 6; the relation with RECIST/Crabb response and progression-free survival (PFS) was assessed. Mean tumour perfusion decreased from 39.2 ml/100 g/min at baseline to 15.1 ml/100 g/min at week 3 (p < 0.001) and 9.4 ml/100 g/min at week 6 (p < 0.001). Tumour perfusion was lower in RECIST and Crabb responders versus non-responders at week 3 (4.2 versus 17.7 ml/100 g/min, p = 0.03) and week 6 (0 versus 13.4 ml/100 g/min, p = 0.04). Patients with a decrease larger than the median at week 6 tended to have a longer PFS (7.1 versus 5.7 months, p = 0.06). Serial DCE-CTs are feasible in patients with NSCLC and demonstrated a significant decrease in tumour BF following sorafenib/erlotinib therapy. Early changes in tumour BF correlated with objective response and showed a trend towards longer PFS. (orig.)

  15. Change in Diffusing Capacity After Radiation as an Objective Measure for Grading Radiation Pneumonitis in Patients Treated for Non-Small-Cell Lung Cancer

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    Lopez Guerra, Jose Luis [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (United States); Department of Radiation Oncology, Hospitales Universitarios Virgen del Rocio, Seville (Spain); Gomez, Daniel, E-mail: dgomez@mdanderson.org [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (United States); Zhuang Yan; Levy, Lawrence B. [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (United States); Eapen, George [Department of Pulmonary Medicine, University of Texas MD Anderson Cancer Center, Houston, TX (United States); Liu Hongmei; Mohan, Radhe; Komaki, Ritsuko; Cox, James D.; Liao Zhongxing [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (United States)

    2012-08-01

    Purpose: Scoring of radiation pneumonitis (RP), a dose-limiting toxicity after thoracic radiochemotherapy, is subjective and thus inconsistent among studies. Here we investigated whether the extent of change in diffusing capacity of the lung for carbon monoxide (DLCO) after radiation therapy (RT) for non-small-cell lung cancer (NSCLC) could be used as an objective means of quantifying RP. Patients and Methods: We analyzed potential correlations between DLCO and RP in 140 patients who received definitive RT ({>=}60 Gy) with or without chemotherapy for primary NSCLC. All underwent DLCO analysis before and after RT. Post-RT DLCO values within 1 week of the RP diagnosis (Grade 0, 1, 2, or 3) were selected and compared with that individual's preradiation values. Percent reductions in DLCO and RP grade were compared by point biserial correlation in the entire patient group and in subgroups stratified according to various clinical factors. Results: Patients experiencing Grade 0, 1, 2, or 3 RP had median percentage changes in DLCO after RT of 10.7%, 13%, 22.1%, or 35.2%. Percent reduction in DLCO correlated with RP Grade {<=}1 vs. {>=}2 (p = 0.0004). This association held for the following subgroups: age {>=}65 years, advanced stage, smokers, use of chemotherapy, volume of normal lung receiving at least 20 Gy {>=}30%, and baseline DLCO or forced expiratory volume in 1 second {>=}60%. Conclusions: By correlating percent change in DLCO from pretreatment values at the time of diagnosis of RP with RP grade, we were able to identify categories of RP based on the change in DLCO. These criteria provide a basis for an objective scoring system for RP based on change in DLCO.

  16. Exercise Training for Patients Pre- and Postsurgically Treated for Non-Small Cell Lung Cancer: A Systematic Review and Meta-analysis.

    Science.gov (United States)

    Ni, Hui-Juan; Pudasaini, Bigyan; Yuan, Xun-Tao; Li, He-Fang; Shi, Lei; Yuan, Ping

    2016-05-05

    Background This meta-analysis examined the effects of exercise training on length of hospital stay, postoperative complications, exercise capacity, 6-minute walking distance (6MWD), and health-related quality of life (HRQoL) in patients following resection of non-small cell lung cancer (NSCLC). Methods This review searched PubMed, EMBASE, and the Cochrane Collaboration data base up to August 16, 2015. It includes 15 studies comparing exercise endurance and quality of life before versus after exercise training in patients undergoing lung resection for NSCLC. Results This review identified 15 studies, 8 of which are randomized controlled trials including 350 patients. Preoperative exercise training shortened length of hospital stay; mean difference (MD): -4.98 days (95% CI = -6.22 to -3.74, P exercise training improved exercise capacity; 6MWD was increased to 39.95 m (95% CI = 5.31 to 74.6, P = .02) .While postoperative exercise training can also effectively improve exercise capacity, it required a longer training period; 6MWD was increased to 62.83 m (95% CI = 57.94 to 67.72) after 12 weeks of training (P exercise, but dyspnea score was decreased -14.31 points (95% CI = -20.03 to -8.58, P exercise training (MD = 3 points, 95% CI = 0.81 to 5.2, P = .007) while there was no difference with regard to mental health. The I(2) statistics of all statistically pooled data were lower than 30%. There was a low amount of heterogeneity among these studies. Conclusions Evidence from this review suggests that preoperative exercise training may shorten length of hospital stay, decrease postoperative complications and increase 6MWD. Postoperative exercise training can also effectively improve both the 6MWD and quality of life in surgical patients with NSCLC, but requiring a longer training period.

  17. 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

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

    Directory of Open Access Journals (Sweden)

    Bearz Alessandra

    2008-07-01

    Full Text Available Abstract Background The main objective of this study was to evaluate the safety of second-line pemetrexed in Stage IIIB or IV NSCLC. Methods 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. Results 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. Conclusion Patients with locally advanced or metastatic NSCLC could benefit from second-line pemetrexed, with a low incidence of hematological and non-hematological toxicities.

  19. 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.

  20. Whole brain radiotherapy plus concurrent chemotherapy in non-small cell lung cancer patients with brain metastases: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Hong Qin

    Full Text Available The aim of the present meta-analysis is to evaluate the response rate, median survival time (MST and toxicity in patients with brain metastases (BM originating from non-small cell lung cancer (NSCLC and who were treated using either whole brain radiotherapy (WBRT plus concurrent chemotherapy or WBRT alone.PubMed, EMBASE, Web of Science, The Cochrane Library, clinical trials and current controlled trials were searched to identify any relevant publications. After screening the literature and undertaking quality assessment and data extraction, the meta-analysis was performed using Stata11.0 software.In total, six randomized controlled trials (RCT involving 910 participants were included in the meta-analysis. The results of the analysis indicate that WBRT plus concurrent chemotherapy was more effective at improving response rate (RR = 2.06, 95% CI [1.13, 3.77]; P = 0.019 than WBRT alone. However, WBRT plus concurrent chemotherapy did not improve median survival time (MST (HR = 1.09, 95%CI [0.94, 1.26]; P = 0.233 or time of neurological progression (CNS-TTP (HR = 0.93, 95%CI [0.75, 1.16]; P = 0.543, and increased adverse events (Grade≥3 (RR = 2.59, 95% CI [1.88, 3.58]; P = 0.000. There were no significant differences in Grade 3-5 neurological or hematological toxicity between two patient groups (RR = 1.08, 95%CI [0.23, 5.1]; P = 0.92.The combination of chemotherapy plus WBRT in patients with BM originating from NSCLC may increase treatment response rates of brain metastases with limited toxicity. Although the therapy schedule did not prolong MST or CNS-TTP, further assessment is warranted.

  1. Non-contrast-enhanced preoperative assessment of lung perfusion in patients with non-small-cell lung cancer using Fourier decomposition magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Sommer, Gregor, E-mail: gregor.sommer@usb.ch [Department of Radiology (E010), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg (Germany); Translational Lung Research Center Heidelberg (TLRC-H), Member of the German Center for Lung Research, Heidelberg (Germany); Clinic of Radiology and Nuclear Medicine, University of Basel Hospital, Petersgraben 4, 4031 Basel (Switzerland); Bauman, Grzegorz, E-mail: gbauman@wisc.edu [Translational Lung Research Center Heidelberg (TLRC-H), Member of the German Center for Lung Research, Heidelberg (Germany); Department of Medical Physics in Radiology (E020), German Cancer Research Center (DKFZ), Heidelberg (Germany); Department of Medical Physics, University of Wisconsin School of Medicine and Public Health, 1111 Highland Avenue, Madison, 53705 WI (United States); Koenigkam-Santos, Marcel, E-mail: marcelk46@yahoo.com.br [Translational Lung Research Center Heidelberg (TLRC-H), Member of the German Center for Lung Research, Heidelberg (Germany); Department of Radiology, University Hospital of the School of Medicine of Ribeirao Preto – University of Sao Paulo, Ribeirao Preto (Brazil); Department of Diagnostic and Interventional Radiology with Nuclear Medicine, Thoraxklinik Heidelberg gGmbH, Amalienstr. 5, 69126 Heidelberg (Germany); Draenkow, Christopher, E-mail: c.draenkow@thoraxklinik-heidelberg.de [Translational Lung Research Center Heidelberg (TLRC-H), Member of the German Center for Lung Research, Heidelberg (Germany); Department of Surgery, Thoraxklinik Heidelberg gGmbH, Amalienstr. 5, 69126 Heidelberg (Germany); Heussel, Claus Peter, E-mail: heussel@uni-heidelberg.de [Translational Lung Research Center Heidelberg (TLRC-H), Member of the German Center for Lung Research, Heidelberg (Germany); Department of Diagnostic and Interventional Radiology with Nuclear Medicine, Thoraxklinik Heidelberg gGmbH, Amalienstr. 5, 69126 Heidelberg (Germany); and others

    2013-12-01

    Objective: To investigate non-contrast-enhanced Fourier decomposition MRI (FD MRI) for assessment of regional lung perfusion in patients with Non-Small-Cell Lung Cancer (NSCLC) in comparison to dynamic contrast-enhanced MRI (DCE MRI). Methods: Time-resolved non-contrast-enhanced images of the lungs were acquired prospectively in 15 patients using a 2D balanced steady-state free precession (b-SSFP) sequence. After non-rigid registration of the native image data, perfusion-weighted images were calculated by separating periodic changes of lung proton density at the cardiac frequency using FD. DCE MRI subtraction datasets were acquired as standard of reference. Both datasets were analyzed visually for perfusion defects. Then segmentation analyses were performed to describe perfusion of pulmonary lobes semi-quantitatively as percentages of total lung perfusion. Overall FD MRI perfusion signal was compared to velocity-encoded flow measurements in the pulmonary trunk as an additional fully quantitative reference. Results: Image quality ratings of FD MRI were significantly inferior to those of DCE MRI (P < 0.0001). Sensitivity, specificity, and accuracy of FD MRI for visual detection of perfusion defects were 84%, 92%, and 91%. Semi-quantitative evaluation of lobar perfusion provided high agreement between FD MRI and DCE MRI for both entire lungs and upper lobes, but less agreement in the lower parts of both lungs. FD perfusion signal showed high linear correlation with pulmonary arterial blood flow. Conclusion: FD MRI is a promising technique that allows for assessing regional lung perfusion in NSCLC patients without contrast media or ionizing radiation. However, for being applied in clinical routine, image quality and robustness of the technique need to be further improved.

  2. Weight Gain in Advanced Non-Small-Cell Lung Cancer Patients During Treatment With Split-Course Concurrent Chemoradiotherapy Is Associated With Superior Survival

    Energy Technology Data Exchange (ETDEWEB)

    Gielda, Benjamin T., E-mail: Benjamin_gielda@rush.edu [Department of Radiation Oncology, Rush University Medical Center, Chicago, IL (United States); Mehta, Par [Department of Radiation Oncology at Rush Copley Medical Center, Aurora, IL (United States); Khan, Atif [Department of Radiation Oncology, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School and Cancer Institute of New Jersey, New Brunswick, NJ (United States); Marsh, James C.; Zusag, Thomas W. [Department of Radiation Oncology, Rush University Medical Center, Chicago, IL (United States); Warren, William H. [Department of Cardiothoracic Surgery, Rush University Medical Center, Chicago, IL (United States); Fidler, Mary Jo [Section of Medical Oncology, Rush University Medical Center, Chicago, IL (United States); Abrams, Ross A. [Department of Radiation Oncology, Rush University Medical Center, Chicago, IL (United States); Bonomi, Philip [Section of Medical Oncology, Rush University Medical Center, Chicago, IL (United States); Liptay, Michael; Faber, L. Penfield [Department of Cardiothoracic Surgery, Rush University Medical Center, Chicago, IL (United States)

    2011-11-15

    Background: Preoperative concurrent chemoradiotherapy (CRT) is an accepted treatment for potentially resectable, locally advanced, non-small-cell lung cancer (NSCLC). We reviewed a decade of single institution experience with preoperative split-course CRT followed by surgical resection to evaluate survival and identify factors that may be helpful in predicting outcome. Methods and Materials: All patients treated with preoperative split-course CRT and resection at Rush University Medical Center (RUMC) between January 1999 and December 2008 were retrospectively analyzed. Endpoints included overall survival (OS), progression-free survival (PFS), local-regional progression-free survival (LRPFS), and distant metastasis-free survival (DMFS). Patient and treatment related variables were assessed for correlation with outcomes. Results: A total of 54 patients were analyzed, 76% Stage IIIA, 18% Stage IIIB, and 6% oligometastatic. The pathologic complete response (pCR) rate was 31.5%, and the absence of nodal metastases (pN0) was 64.8%. Median OS and 3-year actuarial survival were 44.6 months and 50%, respectively. Univariate analysis revealed initial stage (p < 0.01) and percent weight change during CRT (p < 0.01) significantly correlated with PFS/OS. On multivariate analysis initial stage (HR, 2.4; 95% CI, 1.18-4.90; p = 0.02) and percent weight change (HR, 0.79; 95% CI, 0.67-0.93; p < 0.01) maintained significance with respect to OS. There were no cases of Grade 3+ esophagitis, and there was a single case of Grade 3 febrile neutropenia. Conclusions: The strong correlation between weight change during CRT and OS/PFS suggests that this clinical parameter may be useful as a complementary source of predictive information in addition to accepted factors such as pathological response.

  3. Effect of MicroRNA-335 on the Metastasis, Invasion and Proliferation of Cells in Patients with Non-small Cell Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    Wang He; Liu Zhili; Wang Zhaoxia

    2013-01-01

    Objective: To investigate the effect of microRNA-335 on the metastasis, invasion and proliferation of cells in patients with non-small-cell lung cancer (NSCLC). Methods:Real-time PCR was performed to detect the expression differences of microRNA-335 between 12 pairs of NSCLC and normal cancerous peripheral tissues, and between SPCA-1 cells of NSCLC and 16HBE of normal pulmonary epithelial cells, while miR-335 expression in SPCA-1 cells were down-regulated and proved by Lipofectamine 2000 transient transfection and real-time PCR, respectively. Scratch test, Transwell invasion assay as well as MTT and clone formation assays were applied to respectively determine the effect of miR-335 on the metastasis, invasion and proliferation of SPCA-1 cells. Results:Compared with para-carcinoma tissues and 16HBE cells, miR-335 expression was evidently higher in NSCLC and SPCA-1 cells. However, it decreased remarkably after transient transfection of anti-miR-335 by SPCA-1 cells with Lipofectamine 2000 for 24 h. Metastasis and invasion of SPCA-1 cells could be inhibited by suppressing miR-335 expression with suppression rates being (42.8±2.7)%and (73.25±4.4)%, respectively. However, the inhibition of miR-335 expression had no effect on the proliferation of SPCA-1 cells. Conclusion:miR-335 expresses highly in NSCLC and its low expression can obviously inhibit the metastasis and invasion of SPCA-1 cells, but has no effect on the proliferation.

  4. Aggravation of dyspnea in stage I non-small cell lung cancer patients following stereotactic body radiotherapy

    DEFF Research Database (Denmark)

    Paludan, Merete; Traberg Hansen, Anders; Petersen, Jørgen;

    2006-01-01

    In SBRT for NSCLC, highly potent radiation doses are delivered to patients with frequent pre-irradiatory compromise of pulmonary function. For the risk of pulmonary toxicity to be minimized during SBRT planning, data on its dose-volume dependency is needed. In the present study, we analyse the as...

  5. Anti-angiogenic-specific adverse events in patients with non-small cell lung cancer treated with nintedanib and docetaxel

    DEFF Research Database (Denmark)

    Reck, Martin; Mellemgaard, Anders; von Pawel, Joachim

    2015-01-01

    +docetaxel in the overall population and overall survival was significantly improved in the pre-specified analysis of patients with adenocarcinoma. We evaluated the frequency of characteristic adverse events (AEs) commonly seen with existing anti-angiogenic agents. MATERIALS AND METHODS: The incidence and intensity of AEs...... between arms for all grades (5.1% vs 4.6%) and Grade ≥3 (2.1% vs 3.1%). Safety evaluation of the LUME-Lung 1 study showed that the frequency of AEs commonly associated with other anti-angiogenic agents was lower with nintedanib+docetaxel. Survival benefits from addition of nintedanib to docetaxel...

  6. Lived experiences of everyday life during curative radiotherapy in patients with non-small cell lung cancer: A phenomenological study

    DEFF Research Database (Denmark)

    Petri, Suzanne; Berthelsen, Connie Bøttcher

    2015-01-01

    . The constituents of the structure were: Radiotherapy as a life priority, A struggle for acceptance of an altered everyday life, Interpersonal relationships for better or worse, and Meeting the health care system. CONCLUSION: The meaning of hope was essential during radiotherapy treatment and our results suggest...... that interpersonal relationships can be a prerequisite to the experience of hope. "Hope for recovery serving as a compass in a changed everyday life," furthermore identifies the essentials in the patients' assertive approach to believing in recovery and thereby enabling hope in a serious situation....

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

    Directory of Open Access Journals (Sweden)

    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.

  8. Carboplatin plus VP-16 with simultaneous radiotherapy in the treatment of non-small cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Imanaka, Kazufumi; Kodama, Akihisa; Okamoto, Yoshiaki; Izumiyama, Kazutaka; Sakaguchi, Toshiya; Kono, Michio [Kobe Univ. (Japan). School of Medicine

    1995-01-01

    Ten patients with non-small cell lung cancer were treated by concurrent chemoradiotherapy. The protocol consists of split course radiotherapy and simultaneous chemotherapy (carboplatin plus VP-16). All patients tolerated well this treatment with no life-threatening complications and treatment duration was shortened compared to that of sequential chemoradiotherapy. Response rate was 50% (CR: 1, PR: 4), median survival time was 12.8 months and 2-year survival rate was 20%. The major toxicity was leucopenia, with WHO grade 4 leucopenia in 3 patients and grade 3 in 3 patients. This protocol was considered to be tolerable and effective for the treatment of non-small cell lung cancer. (author).

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

    Science.gov (United States)

    Song, Qi; Jiao, Shunchang; Li, Fang

    2016-08-20

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

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

    OpenAIRE

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

    2016-01-01

    Due to high mortality rates of lung cancer, there is a need for identification of new, clinically useful markers, which improve detection of this tumor in early stage of disease. In the current study, serum peptide profiling was evaluated as a diagnostic tool for non-small cell lung cancer patients. The combination of the ZipTip technology with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) for the analysis of peptide pattern of cancer patients (n ...

  11. Targeted Therapy and Immunotherapy for Non-small Cell Lung Cancer 
with Brain Metastasis

    Directory of Open Access Journals (Sweden)

    Qi SONG

    2016-08-01

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

  12. Immune modulations during chemoimmunotherapy & novel vaccine strategies - In metastatic melanoma and non small-cell lung cancer

    DEFF Research Database (Denmark)

    Iversen, Trine Zeeberg

    2013-01-01

    This thesis describes the treatment of metastatic melanoma (MM) and non small-cell lung cancer (NSCLC) from an immunotherapeutic approach. The purpose of the first part of the thesis was to assess how treatment with Temozolomide (TMZ) chemotherapy affects the immune system in patients with metast......This thesis describes the treatment of metastatic melanoma (MM) and non small-cell lung cancer (NSCLC) from an immunotherapeutic approach. The purpose of the first part of the thesis was to assess how treatment with Temozolomide (TMZ) chemotherapy affects the immune system in patients...

  13. Effect of EGFR-TKI retreatment following chemotherapy for advanced non-small cell lung cancer patients who under went EGFR-TKI

    Institute of Scientific and Technical Information of China (English)

    Guo-Hao Xia; Ji-Feng Feng; Yun Zeng; Ying Fang; Shao-Rong Yu; Li Wang; Mei-Qi Shi; Wei-Li Sun; Xin-En Huang; Jia Chen

    2014-01-01

    Objective: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. hTe mechanisms of resistance are complicated. hTe lack of established therapeutic options for patients atfer a failed EGFR-TKI treatment poses a great challenge to physicians in managing this group of lung cancer patients. hTis study evaluates the inlfuence of EGFR-TKI retreatment following chemotherapy atfer failure of initial EGFR-TKI within at least 6 months on NSCLC patients. Methods:hTe data of 27 patients who experienced treatment failure from their initial use of EGFR-TKI within at least 6 months were analyzed. Atfer chemotherapy, the patients were retreated with EGFR-TKI (geiftinib 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. Results: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). hTe disease control rate (DCR) was 85.2%(95%CI:62%-94%). hTe 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. hTe 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. hTe DCR was 85.7%, and the mPFS was 9.5 months. Signiifcant difference was found between the two

  14. Targeted Therapy and Immunotherapy for Non-small Cell Lung Cancer 
with Brain Metastasis

    OpenAIRE

    Song, Qi; Jiao, Shunchang; Li, Fang

    2016-01-01

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

  15. Activated changes of platelet ultra microstructure and plasma granule membrane protein 140 in patients with non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    ZHUGE Yi; ZHOU Jian-ying; YANG Guang-die; ZU De-ling; XU Xiao-liang; TIAN Ming-qing; LU Guo-hua

    2009-01-01

    Background Non-small cell lung cancer (NSCLC) is the leading cause of cancer mortality worldwide. Platelet activation may play an important role in pathologic progress in lung cancer. In this study, we aimed to clarify the influence of activated platelets on lung cancer generation and growth, and the relationship among these functional and ultrastructural changes of platelets and the severity of pathogenetic condition in these patients with NSCLC.Methods One hundred and thirty-six cases of patients with pathologically confirmed NSCLC were included in this study. Fifty-four healthy people were enrolled as controls. The change of ultra microstructure and activity of blood platelets were observed under the transmission and scanning electron microscope. Simultaneous determination of plasma granule membrane protein 140 (GMP-140) was made.Results Transmission electron microscopy showed remarkable changes of ultra microstructure of platelets in patients with NSCLC, including swelling, increase of o-granules, vesicles, and glycogenosome. Scanning electron microscopy showed many more surface processes and wrinkles on platelets in patients with NSCLC. The reference plasma levels of GMP-140 of healthy controls were (18.2±2.7) μg/L. The plasma levels of GMP-140 in patients with NSCLC were (47.8±12.3) μg/L, which were much higher than those of the controls. There was a medium positive correlation between plasma levels of GMP-140 and amount of o-granules (r=0.514, P<0.01) and a high positive correlation between plasma levels of GMP-140 and area of platelet (r=0.84, P<0.01) in patients with NSCLC. The Kaplan-Meier survival curve analysis showed significant shift to the left in patients with NSCLC whose α-granules per platelet were 19 or more compared to those 18 or less (Log rank statistic, X2=17.38, P <0.01).Conclusions There are significant activated changes of ultra microstructure and increased activity of blood platelets in patients with NSCLC. These activated platelets

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

    Directory of Open Access Journals (Sweden)

    Bang Sun-Hwi

    2012-06-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Yip, Connie [King' s College London, St Thomas' Hospital, Department of Cancer Imaging, Division of Imaging Sciences and Biomedical Engineering, London (United Kingdom); National Cancer Centre, Department of Radiation Oncology, Singapore (Singapore); St Thomas' Hospital, Imaging 2, London (United Kingdom); Blower, Philip J. [King' s College London, St Thomas' Hospital, Department of Imaging Chemistry and Biology, Division of Imaging Sciences and Biomedical Engineering, London (United Kingdom); Goh, Vicky [King' s College London, St Thomas' Hospital, Department of Cancer Imaging, Division of Imaging Sciences and Biomedical Engineering, London (United Kingdom); St Thomas' Hospital, Department of Radiology, Guy' s and St Thomas' NHS Foundation Trust, London (United Kingdom); Landau, David B. [King' s College London, St Thomas' Hospital, Department of Cancer Imaging, Division of Imaging Sciences and Biomedical Engineering, London (United Kingdom); St Thomas' Hospital, Department of Clinical Oncology, Guy' s and St Thomas' NHS Foundation Trust, London (United Kingdom); Cook, Gary J.R. [King' s College London, St Thomas' Hospital, Department of Cancer Imaging, Division of Imaging Sciences and Biomedical Engineering, London (United Kingdom); St Thomas' Hospital, Clinical PET Imaging Centre, Guy' s and St Thomas' NHS Foundation Trust, London (United Kingdom)

    2015-05-01

    Non-small-cell lung cancer (NSCLC) is the commonest cancer worldwide but survival remains poor with a high risk of relapse, particularly after nonsurgical treatment. Hypoxia is present in a variety of solid tumours, including NSCLC. It is associated with treatment resistance and a poor prognosis, although when recognised may be amenable to different treatment strategies. Thus, noninvasive assessment of intratumoral hypoxia could be used to stratify patients for modification of subsequent treatment to improve tumour control. Molecular imaging approaches targeting hypoxic cells have shown some early success in the clinical setting. This review evaluates the evidence for hypoxia imaging using PET in NSCLC and explores its potential clinical utility. (orig.)

  18. 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.

  19. Comparison of RECIST, EORTC criteria and PERCIST for evaluation of early response to chemotherapy in patients with non-small-cell lung cancer

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    Shang, Jingjie; Ling, Xueying; Zhang, Linyue; Tang, Yongjin; Xiao, Zeyu; Cheng, Yong; Guo, Bin; Gong, Jian; Huang, Li; Xu, Hao [The First Affiliated Hospital of Jinan University, Department of Nuclear Medicine and PET/CT-MRI Centre, Guangzhou (China)

    2016-10-15

    To compare the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, the European Organization for Research and Treatment of Cancer (EORTC) criteria and the Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST) 1.0 using PET volume computer-assisted reading (PET VCAR) for response evaluation in patients with advanced non-small-cell lung cancer (NSCLC) treated with chemotherapy. A total of 35 patients with NSCLC were included in this prospective study. All patients received standard chemotherapy and underwent {sup 18}F-FDG PET/CT scans before and after treatment. With the assistance of PET VCAR, the chemotherapeutic responses were evaluated according to the RECIST 1.1, EORTC criteria and PERCIST 1.0. Concordance among these protocols was assessed using Cohen's κ coefficient and Wilcoxon's signed-ranks test. Progression-free survival (PFS) was calculated using the Kaplan-Meier test. RECIST 1.1 and EORTC response classifications were discordant in 20 patients (57.1 %; κ = 0.194, P < 0.05), and RECIST 1.1 and PERCIST 1.0 classifications were discordant in 22 patients (62.9 %; κ = 0.139, P < 0.05). EORTC and PERCIST 1.0 classifications were discordant in only 4 patients (11.4 %), resulting in better concordance (κ = 0.804, P > 0.05). Patients with a partial remission according to RECIST 1.1 had significantly longer PFS (P < 0.001) than patients with progressive disease, but not significantly longer than patients with stable disease (P = 0.855). According to both the EORTC criteria and PERCIST 1.0, patients with a partial metabolic response had a significantly longer PFS than those with stable metabolic disease and those with progressive metabolic disease (P = 0.020 and P < 0.001, respectively, for EORTC; both P < 0.001 for PERCIST 1.0). EORTC criteria and PERCIST 1.0 are more sensitive and accurate than RECIST 1.1 for the detection of an early therapeutic response to chemotherapy in patients with NSCLC. Although EORTC criteria and

  20. Effects of Combined Chinese Drugs and Chemotherapy in Treating Advanced Non-small Cell Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    陈衍智; 李占东; 高非; 张莹; 孙红; 李萍萍

    2009-01-01

    Objective:To evaluate the efficacy and side effects of combined Chinese drugs and chemotherapy in treating advanced non-small cell lung cancer(NSCLC).Methods:Sixty-three patients with stageⅢB andⅣNSCLC hospitalized from October 2001 to October 2008 were enrolled and assigned to two groups using a randomizing digital table,with 33 patients in the treatment group and 30 in the control group. They were all treated with the Navelbine and Cisplatin(NP) chemotherapy,but to the treatment group the Chinese drugs...

  1. Interstitial lung abnormalities in treatment-naïve advanced non-small-cell lung cancer patients are associated with shorter survival

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    Nishino, Mizuki, E-mail: Mizuki_Nishino@DFCI.HARVARD.EDU [Department of Radiology, Brigham and Women' s Hospital, 75 Francis St., Boston, MA 02115 (United States); Department of Imaging, Dana-Farber Cancer Institute, 450 Brookline Ave., Boston, MA 02215 (United States); Cardarella, Stephanie [Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave., Boston, MA 02215, (United States); Dahlberg, Suzanne E. [Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, 450 Brookline Ave., Boston, MA 02215 (United States); Araki, Tetsuro [Department of Radiology, Brigham and Women' s Hospital, 75 Francis St., Boston, MA 02115 (United States); Lydon, Christine; Jackman, David M.; Rabin, Michael S. [Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave., Boston, MA 02215, (United States); Hatabu, Hiroto [Department of Radiology, Brigham and Women' s Hospital, 75 Francis St., Boston, MA 02115 (United States); Johnson, Bruce E. [Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave., Boston, MA 02215, (United States)

    2015-05-15

    Highlights: • Interstitial lung abnormalities were present in 14% of stage IV NSCLC patients. • ILA was more common in older patients with heavier smoking history. • ILA was associated with shorter survival after adjusting for smoking and therapy. • ILA could be an additional independent marker for survival in advanced NSCLC. - Abstract: Objective: Interstitial lung diseases are associated with increased risk of lung cancer. The prevalence of ILA at diagnosis of advanced non-small-cell lung cancer (NSCLC) and its impact on overall survival (OS) remain to be investigated. Materials and method: The study included 120 treatment-naïve stage IV NSCLC patients (53 males, 67 females). ILA was scored on CT prior to any systemic therapy using a 4-point scale [0 = no evidence of ILA, 1 = equivocal for ILA, 2 = suspicious for ILA, 3 = ILA] by a sequential reading method previously reported. ILA scores of 2 or 3 indicated the presence of ILA. Results: ILA was present in 17 patients (14%) with advanced NSCLC prior to any treatment (score3: n = 2, score2: n = 15). These 17 patients were significantly older (median age: 69 vs. 63, p = 0.04) and had a heavier smoking history (median: 40 vs. 15.5 pack-year, p = 0.003) than those with ILA score 0 or 1. Higher ILA scores were associated with shorter OS (p = 0.001). Median OS of the 17 patients with ILA was 7.2 months [95%CI: 2.9–9.4] compared to 14.8 months [95%CI: 11.1–18.4] in patients with ILA score 0 or 1 (p = 0.002). In a multivariate model, the presence of ILA remained significant for increased risk for death (HR = 2.09, p = 0.028) after adjusting for first-line systemic therapy (chemotherapy, p < 0.001; TKI, p < 0.001; each compared to no therapy) and pack years of smoking (p = 0.40). Conclusion: Radiographic ILA was present in 14% of treatment-naïve advanced NSCLC patients. Higher ILA scores were associated with shorter OS, indicating that ILA could be a marker of shorter survival in advanced NSCLC.

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

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    Hesselius Patrik

    2004-09-01

    Full Text Available Abstract Background 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. Methods 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. Results 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

  3. Identification of enriched driver gene alterations in subgroups of non-small cell lung cancer patients based on histology and smoking status.

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    She-Juan An

    Full Text Available BACKGROUND: Appropriate patient selection is needed for targeted therapies that are efficacious only in patients with specific genetic alterations. We aimed to define subgroups of patients with candidate driver genes in patients with non-small cell lung cancer. METHODS: Patients with primary lung cancer who underwent clinical genetic tests at Guangdong General Hospital were enrolled. Driver genes were detected by sequencing, high-resolution melt analysis, qPCR, or multiple PCR and RACE methods. RESULTS: 524 patients were enrolled in this study, and the differences in driver gene alterations among subgroups were analyzed based on histology and smoking status. In a subgroup of non-smokers with adenocarcinoma, EGFR was the most frequently altered gene, with a mutation rate of 49.8%, followed by EML4-ALK (9.3%, PTEN (9.1%, PIK3CA (5.2%, c-Met (4.8%, KRAS (4.5%, STK11 (2.7%, and BRAF (1.9%. The three most frequently altered genes in a subgroup of smokers with adenocarcinoma were EGFR (22.0%, STK11 (19.0%, and KRAS (12.0%. We only found EGFR (8.0%, c-Met (2.8%, and PIK3CA (2.6% alterations in the non-smoker with squamous cell carcinoma (SCC subgroup. PTEN (16.1%, STK11 (8.3%, and PIK3CA (7.2% were the three most frequently enriched genes in smokers with SCC. DDR2 and FGFR2 only presented in smokers with SCC (4.4% and 2.2%, respectively. Among these four subgroups, the differences in EGFR, KRAS, and PTEN mutations were statistically significant. CONCLUSION: The distinct features of driver gene alterations in different subgroups based on histology and smoking status were helpful in defining patients for future clinical trials that target these genes. This study also suggests that we may consider patients with infrequent alterations of driver genes as having rare or orphan diseases that should be managed with special molecularly targeted therapies.

  4. Phase Ⅰ trial of icotinib, a novel epidermal growth factor receptor tyrosine kinase inhibitor, in Chinese patients with non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    WANG Han-ping; XIAO Yi; ZHANG Li; WANG Yin-xiang; TAN Fen-lai; XIA Ying; REN Guan-jun; HU Pei; JIANG Ji; WANG Meng-zhao

    2011-01-01

    Background The preclinical experiments and studies of congener drugs show icotinib, a new epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, can specifically bind to the tyrosine kinase domain of the EGFR, block the EGFR related signal, thereby inhibit the growth of tumor cell. The objective of this study was to investigate the safety, tolerability and dose-related biologic effects of icotinib in patients with non-small cell lung cancer (NSCLC) in a Chinese patient population.Methods This was an open-label, phase Ⅰ, dose escalation, safety/tolerability trial of oral icotinib (100 to 400 mg), administered twice per day for 28-continuous-day cycles until disease progression or undue toxiclty.Results Forty patients with stage ⅢB (15%) or Ⅳ (85%) NSCLC were included in the study. They had mainly adenocarcinoma (85%), with a performance status (PS) of 0 (45%) or 1 (55%) and less than half the patients (45%) had histories of smoking and all were pretreated by at least one regimen of chemotherapy. Patients were assigned to three dose levels of 150 mg b.i.d, 200 mg b.i.d, or 125 mg t.i.d. The follow-up periods ranged from 5 to 80 weeks. Adverse events were found in 35% patients, most of which were mild and reversible. The adverse events mainly occurred in the first 4 weeks and included rash (25%), diarrhea, nausea and abdominal distention. One definite interstitial lung disease (ILD) was found in a patient in the dose of 200 mg b.i.d. According to an 8-week assessment, one (2.5%) patient receiving 150 mg gained complete response (CR) that persisted for 44 weeks, seven (17.50%) patients had partial remission (PR), and 18 (45%) patients had stable disease (SD). The objective response including CR+PR was 20%. The median time of progression-free survival for the 40 patients was 20 weeks (range: 12 to 32 weeks). The response was not affected by pathological type, history of smoking, or numbers of previous therapeutic regimens. No relationship between dose

  5. Comparison of three methods for detecting epidermal growth factor receptor mutations in plasma DNA samples of Chinese patients with advanced non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    QIN Ling; ZHONG Wei; ZHANG Li; LI Long-yun; WANG Meng-zhao

    2011-01-01

    Background Epidermal growth factor receptor (EGFR) mutations can predict tumor response to tyrosine kinase inhibitors (TKIs). Detecting EGFR mutations in plasma DNA samples in patients with advanced non-small cell lung cancer is challenging and promising. We compared three methods for detecting plasma EGFR mutations, including direct DNA sequencing, denaturing high-performance liquid chromatography (DHPLC) and Scorpions Amplification Refractory Mutation System (Scorpions ARMS).Methods Plasma DNA samples from 73 patients with stage ⅢB to Ⅳ adenocarcinoma were analyzed for EGFR mutations in exons 19 (deletion mutation) and 21(L858R mutation) using direct DNA sequencing, DHPLC and Scorpions ARMS. Sensitivities of the three methods were compared and the relationship between EGFR mutations and patients'survival was analyzed.Results In 73 patients, we detected EGFR mutations in 5 samples (6.9%) by direct DNA sequencing, in 22 samples (30.1%) by DHPLC, and in 28 samples (38.4%) by Scorpions ARMS. EGFR mutations were found in 13 samples in exon 19 and in 9 samples in exon 21 by DHPLC, while we found mutations in 15 samples in exon 19 and in 13 samples in exon 21 by Scorpions ARMS. Among the 73 patients, there was 90.4% concordance between DHPLC and Scorpions ARMS (66/73, K=0.79, P=0.07). Of the 73 patients, 46 patients were treated with gefitinib, including 18 patients with mutations and 28 patients without mutations as determined by Scorpions ARMS. The 18 patients with mutations had a significantly longer progression-free survival (PFS) time (median PFS was 21.0 months) than the 28 patients without mutations (median PFS was 7.0 months) (P=0.022).Conclusions Among the three methods for detecting EGFR mutations in plasma DNA samples of patients with advanced lung adenocarcinoma, direct gene sequencing had the lowest sensitivity, while Scorpion ARMS showed the highest mutation detecting capability. DHPLC is slightly less sensitive than Scorpion ARMS. EGFR

  6. 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

  7. EGFR-TKI therapy for patients with brain metastases from non-small-cell lung cancer: a pooled analysis of published data

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    Fan Y

    2014-11-01

    Full Text Available Yun Fan,1,2 Xiaoling Xu,3 Conghua Xie4 1Zhongnan Hospital of Wuhan University, Department of Radiation Oncology, Wuhan, People's Republic of China; 2Department of Chemotherapy, Zhejiang Cancer Hospital, Hangzhou, People’s Republic of China; 3Zhejiang Cancer Hospital, Hangzhou, People’s Republic of China; 4Zhongnan Hospital of Wuhan University, Department of Radiation Oncology, Wuhan, People’s Republic of China Introduction: Brain metastases are one of the leading causes of death from non-small-cell lung cancer (NSCLC. The use of epidermal growth factor receptor (EGFR tyrosine kinase inhibitors (TKIs to treat brain metastases remains controversial. Thus, we performed a pooled analysis of published data to evaluate the efficacy of EGFR-TKIs in NSCLC patients with brain metastases, particularly for tumors with activating EGFR mutations. Methods: Several data sources were searched, including PubMed, Web of Science, and ASCO Annual Meetings databases. The end points were intracranial overall response rate (ORR, disease control rate (DCR, progression-free survival (PFS, overall survival (OS, and adverse events. The pooled ORR, DCR, PFS, and OS with 95% confidence intervals (CIs were calculated employing fixed- or random-effect models, depending on the heterogeneity of the included studies. Results: Sixteen published studies were included in this analysis, with a total of 464 enrolled patients. The EGFR mutational status was unknown for 362 (unselected group, and 102 had activating EGFR mutations. The pooled intracranial ORR and DCR were 51.8% (95% CI: 45.8%–57.8% and 75.7% (95% CI: 70.3%–80.5%, respectively. A higher ORR was observed in the EGFR mutation group than in the unselected group (85.0% vs 45.1%; a similar trend was observed for the DCR (94.6% vs 71.3%. The pooled median PFS and OS were 7.4 months (95% CI, 4.9–9.9 and 11.9 months (95% CI, 7.7–16.2, respectively, with longer PFS (12.3 months vs 5.9 months and OS (16.2 months vs

  8. High plasma exposure to pemetrexed leads to severe hyponatremia in patients with advanced non small cell lung cancer receiving pemetrexed-platinum doublet chemotherapy

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    Gota V

    2014-06-01

    Full Text Available Vikram Gota,1 Krunal Kavathiya,1 Kartik Doshi,1 Murari Gurjar,1 Solai E Damodaran,1 Vanita Noronha,2 Amit Joshi,2 Kumar Prabhash2 1Department of Clinical Pharmacology, Advanced Centre for Treatment Research and Education in Cancer, 2Department of Medical Oncology, Tata Memorial Hospital, Mumbai, India Background: Pemetrexed-platinum doublet therapy is a standard treatment for stage IIIb/IV nonsquamous non small cell lung cancer (NSCLC. While the regimen is associated with several grade ≥3 toxicities, hyponatremia is not a commonly reported adverse effect. Here we report an unusually high incidence of grade ≥3 hyponatremia in Indian patients receiving pemetrexed-platinum doublet, and the pharmacological basis for this phenomenon. Methods: Forty-six patients with advanced NSCLC were enrolled for a bioequivalence study of two pemetrexed formulations. All patients received the pemetrexed-platinum doublet for six cycles followed by single-agent pemetrexed maintenance until progression. Pharmacokinetic blood samples were collected at predefined time points during the first cycle and the concentration-time profile of pemetrexed was investigated by noncompartmental analysis. Hyponatremic episodes were investigated with serum electrolytes, serum osmolality, urinary sodium, and urine osmolality. Results: Sixteen of 46 patients (35% had at least one episode of grade ≥3 hyponatremia. Twenty-four episodes of grade ≥3 hyponatremia were observed in 200 cycles of doublet chemotherapy. Plasma exposure to pemetrexed was significantly higher in patients with high-grade hyponatremia than in those with low-grade or no hyponatremia (P=0.063 and P=0.001, respectively. Pemetrexed clearance in high-grade hyponatremia was quite low compared with normal and low-grade hyponatremia (P=0.001 and P=0.055, respectively. Median pemetrexed exposure in this cohort was much higher than that reported in the literature from Western studies. Conclusion: Higher exposure to

  9. Role of [{sup 18}F]FDG PET in prediction of KRAS and EGFR mutation status in patients with advanced non-small-cell lung cancer

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    Caicedo, Carlos; Garcia-Velloso, Maria Jose; Vigil Diaz, Carmen; Richter Echevarria, Jose Angel [University of Navarra, Nuclear Medicine Department, University Clinic of Navarra, Pamplona (Spain); Lozano, Maria Dolores; Labiano, Tania [University of Navarra, Pathology Department, University Clinic of Navarra, Pamplona (Spain); Lopez-Picazo, Jose Maria; Gurpide, Alfonso; Perez Gracia, Jose Luis [University of Navarra, Oncology Department, University Clinic of Navarra, Pamplona (Spain); Zulueta, Javier [University of Navarra, Pulmonology Department, University Clinic of Navarra, Pamplona (Spain)

    2014-11-15

    The tumour molecular profile predicts the activity of epidermal growth factor receptor (EGFR) inhibitors in non-small-cell lung cancer (NSCLC). However, tissue availability and tumour heterogeneity limit its assessment. We evaluated whether [{sup 18}F]FDG PET might help predict KRAS and EFGR mutation status in NSCLC. Between January 2005 and October 2011, 340 NSCLC patients were tested for KRAS and EGFR mutation status. We identified patients with stage III and IV disease who had undergone [{sup 18}F]FDG PET/CT scanning for initial staging. SUVpeak, SUVmax and SUVmean of the single hottest tumour lesions were calculated, and their association with KRAS and EGFR mutation status was assessed. A receiver operator characteristic (ROC) curve analysis and a multivariate analysis (including SUVmean, gender, age and AJCC stage) were performed to identify the potential value of [{sup 18}F]FDG PET/CT for predicting KRAS mutation. From 102 patients staged using [{sup 18}F]FDG PET/CT, 28 (27 %) had KRAS mutation (KRAS+), 22 (22 %) had EGFR mutation (EGFR+) and 52 (51 %) had wild-type KRAS and EGFR profiles (WT). KRAS+ patients showed significantly higher [{sup 18}F]FDG uptake than EGFR+ and WT patients (SUVmean 9.5, 5.7 and 6.6, respectively; p < 0.001). No significant differences were observed in [{sup 18}F]FDG uptake between EGFR+ patients and WT patients. ROC curve analysis for KRAS mutation status discrimination yielded an area under the curve of 0.740 for SUVmean (p < 0.001). The multivariate analysis showed a sensitivity and specificity of 78.6 % and 62.2 %, respectively, and the AUC was 0.773. NSCLC patients with tumours harbouring KRAS mutations showed significantly higher [{sup 18}F]FDG uptake than WT patients, as assessed in terms of SUVpeak, SUVmax and SUVmean. A multivariate model based on age, gender, AJCC stage and SUVmean might be used as a predictive marker of KRAS mutation status in patients with stage III or IV NSCLC. (orig.)

  10. Evaluating Tumor Response of Non-Small Cell Lung Cancer Patients With {sup 18}F-Fludeoxyglucose Positron Emission Tomography: Potential for Treatment Individualization

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    Toma-Dasu, Iuliana, E-mail: Iuliana.Livia.Dasu@ki.se [Medical Radiation Physics, Stockholm University and Karolinska Institutet, Stockholm (Sweden); Uhrdin, Johan [RaySearch Laboratories AB, Stockholm (Sweden); Lazzeroni, Marta [Medical Radiation Physics, Karolinska Institutet, Stockholm (Sweden); Carvalho, Sara; Elmpt, Wouter van; Lambin, Philippe [Department of Radiation Oncology, GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht (Netherlands); Dasu, Alexandru [Department of Radiation Physics and Department of Medical and Health Sciences, Linköping University, Linköping (Sweden)

    2015-02-01

    Objective: To assess early tumor responsiveness and the corresponding effective radiosensitivity for individual patients with non-small cell lung cancer (NSCLC) based on 2 successive {sup 18}F-fludeoxyglucose positron emission tomography (FDG-PET) scans. Methods and Materials: Twenty-six NSCLC patients treated in Maastricht were included in the study. Fifteen patients underwent sequential chemoradiation therapy, and 11 patients received concomitant chemoradiation therapy. All patients were imaged with FDG before the start and during the second week of radiation therapy. The sequential images were analyzed in relation to the dose delivered until the second image. An operational quantity, effective radiosensitivity, α{sub eff}, was determined at the voxel level. Correlations were sought between the average α{sub eff} or the fraction of negative α{sub eff} values and the overall survival at 2 years. Separate analyses were performed for the primary gross target volume (GTV), the lymph node GTV, and the clinical target volumes (CTVs). Results: Patients receiving sequential treatment could be divided into responders and nonresponders, using a threshold for the average α{sub eff} of 0.003 Gy{sup −1} in the primary GTV, with a sensitivity of 75% and a specificity of 100% (P<.0001). Choosing the fraction of negative α{sub eff} as a criterion, the threshold 0.3 also had a sensitivity of 75% and a specificity of 100% (P<.0001). Good prognostic potential was maintained for patients receiving concurrent chemotherapy. For lymph node GTV, the correlation had low statistical significance. A cross-validation analysis confirmed the potential of the method. Conclusions: Evaluation of the early response in NSCLC patients showed that it is feasible to determine a threshold value for effective radiosensitivity corresponding to good response. It also showed that a threshold value for the fraction of negative α{sub eff} could also be correlated with poor response. The proposed

  11. Effect of the XRCC1 and XRCC3 Genetic Polymorphisms on the Efficacy of Platinum-based Chemotherapy in Patients with Advanced Non-small Cell Lung Cancer

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    Chong’an XU

    2011-12-01

    Full Text Available Background and objective DNA repair gene polymorphisms can be used to predict the sensitivity of platinum-based chemotherapy. Thus, such polymorphisms are important for the individual treatment of non-small cell lung cancer (NSCLC. The aim of this study is to investigate the relationship between X-ray repair cross complementing protein 1 (XRCC1 and X-ray repair cross complementing protein 3 (XRCC3 gene polymorphisms and the chemosensitivity of platinum-based chemotherapy in patients with advanced NSCLC. Methods Genomic DNA were extracted from the sera of a total of 130 patients with advanced NSCLC who received platinum-based chemotherapy. XRCC1 Arg194 Trp, Arg399 Gln, and XRCC3 Thr241 Met were genotyped using the polymerase chain reaction-restriction fragment length polymorphism method, and the relationship between XRCC1 and XRCC3 polymorphisms and chemotherapy sensitivity was analyzed. Results A total of 130 patients with advanced NSCLC received platinum-based chemotherapy, with an overall response rate of 33.8% after two chemotherapy cycles. The XRCC1 194 and 399 genetic polymorphisms, but not XRCC3 241, were found to be related to the chemosensitivity. The objective response rate of the patients with at least one XRCC1 194 Trp allele was 2.5 times higher than that of Arg/Arg genotype carriers (42.1% vs 22.2%, OR=2.545, 95%CI: 1.159-5.590, P=0.020. The objective response rate of the XRCC1 399 Arg/Arg genotype carriers was significantly higher than that of the patients with at least one Gln allele (45.5% vs 21.9%, OR=0.336, 95%CI: 0.156-0.722, P=0.005. Combined effects between XRCC1 194 and XRCC1 399 were observed. The objective response rate of the patients with at least one XRCC1 194 Trp allele and a 399 Arg/Arg genotype was significantly higher than that of patients with 194 Arg/Arg and 399 Arg/Gln genotypes (44.4% vs 18.8%, OR=3.467, 95%CI: 1.223-9.782, P=0.019. Moreover, XRCC1 and XRCC3 have a combined effect in predicting chemosensitivity

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

    Science.gov (United States)

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

    2015-06-01

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

  13. Neoadjuvant therapy and surgical resection for locally advanced non-small cell lung cancer.

    Science.gov (United States)

    Meko, J; Rusch, V W

    2000-10-01

    During the past 15 years, treatment of stage IIIA (N2) non-small cell lung cancer has evolved considerably because of improvements in patients selection, staging, and combined modality therapy. Results of several clinical trials suggest that induction chemotherapy or chemoradiation and surgical resection is superior to surgery alone. However, the optimal induction regimen has not been defined. An intergroup trial is also underway to determine whether chemoradiation and surgical resection leads to better survival than chemotherapy and radiation alone. Future studies will assess ways to combine radiation and novel chemotherapeutic agents, and will identify molecular abnormalities that predict response to induction therapy.

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

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    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.

  15. Potential role of immunotherapy in advanced non-small-cell lung cancer

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    de Mello RA

    2016-12-01

    Full Text Available Ramon Andrade de Mello,1–3 Ana Flávia Veloso,4 Paulo Esrom Catarina,4 Sara Nadine,5 Georgios Antoniou6 1Department of Biomedical Sciences and Medicine, University of Algarve, Faro, 2Faculty of Medicine, University of Porto, Porto, Portugal; 3Research Center, Cearense School of Oncology, Instituto do Câncer do Ceará, 4Oncology & Hematology League, School of Medicine, State University of Ceará (UECE, Fortaleza, Brazil; 5Instituto de Ciências Biomédicas Abel Salazar (ICBAS, University of Porto, Porto, Portugal; 6Department of Medical Oncology, The Royal Marsden NHS Foundation Trust, London, UK Abstract: Immuno checkpoint inhibitors have ushered in a new era with respect to the treatment of advanced non-small-cell lung cancer. Many patients are not suitable for treatment with epidermal growth factor receptor tyrosine kinase inhibitors (eg, gefitinib, erlotinib, and afatinib or with anaplastic lymphoma kinase inhibitors (eg, crizotinib and ceritinib. As a result, anti-PD-1/PD-L1 and CTLA-4 inhibitors may play a novel role in the improvement of outcomes in a metastatic setting. The regulation of immune surveillance, immunoediting, and immunoescape mechanisms may play an interesting role in this regard either alone or in combination with current drugs. Here, we discuss advances in immunotherapy for the treatment of metastatic non-small-cell lung cancer as well as future perspectives within this framework. Keywords: immunotherapy, non-small-cell lung cancer, nivolumab, pembrolizumab, ipilimumab, clinical trials, PD1, PDL1, CTLA4

  16. Pemetrexed induced thymidylate synthase inhibition in non-small cell lung cancer patients: a pilot study with 3'-deoxy-3'-[¹⁸F]fluorothymidine positron emission tomography.

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    Virginie Frings

    Full Text Available OBJECTIVES: Pemetrexed is a thymidylate synthase (TS inhibitor and is effective in non-small cell lung cancer (NSCLC. 3'-deoxy-3'-[¹⁸F]fluorothymidine (¹⁸F-FLT, a proliferation marker, could potentially identify tumor specific TS-inhibition. The aim of this study was to investigate the effect of pemetrexed-induced TS-inhibition on ¹⁸F-FLT uptake 4 hours after pemetrexed administration in metastatic NSCLC patients. METHODS: Fourteen NSCLC patients underwent dynamic ¹⁸F-FLT positron emission tomography (PET scans at baseline and 4 hours after the first dose of pemetrexed. Volumes of interest were defined with a 41%, 50% and 70% threshold of the maximum pixel. Kinetic analysis and simplified measures were performed. At one, two, four and six hours after pemetrexed, plasma deoxyuridine was measured as systemic indicator of TS-inhibition. Tumor response measured with response evaluation criteria in solid tumors (RECIST, time to progression (TTP and overall survival (OS were determined. RESULTS: Eleven patients had evaluable ¹⁸F-FLT PET scans at baseline and 4 hours after pemetrexed. Two patients had increased ¹⁸F-FLT uptake of 35% and 31% after pemetrexed, whereas two other patients had decreased uptake of 31%. In the remaining seven patients ¹⁸F-FLT uptake did not change beyond test-retest borders. In all patients deoxyuridine levels raised after administration of pemetrexed, implicating pemetrexed-induced TS-inhibition. ¹⁸F-FLT uptake in bone marrow was significantly increased 4 hours after pemetrexed administration. Six weeks after the start of treatment 5 patients had partial response, 4 stable disease and 2 progressive disease. Median TTP was 4.2 months (range 3.0-7.4 months; median OS was 13.0 months (range 5.1-30.8 months. Changes in ¹⁸F-FLT uptake were not predictive for tumor response, TTP or OS. CONCLUSIONS: Measuring TS-inhibition in a clinical setting 4 hours after pemetrexed revealed a non-systematic change in

  17. FDG PET during radiochemotherapy is predictive of outcome at 1 year in non-small-cell lung cancer patients: a prospective multicentre study (RTEP2)

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    Vera, Pierre; Edet-Sanson, Agathe; Modzelewski, Romain [Henri Becquerel Center and QuantIF - Litis EA-Equipe d' Accueil-4108 and Rouen University Hospital, Department of Nuclear Medicine, Henri Becquerel Cancer Center, Rouen (France); Mezzani-Saillard, Sandrine; Thureau, Sebastien; Dubray, Bernard [Henri Becquerel Center and QuantIF - Litis ' ' EA (Equipe d' Accueil) 4108' ' and Rouen University Hospital, Department of Radiation Oncology and Medical Physics, Henri Becquerel Cancer Center, Rouen (France); Menard, Jean-Francois [Rouen University Hospital and University of Rouen, Department of Biostatistics, Rouen (France); Meyer, Marc-Etienne [Amiens University Hospital, Department of Nuclear Medicine, Amiens (France); Jalali, Khadija [Amiens University Hospital, Department of Radiation Oncology, Amiens (France); Bardet, Stephane [Francois Baclesse Cancer Center, Department of Nuclear Medicine, Caen (France); Lerouge, Delphine [Francois Baclesse Cancer Center, Department of Radiation Oncology, Caen (France); Houzard, Claire [Hospices Civils de Lyon, Department of Nuclear Medicine, Lyon (France); Mornex, Francoise [Hospices Civils de Lyon, Department of Radiation Oncology, Lyon (France); Olivier, Pierre [Brabois University Hospital, Department of Nuclear Medicine, Nancy (France); Faure, Guillaume [Centre prive de Radiotherapie de Metz, Department of Radiation Oncology, Metz (France); Rousseau, Caroline [Renee Gauducheau Cancer Center, Department of Nuclear Medicine, Nantes (France); Mahe, Marc-Andre [Institut de Cancerologie-Rene Gauducheau, Department of Radiation Oncology, Nantes (France); Gomez, Philippe [Centre Frederic Joliot, Radiation Oncology, Rouen (France); Clinique Saint-Hilaire, Rouen (France); Brenot-Rossi, Isabelle [Institut Paoli Calmette, Department of Nuclear Medicine, Marseille (France); Salem, Naji [Institut Paoli Calmette, Department of Radiation Oncology, Marseille (France)

    2014-06-15

    To assess prospectively the prognostic value of FDG PET/CT during curative-intent radiotherapy (RT) with or without concomitant chemotherapy in patients with non-small-cell lung cancer (NSCLC). Patients with histological proof of invasive localized NSCLC and evaluable tumour, and who were candidates for curative-intent radiochemotherapy (RCT) or RT were preincluded after providing written informed consent. Definitive inclusion was conditional upon significant FDG uptake before RT (PET{sub 1}). All included patients had a FDG PET/CT scan during RT (PET{sub 2}, mean dose 43 Gy) and were evaluated by FDG PET/CT at 3 months and 1 year after RT. The main endpoint was death (from whatever cause) or tumour progression at 1 year. Of 77 patients preincluded, 52 were evaluable. Among the evaluable patients, 77 % received RT with induction chemotherapy and 73 % RT with concomitant chemotherapy. At 1 year, 40 patients (77 %) had died or had tumour progression. No statistically significant association was found between stage (IIIB vs. other), histology (squamous cell carcinoma vs. other), induction or concomitant chemotherapy, and death/tumour progression at 1 year. The SUV{sub max} in the PET{sub 2} scan was the single variable predictive of death or tumour progression at 1 year (odds ratio 1.97, 95 % CI 1.25 - 3.09, p = 0.003) in multivariate analysis. The area under the receiver operating characteristic curve was 0.85 (95 % CI 0.73 - 0.94, p < 10{sup -4}). A SUV{sub max} value of 5.3 in the PET{sub 2} scan yielded a sensitivity of 70 % and a specificity of 92 % for predicting tumour progression or death at 1 year. This prospective multicentre study demonstrated the prognostic value in terms of disease-free survival of SUV{sub max} assessed during the 5th week of curative-intent RT or RCT in NSCLC patients (NCT01261598; RTEP2 study). (orig.)

  18. Study of 201 Non-Small Cell Lung Cancer Patients Given Stereotactic Ablative Radiation Therapy Shows Local Control Dependence on Dose Calculation Algorithm

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    Latifi, Kujtim, E-mail: Kujtim.Latifi@Moffitt.org [Department of Radiation Oncology, Moffitt Cancer Center, Tampa, Florida (United States); Oliver, Jasmine [Department of Radiation Oncology, Moffitt Cancer Center, Tampa, Florida (United States); Department of Physics, University of South Florida, Tampa, Florida (United States); Baker, Ryan [University of South Florida School of Medicine, Tampa, Florida (United States); Dilling, Thomas J.; Stevens, Craig W. [Department of Radiation Oncology, Moffitt Cancer Center, Tampa, Florida (United States); Kim, Jongphil; Yue, Binglin [Department of Biostatics and Bioinformatics, Moffitt Cancer Center, Tampa, Florida (United States); DeMarco, MaryLou; Zhang, Geoffrey G.; Moros, Eduardo G.; Feygelman, Vladimir [Department of Radiation Oncology, Moffitt Cancer Center, Tampa, Florida (United States)

    2014-04-01

    Purpose: Pencil beam (PB) and collapsed cone convolution (CCC) dose calculation algorithms differ significantly when used in the thorax. However, such differences have seldom been previously directly correlated with outcomes of lung stereotactic ablative body radiation (SABR). Methods and Materials: Data for 201 non-small cell lung cancer patients treated with SABR were analyzed retrospectively. All patients were treated with 50 Gy in 5 fractions of 10 Gy each. The radiation prescription mandated that 95% of the planning target volume (PTV) receive the prescribed dose. One hundred sixteen patients were planned with BrainLab treatment planning software (TPS) with the PB algorithm and treated on a Novalis unit. The other 85 were planned on the Pinnacle TPS with the CCC algorithm and treated on a Varian linac. Treatment planning objectives were numerically identical for both groups. The median follow-up times were 24 and 17 months for the PB and CCC groups, respectively. The primary endpoint was local/marginal control of the irradiated lesion. Gray's competing risk method was used to determine the statistical differences in local/marginal control rates between the PB and CCC groups. Results: Twenty-five patients planned with PB and 4 patients planned with the CCC algorithms to the same nominal doses experienced local recurrence. There was a statistically significant difference in recurrence rates between the PB and CCC groups (hazard ratio 3.4 [95% confidence interval: 1.18-9.83], Gray's test P=.019). The differences (Δ) between the 2 algorithms for target coverage were as follows: ΔD99{sub GITV} = 7.4 Gy, ΔD99{sub PTV} = 10.4 Gy, ΔV90{sub GITV} = 13.7%, ΔV90{sub PTV} = 37.6%, ΔD95{sub PTV} = 9.8 Gy, and ΔD{sub ISO} = 3.4 Gy. GITV = gross internal tumor volume. Conclusions: Local control in patients receiving who were planned to the same nominal dose with PB and CCC algorithms were statistically significantly different. Possible

  19. Prognostic value of MET gene copy number and protein expression in patients with surgically resected non-small cell lung cancer: a meta-analysis of published literatures.

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    Baoping Guo

    Full Text Available BACKGROUND: The prognostic value of the copy number (GCN and protein expression of the mesenchymal-epithelial transition (MET gene for survival of patients with non-small cell lung cancer (NSCLC remains controversial. This study aims to comprehensively and quantitatively asses the suitability of MET GCN and protein expression to predict patients' survival. METHODS: PubMed, Embase, Web of Science and Google Scholar were searched for articles comparing overall survival in patients with high MET GCN or protein expression with those with low level. Pooled hazard ratio (HR and 95% confidence intervals (CIs were calculated using the random and the fixed-effects models. Subgroup and sensitivity analyses were also performed. RESULTS: Eighteen eligible studies enrolling 5,516 patients were identified. Pooled analyses revealed that high MET GCN or protein expression was associated with poor overall survival (OS (GCN: HR = 1.90, 95% CI 1.35-2.68, p<0.001; protein expression: HR = 1.52, 95% CI 1.08-2.15, p = 0.017. In Asian populations (GCN: HR = 2.22, 95% CI 1.46-3.38, p<0.001; protein expression: HR = 1.89, 95% CI 1.34-2.68, p<0.001, but not in the non-Asian subset. For adenocarcinoma, high MET GCN or protein expression indicated decreased OS (GCN: HR = 1.49, 95% CI 1.05-2.10, p = 0.025; protein expression: HR = 1.69, 95% CI 1.31-2.19, p<0.001. Results were similar for multivariate analysis (GCN: HR = 1.61, 95% CI 1.15-2.25, p = 0.005; protein expression: HR = 2.18, 95% CI 1.60-2.97, p<0.001. The results of the sensitivity analysis were not materially altered and did not draw different conclusions. CONCLUSIONS: Increased MET GCN or protein expression was significantly associated with poorer survival in patients with surgically resected NSCLC; this information could potentially further stratify patients in clinical treatment.

  20. Plasma fibrinogen levels are associated with epidermal growth factor receptor gene mutation in Chinese patients with non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    Jianfei Zhu; Ling Cai; Haoxian Yang; Yinsheng Wen; Junye Wang; Tiehua Rong; Lanjun Zhang

    2013-01-01

    Objective: The plasma fibrinogen levels had not only been used as an independent prognostic parameter for thepatients with non-small cell lung cancer (NSCLC), but also as a promising biomarker for evaluating the efficacy of chemotherapy. This study aimed to investigate the correlation between the plasma fibrinogen levels and epidermal growth factor receptor (EGFR) gene mutation and clinical-pathological characteristics of Chinese patients with NSCLC. Methods: In this retrospective study, NSCLC specimens collected from 352 patients between November 2009 and November 2011 were selected to detect EGFR gene mutation with real-time polymerase chain reaction (RT-PCR). In these specimens, 308 ones were also detected EGFR gene copy number with fluorescence in situ hybridization (FISH). Coagulation makers were examined prior to the operations. The association between the plasma fibrinogen levels and EGFR gene mutation and clinical-pathological characteristics were analyzed using SPSS 16.0 software. Results: The median pre-operation plasma fibrinogen level was 3.55 g/L (109/352) patients with higher plasma fibrinogen level (> 4.0 g/L). The lower plasma fibrinogen levels correlated significantly with EGFR gene mutations (P < 0.001), the similar result was seen in platelet counts (P = 0.026). A linear correlation was found between the plasma fibrinogen levels and the platelet counts in NSCLC patients (R2 = 0.209, P < 0.001). Pre-operationplasma fibrinogen levels correlated with gender (P < 0.001), smoking status (P < 0.001), and histology (P < 0.001). There weresignificant link between the above clinical-pathological characteristics and EGFR gene mutations. In addition, EGFR gene mutationwas correlated with FISH-positive status (P < 0.001). Moreover, both plasma fibrinogen level (P = 0.024) and the EGFRgene copy number (P = 0.040) had significant relationships with the pathological TNM stage. Conclusion: This study showedthat a significant relevance between plasma fibrinogen

  1. Detection of epidermal growth factor receptor mutation in plasma as a biomarker in Chinese patients with early-stage non-small cell lung cancer

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    Guo K

    2015-11-01

    Full Text Available Kai Guo,1,* ZhiPei Zhang,1,* Lu Han,2,* Jing Han,3 Jian Wang,1 YongAn Zhou,1 HongGang Liu,1 LiPing Tong,1 XiaoFei Li,1 XiaoLong Yan11Department of Thoracic Surgery, Tangdu Hospital, 2Department of Ultrasound, Xijing Hospital, 3Department of Ophthalmology, Tangdu Hospital, The Fourth Military Medical University, Xi’an, People’s Republic of China*These authors contributed equally to this workPurpose: This preplanned exploratory analysis was conducted to reveal the true status of correlation between tissue and plasma detection for early-stage non-small cell lung cancer (NSCLC epidermal growth factor receptor (EGFR mutations, knowing that specific subgroups of NSCLC patients may be potential candidates for EGFR mutation analysis by using plasma samples.Materials and methods: Tissue samples were surgically resected from 198 patients with stage I–IV NSCLC, where stage IA to IIIA accounted for 92.4%. EGFR mutations in all these tissues were positive. Paired plasma EGFR mutations were detected by real-time polymerase chain reaction; concentration of cell-free DNA (cfDNA in plasma was measured by ultraviolet spectrophotometry.Results: EGFR-activating mutation was detected in 34 plasma samples, and their mutation types were matched with that in tissue. The sensitivity of EGFR mutation for the 198 paired tissue and plasma samples was 17.2%. The sensitivity positively correlated with disease stage and negatively correlated with tumor differentiation. The sensitivity of stage IA, IB, IIA, IIB, and IIIA was 1.6%, 7.9%, 11.1%, 20%, and 33.3%, respectively; the sensitivity of high differentiation was 0% versus 36.8% for poor differentiation. There was no correlation between plasma cfDNA concentration and patient characteristics.Conclusion: We recommend using plasma cfDNA as a biomarker in stage IIIA or poorly differentiated tumors for gene diagnosis, especially in patients whose tissue samples cannot be obtained by surgery. Plasma samples can really

  2. 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

  3. Lymphopenia Association With Gross Tumor Volume and Lung V5 and Its Effects on Non-Small Cell Lung Cancer Patient Outcomes

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    Tang, Chad [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Liao, Zhongxing, E-mail: zliao@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Gomez, Daniel; Levy, Lawrence; Zhuang, Yan; Gebremichael, Rediet A. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Hong, David S. [Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Komaki, Ritsuko; Welsh, James W. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2014-08-01

    Purpose: Radiation therapy (RT) can both suppress and stimulate the immune system. We sought to investigate the mechanisms underlying radiation-induced lymphopenia and its associations with patient outcomes in non-small cell lung cancer (NSCLC). Methods and Materials: Subjects consisted of 711 patients who had received definitive RT for NSCLC. A lymphocyte nadir was calculated as the minimum lymphocyte value measured during definitive RT. Associations between gross tumor volumes (GTVs) and lung dose-volume histogram (DVH) parameters with lymphocyte nadirs were assessed with Spearman correlation coefficients. Relationships between lymphocyte nadirs with overall survival (OS) and event free survival (EFS) were evaluated with Kaplan-Meier analysis and compared with log-rank test results. Multivariate regressions were conducted with linear and Cox regression analyses. All variables were analyzed as continuous if possible. Results: Larger GTVs were correlated with lower lymphocyte nadirs regardless of concurrent chemotherapy receipt (with concurrent: r = −0.26, P<.0001; without: r = −0.48, P<.0001). Analyses of lung DVH parameters revealed significant correlations at lower doses (lung V5-V10: P<.0001) that incrementally decreased and became nonsignificant at higher doses (lung V60-V70: P>.05). Of note, no significant associations were detected between GTV and lung DVH parameters with total leukocyte, neutrophil, or monocyte nadirs during RT or with lymphocyte count prior to RT. Multivariate analysis revealed larger GTV (P<.0001), receipt of concurrent chemotherapy (P<.0001), twice-daily radiation fractionation (P=.02), and stage III disease (P=.05) to be associated with lower lymphocyte nadirs. On univariate analysis, patients with higher lymphocyte nadirs exhibited significantly improved OS (hazard ratio [HR] = 0.51 per 10{sup 3} lymphocytes/μL, P=.01) and EFS (HR = 0.46 per 10{sup 3} lymphocytes/μL, P<.0001). These differences held on multivariate analyses

  4. {sup 18}F-alfatide PET/CT may predict short-term outcome of concurrent chemoradiotherapy in patients with advanced non-small cell lung cancer

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    Luan, Xiaohui [Shandong Cancer Hospital affiliated to Shandong University, Department of Radiation Oncology, Jinan, Shandong (China); University of Jinan-Shandong Academy of Medical Sciences, School of Medicine and Life Sciences, Jinan (China); Huang, Yong; Sun, Xiaorong; Ma, Li; Teng, Xuepeng; Lu, Hong [Shandong Cancer Hospital affiliated to Shandong University, Department of Radiology, Jinan, Shandong (China); Gao, Song [Jining Infectious Diseases Hospital, Department of Oncology, Jining, Shandong (China); Wang, Suzhen; Yu, Jinming; Yuan, Shuanghu [Shandong Cancer Hospital affiliated to Shandong University, Department of Radiation Oncology, Jinan, Shandong (China)

    2016-12-15

    The study aims to investigate the role of {sup 18}F-alfatide positron emission tomography/computed tomography (PET/CT) in predicting the short-term outcome of concurrent chemoradiotherapy (CCRT) in patients with advanced non-small cell lung cancer (NSCLC). Eighteen patients with advanced NSCLC had undergone {sup 18}F-alfatide PET/CT scans before CCRT and PET/CT parameters including maximum and mean standard uptake values (SUV{sub max}/SUV{sub mean}), peak standard uptake values (SUV{sub peak}) and tumor volume (TV{sub PET} and TV{sub CT}) were obtained. The SUV{sub max} of tumor and normal tissues (lung, blood pool and muscle) were measured, and their ratios were denoted as T/NT (T/NT{sub lung}, T/NT{sub blood} and T/NT{sub muscle}). Statistical methods included the Two-example t test, Wilcoxon rank-sum test, Receiver-operating characteristic (ROC) curve analysis and logistic regression analyses. We found that SUV{sub max}, SUV{sub peak}, T/NT{sub lung}, T/NT{sub blood} and T/NT{sub muscle} were higher in non-responders than in responders (P = 0.0024, P = 0.016, P < 0.001, P = 0.003, P = 0.004). According to ROC curve analysis, the thresholds of SUV{sub max}, SUV{sub peak}, T/NT{sub lung}, T/NT{sub blood} and T/NT{sub muscle} were 5.65, 4.46, 7.11, 5.41, and 11.75, respectively. The five parameters had high sensitivity, specificity and accuracy in distinguishing non-responders and responders. Multivariate logistic regression analyses showed that T/NT{sub lung} was an independent predictor of the short-term outcome of CCRT in patients with advanced NSCLC (P = 0.032). {sup 18}F-alfatide PET/CT may be useful in predicting the short-term outcome of CCRT in patients with advanced NSCLC. (orig.)

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

    OpenAIRE

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

    1997-01-01

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

  6. Network meta-analysis of erlotinib, gefitinib, afatinib and icotinib in patients with advanced non-small-cell lung cancer harboring EGFR mutations.

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    Wenhua Liang

    Full Text Available BACKGROUND: Several EGFR-tyrosine kinase inhibitors (EGFR-TKIs including erlotinib, gefitinib, afatinib and icotinib are currently available as treatment for patients with advanced non-small-cell lung cancer (NSCLC who harbor EGFR mutations. However, no head to head trials between these TKIs in mutated populations have been reported, which provides room for indirect and integrated comparisons. METHODS: We searched electronic databases for eligible literatures. Pooled data on objective response rate (ORR, progression free survival (PFS, overall survival (OS were calculated. Appropriate networks for different outcomes were established to incorporate all evidences. Multiple-treatments comparisons (MTCs based on Bayesian network integrated the efficacy and specific toxicities of all included treatments. RESULTS: Twelve phase III RCTs that investigated EGFR-TKIs involving 1821 participants with EGFR mutation were included. For mutant patients, the weighted pooled ORR and 1-year PFS of EGFR-TKIs were significant superior to that of standard chemotherapy (ORR: 66.6% vs. 30.9%, OR 5.46, 95%CI 3.59 to 8.30, P<0.00001; 1-year PFS: 42.9% vs. 9.7%, OR 7.83, 95%CI 4.50 to 13.61; P<0.00001 through direct meta-analysis. In the network meta-analyses, no statistically significant differences in efficacy were found between these four TKIs with respect to all outcome measures. Trend analyses of rank probabilities revealed that the cumulative probabilities of being the most efficacious treatments were (ORR, 1-year PFS, 1-year OS, 2-year OS: erlotinib (51%, 38%, 14%, 19%, gefitinib (1%, 6%, 5%, 16%, afatinib (29%, 27%, 30%, 27% and icotinib (19%, 29%, NA, NA, respectively. However, afatinib and erlotinib showed significant severer rash and diarrhea compared with gefitinib and icotinib. CONCLUSIONS: The current study indicated that erlotinib, gefitinib, afatinib and icotinib shared equivalent efficacy but presented different efficacy-toxicity pattern for EGFR

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

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    Burns MW

    2015-05-01

    Full Text Available Mark W Burns, Eric S Kim Wilmot Cancer Center, University of Rochester, Rochester, NY, USA Abstract: Lung cancer has become one of the leading causes of death in both men and women in the United States, with approximately 230,000 new cases and 160,000 deaths each year. Approximately 80% of lung cancer patients are diagnosed with non-small-cell lung cancer (NSCLC, a subset of epithelial lung cancers that are generally insensitive to chemotherapy. An estimated 3%–7% of NSCLC patients harbor tumors containing anaplastic lymphoma kinase (ALK gene rearrangement as an oncogenic driver. Subsequent development of the first-generation tyrosine kinase inhibitor crizotinib demonstrated substantial initial ALK+-tumor regression, yet ultimately displayed resistance in treated patients. The recently approved tyrosine kinase inhibitor ceritinib has been shown to be an effective antitumor agent against crizotinib-naïve and -resistant ALK+-NSCLC patients. In this review, we will provide an overview of biology and management of ALK+-NSCLC with a special focus on clinical development of ceritinib. Keywords: ceritinib, anaplastic lymphoma kinase, non-small-cell lung cancer

  8. Spotlight on crizotinib in the first-line treatment of ALK-positive advanced non-small-cell lung cancer: patients selection and perspectives

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    Giroux Leprieur E

    2016-06-01

    Full Text Available Etienne Giroux Leprieur,1,2 Vincent Fallet,3,4 Jacques Cadranel,3,4 Marie Wislez3,4 1Respiratory Diseases and Thoracic Oncology Department, APHP-Ambroise Paré Hospital, Boulogne-Billancourt, France; 2EA4340 Laboratory, UVSQ, Paris-Saclay University, France; 3Respiratory Diseases Department, APHP – Tenon Hospital, Paris, France; 4Sorbonne University, GRC 04, UPMC Univ Paris 06, France Abstract: Around 4% of advanced non-small-cell lung cancers (NSCLCs have an ALK rearrangement at the time of diagnosis. This molecular feature is more frequent in young patients, with no/light smoking habit and with adenocarcinoma pathological subtype. Crizotinib is a tyrosine kinase inhibitor, targeting ALK, ROS1, RON, and MET. The preclinical efficacy results led to a fast-track clinical development. The US Food and Drug Administration (FDA approval was achieved after the Phase I clinical trial in 2011 in ALK-rearranged advanced NSCLC progressing after a first-line treatment. In 2013, the randomized Phase III trial PROFILE-1007 confirmed the efficacy of crizotinib in ALK-rearranged NSCLC, compared to cytotoxic chemotherapy, in second-line setting or more. In 2014, the PROFILE-1014 trial showed the superiority of crizotinib in the first-line setting compared to the pemetrexed platinum doublet chemotherapy. The response rate was 74%, and the progression-free survival was 10.9 months with crizotinib. Based on these results, crizotinib received approval from the FDA and European Medicines Agency for first-line treatment of ALK-rearranged NSCLC. The various molecular mechanisms at the time of the progression (ALK mutations or amplification, ALK-independent mechanisms encourage performing re-biopsy at the time of progression under crizotinib. The best treatment strategy at the progression (crizotinib continuation beyond progression, switch to second-generation tyrosine kinase inhibitors, or cytotoxic chemotherapy depends on the phenotype of the progression, the

  9. Erlotinib and Cetuximab With or Without Bevacizumab in Treating Patients With Metastatic or Unresectable Kidney, Colorectal, Head and Neck, Pancreatic, or Non-Small Cell Lung Cancer

    Science.gov (United States)

    2014-06-10

    Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma; Recurrent Adenoid Cystic Carcinoma of the Oral Cavity; Recurrent Basal Cell Carcinoma of the Lip; Recurrent Colon Cancer; Recurrent Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; 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 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; Stage III Adenoid Cystic Carcinoma of the Oral Cavity; Stage III Basal Cell Carcinoma of the Lip; Stage III Colon Cancer; Stage III Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Stage III Inverted Papilloma of the Paranasal Sinus and Nasal Cavity; Stage III Lymphoepithelioma of the Nasopharynx; Stage III Lymphoepithelioma of the Oropharynx; Stage III Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity; Stage III Mucoepidermoid Carcinoma of the Oral Cavity; Stage III Pancreatic Cancer; Stage III Rectal Cancer; Stage III Salivary Gland Cancer; Stage III Squamous Cell Carcinoma of the Hypopharynx; Stage III Squamous Cell Carcinoma of the Larynx; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Squamous Cell Carcinoma of the Nasopharynx

  10. Efficacy and Toxicity of Pemetrexed or Gemcitabine Combined with Cisplatin in the Treatment of Patients with Advanced Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Xingsheng HU

    2012-10-01

    Full Text Available Background and objective Due to the various inter-individual differences in the biological characteristics of tumor cells, as well as issues on the efficacy, adverse reactions, and defects of existing drugs, we compared the clinical efficacy and toxicity of pemetrexed and gemcitabine combined with cisplatin for the treatment of previously untreated advanced non-small cell lung cancer (NSCLC. Methods 251 patients were randomly divided into pemetrexed combined with cisplatin group (PP group with 127 cases and gemcitabine combined with cisplatin group (GP group with 124 cases. PP group received pemetrexed 500 mg/m2 iv infusion d1 and cisplatin 75 mg/m2 iv infusion d1, whereas GP group received gemcitabine 1,000 mg/m2 iv infusion d1,8 and cisplatin 75 mg/m2 iv infusion d1. The treatment cycle was once every three weeks. In addition, folic acid, vitamin B12, and dexamethasone were administered in both groups. Results The total clinical effective rates in PP group and GP group were 25.20% and 17.74%, respectively. The total efficiencies of non-squamous cell carcinoma were 27.62% and 16.00%. The tumor progression duration in these two groups was 6.5 and 5.6 months, respectively. The median survival time in the two groups was 16.9 and 17.0 months, respectively, with 59.62% and 65.87% survival rates of 1 year and 27.28% and 27.93% survival rates of 2 years, respectively. The total efficacy of non-squamous cell carcinoma in the PP group was significantly higher than that in GP group. The results were statistically significant. However, there were no significant differences in total response rates, tumor progression duration, and median survival rates of 1 and 2 years. The rate of adverse reactions, including white blood cell reduction, lower platelet count, lower hemoglobin, and hair loss in the PP group was significantly lower than that in the GP group. The results were statistically significant. Conclusion The clinical efficacy of pemetrexed and

  11. Six versus fewer planned cycles of first-line platinum-based chemotherapy for non-small-cell lung cancer

    DEFF Research Database (Denmark)

    Rossi, Antonio; Chiodini, Paolo; Sun, Jong-Mu;

    2014-01-01

    BACKGROUND: Platinum-based chemotherapy is the standard first-line treatment for patients with advanced non-small-cell lung cancer. However, the optimum number of treatment cycles remains controversial. Therefore, we did a systematic review and meta-analysis of individual patient data to compare ...

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

    NARCIS (Netherlands)

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

    2006-01-01

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

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

    NARCIS (Netherlands)

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

    2012-01-01

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

  14. Upregulation of APE/ref-1 in recurrence stage I, non small cell lung cancer.

    Science.gov (United States)

    Kang, Min-Woong; Kang, Shin Kwang; Choi, Songyi; Lee, Choong Sik; Jeon, Byeong Hwa; Lim, Seung Pyung

    2012-02-01

    Lung cancer, the leading cause of cancer-related death, still lacks reliable biomarkers. Apurinic/apyrimidinic endonuclease 1/Ref-1 is a multifunctional protein involved in the base excision repair of DNA damaged by oxidative stress or alkylating compounds, as well as in the regulation of multiple transcription factors. To validate apurinic/apyrimidinic endonuclease 1/Ref-1 as a biomarker for prediction of lung cancer recurrence, we studied 42 patients who received curative resection and mediastinal lymph node dissection for stage I non-small-cell lung cancer. They were divided into 2 groups based on recurrence, and compared by immunohistochemistry staining of paraffin-embedded tissues and Western blot analysis. Immunohistochemical staining showed a significant difference between the cytoplasm and nucleus in patients who had a recurrence compared to those with nonrecurrent adenocarcinoma. In Western blot analysis, the recurrent adenocarcinoma group showed increased expression of apurinic/apyrimidinic endonuclease 1/Ref-1 in cytoplasm, nucleus, and in total. This indicates that apurinic/apyrimidinic endonuclease 1/Ref-1 is unregulated in recurrent stage I adenocarcinoma. For clinical application as a prognostic marker for non-small-cell lung cancer, further investigation into the role of apurinic/apyrimidinic endonuclease 1/Ref-1 in carcinogenesis is needed in an expanded prospective study.

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

    Institute of Scientific and Technical Information of China (English)

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

    2003-01-01

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

  16. Adrenalectomy for isolated metastasis from operable non-small-cell lung cancer

    Science.gov (United States)

    Sastry, Priya; Tocock, Adam; Coonar, Aman S.

    2014-01-01

    A best evidence topic in cardiothoracic surgery was written according to a structured protocol. The question addressed was ‘in [patients with isolated adrenal metastasis from operable/operated non-small cell lung cancer] is [adrenalectomy] superior [to chemo/radiotherapy alone for achieving long-term survival]?’ Altogether >160 papers were found using the reported search, of which 3 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. We conclude that the body of evidence is small, retrospective and not formally controlled. As such interpretation is limited by selection bias in assignment of patients. These limitations notwithstanding, surgical resection is associated with prolonged survival for patients with isolated adrenal metastasis from non-small cell lung cancer (NSCLC). Patient selection is probably critical. Factors that are important are: otherwise early tumour, node (TN) status of the lung primary and R0 resection, long disease-free interval and confidence that there are no other sites of metastasis. Patients with ipsilateral adrenal metastasis may derive the greatest survival benefit from adrenalectomy, since spread to the ipsilateral gland may occur via direct lymphatic channels in the retroperitoneum. Involvement of the contralateral adrenal may signify haematogenous spread and therefore, a more aggressive process. Adrenalectomy must be accompanied by regional lymph node clearance to reduce the chance of further spread from the adrenal itself. PMID:24357471

  17. Spotlight on pembrolizumab in non-small cell lung cancer: the evidence to date

    Directory of Open Access Journals (Sweden)

    Vachhani P

    2016-09-01

    Full Text Available Pankit Vachhani, Hongbin Chen Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY, USA Abstract: Immunotherapy with immune checkpoint inhibitors has opened a new arena in cancer therapeutics. Pembrolizumab is a highly selective anti-programmed cell death protein 1 (PD-1 antibody that has shown efficacy, leading to survival benefit and durable responses, in some patients with non-small cell lung cancer (NSCLC. It has been approved by the US Food and Drug Administration for the treatment of patients with metastatic NSCLC, whose tumors express PD-1 ligand 1 (PD-L1, with disease progression on or after platinum-containing chemotherapy. Here, we briefly discuss the PD-1/PD-L1 pathway and pembrolizumab before delving into the clinical trials that have led to its just-mentioned approval in NSCLC and ongoing clinical trials. Finally, we discuss the use of biomarkers, primarily PD-L1, in the context of pembrolizumab and NSCLC. Keywords: pembrolizumab, KEYNOTE, non-small cell lung cancer 

  18. Extent and computed tomography appearance of early radiation induced lung injury for non-small cell lung cancer

    DEFF Research Database (Denmark)

    Bernchou, Uffe; Christiansen, Rasmus Lübeck; Asmussen, Jon Thor

    2017-01-01

    BACKGROUND AND PURPOSE: The present study investigates the extent and appearance of radiologic injury in the lung after radiotherapy for non-small cell lung cancer (NSCLC) patients and correlates radiologic response with clinical and dosimetric factors. METHODS AND MATERIALS: Eligible follow-up C...

  19. Individualized dose prescription for hypofractionation in advanced non-small-cell lung cancer radiotherapy: an in silico trial.

    NARCIS (Netherlands)

    Hoffmann, A.L.; Troost, E.G.C.; Huizenga, H.; Kaanders, J.H.A.M.; Bussink, J.

    2012-01-01

    PURPOSE: Local tumor control and outcome remain poor in patients with advanced non-small-cell lung cancer (NSCLC) treated by external beam radiotherapy. We investigated the therapeutic gain of individualized dose prescription with dose escalation based on normal tissue dose constraints for various h

  20. Prospective study on quality of life before and after radical radiotherapy in non-small-cell lung cancer

    NARCIS (Netherlands)

    Langendijk, JA; Aaronson, NK; de Jong, JMA; ten Velde, GPM; Muller, MJ; Lamers, RJ; Slotman, BJ; Wouters, EFM

    2001-01-01

    Purpose: The purpose of this study was to investigate changes in respiratory symptoms and quality of life (QoL) in patients with non-small-cell lung cancer (NSCLC) receiving radical radiotherapy (60 Gy). Additionally, the association between the level of symptom relief and objective tumor response,

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

    DEFF Research Database (Denmark)

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

    2016-01-01

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

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

    DEFF Research Database (Denmark)

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

    2014-01-01

    Non-small cell lung cancer (NSCLC) is associated with poor survival even though patients are treated with curatively intended radiotherapy. Survival is affected negatively by lack of loco-regional tumour control, but survival is also influenced by comorbidity caused by age and smoking, and occurr......Non-small cell lung cancer (NSCLC) is associated with poor survival even though patients are treated with curatively intended radiotherapy. Survival is affected negatively by lack of loco-regional tumour control, but survival is also influenced by comorbidity caused by age and smoking......, and occurrence of distant metastasis. It is challenging to evaluate loco-regional control after definitive radiotherapy for NSCLC since it is difficult to distinguish between radiation-induced damage to the lung tissue and tumour progression/recurrence. In addition it may be useful to distinguish between...... intrapulmonary failure and mediastinal failure to be able to optimize radiotherapy in order to improve loco-regional control even though it is not easy to discriminate between the two sites of failure. Material and methods. This study is a retrospective analysis of 331 NSCLC patients treated with definitive...

  3. Controversies in the management of stage IIIA non-small-cell lung cancer.

    Science.gov (United States)

    Santos, Edgardo S; Castrellon, Aurelio; Blaya, Marcelo; Raez, Luis E

    2008-12-01

    New developments in the management of non-small-cell lung cancer, as well as recent proposals for changing the current lung cancer staging system, are posing a challenge in the therapeutic decision making regarding this disease. For the last two decades, the management of stage IIIA (N2) disease has been controversial and the target for clinical trials has been to determine the best therapeutic approach that may result in better survival outcomes without increasing toxicity. For many years, combined modality treatment (systemic chemotherapy plus radiation therapy) became the standard of care in this setting. However, the poor outcomes seen with combined modality for N2 has obligated us to explore other possibilities. In this sense, recent clinical trials in the neoadjuvant setting using chemotherapy alone or combined modality are providing fruitful results and shifting the paradigm on this stage. A recent, large randomized multicenter trial argues against what has slowly become a current practice in some centers - the use of preoperative modality for N2 disease. Another controversy that we will discuss here is the acceptance of adjuvant therapy for resected stage IB-IIIA non-small-cell lung cancer. It was not long ago that adjuvant radiation therapy was still the standard of care for patients who have pathological nodal disease. We will present the current data on these debatable issues and how to implement this new knowledge into clinical practice.

  4. Radiological response and survival in locally advanced non-small-cell lung cancer patients treated with three-drug induction chemotherapy followed by radical local treatment

    Directory of Open Access Journals (Sweden)

    Bonanno L

    2016-06-01

    Full Text Available Laura Bonanno,1 Giulia Zago,1 Giuseppe Marulli,2 Paola Del Bianco,3 Marco Schiavon,2 Giulia Pasello,1 Valentina Polo,1,4 Fabio Canova,1 Fabrizio Tonetto,5 Lucio Loreggian,5 Federico Rea,2 PierFranco Conte,1,4 Adolfo Favaretto1 1Medical Oncology Unit 2, Veneto Institute of Oncology IOV-IRCCS, 2Thoracic Surgery Department, University of Padova, 3Clinical Trials and Biostatistics Unit, Veneto Institute of Oncology IOV-IRCCS, 4Department of Surgery, Oncology and Gastroenterology, University of Padova, 5Radiotherapy Unit, Veneto Institute of Oncology IOV-IRCCS, Padova, Italy Objectives: If concurrent chemoradiotherapy cannot be performed, induction chemotherapy followed by radical-intent surgical treatment is an acceptable option for non primarily resectable non-small-cell lung cancers (NSCLCs. No markers are available to predict which patients may benefit from local treatment after induction. This exploratory study aims to assess the feasibility and the activity of multimodality treatment, including triple-agent chemotherapy followed by radical surgery and/or radiotherapy in locally advanced NSCLCs. Methods: We retrospectively collected data from locally advanced NSCLCs treated with induction chemotherapy with carboplatin (area under the curve 6, d [day]1, paclitaxel (200 mg/m2, d1, and gemcitabine (1,000 mg/m2 d1, 8 for three to four courses, followed by radical surgery and/or radiotherapy. We analyzed radiological response and toxicity. Estimated progression-free survival (PFS and overall survival (OS were correlated to response, surgery, and clinical features. Results: In all, 58 NSCLCs were included in the study: 40 staged as IIIA, 18 as IIIB (according to TNM Classification of Malignant Tumors–7th edition staging system. A total of 36 (62% patients achieved partial response (PR, and six (10% progressions were recorded. Grade 3–4 hematological toxicity was observed in 36 (62% cases. After chemotherapy, 37 (64% patients underwent surgery

  5. Adjuvant therapeutic vaccination in patients with non-small cell lung cancer made lymphopenic and reconstituted with autologous PBMC: first clinical experience and evidence of an immune response

    Directory of Open Access Journals (Sweden)

    Schendel Dolores J

    2007-09-01

    Full Text Available Abstract Background Given the considerable toxicity and modest benefit of adjuvant chemotherapy for non-small cell lung cancer (NSCLC, there is clearly a need for new treatment modalities in the adjuvant setting. Active specific immunotherapy may represent such an option. However, clinical responses have been rare so far. Manipulating the host by inducing lymphopenia before vaccination resulted in a magnification of the immune response in the preclinical setting. To evaluate feasibility and safety of an irradiated, autologous tumor cell vaccine given following induction of lymphopenia by chemotherapy and reinfusion of autologous peripheral blood mononuclear cells (PBMC, we are currently conducting a pilot-phase I clinical trial in patients with NSCLC following surgical resection. This paper reports on the first clinical experience and evidence of an immune response in patients suffering from NSCLC. Methods NSCLC patients stages I-IIIA are recruited. Vaccines are generated from their resected lung specimens. Patients undergo leukapheresis to harvest their PBMC prior to or following the surgical procedure. Furthermore, patients receive preparative chemotherapy (cyclophosphamide 350 mg/m2 and fludarabine 20 mg/m2 on 3 consecutive days for induction of lymphopenia followed by reconstitution with their autologous PBMC. Vaccines are administered intradermally on day 1 following reconstitution and every two weeks for a total of up to five vaccinations. Granulocyte-macrophage-colony-stimulating-factor (GM-CSF is given continuously (at a rate of 50 μg/24 h at the site of vaccination via minipump for six consecutive days after each vaccination. Results To date, vaccines were successfully manufactured for 4 of 4 patients. The most common toxicities were local injection-site reactions and mild constitutional symptoms. Immune responses to chemotherapy, reconstitution and vaccination are measured by vaccine site and delayed type hypersensitivity (DTH skin

  6. Toxic epidermal necrolysis related to AP (pemetrexed plus cisplatin) and gefitinib combination therapy in a patient with metastatic non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    Ji-Jie Huang; Shu-Xiang Ma; Xue Hou; Zhao Wang; Yin-Duo Zeng; Tao Qin; Xiao-Xiao Dinglin; Li-Kun Chen

    2015-01-01

    Toxic epidermal necrolysis (TEN) is a rare acute life-threatening mucocutaneous disorder that is mostly drug-related (80%-95%). It is clinical y characterized as a widespread sloughing of the skin and mucosa. AP regimen (pemetrexed plus cisplatin) has been the preferred first-line chemotherapy for metastatic non-squamous non-small cell lung cancer (NSCLC). Gefitinib, a small-molecule epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), has already been recommended as a first-line treatment in EGFR-mutant metastatic NSCLC. We report rare presentation of TEN involving adverse effects of AP and gefitinib combination treatment in a 42-year-old woman diagnosed with metastatic NSCLC harboring an EGFR mutation. On the 21st day after administration of the first cycle of AP regimen and the 8th day after the initiation of gefitinib treatment, she developed an acne-like rash, oral ulcer, and conjunctivitis, which later became blisters and ultimately denuded. The characteristic clinical courses were decisive for the diagnosis of TEN. Treatment with systemic steroids and immunoglobulin as well as supportive treatment led to an improvement of her general condition and a remarkable recovery.

  7. Societal savings in patients with advanced non-squamous non-small-cell lung cancer receiving bevacizumab-based versus non-bevacizumab-based treatments in France, Germany, Italy, and Spain

    Directory of Open Access Journals (Sweden)

    Lister J

    2012-10-01

    Full Text Available Johanna Lister,1 Sanja Stanisic,1 Klaus Kaier,2 Christian Hagist,2 Dmitry Gultyaev,1 Stefan Walzer31Analytica LA-SER International Inc, Lörrach, Germany; 2Research Centre for Generational Contracts, University of Freiburg, Freiburg, Germany; 3F Hoffmann-La Roche Ltd, Pharmaceuticals Division, Basel, SwitzerlandBackground: The purpose of this study was to investigate the savings accrued using bevacizumab-based treatment for non-small-cell lung cancer from the societal perspective, taking only public costs into account, in France, Germany, Italy, and Spain.Methods: Societal costs were estimated by collecting and analyzing labor costs, carer costs, sickness benefits, disability benefits, and home care benefits. Cost inputs were derived from publicly available databases or from the published literature. Expert opinion was only used if no other source was available. Efficacy data from two randomized clinical trials were used. The time horizon in the health economic model was lifetime. Efficacy and costs were discounted by 3.5%. All main model parameters were tested in deterministic and probabilistic sensitivity analyses.Results: Mean incremental savings to society per patient ranged from €2277 in Italy to €4461 in Germany. The results were most sensitive to the change in proportion of patients working full-time and the proportion of patients who were able to return to work.Conclusion: This analysis shows that bevacizumab-based treatment in non-small-cell lung cancer is associated with more savings to society compared to standard chemotherapy in terms of increased productivity and decreased social benefits paid to patients who are able to work in France, Germany, Italy, and Spain.Keywords: non-small-cell lung cancer, bevacizumab, chemotherapy, economic model, France, Germany, Italy, Spain

  8. Prognostic significance of Ki67 proliferation index, HIF1 alpha index and microvascular density in patients with non-small cell lung cancer brain metastases

    Energy Technology Data Exchange (ETDEWEB)

    Berghoff, A.S. [Medical University of Vienna, Institute of Neurology, Vienna (Austria); Medical University of Vienna, Comprehensive Cancer Center CNS Tumors Unit, Vienna (Austria); Medical University of Vienna, Department of Medicine I, Vienna (Austria); Ilhan-Mutlu, A.; Preusser, M. [Medical University of Vienna, Comprehensive Cancer Center CNS Tumors Unit, Vienna (Austria); Medical University of Vienna, Department of Medicine I, Vienna (Austria); Woehrer, A.; Hainfellner, J.A. [Medical University of Vienna, Institute of Neurology, Vienna (Austria); Medical University of Vienna, Comprehensive Cancer Center CNS Tumors Unit, Vienna (Austria); Hackl, M. [Austrian National Cancer Registry, Statistics Austria, Vienna (Austria); Widhalm, G. [Medical University of Vienna, Comprehensive Cancer Center CNS Tumors Unit, Vienna (Austria); Medical University of Vienna, Department of Neurosurgery, Vienna (Austria); Dieckmann, K. [Medical University of Vienna, Comprehensive Cancer Center CNS Tumors Unit, Vienna (Austria); Medical University of Vienna, Department of Radiotherapy, Vienna (Austria); Melchardt, T. [Paracelsus Medical University Hospital Salzburg, Third Medical Department, Salzburg (Austria); Dome, B. [Medical University of Vienna, Department of Surgery, Vienna (Austria); Heinzl, H. [Medical University of Vienna, Comprehensive Cancer Center CNS Tumors Unit, Vienna (Austria); Medical University of Vienna, Center for Medical Statistics, Informatics, and Intelligent Systems, Vienna (Austria); Birner, P. [Medical University of Vienna, Comprehensive Cancer Center CNS Tumors Unit, Vienna (Austria); Medical University of Vienna, Institute of Clinical Pathology, Vienna (Austria)

    2014-07-15

    Survival upon diagnosis of brain metastases (BM) in patients with non-small cell lung cancer (NSCLC) is highly variable and established prognostic scores do not include tissue-based parameters. Patients who underwent neurosurgical resection as first-line therapy for newly diagnosed NSCLC BM were included. Microvascular density (MVD), Ki67 tumor cell proliferation index and hypoxia-inducible factor 1 alpha (HIF-1 alpha) index were determined by immunohistochemistry. NSCLC BM specimens from 230 patients (151 male, 79 female; median age 56 years; 199 nonsquamous histology) and 53/230 (23.0 %) matched primary tumor samples were available. Adjuvant whole-brain radiation therapy (WBRT) was given to 153/230 (66.5 %) patients after neurosurgical resection. MVD and HIF-1 alpha indices were significantly higher in BM than in matched primary tumors. In patients treated with adjuvant WBRT, low BM HIF-1 alpha expression was associated with favorable overall survival (OS), while among patients not treated with adjuvant WBRT, BM HIF-1 alpha expression did not correlate with OS. Low diagnosis-specific graded prognostic assessment score (DS-GPA), low Ki67 index, high MVD, low HIF-1 alpha index and administration of adjuvant WBRT were independently associated with favorable OS. Incorporation of tissue-based parameters into the commonly used DS-GPA allowed refined discrimination of prognostic subgroups. Ki67 index, MVD and HIF-1 alpha index have promising prognostic value in BM and should be validated in further studies. (orig.) [German] Die Ueberlebensprognose von Patienten mit zerebralen Metastasen eines nicht-kleinzelligen Lungenkarzinoms (NSCLC) ist sehr variabel. Bisher werden gewebsbasierte Parameter nicht in die prognostische Beurteilung inkludiert. Neurochirurgische Resektate zerebraler NSCLC-Metastasen wurden in dieser Studie untersucht. Die Gefaessdichte (''microvascular density'', MVD), der Ki67-Proliferationsindex sowie der HIF-1α-Index wurden mittels

  9. 274例非小细胞肺癌临床特点分析%Clinical features with non- small- cell lung cancer: An analysis of 274 patients

    Institute of Scientific and Technical Information of China (English)

    陈衍; 韩晟; 薛妍; 刘文超

    2012-01-01

    目的 了解我国非小细胞肺癌(NSCLC)患者流行病学特点,为临床NSCLC的防治提供参考数据.方法 对某医科大学附属医院肿瘤科组织学确诊的274例NSCLC患者临床特点及其相关因素进行回顾性研究,并分析影响临床分期和病理的独立风险因子.结果 男女比例为1.88∶1.腺癌和鳞癌约占总样本的90%,晚期患者占67.88%.47.45%有吸烟史,约28.83%来自农村.女性、农村患者发病年龄明显低于男性及城市患者.性别、病理类型及手术史是影响临床分期的独立风险因素.女性、腺癌及未进行手术的患者,晚期的比例更高.性别、年龄及吸烟状态均为影响病理的独立风险因素.男性、≤60岁以及吸烟患者更易患鳞癌.无论吸烟与否,男性较女性更易患鳞癌.即使排除吸烟因素,女性也较男性更易患腺癌.结论 NSCLC的发病特点发生变化,应加强对女性、农村人群及中青年的肺癌普查,提高早期NSCLC的筛查率.%Objective To investigate the clinical features of patients with non- small - cell lung cancer (NSCLC) in China in order to provide clinical reference data for further prevention and treatment of NSCLC. Methods The clinical features of 274 cases of NSCLC histologically diagnosed in a university hospital were retrospectively analyzed. The independent influencing factors related to stage and pathology with Cox's regression analysis were studied. Results The male to female ratio was 1.88:1. Squamous cell carcinoma and adenocarcinoma accounted for neatly 90 % in the total sample. Patients were diagnosed with advanced stage (Ⅲ B - Ⅳ) accounted for 67.88 % . Patients with smoking habits accounted for 47.45 % and 28.83 % of them lived in ruraLareas. Multiple regression analysis showed that gender, pathology and surgery were the independent variables influencing clinical stage. Female who had adenocarcinoma and received no surgery had higher incidence of caner in their late

  10. Phase III trial comparing vinflunine with docetaxel in second-line advanced non-small-cell lung cancer previously treated with platinum-containing chemotherapy

    DEFF Research Database (Denmark)

    Krzakowski, Maciej; Ramlau, Rodryg; Jassem, Jacek;

    2010-01-01

    To compare vinflunine (VFL) to docetaxel in patients with stage IIIB/IV non-small-cell lung cancer (NSCLC) who have experienced treatment failure with first-line platinum-based chemotherapy.......To compare vinflunine (VFL) to docetaxel in patients with stage IIIB/IV non-small-cell lung cancer (NSCLC) who have experienced treatment failure with first-line platinum-based chemotherapy....

  11. Surgical treatment of T3 and T4 non-small cell lung cancer

    NARCIS (Netherlands)

    Pitz, Cordula Catharina Maria

    2004-01-01

    The primary goal of lung cancer therapy is complete eradication of the disease. Surgery remains the most curative modality for non-small cell lung cancer. The goal of surgical treatment is to perform a complete resection. Resectability is closely related to the stage of the disease. The thesis focu

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

    Science.gov (United States)

    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 combination with other cytotoxic or targeted agents in the treatment of NSCLC. Its safety has been well established with neutropenia, anemia, nausea, and vomiting being the most frequently encountered toxicities. The data defining the risks and benefits of vinorelbine in the treatment of NSCLC will be summarized. PMID:21695100

  13. Second primary cancer in survivors following concurrent chemoradiation for locally advanced non-small-cell lung cancer

    Science.gov (United States)

    Takigawa, N; Kiura, K; Segawa, Y; Watanabe, Y; Kamei, H; Moritaka, T; Shibayama, T; Ueoka, H; Gemba, K; Yonei, T; Tabata, M; Shinkai, T; Hiraki, S; Takemoto, M; Kanazawa, S; Matsuo, K; Tanimoto, M

    2006-01-01

    Long-term cancer survivors risk development of second primary cancers (SPC). Vigilant follow-up may be required. We report outcomes of 92 patients who underwent chemoradiation for unresectable stage III non-small-cell lung cancer, with a median follow-up of 8.9 years. The incidence of SPC was 2.4 per 100 patient-years (95% confidence interval: 1.0–4.9). PMID:17031394

  14. Notch signaling and EMT in non-small cell lung cancer: biological significance and therapeutic application.

    Science.gov (United States)

    Yuan, Xun; Wu, Hua; Han, Na; Xu, Hanxiao; Chu, Qian; Yu, Shiying; Chen, Yuan; Wu, Kongming

    2014-12-05

    Through epithelial-mesenchymal transition (EMT), cancer cells acquire enhanced ability of migration and invasion, stem cell like characteristics and therapeutic resistance. Notch signaling regulates cell-cell connection, cell polarity and motility during organ development. Recent studies demonstrate that Notch signaling plays an important role in lung cancer initiation and cross-talks with several transcriptional factors to enhance EMT, contributing to the progression of non-small cell lung cancer (NSCLC). Correspondingly, blocking of Notch signaling inhibits NSCLC migration and tumor growth by reversing EMT. Clinical trials have showed promising effect in some cancer patients received treatment with Notch1 inhibitor. This review attempts to provide an overview of the Notch signal in NSCLC: its biological significance and therapeutic application.

  15. Plasma and EBC microRNAs as early biomarkers of non-small-cell lung cancer.

    Science.gov (United States)

    Mozzoni, Paola; Banda, Iris; Goldoni, Matteo; Corradi, Massimo; Tiseo, Marcello; Acampa, Olga; Balestra, Valeria; Ampollini, Luca; Casalini, Angelo; Carbognani, Paolo; Mutti, Antonio

    2013-12-01

    Lung cancer is a major cause of death in Western countries. Current screening methods are invasive and still lead to a high percentage of false positives. There is, therefore, a need to find biomarkers that increase the probability of detecting lung cancer early. MicroRNAs (miRNAs) are stable molecules in blood plasma and exhaled breath condensate (EBC). We quantified miRNA-21 and miRNA-486 expression from plasma and EBC samples from patients with a diagnosis of non-small-cell lung cancer (NSCLC) and controls. miRNA-21 was significantly higher in plasma and in EBC of the NSCLC patients and miRNA-486 was significantly lower. This difference indicates a significantly improved diagnostic value, and suggests that these miRNAs could be clinically used as a first-line screening test in high-risk subjects.

  16. PD-L1 expression in non-small cell lung cancer : Correlations with genetic alterations

    NARCIS (Netherlands)

    Scheel, Andreas H.; Ansen, Sascha; Schultheis, Anne M.; Scheffler, Matthias; Fischer, Rieke N.; Michels, Sebastian; Hellmich, Martin; George, Julie; Zander, Thomas; Brockmann, Michael; Stoelben, Erich; Groen, Harry; Timens, Wim; Perner, Sven; von Bergwelt-Baildon, Michael; Buettner, Reinhard; Wolf, Juergen

    2016-01-01

    Inhibition of the PD-1/PD-L1 pathway may induce anticancer immune responses in non-small cell lung cancer (NSCLC). Two PD-L1 immunohistochemistry (IHC) assays have been approved as companion diagnostic tests for therapeutic anti-PD-1 antibodies. However, many aspects of PD-L1 prevalence and associat

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

    Science.gov (United States)

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

  18. FGFR as potential target in the treatment of squamous non small cell lung cancer.

    Science.gov (United States)

    Tiseo, Marcello; Gelsomino, Francesco; Alfieri, Roberta; Cavazzoni, Andrea; Bozzetti, Cecilia; De Giorgi, Anna Maria; Petronini, Pier Giorgio; Ardizzoni, Andrea

    2015-06-01

    To date therapeutic options for squamous cell lung cancer patients remain scarce because no druggable targets have been identified so far. Aberrant signaling by FGFs (fibroblast growth factors) and FGFRs (fibroblast growth factors receptors) has been implicated in several human cancers and, particularly, in squamous non-small cell lung cancer (NSCLC). FGFR gene amplifications, somatic missense mutations, chromosomal translocations are the most frequent mechanisms able to induce aberrant activation of this pathway. Data from literature have established that the presence of an aberrant FGFR signaling has to be considered a possible negative prognostic factor but predictive of potential sensitivity to FGFR inhibitors. In the last years, clinical research efforts allowed to identify and evaluate promising FGFR inhibitors, such as monoclonal antibodies, ligand traps, non-selective or selective tyrosine kinase inhibitors. This review summarizes the current knowledge about FGFR alterations in NSCLC and the relative inhibitors in development, in particular in squamous NSCLC.

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

    Directory of Open Access Journals (Sweden)

    Zago G

    2016-08-01

    Full Text Available Giulia Zago,1,2,* Mirte Muller,1,* Michel van den Heuvel,1 Paul Baas1 1Department of Thoracic Oncology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek (NKI-AvL, Amsterdam, the Netherlands; 2Medical Oncology 2, Istituto Oncologico Veneto (IOV, Padova, Italy *These authors contributed equally to this work Abstract: Non-small-cell lung cancer (NSCLC is often diagnosed at an advanced stage of disease, where it is no longer amenable to curative treatment. During the last decades, the survival has only improved significantly for lung cancer patients who have tumors harboring a driver mutation. Therefore, there is a clear unmet need for effective therapies for patients with no mutation. Immunotherapy has emerged as an effective treatment for different cancer types. Nivolumab, a monoclonal inhibitory antibody against PD-1 receptor, can prolong survival of NSCLC patients, with a manageable toxicity profile. In two Phase III trials, nivolumab was compared to docetaxel in patients with, respectively, squamous (CheckMate 017 and non-squamous NSCLC (CheckMate 057. In both trials, nivolumab significantly reduced the risk of death compared to docetaxel (41% and 27% lower risk of death for squamous and non-squamous NSCLC, respectively. Therefore, nivolumab has been approved in the US and in Europe as second-line treatment for advanced NSCLC. Unfortunately, accurate predictive factors for patient selection are lacking, making it difficult to decide who will benefit and who will not. Currently, there are many ongoing trials that evaluate the efficacy of nivolumab in different settings and in combination with other agents. This paper reviews the present literature about the role of nivolumab in the treatment of NSCLC. Particular attention has been given to efficacy studies, toxicity profile, and current and emerging predictive factors. Keywords: nivolumab, advanced non-small-cell lung cancer, immunotherapy, anti-PD-1

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

    Institute of Scientific and Technical Information of China (English)

    Maimon C Rose; Elina Kostyanovskaya; R Stephanie Huang

    2014-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Maimon C. Rose

    2014-10-01

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

  2. The clinical significance of preoperative serum CEA,β-HCG and CXs detection in the diagnosis of non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    Xian-Hua Yang; Juan Chen

    2016-01-01

    Objective:To study the clinical significance of preoperative serum CEA,β-HCG and CXs detection in the diagnosis of non-small cell lung cancer and provide reference for clinical diagnosis and disease treatment.Methods:Non-small cell lung cancer patients treated in our hospital from April 2009 to April 2014 were analyzed. Correlation between preoperative serum CEA,β-HCG as well as Cxs and clinical stages as well as prognosis of non-small cell lung cancer was assayed. Healthy subjects in our hospital during the same period were taken as control group.Results:Serum CEA,β-HCG and Cxs had no obvious correlation with patients’ age and gender, but CEA andβ-HCG had negative correlation with the clinical stages and prognosis of non-small cell lung cancer while Connexin43 had positive correlation with the clinical stages and prognosis of non-small cell lung cancer.Conclusions:Preoperative serum CEA combined withβ-HCG and CXs detection can be taken as key molecules in clinical diagnosis and prognosis of non-small cell lung cancer.

  3. Diagnosis and Treatment of Leptomeningeal Metastasis in Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Yan XU

    2015-10-01

    Full Text Available Leptomeningeal metastasis (LM is one of the disastrous events in managing advanced non-small cell lung cancer (NSCLC due to severe clinical symptoms and a grave prognosis. Although intrathecal (IT chemotherapy show some effects for LM in advanced NSCLC, the prognosis is still poor (12 wk-14 wk. A large majority (84%-97% of the patients were found to have adenocarcinoma histology. Epidermal growth factor receptor (EGFR senstive mutations were detected in 43.0%-70.5% adenocarcinoma patients with LM. EGFR tyrosine kinase inhibitors (TKIs showed to be effective for LM in selected NSCLC patients in some reseaches, and confer a survival benefit. Furthermore, future trials need be done to determine the effect of EGFR-TKIs treatment in NSCLC-LM patients.

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

    Science.gov (United States)

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

    2016-02-01

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

  5. Phase 2 trial of erlotinib with or without PF-3512676 (CPG 7909, a Toll-like receptor 9 agonist) in patients with advanced recurrent EGFR-positive non-small cell lung cancer.

    Science.gov (United States)

    Belani, Chandra P; Nemunaitis, John J; Chachoua, Abraham; Eisenberg, Peter D; Raez, Luiz E; Cuevas, J Daniel; Mather, Cecile B; Benner, Rebecca J; Meech, Sandra J

    2013-07-01

    This phase 2 study assessed PF-3512676 plus erlotinib in patients with epidermal growth factor receptor-positive advanced non-small cell lung cancer after prior chemotherapy failure. Patients were randomized 1:1 to PF-3512676 (0.20 mg/kg injected subcutaneously once weekly) plus erlotinib (150 mg daily) or erlotinib alone. The primary objective was to estimate progression-free survival (PFS). Patients received PF-3512676 plus erlotinib (n = 18) or erlotinib alone (n = 21). The study was halted because an unplanned interim analysis indicated that large improvement in PFS with addition of PF-3512676 would be unlikely. In the PF-3512676-plus-erlotinib and erlotinib-alone arms, median PFS was 1.6 and 1.7 mo (hazard ratio, 1.00; 95% confidence interval, 0.5-2.0; P = 0.9335), respectively. Salient grade ≥ 3 adverse events in PF-3512676-plus-erlotinib and erlotinib-alone arms were diarrhea (5/0), dyspnea (5/6), fatigue (4/1), other flu-like symptoms (2/0), anemia (2/1), and lymphocytopenia (based on laboratory values, 1/4). Adding PF-3512676 to erlotinib did not show potential for increased progression-free survival over erlotinib alone in patients with advanced recurrent epidermal growth factor receptor-positive non-small cell lung cancer.

  6. Gefitinib: new preparation. Non small-cell lung cancer: stricter assessment needed.

    Science.gov (United States)

    2004-10-01

    (1) Platinum-based chemotherapy is generally used to treat advanced-stage non small-cell lung cancer (stages III and IV), but has only a modest impact on survival. There is no reference treatment. (2) Gefitinib inhibits the tyrosine kinase activity of the receptor for EGF (epidermal growth factor), which is thought to be involved in tumour growth. It has a temporary licence in France and is used on a named-patient basis, but full marketing authorisation has already been granted in Japan, the United States, and elsewhere. (3) Two double-blind dose-finding studies compared two doses of oral gefitinib monotherapy (250 mg/day and 500 mg/day) in patients in whom at least two lines of chemotherapy had failed. The results were favourable, with a median survival of 6 months and a symptomatic improvement in some patients, but they are undermined by the absence of a placebo group and by major protocol violations. (4) Two double-blind trials, each in more than 1000 patients, showed that gefitinib does not increase the efficacy of first-line platinum combinations. (5) About 15% of patients receiving gefitinib monotherapy in clinical trials stopped taking the treatment because of adverse events. The most frequent were gastrointestinal (diarrhea, nausea, vomiting) and cutaneous (rash, acne, dry skin, pruritus). (6) Interstitial pneumonitis occurred in about 1% of patients, and was fatal in about one-third of cases. (7) Gefitinib is metabolised by the cytochrome P450 isoenzyme CYP3A4, so carries a potentially high risk of interactions. (8) In practice, more thorough assessment of gefitinib is needed to determine whether this new drug is beneficial for patients with non small-cell lung cancer. Marketing authorisation is not currently justified.

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

    DEFF Research Database (Denmark)

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

    2006-01-01

    Purpose: To test the effect of stereotactic body radiotherapy (SBRT) in       the treatment of medically inoperable patients with limited-stage       non-small-cell lung cancer (NSCLC) in a Phase II trial. Methods and       Materials: Forty patients with Stage I NSCLC were treated with SBRT...... resulted in a high       probability of local control and a promising survival rate. The toxicity       after SBRT of lung tumors was moderate. However, deterioration in       performance status, respiratory insufficiency, and other side effects were       observed...

  8. Novel treatment options in stage I non-small-cell lung cancer.

    Science.gov (United States)

    Tarasevych, Svitlana; Lauwers, Patrick; Vandaele, Frederik; van Meerbeeck, Jan P

    2014-09-01

    In the last 5 years, the current management of stage I non-small-cell lung cancer has been challenged due to novel surgical approaches and advances in radiation technology. The outcome after a sublobar resection is promising, especially for tumors less than 2 cm. Other treatment opportunities are available for high risk patients with comorbidity and impaired pulmonary function. Stereotactic ablative body radiotherapy is a good alternative treatment to surgery, especially in elderly and comorbid patients. However, randomized evidence comparing sublobar resection and stereotactic radiotherapy is presently lacking. The most recent development in radiotherapy is hadron therapy with a presumed reduced toxicity because of its peculiar physical and biological effects. Promising thermal and microwave ablative techniques are in development and have specific niche indications.

  9. Molecular targeted therapy in the treatment of advanced stage non-small cell lung cancer (NSCLC).

    Science.gov (United States)

    Kumarakulasinghe, Nesaretnam Barr; van Zanwijk, Nico; Soo, Ross A

    2015-04-01

    Historically, patients with advanced stage non-small cell lung cancer (NSCLC) were treated with chemotherapy alone, but a therapeutic plateau has been reached. Advances in the understanding of molecular genetics have led to the recognition of multiple molecularly distinct subsets of NSCLC. This in turn has led to the development of rationally directed molecular targeted therapy, leading to improved clinical outcomes. Tumour genotyping for EGFR mutations and ALK rearrangement has meant chemotherapy is no longer given automatically as first-line treatment but reserved for when patients do not have a 'druggable' driver oncogene. In this review, we will address the current status of clinically relevant driver mutations and emerging new molecular subsets in lung adenocarcinoma and squamous cell carcinoma, and the role of targeted therapy and mechanisms of acquired resistance to targeted therapy.

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

    Directory of Open Access Journals (Sweden)

    Bamousa Ahmed

    2008-10-01

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

  11. Tumor angiogenesis correlates with histologic type and metastasis in non-small-cell lung cancer.

    Science.gov (United States)

    Yuan, A; Yang, P C; Yu, C J; Lee, Y C; Yao, Y T; Chen, C L; Lee, L N; Kuo, S H; Luh, K T

    1995-12-01

    This study investigated the clinico-pathologic correlation of tumor angiogenesis in non-small-cell lung cancers. Formalin-fixed, paraffin-embedded surgical specimens of 55 consecutive patients with primary non-small-cell lung cancers were examined. Included were 26 squamous cell carcinomas and 29 adenocarcinomas. Twenty-five patients had stage I disease, eight patients had stage II disease, and 22 patients had stage IIIA or IIIB disease. Among them, 28 had nodal metastasis and 27 did not. The microvessel was demonstrated by immunocytochemical staining for factor VIII and platelet endothelial cell adhesion molecules (PECAM-1). The microvessels in the areas of highest neovascularization were counted under light microscopy in 200x field by two independent observers without knowledge of clinical information. At least three separate fields were counted for each specimen. The Mann-Whitney U test was used for statistical analysis. The microvessel counts in adenocarcinoma were significantly higher than in the squamous cell carcinoma (54.4 +/- 35.65 versus 26.16 +/- 20.46 in factor VIII staining and 80.52 +/- 48.42 versus 40.04 +/- 32.33 in PECAM-1 staining; p < 0.001). The microvessel counts in patients with Stages I-II disease were significantly lower than that of stages IIIA-IIIB disease (23.63 +/- 16.21 versus 65.36 +/- 31.92 in factor VIII staining and 41.85 +/- 36.76 versus 93.00 +/- 43.08 in PECAM-1; p < 0.001). Patients with nodal metastasis had higher microvessel density than those without nodal metastasis (56.67 +/- 35.55 versus 23.44 +/- 15.77 in factor VIII staining and 86.89 +/- 46.46 versus 36.30 +/- 25.83 in PECAM-1 staining; p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

  12. Afatinib for the treatment of metastatic non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Joshi M

    2015-02-01

    Full Text Available Monika Joshi, Syed M Rizvi, Chandra P Belani Penn State Milton S Hershey Medical Center, Department of Medicine, Division of Hematology-Oncology, Hershey, PA, USA Abstract: 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. Keywords: afatinib, non-small cell lung cancer, epidermal growth factor receptor, tyrosine kinase inhibitor

  13. Clinical Research of Crizotinib in Advanced Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Haibo ZHU

    2013-06-01

    Full Text Available At present, in the treatment of non-small cell lung cancer (NSCLC, targeted therapy has an important status. After epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKIs, crizotinib targeted at EML4-ALK fusion gene becomes a significant drug of molecular targeted therapy in NSCLC. Phase I and II clinical trials prove that crizotinib is effective for treatment of activating EML4-ALK mutation in advanced NSCLC patients, little side-effect, and well tolerated. Recently, crizotinib can inhibit ROS1 receptor tyrosine kinase and show extraordinary significant antitumor activity in ROS1-rearranged NSCLC. Drug resistance also exists in crizotinib. The mechanism of drug resistance needs further research. In this study, a review is performed in the mechanism and pharmacokinetics of crizotinib, and the clinical progress of treatment in advanced NSCLC.

  14. THE MANAGEMENT OF BRAIN METASTASES IN NON-SMALL CELL LUNG CANCER

    Directory of Open Access Journals (Sweden)

    Scott eOwen

    2014-09-01

    Full Text Available Brain metastases (BM are a common and lethal complication of non-small cell lung cancer (NSCLC which portend a poor prognosis. In addition, their management implies several challenges including preservation of neurological and neuro-cognitive function during surgery or radiation -therapy, minimizing iatrogenic complications of supportive medications, and optimizing drug delivery across the blood brain barrier (BBB. Despite these challenges, advancements in combined modality approaches can deliver hope of improved overall survival and quality of life for a subset of NSCLC patients with BM. Moreover, new drugs harnessing our greater understanding of tumour biology promise to build on this hope. In this mini-review, we revised the management of BM in NSCLC including advancements in neurosurgery, radiation therapy, as well as systemic and supportive therapy.

  15. 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.

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

    Directory of Open Access Journals (Sweden)

    Paleiron N

    2016-07-01

    Full Text Available Nicolas Paleiron,1 Olivier Bylicki,2 Michel André,1 Emilie Rivière,1 Frederic Grassin,1 Gilles Robinet,3 Christos Chouaïd4 On behalf of the GFPC Group 1Chest Department, HIA Clermont Tonnerre, Brest, 2Chest Department, HIA Percy, Clamart, 3Chest Department, CHU de Brest, Brest, 4GRC OncoEst, Université Paris XII, Paris, France Abstract: Targeted therapies have markedly improved the management of patients with advanced non-small-cell lung cancer (NSCLC, but their efficacy in localized NSCLC is less well established. The aim of this review is to analyze trials of targeted therapies in localized NSCLC. In patients with wild-type EGFR, tyrosine kinase inhibitors have shown no efficacy in Phase III trials. Few data are available for EGFR-mutated localized NSCLC, as routine biological profiling is not recommended. Available studies are small, often retrospectives, and/or conducted in a single-center making it difficult to draw firm conclusions. Ongoing prospective Phase III trials are comparing adjuvant tyrosine kinase inhibitor administration versus adjuvant chemotherapy. By analogy with the indication of bevacizumab in advanced NSCLC, use of antiangiogenic agents in the perioperative setting is currently restricted to nonsquamous NSCLC. Several trials of adjuvant or neoadjuvant bevacizumab are planned or ongoing, but for the moment there is no evidence of efficacy. Data on perioperative use of biomarkers in early-stage NSCLC come mainly from small, retrospective, uncontrolled studies. Assessment of customized adjuvant or neoadjuvant therapy in localized NSCLC (with or without oncogenic driver mutations is a major challenge. Keywords: targeted therapy, non-small-cell lung cancer, adjuvant, neo-adjuvant, surgery 

  17. Liquid Biopsy in Non-Small Cell Lung Cancer

    Science.gov (United States)

    Molina-Vila, Miguel A.; Mayo-de-las-Casas, Clara; Giménez-Capitán, Ana; Jordana-Ariza, Núria; Garzón, Mónica; Balada, Ariadna; Villatoro, Sergi; Teixidó, Cristina; García-Peláez, Beatriz; Aguado, Cristina; Catalán, María José; Campos, Raquel; Pérez-Rosado, Ana; Bertran-Alamillo, Jordi; Martínez-Bueno, Alejandro; Gil, María-de-los-Llanos; González-Cao, María; González, Xavier; Morales-Espinosa, Daniela; Viteri, Santiago; Karachaliou, Niki; Rosell, Rafael

    2016-01-01

    Liquid biopsy analyses are already incorporated in the routine clinical practice in many hospitals and oncology departments worldwide, improving the selection of treatments and monitoring of lung cancer patients. Although they have not yet reached its full potential, liquid biopsy-based tests will soon be as widespread as “standard” biopsies and imaging techniques, offering invaluable diagnostic, prognostic, and predictive information. This review summarizes the techniques available for the isolation and analysis of circulating free DNA and RNA, exosomes, tumor-educated platelets, and circulating tumor cells from the blood of cancer patients, presents the methodological challenges associated with each of these materials, and discusses the clinical applications of liquid biopsy testing in lung cancer. PMID:28066769

  18. CLINICAL SIGNIFICANCE OF THE LYMPH NODE MICRO-METASTASIS IN PATEINTS WITH EARLY STAGE NON-SMALL-CELL LUNG CANCER

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    @@ The postoperative 5-year survival rate is about 50-85% in the patient with the stage I non-small-cell lung cancer (NSCLC). It is remains unclear how we should give these patients adjuvant radiotherapy and chemotherapy after operation. We performed a postspective study to assess the prognostic and treatment guiding significance of lymph nodes micrometastasis (LMM) in patients with completely resected NSCLC at stage I.

  19. Comparison of liposomal cisplatin versus cisplatin in non-squamous cell non-small-cell lung cancer

    OpenAIRE

    Stathopoulos, G. P.; Antoniou, D.; Dimitroulis, J.; STATHOPOULOS, J.; Marosis, K.; Michalopoulou, P.

    2011-01-01

    Purpose Liposomal cisplatin was developed to reduce the systemic toxicity of cisplatin, particularly the nephrotoxicity, and it has been used in combination with other agents in pancreatic and head and neck cancers and non-small-cell lung cancer (NSCLC). Our objective was to compare the effectiveness of lipoplatin combined with paclitaxel versus cisplatin with paclitaxel in advanced non-squamous NSCLC. Methods During 2007–2010, 202 patients with non-squamous NSCLC (stage IIIB and IV) were rec...

  20. Maintenance therapies for non small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Normand eBlais

    2014-08-01

    Full Text Available Treatment of lung cancer had evolved during the last decade with the introduction of new chemotherapeutic regimens and targeted therapies. However, the maximum benefit reached after first line therapy is limited by the cumulative toxicity of platinum drugs and the subsequent deterioration in performance status in a high percentage of patients who end up receiving not more than one line of treatment. Maintenance therapy had been introduced and evaluated in many large randomized trials showing a delay in tumour progression and an improvement in overall survival. This effective strategy should be taken into account when discussing the initial treatment plan and tailored according to the preferences of both patients and physicians.

  1. Deletion and Mutation of WWOX Exons 6-8 in Human Non-small Cell Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    To examine the deletion and point mutation of WWOX (WW domain containing oxidoreductase) exons 6-8 in human non-small cell lung cancer and their possible relationship with pathological stages, tumor tissues and the corresponding normal tissues were obtained from 44 Chinese patients who had undergone surgery for non-small cell lung cancer. RNA was extracted from each sample and deletion and mutation of WWOX exons 6-8 were analyzed by RT-PCR and DNA sequencing. Our results showed that 28 of 44 (63.6 %) lung cancer samples showed loss of WWOX exons 6-8 transcript and the deletion was detected in only 3 of 44 (6.8 %) corresponding adjacent normal tissues (P<0.05). The transcript sequencing analyses of the 16 lung cancer samples without transcript loss of WWOX exons 6-8 revealed no difference from the sequence of GenBank. Moreover, the deletion of WWOX exons 6-8 was significantly higher in the smokers when compared with the non-smokers. It is also higher in the men and squamous carcinomas than in women and adenocarcinomas (P<0.05). The deletion, however, was not found to be associated with pathological stages of the tumors. Our study documented a high incidence of deletion of WWOX exons 6-8 in non-small cell lung cancer in Chinese patients and suggested that the frequent loss of WWOX exons 6-8 might play an important role in the tumorigenesis of non-small cell lung cancer in Chinese. WWOX exons 6-8 may serves as a candidate molecular target of smoking carcinogenesis, and point mutation is not a predominant way of alteration of WWOX exons 6-8.

  2. Synergistic effect of phenformin in non-small cell lung cancer (NSCLC) ionizing radiation treatment.

    Science.gov (United States)

    Wang, Jia; Xia, Shi'an; Zhu, Zhizhen

    2015-03-01

    Biguanides, used for anti-diabetic drugs, bring more attention in cancer research for their beneficial effects. Phenformin is more potent than metformin. However its potential application as a anti-cancer regent is far behind metformin. In order to investigate any beneficial effect of combination of Phenformin and radiotherapy, non-small cell lung cancer cell lines A549 and H1299 were exposure under different dose of ionizing radiation with or without Phenformin. Results indicated Phenformin showed synergistic effect and could induce more cancer cell apoptosis and inhibition of tumor growth compared with ionizing radiation alone. Furthermore, this synergistic effect may be through different pathway according to cancer cell genotype background. Our results showed Phenformin induced AMPK activation in A549 but not H1299. However, Phenformin activated eIF2α in both cell lines. Our findings implicated Phenformin may be used as radiosensitizer for non-small cell lung cancer therapy.

  3. Diagnostic procedures for non-small-cell lung cancer (NSCLC): recommendations of the European Expert Group

    OpenAIRE

    Dietel, Manfred; Bubendorf, Lukas; Dingemans, Anne-Marie C; Dooms, Christophe; Elmberger, Göran; García, Rosa Calero; Keith M Kerr; Lim, Eric; López-Ríos, Fernando; Thunnissen, Erik; Van Schil, Paul E.; von Laffert, Maximilian

    2015-01-01

    Background There is currently no Europe-wide consensus on the appropriate preanalytical measures and workflow to optimise procedures for tissue-based molecular testing of non-small-cell lung cancer (NSCLC). To address this, a group of lung cancer experts (see list of authors) convened to discuss and propose standard operating procedures (SOPs) for NSCLC. Methods Based on earlier meetings and scientific expertise on lung cancer, a multidisciplinary group meeting was aligned. The aim was to inc...

  4. Prognostic factors in patients with stage Ⅳ non-small cell lung cancer%Ⅳ期非小细胞肺癌预后影响因素分析

    Institute of Scientific and Technical Information of China (English)

    马美丽; 沈洁; 姜丽岩

    2006-01-01

    Objective: To investigate the prognostic factors for stage Ⅳ non-small cell lung cancer (NSCLC) with distant metastasis and establish a reliable model of clinical prognostic index.Methods: From January 1990 to April 2005,313 primary NSCLC patients with metastasis,who had been treated in Shanghai Chest Hospital,were reviewed.Survival time was estimated according to the Kaplan-Meier method.Cox proportional hazard regression model was used for multivariate analysis.Results: Among the 313 cases of non-small cell lung cancer (NSCLC) at stage Ⅳ,there were 218 and 95 patients with metastasis to single and different organs,respectively.The overall median survival time for all 313 cases of NSCLC patients was 10.8 (9.00,12.30)months and the overall 1-,2-,3-,4- and 5-year survival rate was 45%,18%,12%,4% and 0%.There were 63,174,127,36,18,11 and 5 patients with metastasis to brain (20.13%),bone (55.59%),lung (40.58%),liver (11.50%),adrenal gland (5.75%),subcutaneous (3.51%) and others,respectively.The survival time was shortest in subcutaneous metastasis (4.6 months),and liver 7.0 months,brain 8.0 months,adrenal gland 8.6 months,bone 10.6 months,lung 11.8 months.Kaplan-Meier estimation showed that patients anatomic typing,KPS,numbers of organ with metastasis,appetite,liver,adrenal gland and subcutaneous metastasis,body weight loss,smoking,index of smoking,chemotherapy,cycles of chemotherapy were the predictors of survival.Multivariate analysis showed survival statistically significant correlation with anatomic typing,KPS,appetite,liver and subcutaneous metastasis,body weight loss,cycles of chemotherapy.The relative risk (RR) was 1.51,1.97,1.55,1.67,2.56,and 2.56 respectively.Conclusion: Survival time decreases distinctly in patients who had distant metastasis to more than two different organs (P<0.01).Bone is the commonest organ for distant metastasis in lung cancer.The prognosis is poor when lung cancer appears subcutaneous metastasis and liver metastasis

  5. Stages of Non-Small Cell Lung Cancer

    Science.gov (United States)

    ... have spread to the nerve that controls the larynx (not shown). (3) Cancer has not spread to the lymph nodes and ... or the nerves that control the diaphragm and larynx (not shown). (1) Cancer has spread to lymph nodes above the collarbone ...

  6. General Information about Non-Small Cell Lung Cancer

    Science.gov (United States)

    ... have spread to the nerve that controls the larynx (not shown). (3) Cancer has not spread to the lymph nodes and ... or the nerves that control the diaphragm and larynx (not shown). (1) Cancer has spread to lymph nodes above the collarbone ...

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

    Science.gov (United States)

    ... have spread to the nerve that controls the larynx (not shown). (3) Cancer has not spread to the lymph nodes and ... or the nerves that control the diaphragm and larynx (not shown). (1) Cancer has spread to lymph nodes above the collarbone ...

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

    OpenAIRE

    Deisboeck Thomas S; Sagotsky Jonathan; Zhang Le; Wang Zhihui

    2007-01-01

    Abstract Background The epidermal growth factor receptor (EGFR) is frequently overexpressed in many cancers, including non-small cell lung cancer (NSCLC). In silico modeling is considered to be an increasingly promising tool to add useful insights into the dynamics of the EGFR signal transduction pathway. However, most of the previous modeling work focused on the molecular or the cellular level only, neglecting the crucial feedback between these scales as well as the interaction with the hete...

  9. Radiosensitization of non-small cell lung cancer by kaempferol.

    Science.gov (United States)

    Kuo, Wei-Ting; Tsai, Yuan-Chung; Wu, His-Chin; Ho, Yung-Jen; Chen, Yueh-Sheng; Yao, Chen-Han; Yao, Chun-Hsu

    2015-11-01

    The aim of the present study was to determine whether kaempferol has a radiosensitization potential for lung cancer in vitro and in vivo. The in vitro radio-sensitization activity of kaempferol was elucidated in A-549 lung cancer cells by using an MTT (3-(4 5-dimethylthiazol-2-yl)-25-diphenyl-tetrazolium bromide) assay, cell cycle analysis and clonogenic assay. The in vivo activity was evaluated in the BALB/c nude mouse xenograft model of A-549 cells by hematoxylin and eosin staining and immunohistochemistry, and the tumor volume was recorded. Protein levels of the apoptotic pathway were detected by western blot analysis. Treatment with kaempferol inhibited the growth of A-549 cells through activation of apoptotic pathway. However, the same doses did not affect HFL1 normal lung cell growth. Kaempferol induced G2/M cell cycle arrest and the enhancement of radiation-induced death and clonogenic survival inhibition. The in vivo data showed that kaempferol increased tumor cell apoptosis and killing of radiation. In conclusion, the findings demonstrated that kaempferol increased tumor cell killing by radiation in vitro and in vivo through inhibition of the AKT/PI3K and ERK pathways and activation of the mitochondria apoptosis pathway. The results of the present study provided solid evidence that kaempferol is a safe and potential radiosensitizer.

  10. correlation factors of postoperative complications in 52 patients with non-small cell lung cancer%52例非小细胞肺癌术后心肺并发症相关因素分析

    Institute of Scientific and Technical Information of China (English)

    胡晓俭; 任高飞

    2012-01-01

    目的 探讨非小细胞肺癌术后心肺并发症相关因素.方法 分析本院行根治术的52例非小细胞肺癌患者的临床资料,观察指标包括肺部感染、严重心律失常、低血容量性循环障碍及急性呼吸窘迫综合症等常见心肺并发症.结果 围术期无死亡病例,10例患者术后出现严重并发症,主要为肺部感染2例,严重心律失常4例(如阵发性室上性心动过速或频发性室性期前收缩,不包括窦性心动过速),低血容量性循环障碍3例,急性呼吸窘迫综合症1例.结论 非小细胞肺癌术后易发生心肺并发症,需完善术前心肺功能评估.%Objective To explore the correlation fart ors of postoperative complications in 52 patients with non-small cell lung cancer. Methods The clinical data of 52 patients with non-small cell lung cancer who undergone radical surgery in our hospital from February 2008 to February 2011 were retrospectively analyzed and observation index included lung infection, severe arrhythmia, hypovolemie circulatory disorders, and acute respiratory distress syndrome and other common cardiac and pulmonary complications. Results There was no death in peroperative period. 10 cases had serious postoperative complications including pulmonary infection in 2 cases, 4 cases of severe arrhythmia ( such as paroxysmal supraventricular tachycardia or frequent premature ventricular beats ) , 3 cases of hypovolemic circulatory disorders, and 1 case of acute respiratory distress syndrome ( ARDS ). Conclusions Patient with non-small cell lung cancer after surgey is prone to developed cardiopulmonary complications, so the preoperative assessment in heart and lung function should be improved.

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

    Institute of Scientific and Technical Information of China (English)

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

    2009-01-01

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

  12. Kaempferol modulates the metastasis of human non-small cell lung cancer cells by inhibiting epithelial-mesenchymal transition

    Directory of Open Access Journals (Sweden)

    Meng Hang

    2015-06-01

    Full Text Available The present study was done to determine whether kaempferol, a natural polyphenol of the flavonoid family, affects Epithelial-Mesenchymal Transition (EMT in non-small cell lung cancer cells. Kaempferol not only inhibited cancer cell proliferation and migration in a dose-dependent manner but also modulated the expression of EMT-related proteins E-cadherin and vimentin which are indispensible to cellular motility, invasiveness and metastasis. These results indicate that kaempferol suppresses non-small cell lung cancer migration by modulating the expression of EMT proteins. Therefore, kaempferol may be useful as a potential anticancer agent for non-small cell lung cancer.

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

    DEFF Research Database (Denmark)

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

    2014-01-01

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

  14. Neuroendocrine differentiation as a survival prognostic factor in advanced non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Petrović Marina

    2007-01-01

    Full Text Available Beckground/Aim. Neuroendrocine lung tumors are histologically heterogenous group of cancers with different clinical progression. In non-small cell lung cancer (NSCLC neuroendocrine differentiation exists in 10-30% of patients. The aim of this study was to determine the frequency and influence of neuroendocrine differentiation on survival of treated patients with advanced non-small cell lung cancer (NSCLC. Methods. A clinical trial included 158 patients (74% males and 26% females, with the diagnosis of NSCLC, determined by histological verification. The patients were treated by combined chemo - and X-ray therapy in stage III (without pleural effusion or chemotherapy only in stage III (with pleural effusion and stage IV. Chemotherapy was conducted until progression of the disease, but no more than six cycles. When the progression had been noted in stage III (without pleural effusion, the treatment was continued with X-ray therapy. Neuron specific enolase, chromogranin A, as well as synapthophysin expression in tissue examples were determined by immunohistochemical analysis with monoclonal mouse anti-human-bodies. Survival was assessed within a year and two years follow-up examination. Results. A total of 53 patients (34% had NSCLC with neuroendocrine differentiation, confirmed rather in large cell lung cancer and lung adenocarcinoma (66.7% and 40%, respectively. Neuron specific enolase, chromogranin A and synapthophysin expression was noted in 45 (28.5%, 34 (21.5% and 33 (20.1% patients, respectively. The one year and two years follow-up survival periods were confirmed in 39% and 17% of patients respectively. The median survival time in the patients with the neuroendocrine expression as compared to those without the expression was 15.6 vs 10.8 months; one year survival time with the expression compared to those without the expression achieved in 62% vs 27% of the patients, (p < 0.001; a two - year survival time noted in 30% of the patients (p = 0

  15. Adjuvant chemotherapy for completely resected non-small-cell lung cancer

    Directory of Open Access Journals (Sweden)

    Toyooka,Shinichi

    2009-10-01

    Full Text Available For many years, surgery alone was the standard treatment for patients with stage I-IIIA non-small-cell lung cancer (NSCLC. However, recent studies have demonstrated that adjuvant chemotherapy provides a survival benefit. The first adjuvant chemotherapy for NSCLC was performed in the 1960s using a key drug known as cyclophosphamide. In the 1980s and early 1990s, a new anti-cancer drug, cisplatin, was developed. The first meta-analysis of this drug was conducted by the Non-small Cell Lung Cancer Collaborative Group in 1995. This analysis comparing surgery with surgery plus chemotherapy containing cisplatin produced a hazard ratio of 0.87 and suggested an absolute benefit of chemotherapy of 5% at 5 years;this difference was not statistically significant (p0.08. Several clinical trials of adjuvant chemotherapy were planned after the meta-analysis conducted in 1995, but the efficacy of adjuvant chemotherapy remained a matter of controversy. However, useful evidence was reported after 2003. The International Adjuvant Lung Cancer Collaborative Group Trial (IALT demonstrated a 4.1% improvement in survival for patients with stage I to III NSCLC. The JBR. 10 trial demonstrated a 15% improvement in 5-year survival for the adjuvant chemotherapy arm in stage IB or II (excluding T3N0 patients. The Adjuvant Navelbine International Trialist Association (ANITA trial reported that the overall survival at 5 years improved by 8.6% in the chemotherapy arm and that this survival rate was maintained at 7 years (8.4% in stage II and IIIA patients. A meta-analysis based on collected and pooled individual patient data from the 5 largest randomized trials was conducted by the Lung Adjuvant Cisplatin Evaluation (LACE. This analysis demonstrated that cisplatin-based adjuvant chemotherapy improved survival in patients with stage II or III cancer. Alterna-tively, uracil-tegafur has been developed and tested in Japan. The Japan Lung Cancer Research Group (JLCRG on Postsurgical

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

    Directory of Open Access Journals (Sweden)

    Xin-en HUANG

    2015-06-01

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

  17. EGFR gene copy number as a predictive/biomarker for patients with non-small-cell lung cancer receiving tyrosine kinase inhibitor treatment: a systematic review and meta-analysis.

    Science.gov (United States)

    Zhang, Xin; Zhang, Yiwen; Tang, Hailing; He, Jianxing

    2017-01-01

    Epidermal growth factor receptor (EGFR) gene copy number has been proposed as a candidate biomarker for predicting treatment response to EGFR tyrosine kinase inhibitors (EGFR-TKIs) in patients with advanced non-small-cell lung cancer (NSCLC). MEDLINE, PubMed, Cochrane, and Google Scholar databases were searched until October 21, 2015 using the following search terms: lung neoplasms/lung cancer/non-small cell lung cancer/NSCLC, EGFR, gene amplification, copy number, erlotinib, gefitinib, tyrosine-kinase inhibitor/TKI, predictor. 17 studies were included in the analysis with a total of 2047 patients. The overall analysis found that increased EGFR gene copy number was associated with higher overall response rate (ORR), overall survival (OS) and progression-free survival (PFS; p values ≤0.008) compared with patients without a high EGFR gene copy number. Subgroup analysis found that in a population of patients who were primarily Caucasian, a higher EGFR gene copy number was also associated with increased ORR, OS, and PFS (p values ≤0.018). The results were similar in a population of Asian patients, except that a higher EGFR gene copy number was not associated with improved OS (p=0.248). Sensitivity analysis indicated that no one study overly influenced the results and that the findings are robust. The result of the analysis found that EGFR gene copy number was associated with increased OS and PFS, supporting the idea that EGFR gene copy number is a biomarker for response to EGFR-TKI therapy in patients with advanced NSCLC.

  18. 83例局部晚期非小细胞肺癌同步放化疗临床分析%Clinical analysis of concurrent chemoradiotherapy in 83 patients with locally advanced non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    Zhihua Sun; Qinfeng Li; Zhenyu Li; Yeshan Chen; Yao Jiang; Gang Wu

    2012-01-01

    Objective: The purpose of this study was to evaluate the efficacy and safety of concurrent chemoradiotherapy (CCRT) in patients with locally advanced non-small cell lung cancer (LANSCLC). Methods: 83 cases of patients who have been diagnosed for locally advanced NSCLC by determined cytology or pathology were divided into two groups randomly, 42 patients in NP group and 41 patients in EP group. All patients accepted thoracic three-dimensional conformal radiotherapy (3D-CRT) and concurrent either NP chemotherapy in NP group or EP chemotherapy in EP group. 3D-CRT were started on day 1 in the first cycle of chemotherapy. Chemotherapy were carried out for 4 cycles, every cycle was 21 days. Thoracic radiotherapy adopted conventional fractionated irradiation with 15 MeV-X ray, a total dose of 60 Gy. Results: In 83 patients were evaluable, there were 5 cases complete regression to be observed, 29 cases had partial regression (PR), 7 cases with stable disease (SD) and 1 case with progression disease (PD) in NP group. CR 3 cases, PR 27 cases, SD 9 cases and PD 2 cases in EP group. The overall response rate (RR) both NP group and EP group were 80.9%, 73.2%, respectively (P = 0.785).1-, 2-, 3-year survival rate were 90.5%, 69.0%, 28.6% and 82.9%, 51.2%, 21.9%, respectively (P = 0.393). The incidence of leukopenia and thrombocytopenia in NP group was higher than that in the EP group (P < 0.05). Conclusion: CCRT in patients with locally advanced non-small cell lung cancer, 3D-CRT with concurrent NP or EP chemotherapy. 1-, 2-, 3-year overall survival (OS) and average survival time (AST) were not statistically differences, a higher incidence of toxicities were observed in NP group but can be tolerable.

  19. Cancer immunotherapy: a future paradigm shift in the treatment of non-small cell lung cancer.

    Science.gov (United States)

    Anagnostou, Valsamo K; Brahmer, Julie R

    2015-03-01

    Emerging evidence on the role of the antitumor activity of the immune system has generated great interest in immunotherapy even for tumors that were historically considered as nonimmunogenic. Immunotherapy is emerging as a major modality in non-small cell lung cancer (NSCLC) treatment focusing on vaccine approaches to elicit specific immune responses and development of inhibitors of the molecular mediators of cancer-induced immunosuppression (immune checkpoints) to boost antitumor immune responses. Amplification of the host response against evolving tumors through vaccination is being investigated in ongoing clinical trials with tumor cell vaccines; however, the clinical efficacy of these agents has been limited. Blocking inhibitory pathways such as the CTL antigen 4 (CTLA-4) and programmed cell death 1 (PD-1) checkpoint pathways with mAbs has generated antitumor immune responses that are transforming cancer therapeutics. PD-1 and programmed cell death ligand 1 (PD-L1) antibodies have shown durable responses in NSCLC, with a favorable safety profile and manageable side effects. The activity of immune checkpoint inhibitors is currently been assessed in treatment-naïve patients with PD-L1-positive advanced NSCLC. Combinatorial approaches with other immune checkpoint inhibitors, chemotherapy, or targeted agents are being explored in ongoing clinical trials, and may improve outcome in NSCLC.

  20. Survival after Pneumonectomy for Stage III Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Sibu P. Saha

    2014-01-01

    Full Text Available Objectives: Stage III non-small cell lung cancer (NSCLC has a poor prognosis. Reports suggest that five-year survival after current treatment is between 14 to 24 percent. The purpose of this retrospective study was to investigate the morbidity and mortality of patients diagnosed with stage III NSCLC and treated with pneumonectomy at the University of Kentucky Medical Center in Lexington, KY. Methods: We reviewed the medical record and tumor registry follow-up data on 100 consecutive patients who underwent pneumonectomy for lung cancer at the University of Kentucky. Results: We identified thirty-six patients in stage III who underwent pneumonectomy. Ten patients had surgery only, eight patients received adjuvant chemotherapy, and eighteen patients received neoadjuvant therapy. There was one surgical death in this series. Mean follow-up was 2.9 years. One-, three-, and five-year survival was 66%, 38%, and 38%, respectively. Five-year survival for the group with adjuvant therapy was 60%. Conclusion: Most lung cancer patients present with advanced disease and the prognosis remains poor. Our experience indicates resection offers an above average chance of long-term survival when supplemented with neoadjuvant and/or adjuvant therapy.

  1. Nestin servers as a promising prognostic biomarker in non-small cell lung cancer.

    Science.gov (United States)

    Liu, Fang; Zhang, Yuan; Lu, Ming; Wang, Cong; Li, Qingbao; Gao, Yongsheng; Mu, Dianbin; Cao, Yan; Li, Miaomiao; Meng, Xiangjiao

    2017-01-01

    Lung cancer is currently the leading cause of cancer-related death worldwide and it is important to identify the predictive and/or prognostic markers for the cancer. Nestin, a proliferative and multipotent biomarker has been reported to be associated with prognosis in non-small cell lung cancer (NSCLC) in a few studies. In the present study, we retrospectively recruited 153 patients with NSCLC. Nestin protein expression in tumor samples was determined by immunohistochemistry staining. Nestin expression was related with tumor differentiation (P=0.036), lymphatic metastasis (N stage, P=0.011), and p-TNM stage (P=0.013), while there was no significant association between Nestin expression level and age, smoking habits, gender, histologic type, and T stage. Nestin was an independent prognostic factor for overall survival in NSCLC with an adjusted hazard ratio of 2.701 (95% CI, 1.616-4.513, PCRISPR/Cas9 mediated genome editing. It was observed that knockout of Nestin caused enhancement of cancer cell apoptosis and inhibition of cell proliferation, colony formation, and invasion in A549 and H1299 cell lines. Furthermore, we examined the expression of epithelial-mesenchymal transition (EMT) related biomarkers such as E-cadherin and Vimentin in Nestin-depleted lung cancer cells and knockout of Nestin was found to inhibit EMT, suggesting the involvement of Nestin mediated EMT signaling in lung cancer. The finding above demonstrated that Nestin might serve as a prognostic factor and therapeutic target in NSCLCs.

  2. PD-L1 biomarker testing for non-small cell lung cancer: truth or fiction?

    Science.gov (United States)

    Grigg, Claud; Rizvi, Naiyer A

    2016-01-01

    Research in cancer immunology is currently accelerating following a series of cancer immunotherapy breakthroughs during the last 5 years. Various monoclonal antibodies which block the interaction between checkpoint molecules PD-1 on immune cells and PD-L1 on cancer cells have been used to successfully treat non-small cell lung cancer (NSCLC), including some durable responses lasting years. Two drugs, nivolumab and pembrolizumab, are now FDA approved for use in certain patients who have failed or progressed on platinum-based or targeted therapies while agents targeting PD-L1, atezolizumab and durvalumab, are approaching the final stages of clinical testing. Despite impressive treatment outcomes in a subset of patients who receive these immune therapies, many patients with NSCLC fail to respond to anti-PD-1/PD-L1 and the identification of a biomarker to select these patients remains highly sought after. In this review, we discuss the recent clinical trial results of pembrolizumab, nivolumab, and atezolizumab for NSCLC, and the significance of companion diagnostic testing for tumor PD-L1 expression.

  3. Non-small cell lung cancer therapy: safety and efficacy in the elderly

    Directory of Open Access Journals (Sweden)

    Glotzer OS

    2013-04-01

    Full Text Available Owen S Glotzer,1 Thomas Fabian,1 Anurag Chandra,2 Charles T Bakhos21Division of Thoracic Surgery, Albany Medical Center, Department of Surgery, Albany Medical College, Albany, New York, USA; 2Department of Radiation Oncology, Albany Medical Center, Albany Medical College, Albany, New York, USABackground: Our objective was to evaluate and review the current literature on the treatment of non-small cell lung cancer (NSCLC in the elderly.Methods: We selected recent peer-reviewed articles addressing ageing, cancer treatment in the elderly, and lung cancer treatment in the elderly. We defined elderly as over the age of 70.Results: The population is ageing dramatically throughout most of the world. Given that situation, clinicians are seeing and being asked to treat more elderly patients that have NSCLC. Elderly patients are less likely to participate or be allowed to participate in prospective or retrospective studies of treatments for NSCLC. Elderly patients are also less likely to be staged appropriately for their advanced tumors, and are less likely to be referred for surgery or adjuvant therapy after surgery. When treatment is tailored to patient comorbidities but not to age, the data support survival and outcomes comparable to those of younger patients.Conclusions: Data are limited on the treatment of elderly patients with NSCLC. No data exist to support limiting recommendations for treatment based on age alone. Treatments should be determined on an individual basis.Keywords: thoracic surgery, radiation therapy, chemotherapy, pulmonary, physiology, ageing, SBRT

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

    Institute of Scientific and Technical Information of China (English)

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

    2008-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    MENG Xue; YU Jin-ming

    2011-01-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

  7. 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.

  8. Metastin is not involved in metastatic potential of non-small cell lung cancer.

    Science.gov (United States)

    Karapanagiotou, Eleni M; Dilana, Kalliopi D; Gkiozos, Ioannis; Gratsias, Ioannis; Tsimpoukis, Sotirios; Polyzos, Aris; Syrigos, Kostas N

    2011-06-01

    Metastin, the product of the KISS-1 gene, seems to represent a strong suppressant of metastasis for some types of cancer. The aim of this study is to explore whether circulating levels of metastin could be used as a marker for the metastatic potential of non-small cell lung cancer (NSCLC) as well as a diagnostic marker in NSCLC patients. The possible correlation between metastin and leptin circulating levels was also evaluated. Fasting serum levels of metastin and leptin were determined in 96 NSCLC patients at diagnosis (76 with metastatic disease and 21 with locally advanced disease) and 49 healthy volunteers using commercial available ELISA. Serum metastin levels presented no differences between NSCLC patients and healthy volunteers (1.18 ± 0.98 vs. 1.17 ± 0.39 ng/ml, P = 0.979) as well as between patients with metastatic and locally advanced disease (1.17 ± 1.05 vs. 1.21 ± 0.64 ng/ml, P = 0.872). There was no statistically significant correlation between circulating metastin and leptin levels in NSCLC patients and patients with locally advanced and metastatic disease. This study shows a lack of direct involvement of metastin in the diagnosis and metastatic potential of NSCLC.

  9. Drug Repositioning Discovery for Early- and Late-Stage Non-Small-Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Chien-Hung Huang

    2014-01-01

    Full Text Available Drug repositioning is a popular approach in the pharmaceutical industry for identifying potential new uses for existing drugs and accelerating the development time. Non-small-cell lung cancer (NSCLC is one of the leading causes of death worldwide. To reduce the biological heterogeneity effects among different individuals, both normal and cancer tissues were taken from the same patient, hence allowing pairwise testing. By comparing early- and late-stage cancer patients, we can identify stage-specific NSCLC genes. Differentially expressed genes are clustered separately to form up- and downregulated communities that are used as queries to perform enrichment analysis. The results suggest that pathways for early- and late-stage cancers are different. Sets of up- and downregulated genes were submitted to the cMap web resource to identify potential drugs. To achieve high confidence drug prediction, multiple microarray experimental results were merged by performing meta-analysis. The results of a few drug findings are supported by MTT assay or clonogenic assay data. In conclusion, we have been able to assess the potential existing drugs to identify novel anticancer drugs, which may be helpful in drug repositioning discovery for NSCLC.

  10. 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.

  11. Stathmin1 increases radioresistance by enhancing autophagy in non-small-cell lung cancer cells

    Directory of Open Access Journals (Sweden)

    Zhang X

    2016-04-01

    Full Text Available Xi Zhang,1,2 Jingfen Ji,3 Yu Yang,4 Juan Zhang,2 Liangfang Shen1 1Department of Oncology, Xiangya Hospital of Central South University, 2Department of Oncology, The Third Xiangya Hospital of Central South University