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Sample records for advanced refractory lung

  1. Chimeric antigen receptor-modified T cells for the immunotherapy of patients with EGFR-expressing advanced relapsed/refractory non-small cell lung cancer.

    PubMed

    Feng, Kaichao; Guo, Yelei; Dai, Hanren; Wang, Yao; Li, Xiang; Jia, Hejin; Han, Weidong

    2016-05-01

    The successes achieved by chimeric antigen receptor-modified T (CAR-T) cells in hematological malignancies raised the possibility of their use in non-small lung cancer (NSCLC). In this phase I clinical study (NCT01869166), patients with epidermal growth factor receptor (EGFR)-positive (>50% expression), relapsed/refractory NSCLC received escalating doses of EGFR-targeted CAR-T cell infusions. The EGFR-targeted CAR-T cells were generated from peripheral blood after a 10 to 13-day in vitro expansion. Serum cytokines in peripheral blood and copy numbers of CAR-EGFR transgene in peripheral blood and in tissue biopsy were monitored periodically. Clinical responses were evaluated with RECIST1.1 and immune- related response criteria, and adverse events were graded with CTCAE 4.0. The EGFR-targeted CAR-T cell infusions were well-tolerated without severe toxicity. Of 11 evaluable patients, two patients obtained partial response and five had stable disease for two to eight months. The median dose of transfused CAR(+) T cells was 0.97×10(7) cells kg(-1) (interquartile range (IQR), 0.45 to 1.09×10(7) cells kg(-1)). Pathological eradication of EGFR positive tumor cells after EGFR-targeted CAR-T cell treatment can be observed in tumor biopsies, along with the CAR-EGFR gene detected in tumor-infiltrating T cells in all four biopsied patients. The EGFR-targeted CAR-T cell therapy is safe and feasible for EGFR-positive advanced relapsed/refractory NSCLC.

  2. [Trans-Arterial Chemoembolization Therapy for Refractory Advanced Non-Small Cell Lung Cancer with Spherical Embolic Material--A Single Case Report].

    PubMed

    Kennoki, Norifumi; Hori, Shinichi; Yuki, Takeo; Sueyoshi, Satoshi; Hori, Atsushi

    2015-11-01

    Here, we report the use of trans-arterial chemoembolization for primary lung cancer. The patient was a 56-year-old woman with refractory Stage Ⅳ non-small cell lung cancer who had been treated with repeated systemic chemotherapy. The primary lesion in the right lower lobe was 75 mm in size, with multiple lung metastases. It invaded the right main bronchus and caused severe cough. Radiotherapy was not indicated because of the size and extent of the lesion. During a period of 6 months, chemoembolization of the bilateral bronchial arteries using cisplatin 20 mg, docetaxel 20 mg, and 5-FU 250 mg with HepaSphere (super-absorbent polymer microspheres) was performed 5 times. Twenty mg of docetaxel was loaded onto 25 mg of HepaSphere. The microspheres were between 50 and 100 microns in the dry state. The endpoint of embolization was not stasis but the reduction of arterial flow. There were no serious complications during or after the procedure. Immediately after the first session, the patient's cough was significantly improved. After 5 sessions of the same treatment, the primary lesion was reduced to 48 mm and the level of CEA was reduced from 9.8 to 4.3 ng/mL. The invasion to the right main bronchus was reduced. The patient has been well without any symptoms for 9 months after initiation of trans-arterial chemoembolization.

  3. Advances in artificial lungs.

    PubMed

    Ota, Kei

    2010-04-01

    Artificial lungs have already been developed as complete artificial organs, and results of many investigations based on innovative concepts have been reported continuously. In open-heart surgery, artificial lungs are used for extracorporeal circulation to maintain gas exchange, and the commercial products currently available perform adequately, including providing for antithrombogenicity. However, patients after cardiopulmonary arrest or severe respiratory/circulatory failure have required long-term assist with extracorporeal membrane oxygenation (ECMO). The number of artificial lungs used for ECMO in those cases has shown significant growth in recent years. Therefore, it is expected that durability and antithrombogenicity will ensure the prolonged use of an artificial lung for several weeks or months. Furthermore, interests in research are shifting to use of oxygenators as a bridge to lung transplantation and an implantable artificial lung. This paper discusses recent advances in artificial lungs, focusing on the current state and on trends in research and development.

  4. Recent advances and developments in refractory alloys

    SciTech Connect

    Nieh, T.G.; Wadsworth, J.

    1993-11-01

    Refractory metal alloys based on Mo, W, Re, Ta, and Nb (Cb) find applications in a wide range of aerospace applications because of their high melting points and high-temperature strength. This paper, presents recent progress in understanding and applications of these alloys. Recent studies to improve the oxidation and mechanical behavior of refractory metal alloys, and particularly Nb alloys, are also discussed. Some Re structures, for extremely high temperature applications (> 2000C), made by CVD and P/M processes, are also illustrated. Interesting work on the development of new W alloys (W-HfC-X) and the characterization of some commercial refractory metals, e.g., K-doped W, TZM, and Nb-1%Zr, continues. Finally, recent developments in high temperature composites reinforced with refractory metal filaments, and refractory metal-based intermetallics, e.g., Nb{sub 3}Al, Nb{sub 2}Be{sub 17}, and MoSi{sub 2}, are briefly described.

  5. Advances in nondestructive evaluation methods for inspection of refractory concretes

    SciTech Connect

    Ellingson, W. A.

    1980-01-01

    Refractory concrete linings are essential to protect steel pressure boundaries from high-temperature agressive erosive/corrosive environments. Castable refractory concretes have been gaining more acceptance as information about their performance increases. Economic factors, however, have begun to impose high demands on the reliability of refractory materials. Advanced nondestructive evaluation methods are being developed to assist the refractory user. Radiographic techniques, thermography, acoustic-emission detection, and interferometry have been shown to yield information on the structural status of refractory concrete. Methods using /sup 60/Co radiation sources are capable of yielding measurements of refractory wear rate as well as images of cracks and/or voids in pre- and post-fired refractory linings up to 60 cm thick. Thermographic (infrared) images serve as a qualitative indicator of refractory spalling, but quantitative measurements are difficult to obtain from surface-temperature mapping. Acoustic emission has been shown to be a qualitative indicator of thermomechanical degradation of thick panels of 50 and 95% Al/sub 2/O/sub 3/ during initial heating and cooling at rates of 100 to 220/sup 0/C/h. Laser interferometry methods have been shown to be capable of complete mappings of refractory lining thicknesses. This paper will present results obtained from laboratory and field applications of these methods in petrochemical, steel, and coal-conversion plants.

  6. Advances in lung ultrasound.

    PubMed

    Francisco, Miguel José; Rahal, Antonio; Vieira, Fabio Augusto Cardillo; Silva, Paulo Savoia Dias da; Funari, Marcelo Buarque de Gusmão

    2016-01-01

    Ultrasound examination of the chest has advanced in recent decades. This imaging modality is currently used to diagnose several pathological conditions and provides qualitative and quantitative information. Acoustic barriers represented by the aerated lungs and the bony framework of the chest generate well-described sonographic artifacts that can be used as diagnostic aids. The normal pleural line and A, B, C, E and Z lines (also known as false B lines) are artifacts with specific characteristics. Lung consolidation and pneumothorax sonographic patterns are also well established. Some scanning protocols have been used in patient management. The Blue, FALLS and C.A.U.S.E. protocols are examples of algorithms using artifact combinations to achieve accurate diagnoses. Combined chest ultrasonography and radiography are often sufficient to diagnose and manage lung and chest wall conditions. Chest ultrasonography is a highly valuable diagnostic tool for radiologists, emergency and intensive care physicians. RESUMO O exame ultrassonográfico do tórax avançou nas últimas décadas, sendo utilizado para o diagnóstico de inúmeras condições patológicas, e fornecendo informações qualitativas e quantitativas. Os pulmões aerados e o arcabouço ósseo do tórax representam barreira sonora para o estudo ultrassonográfico, gerando artefatos que, bem conhecidos, são utilizados como ferramentas diagnósticas. Eco pleural normal, linhas A, linhas B, linhas C, linhas E e Z (conhecidas como falsas linhas B) são artefatos com características peculiares. Os padrões de consolidação e de pneumotórax também são bem estabelecidos. Alguns protocolos têm sido utilizados no manuseio dos pacientes: Blue Protocol, Protocolo FALLS e Protocolo C.A.U.S.E são exemplos de três propostas que, por meio da associação entre os artefatos, permitem sugerir diagnósticos precisos. A ultrassonografia de tórax, aliada à radiografia de tórax, muitas vezes é suficiente para o diagn

  7. Refractory gastroesophageal reflux disease: advances and treatment.

    PubMed

    Ates, Fehmi; Francis, David O; Vaezi, Michael F

    2014-08-01

    'Refractory gastroesophageal reflux disease' is one of the most common misnomers in the area of gastroesophageal reflux disease. The term implies reflux as the underlying etiology despite unresponsiveness to aggressive proton pump inhibitor therapy. The term should be replaced with 'refractory symptoms.' We must acknowledge that in many patients symptoms of reflux often overlap with non-GERD causes such as gastroparesis, dyspepsia, hypersensitive esophagus and functional disorders. Lack of response to aggressive acid suppressive therapy often leads to diagnostic testing. In majority of patients these tests are normal. The role of non-acid reflux in this group is uncertain and patients should not undergo surgical fundoplication based on this parameter. In patients unresponsive to acid suppressive therapy GERD is most commonly not causal and a search for non-GERD causes must ensue.

  8. Radiographic Differentiation of Advanced Fibrocystic Lung Diseases.

    PubMed

    Akira, Masanori

    2017-03-01

    The concept of end-stage lung disease suggests a final common pathway for most diffuse parenchymal lung diseases. In accordance with this concept, end-stage disease is characterized radiographically and pathologically by the presence of extensive honeycombing. However, sequential computed tomographic (CT) scans obtained from patients with chronic diffuse lung disease evolve over time to show various advanced lung disease patterns other than honeycombing. In addition, several radiographically distinct honeycomb patterns, including microcystic, macrocystic, mixed, and combined emphysema and honeycombing, differentiate one advanced lung disease from another. For example, usual interstitial pneumonia (IP) usually shows mixed microcystic and macrocystic honeycombing. In contrast, CT images of long-standing fibrotic nonspecific IP typically show only small, scattered foci of honeycombing; instead, most enlarged airspaces observed in the advanced stage of this disease represent dilatation of bronchioles. In desquamative IP and pulmonary Langerhans cell histiocytosis, focal opacities typically evolve into emphysema-like lesions seen on CT imaging. In combined pulmonary fibrosis and emphysema and sarcoidosis, the cysts tend to be larger than those observed in usual IP. Sequential CT scans in other chronic, diffuse lung diseases also show various distinctive changes. This article highlights radiographic patterns of lung destruction that belie a single common pathway to end-stage lung disease. Recognition of distinct radiographic patterns of lung destruction can help differentiate diffuse parenchymal lung diseases, even in advanced stages of disease evolution.

  9. Test model designs for advanced refractory ceramic materials

    NASA Technical Reports Server (NTRS)

    Tran, Huy Kim

    1993-01-01

    The next generation of space vehicles will be subjected to severe aerothermal loads and will require an improved thermal protection system (TPS) and other advanced vehicle components. In order to ensure the satisfactory performance system (TPS) and other advanced vehicle materials and components, testing is to be performed in environments similar to space flight. The design and fabrication of the test models should be fairly simple but still accomplish test objectives. In the Advanced Refractory Ceramic Materials test series, the models and model holders will need to withstand the required heat fluxes of 340 to 817 W/sq cm or surface temperatures in the range of 2700 K to 3000 K. The model holders should provide one dimensional (1-D) heat transfer to the samples and the appropriate flow field without compromising the primary test objectives. The optical properties such as the effective emissivity, catalytic efficiency coefficients, thermal properties, and mass loss measurements are also taken into consideration in the design process. Therefore, it is the intent of this paper to demonstrate the design schemes for different models and model holders that would accommodate these test requirements and ensure the safe operation in a typical arc jet facility.

  10. Lenvatinib in Advanced, Radioactive Iodine-Refractory, Differentiated Thyroid Carcinoma.

    PubMed

    Yeung, Kay T; Cohen, Ezra E W

    2015-12-15

    Management options are limited for patients with radioactive iodine refractory, locally advanced, or metastatic differentiated thyroid carcinoma. Prior to 2015, sorafenib, a multitargeted tyrosine kinase inhibitor, was the only approved treatment and was associated with a median progression-free survival (PFS) of 11 months and overall response rate (ORR) of 12% in a phase III trial. Lenvatinib, a multikinase inhibitor with high potency against VEGFR and FGFR demonstrated encouraging results in phase II trials. Recently, the pivotal SELECT trial provided the basis for the FDA approval of lenvatinib as a second targeted therapy for these patients. Median PFS of 18.3 months in the lenvatinib group was significantly improved from 3.6 months in the placebo group, with an HR of 0.21 (95% confidence interval, 0.4-0.31; P < 0.0001). ORR was also significantly increased in the lenvatinib arm (64.7%) compared with placebo (1.5%). In this article, we will review the molecular mechanisms of lenvatinib, the data from preclinical studies to the recent phase III clinical trial, and the biomarkers being studied to further guide patient selection and predict treatment response.

  11. Intravenous immunoglobulin therapy for refractory interstitial lung disease associated with polymyositis/dermatomyositis.

    PubMed

    Suzuki, Yuzo; Hayakawa, Hiroshi; Miwa, Seiichi; Shirai, Masahiro; Fujii, Masato; Gemma, Hitoshi; Suda, Takafumi; Chida, Kingo

    2009-01-01

    Interstitial lung disease (ILD) associated with polymyositis/dermatomyositis (ILD-PM/DM), including amyopathic dermatomyositis (ADM), is recognized as an important condition because it frequently causes death, despite intensive therapy with high-dose corticosteroid and immunosuppressive agents, such as cyclosporine A and cyclophosphamide. Intravenous immunoglobulin therapy (IVIG) has shown efficacy for myopathy associated with PM/DM, but its usefulness for ILD-PM/DM is unclear. This study was designed to investigate the efficacy of IVIG for refractory ILD-PM/DM. A review was made of medical charts of five patients (2 men and 3 women) who were treated with IVIG for refractory ILD-PM/DM resistant to high-dose corticosteroid and cyclosporine A and/or cyclophosphamide. One patient had acute ILD-PM and four patients had acute ILD-ADM. Of the five patients, one patient with ILD-PM and one patient with ILD-ADM survived. No adverse reactions were seen due to IVIG treatment. There were no critical differences in the clinical parameters and clinical courses between survivors and nonsurvivors. IVIG treatment is safe and could be an effective salvage therapy for refractory ILD-PM/DM in certain cases, suggesting that further controlled trials are worthwhile.

  12. Non-invasive ventilation in prone position for refractory hypoxemia after bilateral lung transplantation.

    PubMed

    Feltracco, Paolo; Serra, Eugenio; Barbieri, Stefania; Persona, Paolo; Rea, Federico; Loy, Monica; Ori, Carlo

    2009-01-01

    Temporary graft dysfunction with gas exchange abnormalities is a common finding during the postoperative course of a lung transplant and is often determined by the post-reimplantation syndrome. Supportive measures including oxygen by mask, inotropes, diuretics, and pulmonary vasodilators are usually effective in non-severe post-reimplantation syndromes. However, in less-responsive clinical pictures, tracheal intubation with positive pressure ventilation, or non-invasive positive pressure ventilation (NIV), is necessary. We report on the clinical course of two patients suffering from refractory hypoxemia due to post-reimplantation syndrome treated with NIV in the prone and Trendelenburg positions. NIV was well tolerated and led to resolution of atelectactic areas and dishomogeneous lung infiltrates. Repeated turning from supine to prone under non invasive ventilation determined a stable improvement of gas exchange and prevented a more invasive approach. Even though NIV in the prone position has not yet entered into clinical practice, it could be an interesting option to achieve a better match between ventilation and perfusion. This technique, which we successfully applied in lung transplantation, can be easily extended to other lung diseases with non-recruitable dorso-basal areas.

  13. Refractory Pulmonary Edema Caused by Late Pulmonary Vein Thrombosis After Lung Transplantation: A Rare Adverse Event.

    PubMed

    Denton, Eve J; Rischin, Adam; McGiffin, David; Williams, Trevor J; Paraskeva, Miranda A; Westall, Glen P; Snell, Greg

    2016-09-01

    After lung transplantation, pulmonary vein thrombosis is a rare, potentially life-threatening adverse event arising at the pulmonary venous anastomosis that typically occurs early and presents as graft failure and hemodynamic compromise with an associated mortality of up to 40%. The incidence, presentation, outcomes, and treatment of late pulmonary vein thrombosis remain poorly defined. Management options include anticoagulant agents for asymptomatic clots, and thrombolytic agents or surgical thrombectomy for hemodynamically significant clots. We present a rare case highlighting a delayed presentation of pulmonary vein thrombosis occurring longer than 2 weeks after lung transplantation and manifesting clinically as graft failure secondary to refractory pulmonary edema. The patient was treated successfully with surgical thrombectomy and remains well. We recommend a high index of suspicion of pulmonary vein thrombosis when graft failure after lung transplantation occurs and is not responsive to conventional therapy, and consideration of investigation with transesophageal echocardiography or computed tomography with venous phase contrast in such patients even more than 2 weeks after lung transplantation.

  14. Immunotherapy for lung cancer: advances and prospects

    PubMed Central

    Yang, Li; Wang, Liping; Zhang, Yi

    2016-01-01

    Lung cancer is the most commonly diagnosed cancer as well as the leading cause of cancer-related deaths worldwide. To date, surgery is the first choice treatment, but most clinically diagnosed cases are inoperable. While chemotherapy and/or radiotherapy are the next considered options for such cases, these treatment modalities have adverse effects and are sometimes lethal to patients. Thus, new effective strategies with minimal side effects are urgently needed. Cancer immunotherapy provides either active or passive immunity to target tumors. Multiple immunotherapy agents have been proposed and tested for potential therapeutic benefit against lung cancer, and some pose fewer side effects as compared to conventional chemotherapy and radiotherapy. In this article, we discuss studies focusing on interactions between lung cancer and the immune system, and we place an emphasis on outcome evidence in order to create a knowledge base well-grounded in clinical reality. Overall, this review highlights the need for new lung cancer treatment options, with much ground to be paved for future advances in the field. We believe that immunotherapy agents alone or with other forms of treatment can be recognized as next modality of lung cancer treatment. PMID:27168951

  15. Novel Engineered Refractory Materials for Advanced Reactor Applications

    SciTech Connect

    Shannon, Steven; Eapen, Jacob; Maria, Jon-Paul; Weber, William

    2016-03-14

    This report summarizes the results of DOE-NEUP grant 10-853. The project spanned 48 months (36 months under the original grant plus a 12 month no cost extension). The overarching goal of this work was to fabricate and characterize refractory materials engineered at the atomic scale with emphasis on their tolerance to accumulated radiation damage. With an emphasis on nano-scale structure, this work included atomic scale simulation to study the underlying mechanisms for modified radiation tolerance at these atomic scales.

  16. Advanced refractory metals and composites for extraterrestrial power systems

    NASA Technical Reports Server (NTRS)

    Titran, R. H.; Grobstein, Toni L.

    1990-01-01

    Concepts for future space power systems include nuclear and focused solar heat sources coupled to static and dynamic power-conversion devices; such systems must be designed for service lives as long as 30 years, despite service temperatures of the order of 1600 K. Materials are a critical technology-development factor in such aspects of these systems as reactor fuel containment, environmental protection, power management, and thermal management. Attention is given to the prospective performance of such refractory metals as Nb, W, and Mo alloys, W fiber-reinforced Nb-matrix composites, and HfC precipitate-strengthened W-Re alloys.

  17. Design and development of advanced castable refractory materials

    NASA Astrophysics Data System (ADS)

    Davis, Robert Bruce

    New formulations of castable refractory composite materials were studied. This technology is used to produce low cost composite concrete structures designed for high temperature stability, superior wear resistance and improved strength. An in situ fired, castable cement installation is a heterogeneous structure divided into three zones according to the temperature history and microstructure. The properties of each zone depend on the predominant bonding mode between constituents. Each zone has a characteristic microstructure that influences the integrity of the monolith. The hot side may have a highly dense and developed network of ceramic bonds between constituent particles while the cold side may never reach temperatures sufficient to drive off free water. The thermal, structural and tribological properties depend on the microstructure and the type of bonding that holds the monolith together. The phase distributions are defined by sets of metastable phase conditions driven by the local hydrated chemistry, nearest neighbor oxide compounds, impurities and sintering temperature. Equilibrium phase diagrams were used to select optimum compositions based on higher melting point phases. The phase diagrams were also used to target high temperature phase fields that are stable over wide temperature and stoichiometric ranges. Materials selection of candidate hydraulic clinkers, high temperature oxides, and reinforcement phases were based on requirements for high temperature stability. The calcium aluminate (CaO-Al2O3) and calcium dialuminate (CaO-(Al2O3)2) are common refractory clinkers used in castable refractory cements. The thermodynamics and kinetics of cement hydrate formation are well studied and suited to become the building block of a design for a superior refractory castable cement. The inert oxides mixed with the calcium aluminate clinkers are magnesia (MgO), alumina (Al 2O3), spinel (MgAl2O4) and chromic (Cr2O3). The bulk of the experiments concentrated in the Al

  18. Antisynthetase syndrome with refractory lung involvement and myositis successfully treated with double filtration plasmapheresis.

    PubMed

    Bozkirli, Duygu Emine Ersozlu; Kozanoglu, Ilknur; Bozkirli, Emre; Yucel, Eftal

    2013-12-01

    Antisynthetase syndrome (ASS) is characterized by inflammatory muscle disease, pulmonary and joint involvement, and antisynthetase autoantibodies, with anti-Jo-1 antibody being the most common. Despite the use of immunosuppressive drugs, the prognosis of lung involvement seems poor. Herein, we report a case of refractory ASS, which maintained long-term remission by double filtration plasmapheresis (DFPP) combined with immunosuppressive therapy. For a 65-year-old woman, who was diagnosed with ASS, immunosuppressive therapy was initiated and plasmapheresis (PP) was performed five times due to acute interstitial pulmonary disease and inflammatory myopathy. She remained in remission for eight months following PP. Increase in interstitial involvement was identified by lung tomography when the patient presented again with complaint of progressive increase in dyspnea and muscle pain. Although the immunosuppressive therapy was increased for the patient with elevated creatine phosphokinase (CPK) (2776 IU/mL), a rapid decrease in diffusion capacity of the lung for carbon monoxide (DLCO) was observed and the patient underwent PP. After four sessions of therapy, insufficient clinical and laboratory response was obtained (control CPK 1797 IU/mL) and because of that issue DFPP using a 2A filter was performed to the patient. There was a marked improvement in complaints of the patient, DLCO, and laboratory findings (control CPK 508 IU/mL) after three sessions of DFPP. The patient, who continued the immunosuppressive therapy after DFPP procedure, is being followed for 12 months in remission. Although our experience is limited with only one patient, DFPP seems promising as a treatment option for ASS with severe lung involvement.

  19. ENERGY EFFICIENCY CHALLENGES ADDRESSED THROUGH THE USE OF ADVANCED REFRACTORY CERAMIC MATERIALS

    SciTech Connect

    Hemrick, James Gordon

    2014-01-01

    Refractory ceramics can play a critical role in improving the energy efficiency of traditional industrial processes through increased furnace efficiency brought about by the employment of novel refractory systems and techniques. Examples of advances in refractory materials related to aluminum, gasification, glass, and lime are highlighted. Energy savings are realized based on reduction of chemical reactions, elimination of mechanical degradation caused by the service environment, reduction of temperature limitations of materials, and elimination of costly installation and repair needs. Key results of projects resulting from US Department of Energy (DOE) funded research programs are discussed with emphasis on applicability of these results to high temperature furnace applications and needed research directions for the future.

  20. Successful cinacalcet treatment of refractory secondary hyperparathyroidism due to multiple lung parathyroid adenomas

    PubMed Central

    Sugi, Orie; Kimata, Naoki; Miwa, Naoko; Otsubo, Shigeru; Nitta, Kosaku; Akiba, Takashi

    2010-01-01

    We describe a 56-year-old woman who presented with end-stage renal disease due to pregnancy-induced hypertension and secondary hyperparathyroidism (sHPT). She had started hemodialysis and underwent a subtotal parathyroidectomy (PTx). However, intact parathyroid hormone (iPTH) levels increased gradually. Eventually, she underwent a second PTx. However, therapy failed to significantly decrease iPTH levels. A third PTx was performed, but no pathological parathyroid tissue was found. Computed tomography scan indicated the presence of multiple ectopic lung nodules and 26 nodules were surgically removed from the left lung. Despite surgical treatment, iPTH levels remained high. Additional maxacalcitol failed to decrease iPTH levels, cinacalcet was then started. iPTH levels decreased and the cinacalcet dose could be reduced to maintenance doses of 60 mg/day. Throughout the 1.6 years of treatment, serum iPTH, alkaline phosphatase (ALP) and bone alkaline phosphatase (BAP) were normalized. As a consequence, bone pain gradually disappeared. Bone mineral density (BMD) was improved by administration of cinacalcet. In conclusion, cinacalcet was effective in this patient with refractory and inoperable sHPT. In addition, it improves their BMD and relieves bone pain. PMID:25984040

  1. Lung cytotoxicity of combined exposure to refractory ceramic fibres and cigarette smoke.

    PubMed

    Cerná, Silvia; Hurbánková, Marta; Kováciková, Zuzana; Beno, Milan; Wimmerová, Sona

    2005-12-01

    Changes in some lung cytotoxic parameters after exposure to refractory ceramic fibres (RCF) or to cigarette smoke (S) and after combined exposure to RCF+S were studied in male Wistar rats in order to evaluate their potential adverse health effects. Four groups of rats were treated as follows : 1) intratracheally instilled by saline solution (0.4 ml); 2) intratracheally instilled by 4 mg of RCF; 3) exposed only to S (85 mg of total particulate matter/m(3) air ) for two hours daily; 4) exposed to RCF+S. After 6 months the animals were exsanguinated and the bronchoalveolar lavage (BAL) was perfomed. Viability and phagocytic activity of alveolar macrophages (AM), activity of lactate dehydrogenase (LDH) in cell-free BAL fluid (cf-BALF), acid phosphatase (ACP) and cathepsin D (CATD) in cfBALF, in BALF cells and in the lung tissue were estimated. Viability of AM was depressed by every type of exposure with RCF+S effect being at least additive. Phagocytic activity of AM increased in the presence of RCF. No significant changes in LDH activity were found. Activities of lysosomal enzymes measured in the lung tissue homogenates were not significantly changed, but those in the cfBALF increased especially after exposure to S with most expressive increase in BALF cells after exposure to S and RCF+S. In the case of CATD the effect of RCF+S was more than additive. The results point out to the persistence of the RCF exposure cytotoxic effects and their amplification by cigarette smoke.

  2. Talimogene Laherparepvec and Nivolumab in Treating Patients With Refractory Lymphomas or Advanced or Refractory Non-melanoma Skin Cancers

    ClinicalTrials.gov

    2017-01-31

    Adenoid Cystic Carcinoma; Adnexal Carcinoma; Apocrine Carcinoma; Eccrine Porocarcinoma; Extraocular Cutaneous Sebaceous Carcinoma; Hidradenocarcinoma; Keratoacanthoma; Malignant Sweat Gland Neoplasm; Merkel Cell Carcinoma; Microcystic Adnexal Carcinoma; NK-Cell Lymphoma, Unclassifiable; Non-Melanomatous Lesion; Paget Disease; Papillary Adenocarcinoma; Primary Cutaneous Mucinous Carcinoma; Refractory Anaplastic Large Cell Lymphoma; Refractory Cutaneous T-Cell Non-Hodgkin Lymphoma; Refractory Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Refractory Mycosis Fungoides; Refractory T-Cell Non-Hodgkin Lymphoma; Sezary Syndrome; Signet Ring Cell Carcinoma; Skin Basal Cell Carcinoma; Skin Basosquamous Cell Carcinoma; Skin Squamous Cell Carcinoma; Spiradenocarcinoma; Squamous Cell Carcinoma of Unknown Primary Origin; Stage III Skin Cancer; Stage IV Skin Cancer; Sweat Gland Carcinoma; Trichilemmocarcinoma; Vulvar Squamous Cell Carcinoma

  3. A Phase II Clinical Trial of CPI-613 in Patients with Relapsed or Refractory Small Cell Lung Carcinoma

    PubMed Central

    Pardee, Timothy S.; Petty, William J.; Bonomi, Marcelo; Alistar, Angela; Lamar, Zanetta S.; Isom, Scott; Chan, Michael D.; Miller, Antonius A.; Ruiz, Jimmy

    2016-01-01

    Background Small cell lung cancer (SCLC) is a common lung cancer which presents with extensive stage disease at time of diagnosis in two-thirds of patients. For treatment of advanced disease, traditional platinum doublet chemotherapy induces response rates up to 80% but with few durable responses. CPI-613 is a novel anti-cancer agent that selectively inhibits the altered form of mitochondrial energy metabolism in tumor cells. Methods We evaluated CPI-613 with a single-arm, open-label phase II study in patients with relapsed or refractory SCLC. CPI-613 was given at a dose of 3,000 mg/m2 on days 1 and 4 of weeks 1–3 of 4 week cycle. The primary outcome was response rate as assessed by CT imaging using RECIST v1.1 criteria. Secondary outcomes were progression-free survival (PFS), overall survival (OS), and toxicity. Twelve patients were accrued (median age 57yo) who had previously received between 1 and 4 lines of chemotherapy (median 1) for SCLC with a treatment-free interval of less than 60 days in 9 of the 12 patients. Results No complete or partial responses were seen. Ten patients (83%) progressed as best response and 2 (17%) were not evaluable for response. Median time to progression was 1.7 months (range 0.7 to 1.8 months). Eleven patients (92%) died with median overall survival of 4.3 months (range 1.2 to 18.2 months). The study was closed early due to lack of efficacy. Of note, three out of three patients who progressed after CPI-613 and were subsequently treated with standard topotecan then demonstrated treatment response with survival for 18.2, 7.4, and 5.1 months. We conducted laboratory studies which found synergy in-vitro for CPI-613 with topotecan. Conclusions Single agent CPI-613 had no efficacy in this study. Further study of CPI 613 in combination with a topoisomerase inhibitor is warranted. PMID:27732654

  4. Crizotinib for Advanced Non-Small Cell Lung Cancer

    Cancer.gov

    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.

  5. Recent advances in lung cancer biology

    SciTech Connect

    Lechner, J.

    1995-12-31

    This paper provides an overview of carcinogenesis, especially as related to lung cancers. Various growth factors and their mutated forms as oncogenes are discussed with respect to gene location and their role in the oncogenic process. Finally the data is related to lung cancer induction in uranium miners and exposure to radon.

  6. Lung Cancer Clinical Trials: Advances in Immunotherapy

    Cancer.gov

    New treatments for lung cancer and aspects of joining a clinical trial are discussed in this 30-minute Facebook Live event, hosted by NCI’s Dr. Shakun Malik, head of thoracic oncology therapeutics, and Janet Freeman-Daily, lung cancer patient activist and founding member of #LCSM.

  7. VAC chemotherapy with valproic acid for refractory/relapsing small cell lung cancer: a phase II study.

    PubMed

    Berghmans, Thierry; Lafitte, Jean-Jacques; Scherpereel, Arnaud; Ameye, Lieveke; Paesmans, Marianne; Meert, Anne-Pascale; Colinet, Benoit; Tulippe, Christian; Willems, Luc; Leclercq, Nathalie; Sculier, Jean-Paul

    2015-10-01

    Salvage chemotherapy (CT) for relapsing or refractory small cell lung cancer (SCLC) remains disappointing. In vitro experiments showed that valproic acid increases apoptosis of SCLC cell lines exposed to doxorubicin, vindesine and bis(2-chloroethyl)amine. The primary objective of this phase II study was to determine whether epigenetic modulation with valproic acid in addition to a doxorubicin, vindesine and cyclophosphamide (VAC) regimen improves 6-month progression-free survival (PFS). Patients with pathologically proven SCLC refractory to prior platinum derivatives and etoposide were eligible. After central registration, patients received VAC plus daily oral valproic acid. 64 patients were registered, of whom six were ineligible. Seven patients did not receive any CT, leaving 51 patients assessable for the primary end-point. The objective response rate was 19.6%. Median PFS was 2.8 months (95% CI 2.5-3.6 months) and 6-month PFS was 6%. Median survival time was 5.9 months (95% CI 4.7-7.5 months). Toxicity was mainly haematological, with 88% and 26% grade 3-4 neutropenia and thrombopenia, respectively. Despite an interesting response rate, the addition of valproic acid to VAC did not translate into adequate PFS in relapsing SCLC or SCLC refractory to platinum-etoposide.

  8. Emerging challenges of advanced squamous cell lung cancer

    PubMed Central

    Zhang, Yi-Chen; Zhou, Qing

    2016-01-01

    Squamous cell lung cancer (SQCLC) is an aggressive type of lung cancer and most are diagnosed at advanced stage. Patients with advanced SQCLC tend to be older, current or former smoker, with central type tumour located near large blood vessels and seldom with druggable genetic alternations. Consequently, progress of targeted therapy and antivascular agents available in lung adenocarcinoma could not be duplicated in this subset of patients. The treatment paradigms have long been dominant by cytotoxic agents and posed many therapeutic challenges. Until recent years, immune checkpoint inhibitors, other monoclonal antibodies and afatinib have been approved for treatment of advanced SQCLC, presenting a novel treatment landscape and initiating the era of precision medicine in this subset of patients. This review will summarise the recent treatment progresses in advanced SQCLC with a focus on checkpoint inhibitors of programmed cell death-1 receptor or its ligand, and discuss the emerging challenges in this new era. PMID:28255454

  9. Recent advances in personalized lung cancer medicine

    PubMed Central

    Okimoto, Ross A; Bivona, Trever G

    2014-01-01

    The identification of molecular subtypes of non-small-cell lung cancer has transformed the clinical management of this disease. This is best exemplified by the clinical success of targeting the EGFR or ALK with tyrosine kinase inhibitors in the front-line setting. Our ability to further improve patient outcomes with biomarker-based targeted therapies will depend on a more comprehensive genetic platform that can rationally interrogate the cancer genome of an individual patient. Novel technologies, including multiplex genotyping and next-generation sequencing are rapidly evolving and will soon challenge the oncologist with a wealth of genetic information for each patient. Although there are many barriers to overcome, the integration of these genetic platforms into clinical care has the potential to transform the management of lung cancer through improved molecular categorization, patient stratification, and drug development, thereby, improving clinical outcomes through personalized lung cancer medicine. PMID:25506379

  10. Serum amyloid A opposes lipoxin A₄ to mediate glucocorticoid refractory lung inflammation in chronic obstructive pulmonary disease.

    PubMed

    Bozinovski, Steven; Uddin, Mohib; Vlahos, Ross; Thompson, Michelle; McQualter, Jonathan L; Merritt, Anne-Sophie; Wark, Peter A B; Hutchinson, Anastasia; Irving, Louis B; Levy, Bruce D; Anderson, Gary P

    2012-01-17

    Chronic obstructive pulmonary disease (COPD) will soon be the third most common cause of death globally. Despite smoking cessation, neutrophilic mucosal inflammation persistently damages the airways and fails to protect from recurrent infections. This maladaptive and excess inflammation is also refractory to glucocorticosteroids (GC). Here, we identify serum amyloid A (SAA) as a candidate mediator of GC refractory inflammation in COPD. Extrahepatic SAA was detected locally in COPD bronchoalveolar lavage fluid, which correlated with IL-8 and neutrophil elastase, consistent with neutrophil recruitment and activation. Immunohistochemistry detected SAA was in close proximity to airway epithelium, and in vitro SAA triggered release of IL-8 and other proinflammatory mediators by airway epithelial cells in an ALX/FPR2 (formyl peptide receptor 2) receptor-dependent manner. Lipoxin A(4) (LXA(4)) can also interact with ALX/FPR2 receptors and lead to allosteric inhibition of SAA-initiated epithelial responses (pA(2) 13 nM). During acute exacerbation, peripheral blood SAA levels increased dramatically and were disproportionately increased relative to LXA(4). Human lung macrophages (CD68(+)) colocalized with SAA and GCs markedly increased SAA in vitro (THP-1, pEC(50) 43 nM). To determine its direct actions, SAA was administered into murine lung, leading to induction of CXC chemokine ligand 1/2 and a neutrophilic response that was inhibited by 15-epi-LXA(4) but not dexamethasone. Taken together, these findings identify SAA as a therapeutic target for inhibition and implicate SAA as a mediator of GC-resistant lung inflammation that can overwhelm organ protective signaling by lipoxins at ALX/FPR2 receptors.

  11. [Advances of molecular targeted therapy in squamous cell lung cancer].

    PubMed

    Ma, Li; Zhang, Shucai

    2013-12-01

    Squamous cell lung cancer (SQCLC) is one of the most prevalent subtypes of lung cancer worldwide, about 400,000 persons die from squamous-cell lung cancer around the world, and its pathogenesis is closely linked with tobacco exposure. Unfortunately, squamous-cell lung cancer patients do not benefit from major advances in the development of targeted therapeutics such as epidermal growth factor receptor (EGFR) inhibitors or anaplastic lymphoma kinase (ALK) inhibitors that show exquisite activity in lung adenocarcinomas with EGFR mutations or echinoderm microtubule associated protein like-4 (EML4)-ALK fusions, respectively. Major efforts have been launched to characterize the genomes of squamous-cell lung cancers. Among the new results emanating from these efforts are amplifications of the fibroblast growth factor receptor 1 (FGFR1) gene, the discoidin domain receptor 2 (DDR2) gene mutation as potential novel targets for the treatment of SQCLCs. Researchers find that there are many specific molecular targeted genes in the genome of squamous-cell lung cancer patients. These changes play a vital role in cell cycle regulation, oxidative stress, cell apoptosis, squamous epithelium differentiation, may be the candidate targeted moleculars in SQCLCs. Here, we provide a review on these discoveries and their implications for clinical trials in squamous-cell lung cancer assessing the value of novel therapeutics addressing these targets.

  12. Advances and Implications in Nanotechnology for Lung Cancer Management.

    PubMed

    Sarkar, Sana; Osama, Khwaja; Jamal, Qazi Mohammad Sajid; Kamal, Mohammad Amjad; Sayeed, Usman; Khan, M Kalim A; Siddiqui, Mohd Haris; Akhtar, Salman

    2016-11-14

    Lung cancer is one of the most important chronic diseases in the field of respiratory medicine. Conventional treatment strategies for lung cancer include chemotherapy, surgery and radiation therapy. These current therapies lack specificity and are limited by undesirable toxicities in normal cells, as well as a high rate of recurrence.Nanotechnological intervention has greatly revolutionized the therapy of lung cancer by surmounting the current limitations in conventional therapies. Nanoparticles (NPs) achieve preferential accumulation in the tumor cells by employing two mechanisms: passive and active targeting. Several nanoscale drug delivery systems for lung cancer treatment are currently in clinical trials and few of them are already commercially available. Recently, the interest to develop pulmonary delivery system of nano-based drug formulations suitable for lung cancer has been also increased which have resulted in more effective and advanced treatment of Lung cancer. However, although nanotechnology based drug carriers for lung cancer treatment have established outstanding therapeutic potential at both preclinical and clinical Phases, but there are still many limitations to be solved. This review details the till date drug nanocarriers researches performed for lung cancer therapy.

  13. Weekly CODE chemotherapy with recombinant human granulocyte colony-stimulating factor for relapsed or refractory small cell lung cancer.

    PubMed

    Sato, K; Tsuchiya, S; Minato, K; Sunaga, N; Ishihara, S I; Makimoto, T; Naruse, I; Hoshino, H; Watanabe, S; Saitoh, R; Mori, M

    2000-01-01

    We used cisplatin, vincristine, doxorubicin, and etoposide (CODE) plus recombinant human granulocyte colony-stimulating factor (rhG-CSF) weekly for salvage chemotherapy in relapsed or refractory small cell lung cancer (SCLC). We reviewed the medical charts of patients between January 1993 and December 1996 at the National Nishi-Gunma Hospital. Twenty patients were treated with salvage chemotherapy. The overall response rate was 55.0%. The median survival time of extensive disease patients from the start of CODE therapy was 23 weeks and the 1-year survival rate was 21.0%. Toxicities were severe, especially in myelosuppression. CODE could be selected as a salvage therapy for chemotherapy- relapsed SCLC cases.

  14. Practical use of advanced mouse models for lung cancer.

    PubMed

    Safari, Roghaiyeh; Meuwissen, Ralph

    2015-01-01

    To date a variety of non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) mouse models have been developed that mimic human lung cancer. Chemically induced or spontaneous lung cancer in susceptible inbred strains has been widely used, but the more recent genetically engineered somatic mouse models recapitulate much better the genotype-phenotype correlations found in human lung cancer. Additionally, improved orthotopic transplantation of primary human cancer tissue fragments or cells into lungs of immune-compromised mice can be valuable tools for preclinical research such as antitumor drug tests. Here we give a short overview of most somatic mouse models for lung cancer that are currently in use. We accompany each different model with a description of its practical use and application for all major lung tumor types, as well as the intratracheal injection or direct injection of fresh or freeze-thawed tumor cells or tumor cell lines into lung parenchyma of recipient mice. All here presented somatic mouse models are based on the ability to (in) activate specific alleles at a time, and in a tissue-specific cell type, of choice. This spatial-temporal controlled induction of genetic lesions allows the selective introduction of main genetic lesions in an adult mouse lung as found in human lung cancer. The resulting conditional somatic mouse models can be used as versatile powerful tools in basic lung cancer research and preclinical translational studies alike. These distinctively advanced lung cancer models permit us to investigate initiation (cell of origin) and progression of lung cancer, along with response and resistance to drug therapy. Cre/lox or FLP/frt recombinase-mediated methods are now well-used techniques to develop tissue-restricted lung cancer in mice with tumor-suppressor gene and/or oncogene (in)activation. Intranasal or intratracheal administration of engineered adenovirus-Cre or lentivirus-Cre has been optimized for introducing Cre

  15. Advanced treatment of refractory organic pollutants in petrochemical industrial wastewater by bioactive enhanced ponds and wetland system.

    PubMed

    Liu, Shuo; Ma, Qiusha; Wang, Baozhen; Wang, Jifu; Zhang, Ying

    2014-05-01

    A large-scale combined ponds-wetland system was applied for advanced treatment of refractory pollutants in petrochemical industrial wastewater. The system was designed to enhance bioactivity and biological diversity, which consisted of anaerobic ponds (APs), facultative ponds (FPs), aerobic pond and wetland. The refractory pollutants in the petrochemical wastewater to be treated were identified as alkanes, chloroalkanes, aromatic hydrocarbons, and olefins, which were significantly degraded and transformed along with the influent flowing through the enhanced bioactive ponds-wetland system. 8 years of recent operational data revealed that the average removal rate of stable chemical oxygen demand (COD) was 42.7 % and that influent COD varied from 92.3 to 195.6 mg/L. Final effluent COD could reach 65.8 mg/L (average). COD removal rates were high in the APs and FPs and accounted for 75 % of the total amount removed. This result indicated that the APs and FPs degraded refractory pollutants through the facilitation of bacteria growth. The changes in the community structures of major microbes were assessed by 16SrDNA-denaturing gradient gel electrophoresis. The same analysis was used to identify the main bacterial function for the removal of refractory pollutants in the APs and FPs. The APs and FPs displayed similar microbial diversities, and some of the identified bacteria degraded and removed refractory pollutants. The overall results proved the applicability, stability, and high efficiency of the ponds-wetland system with enhanced bioactivity in the advanced removal of refractory pollutants from petrochemical industrial wastewater.

  16. Advances in antiangiogenic treatment of small-cell lung cancer

    PubMed Central

    Lu, Hongyang; Jiang, Zhiming

    2017-01-01

    Small-cell lung cancer (SCLC), a poorly differentiated neuroendocrine malignancy, has a rapid growth rate, strong aggressiveness, early metastases, and poor prognosis. Angiogenesis greatly contributes to the metastatic process of SCLC, which has a higher vascularization compared with non-small-cell lung cancer (NSCLC). SCLC might constitute an ideal malignancy for assessing new antiangiogenic drugs and therapeutic strategies. Combining bevacizumab with paclitaxel has therapeutic benefits in chemoresistant, relapsed SCLC. The cisplatin–etoposide and bevacizumab combination, as the first-line treatment for extensive-stage SCLC, can improve progression-free survival (PFS), with an acceptable toxicity profile. Ziv-aflibercept combined with topotecan is promising for platinum-refractory SCLC. Chemotherapy combined with thalidomide cannot prolong survival. Maintenance sunitinib of 37.5 mg/day in extensive-stage SCLC patients following induction chemotherapy with platinum/etoposide improves median PFS by 1.6 months. Serum angiopoietin-2 concentrations and vascular endothelial growth factor levels correlate with poor prognosis. Bevacizumab, ziv-aflibercept, and sunitinib are worthy of further evaluation. Thalidomide, sorafenib, pomalidomide, and cediranib may not be suitable for SCLC. PMID:28138259

  17. The efficacy and safety of anti-PD-1/PD-L1 antibodies for treatment of advanced or refractory cancers: a meta-analysis

    PubMed Central

    Arai, Seiji; Wang, Liping; Shi, Xuezhong; Shi, Ni; Ma, Fen; Chen, Sen; Huang, Lan; Yang, Li; Ma, Wang; Zhang, Bin; Han, Weidong; Xia, Jianchuan; Chen, Hu; Zhang, Yi

    2016-01-01

    Purpose To systematically evaluate the overall efficacy and safety of current anti-PD-1/PD-L1 antibodies for treatment of patients with advanced or refractory cancer. Results Fifty-one trials including 6,800 patients were included. The overall response rates for melanoma, non-small cell lung cancer (NSCLC), and renal cell carcinoma (RCC) were 29% (95% CI: 1.53−2.41), 21% (95% CI: 17%−25%) and 21% (95% CI: 16%−27%) respectively. While the overall adverse effects rate for melanoma, NSCLC, RCC were 16% (95% CI: 6%−28%), 11% (95% CI: 8%−14%) and 20% (95% CI: 11%−32%) respectively. Tumor PD-L1 expression and patient smoking status might serve as biomarkers to predict response of anti-PD-1/PD-L1 antibody treatment. Compared to tumors with negative PD-L1 expression, tumors with positive PD-L1 expression had a significantly higher clinical response rate (41.4% versus 26.5%) with RR = 1.92 (95% CI: 1.53−2.41, P < 0.001). Smoker patients also showed a significantly higher response rate (33.7%) than patients who never smoked (4.2%) with RR = 6.02 (95% CI: 1.22−29.75, P = 0.028). Nivolumab and Pembrolizumab were associated with significantly increased response rate (RR = 2.89, 95% CI: 2.46−3.40, P < 0.001), reduced death risk (HR= 0.53; 95% CI: 0.48−0.57; P < 0.001), and decreased adverse effect rate (RR = 0.49, 95% CI: 0.30−0.80, P = 0.004) compared with other therapies. Experimental Design Clinical trials reporting response or safety of anti-PD-1/PD-L1 antibodies for advanced or refractory cancer patients published before January 31th 2016 were searched in PubMed and EMBASE database. Meta-analyses using random effects models were used to calculate the overall estimate. Conclusions Anti-PD-1/PD-L1 antibodies have high response rates and low adverse effect rates for advanced or refractory cancers. PMID:27683031

  18. Partial Response in an RRx-001-Primed Patient with Refractory Small-Cell Lung Cancer after a Third Introduction of Platinum Doublets

    PubMed Central

    Carter, Corey A.; Oronsky, Bryan; Caroen, Scott; Scicinski, Jan; Degesys, Aiste; Cabrales, Pedro; Reid, Tony R.; Brzezniak, Christina

    2016-01-01

    Small-cell lung cancer (SCLC), initially exquisitely sensitive to first-line cisplatin/etoposide, invariably relapses and acquires a multidrug chemoresistant phenotype that generally renders retreatment with first-line therapy both futile and counterproductive. This report presents the case of a 77-year-old Caucasian male with extensive-stage refractory SCLC who was restarted on platinum doublets as part of a clinical trial called TRIPLE THREAT (NCT02489903) involving pretreatment with the epi-immunotherapeutic agent RRx-001, and who achieved a partial response after only 4 cycles. The patient had received a platinum drug twice before, in 2009 for a diagnosis of non-small-cell lung cancer (squamous cell carcinoma) and in 2015 for SCLC, suggesting that RRx-001 pretreatment may sensitize or resensitize refractory SCLC patients to first-line chemotherapy. PMID:27403127

  19. Pumped lithium loop test to evaluate advanced refractory metal alloys and simulated nuclear fuel elements

    NASA Technical Reports Server (NTRS)

    Brandenburf, G. P.; Hoffman, E. E.; Smith, J. P.

    1974-01-01

    The performance was determined of refractory metal alloys and uranium nitride fuel element specimens in flowing 1900F (1083C) lithium. The results demonstrate the suitability of the selected materials to perform satisfactorily from a chemical compatibility standpoint.

  20. Chemical vapor deposition of refractory ternary nitrides for advanced diffusion barriers

    SciTech Connect

    Custer, Jonathan S.; Fleming, James G.; Roherty-Osmun, Elizabeth; Smith, Paul Martin

    1998-09-22

    Refractory ternary nitride films for diffusion barriers in microelectronics have been grown using chemical vapor deposition. Thin films of titanium-silicon-nitride, tungsten-boron-nitride, and tungsten-silicon-nitride of various compositions have been deposited on 150 mm Si wafers. The microstructure of the films are either fully amorphous for the tungsten based films, or nauocrystalline TiN in an amorphous matrix for titanium-silicon-nitride. All films exhibit step coverages suitable for use in future microelectronics generations. Selected films have been tested as diffusion barriers between copper and silicon, and generally perform extremely weH. These fiIms are promising candidates for advanced diffusion barriers for microelectronics applications. The manufacturing of silicon wafers into integrated circuits uses many different process and materials. The manufacturing process is usually divided into two parts: the front end of line (FEOL) and the back end of line (BEOL). In the FEOL the individual transistors that are the heart of an integrated circuit are made on the silicon wafer. The responsibility of the BEOL is to wire all the transistors together to make a complete circuit. The transistors are fabricated in the silicon itself. The wiring is made out of metal, currently aluminum and tungsten, insulated by silicon dioxide, see Figure 1. Unfortunately, silicon will diffuse into aluminum, causing aluminum spiking of junctions, killing transistors. Similarly, during chemical vapor deposition (CVD) of tungsten from ~fj, the reactivity of the fluorine can cause "worn-holes" in the silicon, also destroying transistors. The solution to these problems is a so-called diffusion barrier, which will allow current to pass from the transistors to the wiring, but will prevent reactions between silicon and the metal.

  1. Low cost biological lung volume reduction therapy for advanced emphysema

    PubMed Central

    Bakeer, Mostafa; Abdelgawad, Taha Taha; El-Metwaly, Raed; El-Morsi, Ahmed; El-Badrawy, Mohammad Khairy; El-Sharawy, Solafa

    2016-01-01

    Background Bronchoscopic lung volume reduction (BLVR), using biological agents, is one of the new alternatives to lung volume reduction surgery. Objectives To evaluate efficacy and safety of biological BLVR using low cost agents including autologous blood and fibrin glue. Methods Enrolled patients were divided into two groups: group A (seven patients) in which autologous blood was used and group B (eight patients) in which fibrin glue was used. The agents were injected through a triple lumen balloon catheter via fiberoptic bronchoscope. Changes in high resolution computerized tomography (HRCT) volumetry, pulmonary function tests, symptoms, and exercise capacity were evaluated at 12 weeks postprocedure as well as for complications. Results In group A, at 12 weeks postprocedure, there was significant improvement in the mean value of HRCT volumetry and residual volume/total lung capacity (% predicted) (P-value: <0.001 and 0.038, respectively). In group B, there was significant improvement in the mean value of HRCT volumetry and (residual volume/total lung capacity % predicted) (P-value: 0.005 and 0.004, respectively). All patients tolerated the procedure with no mortality. Conclusion BLVR using autologous blood and locally prepared fibrin glue is a promising method for therapy of advanced emphysema in term of efficacy, safety as well as cost effectiveness. PMID:27536091

  2. Sorafenib treatment of radioiodine-refractory advanced thyroid cancer in daily clinical practice: a cohort study from a single center.

    PubMed

    Gallo, Marco; Michelon, Federica; Castiglione, Anna; Felicetti, Francesco; Viansone, Alessandro Adriano; Nervo, Alice; Zichi, Clizia; Ciccone, Giovannino; Piovesan, Alessandro; Arvat, Emanuela

    2015-08-01

    Treatment options for recurrent or metastatic differentiated thyroid cancer (DTC) refractory to radioactive iodine (RAI) are inadequate. Multitargeted kinase inhibitors have recently shown promising results in phase 2-3 studies. This retrospective study aimed to document our clinical experience on the effects of sorafenib in the setting of daily clinical practice. Retrospective study evaluating the efficacy and safety of sorafenib in a cohort of patients consecutively treated with sorafenib at a single center. Twenty patients with advanced RAI-refractory thyroid carcinoma were enrolled (March 2011-March 2014). Patients generally started with 400 mg of sorafenib twice daily, tapering the dose in case of side effects. Radiological response and toxicity were measured during follow-up, together with safety parameters. CT scans were performed by a single experienced radiologist every 3-4 months. Five patients stopped sorafenib within 90 days due to severe toxicities. Median progression-free survival was 248 days. Five patients had a partial response (PR), achieved in all cases within 3 months, whereas 5 had stable disease (SD) at 12 months. Durable response rate (PR plus SD) for at least 6 months was 50 %, among those who received sorafenib for at least 3 months. Commonest adverse events included skin toxicity, gastrointestinal and constitutional symptoms. In our cohort of patients with advanced RAI-refractory thyroid carcinoma, sorafenib confirmed antitumor activity leading to SD or PR in the majority of cases, at the expense of clinically relevant side effects. More effective and tolerable agents are still needed in the treatment of RAI-refractory DTC.

  3. An advanced case of indium lung disease with progressive emphysema

    PubMed Central

    Nakano, Makiko; Tanaka, Akiyo; Hirata, Miyuki; Kumazoe, Hiroyuki; Wakamatsu, Kentaro; Kamada, Dan; Omae, Kazuyuki

    2016-01-01

    Objectives: To report the occurrence of an advanced case of indium lung disease with severely progressive emphysema in an indium-exposed worker. Case report: A healthy 42-year-old male smoker was employed to primarily grind indium-tin oxide (ITO) target plates, exposing him to indium for 9 years (1998-2008). In 2004, an epidemiological study was conducted on indium-exposed workers at the factory in which he worked. The subject's serum indium concentration (In-S) was 99.7 μg/l, while his serum Krebs von den Lungen-6 level was 2,350 U/ml. Pulmonary function tests showed forced vital capacity (FVC) of 4.17 l (91.5% of the JRS predicted value), forced expiratory volume in 1 s (FEV1) of 3.19 l (80.8% of predicted), and an FEV1-to-FVC ratio of 76.5%. A high-resolution chest computed tomography (HRCT) scan showed mild interlobular septal thickening and mild emphysematous changes. In 2008, he was transferred from the ITO grinding workplace to an inspection work section, where indium concentrations in total dusts had a range of 0.001-0.002 mg/m3. In 2009, the subject's In-S had increased to 132.1 μg/l, and pulmonary function tests revealed obstructive changes. In addition, HRCT scan showed clear evidence of progressive lung destruction with accompanying severe centrilobular emphysema and interlobular septal thickening in both lung fields. The subject's condition gradually worsened, and in 2015, he was registered with the Japan Organ Transplant Network for lung transplantation (LTx). Conclusions: Heavy indium exposure is a risk factor for emphysema, which can lead to a severity level that requires LTx as the final therapeutic option. PMID:27488043

  4. Pulmonary Rehabilitation in Advanced Lung Cancer Patients During Chemotherapy.

    PubMed

    Jastrzębski, D; Maksymiak, M; Kostorz, S; Bezubka, B; Osmanska, I; Młynczak, T; Rutkowska, A; Baczek, Z; Ziora, D; Kozielski, J

    2015-01-01

    The aim of this study was to investigate the utility of pulmonary rehabilitation for improving of exercises efficiency, dyspnea, and quality of life of patients with lung cancer during chemotherapy. After the enrollment selection, the study included 20 patients with newly diagnosed advanced lung cancer and performance status 0-2. There were 12 patients randomly allocated to the pulmonary rehabilitation group and another 8 constituted the control group that did not undergo physical rehabilitation. Both groups of patients had continual cycles of chemotherapy. Data were analyzed before and after 8 weeks of physical rehabilitation, and before and after 8 weeks of observation without rehabilitation in controls. The inpatient rehabilitation program was based on exercise training with ski poles and respiratory muscle training. We found a tendency for enhanced mobility (6 Minute Walk Test: 527.3 ± 107.4 vs. 563.9 ±64.6 m; p > 0.05) and a significant increase in forced expired volume in 1 s (66.9 ± 13.2 vs. 78.4 ± 17.7 %predicted; p = 0.016), less dyspnea (p = 0.05), and a tendency for improvement in the general quality of life questionnaire after completion of pulmonary rehabilitation as compared with the control group. This report suggests that pulmonary rehabilitation in advanced lung cancer patients during chemotherapy is a beneficial intervention to reduce dyspnea and enhance the quality of life and mobility.

  5. Pneumocystis jiroveci pneumonia and colonization in patients with advanced lung cancer

    PubMed Central

    TOGASHI, YOSUKE; MASAGO, KATSUHIRO; ITO, YUTAKA; SAKAMORI, YUICHI; OKUDA, CHIYUKI; FUKUHARA, AKIKO; NAGAI, HIROKI; KIM, YOUNG HAK; MISHIMA, MICHIAKI

    2013-01-01

    Pneumocystis jiroveci pneumonia (PCP) has long been recognized as a cause of mortality in immuno-compromised populations, including those with advanced lung cancer. Although Pneumocystis colonization has only recently been described due to the development of more sensitive molecular techniques, including polymerase chain reaction (PCR), it is unknown whether Pneumocystis colonization leads to the development of PCP. In the present study, we aimed to determine the prevalence of Pneumocystis colonization in advanced lung cancer patients. Furthermore, the association between PCP and Pneumocystis colonization was also investigated. Advanced lung cancer patients with no indication of PCP were evaluated to determine the prevalence of Pneumocystis colonization. We analyzed their oral wash (OW) samples and retrospectively evaluated advanced lung cancer patients with PCP by analyzing their sections of formalin-fixed, paraffin-embedded lung tissues obtained following a diagnosis of lung cancer. Pneumocystis colonization was determined by a PCR test for Pneumocystis jiroveci (P. jiroveci). No P. jiroveci was detected by PCR in the OW samples of 47 advanced lung cancer patients with no indication of PCP, or in the lung tissues of four advanced lung cancer patients with PCP. These results indicate that PCP is not associated with Pneumocystis colonization in advanced lung cancer patients, although this study is limited since this was a cross-sectional and retrospective study. PMID:23420670

  6. Advances and perspectives in lung cancer imaging using multidetector row computed tomography.

    PubMed

    Coche, Emmanuel

    2012-10-01

    The introduction of multidetector row computed tomography (CT) into clinical practice has revolutionized many aspects of the clinical work-up. Lung cancer imaging has benefited from various breakthroughs in computing technology, with advances in the field of lung cancer detection, tissue characterization, lung cancer staging and response to therapy. Our paper discusses the problems of radiation, image visualization and CT examination comparison. It also reviews the most significant advances in lung cancer imaging and highlights the emerging clinical applications that use state of the art CT technology in the field of lung cancer diagnosis and follow-up.

  7. Chemotherapy in Treating Patients With Refractory Advanced Solid Tumors or Hematologic Cancer

    ClinicalTrials.gov

    2013-06-20

    Bladder Cancer; Breast Cancer; Colorectal Cancer; Gastric Cancer; Head and Neck Cancer; Kidney Cancer; Leukemia; Lung Cancer; Melanoma (Skin); Ovarian Cancer; Prostate Cancer; Unspecified Adult Solid Tumor, Protocol Specific

  8. Biologic lung volume reduction therapy for advanced homogeneous emphysema.

    PubMed

    Refaely, Y; Dransfield, M; Kramer, M R; Gotfried, M; Leeds, W; McLennan, G; Tewari, S; Krasna, M; Criner, G J

    2010-07-01

    This report summarises phase 2 trial results of biologic lung volume reduction (BioLVR) for treatment of advanced homogeneous emphysema. BioLVR therapy was administered bronchoscopically to 25 patients with homogeneous emphysema in an open-labelled study. Eight patients received low dose (LD) treatment with 10 mL per site at eight subsegments; 17 received high dose (HD) treatment with 20 mL per site at eight subsegments. Safety was assessed in terms of medical complications during 6-month follow-up. Efficacy was assessed in terms of change from baseline in gas trapping, spirometry, diffusing capacity, exercise capacity, dyspnoea and health-related quality of life. There were no deaths or serious medical complications during the study. A statistically significant reduction in gas trapping was observed at 3-month follow-up among HD patients, but not LD patients. At 6 months, changes from baseline in forced expiratory volume in 1 s (-8.0+/-13.93% versus +13.8+/-20.26%), forced vital capacity (-3.9+/-9.41% versus +9.0+/-13.01%), residual volume/total lung capacity ratio (-1.4+/-13.82% versus -5.4+/-12.14%), dyspnoea scores (-0.4+/-1.27 versus -0.8+/-0.73 units) and St George's Respiratory Questionnaire total domain scores (-4.9+/-8.3 U versus -12.2+/-12.38 units) were better with HD than with LD therapy. BioLVR therapy with 20 mL per site at eight subsegmental sites may be a safe and effective therapy in patients with advanced homogeneous emphysema.

  9. Plasma Processed Nanosized-Powders of Refractory Compounds for Obtaining Fine-Grained Advanced Ceramics

    NASA Astrophysics Data System (ADS)

    I, Zalite; J, Grabis; E, Palcevskis; M, Herrmann

    2011-10-01

    One of the ways for the production of ceramic materials with a fine-grained structure is the use of nanopowders. Different methods are used for the production of nanopowders. One of them is the method of plasmachemical synthesis. Different nanopowders of refractory materials can be obtained by this method. The preparation of nanosized powders of nitrides and oxides and their composites by the method of plasmachemical synthesis, the possibilities to receive nanopowders with different particle size and the potential advantages of nanopowders were investigated.

  10. Processing of solid solution, mixed uranium/refractory metal carbides for advanced space nuclear power and propulsion systems

    NASA Astrophysics Data System (ADS)

    Knight, Travis Warren

    Nuclear thermal propulsion (NTP) and space nuclear power are two enabling technologies for the manned exploration of space and the development of research outposts in space and on other planets such as Mars. Advanced carbide nuclear fuels have been proposed for application in space nuclear power and propulsion systems. This study examined the processing technologies and optimal parameters necessary to fabricate samples of single phase, solid solution, mixed uranium/refractory metal carbides. In particular, the pseudo-ternary carbide, UC-ZrC-NbC, system was examined with uranium metal mole fractions of 5% and 10% and corresponding uranium densities of 0.8 to 1.8 gU/cc. Efforts were directed to those methods that could produce simple geometry fuel elements or wafers such as those used to fabricate a Square Lattice Honeycomb (SLHC) fuel element and reactor core. Methods of cold uniaxial pressing, sintering by induction heating, and hot pressing by self-resistance heating were investigated. Solid solution, high density (low porosity) samples greater than 95% TD were processed by cold pressing at 150 MPa and sintering above 2600 K for times longer than 90 min. Some impurity oxide phases were noted in some samples attributed to residual gases in the furnace during processing. Also, some samples noted secondary phases of carbon and UC2 due to some hyperstoichiometric powder mixtures having carbon-to-metal ratios greater than one. In all, 33 mixed carbide samples were processed and analyzed with half bearing uranium as ternary carbides of UC-ZrC-NbC. Scanning electron microscopy, x-ray diffraction, and density measurements were used to characterize samples. Samples were processed from powders of the refractory mono-carbides and UC/UC 2 or from powders of uranium hydride (UH3), graphite, and refractory metal carbides to produce hypostoichiometric mixed carbides. Samples processed from the constituent carbide powders and sintered at temperatures above the melting point of UC

  11. Advanced Characterization of Slags and Refractory Bricks Using Electron Backscatter Diffraction

    SciTech Connect

    John Kay; Kurt Eylands

    2007-09-30

    slag. Analysis of these crystals identified the crystalline phase epidote - Ca{sub 2}Al{sub 2}O(Al, Fe{sup 3+})OH(Si{sub 2}O{sub 7})(SiO{sub 4}). The identification could not have been performed from EDS alone because of Ca deficiency. However, looking at the crystal structure combined with EDS shows that the phase present is a Ca-deficient epidote. From this information, a temperature range of formation was determined. This gives a good example of the additional clarity that can be derived from utilizing EBSD. Evaluation of corrosion products by EBSD at the refractory brick and slag interface did reveal penetration and corrosion of slag into the brick through examination of crystalline phases alone. The degree of corrosion was dependent on the type of refractory and chemical makeup of the slag. This technique has not been used before to analyze slags and slag/refractory interactions. More work needs to be performed to better utilize EBSD for this type of analysis. This project demonstrates that the method is a valid technique that can be used to characterize slags and their interactions with refractory materials.

  12. Gemcitabine for the treatment of advanced nonsmall cell lung cancer.

    PubMed

    Toschi, Luca; Cappuzzo, Federico

    2009-02-18

    Gemcitabine is a pyrimidine nucleoside antimetabolite agent which is active in several human malignancies, including nonsmall cell lung cancer (NSCLC). Because of its acceptable toxicity profile, with myelosuppression being the most common adverse event, gemcitabine can be safely combined with a number of cytotoxic agents, including platinum derivatives and new-generation anticancer compounds. In fact, the combination of gemcitabine and cisplatin is a first-line treatment for patients with advanced NSCLC, pharmacoeconomic data indicating that it represents the most cost-effective regimen among platinum-based combinations with third-generation cytotoxic drugs. The drug has been investigated in the context of nonplatinum-based regimens in a number of prospective clinical trials, and might provide a suitable alternative for patients with contraindications to platinum. Recently, gemcitabine-based doublets have been successfully tested in association with novel targeted agents with encouraging results, providing further evidence for the role of the drug in the treatment of NSCLC. In the last few years several attempts have been pursued in order to identify molecular predictors of gemcitabine activity, and recent data support the feasibility of genomic-based approaches to customize treatment with the ultimate goal of improving patient outcome.

  13. SU-E-J-87: Ventilation Weighting Effect On Mean Doses of Both Side Lungs for Patients with Advanced Stage Lung Cancer

    SciTech Connect

    Qu, H; Xia, P; Yu, N

    2015-06-15

    Purpose: To study ventilation weighting effect on radiation doses to both side lungs for patients with advanced stage lung cancer. Methods: Fourteen patients with advanced stage lung cancer were included in this retrospective study. Proprietary software was developed to calculate the lung ventilation map based on 4DCT images acquired for radiation therapy. Two phases of inhale (0%) and exhale (50%) were used for the lung ventilation calculations. For each patient, the CT images were resampled to the same dose calculation resolution of 3mmx3mmx3mm. The ventilation distribution was then normalized by the mean value of the ventilation. The ventilation weighted dose was calculated by applying linearly weighted ventilation to the dose of each pixel. The lung contours were automatically delineated from patient CT image with lung window, excluding the tumor and high density tissues. For contralateral and ipsilateral lungs, the mean lung doses from the original plan and ventilation weighted mean lung doses were compared using two tail t-Test. Results: The average of mean dose was 6.1 ±3.8Gy for the contralateral lungs, and 26.2 ± 14.0Gy for the ipsilateral lungs. The average of ventilation weighted dose was 6.3± 3.8Gy for the contralateral lungs and 24.6 ± 13.1Gy for the ipsilateral lungs. The statistics analysis shows the significance of the mean dose increase (p<0.015) for the contralateral lungs and decrease (p<0.005) for the ipsilateral lungs. Conclusion: Ventilation weighted doses were greater than the un-weighted doses for contralateral lungs and smaller for ipsilateral lungs. This Result may be helpful to understand the radiation dosimetric effect on the lung function and provide planning guidance for patients with advance stage lung cancer.

  14. Lenvatinib: a new option for the treatment of advanced iodine refractory differentiated thyroid cancer?

    PubMed

    Lorusso, Loredana; Newbold, Kate

    2015-01-01

    Lenvatinib mesylate (E7080; 4-[3-chloro-4-(N'-cyclopropylureido) phenoxy] 7-methoxyquinoline-6-carboxamide mesylate) is an oral molecule that inhibits multiple tyrosine kinase receptors such as VEGF-R-1-3, FGF-R-1-4, RET, c-KIT and PDGF-R-β. Phase I studies identified the maximum tolerated dose to be 25 mg daily that, in fasting treated patients, is rapidly absorbed with maximum concentrations achieved within 3 h of administration. In these studies, lenvatinib showed activity in solid tumors. Subsequently, Phase II studies in thyroid cancer, in particular differentiated thyroid cancer (DTC), confirmed good clinically significant activity and the recently published Phase III SELECT trial reported median progression-free survival was 18.3 months with lenvatinib versus 3.6 months with placebo (hazard ratio for progression or death: 0.21; 99% CI: 0.14-0.31; p < 0.001). Treatment-related adverse effects occurred in more than 40% of patients on lenvatinib. These were hypertension (in 67.8% of the patients), diarrhea (in 59.4%), fatigue or asthenia (in 59.0%), decreased appetite (in 50.2%), decreased weight (in 46.4%) and nausea (in 41.0%). Discontinuations of lenvatinib because of adverse effects occurred in 37 patients (14.2%) compared with three patients who received placebo (2.3%). Six of 20 deaths in patients on lenvatinib were considered to be drug-related. Lenvatinib has been licensed by the US FDA and EMA based on these data and provides an option for the treatment of radioiodine refractory DTC.

  15. 2nd ESMO Consensus Conference in Lung Cancer: locally advanced stage III non-small-cell lung cancer.

    PubMed

    Eberhardt, W E E; De Ruysscher, D; Weder, W; Le Péchoux, C; De Leyn, P; Hoffmann, H; Westeel, V; Stahel, R; Felip, E; Peters, S

    2015-08-01

    To complement the existing treatment guidelines for all tumour types, ESMO organises consensus conferences to focus on specific issues in each type of tumour. The 2nd ESMO Consensus Conference on Lung Cancer was held on 11-12 May 2013 in Lugano. A total of 35 experts met to address several questions on non-small-cell lung cancer (NSCLC) in each of four areas: pathology and molecular biomarkers, first-line/second and further lines of treatment in advanced disease, early-stage disease and locally advanced disease. For each question, recommendations were made including reference to the grade of recommendation and level of evidence. This consensus paper focuses on locally advanced disease.

  16. Radiosensitization of Chemotherapy-Refractory, Locally Advanced or Locally Recurrent Breast Cancer With Trastuzumab: A Phase II Trial

    SciTech Connect

    Horton, Janet K.; Halle, Jan; Ferraro, Madlyn; Carey, Lisa; Moore, Dominic T.; Ollila, David; Sartor, Carolyn I.

    2010-03-15

    Purpose: Trastuzumab (Herceptin), an anti-human epidermal growth factor receptor 2 (HER2) antibody, has been shown to be an effective radiosensitizer in preclinical studies. The present Phase II trial evaluated trastuzumab plus radiotherapy in patients with HER2-positive, chemotherapy-refractory, locally advanced or locoregionally recurrent breast cancer. Methods and Materials: Eligible patients had measurable disease, normal cardiac function, and biopsy-confirmed residual HER2-positive disease. Patients received weekly trastuzumab (2 mg/kg intravenously), concurrent with radiotherapy (50 Gy) to the breast and regional lymph nodes for 5 weeks. If feasible, surgery followed radiotherapy. The primary endpoint was safety, and the secondary endpoint was efficacy (pathologic response and interval to symptomatic local progression). Results: Of the 19 patients enrolled, 7 were ineligible and received radiotherapy alone and 12 received therapy per protocol. Of these 12 patients, 11 had a Stage T4 diagnosis. Grade 3 toxicities included skin (n = 2) and lymphopenia (n = 1). One patient experienced delayed wound healing after surgery. No patients developed symptomatic cardiac dysfunction. Of the 7 patients who had undergone mastectomy, 3 (43%) had a substantial pathologic response (complete response or microscopic residual disease), significantly more than a comparison cohort (2 of 38 or 5%, p = .02). The median interval to symptomatic local progression was not reached. The median overall survival was 39 months. Conclusion: This is the first prospective trial providing evidence for a radiosensitizing effect of trastuzumab in breast cancer. The combination of trastuzumab and radiotherapy was well tolerated.

  17. Advanced Lung Cancer Screening: An Individualized Molecular Nanotechnology Approach

    DTIC Science & Technology

    2013-08-01

    bivalent genes in stem and progenitor cells that form clusters within NSCLC, genes which may also predict clinical outcomes in resected patients. The...the specificity of lung cancer detection. In the first year of this proposal, we have developed an improved panel of genes hypermethylated in lung...the United States. These novel genes have been used to develop sensitive methylation specific PCR assays suitable for biologic fluid testing (sputum

  18. Olanzapine as an antiemetic in refractory nausea and vomiting in advanced cancer.

    PubMed

    Srivastava, Manish; Brito-Dellan, Norman; Davis, Mellar P; Leach, Marie; Lagman, Ruth

    2003-06-01

    Nausea and vomiting are difficult symptoms to manage in patients with advanced cancer. Several classes of antiemetics are available, including phenothiazines, butyrophenones, substituted benzamides and selective serotonin antagonists, as well as corticosteroids. Most patients will respond to either single agents or combinations that frequently include corticosteroids. A minority of patients will have nausea that fails to respond. The atypical antipsychotic, olanzapine, relieves nausea in some patients failing to respond to the usual antiemetics. Two case reports are presented and the rationale for olanzapine's benefit is discussed.

  19. Total skin electron beam therapy as palliative treatment for cutaneous manifestations of advanced, therapy-refractory cutaneous lymphoma and leukemia

    PubMed Central

    2012-01-01

    Background To retrospectively access the outcome and toxicity of a total skin electron beam therapy (TSEBT) in patients with cutaneous lymphoma (CL) or leukemia. Patients and methods Treatment results of 25 patients (median age 63 years; 5 female, 20 male) with cutaneous manifestations of advanced and therapy-refractory CL (n = 21; T-cell lymphomas n = 18, B-cell lymphomas n = 3) stage IIB-IV or leukemia (n = 4; AML n = 2, CLL n = 1, PDC n = 1) treated between 1993 and 2010 were reviewed. All patients were symptomatic. The median total dose was 29Gy, applied in 29 fractions of median 1 Gy each. Results The median follow-up was 10 months. Palliation was achieved in 23 patients (92%). A clinical complete response was documented in 13 (52%) and a partial response in 10 patients (40%). The median time to skin progression was 5 months (range 1–18 months) and the actuarial one-year progression-free survival 35%. The median overall survival (OS) after the initiation of TSEBT was 10 months (range 1–46 months) and the actuarial one-year OS 45%. TSEBT related acute adverse events (grade 1 or 2) were observed in all patients during the treatment period. An acute grade 3 epitheliolysis developed in eight patients (32%). Long-term adverse events as a hyperpigmentation of the skin (grade 1 or 2) were documented in 19 patients (76%), and a hypohidrosis in seven patients (28%). Conclusion For palliation of symptomatic cutaneous manifestations of advanced cutaneous lymphoma or leukemia, total skin electron beam therapy is an efficient and well tolerated considerable treatment option. PMID:22838493

  20. Partial Response to Platinum Doublets in Refractory EGFR-Positive Non-Small Cell Lung Cancer Patients after RRx-001: Evidence of Episensitization

    PubMed Central

    Carter, Corey A.; Oronsky, Bryan T.; Caroen, Scott Z.; Scicinski, Jan J.; Cabrales, Pedro; Reid, Tony; Degesys, Aiste; Jenkins, John; Brzezniak, Christina

    2016-01-01

    RRx-001, an experimental systemically non-toxic epi-immunotherapeutic agent, which potentiates the resensitization of resistant cancer cells to formerly effective therapies, is under active investigation in several clinical trials that are based on sequential or concomitant rechallenge to resistant first- or second-line regimens. One of these trials is designated TRIPLE THREAT (NCT02489903), because it explores the conditioning or priming effect of RRx-001 on three tumor types – non-small cell lung cancer (NSCLC), small cell lung cancer and high-grade neuroendocrine tumors – prior to re-administration of platinum doublets. In follow-up to a recent case study, which describes early monotherapeutic benefit with RRx-001 in a refractory EGFR-mutated NSCLC tumor, we present subsequent evidence of a radiological partial response to reintroduced platinum doublets after RRx-001. For the 50% of patients with EGFR-mutated NSCLC who progress on EGFR-tyrosine kinase inhibitors (without evidence of a T790M mutations) as well as platinum doublets and pemetrexed/taxane, no other clinically established treatment options exist. A retrial of these therapies in EGFR-positive NSCLC patients via priming with epigenetic agents such as RRx-001 constitutes a strategy to ‘episensitize’ tumors (i.e. reverse resistance by epigenetic means) and to extend overall survival. PMID:26933421

  1. Association between human papillomavirus and EGFR mutations in advanced lung adenocarcinoma

    PubMed Central

    Li, Ming; Deng, Fang; Qian, Li-Ting; Meng, Shui-Ping; Zhang, Yang; Shan, Wu-Lin; Zhang, Xiao-Lei; Wang, Bao-Long

    2016-01-01

    Previous studies have demonstrated an association between human papillomavirus (HPV) and mutations in the epidermal growth factor receptor (EGFR) gene in lung cancer patients; however, few studies have investigated this association in advanced lung adenocarcinoma patients undergoing gefitinib treatment. The present study investigated the association between HPV and EGFR mutations in advanced lung adenocarcinoma patients. A total of 95 advanced lung adenocarcinoma patients were enrolled in the study. The HPV infection status and presence of EGFR mutations in tumor tissue was evaluated. Patient clinical characteristics were also determined and compared with HPV infection and EGFR mutation status to analyze their impact on progression-free survival. HPV DNA was identified in 27/95 (28.4%) lung adenocarcinoma tumors and was most common in patients with lymph node metastasis (P=0.016). A total of 44/95 (46.3%) cases exhibited EGFR mutations, which were predominantly observed in female patients and non-smokers. The presence of HPV DNA was significantly associated with EGFR mutations (P=0.012) and multivariate analysis also revealed that HPV DNA was significantly associated with EGFR mutations (odds ratio=3.971) in advanced lung adenocarcinoma. Patients with both HPV infections and EGFR mutations exhibit a marked decrease in the risk of lung cancer progression when compared with those without HPV infection or EGFR mutations (adjusted HR=0.640; 95% confidence interval: 0.488–0.840; P=0.001). HPV infection was significantly associated with EGFR mutations in advanced lung adenocarcinoma patients. Furthermore, patients with HPV infections exhibited the longest progression-free survival times, which may be due to good response to tyrosine kinase inhibitor- or platinum-based-adjuvant therapy in these patients. Patients with EGFR mutations exhibited a better prognosis when compared with those exhibiting wild-type EGFR, regardless of HPV status. PMID:27602120

  2. Application of radiofrequency thermocoagulation combined with adriamycin injection in dorsal root ganglia for controlling refractory pain induced by rib metastasis of lung cancer (a STROBE-compliant article)

    PubMed Central

    Xie, Guang-lun; Guo, Da-peng; Li, Zhi-gang; Liu, Chang; Zhang, Wei

    2016-01-01

    Abstract This study aimed to observe the therapeutic effects and adverse reactions of radiofrequency thermocoagulation combined with adriamycin injection in dorsal root ganglia on lung cancer rib metastasis-related refractory pain which has no response to conventional therapy. This study contained 27 patients with lung cancer rib metastasis-related moderate or severe pain which had no response to conventional therapy. Under computed tomography (CT)-guidance, radiofrequency puncture need reached the corresponding intervertebral foramens to ensure needle point near dorsal root ganglia (DRG) by sensory and motor stimulation tests, and then radiofrequency thermocoagulation was performed on each corresponding DRG followed by injection of 0.5 to 1 mL of adriamycin (0.5%). The conditions of pain and complications were observed before management and 3 days, 1 month, and 3 months after management, respectively. Numerical rating scale (NRS) scores and dosage of morphine were all significantly decreased after management as compared with those before management (all P < 0.01). Although the number of patients with chest wall numbness was significantly increased after management as compared with that before management (all P < 0.01), the degree of chest wall numbness was tolerable. There were no statistical differences between before and after management in nausea and vomiting, and constipation. CT-guided radiofrequency thermocoagulation combined with adriamycin injection in DRG can effectively control lung cancer rib metastasis-related pain which has no response to conventional therapy. This combinatory treatment regimen is featured by better therapeutic effects and a few complications, so it is worthy of being recommended in clinical application. PMID:27749531

  3. Development of improved refractories

    SciTech Connect

    Wereszczak, A.A.; Ferber, M.K.; Liu, K.C.; Moore, R.E.

    1997-04-01

    The goal of the proposed project is to provide expertise and facilities for the high temperature mechanical properties characterization of refractory materials which are of interest to the US DOE`s Office of Industrial Technologies Advanced Industrial Materials Project. Initially the project would establish dedicated refractory testing facilities which would be capable of generating representative engineering creep and high temperature modulus of elasticity (MOE) data to a temperature of 3300{degrees}F (1815{degrees}C) in ambient air. The generated engineering creep and MOE data would serve R&D requirements of refractories-manufacturers and its glass-manufacturer end-users and designers. The relevance of this effort to the refractory and glass-making industries would be ensured by coordinating the research activities through a membership with Alfred University`s Center for Glass Research (CGR) Satellite Center at the University of Missouri-Rolla (UMR), an NSF Center. Valid engineering creep and high temperature MOE data currently do not exist for almost all commercial refractories. Refractory end-users such as glass-manufacturers require such data for efficient and economical design of their various glass-melting furnace superstructures (e.g., furnace crowns). Refractories in glass production furnaces may be subjected to extreme temperatures as high as 3200{degrees}F (1760{degrees}C). With the simultaneous imposition of mechanical and thermal stresses, creep deformation of the refractory material will assuredly occur as a consequence. Designers must ensure that the structural integrity is maintained, so these high temperature deformations must be considered for successful glass furnace superstructure design. These criteria can only be satisfied with the utilization of representative engineering creep and high temperature MOE data for the refractory materials that are chosen for the design of the refractory superstructures.

  4. Clinical Management of Pain in Advanced Lung Cancer

    PubMed Central

    Simmons, Claribel P.L.; MacLeod, Nicholas; Laird, Barry J.A.

    2012-01-01

    Lung cancer is the most common cancer in the world and pain is its most common symptom. Pain can be brought about by several different causes including local effects of the tumor, regional or distant spread of the tumor, or from anti-cancer treatment. Patients with lung cancer experience more symptom distress than patients with other types of cancer. Symptoms such as pain may be associated with worsening of other symptoms and may affect quality of life. Pain management adheres to the principles set out by the World Health Organization’s analgesic ladder along with adjuvant analgesics. As pain can be caused by multiple factors, its treatment requires pharmacological and non-pharmacological measures from a multidisciplinary team linked in with specialist palliative pain management. This review article examines pain management in lung cancer. PMID:23115483

  5. [Status and advances of RGD molecular imaging in lung cancer].

    PubMed

    Yue, Ning; Yuan, Shuanghu; Yang, Guoren

    2014-12-01

    Lung cancer has been one of the most common and the highest mortality rates malignant tumors at home and abroad. Sustained angiogenesis was not only the characteristic of malignant tumors, but also the foundation of tumor proliferation, invasion, recurrence and metastasis, it was also one of the hot spots of treatments in lung cancer biology currently. Integrins played an important part in tumor angiogenesis. Arg-Gly-Asp (RGD) peptides could combine with integrins specifically, and the application of radionuclide-labeled RGD molecular probes enabled imaging of tumor blood vessels to reflect its changes. The lung cancer imaging of RGD peptides at home and abroad in recent years was reviewed in this article.

  6. Advanced Therapeutic Strategies for Chronic Lung Disease Using Nanoparticle-Based Drug Delivery

    PubMed Central

    Yhee, Ji Young; Im, Jintaek; Nho, Richard Seonghun

    2016-01-01

    Chronic lung diseases include a variety of obstinate and fatal diseases, including asthma, chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), idiopathic pulmonary fibrosis (IPF), and lung cancers. Pharmacotherapy is important for the treatment of chronic lung diseases, and current progress in nanoparticles offers great potential as an advanced strategy for drug delivery. Based on their biophysical properties, nanoparticles have shown improved pharmacokinetics of therapeutics and controlled drug delivery, gaining great attention. Herein, we will review the nanoparticle-based drug delivery system for the treatment of chronic lung diseases. Various types of nanoparticles will be introduced, and recent innovative efforts to utilize the nanoparticles as novel drug carriers for the effective treatment of chronic lung diseases will also be discussed. PMID:27657144

  7. [Advanced and Metastatic Lung Cancer – What is new in the Diagnosis and Therapy?].

    PubMed

    Rothschild, Sacha I

    2015-07-01

    Lung cancer is one of the most common types of malignancies worldwide. The majority of patients are diagnosed with an incurable advanced/metastatic stage disease. Palliative treatment approaches improve the survival and the quality of life of these patients. Lung cancer is subdivided according to histology and molecular biology. The most important classification separates small cell from non-small cell lung cancer. In the subgroup of non-small cell lung cancer novel treatment approaches coming along with an improved prognosis have been established during the last decade. The current manuscript provides an overview on current treatment options for metastatic lung cancer. Furthermore, an outlook on promising future treatment options is provided.

  8. Perspectives of patients, family caregivers and physicians about the use of opioids for refractory dyspnea in advanced chronic obstructive pulmonary disease

    PubMed Central

    Rocker, Graeme; Young, Joanne; Donahue, Margaret; Farquhar, Morag; Simpson, Catherine

    2012-01-01

    Background: A recent national practice guideline recommends the use of opioids for the treatment of refractory dyspnea in patients with advanced chronic obstructive pulmonary disease (COPD). We conducted two qualitative studies to explore the experiences of patients and family caregivers with opioids for refractory COPD-related dyspnea and the perspectives and attitudes of physicians toward opioids in this context. Methods: Patients (n = 8; 5 men, 3 women), their caregivers (n = 12; 5 men, 7 women) and physicians (n = 28, 17 men, 11 women) in Nova Scotia participated in the studies. Semistructured interviews were recorded, transcribed verbatim, coded conceptually and analyzed for emergent themes using interpretive description methodology. Results: Patients reported that opioids provided a sense of calm and relief from severe dyspnea. Family caregivers felt that opioids helped patients to breathe more “normally,” observed improvements in patients’ symptoms of anxiety and depression, and experienced reductions in their own stress. Patients reported substantial improvements in their quality of life. All patients and family caregivers wanted opioid therapy to continue. Most physicians were reluctant to prescribe opioids for refractory dyspnea, describing a lack of related knowledge and experience, and fears related to the potential adverse effects and legal censure. Interpretation: Discrepancies between the positive experiences of patients and family caregivers with opioids and the reluctance of physicians to prescribe opioids for refractory dyspnea constitute an important gap in care. Bridging this gap will require initiatives to improve the uptake of practice guidelines and to increase confidence in prescribing opioids for dyspnea refractory to conventional treatment. PMID:22529167

  9. Lenvatinib and other tyrosine kinase inhibitors for the treatment of radioiodine refractory, advanced, and progressive thyroid cancer

    PubMed Central

    Lorusso, Loredana; Pieruzzi, Letizia; Biagini, Agnese; Sabini, Elena; Valerio, Laura; Giani, Carlotta; Passannanti, Paolo; Pontillo-Contillo, Benedetta; Battaglia, Valentina; Mazzeo, Salvatore; Molinaro, Eleonora; Elisei, Rossella

    2016-01-01

    Lenvatinib is a small oral molecule able to inhibit three of the extracellular and intracellular molecules involved in the modulation of angiogenesis and lymphangiogenesis: vascular endothelial growth factor receptor 1–3, fibroblast growth factor receptor 1–4, and platelet-derived growth factor receptor alpha. Since it is also able to inhibit the REarranged during Transfection oncogene and the protooncogene c-KIT, this drug can also be used to control tumor cell proliferation. The maximum tolerated dose, as demonstrated in Phase I studies, is 25 mg daily. The drug is rapidly absorbed with maximum concentrations achieved within 3 and 5 hours after administration in fasting and nonfasting treated patients, respectively. The most common adverse events, reported in Phase I study and confirmed in the subsequent Phase II and III studies, are hypertension, proteinuria, and gastrointestinal symptoms such as nausea, diarrhea, and stomatitis. In Phase I studies, efficacy of lenvatinib in solid tumors was demonstrated, and these encouraging results have led to the development of a Phase II study using lenvatinib in advance radioiodine-refractory differentiated thyroid cancer (DTCs) patients. Since an overall response rate of 50% was reported, this study also confirmed the efficacy of lenvatinib in DTCs patients with an acceptable toxicity profile. Recently, a Phase III study in patients with DTCs (SELECT study) demonstrated the lenvatinib efficacy in prolonging progression-free survival with respect to the placebo (18.3 vs 3.6 months; P<0.001). Although there was no statistically significant difference in the overall survival of the entire group, this result was observed when the analysis was restricted to both the follicular histotype and the group of senior patients (>65 years). The study confirmed that the most common side effects of this drug are hypertension, diarrhea, decreased appetite, weight loss, nausea, and proteinuria. In this review, we report the results of

  10. Lenvatinib and other tyrosine kinase inhibitors for the treatment of radioiodine refractory, advanced, and progressive thyroid cancer.

    PubMed

    Lorusso, Loredana; Pieruzzi, Letizia; Biagini, Agnese; Sabini, Elena; Valerio, Laura; Giani, Carlotta; Passannanti, Paolo; Pontillo-Contillo, Benedetta; Battaglia, Valentina; Mazzeo, Salvatore; Molinaro, Eleonora; Elisei, Rossella

    2016-01-01

    Lenvatinib is a small oral molecule able to inhibit three of the extracellular and intracellular molecules involved in the modulation of angiogenesis and lymphangiogenesis: vascular endothelial growth factor receptor 1-3, fibroblast growth factor receptor 1-4, and platelet-derived growth factor receptor alpha. Since it is also able to inhibit the REarranged during Transfection oncogene and the protooncogene c-KIT, this drug can also be used to control tumor cell proliferation. The maximum tolerated dose, as demonstrated in Phase I studies, is 25 mg daily. The drug is rapidly absorbed with maximum concentrations achieved within 3 and 5 hours after administration in fasting and nonfasting treated patients, respectively. The most common adverse events, reported in Phase I study and confirmed in the subsequent Phase II and III studies, are hypertension, proteinuria, and gastrointestinal symptoms such as nausea, diarrhea, and stomatitis. In Phase I studies, efficacy of lenvatinib in solid tumors was demonstrated, and these encouraging results have led to the development of a Phase II study using lenvatinib in advance radioiodine-refractory differentiated thyroid cancer (DTCs) patients. Since an overall response rate of 50% was reported, this study also confirmed the efficacy of lenvatinib in DTCs patients with an acceptable toxicity profile. Recently, a Phase III study in patients with DTCs (SELECT study) demonstrated the lenvatinib efficacy in prolonging progression-free survival with respect to the placebo (18.3 vs 3.6 months; P<0.001). Although there was no statistically significant difference in the overall survival of the entire group, this result was observed when the analysis was restricted to both the follicular histotype and the group of senior patients (>65 years). The study confirmed that the most common side effects of this drug are hypertension, diarrhea, decreased appetite, weight loss, nausea, and proteinuria. In this review, we report the results of the

  11. Advances in physiologic lung assessment via electron beam computed tomography (EBCT)

    NASA Astrophysics Data System (ADS)

    Hoffman, Eric A.

    1999-09-01

    Lung function has been evaluated in both health and disease states by techniques, such as pulmonary function tests, which generally study aggregate function. These decades old modalities have yielded a valuable understanding of global physiologic and pathophysiologic structure-to-function relationships. However, such approaches have reached their limits. They cannot meet the current and anticipated needs of new surgical and pharmaceutical treatments. 4-D CT can provide insights into regional lung function (ventilation and blood flow) and thus can provide information at an early stage of disease when intervention will have the greatest impact. Lung CT over the last decade has helped with further defining anatomic features in disease, but has lagged behind advances on the cellular and molecular front largely because of the failure to account for functional correlates to structural pathology. Commercially available CT scanners are now capable of volumetric data acquisition in a breath-hold and capable of multi-level slice acquisitions of the heart and lungs with a per slice scan aperture of 50 - 300 msec, allowing for regional blood flow measurements. Static, volumetric imaging of the lung is inadequate in that much of lung pathology is a dynamic phenomenon and, thus, is only detectable if the lung is imaged as air and blood are flowing. This paper review the methodologies and early physiologic findings associated with our measures of lung tissue properties coupled with regional ventilation and perfusion.

  12. Advanced Lung Cancer Screening: An Individualized Molecular Nanotechnology Approach

    DTIC Science & Technology

    2016-03-01

    improved panel of genes hypermethylated in lung cancer, with extraordinarily high specificity and sensitivity, we combined the improved methods of MOB ...final results using this approach is provided in figure 3. Figure 2. Overview of the Methylation- on-Beads ( MOB ) Process. Circulating DNA from up...magnetic decantation, and removal of supernatant. Figure 3 ß-Actin Ct values for MOB processed vs. Phenol Chloroform extracted and traditionally

  13. Advanced Lung Cancer Screening: An Individualized Molecular Nanotechnology Approach

    DTIC Science & Technology

    2014-08-01

    majority of them (38 of 48) interpreted as nonsus- picious by our radiologists due to active infection such as tuberculosis and pneumonia, scarring from...references 8 752 Journal of Thoracic Oncology ®  •  Volume 9, Number 6, June 2014 Background: Epidemiological evidence suggests that HIV- infected ... infected participants. Methods: From 2006 to 2013, we conducted the world’s first lung cancer screening trial of 224 HIV- infected current/former smokers to

  14. Pembrolizumab in Treating Patients With HIV and Relapsed, Refractory, or Disseminated Malignant Neoplasms

    ClinicalTrials.gov

    2017-03-22

    AIDS-Related Non-Hodgkin Lymphoma; Classical Hodgkin Lymphoma; HIV Infection; Locally Advanced Malignant Neoplasm; Metastatic Malignant Neoplasm; Recurrent Hepatocellular Carcinoma; Recurrent Hodgkin Lymphoma; Recurrent Kaposi Sarcoma; Recurrent Malignant Neoplasm; Recurrent Melanoma of the Skin; Recurrent Non-Hodgkin Lymphoma; Recurrent Non-Small Cell Lung Carcinoma; Refractory Hodgkin Lymphoma; Refractory Malignant Neoplasm; Solid Neoplasm; Stage IIIA Hepatocellular Carcinoma; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIA Skin Melanoma; Stage IIIB Hepatocellular Carcinoma; Stage IIIB Non-Small Cell Lung Cancer; Stage IIIB Skin Melanoma; Stage IIIC Hepatocellular Carcinoma; Stage IIIC Skin Melanoma; Stage IV Non-Small Cell Lung Cancer; Stage IV Skin Melanoma; Stage IVA Hepatocellular Carcinoma; Stage IVB Hepatocellular Carcinoma

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

    ClinicalTrials.gov

    2017-01-05

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

  16. Lung Cancer Workshop XI: Tobacco-Induced Disease: Advances in Policy, Early Detection and Management.

    PubMed

    Mulshine, James L; Avila, Rick; Yankelevitz, David; Baer, Thomas M; Estépar, Raul San Jose; Ambrose, Laurie Fenton; Aldigé, Carolyn R

    2015-05-01

    The Prevent Cancer Foundation Lung Cancer Workshop XI: Tobacco-Induced Disease: Advances in Policy, Early Detection and Management was held in New York, NY on May 16 and 17, 2014. The two goals of the Workshop were to define strategies to drive innovation in precompetitive quantitative research on the use of imaging to assess new therapies for management of early lung cancer and to discuss a process to implement a national program to provide high quality computed tomography imaging for lung cancer and other tobacco-induced disease. With the central importance of computed tomography imaging for both early detection and volumetric lung cancer assessment, strategic issues around the development of imaging and ensuring its quality are critical to ensure continued progress against this most lethal cancer.

  17. Clinical report of the treatment of locally advanced lung cancer.

    PubMed

    Petrovich, Z; Mietlowski, W; Ohanian, M; Cox, J

    1977-07-01

    This paper discusses the results of the treatment of 345 patients entered in the Veterans Administration Lung Group Protocol 13L. The study was activated March 1972, and closed for the patient accesion March 1975. All patients had a histological diagnosis of primary lung cancer considered clinically non-resectable or inoperable. Patients were equally randomized into two groups, radiotherapy alone or radiotherapy with chemotherapy. The analysis of the data included: treatment regimen, radiation dose, initial performance status, performance status change, cell type, duration of survival, quality of survival and age. The strongest influence on median survival was the level of radiation dose. The small cell carcinoma patients treated with radiotherapy and chemotherapy showed significant improvement in the median survival (38.2 weeks) over the patients treated with radiotherapy alone (20.6 weeks). The patients treated with radiotherapy and chemotherapy also showed improvement in performance status more frequently than the patients treated with radiotherapy alone. Other parameters of the analysis will be presented.

  18. Advanced SEM-EDX and Isotope Mapping of a Refractory Grain in a Fine-Grained IDP

    NASA Astrophysics Data System (ADS)

    Starkey, N. A.; Franchi, I. A.; Salge, T.; Brearley, A. J.

    2015-07-01

    We present high spatial resolution SEM-EDX and O isotope mapping to reveal the presence of a melilite-olivine refractory grain in a fine-grained IDP. We use this to discuss transport of material from the inner solar system and formation of comets.

  19. Exercise and relaxation intervention for patients with advanced lung cancer: a qualitative feasibility study.

    PubMed

    Adamsen, L; Stage, M; Laursen, J; Rørth, M; Quist, M

    2012-12-01

    Lung cancer patients experience loss of physical capacity, dyspnea, pain, reduced energy and psychological distress. The aim of this study was to explore feasibility, health benefits and barriers of exercise in former sedentary patients with advanced stage lung cancer, non-small cell lung cancer (NSCLC) (III-IV) and small cell lung cancer (SCLC) (ED), undergoing chemotherapy. The intervention consisted of a hospital-based, supervised, group exercise and relaxation program comprising resistance-, cardiovascular- and relaxation training 4 h weekly, 6 weeks, and a concurrent unsupervised home-based exercise program. An explorative study using individual semi-structured interviews (n=15) and one focus group interview (n=8) was conducted among the participants. Throughout the intervention the patients experienced increased muscle strength, improvement in wellbeing, breathlessness and energy. The group exercise and relaxation intervention showed an adherence rate of 76%, whereas the patients failed to comply with the home-based exercise. The hospital-based intervention initiated at time of diagnosis encouraged former sedentary lung cancer patients to participation and was undertaken safely by cancer patients with advanced stages of disease, during treatment. The patients experienced physical, functional and emotional benefits. This study confirmed that supervised training in peer-groups was beneficial, even in a cancer population with full-blown symptom burden and poor prognosis.

  20. Locally Advanced Lung Cancer: An Optimal Setting for Vaccines and Other Immunotherapies

    PubMed Central

    Iyengar, Puneeth; Gerber, David E.

    2013-01-01

    Lung cancer has traditionally been considered relatively resistant to immunotherapies. However, recent advances in the understanding of tumor-associated antigens, anti-tumor immune responses, and tumor immunosuppression mechanisms have resulted in a number of promising immunomodulatory therapies such as vaccines and checkpoint inhibitors. Locally advanced non-small cell lung cancer (NSCLC) is an optimal setting for these treatments because standard therapies such as surgery, radiation, and chemotherapy may enhance anti-tumor immune effects by debulking the tumor, increasing tumor antigen presentation, and promoting T-cell response and trafficking. Clinical trials incorporating immunomodulatory agents into combined modality therapy of locally advanced NSCLC have shown promising results. Future challenges include identifying biomarkers to predict those patients most likely to benefit from this approach, radiographic assessment of treatment effects, the timing and dosing of combined modality treatment including immunotherapies, and avoidance of potentially overlapping toxicities. PMID:23708072

  1. Antiangiogenic Agents in Combination with Chemotherapy in Patients with Advanced Non-Small Cell Lung Cancer

    PubMed Central

    Ulahannan, Susanna V; Brahmer, Julie R

    2011-01-01

    Most patients with non-small cell lung cancer (NSCLC) present with advanced disease requiring systemic chemotherapy. Treatment with the antiangiogenic agent bevacizumab in combination with standard platinum-based doublet chemotherapy has been shown to improve outcomes in patients with advanced NSCLC. Several multitargeted antiangiogenic tyrosine kinase inhibitors (e.g., sorafenib, sunitinib, cediranib, vandetanib, BIBF 1120, pazopanib, and axitinib) are also being evaluated in combination with standard chemotherapy. Here we review current clinical data with combination therapy involving antiangiogenic agents and cytotoxic chemotherapy in patients with advanced NSCLC. PMID:21469981

  2. A Structured Exercise Program for Patients with Advanced Non-small Cell Lung Cancer

    PubMed Central

    Temel, Jennifer S.; Greer, Joseph A.; Goldberg, Sarah; Vogel, Paula Downes; Sullivan, Michael; Pirl, William F.; Lynch, Thomas J.; Christiani, David C.; Smith, Matthew R.

    2010-01-01

    Introduction Exercise improves functional outcome and symptoms for certain cancer populations, but the feasibility, efficacy, and safety of structured exercise in patients with lung cancer is unknown. In this study, we examined the feasibility of a hospital-based exercise program for patients with advanced non-small cell lung cancer. Methods This study included patients with newly diagnosed advanced stage non-small cell lung cancer and Eastern Cooperative Oncology Group performance status 0–1. A physical therapist facilitated twice-weekly sessions of aerobic exercise and weight training over an 8-week period. The primary end point was feasibility of the intervention, defined as adherence to the exercise program. Secondary endpoints included functional capacity, measured by the 6-minute walk test and muscle strength, as well as quality of life, lung cancer symptoms and fatigue, measured by the Functional Assessment of Cancer Therapy-lung and Functional Assessment of Cancer Therapy-fatigue scales. Results Between October 2004 and August 2007, 25 patients enrolled in the study. All participants received anticancer therapy during the study period. Twenty patients (80%) underwent the baseline physical therapy evaluation. Eleven patients (44%) completed all 16 sessions. An additional 6 patients attended at least 6 sessions (range, 6–15), and 2 patients only attended one session. Study completers experienced a significant reduction in lung cancer symptoms and no deterioration in their 6-minute walk test or muscle strength. Conclusions Although the majority of participants attempted the exercise program, less than half were able to complete the intervention. Those who completed the program experienced an improvement in their lung cancer symptoms. Community-based or briefer exercise interventions may be more feasible in this population. PMID:19276834

  3. Dietary patterns of patients with advanced lung or colorectal cancer.

    PubMed

    Prado, Carla M M; Lieffers, Jessica R; Bergsten, Gabriella; Mourtzakis, Marina; Baracos, Vickie E; Reiman, Tony; Sawyer, Michael B; McCargar, Linda J

    2012-01-01

    The purpose of this study was to identify dietary patterns among patients with advanced cancer. Differences between cancer groups are described, and food groups contributing higher proportions to overall caloric intake are identified. Patients with advanced cancer (n=51) were recruited from a regional cancer centre and completed a three-day dietary record. Food items were categorized according to macronutrient content. After adjustment for body weight, substantial variation in energy intake was observed (range: 13.7 to 55.4 kcal/kg/day). For 49% of patients, protein intake was below recommendations. Overall, patients consumed the largest proportion of their calories from meat (16%), other foods (11%), dessert (9%), fruit (9%), white bread (7%), and milk (7%). Only 5% of patients consumed meal replacement supplements. The results of this descriptive study provide important insights into the dietary habits of patients with advanced cancer. These insights could be translated into the development of effective recommendations for maintaining or improving health and quality of life.

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

    PubMed Central

    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. PMID:26870160

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

    PubMed

    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.

  6. Mustard vesicant-induced lung injury: Advances in therapy.

    PubMed

    Weinberger, Barry; Malaviya, Rama; Sunil, Vasanthi R; Venosa, Alessandro; Heck, Diane E; Laskin, Jeffrey D; Laskin, Debra L

    2016-08-15

    Most mortality and morbidity following exposure to vesicants such as sulfur mustard is due to pulmonary toxicity. Acute injury is characterized by epithelial detachment and necrosis in the pharynx, trachea and bronchioles, while long-term consequences include fibrosis and, in some instances, cancer. Current therapies to treat mustard poisoning are primarily palliative and do not target underlying pathophysiologic mechanisms. New knowledge about vesicant-induced pulmonary disease pathogenesis has led to the identification of potentially efficacious strategies to reduce injury by targeting inflammatory cells and mediators including reactive oxygen and nitrogen species, proteases and proinflammatory/cytotoxic cytokines. Therapeutics under investigation include corticosteroids, N-acetyl cysteine, which has both mucolytic and antioxidant properties, inducible nitric oxide synthase inhibitors, liposomes containing superoxide dismutase, catalase, and/or tocopherols, protease inhibitors, and cytokine antagonists such as anti-tumor necrosis factor (TNF)-α antibody and pentoxifylline. Antifibrotic and fibrinolytic treatments may also prove beneficial in ameliorating airway obstruction and lung remodeling. More speculative approaches include inhibitors of transient receptor potential channels, which regulate pulmonary epithelial cell membrane permeability, non-coding RNAs and mesenchymal stem cells. As mustards represent high priority chemical threat agents, identification of effective therapeutics for mitigating toxicity is highly significant.

  7. Treatment of advanced squamous cell carcinoma of the lung: a review

    PubMed Central

    Mileham, Kathryn F.; Bonomi, Philip D.; Batus, Marta; Fidler, Mary J.

    2015-01-01

    Lung cancer remains the single deadliest cancer both in the US and worldwide. The great majority of squamous cell carcinoma (SCC) is attributed to cigarette smoking, which fortunately is declining alongside cancer incidence. While we have been at a therapeutic plateau for advanced squamous cell lung cancer patients for several decades, recent observations suggest that we are on the verge of seeing incremental survival improvements for this relatively large group of patients. Current studies have confirmed an expanding role for immunotherapy [including programmed cell death-1 (PD-1)/programmed cell death ligand 1 (PD-L1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibition], a potential opportunity for VEGFR inhibition, and even future targets in fibroblast growth factor receptor (FGFR) and PI3K-AKT that collectively should improve survival as well as quality of life for those affected by squamous cell lung cancer over the next decade. PMID:26629421

  8. The Receptor for Advanced Glycation End Products (RAGE) and the Lung

    PubMed Central

    Buckley, Stephen T.; Ehrhardt, Carsten

    2010-01-01

    The receptor for advanced glycation end products (RAGE) is a member of the immunoglobulin superfamily of cell surface molecules. As a pattern-recognition receptor capable of binding a diverse range of ligands, it is typically expressed at low levels under normal physiological conditions in the majority of tissues. In contrast, the lung exhibits high basal level expression of RAGE localised primarily in alveolar type I (ATI) cells, suggesting a potentially important role for the receptor in maintaining lung homeostasis. Indeed, disruption of RAGE levels has been implicated in the pathogenesis of a variety of pulmonary disorders including cancer and fibrosis. Furthermore, its soluble isoforms, sRAGE, which act as decoy receptors, have been shown to be a useful marker of ATI cell injury. Whilst RAGE undoubtedly plays an important role in the biology of the lung, it remains unclear as to the exact nature of this contribution under both physiological and pathological conditions. PMID:20145712

  9. Challenges in Facing the Lung Cancer Epidemic and Treating Advanced Disease in Latin America.

    PubMed

    Raez, Luis E; Santos, Edgardo S; Rolfo, Christian; Lopes, Gilberto; Barrios, Carlos; Cardona, Andres; Mas, Luis A; Arrieta, Oscar; Richardet, Eduardo; Vallejos S, Carlos; Wistuba, Ignacio; Gandara, David; Hirsch, Fred R

    2017-01-01

    Lung cancer, the deadliest cancer worldwide, is of particular concern in Latin America. The rising incidence poses a myriad of challenges for the region, which struggles with limited resources to meet the health care needs of its low- and middle-income populations. In this environment, we are concerned that governments are relatively unaware of the pressing need to implement effective strategies for screening, diagnosis, and treatment of lung cancer. The region has also been slow in adopting molecularly-based therapies in the treatment of advanced disease: testing for epidermal growth factor receptor mutations and anaplastic lymphoma kinase rearrangements are not routine, and access to targeted agents such as monoclonal antibodies and tyrosine kinase inhibitors is problematic. In this paper, we review the current situation in the management of lung cancer in Latin America, hoping that this initiative will help physicians, patient associations, industry, governments, and other stakeholders better face this epidemic in the near future.

  10. Prognostic significance of CT-emphysema score in patients with advanced squamous cell lung cancer

    PubMed Central

    Kim, Young Saing; Ahn, Hee Kyung; Cho, Eun Kyung; Jeong, Yu Mi; Kim, Jeong Ho

    2016-01-01

    Background Although emphysema is a known independent risk factor of lung cancer, no study has addressed the prognostic impact of computed tomography (CT)-emphysema score in advanced stage lung cancer. Methods For 84 consecutive patients with stage IIIB and IV squamous cell lung cancer that underwent palliative chemotherapy, severity of emphysema was semi-quantitatively scored using baseline chest CT images according to the Goddard scoring system (possible scores range, 0–24). The cutoff of high CT-emphysema score was determined using the maximum chi-squared test and the prognostic significance of the high CT-emphysema score was evaluated using Kaplan-Meier analysis and Cox proportional hazards analysis. Results The median CT-emphysema score was 5 (range, 0–22). Patients with a high CT-emphysema score (≥4) tended to have poorer overall survival (OS) (median: 6.3 vs. 13.7 months) than those with a score of <4 (P=0.071). Multivariable analysis revealed that a higher CT-emphysema score was a significant independent prognostic factor for poor OS [hazard ratio (HR) =2.06; 95% confidence interval (CI), 1.24–3.41; P=0.005), along with no response to first-line therapy (P=0.009) and no second-line therapy (P<0.001). Conclusions CT-emphysema score is significantly associated with poor prognosis in patients with advanced squamous cell lung cancer. PMID:27621848

  11. Molecular targeted therapy in the treatment of advanced stage non-small cell lung cancer (NSCLC).

    PubMed

    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.

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

    PubMed Central

    de Mello, Ramon Andrade; Veloso, Ana Flávia; Esrom Catarina, Paulo; Nadine, Sara; Antoniou, Georgios

    2017-01-01

    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. PMID:28031719

  13. Methoxyamine, Cisplatin, and Pemetrexed Disodium in Treating Patients With Advanced Solid Tumors or Mesothelioma That Cannot Be Removed by Surgery or Mesothelioma That Is Refractory to Pemetrexed Disodium and Cisplatin or Carboplatin

    ClinicalTrials.gov

    2017-03-23

    Advanced Malignant Solid Neoplasm; Advanced Peritoneal Malignant Mesothelioma; Advanced Pleural Malignant Mesothelioma; Recurrent Malignant Solid Neoplasm; Recurrent Peritoneal Malignant Mesothelioma; Recurrent Pleural Malignant Mesothelioma; Stage III Non-Small Cell Lung Cancer; Stage III Ovarian Cancer; Stage III Pleural Mesothelioma; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIA Ovarian Cancer; Stage IIIB Non-Small Cell Lung Cancer; Stage IIIB Ovarian Cancer; Stage IIIC Ovarian Cancer; Stage IV Non-Small Cell Lung Cancer; Stage IV Ovarian Cancer; Stage IV Pleural Mesothelioma; Thymoma; Unresectable Solid Neoplasm

  14. -C Refractories

    NASA Astrophysics Data System (ADS)

    Xu, Yibiao; Sang, Shaobai; Li, Yawei; Ren, Bo; Zhao, Lei; Li, Yuanbing; Li, Shujing

    2014-06-01

    Al2O3-C refractories were first fabricated in a coke bed at 1673 K (1400 °C) using tabular corundum, reactive alumina, carbon black, silicon, and microsilica as the starting materials and phenol resin as the binder. Then the alkali attack resistance of those materials was conducted in the powder mixture of carbon black and potassium carbonate (1:1 wt pct) in a graphite crucible at 1273 K (1000 °C) for 10 hours. The correlation between pore size, permeability of Al2O3-C refractories, and their alkali (K2CO3) attack was investigated by means of mercury intrusion porosimetry, X-ray diffraction (XRD), and scanning electron microscopy (SEM). The results showed that the pore structure of Al2O3-C refractories was controlled by the addition of silicon, ultrafine reactive alumina, and microsilica to in-situ form SiC whiskers and mullite in the preparation process. The mean pore size of Al2O3-C refractories was strongly associated with permeability. With the decrease of the mean pore size, the permeability of the Al2O3-C refractories reduced constantly. The alkali attack test also verified that the Al2O3-C refractories with lower permeability had better alkali corrosion resistance, because the penetration of K vapor into the materials could be restricted effectively. The corrosion mechanism of Al2O3-C refractories supposes that (1) K2CO3 was reduced to K vapor and penetrated into the specimen through the open pores and (2) K vapor reacted with SiC, SiO2, and alumina to form KAlSi2O6 and KAlSiO4, which is in agreement with the thermodynamic prediction.

  15. Palliative Care Improves Survival, Quality of Life in Advanced Lung Cancer | Division of Cancer Prevention

    Cancer.gov

    Results from the first randomized clinical trial of its kind have revealed a surprising and welcome benefit of early palliative care for patients with advanced lung cancer—longer median survival. Although several researchers said that the finding needs to be confirmed in other trials of patients with other cancer types, they were cautiously optimistic that the trial results could influence oncologists’ perceptions and use of palliative care. |

  16. Personalized Combined Modality Therapy for Locally Advanced Non-small Cell Lung Cancer

    PubMed Central

    Kim, D. Nathan; Nam, Taek-Keun; Choe, Kevin S.

    2012-01-01

    Locally advanced non-small cell lung cancer (NSCLC) is a heterogeneous disease, and we have embarked on an era where patients will benefit from individualized therapeutic strategies based on identifiable molecular characteristics of the tumor. The landmark studies demonstrating the importance of molecular characterization of tumors for NSCLC patients, the promising molecular pathways, and the potential molecular targets/agents for treatment of this disease will be reviewed. Understanding these issues will aid in the development of rationally designed clinical trials, so as to determine best means of appropriately incorporating these molecular strategies, to the current standard of radiation and chemotherapy regimens, for the treatment of locally advanced NSCLC. PMID:22802745

  17. Dissociative stupor mimicking consciousness disorder in an advanced lung cancer patient.

    PubMed

    Tada, Yukio; Okano, Tetsuya; Kaga, Akiko; Yamazaki, Susumu; Kawada, Satoshi; Ishida, Mayumi; Kobayashi, Kunihiko; Onishi, Hideki

    2012-06-01

    Although there are three kinds of stupor in psychiatry, dissociative stupor is the most commonly recognized. In psychiatric clinics or emergency rooms, dissociative stupor is common, but in an oncology setting it is hardly known. Therefore, distinguishing dissociative stupor from consciousness disorder is occasionally difficult, especially in the advanced or terminal phase. We report an advanced lung cancer patient who presented dissociative stupor mimicking consciousness disorder. It is necessary to distinguish between consciousness disorder and dissociative stupor. In addition, consultation with a psychiatrist should be taken into consideration.

  18. Prognostic factors of advanced stage non-small-cell lung cancer.

    PubMed

    Ben Amar, Jihen; Ben Safta, Boutheina; Zaibi, Haifa; Dhahri, Besma; Baccar, Mohamed Ali; Azzabi, Saloua

    2016-05-01

    Background Lung cancer is the main cause of death from cancer in the world. The 5-year survival is about 15%. Despite the progress of medicine the mortality rate decreased only marginally. This poor prognosis is due to late diagnosis. Aim To evaluate overall survival and prognostic factors in patients locally advanced or metastatic non small cell lung cancer (NSCLC). Methods Retrospective study including 180 patients with non-small cell lung cancer hospitalized in the department of Charles Nicolle Hospital of Tunis between January 2007 and December 2014. Results The mean age was 61.5 years with a male predominance (93.3%). The median overall survival was 6 months. The poor prognostic factors were the performans status (PS) and early delays of management (<30 days). The factors that improve survival were surgical treatment and delays of management more than 45 days.  Conclusion The prognostic factors in locally advanced and metastatic NSLC in our patient were: PS, management delay and treatment. These factors should be considered in management of patient with advanced stage NSCLC.

  19. Expressed wishes and incidence of euthanasia in advanced lung cancer patients.

    PubMed

    Pardon, Koen; Deschepper, Reginald; Vander Stichele, Robert; Bernheim, Jan L; Mortier, Freddy; Schallier, Denis; Germonpré, Paul; Galdermans, Daniella; Van Kerckhoven, Willem; Deliens, Luc

    2012-10-01

    This study explores expressed wishes and requests for euthanasia (i.e. administration of lethal drugs at the explicit request of the patient), and incidence of end-of-life decisions with possible life-shortening effects (ELDs) in advanced lung cancer patients in Flanders, Belgium. We performed a prospective, longitudinal, observational study of a consecutive sample of advanced lung cancer patients and selected those who died within 18 months of diagnosis. Immediately after death, the pulmonologist/oncologist and general practitioner (GP) of the patient filled in a questionnaire. Information was available for 105 out of 115 deaths. According to the specialist or GP, one in five patients had expressed a wish for euthanasia; and three in four of these had made an explicit and repeated request. One in two of these received euthanasia. Of the patients who had expressed a wish for euthanasia but had not made an explicit and repeated request, none received euthanasia. Patients with a palliative treatment goal at inclusion were more likely to receive euthanasia. Death was preceded by an ELD in 62.9% of patients. To conclude, advanced lung cancer patients who expressed a euthanasia wish were often determined. Euthanasia was performed significantly more among patients whose treatment goal after diagnosis was exclusively palliative.

  20. Nivolumab: a review in advanced squamous non-small cell lung cancer.

    PubMed

    Keating, Gillian M

    2015-11-01

    Nivolumab (Opdivo(®); Nivolumab BMS™) was the first programmed death (PD)-1 immune checkpoint inhibitor to be approved for use in advanced, squamous non-small cell lung cancer (NSCLC) following prior chemotherapy. In the pivotal CheckMate 017 trial, intravenous nivolumab 3 mg/kg every 2 weeks was associated with significantly better overall survival and progression-free survival and a significantly higher overall response rate than intravenous docetaxel in the second-line treatment of advanced, squamous NSCLC. Nivolumab was also better tolerated than docetaxel in CheckMate 017, and its adverse event profile (which included immune-mediated adverse events) was manageable. In conclusion, nivolumab represents an important advance in previously-treated, advanced, squamous NSCLC.

  1. Pharmacological and clinical profile of lenvatinib (E-7080) in the treatment of advanced, radioiodine-refractory, differentiated thyroid cancer.

    PubMed

    Hegazi, M; Azadi, A; Jain, D; Redman, R; Perez, C A

    2015-12-01

    After the pathogenesis of thyroid carcinomas was better understood and the role of molecular alterations in RET, BRAF and RET/PTC rearrangement was revealed, several trials using multikinase inhibitors were developed during the last decade for the treatment of recurrent radioactive iodine (RAI)-refractory differentiated thyroid cancer (DTC), achieving a remarkable success. Sorafenib became the first drug approved for this indication in more than two decades after a significant improvement in the progression-free survival was demonstrated. Lenvatinib (E-7080), an orally active inhibitor of multiple receptor tyrosine kinases including vascular endothelial growth factor receptors (VEGFR) 1, 2 and 3, proto-oncogene tyrosine-protein kinase receptor Ret and mast/stem cell growth factor receptor Kit, yielded highly promising early clinical data, even when given after progression on first-line therapy. The phase III SELECT trial recently demonstrated the impressive clinical activity of the drug in RAI-refractory thyroid cancer, leading to the drug's approval by the regulatory agencies and potentially making lenvatinib the most effective drug available to date for the treatment of the disease.

  2. Validation of actigraphy to assess circadian organization and sleep quality in patients with advanced lung cancer

    PubMed Central

    2011-01-01

    Background Many cancer patients report poor sleep quality, despite having adequate time and opportunity for sleep. Satisfying sleep is dependent on a healthy circadian time structure and the circadian patterns among cancer patients are quite abnormal. Wrist actigraphy has been validated with concurrent polysomnography as a reliable tool to objectively measure many standard sleep parameters, as well as daily activity. Actigraphic and subjective sleep data are in agreement when determining activity-sleep patterns and sleep quality/quantity, each of which are severely affected in cancer patients. We investigated the relationship between actigraphic measurement of circadian organization and self-reported subjective sleep quality among patients with advanced lung cancer. Methods This cross-sectional and case control study was conducted in 84 patients with advanced non-small cell lung cancer in a hospital setting for the patients at Midwestern Regional Medical Center (MRMC), Zion, IL, USA and home setting for the patients at WJB Dorn Veterans Affairs Medical Center (VAMC), Columbia, SC, USA. Prior to chemotherapy treatment, each patient's sleep-activity cycle was measured by actigraphy over a 4-7 day period and sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI) questionnaire. Results The mean age of our patients was 62 years. 65 patients were males while 19 were females. 31 patients had failed prior treatment while 52 were newly diagnosed. Actigraphy and PSQI scores showed significantly disturbed daily sleep-activity cycles and poorer sleep quality in lung cancer patients compared to healthy controls. Nearly all actigraphic parameters strongly correlated with PSQI self-reported sleep quality of inpatients and outpatients. Conclusions The correlation of daily activity/sleep time with PSQI-documented sleep indicates that actigraphy can be used as an objective tool and/or to complement subjective assessments of sleep quality in patients with advanced

  3. End-of-life care in patients with advanced lung cancer.

    PubMed

    Lim, Richard B L

    2016-10-01

    Despite advances in the detection, pathological diagnosis and therapeutics of lung cancer, many patients still develop advanced, incurable and progressively fatal disease. As physicians, the duties to cure sometimes, relieve often and comfort always should be a constant reminder to us of the needs that must be met when caring for a patient with lung cancer. Four key areas of end-of-life care in advanced lung cancer begin with first recognizing 'when a patient is approaching the end of life'. The clinician should be able to recognize when the focus of care needs to shift from an aggressive life-sustaining approach to an approach that helps prepare and support a patient and family members through a period of progressive, inevitable decline. Once the needs are recognized, the second key area is appropriate communication, where the clinician should assist patients and family members in understanding where they are in the disease trajectory and what to expect. This involves developing rapport, breaking bad news, managing expectations and navigating care plans. Subsequently, the third key area is symptom management that focuses on the goals to first and foremost provide comfort and dignity. Symptoms that are common towards the end of life in lung cancer include pain, dyspnoea, delirium and respiratory secretions. Such symptoms need to be anticipated and addressed promptly with appropriate medications and explanations to the patient and family. Lastly, in order for physicians to provide quality end-of-life care, it is necessary to understand the ethical principles applied to end-of-life-care interventions. Misconceptions about euthanasia versus withholding or withdrawing life-sustaining treatments may lead to physician distress and inappropriate decision making.

  4. Eligibility of patients with advanced non-small cell lung cancer for phase III chemotherapy trials

    PubMed Central

    2009-01-01

    Background Evidence that chemotherapy improves survival and quality of life in patients with stage IIIB & IV non small cell lung cancer (NSCLC) is based on large randomized controlled trials. The purpose of this study was to determine eligibility of patients with advanced NSCLC for major chemotherapy trials. Methods Physicians treating stage IIIB/IV NSCLC at Sydney Cancer Centre assessed patient eligibility for the E1594, SWOG9509 and TAX326 trials for patients presenting from October 2001 to December 2002. A review of the centre's registry was used to obtain missing data. Results 199 patients with advanced NSCLC were registered during the 14-month period. Characteristics of 100 patients were defined prospectively, 85 retrospectively: 77% males, median age 68 (range 32–88), 64% stage IV disease. Only 35% met trial eligibility for E1594 and 28% for SWOG9509 and TAX326. Common reasons for ineligibility were: co-morbidities 75(40%); ECOG Performance Status ≥2 72(39%); symptomatic brain metastasis 15(8%); and previous cancers 21(11%). Many patients were ineligible by more than one criterion. Conclusion The majority of patients with advanced NSCLC were ineligible for the large chemotherapy trials. The applicability of trial results to advanced lung cancer populations may be limited. Future trials should be conducted in a more representative population. PMID:19402889

  5. Two-year follow-up in patients treated with emphysematous lung sealant for advanced emphysema.

    PubMed

    Kramer, Mordechai R; Refaely, Yael; Maimon, Nimrod; Rosengarten, Dror; Fruchter, Oren

    2013-11-01

    Endoscopic lung volume-reduction therapy for emphysema has been associated with therapeutic responses smaller in magnitude and less durable than surgical volume reduction (LVRS). Bronchoscopic emphysematous lung sealant (ELS) therapy has been shown to produce improvements in pulmonary function similar to surgery at 1 year. This case series summarizes safety and efficacy data of all patients from the initial ELS study out to 2 years. Between 1 and 2 years, there were three all-cause adverse events requiring hospitalization. One patient went on to successful lung transplant. Improvements relative to baseline in spirometry (change in FEV1: + 14.3 ± 33.1%; change in FVC: + 5.8 ± 23.2%) and diffusing capacity (change in diffusing capacity of the lung for carbon monoxide: + 10.6 ± 20.6%) were observed at 2 years. An exponential model fit to FEV₁ data at 6, 12, 18, and 24 months predicted improvements from a baseline of > 5% out to 4.1 years, similar to what has been reported following surgery. This report confirms long-term safety and efficacy following ELS therapy in advanced emphysema. Studies in a larger cohort are needed to define the role of ELS therapy in the treatment algorithm of patients with this condition.

  6. A randomised trial of lung sealant versus medical therapy for advanced emphysema.

    PubMed

    Come, Carolyn E; Kramer, Mordechai R; Dransfield, Mark T; Abu-Hijleh, Muhanned; Berkowitz, David; Bezzi, Michela; Bhatt, Surya P; Boyd, Michael B; Cases, Enrique; Chen, Alexander C; Cooper, Christopher B; Flandes, Javier; Gildea, Thomas; Gotfried, Mark; Hogarth, D Kyle; Kolandaivelu, Kumaran; Leeds, William; Liesching, Timothy; Marchetti, Nathaniel; Marquette, Charles; Mularski, Richard A; Pinto-Plata, Victor M; Pritchett, Michael A; Rafeq, Samaan; Rubio, Edmundo R; Slebos, Dirk-Jan; Stratakos, Grigoris; Sy, Alexander; Tsai, Larry W; Wahidi, Momen; Walsh, John; Wells, J Michael; Whitten, Patrick E; Yusen, Roger; Zulueta, Javier J; Criner, Gerard J; Washko, George R

    2015-09-01

    Uncontrolled pilot studies demonstrated promising results of endoscopic lung volume reduction using emphysematous lung sealant (ELS) in patients with advanced, upper lobe predominant emphysema. We aimed to evaluate the safety and efficacy of ELS in a randomised controlled setting.Patients were randomised to ELS plus medical treatment or medical treatment alone. Despite early termination for business reasons and inability to assess the primary 12-month end-point, 95 out of 300 patients were successfully randomised, providing sufficient data for 3- and 6-month analysis.57 patients (34 treatment and 23 control) had efficacy results at 3 months; 34 (21 treatment and 13 control) at 6 months. In the treatment group, 3-month lung function, dyspnoea, and quality of life improved significantly from baseline when compared to control. Improvements persisted at 6 months with >50% of treated patients experiencing clinically important improvements, including some whose lung function improved by >100%. 44% of treated patients experienced adverse events requiring hospitalisation (2.5-fold more than control, p=0.01), with two deaths in the treated cohort. Treatment responders tended to be those experiencing respiratory adverse events.Despite early termination, results show that minimally invasive ELS may be efficacious, yet significant risks (probably inflammatory) limit its current utility.

  7. Erlotinib in the treatment of advanced non-small cell lung cancer: an update for clinicians

    PubMed Central

    Wang, Yongsheng; Schmid-Bindert, Gerald

    2012-01-01

    Inhibition of epidermal growth factor receptor (EGFR) has become an important target in the treatment of advanced non-small cell lung cancer (NSCLC). Erlotinib and gefitinib, two small molecular agents that target the tyrosine kinase domain of the EGFR, were approved in many countries for the treatment of locally advanced or metastatic NSCLC as a second- or third-line regimen. Since then, randomized trials have evaluated the role of these two targeted agents alone or combined with chemotherapy in maintenance and first-line settings. This review summarizes the results of recent clinical trials with these tyrosine kinase inhibitors, with a focus on erlotinib, as first-line treatment towards a form of personalized medicine aimed at improving clinical outcome in advanced NSCLC. PMID:22229045

  8. Brentuximab Vedotin Treatment for Primary Refractory Hodgkin Lymphoma

    PubMed Central

    Yeh, Shyh-An; Chen, Huei-Yung

    2013-01-01

    Up to 40% of patients with advanced Hodgkin lymphoma (HL) become refractory or relapsed after current standard chemotherapy, among which primary refractory HL confers a particularly poor outcome. With intensive salvage chemotherapy and autologous stem cell transplantation, the long-term remission rate for these patients was only 30%, but more selective treatments with higher therapeutic index are needed. We report the experience of using a new anti-CD30 immunotoxin, brentuximab vedotin, in salvage treatment of a 30-year-old woman with primary refractory Hodgkin lymphoma. The patient presented with SVC syndrome due to the bulky mediastinal tumor and was confirmed to have classical Hodgkin lymphoma, nodular sclerosis type, stage IIIA. The tumor responded to induction chemotherapy transiently, but local progression was noted during subsequent cycles of treatment. Salvage radiotherapy to the mediastinal tumor, obtained no remission but was followed by rapid in-field progression and then lung metastasis. She declined stem cell transplantation and received salvage brentuximab vedotin (BV) therapy, which induced dramatic shrinkage of tumor without significant side effects. Serial followup of PET/CT imaging confirmed a rapid and continuous complete remission for 12 months. Although durability of the remission needs further observation, this case illustrates the excellent efficacy of brentuximab vedotin in primary refractory Hodgkin lymphoma. PMID:24198983

  9. Brentuximab vedotin treatment for primary refractory hodgkin lymphoma.

    PubMed

    Wu, Hung-Bo; Yeh, Shyh-An; Chen, Huei-Yung

    2013-01-01

    Up to 40% of patients with advanced Hodgkin lymphoma (HL) become refractory or relapsed after current standard chemotherapy, among which primary refractory HL confers a particularly poor outcome. With intensive salvage chemotherapy and autologous stem cell transplantation, the long-term remission rate for these patients was only 30%, but more selective treatments with higher therapeutic index are needed. We report the experience of using a new anti-CD30 immunotoxin, brentuximab vedotin, in salvage treatment of a 30-year-old woman with primary refractory Hodgkin lymphoma. The patient presented with SVC syndrome due to the bulky mediastinal tumor and was confirmed to have classical Hodgkin lymphoma, nodular sclerosis type, stage IIIA. The tumor responded to induction chemotherapy transiently, but local progression was noted during subsequent cycles of treatment. Salvage radiotherapy to the mediastinal tumor, obtained no remission but was followed by rapid in-field progression and then lung metastasis. She declined stem cell transplantation and received salvage brentuximab vedotin (BV) therapy, which induced dramatic shrinkage of tumor without significant side effects. Serial followup of PET/CT imaging confirmed a rapid and continuous complete remission for 12 months. Although durability of the remission needs further observation, this case illustrates the excellent efficacy of brentuximab vedotin in primary refractory Hodgkin lymphoma.

  10. Bronchodilator response of advanced lung function parameters depending on COPD severity

    PubMed Central

    Jarenbäck, Linnea; Eriksson, Göran; Peterson, Stefan; Ankerst, Jaro; Bjermer, Leif; Tufvesson, Ellen

    2016-01-01

    Background COPD is defined as partly irreversible airflow obstruction. The response pattern of bronchodilators has not been followed in advanced lung function parameters. Purpose The aim of this study was to investigate bronchodilator response pattern in advanced lung function parameters in a continuous fashion along forced expiratory volume in 1 second (FEV1) percent predicted (%p) in COPD patients and controls. Patients and methods Eighty-one smokers/ex-smokers (41 controls and 40 COPD) performed spirometry, body plethysmography, impulse oscillometry and single-breath helium dilution carbon monoxide diffusion at baseline, after salbutamol inhalation and then after an additional inhalation of ipratropium. Results Most pulmonary function parameters showed a linear increase in response to decreased FEV1%p. The subjects were divided into groups of FEV1%p <65 and >65, and the findings from continuous analysis were verified. The exceptions to this linear response were inspiratory capacity (IC), forced vital capacity (FVC), FEV1/FVC and expiratory resistance (Rex), which showed a segmented response relationship to FEV1%p. IC and FVC, with break points (BP) of 57 and 58 FEV1%p respectively, showed no response above, but an incresed slope below the BP. In addition, in patients with FEV1%p <65 and >65, response of FEV1%p did not correlate to response of volume parameters. Conclusion Response of several advanced lung function parameters differs depending on patients’ baseline FEV1%p, and specifically response of volume parameters is most pronounced in COPD patients with FEV1%p <65. Volume and resistance responses do not follow the flow response measured with FEV1 and may thus be used as a complement to FEV1 reversibility to identify flow, volume and resistance responders. PMID:27932874

  11. Long-lasting control with erlotinib in advanced non-small cell lung cancer (NSCLC).

    PubMed

    Guimarães, Teresa; Castro, Ana; Cortesão, Nuno; Ferreira, Jorge; João, Fernanda

    2008-10-01

    The authors present a clinical case of a caucasian male patient, 59 years-old, non-smoker, with an advanced non-small cell lung carcinoma (NSCLC), with 3 years of follow-up, received erlotinib for 18 months, after failure of more than one chemotherapy schedule, without evidence of oncologic progression. The patient evidences excellent quality of life, controlled sintomatology, recovery of the capacity of tolerance to the effort and it maintains his professional activities. The treatment with erlotinib has been well tolerated, although exhibiting grade 1 cutaneous toxicity. Rev Port Pneumol 2008; XIV (Supl 3): S9-S15.

  12. Survival analysis of platinum-refractory patients with advanced esophageal cancer treated with docetaxel or best supportive care alone: a retrospective study.

    PubMed

    Moriwaki, T; Kajiwara, T; Matsumoto, T; Suzuki, H; Hiroshima, Y; Matsuda, K; Hirai, S; Yamamoto, Y; Yamada, T; Sugaya, A; Kobayashi, M; Endo, S; Ishige, K; Nishina, T; Hyodo, I

    2014-01-01

    The survival benefit of second-line chemotherapy with docetaxel in platinum-refractory patients with advanced esophageal cancer (AEC) remains unclear. A retrospective analysis of AEC patients with Eastern Cooperative Oncology Group performance status (PS)≤2 was performed, and major organ functions were preserved, who determined to receive docetaxel or best supportive care (BSC) alone after failure of platinum-based chemotherapy. The post-progression survival (PPS), defined as survival time after disease progression following platinum-based chemotherapy, was analyzed by multivariate Cox regression analysis using factors identified as significant in univariate analysis of various 20 characteristics (age, sex, PS, primary tumor location, etc) including Glasgow prognostic score (GPS), which is a well-known prognostic factor in many malignant tumors. Sixty-six and 45 patients were determined to receive docetaxel and BSC between January 2007 and December 2011, respectively. The median PPS was 5.4 months (95% confidence interval [CI] 4.8-6.0) in the docetaxel group and 3.3 months (95% CI 2.5-4.0) in the BSC group (hazard ratio [HR] 0.56, 95% CI 0.38-0.84, P=0.005). Univariate analysis revealed six significant factors: treatment, PS, GPS, number of metastatic organs, liver metastasis, and bone metastasis. Multivariate analysis including these significant factors revealed three independent prognostic factors: docetaxel treatment (HR 0.62, 95% CI 0.39-0.99, P=0.043), better GPS (HR 0.61, 95% CI 0.46-0.81, P=0.001), and no bone metastasis (HR 0.31, 95% CI 0.15-0.68, P=0.003). There was a trend for PPS in favor of the docetaxel group compared with patients who refused docetaxel treatment in the BSC group (adjusted HR 0.61, 95% CI 0.29-1.29, P=0.20). Docetaxel treatment may have prolonged survival in platinum-refractory patients with AEC.

  13. Weekly administration of docetaxel in combination with estramustine and celecoxib in patients with advanced hormone-refractory prostate cancer: final results from a phase II study

    PubMed Central

    Carles, J; Font, A; Mellado, B; Domenech, M; Gallardo, E; González-Larriba, J L; Catalan, G; Alfaro, J; Gonzalez del Alba, A; Nogué, M; Lianes, P; Tello, J M

    2007-01-01

    The objective of this study was to evaluate the efficacy and safety profile of weekly docetaxel, estramustine and celecoxib in patients with advanced hormone-refractory prostate cancer. Forty-eight patients received 35 mg m−2 of weekly docetaxel for 3 out of every 4 weeks, 280 mg of estramustine twice daily on days 1–3, 8–10, 15–17 and 400 mg of celecoxib twice daily until progression or toxicity. Cycles were repeated every 28 days for at least six cycles. Patients were evaluated for response and toxicity. Patients received a median of four cycles (range: 1–9). On an intention-to-treat analysis, prostate-specific antigen (PSA) was decreased greater than 50% in 28 out of 48 patients (overall response rate: 58%, 95% confidence interval (CI): 44–72) and median duration of PSA response was 8.0 months (95% CI: 6.9–9.0). After a median follow-up of 11.3 months, the median time to progression was 7.1 months and the median overall survival was 19.2 months. The most frequent severe toxicity was asthenia (15% of patients), diarrhoea and stomatitis (8% of patients, each). Grade 3/4 neutropenia was reported in two patients. There was a toxic death during the study due to a gastric perforation. Celecoxib with weekly docetaxel and estramustine is an effective and safe treatment for patients with hormone-refractory prostate cancer, but it does not seem to add any benefit to docetaxel. PMID:17955053

  14. Advances in the Evaluation of Respiratory Pathophysiology during Exercise in Chronic Lung Diseases

    PubMed Central

    O'Donnell, Denis E.; Elbehairy, Amany F.; Berton, Danilo C.; Domnik, Nicolle J.; Neder, J. Alberto

    2017-01-01

    Dyspnea and exercise limitation are among the most common symptoms experienced by patients with various chronic lung diseases and are linked to poor quality of life. Our understanding of the source and nature of perceived respiratory discomfort and exercise intolerance in chronic lung diseases has increased substantially in recent years. These new mechanistic insights are the primary focus of the current review. Cardiopulmonary exercise testing (CPET) provides a unique opportunity to objectively evaluate the ability of the respiratory system to respond to imposed incremental physiological stress. In addition to measuring aerobic capacity and quantifying an individual's cardiac and ventilatory reserves, we have expanded the role of CPET to include evaluation of symptom intensity, together with a simple “non-invasive” assessment of relevant ventilatory control parameters and dynamic respiratory mechanics during standardized incremental tests to tolerance. This review explores the application of the new advances in the clinical evaluation of the pathophysiology of exercise intolerance in chronic obstructive pulmonary disease (COPD), chronic asthma, interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH). We hope to demonstrate how this novel approach to CPET interpretation, which includes a quantification of activity-related dyspnea and evaluation of its underlying mechanisms, enhances our ability to meaningfully intervene to improve quality of life in these pathologically-distinct conditions. PMID:28275353

  15. Update on targeted therapies for advanced non-small cell lung cancer: nivolumab in context

    PubMed Central

    Le, Alexander D; Alzghari, Saeed K; Jean, Gary W; La-Beck, Ninh M

    2017-01-01

    While the initial treatment of non-small cell lung cancer (NSCLC) usually relies on surgical resection followed by systemic cytotoxic chemotherapy and/or radiation therapy, recent advances in understanding of NSCLC biology and immunology have spurred the development of numerous targeted therapies. In particular, a class of immune modulatory drugs targeting the immune checkpoint pathways has demonstrated remarkable durable remissions in a select minority of advanced NSCLC patients, potentially heralding the elusive “cancer cure”. This review focuses on the clinical evidence for one of these agents, nivolumab, and clarifies the role of this drug in the context of the other targeted therapies currently available for the treatment of NSCLC. We also discuss the impact of nivolumab on patient quality of life and health economics. PMID:28260909

  16. Clinicopathological features and outcomes in advanced nonsmall cell lung cancer with tailored therapy

    PubMed Central

    Bala, Stalin; Gundeti, Sadashivudu; Linga, Vijay Gandhi; Maddali, Lakshmi Srinivas; Digumarti, Raghunadha Rao; Uppin, Shantveer G.

    2016-01-01

    Context: Lung cancer is an important cause of cancer-related deaths worldwide. There is an increasing incidence of lung cancer in never smokers and a shift of histology from squamous cell to adenocarcinoma globally in the recent past. Data on treatment outcomes with newer platinum doublets is scant from India. Aims: To study the clinicopathological features, response rates (RRs), progression-free survival (PFS), overall survival (OS), and the 1, 2, and 3 years survival, in patients with advanced nonsmall cell lung cancer (NSCLC). Materials and Methods: Data of all patients who received chemotherapy for Stage IIIB and IV NSCLC between January 2010 and June 2014 were retrospectively analyzed. Statistical Analysis Used: Univariate analysis for OS was done by plotting Kaplan–Meier curves and the log-rank test was used to calculate P values. Logistic regression analysis for OS was carried out using MedCalc statistical software. Results: A total of 353 patients received chemotherapy. Of these, 256 were evaluable for outcome parameters. The median age at presentation was 58 years with a male:female ratio of 2.53:1. The smoker:nonsmoker ratio was 1:1. Adenocarcinomatous histology was the most common both in smokers and nonsmokers reported in 70.8% patients. Epidermal growth factor receptor (EGFR) mutation and echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase translocation were seen in 35% and 3% of patients, respectively. The RR, median PFS, OS, 1, 2, and 3 years survival were 80%, 8 months, 12.1 months, 51.5%, 12.7%, and 4.2%, respectively. There was no significant survival difference among the treatment regimen used but the response to I line chemotherapy impacted survival. Female gender, performance status, and nonsquamous histology were significant predictors of OS (P = 0.0443, P = 0.0003, P = 0.048, respectively). Conclusions: There was an increase in the incidence of nonsmokers. Adenocarcinoma was the most common histology in both smokers

  17. Photodynamic Therapy (PDT) with Chemotherapy for Advanced Lung Cancer with Airway Stenosis.

    PubMed

    Kimura, Masakazu; Miyajima, Kuniharu; Kojika, Masakazu; Kono, Takafumi; Kato, Harubumi

    2015-10-23

    Intractable advanced lung cancer can be treated palliatively with photodynamic therapy (PDT) combined with chemotherapy to remove central and peripheral (lobar or segmental bronchi) bronchial stenosis and obstruction. We present data for 12 (eight men, four women) consecutive patients with 13 advanced non-small cell lung carcinomas in whom curative operations were contraindicated, who underwent PDT combined with chemotherapy for local control of the intraluminal lesions. The mean age was 73.3 years (range, 58-80 years), and the stages of cancer were IIA-IV. The median stenosis rates before treatment, one week post-treatment, and one month post-treatment were 60% (range, 30%-100%), 15% (range, 15%-99%), and 15% (range 15%-60%), respectively. The mean and median survival times were 9.3 and 5.9 months, respectively. The overall 1-year survival rate was 30.0%. No PDT-related morbidity or mortality occurred. In this single-institution study, all patients experienced improved symptoms and quality of life at one week after treatment; furthermore, an objective response was evidenced by the substantial increase in the openings of the bronchial lumen and prevention of obstructive pneumonia. Therefore, PDT with chemotherapy was useful and safe for the treatment of bronchial obstruction.

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

    ClinicalTrials.gov

    2013-07-01

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

  19. [Refractory anemias].

    PubMed

    Efira, A; Azerad, M-A

    2013-09-01

    Refractory anemia, also known as myelodysplastic syndromes, forms a group of clonal diseases characterized by cytopenias with mostly rich bone marrow. Preferentially reaching an older population, the prognosis depends on both comorbidities and characteristics of the disease, which have been grouped into a score established in 1997 ("IPSS = International Prognostic Scoring System") and revised in 2012 ("R-IPSS = Revised IPSS"). Overall survival and risk of transformation into acute nonlymphoblastic leukemia can now be estimated fairly accurately. Based on these characteristics, the treatment will be mainly supportive or will use several new molecules: growth factors, lenalidomide, 5-azacitidine, etc. A minority of patients may also benefit from allogeneic BMT or sometimes immunosuppressive therapy.

  20. Advanced lung adenocarcinomas with ROS1-rearrangement frequently show hepatoid cell

    PubMed Central

    Kong, Mei; Zhou, Jianya; Ding, Wei; Zhou, Jianying

    2016-01-01

    Defining distinctive histologic characteristics of ROS1-rearranged non-small-cell lung carcinomas (NSCLCs) may help identify cases that merit molecular testing. However, the majority of previous reports have focused on surgical specimens but only limited studies assessed histomorphology of advanced NSCLCs. In order to identify the clinical and histological characteristics of ROS1-rearranged advanced NSCLCs, we examined five hundred sixteen Chinese patients with advanced NSCLCs using ROS1 fluorescence in situ hybridization and real-time polymerase chain reaction and then analyzed for clinical and pathological features. We performed univariate and multivariate analyses to identify predictive factors associated with ROS1 rearrangement. 19 tumors were identified with ROS1 rearrangement (3.7% of adenocarcinomas). 16 ROS1+ and 122 ROS1- samples with available medical records and enough tumor cells were included for histological analysis. Compared with ROS1-negative advanced NSCLCs, ROS1-rearranged advanced NSCLCs were associated with a younger age at presentation. ROS1 rearrangements were not significantly associated with sex, smoking history, drinking history and metastatic sites. The most common histological pattern was solid growth (12/16), followed by acinar (4/16) growth. 66.7% cases with solid growth pattern showed hepatoid cytology (8/12) and 75% cases with acinar growth pattern showed a cribriform structure (3/4). 18.8% cases were found to have abundant extracellular mucus or signet-ring cells (3/16). Only one case with solid growth pattern showed psammomatous calcifications. In conclusion, age, hepatoid cytology and cribriform structure are the independent predictors for ROS1-rearranged advanced NSCLCs, recognizing these may be helpful in finding candidates for genomic alterations, especially when available tissue samples are limited. PMID:27708233

  1. Exercise and nutrition interventions in advanced lung cancer: a systematic review

    PubMed Central

    Payne, C.; Larkin, P.J.; McIlfatrick, S.; Dunwoody, L.; Gracey, J.H.

    2013-01-01

    In this systematic review, we sought to evaluate the effect of physical activity or nutrition interventions (or both) in adults with advanced non-small-cell lung cancer (nsclc). Methods A systematic search for relevant clinical trials was conducted in 6 electronic databases, by hand searching, and by contacting key investigators. No limits were placed on study language. Information about recruitment rates, protocol adherence, patient-reported and clinical outcome measures, and study conclusions was extracted. Methodologic quality and risk of bias in each study was assessed using validated tools. Main Results Six papers detailing five studies involving 203 participants met the inclusion criteria. Two of the studies were single-cohort physical activity studies (54 participants), and three were controlled nutrition studies (149 participants). All were conducted in an outpatient setting. None of the included studies combined physical activity with nutrition interventions. Conclusions Our systematic review suggests that exercise and nutrition interventions are not harmful and may have beneficial effects on unintentional weight loss, physical strength, and functional performance in patients with advanced nsclc. However, the observed improvements must be interpreted with caution, because findings were not consistent across the included studies. Moreover, the included studies were small and at significant risk of bias. More research is required to ascertain the optimal physical activity and nutrition interventions in advanced inoperable nsclc. Specifically, the potential benefits of combining physical activity with nutrition counselling have yet to be adequately explored in this population. PMID:23904771

  2. Nivolumab: A Review in Advanced Nonsquamous Non-Small Cell Lung Cancer.

    PubMed

    Keating, Gillian M

    2016-06-01

    The programmed death (PD)-1 immune checkpoint inhibitor nivolumab (Opdivo(®)) is approved in the USA for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) who have progression on or after platinum-based chemotherapy and in the EU for the treatment of adults with locally advanced or metastatic NSCLC after prior chemotherapy. In previously-treated patients with advanced nonsquamous NSCLC, overall survival was significantly prolonged and the overall response rate was significantly higher in patients who received intravenous nivolumab 3 mg/kg every 2 weeks versus intravenous docetaxel in the pivotal CheckMate 057 trial. Progression-free survival did not significantly differ between patients receiving nivolumab and those receiving docetaxel. Intravenous nivolumab had a manageable adverse event profile (including immune-mediated adverse events) and was better tolerated than docetaxel in the CheckMate 057 trial. Thus, nivolumab is an important new option for use in previously-treated patients with advanced nonsquamous NSCLC.

  3. Salvage treatment with apatinib for advanced non-small-cell lung cancer

    PubMed Central

    Song, Zhengbo; Yu, Xinmin; Lou, Guangyuan; Shi, Xun; Zhang, Yiping

    2017-01-01

    Objective No definitive chemotherapeutic regimen has been established in patients with non-small-cell lung cancer (NSCLC) who failed second- or third-line treatment. The aim of this study was to evaluate apatinib, a VEGFR-2 inhibitor, in advanced NSCLC as salvage treatment. Methods We evaluated the efficacy and toxicity of apatinib in patients with previously treated advanced NSCLC from 2014 to 2015 in Zhejiang Cancer Hospital. Survival analysis was performed by the Kaplan–Meier method. Results Forty-two patients were included in the present study. Four patients achieved partial response, and 22 achieved stable disease, representing a response rate of 9.5% and a disease control rate of 61.9%. Median progression-free survival and overall survival were 4.2 and 6.0 months, respectively. The toxicities associated with apatinib were generally acceptable with a total grade 3/4 toxicity of 50%. Conclusion Apatinib appears to have some activity against advanced NSCLC when utilized as salvage treatment. PMID:28367065

  4. Quality-of-life assessment in advanced lung cancer: considerations for evaluation in patients receiving chemotherapy.

    PubMed

    Gralla, Richard J; Thatcher, Nick

    2004-12-01

    There is increasing awareness of the need for accurate assessment of quality of life in patients with lung cancer who are on clinical trials and in patient management. Self-reported multidimensional, validated, quality-of-life instruments assess physical, functional, psychological, social, and spiritual dimensions associated with lung cancer and its treatment. Such validated instruments are now available and are being utilized more frequently in clinical trials assessing the value of particular anticancer therapies. Such findings may influence the treatment of choice for patients with non-small-cell lung cancer (NSCLC), particularly in the advanced-disease setting where survival benefits from current treatments are modest, and the majority of patients present with three or more symptoms. Recently, a number of studies assessing quality of life in NSCLC have been published providing more insight into the effects of the disease and its treatment on the patient's perspective. Quality-of-life instruments that include patient reported outcomes ("PROS") and quality-of-life and symptom assessment are the only way to evaluate this crucial aspect of cancer care. As an example, Fossella and colleagues reported notable findings from the largest prospective evaluation (the TAX 326 trial) of quality of life using validated instruments in patients with NSCLC who received chemotherapy. Patients who received a docetaxel plus platinum combination regimen reported modest benefits in both quality of life and in disease-related parameters, such as pain control, weight loss, and performance status, compared to patients randomly assigned to the combination of vinorelbine and cisplatin. Compliance with the PRO assessment was high, supporting the feasibility of prospective quality-of-life evaluations in NSCLC. Important goals include building on these results by including quality-of-life assessment in all major clinical trials, and demonstrating feasible ways to incorporate this evaluation

  5. Overview of chemoradiation clinical trials for locally advanced non-small cell lung cancer in Japan.

    PubMed

    Okamoto, Isamu

    2008-04-01

    The standard of care for unresectable stage III non-small cell lung cancer (NSCLC) is combined-modality therapy with both chemotherapy and thoracic radiation therapy (TRT). A phase III trial by the West Japan Lung Cancer Group revealed that the combination of mitomycin, vindesine, and cisplatin (MVP) with concurrent TRT yielded a median survival time of 16.6 months and a 5-year survival rate of 16% in patients with unresectable stage III NSCLC. Although evidence indicates that concurrent chemotherapy and TRT (chemoradiation) increases survival to a moderately greater extent than sequential therapeutic approaches, the optimal strategies for such concurrent treatment remain to be defined, and differ between full-dose systemic and low-dose radio-enhancing protocols. Two phase III trials have been initiated in Japan to address these issues and they have recently reported preliminary data. Early results of the Okayama Lung Cancer Study Group (OLCSG) trial, comparing chemoradiation based on divided docetaxel and cisplatin chemotherapy with MVP-based chemoradiation, have been reported. The West Japan Oncology Group (WJOG) is comparing the efficacy and toxicity of TRT and concurrent chemotherapy with either carboplatin-paclitaxel or carboplatin-irinotecan, followed by full-dose consolidation chemotherapy, with the efficacy and toxicity of MVP-based chemoradiation. Several phase I/II studies to test the optimal use of new agents such as S-1 (an oral anticancer drug combining tegafur, 5-chloro-2, 4-dihydroxypyridine, and potassium oxonate) and gefitinib (an inhibitor of the tyrosine kinase activity of the epidermal growth factor receptor) are also ongoing. In addition, radiation dose intensification with three-dimensional planning approaches is currently under evaluation. A phase I clinical trial by WJOG to establish, prospectively, the maximum tolerated dose of three-dimensional hyperfractionated radiotherapy with concurrent weekly chemotherapy (carboplatin-paclitaxel) is

  6. Molecularly targeted therapies for advanced or metastatic non-small-cell lung carcinoma

    PubMed Central

    Bayraktar, Soley; Rocha-Lima, Caio M

    2013-01-01

    Non-small-cell lung cancer (NSCLC) remains the leading cause of cancer-related death in both men and women in the United States. Platinum-based doublet chemotherapy has been a standard for patients with advanced stage disease. Improvements in overall survival and quality of life have been modest. Improved knowledge of the aberrant molecular signaling pathways found in NSCLC has led to the development of biomarkers with associated targeted therapeutics, thus changing the treatment paradigm for many NSCLC patients. In this review, we present a summary of many of the currently investigated biologic targets in NSCLC, discuss their current clinical trial status, and also discuss the potential for development of other targeted agents. PMID:23696960

  7. Chemotherapy and targeted therapeutics as maintenance of response in advanced non-small cell lung cancer.

    PubMed

    Johnson, Melissa L; Patel, Jyoti D

    2014-02-01

    Non-small cell lung cancer (NSCLC) remains the most common cause of cancer-related death in the United States. Survival for patients with advanced disease remains meager with standard platinum-based doublet therapy even given initially. Improved efficacy and tolerability of third-generation chemotherapies and small-molecule inhibitors has prompted the evaluation of these agents in the maintenance setting in order to enhance current outcomes. Two separate strategies have evolved: the introduction of a non-cross-resistant drug immediately following first-line or induction chemotherapy (switch maintenance), or the continuation of the non-platinum partner initially introduced during induction (continuation maintenance). Here we review the available clinical trial data evaluating both maintenance strategies, and offer our assessment of their contemporary clinical implications and cost-effectiveness.

  8. Impact of Disease Progression Date Determination on Progression-free Survival Estimates in Advanced Lung Cancer

    PubMed Central

    Qi, Yingwei; Ziegler, Allen; Katie, L.; Hillman, Shauna L.; Redman, Mary W.; Schild, Steven E.; Gandara, David R.; Adjei, Alex A.; Mandrekar, Sumithra J.

    2012-01-01

    PURPOSE Progression-free survival (PFS) based endpoints are controversial; however in advanced lung cancer, overall survival is largely influenced by the progression status. We thus evaluated the impact of progression date (PD) determination approach on PFS estimates. METHODS Individual patient data from 21 trials (14 NCCTG; 7 SWOG) were used. Reported progression date (RPD) was defined as either the scan date or the clinical deterioration date. PD was determined using 4 methods (M): RPD (M1), one day after last progression-free scan (M2), midpoint between last progression-free scan and RPD (M3), and using an interval censoring approach (M4). PFS was estimated using Kaplan-Meier (M1, M2, M3), and maximum likelihood (M4). Simulation studies were performed to understand the impact of the length of time elapsed between the last progression-free scan and the PD on time to progression (TTP) estimates. RESULTS PFS estimates using RPD were the highest, with M2 being the most conservative. M3 and M4 were similar due to majority of progressions occurring during treatment (i.e., frequent disease assessments). M3 was less influenced by the length of the assessment schedules (%difference from true TTP <1.5%) compared to M1 (11% to 30%) and M2 (-8% to -29%). The overall study conclusion was unaffected by the method used for randomized trials. CONCLUSION The magnitude of difference in the PFS estimates is large enough to alter trial conclusions in advanced lung cancer. Standards for PD determination, use of sensitivity analyses, and randomized trials are critical when designing trials and reporting efficacy using PFS based endpoints. PMID:22434489

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

    PubMed Central

    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. PMID:28348561

  10. Advances in the early detection of lung cancer using analysis of volatile organic compounds: from imaging to sensors.

    PubMed

    Li, Wang; Liu, Hong-Ying; Jia, Zi-Ru; Qiao, Pan-Pan; Pi, Xi-Tian; Chen, Jun; Deng, Lin-Hong

    2014-01-01

    According to the World Health Organization (WHO), 1.37 million people died of lung cancer all around the world in 2008, occupying the first place in all cancer-related deaths. However, this number might be decreased if patients were detected earlier and treated appropriately. Unfortunately, traditional imaging techniques are not sufficiently satisfactory for early detection of lung cancer because of limitations. As one alternative, breath volatile organic compounds (VOCs) may reflect the biochemical status of the body and provide clues to some diseases including lung cancer at early stage. Early detection of lung cancer based on breath analysis is becoming more and more valued because it is non-invasive, sensitive, inexpensive and simple. In this review article, we analyze the limitations of traditional imaging techniques in the early detection of lung cancer, illustrate possible mechanisms of the production of VOCs in cancerous cells, present evidence that supports the detection of such disease using breath analysis, and summarize the advances in the study of E-noses based on gas sensitive sensors. In conclusion, the analysis of breath VOCs is a better choice for the early detection of lung cancer compared to imaging techniques. We recommend a more comprehensive technique that integrates the analysis of VOCs and non-VOCs in breath. In addition, VOCs in urine may also be a trend in research on the early detection of lung cancer.

  11. A block matching-based registration algorithm for localization of locally advanced lung tumors

    SciTech Connect

    Robertson, Scott P.; Weiss, Elisabeth; Hugo, Geoffrey D.

    2014-04-15

    Purpose: To implement and evaluate a block matching-based registration (BMR) algorithm for locally advanced lung tumor localization during image-guided radiotherapy. Methods: Small (1 cm{sup 3}), nonoverlapping image subvolumes (“blocks”) were automatically identified on the planning image to cover the tumor surface using a measure of the local intensity gradient. Blocks were independently and automatically registered to the on-treatment image using a rigid transform. To improve speed and robustness, registrations were performed iteratively from coarse to fine image resolution. At each resolution, all block displacements having a near-maximum similarity score were stored. From this list, a single displacement vector for each block was iteratively selected which maximized the consistency of displacement vectors across immediately neighboring blocks. These selected displacements were regularized using a median filter before proceeding to registrations at finer image resolutions. After evaluating all image resolutions, the global rigid transform of the on-treatment image was computed using a Procrustes analysis, providing the couch shift for patient setup correction. This algorithm was evaluated for 18 locally advanced lung cancer patients, each with 4–7 weekly on-treatment computed tomography scans having physician-delineated gross tumor volumes. Volume overlap (VO) and border displacement errors (BDE) were calculated relative to the nominal physician-identified targets to establish residual error after registration. Results: Implementation of multiresolution registration improved block matching accuracy by 39% compared to registration using only the full resolution images. By also considering multiple potential displacements per block, initial errors were reduced by 65%. Using the final implementation of the BMR algorithm, VO was significantly improved from 77% ± 21% (range: 0%–100%) in the initial bony alignment to 91% ± 8% (range: 56%–100%;p < 0

  12. Canadian consensus: inhibition of ALK-positive tumours in advanced non-small-cell lung cancer

    PubMed Central

    Melosky, B.; Agulnik, J.; Albadine, R.; Banerji, S.; Bebb, D.G.; Bethune, D.; Blais, N.; Butts, C.; Cheema, P.; Cheung, P.; Cohen, V.; Deschenes, J.; Ionescu, D.N.; Juergens, R.; Kamel-Reid, S.; Laurie, S.A.; Liu, G.; Morzycki, W.; Tsao, M.S.; Xu, Z.; Hirsh, V.

    2016-01-01

    Anaplastic lymphoma kinase (alk) is an oncogenic driver in non-small-cell lung cancer (nsclc). Chromosomal rearrangements involving the ALK gene occur in up to 4% of nonsquamous nsclc patients and lead to constitutive activation of the alk signalling pathway. ALK-positive nsclc is found in relatively young patients, with a median age of 50 years. Patients frequently have brain metastasis. Targeted inhibition of the alk pathway prolongs progression-free survival in patients with ALK-positive advanced nsclc. The results of several recent clinical trials confirm the efficacy and safety benefit of crizotinib and ceritinib in this population. Canadian oncologists support the following consensus statement: All patients with advanced nonsquamous nsclc (excluding pure neuroendocrine carcinoma) should be tested for the presence of an ALK rearrangement. If an ALK rearrangement is present, treatment with a targeted alk inhibitor in the first-line setting is recommended. As patients become resistant to first-generation alk inhibitors, other treatments, including second-generation alk inhibitors can be considered. PMID:27330348

  13. Increased level of Hsp90-beta in bronchoalveolar lavage fluid correlates with lymphatic invasion and advanced stage of lung cancer patients

    PubMed Central

    Rong, Biaoxue; Cai, Xiguang; Liu, Hua; Fu, Tian; Gao, Wenlong; Zhao, Chongchong; Lin, Yurong

    2016-01-01

    Background: The purpose of this work is to explore the correlation between Hsp90-beta level in broncheoalveolar lavage fluid (BALF) and lung cancer. Methods: Hsp90-beta level was measured by immunohistochemistry and enzyme-linked immunosorbent assay. Sensitivity and specificity of Hsp90-beta were calculated by receiver operator characteristic curve. Results: BALF in patients with lung cancer showed a higher expression of Hsp90-beta than those with benign lung disease (P<0.05). Elevated Hsp90-beta was closely related to lymphatic invasion and advanced stage of patients with lung cancer (P<0.05). The sensitivity of BALF Hsp90-beta for discerning lung cancer from patients with benign disease was 82.56% and specificity was 97.56%. Conclusion: Increased BALF Hsp90-beta correlates with lymphatic invasion and advanced stage of patients with lung cancer, suggesting it could be a diagnostic indicator for patients with lung cancer. PMID:27829999

  14. A Phase 1 Study of 131I-CLR1404 in Patients with Relapsed or Refractory Advanced Solid Tumors: Dosimetry, Biodistribution, Pharmacokinetics, and Safety

    PubMed Central

    Grudzinski, Joseph J.; Titz, Benjamin; Kozak, Kevin; Clarke, William; Allen, Ernest; Trembath, LisaAnn; Stabin, Michael; Marshall, John; Cho, Steve Y.; Wong, Terence Z.; Mortimer, Joanne; Weichert, Jamey P.

    2014-01-01

    Introduction 131I-CLR1404 is a small molecule that combines a tumor-targeting moiety with a therapeutic radioisotope. The primary aim of this phase 1 study was to determine the administered radioactivity expected to deliver 400 mSv to the bone marrow. The secondary aims were to determine the pharmacokinetic (PK) and safety profiles of 131I-CLR1404. Methods Eight subjects with refractory or relapsed advanced solid tumors were treated with a single injection of 370 MBq of 131I-CLR1404. Whole body planar nuclear medicine scans were performed at 15–35 minutes, 4–6, 18–24, 48, 72, 144 hours, and 14 days post injection. Optional single photon emission computed tomography imaging was performed on two patients 6 days post injection. Clinical laboratory parameters were evaluated in blood and urine. Plasma PK was evaluated on 127I-CLR1404 mass measurements. To evaluate renal clearance of 131I-CLR1404, urine was collected for 14 days post injection. Absorbed dose estimates for target organs were determined using the RADAR method with OLINDA/EXM software. Results Single administrations of 370 MBq of 131I-CLR1404 were well tolerated by all subjects. No severe adverse events were reported and no adverse event was dose-limiting. Plasma 127I-CLR1404 concentrations declined in a bi-exponential manner with a mean t½ value of 822 hours. Mean Cmax and AUC(0-t) values were 72.2 ng/mL and 15753 ng•hr/mL, respectively. An administered activity of approximately 740 MBq is predicted to deliver 400 mSv to marrow. Conclusions Preliminary data suggest that 131I-CLR1404 is well tolerated and may have unique potential as an anti-cancer agent. Trial Registration ClinicalTrials.gov NCT00925275 PMID:25402488

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

    SciTech Connect

    Hong, C; Ju, S; Ahn, Y

    2015-06-15

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

  16. Activity of gefitinib in advanced non-small-cell lung cancer with very poor performance status.

    PubMed

    Chang, Gee-Chen; Chen, Kun-Chieh; Yang, Tsung-Ying; Yin, Ming-Chang; Lin, Ching-Pei; Kuo, Benjamin Ing-Tiau; Hsu, Jeng-Yuan

    2005-01-01

    Advanced non-small-cell lung cancer (NSCLC) patients with poor performance status (PS) are less likely to respond to chemotherapy, or to have an improvement in survival, but more likely to experience toxicity. We retrospectively evaluated the efficacy and tolerability of gefitinib in patients with advanced NSCLC and very poor PS in Taiwan. Patients with stage IIIB, IV NSCLC with an Eastern Cooperative Oncology Group (ECOG) PS of 3-4 received oral gefitinib 250 mg once daily. Totally, 52 patients were included (25 men, 27 women). Forty-three patients (82.7%) were in a PS of 3. Tumor response rate was 25.0% (13/52). Tumor response rate to gefitinib was highest in chemonaive patients 38.1% (8/21) vs. failed 1 chemotherapy regimen 13.3% (2/15) vs. failed 2 or more chemotherapy regimens 18.8% (3/16), p = 0.015. The median overall survival was 2.5 months (response group 9.1 months, stable disease 3.1 months, and progressive group 0.8 month, p < 0.001). Adverse events, mainly skin reactions and diarrhea, were generally mild (grade 1 or 2) except paronychia and acne. Thus, gefitinib has clinically antitumor activity and good tolerability in Taiwan patients with advanced NSCLC and very poor performance status, with a higher response rate than that seen Europe or in European heritage Americans. Chemonaive patients responded better than patients with prior chemotherapy. Formal clinical trials are warranted to evaluate the role of gefitinib in this situation.

  17. Sulfate radical-advanced oxidation process (SR-AOP) for simultaneous removal of refractory organic contaminants and ammonia in landfill leachate.

    PubMed

    Deng, Yang; Ezyske, Casey M

    2011-11-15

    Typically, a mature landfill leachate contains high levels of non-biodegradable organics and ammonia nitrogen. Simultaneous removal of the both persistent leachate pollutants is a significant challenge. This paper reports the first scientific study to apply a sulfate radical (SO(4)(·-)) - based advanced oxidation process (SR-AOP) to treat a mature leachate, with an emphasis of concurrent removal of refractory organics and ammonia. In this study, all the experiments were run in a batch reactor with temperature control. In the thermal persulfate oxidation (TPO) process, persulfate (S(2)O(8)(2-)) was activated by heat to produce powerful oxidants, SO(4)(·-) (E(o) = 2.6 V). Three factors affecting the removal efficiencies of chemical oxygen demand (COD) and ammonia nitrogen were investigated, including initial solution pH (3-8.3), temperature (27-50 °C), and chemical dose (S(2)O(8)(2-):12COD(0) = 0.25-2.0). Typically, acidic pH (3-4), higher temperature, and higher dose favored the removal of COD and ammonia. At S(2)O(8)(2-):12COD(0) = 2 and 50 °C, the COD removal rates were 79% and 91% at pH 8.3 (no pH adjustment) and 4, respectively; and the ammonia nitrogen removal reached 100% at pH 8.3 or 4. SR-AOP appears to be more advantageous over hydroxyl radical (OH∙)-based advanced oxidation processes (HR-AOPs) because OH∙ almost does not oxidize ammonia. Furthermore, compared with Fenton treatment of the same batch leachate sample, the TPO could achieve a higher COD removal at an identical chemical dose. For example, COD removal was 40% at H(2)O(2):2.125COD(0) = 2 during Fenton treatment (pH 3), but 91% at S(2)O(8)(2-):12COD(0) = 2 during TPO (pH 4). These findings demonstrate that SR-AOP is a promising landfill leachate treatment method.

  18. Receptor for advanced glycation end products contributes to postnatal pulmonary development and adult lung maintenance program in mice.

    PubMed

    Fineschi, Silvia; De Cunto, Giovanna; Facchinetti, Fabrizio; Civelli, Maurizio; Imbimbo, Bruno P; Carnini, Chiara; Villetti, Gino; Lunghi, Benedetta; Stochino, Stefania; Gibbons, Deena L; Hayday, Adrian; Lungarella, Giuseppe; Cavarra, Eleonora

    2013-02-01

    The role of the receptor for advanced glycation end products (RAGE) in promoting the inflammatory response through activation of NF-κB pathway is well established. Recent findings indicate that RAGE may also have a regulative function in apoptosis, as well as in cellular proliferation, differentiation, and adhesion. Unlike other organs, lung tissue in adulthood and during organ development shows relatively high levels of RAGE expression. Thus a role for the receptor in lung organogenesis and homeostasis may be proposed. To evaluate the role of RAGE in lung development and adult lung homeostasis, we generated hemizygous and homozygous transgenic mice overexpressing human RAGE, and analyzed their lungs from the fourth postnatal day to adulthood. Moderate RAGE hyperexpression during lung development influenced secondary septation, resulting in an impairment of alveolar morphogenesis and leading to significant changes in morphometric parameters such as airspace number and the size of alveolar ducts. An increase in alveolar cell apoptosis and a decrease in cell proliferation were demonstrated by the terminal deoxy-nucleotidyltransferase-mediated dUTP nick end labeling reaction, active caspase-3, and Ki-67 immunohistochemistry. Alterations in elastin organization and deposition and in TGF-β expression were observed. In homozygous mice, the hyperexpression of RAGE resulted in histological changes resembling those changes characterizing human bronchopulmonary dysplasia (BPD). RAGE hyperexpression in the adult lung is associated with an increase of the alveolar destructive index and persistent inflammatory status leading to "destructive" emphysema. These results suggest an important role for RAGE in both alveolar development and lung homeostasis, and open new doors to working hypotheses on the pathogenesis of BPD and chronic obstructive pulmonary disease.

  19. Cost-effectiveness of paclitaxel plus cisplatin in advanced non-small-cell lung cancer

    PubMed Central

    Earle, C C; Evans, W K

    1999-01-01

    The aim of this study was to assess the cost-effectiveness of combination chemotherapy with paclitaxel/cisplatin, compared with standard etoposide/cisplatin in patients with advanced non-small cell lung cancer (NSCLC). We obtained the primary survival and resource utilization data from a large three-arm randomized trial comparing: paclitaxel 135 mg m−2 by 24-h intravenous (i.v.) infusion + cisplatin; paclitaxel 250 mg m−2 by 24-h i.v. infusion + cisplatin + granulocyte colony-stimulating factor (G-CSF); and standard etoposide/cisplatin in patients with stage IIIb or IV NSCLC. We also modelled the regimens with paclitaxel 135 mg m−2 + cisplatin administered as an outpatient by 3-h infusion, as clinical data suggest that this is equivalent to 24-h infusion. We collected costing data from the Ottawa Regional Cancer Centre and applied it to the resources consumed in the randomized trial. We integrated these data into the Statistics Canada POpulation HEalth Model (POHEM), which generated hypothetical cohorts of patients treated with each regimen. The POHEM model assigned diagnostic work-up, treatment, disease progression and survival characteristics to each individual in these cohorts and tabulated the costs associated with each. We did sensitivity analyses around the costs of chemotherapy and its administration, and the survival differences between the two regimens. All costs are in 1997 Canadian dollars ($1.00 Canadian ˜ £0.39 sterling). The perspective is that of the Canadian health care system. In the trial, the two paclitaxel-containing arms had almost identical survival curves with a median survival of 9.7 months compared with 7.4 months for etoposide/cisplatin. As administered in the trial, paclitaxel/cisplatin cost $76 370 per life-year gained (LYG) and paclitaxel/cisplatin/G-CSF $138 578 per LYG relative to etoposide/cisplatin. However, when modelled as an outpatient 3-h infusion, paclitaxel/cisplatin was moderately cost-effective at $30 619 per LYG

  20. Update on taxanes in the first-line treatment of advanced non-small-cell lung cancer.

    PubMed

    Socinski, M A

    2014-10-01

    Based on demonstrated favourable risk-benefit profiles, taxanes remain a key component in the first-line standard of care for advanced non-small-cell lung cancer (nsclc) and nsclc subtypes. In 2012, a novel taxane, nab-paclitaxel (Abraxane: Celgene Corporation, Summit, NJ, U.S.A.), was approved, in combination with carboplatin, for the first-line treatment of locally advanced or meta-static nsclc. The approval was granted because of demonstrated improved antitumour activity and tolerability compared with solvent-based paclitaxel-carboplatin in a phase iii trial. This review focuses on the evolution of first-line taxane therapy for advanced nsclc and the new options and advances in taxane therapy that might address unmet needs in advanced nsclc.

  1. Is the chemotherapy era in advanced non-small cell lung cancer really over? Maybe not yet.

    PubMed

    Lo Russo, Giuseppe; Imbimbo, Martina; Garassino, Marina Chiara

    2016-06-02

    Lung cancer is one of the most frequently diagnosed tumors in both the male and female population. In Italy it is the leading cause of cancer deaths in men and the third in women. Although the 5-year survival rate has moderately increased in the last years, the diagnosis remains associated with a very poor prognosis. However, in the last decade significant progress has been made, also in the treatment of advanced-stage non-small cell lung cancer. The advent of targeted therapies and the recent explosion of immunotherapy seem to have limited the role of chemotherapy. But is this completely true? The aim of this editorial is to discuss some of the most controversial aspects of the therapeutic scenario in non-small cell lung cancer, with particular attention to the role that chemotherapy still plays.

  2. Molecular Evolution Patterns in Metastatic Lymph Nodes Reflect the Differential Treatment Response of Advanced Primary Lung Cancer.

    PubMed

    Um, Sang-Won; Joung, Je-Gun; Lee, Hyun; Kim, Hojoong; Kim, Kyu-Tae; Park, Jinha; Hayes, D Neil; Park, Woong-Yang

    2016-11-15

    Tumor heterogeneity influences the clinical outcome of patients with cancer, and the diagnostic method to measure the tumor heterogeneity needs to be developed. We analyzed genomic features on pairs of primary and multiple metastatic lymph nodes from six patients with lung cancer using whole-exome sequencing and RNA sequencing. Although somatic single-nucleotide variants were shared in primary lung cancer and metastases, tumor evolution predicted by the pattern of genomic alterations was matched to anatomic location of the tumors. Four of six cases exhibited a branched clonal evolution pattern. Lymph nodes with acquired somatic variants demonstrated resistance to the cancer treatment. In this study, we demonstrated that multiple biopsies and sequencing strategies for different tumor regions are required for a comprehensive understanding of the landscape of genetic alteration and for guiding targeted therapy in advanced primary lung cancer. Cancer Res; 76(22); 6568-76. ©2016 AACR.

  3. Advances in the Development of Molecularly Targeted Agents in Non-Small-Cell Lung Cancer.

    PubMed

    Dolly, Saoirse O; Collins, Dearbhaile C; Sundar, Raghav; Popat, Sanjay; Yap, Timothy A

    2017-04-04

    Non-small-cell lung cancer (NSCLC) remains a significant global health challenge and the leading cause of cancer-related mortality. The traditional 'one-size-fits-all' treatment approach has now evolved into one that involves personalized strategies based on histological and molecular subtypes. The molecular era has revolutionized the treatment of patients harboring epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK) and ROS1 gene aberrations. In the appropriately selected population, anti-tumor agents against these molecular targets can significantly improve progression-free survival. However, the emergence of acquired resistance is inevitable. Novel potent compounds with much improved and rational selectivity profiles, such as third-generation EGFR T790M resistance mutation-specific inhibitors, have been developed and added to the NSCLC armamentarium. To date, attempts to overcome resistance bypass pathways through downstream signaling blockade has had limited success. Furthermore, the majority of patients still do not harbor known driver genetic or epigenetic alterations and/or have no new available treatment options, with chemotherapy remaining their standard of care. Several potentially actionable driver aberrations have recently been identified, with the early clinical development of multiple inhibitors against these promising targets currently in progress. The advent of immune checkpoint inhibitors has led to significant benefit for advanced NSCLC patients with durable responses observed. Further interrogation of the underlying biology of NSCLC, coupled with modern clinical trial designs, is now required to develop novel targeted therapeutics rationally matched with predictive biomarkers of response, so as to further advance NSCLC therapeutics through the next decade.

  4. Individual difficulties and resources – a qualitative analysis in patients with advanced lung cancer and their relatives

    PubMed Central

    Sparla, Anika; Flach-Vorgang, Sebastian; Villalobos, Matthias; Krug, Katja; Kamradt, Martina; Coulibaly, Kadiatou; Szecsenyi, Joachim; Thomas, Michael; Gusset-Bährer, Sinikka; Ose, Dominik

    2016-01-01

    Purpose Lung cancer is a disease with a high percentage of patients diagnosed in an advanced stage. In a situation of palliative treatment, both patients and their relatives experience diverse types of distress and burden. Little research has been done to identify the individual difficulties and resources for patients with advanced lung cancer and their relatives. Especially, standardized questionnaire-based exploration may not assess the specific distressing issues that pertain to each individual on a personal level. The purpose of this qualitative study is to explore and compare individual difficulties and resources for lung cancer patients and their relatives within the palliative care context. Methods Data were collected by qualitative interviews. A total of 18 participants, nine patients diagnosed with advanced lung cancer (International Classification of Diseases, tenth edition, diagnosis C-34, stage IV) starting or receiving palliative treatment and nine relatives, were interviewed. Data were interpreted through qualitative content analysis. Results We identified four main categories of difficulties: communication and conflicts, home and everyday life, thinking about cancer, and treatment trajectory. In general, difficulties were related to interpersonal relationships as well as to impact of chemotherapy. Family, professional caregivers, and social life were significant resources and offered support to both patients and relatives. Conclusion Results suggest that patient and relative education could reduce difficulties in several areas. Patients seem to struggle with the fear of not having any perspective in therapy. Relatives seem to experience helplessness regarding their partner’s deterioration and have to handle their own life and the care work simultaneously. The most important resource for both patients and relatives is their family. In addition, professional lung cancer nurses support relatives in an emotional and organizational way. Intense

  5. Combining chemotherapy with epidermal growth factor receptor inhibition in advanced non-small cell lung cancer

    PubMed Central

    Leung, Linda; Loong, Herbert

    2012-01-01

    Treatment of advanced stage lung cancer is changing rapidly. With the new found knowledge on molecular targets such as the epidermal growth factor receptor (EGFR), effective therapy is now available in a selected population with the target mutation. Single-agent epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) is a standard first-line therapy for patients with activating-EGFR mutation such as base-pair deletion in exon 19 or point mutation at exon 21. At the same time, this class of drugs may be combined with chemotherapy. Studies on the concurrent combination of chemotherapy and EGFR-TKI confirmed a lack of efficacy. A phase II study on sequential intercalated combination has demonstrated an improvement in progression-free survival (PFS), but this needs to be validated by the ongoing phase III study. The third approach is to combine EGFR-TKI as maintenance therapy after tumour response or stable disease to cytotoxic chemotherapy. Two phase III studies have shown improvement in PFS, but the use of biomarkers for the selection of maintenance therapy remains debatable. Cetuximab is a monoclonal antibody against EGFR and its combination with chemotherapy was shown to improve overall survival in an unselected population. A new biomarker using the H-score will help to select patients for this combination. PMID:22754591

  6. EGFR Testing in Advanced Non-Small-Cell Lung Cancer, A Mini-Review.

    PubMed

    Sheikine, Yuri; Rangachari, Deepa; McDonald, Danielle C; Huberman, Mark S; Folch, Erik S; VanderLaan, Paul A; Costa, Daniel B

    2016-11-01

    Expert consensus guidelines have defined minimum requirements for routine testing and identification of classical epidermal growth factor (EGFR) mutations (ie, exon 19 deletions and exon 21 L858R substitution) and anaplastic lymphoma kinase (ALK) rearrangements in advanced non-small-cell lung cancers of adenocarcinoma histology, with the intent of permitting use of these predictive biomarkers to select patients who will derive maximal benefit from approved oral tyrosine kinase inhibitors (TKIs) directed against EGFR and ALK, respectively. However, the practice of precision medicine is incumbent upon optimal tumor sampling, accurate tumor testing, and informed application of results to patient care. We report on a brief review of EGFR testing methodologies (Sanger sequencing, allele-specific polymerase chain reaction, and targeted next-generation sequencing) to identify classical and other (ie, exon 18 G719X, exon 19 insertions, exon 20 insertions, exon 21 L861Q) EGFR mutations; practical considerations (type of tissue/biopsies with different success rates of DNA isolation, and timeliness of result-reporting to facilitate therapeutic decision-making); role of rebiopsy (to identify mechanisms of acquired resistance to first- and second-generation EGFR TKIs, most importantly EGFR-T790M); and clinical vignettes highlighting the nuances of testing in day-to-day practice.

  7. Advanced Mesodermal (Müllerian) Adenosarcoma of the Ovary: Metastases to the Lungs, Mouth, and Brain

    PubMed Central

    Daskalaki, A.; Xenaki, S.; Athanasakis, E.; Chrysos, E.; Chalkiadakis, G.

    2015-01-01

    Background. A malignant mixed Müllerian tumor (MMMT) is a malignant neoplasm found in the uterus, the ovaries, the fallopian tubes, and other parts of the body that contains both carcinomatous (epithelial tissue) and sarcomatous (connective tissue) components. Outcome of MMMTs is determined primarily by depth of invasion and stage. The metastatic background of these lesions is controversial and unknown. Case Report. A 75-year-old woman was admitted to the hospital with anorexia, weakness, and persistent coughing. The imaging exams revealed a solid, promiscuous lesion of 16 × 14 cm in dimensions located into the small pelvis, surrounding the uterus and the ovaries. The patient underwent exploratory laparotomy. The mass was removed and the histological examination of the specimen revealed an advanced mesodermal adenocarcinoma of the ovary (MMMT). Nine days after the operation the patient presented with metastatic lesions in the mouth as well as the lungs. Within a month after the discharge from the hospital metastatic lesions of the MMMT were also depicted in the CT brain scan. Conclusion. Despite the fact that sarcomas have a long-term metastatic potential, to our knowledge this is the first case of Müllerian adenosarcoma presenting with such extraperitoneal metastases. PMID:26844003

  8. Next Generation Respiratory Viral Vaccine System: Advanced and Emerging Bioengineered Human Lung Epithelia Model (HLEM) Organoid Technology

    NASA Technical Reports Server (NTRS)

    Goodwin, Thomas J.; Schneider, Sandra L.; MacIntosh, Victor; Gibbons, Thomas F.

    2010-01-01

    Acute respiratory infections, including pneumonia and influenza, are the S t" leading cause of United States and worldwide deaths. Newly emerging pathogens signaled the need for an advanced generation of vaccine technology.. Human bronchial-tracheal epithelial tissue was bioengineered to detect, identify, host and study the pathogenesis of acute respiratory viral disease. The 3-dimensional (3D) human lung epithelio-mesechymal tissue-like assemblies (HLEM TLAs) share characteristics with human respiratory epithelium: tight junctions, desmosomes, microvilli, functional markers villin, keratins and production of tissue mucin. Respiratory Syntial Virus (RSV) studies demonstrate viral growth kinetics and membrane bound glycoproteins up to day 20 post infection in the human lung-orgainoid infected cell system. Peak replication of RSV occurred on day 10 at 7 log10 particles forming units per ml/day. HLEM is an advanced virus vaccine model and biosentinel system for emergent viral infectious diseases to support DoD global surveillance and military readiness.

  9. Detection of Chlamydia pneumoniae on cytospin preparations from bronchoalveolar lavage in COPD patients and in lung tissue from advanced emphysema.

    PubMed

    Brandén, Eva; Gnarpe, Judy; Hillerdal, Gunnar; Orre, Lotta; Sköld, C Magnus; Löfdahl, Magnus; Koyi, Hirsh; Tornling, Göran

    2007-01-01

    Chronic obstructive pulmonary disease (COPD) is associated with smoking but other etiological factors contribute. Chlamydia pneumoniae is an obligate intracellular bacterium causing both acute and chronic respiratory tract infections. Studies have revealed an association between chronic C. pneumoniae infection and COPD, asthma and lung cancer but there have been difficulties detecting C. pneumoniae in the bronchial tree. Cytospin slides prepared from bronchoalveolar lavage (BAL) fluid from 14 patients with COPD, 10 healthy smokers (S) and 7 non smokers (NS) were analyzed with a fluorescein isothiocyanate labeled monoclonal antibody to C. pneumoniae. Lung tissue from 24 patients with advanced emphysema who had undergone lung volume reduction surgery (LVRS) was examined with immunohistochemistry for C. pneumoniae. Archived serum samples for detection of specific C. pneumoniae antibodies by microimmunofluorescence were available for 30 of the BAL subjects and 11 of LVRS patients. C. pneumoniae elementary body like structures were found in 29% of cytospin specimens from COPD patients, 14% of NS and 10% of HS. C. pneumoniae was detected in lung tissue in 8%. COPD patients had higher titres of IgG and IgA than NS and S. There was no association between occurrence of C. pneumoniae in BAL fluid and antibody titres. In conclusion, the assays used for detection of C. pneumoniae in lung tissue are feasible, and could be adapted in adequately powered studies to further confirm an association between C. pneumoniae infection and COPD.

  10. Clinical outcomes of cytoreductive surgery combined with intrapleural perfusion of hyperthermic chemotherapy in advanced lung adenocarcinoma with pleural dissemination

    PubMed Central

    Yi, Eunjue; Kim, Daejoong; Cho, Sukki; Kim, Kwhanmien

    2016-01-01

    Background This study aimed to investigate the safety and feasibility of intrapleural perfusion hyperthermic chemotherapy (IPHC) followed by cytoreductive surgery as a part of multimodal strategy for the treatment of advanced lung adenocarcinoma. Methods Medical records of advanced lung cancer patients with pleural dissemination who underwent surgical treatment between 2003 and 2013 were reviewed retrospectively. Enrolled patients were divided into a surgery group comprising patients who underwent surgery only and an IPHC group, which consisted of patients who underwent surgery combined with IPHC. Results A total of 33 patients were enrolled in this study. Twenty-three patients underwent IPHC after surgical resection, and 10 patients underwent surgical resection only. The complication rate of the IPHC group was estimated to be 34.8% (8 cases), none of which included postoperative mortality. The complication rate of the surgery group was 40.0% (4 cases), which included one postoperative mortality. The 6-month, 1-year, and 3-year overall survival rates for the IPHC group were 95.7%, 91.3% and 38.6%, respectively, while those of the surgery group were 80.0%, 80.0% and 37.5%. The 6-month, 1-year and 3-year progression-free survival rates for the IPHC group were 87.0%, 47.8% and 24.3%, while those of surgery group were 44.4%, 33.3% and 0.0%, respectively. There were significant differences in overall survival rates between two groups (P=0.045); however, progression-free survival was not different between the two groups. Conclusions IPHC combined with cytoreductive surgery for advanced lung adenocarcinoma associated with pleural seeding could be performed safely and feasible. It would be part of multimodality therapy for certain category of advanced lung adenocarcinoma. However, the long-term benefits for survival is uncertain. More extensive and precisely designed studies are warranted to further evaluate the effectiveness of IPHC. PMID:27499943

  11. Caspase 8 polymorphisms contribute to the prognosis of advanced lung adenocarcinoma patients after platinum-based chemotherapy.

    PubMed

    Liu, Di; Xu, Wen; Ding, Xi; Yang, Yang; Lu, Yanlin; Fei, Ke; Su, Bo

    2017-02-16

    Lung cancer is the leading cause of cancer deaths in China, and about 60% of the cases are diagnosed with histological adenocarcinoma. The caspase 8 (CASP8) gene is a critical initiator of the extrinsic apoptosis pathway. To explore the relationship between tagSNPs or haplotypes of CASP8 and the efficacy of platinum-based chemotherapy in advanced lung adenocarcinoma patients of China, we recruited 555 advanced adenocarcinoma patients. We extracted the genomic DNA from patients' peripheral blood samples and sequenced tagSNPs of CASP8. We calculated the individual haplotype of CASP8 frequencies using the PHASE 2.0 program. The association between CASP8 tagSNPs and overall survival (OS) was calculated by univariate and multivariate Cox regression analysis. A univariate logistic regression analysis was done to analyze the CASP8 tagSNPs and the toxicity of platinum-based chemotherapy. The same statistical methods were used for exploring haplotypes of CASP8. Rs3769821 and rs1045494 of CASP8 were independent prognosis factors for overall survival (OS) using multivariate Cox's regression models. For the haplotype of the seven tagSNPs, haplotype AGGAAAGA was correlated with the efficacy of platinum-based chemotherapy. The polymorphisms of CASP8, rs7608692, and haplotype AGAACAG correlated with neutropenia toxicity. The haplotype GGGGAAA was associated with thrombocytopenia toxicity. We conclude that the polymorphisms of CASP8 contribute to the prognosis of advanced lung adenocarcinoma and influence the quality of life and survival.

  12. Apatinib as post second-line therapy in EGFR wild-type and ALK-negative advanced lung adenocarcinoma

    PubMed Central

    Fang, Shen-Cun; Zhang, Hai-Tao; Zhang, Ying-Ming; Xie, Wei-Ping

    2017-01-01

    In the absence of a driver mutation, chemotherapy is the standard treatment option as first- and second-line therapy for advanced non-small-cell lung cancer (NSCLC). Though a large number of patients are suitable for post second-line therapies, the quality and quantity of the available drugs in this setting is poor. Apatinib, a small molecule vascular endothelial growth factor receptor-2 (VEGFR-2) tyrosine kinase inhibitor, is a first-generation oral antiangiogenesis drug approved in the People’s Republic of China for use as a subsequent line of treatment for advanced gastric cancer. Herein, we report three cases of advanced NSCLC with epidermal growth factor receptor wild-type and anaplastic lymphoma kinase-negative status, wherein the patients showed partial response to apatinib. Moreover, the three patients have achieved a progression-free survival of 2.8, 5.8, and 6 months, respectively. The main toxicities were hypertension, proteinuria, and hand–foot syndrome. Apatinib may provide an additional option for the treatment of advanced NSCLC, especially for advanced lung adenocarcinoma without a driver mutation. PMID:28176910

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

    PubMed

    Rooney, Claire; Sethi, Tariq

    2015-10-01

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

  14. RFS2000 (9-nitrocamptothecin) in advanced small cell lung cancer, a phase II study of the EORTC New Drug Development Group.

    PubMed

    Punt, C J A; de Jonge, M J A; Monfardini, S; Daugaard, G; Fiedler, W; Baron, B; Lacombe, D; Fumoleau, P

    2004-06-01

    Camptothecins have shown efficacy in terms of response rate in patients with small cell lung cancer (SCLC). RFS2000 is a new camptothecin derivative, which has shown objective responses in various tumour types. The aim of this phase II study was to determine the objective response rate of RFS2000 in patients with sensitive and refractory SCLC. RFS2000 was given orally at 1.5 mg/m(2) per day for five consecutive days (five days on - two days off) on a continuous basis. Patients were evaluated weekly for toxicity and every six weeks for response. Thirty seven patients were included, 36 patients (14 with sensitive and 22 with refractory SCLC) were evaluable for toxicity, and 35 patients were evaluable for response. No objective responses were observed. Toxicity was acceptable, with myelosuppression, nausea/vomiting, and diarrhoea as the main toxicities. RFS2000 therefore has an acceptable toxicity profile but is not active as a single agent in SCLC.

  15. Association between vascular-poor area of primary tumors and epidermal growth factor receptor gene status in advanced lung adenocarcinoma.

    PubMed

    Togashi, Yosuke; Masago, Katsuhiro; Kubo, Takeshi; Fujimoto, Daichi; Sakamori, Yuichi; Nagai, Hiroki; Kim, Young Hak; Togashi, Kaori; Mishima, Michiaki

    2012-12-01

    Mutation of the epidermal growth factor receptor gene (EGFR mutation) is a very important marker in the treatment for non-small cell lung cancer. Since signaling from this receptor induces tumor-associated angiogenesis, we hypothesized that lung cancers with EGFR mutations tend to develop locally with increased angiogenesis. Thus, the association between vascular-poor area of primary tumors and EGFR status was retrospectively investigated in advanced lung adenocarcinomas. To assess vascular-poor area, contrast-enhanced computed tomography scans taken before initial treatment for lung cancer were analyzed, together with primary tumor location (peripheral or central) and size. We analyzed 178 patients with advanced lung adenocarcinoma. EGFR mutations were detected in 95 of the 178 patients (53.4 %). EGFR mutation was found to be significantly related to women (P = 0.0070), never-smokers (P < 0.0001), and tumors without vascular-poor area (P < 0.0001). Based on a multivariate analysis, presence of EGFR mutations was independently associated with never-smokers (P = 0.0046), lack of vascular-poor area (P = 0.0001), and tumor size >30 mm (P = 0.0080). EGFR mutations were found in 41 of 51 never-smokers without vascular-poor area (80.4 %), 19 of 36 never-smokers with vascular-poor area (52.8 %), 19 of 37 current or former-smokers without vascular-poor area (51.4 %), and 16 of 54 current or former-smokers with vascular-poor area (29.6 %). This study showed an association between vascular-poor area of primary tumors and EGFR status. As a consequence, evaluation using a combination of smoking status and vascular-poor area allows us to predict presence of EGFR mutations at a high frequency.

  16. SU-F-BRF-11: Dose Rearrangement in High Dose Locally Advanced Lung Patients Based On Perfusion Imaging

    SciTech Connect

    Matrosic, C; Jarema, D; Kong, F; McShan, D; Stenmark, M; Owen, D; Ten Haken, R; Matuszak, M

    2014-06-15

    Purpose: The use of mean lung dose (MLD) limits allows individualization of lung patient tumor doses at safe levels. However, MLD does not account for local lung function differences between patients, leading to toxicity variability at the same MLD. We investigated dose rearrangement to minimize dose to functional lung, as measured by perfusion SPECT, while maintaining target coverage and conventional MLD limits. Methods: Retrospective plans were optimized for 15 locally advanced NSCLC patients enrolled in a prospective imaging trial. A priority-based optimization system was used. The baseline priorities were (1) meet OAR dose constraints, (2) maximize target gEUD, and (3) minimize physical MLD. As a final step, normal tissue doses were minimized. To determine the benefit of rearranging dose using perfusion SPECT, plans were reoptimized to minimize functional lung gEUD as the 4th priority. Results: When only minimizing physical MLD, the functional lung gEUD was 10.8+/−5.0 Gy (4.3–19.8 Gy). Only 3/15 cases showed a decrease in functional lung gEUD of ≥4% when rearranging dose to minimize functional gEUD in the cost function (10.5+/−5.0 Gy range 4.3−19.7). Although OAR constraints were respected, the dose rearrangement resulted in ≥10% increases in gEUD to an OAR in 4/15 cases. Only slight reductions in functional lung gEUD were noted when omitting the minimization of physical MLD, suggesting that constraining the target gEUD minimizes the potential to redistribute dose. Conclusion: Prioritydriven optimization permits the generation of plans that respect traditional OAR limits and target coverage, but with the ability to rearrange dose based on functional imaging. The latter appears to be limited due to the decreased solution space when constraining target coverage. Since dose rearrangement may increase dose to other OARs, it is also worthwhile to investigate global biomarkers of lung toxicity to further individualize treatment in this population

  17. Advanced sickle cell associated interstitial lung disease presenting with cor pulmonale in a Nigerian.

    PubMed

    Fawibe, Ademola Emmanuel; Kolo, Philip Manman; Ogunmodede, James Ayodele; Desalu, Olufemi Olumuyiwa; Salami, Kazeem Alakija

    2012-04-01

    Previous studies have reported abnormal pulmonary function and pulmonary hypertension among Nigerians with sickle cell disease, but there is no report of interstitial lung disease among them. We report a Nigerian sickle cell patient who presented with computed tomography proven interstitial lung disease complicated by pulmonary hypertension and cor pulmonale.

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

    SciTech Connect

    Rusch, V.W.; Griffin, B.R.; Livingston, R.B. )

    1989-10-01

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

  19. Nivolumab versus Docetaxel in Advanced Squamous-Cell Non–Small-Cell Lung Cancer

    PubMed Central

    Brahmer, Julie; Reckamp, Karen L.; Baas, Paul; Crinò, Lucio; Eberhardt, Wilfried E.E.; Poddubskaya, Elena; Antonia, Scott; Pluzanski, Adam; Vokes, Everett E.; Holgado, Esther; Waterhouse, David; Ready, Neal; Gainor, Justin; Frontera, Osvaldo Arén; Havel, Libor; Steins, Martin; Garassino, Marina C.; Aerts, Joachim G.; Domine, Manuel; Paz-Ares, Luis; Reck, Martin; Baudelet, Christine; Harbison, Christopher T.; Lestini, Brian; Spigel, David R.

    2015-01-01

    Background Patients with advanced squamous-cell non–small-cell lung cancer (NSCLC) who have disease progression during or after first-line chemotherapy have limited treatment options. This randomized, open-label, international, phase 3 study evaluated the efficacy and safety of nivolumab, a fully human IgG4 programmed death 1 (PD-1) immune-checkpoint–inhibitor antibody, as compared with docetaxel in this patient population. Methods We randomly assigned 272 patients to receive nivolumab, at a dose of 3 mg per kilogram of body weight every 2 weeks, or docetaxel, at a dose of 75 mg per square meter of body-surface area every 3 weeks. The primary end point was overall survival. Results The median overall survival was 9.2 months (95% confidence interval [CI], 7.3 to 13.3) with nivolumab versus 6.0 months (95% CI, 5.1 to 7.3) with docetaxel. The risk of death was 41% lower with nivolumab than with docetaxel (hazard ratio, 0.59; 95% CI, 0.44 to 0.79; P<0.001). At 1 year, the overall survival rate was 42% (95% CI, 34 to 50) with nivolumab versus 24% (95% CI, 17 to 31) with docetaxel. The response rate was 20% with nivolumab versus 9% with docetaxel (P = 0.008). The median progression-free survival was 3.5 months with nivolumab versus 2.8 months with docetaxel (hazard ratio for death or disease progression, 0.62; 95% CI, 0.47 to 0.81; P<0.001). The expression of the PD-1 ligand (PD-L1) was neither prognostic nor predictive of benefit. Treatment-related adverse events of grade 3 or 4 were reported in 7% of the patients in the nivolumab group as compared with 55% of those in the docetaxel group. Conclusions Among patients with advanced, previously treated squamous-cell NSCLC, overall survival, response rate, and progression-free survival were significantly better with nivolumab than with docetaxel, regardless of PD-L1 expression level. (Funded by Bristol-Myers Squibb; CheckMate 017 ClinicalTrials.gov number, NCT01642004.) PMID:26028407

  20. Biomarkers and Targeted Systemic Therapies in Advanced Non-Small Cell Lung Cancer

    PubMed Central

    Kumar, Mukesh; Vinicius, Ernani; Owonikoko, Taofeek K.

    2015-01-01

    The last decade has witnessed significant growth in therapeutic options for patients diagnosed with lung cancer. This is due in major part to our improved technological ability to interrogate the genomics of cancer cells, which has enabled the development of biologically rational anticancer agents. The recognition that lung cancer is not a single disease entity dates back many decades to the histological subclassification of malignant neoplasms of the lung into subcategories of small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). While SCLC continues to be regarded as a single histologic and therapeutic category, the NSCLC subset has undergone additional subcategorizations with distinct management algorithms for specific histologic and molecular subtypes. The defining characteristics of these NSCLC subtypes have evolved into important tools for prognosis and for predicting the likelihood of benefit when patients are treated with anticancer agents. PMID:26187108

  1. Management of advanced non-small cell lung cancers with known mutations or rearrangements: latest evidence and treatment approaches.

    PubMed

    Shea, Meghan; Costa, Daniel B; Rangachari, Deepa

    2016-04-01

    Precision oncology is now the evidence-based standard of care for the management of many advanced non-small cell lung cancers (NSCLCs). Expert consensus has defined minimum requirements for routine testing and identification of epidermal growth factor (EGFR) mutations (15% of tumors harbor EGFR exon 19 deletions or exon 21 L858R substitutions) and anaplastic lymphoma kinase (ALK) rearrangements (5% of tumors) in advanced lung adenocarcinomas (ACs). Application of palliative targeted therapies with oral tyrosine kinase inhibitors (TKIs) in advanced/metastatic lung ACs harboring abnormalities in EGFR (gefitinib, erlotinib, afatinib) and ALK/ROS1/MET (crizotinib) has consistently led to more favorable outcomes compared with traditional cytotoxic agents. In addition, mutations leading to resistance to first-line EGFR and ALK TKIs can now be successfully inhibited by soon to be approved third-generation EGFR TKIs (osimertinib, rociletinib) and second-generation ALK TKIs (ceritinib, alectinib). Notably, increasing feasibility, accessibility, and application of molecular profiling technologies has permitted dynamic growth in the identification of actionable driver oncogenes. Emerging genomic aberrations for which TKIs have shown impressive results in clinical trials and expansion of drug labels for approved agents are awaited include ROS1 rearrangements (1-2% of tumors, drug: crizotinib) and BRAF-V600E mutations (1-3% of tumors, drugs: vemurafenib, dafrafenib + trametinib). Evolving genomic events in which TKI responses have been reported in smaller series include MET exon 14 skipping mutations (2-4% of tumors, drug: crizotinib); high-level MET amplification (1-2% of tumors, drug: crizotinib); RET rearrangements (1% of tumors, drug: cabozantinib); and ERBB2 mutations (2-3% of tumors, drug: afatinib), among others. Unfortunately, the most common genomic event in NSCLC, KRAS mutations (25-30% of tumors), is not targetable with approved or in development small molecule

  2. Clinical efficacy of CyberKnife combined with chemotherapy and hyperthermia for advanced non-small cell lung cancer.

    PubMed

    Wang, Yuan-Yuan; Lin, Si-Xiang; Yang, Gui-Qing; Liu, Han-Chen; Sun, Dong-Ning; Wang, Yi-Shan

    2013-05-01

    Non-small cell lung cancer (NSCLC) is responsible for at least 80% of all lung tumors and has a poor prognosis, since 75% of NSCLCs are first diagnosed at an advanced stage. This study was conducted to evaluate the therapeutic efficacy of CyberKnife in combination with chemotherapy and hyperthermia for selected patients with advanced non-small cell lung cancer (NSCLC). Clinical charts, imaging and pathology reports of patients with advanced NSCLC who underwent CyberKnife therapy in our Tumor Therapy Center were retrospectively reviewed. Clinical efficacy was evaluated for local control, Karnofsky performance status scale (KPS) and toxicity analysis. A total of 119 patients with 136 target areas were evaluated. A prescribed dose of 24-51 Gy to the gross tumor volume was delivered in 3-6 fractions. The median prescription dose was 35 Gy (mean, 34.73±4.80 Gy), with an average of five fractions. Patients, who voluntarily participated in the study, were assigned to one of three groups, which were as follows: CyberKnife therapy alone, CyberKnife combined with chemotherapy and CyberKnife combined with chemotherapy and hyperthermia. The median follow-up period was 6 months and curative efficiencies were 62.16, 71.79 and 90.70%, respectively, as determined by radiographic and clinical re-examinations. Patients treated by CyberKnife combined with chemotherapy and hyperthermia achieved optimal improvement in the aspect of KPS, which was statistically different compared to the other two groups (P<0.05). In conclusion, our results indicated that CyberKnife combined with chemotherapy and hyperthermia achieved favorable short-term outcomes and may be a more viable option for patients with advanced NSCLC. However, further investigations are required to evaluate long-term outcomes.

  3. Clinical outcomes of advanced non-small-cell lung cancer patients with EGFR mutation, ALK rearrangement and EGFR/ALK co-alterations

    PubMed Central

    Chen, Hua-Jun; Zhou, Qing; Yan, Li-Xu; Xie, Zhi; Su, Jian; Chen, Zhi-Hong; Tu, Hai-Yan; Yan, Hong-Hong; Wang, Zhen; Xu, Chong-Rui; Jiang, Ben-Yuan; Wang, Bin-Chao; Bai, Xiao-Yan; Zhong, Wen-Zhao; Wu, Yi-Long; Yang, Jin-Ji

    2016-01-01

    The co-occurrence of epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements constitutes a rare molecular subtype of non-small-cell lung cancer (NSCLC). Herein, we assessed the clinical outcomes and incidence of acquired resistance to tyrosine kinase inhibitors (TKIs) in this subtype. So we enrolled 118 advanced NSCLC treated with TKIs. EGFR mutations and ALK rearrangements were detected by DNA sequencing or Scorpion amplification refractory mutation system and fluorescence in situ hybridization respectively. Immunohistochemistry was used to evaluate the activation of associated proteins. We found that nine in ten patients with EGFR/ALK co-alterations had good response with first-line EGFR TKI, and the objective response rate (ORR) of EGFR TKIs was 80% (8/10) for EGFR/ALK co-altered and 65.5% (55/84) for EGFR-mutant (P = 0.57), with a median progression-free survival (PFS) of 11.2 and 13.2 months, (hazard ratio [HR]=0.95, 95% [CI], 0.49-1.84, P= 0.87). ORR of crizotinib was 40% (2/5) for EGFR/ALK co-altered and 73.9% (17/23) for ALK-rearranged (P= 0.29), with a median PFS of 1.9 and 6.9 months (hazard ratio [HR], 0.40; 95% [CI] 0.15-1.10, P = 0.08). The median overall survival (OS) was 21.3, 23.7, and 18.5 months in EGFR-mutant, ALK-rearranged, and EGFR/ALK co-altered (P= 0.06), and there existed a statistically significant difference in OS between ALK-rearranged and EGFR/ALK co-altered (P=0.03). Taken together, the first-line EGFR-TKI might be the reasonable care for advanced NSCLC harbouring EGFR/ALK co-alterations, whether or nor to use sequential crizotinib should be guided by the status of ALK rearrangement and the relative level of phospho-EGFR and phospho-ALK. PMID:27533086

  4. Combined therapy of percutaneous cryoablation and traditional Chinese medicine can be a promising strategy for elderly or advanced lung cancer patients based on a retrospective clinical study.

    PubMed

    Gao, Lei; Li, Quanwang; Jiang, Min; Liu, Chuanbo; Song, Zilin; Bao, Xiaoling; Shen, Yang; Liu, Guijian; Hu, Kaiwen

    2014-08-01

    Presently, elderly and advanced lung cancer patients have very limited treatment options. With no promising therapy, treatment of these patients is challenging. We have reviewed 119 primary lung cancer patients who received a combined percutaneous cryoablation and traditional Chinese medicine therapy (Cryo-TCM therapy) between 2005 and 2013. Out of 119 patients, 84.1% patients were elderly or advanced lung cancer when receiving cryoablation. Overall Survival time from the time of Diagnosis (DOS) and Cryoablation (COS) was 19 and 10 months respectively, which were longer than data previously published. Patients who accepted only Cryo-TCM therapy got similar DOS as those who were treated with Cryo-TCM and other classic anticancer therapies. Thus, Cryo-TCM therapy can prolong the survival time and can be used as the main therapy for the elderly or advanced lung cancer patients in China both in quality of life and cost effectiveness.

  5. Managing treatment-related adverse events associated with egfr tyrosine kinase inhibitors in advanced non-small-cell lung cancer

    PubMed Central

    Hirsh, V.

    2011-01-01

    Non-small-cell lung cancer (nsclc) has the highest prevalence of all types of lung cancer, which is the second most common cancer and the leading cause of cancer-related mortality in Canada. The need for more effective and less toxic treatment options for nsclc has led to the development of agents targeting the epidermal growth factor receptor (egfr)–mediated signalling pathway, such as egfr tyrosine kinase inhibitors (egfr-tkis). Although egfr-tkis are less toxic than traditional anti-neoplastic agents, they are commonly associated with acneiform-like rash and diarrhea. This review summarizes the clinical presentation and causes of egfr-tki–induced rash and diarrhea, and presents strategies for effective assessment, monitoring, and treatment of these adverse effects. Strategies to improve the management of egfr-tki–related adverse events should improve clinical outcomes, compliance, and quality of life in patients with advanced nsclc. PMID:21655159

  6. Pulmonary neuroendocrine cell system in pediatric lung disease-recent advances.

    PubMed

    Cutz, Ernest; Yeger, Herman; Pan, Jie

    2007-01-01

    The airway epithelium of human and animal lungs contains highly specialized pulmonary neuroendocrine cells (PNEC), distributed as solitary cells and as innervated clusters, neuroepithelial bodies (NEB). The designation "PNEC system" stems from the expression of both neural and endocrine cell phenotypes, including the synthesis and release of amine (serotonin, 5-HT) and a variety of neuropeptides (that is, bombesin). The role and function of PNEC in the lung have remained a subject of speculation for many years. During the last decade, studies using modern techniques of cellular and molecular biology revealed a complex functional role for PNEC, beginning during the early stages of lung development as modulators of fetal lung growth and differentiation and at the time of birth as airway O2 sensors involved in neonatal adaptation. Postnatally and beyond, PNEC/NEB are providers of a lung stem cell niche that is important in airway epithelial regeneration and lung carcinogenesis. The focus of this review is to present and discuss recent findings pertaining to the responses of PNEC to intrauterine environmental stimuli, ontogeny and molecular regulation of PNEC differentiation, innervation of NEB, and their role as airway chemoreceptors, including mechanisms of O2 sensing and chemotransmission of hypoxia stimulus. Abnormalities of PNEC/NEB have been reported in a variety of pediatric pulmonary disorders but the clinical significance or the mechanisms involved are unknown. The discussion on the possible role of PNEC/NEB in the pathogenesis and pathobiology of pediatric lung diseases includes congenital lung disorders, bronchopulmonary dysplasia, disorders of respiratory control, neuroendocrine hyperplasia of infancy, cystic fibrosis, bronchial asthma, and pulmonary hypertension.

  7. Limiting the risk of cardiac toxicity with esophageal-sparing intensity modulated radiotherapy for locally advanced lung cancers

    PubMed Central

    Panettieri, Vanessa; Ruben, Jeremy D.; Senthi, Sashendra

    2016-01-01

    Background Intensity modulated radiotherapy (IMRT) is routinely utilized in the treatment of locally advanced non-small cell lung cancer (NSCLC). RTOG 0617 found that overall survival was impacted by increased low (5 Gy) and intermediate (30 Gy) cardiac doses. We evaluated the impact of esophageal-sparing IMRT on cardiac doses with and without the heart considered in the planning process and predicted toxicity compared to 3D-conventional radiotherapy (3DCRT). Methods Ten consecutive patients with N2 Stage III NSCLC treated to 60 Gy in 30 fractions, between February 2012 and September 2014, were evaluated. For each patient, 3DCRT and esophageal-sparing IMRT plans were generated. IMRT plans were then created with and without the heart considered in the optimization process. To compare plans, the dose delivered to 95% and 99% of the target (D95% and D99%), and doses to the esophagus, lung and heart were compared by determining the volume receiving X dose (VXGy) and the normal tissue complication probability (NTCP) calculated. Results IMRT reduced maximum esophagus dose to below 60 Gy in all patients and produced significant reductions to V50Gy, V40Gy and esophageal NTCP. The cost of this reduction was a non-statistically, non-clinically significant increase in low dose (5 Gy) lung exposure that did not worsen lung NTCP. IMRT plans produced significant cardiac sparing, with the amount of improvement correlating to the amount of heart overlapping with the target. When included in plan optimization, for selected patients further sparing of the heart and improvement in heart NTCP was possible. Conclusions Esophageal-sparing IMRT can significantly spare the heart even if it is not considered in the optimization process. Further sparing can be achieved if plan optimization constrains low and intermediate heart doses, without compromising lung doses. PMID:27162670

  8. Comparative Effectiveness of Adjunctive Bevacizumab for Advanced Lung Cancer: The Cancer Research Network Experience

    PubMed Central

    Ritzwoller, Debra P.; Carroll, Nikki M.; Delate, Thomas; Hornbrook, Mark C.; Kushi, Lawrence; Aiello Bowles, Erin J.; Loggers, Elizabeth T.; Menter, Alex

    2016-01-01

    Introduction Bevacizumab plus carboplatin-paclitaxel (BCP) chemotherapy has FDA approval for advanced non-squamous, non-small cell lung cancer (NS-NSCLC) based upon improved survival in a clinical trial. However, sub-group analyses of this and other studies have suggested variable results by age and gender. Methods 1,605 HMO NS-NSCLC patients aged ≥ 21 years, diagnosed 2002–2010, who received carboplatin-paclitaxel (CP), with and without bevacizumab for first-line treatment of stage IIIB/IV disease were identified. Patients were categorized into three groups based on year of diagnosis and regimen during 120 days post-diagnosis: 1) diagnosed 2005–2010 and received BCP; 2) 2005–2010, CP (CP2005), and 3) 2002–2004, CP (CP2002). Survival differences between groups were estimated using Cox proportional hazard models with several propensity score adjustments for demographic, comorbidity, and tumor characteristics. Multi-variable sub-analyses were also estimated. Results Median survival was 12.3 months (inter quartile range [IQR] 6.0–29.1) for BCP patients versus 8.8 months (IQR 3.7–21.3) for CP2005 patients, and 7.5 months (IQR 3.8–15.6) for CP2002 patients. In the propensity score adjusted models, BCP demonstrated a significant survival benefit with a hazard ratio of BCP relative to CP2005 and CP2002 patients of 0.79 (95% CI 0.66–0.94) and 0.63 (95% CI 0.52–0.75) respectively. In the multivariable-adjusted sub-analyses, relative to the CP2005 cohort, the BCP hazard ratios for patients age <65 years, age ≥65 years, and females were 0.78 (95% CI 0.62–1.00), 0.74 (95% CI 0.54–1.00) and 0.77 (95% CI 0.58–1.00). Conclusions In this community-based, comparative effectiveness analysis, we found an overall survival benefit for adults receiving BCP compared to CP. PMID:24633407

  9. The National Lung Matrix Trial: translating the biology of stratification in advanced non-small-cell lung cancer

    PubMed Central

    Middleton, G.; Crack, L. R.; Popat, S.; Swanton, C.; Hollingsworth, S. J.; Buller, R.; Walker, I.; Carr, T. H.; Wherton, D.; Billingham, L. J.

    2015-01-01

    Background The management of NSCLC has been transformed by stratified medicine. The National Lung Matrix Trial (NLMT) is a UK-wide study exploring the activity of rationally selected biomarker/targeted therapy combinations. Patients and methods The Cancer Research UK (CRUK) Stratified Medicine Programme 2 is undertaking the large volume national molecular pre-screening which integrates with the NLMT. At study initiation, there are eight drugs being used to target 18 molecular cohorts. The aim is to determine whether there is sufficient signal of activity in any drug–biomarker combination to warrant further investigation. A Bayesian adaptive design that gives a more realistic approach to decision making and flexibility to make conclusions without fixing the sample size was chosen. The screening platform is an adaptable 28-gene Nextera next-generation sequencing platform designed by Illumina, covering the range of molecular abnormalities being targeted. The adaptive design allows new biomarker–drug combination cohorts to be incorporated by substantial amendment. The pre-clinical justification for each biomarker–drug combination has been rigorously assessed creating molecular exclusion rules and a trumping strategy in patients harbouring concomitant actionable genetic abnormalities. Discrete routes of pathway activation or inactivation determined by cancer genome aberrations are treated as separate cohorts. Key translational analyses include the deep genomic analysis of pre- and post-treatment biopsies, the establishment of patient-derived xenograft models and longitudinal ctDNA collection, in order to define predictive biomarkers, mechanisms of resistance and early markers of response and relapse. Conclusion The SMP2 platform will provide large scale genetic screening to inform entry into the NLMT, a trial explicitly aimed at discovering novel actionable cohorts in NSCLC. Clinical Trial ISRCTN 38344105. PMID:26410619

  10. CFB refractory maintenance

    SciTech Connect

    Johnson, R.C.

    1994-12-31

    The CFB maintenance manager has to make rapid-fire decisions regarding refractory maintenance during short or unscheduled turnarounds. This presentation offers a hands-on approach to expedient refractory failure analyses with specific repair recommendations. Photographs of most typical CFB refractory failures and their structural repairs are discussed. The most reliable repairs can be expected by using the latest state-of-the-art refractory materials and installation techniques. Refractory materials are consumable; therefore minor repairs should always be conducted at the first opportunity; this will preclude future major repairs. During a short or unscheduled outage, major repairs should be confined to the specific structural repair site; the removal of good, serviceable refractory is unnecessary under these conditions.

  11. Meta-analysis Exploring the Effectiveness of S-1-Based Chemotherapy for Advanced Non-Small Cell Lung Cancer.

    PubMed

    Sun, Xin; Sun, Li; Zhang, Shu-Ling; Xiong, Zhi-Cheng; Ma, Jie-Tao; Han, Cheng-Bo

    2017-01-01

    S-1 is a new oral fluoropyrimidine formulation that comprises tegafur, 5-chloro-2,4-dihydroxypyridine, and potassium oxonate. S-1 is designed to enhance antitumor activity and to reduce gastrointestinal toxicity. Several studies have demonstrated that both S-1 monotherapy and S-1 combination regimens showed encouraging efficacies and mild toxicities in the treatment of lung squamous cell carcinoma and adenocarcinoma. However, it is unclear whether S-1 can be used as standard care in advanced non-small cell lung cancer (NSCLC). The purpose of this meta-analysis was to assess the efficacy and safety of S-1-based chemotherapy, compared with standard chemotherapy, in patients with locally advanced or metastatic NSCLC. Thirteen randomized controlled trials (RCTs) involving 2,134 patients with a similar ratio of different pathological types were included. In first-line or second-line chemotherapy, compared with standard chemotherapy, S-1-based chemotherapy showed similar efficacy in terms of median overall survival (mOS), median progression free survival (mPFS), and objective response rate (ORR) (all P > 0.1), and significantly reduced the incidence of grade ≥ 3 hematological toxicities. In patients with locally advanced NSCLC receiving concurrent chemoradiotherapy, compared with standard chemoradiotherapy, significantly improved survival in the S-1-based chemotherapy was noted in terms of mOS and mPFS (risk radio [RR] = 1.289, P = 0.009; RR = 1.289, P = 0.000, respectively) with lower incidence of grade ≥ 3 neutropenia (RR = 0.453, P = 0.000). The present meta-analysis demonstrates that S-1-based chemotherapy shows similar benefits in advanced NSCLC and improves survival in locally advanced NSCLC, compared with standard treatment.

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

    PubMed

    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 (P<0.05). However, it showed no relationship with sex, smoking, hemoptysis, chest pain, dyspnea, histological type, clinical stage, and administration of chemotherapy (P>0.05). 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.

  13. Once-Weekly, High-Dose Stereotactic Body Radiotherapy for Lung Cancer: 6-Year Analysis of 60 Early-Stage, 42 Locally Advanced, and 7 Metastatic Lung Cancers

    SciTech Connect

    Salazar, Omar M. Sandhu, Taljit S.; Lattin, Paul B.; Chang, Jung H.; Lee, Choon K.; Groshko, Gayle A.; Lattin, Cheryl J.

    2008-11-01

    Purpose: To explore once-weekly stereotactic body radiotherapy (SBRT) in nonoperable patients with localized, locally advanced, or metastatic lung cancer. Methods and Materials: A total of 102 primary (89 untreated plus 13 recurrent) and 7 metastatic tumors were studied. The median follow-up was 38 months, the average patient age was 75 years. Of the 109 tumors studied, 60 were Stage I (45 IA and 15 IB), 9 were Stage II, 30 were Stage III, 3 were Stage IV, and 7 were metastases. SBRT only was given in 73% (40 Gy in four fractions to the planning target volume to a total dose of 53 Gy to the isocenter for a biologically effective dose of 120 Gy{sub 10}). SBRT was given as a boost in 27% (22.5 Gy in three fractions once weekly for a dose of 32 Gy at the isocenter) after 45 Gy in 25 fractions to the primary plus the mediastinum. The total biologically effective dose was 120 Gy{sub 10}. Respiration gating was used in 46%. Results: The overall response rate was 75%; 33% had a complete response. The overall response rate was 89% for Stage IA patients (40% had a complete response). The local control rate was 82%; it was 100% and 93% for Stage IA and IB patients, respectively. The failure rate was 37%, with 17% within the planning target volume. No Grade 3-4 acute toxicities developed in any patient; 12% and 7% of patients developed Grade 1 and 2 toxicities, respectively. Late toxicity, all Grade 2, developed in 3% of patients. The 5-year cause-specific survival rate for Stage I was 70% and was 74% and 64% for Stage IA and IB patients, respectively. The 3-year Stage III cause-specific survival rate was 30%. The patients with metastatic lung cancer had a 57% response rate, a 27% complete response rate, an 86% local control rate, a median survival time of 19 months, and 23% 3-year survival rate. Conclusions: SBRT is noninvasive, convenient, fast, and economically attractive; it achieves results similar to surgery for early or metastatic lung cancer patients who are older

  14. Talactoferrin in Treating Patients With Relapsed or Refractory Non-Small Cell Lung Cancer or Squamous Cell Head and Neck Cancer

    ClinicalTrials.gov

    2016-07-30

    Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma; Recurrent Metastatic Squamous Neck Cancer With Occult Primary; 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; Salivary Gland Squamous Cell Carcinoma; 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; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage III Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage III Verrucous Carcinoma of the Larynx; Stage III Verrucous Carcinoma of the Oral Cavity; 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

  15. Safety and feasibility of uniportal video-assisted thoracoscopic surgery for locally advanced non-small cell lung cancer

    PubMed Central

    Yao, Jie; Wang, Qi; Chang, Zhibo

    2016-01-01

    Background Conventional video-assisted thoracoscopic surgery (VATS) lobectomy for locally advanced non-small cell lung cancer (NSCLC) is a feasible and safe surgery in high-volume centers with significant VATS experience. Uniportal VATS lobectomy has been recently been reported to be a promising, less invasive approach. The purpose of this study is to explore the safety and feasibility of uniportal video-assisted thoracoscopic surgery (U-VATS) for the treatment of patients with locally advanced NSCLC. Methods From January 2013 to September 2015, a total of 132 patients with locally advanced NSCLC underwent U-VATS or open thoracotomy major pulmonary resections and standard mediastinal lymph node dissection. Patients were divided into two groups: (I) locally advanced NSCLC underwent U-VATS (U-VATS); (II) locally advanced NSCLC underwent open thoracotomy (open). A descriptive and retrospective study was performed, including the operative time, operative blood loss, postoperative chest tube duration, postoperative hospital stay, lymph node dissection, postoperative complications and postoperative recovery. Results A total of 132 patients with locally advanced NSCLC were included in this study: 64 (U-VATS) vs. 68 (open) patients. The patient demographic data was similar in both groups. Median operative time (157.0 vs. 160.6) and median number of lymph nodes (35.5 vs. 32.5) were similar in both groups. Chest tube duration and hospital of stay were statistically shorter in U-VATS group while rate of complications were higher in open thoracotomy group. One patient died on the 55th postoperative day because of tumor metastasis and bronchopleural fistula. A higher percentage of patients who underwent UVATS resections were able to receive adjuvant therapy timely compared to the open group. Conclusions Uniportal VATS major pulmonary resections and mediastinal lymph node dissection is a safe and feasible procedure for the treatment of locally advanced NSCLC. Particularly it is

  16. A phase I trial of temsirolimus and pemetrexed in patients with advanced non-small cell lung cancer

    PubMed Central

    Waqar, Saiama N.; Baggstrom, Maria Q.; Morgensztern, Daniel; Williams, Kristina; Rigden, Caron; Govindan, Ramaswamy

    2017-01-01

    Background Pemetrexed is an anti-folate chemotherapeutic agent approved for use in non-small cell lung cancer. Mammalian target of rapamycin (mTOR) pathway is implicated in lung cancer development, and is inhibited by temsirolimus. Methods We performed a phase I study evaluating the combination of pemetrexed and temsirolimus in advanced non-squamous non-small cell lung cancer (NSCLC). Results Eight patients were enrolled in this study. The dose limiting toxicities included grade 4 thrombocytopenia, grade 3 leukopenia and grade 3 neutopenia. The maximum tolerated dose was determined to be pemetrexed 375 mg/m2 intravenously on day 1 and temsirolimus 25 mg intravenously on days 1,8 and 15. No objective responses were noted, and 3 patients had stable disease as the best response. Conclusion The combination of pemetrexed and temsirolimus is feasible and well tolerated. This combination may be further evaluated in patients with mTOR pathway activation, particularly in patients with TSC1 or STK11 mutations. PMID:26780363

  17. Epidermal Growth Factor Receptor Mutated Advanced Non-Small Cell Lung Cancer: A Changing Treatment Paradigm.

    PubMed

    Pakkala, Suchita; Ramalingam, Suresh S

    2017-02-01

    Activating mutations in the epidermal growth factor receptor (EGFR) are present in approximately 15% of US patients with lung adenocarcinoma. EGFR tyrosine kinase inhibitors are associated with high response rate and progression-free survival for patients with non-small cell lung cancer with this genotype. Gefitinib, erlotinib, and afatinib are the EGFR tyrosine kinase inhibitors that are presently in clinical use. Understanding resistance mechanisms has led to the identification of a secondary mutational target, T790M, in more than half of patients, for which osimertinib has been approved. This article reviews the current treatments, resistance mechanisms, and strategies to overcome resistance.

  18. Pemetrexed for advanced stage nonsquamous non-small cell lung cancer: latest evidence about its extended use and outcomes

    PubMed Central

    Tomasini, Pascale; Barlesi, Fabrice; Mascaux, Celine; Greillier, Laurent

    2016-01-01

    Non-small cell lung cancer (NSCLC) is still the leading cause of cancer-related death, and the treatment of advanced NSCLC relies on systemic treatments. During the last decade, pemetrexed, an antifolate agent, gradually became a key component of the treatment for patients with advanced nonsquamous NSCLC. It has indeed been shown to be efficient for first-line, maintenance and second- or third-line treatment in this subgroup of NSCLC. Moreover, it is usually well tolerated, with few grade 3 and 4 toxicities. Several studies have tried to identify predictive biomarkers of pemetrexed efficacy. Due to pemetrexed’s mechanism of action, thymidilate synthase expression predictive value was investigated but could not be demonstrated. Currently, more than 400 trials of pemetrexed for the treatment of nonsquamous NSCLC are ongoing. PMID:27239238

  19. A comparison of ARMS and mutation specific IHC for common activating EGFR mutations analysis in small biopsy and cytology specimens of advanced non small cell lung cancer.

    PubMed

    Wang, Xueqing; Wang, Guoqing; Hao, Yueyue; Xu, Yinhong; Zhang, Lihua

    2014-01-01

    We have compared mutation analysis by Amplification Refractory Mutation System (ARMS) and epidermal growth factor receptor (EGFR) mutant-specific antibodies for their ability to detect two common activating EGFR mutations in a cohort of 115 advanced non-small cell lung cancer (NSCLC), including cytology material, core biopsy, and bronchoscopic biopsies. Assessment of EGFR mutation status was performed by using antibodies and ARMS assay specific to the two major forms of mutant EGFR, exon 19 deletion E746-A750 (c.2235_2249del15 or c.2236_2250del15, p. Glu746_Ala750 del) and exon 21 L858R point mutation (c.2573T>G, p.Leu858Arg). In this study the optimal buffer for antigen retrieval was sodium citrate (pH 6.0). Q score was used to evaluate the specific mutant EGFR proteins expression. Validation using clinical material showed deletions in exon 19 were detected in 19.1% and L858R mutation in 20% of all cases by ARMS assay. A cutoff value of score 1 was used as positive by IHC. No wild type cases were immuno-reactive. The antibodies performed well in cytology, core biopsies and bronchoscopic biopsies. There were only one false positive case using L858R IHC (sensitivity 100%, specificity 98.5%, positive predictive value 96%, negative predictive value 100%). All 23 E746-A750 exon 19 deletions identified by mutation analysis were positive by IHC. The sensitivity of exon 19 IHC for E746-A750 was 100%, specificity 100%, positive predictive value 100% and negative predictive value 100%. The result of the IHC stains was finely correlated with mutations status determined by ARMS assay. Although inferior to molecular genetic analysis of the EGFR gene, IHC is highly specific and sensitive for the targeted EGFR mutations. The antibodies are likely to be of clinical value in cases especially where limited tumor material is available, or in situations where molecular genetic analysis is not readily available.

  20. Treatment algorithm in 2014 for advanced non-small cell lung cancer: therapy selection by tumour histology and molecular biology.

    PubMed

    Manegold, Christian

    2014-09-01

    The availability of antineoplastic monoclonal antibodies, small molecules and newer cytotoxics such as pemetrexed, the EGFR-tyrosine kinase inhibitors erlotinib, gefitinib, afatinib as well as the anti-angiogenic bevacizumab and the ALK-inhibitor crizotinib has recently changes the treatment algorithm of advanced non-small cell lung cancer. Decision making in 2014 is characterized by customizing therapy, by selecting a specific therapeutic regimen based on the histotype and the genotype of the tumour. This refers to first-line induction therapy and maintenance therapy as well, but also to subsequent lines of therapy since anti-neoplastic drugs and regimens used upfront clinically influence the selection of agents/regimes considered for second-/third-line treatment. Consequently, therapy customization through tumour histology and molecular markers has significantly influenced the work of pathologists around the globe and the process of obtaining an extended therapeutically relevant tumour diagnosis. Not only histological sub-typing became standard but molecular information is also considered of increasing importance for treatment selection. Routine molecular testing in certified laboratories must be established, and the diagnostic process should ideally be performed under the guidance of evidence based recommendation. The process of investigating and implementing medical targeting in lung cancer therefore, requires advanced diagnostic techniques and expertise and because of its large dimension is costly and influenced by the limitation of financial and clinical resources.

  1. Point-of-Care Technologies for the Advancement of Precision Medicine in Heart, Lung, Blood, and Sleep Disorders

    PubMed Central

    Jamieson, Brian G.; Chui, Chi On; Mao, Yufei; Shin, Kyeong-Sik; Huang, Tony Jun; Huang, Po-Hsun; Ren, Liqiang; Adhikari, Bishow; Chen, Jue; Iturriaga, Erin

    2016-01-01

    The commercialization of new point of care technologies holds great potential in facilitating and advancing precision medicine in heart, lung, blood, and sleep (HLBS) disorders. The delivery of individually tailored health care to a patient depends on how well that patient’s health condition can be interrogated and monitored. Point of care technologies may enable access to rapid and cost-effective interrogation of a patient’s health condition in near real time. Currently, physiological data are largely limited to single-time-point collection at the hospital or clinic, whereas critical information on some conditions must be collected in the home, when symptoms occur, or at regular intervals over time. A variety of HLBS disorders are highly dependent on transient variables, such as patient activity level, environment, time of day, and so on. Consequently, the National Heart Lung and Blood Institute sponsored a request for applications to support the development and commercialization of novel point-of-care technologies through small businesses (RFA-HL-14-011 and RFA-HL-14-017). Three of the supported research projects are described to highlight particular point-of-care needs for HLBS disorders and the breadth of emerging technologies. While significant obstacles remain to the commercialization of such technologies, these advancements will be required to achieve precision medicine. PMID:27602308

  2. Intrathoracic impedance monitor alarm in a patient with cardiac resynchronisation therapy and advanced lung carcinoma.

    PubMed

    Cvijić, Marta; Zižek, David; Antolič, Bor; Zupan, Igor

    2013-01-01

    The intrathoracic impedance monitor system measures impedance between the device case and the right ventricular coil and reflects intrathoracic fluid status. It is used to detect early volume overload in patients with chronic heart failure. We report a case of inappropriate activation of the intrathoracic impedance monitor alarm in a patient with epidermoid lung cancer and pleural carcinosis.

  3. Synthesis of refractory materials

    DOEpatents

    Holt, Joseph B.

    1984-01-01

    Refractory metal nitrides are synthesized during a combustion process utilizing a solid source of nitrogen. For this purpose, a metal azide is employed. The azide is combusted with a transition metal of the IIIB, IVB group, or a rare earth metal, and ignited to produce the refractory material.

  4. Synthesis of refractory materials

    DOEpatents

    Holt, J.B.

    Refractory metal nitrides are synthesized during a combustion process utilizing a solid source of nitrogen. For this purpose, a metal azide is employed. The azide is combusted with a transition metal of the IIIB, IVB group, or a rare earth metal, and ignited to produce the refractory material.

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

    PubMed Central

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

    2013-01-01

    Objective To investigate the clinical significance of the expression of MHC class I chain-related gene A (MICA) in patients with advanced non-small cell lung cancer and explore the relationship between MICA expression and the efficacy of cytokine-induced killer cell (CIK) therapy for treating advanced non-small cell lung cancer. Methods We obtained data on 222 patients with advanced non-small cell lung cancer, including data on MICA expression, age, gender, ECOG score, pathological type, stage, treatment history (including 38 patients who were given autologous CIK cell infusion), and overall survival (OS). MICA expression in lung cancer tissue was evaluated by immunohistochemical staining. Analyses of MICA expression, and CIK therapy association with survival outcomes were performed using Cox proportional models, Kaplan-Meier methods, and the log-rank test. Result s MICA was expressed in both membrane and cytoplasm. MICA expression correlated with the stage of lung cancer, ECOG score, gender and age. Multivariate COX regression analysis showed that the expression of MICA was an independent prognostic factor of advanced non-small cell lung cancer (p = 0.002). In subgroup analysis, we divided the 222 patients into CIK and control groups. In the CIK group, the medium OS (mOS) of patients with a high expression of MICA was longer than in those with low expression of MICA (27 months vs. 13 months). In the control group, the mOS in patients with a high expression of MICA was shorter than in patients with low MICA expression (9 months vs. 18 months). COX regression analysis showed that the MICA expression affects the effect of CIK therapy (p<0.0001). Conclusion 1) The high expression of MICA is one of the indicators of a poor prognosis for advanced non-small cell lung cancer patients. 2) The high expression of MICA might be one of the predictive factors for successful CIK therapy. PMID:23935919

  6. TU-F-17A-09: Four-Dimensional Cone Beam CT Ventilation Imaging Can Detect Interfraction Lung Function Variations for Locally Advanced Lung Cancer Patients

    SciTech Connect

    Kipritidis, J; Keall, P; Hugo, G; Weiss, E; Williamson, J

    2014-06-15

    Purpose: Four-dimensional cone beam CT ventilation imaging (4D-CBCT VI) is a novel functional lung imaging modality requiring validation. We hypothesize that 4D-CBCT VI satisfies a necessary condition for validity: that intrafraction variations (e.g. due to poor 4D-CBCT image quality) are substantially different to interfraction variations (e.g. due to changes in underlying function). We perform the first comparison of intrafraction (pre/post fraction) and interfraction (week-to-week) 4D-CBCT VIs for locally advanced non small cell lung cancer (LA NSCLC) patients undergoing radiation therapy. Methods: A total of 215 4D-CBCT scans were acquired for 19 LA NSCLC patients over 4-6 weeks of radiation therapy, including 75 pairs of pre-/post-fraction scans on the same day. 4D-CBCT VIs were obtained by applying state-of-the-art, B-spline deformable image registration to obtain the Jacobian determinant of deformation between the end-exhale and end-inhale phases. All VIs were deformably registered to the corresponding first day scan, normalized between the 10th and 90th percentile values and cropped to the ipsilateral lung only. Intrafraction variations were assessed by computing the mean and standard deviation of voxel-wise differences between all same-day pairs of pre-/post-fraction VIs. Interfraction differences were computed between first-day VIs and treatment weeks 2, 4 and 6 for all 19 patients. We tested the hypothesis by comparing cumulative distribution functions (CDFs) of intrafraction and interfraction ventilation differences using two-sided Kolmogorov-Smirnov goodness-of-fit tests. Results: The (mean ± std. dev.) of intrafraction differences was (−0.007 ± 0.079). Interfraction differences for weeks 2, 4 and 6 were (−0.035 ± 0.103), (−0.006 ± 0.094) and (−0.019 ± 0.127) respectively. For week 2, the changes in CDFs for intrafraction and interfraction differences approached statistical significance (p=0.099). Conclusion: We have shown that 4D-CBCT VI

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

    ClinicalTrials.gov

    2012-12-13

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

  8. Prognostic Significance of Modified Advanced Lung Cancer Inflammation Index (ALI) in Patients with Small Cell Lung Cancer_ Comparison with Original ALI

    PubMed Central

    Kim, Young Saing; Seo, Ja-Young; Park, Inkeun; Ahn, Hee Kyung; Jeong, Yu Mi; Kim, Jeong Ho

    2016-01-01

    Background Advanced lung cancer inflammation index (ALI, body mass index [BMI] x serum albumin/neutrophil-lymphocyte ratio [NLR]) has been shown to predict overall survival (OS) in small cell lung cancer (SCLC). CT enables skeletal muscle to be quantified, whereas BMI cannot accurately reflect body composition. The purpose was to evaluate prognostic value of modified ALI (mALI) using CT-determined L3 muscle index (L3MI, muscle area at L3/height2) beyond original ALI. Methods L3MIs were calculated using the CT images of 186 consecutive patients with SCLC taken at diagnosis, and mALI was defined as L3MI x serum albumin/NLR. Using chi-squared test determined maximum cut-offs for low ALI and low mALI, the prognostic values of low ALI and low mALI were tested using Kaplan-Meier method and Cox proportional hazards analysis. Finally, deviance statistics was used to test whether the goodness of fit of the prognostic model is improved by adding mALI as an extra variable. Results Patients with low ALI (cut-off, 31.1, n = 94) had shorter OS than patients with high ALI (median, 6.8 months vs. 15.8 months; p < 0.001), and patients with low mALI (cut-off 67.7, n = 94) had shorter OS than patients with high mALI (median, 6.8 months vs. 16.5 months; p < 0.001). There was no significant difference in estimates of median survival time between low ALI and low mALI (z = 0.000, p = 1.000) and between high ALI and high mALI (z = 0.330, p = 0.740). Multivariable analysis showed that low ALI was an independent prognostic factor for shorter OS (HR, 1.67, p = 0.004), along with advanced age (HR, 1.49, p = 0.045), extensive disease (HR, 2.27, p < 0.001), supportive care only (HR, 7.86, p < 0.001), and elevated LDH (HR, 1.45, p = 0.037). Furthermore, goodness of fit of this prognostic model was not significantly increased by adding mALI as an extra variable (LR difference = 2.220, p = 0.136). Conclusion The present study confirms mALI using CT-determined L3MI has no additional prognostic

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

    PubMed

    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.

  10. Outcomes of chemotherapies and HER2 directed therapies in advanced HER2-mutant lung cancers.

    PubMed

    Eng, Juliana; Hsu, Meier; Chaft, Jamie E; Kris, Mark G; Arcila, Maria E; Li, Bob T

    2016-09-01

    Human epidermal growth factor receptor 2 (HER2, ERBB2) mutations occur in 3% of lung adenocarcinomas. While case reports and series have shown activity of HER2 targeted agents in these patients, little is known about outcomes of chemotherapies. Patients with stage IV HER2-mutant lung cancers at Memorial Sloan Kettering were reviewed. Patient demographics, types of HER2 mutations, duration of systemic treatments and survival were analyzed. We identified 38 patients with HER2-mutant lung cancers: median age 62; majority were women (n=24), never smokers (n=22), and all had adenocarcinomas. A 12 base pair in-frame insertion YVMA in exon 20 (p.A775_G776insYVMA) was present in 24 (63%, 95% CI 46-78%) patients. In addition, there were four 9 base pair insertions, one 6 base pair insertion, and five 3 base pair insertions in exon 20, and four single bp substitutions (exon 20 L755F, V777L, D769H, exon 8 S310F). The median overall survival from date of diagnosis of stage IV disease was 2.3 years (95% CI 1.2-2.6). The median duration of chemotherapy was 4.3 months (68 treatments, range 0-21 months): 6.2 months for pemetrexed ±platinum/bevacizumab, 4 months for taxane ±platinum/bevacizumab, 2.6 months for gemcitabine, 3.5 months for vinorelbine. The median duration of HER2 tyrosine kinase inhibitors was 2.2 months (28 treatments, range 0.3-16.3 months). As we search for better targeted therapies for patients with HER2-mutant lung cancers, chemotherapy remains an important component of care.

  11. Inhaled sodium cromoglycate to treat cough in advanced lung cancer patients.

    PubMed

    Moroni, M; Porta, C; Gualtieri, G; Nastasi, G; Tinelli, C

    1996-07-01

    C-fibres probably represent the common final pathway in both ACE inhibitors and neoplastic cough. A recent report demonstrated that inhaled sodium cromoglycate is an effective treatment for ACE inhibitors' cough; this effect might be due to the suppression of afferent unmyelinated C-fibres. We tested the hypothesis that inhaled sodium cromoglycate might also be effective in lung cancer patients who presented with irritative neoplastic cough. Twenty non-small-cell lung cancer (NSCLC) patients complaining of cough resistant to conventional treatment were randomised to receive, in a double-blind trial, either inhaled sodium cromoglycate or placebo. Patients recorded cough severity daily, before and during treatment, on a 0 to 4 scale. The efficacy of treatment was tested with the Mann-Whitney U-test for non-parametric measures, comparing the intergroup differences in the measures of summary of symptom scores calculated in each patient before and after treatment. We report that inhaled sodium cromoglycate can reduce cough, also in NSCLC patients and that such reduction, observed in all patients treated, is statistically significant (P < 0.001). Inhaled sodium cromoglycate appears to be a cost-effective and safe treatment for lung cancer-related cough.

  12. National Institute of Environmental Health Sciences: 50 Years of Advancing Science and Improving Lung Health.

    PubMed

    Antony, Veena B; Redlich, Carrie A; Pinkerton, Kent E; Balmes, John; Harkema, Jack R

    2016-11-15

    The American Thoracic Society celebrates the 50th anniversary of the National Institute of Environmental Health Sciences (NIEHS). The NIEHS has had enormous impact through its focus on research, training, and translational science on lung health. It has been an advocate for clean air both in the United States and across the world. The cutting-edge science funded by the NIEHS has led to major discoveries that have broadened our understanding of the pathogenesis and treatment for lung disease. Importantly, the NIEHS has developed and fostered mechanisms that require cross-cutting science across the spectrum of areas of inquiry, bringing together environmental and social scientists with clinicians to bring their expertise on specific areas of investigation. The intramural program of the NIEHS nurtures cutting-edge science, and the extramural program encourages investigator-initiated research while at the same time providing broader direction through important initiatives. Under the umbrella of the NIEHS and guided by Dr. Linda Birnbaum, the director of the NIEHS, important collaborative programs, such as the Superfund Program and the National Toxicology Program, work to discover mechanisms to protect from environmental toxins. The American Thoracic Society has overlapping goals with the NIEHS, and the strategic plans of both august bodies converge to synergize on population lung health. These bonds must be tightened and highlighted as we work toward our common goals.

  13. Inhaled sodium cromoglycate to treat cough in advanced lung cancer patients.

    PubMed Central

    Moroni, M.; Porta, C.; Gualtieri, G.; Nastasi, G.; Tinelli, C.

    1996-01-01

    C-fibres probably represent the common final pathway in both ACE inhibitors and neoplastic cough. A recent report demonstrated that inhaled sodium cromoglycate is an effective treatment for ACE inhibitors' cough; this effect might be due to the suppression of afferent unmyelinated C-fibres. We tested the hypothesis that inhaled sodium cromoglycate might also be effective in lung cancer patients who presented with irritative neoplastic cough. Twenty non-small-cell lung cancer (NSCLC) patients complaining of cough resistant to conventional treatment were randomised to receive, in a double-blind trial, either inhaled sodium cromoglycate or placebo. Patients recorded cough severity daily, before and during treatment, on a 0 to 4 scale. The efficacy of treatment was tested with the Mann-Whitney U-test for non-parametric measures, comparing the intergroup differences in the measures of summary of symptom scores calculated in each patient before and after treatment. We report that inhaled sodium cromoglycate can reduce cough, also in NSCLC patients and that such reduction, observed in all patients treated, is statistically significant (P < 0.001). Inhaled sodium cromoglycate appears to be a cost-effective and safe treatment for lung cancer-related cough. PMID:8688342

  14. Refractory Ulcerative Colitis Treatment

    PubMed Central

    Green, Jesse A.

    2007-01-01

    Treatment of refractory ulcerative colitis (UC) is a common clinical challenge. In either acute or chronic refractory UC, the disease may continue to remain active, even though the patient is on appropriate therapy. It is important to reassess and characterize the patient's disease before adding new medications to the current medical regimen. After determining the current extent and severity of the UC—ruling out other causes of bloody diarrhea and determining what complications are present—new treatment approaches can then be started. It is critical to first optimize oral 5-aminosalicylic acid (5-ASA) therapy combined with rectal 5-ASA or corticosteroid suppositories, plus corticosteroid or 5-ASA enemas or foam preparations. Oral or intravenous corticosteroids are appropriate to use if needed, but alternative approaches must be used for long-term maintenance. 6-Mercaptopurine (6-MP) or azathioprine can be very helpful for severe chronic refractory UC. In those patients who do not respond to 5-ASA medications, corticosteroids, and 6-MP or azathioprine, infliximab offers an important approach for induction and maintenance of remission for refractory chronic ulcerative colitis as well as for select cases of refractory acute UC. Cyclosporine use is an alternative medical approach for the refractory acute UC patient. Colectomy with ileal pouch-anal anastomosis remains a valuable option for the refractory chronic or acute UC patient, because it can provide both a “cure” for the disease, as well as eliminate ineffective medications with their associated side effects. PMID:21960779

  15. Refractory duodenal ulcer.

    PubMed Central

    Bardhan, K D

    1984-01-01

    A refractory duodenal ulcer was arbitrarily defined as one that had failed to heal completely after treatment with cimetidine 1 g daily for three months. Of 66 patients with refractory duodenal ulcer, healing eventually occurred in 37 patients, after treatment for an average of 7.4 months. But 28 patients did not heal despite treatment for an average of 9.4 months; and one patient defaulted. In 41 patients the daily dose of cimetidine was increased to 2 g: the ulcers in 31 patients healed. In eight patients the daily dose was increased to 3 g and healing occurred in four patients. Eighteen patients required admission on 22 occasions because of severe symptoms despite treatment. Nine patients underwent surgery but in five the results were poor. Differences in clinical and endoscopic features between refractory and non-refractory ulcer patients were small. Acid and pepsin secretion were similar and gastrin concentrations normal. Blood levels of the drug and suppression of acid secretion were both satisfactory. Identification of refractory ulcer patients at the start of treatment was therefore not possible. Refractoriness could occur at any time during the course of the disease, previous treatment with cimetidine often having resulted in rapid healing, but subsequent relapses were also usually refractory. The cause of refractoriness remains unknown and the rather poor results of surgery in this series suggests that optimal management of these patients remains to be determined. Refractoriness probably indicates a changed natural history of the disease and in some patients a more poor prognosis. PMID:6428982

  16. Advance care planning uptake among patients with severe lung disease: a randomised patient preference trial of a nurse-led, facilitated advance care planning intervention

    PubMed Central

    Sinclair, Craig; Auret, Kirsten Anne; Evans, Sharon Frances; Williamson, Fiona; Dormer, Siobhan; Greeve, Kim; Koay, Audrey; Price, Dot; Brims, Fraser

    2017-01-01

    Objective Advance care planning (ACP) clarifies goals for future care if a patient becomes unable to communicate their own preferences. However, ACP uptake is low, with discussions often occurring late. This study assessed whether a systematic nurse-led ACP intervention increases ACP in patients with advanced respiratory disease. Design A multicentre open-label randomised controlled trial with preference arm. Setting Metropolitan teaching hospital and a rural healthcare network. Participants 149 participants with respiratory malignancy, chronic obstructive pulmonary disease or interstitial lung disease. Intervention Nurse facilitators offered facilitated ACP discussions, prompted further discussions with doctors and loved ones, and assisted participants to appoint a substitute medical decision-maker (SDM) and complete an advance directive (AD). Outcome measures The primary measure was formal (AD or SDM) or informal (discussion with doctor) ACP uptake assessed by self-report (6 months) and medical notes audit. Secondary measures were the factors predicting baseline readiness to undertake ACP, and factors predicting postintervention ACP uptake in the intervention arm. Results At 6 months, formal ACP uptake was significantly higher (p<0.001) in the intervention arm (54/106, 51%), compared with usual care (6/43, 14%). ACP discussions with doctors were also significantly higher (p<0.005) in the intervention arm (76/106, 72%) compared with usual care (20/43, 47%). Those with a strong preference for the intervention were more likely to complete formal ACP documents than those randomly allocated. Increased symptom burden and preference for the intervention predicted later ACP uptake. Social support was positively associated with ACP discussion with loved ones, but negatively associated with discussion with doctors. Conclusions Nurse-led facilitated ACP is acceptable to patients with advanced respiratory disease and effective in increasing ACP discussions and completion

  17. Lung Organogenesis

    PubMed Central

    Warburton, David; El-Hashash, Ahmed; Carraro, Gianni; Tiozzo, Caterina; Sala, Frederic; Rogers, Orquidea; De Langhe, Stijn; Kemp, Paul J.; Riccardi, Daniela; Torday, John; Bellusci, Saverio; Shi, Wei; Lubkin, Sharon R; Jesudason, Edwin

    2011-01-01

    Developmental lung biology is a field that has the potential for significant human impact: lung disease at the extremes of age continues to cause major morbidity and mortality worldwide. Understanding how the lung develops holds the promise that investigators can use this knowledge to aid lung repair and regeneration. In the decade since the “molecular embryology” of the lung was first comprehensively reviewed, new challenges have emerged—and it is on these that we focus the current review. Firstly, there is a critical need to understand the progenitor cell biology of the lung in order to exploit the potential of stem cells for the treatment of lung disease. Secondly, the current familiar descriptions of lung morphogenesis governed by growth and transcription factors need to be elaborated upon with the reinclusion and reconsideration of other factors, such as mechanics, in lung growth. Thirdly, efforts to parse the finer detail of lung bud signaling may need to be combined with broader consideration of overarching mechanisms that may be therapeutically easier to target: in this arena, we advance the proposal that looking at the lung in general (and branching in particular) in terms of clocks may yield unexpected benefits. PMID:20691848

  18. Impact of Symptom Clusters on Quality of Life Outcomes in Patients from Japan with Advanced Nonsmall Cell Lung Cancers

    PubMed Central

    Hamada, Tamami; Komatsu, Hiroko; Rosenzweig, Margaret Quinn; Chohnabayashi, Naohiko; Nishimura, Naoki; Oizumi, Satoshi; Ren, Dianxu

    2016-01-01

    Objective: Identify symptom clusters based on symptoms experienced by patients with advanced nonsmall cell lung cancers (NSCLCs), and examine the relationship between the symptom clusters and impairment in everyday life and quality of life (QOL). Methods: Using the M.D. Anderson Symptom Inventory, 9 symptom items and the QOL Questionnaire (QLQ-C-30) evaluation apparatus from the European Organization for Research and Treatment of Cancer, we evaluated symptom severity, interference in daily life, and QOL. Factor analysis and multiple regression analysis techniques were used. Results: Sixty patients with advanced NSCLCs seen in pulmonary medicine departments were included in the study. The average age of patients was 64.33 (standard deviation = 11.40). Thirty-six were male and 24 were female. Three symptom clusters were identified as fatigue/anorexia cluster (dry mouth, altered the sense of taste, drowsiness, fatigue/tiredness, and lack of appetite), pain cluster (anxiety, sadness, and pain), numbness cluster (numbness, leg weakness, and distress). The pain cluster had the strongest influence (adjusted R2 = 0.355) on daily life (emotions) while the numbness cluster most strongly affected walking. The fatigue/anorexia cluster explained 22.7% of role function variance. This symptom clustering may be unique among patients with advanced NSCLCs. Conclusions: Each of these clusters affected QOL and everyday life with varying degrees of influence. In clinical screening assessments, focusing on symptom clusters could provide tailored management strategies for patients with advanced NSCLCs. These care strategies may improve outcomes specifically for advanced NSCLCs patients. PMID:28083555

  19. Mature autologous dendritic cell vaccines in advanced non-small cell lung cancer: a phase I pilot study

    PubMed Central

    2011-01-01

    Background Overall therapeutic outcomes of advanced non-small-cell lung cancer (NSCLC) are poor. The dendritic cell (DC) immunotherapy has been developed as a new strategy for the treatment of lung cancer. The purpose of this study was to evaluate the feasibility, safety and immunologic responses in use in mature, antigen-pulsed autologous DC vaccine in NSCLC patients. Methods Five HLA-A2 patients with inoperable stage III or IV NSCLC were selected to receive two doses of 5 × 107 DC cells administered subcutaneous and intravenously two times at two week intervals. The immunologic response, safety and tolerability to the vaccine were evaluated by the lymphoproliferation assay and clinical and laboratorial evolution, respectively. Results The dose of the vaccine has shown to be safe and well tolerated. The lymphoproliferation assay showed an improvement in the specific immune response after the immunization, with a significant response after the second dose (p = 0.005). This response was not long lasting and a tendency to reduction two weeks after the second dose of the vaccine was observed. Two patients had a survival almost twice greater than the expected average and were the only ones that expressed HER-2 and CEA together. Conclusion Despite the small sample size, the results on the immune response, safety and tolerability, combined with the results of other studies, are encouraging to the conduction of a large clinical trial with multiples doses in patients with early lung cancer who underwent surgical treatment. Trial Registration Current Controlled Trials: ISRCTN45563569 PMID:21682877

  20. Effect of Image-Guidance Frequency on Geometric Accuracy and Setup Margins in Radiotherapy for Locally Advanced Lung Cancer

    SciTech Connect

    Higgins, Jane; Bezjak, Andrea; Hope, Andrew; Panzarella, Tony; Li, Winnie; Cho, John B.C.; Craig, Tim; Brade, Anthony; Sun, Alexander; Bissonnette, Jean-Pierre

    2011-08-01

    Purpose: To assess the relative effectiveness of five image-guidance (IG) frequencies on reducing patient positioning inaccuracies and setup margins for locally advanced lung cancer patients. Methods and Materials: Daily cone-beam computed tomography data for 100 patients (4,237 scans) were analyzed. Subsequently, four less-than-daily IG protocols were simulated using these data (no IG, first 5-day IG, weekly IG, and alternate-day IG). The frequency and magnitude of residual setup error were determined. The less-than-daily IG protocols were compared against the daily IG, the assumed reference standard. Finally, the population-based setup margins were calculated. Results: With the less-than-daily IG protocols, 20-43% of fractions incurred residual setup errors {>=}5 mm; daily IG reduced this to 6%. With the exception of the first 5-day IG, reductions in systematic error ({Sigma}) occurred as the imaging frequency increased and only daily IG provided notable random error ({sigma}) reductions ({Sigma} = 1.5-2.2 mm, {sigma} = 2.5-3.7 mm; {Sigma} = 1.8-2.6 mm, {sigma} = 2.5-3.7 mm; and {Sigma} = 0.7-1.0 mm, {sigma} = 1.7-2.0 mm for no IG, first 5-day IG, and daily IG, respectively. An overall significant difference in the mean setup error was present between the first 5-day IG and daily IG (p < .0001). The derived setup margins were 5-9 mm for less-than-daily IG and were 3-4 mm with daily IG. Conclusion: Daily cone-beam computed tomography substantially reduced the setup error and could permit setup margin reduction and lead to a reduction in normal tissue toxicity for patients undergoing conventionally fractionated lung radiotherapy. Using first 5-day cone-beam computed tomography was suboptimal for lung patients, given the inability to reduce the random error and the potential for the systematic error to increase throughout the treatment course.

  1. Lung transplantation

    PubMed Central

    Afonso, José Eduardo; Werebe, Eduardo de Campos; Carraro, Rafael Medeiros; Teixeira, Ricardo Henrique de Oliveira Braga; Fernandes, Lucas Matos; Abdalla, Luis Gustavo; Samano, Marcos Naoyuki; Pêgo-Fernandes, Paulo Manuel

    2015-01-01

    ABSTRACT Lung transplantation is a globally accepted treatment for some advanced lung diseases, giving the recipients longer survival and better quality of life. Since the first transplant successfully performed in 1983, more than 40 thousand transplants have been performed worldwide. Of these, about seven hundred were in Brazil. However, survival of the transplant is less than desired, with a high mortality rate related to primary graft dysfunction, infection, and chronic graft dysfunction, particularly in the form of bronchiolitis obliterans syndrome. New technologies have been developed to improve the various stages of lung transplant. To increase the supply of lungs, ex vivo lung reconditioning has been used in some countries, including Brazil. For advanced life support in the perioperative period, extracorporeal membrane oxygenation and hemodynamic support equipment have been used as a bridge to transplant in critically ill patients on the waiting list, and to keep patients alive until resolution of the primary dysfunction after graft transplant. There are patients requiring lung transplant in Brazil who do not even come to the point of being referred to a transplant center because there are only seven such centers active in the country. It is urgent to create new centers capable of performing lung transplantation to provide patients with some advanced forms of lung disease a chance to live longer and with better quality of life. PMID:26154550

  2. Levels of Soluble Receptor for Advanced Glycation End Products in Bronchoalveolar Lavage Fluid in Patients with Various Inflammatory Lung Diseases

    PubMed Central

    Kamo, Tetsuro; Tasaka, Sadatomo; Tokuda, Yuriko; Suzuki, Shoji; Asakura, Takanori; Yagi, Kazuma; Namkoong, Ho; Ishii, Makoto; Hasegawa, Naoki; Betsuyaku, Tomoko

    2015-01-01

    Receptor for advanced glycation end products (RAGE) is a multiligand receptor of S100/calgranulins, high-mobility group box 1, and others, and it is associated with the pathogenesis of various inflammatory and circulatory diseases. The soluble form of RAGE (sRAGE) is a decoy receptor and competitively inhibits membrane-bound RAGE activation. In this study, we measured sRAGE levels in bronchoalveolar lavage fluid (BALF) of 78 patients, including 41 with interstitial pneumonia, 11 with sarcoidosis, 9 with respiratory infection, 7 with ARDS, 5 with lung cancer, and 5 with vasculitis. Among them, sRAGE was detectable in BALF of 73 patients (94%). In patients with ARDS and vasculitis, the sRAGE levels were significantly higher than in the control subjects and those with interstitial pneumonia. The sRAGE levels were positively correlated with total cell counts in BALF and serum levels of surfactant protein-D, lactate dehydrogenase, and C-reactive protein. There was an inverse correlation between PaO2/FIO2 ratio and sRAGE levels. These results indicate that sRAGE in BALF might be considered as a biomarker of lung inflammatory disorders, especially ARDS and vasculitis. PMID:27147899

  3. A randomised trial of MACC chemotherapy with or without lonidamine in advanced non-small cell lung cancer. Cuneo Lung Cancer Study Group (CuLCaSG)

    PubMed

    Buccheri, G; Ferrigno, D

    1994-01-01

    Combination chemotherapy with anti-proliferative agents is the usual treatment for patients with advanced non-small cell lung cancer (NSCLC), good performance status and no major clinical contraindications. Lonidamine (LND), a new drug with an innovative mechanism of action, might potentiate anti-cancer activity of conventional cytotoxic drugs, with no increase of specific toxicity. Following a pilot study of feasibility, we now report the results of a randomised trial evaluating MACC chemotherapy, as originally described, versus the same regimen+LND. 151 patients with advanced NSCLC were assigned at random to the two treatment arms. LND 150 mg was given orally three times daily. Treatment was continued until progression of disease, unacceptable toxicity or refusal by the patient (median number of cycles of MACC, three for both arms; median duration of LND administration, 8 weeks in the arm concerned). Actual dose intensities (DI) of MACC and LND were, respectively, 100 and 83% of those intended (median values). There was a negative correlation between duration of chemotherapy and the DI of MACC reached in each patient, but no correlation between the duration of treatment with LND and its DI. DIs of LND and MACC were not correlated with each other. In all, 15 objective responses (one complete and four partial responses in the MACC group, 10 partial responses in patients on MACC+LND) were observed. Median progression-free survivals were 20 weeks (confidence interval, CI 14-22) for the group on LND and 17 weeks (CI 12-17) for the control group (non-significant difference). Median overall survivals were, respectively, 30 weeks (CI 23-40) and 27 weeks (CI 22-34), P = non-significant. Toxicity was as expected by the use of MACC, and similar in both arms, except for more severe anaemia and gastric toxicity in the group on MACC+LND. Other uncommon side-effects, seen only in this latter group, were mild to moderate and reversible and included myalgia, asthenia, testicle

  4. Is lung volume reduction surgery effective in the treatment of advanced emphysema?

    PubMed

    Zahid, Imran; Sharif, Sumera; Routledge, Tom; Scarci, Marco

    2011-03-01

    A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was whether lung volume reduction surgery (LVRS) might be superior to medical treatment in the management of patients with severe emphysema. Overall 497 papers were found using the reported search, of which 12 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 are tabulated. We conclude that LVRS produces superior patient outcomes compared to medical treatment in terms of exercise capacity, lung function, quality of life and long-term (>1 year postoperative) survival. A large proportion of the best evidence on this topic is based on analysis of the National Emphysema Treatment Trial (NETT). Seven studies compared LVRS to medical treatment alone (MTA) using data generated by the NETT trial. They found higher quality of life scores (45.3 vs. 27.5, P<0.001), improved maximum ventilation (32.8 vs. 29.6 l/min, P=0.001) and lower exacerbation rate per person-year (0.27 vs. 0.37%, P=0.0005) with LVRS than MTA. Mortality rates for LVRS were greater up to one year (P=0.01), equivalent by three years (P=0.15) and lower after four years (P=0.06) postoperative compared to MTA. Patients with upper-lobe-predominant disease and low exercise capacity (0.36 vs. 0.54, P=0.003) benefited the most from undergoing LVRS rather than MTA in terms of probability of death at five years compared to patients with non-upper-lobe disease (0.38 vs. 0.45, P=0.03) or upper-lobe-disease with high exercise capacity (0.33 vs. 0.38, P=0.32). Five studies compared LVRS to MTA using data independent from the NETT trial. They found greater six-minute walking distances (433 vs. 300 m, P<0.002), improved total lung capacity (18.8 vs. 7.9% predicted, P<0.02) and quality of life scores (47 vs. 23.2, P<0.05) with LVRS compared to MTA. Even though LVRS has a much

  5. Refractory Materials for Flame Deflector Protection System Corrosion Control: Refractory Ceramics Literature Survey

    NASA Technical Reports Server (NTRS)

    Calle, Luz Marina; Hintze, Paul E.; Parlier, Christopher R.; Curran, Jerome P.; Kolody, Mark; Perusich, Stephen; Whitten, Mary C.; Trejo, David; Zidek, Jason; Sampson, Jeffrey W.; Coffman, Brekke E.

    2009-01-01

    Ceramics can be defmed as a material consisting of hard brittle properties produced from inorganic and nonmetallic minerals made by firing at high temperatures. These materials are compounds between metallic and nonmetallic elements and are either totally ionic, or predominately ionic but having some covalent character. This definition allows for a large range of materials, not all applicable to refractory applications. As this report is focused on potential ceramic materials for high temperature, aggressive exposure applications, the ceramics reviewed as part of this report will focus on refractory ceramics specifically designed and used for these applications. Ceramic materials consist of a wide variety of products. Callister (2000) 1 characterized ceramic materials into six classifications: glasses, clay products, refractories, cements, abrasives, and advanced ceramics. Figure 1 shows this classification system. This review will focus mainly on refractory ceramics and cements as in general, the other classifications are neither applicable nor economical for use in large structures such as the flame trench. Although much work has been done in advanced ceramics over the past decade or so, these materials are likely cost prohibitive and would have to be fabricated off-site, transported to the NASA facilities, and installed, which make these even less feasible. Although the authors reviewed the literature on advanced ceramic refractories 2 center dot 3 center dot 4 center dot 5 center dot 6 center dot 7 center dot 8 center dot 9 center dot 10 center dot 11 center dot 12 after the review it was concluded that these materials should not be ' the focus of this report. A review is in progress on materials and systems for prefabricated refractory ceramic panels, but this review is focusing more on typical refractory materials for prefabricated systems, which could make the system more economically feasible. Refractory ceramics are used for a wide variety of applications

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

    PubMed

    Wang, Shuhang; Cang, Shundong; Liu, Delong

    2016-04-12

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

  7. Treatment Recommendations for Locally Advanced, Non-Small-Cell Lung Cancer: The Influence of Physician and Patient Factors

    SciTech Connect

    Lee, Irwin H.; Hayman, James A.; Landrum, Mary Beth; Tepper, Joel; Goodman, Karyn A.; Keating, Nancy L.

    2009-08-01

    Purpose: To determine the impact of patient age, comorbidity, and physician factors on treatment recommendations for locally advanced, unresectable non-small-cell lung cancer (NSCLC). Methods and Materials: We surveyed radiation oncologists regarding their recommendations for treatment (chemoradiation, radiation alone, chemotherapy alone, or no therapy) for hypothetical patients with Stage IIIB NSCLC who varied by age (55 vs. 80 years) and comorbid illness (none, moderate, or severe chronic obstructive pulmonary disease [COPD]). Multinomial logistic regression was used to assess the impact of physician and practice characteristics on radiation oncologists' treatment recommendations for three scenarios with the least agreement. Results: Of 214 radiation oncologists, nearly all (99%) recommended chemoradiation for a healthy 55 year old. However, there was substantial variability in recommendations for a 55 year old with severe COPD, an 80-year-old with moderate COPD, and an 80-year-old with severe COPD. Physicians seeing a lower volume of lung cancer patients were statistically less likely to recommend radiotherapy for younger or older patients with severe COPD (both p < 0.05), but the impact was modest. Conclusions: Nearly all radiation oncologists report following the evidence-based recommendation of chemoradiation for young, otherwise healthy patients with locally advanced, unresectable NSCLC, but there is substantial variability in treatment recommendations for older or sicker patients, probably related to the lack of clinical trial data for such patients. The physician and practice characteristics we examined only weakly affected treatment recommendations. Additional clinical trial data are necessary to guide recommendations for treatment of elderly patients and patients with poor pulmonary function to optimize their management.

  8. Preliminary results of combined therapy with topotecan and carboplatin in advanced non-small-cell lung cancer.

    PubMed

    Pujol, J L; von Pawel, J; Tumolo, S; Martoni, A; Hearn, S; Fields, S Z; Ross, G

    2001-01-01

    Topotecan is a topoisomerase I inhibitor and an analogue of camptothecin with demonstrated activity in small-cell lung cancer. However, less is known about the potential role of topotecan in advanced non-small-cell lung cancer (NSCLC). Platinum-based combination therapy is currently recommended in NSCLC patients presenting with good performance status. Because topotecan demonstrates a novel mechanism of action, its investigation in platinum combinations is warranted. In phase I/II trials of topotecan given as part of a cisplatin-based regimen, significant antitumor activity has been observed, providing the rationale for conducting further studies aimed at assessing survival benefit. However, this combination exhibits sequence dependence, with increasing hematologic toxicity observed when cisplatin is administered on day 1 of a 5-day topotecan course. Cisplatin has been associated with dose-limiting nonhematologic toxicities. Carboplatin exhibits a different toxicity profile compared with cisplatin, which makes it an attractive agent to study in combination. A hypothesis can be made that carboplatin in combination with newer agents such as topotecan might compare favorably with classic cisplatin-based regimens, particularly with respect to efficacy:toxicity ratio. Therefore, a phase II study was initiated to determine the efficacy, toxicity, and safety of carboplatin-topotecan combination in advanced NSCLC. Preliminary results reported here show that topotecan with carboplatin is generally well tolerated with manageable hematologic toxicity. Indirect comparison with cisplatin-topotecan combination suggests a lower incidence of dose-limiting nonhematologic toxicity. Whether or not the carboplatin-topotecan regimen is able to offer tumor response and survival benefit comparable to those observed with cisplatin-based combinations remains to be established.

  9. PD-L1 expression is associated with advanced non-small cell lung cancer

    PubMed Central

    Chen, Zhiquan; Mei, Jiandong; Liu, Lunxu; Wang, Guochen; Li, Zuosheng; Hou, Jingpu; Zhang, Qiuyang; You, Zongbing; Zhang, Liu

    2016-01-01

    Lung cancer is the most common cause of cancer-associated mortalities worldwide. Novel immunotherapies have been developed to improve the clinical outcomes of non-small cell lung cancer (NSCLC). Antibodies against programmed cell death protein 1 (PD-1) and programmed cell death protein 1 ligand 1 (PD-L1) have been tested in clinical trials, and anti-PD-1 antibody has been approved for the treatment of NSCLC. The aim of the present study was to assess expression of PD-1, PD-L1 and programmed cell death protein 1 ligand 2 (PD-L2) in 48 patients with NSCLC, using immunohistochemical staining. The results found that 35.4% (17/48) of patients were positive for PD-1 expression, 64.6% (31/48) were positive for PD-L1 expression and 45.8% (22/48) were positive for PD-L2 expression. Neither PD-1 nor PD-L2 expression was associated with gender, histology, differentiation status, tumor stage or lymph node metastasis. PD-L1 expression was not associated with gender, histology, differentiation status or lymph node metastasis; however, PD-L1 expression was significantly increased in stage III NSCLC (85.7% PD-L1+) compared with stage I/II NSCLC (55.9% PD-L1+) (P=0.049). PMID:27446371

  10. Small cell lung cancer (SCLC): no treatment advances in recent years

    PubMed Central

    Kotsakis, Athanasios; Georgoulias, Vasileios

    2016-01-01

    Small cell lung cancer (SCLC) is an aggressive malignancy with a distinct natural history and dismal prognosis. Given its predisposition for early dissemination, patients are commonly diagnosed with metastatic disease and chemotherapy is regarded as the cornerstone of approved treatment strategies. However, over the last 30 years there has been a distinct paucity of significant breakthroughs in SCLC therapy. Thus, SCLC is characterized as a recalcitrant neoplasm with limited therapeutic options. By employing well-established research approaches, proven to be efficacious in non-small cell lung cancer (NSCLC), a growing amount of data has shed light on the molecular biology of SCLC and enhanced our knowledge of the “drivers” of tumor cell survival and proliferation. New therapeutic targets have emerged, but no significant improvement in patients’ survival has been demonstrated thus far. In a sense, the more we know, the more we fail. Nowadays this is starting to change and methodical research efforts are underway. It is anticipated that the next decade will see a revolution in the treatment of SCLC patients with the application of effective precision medicine and immunotherapy strategies. PMID:26958492

  11. Metronomic treatment of advanced non-small-cell lung cancer with daily oral vinorelbine – a Phase I trial

    PubMed Central

    Guetz, Sylvia; Tufman, Amanda; von Pawel, Joachim; Rittmeyer, Achim; Borgmeier, Astrid; Ferré, Pierre; Edlich, Birgit; Huber, Rudolf Maria

    2017-01-01

    Micro-abstract In a Phase I dose-finding study of metronomic daily oral vinorelbine in advanced non-small-cell lung cancer, a recommended dose was established for this therapeutic approach. In addition, this trial revealed promising efficacy data and an acceptable tolerability profile. The observed vinorelbine blood concentrations suggest continuous anti-angiogenic coverage. Introduction We present a Phase I dose-finding study investigating metronomic daily oral vinorelbine (Navelbine® Oral, NVBo) in advanced non-small-cell lung cancer (NSCLC). Patients and methods Patients with stage III/IV NSCLC received daily NVBo at fixed dose levels of 20–50 mg/d for 21 days of each 4-week cycle. Primary end point was the maximum tolerated dose. Secondary end points included tumor response, time to progression (TTP), overall survival (OS) and tolerability. Results Twenty-seven patients with advanced NSCLC were enrolled. Most of them were extensively pretreated. Daily NVBo was well tolerated up to 30 mg/d. At 40 mg/d, two of five patients experienced dose-limiting toxicities (DLTs). Three of six patients had DLTs at the 50 mg/d level. The recommended dose was established at 30 mg/d in cycle 1, with escalation to 40 mg/d in cycle 2, if tolerated. Pharmacokinetic analyses showed continuous blood exposure over 21 days and only marginal accumulation. The tolerability profile was acceptable (all dose levels – all grades: decreased appetite 33%, diarrhea 33%, leukopenia 33%, nausea 30%, vomiting 26%; ≥grade 3: leukopenia 30%, lymphopenia 19%, neutropenia 19%, febrile neutropenia 15%). Disease control rate, OS and TTP signaled a treatment effect. Conclusion Daily metronomic NVBo therapy in extensively pretreated patients with advanced NSCLC is feasible and safe at the recommended dose of 30 mg/d. Escalation to 40 mg/d in the second cycle is possible. The blood concentrations of vinorelbine after daily metronomic dosing reached lower peaks than intravenous or oral conventional

  12. Potential of Adaptive Radiotherapy to Escalate the Radiation Dose in Combined Radiochemotherapy for Locally Advanced Non-Small Cell Lung Cancer

    SciTech Connect

    Guckenberger, Matthias; Wilbert, Juergen; Richter, Anne; Baier, Kurt; Flentje, Michael

    2011-03-01

    Purpose: To evaluate the potential of adaptive radiotherapy (ART) for advanced-stage non-small cell lung cancer (NSCLC) in terms of lung sparing and dose escalation. Methods and Materials: In 13 patients with locally advanced NSCLC, weekly CT images were acquired during radio- (n = 1) or radiochemotherapy (n = 12) for simulation of ART. Three-dimensional (3D) conformal treatment plans were generated: conventionally fractionated doses of 66 Gy were prescribed to the planning target volume without elective lymph node irradiation (Plan{sub 3}D). Using a surface-based algorithm of deformable image registration, accumulated doses were calculated in the CT images acquired during the treatment course (Plan{sub 4}D). Field sizes were adapted to tumor shrinkage once in week 3 or 5 and twice in weeks 3 and 5. Results: A continuous tumor regression of 1.2% per day resulted in a residual gross tumor volume (GTV) of 49% {+-} 15% after six weeks of treatment. No systematic differences between Plan{sub 3}D and Plan{sub 4}D were observed regarding doses to the GTV, lung, and spinal cord. Plan adaptation to tumor shrinkage resulted in significantly decreased lung doses without compromising GTV coverage: single-plan adaptation in Week 3 or 5 and twice-plan adaptation in Weeks 3 and 5 reduced the mean lung dose by 5.0% {+-} 4.4%, 5.6% {+-} 2.9% and 7.9% {+-} 4.8%, respectively. This lung sparing with twice ART allowed an iso-mean lung dose escalation of the GTV dose from 66.8 Gy {+-} 0.8 Gy to 73.6 Gy {+-} 3.8 Gy. Conclusions: Adaptation of radiotherapy to continuous tumor shrinkage during the treatment course reduced doses to the lung, allowed significant dose escalation and has the potential of increased local control.

  13. Efficacy of goserelin plus anastrozole in premenopausal women with advanced or recurrent breast cancer refractory to an LH-RH analogue with tamoxifen: results of the JMTO BC08-01 phase II trial.

    PubMed

    Nishimura, Reiki; Anan, Keisei; Yamamoto, Yutaka; Higaki, Kenji; Tanaka, Maki; Shibuta, Kenji; Sagara, Yasuaki; Ohno, Shinji; Tsuyuki, Shigeru; Mase, Takahiro; Teramukai, Satoshi

    2013-05-01

    The aim of the present study was to assess the efficacy and tolerability of a luteinizing hormone-releasing hormone (LH-RH) analogue plus an aromatase inhibitor following failure to respond to standard LH-RH analogue plus tamoxifen (TAM) in premenopausal patients. Premenopausal women with estrogen receptor (ER)-positive and/or progesterone-receptor positive, advanced or recurrent breast cancer refractory to an LH-RH analogue plus TAM received goserelin (GOS) in conjunction with anastrozole (ANA). The primary endpoint was the objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), clinical benefit rate (CBR) and safety. Between September 2008 and November 2010, 37 patients were enrolled. Thirty-five patients (94.6%) had ER-positive tumors, and 36 (97.3%) had human epidermal growth factor receptor (HER) 2-negative tumors. Thirty-six (97.3%) had measurable lesions and 1 (2.7%) had only bone metastasis. The ORR was 18.9% [95% confidence interval (CI), 8.0-35.2%], the CBR was 62.2% (95% CI, 44.8-77.5%) and the median PFS was 7.3 months. Eight patients had adverse drug reactions but none resulted in discontinuation of treatment. GOS plus ANA is a safe effective treatment for premenopausal women with hormone receptor-positive, recurrent or advanced breast cancer. The treatment may become viable treatment in the future, particularly when TAM is ineffective or contraindicated. Further studies and discussion are warranted.

  14. Treatment modalities for advanced ALK-rearranged non-small-cell lung cancer.

    PubMed

    Sullivan, Ivana; Planchard, David

    2016-04-01

    The ALK gene plays a key role in the pathogenesis of non-small-cell lung cancer (NSCLC). Patients with NSCLC harboring an ALK-rearrangement represent the second oncogene addiction to be identified in this disease. Crizotinib was the first ALK inhibitor showing pronounced clinical activity, and is now a reference treatment for ALK-positive NSCLC disease. However, despite initial impressive responses to crizotinib, acquired resistance almost invariably develops within 12 months. The pressing need for effective second-line agents has prompted the rapid development of next-generation ALK inhibitors. These agents, notably ceritinib and alectinib as the most developed, have a higher potency against ALK than crizotinib, along with activity against tumors harboring crizotinib-resistant mutations and potentially improved CNS penetration.

  15. Death awareness, feelings of uncertainty, and hope in advanced lung cancer patients: can they coexist?

    PubMed

    Borneman, Tami; Irish, Terry; Sidhu, Rupinder; Koczywas, Marianna; Cristea, Mihaela

    2014-06-01

    Patients diagnosed with stage-IV lung cancer are forced to quickly transition from a cancer-free and perhaps healthy life to one of serious illness, uncertainty, and anticipation of a premature death. Health professionals may be too quick to label the patient as being in denial if they hope for healing. Hope may not be lost when reality is accepted. Studies have investigated what it is like to live with awareness of impending death. Using a patient case study this paper discusses the concepts of death awareness, uncertainty, and hope. The aim is to provide a deeper understanding of how these seemingly antithetical emotions can coexist to the benefit of the patient, and to provide clinicians with practical considerations for supporting patients' hope throughout their terminal illness.

  16. Mesenchymal stem cells protects hyperoxia-induced lung injury in newborn rats via inhibiting receptor for advanced glycation end-products/nuclear factor κB signaling.

    PubMed

    Tian, Zhaofang; Li, Yuhong; Ji, Ping; Zhao, Sai; Cheng, Huaipin

    2013-02-01

    Bone marrow-derived mesenchymal stem cells (BMSCs) have been shown recently to ameliorate hyperoxia-induced lung injury, but the underlying mechanism remains unclear. This study aimed to determine whether BMSCs attenuate hyperoxia-induced lung injury by down-modulating the inflammatory RAGE/NF-κB (receptor for advanced glycation end-products/nuclear factor-κB) signaling. Thirty Sprague-Dawley newborn rats were randomly divided into three groups (n = 10): sham control (C); hyperoxia-induced acute lung injury (ALI) (B) and ALI with BMSCs transplantation (A). Rats were sacrificed at three-day post-transplantation. RAGE and NF-κB expression in lung tissue was detected by reverse transcription polymerase chain reaction, Western blot and immunohistochemistry analysis. The levels of tumor necrosis factor α (TNF-α) and RAGE in bronchoalveolar lavage fluid (BALF) and in serum were detected by enzyme-linked immunosorbent assay. The lung damage was evaluated by histological examination. The results showed that RAGE and TNF-α concentrations in BALF were significantly lower in Group A than in Group B. Moreover, RAGE and NF-κB expression in lung tissue at mRNA and protein concentrations was significantly lower in Group A than in Group B. The lung damage score was significantly lower in Group A than in Group B. These data demonstrate that hyperoxia induces the inflammation and causes damage in the lung but BMSC transplantation could alleviate hyperoxia-induced lung injury by inhibiting the inflammatory process mediated by RAGE/NF-κB signaling.

  17. Intrinsic resistance to EGFR tyrosine kinase inhibitors in advanced non-small-cell lung cancer with activating EGFR mutations

    PubMed Central

    Wang, Jun; Wang, Baocheng; Chu, Huili; Yao, Yunfeng

    2016-01-01

    Identifying activating EGFR mutations is a useful predictive strategy that helps select a population of advanced non-small-cell lung cancer (NSCLC) patients for treatment with EGFR tyrosine kinase inhibitors (TKIs). Patients with sensitizing EGFR mutations (predominantly an in-frame deletion in exon 19 and an L858R substitution) are highly responsive to first-generation EGFR TKIs, such as gefitinib and erlotinib, and show improved progression-free survival without serious side effects. However, all patients with activating EGFR mutations who are initially responsive to EGFR TKIs eventually develop acquired resistance after a median progression-free survival of 10–16 months, followed by disease progression. Moreover, ~20%–30% of NSCLC patients have no objective tumor regression on initial EGFR TKI treatment, although they harbor an activating EGFR mutation. These patients represent an NSCLC subgroup that is defined as having intrinsic or primary resistance to EGFR TKIs. Different mechanisms of acquired EGFR TKI resistance have been identified, and several novel compounds have been developed to reverse acquired resistance, but little is known about EGFR TKI intrinsic resistance. In this review, we summarize the latest findings involving mechanisms of intrinsic resistance to EGFR TKIs in advanced NSCLC with activating EGFR mutations and present possible therapeutic strategies to overcome this resistance. PMID:27382309

  18. Matrine promotes the efficacy and safety of platinum-based doublet chemotherapy for advanced non-small cell lung cancer

    PubMed Central

    Rong, Biaoxue; Zhao, Chongchong; Gao, Wenlong; Yang, Shuanying

    2015-01-01

    Purpose: Many studies have investigated the efficacy of matrine combined with platinum-based doublet chemotherapy (PBDC) versus PBDC alone for treating advanced non-small cell lung cancer (NSCLC). This study is an analytic value of available evidence. Methods: twenty-two studies reporting matrine combined with PBDC versus PBDC alone for treating advanced NSCLC were reviewed. Pooled odds ratios and hazard ratio with 95% confidence intervals were calculated using either the fixed effects model or random effects model. Results: The overall response rate (ORR) and disease control rate (DCR) of matrine combined with PBDC for treating NSCLC were significantly higher than those of PBDC alone, with 15.1% and 19.7% improvement, respectively (P < 0.00001). In addition, the mean survival time (MST) and quality of life (QOL) were improved after the treatment of matrine combined with PBDC (P < 0.00001). The main adverse effects found in this review were hematological reactions, nausea and vomiting. Matrine combined with PBDC had a lower incidence of adverse reactions compared with PBDC alone (P < 0.05). Conclusions: Matrine combined with PBDC was associated with higher RR, DCR, and MST as well as superior QOL profiles compared with PBDC alone. Matrine combined with PBDC decrease the incidence of adverse reactions compared with PBDC alone. PMID:26628952

  19. Development of phantom and methodology for 3D and 4D dose intercomparisons for advanced lung radiotherapy

    NASA Astrophysics Data System (ADS)

    Caloz, Misael; Kafrouni, Marilyne; Leturgie, Quentin; Corde, Stéphanie; Downes, Simon; Lehmann, Joerg; Thwaites, David

    2015-01-01

    There are few reported intercomparisons or audits of combinations of advanced radiotherapy methods, particularly for 4D treatments. As part of an evaluation of the implementation of advanced radiotherapy technology, a phantom and associated methods, initially developed for in-house commissioning and QA of 4D lung treatments, has been developed further with the aim of using it for end-to-end dose intercomparison of 4D treatment planning and delivery. The respiratory thorax phantom can house moving inserts with variable speed (breathing rate) and motion amplitude. In one set-up mode it contains a small ion chamber for point dose measurements, or alternatively it can hold strips of radiochromic film to measure dose distributions. Initial pilot and feasibility measurements have been carried out in one hospital to thoroughly test the methods and procedures before using it more widely across a range of hospitals and treatment systems. Overall, the results show good agreement between measured and calculated doses and distributions, supporting the use of the phantom and methodology for multi-centre intercomparisons. However, before wider use, refinements of the method and analysis are currently underway particularly for the film measurements.

  20. Pilot study of a novel combination of two therapeutic vaccines in advanced non-small-cell lung cancer patients.

    PubMed

    Herrera, Zaima Mazorra; Ramos, Tania Crombet

    2014-07-01

    Cancer vaccines contain tumor antigens in a pro-inflammatory context with the purpose to generate potent antitumor immune responses. However, tumor cells develop different immunosuppressive mechanisms that limit the effectiveness of an anticancer immune response. Therefore, therapeutic vaccine treatment alone is usually not sufficient to generate tumor regression or survival improvement, especially in the advanced disease scenario in which most clinical studies have been conducted. Combining cancer vaccines with different anticancer therapies such as chemotherapy, radiotherapy and other immunotherapeutic agents has had different levels of success. However, the combination of cancer vaccines with different mechanisms of action has not been explored in clinical trials. To address this issue, the current review summarizes the main clinical and immunological results obtained with two different therapeutic vaccines used in advanced non-small-cell lung cancer patients, inducing an immune response against epidermal growth factor (CIMAvax-EGF) and NGcGM3 ganglioside (racotumomab). We also discuss preliminary findings obtained in a trial of combination of these two vaccines and future challenges with these therapies.

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

    PubMed

    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 <28 days and those who received WBCT for ≥28 days were 16.2 (95% CI = 13.3-19.2) and 45.2 (95% CI = 14.4-76.0) months, respectively (P = .437). The median OS rates of patients who had undergone prior conventional 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 <3 could not be calculated. However, the mean OS rates of patients with ECOG PS <3 and with ECOG PS ≥3 were 85.7 (95% CI = 58.4-113.0) and 12.7 (95% CI = 8.5-16.9) months, respectively (P = .000). No severe adverse events were encountered. Conclusions Our study

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

    PubMed

    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.

  3. Adverse events risk associated with anti-VEGFR agents in the treatment of advanced nonsmall-cell lung cancer

    PubMed Central

    Gu, Biao; Gao, WenChuang; Chu, HongJun; Gao, Jian; Fu, Zhi; Ding, Hui; Lv, JunJie; Wu, QingQuan

    2016-01-01

    Abstract To perform this meta-analysis, we investigated the risk of the most clinically relevant adverse events related to antivascular endothelial growth factor receptor (VEGFR) agents in advanced nonsmall-cell lung cancer (NSCLC). A comprehensive literature search for studies published up to October 2015 was performed. Prospective randomized controlled phase II/III clinical trials that comparing therapy with or without anti-VEGFR agents for advanced NSCLC were included for analysis. Summary relative risk (RR) and 95% confidence intervals (CIs) were calculated using random effects or fixed effects according to the heterogeneity among included trials. A total of 11,701 patients from 18 clinical trials were included for analysis. Pooled RR showed that the use of anti-VEGFR agents significantly increased the risk of developing hypertension (RR 4.71, 95% CI 3.29–6.73, P < 0.001) and fatal adverse events (RR 1.33, 95% CI 1.12–1.58, P = 0.001). No statistically significant differences were found for gastrointestinal (GI) perforation (P = 0.41), arterial or venous thromboembolic events (P = 0.49 and P = 0.16, respectively), or hemorrhagic events (P = 0.81). Sensitive analysis indicated that the significance estimate of pooled RR of fatal adverse event (FAEs) was not significantly influenced by omitting any single study. The use of anti-VEGFR agents in advanced NSCLC does significantly increase the risk of hypertension and fatal adverse events, but not for arterial or venous thromboembolic events, GI perforation, or hemorrhagic events. PMID:27902583

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

    SciTech Connect

    Wei, Zhigang Ye, Xin Yang, Xia Zheng, Aimin Huang, Guanghui Li, Wenhong Ni, Xiang Wang, Jiao; Han, Xiaoying

    2015-02-15

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

  5. Recent advances in the management of chronic stable angina II. Anti-ischemic therapy, options for refractory angina, risk factor reduction, and revascularization

    PubMed Central

    Kones, Richard

    2010-01-01

    The objectives in treating angina are relief of pain and prevention of disease progression through risk reduction. Mechanisms, indications, clinical forms, doses, and side effects of the traditional antianginal agents – nitrates, β-blockers, and calcium channel blockers – are reviewed. A number of patients have contraindications or remain unrelieved from anginal discomfort with these drugs. Among newer alternatives, ranolazine, recently approved in the United States, indirectly prevents the intracellular calcium overload involved in cardiac ischemia and is a welcome addition to available treatments. None, however, are disease-modifying agents. Two options for refractory angina, enhanced external counterpulsation and spinal cord stimulation (SCS), are presented in detail. They are both well-studied and are effective means of treating at least some patients with this perplexing form of angina. Traditional modifiable risk factors for coronary artery disease (CAD) – smoking, hypertension, dyslipidemia, diabetes, and obesity – account for most of the population-attributable risk. Individual therapy of high-risk patients differs from population-wide efforts to prevent risk factors from appearing or reducing their severity, in order to lower the national burden of disease. Current American College of Cardiology/American Heart Association guidelines to lower risk in patients with chronic angina are reviewed. The Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial showed that in patients with stable angina, optimal medical therapy alone and percutaneous coronary intervention (PCI) with medical therapy were equal in preventing myocardial infarction and death. The integration of COURAGE results into current practice is discussed. For patients who are unstable, with very high risk, with left main coronary artery lesions, in whom medical therapy fails, and in those with acute coronary syndromes, PCI is indicated. Asymptomatic

  6. Increased NDRG1 expression is associated with advanced T stages and poor vascularization in non-small cell lung cancer.

    PubMed

    Fan, Chuifeng; Yu, Juanhan; Liu, Yang; Xu, Hongtao; Wang, Enhua

    2012-07-01

    N-myc downstream regulated gene 1 (NDRG1) is a member of the N-myc downstream regulated gene family which belongs to the alpha/beta hydrolase superfamily. Earlier studies have shown its association with inhibition of tumor metastasis. However, its function in malignant tumors is not fully enunciated. Recently there was increasing evidence that NDRG1 is involved in stress responses. In the current study, we examined the expression of NDRG1 and its correlation with clinicopathological factors and microvessel density (MVD) in non-small cell lung cancer (NSCLC) using immunohistochemistry (IHC). NDRG1 expression in NSCLC (71/115, 61.7%) was higher than that in normal lung tissues (32/115, 27.8%) (p < 0.05). NDRG1 expression in NSCLC cells was found in cytoplasm (63/115, 54.8%), nuclear (24/115, 20.9%) and cell membrane (13/115, 11.3%). NDRG1 expression in NSCLC with advanced T stages (T2-4) (63/84, 75.0%) was significantly higher than that with T1 stage (8/31, 25.8%) (P < 0.05). No other clinicopathological factors including lymph node metastasis were found to be associated with NDRG1 expression (p > 0.05). Moreover increased NDRG1 expression was associated with lower MVD in NSCLC (P < 0.05). MVD in adenocarcinoma (33.4 ± 8.4/HP) was significantly higher than that in squamous cell carcinoma (SCC) (19.3 ± 8.1/HP) (P < 0.05). No other clinicopathological factors were associated with MVD in NSCLC (p > 0.05). The present findings indicate an increase of NDRG1 expression with the progress of tumour extent which may be due to unbalanced tumor oxygenation on account of poor vascularization in NSCLC.

  7. Effect of n-3 fatty acids on patients with advanced lung cancer: a double-blind, placebo-controlled study.

    PubMed

    Finocchiaro, Concetta; Segre, Olivia; Fadda, Maurizio; Monge, Taira; Scigliano, Mara; Schena, Marina; Tinivella, Marco; Tiozzo, Elisa; Catalano, Maria G; Pugliese, Mariateresa; Fortunati, Nicoletta; Aragno, Manuela; Muzio, Giuliana; Maggiora, Marina; Oraldi, Manuela; Canuto, Rosa A

    2012-07-01

    PUFA from fish oil appear to have anti-inflammatory and anti-oxidative effects and improve nutritional status in cancer patients. With this as background, the aim of the present study was to investigate the effect of EPA plus DHA on inflammatory condition, and oxidative and nutritional status in patients with lung cancer. In our multicentre, randomised, double-blind trial, thirty-three patients with a diagnosis of advanced inoperable non-small-cell lung cancer and undergoing chemotherapy were divided into two groups, receiving four capsules/d containing 510 mg of EPA and 340 mg of DHA, or 850 mg of placebo, for 66 d. At the start of chemotherapy (T₀), after 8 d (T₁), 22 d (T₂) and 66 d (T₃), biochemical (inflammatory and oxidative status parameters) and anthropometric parameters were measured in both groups. A significant increase of body weight in the n-3 group at T₃ v. T₀ was observed. Concerning inflammation, C-reactive protein and IL-6 levels differed significantly between the n-3 and placebo groups at T₃, and progressively decreased during chemotherapy in the n-3 group, evidencing n-3 PUFA anti-inflammatory action. Concerning oxidative status, plasma reactive oxygen species levels increased in the placebo group v. the n-3 group at the later treatment times. Hydroxynonenal levels increased in the placebo group during the study, while they stabilised in the n-3 group. Our data confirm that the continual assumption of EPA plus DHA determined an anti-inflammatory and anti-oxidative action which could be considered a preliminary goal in anti-cachectic therapy.

  8. Nivolumab-Induced Severe Akathisia in an Advanced Lung Cancer Patient.

    PubMed

    Abe, Jiro; Sato, Taku; Tanaka, Ryota; Okazaki, Toshimasa; Takahashi, Satomi

    2016-11-23

    BACKGROUND Nivolumab is an anti-PD-1 immune checkpoint inhibitor that was recently developed for cancer immunotherapy. In the clinical trials of nivolumab, its adverse effects were reported to be less likely than those of conventional anti-cancer agents; however, after practical clinical distribution, it has come to be known that nivolumab induces various immune-related adverse events. CASE REPORT A 58-year-old male with a recurrence of lung adenocarcinoma was treated with nivolumab. Only four days after the initial administration of nivolumab, the patient presented with unbearable restlessness and distress that was resistant to all therapeutic agents used, and it gradually became worse. He finally came to need deep sedation despite his cancer status being stable during the course. Clinical tests including magnetic resonance imaging, cerebrospinal fluid cytology, and antibodies of paraneoplastic syndrome exhibited no signs of encephalitis or another possible cause of the neuropathy. The diagnosis of akathisia could be made only by his somatoform presentation. It was uncertain whether or not this complication was correlated with the activation of his immune system. CONCLUSIONS Anti-immune check point inhibitors may induce many unknown adverse events. Severe akathisia induced by nivolumab, as in our case, has not been reported yet. Collecting every adverse event of nivolumab may be important to make a better algorithm to manage its huge variety of complications.

  9. Critical Appraisal of Acuros XB and Anisotropic Analytic Algorithm Dose Calculation in Advanced Non-Small-Cell Lung Cancer Treatments

    SciTech Connect

    Fogliata, Antonella; Nicolini, Giorgia; Clivio, Alessandro; Vanetti, Eugenio; Cozzi, Luca

    2012-08-01

    Purpose: To assess the clinical impact of the Acuros XB algorithm (implemented in the Varian Eclipse treatment-planning system) in non-small-cell lung cancer (NSCLC) cases. Methods and Materials: A CT dataset of 10 patients presenting with advanced NSCLC was selected and contoured for planning target volume, lungs, heart, and spinal cord. Plans were created for 6-MV and 15-MV beams using three-dimensional conformal therapy, intensity-modulated therapy, and volumetric modulated arc therapy with RapidArc. Calculations were performed with Acuros XB and the Anisotropic Analytical Algorithm. To distinguish between differences coming from the different heterogeneity management and those coming from the algorithm and its implementation, all the plans were recalculated assigning Hounsfield Unit (HU) = 0 (Water) to the CT dataset. Results: Differences in dose distributions between the two algorithms calculated in Water were <0.5%. This suggests that the differences in the real CT dataset can be ascribed mainly to the different heterogeneity management, which is proven to be more accurate in the Acuros XB calculations. The planning target dose difference was stratified between the target in soft tissue, where the mean dose was found to be lower for Acuros XB, with a range of 0.4% {+-} 0.6% (intensity-modulated therapy, 6 MV) to 1.7% {+-} 0.2% (three-dimensional conformal therapy, 6 MV), and the target in lung tissue, where the mean dose was higher for 6 MV (from 0.2% {+-} 0.2% to 1.2% {+-} 0.5%) and lower for 15 MV (from 0.5% {+-} 0.5% to 2.0% {+-} 0.9%). Mean doses to organs at risk presented differences up to 3% of the mean structure dose in the worst case. No particular or systematic differences were found related to the various modalities. Calculation time ratios between calculation time for Acuros XB and the Anisotropic Analytical Algorithm were 7 for three-dimensional conformal therapy, 5 for intensity-modulated therapy, and 0.2 for volumetric modulated arc therapy

  10. Selumetinib and Akt Inhibitor MK-2206 in Treating Patients With Refractory or Advanced Gallbladder or Bile Duct Cancer That Cannot Be Removed By Surgery

    ClinicalTrials.gov

    2014-09-08

    Adenocarcinoma of the Gallbladder; Adenocarcinoma With Squamous Metaplasia of the Gallbladder; Adult Primary Cholangiocellular Carcinoma; Advanced Adult Primary Liver Cancer; Cholangiocarcinoma of the Extrahepatic Bile Duct; Localized Unresectable Adult Primary Liver Cancer; Metastatic Extrahepatic Bile Duct Cancer; Recurrent Adult Primary Liver Cancer; Recurrent Extrahepatic Bile Duct Cancer; Stage II Gallbladder Cancer; Stage IIIA Gallbladder Cancer; Stage IIIB Gallbladder Cancer; Stage IVA Gallbladder Cancer; Stage IVB Gallbladder Cancer; Unresectable Extrahepatic Bile Duct Cancer

  11. A phase 2 study of fluorouracil/leucovorin in combination with paclitaxel and oxaliplatin as a salvage treatment in patients with refractory or relapsed advanced gastric cancer.

    PubMed

    Lin, Rongbo; Fan, Nanfeng; Wu, Guangfeng; Chen, Ying; Guo, Zengqing; Wang, Xiaojie; Jin, Feng; Chen, Ling; Liu, Jie

    2015-02-01

    The aim of this study was to evaluate the efficacy and safety of paclitaxel plus oxaliplatin plus fluorouracil/leucovorin (POF) as salvage chemotherapy in pretreated advanced gastric cancer. Fifty-two pretreated patients with the advanced gastric cancer were eligible for this study. The POF regimen consisted of a 3-hour infusion of paclitaxel (135 mg/m(2)) followed by oxaliplatin (85 mg/m(2)) and leucovorin (400 mg/m(2)), administered simultaneously over a 2-hour infusion period, followed by an infusion of fluorouracil (2400 mg/m(2)) over a 46-hour period, every 14 days. From an intention-to-treat analysis, overall response rate and stable disease rate were 28.8 and 38.5%, respectively. The median time to progression and overall survival were 4.1 and 7.9 months, respectively. Grade 3 or 4 neutropaenia, thrombocytopaenia, fatigue, and neuropathy were 38.5, 15.4, 17.3, and 15.4%, respectively. The POF regimen is active in pretreated advanced gastric cancer as salvage chemotherapy, with a favourable toxicity profile.

  12. [Treatment of refractory ascites].

    PubMed

    Martínez, Javier; Albillos, Agustín

    2014-07-01

    Ascites is a common complication of hepatic cirrhosis and portal hypertension. Patients present systemic and splanchnic circulation disorders, which cause central hypovolemia and arterial hypotension, with the subsequent activation of vasoconstrictor systems and increased renal reabsorption of sodium and water. Approximately 5%-10% of patients present refractory ascites. Refractory ascites is considered when it is not controllable with standard dietary (sodium restriction) and diuretic (furosemide up to 160 mg a day and spironolactone up to 400mg a day) treatment or when patients present adverse effects due to diuretics that impede their administration at optimum dosages. The current therapeutic options for these patients are repeated evacuative paracentesis and the percutaneous intrahepatic portosystemic shunt. Despite these treatments, refractory ascites has a poor prognosis; patients should therefore be assessed for liver transplantation.

  13. Nivolumab-Induced Severe Akathisia in an Advanced Lung Cancer Patient

    PubMed Central

    Abe, Jiro; Sato, Taku; Tanaka, Ryota; Okazaki, Toshimasa; Takahashi, Satomi

    2016-01-01

    Patient: Male, 58 Final Diagnosis: Nivolumab induced severe akathisia Symptoms: Distress fidgety • restlessness Medication: — Clinical Procedure: Methylprednisolone pulse therapy and other drugs Specialty: Oncology Objective: Adverse events of drug therapy Background: Nivolumab is an anti-PD-1 immune checkpoint inhibitor that was recently developed for cancer immunotherapy. In the clinical trials of nivolumab, its adverse effects were reported to be less likely than those of conventional anti-cancer agents; however, after practical clinical distribution, it has come to be known that nivolumab induces various immune-related adverse events. Case Report: A 58-year-old male with a recurrence of lung adenocarcinoma was treated with nivolumab. Only four days after the initial administration of nivolumab, the patient presented with unbearable restlessness and distress that was resistant to all therapeutic agents used, and it gradually became worse. He finally came to need deep sedation despite his cancer status being stable during the course. Clinical tests including magnetic resonance imaging, cerebrospinal fluid cytology, and antibodies of paraneoplastic syndrome exhibited no signs of encephalitis or another possible cause of the neuropathy. The diagnosis of akathisia could be made only by his somatoform presentation. It was uncertain whether or not this complication was correlated with the activation of his immune system. Conclusions: Anti-immune check point inhibitors may induce many unknown adverse events. Severe akathisia induced by nivolumab, as in our case, has not been reported yet. Collecting every adverse event of nivolumab may be important to make a better algorithm to manage its huge variety of complications. PMID:27893699

  14. Chemotherapy in recurrent advanced non-small-cell lung cancer after adjuvant chemotherapy

    PubMed Central

    Valdes, M.; Nicholas, G.; Goss, G.D.; Wheatley-Price, P.

    2016-01-01

    Introduction Despite adjuvant systemic therapy in patients with completely resected non-small-cell lung cancer (nsclc), many will subsequently relapse. We investigated treatment choices at relapse and assessed the effect of palliative platinum doublet systemic therapy in this population. Methods With research ethics board approval, we performed a retrospective chart review of all patients with resected nsclc who received adjuvant systemic therapy from January 2002 until December 2008 at our institution. The primary outcome was the response rate to first-line palliative systemic therapy among patients who relapsed. Results We identified 176 patients who received adjuvant platinum doublet systemic therapy (82% received cisplatin–vinorelbine). In the 85 patients who relapsed (48%), median time to relapse was 18.5 months (95% confidence interval: 15 months to 21.3 months). Palliative systemic therapy was given in 43 patients. Of those 43 patients, 25 (58%) were re-challenged with platinum doublet systemic therapy, with a response rate of 29% compared with 18% in 18 patients who received other systemic therapy (p = 0.48). We observed a trend toward an increased clinical benefit rate (complete response + partial response + stable disease) in patients who were treated with a platinum doublet (67% vs. 41%, p = 0.12). Median overall survival (os) from relapse was 15.3 months in patients receiving palliative systemic therapy and 7.8 months in those receiving best supportive care alone. Compared with patients treated with non-platinum regimens, the platinum-treated group experienced longer survival after relapse (18.4 months vs. 9.7 months, p = 0.041). Conclusions In patients previously treated with adjuvant systemic therapy, re-treatment with platinum doublet chemotherapy upon relapse is feasible. Moreover, compared with patients receiving other first-line systemic therapy, patients receiving platinum doublets experienced higher response rates and significantly longer

  15. Cryotherapy in Treating Patients With Lung Cancer That Has Spread to the Other Lung or Parts of the Body

    ClinicalTrials.gov

    2017-01-17

    Advanced Malignant Mesothelioma; Extensive Stage Small Cell Lung Cancer; Lung Metastases; Recurrent Malignant Mesothelioma; Recurrent Non-small Cell Lung Cancer; Recurrent Small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer

  16. SINTERED REFRACTORY MASS

    DOEpatents

    Williams, A.E.

    1955-09-01

    A method is given for joining sintered masses of refractory compounds. It consists in maintaining the masses in contact with each other by application of a moderate pressure, while they are at sintering temperature. The sintered masses are subjected to am applied pressure of about 1/2 to 1 ton per square inch of the surface in contact for about 10 minutes, and the temperature employed may be fropn about 1400 deg C to 2000 deg C. Refractory oxides to which the invention may be applied are beryllia, alumina, thoria, and magnesia.

  17. Refractory peptic ulcer disease.

    PubMed

    Napolitano, Lena

    2009-06-01

    Refractory PUD is a diagnostic and therapeutic challenge. Optimal management of severe or refractory PUD requires a multidisciplinary team approach, using primary care providers, gastroenterologists, and general surgeons. Medical management has become the cornerstone of therapy. Identification and eradication of H pylori infection combined with acid reduction regimens can heal ulceration and also prevent recurrence. Severe, intractable or recurrent PUD and associated complications mandates a careful and methodical evaluation and management strategy to determine the potential etiologies and necessary treatment (medical or surgical) required.

  18. Trametinib or Combination Chemotherapy in Treating Patients With Refractory or Advanced Biliary or Gallbladder Cancer or That Cannot Be Removed by Surgery

    ClinicalTrials.gov

    2017-01-06

    Adult Cholangiocarcinoma; Advanced Adult Hepatocellular Carcinoma; BCLC Stage C Adult Hepatocellular Carcinoma; BCLC Stage D Adult Hepatocellular Carcinoma; Hilar Cholangiocarcinoma; Localized Non-Resectable Adult Liver Carcinoma; Recurrent Adult Liver Carcinoma; Recurrent Childhood Liver Cancer; Recurrent Extrahepatic Bile Duct Carcinoma; Recurrent Gallbladder Carcinoma; Stage II Gallbladder Cancer; Stage III Childhood Hepatocellular Carcinoma; Stage IIIA Gallbladder Cancer; Stage IIIB Gallbladder Cancer; Stage IV Childhood Hepatocellular Carcinoma; Stage IV Distal Bile Duct Cancer; Stage IVA Gallbladder Cancer; Stage IVB Gallbladder Cancer; Unresectable Extrahepatic Bile Duct Carcinoma

  19. Anti-PD-1/PD-L1 antibody therapy for pretreated advanced nonsmall-cell lung cancer

    PubMed Central

    Zhou, Guo-Wu; Xiong, Ye; Chen, Si; Xia, Fan; Li, Qiang; Hu, Jia

    2016-01-01

    Abstract Background: Anti-PD-1/PD-L1 antibody therapy is a promising clinical treatment for nonsmall-cell lung cancer (NSCLC). However, whether anti-PD-1/PD-L1 antibody therapy can provide added benefits for heavily pretreated patients with advanced NSCLC and whether the efficacy of anti-PD-1/PD-L1 antibody therapy relates to the tumor PD-L1 expression level remain controversial. Thus, this meta-analysis evaluated the efficacy and safety of anti-PD-1/PD-L1 antibody therapy for pretreated patients with advanced NSCLC. Methods: Randomized clinical trials were retrieved by searching the PubMed, EMBASE, ASCO meeting abstract, clinicaltrial.gov, and Cochrane library databases. The pooled hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS), and odds ratios for the overall response rate and adverse events (AEs) were calculated by STATA software. Results: Three randomized clinical trials involving 1141 pretreated patients with advanced NSCLC were included. These trials all compared the efficacy and safety of anti-PD-1/PD-L1 antibodies (nivolumab and MPDL3280A) with docetaxel. The results suggested that, for all patients, anti-PD-1/PD-L1 therapy could acquire a greater overall response (odds ratio = 1.50, 95% CI: 1.08–2.07, P = 0.015, P for heterogeneity [Ph] = 0.620) and longer OS (HR = 0.71, 95% CI: 0.61–0.81, P < 0.001, Ph = 0.361) than docetaxel, but not PFS (HR = 0.83, 95% CI: 0.65–1.06, P = 0.134; Ph = 0.031). Subgroup analyses according to the tumor PD-L1 expression level showed that anti-PD-1/PD-L1 therapy could significantly improve both OS and PFS in patients with high expressions of PD-L1, but not in those with low expressions. Generally, the rates of grade 3 or 4 AEs of anti-PD-1/PD-L1 therapy were significantly lower than that of docetaxel. However, the risks of pneumonitis and hypothyroidism were significantly higher. Conclusion: Anti-PD-1/PD-L1 antibody therapy may significantly improve

  20. Efficacy of goserelin plus anastrozole in premenopausal women with advanced or recurrent breast cancer refractory to an LH-RH analogue with tamoxifen: Results of the JMTO BC08-01 phase II trial

    PubMed Central

    NISHIMURA, REIKI; ANAN, KEISEI; YAMAMOTO, YUTAKA; HIGAKI, KENJI; TANAKA, MAKI; SHIBUTA, KENJI; SAGARA, YASUAKI; OHNO, SHINJI; TSUYUKI, SHIGERU; MASE, TAKAHIRO; TERAMUKAI, SATOSHI

    2013-01-01

    The aim of the present study was to assess the efficacy and tolerability of a luteinizing hormone-releasing hormone (LH-RH) analogue plus an aromatase inhibitor following failure to respond to standard LH-RH analogue plus tamoxifen (TAM) in premenopausal patients. Premenopausal women with estrogen receptor (ER)-positive and/or progesterone-receptor positive, advanced or recurrent breast cancer refractory to an LH-RH analogue plus TAM received goserelin (GOS) in conjunction with anastrozole (ANA). The primary endpoint was the objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), clinical benefit rate (CBR) and safety. Between September 2008 and November 2010, 37 patients were enrolled. Thirty-five patients (94.6%) had ER-positive tumors, and 36 (97.3%) had human epidermal growth factor receptor (HER) 2-negative tumors. Thirty-six (97.3%) had measurable lesions and 1 (2.7%) had only bone metastasis. The ORR was 18.9% [95% confidence interval (CI), 8.0–35.2%], the CBR was 62.2% (95% CI, 44.8–77.5%) and the median PFS was 7.3 months. Eight patients had adverse drug reactions but none resulted in discontinuation of treatment. GOS plus ANA is a safe effective treatment for premenopausal women with hormone receptor-positive, recurrent or advanced breast cancer. The treatment may become viable treatment in the future, particularly when TAM is ineffective or contraindicated. Further studies and discussion are warranted. PMID:23446822

  1. [Correlation between pulmonary function indexes and survival time in patients with advanced lung cancer].

    PubMed

    Ge, Hui; Jiang, Zhenghua; Huang, Qian; Zhu, Muyun; Yang, Jie

    2013-07-01

    背景与目的 晚期肺癌患者的治疗以提高疗效和改善生活质量为最终目的,肺功能指标是较好的评价指标。本研究探讨晚期肺癌患者肺功能改变及肺功能指标与患者生存期的相关性。方法 通过对59例晚期肺癌患者的肺功能进行检测,且与患者生存期进行相关性分析,并与63例健康人进行对照。结果 晚期肺癌患者的肺通气及弥散功能指标明显低于正常,与对照相比有统计学差异。肺功能指标中肺活量(vital capacity, VC)、第1秒用力呼出量(forced expiratory volume in one second, FEV1)、用力肺活量(gorced vital capacity, FVC)、最大呼气流速(peak expiratory flow, PEF)、最大呼气流速%(peak expiratory flow%, PEF%)、最大通气量(maximal ventilatory volume, MVV)与患者生存期呈正相关(r分别为0.29、0.28、0.28、0.27、0.26、0.28,P<0.05),残气量/肺总量(residual volume/total lung, RV/TLC)值与患者生存期呈负相关(r=-0.31, P<0.05)。结论 肺癌患者存在肺功能的减退,肺癌患者肺功能指标中VC、FEV1、FVC、PEF、PEF%、MVV、RV/TCL值与患者生存期具有相关性,肺功能的部分指标可作为肺癌患者预后评估的重要因素之一。

  2. Effect of vinorelbine, ifosfamide, and cisplatin combination chemotherapy in advanced non-small-cell lung cancer.

    PubMed

    Ahn, J B; Ko, W K; Lee, J G; Shim, K Y; Jeung, H C; Park, J O; Yoo, N C; Kim, B S; Kim, S K; Kim, S K; Kim, J H

    2000-12-01

    Cisplatin-based chemotherapy is being tried in the treatment of nonoperable cases of non-small-cell lung cancer (NSCLC). However, the prognosis is unfavorable and to improve survival, clinical studies using various combinations of a variety of drugs as well as experimental material are in progress. We compared the efficacy and toxicities of combination chemotherapy using different doses of vinorelbine and ifosfamide with a constant dose of cisplatin in this study. Patients diagnosed with inoperable stage III or IV NSCLC between June 1997 and December 1998 were included. Cisplatin was administered at a constant dose of 80 mg/m2 on day 5, whereas vinorelbine on days 1 and 5 and ifosfamide on day 5 were administered in one of two different doses. In arm A, vinorelbine 25 mg/m2 and ifosfamide 3.0 g/m2 were administered. In arm B, vinorelbine 20 mg/m2 and ifosfamide 2.5 g/m2 were administered. Also, we reviewed for phase II and III studies that test 1) cisplatin, 2) vinorelbine monotherapy, and 3) vinorelbine/cisplatin/ifosfamide combination chemotherapy for stage IIIb-IV non-SCLC. Summation dose intensity (SDI) was calculated in each published and current study. Twenty patients in arm A and 35 patients in arm B were available for evaluation. There was no difference in patient activity, pathologic diagnosis, and differentiation or stage between the two arms. The median number of cycles was four in both arms. The response rate was 50% in arm A and 30% in arm B. The median survival times for arm A and B were 40 and 42 weeks, respectively, whereas the SDI was 1.94 and 1.7, respectively. More than grade III leukopenia was observed in 28.9% in arm A, which is more frequent than the 17.2% in arm B. There was a significant correlation between the SDIs and response rates and median survival (r2 = 0.629, p = 0.001; r2 = 0.453, p = 0.001, respectively). Although the follow-up period is relatively short, the survival time was similar in both arms. Because a high response rate may

  3. Dynamic Testing of Gasifier Refractory

    SciTech Connect

    Michael D. Mann; Wayne S. Seames; Devdutt Shukla; Xi Hong; John P. Hurley

    2005-12-01

    The University of North Dakota (UND) Chemical Engineering Department in conjunction with the UND Energy & Environmental Research Center (EERC) have initiated a program to examine the combined chemical (reaction and phase change) and physical (erosion) effects experienced by refractory materials under slagging coal gasification conditions. The goal of this work is to devise a mechanism of refractory loss under these conditions. The controlled-atmospheric dynamic corrodent application furnace (CADCAF) was utilized to simulate refractory/slag interactions under dynamic conditions that more realistically simulate the environment in a slagging coal gasifier than any of the static tests used previously by refractory manufacturers and researchers. High-alumina and high-chromia refractory bricks were tested using slags obtained from two solid fuel gasifiers. Testing was performed at 1475 C in a reducing atmosphere (2% H{sub 2} in N{sub 2}) The CADCAF tests show that high-chrome refractories have greater corrosion resistance than high-aluminum refractories; coal slag readily diffuses into the refractory through its grain boundaries; the refractory grains are more stable than the matrix in the tests, and the grains are the first line of defense against corrosion; calcium and alkali in the slag are more corrosive than iron; and silicon and calcium penetrate the deepest into the refractory. The results obtained from this study are preliminary and should be combined with result from other research programs. In particular, the refractory corrosion results from this study should be compared with refractories removed from commercial gasifiers.

  4. Antiangiogenic Therapy in Advanced Non-small-cell Lung Cancer: A Meta-analysis of Phase III Randomized Trials.

    PubMed

    Raphael, Jacques; Chan, Kelvin; Karim, Safiya; Kerbel, Robert; Lam, Henry; Santos, Keemo Delos; Saluja, Ronak; Verma, Sunil

    2017-01-12

    We conducted a meta-analysis to evaluate the efficacy of adding any antiangiogenic therapy (AT) to the standard of care in advanced non-small-cell lung cancer (NSCLC). The electronic databases Ovid PubMed, Cochrane Central Register of Controlled Trials, and Embase were searched to identify eligible trials. We included all phase III randomized trials with any line and type of treatment, histology. and AT dose. Pooled hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS), and pooled odds ratio (OR) for overall response rates (RR) were calculated. We divided the population into 2 subgroups based on the bevacizumab dose. Data of 19,098 patients from 25 phase III trials were analyzed. Compared with the standard of care, the addition of AT did not prolong OS (HR 0.98; 95% confidence interval [CI], 0.96-1.00; P = .1 and HR 0.97; 95% CI, 0.94-1.00; P = .06 for groups 1 and 2, respectively). However, there was a significant improvement in PFS with the addition of AT (HR 0.85; 95% CI, 0.79-0.91; P < .00001 and HR 0.81; 95% CI, 0.75-0.88; P < .00001 for groups 1 and 2, respectively) and overall RR (OR 1.61; 95% CI, 1.30-2.01; P < .0001 and OR 1.72; 95% CI, 1.39-2.14; P < .00001 for groups 1 and 2, respectively). This is the first meta-analysis including only all phase III trials with AT in NSCLC showing no significant effect on OS and an improvement in PFS and RR only. The role of AT in advanced NSCLC is still questionable; strong validated biomarkers are eagerly needed to predict which subgroup might benefit the most from such therapy.

  5. Efficacy and safety of nivolumab in Japanese patients with advanced or recurrent squamous non-small cell lung cancer.

    PubMed

    Hida, Toyoaki; Nishio, Makoto; Nogami, Naoyuki; Ohe, Yuichiro; Nokihara, Hiroshi; Sakai, Hiroshi; Satouchi, Miyako; Nakagawa, Kazuhiko; Takenoyama, Mitsuhiro; Isobe, Hiroshi; Fujita, Shiro; Tanaka, Hiroshi; Minato, Koichi; Takahashi, Toshiaki; Maemondo, Makoto; Takeda, Koji; Saka, Hideo; Goto, Koichi; Atagi, Shinji; Hirashima, Tomonori; Sumiyoshi, Naoki; Tamura, Tomohide

    2017-03-07

    Limited treatment options are available for stage IIIB/IV non-small cell lung cancer (NSCLC). Nivolumab, a programmed cell death-1 immune checkpoint inhibitor antibody, has been shown to be effective for the treatment of NSCLC. This study investigated the effectiveness and safety of nivolumab in Japanese patients with advanced or recurrent squamous NSCLC that progressed after platinum-containing chemotherapy. In this multicenter phase II study, patients were treated with nivolumab (3mg/kg, intravenously) every 2 weeks until progressive disease or unacceptable toxicity was seen. The primary endpoint was overall response rate (ORR) assessed by independent radiology review committee (IRC) and secondary endpoints included a study site-assessed ORR, overall survival (OS), progression-free survival (PFS), duration of response, time to response, best overall response (BOR), and safety. The study included 35 patients from 17 sites in Japan. Patients had IRC-assessed ORR of 25.7% (95% CI 14.2, 42.1) and the study site-assessed ORR was 20.0% (95% CI 10.0, 35.9). The median OS, median time to response and median PFS were 16.3 (95% CI 12.4-25.4), 2.7 (range 1.2-5.5) and 4.2 (95% CI 1.4-7.1) months, respectively. The IRC-assessed BOR was partial response, stable disease, and progressive disease for 25.7%, 28.6%, and 45.7% of patients, respectively. Treatment-related adverse events were reported in 24 patients (68.6%), most of which resolved with appropriate treatment including steroid therapy or ‎discontinuation of nivolumab. Nivolumab was effective and well tolerated in Japanese patients with advanced or recurrent squamous NSCLC that progressed after platinum-containing chemotherapy. This article is protected by copyright. All rights reserved.

  6. Circulating DNA in diagnosis and monitoring EGFR gene mutations in advanced non-small cell lung cancer

    PubMed Central

    Del Re, Marzia; Danesi, Romano; Tiseo, Marcello

    2015-01-01

    Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are current treatments for advanced non-small cell lung cancer (NSCLC) harboring activating EGFR gene mutations. Histological or cytological samples are the standard tumor materials for EGFR mutation analysis. However, the accessibility of tumor samples is not always possible and satisfactory in advanced NSCLC patients. Moreover, totality of EGFR mutated NSCLC patients will develop resistance to EGFR-TKIs. Repeat biopsies to study genetic evolution as a result of therapy are difficult, invasive and may be confounded by intra-tumor heterogeneity. Thus, exploring accurate and less invasive techniques to (I) diagnosis EGFR mutation if tissue is not available or not appropriate for molecular analysis and to (II) monitor EGFR-TKI treatment are needed. Circulating DNA fragments carrying tumor specific sequence alterations [circulating cell-free tumor DNA (cftDNA)] are found in the cell-free fraction of blood, representing a variable and generally small fraction of the total circulating DNA. cftDNA has a high degree of specificity to detect EGFR gene mutations in NSCLC. Studies have shown the feasibility of using cftDNA to diagnosis of EGFR activating gene mutations and also to monitor tumor dynamics in NSCLC patients treated with EGFR-TKIs. These evidences suggested that non-invasive techniques based on blood samples had a great potential in EGFR mutated NSCLC patients. In this review, we summarized these non-invasive approaches and relative scientific data now available, considering their possible applications in clinical practice of NSCLC treatment. PMID:26629427

  7. Oxidative stress, redox signaling pathways, and autophagy in cachectic muscles of male patients with advanced COPD and lung cancer.

    PubMed

    Puig-Vilanova, Ester; Rodriguez, Diego A; Lloreta, Josep; Ausin, Pilar; Pascual-Guardia, Sergio; Broquetas, Joan; Roca, Josep; Gea, Joaquim; Barreiro, Esther

    2015-02-01

    Muscle dysfunction and wasting are predictors of mortality in advanced COPD and malignancies. Redox imbalance and enhanced protein catabolism are underlying mechanisms in COPD. We hypothesized that the expression profile of several biological markers share similarities in patients with cachexia associated with either COPD or lung cancer (LC). In vastus lateralis of cachectic patients with either LC (n=10) or advanced COPD (n=16) and healthy controls (n=10), markers of redox balance, inflammation, proteolysis, autophagy, signaling pathways, mitochondrial function, muscle structure, and sarcomere damage were measured using laboratory and light and electron microscopy techniques. Systemic redox balance and inflammation were also determined. All subjects were clinically evaluated. Compared to controls, in both cachectic groups of patients, a similar expression profile of different biological markers was observed in their muscles: increased levels of muscle protein oxidation and ubiquitination (p<0.05, both), which positively correlated (r=0.888), redox-sensitive signaling pathways (NF-κB and FoxO) were activated (p<0.05, all), fast-twitch fiber sizes were atrophied, muscle structural abnormalities and sarcomere disruptions were significantly greater (p<0.05, both). Structural and functional protein levels were lower in muscles of both cachectic patient groups than in controls (p<0.05, all). However, levels of autophagy markers including ultrastructural autophagosome counts were increased only in muscles of cachectic COPD patients (p<0.05). Systemic oxidative stress and inflammation levels were also increased in both patient groups compared to controls (p<0.005, both). Oxidative stress and redox-sensitive signaling pathways are likely to contribute to the etiology of muscle wasting and sarcomere disruption in patients with respiratory cachexia: LC and COPD.

  8. Impact of COPD in patients with lung cancer and advanced disease treated with chemotherapy and/or tyrosine kinase inhibitors.

    PubMed

    Izquierdo, José Luis; Resano, Pilar; El Hachem, Abdulkader; Graziani, Desiré; Almonacid, Carlos; Sánchez, Ignacio M

    2014-01-01

    While it is relatively well known that the prognosis of patients with lung cancer (LC) treated with surgery is worse in the presence of chronic obstructive pulmonary disease (COPD), it is unknown if this assessment can be extrapolated to patients with advanced disease treated with chemotherapy and/or tyrosine kinase inhibitors. The aim of our study is to analyze the clinical characteristics and survival rates in patients with LC and COPD, and to compare these to the patients without airflow obstruction. From 471 evaluable patients, 324 (69%) were not treated with surgery due to disseminated disease (stages 3B and 4). Of them, 47.7% also had COPD. All patients were treated at the moment of diagnosis according to National Comprehensive Cancer Network guidelines with platinum-based chemotherapy or tyrosine kinase inhibitors. Kaplan-Meier curves showed no significant differences in overall survival between COPD and non-COPD patients (log-rank P=0.65). In the multivariate Cox proportional hazard model adjusting for the most relevant variables, the adjusted hazard ratio (HRadj) was statistically significant for performance status (HRadj =1.33, 95% confidence interval [CI]: 1.11-1.59; P=0.002) and clinical stage (HRadj =0.67, 95% CI: 0.50-0.89; P=0.006), but not for COPD status (HRadj =1.20, 95% CI: 0.83-1.50; P=0.46). Our conclusion is that at present, when using standard care in advanced LC (stages 3B and 4), COPD does not have a significant deleterious impact on overall survival.

  9. SHS of refractory materials

    NASA Astrophysics Data System (ADS)

    Ismailov, M. B.; Gabayev, Zh. A.

    1993-09-01

    In the SHS production of refractory materials (concretes, coating mixtures) the basic problem is overcoming the scale factor. This is done by imparting a granular structure to the mass being synthesized. Requirements for the granular and chemical composition of the filler are obtained.

  10. Refractory ceramic fibers

    Integrated Risk Information System (IRIS)

    Refractory ceramic fibers ; CASRN Not found Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcino

  11. Pretreatment Quality of Life Is an Independent Prognostic Factor for Overall Survival in Patients with Advanced Stage Non-small Cell Lung Cancer

    PubMed Central

    Qi, Yingwei; Schild, Steven E.; Mandrekar, Sumithra J.; Tan, Angelina D.; Krook, James E.; Rowland, Kendrith M.; Garces, Yolanda I.; Soori, Gamini S.; Adjei, Alex A.; Sloan, Jeff A.

    2010-01-01

    Hypothesis We conducted this pooled analysis to assess the prognostic value of pretreatment Quality of Life (QOL) assessments on overall survival (OS) in advanced non-small cell lung cancer (NSCLC). Methods Four hundred twenty patients with advanced NSCLC (stages IIIB with pleural effusion and IV) from six North Central Cancer Treatment Group trials were included in this study. QOL assessments included the single-item Uniscale (355 patients), Lung Cancer Symptom Scale (217 patients), and Functional Assessment of Cancer Therapy-Lung (197 patients). QOL scores were transformed to a 0 to 100 scale with higher scores representing better status and categorized using the sample median or clinically deficient score (CDS, ≤50 versus >50). Cox proportional hazards models stratified by study were used to evaluate the prognostic importance of QOL on OS alone and in the presence of other prognostic factors such as performance status, age, gender, body mass index, and laboratory parameters. Results Pretreatment QOL accessed by Uniscale was significantly associated with OS univariately (p < 0.0001). Uniscale (p < 0.0001; hazard ratio = 1.6 for the sample median and 2.0 for the CDS categorization) and body mass index were the only significant predictors of OS multivariately. The median survival of patients who had a Uniscale score less than or equal to the CDS (≤50) was 5.7 versus 11.1 months for the >50 group; and 7.8 versus 13 months for the less than or equal to sample median (≤83) group and >83 group, respectively. The Lung Cancer Symptom Scale and the Functional Assessment of Cancer Therapy-Lung total scores were not significant predictors of OS. Conclusions Pretreatment QOL measured by Uniscale is a significant and an independent prognostic factor for OS, and QOL should be routinely integrated as a stratification factor in advanced NSCLC trials. PMID:19546817

  12. Optimizing the use of epidermal growth factor receptor inhibitors in advanced non-small-lung cancer (NSCLC)

    PubMed Central

    Shash, Emad; Peccatori, Fedro Alessandro; Azim, Hatem A

    2011-01-01

    Lung cancer is the leading cause of cancer-related death in US and Europe. Treatment with a platinum-based chemotherapy remains the standard of care, however with modest effect on quality of life and overall survival which seldom reaches 1 year. Recently, several classes of targeted agents have emerged showing promising results. In particular, agents targeting the epidermal growth factor receptor (EGFR) showed impressive clinical activity both in the first line and salvage settings. However, it is evident that these drugs are not effective in all patients. Putting into consideration the very high cost of these agents, there is an urgent need to provide reliable tools to identify those patients that would derive the maximum benefit from these drugs. Several predictive biomarkers were developed to identify those patients who would derive the maximal benefit of these drugs. In this review we will discuss the recent updates on the role of EGFR inhibitors in the treatment of advanced NSCLC and the role of predictive bio-markers in patient selection. PMID:22263061

  13. Incremental Innovation and Progress in Advanced Squamous Cell Lung Cancer: Current Status and Future Impact of Treatment.

    PubMed

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

    2016-12-01

    Squamous cell lung cancer (sqCLC) is an aggressive form of cancer that poses many therapeutic challenges. Patients tend to be older, present at a later stage, and have a high incidence of comorbidities, which can compromise treatment delivery and exacerbate toxicity. In addition, certain agents routinely available for nonsquamous cell histologic subtypes, such as bevacizumab and pemetrexed, are contraindicated or lack efficacy in sqCLC. Therapeutic progress has been much slower for advanced sqCLC, with median survival times of approximately 9 to 11 months in most studies. Herein, we discuss the current therapeutic landscape for patients with sqCLC versus with nonsquamous NSCLC. Current evidence indicates that new targeted treatments, notably monoclonal antibodies such as ramucirumab and necitumumab, and immunotherapies such as nivolumab and pembrolizumab can provide survival prolongation, although the benefits are still relatively modest. These incremental improvements, all realized since 2012, in aggregate, will very likely have a clinically meaningful impact for patients with sqCLC. We also discuss recent genomic studies of sqCLC that have identified potentially actionable molecular targets, as well as the relevant targeted agents in clinical development. Finally, we discuss the magnitude of survival benefit and the risk-to-benefit ratio that would prove clinically meaningful in this underserved patient population with unmet needs.

  14. Phase II study of SPI-77 (sterically stabilised liposomal cisplatin) in advanced non-small-cell lung cancer.

    PubMed

    White, S C; Lorigan, P; Margison, G P; Margison, J M; Martin, F; Thatcher, N; Anderson, H; Ranson, M

    2006-10-09

    To determine the efficacy and tolerability of SPI-77 (sterically stabilised liposomal cisplatin) at three dose levels in patients with advanced non-small-cell lung cancer (NSCLC). Patients had Stage IIIB or IV NSCLC and were chemo-naïve, and Eastern Oncology Cooperative Group 0-2. The first cohort received SPI-77 at 100 mg m-2, the second 200 mg m-2 and the final cohort 260 mg m-2. Patients had also pharmacokinetics and analysis of leucocyte platinum (Pt)-DNA adducts performed. Twenty-six patients were treated, with 22 patients being evaluable for response. Only one response occurred at the 200 mg m-2 dose level for an overall response rate of 4.5% (7.1% at >or=200 mg m-2). No significant toxicity was noted including nephrotoxicity or ototoxicity aside from two patients with Grade 3 nausea. No routine antiemetics or hydration was used. The pharmacokinetic profile of SPI-77 was typical for a liposomally formulated drug, and the AUC appeared to be proportional to the dose of SPI-77. Plasma Pt levels and leucocyte DNA adduct levels did not appear to rise with successive doses. SPI-77 demonstrates only modest activity in patients with NSCLC.

  15. Phase II study of SPI-77 (sterically stabilised liposomal cisplatin) in advanced non-small-cell lung cancer

    PubMed Central

    White, S C; Lorigan, P; Margison, G P; Margison, J M; Martin, F; Thatcher, N; Anderson, H; Ranson, M

    2006-01-01

    To determine the efficacy and tolerability of SPI-77 (sterically stabilised liposomal cisplatin) at three dose levels in patients with advanced non-small-cell lung cancer (NSCLC). Patients had Stage IIIB or IV NSCLC and were chemo-naïve, and Eastern Oncology Cooperative Group 0–2. The first cohort received SPI-77 at 100 mg m−2, the second 200 mg m−2 and the final cohort 260 mg m−2. Patients had also pharmacokinetics and analysis of leucocyte platinum (Pt)-DNA adducts performed. Twenty-six patients were treated, with 22 patients being evaluable for response. Only one response occurred at the 200 mg m−2 dose level for an overall response rate of 4.5% (7.1% at ⩾200 mg m−2). No significant toxicity was noted including nephrotoxicity or ototoxicity aside from two patients with Grade 3 nausea. No routine antiemetics or hydration was used. The pharmacokinetic profile of SPI-77 was typical for a liposomally formulated drug, and the AUC appeared to be proportional to the dose of SPI-77. Plasma Pt levels and leucocyte DNA adduct levels did not appear to rise with successive doses. SPI-77 demonstrates only modest activity in patients with NSCLC. PMID:16969346

  16. Weight gain as a surrogate marker of longer survival in advanced non-small cell lung cancer patients

    PubMed Central

    2016-01-01

    Weight loss (WL), as a key step of the irreversible and fatal cancer-related anorexia cachexia syndrome is present to some degree in 80% of non-small cell lung cancer (NSCLC) patients upon diagnosis which has been clearly proved to negatively alter patients’ performance status, quality of life (QOL), response to treatment, and prognosis. However, WL is not a problem encountered only upon diagnosis but is also commonly reported during the course of aggressive chemotherapy, radiotherapy (RT) and particularly the concurrent chemoradiotherapy (C-CRT) which may further diminish QOL measures and clinical outcomes. In general, the NSCLC literature has concentrated on WL during the treatment course, but recent studies have demonstrated that it is possible to preserve or even experience weight gain (WG) during or just short after the discontinuation of various cancer treatments in approximately 40% to 45% NSCLC patients. Considering the fact that recent evidence suggest a prognostic and predictive role for WG in anticipation of longer survival times and better response rates in weight gainers, this current manuscript will specifically aim to realize the actual value of WG in locally advanced and metastatic NSCLC patients which may potentially be added to the conventional prognostic and predictive factors as a novel surrogate marker of outcomes in such patients. PMID:27826583

  17. Receptor for advanced glycation end products involved in lung ischemia reperfusion injury in cardiopulmonary bypass attenuated by controlled oxygen reperfusion in a canine model.

    PubMed

    Rong, Jian; Ye, Sheng; Liang, Meng-ya; Chen, Guang-xian; Liu, Hai; Zhang, Jin-Xin; Wu, Zhong-kai

    2013-01-01

    Controlled oxygen reperfusion could protect the lung against ischemia-reperfusion injury in cardiopulmonary bypass (CPB) by downregulating high mobility group box 1 (HMGB1), a high affinity receptor of HMGB1. This study investigated the effect of controlled oxygen reperfusion on receptor for advanced glycation end products (RAGE) expression and its downstream effects on lung ischemia-reperfusion injury. Fourteen canines received CPB with 60 minutes of aortic clamping and cardioplegic arrest followed by 90 minutes of reperfusion. Animals were randomized to receive 80% FiO2 during the entire procedure (control group) or to a test group receiving a controlled oxygen reperfusion protocol. Pathologic changes in lung tissues, RAGE expression, serum interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were evaluated. The lung pathologic scores after 25 and 90 minutes of reperfusion were significantly lower in the test group compared with the control group (p < 0.001). RAGE expression, TNF-α, and IL-6 were downregulated by controlled oxygen treatment (p < 0.001). RAGE might be involved in the lung ischemia-reperfusion injury in canine model of CPB, which was downregulated by controlled oxygen reperfusion.

  18. Gallic acid inhibition of Src-Stat3 signaling overcomes acquired resistance to EGF receptor tyrosine kinase inhibitors in advanced non-small cell lung cancer

    PubMed Central

    Phan, Ai N.H.; Hua, Tuyen N.M.; Kim, Min-Kyu; Vo, Vu T.A.; Choi, Jong-Whan; Kim, Hyun-Won; Rho, Jin Kyung; Kim, Ki Woo; Jeong, Yangsik

    2016-01-01

    Tyrosine kinase inhibitors (TKIs) targeting epidermal growth factor receptor (EGFR) have clinically benefited to lung cancer patients harboring a subset of activating EGFR mutations. However, even with the remarkable therapeutic response at the initial TKI treatment, most lung cancer patients eventually have relapsed aggressive tumors due to acquired resistance to the TKIs. Here, we report that 3, 4, 5-trihydroxybenzoic acid or gallic acid (GA), a natural polyphenolic compound, shows anti-tumorigenic effects in TKI-resistant non-small cell lung cancer (NSCLC). Using both in vitro growth assay and in vivo xenograft animal model, we demonstrated tumor suppressive effect of GA was more selective for the TKI-resistant cancer compared to the TKI-sensitive one. Mechanistically, GA treatment inhibited Src-Stat3-mediated signaling and decreased the expression of Stat3-regulated tumor promoting genes, subsequently inducing apoptosis and cell cycle arrest in the TKI-resistant lung cancer but not in the TKI-sensitive one. Consistent with the in vitro results, in vivo xenograft experiments showed the TKI-resistant tumor-selective growth inhibition and suppression of Src-Stat3-dependent signaling in the GA-treated tumors isolated from the xenograft model. This finding identified an importance of Src-Stat3 signaling cascade in GA-mediated tumor-suppression activity and, more importantly, provides a novel therapeutic insight of GA for advanced TKI-resistant lung cancer. PMID:27419630

  19. Status epilepticus: Refractory and super-refractory.

    PubMed

    Dubey, Deepanshu; Kalita, Jayantee; Misra, Usha K

    2017-01-01

    Status epilepticus (SE) is an important neurological emergency. It is defined as seizures lasting for 5 minutes or more or recurrent seizures without recovery of consciousness to baseline between the attacks. Refractory SE (RSE) is defined as SE persisting despite sufficient dose of benzodiazepines and at least one antiepileptic drug (AED), irrespective of time. Super refractory SE (SRSE) is defined as SE that continues for 24 hours or more after the use of anesthetic therapy, including cases that recur on weaning of the anesthestic agent. RSE occurs in 23%-48% of the patients and SRSE in approximately 22% of the patients with SE. In general, RSE occurs in patients with new-onset seizures rather than in patients with chronic epilepsy. The etiology of RSE in developing countries is dominated by central nervous system (CNS) infections and head injury compared to stroke and drug withdrawal in the developed countries. The treatment of RSE and SRSE is not evidence based. Following benzodiazepines, the second line antiepileptic drugs include sodium valproate, phenytoin, levetiracetam, and anesthetic drugs such as midazolam, phenobarbital, and propofol. Most intravenous anesthetic drugs produce hypotension and respiratory suppression; therefore, patients with RSE are managed in intensive care units (ICUs). In RSE patients, electroencephalogram (EEG) burst suppression with interburst interval of 2-20 s or even flat EEG has been tried. Recently, concerns have been raised on the safety of burst suppression in RSE and SRSE. The paucity of ICUs in developing countries limits the use of these management protocols. There is a need to explore intravenous AEDs with safer cardiovascular and respiratory profile for the management of SE.

  20. Expression of RNA-binding motif 10 is associated with advanced tumor stage and malignant behaviors of lung adenocarcinoma cancer cells.

    PubMed

    Guan, Guofang; Li, Ranwei; Tang, Wenfang; Liu, Tiecheng; Su, Zhenzhong; Wang, Yan; Tan, Jingjin; Jiang, Shan; Wang, Ke

    2017-03-01

    This study assessed RNA-binding motif 10 expression in lung adenocarcinoma tissues and examined the role and mechanism of RNA-binding motif 10 in the regulation of lung adenocarcinoma malignancy. Lung adenocarcinoma and corresponding adjacent non-tumor lung tissues from 41 patients were subjected to reverse transcription-polymerase chain reaction and Western blot assessment to detect RNA-binding motif 10 expression. Recombinant lentivirus carrying RNA-binding motif 10 complementary DNA was used to infect lung adenocarcinoma cell lines, A549 and H1299 cells. Complementary DNA microarray was used to profile RNA-binding motif 10-regulated genes. Levels of RNA-binding motif 10 messenger RNA and protein were significantly lower in lung adenocarcinoma tissues than those in paired non-tumor tissues (p < 0.001). Reduced RNA-binding motif 10 expression was found to be associated with an advanced tumor stage. RNA-binding motif 10 overexpression inhibited viability and colony formation capacity of lung adenocarcinoma cell lines and induced cell-cycle arrest at G0/G1 phase in A549 cells and at S phase in H1299 cells. Complementary DNA microarray analysis identified 304 upregulated and 386 downregulated genes induced by RNA-binding motif 10 overexpression, which may be involved in cancer, focal adhesion, peroxisome proliferator-activated receptor-regulated gene pathway, cytokine-cytokine receptor interaction, mitogen-activated protein kinase signaling, complement and coagulation cascades, platelet amyloid precursor protein pathway, extracellular matrix-receptor interaction, and small cell lung cancer-related genes. Expression of FGF2, EGFR, WNT5A, NF-κB, and RAP1A was downregulated, whereas expression of AKT2, BIRC3, and JUN was upregulated. RNA-binding motif 10 messenger RNA and protein were reduced in lung adenocarcinoma tissues, and RNA-binding motif 10 overexpression inhibited lung adenocarcinoma cancer cell malignant behavior in vitro. Molecularly, RNA-binding motif

  1. Therapeutic strategies for combined-modality therapy of locally advanced non-small-cell lung cancer: rationale for consolidation docetaxel therapy.

    PubMed

    Gandara, David R; Vallières, Eric; Gaspar, Laurie E; Kelly, Karen; Albain, Kathy S; Herbst, Roy S; Lara, Primo N; Mack, Philip; Gumerlock, Paul H; Crowley, John J

    2005-12-01

    Currently, there is no accepted standard of care for locally advanced and surgically unresectable non-small-cell lung cancer. Typically, treatment for patients with good performance status consists of a combination of chemotherapy and thoracic radiation therapy (RT), but the integration of these modalities and the respective dose schedules vary considerably. Herein, we review the rationale for a treatment paradigm employing consolidation docetaxel therapy after concurrent chemotherapy/RT and the results of recent clinical trials using this approach.

  2. Prognostic Value of Baseline 18F-FDG PET/CT Functional Parameters in Patients with Advanced Lung Adenocarcinoma Stratified by EGFR Mutation Status

    PubMed Central

    Wang, Dalong; Zhang, Minghui; Gao, Xuan; Yu, Lijuan

    2016-01-01

    The study objective was to retrospectively analyze the metabolic variables derived from 18 F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) as predictors of progression-free survival (PFS) and overall survival (OS) in advanced lung adenocarcinoma stratified by epidermal growth factor receptor (EGFR) mutation status. A total of 176 patients (91, EGFR mutation; 85, wild-type EGFR) who underwent 18F-FDG PET/CT before treatment were enrolled. The main 18F-FDG PET/CT-derived variables: primary tumor maximum standardized uptake value (SUVmaxT), primary tumor total lesion glycolysis (TLGT), the maximum SUVmax of all selected lesions in whole body determined using the Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria (SUVmaxWBR), and whole-body total TLG determined using the RECIST 1.1 criteria (TLGWBR) were measured. Survival analysis regarding TLGWBR, and other factors in advanced lung adenocarcinoma patients stratified using EGFR mutation status, were evaluated. The results indicated that high TLGWBR (≥259.85), EGFR wild-type, and high serum LDH were independent predictors of worse PFS and OS in all patients with advanced lung adenocarcinoma. Among patients with wild-type EGFR, only TLGWBR retained significance as an independent predictor of both PFS and OS. Among patients with the EGFR mutation, high serum LDH level was an independent predictor of worse PFS and OS, and high TLGWBR (≥259.85) was an independent predictor of worse PFS but not worse OS. In conclusion, TLGWBR is a promising parameter for prognostic stratification of patients with advanced lung adenocarcinoma and EGFR status; however, it cannot be used to further stratify the risk of worse OS for patients with the EGFR mutation. Further prospective studies are needed to validate our findings. PMID:27336755

  3. Evaluation of plasma microRNA levels to predict insensitivity of patients with advanced lung adenocarcinomas to pemetrexed and platinum.

    PubMed

    Zhu, Jinghua; Qi, Yuhua; Wu, Jianzhong; Shi, Meiqi; Feng, Jifeng; Chen, Longbang

    2016-12-01

    Pemetrexed combined with platinum is a first-line therapy used to treat patients with advanced non-small cell lung cancer (NSCLC) that exhibit negative or unknown epidermal growth factor receptor (EGFR) mutational status or anaplastic lymphoma kinase (ALK) rearrangements. Lung adenocarcinoma (LAC) is the primary type of NSCLC. In order to prevent overtreatment, it is necessary to identify patients with LAC who may not benefit from certain chemotherapies. Patients recruited in the present study (n=129) were diagnosed with advanced LAC and received first-line pemetrexed and platinum-based chemotherapy. A microRNA (miR) microarray was used to screen the plasma miR expression profiles in a screening set of eight patients prior to and following treatment. Specifically, plasma miR-25, miR-21, miR-27b, miR-326, miR-483-5p and miR-920 were selected for reverse transcription-quantitative polymerase chain reaction analysis in a training set (n=44) prior to treatment. The screening and training set patients were all non-smokers with no prior history of serious or chronic disease. The ∆∆Cq values of these miRs were compared between the group that showed benefit from pemetrexed and platinum treatment and the group that did not. Consequently, the ∆∆Cq values of miR-25, miR-21, miR-27b and miR-326 were further determined in a validation set (n=77). The results of the present study demonstrate that plasma expression levels of miR-25, miR-21, miR-27b and miR-326, in the training and validation sets prior to treatment, were significantly different between the benefit and non-benefit groups (P≤0.001). The expression of miR-25, miR-21, miR-27b and miR-326 was upregulated in the non-benefit group and this elevation was positively correlated with decreased progression-free survival (PFS; P≤0.001). In addition, the predictive power of each miR was evaluated through receiver operating characteristic curves, in which miR-25 exhibited the highest degree of accuracy (area under

  4. Image Guided Hypofractionated 3-Dimensional Radiation Therapy in Patients With Inoperable Advanced Stage Non-Small Cell Lung Cancer

    SciTech Connect

    Osti, Mattia Falchetto; Agolli, Linda; Valeriani, Maurizio; Falco, Teresa; Bracci, Stefano; De Sanctis, Vitaliana; Enrici, Riccardo Maurizi

    2013-03-01

    Purpose: Hypofractionated radiation therapy (HypoRT) can potentially improve local control with a higher biological effect and shorter overall treatment time. Response, local control, toxicity rates, and survival rates were evaluated in patients affected by inoperable advanced stage non-small cell lung cancer (NSCLC) who received HypoRT. Methods and Materials: Thirty patients with advanced NSCLC were enrolled; 27% had stage IIIA, 50% had stage IIIB, and 23% had stage IV disease. All patients underwent HypoRT with a prescribed total dose of 60 Gy in 20 fractions of 3 Gy each. Radiation treatment was delivered using an image guided radiation therapy technique to verify correct position. Toxicities were graded according to Radiation Therapy Oncology Group morbidity score. Survival rates were estimated using the Kaplan-Meier method. Results: The median follow-up was 13 months (range, 4-56 months). All patients completed radiation therapy and received the total dose of 60 Gy to the primary tumor and positive lymph nodes. The overall response rate after radiation therapy was 83% (3 patients with complete response and 22 patients with partial response). The 2-year overall survival and progression-free survival rates were 38.1% and 36%, respectively. Locoregional recurrence/persistence occurred in 11 (37%) patients. Distant metastasis occurred in 17 (57%) patients. Acute toxicities occurred consisting of grade 1 to 2 hematological toxicity in 5 patients (17%) and grade 3 in 1 patient; grade 1 to 2 esophagitis in 12 patients (40%) and grade 3 in 1 patient; and grade 1 to 2 pneumonitis in 6 patients (20%) and grade 3 in 2 patients (7%). Thirty-three percent of patients developed grade 1 to 2 late toxicities. Only 3 patients developed grade 3 late adverse effects: esophagitis in 1 patient and pneumonitis in 2 patients. Conclusions: Hypofractionated curative radiation therapy is a feasible and well-tolerated treatment for patients with locally advanced NSCLC. Randomized

  5. Optimal tumor shrinkage predicts long-term outcome in advanced nonsmall cell lung cancer (NSCLC) treated with target therapy

    PubMed Central

    He, Xiaobo; Zhang, Yang; Ma, Yuxiang; Zhou, Ting; Zhang, Jianwei; Hong, Shaodong; Sheng, Jin; Zhang, Zhonghan; Yang, Yunpeng; Huang, Yan; Zhang, Li; Zhao, Hongyun

    2016-01-01

    Abstract Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are used as standard therapies for advanced nonsmall cell lung cancer (NSCLC) patients with EGFR mutation positive. Because these targeted therapies could cause tumor necrosis and shrinkage, the purpose of the study is to search for a value of optimal tumor shrinkage as an appropriate indicator of outcome for advanced NSCLC. A total of 88 NSCLC enrollees of 3 clinical trials (IRESSA registration clinical trial, TRUST study and ZD6474 study), who received Gefitinib (250 mg, QD), Erlotinib (150 mg, QD), and ZD6474 (100 mg, QD), respectively, during December 2003 and October 2007, were retrospectively analyzed. The response evaluation criteria in solid tumors (RECIST) were used to identify responders, who had complete response (CR) or partial responses (PR) and nonresponders who had stable disease (SD) or progressive disease (PD). Receiver operating characteristics (ROC) analysis was used to find the optimal tumor shrinkage as an indicator for tumor therapeutic outcome. Univariate and multivariate Cox regression analyses were performed to compare the progression-free survival (PFS) and overall survival (OS) between responders and nonresponders stratified based on radiologic criteria. Among the 88 NSCLC patients, 26 were responders and 62 were nonresponders based on RECIST 1.0. ROC indicated that 8.32% tumor diameter shrinkage in the sum of the longest tumor diameter (SLD) was the cutoff point of tumor shrinkage outcomes, resulting in 46 responders (≤8.32%) and 42 nonresponders (≥8.32%). Univariate and multivariate Cox regression analyses indicated that (1) the responders (≤8.32%) and nonresponders (≥ −8.32%) were significantly different in median PFS (13.40 vs 1.17 months, P < 0.001) and OS (19.80 vs 7.90 months, P < 0.001) and (2) –8.32% in SLD could be used as the optimal threshold for PFS (hazard ratio [HR], 8.11, 95% CI, 3.75 to 17.51, P < 0.001) and OS

  6. Bronchoscopic lung volume reduction by endobronchial valve in advanced emphysema: the first Asian report

    PubMed Central

    Park, Tai Sun; Hong, Yoonki; Lee, Jae Seung; Oh, Sang Young; Lee, Sang Min; Kim, Namkug; Seo, Joon Beom; Oh, Yeon-Mok; Lee, Sang-Do; Lee, Sei Won

    2015-01-01

    Purpose Endobronchial valve (EBV) therapy is increasingly being seen as a therapeutic option for advanced emphysema, but its clinical utility in Asian populations, who may have different phenotypes to other ethnic populations, has not been assessed. Patients and methods This prospective open-label single-arm clinical trial examined the clinical efficacy and the safety of EBV in 43 consecutive patients (mean age 68.4±7.5, forced expiratory volume in 1 second [FEV1] 24.5%±10.7% predicted, residual volume 208.7%±47.9% predicted) with severe emphysema with complete fissure and no collateral ventilation in a tertiary referral hospital in Korea. Results Compared to baseline, the patients exhibited significant improvements 6 months after EBV therapy in terms of FEV1 (from 0.68±0.26 L to 0.92±0.40 L; P<0.001), 6-minute walk distance (from 233.5±114.8 m to 299.6±87.5 m; P=0.012), modified Medical Research Council dyspnea scale (from 3.7±0.6 to 2.4±1.2; P<0.001), and St George’s Respiratory Questionnaire (from 65.59±13.07 to 53.76±11.40; P=0.028). Nine patients (20.9%) had a tuberculosis scar, but these scars did not affect target lobe volume reduction or pneumothorax frequency. Thirteen patients had adverse events, ten (23.3%) developed pneumothorax, which included one death due to tension pneumothorax. Conclusion EBV therapy was as effective and safe in Korean patients as it has been shown to be in Western countries. (Trial registration: ClinicalTrials.gov: NCT01869205). PMID:26251590

  7. Effect of Amifostine on Response Rates in Locally Advanced Non-Small-Cell Lung Cancer Patients Treated on Randomized Controlled Trials: A Meta-Analysis

    SciTech Connect

    Mell, Loren K. . E-mail: lmell@radonc.uchicago.edu; Malik, Renuka; Komaki, Ritsuko; Movsas, Benjamin; Swann, R. Suzanne; Langer, Corey; Antonadou, Dosia; Koukourakis, Michael

    2007-05-01

    Purpose: Amifostine can reduce the cytotoxic effects of chemotherapy and radiotherapy in patients with locally advanced non-small-cell lung cancer, but concerns remain regarding its possible tumor-protective effects. Studies with sufficient statistical power to address this question are lacking. Methods and Materials: We performed a meta-analysis of all published clinical trials involving locally advanced non-small-cell lung cancer patients treated with radiotherapy with or without chemotherapy, who had been randomized to treatment with amifostine vs. no amifostine or placebo. Random effects estimates of the relative risk of overall, partial, and complete response were obtained. Results: Seven randomized trials involving 601 patients were identified. Response rate data were available for six studies (552 patients). The pooled relative risk (RR) estimate was 1.07 (95% confidence interval, 0.97-1.18; p = 0.18), 1.21 (95% confidence interval, 0.83-1.78; p = 0.33), and 0.99 (95% confidence interval, 0.78-1.26; p = 0.95) for overall, complete, and partial response, respectively (a RR >1 indicates improvement in response with amifostine compared with the control arm). The results were similar after sensitivity analyses. No evidence was found of treatment effect heterogeneity across the studies. Conclusions: Amifostine has no effect on tumor response in patients with locally advanced non-small-cell lung cancer treated with radiotherapy with or without chemotherapy.

  8. Phase IB Study of Selinexor, a First-in-Class Inhibitor of Nuclear Export, in Patients With Advanced Refractory Bone or Soft Tissue Sarcoma

    PubMed Central

    Zer, Alona; Tap, William D.; Salah, Samer; Dickson, Mark A.; Gupta, Abha A.; Keohan, Mary Louise; Loong, Herbert H.; D’Angelo, Sandra P.; Baker, Stephanie; Condy, Mercedes; Nyquist-Schultz, Kjirsten; Tanner, Lanier; Erinjeri, Joseph P.; Jasmine, Francis H.; Friedlander, Sharon; Carlson, Robert; Unger, Thaddeus J.; Saint-Martin, Jean-Richard; Rashal, Tami; Ellis, Joel; Kauffman, Michael; Shacham, Sharon; Schwartz, Gary K.; Abdul Razak, Albiruni Ryan

    2016-01-01

    Purpose We evaluated the pharmacokinetics (PKs), pharmacodynamics, safety, and efficacy of selinexor, an oral selective inhibitor of nuclear export compound, in patients with advanced soft tissue or bone sarcoma with progressive disease. Patients and Methods Fifty-four patients were treated with oral selinexor twice per week (on days 1 and 3) at one of three doses (30 mg/m2, 50 mg/m2, or flat dose of 60 mg) either continuously or on a schedule of 3 weeks on, 1 week off. PK analysis was performed under fasting and fed states (low v high fat content) and using various formulations of selinexor (tablet, capsule, or suspension). Tumor biopsies before and during treatment were evaluated for pharmacodynamic changes. Results The most commonly reported drug-related adverse events (grade 1 or 2) were nausea, vomiting, anorexia, and fatigue, which were well managed with supportive care. Commonly reported grade 3 or 4 toxicities were fatigue, thrombocytopenia, anemia, lymphopenia, and leukopenia. Selinexor was significantly better tolerated when administered as a flat dose on an intermittent schedule. PK analysis of selinexor revealed a clinically insignificant increase (approximately 15% to 20%) in drug exposure when taken with food. Immunohistochemical analysis of paired tumor biopsies revealed increased nuclear accumulation of tumor suppressor proteins, decreased cell proliferation, increased apoptosis, and stromal deposition. Of the 52 patients evaluable for response, none experienced an objective response by RECIST (version 1.1); however, 17 (33%) showed durable (≥ 4 months) stable disease, including seven (47%) of 15 evaluable patients with dedifferentiated liposarcoma. Conclusion Selinexor was well tolerated at a 60-mg flat dose on a 3-weeks-on, 1-week-off schedule. There was no clinically meaningful impact of food on PKs. Preliminary evidence of anticancer activity in sarcoma was demonstrated. PMID:27458288

  9. Catalytic, hollow, refractory spheres

    NASA Technical Reports Server (NTRS)

    Wang, Taylor G. (Inventor); Elleman, Daniel D. (Inventor); Lee, Mark C. (Inventor); Kendall, Jr., James M. (Inventor)

    1987-01-01

    Improved, heterogeneous, refractory catalysts are in the form of gas-impervious, hollow, thin-walled spheres (10) suitable formed of a shell (12) of refractory such as alumina having a cavity (14) containing a gas at a pressure greater than atmospheric pressure. The wall material may be itself catalytic or a catalytically active material coated onto the sphere as a layer (16), suitably platinum or iron, which may be further coated with a layer (18) of activator or promoter. The density of the spheres (30) can be uniformly controlled to a preselected value within .+-.10 percent of the density of the fluid reactant such that the spheres either remain suspended or slowly fall or rise through the liquid reactant.

  10. Refractory rheumatoid vasculitis

    PubMed Central

    Kumar, Ashok; Goel, Anshul; Lapsiwala, Mehul; Singhal, Suman

    2016-01-01

    Systemic rheumatoid vasculitis (SRV) can develop in rheumatoid arthritis of long duration and high disease activity. It most commonly manifests as cutaneous vasculitis and mononeuritis multiplex. This can involve any organ of the body and carries very high mortality. We report a case of a young male who had rheumatoid arthritis for the past 15 years and became refractory to standard drugs and anti-TNF agents. He subsequently developed SRV, which started as mononeuritis multiplex. Disease progressed to result in gangrene of hands and feet despite receiving intravenous cyclophosphamide. Intravenous immunoglobulin and rituximab also could not provide any response. Prolonged ICU stay resulted in critical care neuromyopathy. Central nervous system vasculitis developed even after repeated infusions of intravenous immunoglobulins and at last he died of complications. In this case report, we have presented rare and chronic protracted presentation of rheumatoid vasculitis involving skin, nerves, brain and testis, which was refractory to the recommended therapies. PMID:28031844

  11. [Cisplatin and vinca alkaloid combination chemotherapy of advanced non-small-cell lung cancer in the aged].

    PubMed

    Teramoto, S; Nagase, T; Fukuchi, Y; Ishida, K; Yamaoka, M; Matsuse, T; Jo, C; Orimo, H

    1990-11-01

    Fifteen patients aged over 65 years of age with advanced non-small-cl lung cancer (mean age = 70.7, stage IIIb: IV = 4:11) were treated with combination chemotherapy consisting of Cisplatin (50 or 80 mg/m2) and a vinca-alkaloid (Vindesine 3 mg/m2 or Etoposide 80 mg/m2). The effectiveness and side effects of this cisplatin therapy in different combinations of vinca-alkaloid regimens (Vindesine vs Etoposide) were examined. The mean dose of Cisplatin in the Etoposide combination group (75.2 mg/m2) was significantly higher than that in the Vindesine combination group (54.3 mg/m2) (p less than 0.01). A notable reduction the tumor size was observed in 25% of the Etoposide group, only. The 6-month survival rate and one-year survival rate were respectively 85.7%, 57.1% in the Vindesine + Cisplatin group, and 87.5%, 50% in the Etoposide + Cisplatin group. The common side effects were nausea, vomiting, anorexia, and alopecia. These symptoms were either alleviated by antiemetic drugs or followed by spontaneous recovery. Leucopenia, anemia and thrombocytopenia were found in both groups, and there was no difference in the time course of myelosuppression between the two groups. The extent of nephrotoxicity was assessed by creatinine clearance rate. Its decrease in the Vindesine group (60.1----38.9 ml/min) was higher than that in the Etoposide group (64.9----48.9 ml/min), while there was no significant change in BUN, serum creatinine and urine NAG between the two groups. There were no cases in which chemotherapy schedules had to be interrupted due to myelosuppression and nephrotoxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

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

    PubMed

    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.

  13. cN-II expression predicts survival in patients receiving gemcitabine for advanced non-small cell lung cancer.

    PubMed

    Sève, Pascal; Mackey, John R; Isaac, Sylvie; Trédan, Olivier; Souquet, Pierre Jean; Pérol, Maurice; Cass, Carol; Dumontet, Charles

    2005-09-01

    Resistance to gemcitabine is likely to be multifactorial and could involve a number of mechanisms involved in drug penetration, metabolism and targeting. In vitro studies of resistant human cell lines have confirmed that human equilibrative nucleoside transporter 1 (hENT1)-deficient cells display resistance to gemcitabine. Overexpression of certain nucleotidases, such as cN-II, has also been frequently shown in gemcitabine-resistant models. In this study, we applied immunohistochemical methods to assess the protein abundance of cN-II, hENT1, human concentrative nucleoside transporter 3 (hCNT3) and deoxycitidine kinase (dCK) in malignant cells in from 43 patients with treatment-naïve locally advanced or metastatic non-small cell lung cancer (NSCLC). All patients subsequently received gemcitabine-based chemotherapy. Response to chemotherapy, progression-free survival (PFS), and overall survival (OS) were correlated with abundance of these proteins. Among the 43 samples, only 7 (16%) expressed detectable hENT1, with a low percentage of positive cells, 18 expressed hCNT3 (42%), 36 (86%) expressed cN-II and 28 (66%) expressed dCK. In univariate analysis, only cN-II expression levels were correlated with overall survival. None of the parameters were correlated with freedom from progression survival nor with response. Patients with low levels of expression of cN-II (less than 40% positively stained cells) had worse overall survival than patients with higher levels of cN-II expression (6 months and 11 months, respectively). In a multivariate analysis taking into account age, sex, weight loss, stage and immunohistochemical results, cN-II was the only predictive factor associated with overall survival. This study suggests that cN-II nucleotidase expression levels identify subgroups of NSCLC patients with different outcomes under gemcitabine-based therapy. Larger prospective studies are warranted to confirm the predictive value of cN-II in these patients.

  14. Response to combined modality therapy correlates with survival in locally advanced non-small-cell lung cancer

    SciTech Connect

    Kim, Dong Wook; Shyr, Yu; Chen, Heidi; Akerley, Wallace; Johnson, David H.; Choy, Hak . E-mail: Hak.Choy@utsouthwestern.edu

    2005-11-15

    Purpose: Although concurrent chemoradiotherapy can now achieve demonstrated long-term survival in patients with locally advanced non-small-cell lung cancer (LANSCLC), it is difficult to predict which patients will benefit most from this therapeutic approach. Studies have suggested that local control, and the response to therapy, may be linked to improved survival; however, detailed analysis of the impact of tumor response to chemoradiotherapy on survival has not been thoroughly reported. Therefore, we sought to determine the impact of the response rate on survival for patients who were treated with combined modality therapy for LANSCLC. Methods and Materials: We reviewed the data from 116 patients enrolled between 1994 and 1997 in three trials investigating paclitaxel-based concurrent chemoradiotherapy for LANSCLC. Tumor size measurements were assessed immediately before and 2 months after completion of combined modality therapy to determine the response and to calculate the percentage of decrease in tumor size. Results: Patients with a response (complete or partial) had an improved 4-year overall survival rate compared with patients with no response (stable or progressive disease; 21.1% vs. 3.3%, p <0.0001) in the 109 assessable patients. Progression-free survival also improved significantly with response. An analysis of the percentage of decrease in tumor size vs. survival was performed (n = 74) using Cox proportion model analysis. After combined modality therapy, a 20%, 40%, 60%, 80%, and 100% decrease in tumor size conferred a 39%, 63%, 78%, 86%, and 92% reduction in risk of death compared with a 0% decrease in tumor size (p <0.0001). Conclusion: The response by conventional response criteria correlated strongly with improved overall survival and progression-free survival and an increasing percentage of decrease in tumor size resulted in a reduction in the risk of death. Additional investigation of the degree of response as a factor predictive of improved

  15. Toxicity of concurrent radiochemotherapy for locally advanced non--small-cell lung cancer: a systematic review of the literature.

    PubMed

    Koning, Caro C; Wouterse, Sanne J; Daams, Joost G; Uitterhoeve, Lon L; van den Heuvel, Michel M; Belderbos, José S

    2013-09-01

    Concurrent radiochemotherapy (RCT) is the treatment of choice for patients with locally advanced non-small-cell lung cancer (NSCLC). Two meta-analyses were inconclusive in an attempt to define the optimal concurrent RCT scheme. Besides efficacy, treatment toxicity will influence the appointed treatment of choice. A systematic review of the literature was performed to record the early and late toxicities, as well as overall survival, of concurrent RCT regimens in patients with NSCLC. The databases of PubMed, Ovid, Medline, and the Cochrane Library were searched for articles on concurrent RCT published between January 1992 and December 2009. Publications of phase II and phase III trials with ≥ 50 patients per treatment arm were selected. Patient characteristics, chemotherapy regimen (mono- or polychemotherapy, high or low dose) and radiotherapy scheme, acute and late toxicity, and overall survival data were compared. Seventeen articles were selected: 12 studies with cisplatin-containing regimens and 5 studies using carboplatin. A total of 13 series with mono- or polychemotherapy schedules--as single dose or double or triple high-dose or daily cisplatin-containing (≤ 30 mg/m(2)/wk) chemotherapy were found. Acute esophagitis ≥ grade 3 was observed in up to 18% of the patients. High-dose cisplatin regimens resulted in more frequent and severe hematologic toxicity, nausea, and vomiting than did other schemes. The toxicity profile was more favorable in low-dose chemotherapy schedules. From phase II and III trials published between 1992 and 2010, it can be concluded that concurrent RCT with monochemotherapy consisting of daily cisplatin results in favorable acute and late toxicity compared with concurrent RCT with single high-dose chemotherapy, doublets, or triplets.

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

    PubMed Central

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

    2001-01-01

    INTRODUCTION: Significant problems in clinician-patient communication have been described in the oncology literatures. Advanced stage non-small lung cancer a devastating disease, can cause the communication between survivors, significant others, and clinicians to falter. To date, however, no studies have used qualitative methods to examine experiential aspects of living with non-small cell lung cancer. Nor have any studies evaluated the tools survivors might use to repair some of the damage caused by living with this disease. METHODS: Exploratory, two-part qualitative design. RESULTS: Survivors of non-small cell lung cancer live with multiple fears and losses. These include a diminished sense of self, the loss of health, fears of pain in a future tainted by the threat of death, and increased feelings of alienation due to the loss of previous sources of meaning in life. These experiences significantly affect cancer survivors abilities to communicate with clinicians and significant others. CONCLUSIONS: Survivors of non-small cell lung cancer often have difficulty sharing their experiences with others not suffering a similar affliction. Through their narratives with other survivors, however, patients are better able to initiate a biopsychosocial mechanism which enables them to create a cognitive map. This cognitive map helps survivors share their experiences with others, thereby repairing some of the damage caused by this disease, including the harm done to their communication with other people. PMID:11922184

  17. A Biochemical Approach to Understand the Pathogenesis of Advanced Pulmonary Arterial Hypertension: Metabolomic Profiles of Arginine, Sphingosine-1-Phosphate, and Heme of Human Lung.

    PubMed

    Zhao, Yidan D; Chu, Lei; Lin, Kathleen; Granton, Elise; Yin, Li; Peng, Jenny; Hsin, Michael; Wu, Licun; Yu, Amy; Waddell, Thomas; Keshavjee, Shaf; Granton, John; de Perrot, Marc

    2015-01-01

    Pulmonary arterial hypertension (PAH) is a vascular disease characterized by persistent precapillary pulmonary hypertension (PH), leading to progressive right heart failure and premature death. The pathological mechanisms underlying this condition remain elusive. Analysis of global metabolomics from lung tissue of patients with PAH (n = 8) and control lung tissue (n = 8) leads to a better understanding of disease progression. Using a combination of high-throughput liquid-and-gas-chromatography-based mass spectrometry, we showed unbiased metabolomic profiles of disrupted arginine pathways with increased Nitric oxide (NO) and decreased arginine. Our results also showed specific metabolic pathways and genetic profiles with increased Sphingosine-1-phosphate (S1P) metabolites as well as increased Heme metabolites with altered oxidative pathways in the advanced stage of the human PAH lung. The results suggest that PAH has specific metabolic pathways contributing to the vascular remodeling in severe pulmonary hypertension. Profiling metabolomic alterations of the PAH lung has provided a new understanding of the pathogenic mechanisms of PAH, which benefits therapeutic targeting to specific metabolic pathways involved in the progression of PAH.

  18. Is there a role of nab-paclitaxel in the treatment of advanced non-small cell lung cancer? The data suggest yes

    PubMed Central

    Villaruz, Liza C.; Socinski, Mark A.

    2016-01-01

    Nab-paclitaxel is a novel therapeutic agent, which was approved in combination with carboplatin in the first-line treatment of advanced non-small cell lung cancer (NSCLC) regardless of histologic subtype in the United States of America by the Food and Drug Administration in 2012 and by the European Commission in 2015. This approval was based on the results of a phase III clinical trial showing superior response rates compared with solvent-based paclitaxel in combination with carboplatin. This review will focus on the early development and clinical data to date supporting the use of nab-paclitaxel in advanced NSCLC. The clinical question central to this review is whether nab-paclitaxel has a place in the current therapeutic landscape of advanced NSCLC. PMID:26875112

  19. [A long-term survival case of far-advanced colon cancer with Virchow's lymph node and lung metastasis that responded to multidisciplinary therapy].

    PubMed

    Takahashi, Satoshi; Iiai, Tsuneo; Shimada, Yoshifumi; Kobayashi, Yasuo; Suda, Kazutaka; Iwaya, Akira; Maruyama, Satoshi; Tani, Tatsuo; Hatakeyama, Katsuyoshi

    2009-01-01

    The patient was a 73-year-old male. Under a diagnosis of advanced cecal colon cancer with metastasis to Virchow's and paraaortic lymph nodes and lungs, a laparoscopic-assisted ileocecal resection with D2 lymph node dissection was performed. Histological examination of the resected specimens revealed moderately-differentiated adenocarcinoma which had invaded the terminal ileum. The lesion was judged to be SI(ileum), N2, H0, P0, M1(Virchow's lymph node, No. 216, lungs), Stage IV. After the operation, he received chemotherapy with 5-FU/l-LV(RPMI method), LV/UFT, FOLFOX, FOLFIRI in succession, and cancer aggravation was generally controlled. He has survived for 3 years since operation, and shows good QOL under the treatment.

  20. Dynamic Contrast Enhanced MRI in Patients With Advanced Breast or Pancreatic Cancer With Metastases to the Liver or Lung

    ClinicalTrials.gov

    2014-05-28

    Acinar Cell Adenocarcinoma of the Pancreas; Duct Cell Adenocarcinoma of the Pancreas; Liver Metastases; Lung Metastases; Recurrent Breast Cancer; Recurrent Pancreatic Cancer; Stage IV Breast Cancer; Stage IV Pancreatic Cancer

  1. Effects of docetaxel plus three-dimensional conformal radiation therapy on microvessel density and apoptosis expression in local advanced squamous non-small-cell lung cancer.

    PubMed

    Zhai, X J; Cheng, H R; Long, H L; Mao, W K; Cao, L; Xiao, B R; Li, R Q

    2015-05-22

    We examined the effects of weekly single-agent docetaxel plus three-dimensional conformal radiation therapy (3D-CRT) on apoptotic index (AI) and microvessel density (MVD) in local advanced non-small-cell lung squamous cancer patients and analyzed the correlation of MVD, AI, and 50% tumor shrinkage time (T0.5) The molecular mechanism of docetaxel radiosensitization was investigated. Sixty untreated patients with stage IIIA or IIIB lung squamous cancer were enrolled and randomly divided into two groups: observation (N = 30; 3D-CRT + docetaxel + adjuvant chemotherapy) and control (N = 30; 3D-CRT + adjuvant chemotherapy). From day 1 radiotherapy, the observation group received intravenous docetaxel (36 mg/m(2)) once weekly for 6 weeks. Post-radiotherapy, chemotherapy of docetaxel combined with cisplatin lasted 4-6 cycles in both groups. Before radiotherapy and within 24 h after radiotherapy (20 Gy), bronchoscopic biopsy was performed twice at the same site. To analyze the MVD of tumor specimens with immunohistochemical staining . The AI of lung cancer cells was assessed with TUNEL assay, T0.5 values were calculated. The observation group had significantly lower MVD than the control group (P < 0.05). AI significantly increased before and after treatment in the observation group compared with the control group (P < 0.05). The decreased MVD values negatively correlated with T0.5 values (r = -0.624, P < 0.05), whereas the increased AI values did not correlate with the T0.5 values. Docetaxel radiosensitization may occur by decrease in MVD and increase in AI values. Weekly single-agent docetaxel plus 3D-CRT can improve prognosis and quality of life in local advanced non-small-cell lung squamous cancer patients.

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

    PubMed

    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.

  3. Leptin role in advanced lung cancer. A mediator of the acute phase response or a marker of the status of nutrition?

    PubMed

    Alemán, María Remedios; Santolaria, Francisco; Batista, Norberto; de La Vega, María; González-Reimers, Emilio; Milena, Antonio; Llanos, Marta; Gómez-Sirvent, Juan Luis

    2002-07-07

    Leptin is an anorexia inductor peptide produced by adipocytes and related to fat mass. Leptin is also produced by fat under proinflammatory cytokine action. Our objective is to study serum leptin levels in relation to nutritional status and acute phase response in advanced-stage non-small cell lung cancer.Seventy-six patients newly diagnosed of non surgical non-small cell lung cancer before chemotherapy treatment and 30 healthy controls were included. BMI, serum leptin and cholesterol levels and lymphocyte count were decreased in lung cancer patients. Cytokine IL-6, TNF-alpha, sTNF-RII, sIL-2R, IL-12, IL-10 and IFN-gamma, and other acute phase reactants as alpha1 antitrypsin, ferritin, CRP and platelets were all raised in patients, whereas the IL-2 was decreased. We found a direct relationship between leptin and other indicators of the status of nutrition, especially total fat mass. We also found a close relationship between the status of nutrition and the performance status (Karnofsky index). However, serum leptin and nutritional status were inversely correlated with acute phase proteins and proinflammatory cytokines, suggesting a stress-type malnutrition. Although serum leptin levels, nutritional status and Karnofsky index are related to survival, at multivariate analysis they all were displaced by the acute phase reaction markers. These results suggest that cancer anorexia and cachexia are not due to a dysregulation of leptin production. Circulating leptin concentrations are not elevated in weight-losing cancer patients and are inversely related to the intensity of the inflammatory response. In advanced lung cancer patients serum leptin concentrations only depend on the total amount of fat.

  4. Afatinib versus cisplatin plus pemetrexed in Japanese patients with advanced non-small cell lung cancer harboring activating EGFR mutations: Subgroup analysis of LUX-Lung 3

    PubMed Central

    Kato, Terufumi; Yoshioka, Hiroshige; Okamoto, Isamu; Yokoyama, Akira; Hida, Toyoaki; Seto, Takashi; Kiura, Katsuyuki; Massey, Dan; Seki, Yoko; Yamamoto, Nobuyuki

    2015-01-01

    In LUX-Lung 3, afatinib significantly improved progression-free survival (PFS) versus cisplatin/pemetrexed in EGFR mutation-positive lung adenocarcinoma patients and overall survival (OS) in Del19 patients. Preplanned analyses in Japanese patients from LUX-Lung 3 were performed. Patients were randomized 2:1 to afatinib or cisplatin/pemetrexed, stratified by mutation type (Del19/L858R/Other). Primary endpoint was PFS (independent review). Secondary endpoints included OS, objective response, and safety. Median PFS (data cut-off: February 2012) for afatinib versus cisplatin/pemetrexed was 13.8 vs 6.9 months (hazard ratio [HR], 0.38; 95% confidence interval [CI], 0.20–0.70; P = 0.0014) in all Japanese patients (N = 83), with more pronounced improvements in those with common mutations (Del19/L858R; HR, 0.28; 95% CI, 0.15–0.52; P < 0.0001) and Del19 mutations (HR, 0.16; 95% CI, 0.06–0.39; P < 0.0001). PFS was also improved in L858R patients (HR, 0.50; 95% CI, 0.20–1.25; P = 0.1309). Median OS (data cut-off: November 2013) with afatinib versus cisplatin/pemetrexed was 46.9 vs 35.8 months (HR, 0.75; 95% CI, 0.40–1.43; P = 0.3791) in all Japanese patients, with greater benefit in patients with common mutations (HR, 0.57; 95% CI, 0.29–1.12; P = 0.0966) and Del19 mutations (HR, 0.34; 95% CI, 0.13–0.87; P = 0.0181); OS was not significantly different in L858R patients (HR, 1.13; 95% CI, 0.40–3.21; P = 0.8212). Following study treatment discontinuation, most patients (93.5%) received subsequent anticancer therapy. The most common treatment-related adverse events were diarrhea, rash/acne, nail effects and stomatitis with afatinib and nausea, decreased appetite, neutropenia, and leukopenia with cisplatin/pemetrexed. Afatinib significantly improved PFS versus cisplatin/pemetrexed in Japanese EGFR mutation-positive lung adenocarcinoma patients and OS in Del19 but not L858R patients (www.clinicaltrials.gov; NCT00949650). PMID:26094656

  5. Synthesis of refractory materials

    DOEpatents

    Holt, Joseph B.

    1984-01-01

    Refractory metal nitrides are synthesized during a self-propagating combustion process utilizing a solid source of nitrogren. For this purpose, a metal azide is employed, preferably NaN.sub.3. The azide is combusted with Mg or Ca, and a metal oxide is selected from Groups III-A, IV-A, III-B, IV-B, or a rare earth metal oxide. The mixture of azide, Ca or Mg and metal oxide is heated to the mixture's ignition temperature. At that temperature the mixture is ignited and undergoes self-sustaining combustion until the starter materials are exhausted, producing the metal nitride.

  6. Synthesis of refractory materials

    DOEpatents

    Holt, J.B.

    1983-08-16

    Refractory metal nitrides are synthesized during a self-propagating combustion process utilizing a solid source of nitrogen. For this purpose, a metal azide is employed, preferably NaN/sub 3/. The azide is combusted with Mg or Ca, and a metal oxide is selected from Groups III-A, IV-A, III-B, IV-B, or a rare earth metal oxide. The mixture of azide, Ca or Mg and metal oxide is heated to the mixture's ignition temperature. At that temperature the mixture is ignited and undergoes self-sustaining combustion until the starter materials are exhausted, producing the metal nitride.

  7. Afatinib in Advanced Refractory Urothelial Cancer

    ClinicalTrials.gov

    2017-03-06

    Distal Urethral Cancer; Proximal Urethral Cancer; Recurrent Bladder Cancer; Recurrent Urethral Cancer; Stage III Bladder Cancer; Stage III Urethral Cancer; Stage IV Bladder Cancer; Stage IV Urethral Cancer; Ureter Cancer

  8. Randomized Phase II Trial of Erlotinib Beyond Progression in Advanced Erlotinib-Responsive Non-Small Cell Lung Cancer

    PubMed Central

    Pennell, Nathan A.; Fu, Pingfu; Saad, Shumaila; Gadgeel, Shirish; Otterson, Gregory A.; Mekhail, Tarek; Snell, Michael; Kuebler, J. Philip; Sharma, Neelesh

    2015-01-01

    Background. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) therapy is clearly beneficial in patients with advanced EGFR-mutated non-small cell lung cancer (NSCLC). However, acquired resistance develops uniformly and the benefit of continuation of EGFR TKI therapy beyond progression remains unclear. Materials and Methods. This was a randomized phase II study of chemotherapy (arm A: pemetrexed or docetaxel) versus chemotherapy plus erlotinib (ERL) (arm B) in patients with progressive NSCLC following clinical benefit from erlotinib. In arm B, chemotherapy was given with erlotinib at an oral daily dose of 150 mg on days 2–19 of each cycle to minimize negative pharmacodynamic interactions. The primary endpoint was that continuation of erlotinib in this patient population could extend progression-free survival (PFS) by 50%. Results. A total of 46 patients were randomized (arm A: 24; arm B: 22). Patient characteristics were well balanced except there were more female patients in arm A (p = .075). The median PFS of patients in arm A was 5.5 months and for those in arm B, 4.4 months (p = .699). The response rates were 13% and 16% in arms A and B, respectively (p = .79). EGFR status data were available for 39 of the 46 patients and no significant difference in PFS was seen for continuing ERL beyond progression in mutation-positive patients. Substantially more toxicity was seen in arm B than arm A. Conclusion. There was added toxicity but no benefit with the continuation of ERL beyond progression along with chemotherapy as compared with chemotherapy alone. Implications for Practice: The benefits of continuing erlotinib upon progression alongside conventional chemotherapy are unclear. This randomized phase II study, initiated prior to the establishment of routine epidermal growth factor receptor (EGFR) mutation testing, addressed this clinically relevant issue through randomizing patients with prior clinical benefit from erlotinib (thereby enriching

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

    SciTech Connect

    Ji, Zhe; Bi, Nan; Wang, Jingbo; Hui, Zhouguang; Xiao, Zefen; Feng, Qinfu; Zhou, Zongmei; Chen, Dongfu; Lv, Jima; Liang, Jun; Fan, Chengcheng; Liu, Lipin; Wang, Luhua

    2014-06-01

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

  10. Phase II study of S-1, a novel oral fluorouracil, in advanced non-small-cell lung cancer

    PubMed Central

    Kawahara, M; Furuse, K; Segawa, Y; Yoshimori, K; Matsui, K; Kudoh, S; Hasegawa, K; Niitani, H

    2001-01-01

    The purpose of this study was to evaluate the efficacy and safety of a novel oral anticancer fluoropyrimidine derivative, S-1, in patients receiving initial chemotherapy for unresectable, advanced non-small-cell lung cancer (NSCLC). Between June 1996 and July 1998, 62 patients with NSCLC who had not received previous chemotherapy for advanced disease were enrolled in this study. 59 patients (22 stage IIIB and 37 stage IV) were eligible for the evaluation of efficacy and safety. S-1 was administered orally, twice daily, after meals. 3 dosages of S-1 were prescribed according to body surface area (BSA) so that they would be approximately equivalent to 80 mg m−2day−1: BSA < 1.25 m2, 40 mg b.i.d.; BSA≥1.25 but <1.5 m2; 50 mg b.i.d., and BSA≥1.5 m2: 60 mg b.i.d. One cycle consisted of consecutive administration of S-1 for 28 days followed by a 2-week rest period, and cycles were repeated up to 4 times. The partial response (PR) rate of the eligible patients was 22.0% (13/59); (95% confidence interval: 12.3–34.7%). A PR was observed in 22.7% (5/22) of the stage IIIB patients and 21.6% (8/37) of the stage IV patients. The median response duration was 3.4 months (1.1–13.7 months or longer). Grade 4 neutropenia was observed in one of the 59 patients (1.7%). The grade 3 or 4 toxicities consisted of decreased haemoglobin level in 1.7% of patients (1/59), neutropenia in 6.8% (4/59), thrombocytopenia in 1.7% (1/59), anorexia in 10.2% (6/59), diarrhoea in 8.5% (5/59), stomatitis in 1.7% (1/59), and malaise in 6.8% (4/59), and their incidences were relatively low. There were no irreversible, severe or unexpected toxicities. The median survival time (MST) of all patients was 10.2 months (95% confidence interval: 7.7–14.5 months), and the one-year survival rate was 41.1%. The MST of the stage IIIB patients was 7.9 months, and that of the stage IV patients was 11.1 months. The one-year survival rates of the stage IIIB and IV patients were 30.7% and 47

  11. Approaches to refractory epilepsy

    PubMed Central

    Engel, Jerome

    2014-01-01

    Epilepsy is one of the most common serious neurological conditions, and 30 to 40% of people with epilepsy have seizures that are not controlled by medication. Patients are considered to have refractory epilepsy if disabling seizures continue despite appropriate trials of two antiseizure drugs, either alone or in combination. At this point, patients should be referred to multidisciplinary epilepsy centers that perform specialized diagnostic testing to first determine whether they are, in fact, pharmacoresistant, and then, if so, offer alternative treatments. Apparent pharmacoresistance can result from a variety of situations, including noncompliance, seizures that are not epileptic, misdiagnosis of the seizure type or epilepsy syndrome, inappropriate use of medication, and lifestyle issues. For patients who are pharmacoresistant, surgical treatment offers the best opportunity for complete freedom from seizures. Surgically remediable epilepsy syndromes have been identified, but patients with more complicated epilepsy can also benefit from surgical treatment and require more specialized evaluation, including intracranial EEG monitoring. For patients who are not surgical candidates, or who are unwilling to consider surgery, a variety of other alternative treatments can be considered, including peripheral or central neurostimulation, ketogenic diet, and complementary and alternative approaches. When such alternative treatments are not appropriate or effective, quality of life can still be greatly improved by the psychological and social support services offered by multidisciplinary epilepsy centers. A major obstacle remains the fact that only a small proportion of patients with refractory epilepsy are referred for expert evaluation and treatment. PMID:24791078

  12. [Advances in Liquid Biopsy and its Clinical Application in the Diagnosis 
and Treatment of Non-small Cell Lung Cancer].

    PubMed

    Zheng, Difan; Chen, Haiquan

    2016-06-20

    With the advances of technology, great progresses have been made in liquid biopsy in recent years. Liquid biopsy is currently playing a more and more important role in early diagnosis and treatment of cancer. Compared with traditional tissue biopsy, liquid biopsy is more popular in clinical practice due to its non-invasiveness, convenience and high repeatability. It has huge potential in the future. This review introduces circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) as the most important objects in liquid biopsy, mainly focusing on their history, biological characteristics, detection technologies, limitations and applications in non-small cell lung cancer.

  13. REFRACTORY COATING FOR GRAPHITE MOLDS

    DOEpatents

    Stoddard, S.D.

    1958-06-24

    Refractory coating for graphite molds used in the casting of uranium is described. The coating is an alumino-silicate refractory composition which may be used as a mold surface in solid form or as a coating applied to the graphite mold. The composition consists of a mixture of ball clay, kaolin, alumina cement, alumina, water, sodium silicate, and sodium carbonate.

  14. Refractory giardiasis in Spanish travellers.

    PubMed

    Muñoz Gutiérrez, Jose; Aldasoro, Edelweiss; Requena, Ana; Comin, Ana M; Pinazo, Maria Jesús; Bardají, Azucena; Oliveira, Inés; Valls, Maria Eugenia; Gascon, Joaquim

    2013-01-01

    Drug failure is a common cause of symptom persistence after treatment of imported Giardia duodenalis. In this retrospective study we describe a high prevalence of refractory giardiasis in people attended in a travel clinic in Spain, especially those with infections acquired in Asia. Moreover, we discuss various treatment strategies to tackle G. duodenalis that is refractory to nitroimidazoles.

  15. Continuation maintenance therapy with S-1 in chemotherapy-naïve patients with advanced squamous cell lung cancer.

    PubMed

    Suzuki, Seiichiro; Karayama, Masato; Inui, Naoki; Fujisawa, Tomoyuki; Enomoto, Noriyuki; Nakamura, Yutaro; Kuroishi, Shigeki; Matsuda, Hiroyuki; Yokomura, Koshi; Koshimizu, Naoki; Toyoshima, Mikio; Imokawa, Shiro; Asada, Kazuhiro; Masuda, Masafumi; Yamada, Takashi; Watanabe, Hiroshi; Suda, Takafumi

    2016-08-01

    Objectives Maintenance therapy is a standard therapeutic strategy in non-squamous non-small-cell lung cancer. However, there is no consensus regarding the benefit of maintenance therapy for patients with squamous cell lung cancer. We assessed maintenance therapy with S-1, an oral fluoropyrimidine agent, following induction therapy with carboplatin and S-1 in patients with squamous cell lung cancer. Methods In this phase II trial, chemotherapy-naïve patients with squamous cell lung cancer were enrolled to induction therapy with four cycles of carboplatin (at an area under the curve of 5 on day 1) and S-1 (80 mg/m(2)/day on days 1-14) in a 28-day cycle. Patients who achieved disease control after induction therapy received maintenance therapy with S-1 in a 21-day cycle until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival after administration of maintenance therapy. Results Fifty-one patients were enrolled in the study. The median progression-free survival from the start of maintenance therapy was 3.0 months (95 % confidence interval, 2.5-3.5). The most common toxicities associated with maintenance therapy were anemia, thrombocytopenia, and fatigue, but they were not severe. Conclusion S-1 maintenance therapy might be a feasible treatment option in patients with squamous cell lung cancer.

  16. Advances in molecular-based personalized non-small-cell lung cancer therapy: targeting epidermal growth factor receptor and mechanisms of resistance

    PubMed Central

    Jotte, Robert M; Spigel, David R

    2015-01-01

    Molecularly targeted therapies, directed against the features of a given tumor, have allowed for a personalized approach to the treatment of advanced non-small-cell lung cancer (NSCLC). The reversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) gefitinib and erlotinib had undergone turbulent clinical development until it was discovered that these agents have preferential activity in patients with NSCLC harboring activating EGFR mutations. Since then, a number of phase 3 clinical trials have collectively shown that EGFR-TKI monotherapy is more effective than combination chemotherapy as first-line therapy for EGFR mutation-positive advanced NSCLC. The next generation of EGFR-directed agents for EGFR mutation-positive advanced NSCLC is irreversible TKIs against EGFR and other ErbB family members, including afatinib, which was recently approved, and dacomitinib, which is currently being tested in phase 3 trials. As research efforts continue to explore the various proposed mechanisms of acquired resistance to EGFR-TKI therapy, agents that target signaling pathways downstream of EGFR are being studied in combination with EGFR TKIs in molecularly selected advanced NSCLC. Overall, the results of numerous ongoing phase 3 trials involving the EGFR TKIs will be instrumental in determining whether further gains in personalized therapy for advanced NSCLC are attainable with newer agents and combinations. This article reviews key clinical trial data for personalized NSCLC therapy with agents that target the EGFR and related pathways, specifically based on molecular characteristics of individual tumors, and mechanisms of resistance. PMID:26310719

  17. Extracorporeal life support for refractory ventricular tachycardia

    PubMed Central

    Joseph, Nicholas; Hofmann, James P.; Saranteas, Theodosios; Papadimos, Thomas J.

    2017-01-01

    Extracorporeal life support (ECLS) is a very effective bridging therapy in patients with refractory ventricular tachycardia (VT) associated with cardiogenic shock. A moribund patient in extremis, is not amenable to optimization by standard ACC/AHA guidelines. New approaches and novel salvage techniques are necessary to improve outcomes in patients with refractory clinical settings such as malignant ventricular arrhythmias, cardiac arrest, cardiogenic shock and/or pulmonary failure until further management options are explored. Data base searches were done using key words such as ECLS, VT, cardiac arrest, VT ablation, venoarterial extra-corporeal membrane oxygenation (VA-ECMO). The use of ECLS has been described in a few case reports to facilitate VT ablation for incessant VT refractory to medical therapy. For patients with, out-of- hospital ventricular fibrillation (VF) and VT, Minnesota Resuscitation Consortium has implemented emergent advanced perfusion and reperfusion strategy, followed by coronary angiography and primary coronary intervention to improve outcome. The major indications for ECLS are cardiogenic shock related to acute myocardial infarction, myocarditis, post embolic acute cor pulmonale, drug intoxication and post cardiac arrest syndrome with the threat of multi-organ failure. ECLS permits the use of negative inotropic antiarrhythmic drug therapy, facilitates the weaning of catecholamine administration, thereby ending the vicious cycle of catecholamine driven electric storm. ECLS provides hemodynamic support during ablation procedure, while mapping and induction of VT is undertaken. ECLS provides early access to cardiac catheterization laboratory in patients with cardiac arrest due to shockable rhythm. The current evidence from literature, supports the use of ECLS to ensure adequate vital organ perfusion in patients with refractory VT. ECLS is a safe, feasible and effective therapeutic option when conventional therapies are insufficient to support

  18. Characterization and aerosol dispersion performance of advanced spray-dried chemotherapeutic PEGylated phospholipid particles for dry powder inhalation delivery in lung cancer.

    PubMed

    Meenach, Samantha A; Anderson, Kimberly W; Zach Hilt, J; McGarry, Ronald C; Mansour, Heidi M

    2013-07-16

    Pulmonary inhalation chemotherapeutic drug delivery offers many advantages for lung cancer patients in comparison to conventional systemic chemotherapy. Inhalable particles are advantageous in their ability to deliver drug deep in the lung by utilizing optimally sized particles and higher local drug dose delivery. In this work, spray-dried and co-spray dried inhalable lung surfactant-mimic PEGylated lipopolymers as microparticulate/nanoparticulate dry powders containing paclitaxel were rationally designed via organic solution advanced spray drying (no water) in closed-mode from dilute concentration feed solution. Dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylethanolamine poly(ethylene glycol) (DPPE-PEG) with varying PEG chain length were mixed with varying amounts of paclitaxel in methanol to produce co-spray dried microparticles and nanoparticles. Scanning electron microscopy showed the spherical particle morphology of the inhalable particles. Thermal analysis and X-ray powder diffraction confirmed the retention of the phospholipid bilayer structure in the solid-state following spray drying, the degree of solid-state molecular order, and solid-state phase transition behavior. The residual water content of the particles was very low as quantified analytically Karl Fisher titration. The amount of paclitaxel loaded into the particles was quantified which indicated high encapsulation efficiencies (43-99%). Dry powder aerosol dispersion performance was measured in vitro using the Next Generation Impactor (NGI) coupled with the Handihaler dry powder inhaler device and showed mass median aerodynamic diameters in the range of 3.4-7 μm. These results demonstrate that this novel microparticulate/nanoparticulate chemotherapeutic PEGylated phospholipid dry powder inhalation aerosol platform has great potential in lung cancer drug delivery.

  19. Conditional overexpression of receptors for advanced glycation end-products in the adult murine lung causes airspace enlargement and induces inflammation.

    PubMed

    Stogsdill, Megan P; Stogsdill, Jeffrey A; Bodine, B Garrett; Fredrickson, Ali C; Sefcik, Tayler L; Wood, Tyler T; Kasteler, Stephen D; Reynolds, Paul R

    2013-07-01

    Receptors for advanced glycation end-products (RAGE) are multiligand surface receptors detected abundantly in pulmonary tissue. Our previous work revealed increased RAGE expression in cells and lungs exposed to tobacco smoke and RAGE-mediated cytokine expression via proinflammatory mechanisms involving NF-κB. RAGE expression is elevated in various pathological states, including chronic obstructive pulmonary disease; however, precise contributions of RAGE to the progression of emphysema and pulmonary inflammation in the adult lung are unknown. In the current study, we generated a RAGE transgenic (RAGE TG) mouse and conditionally induced adult alveolar epithelium to overexpress RAGE. RAGE was induced after the period of alveologenesis, from weaning (20 d of age) until animals were killed at 50, 80, and 110 days (representing 30, 60, and 90 d of RAGE overexpression). Hematoxylin and eosin staining and mean chord length revealed incremental dilation of alveolar spaces as RAGE overexpression persisted. TUNEL staining and electron microscopy confirmed increased apoptosis and blebbing of alveolar epithelium in lungs from RAGE TG mice when compared with control mice. Immunohistochemistry for matrix metalloproteinase 9 revealed an overall increase in matrix metalloproteinase 9, which correlated with decreased elastin expression in RAGE TG mice. Furthermore, RAGE TG mice manifested significant inflammation measured by elevated bronchoalveolar lavage protein, leukocyte infiltration, and secreted cytokines. These data support the concept that innovative transgenic mice that overexpress RAGE may model pulmonary inflammation and alveolar destabilization independent of tobacco smoke and validate RAGE signaling as a target pathway in the prevention or attenuation of smoke-related inflammatory lung diseases.

  20. Molecular Profiling of Circulating Tumour Cells Identifies Notch1 as a Principal Regulator in Advanced Non-Small Cell Lung Cancer

    PubMed Central

    Mariscal, Javier; Alonso-Nocelo, Marta; Muinelo-Romay, Laura; Barbazan, Jorge; Vieito, Maria; Abalo, Alicia; Gomez-Tato, Antonio; Maria de los Angeles, Casares de Cal; Garcia-Caballero, Tomas; Rodriguez, Carmela; Brozos, Elena; Baron, Francisco; Lopez-Lopez, Rafael; Abal, Miguel

    2016-01-01

    Knowledge on the molecular mechanisms underlying metastasis colonization in Non-Small Cell Lung Cancer (NSCLC) remains incomplete. A complete overview integrating driver mutations, primary tumour heterogeneity and overt metastasis lacks the dynamic contribution of disseminating metastatic cells due to the inaccessibility to the molecular profiling of Circulating Tumour Cells (CTCs). By combining immunoisolation and whole genome amplification, we performed a global gene expression analysis of EpCAM positive CTCs from advanced NSCLC patients. We identified an EpCAM+ CTC-specific expression profile in NSCLC patients mostly associated with cellular movement, cell adhesion and cell-to-cell signalling mediated by PI3K/AKT, ERK1/2 and NF-kB pathways. NOTCH1 emerged as a driver connecting active signalling pathways, with a reduced number of related candidate genes (NOTCH1, PTP4A3, LGALS3 and ITGB3) being further validated by RT-qPCR on an independent cohort of NSCLC patients. In addition, these markers demonstrated high prognostic value for Progression-Free Survival (PFS). In conclusion, molecular characterization of EpCAM+ CTCs from advanced NSCLC patients provided with highly specific biomarkers with potential applicability as a “liquid biopsy” for monitoring of NSCLC patients and confirmed NOTCH1 as a potential therapeutic target to block lung cancer dissemination. PMID:27901069

  1. An Online Learning Module to Increase Self-Efficacy and Involvement in Care for Patients With Advanced Lung Cancer: Research Protocol

    PubMed Central

    Nagrial, Adnan; Pene, Christopher; Rabbets, Melanie; Carlino, Matteo; Zachulski, Clare; Phillips, Jane; Birnbaum, Robert; Gandhi, Tejal; Harnett, Paul

    2016-01-01

    Background Improving patient care for individuals with lung cancer is a priority due to the increasing burden of the disease globally. One way this can be done is by improving patient self-management capabilities through increasing their self-efficacy. This can improve positive outcomes for patients with chronic conditions and increase their ability to manage the challenges of such illnesses. Unfortunately, patients with chronic conditions often struggle to travel far from home to engage with patient education events, a common means of improving self-efficacy. The development of more accessible tools for improving patient self-efficacy is required to increase quality of life for patients with chronic conditions. Objective To evaluate the feasibility of delivering symptom identification and management information to patients with advanced lung cancer using an online program. Methods This article describes a pre-post test study to evaluate a Qstream online learning platform to improve patient self-efficacy for managing advanced lung cancer symptoms. Undertaking this program should increase participant knowledge about the side-effects they may experience as a result of their treatment and in turn increase help-seeking behavior and self-efficacy for the participant cohort. Quantitative data collected by the Qstream platform on the completion rates of participants will be used as a tool to evaluate the intervention. Additionally, validated scales will be used to collect data on patient self-efficacy. Qualitative data will also be collected via an exit survey and thematic content analysis of semi-structured interviews. Results The research is in the preliminary stages but thus far a protocol has been approved in support of the project. Additionally, advisory committee members have been identified and initial meetings have been undertaken. Conclusions Development of new approaches for increasing patient understanding of their care is important to ensure high quality care

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

    PubMed

    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.

  3. Osimertinib and Navitoclax in Treating Patients With EGFR-Positive Previously Treated Advanced or Metastatic Non-small Cell Lung Cancer

    ClinicalTrials.gov

    2017-01-31

    EGFR Activating Mutation; Recurrent Non-Small Cell Lung Carcinoma; Stage III 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

  4. Surgical Options for Drug-Refractory Overactive Bladder Patients

    PubMed Central

    Starkman, Jonathan S; Smith, Christopher P; Staskin, David R

    2010-01-01

    Overactive bladder (OAB) is a symptom complex of urinary frequency, urinary urgency, and nocturia, with or without urgency incontinence. This syndrome is idiopathic in most instances without clearly defined pathophysiology. Studies clearly show that OAB negatively impacts health-related quality of life and impairs daily functioning in a large proportion of patients. Despite recent advances in drug delivery and improved tolerability of antimuscarinic drug class, a large percentage of patients remain refractory to conventional pharmacological therapy for this chronic condition. There are several unique and effective treatments that are available for this difficult population. We review the various surgical options within the urological armamentarium to treat patients with refractory OAB. PMID:20811558

  5. Preliminary safety, pharmacokinetics, and efficacy of regorafenib, cisplatin, and pemetrexed in patients with advanced non-squamous non-small cell lung cancers

    PubMed Central

    Hellmann, Matthew D; Sturm, Isrid; Trnkova, Zuzana Jirakova; Lettieri, John; Diefenbach, Konstanze; Rizvi, Naiyer A.; Gettinger, Scott N.

    2016-01-01

    Structured Abstract Purpose The addition of bevacizumab, an anti-angiogenesis agent, to cytotoxic chemotherapy improves survival in patients with advanced non-squamous non-small cell lung cancers (nsNSCLCs). Regorafenib is an oral multi-targeted kinase inhibitor with potent anti-angiogenic activity that is approved for patients with advanced colorectal cancer and gastrointestinal stromal tumors. This phase I trial evaluated the safety, pharmacokinetics, and efficacy of regorafenib with cisplatin and pemetrexed for patients with advanced nsNSCLCs. Methods Chemotherapy-naïve patients with advanced nsNSCLCs were treated with regorafenib 60mg/day continuously and cisplatin 75mg/m2 plus pemetrexed 500mg/m2 once every three weeks for up to six cycles. Thereafter, regorafenib with or without pemetrexed could be continued as maintenance. Results Nine patients enrolled prior to premature termination of the study due to slow recruitment and a change in the development strategy of regorafenib by the study sponsor, partially due to slow enrollment. Five patients experienced at least one treatment-related Grade 3 adverse event. No grade 4–5 toxicity occurred. 5 of 9 (56%) patients had a partial response and the median progression-free survival was 7 months (range 1.5–15.1). Minor pharmacokinetic (PK) interactions between regorafenib and chemotherapy were observed. Conclusions Regorafenib had acceptable tolerability and minor PK interactions in combination with standard doses of cisplatin and pemetrexed in patients with advanced nsNSCLCs. Encouraging activity was appreciated in chemotherapy-naïve patients with advanced nsNSCLCs. However, the small number of patients treated limits conclusions that can be drawn from these results. PMID:26003007

  6. Correlation between epidermal growth factor receptor tyrosine kinase inhibitor efficacy and circulating tumor cell levels in patients with advanced non-small cell lung cancer

    PubMed Central

    He, Wenjie; Li, Wenhui; Jiang, Bo; Chang, Li; Jin, Congguo; Tu, Changlin; Li, Yunfen

    2016-01-01

    Objective The aim of this study was to investigate the correlation between the efficacy of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) and circulating tumor cell (CTC) levels in patients with advanced non-small cell lung cancer (NSCLC). The efficacy of EGFR-TKIs in reducing CTC counts in patients with advanced NSCLC was studied. Patients and methods A total of 66 patients with advanced NSCLC were enrolled and divided into two groups (those with high CTC counts and those with low CTC counts) based on the patients’ median CTC counts. All the patients were treated with an EGFR-TKI, and the treatment efficacy and prognoses were compared. Results The treatment efficacies were 53.3% (16/30) and 27.8% (10/36) for the low CTC group and high CTC group, respectively, and this difference was statistically significant (P<0.05). The median overall survival was 22.8 months (95% confidence interval [CI]: 18.9–26.8 months) for the low CTC group and 18.3 months (95% CI: 2.9–8.2 months) for the high CTC group. The median progression-free survival was 11.5 months (95% CI: 8.1–15 months) and 5.6 months (95% CI: 2.9–8.2 months) for the low and high CTC groups, respectively, and the difference was statistically significant (P<0.05). Conclusion The CTC count can be used as an index for predicting the EGFR-TKI effect on patients with advanced NSCLC. Efficacy and prognosis of EGFR-TKI treatment and CTC count were considered important, and the CTC count could be used to predict the efficacy of EGFR-TKI treatment and prognosis of advanced NSCLC. The change in CTC expression levels can be used as an index for evaluating the prognosis of patients with advanced NSCLC. PMID:28003764

  7. A plasmapheresis protocol for refractory pulmonary alveolar proteinosis.

    PubMed

    Garber, Bryan; Albores, Jeffrey; Wang, Tisha; Neville, Thanh H

    2015-04-01

    Pulmonary alveolar proteinosis (PAP) is a rare lung disease characterized by the accumulation of proteinaceous material within the lungs. While typically managed with whole lung lavage (WLL), more recent PAP therapies aimed at reducing granulocyte-macrophage colony stimulating factor autoantibodies (anti-GM-CSF) have reduced symptoms and improved lung function. We present a patient with PAP refractory to WLL, exogenous GM-CSF and rituximab who underwent a novel plasmapheresis protocol as a therapeutic trial. While previously reported regimens have utilized plasmapheresis sessions distributed over months, our patient underwent five consecutive days of plasmapheresis, followed by rituximab. Anti-GM-CSF levels decreased from 24.8 to 2.7 mcg/mL post-plasmapheresis. This reduction of autoantibody correlated with reduction in WLL frequency, increase in diffusing capacity for carbon monoxide, and subjective improvement in dyspnea. Our case suggests that five consecutive days of plasmapharesis results in increased clearance of anti-GM-CSF and may be potentially efficacious in cases of refractory PAP.

  8. Feasibility, tolerability, and efficacy of the concurrent addition of erlotinib to thoracic radiotherapy in locally advanced unresectable non-small-cell lung cancer: a Phase II trial

    PubMed Central

    Martínez, Enrique; Martínez, Maite; Rico, Mikel; Hernández, Berta; Casas, Francesc; Viñolas, Nuria; Pérez-Casas, Ana; Dómine, Manuel; Mínguez, Julián

    2016-01-01

    Purpose Although many studies have confirmed the synergic effects of combining chemotherapy (CT) and radiotherapy (RT), clinical data evaluating safety and efficacy of erlotinib in combination with RT in locally advanced non-small-cell lung cancer (NSCLC) are limited. The aim of this study was to determine the feasibility, tolerability, and efficacy of the concurrent addition of erlotinib to the standard three-dimensional conformal thoracic RT in patients with unresectable or locally advanced NSCLC who are not candidates for receiving standard CT. Patients and methods Feasibility and tolerability, assessed by evaluating adverse events (AEs), and effectiveness, by calculating progression-free survival (PFS), overall survival (OS), cancer-specific survival (CSS), and objective response rate (ORR), were analyzed in 30 patients receiving RT alone and 60 receiving RT and erlotinib. Results Erlotinib with RT showed an extended CSS and a higher rate of complete responses compared with RT alone. No differences between groups were found regarding OS, PFS, and ORR. AEs were significantly higher in the combined treatment, which mainly included cutaneous toxicity, dyspnea, fatigue, hyporexia, diarrhea, and infection. Erlotinib did not increase the toxicity produced by RT. Conclusion The combination of erlotinib with RT produced, in our study, a scarce clinical benefit in the treatment of unresectable or locally advanced NSCLC, limited to complete responses and longer CSS rate compared with RT alone. Increased toxicity events were associated with combined therapy, which mainly included cutaneous toxicity. In our opinion, further studies in molecularly unselected lung cancer patients treated with EGFR TKIs and RT are not indicated. The use of biomarkers for the identification of patients that are most likely to benefit from this treatment is an essential next step in the research of this condition. PMID:27042098

  9. Interfraction Displacement of Primary Tumor and Involved Lymph Nodes Relative to Anatomic Landmarks in Image Guided Radiation Therapy of Locally Advanced Lung Cancer

    SciTech Connect

    Jan, Nuzhat; Balik, Salim; Hugo, Geoffrey D.; Mukhopadhyay, Nitai; Weiss, Elisabeth

    2014-01-01

    Purpose: To analyze primary tumor (PT) and lymph node (LN) position changes relative to each other and relative to anatomic landmarks during conventionally fractionated radiation therapy for patients with locally advanced lung cancer. Methods and Materials: In 12 patients with locally advanced non-small cell lung cancer PT, LN, carina, and 1 thoracic vertebra were manually contoured on weekly 4-dimensional fan-beam CT scans. Systematic and random interfraction displacements of all contoured structures were identified in the 3 cardinal directions, and resulting setup margins were calculated. Time trends and the effect of volume changes on displacements were analyzed. Results: Three-dimensional displacement vectors and systematic/random interfraction displacements were smaller for carina than for vertebra both for PT and LN. For PT, mean (SD) 3-dimensional displacement vectors with carina-based alignment were 7 (4) mm versus 9 (5) mm with bony anatomy (P<.0001). For LN, smaller displacements were found with carina- (5 [3] mm, P<.0001) and vertebra-based (6 [3] mm, P=.002) alignment compared with using PT for setup (8 [5] mm). Primary tumor and LN displacements relative to bone and carina were independent (P>.05). Displacements between PT and bone (P=.04) and between PT and LN (P=.01) were significantly correlated with PT volume regression. Displacements between LN and carina were correlated with LN volume change (P=.03). Conclusions: Carina-based setup results in a more reproducible PT and LN alignment than bony anatomy setup. Considering the independence of PT and LN displacement and the impact of volume regression on displacements over time, repeated CT imaging even with PT-based alignment is recommended in locally advanced disease.

  10. Intrathecal ziconotide for refractory pain.

    PubMed

    Doggrell, Sheila A

    2004-07-01

    For cancer and AIDS patients, 10-30% of pain is refractory to strong opioids, requiring intraspinal administration for pain management. Ziconotide is a selective N-type calcium channel blocker, which inhibits neurotransmitter release, and following intrathecal administration will affect primary nociceptive afferents. In 108 patients with previously unmanaged refractory pain despite the use of systemic or intrathecal opioids, in the initial titration phase, the mean Visual Analogue Scale of Pain Intensity scores improved more in the ziconotide group (53%) than the placebo group (18%). Serious adverse effects were more common in the ziconotide group (31%) than placebo group (10%) in the initial titration phase. In the 48 patients receiving ziconotide, who proceeded to the maintenance phase, the benefit of ziconotide was continued. Until a new approach with a better effectiveness/adverse effects profile than ziconotide for refractory pain emerges, further optimisation of ziconotide for use in the treatment of refractory pain should be undertaken.

  11. Consensus on the management of advanced radioactive iodine-refractory differentiated thyroid cancer on behalf of the Spanish Society of Endocrinology Thyroid Cancer Working Group (GTSEEN) and Spanish Rare Cancer Working Group (GETHI).

    PubMed

    Capdevila, J; Galofré, J C; Grande, E; Zafón Llopis, C; Ramón Y Cajal Asensio, T; Navarro González, E; Jiménez-Fonseca, P; Santamaría Sandi, J; Gómez Sáez, J M; Riesco Eizaguirre, G

    2017-03-01

    Thyroid cancer is the single most prevalent endocrine malignancy; differentiated thyroid cancer (DTC) accounts for more than 90 % of all malignancies and its incidence has been rising steadily. For more patients, surgical treatment, radioactive iodine (RAI) ablation, and thyroid-stimulating hormone (TSH) suppressive therapy achieve an overall survival (OS) rate of 97.7 % at 5 years. Nevertheless, locoregional recurrence occurs in up to 20 % and distant metastases in approximately 10 % at 10 years. Two-thirds of these patients will never be cured with radioactive iodine therapy and will become RAI-refractory, with a 3-year OS rate of less than 50 %. Over the last decade, substantial progress has been made in the management of RAI-refractory DTC. Given the controversy in some areas, the Spanish Task Force for Thyroid Cancer on behalf of Spanish Society of Endocrinology Thyroid Cancer Working Group (GTSEEN) and the Spanish Rare Cancer Working Group (GETHI) have created a national joint task force to reach a consensus addressing the most challenging aspects of management in these patients. In this way, multidisciplinary management should be mandatory and nuclear medicine targeted therapy, novel molecular targeted agents, and combinations are currently changing the natural history of RAI-refractory DTC.

  12. Localization accuracy from automatic and semi-automatic rigid registration of locally-advanced lung cancer targets during image-guided radiation therapy

    SciTech Connect

    Robertson, Scott P.; Weiss, Elisabeth; Hugo, Geoffrey D.

    2012-01-15

    Purpose: To evaluate localization accuracy resulting from rigid registration of locally-advanced lung cancer targets using fully automatic and semi-automatic protocols for image-guided radiation therapy. Methods: Seventeen lung cancer patients, fourteen also presenting with involved lymph nodes, received computed tomography (CT) scans once per week throughout treatment under active breathing control. A physician contoured both lung and lymph node targets for all weekly scans. Various automatic and semi-automatic rigid registration techniques were then performed for both individual and simultaneous alignments of the primary gross tumor volume (GTV{sub P}) and involved lymph nodes (GTV{sub LN}) to simulate the localization process in image-guided radiation therapy. Techniques included ''standard'' (direct registration of weekly images to a planning CT), ''seeded'' (manual prealignment of targets to guide standard registration), ''transitive-based'' (alignment of pretreatment and planning CTs through one or more intermediate images), and ''rereferenced'' (designation of a new reference image for registration). Localization error (LE) was assessed as the residual centroid and border distances between targets from planning and weekly CTs after registration. Results: Initial bony alignment resulted in centroid LE of 7.3 {+-} 5.4 mm and 5.4 {+-} 3.4 mm for the GTV{sub P} and GTV{sub LN}, respectively. Compared to bony alignment, transitive-based and seeded registrations significantly reduced GTV{sub P} centroid LE to 4.7 {+-} 3.7 mm (p = 0.011) and 4.3 {+-} 2.5 mm (p < 1 x 10{sup -3}), respectively, but the smallest GTV{sub P} LE of 2.4 {+-} 2.1 mm was provided by rereferenced registration (p < 1 x 10{sup -6}). Standard registration significantly reduced GTV{sub LN} centroid LE to 3.2 {+-} 2.5 mm (p < 1 x 10{sup -3}) compared to bony alignment, with little additional gain offered by the other registration techniques. For simultaneous target alignment, centroid LE as low

  13. Second primary cancer in survivors following concurrent chemoradiation for locally advanced non-small-cell lung cancer

    PubMed Central

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

    SciTech Connect

    Liu, Z; Kennedy, A; Larsen, E; Hayes, C; Grow, A; Bahamondes, S.; Zheng, Y; Wu, X; Choi, M; Pai, S; Li, J; Cranford, K

    2015-06-15

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

  15. Imaging Characteristics of Driver Mutations in EGFR, KRAS, and ALK among Treatment-Naïve Patients with Advanced Lung Adenocarcinoma

    PubMed Central

    Park, Jangchul; Kobayashi, Yoshihisa; Urayama, Kevin Y.; Yamaura, Hidekazu; Yatabe, Yasushi; Hida, Toyoaki

    2016-01-01

    This study aimed to identify the computed tomography characteristics of treatment-naïve patients with lung adenocarcinoma and known driver mutations in EGFR, KRAS, or ALK. Patients with advanced lung adenocarcinoma (stage IIIB–IV) and known mutations in EGFR, KRAS, or ALK were assessed. The radiological findings for the main tumor and intra-thoracic status were retrospectively analyzed in each group, and the groups’ characteristics were compared. We identified 265 treatment-naïve patients with non-small-cell carcinoma, who had EGFR mutations (n = 159), KRAS mutations (n = 55), or ALK rearrangements (n = 51). Among the three groups, we evaluated only patients with stage IIIB–IV lung adenocarcinoma who had EGFR mutations (n = 126), KRAS mutations (n = 35), or ALK rearrangements (n = 47). We found that ground-glass opacity at the main tumor was significantly more common among EGFR-positive patients, compared to ALK-positive patients (p = 0.009). Lymphadenopathy was significantly more common among ALK-positive patients, compared to EGFR-positive patients (p = 0.003). Extranodal invasion was significantly more common among ALK-positive patients, compared to EGFR-positive patients and KRAS-positive patients (p = 0.001 and p = 0.049, respectively). Lymphangitis was significantly more common among ALK-positive patients, compared to EGFR-positive patients (p = 0.049). Pleural effusion was significantly less common among KRAS-positive patients, compared to EGFR-positive patients and ALK-positive patients (p = 0.046 and p = 0.026, respectively). Lung metastases were significantly more common among EGFR-positive patients, compared to KRAS-positive patients and ALK-positive patients (p = 0.007 and p = 0.04, respectively). In conclusion, EGFR mutations were associated with ground-glass opacity, KRAS-positive tumors were generally solid and less likely to metastasize to the lung and pleura, and ALK-positive tumors tended to present with lymphadenopathy, extranodal

  16. Compatibility of refractory materials for nuclear reactor poison control systems

    NASA Technical Reports Server (NTRS)

    Sinclair, J. H.

    1974-01-01

    Metal-clad poison rods have been considered for the control system of an advanced space power reactor concept studied at the NASA Lewis Research Center. Such control rods may be required to operate at temperatures of about 140O C. Selected poison materials (including boron carbide and the diborides of zirconium, hafnium, and tantalum) were subjected to 1000-hour screening tests in contact with candidate refractory metal cladding materials (including tungsten and alloys of tantalum, niobium, and molybdenum) to assess the compatibility of these materials combinations at the temperatures of interest. Zirconium and hafnium diborides were compatible with refractory metals at 1400 C, but boron carbide and tantalum diboride reacted with the refractory metals at this temperature. Zirconium diboride also showed promise as a reaction barrier between boron carbide and tungsten.

  17. A Case Report of 20 Lung Radiofrequency Ablation Sessions for 50 Lung Metastases from Parathyroid Carcinoma Causing Hyperparathyroidism

    SciTech Connect

    Tochio, Maki Takaki, Haruyuki; Yamakado, Koichiro; Uraki, Junji; Kashima, Masataka; Nakatsuka, Atsuhiro; Takao, Motoshi; Shimamoto, Akira; Tarukawa, Tomohito; Shimpo, Hideto; Takeda, Kan

    2010-06-15

    A 47-year-old man presented with multiple lung metastases from parathyroid carcinoma that caused hyperparathyroidism and refractory hypercalcemia. Lung radiofrequency (RF) ablation was repeated to decrease the serum calcium and parathyroid hormone levels and improve general fatigue. Pulmonary resection was combined for lung hilum metastases. The patient is still alive 4 years after the initial RF session. He has received 20 RF sessions for 50 lung metastases during this period.

  18. Abemaciclib in Children With DIPG or Recurrent/Refractory Solid Tumors

    ClinicalTrials.gov

    2017-02-10

    Diffuse Intrinsic Pontine Glioma; Brain Tumor, Recurrent; Solid Tumor, Recurrent; Neuroblastoma, Recurrent, Refractory; Ewing Sarcoma, Recurrent, Refractory; Rhabdomyosarcoma, Recurrent, Refractory; Osteosarcoma, Recurrent, Refractory; Rhabdoid Tumor, Recurrent, Refractory

  19. Radiotherapy and chemotherapy in locally advanced non-small cell lung cancer: preclinical and early clinical data.

    PubMed

    Reboul, François L

    2004-02-01

    Over the past 20 years, combined treatment with radiotherapy and second-generation chemotherapy drugs was extensively studied in patients with locally advanced NSCLC and became the standard over radiotherapy alone in patients with good performance status. Radiosensitizing properties of cisplatin have been identified in the laboratory. Close temporal administration of cisplatin and radiation is mandatory for enhanced antitumor efficacy, but results in significant toxicity to normal tissues. Early clinical studies demonstrated that the concurrent administration of cisplatin during STD-RT was feasible, with acceptable esophageal toxicity, and had the potential of significantly improving locoregional control. Carboplatin administered concurrently with accelerated HFX-RT was responsible for a higher rate of esophageal toxicity. Further improvement in survival also requires an effective treatment of micro-metastatic disease through full-dose delivery of cytotoxic drugs and the addition of at least one more active drug in conjunction with cisplatin and radiotherapy to further improve locoregional control of the disease. In most clinical studies, etoposide was the second drug of choice because of its own radiosensitizing properties and possible synergy with cisplatin. In numerous phase II studies, concurrent radiotherapy and PE resulted in reproducible results in terms of local control (30%-40%), median survival (15-18 months), survival at 2 years (35%-40%), and survival at 5 years (25%-30%). In phase III studies, these results were shown to be superior to radiotherapy alone and to induction chemotherapy followed by STD-RT. The question of the potential benefit of HFX-RT combined with PE has been addressed in phase II and III studies. At this time, there is no firm evidence that concurrent chemotherapy with HFX-RT is superior to concurrent chemotherapy with STD-RT in terms of local control and survival. Only a significant benefit in terms of local control or survival would

  20. Characteristics and Prognostic Impact of Pneumonitis during Systemic Anti-Cancer Therapy in Patients with Advanced Non-Small-Cell Lung Cancer

    PubMed Central

    Fujimoto, Daichi; Kato, Ryoji; Morimoto, Takeshi; Shimizu, Ryoko; Sato, Yuki; Kogo, Mariko; Ito, Jiro; Teraoka, Shunsuke; Nagata, Kazuma; Nakagawa, Atsushi; Otsuka, Kojiro; Tomii, Keisuke

    2016-01-01

    Background Data on characteristics, outcomes, and prognosis of advanced non-small-cell lung cancer (NSCLC) patients who develop pneumonitis during systemic anti-cancer therapy (pneumonitis) are currently lacking. Methods We conducted a retrospective cohort study of 910 consecutive patients diagnosed with advanced NSCLC between January 2004 and January 2014. Of these, 140 patients were excluded because they did not receive systemic anti-cancer therapy at this hospital. Results A total of 770 patients were included in the study, of whom 44 (6%) were diagnosed with pneumonitis. The mortality rate of pneumonitis was 36%. The incidence of pneumonitis was independently associated with pre-existing ILD (adjusted odds ratio, 2.99, P = 0.008), and survivors were significantly associated with younger age (P = 0.003) and radiographic non-acute interstitial pneumonia pattern (P = 0.004). In all patients, pneumonitis was identified as an independent predictor of overall survival (OS) (adjusted hazard ratio 1.53, 95% CI, 1.09–2.09, P = 0.015). Performance status was poor in 82% of survivors of pneumonitis; in 62% of survivors, the PS worsened after the pneumonitis improved. Additionally, 54% of survivors received no further systemic anti-cancer therapy after pneumonitis. The median survival time of survivors after pneumonitis was 3.5 months (95% CI, 2.3–7.2 months). Conclusions Our study indicated that 6% of patients with advanced NSCLC developed pneumonitis during systemic anti-cancer therapy. The early mortality rate of pneumonitis is high, and the survival and PS after pneumonitis is extremely poor. Additionally, pneumonitis has an adverse impact on the survival of patients with advanced NSCLC. These data should be considered for the management of pneumonitis, and we recommend that future work focuses on pneumonitis particularly to improve the survival of patients with advanced NSCLC. PMID:28006019

  1. Gefitinib Combined With Standard Chemoradiotherapy in EGFR-Mutant Locally Advanced Non-Small-Cell Lung Cancer: The LOGIK0902/OLCSG0905 Intergroup Study Protocol.

    PubMed

    Hotta, Katsuyuki; Sasaki, Jiichiro; Saeki, Sho; Takigawa, Nagio; Katsui, Kuniaki; Takayama, Koichi; Nogami, Naoyuki; Shioyama, Yoshiyuki; Bessho, Akihiro; Kishimoto, Junji; Tanimoto, Mitsune; Kiura, Katsuyuki; Ichinose, Yukito

    2016-01-01

    Herein, we describe an ongoing phase II trial in patients with locally advanced non-small-cell lung cancer (NSCLC) with mutated epidermal growth factor receptor (EGFR). Patients with chemotherapy-naive locally advanced disease with active EGFR mutations will receive the induction treatment, specified as gefitinib monotherapy (250 mg/body) for 8 weeks. Patients whose disease has not progressed during the induction therapy will receive cisplatin and docetaxel (40 mg/m(2)) on days 1, 8, 29, and 36, and concurrent 3-dimensional conformal thoracic radiotherapy with a single daily fraction of 2 Gy, for 5 consecutive days each week to provide a total dose of 60 Gy. The primary end point is overall survival at 24 months. A target sample size of 21 evaluable patients is considered sufficient to validate an expected rate of 85%, and 60% would be the lower limit of interest, with 80% power and a 1-sided α of 5%. Secondary end points include toxicity, response rate, and overall survival. This study will clarify whether tyrosine kinase inhibitors targeted to EGFR can produce a maximal effect in selected NSCLC patients with the relevant driver mutation, even in the locally advanced setting.

  2. Stereotactic Body Radiation Therapy Can Be Used Safely to Boost Residual Disease in Locally Advanced Non-Small Cell Lung Cancer: A Prospective Study

    SciTech Connect

    Feddock, Jonathan; Arnold, Susanne M.; Shelton, Brent J.; Sinha, Partha; Conrad, Gary; Chen, Li; Rinehart, John; McGarry, Ronald C.

    2013-04-01

    Purpose: To report the results of a prospective, single-institution study evaluating the feasibility of conventional chemoradiation (CRT) followed by stereotactic body radiation therapy (SBRT) as a means of dose escalation for patients with stage II-III non-small cell lung cancer (NSCLC) with residual disease. Methods and Materials: Patients without metastatic disease and with radiologic evidence of limited residual disease (≤5 cm) within the site of the primary tumor and good or complete nodal responses after standard CRT to a target dose of 60 Gy were considered eligible. The SBRT boost was done to achieve a total combined dose biological equivalent dose >100 Gy to the residual primary tumor, consisting of 10 Gy × 2 fractions (20 Gy total) for peripheral tumors, and 6.5 Gy × 3 fractions (19.5 Gy total) for medial tumors using the Radiation Therapy Oncology Group protocol 0813 definitions. The primary endpoint was the development of grade ≥3 radiation pneumonitis (RP). Results: After a median follow-up of 13 months, 4 patients developed acute grade 3 RP, and 1 (2.9%) developed late and persistent grade 3 RP. No patients developed grade 4 or 5 RP. Mean lung dose, V2.5, V5, V10, and V20 values were calculated for the SBRT boost, and none were found to significantly predict for RP. Only advancing age (P=.0147), previous smoking status (P=.0505), and high CRT mean lung dose (P=.0295) were significantly associated with RP development. At the time of analysis, the actuarial local control rate at the primary tumor site was 82.9%, with only 6 patients demonstrating recurrence. Conclusions: Linear accelerator-based SBRT for dose escalation of limited residual NSCLC after definitive CRT was feasible and did not increase the risk for toxicity above that for standard radiation therapy.

  3. MicroRNA-490 regulates lung cancer metastasis by targeting poly r(C)-binding protein 1.

    PubMed

    Li, Jindong; Feng, Qingchuan; Wei, Xudong; Yu, Yongkui

    2016-11-01

    Lung cancer remains a leading cause of cancer-related mortality, with metastatic progression remaining the single largest cause of lung cancer mortality. Hence, it is imperative to determine reliable biomarkers of lung cancer prognosis. MicroRNA-490-3p has been previously reported to be a positive prognostic biomarker for hepatocellular cancer. However, its role in human lung cancer has not yet been elucidated. Here, we report that hsa-miR-490-3p expression is significantly higher in human lung cancer tissue specimens and cell line. Gain- and loss-of-function studies of hsa-miR-490-3p showed that it regulates cell proliferation and is required for induction of in vitro migration and invasion-the latter being a hallmark of epithelial to mesenchymal transition. In situ analysis revealed that hsa-miR-490-3p targets poly r(C)-binding protein 1 (PCBP1), which has been previously shown to be a negative regulator of lung cancer metastasis. Reporter assays confirmed PCBP1 as a bona fide target of miR-490-3p, and metagenomic analysis revealed an inverse relation between expression of miR-490-3p and PCBP1 in metastatic lung cancer patients. In fact, PCBP1 expression, as detected by immunohistochemistry, was undetectable in advanced stages of lung cancer patients' brain and lymph node tissues. Xenograft tail vein colonization assays proved that high expression of miR-490-3p is a prerequisite for metastatic progression of lung cancer. Our results suggest that hsa-miR-490-3p might be a potential biomarker for lung cancer prognosis. In addition, we can also conclude that the lung cancer cells have evolved refractory mechanisms to downregulate the expression of the metastatic inhibitor, PCBP1.

  4. Interstitial lung disease

    MedlinePlus

    ... advanced ILD may have: Abnormal enlargement of the base of the fingernails ( clubbing ) Blue color of the ... scan of the chest Echocardiogram Open lung biopsy Measurement of the blood oxygen level at rest or ...

  5. What is changing in radiotherapy for the treatment of locally advanced nonsmall cell lung cancer patients? A review.

    PubMed

    Giaj-Levra, Niccoló; Ricchetti, Francesco; Alongi, Filippo

    2016-01-01

    Radiotherapy treatment continues to have a relevant impact in the treatment of nonsmall cell cancer (NSCLC). Use of concurrent chemotherapy and radiotherapy is considered the gold standard in the treatment of locally advanced NSCLC but clinical outcomes are not satisfactory. Introduction of new radiotherapy technology and chemotherapy regimens are under investigation in this setting with the goal to improve unsatisfactory results. We report how radiotherapy is changing in the treatment of locally advanced NSCLC.

  6. Interfractional Positional Variability of Fiducial Markers and Primary Tumors in Locally Advanced Non-Small-Cell Lung Cancer During Audiovisual Biofeedback Radiotherapy

    SciTech Connect

    Roman, Nicholas O.; Shepherd, Wes; Mukhopadhyay, Nitai; Hugo, Geoffrey D.; Weiss, Elisabeth

    2012-08-01

    Purpose: To evaluate implanted markers as a surrogate for tumor-based setup during image-guided lung cancer radiotherapy with audiovisual biofeedback. Methods and Materials: Seven patients with locally advanced non-small-cell lung cancer were implanted bronchoscopically with gold coils. Markers, tumor, and a reference bony structure (vertebra) were contoured for all 10 phases of the four-dimensional respiration-correlated fan-beam computed tomography and weekly four-dimensional cone-beam computed tomography. Results: The systematic/random interfractional marker-to-tumor centroid displacements were 2/3, 2/2, and 3/3 mm in the x (lateral), y (anterior-posterior), and z (superior-inferior) directions, respectively. The systematic/random interfractional marker-to-bone displacements were 2/3, 2/3, and 2/3 mm in the x, y, and z directions, respectively. The systematic/random tumor-to-bone displacements were 2/3, 2/4, and 4/4 mm in the x, y, and z directions, respectively. All displacements changed significantly over time (p < 0.0001). Conclusions: Although marker-based image guidance may decrease the risk for geometric miss compared with bony anatomy-based positioning, the observed displacements between markers and tumor centroids indicate the need for repeated soft tissue imaging, particularly in situations with large tumor volume change and large initial marker-to-tumor centroid distance.

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

    PubMed Central

    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

  8. Radiation Effects in Refractory Alloys

    NASA Astrophysics Data System (ADS)

    Zinkle, Steven J.; Wiffen, F. W.

    2004-02-01

    In order to achieve the required low reactor mass per unit electrical power for space reactors, refractory alloys are essential due to their high operating temperature capability that in turn enables high thermal conversion efficiencies. One of the key issues associated with refractory alloys is their performance in a neutron irradiation environment. The available radiation effects data are reviewed for alloys based on Mo, W, Re, Nb and Ta. The largest database is associated with Mo alloys, whereas Re, W and Ta alloys have the least available information. Particular attention is focused on Nb-1Zr, which is a proposed cladding and structural material for the reactor in the Jupiter Icy Moons Orbiter (JIMO) project. All of the refractory alloys exhibit qualitatively similar temperature-dependent behavior. At low temperatures up to ~0.3TM, where TM is the melting temperature, the dominant effect of radiation is to produce pronounced radiation hardening and concomitant loss of ductility. The radiation hardening also causes a dramatic decrease in the fracture toughness of the refractory alloys. These low temperature radiation effects occur at relatively low damage levels of ~0.1 displacement per atom, dpa (~2×1024 n/m2, E>0.1 MeV). As a consequence, operation at low temperatures in the presence of neutron irradiation must be avoided for all refractory alloys. At intermediate temperatures (0.3 to 0.6 TM), void swelling and irradiation creep are the dominant effects of irradiation. The amount of volumetric swelling associated with void formation in refractory alloys is generally within engineering design limits (<5%) even for high neutron exposures (>>10 dpa). Very little experimental data exist on irradiation creep of refractory alloys, but data for other body centered cubic alloys suggest that the irradiation creep will produce negligible deformation for near-term space reactor applications.

  9. GTI-2040 and Docetaxel in Treating Patients With Recurrent, Metastatic, or Unresectable Locally Advanced Non-Small Cell Lung Cancer, Prostate Cancer, or Other Solid Tumors

    ClinicalTrials.gov

    2013-01-23

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

  10. Osimertinib in Pretreated T790M-Positive Advanced Non-Small-Cell Lung Cancer: AURA Study Phase II Extension Component.

    PubMed

    Yang, James Chih-Hsin; Ahn, Myung-Ju; Kim, Dong-Wan; Ramalingam, Suresh S; Sequist, Lecia V; Su, Wu-Chou; Kim, Sang-We; Kim, Joo-Hang; Planchard, David; Felip, Enriqueta; Blackhall, Fiona; Haggstrom, Daniel; Yoh, Kiyotaka; Novello, Silvia; Gold, Kathryn; Hirashima, Tomonori; Lin, Chia-Chi; Mann, Helen; Cantarini, Mireille; Ghiorghiu, Serban; Jänne, Pasi A

    2017-02-21

    Purpose Osimertinib is an irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) selective for both EGFR-TKI sensitizing ( EGFRm) and T790M resistance mutations. AURA (NCT01802632) is a phase I/II clinical trial to determine the dose, safety, and efficacy of osimertinib. This article reports the results from the phase II extension component. Patients and Methods Patients with EGFR-TKI-pretreated EGFRm- and T790M-positive advanced non-small-cell lung cancer (NSCLC) received once-daily osimertinib 80 mg. T790M status was confirmed by central testing from a tumor sample taken after the most recent disease progression. Patients with asymptomatic, stable CNS metastases that did not require corticosteroids were allowed to enroll. The primary end point was objective response rate (ORR) by independent radiology assessment. Secondary end points were disease control rate, duration of response, progression-free survival (PFS), and safety. Patient-reported outcomes comprised an exploratory objective. Results In total, 201 patients received treatment, with a median treatment duration of 13.2 months at the time of data cutoff (November 1, 2015). In evaluable patients (n = 198), ORR was 62% (95% CI, 54% to 68%), and the disease control rate was 90% (95% CI, 85 to 94). Median duration of response in 122 responding patients was 15.2 months (95% CI, 11.3 to not calculable). Median PFS was 12.3 months (95% CI, 9.5 to 13.8). The most common possibly causally related adverse events (investigator assessed) were diarrhea (43%; grade ≥ 3, < 1%) and rash (grouped terms; 40%; grade ≥ 3, < 1%). Interstitial lung disease (grouped terms) was reported in eight patients (4%; grade 1, n = 2; grade 3, n = 3; grade 5, n = 3). Conclusion In patients with EGFRm T790M advanced NSCLC who progress after EGFR-TKI treatment, osimertinib provides a high ORR, encouraging PFS, and durable response.

  11. Economic Evaluation of Companion Diagnostic Testing for EGFR Mutations and First-Line Targeted Therapy in Advanced Non-Small Cell Lung Cancer Patients in South Korea

    PubMed Central

    Lim, Eun-A; Bae, Eunmi; Lim, Jaeok; Shin, Young Kee; Choi, Sang-Eun

    2016-01-01

    Background As targeted therapy becomes increasingly important, diagnostic techniques for identifying targeted biomarkers have also become an emerging issue. The study aims to evaluate the cost-effectiveness of treating patients as guided by epidermal growth factor receptor (EGFR) mutation status compared with a no-testing strategy that is the current clinical practice in South Korea. Methods A cost-utility analysis was conducted to compare an EGFR mutation testing strategy with a no-testing strategy from the Korean healthcare payer’s perspective. The study population consisted of patients with stage 3b and 4 lung adenocarcinoma. A decision tree model was employed to select the appropriate treatment regimen according to the results of EGFR mutation testing and a Markov model was constructed to simulate disease progression of advanced non-small cell lung cancer. The length of a Markov cycle was one month, and the time horizon was five years (60 cycles). Results In the base case analysis, the testing strategy was a dominant option. Quality-adjusted life-years gained (QALYs) were 0.556 and 0.635, and total costs were $23,952 USD and $23,334 USD in the no-testing and testing strategy respectively. The sensitivity analyses showed overall robust results. The incremental cost-effectiveness ratios (ICERs) increased when the number of patients to be treated with erlotinib increased, due to the high cost of erlotinib. Conclusion Treating advanced adenocarcinoma based on EGFR mutation status has beneficial effects and saves the cost compared to no testing strategy in South Korea. However, the cost-effectiveness of EGFR mutation testing was heavily affected by the cost-effectiveness of the targeted therapy. PMID:27483001

  12. Cancer-related inflammation as predicting tool for treatment outcome in locally advanced and metastatic non-small cell lung cancer

    PubMed Central

    Korsic, Marta; Mursic, Davorka; Samarzija, Miroslav; Cucevic, Branka; Roglic, Mihovil; Jakopovic, Marko

    2016-01-01

    Background Lung cancer is the leading cause of cancer deaths and the non-small cell lung cancer (NSCLC) represents 80% of all cases. In most cases when diagnosed, it is in locally advanced or metastatic stage, when platinum based doublet chemotherapy is the established therapeutic option for majority of the patients. Predictive factors to filter the patients who will benefit the most from the chemotherapy are not clearly defined. Objective of this study was to explore predictive value of pre-treatment C-reactive protein (CRP), fibrinogen and their interaction, for the response to the frontline chemotherapy. Methods In this retrospective cohort study 170 patients with locally advanced and metastatic NSCLC were included. Relationship between baseline level of CRP and fibrinogen and response to the frontline chemotherapy was assessed. Results We found that pre-treatment CRP and fibrinogen values were statistically significantly correlated. Chemotherapy and CRP, fibrinogen, and their interaction were independently significantly associated with disease control rate at re-evaluation. There was statistically significant difference in median pre-treatment CRP level between the patients with disease control or progression at re-evaluation, 13.8 vs. 30.0 mg/L respectively, P=0.026. By Johnson-Neyman technique we found that in patients with initial fibrinogen value below 3.5 g/L, CRP level was significantly associated with disease control or progression of the disease. Above this fibrinogen value the association of CRP and disease control was lost. Conclusions The findings from this study support the growing evidence of inflammation and cancer relationship, where elevated pre-treatment level of CRP has negative predictive significance on the NSCLC frontline chemotherapy response. PMID:27499936

  13. Phase II Clinical Trial of Gefitinib for the Treatment of Chemonaïve Patients with Advanced Non-small Cell Lung Cancer with Poor Performance Status

    PubMed Central

    Karim, Nagla Abdel; Musaad, Salma; Zarzour, Ahmad; Patil, Sadanand; Jazieh, Abdul Rahman

    2014-01-01

    BACKGROUND Patients with advanced non-small cell lung cancer (NSCLC) have no curative treatment options; therefore, improving their quality of life (QOL) is an important goal. Gefitinib, an epidermal growth factor receptor (EGFR) inhibitor, is a safe oral agent that may be of benefit to a specific population of NSCLC. PATIENTS AND METHODS A Phase II clinical trial included chemonaïve patients with advanced NSCLC and poor performance status (PS). Response rate, progression-free survival, overall survival, QOL using the Functional Assessment of Cancer Therapy – Lung (FACT-L) questionnaire, and Trial Outcome Index (TOI) were evaluated. RESULTS Twelve out of 19 enrolled patients were evaluable. The median age for the evaluable patients was 68.8 years (59.7–74.6). Out of all the patients, 7 (58.3%) had adenocarcinoma and 5 (41.7%) had squamous cell carcinoma. The median duration of treatment was 62.5 days (26.5–115.0) in the evaluable patients. Grade 3/4 toxicities included fatigue, rash, diarrhea, and nausea. One patient had partial response, eight patients had stable disease (SD), and three patients progressed. The median overall survival for the evaluable population was 4.9 months (2.3–16). The median progression-free survival was 3.7 months (1.9–6.6). TOI was marginally associated with the overall survival, with a hazard ratio of 0.92 (95% confidence interval: 0.84, 1.0) (P = 0.061). FACT-L score and the TOI were highly correlated (r = 0.96, P < 0.0001). TOI scores were higher in African Americans compared to Caucasians and increased with age. CONCLUSION Our results suggest that gefitinib use in patients with NSCLC and poor PS may improve the QOL of older patients and African American patients. PMID:25520566

  14. Compressive Creep Performance and High Temperature Dimensional Stability of Conventional Silica Refractories

    SciTech Connect

    Karakus, M.; Kirkland, T.P.; Liu, K.C.; Moore, R.E.; Pint, B.A.; Wereszczak, A.A.

    1999-03-01

    Furnace designers and refractory engineers recognize that optimized furnace superstructure design and refractory selection are needed as glass production furnaces are continually striving toward greater output and efficiencies. Harsher operating conditions test refractories to the limit, while changing production technology (such as the conversion to oxy-fuel from traditional air-fuel firing) can alter the way the materials perform. Refractories for both oxy- and air-fuel fired furnace superstructures are subjected to high temperatures during service that may cause them to excessively creep or subside if the refractory material is not creep resistant, or if it is subjected to high stress, or both. Furnace designers can ensure that superstructure structural integrity is maintained if the creep behavior of the refractory material is well understood and well represented by appropriate engineering creep models. Several issues limit the abilities of furnace designers to (1) choose the optimum refractory for their applications, (2) optimize the engineering design, or (3) predict the service mechanical integrity of their furnace superstructures. Published engineering creep data are essentially non-existent for almost all commercially available refractories used for glass furnace superstructures. The limited data that do exist are supplied by the various refractory suppliers. Unfortunately, these suppliers generally have different ways of conducting their mechanical testing and they also interpret and report their data differently; this makes it hard for furnace designers to draw fair comparisons between competing grades of candidate refractories. Furthermore, the refractory supplier's data are often not available in a form that can be readily used for furnace design and for the prediction and design of long-term structural integrity of furnace superstructures. With the aim of providing such comparable data, the US DOE's Office of Industrial Technology and its Advanced

  15. Testing Requirements for Refractory Materials

    NASA Technical Reports Server (NTRS)

    Calle, Luz Marina; Hintze, Paul E.; Parlier, Christopher R.; Curran, Jerome P.; Kolody, Mark R.; Sampson, Jeffrey W.; Montgomery, Eliza M.

    2010-01-01

    Launch Pads 39A and 39B currently use refractory material (Fondu Fyre) in the flame trenches. This material was initially approved for the Saturn program. This material had a lifetime of 10 years according to the manufacturer, and it has been used for over 40 years. As a consequence, the Fondu Fyre at Launch Complex 39 requires repair subsequent to almost every launch. A review of the literature indicates that the gunned Fondu Fyre refractory product (WA-1G) was never tested prior to use. With the recent severe damage to the flame trenches, a new refractory material is sought to replace Fondu Fyre. In order to replace Fondu Fyre, a methodology to test and evaluate refractory products was developed. This paper outlines this methodology and discusses current testing requirements, as well as the laboratory testing that might be required. Furthermore, this report points out the necessity for subscale testing, the locations where this testing can be performed, and the parameters that will be necessary to qualify a product. The goal is to identify a more durable refractory material that has physical, chemical, and thermal properties suitable to withstand the harsh environment of the launch pads at KSC.

  16. Testing Requirements for Refractory Materials

    NASA Technical Reports Server (NTRS)

    Calle, Luz Marina; Hintze, Paul E.; Parlier, Christopher R.; Curran, Jerome P.; Kolody, Mark R.; Sampson, Jeffrey W.; Montgomery, Eliza M.

    2011-01-01

    Launch Pads 39A and 39B currently use refractory material (Fondu Fyre) in the flame trenches. This material was initially approved for the Saturn program. This material had a lifetime of 10 years according to the manufacturer, and it has been used for over 40 years. As a consequence, the Fondu Fyre at Launch Complex 39 requires repair subsequent to almost every launch. A review of the literature indicates that the gunned Fondu Fyre refractory product (WA-1G) was never tested prior to use. With the recent severe damage to the flame trenches, a new refractory material is sought to replace Fondu Fyre. In order to replace Fondu Fyre, a methodology to test and evaluate refractory products was developed. This paper outlines this methodology and discusses current testing requirements, as well as the laboratory testing that might be required. Furthermore, this report points out the necessity for subscale testing, the locations where this testing can be performed, and the parameters that will be necessary to qualify a product. The goal is to identify a more durable refractory material that has physical, chemical, and thermal properties suitable to withstand the harsh environment of the launch pads at KSC.

  17. Testing Requirements for Refractory Materials

    NASA Technical Reports Server (NTRS)

    Calle, Luz Marina; Hintze, Paul E.; Parlier, Christopher R.; Curran, Jerome P.; Kolody, Mark R.; Sampson, Jeffrey W,; Montgomery, Eliza M.

    2012-01-01

    Launch Pads 39A and 39B currently use refractory material (Fondu Fyre) in the flame trenches. This material was initially approved for the Saturn program. This material had a lifetime of 10years according to the manufacturer, and it has been used for over 40 years. As a consequence, the Fondu Fyre at Launch Complex 39 requires repair subsequent to almost every launch. A review of the literature indicates that the gunned Fondu Fyre refractory product (WA-1 G) was never tested prior to use. With the recent severe damage to the flame trenches, a new refractory material is sought to replace Fondu Fyre. In order to replace Fondu Fyre, a methodology to test and evaluate refractory products was developed. This paper outlines this methodology and discusses current testing requirements, as well as the laboratory testing that might be required. Furthermore, this report points out the necessity for subscale testing, the locations where this testing can be performed, and the parameters that will be necessary to qualify a product. The goal is to identify a more durable refractory material that has physical, chemical, and thermal properties suitable to withstand the harsh environment of the launch pads at KSC.

  18. Receptor for advanced glycation end-products regulates lung fluid balance via protein kinase C-gp91(phox) signaling to epithelial sodium channels.

    PubMed

    Downs, Charles A; Kreiner, Lisa H; Johnson, Nicholle M; Brown, Lou Ann; Helms, My N

    2015-01-01

    The receptor for advanced glycation end-products (RAGE), a multiligand member of the Ig family, may play a crucial role in the regulation of lung fluid balance. We quantified soluble RAGE (sRAGE), a decoy isoform, and advanced glycation end-products (AGEs) from the bronchoalveolar lavage fluid of smokers and nonsmokers, and tested the hypothesis that AGEs regulate lung fluid balance through protein kinase C (PKC)-gp91(phox) signaling to the epithelial sodium channel (ENaC). Human bronchoalveolar lavage samples from smokers showed increased AGEs (9.02 ± 3.03 μg versus 2.48 ± 0.53 μg), lower sRAGE (1,205 ± 292 pg/ml versus 1,910 ± 263 pg/ml), and lower volume(s) of epithelial lining fluid (97 ± 14 ml versus 133 ± 17 ml). sRAGE levels did not predict ELF volumes in nonsmokers; however, in smokers, higher volumes of ELF were predicted with higher levels of sRAGE. Single-channel patch clamp analysis of rat alveolar epithelial type 1 cells showed that AGEs increased ENaC activity measured as the product of the number of channels (N) and the open probability (Po) (NPo) from 0.19 ± 0.08 to 0.83 ± 0.22 (P = 0.017) and the subsequent addition of 4-hydroxy-2, 2, 6, 6-tetramethylpiperidine-N-oxyl decreased ENaC NPo to 0.15 ± 0.07 (P = 0.01). In type 2 cells, human AGEs increased ENaC NPo from 0.12 ± 0.05 to 0.53 ± 0.16 (P = 0.025) and the addition of 4-hydroxy-2, 2, 6, 6-tetramethylpiperidine-N-oxyl decreased ENaC NPo to 0.10 ± 0.03 (P = 0.013). Using molecular and biochemical techniques, we observed that inhibition of RAGE and PKC activity attenuated AGE-induced activation of ENaC. AGEs induced phosphorylation of p47(phox) and increased gp91(phox)-dependent reactive oxygen species production, a response that was abrogated with RAGE or PKC inhibition. Finally, tracheal instillation of AGEs promoted clearance of lung fluid, whereas concomitant inhibition of RAGE, PKC, and gp91(phox) abrogated the response.

  19. Prospective Study of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors Concurrent With Individualized Radiotherapy for Patients With Locally Advanced or Metastatic Non-Small-Cell Lung Cancer

    SciTech Connect

    Wang Jing; Xia Tingyi; Wang Yingjie; Li Hongqi; Li Ping; Wang Jidong; Chang Dongshu; Liu Liyyuan; Di Yupeng; Wang Xuan; Wu Weizhang

    2011-11-01

    Purpose: To establish the safety profile and efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) concurrent with individualized radiotherapy (RT) in patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC). Patients and Methods: Between June 2007 and January 2010, 26 patients with Stage III/IV NSCLC were enrolled in this prospective study. These patients were treated with EGFR-TKIs (gefitinib 250 mg or erlotinib 150 mg, oral daily) concurrent with individualized RT with curative intent. The thoracic RT plans were individually designed on the basis of tumor size and normal tissue volume constraints. All patients were assessed for toxicity, and 25 patients were available for efficacy. The primary endpoints were acute toxicity, overall survival, and median survival time. The secondary endpoints included local control rate, time to tumor progression, and progression-free survival (PFS). Results: Median gross tumor volume, mean lung dose, and lung V20 were 56 cm{sup 3}, 8.6 Gy, and 14%, respectively. Median thoracic radiation dose was 70 Gy at a margin of gross tumor volume (range, 42-82 Gy), and median biological equivalent dose was 105 Gy (range, 60-119 Gy). Acute skin, hematologic, esophageal, and pulmonary toxicities were acceptable and manageable. Severe adverse events included neutropenia (Grade 4, 4%) and thrombocytopenia (Grade 4, 8%), esophagitis (Grade 3, 4%), and pneumonitis (Grade 3, 4%). With a median follow-up of 10.2 months, a local control rate of 96% was achieved for thoracic tumor. Median time to progression, median PFS, and median survival time were 6.3, 10.2, and 21.8 months, respectively. The 1- and 2-year PFS rates were both 42%, and 1-, 2-, and 3-year overall survival rates were 57%, 45%, and 30%, respectively. Conclusion: Concurrent EGFR-TKIs with individualized RT shows a favorable safety profile and promising outcome, therefore serving as a therapeutic option for patients with locally

  20. A large, single-center, real-world study of clinicopathological characteristics and treatment in advanced ALK-positive non-small-cell lung cancer.

    PubMed

    Chen, Gang; Chen, Xi; Zhang, Yaxiong; Yan, Fang; Fang, Wenfeng; Yang, Yunpeng; Hong, Shaodong; Miao, Siyu; Wu, Manli; Huang, Xiaodan; Luo, Youli; Zhou, Cong; Gong, Run; Huang, Yan; Zhou, Ningning; Zhao, Hongyun; Zhang, Li

    2017-04-04

    Crizotinib has achieved astonishing success in advanced non-small-cell lung cancer (NSCLC) patients harboring anaplastic lymphoma kinase (ALK) rearrangement. However, no real-world studies described the clinicopathological characteristics and treatment of such patients in China. Patients were consecutively collected from Sun Yat-sen University Cancer Center. Chi-square test was applied to explore the relationship between ALK fusion status and metastasis sites. Kaplan-Meier methods and multivariable analyses were used to estimate progression-free survival (PFS). A total of 291 advanced NSCLC patients (ALK (+), N = 97; both ALK & epidermal growth factor receptor (EGFR) (-), N = 194) were enrolled. The occurrence of brain metastasis in ALK-positive patients was significantly higher than double-negative ones both at baseline (26.5% vs. 16.5%, P = 0.038) and during treatment (25.8% vs. 11.9%, P = 0.003), but opposite for pleural effusion (6.2% vs. 26.9%, P < 0.001 at baseline; 3.1% vs. 10.3%, P = 0.031 during treatment). ALK-positive patients of 53.6% used crizotinib, whereas others only received chemotherapy (37.1%) or supportive care (9.3%). Usage of crizotinib prolonged PFS compared with chemotherapy in ALK-positive patients (median PFS 17.6 m vs. 4.8 m, P < 0.001). ALK-positive NSCLC had more brain metastasis and less pleural effusion than double-negative ones. Crizotinib showed better PFS than chemotherapy in advanced ALK-positive NSCLC at any line. However, half advanced ALK-positive patients never received crizotinib, which was grim and need improving.

  1. High Temperature Silicides and Refractory Alloys Symposium Held in Boston, Massachusetts on November 29 -December 2, 1993. Volume 322

    DTIC Science & Technology

    1993-12-02

    297 Gaurav Agarwal, Wen-yi Lin, and Robert F. Speyer PART V: RECENT ADVANCES IN REFRACTORY ALLOYS AND PROCESSING THE PROPERTIES AND...Jackson PART VIII: APPLICATIONS OF REFRACTORY ALLOYS *PROCESSING, PROPERTIES AND APPLICATIONS OF HIGH- TEMPERATURE NIOBIUM ALLOYS ...Potential higher fracture toughness at operating temperatures o Alloying may be extensively employed to improve mechanical properties "o Thcinnodrnas•kally

  2. Lung Transplant

    MedlinePlus

    Lung transplant Overview By Mayo Clinic Staff A lung transplant is a surgical procedure to replace a diseased or ... lung, usually from a deceased donor. A lung transplant is reserved for people who have tried other ...

  3. Lung Emergencies

    MedlinePlus

    ... Emergencies Cardiac Emergencies Eye Emergencies Lung Emergencies Surgeries Lung Emergencies People with Marfan syndrome can be at ... should be considered an emergency. Symptoms of sudden lung collapse (pneumothorax) Symptoms of a sudden lung collapse ...

  4. Evaluation of olivine refractories for TES

    NASA Astrophysics Data System (ADS)

    Gay, B. M.; Cochrane, R. L.; Palmour, H., III; Paisley, M. J.

    1982-02-01

    The principal objectives of this program are to (1) experimentally determine the degree of improvement in thermal and mechanical performance that can be obtained with an olivine thermal storage brick made of domestic materials using advanced processing techniques compared with state-of-the-art as represented by commercial European bricks, (2) conduct an assessment of existing German ceramic process technology and determine its adaptability to domestic raw materials and manufacturing practices, and (3) investigate, on a limited basis, method for further improvement of domestic-olivine brick. To date, accomplishments include (1) installation of improved, computer-based instrumentation, (2) the use of this system to determine performance characteristics of a set of heat storage refractories under cyclic use conditions, (3) acquisition of the services of a knowledgeable European consultant, (4) continued lab-scale process/property optimization studies, and (5) comparative testing of olivine-based and magnesite-based heat storage refractories in the calorimetric test facility at Purdue University.

  5. Unravelling signal escape through maintained EGFR activation in advanced non-small cell lung cancer (NSCLC): new treatment options.

    PubMed

    Remon, Jordi; Besse, Benjamin

    2016-01-01

    The discovery of activating epidermal growth factor receptor (EGFR) mutations has opened up a new era in the development of more effective treatments for patients with non-small cell lung cancer (NSCLC). However, patients with EGFR-activating mutated NSCLC treated with EGFR tyrosine kinase inhibitors (TKIs) ultimately develop acquired resistance (AR). Among known cases of patients with AR, 70% of the mechanisms involved in the development of AR to EGFR TKI have been identified and may be categorised as either secondary EGFR mutations such as the T790M mutation, activation of bypass track signalling pathways such as MET amplification, or histologic transformation. EGFR-mutant NSCLC tumours maintain oncogenic addiction to the EGFR pathway beyond progression with EGFR TKI. Clinical strategies that can be implemented in daily clinical practice to potentially overcome this resistance and prolong the outcome in this subgroup of patients are presented.

  6. Personalized treatment in advanced ALK-positive non-small cell lung cancer: from bench to clinical practice

    PubMed Central

    Passaro, Antonio; Lazzari, Chiara; Karachaliou, Niki; Spitaleri, Gianluca; Pochesci, Alessia; Catania, Chiara; Rosell, Rafael; de Marinis, Filippo

    2016-01-01

    The discovery of anaplastic lymphoma kinase (ALK) gene rearrangements and the development of tyrosine kinase inhibitors (TKI) that target them have achieved unprecedented success in the management of patients with ALK-positive non-small cell lung cancer (NSCLC). Despite the high efficacy of crizotinib, the first oral ALK TKI approved for the treatment of ALK-positive NSCLC, almost all patients inevitably develop acquired resistance, showing disease progression in the brain or in other parenchymal sites. Second- or third-generation ALK TKIs have shown to be active in crizotinib-pretreated or crizotinib-naïve ALK-positive patients, even in those with brain metastases. In this review, the current knowledge regarding ALK-positive NSCLC, focusing on the biology of the disease and the available therapeutic options are discussed. PMID:27799783

  7. Unravelling signal escape through maintained EGFR activation in advanced non-small cell lung cancer (NSCLC): new treatment options

    PubMed Central

    Remon, Jordi; Besse, Benjamin

    2016-01-01

    The discovery of activating epidermal growth factor receptor (EGFR) mutations has opened up a new era in the development of more effective treatments for patients with non-small cell lung cancer (NSCLC). However, patients with EGFR-activating mutated NSCLC treated with EGFR tyrosine kinase inhibitors (TKIs) ultimately develop acquired resistance (AR). Among known cases of patients with AR, 70% of the mechanisms involved in the development of AR to EGFR TKI have been identified and may be categorised as either secondary EGFR mutations such as the T790M mutation, activation of bypass track signalling pathways such as MET amplification, or histologic transformation. EGFR-mutant NSCLC tumours maintain oncogenic addiction to the EGFR pathway beyond progression with EGFR TKI. Clinical strategies that can be implemented in daily clinical practice to potentially overcome this resistance and prolong the outcome in this subgroup of patients are presented. PMID:27843631

  8. Cytomorphologic features of advanced lung adenocarcinomas tested for EGFR and KRAS mutations: a retrospective review of 50 cases.

    PubMed

    Marotti, Jonathan D; Schwab, Mary C; McNulty, Nancy J; Rigas, James R; DeLong, Peter A; Memoli, Vincent A; Tsongalis, Gregory J; Padmanabhan, Vijayalakshmi

    2013-01-01

    Associations between bronchioloalveolar carcinoma (BAC), mucinous differentiation, and epidermal growth factor receptor (EGFR) and KRAS mutations have been previously reported in studies of surgical specimens. We present the cytomorphology of lung adenocarcinomas, including metastases that were diagnosed by cytologic methods and the relationship to both EGFR and KRAS mutational status. We retrospectively reviewed the clinical and cytomorphologic features of 50 lung adenocarcinomas that were tested for both EGFR and KRAS mutations. Cytomorphologic features evaluated included cell size, architectural pattern, nucleoli, intranuclear cytoplasmic inclusions (INCI), mucin, necrosis, squamoid features, lymphocytic response, and histologic features of BAC differentiation. DNA was extracted from a paraffin-embedded cell block or frozen needle core fragments. Exon 19 deletions and the L858R mutation in exon 21 of EGFR were detected using PCR followed by capillary electrophoresis for fragment sizing. KRAS mutational analysis was performed by real-time PCR using a set of seven different Taqman(r) allelic discrimination assays to detect six mutations in codon 12 and one mutation in codon 13. Six cases (12%) showed EGFR mutations, 12 (24%) showed KRAS mutations, and 38 (62%) contained neither EGFR nor KRAS mutations. The majority of patients had stage IV disease (78%); 20 samples (40%) were from metastatic sites. The presence of prominent INCI (P = 0.036), papillary fragments (P = 0.041), and histologic features of BAC on paraffin block (P = 0.039) correlated with the presence of EGFR mutations. The presence of necrosis (P = 0.030), squamoid features (P = 0.048), and poorly differentiated tumors (P = 0.025) were more likely to be identified in the KRAS positive group.

  9. Lung cancer

    SciTech Connect

    Aisner, J.

    1985-01-01

    This book contains 13 chapters. Some of the chapter titles are: The Pathology of Lung Cancer; Radiotherapy for Non-Small-Cell Cancer of the Lung; Chemotherapy for Non-Small-Cell Lung Cancer; Immunotherapy in the Management of Lung Cancer; Preoperative Staging and Surgery for Non-Small-Cell Lung Cancer; and Prognostic Factors in Lung Cancer.

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

    PubMed

    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.

  11. A phase I study of combination S-1 plus cisplatin chemotherapy with concurrent thoracic radiation for locally advanced non-small cell lung cancer.

    PubMed

    Chikamori, Kenichi; Kishino, Daizo; Takigawa, Nagio; Hotta, Katsuyuki; Nogami, Naoyuki; Kamei, Haruhito; Kuyama, Shoichi; Gemba, Kenichi; Takemoto, Mitsuhiro; Kanazawa, Susumu; Ueoka, Hiroshi; Segawa, Yoshihiko; Takata, Saburo; Tabata, Masahiro; Kiura, Katsuyuki; Tanimoto, Mitsune

    2009-07-01

    A combination of S-1, a newly developed oral 5-fluorouracil derivative, and cisplatin is reported to show anti-tumour activity against advanced non-small cell lung cancer (NSCLC). Because S-1 shows synergistic effects with radiation, we conducted a phase I study to evaluate the maximum tolerated doses (MTDs), recommended doses (RDs), and dose-limiting toxicities (DLTs) of cisplatin and S-1 when combined with concurrent thoracic radiation (total dose of 60 Gy with 2 Gy per daily fraction) in patients with locally advanced NSCLC. Chemotherapy consisted of two 4-week cycles of cisplatin administered on days 1 and 8, and S-1 administered on days 1-14. S-1/cisplatin dosages (mg/m(2)/day) were escalated as follows: 60/30, 60/40, 70/40, 80/40 and 80/50. Twenty-two previously untreated patients were enrolled. The MTDs and RDs for S-1/cisplatin were 80/50 and 80/40, respectively. DLTs included febrile neutropaenia, thrombocytopaenia, bacterial pneumonia and delayed second cycle of chemotherapy. No patient experienced radiation pneumonitis>grade 2 and only one patient experienced grade 3 radiation oesophagitis. The overall response rate was 86.4% with a median survival time of 24.4 months. These results indicate that combination cisplatin-S-1 chemotherapy with concurrent thoracic radiation would be a feasible treatment option and a phase II study is currently under way.

  12. U.S. Food and Drug Administration approval: crizotinib for treatment of advanced or metastatic non-small cell lung cancer that is anaplastic lymphoma kinase positive.

    PubMed

    Malik, Shakun M; Maher, Virginia Ellen; Bijwaard, Karen E; Becker, Robert L; Zhang, Lijun; Tang, Shenghui W; Song, Pengfei; Liu, Qi; Marathe, Anshu; Gehrke, Brenda; Helms, Whitney; Hanner, Diane; Justice, Robert; Pazdur, Richard

    2014-04-15

    On August 26, 2011, the U.S. Food and Drug Administration (FDA) approved crizotinib (XALKORI Capsules, Pfizer Inc.) for treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) that is anaplastic lymphoma kinase (ALK) positive as detected by an FDA-approved test. The Vysis ALK Break-Apart FISH Probe Kit (Abbott Molecular, Inc.) was approved concurrently. In two multicenter, single-arm trials, patients with locally advanced or metastatic ALK-positive NSCLC previously treated with one or more systemic therapies received crizotinib orally at a dose of 250 mg twice daily. In 119 patients with ALK-positive NSCLC by local trial assay, the objective response rate (ORR) was 61% [95% confidence intervals (CI), 52%-70%] with a median response duration of 48 weeks. In 136 patients with ALK-positive NSCLC by the to-be-marketed test, the ORR was 50% (95% CI, 42%-59%) with a median response duration of 42 weeks. The most common adverse reactions (≥25%) were vision disorder, nausea, diarrhea, vomiting, edema, and constipation. Accelerated approval was granted on the basis of the high ORRs and durable responses. On November 20, 2013, crizotinib received full approval based on an improvement in progression-free survival in patients with metastatic ALK-positive NSCLC previously treated with one platinum-based chemotherapy regimen.

  13. Accelerating Scientific Advancement for Pediatric Rare Lung Disease Research. Report from a National Institutes of Health-NHLBI Workshop, September 3 and 4, 2015.

    PubMed

    Young, Lisa R; Trapnell, Bruce C; Mandl, Kenneth D; Swarr, Daniel T; Wambach, Jennifer A; Blaisdell, Carol J

    2016-12-01

    Pediatric rare lung disease (PRLD) is a term that refers to a heterogeneous group of rare disorders in children. In recent years, this field has experienced significant progress marked by scientific discoveries, multicenter and interdisciplinary collaborations, and efforts of patient advocates. Although genetic mechanisms underlie many PRLDs, pathogenesis remains uncertain for many of these disorders. Furthermore, epidemiology and natural history are insufficiently defined, and therapies are limited. To develop strategies to accelerate scientific advancement for PRLD research, the NHLBI of the National Institutes of Health convened a strategic planning workshop on September 3 and 4, 2015. The workshop brought together a group of scientific experts, intramural and extramural investigators, and advocacy groups with the following objectives: (1) to discuss the current state of PRLD research; (2) to identify scientific gaps and barriers to increasing research and improving outcomes for PRLDs; (3) to identify technologies, tools, and reagents that could be leveraged to accelerate advancement of research in this field; and (4) to develop priorities for research aimed at improving patient outcomes and quality of life. This report summarizes the workshop discussion and provides specific recommendations to guide future research in PRLD.

  14. Safety, immunogenicity and preliminary efficacy of multiple-site vaccination with an Epidermal Growth Factor (EGF) based cancer vaccine in advanced non small cell lung cancer (NSCLC) patients

    PubMed Central

    2011-01-01

    The prognosis of patients with advanced non small cell lung (NSCLC) cancer remains dismal. Epidermal Growth Factor Receptor is over-expressed in many epithelial derived tumors and its role in the development and progression of NSCLC is widely documented. CimaVax-EGF is a therapeutic cancer vaccine composed by human recombinant Epidermal Growth Factor (EGF) conjugated to a carrier protein, P64K from Neisseria Meningitides. The vaccine is intended to induce antibodies against self EGF that would block EGF-EGFR interaction. CimaVax-EGF has been evaluated so far in more than 1000 advanced NSCLC patients, as second line therapy. Two separate studies were compared to assess the impact of high dose vaccination at multiple anatomic sites in terms of immunogenicity, safety and preliminary efficacy in stage IIIb/IV NSCLC patients. In both clinical trials, patients started vaccination 1 month after finishing first line chemotherapy. Vaccination at 4 sites with 2.4 mg of EGF (high dose) was very safe. The most frequent adverse events were grade 1 or 2 injection site reactions, fever, headache and vomiting. Patients had a trend toward higher antibody response. The percent of very good responders significantly augmented and there was a faster decrease of circulating EGF. All vaccinated patients and those classified as good responders immunized with high dose at 4 sites, had a large tendency to improved survival. PMID:22024351

  15. Impact of gefitinib in early stage treatment on circulating cytokines and lymphocytes for patients with advanced non-small cell lung cancer

    PubMed Central

    Sheng, Jin; Fang, Wenfeng; Liu, Xia; Xing, Shan; Zhan, Jianhua; Ma, Yuxiang; Huang, Yan; Zhou, Ningning; Zhao, Hongyun; Zhang, Li

    2017-01-01

    Objectives The impact of epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitors (TKIs) on the human immune system remains undefined. This study illustrates the immunomodulatory effect of gefitinib in patients with advanced non-small cell lung cancer (NSCLC) and its relevant prognostic significance. Patients and methods Peripheral blood samples were collected from 54 patients at baseline and after 4 weeks of gefitinib treatment. Circulating lymphocyte populations and cytokine levels were measured. Pilot investigation of the impact of gefitinib on programmed cell death ligand-1 (PD-L1) expression was conducted by immunohistochemistry (IHC). Results and conclusion A significant increase of peripheral natural killer cells and interferon-gamma (INF-γ) after 4 weeks of gefitinib treatment (P=0.005 and 0.02, respectively). In addition, circulating interleukin (IL)-6 was significantly decreased, especially in patients sensitive to gefitinib (P<0.001). Higher levels of IL-6 at baseline independently correlated with poorer progression-free survival. Experiments with NSCLC specimens illustrated that PD-L1 expression were downregulated after 4 weeks of gefitinib treatment. In summary, it was found that gefitinib treatment can alter circulating cytokines and lymphocytes. Dynamic changes of circulating lymphocytes, cytokines, and even PD-L1 IHC expression around gefitinib treatment support the specific immunomodulatory effect of this agent for advanced NSCLC. PMID:28260924

  16. Serum proteomic test in advanced non-squamous non-small cell lung cancer treated in first line with standard chemotherapy

    PubMed Central

    Grossi, F; Rijavec, E; Genova, C; Barletta, G; Biello, F; Maggioni, C; Burrafato, G; Sini, C; Dal Bello, M G; Meyer, K; Roder, J; Roder, H; Grigorieva, J

    2017-01-01

    Background: VeriStrat is a blood-based proteomic test with predictive and prognostic significance in second-line treatments for non-small cell lung cancer (NSCLC). This trial was designed to investigate the role of VeriStrat in first-line treatment of advanced NSCLC with standard chemotherapy. Here we present the results for 76 non-squamous patients treated with a combination of carboplatin or cisplatin with pemetrexed. Methods: The test-assigned classifications of VeriStrat Good or VeriStrat Poor to samples collected at baseline. The primary end point was progression-free survival (PFS); secondary end points included overall survival (OS) and objective response. Exploratory analyses of end points separately in carboplatin/pemetrexed and cisplatin/pemetrexed subgroups were also conducted. Results: Patients classified as VeriStrat Good had longer PFS and OS than VeriStrat Poor: 6.5 vs 1.6 months and 10.8 vs 3.4 months, respectively; the corresponding hazard ratios (HRs) were 0.36 (P<0.0001) and 0.26 (P<0.0001); they were also more likely to achieve objective response. Prognostic significance of VeriStrat was confirmed in multivariate analysis. Significant differences in OS and PFS between Veristrat classifications were also found when treatment subgroups were analysed separately. Conclusions: The trial demonstrated clinical utility of VeriStrat as a prognostic test for standard first-line chemotherapy of non-squamous advanced NSCLC. PMID:27898657

  17. Single pemetrexed is noninferior to platinum-based pemetrexed doublet as first-line treatment on elderly Chinese patients with advanced nonsquamous nonsmall cell lung cancer

    PubMed Central

    Pu, Xiaolin; Li, Wei; Lu, Binbin; Wang, Zhaoxia; Yang, Min; Fan, Weifei; Meng, Lijuan; Lv, Zhigang; Xie, Yuchun; Wang, Jun

    2017-01-01

    Abstract Background: To evaluate the clinical efficacy and toxicity of single pemetrexed treatment compared with platinum-based pemetrexed doublet pemetrexed-based as first-line treatment for advanced nonsquamous nonsmall cell lung cancer (NS-NSCLC) in elderly Chinese patients. Methods: The study retrospectively reviewed 175 elderly Chinese patients with NS-NSCLC from June 2010 to September 2013: 90 patients received single pemetrexed treatment, 45 received pemetrexed plus oxaliplatin, and 40 received pemetrexed plus carboplatin. Clinical efficacy was assessed using disease control rate (DCR), overall survival (OS), and progression-free survival (PFS). Results: DCR, OS, and PFS did not significantly differ between single pemetrexed treatment (OS: 14.9 months; DCR: 62.2%; PFS: 3.3 months), pemetrexed plus oxaliplatin (OS: 16.5 months; DCR: 71.1%; PFS: 4.5 months), and pemetrexed plus carboplatin (OS: 15.5 months; DCR: 70.0%; PFS: 4.6 months) groups. Pemetrexed treatment caused significantly lower incidences of adverse events, such as hepatotoxicity and peripheral nerve injury. Performance status (PS), TNM stage, and Thymidylate synthase (TS) expression were predictive factors of DCR. Pemetrexed chemotherapy cycles, PS, and TNM stage were independent prognostic factors. Conclusions: Single pemetrexed was noninferior to platinum-based pemetrexed doublet for clinical efficacy and safety in elderly Chinese patients with advanced NS-NSCLC. Chemotherapy cycles, performance status, and TNM stage were independent prognostic factors. PMID:28296721

  18. Failure Mechanisms in High Chrome Oxide Gasifier Refractories

    NASA Astrophysics Data System (ADS)

    Bennett, James P.; Kwong, Kyei-Sing

    2011-04-01

    Gasification is a high-temperature, high-pressure chemical process used to convert a carbon feedstock into CO and H2 (syngas) for use in power generation and the production of chemicals. It is also a leading candidate as a source of hydrogen in a hydrogen economy and is one of several technologies expected to see increased use in advanced fossil fuel power systems in the future. Gasification is being evaluated because of its high efficiency, its ability to capture CO2 for sequestration or reuse in other applications, and its potential for carbon feedstock fuel flexibility. At the heart of the gasification process is a gasifier, a high pressure chemical reaction vessel used to contain the interactions between carbon and water in a shortage of oxygen, producing syngas. The gasifier is lined with high chrome oxide materials to protect the containment vessel. Gasifiers are complex systems, and failure of the refractories used to line them was identified by industry as a limitation to their reliability and availability and to their increased use. NETL researchers have examined spent high-Cr2O3 (over 90 pct Cr2O3) refractories from numerous gasifiers to determine in-service failure mechanisms. This analysis revealed that premature failure of the high chrome oxide refractories was related to ash in the carbon feedstock, which liquefies during gasification and interacts with the refractories, leading to wear by chemical dissolution or spalling (structural and chemical). A discussion of this postmortem wear of spent refractory materials and of thermodynamic modeling used to explain microstructural changes leading to wear are explained in this article. This information will serve the basis to develop improved performance refractory materials.

  19. Lung cancer in women

    PubMed Central

    Barrera-Rodriguez, Raúl; Morales-Fuentes, Jorge

    2012-01-01

    Recent biological advances in tumor research provide clear evidence that lung cancer in females is different from that in males. These differences appear to have a direct impact on the clinical presentation, histology, and outcomes of lung cancer. Women are more likely to present with lung adenocarcinoma, tend to receive a diagnosis at an earlier age, and are more likely to be diagnosed with localized disease. Women may also be more predisposed to molecular aberrations resulting from the carcinogenic effects of tobacco, but do not appear to be more susceptible than men to developing lung cancer. The gender differences found in female lung cancer make it mandatory that gender stratification is used in clinical trials in order to improve the survival rates of patients with lung cancer. PMID:28210127

  20. A Randomized, Phase II, Biomarker-Selected Study Comparing Erlotinib to Erlotinib Intercalated With Chemotherapy in First-Line Therapy for Advanced Non–Small-Cell Lung Cancer

    PubMed Central

    Hirsch, Fred R.; Kabbinavar, Fairooz; Eisen, Tim; Martins, Renato; Schnell, Fredrick M.; Dziadziuszko, Rafal; Richardson, Katherine; Richardson, Frank; Wacker, Bret; Sternberg, David W.; Rusk, Jason; Franklin, Wilbur A.; Varella-Garcia, Marileila; Bunn, Paul A.; Camidge, D. Ross

    2011-01-01

    Purpose Erlotinib prolongs survival in patients with advanced non–small-cell lung cancer (NSCLC). We report the results of a randomized, phase II study of erlotinib alone or intercalated with chemotherapy (CT + erlotinib) in chemotherapy-naïve patients with advanced NSCLC who were positive for epidermal growth factor receptor (EGFR) protein expression and/or with high EGFR gene copy number. Patients and Methods A total of 143 patients were randomly assigned to either erlotinib 150 mg daily orally until disease progression (PD) occurred or to chemotherapy with paclitaxel 200 mg/m2 intravenously (IV) and carboplatin dosed by creatinine clearance (AUC 6) IV on day 1 intercalated with erlotinib 150 mg orally on days 2 through 15 every 3 weeks for four cycles followed by erlotinib 150 mg orally until PD occurred (CT + erlotinib). The primary end point was 6-month progression-free survival (PFS); secondary end points included response rate, PFS, and survival. EGFR, KRAS mutation, EGFR fluorescent in situ hybridization and immunohistochemistry, and E-cadherin and vimentin protein levels were also assessed. Results Six-month PFS rates were 26% and 31% for the two arms (CT + erlotinib and erlotinib alone, respectively). Both were less than the historical control of 45% (P = .001 and P = .011, respectively). Median PFS times were 4.57 and 2.69 months, respectively. Patients with tumors harboring EGFR activating mutations fared better on erlotinib alone (median PFS, 18.2 months v 4.9 months for CT + erlotinib). Conclusion The feasibility of a multicenter biomarker-driven study was demonstrated, but neither treatment arms exceeded historical controls. This study does not support combined chemotherapy and erlotinib in first-line treatment of EGFR-selected advanced NSCLC, and the patients with tumors harboring EGFR mutations had a better outcome on erlotinib alone. PMID:21825259

  1. Phase II trial of sequential gefitinib after minor response or partial response to chemotherapy in Chinese patients with advanced non-small-cell lung cancer

    PubMed Central

    Xu, Jian Ming; Han, Yu; Li, Yue Min; Zhao, Chuan Hua; Wang, Yan; Paradiso, Angelo

    2006-01-01

    Background Basic research of gefitinib (Iressa, ZD1839) has demonstrated the combination effects of gefitinib and chemotherapy were sequence-dependent. To evaluate the efficacy of sequential administration of gefitinib following a minor response or partial response to two to three cycles of chemotherapy, a phase II clinical trial was done in Chinese patients with advanced non-small-cell lung cancer (NSCLC). Methods Thirty-three consecutive patients with advanced NSCLC that had been pretreated with at least one chemotherapeutic regimen and were responding to chemotherapy following 2 to 3 cycles of treatment, entered the trial from May 2004 to February 2006. Patients received gefitinib at an oral dose of 250 mg once daily for 4 weeks. Results Thirty-three patients were evaluable for response and toxicity. The objective response rate was 24.2% (8 of 33)(95% CI, 11% to 42%). The symptom improvement rate was 54.5% (18 of 33) (95% CI, 41% to 69%). The median duration of response was 7 months (95%CI, 4.0 to 13.2 months). The median time to disease progression (TTP) was 6.5 months (95%CI, 0.7 to 16.6 months). The median overall survival time (OS) was 9.8 months (range, 2.1 to 18.0 months), and the actuarial 1-year survival was 36.4%. Toxicity was relatively mild and included only one patient (3.0%) with grade 4 diarrhea, 1 (3.0%) with grade 3 rash, 1 (3.0%) with grade 3 nausea, and 1 with grade 3 vomiting (3.0%). Conclusion Preliminary results suggest that sequential administration of gefitinib following a response to chemotherapy may be beneficial for Chinese patients with advanced NSCLC. Further randomized clinical trials are needed. PMID:17173694

  2. 125I brachytherapy of locally advanced non-small-cell lung cancer after one cycle of first-line chemotherapy: a comparison with best supportive care

    PubMed Central

    Song, Jingjing; Fan, Xiaoxi; Zhao, Zhongwei; Chen, Minjiang; Chen, Weiqian; Wu, Fazong; Zhang, Dengke; Chen, Li; Tu, Jianfei; Ji, Jiansong

    2017-01-01

    Objectives The objective of this study was to assess the efficacy of computed tomography (CT)-guided 125I brachytherapy alone in improving the survival and quality of life of patients with unresectable locally advanced non-small-cell lung cancer (NSCLC) after one cycle of first-line chemotherapy. Patients and methods Sixteen patients with locally advanced NSCLC were treated with CT-guided 125I brachytherapy after one cycle of first-line chemotherapy (group A). Sixteen patients who received only best supportive care (group B) were matched up with the patients in group A. Primary end point included survival, and secondary end point included assessment of safety, effectiveness of CT-guided 125I brachytherapy, and improvement in the quality of life. Results The two groups were well balanced in terms of age, disease histology, tumor stage, tumor location, and performance status (P>0.05). The median follow-up time was 16 months (range, 3–30). The total tumor response rate was 75.0% in group A, which was significantly higher than that in group B (0.0%) (P<0.01). The median progression-free survival time was 4.80 months for patients in group A and 1.35 months for patients in group B (P<0.001). Kaplan–Meier survival analysis showed that the median survival time of group A was 9.4±0.3 months versus 8.4±0.1 months in group B (P=0.013). Tumor-related symptoms of patients were significantly relieved, and the quality of life was markedly improved in group A than in group B. Conclusion CT-guided 125I brachytherapy improved the survival of patients with locally advanced NSCLC and quality of life after one cycle of first-line chemotherapy compared with best supportive care. PMID:28280369

  3. Mutation and expression of multiple treatment response-related genes in a population with locally advanced non-small cell lung cancer

    PubMed Central

    LU, HONG-YANG; SU, DAN; PAN, XIAO-DAN; JIANG, HONG; MA, SHENG-LIN

    2012-01-01

    Individual therapy based on various pathohistological types and biological characteristics may be the practical trend of advanced non-small cell lung cancer (NSCLC) treatment. To provide a molecular criterion for drug selection, we investigated the incidence of somatic mutation and mRNA expression levels of common genes relevant to treatment response in a population with locally advanced NSCLC. Mutant-enriched and branched DNA-liquidchip technology (bDNA-LCT) were used to detect the somatic mutations in the epidermal growth factor receptor (EGFR), KRAS, BRAF and phosphatidylinositol-3-kinase catalytic α (PIK3CA) genes, and mRNA levels of EGFR, ERCC1, class III β-tubulin (TUBB3) and TYMS, separately, in paraffin tissue blocks from 30 patients with stage IIIA NSCLC. Our current findings revealed that 6, 4 and 2 out of 30 samples were found with mutations in exons 19, 21 and 20 of the EGFR gene, respectively. The mutation incidence of exons 19 and 21 had a positive correlation with EGFR mRNA expression. Mutations in exons 12 and 13 of the K-ras gene were found in 2 out of 30, and 1 out of 30 samples, separately. Three out of 30 samples were found with mutations in codon 542 of the PIK3CA gene. No mutations were found in the BRAF gene. The expression levels of ERCC1 and TUBB3 mRNAs were higher in patients with adenocarcinoma than those in patients with squamous cell carcinoma. The expression of TYMS mRNA in patients with adenocarcinoma was lower than that in patients with squamous cell carcinoma. In conclusion, mutations and mRNA expression of these commonly studied genes provides a basis for the selection of suitable molecular markers for individual treatment in a population with locally advanced NSCLC. PMID:22740923

  4. P73 G4C14‐to‐A4T14 polymorphism is associated with survival in advanced non‐small cell lung cancer patients

    PubMed Central

    Ge, Lei; Yang, Yang; Sun, Yifeng; Xu, Wen

    2017-01-01

    Background p73, a structural and functional homolog of p53, plays an important role in modulating cell cycle arrest. This study investigated the association between p73 G4C14‐to‐A4T14 polymorphism and survival outcomes in a Chinese population of advanced non‐small cell lung cancer (NSCLC) patients treated with platinum agents. Methods The p73 G4C14‐to‐A4T14 polymorphism was genotyped using DNA from blood samples of advanced NSCLC patients (642 in the discovery set and 330 in the replication set). The relationship of the p73 G4C14‐to‐A4T14 polymorphism with clinical outcomes was analyzed. Results Compared with the GC/GC genotype, the genotypes containing AT allele (GC/AT + AT/AT genotypes) were associated with significantly prolonged overall survival (P = 0.040) in the discovery set and after pooling results from the replication set. Stratification analysis revealed that the association was more pronounced in subjects who were older (P = 0.001), male (P = 0.007), smokers (P = 0.006), had a low Eastern Cooperative Oncology Group performance status (P = 0.001), in tumor node metastasis stage IV (P = 0.008), and with adenocarcinoma (P = 0.002). The objective response rates of patients with GC/AT + AT/AT genotypes were statistically higher than those with the GC/GC genotype (P = 0.047). Conclusion Our findings suggest that the p73 G4C14‐to‐A4T14 polymorphism may be related to survival outcome in advanced NSCLC patients. PMID:28134496

  5. Dendritic cell vaccine and cytokine-induced killer cell therapy for the treatment of advanced non-small cell lung cancer

    PubMed Central

    ZHANG, LIHONG; YANG, XUEJING; SUN, ZHEN; LI, JIALI; ZHU, HUI; LI, JING; PANG, YAN

    2016-01-01

    The present study aimed to evaluate the survival time, immune response and safety of a dendritic cell (DC) vaccine and cytokine-induced killer (CIK) cell therapy (DC-CIK) in advanced non-small cell lung cancer (NSCLC). The present retrospective study enrolled 507 patients with advanced NSCLC; 99 patients received DC-CIK [immunotherapy group (group I)] and 408 matched patients did not receive DC-CIK, and acted as the control [non-immunotherapy group (group NI)]. Delayed-type hypersensitivity (DTH), quality of life (QOL) and safety were analyzed in group I. The follow-up period for the two groups was 489.2±160.4 days. The overall survival (OS) time was calculated using the Kaplan-Meier method. DTH was observed in 59 out of 97 evaluated patients (60.8%) and 67 out of 98 evaluated patients (68.4%) possessed an improved QOL. Fever and a skin rash occurred in 36 out of 98 patients (36.7%) and 7 out of 98 patients (7.1%) in group I. DTH occurred more frequently in patients with squamous cell carcinoma compared with patients with adenocarcinoma (77.1 vs. 40.4%; P=0.0013). Radiotherapy was not associated with DC-CIK-induced DTH (72.7 vs. 79.6%; P=0.18), but chemotherapy significantly reduced the rate of DTH (18.2 vs. 79.6%; P=0.00). The OS time was significantly increased in group I compared with group NI (P=0.03). In conclusion, DC-CIK may induce an immune response against NSCLC, improve the QOL, and prolong the OS time of patients, without adverse effects. Therefore, the present study recommends DC-CIK for the treatment of patients with advanced NSCLC. PMID:27073525

  6. The relevance of serum carcinoembryonic antigen as an indicator of brain metastasis detection in advanced non-small cell lung cancer.

    PubMed

    Lee, Dong-Soo; Kim, Yeon-Sil; Jung, So-Lyoung; Lee, Kyo-Young; Kang, Jin-Hyoung; Park, Sarah; Kim, Young-Kyoon; Yoo, Ie-Ryung; Choi, Byung-Ock; Jang, Hong-Seok; Yoon, Sei-Chul

    2012-08-01

    Although many biomarkers have emerged in non-small cell lung cancer (NSCLC), the predictive value of site-specific spread is not fully defined. We designed this study to determine if there is an association between serum biomarkers and brain metastasis in advanced NSCLC. We evaluated 227 eligible advanced NSCLC patients between May 2005 and March 2010. Patients who had been newly diagnosed with stage IV NSCLC but had not received treatment previously, and had available information on at least one of the following pretreatment serum biomarkers were enrolled: carcinoembryonic antigen (CEA), cytokeratin 19 fragments (CYFRA 21-1), cancer antigen 125 (CA 125), cancer antigen 19-9, and squamous cancer cell antigen. Whole body imaging studies and magnetic resonance imaging of the brain were reviewed, and the total number of metastatic regions was scored. Brain metastasis was detected in 66 (29.1%) patients. Although serum CEA, CYFRA 21-1, and CA 125 levels were significantly different between low total metastatic score group (score 1-3) and high total metastatic score group (score 4-7), only CEA level was significantly different between patients with brain metastasis and those without brain metastasis (p < 0.0001). The area under the receiver operating curve of serum CEA for the prediction of brain metastasis was 0.724 (p = 0.0001). The present study demonstrated that the pretreatment serum CEA level was significantly correlated with brain metastasis in advanced NSCLC. These findings suggested the possible role of CEA in the pathogenesis of brain invasion. More vigilant surveillance would be warranted in the high-risk group of patients with high serum CEA level and multiple synchronous metastasis.

  7. Basic Fibroblast Growth Factor-2/beta3 Integrin Expression Profile: Signature of Local Progression After Chemoradiotherapy for Patients With Locally Advanced Non-Small-Cell Lung Cancer

    SciTech Connect

    Massabeau, Carole; Rouquette, Isabelle; Lauwers-Cances, Valerie; Mazieres, Julien; Bachaud, Jean-Marc; Armand, Jean-Pierre; Delisle, Marie-Bernadette; Favre, Gilles; Toulas, Christine; Cohen-Jonathan-Moyal, Elizabeth

    2009-11-01

    Purpose: No biologic signature of chemoradiotherapy sensitivity has been reported for patients with locally advanced non-small-cell lung cancer (NSCLC). We have previously demonstrated that basic fibroblast growth factor (FGF-2) and alphavbeta3 integrin pathways control tumor radioresistance. We investigated whether the expression of the proteins involved in these pathways might be associated with the response to treatment and, therefore, the clinical outcome. Methods and Materials: FGF-2, beta3 integrin, angiopoietin-2, and syndecan-1 expression was studied using immunohistochemistry performed on biopsies obtained, before any treatment, from 65 patients exclusively treated with chemoradiotherapy for locally advanced NSCLC. The response to treatment was evaluated according to the Response Evaluation Criteria in Solid Tumors criteria using computed tomography at least 6 weeks after the end of the chemoradiotherapy. Local progression-free survival, metastasis-free survival, and disease-free survival were studied using the log-rank test and Cox proportional hazard analysis. Results: Among this NSCLC biopsy population, 43.7% overexpressed beta3 integrin (beta3{sup +}), 43% FGF-2 (FGF-2{sup +}), 41.5% syndecan-1, and 59.4% angiopoietin-2. Our results showed a strong association between FGF-2 and beta3 integrin expression (p = .001). The adjusted hazard ratio of local recurrence for FGF-2{sup +}/beta3{sup +} tumors compared with FGF-2{sup -}/beta3{sup -} tumors was 6.1 (95% confidence interval, 2.6-14.6, p = .005). However, the risk of local recurrence was not increased when tumors overexpressed beta3 integrin or FGF-2 alone. Moreover, the co-expression of these two proteins was marginally associated with the response to chemoradiotherapy and metastasis-free survival. Conclusion: The results of this study have identified the combined profile FGF-2/beta3 integrin expression as a signature of local control in patients treated with chemoradiotherapy for locally advanced

  8. The Efficacy of Brucea javanica Oil Emulsion Injection as Adjunctive Therapy for Advanced Non-Small-Cell Lung Cancer: A Meta-Analysis

    PubMed Central

    Xu, Wei; Xu, Zhengyuan; Ye, Tong; Shi, Qionghua

    2016-01-01

    Purpose. To evaluate the efficacy of Brucea javanica oil emulsion injection (BJOEI) in patients with advanced non-small-cell lung cancer (NSCLC) during chemotherapy. Method. Electronic database of EMBASE and PubMed and the conference proceeding of ASCO, CNKI, CBMdisc, VIP, and Wanfang database were searched to select RCTs comparing BJOEI plus chemotherapy with chemotherapy alone in the treatment of advanced NSCLC, until June 1, 2016. Two reviewers independently performed the analysis according to the inclusion and exclusion criteria. Review Manager 5.3 and STATA 12.0 were employed for data analysis. Result. Twenty-one studies including 2234 cases were included. The pooled result indicated that there were significant differences in ORR (RR = 1.25; 95% CI: 1.14–1.36; P < 0.00001), improvement of QOL (RR = 1.87; 95% CI: 1.63–2.15; P < 0.00001), nausea and vomiting (RR = 0.67; 95% CI: 0.46–0.98; P = 0.04), leukopenia (RR = 0.63; 95% CI: 0.52–0.75; P < 0.00001), but there was no difference in thrombocytopenia (RR = 0.78; 95% CI: 0.49–1.23; P = 0.29). Begg's funnel plot and Egger's test indicated that no publication bias was found. The sensitivity analysis suggested the stability of the pooled result. Conclusion. The addition of BJOEI can enhance efficacy, improve QOL, and decrease incidence of nausea and vomiting and leukopenia for advanced NSCLC patients. However, higher quality RCTs are needed to further confirm this finding. PMID:28050192

  9. Pretreatment direct bilirubin and total cholesterol are significant predictors of overall survival in advanced non-small-cell lung cancer patients with EGFR mutations.

    PubMed

    Zhang, Yanwei; Xu, Jianlin; Lou, Yuqing; Hu, Song; Yu, Keke; Li, Rong; Zhang, Xueyan; Jin, Bo; Han, Baohui

    2017-04-01

    This study was designed to examine the prediction of pretreatment circulating bilirubin and cholesterol for overall survival in 459 advanced non-small-cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations. Circulating total bilirubin, direct bilirubin (DB), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) levels were measured at baseline. The mean age (standard deviation) of all study patients was 58.7 (10.5) years, and 42.9% of them was males. Ever smokers accounted for 27.0% and lung adenocarcinoma for 90.4%. The median follow-up time and survival time were 29.5 and 34.9 months, respectively. Patients with higher DB had a 1.68-fold increased risk of death compared with patients with lower DB (hazard ratio [HR] = 1.68, 95% confidence interval [CI]: 1.22-2.30, p = 0.001), while patients with higher TC were at a 63% reduced risk of death compared with patients with lower TC (HR = 0.37, 95% CI: 0.20-0.67, p = 0.001). As for HDL-C, patients with higher levels had the risk of death reduced by 46% (HR = 0.54, 95% CI: 0.29-1.00, p = 0.049) compared with patients with lower levels. After the Bonferroni correction, only DB and TC were significantly associated with NSCLC survival. Our findings demonstrate for the first time that pretreatment DB was identified as a significant risk factor, yet TC as a protective factor, for overall survival in NSCLC patients with EGFR mutations.

  10. Refractory lining for electrochemical cell

    DOEpatents

    Blander, Milton; Cook, Glenn M.

    1987-01-01

    Apparatus for processing a metallic fluid containing iron oxide, container for a molten metal including an electrically conductive refractory disposed for contact with the molten metal which contains iron oxide, an electrolyte in the form of a basic slag on top of the molten metal, an electrode in the container in contcat with the slag electrically separated from the refractory, and means for establishing a voltage across the refractory and the electrode to reduce iron oxide to iron at the surface of the refractory in contact with the iron oxide containing fluid. A process is disclosed for refining an iron product containing not more than about 10% by weight oxygen and not more than about 10% by weight sulfur, comprising providing an electrolyte of a slag containing one or more of calcium oxide, magnesium oxide, silica or alumina, providing a cathode of the iron product in contact with the electrolyte, providing an anode in contact with the electrolyte electrically separated from the cathode, and operating an electrochemical cell formed by the anode, the cathode and the electrolyte to separate oxygen or sulfur present in the iron product therefrom.

  11. Management of chronic refractory cough.

    PubMed

    Gibson, Peter G; Vertigan, Anne E

    2015-12-14

    Chronic refractory cough (CRC) is defined as a cough that persists despite guideline based treatment. It is seen in 20-46% of patients presenting to specialist cough clinics and it has a substantial impact on quality of life and healthcare utilization. Several terms have been used to describe this condition, including the recently introduced term cough hypersensitivity syndrome. Key symptoms include a dry irritated cough localized around the laryngeal region. Symptoms are not restricted to cough and can include globus, dyspnea, and dysphonia. Chronic refractory cough has factors in common with laryngeal hypersensitivity syndromes and chronic pain syndromes, and these similarities help to shed light on the pathophysiology of the condition. Its pathophysiology is complex and includes cough reflex sensitivity, central sensitization, peripheral sensitization, and paradoxical vocal fold movement. Chronic refractory cough often occurs after a viral infection. The diagnosis is made once the main diseases that cause chronic cough have been excluded (or treated) and cough remains refractory to medical treatment. Several treatments have been developed over the past decade. These include speech pathology interventions using techniques adapted from the treatment of hyperfunctional voice disorders, as well as the use of centrally acting neuromodulators such as gabapentin and pregabalin. Potential new treatments in development also show promise.

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

    ClinicalTrials.gov

    2016-05-05

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

  13. Adaptive Radiotherapy for Locally Advanced Non-Small-Cell Lung Cancer Does Not Underdose the Microscopic Disease and has the Potential to Increase Tumor Control

    SciTech Connect

    Guckenberger, Matthias; Richter, Anne; Wilbert, Juergen; Flentje, Michael; Partridge, Mike

    2011-11-15

    Purpose: To evaluate doses to the microscopic disease (MD) in adaptive radiotherapy (ART) for locally advanced non-small-cell lung cancer (NSCLC) and to model tumor control probability (TCP). Methods and Materials: In a retrospective planning study, three-dimensional conformal treatment plans for 13 patients with locally advanced NSCLC were adapted to shape and volume changes of the gross tumor volume (GTV) once or twice during conventionally fractionated radiotherapy with total doses of 66 Gy; doses in the ART plans were escalated using an iso-mean lung dose (MLD) approach compared to non-adapted treatment. Dose distributions to the volumes of suspect MD were simulated for a scenario with synchronous shrinkage of the MD and GTV and for a scenario of a stationary MD despite GTV shrinkage; simulations were performed using deformable image registration. TCP calculations considering doses to the GTV and MD were performed using three different models. Results: Coverage of the MD at 50 Gy was not compromised by ART. Coverage at 60 Gy in the scenario of a stationary MD was significantly reduced from 92% {+-} 10% to 73% {+-} 19% using ART; however, the coverage was restored by iso-MLD dose escalation. Dose distributions in the MD were sufficient to achieve a TCP >80% on average in all simulation experiments, with the clonogenic cell density the major factor influencing TCP. The combined TCP for the GTV and MD was 19.9% averaged over all patients and TCP models in non-adaptive treatment with 66 Gy. Iso-MLD dose escalation achieved by ART increased the overall TCP by absolute 6% (adapting plan once) and by 8.7% (adapting plan twice) on average. Absolute TCP values were significantly different between the TCP models; however, all TCP models suggested very similar TCP increase by using ART. Conclusions: Adaptation of radiotherapy to the shrinking GTV did not compromise dose coverage of volumes of suspect microscopic disease and has the potential to increase TCP by >40

  14. Home administration of maintenance pemetrexed for patients with advanced non-squamous non-small cell lung cancer: rationale, practicalities and phase II feasibility study design

    PubMed Central

    2013-01-01

    Background Home-based care in oncology is mainly reserved for patients at the end of life. Regulations regarding home delivery of cytotoxics differ across Europe, with a notable lack of practice guidelines in most countries. This has led to a lack of data addressing the feasibility of home-based administration of cytotoxic chemotherapy. In advanced non-squamous non-small cell lung cancer, pemetrexed is approved as maintenance therapy after first-line chemotherapy. In this setting, patients have the potential to be treated long-term with maintenance therapy, which, in the absence of unacceptable toxicity, is continued until disease progression. The favourable safety profile of pemetrexed and the ease of its administration by 10-minute intravenous infusion every 3 weeks make this drug a suitable candidate for administration in a home setting. Methods Literature and regulations relevant to the home-based delivery of cytotoxic therapy were reviewed, and a phase II feasibility study of home administration of pemetrexed maintenance therapy was designed. At least 50 patients with advanced non-squamous non-small cell lung cancer, Eastern Cooperative Oncology Group performance status 0–1 and no progressive disease after four cycles of platinum-based first-line therapy are required to allow investigation of the feasibility of home-based administration of pemetrexed maintenance therapy (500 mg/m2 every 3 weeks until progressive disease or unacceptable toxicity). Feasibility is being assessed as adherence to the home-based administration process (primary endpoint), patient safety, impact on patients’ quality of life, patient and physician satisfaction with home care, and healthcare resource use and costs. Enrolment of patients from the UK and Sweden, where home-based care is relatively well developed, commenced in December 2011. Discussion This feasibility study addresses an important aspect of maintenance therapy, that is, patient comfort during protracted home

  15. Molecular heterogeneity assessment by next-generation sequencing and response to gefitinib of EGFR mutant advanced lung adenocarcinoma

    PubMed Central

    Amato, Eliana; Fassan, Matteo; Novello, Silvia; Peretti, Umberto; Vavalà, Tiziana; Kinspergher, Stefania; Righi, Luisella; Santo, Antonio; Brunelli, Matteo; Corbo, Vincenzo; Giglioli, Eliana; Sperduti, Isabella; Milella, Michele; Chilosi, Marco; Scarpa, Aldo; Tortora, Giampaolo

    2015-01-01

    Cancer molecular heterogeneity might explain the variable response of EGFR mutant lung adenocarcinomas to tyrosine kinase inhibitors (TKIs). We assessed the mutational status of 22 cancer genes by next-generation sequencing (NGS) in poor, intermediate or good responders to first-line gefitinib. Clinical outcome was correlated with Additional Coexisting Mutations (ACMs) and the EGFR Proportion of Mutated Alleles (PMA). Thirteen ACMs were found in 10/17 patients: TP53 (n=6), KRAS (n=2), CTNNB1 (n=2), PIK3CA, SMAD4 and MET (n=1 each). TP53 mutations were exclusive of poor/intermediate responders (66.7% versus 0, p=0.009). Presence of ACMs significantly affected both PFS (median 3.0 versus 12.3 months, p=0.03) and survival (3.6 months versus not reached, p=0.03). TP53 mutation was the strongest negative modifier (median PFS 4.0 versus 14.0 months). Higher EGFR PMA was present in good versus poor/intermediate responders. Median PFS and survival were longer in patients with EGFR PMA ≥0.36 (12.0 versus 4.0 months, p=0.31; not reached versus 18.0 months, p=0.59). Patients with an EGFR PMA ≥0.36 and no ACMs fared significantly better (p=0.03), with a trend towards increased survival (p=0.06). Our exploratory data suggest that a quantitative (PMA) and qualitative (ACMs) molecular heterogeneity assessment using NGS might be useful for a better selection of patients. PMID:25904052

  16. Molecular heterogeneity assessment by next-generation sequencing and response to gefitinib of EGFR mutant advanced lung adenocarcinoma.

    PubMed

    Bria, Emilio; Pilotto, Sara; Amato, Eliana; Fassan, Matteo; Novello, Silvia; Peretti, Umberto; Vavalà, Tiziana; Kinspergher, Stefania; Righi, Luisella; Santo, Antonio; Brunelli, Matteo; Corbo, Vincenzo; Giglioli, Eliana; Sperduti, Isabella; Milella, Michele; Chilosi, Marco; Scarpa, Aldo; Tortora, Giampaolo

    2015-05-20

    Cancer molecular heterogeneity might explain the variable response of EGFR mutant lung adenocarcinomas to tyrosine kinase inhibitors (TKIs). We assessed the mutational status of 22 cancer genes by next-generation sequencing (NGS) in poor, intermediate or good responders to first-line gefitinib. Clinical outcome was correlated with Additional Coexisting Mutations (ACMs) and the EGFR Proportion of Mutated Alleles (PMA). Thirteen ACMs were found in 10/17 patients: TP53 (n=6), KRAS (n=2), CTNNB1 (n=2), PIK3CA, SMAD4 and MET (n=1 each). TP53 mutations were exclusive of poor/intermediate responders (66.7% versus 0, p=0.009). Presence of ACMs significantly affected both PFS (median 3.0 versus 12.3 months, p=0.03) and survival (3.6 months versus not reached, p=0.03). TP53 mutation was the strongest negative modifier (median PFS 4.0 versus 14.0 months). Higher EGFR PMA was present in good versus poor/intermediate responders. Median PFS and survival were longer in patients with EGFR PMA ≥0.36 (12.0 versus 4.0 months, p=0.31; not reached versus 18.0 months, p=0.59). Patients with an EGFR PMA ≥0.36 and no ACMs fared significantly better (p=0.03), with a trend towards increased survival (p=0.06). Our exploratory data suggest that a quantitative (PMA) and qualitative (ACMs) molecular heterogeneity assessment using NGS might be useful for a better selection of patients.

  17. Reproducibility of the EGFR immunohistochemistry scores for tumor samples from patients with advanced non-small cell lung cancer

    PubMed Central

    Avilés-Salas, Alejandro; Muñiz-Hernández, Saé; Maldonado-Martínez, Héctor Aquiles; Chanona-Vilchis, José G.; Ramírez-Tirado, Laura-Alejandra; HernáNdez-Pedro, Norma; Dorantes-Heredia, Rita; RuíZ-Morales, José Manuel; Motola-Kuba, Daniel; Arrieta, Oscar

    2017-01-01

    Epidermal growth factor receptor (EGFR) is overexpressed in >60% of non-small cell lung cancer (NSCLC) cases. In combination with radiotherapy or chemotherapy, first-line treatments with antibodies against EGFR, including cetuximab and necitumumab, have demonstrated benefits by increasing overall survival (OS), particularly in patients who overexpress EGFR. The present study evaluated the interobserver agreement among three senior pathologists, who were blinded to the clinical outcomes and assessed tumor samples from 85 patients with NSCLC using the H-score method. EGFR immunohistochemistry was performed using a qualitative immunohistochemical kit. The reported (mean ± standard deviation) H-scores from each pathologist were 111±102, 127±103 and 128.53±104.03. The patients with average H-scores ≥1, ≥100, ≥200 and between 250–300 were 85.9, 54.1, 28.2 and 12.9, respectively. Patients who had an average H-score >100 had a shorter OS time compared with those with lower scores. Furthermore, patients with EGFR mutations who were treated with EGFR-tyrosine kinase inhibitors (TKIs) and had an average H-score >100 had a longer OS time compared with those with an average H-score <100. The interobserver concordance for the total H-scores were 0.982, 0.980 and 0.988, and for a positive H-score ≥200, the interobserver concordance was 0.773, 0.710 and 0.675, respectively. The determination of EGFR expression by the H-score method is highly reproducible among pathologists and is a prognostic factor associated with a poor OS in all patients. Additionally, the results of the present study suggest that patients with EGFR mutations that are treated with EGFR-TKIs and present with a high H-score have a longer OS time. PMID:28356978

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

    PubMed

    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 level<24.15 ng/ml had a median survival of 23.7 months, but those with TSP-2>24.15 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-2<11.21 pg/ml (7.5 months vs. 16 months, p=0.034). We conclude that NSCLC patients have higher serum concentrations of TSP-2 and FGF-2 than healthy people. High levels of TSP-2 and FGF-2 may predict worse survival.

  19. Chromia refractory brick with carbon treatment

    DOEpatents

    Bennett, James P.; Kwong, Kyei-Sing

    2017-03-21

    The disclosure provides a refractory brick system comprising a chromia refractory brick for operation in the slagging environment of an air-cooled gasifier. The chromia refractory brick comprises a ceramically-bonded porous chromia refractory having a porosity greater than 9% and having carbon deposits residing within the pores. The brick may be further comprised of Al.sub.2O.sub.3. The air-cooled gasifier generates a liquefied slag in contact with the refractory brick and generally operates at temperatures between 1250.degree. C. and 1575.degree. C. and pressures between 300 psi to 1000 psi, with oxygen partial pressures generally between 10.sup.-4 and 10.sup.-10 atm. The refractory brick performs without substantial chromium carbide or chromium metal formation in the low oxygen partial pressure environment. The inclusion of carbon without chromium carbide formation provides for significant mitigation of slag penetration and significantly reduced refractory wear.

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

    PubMed

    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

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

    PubMed Central

    Leprieur, Etienne Giroux; Fallet, Vincent; Cadranel, Jacques; Wislez, Marie

    2016-01-01

    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 molecular status, and the physical condition of the patient. PMID:28210164

  2. Human Leukocyte Antigen G Polymorphism and Expression Are Associated with an Increased Risk of Non-Small-Cell Lung Cancer and Advanced Disease Stage

    PubMed Central

    Ben Amor, Amira; Beauchemin, Karine; Faucher, Marie-Claude; Hamzaoui, Agnes; Hamzaoui, Kamel; Roger, Michel

    2016-01-01

    Human leukocyte antigen (HLA)-G acts as negative regulator of the immune responses and its expression may enable tumor cells to escape immunosurveillance. The purpose of this study was to investigate the influence of HLA-G allelic variants and serum soluble HLA-G (sHLA-G) levels on risk of non-small-cell lung cancer (NSCLC). We analyzed 191 Caucasian adults with NSCLC and 191 healthy subjects recruited between January 2009 and March 2014 in Ariana (Tunisia). Serum sHLA-G levels were measured by immunoassay and HLA-G alleles were determined using a direct DNA sequencing procedures. The heterozygous genotypes of HLA-G 010101 and -G 010401 were associated with increased risks of both NSCLC and advanced disease stages. In contrast, the heterozygous genotypes of HLA-G 0105N and -G 0106 were associated with decreased risks of NSCC and clinical disease stage IV, respectively. Serum sHLA-G levels were significantly higher in patients with NSCLC and particularly in those with advanced disease stages compared to healthy subjects. The area under the receiver-operating characteristic (ROC) curves was 0.82 for controls vs patients. Given 100% specificity, the highest sensitivity achieved to detect NSCLC was 52.8% at a cutoff value of 24.9 U/ml. Patients with the sHLA-G above median level (≥ 50 U/ml) had a significantly shorter survival time. This study demonstrates that HLA-G allelic variants are independent risk factors for NSCLC. Serum sHLA-G levels in NSCLC patients could be useful biomarkers for the diagnostic and prognosis of NSCLC. PMID:27517300

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

    PubMed

    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.

  4. Human Leukocyte Antigen G Polymorphism and Expression Are Associated with an Increased Risk of Non-Small-Cell Lung Cancer and Advanced Disease Stage.

    PubMed

    Ben Amor, Amira; Beauchemin, Karine; Faucher, Marie-Claude; Hamzaoui, Agnes; Hamzaoui, Kamel; Roger, Michel

    2016-01-01

    Human leukocyte antigen (HLA)-G acts as negative regulator of the immune responses and its expression may enable tumor cells to escape immunosurveillance. The purpose of this study was to investigate the influence of HLA-G allelic variants and serum soluble HLA-G (sHLA-G) levels on risk of non-small-cell lung cancer (NSCLC). We analyzed 191 Caucasian adults with NSCLC and 191 healthy subjects recruited between January 2009 and March 2014 in Ariana (Tunisia). Serum sHLA-G levels were measured by immunoassay and HLA-G alleles were determined using a direct DNA sequencing procedures. The heterozygous genotypes of HLA-G 010101 and -G 010401 were associated with increased risks of both NSCLC and advanced disease stages. In contrast, the heterozygous genotypes of HLA-G 0105N and -G 0106 were associated with decreased risks of NSCC and clinical disease stage IV, respectively. Serum sHLA-G levels were significantly higher in patients with NSCLC and particularly in those with advanced disease stages compared to healthy subjects. The area under the receiver-operating characteristic (ROC) curves was 0.82 for controls vs patients. Given 100% specificity, the highest sensitivity achieved to detect NSCLC was 52.8% at a cutoff value of 24.9 U/ml. Patients with the sHLA-G above median level (≥ 50 U/ml) had a significantly shorter survival time. This study demonstrates that HLA-G allelic variants are independent risk factors for NSCLC. Serum sHLA-G levels in NSCLC patients could be useful biomarkers for the diagnostic and prognosis of NSCLC.

  5. Safety and efficacy of nivolumab and standard chemotherapy drug combination in patients with advanced non-small-cell lung cancer: a four arms phase Ib study

    PubMed Central

    Kanda, S.; Goto, K.; Shiraishi, H.; Kubo, E.; Tanaka, A.; Utsumi, H.; Sunami, K.; Kitazono, S.; Mizugaki, H.; Horinouchi, H.; Fujiwara, Y.; Nokihara, H.; Yamamoto, N.; Hozumi, H.; Tamura, T.

    2016-01-01

    Background The human IgG4 monoclonal antibody nivolumab targets programmed cell death-1 (PD-1) and promotes antitumor response by blocking the interaction of PD-1 with its ligands. This single-center phase Ib study investigated the tolerability, safety, and pharmacokinetics of nivolumab combined with standard chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC). Patients and methods Patients who had stage IIIB without indication for definitive radiotherapy, stage IV, or recurrent NSCLC were eligible. Regimens were nivolumab 10 mg/kg + gemcitabine/cisplatin (arm A), pemetrexed/cisplatin (arm B), paclitaxel/carboplatin/bevacizumab (arm C), or docetaxel (arm D). Regimens A, B, and D were repeated every 3 weeks for up to four cycles and regimen C was repeated for up to six cycles; nivolumab alone (arm A), with pemetrexed (arm B), bevacizumab (arm C), or docetaxel (arm D) was continued every 3 weeks as maintenance therapy until disease progression or unacceptable toxicity. Dose-limiting toxicity (DLT) was evaluated during the first treatment cycle. Results As of March 2014, six patients were enrolled in each arm. The combination of nivolumab 10 mg/kg and chemotherapy was well tolerated. DLT was observed in only one patient in arm A (alanine aminotransferase increased). Select adverse events (those with a potential immunologic cause) of any grade were observed in six, four, six, and five patients in arms A, B, C, and D, respectively. Three, three, six, and one patient achieved partial response while median progression-free survival was 6.28, 9.63 months, not reached, and 3.15 months in arms A, B, C, and D, respectively. Conclusions Combination of nivolumab 10 mg/kg and chemotherapy showed an acceptable toxicity profile and encouraging antitumor activity in patients with advanced NSCLC. Clinical trials number Japanese Pharmaceutical Information Center Clinical Trials Information (JapicCTI)-132071. PMID:27765756

  6. Genome-Wide Association Study of Prognosis in Advanced Non–Small Cell Lung Cancer Patients Receiving Platinum-Based Chemotherapy

    PubMed Central

    Hu, Lingmin; Wu, Chen; Zhao, Xueying; Heist, Rebecca; Su, Li; Zhao, Yang; Han, Baohui; Cao, Songyu; Chu, Minjie; Dai, Juncheng; Dong, Jing; Shu, Yongqian; Xu, Lin; Chen, Yijiang; Wang, Yi; Lu, Feng; Jiang, Yue; Yu, Dianke; Chen, Hongyan; Tan, Wen; Ma, Hongxia; Chen, Jiaping; Jin, Guangfu; Wu, Tangchun; Lu, Daru; Christiani, David C.; Lin, Dongxin; Hu, Zhibin; Shen, Hongbing

    2013-01-01

    Purpose Genetic variation may influence chemotherapy response and overall survival in cancer patients. Experimental design We conducted a genome-wide scan in 535 advanced-stage non–small cell lung cancer (NSCLC) patients from two independent cohorts (307 from Nanjing and 228 from Beijing). A replication was carried out on an independent cohort of 340 patients from Southeastern China followed by a second validation on 409 patients from the Massachusetts General Hospital (Boston, MA). Results Consistent associations with NSCLC survival were identified for five single-nucleotide polymorphisms (SNP) in Chinese populations with P values ranging from 3.63 × 10−5 to 4.19 × 10−7 in the additive genetic model. The minor allele of three SNPs (rs7629386 at 3p22.1, rs969088 at 5p14.1, and rs3850370 at 14q24.3) were associated with worse NSCLC survival while 2 (rs41997 at 7q31.31 and rs12000445 at 9p21.3) were associated with better NSCLC survival. In addition, rs7629386 at 3p22.1 (CTNNB1) and rs3850370 at 14q24.3 (SNW1-ALKBH1-NRXN3) were further replicated in the Caucasian population. Conclusion In this three-stage genome-wide association studies, we identified five SNPs as markers for survival of advanced-stage NSCLC patients treated with first-line platinum-based chemotherapy in Chinese Han populations. Two of these SNPs, rs7629386 and rs3850370, could also be markers for survival among Caucasian patients. PMID:22872573

  7. BIM Gene Polymorphism Lowers the Efficacy of EGFR-TKIs in Advanced Nonsmall Cell Lung Cancer With Sensitive EGFR Mutations: A Systematic Review and Meta-Analysis.

    PubMed

    Huang, Wu Feng; Liu, Ai Hua; Zhao, Hai Jin; Dong, Hang Ming; Liu, Lai Yu; Cai, Shao Xi

    2015-08-01

    The strong association between bcl-2-like 11 (BIM) triggered apoptosis and the presence of epidermal growth factor receptor (EGFR) mutations has been proven in nonsmall cell lung cancer (NSCLC). However, the relationship between EGFR-tyrosine kinase inhibitor's (TKI's) efficacy and BIM polymorphism in NSCLC EGFR is still unclear.Electronic databases were searched for eligible literatures. Data on objective response rates (ORRs), disease control rates (DCRs), and progression-free survival (PFS) stratified by BIM polymorphism status were extracted and synthesized based on random-effect model. Subgroup and sensitivity analyses were conducted.A total of 6 studies that involved a total of 773 EGFR mutant advanced NSCLC patients after EGFR-TKI treatment were included. In overall, non-BIM polymorphism patients were associated with significant prolonged PFS (hazard ratio 0.63, 0.47-0.83, P = 0.001) compared to patients with BIM polymorphism. However, only marginal improvements without statistical significance in ORR (odds ratio [OR] 1.71, 0.91-3.24, P = 0.097) and DCR (OR 1.56, 0.85-2.89, P = 0.153) were observed. Subgroup analyses showed that the benefits of PFS in non-BIM polymorphism group were predominantly presented in pooled results of studies involving chemotherapy-naive and the others, and retrospective studies. Additionally, we failed to observe any significant benefit from patients without BIM polymorphism in every subgroup for ORR and DCR.For advanced NSCLC EGFR mutant patients, non-BIM polymorphism ones are associated with longer PFS than those with BIM polymorphism after EGFR-TKIs treatment. BIM polymorphism status should be considered an essential factor in studies regarding EGFR-targeted agents toward EGFR mutant patients.

  8. A phase II study of cetuximab and radiation in elderly and/or poor performance status patients with locally advanced non-small-cell lung cancer (N0422)

    PubMed Central

    Jatoi, A.; Schild, S. E.; Foster, N.; Henning, G. T.; Dornfeld, K. J.; Flynn, P. J.; Fitch, T. R.; Dakhil, S. R.; Rowland, K. M.; Stella, P. J.; Soori, G. S.; Adjei, A. A.

    2010-01-01

    Background: Non-small-cell lung cancer (NSCLC) is a disease of the elderly. Seeking a tolerable but effective regimen, we tested cetuximab + radiation in elderly and/or poor performance status patients with locally advanced NSCLC. Patients and methods: Older patients [≥65 years with an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2] or younger patients (performance status of 2) received cetuximab 400 mg/m2 i.v. on day 1 followed by weekly cetuximab 250 mg/m2 i.v. with concomitant radiation of 6000 cGy in 30 fractions. The primary end point was the percentage who lived 11+ months. Results: This 57-patient cohort had a median age (range) of 77 years (60–87), and 12 (21%) had a performance status of 2. Forty of 57 (70%) lived 11+ months, thus exceeding the anticipated survival rate of 50%. The median survival was 15.1 months [95% confidence interval (CI) 13.1–19.3 months], and the median time to cancer progression was 7.2 months (95% CI 5.8–8.6 months). No treatment-related deaths occurred, but 31 patients experienced grade 3+ adverse events, most commonly fatigue, anorexia, dyspnea, rash, and dysphagia, each of which occurred in <10% of patients. Conclusion: This combination merits further study in this group of patients. PMID:20570832

  9. Erlotinib usage after prior treatment with gefitinib in advanced non-small cell lung cancer: A clinical perspective and review of published literature.

    PubMed

    Singh, Navneet; Jindal, Aditya; Behera, Digambar

    2014-12-10

    Erlotinib and gefitinib are among the most widely researched, used and available molecularly targeted therapies for treatment of advanced non-small cell lung cancer (NSCLC). They are both tyrosine kinase inhibitors (TKIs) of the epidermal growth factor receptor (EGFR). In the past decade, there have been reports on clinical benefit from use of erlotinib after gefitinib failure in NSCLC patients. A review of published literature on this focussed topic is provided herein. Pooled analysis of published literature shows that majority of patients were female (60.6%), non-smokers (64.5%), had adenocarcinoma histology (88.3%) and were of East Asian ethnicity (92.3%). Presence of sensitizing EGFR mutation was detected in 48.4% of subjects. Disease control rates with prior gefitinib therapy and with subsequent erlotinib treatment were 79.4% and 45.4% respectively. Based upon our review, the most important predictive factor for clinical benefit from erlotinib identified was previous response to gefitinib. The exact explanations for the potential benefit from erlotinib use in this patient population is still not known and further studies are required to determine the role of molecular mechanisms especially those related to resistance to initial EGFR TKI therapy.

  10. Intratumoral Epiregulin Is a Marker of Advanced Disease in Non–Small Cell Lung Cancer Patients and Confers Invasive Properties on EGFR-Mutant Cells

    PubMed Central

    Zhang, Jie; Iwanaga, Kentaro; Choi, Kuicheon C.; Wislez, Marie; Raso, Maria Gabriela; Wei, Wei; Wistuba, Ignacio I.; Kurie, Jonathan M.

    2012-01-01

    Non–small cell lung cancer (NSCLC) cells with activating epidermal growth factor receptor (EGFR) somatic mutations have unique biological properties, including high expression of the ErbB ligand epiregulin; however, the biological role of epiregulin in these cells has not been elucidated. To examine its role, we used an immunohistochemical approach to detect epiregulin expression in NSCLC biopsy samples and pharmacologic and genetic approaches to inhibit epiregulin in cultured NSCLC cells. In NSCLC biopsy samples, epiregulin was detected in 237 of 366 (64.7%) tumors, which correlated with nodal metastasis and a shorter duration of survival. In EGFR-mutant NSCLC cell lines, treatment with a small-molecule EGFR tyrosine kinase inhibitor diminished mRNA levels of the gene encoding epiregulin (EREG). The ability of EGFR-mutant NSCLC cells to invade through Matrigel in vitro was inhibited by treatment with an anti-epiregulin neutralizing antibody or by transfection with an EREG short hairpin RNA. Collectively, these findings show that epiregulin expression correlated with advanced disease, was EGFR dependent, and conferred invasive properties on NSCLC cells. Additional studies are warranted in NSCLC patients to evaluate whether epiregulin expression predicts the metastatic potential of primary tumors and whether anti-epiregulin treatment strategies are efficacious in the prevention of metastasis. PMID:19138957

  11. Comparison of outcomes of tyrosine kinase inhibitor in first- or second-line therapy for advanced non-small-cell lung cancer patients with sensitive EGFR mutations.

    PubMed

    Xu, Jianlin; Zhang, Xueyan; Yang, Haitang; Ding, Guozheng; Jin, Bo; Lou, Yuqing; Zhang, Yanwei; Wang, Huimin; Han, Baohui

    2016-10-18

    Direct comparisons between the use of first- and second-line EGFR tyrosine kinase inhibitor (TKI) in patients with sensitive EGFR mutations are limited. A total of 264 advanced non-small-cell lung cancer (NSCLC) patients with sensitive mutations received EGFR TKI therapy as the first-line therapy, and a total of 187 patients received TKI as the second-line therapy at Shanghai Chest Hospital. First-line EGFR TKI therapy [12.9 months, 95% confidence interval (CI), 10.7-15.2] provided longer progression-free survival (PFS) than did second-line EGFR TKI therapy (9.0 months, 95% CI, 7.7-10.2) [hazard ratio (HR): 0.78, P = 0.034]. The objective response rate (ORR) of first-, and second-line TKI therapy were 67.8% (159/233) and 55.6% (94/169), respectively (P = 0.001). The overall survival (OS) for patients (n = 141) receiving first-line TKI followed by second-line chemotherapy were longer than those for patients (n = 187) receiving first-line chemotherapy followed by second-line TKI (HR: 0.69, P = 0.02).Compared with second-line TKI, first-line therapy achieved a significant and longer PFS, and higher ORR in the sensitive EGFR mutated NSCLC patients. The therapeutic strategy of using TKI followed by chemotherapy achieved longer OS than that using chemotherapy followed by TKI.

  12. Alloimmune refractoriness to platelet transfusions.

    PubMed

    Sandler, S G

    1997-11-01

    Patients who are transfused on multiple occasions with red cells or platelets may develop platelet-reactive alloantibodies and experience decreased clinical responsiveness to platelet transfusion. This situation, conventionally described as "refractoriness to platelet transfusions," is defined by an unsatisfactory low post-transfusion platelet count increment. If antibodies to HLAs are detected, improved clinical outcomes may result from transfusions of HLA-matched or donor-recipient cross-matched platelets. Because refractoriness is an expected, frequently occurring phenomenon, prevention of HLA alloimmunization is an important management strategy. Prevention strategies include efforts to decrease the number of transfusions, filtration of cellular components to reduce the number of HLA-bearing leukocytes, or pretransfusion ultraviolet B irradiation of cellular components to decrease their immunogenicity. Other investigational approaches include reducing the expression of HLAs on transfused platelets, inducing a transient reticuloendothelial system blockade by infusions of specialized immunoglobulin products, or transfusing semisynthetic platelet substitutes (thromboerythrocytes, thrombospheres) or modified platelets (infusible platelet membranes, lyophilized platelets).

  13. Cytoreductive treatment with clofarabine/ara-C combined with reduced-intensity conditioning and allogeneic stem cell transplantation in patients with high-risk, relapsed, or refractory acute myeloid leukemia and advanced myelodysplastic syndrome.

    PubMed

    Buchholz, Stefanie; Dammann, Elke; Stadler, Michael; Krauter, Juergen; Beutel, Gernot; Trummer, Arne; Eder, Matthias; Ganser, Arnold

    2012-01-01

    The combination of cytoreductive chemotherapy with reduced-intensity conditioning (RIC) is a highly effective antileukemic therapy. Purpose of this retrospective analysis was to evaluate the antileukemic efficacy and toxicity of clofarabine-based chemotherapy followed by RIC and allogeneic stem cell transplantation (SCT) for high-risk, relapsed, or refractory acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS). From May 2007 until October 2009, a total of 27 patients underwent allogeneic SCT after treatment with clofarabine and ara-C for 5d and RIC (4Gy TBI/cyclophosphamide/ATG). Prophylaxis of graft-versus-host disease (GvHD) consisted of cyclosporine and mycophenolate mofetil. Unmanipulated G-CSF mobilized PBSC (n=26) or bone marrow cells (n=1) were transplanted from unrelated (n=21) or matched related (n=6) donors. Non-hematological toxicities of this regimen mainly affected liver and skin and were all reversible. Seven patients relapsed within a median time of 5.7 months. The overall survival (OS) and relapse-free survival rates were 56% and 52% at 2 yr, respectively. In this cohort of patients, cytoreduction with clofarabine/ara-C (ClAraC) followed by RIC allogeneic SCT was well tolerated and showed good antileukemic efficacy even in patients with high-risk AML or MDS, with engraftment and GvHD-incidence comparable to other RIC regimens.

  14. Lung Transplantation

    MedlinePlus

    ... are used to treat people who have severe COPD Cystic fibrosis Idiopathic pulmonary fibrosis Alpha-1 antitrypsin deficiency Pulmonary hypertension Complications of lung transplantation include rejection of the transplanted lung and infection. NIH: National Heart, Lung, and Blood Institute

  15. Lung transplant

    MedlinePlus

    ... in the arteries of the lungs ( pulmonary hypertension ) Sarcoidosis Lung transplant may not be done for people ... Chronic Cystic fibrosis Idiopathic pulmonary fibrosis Lung disease Sarcoidosis Review Date 4/13/2015 Updated by: Dale ...

  16. Lung disease

    MedlinePlus

    ... they can't breathe deeply. Pulmonary fibrosis and sarcoidosis are examples of lung tissue disease. Lung circulation ... tuberculosis Pulmonary veno-occlusive disease Rheumatoid lung disease Sarcoidosis Simple pulmonary eosinophilia Patient Instructions Chronic obstructive pulmonary ...

  17. REFRACTORY DIE FOR EXTRUDING URANIUM

    DOEpatents

    Creutz, E.C.

    1959-08-11

    A die is presented for the extrusion of metals, said die being formed of a refractory complex oxide having the composition M/sub n/O/sub m/R/sub x/O/sub y/ where M is magnesium, zinc, manganese, or iron, R is aluminum, chromic chromium, ferric iron, or manganic manganese, and m, n, x, and y are whole numbers. Specific examples are spinel, magnesium aluminate, magnetite, magnesioferrite, chromite, and franklinite.

  18. Correlation between EGFR mutation status and response to first-line platinum-based chemotherapy in patients with advanced non-small cell lung cancer

    PubMed Central

    Fang, Shu; Wang, Zhehai; Guo, Jun; Liu, Jie; Li, Changzheng; Liu, Lin; Shi, Huan; Liu, Liyan; Li, Huihui; Xie, Chao; Zhang, Xia; Sun, Wenwen; Li, Minmin

    2014-01-01

    Background The purpose of this research was to investigate the relationship between epidermal growth factor receptor (EGFR) mutations and the response to first-line chemotherapy in patients with advanced non-small cell lung cancer (NSCLC). Methods A total of 266 patients with stage IIIB or IV NSCLC who received platinum-based doublet therapies as first-line chemotherapy were investigated retrospectively, and their clinical data were assessed according to EGFR mutation. Results EGFR mutations were identified in 45.5% of patients. There was no significant difference in response rate between EGFR mutation carriers and EGFR wild-type carriers (P=0.484). Among the patients with Kirsten rat sarcoma viral oncogene homolog (KRAS) wild-type, however, those with EGFR mutations responded better to treatment than EGFR wild-type patients (46.2% versus 20.8%, P=0.043). The disease control rate associated with pemetrexed-based treatments was higher than for vinorelbine-based therapies in EGFR mutation patients (P=0.001). EGFR mutation was found in patients with longer progression-free survival and median survival time, and improved 1-year and 2-year overall survival when compared with EGFR wild-type patients (6.1 versus 5.0 months, P=0.004; 18.9 versus 13.8 months, P=0.001; 81.0% versus 63.4%, P=0.002; and 33.9% versus 22.8% P=0.044, respectively). Patients with the EGFR exon 19 mutation had longer progression-free survival than those with EGFR exon 21 mutation (P=0.007). Multivariate analysis showed that the response to first-line chemotherapy and the presence of EGFR mutations were independent prognostic factors in patients with advanced NSCLC. Conclusion Our data showed that the presence of EGFR mutations meant longer survival times for patients with advanced NSCLC who received platinum-based doublet first-line chemotherapy, especially in those with the exon 19 deletion mutation. Among KRAS wild-type patients, those with EGFR mutation responded better to first

  19. Pretreatment 18F-FDG PET Textural Features in Locally Advanced Non–Small Cell Lung Cancer: Secondary Analysis of ACRIN 6668/RTOG 0235

    PubMed Central

    Ohri, Nitin; Duan, Fenghai; Snyder, Bradley S.; Wei, Bo; Machtay, Mitchell; Alavi, Abass; Siegel, Barry A.; Johnson, Douglas W.; Bradley, Jeffrey D.; DeNittis, Albert; Werner-Wasik, Maria; El Naqa, Issam

    2016-01-01

    In a secondary analysis of American College of Radiology Imaging Network (ACRIN) 6668/RTOG 0235, high pretreatment metabolic tumor volume (MTV) on 18F-FDG PET was found to be a poor prognostic factor for patients treated with chemoradiotherapy for locally advanced non–small cell lung cancer (NSCLC). Here we utilize the same dataset to explore whether heterogeneity metrics based on PET textural features can provide additional prognostic information. Methods Patients with locally advanced NSCLC underwent 18F-FDG PET prior to treatment. A gradient-based segmentation tool was used to contour each patient’s primary tumor. MTV, maximum SUV, and 43 textural features were extracted for each tumor. To address over-fitting and high collinearity among PET features, the least absolute shrinkage and selection operator (LASSO) method was applied to identify features that were independent predictors of overall survival (OS) after adjusting for MTV. Recursive binary partitioning in a conditional inference framework was utilized to identify optimal thresholds. Kaplan–Meier curves and log-rank testing were used to compare outcomes among patient groups. Results Two hundred one patients met inclusion criteria. The LASSO procedure identified 1 textural feature (SumMean) as an independent predictor of OS. The optimal cutpoint for MTV was 93.3 cm3, and the optimal Sum-Mean cutpoint for tumors above 93.3 cm3 was 0.018. This grouped patients into three categories: low tumor MTV (n = 155; median OS, 22.6 mo), high tumor MTV and high SumMean (n = 23; median OS, 20.0 mo), and high tumor MTV and low SumMean (n = 23; median OS, 6.2 mo; log-rank P < 0.001). Conclusion We have described an appropriate methodology to evaluate the prognostic value of textural PET features in the context of established prognostic factors. We have also identified a promising feature that may have prognostic value in locally advanced NSCLC patients with large tumors who are treated with chemoradiotherapy

  20. Intercalated Chemotherapy and Epidermal Growth Factor Receptor Inhibitors for Patients With Advanced Non-Small-cell Lung Cancer: A Systematic Review and Meta-analysis.

    PubMed

    La Salvia, Anna; Rossi, Antonio; Galetta, Domenico; Gobbini, Elisa; De Luca, Emmanuele; Novello, Silvia; Di Maio, Massimo

    2017-01-01

    Randomized clinical trials (RCTs) of concurrent epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) plus chemotherapy for unselected patients with advanced non-small-cell lung cancer (NSCLC) produced negative results. Intercalated administration could avoid the reduction of chemotherapy activity due to G1 cell-cycle arrest from EGFR-TKIs. A PubMed search was performed in December 2015 and updated in February 2016. The references from the selected studies were also checked to identify additional eligible trials. Furthermore, the proceedings of the main international meetings were searched from 2010 onward. We included RCTs comparing chemotherapy intercalated with an EGFR-TKI versus chemotherapy alone for patients with advanced NSCLC. Ten RCTs were eligible (6 with erlotinib, 4 with gefitinib): 39% of patients had a known EGFR mutational status, 43% of whom EGFR mutation positive. The intercalated combination was associated with a significant improvement in overall survival (OS; hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.71-0.95; P = .01), progression-free survival (PFS; HR, 0.60; 95% CI, 0.53-0.68; P < .00001), and objective response rate (ORR; odds ratio [OR], 2.70; 95% CI, 2.08-3.49; P < .00001). Considering only first-line trials, similar differences were found in OS (HR, 0.85; 95% CI, 0.72-1.00; P = .05), PFS (HR, 0.63; 95% CI, 0.55-0.73; P < .00001), and ORR (OR, 2.21; 95% CI, 1.65-2.95; P < .00001). In EGFR mutation-positive patients, the addition of an intercalated EGFR-TKI produced a significant benefit in PFS (129 patients; HR, 0.24; 95% CI, 0.16-0.37; P < .00001) and ORR (168 patients; OR, 11.59; 95% CI, 5.54-24.25; P < .00001). In patients with advanced NSCLC, chemotherapy plus intercalated EGFR-TKIs was superior to chemotherapy alone, although a definitive interpretation was jeopardized by the variable proportion of patients with EGFR mutation-positive tumors included.

  1. A short radiotherapy course for locally advanced non-small cell lung cancer (NSCLC): effective palliation and patients' convenience.

    PubMed

    Plataniotis, G A; Kouvaris, J R; Dardoufas, C; Kouloulias, V; Theofanopoulou, M A; Vlahos, L

    2002-02-01

    In order to facilitate patients with symptomatic locally advanced NSCLC, especially those coming from remote areas we have employed two palliative RT schedules. The first (S1) is the well known from Medical Research Council (MRC) randomized studies 2 x 8.5 Gy one week apart and the second (S2) is a two-day RT schedule: three fractions of 4.25 Gy are given on the first day and two fractions of 4.25 Gy on the second day. The records of 92 patients were reviewed (48 for S1 and 44 for S2). Patients, disease characteristics and results were similar for both groups; rates of symptom disappearance were for S1 and S2, respectively: cough 24 and 20%, hemoptysis 60 and 67%, chest pain 57 and 64% and dyspnoea 55 and 45% The overall condition improved in 39 and 36%, respectively. The median palliation time in days was in S1 and S2, respectively: cough 70 and 66, haemoptysis 133 and 139, chest pain 68 and 62 and dyspnoea 74 and 69 days. The median survival was 25 weeks in both S1 and S2 groups (P=0.89 log-rank test). At 52 weeks (one year), ten (21%) and seven (16%) of the patients were alive in S1 and S2 groups, respectively. At 104 weeks, the corresponding figures were two (4%) and two (4.7%) for S1 and S2. Our results are in accordance to those reported in literature regarding the safety and efficacy of palliative hypofractionated radiotherapy schemes. Their use in selected patients could be cost-effective and convenient for patients especially those coming from remote areas.

  2. Refractory metal alloys and composites for space nuclear power systems

    SciTech Connect

    Titran, R.H.; Stephens, J.R.; Petrasek, D.W.

    1988-01-01

    Space power requirements for future NASA and other United States missions will range from a few kilowatts to megawatts of electricity. Maximum efficiency is a key goal of any power system in order to minimize weight and size so that the space shuttle may be used a minimum number of times to put the power supply into orbit. Nuclear power has been identified as the primary power source to meet these high levels of electrical demand. One method to achieve maximum efficiency is to operate the power supply, energy conversion system, and related components at relatively high temperatures. For systems now in the planning stages, design temperatures range from 1300 K for the immediate future to as high as 1700 K for the advanced systems. NASA Lewis Research Center has undertaken a research program on advanced technology of refractory metal alloys and composites that will provide base line information for space power systems in the 1900's and the 21st century. Special emphasis is focused on the refractory metal alloys of niobium and on the refractory metal composites which utilize tungsten alloy wire for reinforcement. Basic research on the creep and creep-rupture properties of wires, matrices, and composites will be discussed. 20 refs., 27 figs., 1 tab.

  3. Refractory metal alloys and composites for space nuclear power systems

    NASA Technical Reports Server (NTRS)

    Titran, Robert H.; Stephens, Joseph R.; Petrasek, Donald W.

    1988-01-01

    Space power requirements for future NASA and other U.S. missions will range from a few kilowatts to megawatts of electricity. Maximum efficiency is a key goal of any power system in order to minimize weight and size so that the Space Shuttle may be used a minimum number of times to put the power supply into orbit. Nuclear power has been identified as the primary power source to meet these high levels of electrical demand. One method to achieve maximum efficiency is to operate the power supply, energy conservation system, and related components at relatively high temperatures. For systems now in the planning stages, design temperatures range from 1300 K for the immediate future to as high as 1700 K for the advanced systems. NASA Lewis Research Center has undertaken a research program on advanced technology of refractory metal alloys and composites that will provide baseline information for space power systems in the 1900's and the 21st century. Special emphasis is focused on the refractory metal alloys of niobium and on the refractory metal composites which utilize tungsten alloy wires for reinforcement. Basic research on the creep and creep-rupture properties of wires, matrices, and composites are discussed.

  4. Intensified High-Dose Chemoradiotherapy With Induction Chemotherapy in Patients With Locally Advanced Non-Small-Cell Lung Cancer-Safety and Toxicity Results Within a Prospective Trial

    SciTech Connect

    Poettgen, Christoph; Eberhardt, Wilfried E.; Gauler, Thomas; Krbek, Thomas; Berkovic, Katharina; Abu Jawad, Jehad; Korfee, Soenke; Teschler, Helmut; Stamatis, Georgios; Stuschke, Martin

    2010-03-01

    Purpose: To analyze the toxicity profile of an intensified definitive chemoradiotherapy (CRT) schedule in patients with locally advanced non-small-cell lung cancer (Stage IIIA N2/selected IIIB) treated within a prospective multicenter trial. Patients and Methods: After mediastinoscopy and routine staging procedures, three cycles of induction chemotherapy (cisplatin 50 mg/m{sup 2}, Days 1 and 8; paclitaxel 175 mg/m{sup 2} Day 1, every 21 days) were planned, followed by concurrent CRT (accelerated-hyperfractionated regimen, 45 Gy, 2 x 1.5 Gy/d, cisplatin 50 mg/m{sup 2}, Days 64 and 71, vinorelbine 20 mg/m{sup 2}, Days 64 and 71). At 45 Gy, a multidisciplinary panel decision was made regarding operability. Inoperable patients received definitive radiotherapy (total dose 65 or 71 Gy, depending on the mean lung dose) with additional concurrent chemotherapy (cisplatin 40 mg/m{sup 2}, Day 85; vinorelbine 15 mg/m{sup 2}, Days 85 and 92). Results: A total of 28 patients (23 men and 5 women; median age, 58 years; range 41-73; Stage IIIA in 3 and Stage IIIB in 25) were judged ineligible for surgery by the multidisciplinary panel and underwent definitive CRT (75% of the patients received 71 Gy). The maximum toxicity (Grade 3 or greater) during induction chemotherapy included leukopenia (11%) and anemia (4%). During concurrent CRT, leukopenia (Grade 3 or greater) was observed in 39% of the patients. The maximal nonhematologic toxicity during concurrent CRT included esophagitis (Grade 3 or greater) in 18% and pneumonitis (Grade 3 or greater) in 4% of the patients. At 3 years, the locoregional control rate was 52% (95% confidence interval, 29-75%) and the overall survival rate was 31% (95% confidence interval, 12-50%). Conclusion: This intensified treatment protocol with induction chemotherapy and concurrent CRT, including hyperfractionated-accelerated RT, showed only moderate toxicity and proved feasible. This treatment represents the definitive CRT arm of our ongoing

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

    ClinicalTrials.gov

    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

  6. Nintedanib in combination with docetaxel for second-line treatment of advanced non-small-cell lung cancer; GENESIS-SEFH drug evaluation report.

    PubMed

    Espinosa Bosch, María; Asensi Diez, Rocío; García Agudo, Sara; Clopes Estela, Ana

    2016-06-01

    Nintedanib is a triple angiokinase inhibitor that has been approved by the European Agency Medicines (EMA) in combination with docetaxel for the treatment of adult patients with locally advanced, metastatic or locally recurrent non small cell lung cancer (NSCLC) of adenocarcinoma tumour histology, after first-line chemotherapy. In LUME-Lung 1 clinical trial, the combination of nintedanib plus docetaxel vs. placebo plus docetaxel improved progression free survival (PFS) in NSCLC patients, and improved overall survival in the population of adenocarcinoma patients, particularly in those with progression within 9 months after first line treatment initiation, median 10.9 months ( [95% CI 8.5-12.6] vs. 7.9 months [6.7-9.1]; HR 0.75 [95% CI 0.60-0.92], p=0.0073). The toxicity profile of the combination included a higher incidence of neutropenia, gastro-intestinal (GI) disorders, and liver enzyme elevations; however, this did not cause a detrimental effect on patient quality of life. According to data from the clinical trial mentioned, the addition of nintedanib to docetaxel would lead to an estimated incremental cost-effectiveness ratio (ICER) per year of life with PFS in the overall population of 134,274.47 € (notified price). In the adenocarcinoma population per each life of year gained (LYG), the ICER of adding nintedanib to docetaxel would be 40,886.14 €; while by implementing a sensitivity analysis with a 25% discount in the drug price, the cost per LYG would be 32,364.05 €, and would place it close to the threshold of cost-effectiveness usually considered acceptable in our setting. In view of efficacy and safety results the proposed positioning is to recommend its inclusion in the Hospital Formulary only for adult patients with metastatic or locally recurrent NSCLC with adenocarcinoma histology after first line chemotherapy, with progression < 9 months from the initiation of first line treatment, taking into account the inclusion and exclusion criteria in the

  7. Improving outcomes of refractory celiac disease – current and emerging treatment strategies

    PubMed Central

    Woodward, Jeremy

    2016-01-01

    Intestinal inflammation and symptoms of celiac disease (CD) usually respond well to gluten withdrawal, but rare cases are refractory to diet. Two types of refractory CD are discriminated on the basis of the presence or absence of an atypical population of mucosal lymphocytes that may progress to enteropathy-associated T-cell lymphoma. Challenges remain in the secure diagnosis of both types of refractory disease, and evidence on which to base treatment recommendations is flawed by the small numbers of reported patients and the use of different diagnostic strategies. Recent advances in our understanding of the mechanisms of the condition in conjunction with the development of immunomodulatory agents for managing other inflammatory diseases are helping to shape future approaches to targeted therapy. Progression will depend on collaboration and recruitment to trials. In the meantime, there is evidence to suggest that earlier diagnosis and better follow-up and management of CD may prevent the development of refractoriness. PMID:27536154

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

    PubMed Central

    Russo, Francesca; Bearz, Alessandra; Pampaloni, Gianni

    2008-01-01

    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. PMID:18667090

  9. Refractory metal particles in refractory inclusions in the Allende meteorite

    NASA Technical Reports Server (NTRS)

    Fuchs, L. H.; Blander, M.

    1980-01-01

    SEM and X-ray analysis were used to study refractory metal particles in five calcium-aluminum-rich inclusions in the Allende meteorite, and a complex variety of compositions and large departures from equilibrium were found. It is suggested that these particles could have been primordial condensates which were isolated from the nebula and from each other at different times by cocondensing oxides. Selective diffusion and/or oxidation of the more oxidizable metals (Mo, W, Fe, and Ni), phase segregations into different alloy phases (fcc, bcc, hcp, and, possibly, ordered phases), and the formation of metastable condensates could have been involved in the genesis of these materials

  10. Artificial lung: current perspectives.

    PubMed

    Go, T; Macchiarini, P

    2008-10-01

    While the number of the patients suffering from end-stage pulmonary disease has been increasing, the most common treatment for this entity remains mechanical ventilation that entails the risks of lung damage by itself. Although the lung protective strategy for the prevention of further damage to the lung tissue has been elucidated and performed, mechanical ventilation alone as the management tactic coping with the patients of acute respiratory distress syndrome, chronic respiratory failure and lung transplantations has been a frustrated scenario. Extracorporeal membrane oxygenation or extracorporeal lung assist have been applied to these patients with occasional success, but it always accompanies difficulties such as multiple blood transfusion, labor intensity, technically complexity and tendency to infection. In contrast to advances in the development of cardiac or renal support systems for adults, the development of extra-, para- and intracorporeal mechanical systems for acute or chronic lung respiratory failure has logged far behind. It has been mostly due to the lack of the capable technologies. Entering 21st century with advent of new technology especially invention of the low resistance oxygenator, the developments of artificial lungs have entered the new stage. In this report current status of the artificial lungs will be reviewed.

  11. METHOD OF PREPARING COATED REFRACTORY WARE

    DOEpatents

    Perlman, M.L.; Lipkin, D.; Weissman, S.I.

    1959-07-21

    A method is presented for preparing a dense, refractory coating on a vessel adapted to the handling of molten metals such as uranium and plutonium. According to the invention, the inner surface of a heat stable container formed of a refractory metal of either niobium, molybdenum, tantalum, or tungsten is coated with molten thorium within 10 minutes so as to present alloying with the refractory metal and then exposed to a reactive atmosphere of nitrogen at a temperature of about 1750 deg for 30 minutes to form a refractory thorium nitride coating.

  12. Development of refractory concrete for extreme conditions

    NASA Astrophysics Data System (ADS)

    Pundiene, I.; Antonovich, V.; Stonys, R.; Demidova-Buiziniene, I.

    2011-12-01

    Comparative analysis is provided for the properties of medium-cement refractory concrete with microsilica based on mullite filler in relation to different type of deflocculant. The effect of different deflocculants on refractory concrete structure formation, hydration, rheology, strength and heat resistance is discussed. Corrosion resistance test, determined that samples with hybrid deflocculant showed better resistance for slag penetration than samples with only the sodium tripolyphosphate or polycarboxylate ether deflocculant. Moreover, a composition of hybrid deflocculant let to control the rate of the hydration process and to get features of refractory refractory concrete.

  13. The improvement of slagging gasifier refractories

    SciTech Connect

    Kwong, K.-S.; Bennett, J.P.; Powell, C.A.; Krabbe, R.A.

    2006-03-01

    Refractories play a vital role in slagging gasifier on-line availability and profitability for the next clean power generation system. A recent survey of gasifier users by USDOE indicated that a longer service life of refractories is the highest need among gasifier operators. Currently, Cr2O3 based refractories, the best of commercially available materials for use in slagging gasifiers, last between 3 and 24 months. Researchers at Albany Research Center (ARC) have identified structural spalling, caused by slag penetration, as one of the major failure mechanisms of Cr2O3 refractories through postmortem analysis. New Cr2O3 refractories with phosphate additives have been developed by ARC to decrease slag penetration and thus structural spalling. Laboratory physical property tests indicated that ARC developed refractories are superior to other commercial bricks. One of the ARC developed phosphate containing refractories has been installed in a slagging gasifier. Preliminary results of the performance of this refractory in the gasifier will be reported along with research to develop non-chromia refractories.

  14. Erlotinib plus parenteral nutrition: an opportunity to get through the hardest days of advanced non-small cell lung cancer with cancer anorexia-cachexia syndrome.

    PubMed

    Zang, Yuan-Sheng; Fang, Zheng; Li, Bing

    2013-03-01

    This case study details the poor performance status of a patient with non-small cell lung cancer and cancer anorexia-cachexia syndrome got through the hardest days of high tumor burden and malnutrition, by using a combined therapy of lung cancer-targeted therapy drug and parenteral nutrition. The related literatures were reviewed.

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

    PubMed

    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.

  16. Predictive assessment in pharmacogenetics of XRCC1 gene on clinical outcomes of advanced lung cancer patients treated with platinum-based chemotherapy

    PubMed Central

    Yuan, Zhengrong; Li, Jiao; Hu, Ruiqi; Jiao, Yang; Han, Yingying; Weng, Qiang

    2015-01-01

    Published data have shown inconsistent results about the pharmacogenetics of XRCC1 gene on clinical outcomes of advanced lung cancer patients treated with platinum-based chemotherapy. This meta-analysis aimed to summarize published findings and provide more reliable association. A total of 53 eligible studies including 7433 patients were included. Patients bearing the favorable TrpTrp and TrpArg genotypes of Arg194Trp were more likely to better response rates to platinum-based chemotherapy compared to those with the unfavorable ArgArg genotype (TrpTrp+TrpArg vs. ArgArg: odds ratio (OR) = 2.02, 95% CI, 1.66–2.45). The GlnGln and GlnArg genotypes of Arg399Gln were significantly associated with the poorer response rates compared to those with the ArgArg genotype (GlnGln +GlnArg vs. ArgArg: OR = 0.68, 95% CI, 0.54–0.86). The GlnGln genotype might be more closely associated with shorter survival time and higher risks of death for patients (GlnGln vs. ArgArg: hazard ratio (HR) = 1.14, 95% CI, 0.75–1.75). Our cumulative meta-analyses indicated a distinct apparent trend toward a better response rate for Arg194Trp, but a poorer response rate in Arg399Gln. These findings indicate a predictive role of XRCC1 polymorphisms in clinical outcomes. The use of XRCC1 polymorphisms as predictive factor of clinical outcomes in personalized chemotherapy treatment requires further verification from large well-designed pharmacogenetics studies. PMID:26585370

  17. Use of Bevacizumab in Community Settings: Toxicity Profile and Risk of Hospitalization in Patients With Advanced Non–Small-Cell Lung Cancer

    PubMed Central

    Carroll, Nikki M.; Delate, Thomas; Menter, Alex; Hornbrook, Mark C.; Kushi, Lawrence; Aiello Bowles, Erin J.; Loggers, Elizabeth T.; Ritzwoller, Debra P.

    2015-01-01

    Purpose: Little is known regarding toxicities and hospitalizations in community-based settings for patients with advanced non–small-cell lung cancer (NSCLC) who received commonly prescribed carboplatin-paclitaxel (CP) or carboplatin-paclitaxel-bevacizumab (CPB) chemotherapy. Methods: Patients with stages IIIB-IV NSCLC age ≥ 21 years diagnosed between 2005 and 2010 who received first-line CP or CPB were identified at four health maintenance organizations (N = 1,109). Using patient and tumor characteristics and hospital and ambulatory encounters from automated data in the 180 days after chemotherapy initiation, the association between CP and CPB and toxicities and hospitalizations were evaluated with χ2 tests and propensity score–adjusted regression models. Results: Patients who received CPB were significantly younger and had significantly more bleeding, proteinuria, and GI perforation events (all P < .05). For these patients, the unadjusted odds ratio associated with the likelihood of having a hospitalization was 0.46 (95% CI, 0.32 to 0.67). As shown by multivariable and propensity score–adjusted models, patients who received CPB were less likely to have been hospitalized (odds ratio, 0.48; 95% CI, 0.32 to 0.71) and had fewer total hospitalizations (rate ratio, 0.62; 95% CI, 0.47 to 0.82) and hospital days (rate ratio, 0.53; 95% CI, 0.47 to 0.60) than patients who received CP. Conclusion: Consistent with earlier randomized clinical trials, significantly more toxicity events were identified in patients treated with CPB. However, both unadjusted and adjusted models showed that patients who received CPB were less likely than patients who received CP to experience a hospital-related event after the initiation of chemotherapy. Findings here confirm the need for adherence to clinical recommendations for judicious use of CPB, but provide reassurance regarding the relative risk for hospitalizations. PMID:26060223

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

    PubMed Central

    Gota, Vikram; Kavathiya, Krunal; Doshi, Kartik; Gurjar, Murari; Damodaran, Solai E; Noronha, Vanita; Joshi, Amit; Prabhash, Kumar

    2014-01-01

    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 pemetrexed is associated with grade ≥3 hyponatremia. The pharmacogenetic basis for higher exposure to pemetrexed in Indian patients needs further investigation. PMID:24940080

  19. The effect of consolidation chemotherapy after concurrent chemoradiotherapy on the survival of patients with locally advanced non-small cell lung cancer: a meta-analysis.

    PubMed

    Wang, Xinshuai; Ding, Xuezhen; Kong, Dejiu; Zhang, Li; Guo, Yibo; Ren, Jing; Hu, Xiaochen; Yang, Junqiang; Gao, Shegan

    2017-04-01

    Whether consolidation chemotherapy (CCT) after chemoradiotherapy (CRT) helps in the treatment of locally advanced non-small cell lung cancer (LA-NSCLC) is controversial. The aim of this meta-analysis was to evaluate the impact of CCT on overall survival (OS), progression-free survival (PFS), overall response rate (ORR) and toxicities in patients with inoperable LA-NSCLC. PubMed, Embase, The Cochrane Library, WanFang, VIP, and CNKI were searched to identify any relevant publications. After screening the literature and completing quality assessment and data extraction, the meta-analysis was performed using RevMan5.3 software. Ultimately, 5 eligible studies with a total of 1036 patients were selected for the present meta-analysis. The results of the analysis indicated that treatment of LA-NSCLC patients with CRT followed by CCT improved OS (pooled HR 0.85; 95% CI 0.73-0.99; P = 0.03), but did not improve PFS (pooled HR 0.78; 95% CI 0.60-1.02; P = 0.07) and ORR (P = 0.26). Although it could increase the risk of grade ≥3 infection (P = 0.04), it may not increase the risk of grade ≥3 radiation pneumonitis (P = 0.09) during the CCT period. CCT after concurrent CRT may provide additional benefits in the treatment of LA-NSCLC. Although this therapeutic strategy did not prolong PFS, further assessment is warranted.

  20. Cancer Genomics Identifies Regulatory Gene Networks Associated with the Transition from Dysplasia to Advanced Lung Adenocarcinomas Induced by c-Raf-1

    PubMed Central

    Rohrbeck, Astrid; Borlak, Jürgen

    2009-01-01

    Background Lung cancer is a leading cause of cancer morbidity. To improve an understanding of molecular causes of disease a transgenic mouse model was investigated where targeted expression of the serine threonine kinase c-Raf to respiratory epithelium induced initialy dysplasia and subsequently adenocarcinomas. This enables dissection of genetic events associated with precancerous and cancerous lesions. Methodology/Principal Findings By laser microdissection cancer cell populations were harvested and subjected to whole genome expression analyses. Overall 473 and 541 genes were significantly regulated, when cancer versus transgenic and non-transgenic cells were compared, giving rise to three distinct and one common regulatory gene network. At advanced stages of tumor growth predominately repression of gene expression was observed, but genes previously shown to be up-regulated in dysplasia were also up-regulated in solid tumors. Regulation of developmental programs as well as epithelial mesenchymal and mesenchymal endothelial transition was a hall mark of adenocarcinomas. Additionaly, genes coding for cell adhesion, i.e. the integrins and the tight and gap junction proteins were repressed, whereas ligands for receptor tyrosine kinase such as epi- and amphiregulin were up-regulated. Notably, Vegfr- 2 and its ligand Vegfd, as well as Notch and Wnt signalling cascades were regulated as were glycosylases that influence cellular recognition. Other regulated signalling molecules included guanine exchange factors that play a role in an activation of the MAP kinases while several tumor suppressors i.e. Mcc, Hey1, Fat3, Armcx1 and Reck were significantly repressed. Finally, probable molecular switches forcing dysplastic cells into malignantly transformed cells could be identified. Conclusions/Significance This study provides insight into molecular pertubations allowing dysplasia to progress further to adenocarcinoma induced by exaggerted c-Raf kinase activity. PMID:19812696

  1. Concomitant etoposide and cisplatin provided improved survival compared with docetaxel and cisplatin in patients with locally advanced non-small cell lung cancer treated with chemoradiotherapy

    PubMed Central

    Sen, Fatma; Tambas, Makbule; Ozkaya, Kubra; Guveli, Murat Emin; Ciftci, Rumeysa; Ozkan, Berker; Oral, Ethem Nezih; Saglam, Esra Kaytan; Saip, Pinar; Toker, Alper; Demir, Adalet; Firat, Pinar; Aydiner, Adnan; Eralp, Yesim

    2016-01-01

    Abstract Presently, there is no consensus regarding which chemotherapy regimen is best to administer with radiotherapy in patients with locally advanced non-small-cell lung cancer (LA-NSCLC). Herein, our aim was to compare the outcome of patients treated with either etoposide–cisplatin (EP) or docetaxel–cisplatin (DP) in this curative setting. Patients treated with either EP or DP and concurrent radiotherapy from 2004 to2012 were identified and their detailed medical records and follow-up information were obtained for analysis in this retrospective study. Survival rates were compared using Cox proportional hazards regression models with adjustments for confounding parameters provided by propensity score methods. A total of 105 patients were treated with concurrent chemoradiotherapy for LA-NSCLC (stage IIB-IIIA-IIIB). The median ages were 54 years (range, 32–70 years) and 55 years (range, 37–73 years) in the EP (n = 50) and DP (n = 55) groups, respectively. The median follow-up time was 27 months (range, 1–132 months) in the EP group and 19 months (range, 1–96 months) in DP group. There was no significant difference in baseline clinicopathologic features including age, sex, performance status, histologic subtype, and clinical TNM stages between groups. In the univariate analysis, the median overall survival of patients treated with EP was higher than that of patients treated with DP (41 vs. 20 months, P = 0.003). Multivariate analysis further revealed a survival advantage with EP compared with DP (hazard ratio [HR], 0.46; 95% confidence interval: 0.25–0.83; P = 0.009). The toxicity profile of the 2treatment groups was similar except that pulmonary toxicity was higher in the DP group (grade 3–4: 0% vs. 6%, P = 0.024). Concurrent chemoradiotherapy with EP may provide more favorable outcomes than DP and with an acceptable safety profile. PMID:27472701

  2. Usefulness of Serum Carcinoembryonic Antigen (CEA) in evaluating response to chemotherapy in patients with advanced non small-cell lung cancer: a prospective cohort study

    PubMed Central

    2013-01-01

    Background High serum carcinoembryonic antigen (CEA) levels are an independent prognostic factor for recurrence and survival in patients with non-small cell lung cancer (NSCLC). Its role as a predictive marker of treatment response has not been widely characterized. Methods 180 patients with advanced NSCLC (stage IIIB or Stage IV), who had an elevated CEA serum level (>10 ng/ml) at baseline and who had no more than one previous chemotherapy regimen, were included. CEA levels were measured after two treatment cycles of platinum based chemotherapy (93%) or a tyrosine kinase inhibitor (7%). We assessed the change in serum CEA levels and the association with response measured by RECIST criteria. Results After two chemotherapy cycles, the patients who achieved an objective response (OR, 28.3%) had a reduction of CEA levels of 55.6% (95% CI 64.3-46.8) compared to its basal level, with an area under the ROC curve (AURC) of 0.945 (95% CI 0.91-0.99), and a sensitivity and specificity of 90.2 and 89.9%, respectively, for a CEA reduction of ≥14%. Patients that achieved a decrease in CEA levels ≥14% presented an overall response in 78% of cases, stable disease in 20.3% and progression in 1.7%, while patients that did not attain a reduction ≥14% had an overall response of 4.1%, stable disease of 63.6% and progression of 32.2% (p < 0.001). Patients with stable (49.4%) and progressive disease (22.2%) had an increase of CEA levels of 9.4% (95% CI 1.5-17.3) and 87.5% (95% CI 60.9-114) from baseline, respectively (p < 0.001). The AURC for progressive disease was 0.911 (95% CI 0.86-0.961), with sensitivity and specificity of 85 and 15%, respectively, for a CEA increase of ≥18%. PFS was longer in patients with a ≥14% reduction in CEA (8.7 vs. 5.1 months, p < 0.001). Reduction of CEA was not predictive of OS. Conclusions A CEA level reduction is a sensitive and specific marker of OR, as well as a sensitive indicator for progression to chemotherapy in patients

  3. Efficacy of Second-line Tyrosine Kinase Inhibitors in the Treatment of Metastatic Advanced Non-small-cell Lung Cancer Harboring Exon 19 and 21 EGFR Mutations

    PubMed Central

    Zheng, Zhen; Jin, Xiance; Lin, Baochai; Su, Huafang; Chen, Hanbin; Fei, Shaoran; Zhao, Lihao; Deng, Xia; Xie, Deyao; Xie, Congying

    2017-01-01

    Background: Although superior clinical benefits of first-line epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in the treatment of advanced non-small-cell lung cancer (NSCLC) had been reported with different sensitivity, the sensitivity of second-line TKIs in NSCLC patients with different EFGR mutations was unknown. The purpose of this study is to investigate the clinical outcome of second-line EGFR-TKIs in the treatment of NSCLC patients according to different EGFR genotypes. Methods: The treatment outcomes of 166 NSCLC patients with different EGFR mutations treated by second-line TKIs were retrospectively reviewed. The efficacy was evaluated with Pearson chi-square or Fisher's exact tests, Log-rank test and Cox proportional hazards model. Results: The disease control rate (DCR) and objective response rate (ORR) of enrolled NSCLC patients were 77.7% and 11.4%, respectively. The exon 19 deletion group had a significantly longer median progression-free survival (PFS) (6.7 vs. 4.5 months, P=0.002) and overall survival (OS) (13.7 vs. 11.7 months, P=0.02) compared with the exon 19 L858R mutation group for NSCLC patients, as well for patients with brain metastasis [PFS: (6.7 vs. 3.9 months, p<0.001), OS: (13.7 vs. 7.9 months, p=0.006)]. No significant difference on PFS and OS was observed between exon 19 deletion and L858R mutation group for patients with bone metastasis. EGFR genotype and ECOG PS were independent predictors of PFS. Never smoking, exon 19 deletion, EGOC PS (0-1) and no brain metastasis were correlated with longer OS. No significant difference on side effect between exon 19 and 21 mutation group was observed. Conclusions: NSCLC patients harboring exon 19 deletion achieved better PFS and OS than those with L858R mutation, indicating that EGFR mutation is a significant prognostic factor for advanced NSCLC patients with and without brain metastasis receiving second-line EGFR-TKIs treatment. PMID:28367239

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

    PubMed Central

    Dong, Xinzhe; Sun, Xiaorong; Sun, Lu; Maxim, Peter G.; Xing, Lei; Huang, Yong; Li, Wenwu; Wan, Honglin; Yu, Jinming

    2016-01-01

    Introduction 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). Methods 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). Results 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). Conclusions The metabolic tumor heterogeneity change during CCRT characterized by global and local scale textural features may be

  5. Costs of adverse events associated with erlotinib or afatinib in first-line treatment of advanced EGFR-positive non-small cell lung cancer

    PubMed Central

    Isla, Dolores; De Castro, Javier; Juan, Oscar; Grau, Santiago; Orofino, Javier; Gordo, Rocío; Rubio-Terrés, Carlos; Rubio-Rodríguez, Darío

    2017-01-01

    Objectives Epidermal growth factor receptor–tyrosine kinase inhibitors (EGFR-TKIs) are an established treatment for advanced non-small cell lung cancer (NSCLC) with EGFR mutation. According to published meta-analyses, no significant efficacy differences have been demonstrated between erlotinib and afatinib. However, the incidence of EGFR–TKI-related adverse events (AEs) was lower with erlotinib. This study compares the cost of management of the AEs associated with these two drugs from the perspective of the Spanish National Health System (NHS). Methods The frequency of AEs was established from a recently published meta-analysis. In Spain, the daily cost of both drugs can be considered similar; as a result, only the costs of management of the AEs were considered. Costs and resource utilization in the management of the AEs were estimated by a panel of Spanish oncologists and from studies previously carried out in Spain. A probabilistic analysis was performed based on a Monte Carlo simulation. Results The model generated 1,000 simulations. The total cost per patient treated with erlotinib and afatinib was €657.44 and €1,272.15, respectively. With erlotinib, the cost per patient and per AE of grades ≤2 and ≥3 was €550.86 and €106.58, respectively, whereas the cost with afatinib was €980.63 and €291.52, respectively. The reduction in the number of AEs with erlotinib could avoid a mean cost for the NHS of €614.71 (95% CI: €342.57–881.29) per patient. Conclusion In advanced EGFR mutation-positive NSCLC patients, first-line treatment with erlotinib could reduce health care costs for the NHS, due to a decrease in the AE rate compared with afatinib. In long-term treatments, the avoidance of complications and the lowering of costs associated with the management of AEs are relevant factors that contribute to the sustainability of the health system. PMID:28115857

  6. Genetic variations in the transforming growth factor-beta pathway as predictors of survival in advanced non-small cell lung cancer

    PubMed Central

    Stewart, David J.; Spitz, Margaret R.; Hildebrandt, Michelle A.T.; Lu, Charles; Lin, Jie; Gu, Jian; Huang, Maosheng; Lippman, Scott M.; Wu, Xifeng

    2011-01-01

    The magnitude of benefit is variable for advanced non-small cell lung cancer (NSCLC) patients receiving platinum-based chemotherapy. The purpose of this study is to determine whether genetic variations in the transforming growth factor-beta (TGF-β) pathway are associated with clinical outcomes in NSCLC patients receiving first-line platinum-based chemotherapy. Five hundred and ninety-eight advanced-stage NSCLC patients who received first-line platinum-based chemotherapy with or without radiotherapy were recruited at the MD Anderson Cancer Center between 1995 and 2007. DNA from blood was genotyped for 227 single nucleotide polymorphisms (SNPs) in 23 TGF-β pathway-related genes to evaluate their associations with overall survival. In individual SNP analysis, 22 variants were significantly associated with overall survival, of which the strongest associations were found for BMP2:rs235756 [hazard ratio (HR) = 1.45; 95% confidence interval (CI), 1.11–1.90] and SMAD3:rs4776342 (HR = 1.25; 95% CI, 1.06–1.47). Fifteen and 18 genetic loci displayed treatment-specific associations for chemotherapy and chemoradiation, respectively, identifying a majority of the cases who would be predicted to respond favorably to a specific treatment regimen. BMP2:rs235753 and a haplotype in SMAD3 were associated with overall survival for both treatment modalities. Cumulative effect analysis showed that multiple risk genotypes had a significant dose-dependent effect on overall survival (Ptrend = 2.44 x 10−15). Survival tree analysis identified subgroups of patients with dramatically different median survival times of 45.39 versus 13.55 months and 18.02 versus 5.89 months for high- and low- risk populations when treated with chemoradiation and chemotherapy, respectively. These results suggest that genetic variations in the TGF-β pathway are potential predictors of overall survival in NSCLC patients treated with platinum-based chemotherapy with or without radiation. PMID:21515830

  7. Iron refractory iron deficiency anemia

    PubMed Central

    De Falco, Luigia; Sanchez, Mayka; Silvestri, Laura; Kannengiesser, Caroline; Muckenthaler, Martina U.; Iolascon, Achille; Gouya, Laurent; Camaschella, Clara; Beaumont, Carole

    2013-01-01

    Iron refractory iron deficiency anemia is a hereditary recessive anemia due to a defect in the TMPRSS6 gene encoding Matriptase-2. This protein is a transmembrane serine protease that plays an essential role in down-regulating hepcidin, the key regulator of iron homeostasis. Hallmarks of this disease are microcytic hypochromic anemia, low transferrin saturation and normal/high serum hepcidin values. The anemia appears in the post-natal period, although in some cases it is only diagnosed in adulthood. The disease is refractory to oral iron treatment but shows a slow response to intravenous iron injections and partial correction of the anemia. To date, 40 different Matriptase-2 mutations have been reported, affecting all the functional domains of the large ectodomain of the protein. In vitro experiments on transfected cells suggest that Matriptase-2 cleaves Hemojuvelin, a major regulator of hepcidin expression and that this function is altered in this genetic form of anemia. In contrast to the low/undetectable hepcidin levels observed in acquired iron deficiency, in patients with Matriptase-2 deficiency, serum hepcidin is inappropriately high for the low iron status and accounts for the absent/delayed response to oral iron treatment. A challenge for the clinicians and pediatricians is the recognition of the disorder among iron deficiency and other microcytic anemias commonly found in pediatric patients. The current treatment of iron refractory iron deficiency anemia is based on parenteral iron administration; in the future, manipulation of the hepcidin pathway with the aim of suppressing it might become an alternative therapeutic approach. PMID:23729726

  8. Refractories for lining blast furnaces

    SciTech Connect

    Fedoruk, R.M.; Baksheeva, V.S.; Karyakina, E.L.; Khmelenko, T.P.; Pitak, N.V.

    1986-01-01

    The authors develop and introduce a technology for the production of chamotte kaolin refractories with a porosity of not more than 12% and a mass proportion of not less than 42% A1/sub 2/O/sub 3/ on the basis of chamotte from high-grade Polozhe kaolin, and also additions to the batch of finely milled mullite-corundum chamotte. Using the new technology, a batch of goods designated ShPD-42 was produced for lining the shafts, bosh, and upper parts of blast furnaces of large capacity.

  9. Refractory disease in autoimmune diseases.

    PubMed

    Vasconcelos, Carlos; Kallenberg, Cees; Shoenfeld, Yehuda

    2011-09-01

    Refractory disease (RD) definition has different meanings but it is dynamic, according to knowledge and the availability of new drugs. It should be differentiated from severe disease and damage definitions and it must take into account duration of adequate therapy and compliance of the patient. It can be related to inadequate or inefficacious treatment or to pathogenesis. RD definition has multiple implications to clinical guidelines and to the use of off-label drugs. It should not be regarded as lost cases and prospective studies, registries and clinical trials should be planned.

  10. Genetics Home Reference: iron-refractory iron deficiency anemia

    MedlinePlus

    ... refractory iron deficiency anemia iron-refractory iron deficiency anemia Enable Javascript to view the expand/collapse boxes. ... All Close All Description Iron-refractory iron deficiency anemia is one of many types of anemia , which ...

  11. Refractory pulmonary sarcoidosis – proposal of a definition and recommendations for the diagnostic and therapeutic approach

    PubMed Central

    Korsten, Peter; Strohmayer, Katharina; Baughman, Robert P.; Sweiss, Nadera J.

    2015-01-01

    Patients with sarcoidosis undergo spontaneous remission or may be effectively controlled with glucocorticoids alone in many cases. Progressive and refractory pulmonary sarcoidoisis constitute more than 10% of patients seen at specialized centers. Pulmonary fibrosis and associated complications, such as infections and pulmonary hypertension are leading causes of mortality. No universal definition of refractoriness exists, we therefore propose classifying patients as having refractory disease when the following criteria are fulfilled: (1) progressive disease despite at least 10 mg of prednisolone or equivalent for at least three months and need for additional disease-modifying anti-sarcoid drugs due to lack of efficacy, drug toxicity or intolerability and (2) treatment started for significant impairment of life due to progressive pulmonary symptoms. Both criteria should be fulfilled. Treatment options in addition to or instead of glucocorticoids for these patients include second- (methotrexate, azathioprine, leflunomide) and third-line agents (infliximab, adalimumab). Other immunmodulating agents can be used, but the evidence is very limited. Newer agents with anti-fibrotic properties, such as pirfenidone or nintedanib, might hold promise also for the pulmonary fibrosis seen in sarcoidosis. Treating physicians have to actively look for potentially treatable complications, such as pulmonary hypertension, cardiac disease or infections before patients should be classified as treatment-refractory. Ultimately, lung transplantation has to be considered as treatment option for patients not responding to medical therapy. In this review, we aim to propose a new definition of refractoriness, describe the associated clinical features and suggest the therapeutic approach. PMID:26973429

  12. Neuroimaging evaluation in refractory epilepsy

    PubMed Central

    Granados, Ana M; Orejuela, Juan F

    2015-01-01

    Purpose To describe the application of neuroimaging analysis, compared to neuropsychological tests and video-electroencephalogram, for the evaluation of refractory epilepsy in a reference centre in Cali, Colombia. Methods Between March 2013 and November 2014, 29 patients, 19 men and 10 women, aged 9–65 years and with refractory epilepsy, were assessed by structural and functional magnetic resonance imaging while performing tasks related to language, verbal and non-verbal memory. Also, volumetric evaluation was performed. A 1.5 Tesla magnetic resonance imaging scanner was used in all cases. Results Neuroimaging evaluation identified 13 patients with mesial temporal sclerosis. The remaining patients were classified as: 10 patients with neoplastic masses, two patients with cortical atrophy, two patients with scarring lesions and two patients with non-structural aetiology. Among patients with mesial temporal sclerosis, comparison between techniques for lateralising the epileptogenic foci was made; the κ index between functional magnetic resonance imaging and hippocampi volumetry was κ = 1.00, agreement between neuroimaging and video-electroencephalogram was good (κ = 0.78) and comparison with a neuropsychological test was mild (κ = 0.24). Conclusions Neuroimaging studies allow the assessment of functional and structural damage related to epileptogenic lesions and foci, and are helpful to select surgical treatment, conduct intraoperative neuronavigation techniques, predict surgical deficits and evaluate patient recovery. PMID:26427897

  13. Refractory Glass Seals for SOFC

    SciTech Connect

    Chou, Y. S.; Stevenson, Jeffry W.

    2011-07-01

    One of the critical challenges facing planar solid oxide fuel cell (SOFC) technology is the need for reliable sealing technology. Seals must exhibit long-term stability and mechanical integrity in the high temperature SOFC environment during normal and transient operation. Several different approaches for sealing SOFC stacks are under development, including glass or glass-ceramic seals, metallic brazes, and compressive seals. Among glass seals, rigid glass-ceramics, self-healing glass, and composite glass approaches have been investigated under the SECA Core Technology Program. The U.S. Department of Energy's Pacific Northwest National Laboratory (PNNL) has developed the refractory glass approach in light of the fact that higher sealing temperatures (e.g., 930-1000 degrees C) may enhance the ultimate in-service bulk strength and electrical conductivity of contact materials, as well as the bonding strength between contact materials and adjacent SOFC components, such as interconnect coatings and electrodes. This report summarizes the thermal, chemical, mechanical, and electrical properties of the refractory sealing glass.

  14. Spectral reflecting characteristics of dinas refractory

    SciTech Connect

    Zapechnikov, V.N.; Pushkin, V.T.; Zen'kovskii, A.G.

    1987-09-01

    This article outlines a nondestructive testing format which uses spectral reflectance to assess the remaining service life, the thermal degradation, and the insulating effectiveness of refractories used as insulating liners in glass melters. Thermal as well as mechanical influences on the reflectance behavior of several refractories are discussed.

  15. [ENDOSCOPIC LUNG VOLUME REDUCTION IN PULMONARY EMPHYSEMA].

    PubMed

    Duysinx, B; Heinen, V; Louis, R; Corhay, J-L

    2015-12-01

    Emphysema is characterized by an irreversible alveolar destruction, a progressive lung hyperinflation and a dysfunction of respiratory muscles. It induces a respiratory functional limitation and a decrease of quality of life. Endoscopic lung volume reduction represents a potential alternative to surgical treatments for advanced heterogeneous emphysema without concomitant surgical morbidity. The different bronchoscopic systems for lung volume reduction currently under evaluation are presented.

  16. Iron-refractory iron deficiency anemia.

    PubMed

    Yılmaz Keskin, Ebru; Yenicesu, İdil

    2015-03-05

    Iron is essential for life because it is indispensable for several biological reactions, such as oxygen transport, DNA synthesis, and cell proliferation. Over the past few years, our understanding of iron metabolism and its regulation has changed dramatically. New disorders of iron metabolism have emerged, and the role of iron as a cofactor in other disorders has begun to be recognized. The study of genetic conditions such as hemochromatosis and iron-refractory iron deficiency anemia (IRIDA) has provided crucial insights into the molecular mechanisms controlling iron homeostasis. In the future, these advances may be exploited to improve treatment of both genetic and acquired iron disorders. IRIDA is caused by mutations in TMPRSS6, the gene encoding matriptase-2, which downregulates hepcidin expression under conditions of iron deficiency. The typical features of this disorder are hypochromic, microcytic anemia with a very low mean corpuscular volume of erythrocytes, low transferrin saturation, no (or inadequate) response to oral iron, and only a partial response to parenteral iron. In contrast to classic iron deficiency anemia, serum ferritin levels are usually low-normal, and serum or urinary hepcidin levels are inappropriately high for the degree of anemia. Although the number of cases reported thus far in the literature does not exceed 100, this disorder is considered the most common of the "atypical" microcytic anemias. The aim of this review is to share the current knowledge on IRIDA and increase awareness in this field.

  17. Iron-Refractory Iron Deficiency Anemia

    PubMed Central

    Yılmaz Keskin, Ebru; Yenicesu, İdil

    2015-01-01

    Iron is essential for life because it is indispensable for several biological reactions, such as oxygen transport, DNA synthesis, and cell proliferation. Over the past few years, our understanding of iron metabolism and its regulation has changed dramatically. New disorders of iron metabolism have emerged, and the role of iron as a cofactor in other disorders has begun to be recognized. The study of genetic conditions such as hemochromatosis and iron-refractory iron deficiency anemia (IRIDA) has provided crucial insights into the molecular mechanisms controlling iron homeostasis. In the future, these advances may be exploited to improve treatment of both genetic and acquired iron disorders. IRIDA is caused by mutations in TMPRSS6, the gene encoding matriptase-2, which downregulates hepcidin expression under conditions of iron deficiency. The typical features of this disorder are hypochromic, microcytic anemia with a very low mean corpuscular volume of erythrocytes, low transferrin saturation, no (or inadequate) response to oral iron, and only a partial response to parenteral iron. In contrast to classic iron deficiency anemia, serum ferritin levels are usually low-normal, and serum or urinary hepcidin levels are inappropriately high for the degree of anemia. Although the number of cases reported thus far in the literature does not exceed 100, this disorder is considered the most common of the “atypical” microcytic anemias. The aim of this review is to share the current knowledge on IRIDA and increase awareness in this field. PMID:25805669

  18. Sharp Refractory Composite Leading Edges on Hypersonic Vehicles

    NASA Technical Reports Server (NTRS)

    Walker, Sandra P.; Sullivan, Brian J.

    2003-01-01

    On-going research of advanced sharp refractory composite leading edges for use on hypersonic air-breathing vehicles is presented in this paper. Intense magnitudes of heating and of heating gradients on the leading edge lead to thermal stresses that challenge the survivability of current material systems. A fundamental understanding of the problem is needed to further design development. Methodology for furthering the technology along with the use of advanced fiber architectures to improve the thermal-structural response is explored in the current work. Thermal and structural finite element analyses are conducted for several advanced fiber architectures of interest. A tailored thermal shock parameter for sharp orthotropic leading edges is identified for evaluating composite material systems. The use of the tailored thermal shock parameter has the potential to eliminate the need for detailed thermal-structural finite element analyses for initial screening of material systems being considered for a leading edge component.

  19. Low-Chrome/Chrome Free Refractories for Slagging Gasifiers

    SciTech Connect

    Bennett, J.P.; Kwong, K.-S.; Powell, C.P.; Thomas, H.; Petty, A.V., Jr.

    2007-01-01

    Gasifiers are containment vessels used to react carbon-containing materials with oxygen and water, producing syngas (CO and H2) that is used in chemical and power production. It is also a potential source of H2 in a future hydrogen economy. Air cooled slagging gasifiers are one type of gasifier, operating at temperatures from 1275-1575º C and at pressures of 400 psi or higher. They typically use coal or petroleum coke as the carbon source, materials which contain ash impurities that liquefy at the gasification temperatures, producing liquid slag in quantities of 100 or more tons/day, depending on the carbon fed rate and the percent ash present in the feedstock. The molten slag is corrosive to refractory linings, causing chemical dissolution and spalling. The refractory lining is composed of chrome oxide, alumina, and zirconia; and is replaced every 3-24 months. Gasifier users would like greater on-line availability and reliability of gasifier liners, something that has impacted gasifier acceptance by industry. Research is underway at NETL to improve refractory service life and to develop a no-chrome or low-chrome oxide alternative refractory liner. Over 250 samples of no- or low-chrome oxide compositions have been evaluated for slag interactions by cup testing; with potential candidates for further studies including those with ZrO2, Al2O3, and MgO materials. The development of improved liner materials is necessary if technologies such as IGCC and DOE’s Near Zero Emissions Advanced Fossil Fuel Power Plant are to be successful and move forward in the marketplace.

  20. Update in palliative management of hormone refractory cancer of prostate

    PubMed Central

    Singh, Pratipal; Srivastava, Aneesh

    2007-01-01

    Hormone refractory prostate cancer (HRPC) is an incurable disease and as in the pressure sensitive adhesive era the median survival of patients is increasing, these men increasingly develop symptomatic problems as a result of advanced local and or metastatic disease during their progression to death. Recently, it has been shown that it is possible to improve survival in this group of patients with use of chemotherapy which reinforces the need of better options in palliative care. We discus the various clinical problems (Part I) and treatment options of palliative care (Part II) and try to formulate an action plan in this review. PMID:19675762

  1. Combined chemical-biological treatment of wastewater containing refractory pollutants.

    PubMed

    Jeworski, M; Heinzle, E

    2000-01-01

    Biological processes are usually most efficient for degrading pollutants occurring in wastewater. Refractory and toxic compounds contained limit their applicability. In such cases combinations with chemical oxidation processes may improve the overall efficiency and efficacy. Most suitable oxidation processes for combination with biological treatment are wet air oxidation, ozonation, hydrogen peroxide treatment and other advanced oxidation processes. Most effective are OH-radicals produced in all these oxidation processes. Chemical oxidation produces intermediates with usually improved biodegradability. Process combinations may be serial or with recycling between chemical oxidation and biological treatment. Design criteria, control of combined processes and recent applications are reviewed.

  2. Palliative care in lung cancer.

    PubMed

    Ferrell, Betty; Koczywas, Marianna; Grannis, Fred; Harrington, Annie

    2011-04-01

    Advancements in the surgical and medical treatment of lung cancer have resulted in more favorable short-term survival outcomes. After initial treatment, lung cancer requires continued surveillance and follow-up for long-term side effects and possible recurrence. The integration of quality palliative care into routine clinical care of patients with lung cancer after surgical intervention is essential in preserving function and optimizing quality of life through survivorship. An interdisciplinary palliative care model can effectively link patients to the appropriate supportive care services in a timely fashion. This article describes the role of palliative care for patients with lung cancer.

  3. Refractory for Black Liquor Gasifiers

    SciTech Connect

    William L. Headrick Jr; Musa Karakus; Xiaoting Laing

    2005-10-01

    The University of Missouri-Rolla will identify materials that will permit the safe, reliable and economical operation of combined cycle gasifiers by the pulp and paper industry. The primary emphasis of this project will be to resolve the material problems encountered during the operation of low-pressure high-temperature (LPHT) and low-pressure low-temperature (LPLT) gasifiers while simultaneously understanding the materials barriers to the successful demonstration of high-pressure high-temperature (HPHT) black liquor gasifiers. This study will define the chemical, thermal and physical conditions in current and proposed gasifier designs and then modify existing materials and develop new materials to successfully meet the formidable material challenges. Resolving the material challenges of black liquor gasification combined cycle technology will provide energy, environmental, and economic benefits that include higher thermal efficiencies, up to three times greater electrical output per unit of fuel, and lower emissions. In the near term, adoption of this technology will allow the pulp and paper industry greater capital effectiveness and flexibility, as gasifiers are added to increase mill capacity. In the long term, combined-cycle gasification will lessen the industry's environmental impact while increasing its potential for energy production, allowing the production of all the mill's heat and power needs along with surplus electricity being returned to the grid. An added benefit will be the potential elimination of the possibility of smelt-water explosions, which constitute an important safety concern wherever conventional Tomlinson recovery boilers are operated. Developing cost-effective materials with improved performance in gasifier environments may be the best answer to the material challenges presented by black liquor gasification. Refractory materials may be selected/developed that either react with the gasifier environment to form protective surfaces in

  4. REFRACTORY FOR BLACK LIQUOR GASIFIERS

    SciTech Connect

    William L. Headrick Jr; Musa Karakus; Jun Wei

    2005-03-01

    The University of Missouri-Rolla will identify materials that will permit the safe, reliable and economical operation of combined cycle gasifiers by the pulp and paper industry. The primary emphasis of this project will be to resolve the material problems encountered during the operation of low-pressure high-temperature (LPHT) and low-pressure low-temperature (LPLT) gasifiers while simultaneously understanding the materials barriers to the successful demonstration of high-pressure high-temperature (HPHT) black liquor gasifiers. This study will define the chemical, thermal and physical conditions in current and proposed gasifier designs and then modify existing materials and develop new materials to successfully meet the formidable material challenges. Resolving the material challenges of black liquor gasification combined cycle technology will provide energy, environmental, and economic benefits that include higher thermal efficiencies, up to three times greater electrical output per unit of fuel, and lower emissions. In the near term, adoption of this technology will allow the pulp and paper industry greater capital effectiveness and flexibility, as gasifiers are added to increase mill capacity. In the long term, combined-cycle gasification will lessen the industry's environmental impact while increasing its potential for energy production, allowing the production of all the mill's heat and power needs along with surplus electricity being returned to the grid. An added benefit will be the potential elimination of the possibility of smelt-water explosions, which constitute an important safety concern wherever conventional Tomlinson recovery boilers are operated. Developing cost-effective materials with improved performance in gasifier environments may be the best answer to the material challenges presented by black liquor gasification. Refractory materials may be selected/developed that either react with the gasifier environment to form protective surfaces in

  5. A meta-analysis of efficacy and safety of antibodies targeting PD-1/PD-L1 in treatment of advanced nonsmall cell lung cancer

    PubMed Central

    Wang, Cuihua; Yu, Xuetao; Wang, Wei

    2016-01-01

    Abstract Background: Nonsmall cell lung cancer (NSCLC)-patients treated with standard chemotherapy experienced progression rapidly. A novel therapy based on programed death 1 (PD-1)/programed death ligand 1 (PD-L1) inhibitors showed an increasing potential in several malignancies including advanced NSCLC. Objectives: This article is a meta-analysis aiming to systematically evaluate the efficacy and safety profiles of PD-1/PD-L1 agents in patients with NSCLC. Data sources: Data were collected from eligible studies searched from PubMed, ScienceDirect, and Web of Science. Synthesis methods: Pooled hazard ratio (HR) for overall survival (OS) and progression-free survival (PFS) was estimated to assess the efficacy of PD-1/PD-L1 inhibitors versus docetaxel, pooled odds ratio (OR) was calculated for objective response rate (ORR). The overall frequency was estimated for 1-year OS, 1-year progression-free survival, and ORR. A subgroup analysis among NSCLC patients tested with different epidermal growth factor receptor (EGFR) status was also performed to figure out the relationship between EGFR status and efficacy of PD-1/PD-L1 therapies. OR for occurrence of any grade and grade 3 to 5 treatment-related adverse effect was calculated for evaluating the safety of PD-1/PD-L1 therapies. Results: Nine studies were included in this analysis. The pooled HRs for OS and PFS were 0.68 (95% confidence interval [CI] 0.61–0.75) and 0.83 (95% CI 0.75–0.91), respectively, the pooled OR for ORR was 1.83 (95% CI 1.41–2.36), indicating a significant improvement in OS, PFS, and ORR. In the results of subgroup analysis, the HR for OS in NSCLC patients was 1.05 (95% CI 0.69–1.59) in patients with mutant EGFR and 0.66 (95% CI 0.57–0.77) in patients with wild-type EGFR status. OR for occurrence was 0.36 (95% CI 0.28–0.46) in any grade treatment-related adverse effect and 0.18 (95% CI 0.14–0.22) in grade 3 to 5 treatment-related adverse effect, suggesting a superior safety profile of

  6. Does Response to Induction Chemotherapy Predict Survival for Locally Advanced Non-Small-Cell Lung Cancer? Secondary Analysis of RTOG 8804/8808

    SciTech Connect

    McAleer, Mary Frances; Moughan, Jennifer M.S.; Byhardt, Roger W.; Cox, James D.; Sause, William T.; Komaki, Ritsuko

    2010-03-01

    Purpose: Induction chemotherapy (ICT) improves survival compared with radiotherapy (RT) alone in locally advanced non-small-cell lung cancer (LANSCLC) patients with good prognostic factors. Concurrent chemoradiotherapy (CCRT) is superior to ICT followed by RT. The question arises whether ICT response predicts the outcome of patients subsequently treated with CCRT or RT. Methods and Materials: Between 1988 and 1992, 194 LANSCLC patients were treated prospectively with ICT (two cycles of vinblastine and cisplatin) and then CCRT (cisplatin plus 63 Gy for 7 weeks) in the Radiation Therapy Oncology Group 8804 trial (n = 30) or ICT and then RT (60 Gy/6 wk) on Radiation Therapy Oncology Group 8808 trial (n = 164). Of the 194 patients, 183 were evaluable and 141 had undergone a postinduction assessment. The overall survival (OS) of those with complete remission (CR) or partial remission (PR) was compared with that of patients with stable disease (SD) or progressive disease (PD) after ICT. Results: Of the 141 patients, 6, 30, 99, and 6 had CR, PR, SD, and PD, respectively. The log-rank test showed a significant difference (p <0.0001) in OS when the response groups were compared (CR/PR vs. SD/PD). On univariate and multivariate analyses, a trend was seen toward a response to ICT with OS (p = 0.097 and p = 0.06, respectively). A squamous histologic type was associated with worse OS on univariate and multivariate analyses (p = 0.031 and p = 0.018, respectively). SD/PD plus a squamous histologic type had a hazard ratio of 2.25 vs. CR/PR plus a nonsquamous histologic type (p = 0.007) on covariate analysis. Conclusion: The response to ICT was associated with a significant survival difference when the response groups were compared. A response to ICT showed a trend toward, but was not predictive of, improved OS in LANSCLC patients. Patients with SD/PD after ICT and a squamous histologic type had the poorest OS. These data suggest that patients with squamous LANSCLC might benefit

  7. The Impact of Local and Regional Disease Extent on Overall Survival in Patients With Advanced Stage IIIB/IV Non-Small Cell Lung Carcinoma

    SciTech Connect

    Higginson, Daniel S.; Chen, Ronald C.; Tracton, Gregg; Morris, David E.; Halle, Jan; Rosenman, Julian G.; Stefanescu, Mihaela; Pham, Erica; Socinski, Mark A.; Marks, Lawrence B.

    2012-11-01

    Purpose: Patients with advanced stage IIIB or stage IV non-small cell lung carcinoma are typically treated with initial platinum-based chemotherapy. A variety of factors (eg, performance status, gender, age, histology, weight loss, and smoking history) are generally accepted as predictors of overall survival. Because uncontrolled pulmonary disease constitutes a major cause of death in these patients, we hypothesized that clinical and radiographic factors related to intrathoracic disease at diagnosis may be prognostically significant in addition to conventional factors. The results have implications regarding the selection of patients for whom palliative thoracic radiation therapy may be of most benefit. Methods and Materials: We conducted a pooled analysis of 189 patients enrolled at a single institution into 9 prospective phase II and III clinical trials involving first-line, platinum-based chemotherapy. Baseline clinical and radiographic characteristics before trial enrollment were analyzed as possible predictors for subsequent overall survival. To assess the relationship between anatomic location and volume of disease within the thorax and its effect on survival, the pre-enrollment computed tomography images were also analyzed by contouring central and peripheral intrapulmonary disease. Results: On univariate survival analysis, multiple pulmonary-related factors were significantly associated with worse overall survival, including pulmonary symptoms at presentation (P=.0046), total volume of intrathoracic disease (P=.0006), and evidence of obstruction of major bronchi or vessels on prechemotherapy computed tomography (P<.0001). When partitioned into central and peripheral volumes, central (P<.0001) but not peripheral (P=.74) disease was associated with worse survival. On multivariate analysis with known factors, pulmonary symptoms (hazard ratio, 1.46; P=.042), central disease volume (hazard ratio, 1.47; P=.042), and bronchial/vascular compression (hazard ratio, 1

  8. REFRACTORY FOR BLACK LIQUOR GASIFIERS

    SciTech Connect

    William L. Headrick Jr.; Alireza Rezaie

    2003-12-01

    The University of Missouri-Rolla will identify materials that will permit the safe, reliable and economical operation of combined cycle gasifiers by the pulp and paper industry. The primary emphasis of this project will be to resolve the materials problems encountered during the operation of low-pressure high-temperature (LFHT) and low-pressure low-temperature (LPLT) gasifiers while simultaneously understanding the materials barriers to the successful demonstration of high-pressure high-temperature (HPHT) black liquor gasifiers. This study will define the chemical, thermal and physical conditions in current and proposed gasifier designs and then modify existing materials and develop new materials to successfully meet the formidable material challenges. Resolving the material challenges of black liquor gasification combined cycle technology will provide energy, environmental, and economic benefits that include higher thermal efficiencies, up to three times greater electrical output per unit of fuel, and lower emissions. In the near term, adoption of this technology will allow the pulp and paper industry greater capital effectiveness and flexibility, as gasifiers are added to increase mill capacity. In the long term, combined-cycle gasification will lessen the industry's environmental impact while increasing its potential for energy production, allowing the production of all the mill's heat and power needs along with surplus electricity being returned to the grid. An added benefit will be the potential elimination of the possibility of smelt-water explosions, which constitute an important safety concern wherever conventional Tomlinson recovery boilers are operated. Developing cost-effective materials with improved performance in gasifier environments may be the best answer to the material challenges presented by black liquor gasification. Refractory materials may be selected/developed that either react with the gasifier environment to form protective surfaces in

  9. Refractory for Black Liquor Gasifiers

    SciTech Connect

    William L. Headrick Jr; Alireza Rezaie; Xiaoting Liang; Musa Karakus; Jun Wei

    2005-12-01

    The University of Missouri-Rolla identified materials that permit the safe, reliable and economical operation of combined cycle gasifiers by the pulp and paper industry. The primary emphasis of this project was to resolve the material problems encountered during the operation of low-pressure high-temperature (LPHT) and low-pressure low-temperature (LPLT) gasifiers while simultaneously understanding the materials barriers to the successful demonstration of high-pressure high-temperature (HPHT) black liquor gasifiers. This study attempted to define the chemical, thermal and physical conditions in current and proposed gasifier designs and then modify existing materials and develop new materials to successfully meet the formidable material challenges. Resolving the material challenges of black liquor gasification combined cycle technology will provide energy, environmental, and economic benefits that include higher thermal efficiencies, up to three times greater electrical output per unit of fuel, and lower emissions. In the near term, adoption of this technology will allow the pulp and paper industry greater capital effectiveness and flexibility, as gasifiers are added to increase mill capacity. In the long term, combined-cycle gasification will lessen the industry's environmental impact while increasing its potential for energy production, allowing the production of all the mill's heat and power needs along with surplus electricity being returned to the grid. An added benefit will be the potential elimination of the possibility of smelt-water explosions, which constitute an important safety concern wherever conventional Tomlinson recovery boilers are operated. Developing cost-effective materials with improved performance in gasifier environments may be the best answer to the material challenges presented by black liquor gasification. Refractory materials were selected or developed that reacted with the gasifier environment to form protective surfaces in-situ; and

  10. REFRACTORY FOR BLACK LIQUOR GASIFIERS

    SciTech Connect

    William L. Headrick Jr; Musa Karakus; Xiaoting Liang; Jun Wei

    2005-01-01

    The University of Missouri-Rolla will identify materials that will permit the safe, reliable and economical operation of combined cycle gasifiers by the pulp and paper industry. The primary emphasis of this project will be to resolve the material problems encountered during the operation of low-pressure high-temperature (LPHT) and low-pressure low-temperature (LPLT) gasifiers while simultaneously understanding the materials barriers to the successful demonstration of high-pressure high-temperature (HPHT) black liquor gasifiers. This study will define the chemical, thermal and physical conditions in current and proposed gasifier designs and then modify existing materials and develop new materials to successfully meet the formidable material challenges. Resolving the material challenges of black liquor gasification combined cycle technology will provide energy, environmental, and economic benefits that include higher thermal efficiencies, up to three times greater electrical output per unit of fuel, and lower emissions. In the near term, adoption of this technology will allow the pulp and paper industry greater capital effectiveness and flexibility, as gasifiers are added to increase mill capacity. In the long term, combined-cycle gasification will lessen the industry's environmental impact while increasing its potential for energy production, allowing the production of all the mill's heat and power needs along with surplus electricity being returned to the grid. An added benefit will be the potential elimination of the possibility of smelt-water explosions, which constitute an important safety concern wherever conventional Tomlinson recovery boilers are operated. Developing cost-effective materials with improved performance in gasifier environments may be the best answer to the material challenges presented by black liquor gasification. Refractory materials may be selected/developed that either react with the gasifier environment to form protective surfaces in

  11. REFRACTORY FOR BLACK LIQUOR GASIFIERS

    SciTech Connect

    William L. Headrick Jr; Musa Karakus; Xiaoting Liang; Jun Wei

    2005-04-01

    The University of Missouri-Rolla will identify materials that will permit the safe, reliable and economical operation of combined cycle gasifiers by the pulp and paper industry. The primary emphasis of this project will be to resolve the material problems encountered during the operation of low-pressure high-temperature (LPHT) and low-pressure low-temperature (LPLT) gasifiers while simultaneously understanding the materials barriers to the successful demonstration of high-pressure high-temperature (HPHT) black liquor gasifiers. This study will define the chemical, thermal and physical conditions in current and proposed gasifier designs and then modify existing materials and develop new materials to successfully meet the formidable material challenges. Resolving the material challenges of black liquor gasification combined cycle technology will provide energy, environmental, and economic benefits that include higher thermal efficiencies, up to three times greater electrical output per unit of fuel, and lower emissions. In the near term, adoption of this technology will allow the pulp and paper industry greater capital effectiveness and flexibility, as gasifiers are added to increase mill capacity. In the long term, combined-cycle gasification will lessen the industry's environmental impact while increasing its potential for energy production, allowing the production of all the mill's heat and power needs along with surplus electricity being returned to the grid. An added benefit will be the potential elimination of the possibility of smelt-water explosions, which constitute an important safety concern wherever conventional Tomlinson recovery boilers are operated. Developing cost-effective materials with improved performance in gasifier environments may be the best answer to the material challenges presented by black liquor gasification. Refractory materials may be selected/developed that either react with the gasifier environment to form protective surfaces in

  12. Refractory for Black Liquor Gasifiers

    SciTech Connect

    Robert E. Moore; William L. Headrick; Alireza Rezaie

    2003-03-31

    The University of Missouri-Rolla will identify materials that will permit the safe, reliable and economical operation of combined cycle gasifiers by the pulp and paper industry. The primary emphasis of this project will be to resolve the materials problems encountered during the operation of low-pressure high-temperature (LFHT) and low-pressure low-temperature (LPLT) gasifiers while simultaneously understanding the materials barriers to the successful demonstration of high-pressure high-temperature (HPHT) black liquor gasifiers. This study will define the chemical, thermal and physical conditions in current and proposed gasifier designs and then modify existing materials and develop new materials to successfully meet the formidable material challenges. Resolving the material challenges of black liquor gasification combined cycle technology will provide energy, environmental, and economic benefits that include higher thermal efficiencies, up to three times greater electrical output per unit of fuel, and lower emissions. In the near term, adoption of this technology will allow the pulp and paper industry greater capital effectiveness and flexibility, as gasifiers are added to increase mill capacity. In the long term, combined-cycle gasification will lessen the industry's environmental impact while increasing its potential for energy production, allowing the production of all the mill's heat and power needs along with surplus electricity being returned to the grid. An added benefit will be the potential elimination of the possibility of smelt-water explosions, which constitute an important safety concern wherever conventional Tomlinson recovery boilers are operated. Developing cost-effective materials with improved performance in gasifier environments may be the best answer to the material challenges presented by black liquor gasification. Refractory materials may be selected/developed that either react with the gasifier environment to form protective surfaces in

  13. Refractory for Black Liquor Gasifiers

    SciTech Connect

    William L. Headrick Jr; Alireza Rezaie

    2003-12-01

    The University of Missouri-Rolla will identify materials that will permit the safe, reliable and economical operation of combined cycle gasifiers by the pulp and paper industry. The primary emphasis of this project will be to resolve the materials problems encountered during the operation of low-pressure high-temperature (LFHT) and low-pressure low-temperature (LPLT) gasifiers while simultaneously understanding the materials barriers to the successful demonstration of high-pressure high-temperature (HPHT) black liquor gasifiers. This study will define the chemical, thermal and physical conditions in current and proposed gasifier designs and then modify existing materials and develop new materials to successfully meet the formidable material challenges. Resolving the material challenges of black liquor gasification combined cycle technology will provide energy, environmental, and economic benefits that include higher thermal efficiencies, up to three times greater electrical output per unit of fuel, and lower emissions. In the near term, adoption of this technology will allow the pulp and paper industry greater capital effectiveness and flexibility, as gasifiers are added to increase mill capacity. In the long term, combined-cycle gasification will lessen the industry's environmental impact while increasing its potential for energy production, allowing the production of all the mill's heat and power needs along with surplus electricity being returned to the grid. An added benefit will be the potential elimination of the possibility of smelt-water explosions, which constitute an important safety concern wherever conventional Tomlinson recovery boilers are operated. Developing cost-effective materials with improved performance in gasifier environments may be the best answer to the material challenges presented by black liquor gasification. Refractory materials may be selected/developed that either react with the gasifier environment to form protective surfaces in

  14. Refractory for Black Liquor Gasifiers

    SciTech Connect

    William L. Headrick Jr; Alireza Rezaie

    2003-08-01

    The University of Missouri-Rolla will identify materials that will permit the safe, reliable and economical operation of combined cycle gasifiers by the pulp and paper industry. The primary emphasis of this project will be to resolve the materials problems encountered during the operation of low-pressure high-temperature (LFHT) and low-pressure low-temperature (LPLT) gasifiers while simultaneously understanding the materials barriers to the successful demonstration of high-pressure high-temperature (HPHT) black liquor gasifiers. This study will define the chemical, thermal and physical conditions in current and proposed gasifier designs and then modify existing materials and develop new mater