Science.gov

Sample records for advanced refractory lung

  1. Phase II Etirinotecan Pegol in Refractory Brain Metastases & Advanced Lung Cancer / Metastatic Breast Cancer

    ClinicalTrials.gov

    2016-04-18

    Extensive Stage Small Cell Lung Cancer; Recurrent Non-small Cell Lung Cancer; Recurrent Small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer; Tumors Metastatic to Brain; Metastatic Breast Cancer

  2. 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.

  3. SEM evaluation of advanced refractory failures in slagging gasifiers

    SciTech Connect

    Collins, W.Keith; Dahlin, Cheryl L.; Bennett, James P.; Kwong, Kyei-Sing; Rawers, James C.

    2005-08-01

    The SEM is an invaluable tool in the evaluation of advanced refractories and their failure. A reaction vessel?s refractory liner, at minimum, must protect the reaction vessel from elevated temperatures, corrosive slag and thermal cycling. To understand the failure mechanisms ARC staff had first to determine how an advanced chrome rich refractory was attacked by various components that make up a slag. Refractory cups were made from the refractory of interest and various compounds that can be found in a slag such as CaO, SiO2, Fe2O3, NaCl were placed into the test cups and fired for 24 hours at the required temperature with the desired atmosphere. The cups are prepared for examination by embedding in epoxy and cross sectioning. SEM examination revealed how various slag compositions attacked and penetrated the refractory. The slag could corrode, free refractory grains or react with the refractory and from a new compound. It was found that the only way to measure slag component penetration was with multiple elemental X-ray maps. SiO2 penetrated deeply and in many instances moved through the cup. The knowledge of slag refractory interactions gather during cup testing was applied to actual spent refractory from reaction vessels. Obtaining samples from the reaction vessel itself proved difficult due to time constraints imposed in relining. Samples were selected based on spent brick shape, color or location in the heap of spent refractory. Sample preparation affected the results dry, water or oil coolant during cutting may dissolve reaction products. The complex reactions between the slag and refractory made for very interesting and time consuming evaluation. Elemental X-ray maps at low and high magnification combined with point analysis aided in locating regions of interest. Crystals were found growing in voids and appear to be from vapor deposition. Other crystal structures are from the slag refractory interaction. Knowledge gathered from this and other supporting

  4. Advances in lung preservation.

    PubMed

    Machuca, Tiago N; Cypel, Marcelo; Keshavjee, Shaf

    2013-12-01

    After a brief review of conventional lung preservation, this article discusses the rationale behind ex vivo lung perfusion and how it has shifted the paradigm of organ preservation from conventional static cold ischemia to the utilization of functional normothermia, restoring the lung's own metabolism and its reparative processes. Technical aspects and previous clinical experience as well as opportunities to address specific donor organ injuries in a personalized medicine approach are also reviewed. PMID:24206857

  5. RRx-001 in Refractory Small-Cell Lung Carcinoma: A Case Report of a Partial Response after a Third Reintroduction of Platinum Doublets

    PubMed Central

    Carter, Corey A.; Oronsky, Bryan T.; Caroen, Scott Z.; Scicinski, Jan J.; Degesys, Aiste; Kim, Michelle M.; Oronsky, Arnold L.; Lybeck, Harry; Cabrales, Pedro; Oronsky, Neil; Reid, Tony; Roswarski, Joseph; Brzezniak, Christina

    2016-01-01

    RRx-001 is a pan-active, systemically nontoxic epigenetic inhibitor under investigation in advanced non-small cell lung cancer, small-cell lung cancer and high-grade neuroendocrine tumors in a Phase II clinical trial entitled TRIPLE THREAT (NCT02489903), which reexposes patients to previously effective but refractory platinum doublets after treatment with RRx-001. The purpose of this case study is first to report a partial response to carboplatin and etoposide in a patient with small-cell lung cancer pretreated with RRx-001, indicating episensitization or resensitization by epigenetic mechanisms, and second to discuss the literature related to small-cell lung cancer and episensitization. PMID:27065849

  6. 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.

  7. Advanced radioiodine-refractory differentiated thyroid cancer: the sodium iodide symporter and other emerging therapeutic targets.

    PubMed

    Spitzweg, Christine; Bible, Keith C; Hofbauer, Lorenz C; Morris, John C

    2014-10-01

    Approximately 30% of patients with advanced, metastatic differentiated thyroid cancer have radioiodine-refractory disease, based on decreased expression of the sodium iodide symporter SLC5A5 (NIS), diminished membrane targeting of NIS, or both. Patients with radioiodine-refractory disease, therefore, are not amenable to (131)I therapy, which is the initial systemic treatment of choice for non-refractory metastatic thyroid cancer. Patients with radioiodine-refractory cancer have historically had poor outcomes, partly because these cancers often respond poorly to cytotoxic chemotherapy. In the past decade, however, considerable progress has been made in delineating the molecular pathogenesis of radioiodine-refractory thyroid cancer. As a result of the identification of key genetic and epigenetic alterations and dysregulated signalling pathways, multiple biologically targeted drugs, in particular tyrosine-kinase inhibitors, have been evaluated in clinical trials with promising results and have begun to meaningfully impact clinical practice. In this Review, we summarise the current knowledge of the molecular pathogenesis of advanced differentiated thyroid cancer and discuss findings from clinical trials of targeted drugs in patients with radioiodine-refractory disease. Additionally, we focus on the molecular basis of loss of NIS expression, function, or both in refractory disease, and discuss preclinical and clinical data on restoration of radioiodine uptake. PMID:24898835

  8. 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.

  9. 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.

  10. Immunotherapy for lung cancer: advances and prospects.

    PubMed

    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

  11. 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

  12. 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.

  13. 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

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

    ClinicalTrials.gov

    2013-08-14

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

  15. Successful pneumonectomy for invasive pulmonary aspergillosis and advanced non-small cell-lung cancer.

    PubMed

    Minesaki, Shohei; Koyama, Nobuyuki; Ishida, Hironori; Kobayashi, Kunihiko

    2013-01-01

    Aspergillus spp. is a pathogenic fungus in patients with malignancy, immunosuppression or respiratory diseases, and invasive pulmonary aspergillosis (IPA) caused by its infection is an aggressive and often lethal disorder. We report a case of non-small-cell lung cancer (NSCLC) where pneumonectomy concomitantly enabled radical cure of the underlying disease and IPA against which different antifungal drugs had been ineffective. In a patient with locally advanced NSCLC that progressed despite chemoradiation, radiation pneumonitis and subsequently cavitary disease developed following the administration of corticosteroids. Based upon the isolation of Aspergillus spp. from sputum, a diagnosis of IPA was made and since the latter was refractory to multiple antifungal drugs, pneumonectomy was undertaken which resulted in successful treatment of both NSCLC and IPA. Surgical intervention should be considered as a therapeutic option for IPA complicating NSCLC that is refractory to medical management. PMID:23505081

  16. Treatment of recurrent and platinum-refractory stage IV non-small cell lung cancer with nanoparticle albumin-bound paclitaxel (nab-paclitaxel) as a single agent.

    PubMed

    Saxena, Ashish; Schneider, Bryan J; Christos, Paul J; Audibert, Lauren F; Cagney, Jennifer M; Scheff, Ronald J

    2016-02-01

    The role of single-agent nab-paclitaxel in relapsed or platinum-refractory advanced non-small cell lung cancer (NSCLC) has not been well reported in Western populations. We reviewed our own institution's experience using nab-paclitaxel in these settings. We analyzed the records of stage IV NSCLC patients with relapsed or platinum-refractory disease treated with single-agent nab-paclitaxel at Weill Cornell Medical College between October 2008 and December 2013. The primary endpoint of the study was treatment failure-free survival (TFFS), defined as the time from the start of nab-paclitaxel therapy to discontinuation of the drug for any reason. The best overall response was recorded for each patient, and overall response and disease control rates were calculated. Thirty-one stage IV NSCLC patients received a median of 4 cycles (range 1-40) of nab-paclitaxel. Dose reduction or drug discontinuation due to toxicity occurred in 10 patients, mainly because of grade 2/3 fatigue or peripheral neuropathy. The overall response rate was 16.1 %, and the disease control rate was 64.5 %. Median TFFS was 3.5 months (95 % CI 1.3-5.3 months). No statistically significant difference in TFFS based on line of therapy or prior taxane exposure was identified. There was a statistically significant decrease in TFFS for patients with non-adenocarcinoma histology, although there were only five patients in this group. There was a trend toward reduction in the risk of treatment failure with increasing age. One patient remained on nab-paclitaxel therapy for over 3 years. Single-agent nab-paclitaxel was well tolerated and demonstrated efficacy in advanced NSCLC patients with relapsed or platinum-refractory disease. Further prospective clinical trials with nab-paclitaxel in these settings are warranted.

  17. [Advances in Lung Stem Cells and Lung Cancer Stem Cells].

    PubMed

    Yin, Huijing; Deng, Jiong

    2015-10-20

    Cancer stem cells (CSCs) are emerging as a hot topic for cancer research. Lung CSCs share many characteristics with normal lung stem cells (SCs), including self-renewal and multi-potency for differentiation. Many molecular markers expressed in various types of CSCs were also found in lung CSCs, such as CD133, CD44, aldehyde dehydrogenase (ALDH) and ATP-binding cassette sub-family G member 2 (ABCG2). Similarly, proliferation and expansion of lung CSCs are regulated not only by signal transduction pathways functioning in normal lung SCs, such as Notch, Hedgehog and Wnt pathways, but also by those acting in tumor cells, such as epidermal growth factor receptor (EGFR), signal transducer and activator of transcription 3 (STAT3) and phosphatidylinositol 3 kinase (PI3K) pathways. As CSC plays an critical role in tumor recurrence, metastasis and drug-resistance, understanding the difference between lung CSCs and normal lung SCs, identifying and targeting CSC markers or related signaling pathways may increase the efficacy of therapy on lung cancer and improved survival of lung cancer patients.

  18. 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

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

    PubMed Central

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

    2015-01-01

    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. PMID:27730152

  20. 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.

  1. 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.

  2. The Influence of SiC on the Ablation Response of Advanced Refractory Composite Materials

    NASA Technical Reports Server (NTRS)

    Bull, Jeffrey D.; Rasky, Daniel J. (Technical Monitor)

    1994-01-01

    In continuing our studies of advanced refractory composite materials we have recently completed an arc-jet test series of a diverse group of ceramics and ceramic matrix composites. The compositions range from continuous fiber reinforced ceramics to monoliths. Many of these materials contain SiC and one objective of this test series was to identify the influence of SiC oxidation mechanisms on material performance. Hence the arc heater was operated at two conditions; one in which the passive oxidation of SiC would be dominant and the other where the active oxidation of SiC would be dominant. It is shown here that the active oxidation mechanism of SiC does not dominate material performance when it is present at levels equal to or below 20 volume percent.

  3. 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.

  4. Efficacy of short-term nivolumab treatment in a Chinese patient with relapsed advanced-stage lung squamous cell carcinoma

    PubMed Central

    Pi, Guoliang; He, Hanping; Bi, Jianping; Li, Ying; Li, Yanping; Zhang, Yong; Wang, Mingwei; Han, Guang; Lin, Chi

    2016-01-01

    Abstract Introduction: Currently, the options are limited for the treatment of patients who have failed 2 lines of chemotherapy for advanced lung squamous cell carcinoma (SCC). Recently, nivolumab, a fully human IgG4 programmed death 1 immune checkpoint inhibitor antibody, was approved to treat patients with advanced stage, relapsed/refractory lung SCC. Although nivolumab has demonstrated antitumor activity with survival benefit in Caucasian patients, its efficacy in Asian patients is unknown. Case Report: In this report, we describe a Chinese patient with relapsed advanced stage lung SCC who had an excellent response to nivolumab after only 2 doses without any adverse effects. Immunohistochemical analysis indicated the tumor was stained positive for programmed death-ligand 1. Conclusion: To our knowledge, this is the first report of satisfactory efficacy of short-term nivolumab treatment in a Chinese patient with relapsed advanced-stage lung SCC. Further clinical trials in Asian countries are needed to test whether nivolumab immunotherapy is a safe and effective treatment for Asian patients with lung SCC. PMID:27749580

  5. [The Use of Octreotide Acetate in the Management of Refractory Chylothorax Following Surgical Treatment for Lung Cancer].

    PubMed

    Kawakami, Toru; Ishida, Itaru; Sugawara, Takafumi; Oura, Hiroyuki

    2016-06-01

    A 78-year-old man underwent right upper lobectomy with systemic lymph node dissection for lung cancer. On the 1st operative day, chylothorax was suspected by a large amount of yellowish-white fluid through the chest tubes. In spite of stopping the oral intake as a conservative therapy, a lot of chylous drainage was continued, and we chose surgical treatment at day 7 after operation, however, chylous discharge did not decrease significantly. Finally we decided to try octreotide administration subcutaneously. After continuous subcutaneous infusion of octreotide, the amount of chylous discharge was reduced dramatically. Then we have done 2 times of pleurodesis with OK-432. The chest tubes were removed at day 17 after the 2nd operation, and the chylothorax was improved. It was suggested that octreotide administration was a highly effective therapy against postoperative refractory chylothorax.

  6. [The Use of Octreotide Acetate in the Management of Refractory Chylothorax Following Surgical Treatment for Lung Cancer].

    PubMed

    Kawakami, Toru; Ishida, Itaru; Sugawara, Takafumi; Oura, Hiroyuki

    2016-06-01

    A 78-year-old man underwent right upper lobectomy with systemic lymph node dissection for lung cancer. On the 1st operative day, chylothorax was suspected by a large amount of yellowish-white fluid through the chest tubes. In spite of stopping the oral intake as a conservative therapy, a lot of chylous drainage was continued, and we chose surgical treatment at day 7 after operation, however, chylous discharge did not decrease significantly. Finally we decided to try octreotide administration subcutaneously. After continuous subcutaneous infusion of octreotide, the amount of chylous discharge was reduced dramatically. Then we have done 2 times of pleurodesis with OK-432. The chest tubes were removed at day 17 after the 2nd operation, and the chylothorax was improved. It was suggested that octreotide administration was a highly effective therapy against postoperative refractory chylothorax. PMID:27246125

  7. 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.

  8. 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.

  9. Proton beam therapy for locally advanced lung cancer: A review

    PubMed Central

    Schild, Steven E; Rule, William G; Ashman, Jonathan B; Vora, Sujay A; Keole, Sameer; Anand, Aman; Liu, Wei; Bues, Martin

    2014-01-01

    Protons interact with human tissue differently than do photons and these differences can be exploited in an attempt to improve the care of lung cancer patients. This review examines proton beam therapy (PBT) as a component of a combined modality program for locally advanced lung cancers. It was specifically written for the non-radiation oncologist who desires greater understanding of this newer treatment modality. This review describes and compares photon (X-ray) radiotherapy (XRT) to PBT. The physical differences of these beams are described and the clinical literature is reviewed. Protons can be used to create treatment plans delivering significantly lower doses of radiation to the adjacent organs at risk (lungs, esophagus, and bone marrow) than photons. Clinically, PBT combined with chemotherapy has resulted in low rates of toxicity compared to XRT. Early results suggest a possible improvement in survival. The clinical results of proton therapy in lung cancer patients reveal relatively low rates of toxicity and possible survival benefits. One randomized study is being performed and another is planned to clarify the clinical differences in patient outcome for PBT compared to XRT. Along with the development of better systemic therapy, newer forms of radiotherapy such as PBT should positively impact the care of lung cancer patients. This review provides the reader with the current status of this new technology in treating locally advanced lung cancer. PMID:25302161

  10. 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

  11. 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.

  12. 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.

  13. 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. PMID:25414068

  14. Lung volume reduction for advanced emphysema: surgical and bronchoscopic approaches.

    PubMed

    Tidwell, Sherry L; Westfall, Elizabeth; Dransfield, Mark T

    2012-01-01

    Chronic obstructive pulmonary disease is the third leading cause of death in the United States, affecting more than 24 million people. Inhaled bronchodilators are the mainstay of therapy; they improve symptoms and quality of life and reduce exacerbations. These and smoking cessation and long-term oxygen therapy for hypoxemic patients are the only medical treatments definitively demonstrated to reduce mortality. Surgical approaches include lung transplantation and lung volume reduction and the latter has been shown to improve exercise tolerance, quality of life, and survival in highly selected patients with advanced emphysema. Lung volume reduction surgery results in clinical benefits. The procedure is associated with a short-term risk of mortality and a more significant risk of cardiac and pulmonary perioperative complications. Interest has been growing in the use of noninvasive, bronchoscopic methods to address the pathological hyperinflation that drives the dyspnea and exercise intolerance that is characteristic of emphysema. In this review, the mechanism by which lung volume reduction improves pulmonary function is outlined, along with the risks and benefits of the traditional surgical approach. In addition, the emerging bronchoscopic techniques for lung volume reduction are introduced and recent clinical trials examining their efficacy are summarized. PMID:22189668

  15. 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

  16. Crizotinib Improves Progression-Free Survival in Some Patients with Advanced Lung Cancer

    MedlinePlus

    ... Prevention Lung Cancer Screening Research Crizotinib Improves Progression-Free Survival in Some Patients with Advanced Lung Cancer ( ... starting treatment without their disease getting worse (progression-free survival), as assessed by radiologic review. Results Progression- ...

  17. [Advances in the research of treating refractory diabetic wounds with stem cells].

    PubMed

    Gong, Jiahong; Lu, Shuliang

    2014-12-01

    With the growth of aging society, China has become the country of population with the highest incidence of diabetes in the world. Diabetes leads to pathological changes in vascular and nervous system, rendering the diabetic skin fragile and hard to heal if wounded; in the end most diabetic wounds tend to become chronic skin ulcers. The refractory diabetic wound is the result of various endogenous and exogenous factors. It is a quite complicated pathophysiologic event which lacks an effective and specific therapeutic method in clinic. The use of stem cells could be a new approach of treating diabetic chronic wounds since they have a potential ability of self-renovation and multi-directional differentiation which will promote angiogenesis and wound healing process, thus be beneficial in the care of ischemia diseases of the lower limb. This article reviews basic theory of treating diabetic wound and the changes in microenvironment, and prompts many successful cases in curing refractory diabetic wounds.

  18. Chemotherapy advances in small-cell lung cancer

    PubMed Central

    Chan, Bryan A.

    2013-01-01

    Although chemotherapeutic advances have recently been heralded in lung adenocarcinomas, such success with small-cell lung cancer (SCLC) has been ominously absent. Indeed, the dismal outlook of this disease is exemplified by the failure of any significant advances in first line therapy since the introduction of the current standard platinum-etoposide doublet over 30 years ago. Moreover, such sluggish progress is compounded by the dearth of FDA-approved agents for patients with relapsed disease. However, over the past decade, novel formulations of drug classes commonly used in SCLC (e.g. topoisomerase inhibitors, anthracyclines, alkylating and platinum agents) are emerging as potential alternatives that could effectively add to the armamentarium of agents currently at our disposal. This review is introduced with an overview on the historical development of chemotherapeutic regimens used in this disease and followed by the recent encouraging advances witnessed in clinical trials with drugs such as amrubicin and belotecan which are forging new horizons for future treatment algorithms. PMID:24163749

  19. Chemotherapy for Advanced Non-small Cell Lung Cancer.

    PubMed

    Dietrich, Martin F; Gerber, David E

    2016-01-01

    Non-small cell lung cancer has seen an unprecedented augmentation of therapeutic options over the last couple of years. Improved understanding of molecular drivers and the role of the immune system in cancer therapy have brought new drugs to the armamentarium. Despite these advances, cytotoxic chemotherapy remains a substantial part of therapy for most patients in locally advanced and metastatic stage. Initially thought to be a chemotherapy-resistant entity, meta-analyses in the mid-1990s demonstrated modest efficacy of platinum-based therapy. Further combination trials demonstrated enhanced efficacy for several regimen in first and second lines, including the introduction of antimetabolites, taxanes, and anti-angiogenic agents. Maintenance chemotherapy has been another novel, successful approach for management of metastatic disease. Herein, we summarize the current concepts of chemotherapy, its applicability to the different histologies, and novel concepts of therapy. PMID:27535392

  20. Treatment of advanced non-small cell lung cancer.

    PubMed

    De Petris, L; Crinò, L; Scagliotti, G V; Gridelli, C; Galetta, D; Metro, G; Novello, S; Maione, P; Colucci, G; de Marinis, F

    2006-03-01

    In the last decade the treatment of advanced-metastatic non-small cell lung cancer has substantially improved. If in the early 90s there was still concern about the real efficacy of chemotherapy over best suppotive care alone in the advanced setting, constant developments in clinical research have demonstrated the survival advantage of active anti-cancer drugs not only in the first-line setting, but, lately, even in patients with recurrent disease after failure of two previous chemotherapy lines. With the premises of high throughput technologies, translational research is aiming to characterize patients and tumors on a molecular basis. With pharmacogenomics it would then be possible to accurately predict patient outcome and tailor the treatment strategy according to the geno-phenotype of single patients.

  1. 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

  2. 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.

  3. 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.

  4. 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

  5. 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.

  6. Advanced bronchoscopic techniques in diagnosis and staging of lung cancer.

    PubMed

    Zaric, Bojan; Stojsic, Vladimir; Sarcev, Tatjana; Stojanovic, Goran; Carapic, Vladimir; Perin, Branislav; Zarogoulidis, Paul; Darwiche, Kaid; Tsakiridis, Kosmas; Karapantzos, Ilias; Kesisis, Georgios; Kougioumtzi, Ioanna; Katsikogiannis, Nikolaos; Machairiotis, Nikolaos; Stylianaki, Aikaterini; Foroulis, Christophoros N; Zarogoulidis, Konstantinos

    2013-09-01

    The role of advanced brochoscopic diagnostic techniques in detection and staging of lung cancer has steeply increased in recent years. Bronchoscopic imaging techniques became widely available and easy to use. Technical improvement led to merging in technologies making autofluorescence or narrow band imaging incorporated into one bronchoscope. New tools, such as autofluorescence imagining (AFI), narrow band imaging (NBI) or fuji intelligent chromo endoscopy (FICE), found their place in respiratory endoscopy suites. Development of endobronchial ultrasound (EBUS) improved minimally invasive mediastinal staging and diagnosis of peripheral lung lesions. Linear EBUS proven to be complementary to mediastinoscopy. This technique is now available in almost all high volume centers performing bronchoscopy. Radial EBUS with mini-probes and guiding sheaths provides accurate diagnosis of peripheral pulmonary lesions. Combining EBUS guided procedures with rapid on site cytology (ROSE) increases diagnostic yield even more. Electromagnetic navigation technology (EMN) is also widely used for diagnosis of peripheral lesions. Future development will certainly lead to new improvements in technology and creation of new sophisticated tools for research in respiratory endoscopy. Broncho-microscopy, alveoloscopy, optical coherence tomography are some of the new research techniques emerging for rapid technological development.

  7. Radiotherapy for lung cancer: clinical impact of recent technical advances.

    PubMed

    Haasbeek, Cornelis J A; Slotman, Ben J; Senan, Suresh

    2009-04-01

    Radiation oncology plays an important role in the curative treatment of patients with lung cancer. New technological developments have enabled delivery of higher radiation doses while better sparing surrounding normal tissues, thereby increasing the likelihood of local control without increased toxicity. Multi-modality imaging enables better target definition, improved planning software allows for correct calculation of delivered doses, and tools to verify accurate treatment delivery are now available. A good example of the results of applying these developments is the high local control rates achieved in stage I NSCLC with stereotactic radiotherapy (SRT). These advances are rapidly becoming available outside academic institutions, and pulmonologists, surgeons and medical oncologists need to understand and critically assess the potential impact of such developments in the routine care of their patients. Aspects of cost-effectiveness of technical innovations, as well as the level of evidence required before widespread clinical implementation, will be addressed.

  8. High-Dose Vincristine Sulfate Liposome Injection for Advanced, Relapsed, and Refractory Adult Philadelphia Chromosome–Negative Acute Lymphoblastic Leukemia

    PubMed Central

    O'Brien, Susan; Schiller, Gary; Lister, John; Damon, Lloyd; Goldberg, Stuart; Aulitzky, Walter; Ben-Yehuda, Dina; Stock, Wendy; Coutre, Steven; Douer, Dan; Heffner, Leonard T.; Larson, Melissa; Seiter, Karen; Smith, Scott; Assouline, Sarit; Kuriakose, Philip; Maness, Lori; Nagler, Arnon; Rowe, Jacob; Schaich, Markus; Shpilberg, Ofer; Yee, Karen; Schmieder, Guenter; Silverman, Jeffrey A.; Thomas, Deborah; Deitcher, Steven R.; Kantarjian, Hagop

    2013-01-01

    Purpose Relapsed adult acute lymphoblastic leukemia (ALL) is associated with high reinduction mortality, chemotherapy resistance, and rapid progression leading to death. Vincristine sulfate liposome injection (VSLI), sphingomyelin and cholesterol nanoparticle vincristine (VCR), facilitates VCR dose-intensification and densification plus enhances target tissue delivery. We evaluated high-dose VSLI monotherapy in adults with Philadelphia chromosome (Ph) –negative ALL that was multiply relapsed, relapsed and refractory to reinduction, and/or relapsed after hematopoietic cell transplantation (HCT). Patients and Methods Sixty-five adults with Ph-negative ALL in second or greater relapse or whose disease had progressed following two or more leukemia therapies were treated in this pivotal phase II, multinational trial. Intravenous VSLI 2.25 mg/m2, without dose capping, was administered once per week until response, progression, toxicity, or pursuit of HCT. The primary end point was achievement of complete response (CR) or CR with incomplete hematologic recovery (CRi). Results The CR/CRi rate was 20% and overall response rate was 35%. VSLI monotherapy was effective as third-, fourth-, and fifth-line therapy and in patients refractory to other single- and multiagent reinduction therapies. Median CR/CRi duration was 23 weeks (range, 5 to 66 weeks); 12 patients bridged to a post-VSLI HCT, and five patients were long-term survivors. VSLI was generally well tolerated and associated with a low 30-day mortality rate (12%). Conclusion High-dose VSLI monotherapy resulted in meaningful clinical outcomes including durable responses and bridging to HCT in advanced ALL settings. The toxicity profile of VSLI was predictable, manageable, and comparable to standard VCR despite the delivery of large, normally unachievable, individual and cumulative doses of VCR. PMID:23169518

  9. Spontaneous regression in advanced squamous cell lung carcinoma

    PubMed Central

    Park, Yeon Hee; Park, Bo Mi; Park, Se Yeon; Choi, Jae Woo; Kim, Sun Young; Kim, Ju Ock; Jung, Sung Soo; Park, Hee Sun; Moon, Jae Young

    2016-01-01

    Spontaneous regression of malignant tumors is rare especially of lung tumor and biological mechanism of such remission has not been addressed. We report the case of a 79-year-old Korean patient with non-small cell lung cancer, squamous cell cancer with a right hilar tumor and multiple lymph nodes, lung to lung metastasis that spontaneously regressed without any therapies. He has sustained partial remission state for one year and eight months after the first histological diagnosis. PMID:27076978

  10. 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.

  11. VTD combination therapy with bortezomib-thalidomide-dexamethasone is highly effective in advanced and refractory multiple myeloma.

    PubMed

    Pineda-Roman, M; Zangari, M; van Rhee, F; Anaissie, E; Szymonifka, J; Hoering, A; Petty, N; Crowley, J; Shaughnessy, J; Epstein, J; Barlogie, B

    2008-07-01

    Bortezomib (V) was combined with thalidomide (T) and dexamethasone (D) in a phase I/II trial to determine dose-limiting toxicities (DLT's) and clinical activity of the VTD regimen in 85 patients with advanced and refractory myeloma. The starting dose of V was 1.0 mg/m(2) (days 1, 4, 8, 11, every 21 day) with T added from cycle 2 at 50 mg/day, with 50 mg increments per 10 patient cohorts, to a maximum dose of 200 mg. In the absence of DLT's, the same reiteration of T dose increases was applied with a higher dose of V=1.3 mg/m(2). D was added with cycle 4 in the absence of partial response (PR). Ninety-two percent had prior autotransplants, 74% had prior T and 76% abnormal cytogenetics. MTD was reached at V=1.3 mg/m(2) and T=150 mg. Minor response (MR) was recorded in 79%, and 63% achieved PR including 22% who qualified for near-complete remission. At 4 years, 6% remain event-free and 23% alive. Both OS and EFS were significantly longer in the absence of prior T exposure and when at least MR status was attained. The MMSET/FGFR3 molecular subtype was prognostically favorable, a finding since reported for a VTD-incorporating tandem transplant trial (Total Therapy 3) for untreated patients with myeloma (BJH 2008).

  12. 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.

  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. Recent Advances and New Opportunities in Lung Mechanobiology

    PubMed Central

    Tschumperlin, Daniel J.; Boudreault, Francis; Liu, Fei

    2009-01-01

    Lung function is inextricably linked to mechanics. On short timescales every breath generates dynamic cycles of cell and matrix stretch, along with convection of fluids in the airways and vasculature. Perturbations such airway smooth muscle shortening or surfactant dysfunction rapidly alter respiratory mechanics, with profound influence on lung function. On longer timescales, lung development, maturation, and remodeling all strongly depend on cues from the mechanical environment. Thus mechanics has long played a central role in our developing understanding of lung biology and respiratory physiology. This concise review focuses on progress over the past five years in elucidating the molecular origins of lung mechanical behavior, and the cellular signaling events triggered by mechanical perturbations that contribute to lung development, homeostasis, and injury. Special emphasis is placed on the tools and approaches opening new avenues for investigation of lung behavior at integrative cellular and molecular scales. We conclude with a brief summary of selected opportunities and challenges that lie ahead for the lung mechanobiology research community. PMID:19804885

  15. 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

  16. 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.

  17. A phase II study of capecitabine and lapatinib in advanced refractory colorectal adenocarcinoma: A Wisconsin Oncology Network study

    PubMed Central

    Frank, Daniel; Jumonville, Alcee; Schelman, William R; Mulkerin, Daniel; Lubner, Sam; Richter, Katie; Winterle, Natalie; Wims, Mary Beth; Dietrich, Leah; Winkler, J. Mitchell; Volk, Michael; Kim, KyungMann; Holen, Kyle D.

    2012-01-01

    Background Prognosis remains poor after progression on first-line chemotherapy for colorectal adenocarcinoma, and inactivation of the EGFR pathway with monoclonal antibodies is an effective treatment strategy in selected patients with metastatic disease. Lapatinib is an oral EGFR and HER-2 dual tyrosine kinase inhibitor that has not shown significant activity in metastatic colorectal cancer. However, lapatinib may act synergistically with capecitabine in anticancer effects. Methods This was an open-label, non-randomized phase II study of lapatinib 1,250 mg orally daily and capecitabine 2,000 mg/m2 by mouth split into twice-daily dosing for 14 days of a 21 days cycle. Inclusion criteria included metastatic or locally advanced adenocarcinoma of the colon or rectum with progression by RECIST on or within six months of receiving a fluoridopyrimidine-, oxaliplatin- or irinotecan-containing regimen. Prior EGFR monoclonal antibody was permitted. K-ras testing was not routinely performed and was not a part of the study protocol. Results Twenty nine patients (16 M; 13 F) were enrolled in this study. There were no complete or partial responses. 41.4% of patients achieved stable disease as a best response. Median overall survival was 6.8 months, with a 1-year survival rate of 22%, and median progression-free survival was 2.1 months. The combination produced few grade 3 and no grade 4 toxicities. No grade 3 toxicity occurred in more than 10% of patients. Conclusions Although capecitabine and lapatinib is well tolerated, it is not an effective regimen in patients with refractory colorectal adenocarcinoma. PMID:22811876

  18. [Advances in the research of blast lung injury].

    PubMed

    Peng, L H; Guo, G H

    2016-03-01

    In recent years, a variety of explosive weapons become increasingly common used in regional military conflicts and terrorist bomb attacks. Meanwhile, the incidence of accidental explosion also showed an increase in the industries and daily life. The lung is the most labile organ and it is used to be severely injured organ in blast injury although even no signs of external injury could be observed on chest. Blast injury can present the symptoms such as lung rupture, bleeding, edema and emphysema. Respiratory dysfunction can affect oxygen supply to organs and systemic tissue, resulting in rapid and sustained hypoxemia and high mortality rate. Blast lung injury is characterized by respiratory disturbance and hypoxia. This article summarizes the etiology, pathogenesis, pathophysiological changes, diagnosis, and treatment of blast lung injury, with a hope to provide some useful clinical information.

  19. [Advances in the research of blast lung injury].

    PubMed

    Peng, L H; Guo, G H

    2016-03-01

    In recent years, a variety of explosive weapons become increasingly common used in regional military conflicts and terrorist bomb attacks. Meanwhile, the incidence of accidental explosion also showed an increase in the industries and daily life. The lung is the most labile organ and it is used to be severely injured organ in blast injury although even no signs of external injury could be observed on chest. Blast injury can present the symptoms such as lung rupture, bleeding, edema and emphysema. Respiratory dysfunction can affect oxygen supply to organs and systemic tissue, resulting in rapid and sustained hypoxemia and high mortality rate. Blast lung injury is characterized by respiratory disturbance and hypoxia. This article summarizes the etiology, pathogenesis, pathophysiological changes, diagnosis, and treatment of blast lung injury, with a hope to provide some useful clinical information. PMID:27030652

  20. 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

  1. Lung volume reduction therapies for advanced emphysema: an update.

    PubMed

    Berger, Robert L; Decamp, Malcolm M; Criner, Gerard J; Celli, Bartolome R

    2010-08-01

    Observational and randomized studies provide convincing evidence that lung volume reduction surgery (LVRS) improves symptoms, lung function, exercise tolerance, and life span in well-defined subsets of patients with emphysema. Yet, in the face of an estimated 3 million patients with emphysema in the United States, < 15 LVRS operations are performed monthly under the aegis of Medicare, in part because of misleading reporting in lay and medical publications suggesting that the operation is associated with prohibitive risks and offers minimal benefits. Thus, a treatment with proven potential for palliating and prolonging life may be underutilized. In an attempt to lower risks and cost, several bronchoscopic strategies (bronchoscopic emphysema treatment [BET]) to reduce lung volume have been introduced. The following three methods have been tested in some depth: (1) unidirectional valves that allow exit but bar entry of gas to collapse targeted hyperinflated portions of the lung and reduce overall volume; (2) biologic lung volume reduction (BioLVR) that involves intrabronchial administration of a biocompatible complex to collapse, inflame, scar, and shrink the targeted emphysematous lung; and (3) airway bypass tract (ABT) or creation of stented nonanatomic pathways between hyperinflated pulmonary parenchyma and bronchial tree to decompress and reduce the volume of oversized lung. The results of pilot and randomized pivotal clinical trials suggest that the bronchoscopic strategies are associated with lower mortality and morbidity but are also less efficient than LVRS. Most bronchoscopic approaches improve quality-of-life measures without supportive physiologic or exercise tolerance benefits. Although there is promise of limited therapeutic influence, the available information is not sufficient to recommend use of bronchoscopic strategies for treating emphysema. PMID:20682529

  2. 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

  3. 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.

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

    ClinicalTrials.gov

    2016-11-02

    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

  5. Partial atrial resection in advanced lung carcinoma with and without cardiopulmonary bypass.

    PubMed Central

    Shirakusa, T; Kimura, M

    1991-01-01

    Combined pneumonectomy and partial resection of the left atrium was performed in 12 patients with advanced lung carcinoma (T3 and T4 in the new UICC classification). In the eight patients with a T3 lung carcinoma intrapericardial atrial resection with vascular clamping was carried out; four of the patients died within a year. The remaining four patients had a T4 tumour and underwent removal of the right lung and part of the left atrium under total cardiopulmonary bypass. One patient died shortly after the operation from cerebral and cerebellar infarction, and one died 11 months later from brain metastases. Two are alive and well. Complete resection appears to offer a chance for longer survival in patients with advanced lung carcinoma that extends directly into the intrapericardial pulmonary vessels or atrium. Images PMID:1652165

  6. Non-small cell lung cancer: current treatment and future advances.

    PubMed

    Zappa, Cecilia; Mousa, Shaker A

    2016-06-01

    Lung cancer has a poor prognosis; over half of people diagnosed with lung cancer die within one year of diagnosis and the 5-year survival is less than 18%. Non-small cell lung cancer (NSCLC) accounts for the majority of all lung cancer cases. Risk factors for developing NSCLC have been identified, with cigarette smoking being a major factor along with other environmental and genetic risk factors. Depending on the staging of lung cancer, patients are eligible for certain treatments ranging from surgery to radiation to chemotherapy as well as targeted therapy. With the advancement of genetics and biomarkers testing, specific mutations have been identified to better target treatment for individual patients. This review discusses current treatments including surgery, chemotherapy, radiotherapy, and immunotherapy as well as how biomarker testing has helped improve survival in patients with NSCLC. PMID:27413711

  7. Non-small cell lung cancer: current treatment and future advances

    PubMed Central

    Zappa, Cecilia

    2016-01-01

    Lung cancer has a poor prognosis; over half of people diagnosed with lung cancer die within one year of diagnosis and the 5-year survival is less than 18%. Non-small cell lung cancer (NSCLC) accounts for the majority of all lung cancer cases. Risk factors for developing NSCLC have been identified, with cigarette smoking being a major factor along with other environmental and genetic risk factors. Depending on the staging of lung cancer, patients are eligible for certain treatments ranging from surgery to radiation to chemotherapy as well as targeted therapy. With the advancement of genetics and biomarkers testing, specific mutations have been identified to better target treatment for individual patients. This review discusses current treatments including surgery, chemotherapy, radiotherapy, and immunotherapy as well as how biomarker testing has helped improve survival in patients with NSCLC. PMID:27413711

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

    PubMed

    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

  9. 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

  10. [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.

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

    PubMed

    Agrawal, Sushma

    2013-10-01

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

  12. 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.

  13. Advances in Cell and Gene-based Therapies for Cystic Fibrosis Lung Disease

    PubMed Central

    Oakland, Mayumi; Sinn, Patrick L; McCray Jr, Paul B

    2012-01-01

    Cystic fibrosis (CF) is a disease characterized by airway infection, inflammation, remodeling, and obstruction that gradually destroy the lungs. Direct delivery of the cystic fibrosis transmembrane conductance regulator (CFTR) gene to airway epithelia may offer advantages, as the tissue is accessible for topical delivery of vectors. Yet, physical and host immune barriers in the lung present challenges for successful gene transfer to the respiratory tract. Advances in gene transfer approaches, tissue engineering, and novel animal models are generating excitement within the CF research field. This review discusses current challenges and advancements in viral and nonviral vectors, cell-based therapies, and CF animal models. PMID:22371844

  14. Activity of weekly irinotecan (CPT-11) in patients with advanced non-small cell lung cancer pretreated with platinum and taxanes.

    PubMed

    Sánchez, Rosa; Esteban, Emilio; Palacio, Isabel; Fernández, Yolanda; Muñiz, Isabel; Vieitez, Jose M; Fra, Joaquin; Blay, Pilar; Villanueva, Noemí; Uña, Esther; Mareque, Beatriz; Estrada, Enrique; Buesa, Jose M; Lacave, Angel J

    2003-11-01

    Irinotecan (CPT-11), a semisynthetic derivative of camptothecin, is active in the treatment of non-small cell lung cancer (NSCLC). In this report we describe our experience with this drug when used as a single agent in patients with advanced NSCLC refractory to chemotherapy with platinum and taxanes. Nineteen NSCLC patients (thirteen males and six females; 53% adenocarcinoma and 26% squamous cell carcinoma) with a median age of 52 years (range 34-71) and a Karnofsky performance status of 60% (60-80%) were included in the study. At baseline, the patients had a median of two disease sites and had been treated with a median of two prior regimens. Irinotecan was given at a dose of 100 mg/m(2) i.v.) weekly for 4 weeks followed by 1 week of rest. A total of 123 weekly infusions were administered, and each patient received a median of 4 weeks of treatment (range 1-32). All patients were evaluated by intention-to-treat analysis for efficacy and safety. Main toxicities reported were grade 3 neutropenia (10% of patients), diarrhea (10% of patients), and grade 4 thrombocytopenia (5% of patients). The overall clinical response rate was 16% (95% CI: 8-24) with three partial responses and 9 (47%) patients with stable disease. The median time to progression and the median survival time were 7 and 15 weeks, respectively. In conclusion, weekly irinotecan showed antitumoral activity and minimum toxicity in NSCLC patients refractory to platinum and taxanes.

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

    ClinicalTrials.gov

    2015-03-17

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

  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. PMID:25898957

  17. 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.

  18. A randomized phase II study of S-1 plus oral leucovorin versus S-1 monotherapy in patients with gemcitabine-refractory advanced pancreatic cancer†

    PubMed Central

    Ueno, M.; Okusaka, T.; Omuro, Y.; Isayama, H.; Fukutomi, A.; Ikeda, M.; Mizuno, N.; Fukuzawa, K.; Furukawa, M.; Iguchi, H.; Sugimori, K.; Furuse, J.; Shimada, K.; Ioka, T.; Nakamori, S.; Baba, H.; Komatsu, Y.; Takeuchi, M.; Hyodo, I.; Boku, N.

    2016-01-01

    Background We evaluated the efficacy and toxicity of adding oral leucovorin (LV) to S-1 when compared with S-1 monotherapy in patients with gemcitabine-refractory pancreatic cancer (PC). Patients and methods Gemcitabine-refractory PC patients were randomly assigned in a 1:1 ratio to receive S-1 at 40, 50, or 60 mg according to body surface area plus LV 25 mg, both given orally twice daily for 1 week, repeated every 2 weeks (SL group), or S-1 monotherapy at the same dose as the SL group for 4 weeks, repeated every 6 weeks (S-1 group). The primary end point was progression-free survival (PFS). Results Among 142 patients enrolled, 140 were eligible for efficacy assessment (SL: n = 69 and S-1: n = 71). PFS was significantly longer in the SL group than in the S-1 group [median PFS, 3.8 versus 2.7 months; hazard ratio (HR), 0.56; 95% confidence interval (CI), 0.37–0.85; P = 0.003]). The disease control rate was significantly higher in the SL group than in the S-1 group (91% versus 72%; P = 0.004). Overall survival (OS) was similar in both groups (median OS, 6.3 versus 6.1 months; HR, 0.82; 95% CI, 0.54–1.22; P = 0.463). After adjusting for patient background factors in a multivariate analysis, OS tended to be better in the SL group (HR, 0.71; 95% CI, 0.47–1.07; P = 0.099). Both treatments were well tolerated, although gastrointestinal toxicities were slightly more severe in the SL group. Conclusion The addition of LV to S-1 significantly improved PFS in patients with gemcitabine-refractory advanced PC, and a phase III trial has been initiated in a similar setting. Clinical trials number Japan Pharmaceutical Information Center: JapicCTI-111554. PMID:26681680

  19. “EXHALE”: exercise as a strategy for rehabilitation in advanced stage lung cancer patients: a randomized clinical trial comparing the effects of 12 weeks supervised exercise intervention versus usual care for advanced stage lung cancer patients

    PubMed Central

    2013-01-01

    Background Lung cancer is the leading cause of cancer death in North America and Western Europe. Patients with lung cancer in general have reduced physical capacity, functional capacity, poor quality of life and increased levels of anxiety and depression. Intervention studies indicate that physical training can address these issues. However, there is a lack of decisive evidence regarding the effect of physical exercise in patients with advanced lung cancer. The aim of this study is to evaluate the effects of a twelve weeks, twice weekly program consisting of: supervised, structured training in a group of advanced lung cancer patients (cardiovascular and strength training, relaxation). Methods/Design A randomized controlled trial will test the effects of the exercise intervention in 216 patients with advanced lung cancer (non-small cell lung cancer (NSCLC) stage IIIb - IV and small cell lung cancer (SCLC) extensive disease (ED)). Primary outcome is maximal oxygen uptake (VO2peak). Secondary outcomes are muscle strength (1RM), functional capacity (6MWD), lung capacity (Fev1) and patient reported outcome (including anxiety, depression (HADS) and quality of life (HRQOL)). Discussion The present randomized controlled study will provide data on the effectiveness of a supervised exercise intervention in patients receiving systemic therapy for advanced lung cancer. It is hoped that the intervention can improve physical capacity and functional level, during rehabilitation of cancer patients with complex symptom burden and help them to maintain independent function for as long as possible. Trial registration http://ClinicalTrials.gov, NCT01881906 PMID:24124893

  20. 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. PMID:27212445

  1. New and emerging targeted treatments in advanced non-small-cell lung cancer.

    PubMed

    Hirsch, Fred R; Suda, Kenichi; Wiens, Jacinta; Bunn, Paul A

    2016-09-01

    Targeted therapies are substantially changing the management of lung cancers. These treatments include drugs that target driver mutations, those that target presumed important molecules in cancer cell proliferation and survival, and those that inhibit immune checkpoint molecules. This area of research progresses day by day, with novel target discoveries, novel drug development, and use of novel combination treatments. Researchers and clinicians have also extensively investigated the predictive biomarkers and the molecular mechanisms underlying inherent or acquired resistance to these targeted therapies. We review recent progress in the development of targeted treatments for patients with advanced non-small-cell lung cancer, especially focusing on data from published clinical trials. PMID:27598681

  2. Evaluation of refractory organic removal in combined biological powdered activated carbon--microfiltration for advanced wastewater treatment.

    PubMed

    Seo, G T; Ohgaki, S

    2001-01-01

    Biological powdered activated carbon (BPAC) was incorporated with a microfiltration (MF, 0.2 micron pore size) system to remove the refractory organic matter contained in secondary sewage effluent. A synthetic secondary sewage effluent was used as influent in this study, containing both non-biodegradable organic substances (such as humic acid, lignin sulfonate, tannic acid and arabic gum powder) and biodegradable ones. These refractory organic materials were possibly degraded in contact with microorganisms for 20-27 days. Although humic acid and arabic gum were weakly adsorbed on the activated carbon, they could be effectively removed in the BPAC reactor. The TOC removal at a powdered activated carbon (PAC) concentration of 20 g/L was higher than at 0.5-2 g PAC/L (83% and 66-68%, respectively). The higher removal efficiency was due to the increased rejection at the membrane module in which most of the PAC was accumulated. More than 90% of non-biodegradable compounds removal (detected as E280, UV absorption at 280 nm) occurred in the BPAC reactor. The biological growth parameter b/Y, used in system design, was estimated to be 0.017 d-1. Relatively high permeate flux of 1.88 m/d could be obtained even at higher PAC concentration of 20 g/L.

  3. Advances in functional and structural imaging of the human lung using proton MRI.

    PubMed

    Miller, G Wilson; Mugler, John P; Sá, Rui C; Altes, Talissa A; Prisk, G Kim; Hopkins, Susan R

    2014-12-01

    The field of proton lung MRI is advancing on a variety of fronts. In the realm of functional imaging, it is now possible to use arterial spin labeling (ASL) and oxygen-enhanced imaging techniques to quantify regional perfusion and ventilation, respectively, in standard units of measurement. By combining these techniques into a single scan, it is also possible to quantify the local ventilation-perfusion ratio, which is the most important determinant of gas-exchange efficiency in the lung. To demonstrate potential for accurate and meaningful measurements of lung function, this technique was used to study gravitational gradients of ventilation, perfusion, and ventilation-perfusion ratio in healthy subjects, yielding quantitative results consistent with expected regional variations. Such techniques can also be applied in the time domain, providing new tools for studying temporal dynamics of lung function. Temporal ASL measurements showed increased spatial-temporal heterogeneity of pulmonary blood flow in healthy subjects exposed to hypoxia, suggesting sensitivity to active control mechanisms such as hypoxic pulmonary vasoconstriction, and illustrating that to fully examine the factors that govern lung function it is necessary to consider temporal as well as spatial variability. Further development to increase spatial coverage and improve robustness would enhance the clinical applicability of these new functional imaging tools. In the realm of structural imaging, pulse sequence techniques such as ultrashort echo-time radial k-space acquisition, ultrafast steady-state free precession, and imaging-based diaphragm triggering can be combined to overcome the significant challenges associated with proton MRI in the lung, enabling high-quality three-dimensional imaging of the whole lung in a clinically reasonable scan time. Images of healthy and cystic fibrosis subjects using these techniques demonstrate substantial promise for non-contrast pulmonary angiography and detailed

  4. 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 Cisplatin and Pemetrexed

    ClinicalTrials.gov

    2016-09-09

    Advanced Peritoneal Malignant Mesothelioma; Advanced Pleural Malignant Mesothelioma; Recurrent Peritoneal Malignant Mesothelioma; Recurrent Pleural Malignant Mesothelioma; Solid Neoplasm; 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

  5. From Uniplex to Multiplex Molecular Profiling in Advanced Non-Small Cell Lung Carcinoma.

    PubMed

    Ileana, Ecaterina E; Wistuba, Ignacio I; Izzo, Julie G

    2015-01-01

    Non-small cell lung carcinoma is a leading cause of cancer death worldwide. Understanding the molecular biology of survival and proliferation of cancer cells led to a new molecular classification of lung cancer and the development of targeted therapies with promising results. With the advances of image-guided biopsy techniques, tumor samples are becoming smaller, and the molecular testing techniques have to overcome the challenge of integrating the characterization of a panel of abnormalities including gene mutations, copy-number changes, and fusions in a reduced number of assays using only a small amount of genetic material. This article reviews the current knowledge about the most frequent actionable molecular abnormalities in non-small cell lung carcinoma, the new approaches of molecular analysis, and the implications of these findings in the context of clinical practice.

  6. The steady progress of targeted therapies, promising advances for lung cancer

    PubMed Central

    Bombardelli, Lorenzo; Berns, Anton

    2016-01-01

    Lung cancer remains one of the most complex and challenging cancers, being responsible for almost a third of all cancer deaths. This grim picture seems however to be changing, for at least a subset of lung cancers. The number of patients who can benefit from targeted therapies is steadily increasing thanks to the progress made in identifying actionable driver lesions in lung tumours. The success of the latest generation of EGFR and ALK inhibitors in the clinic not only illustrates the value of targeted therapies, but also shows how almost inevitably drug resistance develops. Therefore, more sophisticated approaches are needed to achieve long-term remissions. Although there are still significant barriers to be overcome, technological advances in early detection of relevant mutations and the opportunity to test new drugs in predictive preclinical models justify the hope that we will overcome these obstacles. PMID:27350784

  7. Clinical features and hyperplastic patterns of parathyroid glands in hemodialysis patients with advanced secondary hyperparathyroidism refractory to maxacalcitol treatment and required parathyroidectomy.

    PubMed

    Tominaga, Yoshihiro; Matsuoka, Susumu; Sato, Tetsuhiko; Uno, Nobuyuki; Goto, Norihiko; Katayama, Akio; Haba, Toshihito

    2007-08-01

    We have previously suggested that when parathyroid glands progress to nodular hyperplasia, secondary hyperparathyroidism (2HPT) may be refractory to medical treatments, including treatment with Maxacalcitol (OCT). In the present study we evaluated the clinical features and hyperplastic patterns of parathyroid glands in patients who underwent parathyroidectomy (PTx) after being withdrawn from OCT. One hundred and eighty-seven advanced 2HPT patients who had been withdrawn from OCT and required PTx were enrolled. At the start of OCT treatment, the patients had a mean age of 55.3 years and had been receiving hemodialysis (HD) for a mean period of 149 months. At the start of OCT treatment and at PTx, the mean intact PTH (i-PTH) levels were 772.8 +/- 446.0 and 855.5 +/- 420.5 pg/mL, respectively. The main reasons for withdrawal of OCT treatment were persistently high PTH (n = 148), hypercalcemia (n = 79), hyperphosphatemia (n = 65), and progressive symptoms (n = 60). We classified the parathyroid glands by hyperplastic pattern into four categories: diffuse hyperplastic gland (D), early nodularity in diffuse hyperplastic gland (EN), nodular hyperplastic gland (N), and single nodular gland (SN). The mean total excised gland weight was 2592.6 mg. Out of a total of 706 glands, 118 were classified as D, 66 as EN, 436 as N, and 86 as SN. All patients had at least one nodular hyperplastic gland or single nodular gland. The mean number of nodular hyperplastic glands and/or single nodular glands was 2.9. All hemodialysis patients with advanced OCT-refractory 2HPT who underwent PTx had at least one nodular hyperplastic gland or single nodular gland.

  8. 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

  9. New molecular targeted therapies for advanced non-small-cell lung cancer

    PubMed Central

    Méndez, Míriam; Custodio, Ana; Provencio, Mariano

    2011-01-01

    Non-small-cell lung cancer (NSCLC) is a uniformly fatal disease and most patients will present with advanced stage. Treatment outcomes remain unsatisfactory, with low long-term survival rates. Standard treatment, such as palliative chemotherapy and radiotherapy, offers a median survival not exceeding 1 year. Hence, considerable efforts have started to be made in order to identify new biological agents which may safely and effectively be administered to advanced NSCLC patients. Two cancer cell pathways in particular have been exploited, the epidermal growth factor receptor (EGFR) and the vascular endothelial growth factor receptor (VEGFR) pathways. However, novel targeted therapies that interfere with other dysregulated pathways in lung cancer are already in the clinic. This review outlines the most promising research approaches to the treatment of NSCLC, discussed according to the specific molecular pathway targeted. PMID:22263060

  10. 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. |

  11. 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.

  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. 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. PMID:27585597

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

    PubMed Central

    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.

    2016-01-01

    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 hospitalization (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. PMID:25837041

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

    PubMed

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

    2011-12-01

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

  16. Malignant Pleural Effusion Supernatants Are Substitutes for Metastatic Pleural Tumor Tissues in EGFR Mutation Test in Patients with Advanced Lung Adenocarcinoma

    PubMed Central

    Wu, Ning; Nie, Xiaomeng; Xia, Yang; Han, Yiping; Li, Qiang; Zhu, Guanshan; Bai, Chong

    2014-01-01

    Background Though the possibility of using malignant pleural effusions (MPEs) as alternatives for metastatic pleural tumor tissues (MPTTs) in epidermal growth factor receptor (EGFR) mutation test has been examined, due to the lack of studies comparing the results in matching MPEs and MPTTs, the clinical value of MPEs for advanced adenocarcinoma patients with pleural effusions is not confirmed. Methods EGFR mutation statuses in matching MPTTs, MPE supernatants and cell blocks, of 41 patients with advanced lung adenocarcinoma as diagnosed by thoracoscopy were analyzed using amplification refractory mutation system (ARMS). Results EGFR mutations were detected in 46.3% (19/41) of MPTTs, 43.9% (18/41) of MPE supernatants and 56.3% (18/32) of MPE cell blocks by ARMS analysis. Generally, the same EGFR statuses were identified in both MPTTs and matching MPE cell blocks of 81.3% patients (26/32), whereas MPTTs and matching MPE supernatants of 87.8% (36/41) patients shared the same EGFR status. Compared with EGFR mutation detection in MPTTs, the sensitivity of EGFR mutation detection in MPE-cell blocks was 87.5% (14/16), specificity was 75.0% (12/16), while the sensitivity of EGFR mutation detection in MPE-supernatants was 84.2% (16/19), specificity was 90.9% (20/22). Conclusions The high concordance of EGFR mutation statuses between MPEs and MPTTs in lung adenocarcinoma patients with pleural metastasis as determined by ARMS analysis suggests that MPEs, particularly MPE supernatants, may be substitutes for MPTTs in EGFR mutation test. PMID:24587142

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

    PubMed

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

    1999-01-01

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

  18. Full GMP-Compliant Validation of Bone Marrow-Derived Human CD133+ Cells as Advanced Therapy Medicinal Product for Refractory Ischemic Cardiomyopathy

    PubMed Central

    Belotti, Daniela; Gaipa, Giuseppe; Bassetti, Beatrice; Cabiati, Benedetta; Spaltro, Gabriella; Biagi, Ettore; Parma, Matteo; Biondi, Andrea; Cavallotti, Laura; Gambini, Elisa; Pompilio, Giulio

    2015-01-01

    According to the European Medicine Agency (EMA) regulatory frameworks, Advanced Therapy Medicinal Products (ATMP) represent a new category of drugs in which the active ingredient consists of cells, genes, or tissues. ATMP-CD133 has been widely investigated in controlled clinical trials for cardiovascular diseases, making CD133+ cells one of the most well characterized cell-derived drugs in this field. To ensure high quality and safety standards for clinical use, the manufacturing process must be accomplished in certified facilities following standard operative procedures (SOPs). In the present work, we report the fully compliant GMP-grade production of ATMP-CD133 which aims to address the treatment of chronic refractory ischemic heart failure. Starting from bone marrow (BM), ATMP-CD133 manufacturing output yielded a median of 6.66 × 106 of CD133+ cells (range 2.85 × 106–30.84 × 106), with a viability ranged between 96,03% and 99,97% (median 99,87%) and a median purity of CD133+ cells of 90,60% (range 81,40%–96,20%). Based on these results we defined our final release criteria for ATMP-CD133: purity ≥ 70%, viability ≥ 80%, cellularity between 1 and 12 × 106 cells, sterile, and endotoxin-free. The abovementioned criteria are currently applied in our Phase I clinical trial (RECARDIO Trial). PMID:26495296

  19. Full GMP-compliant validation of bone marrow-derived human CD133(+) cells as advanced therapy medicinal product for refractory ischemic cardiomyopathy.

    PubMed

    Belotti, Daniela; Gaipa, Giuseppe; Bassetti, Beatrice; Cabiati, Benedetta; Spaltro, Gabriella; Biagi, Ettore; Parma, Matteo; Biondi, Andrea; Cavallotti, Laura; Gambini, Elisa; Pompilio, Giulio

    2015-01-01

    According to the European Medicine Agency (EMA) regulatory frameworks, Advanced Therapy Medicinal Products (ATMP) represent a new category of drugs in which the active ingredient consists of cells, genes, or tissues. ATMP-CD133 has been widely investigated in controlled clinical trials for cardiovascular diseases, making CD133(+) cells one of the most well characterized cell-derived drugs in this field. To ensure high quality and safety standards for clinical use, the manufacturing process must be accomplished in certified facilities following standard operative procedures (SOPs). In the present work, we report the fully compliant GMP-grade production of ATMP-CD133 which aims to address the treatment of chronic refractory ischemic heart failure. Starting from bone marrow (BM), ATMP-CD133 manufacturing output yielded a median of 6.66 × 10(6) of CD133(+) cells (range 2.85 × 10(6)-30.84 × 10(6)), with a viability ranged between 96,03% and 99,97% (median 99,87%) and a median purity of CD133(+) cells of 90,60% (range 81,40%-96,20%). Based on these results we defined our final release criteria for ATMP-CD133: purity ≥ 70%, viability ≥ 80%, cellularity between 1 and 12 × 10(6) cells, sterile, and endotoxin-free. The abovementioned criteria are currently applied in our Phase I clinical trial (RECARDIO Trial).

  20. The role of pembrolizumab in the treatment of advanced non-small cell lung cancer

    PubMed Central

    Santabarbara, Giuseppe; Maione, Paolo; Rossi, Antonio; Palazzolo, Giovanni

    2016-01-01

    Lung cancer is the leading cause of death cancer related worldwide. The standard therapies have unmet medical needs both due to the limited activity and relevant toxicity of platinum-based chemotherapy and to the low frequency of specific alterations required to use targeted therapies. Immune checkpoint inhibition due to restoring the immune system’s capacity to eradicate tumors is undergoing in extensive investigation in non-small cell lung cancer (NSCLC) as a new treatment approach. Programmed cell death protein-1 (PD-1) and its ligand, programmed cell death-ligand 1 (PD-L1) have recently led to significantly and durable improvements in the clinical outcome of several kind of tumors including lung cancer. Pembrolizumab, approved by the U.S. FDA for the treatment of advanced NSCLC progressed after other therapies and with expression of PD-L1, has demonstrated durable response and prolonged overall survival (OS) especially in patients with high PD-L1 expression. Further investigation are needed to improve treatment outcomes through combination of immunotherapy or combined with other targeted therapies. PMID:27386489

  1. The role of pembrolizumab in the treatment of advanced non-small cell lung cancer.

    PubMed

    Santabarbara, Giuseppe; Maione, Paolo; Rossi, Antonio; Palazzolo, Giovanni; Gridelli, Cesare

    2016-06-01

    Lung cancer is the leading cause of death cancer related worldwide. The standard therapies have unmet medical needs both due to the limited activity and relevant toxicity of platinum-based chemotherapy and to the low frequency of specific alterations required to use targeted therapies. Immune checkpoint inhibition due to restoring the immune system's capacity to eradicate tumors is undergoing in extensive investigation in non-small cell lung cancer (NSCLC) as a new treatment approach. Programmed cell death protein-1 (PD-1) and its ligand, programmed cell death-ligand 1 (PD-L1) have recently led to significantly and durable improvements in the clinical outcome of several kind of tumors including lung cancer. Pembrolizumab, approved by the U.S. FDA for the treatment of advanced NSCLC progressed after other therapies and with expression of PD-L1, has demonstrated durable response and prolonged overall survival (OS) especially in patients with high PD-L1 expression. Further investigation are needed to improve treatment outcomes through combination of immunotherapy or combined with other targeted therapies.

  2. Phase I and pharmacokinetic study of docetaxel combined with melphalan and carboplatin, with autologous hematopoietic progenitor cell support, in patients with advanced refractory malignancies.

    PubMed

    Nieto, Yago; Shpall, Elizabeth J; Bearman, Scott I; McSweeney, Peter A; Cagnoni, Pablo J; Matthes, Steve; Gustafson, Dan; Long, Michael; Barón, Anna E; Jones, Roy B

    2005-04-01

    The purpose of this study was to define the maximal tolerated dose (MTD), extramedullary toxicities, and pharmacokinetics of docetaxel combined with high-dose melphalan and carboplatin with autologous hematopoietic progenitor cell support. Fifty-nine patients with advanced refractory malignancy (32 breast cancer, 10 non-Hodgkin lymphoma, 6 germ cell tumors, 4 Hodgkin disease, 4 ovarian cancer, 2 sarcoma, and 1 unknown primary adenocarcinoma) with a median of 3 prior chemotherapy regimens and a median of 3 organs involved were enrolled. Treatment included docetaxel (150-550 mg/m2 infused over 2 hours on day -6), melphalan (150-165 mg/m2 infused over 15 minutes from day -5 to -3), and carboplatin (1000-1300 mg/m2 as a 72-hour continuous infusion from day -5). Five patients died from direct regimen-related organ toxicity (2 capillary leak syndrome, 2 enterocolitis, and 1 hepatic toxicity), and 1 additional patient died from pulmonary aspergillosis. The docetaxel MTD was defined as 400 mg/m 2 , combined with melphalan (150 mg/m2 ) and carboplatin (1000 mg/m2 ). The MTD cohort was expanded to enroll a total of 26 patients, 1 of whom died from toxic enterocolitis. The remaining 25 patients presented the following extramedullary toxicity profile, which was manageable and largely reversible: stomatitis, myoarthralgias, peripheral neuropathy, gastrointestinal and cutaneous toxicities, and syndrome of inappropriate antidiuretic hormone secretion. Docetaxel exhibited linear pharmacokinetics in the dose range tested (150-550 mg/m2 ). Pharmacodynamic correlations were noted between the docetaxel area under the curve and peripheral neuropathy or stomatitis. The response rate among 38 patients with measurable disease was 95%, with 47% complete responses. At a median follow-up of 26 months (range, 7-72 months), the 3-year event-free survival and overall survival were 26% and 36%, respectively. In conclusion, a 4-fold dose escalation of docetaxel, combined with melphalan and

  3. Relevance of platinum sensitivity status in relapsed/refractory extensive stage small cell lung cancer (ES-SCLC) in the modern era: A patient level analysis of SWOG trials

    PubMed Central

    Lara, Primo N.; Moon, James; Redman, Mary W.; Semrad, Thomas J.; Kelly, Karen; Allen, Jeffrey W.; Gitlitz, Barbara J.; Mack, Philip C.; Gandara, David R.

    2014-01-01

    Background Extensive stage small cell lung cancer (ES-SCLC) patients who progress following platinum-based chemotherapy are traditionally categorized as platinum-sensitive (progression ≥ 90 days from last platinum dose) or refractory (progression< 90 days), apractice arising from seminal observations of worse survival in refractory patients. Subsequent trials accounted for platinum-sensitivity, resulting in higher sample sizes and increased resource use. Methods To assess whether platinum-sensitivity status remains associated with outcomes, patient-level data from recent SWOG trials in 2nd and/or 3rd line ES-SCLC were pooled. Hazard ratios (HRs) for progression-free (PFS) and overall survival (OS) accounting for platinum sensitivity were calculated using unadjusted and adjusted Cox Proportional Hazard models. Recursive partitioning was performed to define prognostic risk groups. Results Of 329 patients, 151 were platinum-sensitive, 178 refractory. Hazard ratios from unadjusted Cox PFS and OS models for refractory vs. sensitive disease were 1.0 (95% CI 0.81–1.25, p=0.98) and 1.24 (0.99, 1.57; p=0.06), respectively. Adjusted Cox models showed that only elevated serum LDH (HR 2.04, p<0.001), males (HR 1.36, p=0.04), performance status of 1 (HR 1.25, p=0.02), and weight loss ≥ 5% (1.53, p=0.01) were independently associated with OS. Platinum sensitivity status was not associated with PFS (HR 1.11, p=0.49) or OS (HR 1.25, p=0.14), except in a model that excluded 36 patients who received > 1 prior chemotherapy regimen (HR=1.34, p=0.049). Prognostic groups with differential OS outcomes (high, intermediate, and poor risk) were identified. Conclusions Platinum sensitivity status may no longer be strongly associated with PFS or OS in at least one multivariate model. Validation of prognostic risk groups identified here is warranted. These data have critical implications in the design of future SCLC trials. PMID:25490004

  4. Treatment approaches in patients with advanced non-small cell lung cancer and poor performance status.

    PubMed

    Govindan, Ramaswamy; Garfield, David H

    2004-12-01

    It is estimated that 30% to 40% of patients with advanced non-small cell lung cancer (NSCLC) have a poor performance status (PS)-defined as a score of 2 or higher on the Eastern Cooperative Oncology Group scale-because of their disease burden, comorbidities, or both. Survival is shorter in these patients than in those with a better PS, and they do not tolerate chemotherapy as well. There is now evidence that PS2 patients with advanced NSCLC can benefit from single-agent chemotherapy with drugs such as vinorelbine, gemcitabine, paclitaxel, pemetrexed, and docetaxel and that combination chemotherapy may have additional advantages. The optimal treatment for PS2 patients with NSCLC, however, has yet to be determined. The case histories in this article demonstrate that PS2 patients are a heterogeneous group and that selecting the chemotherapy for each patient must take into consideration comorbidities and disease-related symptoms, as well as the potential toxicity of treatment. Large prospective clinical trials are needed to determine whether, and in which patients, combination chemotherapy or novel agents, such as the epidermal growth factor receptor inhibitors or paclitaxel poliglumex, have advantages. Three large phase III trials-Selective Targeting for Efficacy in Lung Cancer, Lower Adverse Reactions trials (STELLAR)-are now being conducted in PS2 patients with NSCLC. It is hoped that their findings will aid in determining the best treatment options for these patients.

  5. 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.

  6. 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

  7. Dynamic Testing of Gasifier Refractory

    SciTech Connect

    Michael D. Mann; John P. Hurley

    2002-09-27

    As DOE continues to advance new power systems, materials issues are often pivotal in determining the ultimate efficiency that can be reached in the system. Refractory performance in slagging gasification represents one of these issues. The University of North Dakota (UND) Chemical Engineering Department in conjunction with the UND Energy & Environmental Research Center (EERC) have initiated a program to thoroughly examine the combined chemical (reaction and phase change) and physical (erosion) effects experienced by a variety of refractory materials during both normal operation and thermal cycling under slagging coal gasification conditions. The goal of this work is to devise a mechanism of refractory loss under these conditions. The focus of the proposed work is to test the corrosion resistance of commercially available refractories to flowing coal slag, and propose the mechanisms of corrosion for the conditions studied. Corrosion is the degradation of material surfaces or grain boundaries by chemical reactions with melts, liquids, or gases, causing loss of material and consequently a decrease in strength of the structure. In order to develop methods of reducing corrosion, the microstructure that is attacked must be identified along with the mechanism and rates of attack. Once these are identified, methods for reducing corrosion rates can be developed. The work will take advantage of equipment and experimental techniques developed at the EERC under funding from several DOE programs. The controlled-atmospheric dynamic corrodent application furnace (CADCAF) will be 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. To date, efforts have focused on final shakedown of the CADCAF and obtaining representative samples of slag and refractory for testing.

  8. Activity of topotecan given intravenously for 5 days every three weeks in patients with advanced non-small cell lung cancer pretreated with platinum and taxanes: a phase II study.

    PubMed

    Gonzalez, Emilio Esteban; Villanueva, Noemi; Fra, Joaquin; Berros, Jose Pablo; Jimenez, Paula; Luque, María; Muñiz, Isabel; Blay, Pilar; Fernandez, Yolanda; Vieitez, José María; Muriel, Carolina; Sanmamed, Miguel; Coto, Pablo Pardo; Izquierdo, Marta; Estrada, Enrique; Lacave, Angel J

    2011-12-01

    Topotecan, a semi-synthetic camptothecin analogue with topoisomerase I interaction, has shown to be an active agent in the treatment of advanced refractory lung cancer. This paper describes the authors' experience with this drug when used as a single agent in patients (pts) with advanced non-small cell lung cancer (NSCLC) refractory to platinum- and taxane-containing chemotherapy regimens. Thirty-five patients with NSCLC refractory to previous chemotherapy and KI ≥ 60% were included in the study. Their characteristics are as follows: median age of 52 years (range 43-69) and Karnofsky PS of 70 (60-80); 27 were male and 8 were female. Twenty-one (60%) patients had adenocarcinoma; eleven (31.4%), squamous cell, and three (8.5%), undifferentiated carcinoma. There was a median of two disease sites and two prior chemotherapy regimens. Topotecan was administered at a dose of 1.25 mg/m(2) I.V. daily for 5 days, repeated every 21 days until disease progression, maximal response, or intolerable toxicity. After 73 cycles, patients received a median of 2 treatment cycles (1-9). All patients except one were considered evaluable for toxicity; eight episodes (24%) of nausea/vomiting and two episodes (6%) of grade 1-2 asthenia, respectively, were reported. Four (12%) patients developed grade 1-2 anemia and two (6%) subjects suffered grade 3 anemia. Seven (21%) patients had grade 1-2 neutropenia and one (3%) presented grade 5 neutropenia. In 33 patients evaluable for activity of the 35 subjects included in the study; one (2.8%) presented a partial response; nine (25.7%) had stable disease, and 23 (65.7%) exhibited disease progression. Median time to progression and overall survival were 54 (12-210) and 70 (12-324) days, respectively. Intravenous topotecan at that dose and administration schedule displays scant activity in terms of response rate in individuals with advanced NSCLC previously treated with platinum and taxanes. The role and usefulness of chemotherapy in this setting

  9. High-dose paclitaxel with granulocyte colony-stimulating factor in patients with advanced breast cancer refractory to anthracycline therapy: a European Cancer Center trial.

    PubMed

    Vermorken, J B; ten Bokkel Huinink, W W; Mandjes, I A; Postma, T J; Huizing, M T; Heimans, J J; Beijnen, J H; Bierhorst, F; Winograd, B; Pinedo, H M

    1995-08-01

    Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) is a novel cytostatic agent that has shown interesting antitumor activity in patients with advanced breast cancer. Depending on variable patient characteristics and amount and type of prior therapy, as well as the applied dose and schedule of paclitaxel, response rates have varied from 13% to 62%. However, optimal dose and schedule are still unknown. We studied a high-dose (250 to 300 mg/m2) 3-hour paclitaxel infusion schedule in a poor prognostic group of breast cancer patients who progressed or relapsed while taking anthracyclines. This regimen was given every 3 weeks. Twenty-one of the 36 patients studied had increased liver enzymes and 18 had documented liver metastases. The objective response rate was only 6%, but response rate by disease site indicated that soft tissue lesions responded in 30% of cases. For a better comparison with other reported data a uniform definition of "anthracycline refractory" is needed. Neuropathy, which was found to be dose limiting, and arthralgia/myalgia syndrome were the most frequently occurring toxicities. Both severe myelosuppression (and infections) and severe diarrhea and mucositis were reported more frequently in patients with liver dysfunction. As higher peak levels, increased areas under the concentration time curves, and longer times during which plasma concentrations were above the threshold level of 0.1 mumol/L were found in patients with elevated liver enzymes, a correlation with the observed toxicities is assumed. Further pharmacodynamic studies in such patients receiving a 3-hour infusion seem warranted.

  10. Modified irinotecan and infusional 5-fluorouracil (mFOLFIRI) in patients with refractory advanced pancreas cancer (APC): a single-institution experience

    PubMed Central

    Bupathi, M.; Ahn, D. H.; Wu, C.; Ciombor, K. K.; Stephens, J. A.; Reardon, J.; Goldstein, D. A.; Bekaii-Saab, T.

    2016-01-01

    Pancreatic adenocarcinoma is the fourth leading cause of cancer death. Recently, MM-398 (nanoliposomal irinotecan) was shown to be associated with significant improvement in outcome measures with acceptable toxicities when combined with 5-fluorouracil (5-FU)/leucovorin (LV) compared to 5-FU/LV alone in patients failing one line of gemcitabine-based therapy. There is a paucity of data evaluating the role of irinotecan in combination with 5FU in advanced pancreas cancer (APC). We performed a retrospective analysis of all patients who received mFOLFIRI (minus bolus 5FU and LV). All patients with metastatic disease who had failed at least one line of gemcitabine-based therapy prior to receiving mFOLFIRI were included in this study. Descriptive statistics were used to assess the continuous variables and adverse events (AEs), and Kaplan–Meier methods were used to calculate the median progression-free survival (PFS) and overall survival (OS). Forty patients were included in this analysis. Patients received 1–5 lines of prior therapy (25 % with more than 3 lines of prior therapy). The mean age at diagnosis was 60, and 98 % had ECOG of 1. The mean CA 19-9 at the start of therapy was 33,169 U/ml. The median PFS was 2.59 months [95 % confidence interval (CI) (1.90, 3.54)], and OS was 4.75 months [95 % CI (3.14, 8.98)]. The most common AEs included fatigue (98 %), neuropathy (83 %), anorexia (68 %), nausea (60 %) and constipation (55 %). Grade 3 toxicities included fatigue (13 %) and rash (3 %). There were no observed grade 4 toxicities. In this single-institution retrospective analysis, mFOLFIRI was found to be both tolerable and relatively effective in a heavily pretreated patient population with APC. Future prospective studies should consider evaluating the role of mFOLFIRI in refractory APC. PMID:26995224

  11. A phase 2 trial of lenvatinib (E7080) in advanced progressive radioiodine-refractory differentiated thyroid cancer: a clinical outcomes and biomarker assessment

    PubMed Central

    Cabanillas, Maria E.; Schlumberger, Martin; Jarzab, Barbara; Martins, Renato G.; Pacini, Furio; Robinson, Bruce; McCaffrey, Judith C.; Shah, Manisha H.; Bodenner, Donald L.; Topliss, Duncan; Andresen, Corina; O'Brien, James P.; Ren, Min; Funahashi, Yasuhiro; Allison, Roger; Elisei, Rossella; Newbold, Kate; Licitra, Lisa F.; Sherman, Steven I.; Ball, Douglas W.

    2016-01-01

    Background Lenvatinib is an oral, multitargeted tyrosine kinase inhibitor of VEGFR1–3, FGFR1–4, PDGFRα, RET, and KIT signaling networks implicated in tumor angiogenesis. Positive phase 1 results in solid tumors prompted a phase 2 trial in advanced radioiodine-refractory differentiated thyroid cancer (RR-DTC). Methods Fifty-eight patients with RR-DTC and disease progression during the prior 12 months were administered lenvatinib 24-mg once daily in 28-day cycles until disease progression, unmanageable toxicity, withdrawal, or death. Prior VEGFR-targeted therapy was permitted. The primary endpoint was objective response rate (ORR) based upon independent imaging review (IIR). Secondary endpoints included progression-free survival (PFS) and safety. Serum levels of 51 circulating cytokines and angiogenic factors were also assessed. Results After ≥14 months of follow-up, patients had ORR of 50% (95% confidence interval [CI] 37–63) with only partial responses reported. Median time to response was 3.6 months; median duration of response was 12.7 months; median PFS was 12.6 months (95% CI 9.9–16.1). ORR for patients with prior VEGF therapy (n=17) was 59% (95% CI 33–82). Lower baseline levels of angiopoietin-2 were suggestive of tumor response and longer PFS. Grade 3/4 treatment-emergent adverse events regardless of relation to treatment occurred in 72% of patients, most frequently weight loss (12%), hypertension (10%), proteinuria (10%), and diarrhea (10%). Conclusion In patients with and without prior exposure to VEGF therapy, the encouraging response rates, median time to response, and PFS for lenvatinib have prompted further investigation in a phase 3 trial. PMID:25913680

  12. 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

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

    ClinicalTrials.gov

    2016-08-25

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

  14. Refractory maintenance and repair

    SciTech Connect

    Biglin, J.

    1996-05-01

    Practical refractory application skills are developed most often through on-the-job experience. Many application decisions are judgment decisions carefully made after evaluating much information. Some decisions are made by trial-and-error--a trial is made on a small controlled area before a larger, permanent solution is implemented. Almost everyone involved in supplying and installing refractories will be called upon, at some time, to explain instances of poor refractory performance and service. The performance of refractories is influenced by: heat processing equipment design; refractory system design and type; operating practices; refractory and installation quality.

  15. Can an 86-year-old woman with advanced lung disease be a world class athlete?

    PubMed

    Guenette, Jordan A; Diane Lougheed, M; Webb, Katherine A; O'Donnell, Denis E

    2012-04-30

    We describe the case of an 86-year-old woman with advanced obstructive lung disease (forced expiratory volume in 1 s/forced vital capacity ratio (FEV(1)/FVC)=34%) who remains capable of superior athletic performance. Detailed pulmonary function testing was performed to characterize this patient's baseline respiratory impairment. An incremental symptom limited cycle exercise test was performed to characterize her sensory, ventilatory, cardiovascular and respiratory mechanical responses to exercise. Despite significant respiratory mechanical constraints, her peak cycle work rate and oxygen uptake were 177 and 175% predicted, respectively, and she achieved this while experiencing only moderate exertional dyspnea. She holds numerous world and national masters swim records despite her substantial objective respiratory impairment and continues to compete and set records to this day. We propose that lifelong participation in rigorous endurance training resulted in desensitization to dyspnea and has led to important cardiorespiratory adaptations that may have counterbalanced the known negative effects of obstructive lung disease on exercise performance and dyspnea.

  16. Differential Patient-Caregiver Opinions of Treatment and Care For Advanced Lung Cancer Patients

    PubMed Central

    Zyzanski, Stephen J; Siminoff, Laura A

    2010-01-01

    This study examined the differences of opinion between cancer patients and caregivers with regard to treatment and care decisions. 184 advanced lung cancer patients and 171 primary caregivers were recruited as a convenience sample from clinics in Cleveland, Ohio. A telephone interview was conducted to collect data using a semi-structured questionnaire. Nonparametric tests and regression analysis were performed. The findings showed that patients and caregivers reported significant disagreement on three main issues: trade-off between treatment side effects and benefits; reporting treatment side effects to physicians, and hospice care. Caregivers were more concerned about patient’s quality of life and more willing to discuss hospice issues than were patients. Perceived family disagreement is associated with depression in both patients and caregivers. The study provided empirical evidence for patient-caregiver disagreement about treatment and care decisions and its significant adverse impact on both patients and caregivers. PMID:20137849

  17. [Two-year survivor in response to gemcitabine-based chemotherapy for advanced pancreatic cancer with multiple lung metastases].

    PubMed

    Takeyama, Osamu; Usui, Yuji

    2005-02-01

    A 65-year-old woman was admitted to our hospital for appetite loss and jaundice. Abdominal CT scan and ultrasonography both revealed a tumor in the head of the pancreas. Chest CT scan showed multiple nodules in both lungs. The patient was diagnosed as having advanced pancreatic cancer with multiple lung metastases. The primary tumor showed a partial response to the administration of gemcitabine 1,000 mg/m2 on days 1, 8 and 15 of a 28-day cycle. Concurrent treatment with 5-fluorouracil (200 mg/day) was efficacious against the lung metastases. One year later the pancreatic and lung tumors had enlarged, and cisplatin (20 mg/body) was added to the protocol. For 20 months the patient was treated as an outpatient, maintaining good quality of life. The patient died of progressive disease 25 months after her first hospital admission.

  18. Treatment of advanced non-small-cell lung cancer in the elderly.

    PubMed

    Gridelli, Cesare; Maione, Paolo; Rossi, Antonio; Ferrara, Marianna Luciana; Castaldo, Vincenzo; Palazzolo, Giovanni; Mazzeo, Nicole

    2009-12-01

    Lung cancer in the older individual is an increasingly common problem faced by the oncologist. Elderly patients have more co-morbidities and tend to tolerate toxic medical treatments more poorly than their younger counterparts. Thus, clinical data obtained in a younger population cannot be automatically extrapolated to the great majority of non-selected elderly patients with non-small-cell lung cancer (NSCLC). The bulk of prospective clinical data regarding chemotherapy and molecularly targeted therapy for elderly NSCLC patients comes from studies in advanced disease. In elderly advanced NSCLC patients single-agent chemotherapy with third-generation agents (vinorelbine, gemcitabine, taxanes) is to be considered as the standard treatment for unselected patients, based on several phase II and III trials specifically designed for this special population. Retrospective analyses found no differences in survival between elderly and younger patients treated with cisplatin-based chemotherapy, with a small but significant increase in toxicity in the elderly. Cisplatin-based chemotherapy with cisplatin at attenuated doses has demonstrated to be an active and feasible option in phase II trials and deserves prospective phase III comparison against monochemotherapy. Among targeted therapies, the epidermal growth factor receptor tyrosine kinase inhibitors erlotinib and gefitinib are the most promising agents and have relevant phase II prospective data showing activity and good tolerability as first-line treatment in this population. Concerning the anti-vascular endothelial growth factor monoclonal antibody bevacizumab, particular care must be taken for elderly patients because of a possible higher incidence of cardiovascular co-morbidities. However its role in this population remains controversial and specific prospective studies are warranted to clarify this topic. Further specifically designed phase III randomized trials are needed to optimize medical treatment of NSCLC in

  19. Tumor heterogeneity and resistance to EGFR-targeted therapy in advanced nonsmall cell lung cancer: challenges and perspectives

    PubMed Central

    Cheng, Xinghua; Chen, Haiquan

    2014-01-01

    Lung cancer, mostly nonsmall cell lung cancer, continues to be the leading cause of cancer-related death worldwide. With the development of tyrosine kinase inhibitors that selectively target lung cancer-related epidermal growth factor receptor mutations, management of advanced nonsmall cell lung cancer has been greatly transformed. Improvements in progression-free survival and life quality of the patients were observed in numerous clinical studies. However, overall survival is not prolonged because of later-acquired drug resistance. Recent studies reveal a heterogeneous subclonal architecture of lung cancer, so it is speculated that the tumor may rapidly adapt to environmental changes via a Darwinian selection mechanism. In this review, we aim to provide an overview of both spatial and temporal tumor heterogeneity as potential mechanisms underlying epidermal growth factor receptor tyrosine kinase inhibitor resistance in nonsmall cell lung cancer and summarize the possible origins of tumor heterogeneity covering theories of cancer stem cells and clonal evolution, as well as genomic instability and epigenetic aberrations in lung cancer. Moreover, investigational measures that overcome heterogeneity-associated drug resistance and new assays to improve tumor assessment are also discussed. PMID:25285017

  20. Optimal pharmacotherapeutic strategies for elderly patients with advanced non-small cell lung cancer.

    PubMed

    Quoix, Elisabeth

    2011-11-01

    Increases in both life expectancy and cancer incidence with age result in a significant rise in lung cancer rates among elderly patients, with a median age at diagnosis of between 63 and 70 years. However, elderly patients are under-represented in clinical trials and generally receive suboptimal treatment, mainly because of fears about increased toxicity of chemotherapy. Indeed, physiological modification of renal and haematopoietic functions with age together with co-morbidity and associated polypharmacy may alter the metabolism of chemotherapy drugs, resulting in greater toxicity. Moreover, performance status (PS), the main prognostic factor in younger patients, does not correlate well with geriatric indexes such as activities of daily living, cognition and physical performance, and comprehensive geriatric assessment is important in elderly patients. Until 2010, based on the small number of clinical trials designed for elderly patients, monotherapy was the recommended treatment for those with advanced non-small cell lung cancer (NSCLC), whereas for fit younger patients, a platinum-based doublet was and continues to be the recommended first-line therapy. However, at the plenary session of the 2010 Annual Meeting of the American Society of Clinical Oncology, results were presented from a randomized controlled trial conducted by the French Intergroup of Thoracic Oncology that demonstrated that in PS 0-2 patients aged≥70 years with advanced NSCLC, monthly carboplatin with weekly paclitaxel resulted in significantly longer survival than single-agent therapy (vinorelbine or gemcitabine). It should be noted that even in a priori unfavourable prognostic subgroups (patients with a PS score of 2, those aged>80 years or those with an activities of daily living scale score of <6), doublet therapy was associated with a survival advantage over monotherapy. Thus, the new paradigm of treatment of elderly patients with advanced NSCLC and a PS score of 0-2 should now be monthly

  1. Coping with Physical and Psychological Symptoms: A Qualitative Study of Advanced Lung Cancer Patients and their Family Caregivers

    PubMed Central

    Mosher, Catherine E.; Ott, Mary A.; Hanna, Nasser; Jalal, Shadia I.; Champion, Victoria L.

    2014-01-01

    Purpose Advanced lung cancer patients have high rates of multiple physical and psychological symptoms, and many of their family caregivers experience significant distress. However, little is known about strategies that these patients and their family caregivers employ to cope with physical and psychological symptoms. This study aimed to identify strategies for coping with various physical and psychological symptoms among advanced, symptomatic lung cancer patients and their primary family caregivers. Methods Patients identified their primary family caregiver. Individual semi-structured qualitative interviews were conducted with 21 advanced, symptomatic lung cancer patients and primary family caregivers. Thematic analysis of interview data was framed by stress and coping theory. Results Patients and caregivers reported maintaining a normal routine and turning to family and friends for support with symptom management, which often varied in its effectiveness. Whereas support from healthcare professionals and complementary and alternative medicine were viewed favorably, reactions to Internet and in-person support groups were mixed due to the tragic nature of participants’ stories. Several cognitive coping strategies were frequently reported (i.e., changing expectations, maintaining positivity, and avoiding illness-related thoughts) as well as religious coping strategies. Conclusions Results suggest that advanced lung cancer patients and caregivers may be more receptive to cognitive and religious approaches to symptom management and less receptive to peer support. Interventions should address the perceived effectiveness of support from family and friends. PMID:25527242

  2. 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

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

    PubMed Central

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

    2014-01-01

    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 cm3), 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 < 0.001). Left

  4. Refractories; At the heart of high-temperature processing

    SciTech Connect

    Ford, E. )

    1992-08-01

    This paper reports that every industry that employs high-temperature process heat, from foundries and steel plants to glass furnaces and cement kilns, depends heavily on refractories. As higher temperatures are demanded in many applications, new materials are processed and new operating techniques employed, the need for refractories is intensified. The ability of refractories to meet the new requirements is due, in no small measure, to the continuing research and development programs of the industry, resulting in new materials with advanced properties to meet changing needs. Although a number of leading British refractory manufacturers undertake much of this work, overall support is provided by the Refractories Association of Great Britain (RAGB).

  5. 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

  6. 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.

  7. Modified irinotecan and infusional 5-fluorouracil (mFOLFIRI) in patients with refractory advanced pancreas cancer (APC): a single-institution experience.

    PubMed

    Bupathi, M; Ahn, D H; Wu, C; Ciombor, K K; Stephens, J A; Reardon, J; Goldstein, D A; Bekaii-Saab, T

    2016-04-01

    Pancreatic adenocarcinoma is the fourth leading cause of cancer death. Recently, MM-398 (nanoliposomal irinotecan) was shown to be associated with significant improvement in outcome measures with acceptable toxicities when combined with 5-fluorouracil (5-FU)/leucovorin (LV) compared to 5-FU/LV alone in patients failing one line of gemcitabine-based therapy. There is a paucity of data evaluating the role of irinotecan in combination with 5FU in advanced pancreas cancer (APC). We performed a retrospective analysis of all patients who received mFOLFIRI (minus bolus 5FU and LV). All patients with metastatic disease who had failed at least one line of gemcitabine-based therapy prior to receiving mFOLFIRI were included in this study. Descriptive statistics were used to assess the continuous variables and adverse events (AEs), and Kaplan-Meier methods were used to calculate the median progression-free survival (PFS) and overall survival (OS). Forty patients were included in this analysis. Patients received 1-5 lines of prior therapy (25 % with more than 3 lines of prior therapy). The mean age at diagnosis was 60, and 98 % had ECOG of 1. The mean CA 19-9 at the start of therapy was 33,169 U/ml. The median PFS was 2.59 months [95 % confidence interval (CI) (1.90, 3.54)], and OS was 4.75 months [95 % CI (3.14, 8.98)]. The most common AEs included fatigue (98 %), neuropathy (83 %), anorexia (68 %), nausea (60 %) and constipation (55 %). Grade 3 toxicities included fatigue (13 %) and rash (3 %). There were no observed grade 4 toxicities. In this single-institution retrospective analysis, mFOLFIRI was found to be both tolerable and relatively effective in a heavily pretreated patient population with APC. Future prospective studies should consider evaluating the role of mFOLFIRI in refractory APC. PMID:26995224

  8. The potential role of bevacizumab in early stages and locally advanced non-small cell lung cancer

    PubMed Central

    Schettino, Clorinda; Bareschino, Maria Anna; Rossi, Antonio; Maione, Paolo; Castaldo, Vincenzo; Mazzeo, Nicole; Sacco, Paola Claudia; Ferrara, Marianna Luciana; Palazzolo, Giovanni; Ciardiello, Fortunato; Gridelli, Cesare

    2009-01-01

    Improving outcomes for early-stage non-small cell lung cancer (NSCLC) is a major research area considering that a significant percentage of such patients develop recurrent disease within 5 years of complete lung resection. Adjuvant chemotherapy prolongs survival, with an absolute improvement in 5-year overall survival of about 5% with drawbacks such as treatment toxicity. Approximately, one third of patients with newly diagnosed NSCLC have locally advanced disease not amenable for surgical resection – in this setting of patients concurrent chemoradiation is the standard of therapy. However, the treatment of locally advanced NSCLC is still controversial and clinical outcomes are disappointing, and so new approaches are required to improve the clinical benefit in this setting of patients. Vascular endothelial growth factor (VEGF) is a key angiogenic factor implicated in tumor blood vessels formation and permeability, and tumor VEGF overexpression in patients with early stage lung cancer has been associated with worse relapse free and overall survival. Several agents have been developed that inhibit VEGF or its receptor signalling system. Bevacizumab is the first recombinant humanized monoclonal antibody binding VEGF to demonstrate clinical benefit or rather a survival prolongation in combination with chemotherapy in the treatment of non-squamous advanced NSCLC patients. These positive results led to a large number of clinical trials to evaluate bevacizumab in combination with other targeted agents in advanced disease, and to define the role of this agent in early stage NSCLC such as the impact of bevacizumab integration in chemoradiotherapy strategy for locally advanced disease. PMID:21789109

  9. The potential role of bevacizumab in early stages and locally advanced non-small cell lung cancer.

    PubMed

    Schettino, Clorinda; Bareschino, Maria Anna; Rossi, Antonio; Maione, Paolo; Castaldo, Vincenzo; Mazzeo, Nicole; Sacco, Paola Claudia; Ferrara, Marianna Luciana; Palazzolo, Giovanni; Ciardiello, Fortunato; Gridelli, Cesare

    2009-07-01

    Improving outcomes for early-stage non-small cell lung cancer (NSCLC) is a major research area considering that a significant percentage of such patients develop recurrent disease within 5 years of complete lung resection. Adjuvant chemotherapy prolongs survival, with an absolute improvement in 5-year overall survival of about 5% with drawbacks such as treatment toxicity. Approximately, one third of patients with newly diagnosed NSCLC have locally advanced disease not amenable for surgical resection - in this setting of patients concurrent chemoradiation is the standard of therapy. However, the treatment of locally advanced NSCLC is still controversial and clinical outcomes are disappointing, and so new approaches are required to improve the clinical benefit in this setting of patients. Vascular endothelial growth factor (VEGF) is a key angiogenic factor implicated in tumor blood vessels formation and permeability, and tumor VEGF overexpression in patients with early stage lung cancer has been associated with worse relapse free and overall survival. Several agents have been developed that inhibit VEGF or its receptor signalling system. Bevacizumab is the first recombinant humanized monoclonal antibody binding VEGF to demonstrate clinical benefit or rather a survival prolongation in combination with chemotherapy in the treatment of non-squamous advanced NSCLC patients. These positive results led to a large number of clinical trials to evaluate bevacizumab in combination with other targeted agents in advanced disease, and to define the role of this agent in early stage NSCLC such as the impact of bevacizumab integration in chemoradiotherapy strategy for locally advanced disease.

  10. Comparison of bevacizumab plus chemotherapy with chemotherapy alone in advanced non-small-lung cancer patients.

    PubMed

    Tang, Ning; Wang, Zhehai

    2016-01-01

    Bevacizumab plus chemotherapy was approved by the US Food and Drug Administration (FDA) as a first-line treatment for advanced nonsquamous, non-small-cell lung cancer (NSCLC) in 2006. This study retrospectively compared the efficacy of bevacizumab plus chemotherapy with chemotherapy alone as the first-line and second-line treatment as well as the maintenance treatment for advanced NSCLC patients. A total of 1,352 patients were included and we analyzed the efficacy evaluation according to the criteria of the Response Evaluation Criteria In Solid Tumors (RECIST), survival, and adverse reactions. The data showed that for bevacizumab plus chemotherapy as the first-line treatment, the median progression-free survival (mPFS) and median overall survival (mOS) were 11.5 and 17.0 months, respectively, compared to 7.0 and 14 months, respectively, in patients who received chemotherapy alone (P<0.01). With bevacizumab plus chemotherapy as maintenance treatment, the mPFS and mOS were 6.0 and 17.4 months, respectively, compared to 3.0 and 15.0 months, respectively, with chemotherapy alone (P<0.01). With bevacizumab plus chemotherapy as the second-line treatment, the mPFS was 3.0 months compared to only 2.0 months with chemotherapy alone (P<0.01). The overall responses to the different regimens showed that the remission rate with bevacizumab plus chemotherapy was higher than that with chemotherapy alone (31.8% vs 25.5%, P<0.05), although there was no statistical difference in the disease control rate with either first- or second-line treatment. In conclusion, chemotherapy plus bevacizumab as the first-line and maintenance treatment, led to better curative rates and tolerable adverse reactions compared with chemotherapy alone in advanced NSCLC patients. Bevacizumab combined with cytotoxic drugs was suitable as the second-line treatment for such patients.

  11. Comparison of bevacizumab plus chemotherapy with chemotherapy alone in advanced non-small-lung cancer patients.

    PubMed

    Tang, Ning; Wang, Zhehai

    2016-01-01

    Bevacizumab plus chemotherapy was approved by the US Food and Drug Administration (FDA) as a first-line treatment for advanced nonsquamous, non-small-cell lung cancer (NSCLC) in 2006. This study retrospectively compared the efficacy of bevacizumab plus chemotherapy with chemotherapy alone as the first-line and second-line treatment as well as the maintenance treatment for advanced NSCLC patients. A total of 1,352 patients were included and we analyzed the efficacy evaluation according to the criteria of the Response Evaluation Criteria In Solid Tumors (RECIST), survival, and adverse reactions. The data showed that for bevacizumab plus chemotherapy as the first-line treatment, the median progression-free survival (mPFS) and median overall survival (mOS) were 11.5 and 17.0 months, respectively, compared to 7.0 and 14 months, respectively, in patients who received chemotherapy alone (P<0.01). With bevacizumab plus chemotherapy as maintenance treatment, the mPFS and mOS were 6.0 and 17.4 months, respectively, compared to 3.0 and 15.0 months, respectively, with chemotherapy alone (P<0.01). With bevacizumab plus chemotherapy as the second-line treatment, the mPFS was 3.0 months compared to only 2.0 months with chemotherapy alone (P<0.01). The overall responses to the different regimens showed that the remission rate with bevacizumab plus chemotherapy was higher than that with chemotherapy alone (31.8% vs 25.5%, P<0.05), although there was no statistical difference in the disease control rate with either first- or second-line treatment. In conclusion, chemotherapy plus bevacizumab as the first-line and maintenance treatment, led to better curative rates and tolerable adverse reactions compared with chemotherapy alone in advanced NSCLC patients. Bevacizumab combined with cytotoxic drugs was suitable as the second-line treatment for such patients. PMID:27536131

  12. Comparison of bevacizumab plus chemotherapy with chemotherapy alone in advanced non-small-lung cancer patients

    PubMed Central

    Tang, Ning; Wang, Zhehai

    2016-01-01

    Bevacizumab plus chemotherapy was approved by the US Food and Drug Administration (FDA) as a first-line treatment for advanced nonsquamous, non-small-cell lung cancer (NSCLC) in 2006. This study retrospectively compared the efficacy of bevacizumab plus chemotherapy with chemotherapy alone as the first-line and second-line treatment as well as the maintenance treatment for advanced NSCLC patients. A total of 1,352 patients were included and we analyzed the efficacy evaluation according to the criteria of the Response Evaluation Criteria In Solid Tumors (RECIST), survival, and adverse reactions. The data showed that for bevacizumab plus chemotherapy as the first-line treatment, the median progression-free survival (mPFS) and median overall survival (mOS) were 11.5 and 17.0 months, respectively, compared to 7.0 and 14 months, respectively, in patients who received chemotherapy alone (P<0.01). With bevacizumab plus chemotherapy as maintenance treatment, the mPFS and mOS were 6.0 and 17.4 months, respectively, compared to 3.0 and 15.0 months, respectively, with chemotherapy alone (P<0.01). With bevacizumab plus chemotherapy as the second-line treatment, the mPFS was 3.0 months compared to only 2.0 months with chemotherapy alone (P<0.01). The overall responses to the different regimens showed that the remission rate with bevacizumab plus chemotherapy was higher than that with chemotherapy alone (31.8% vs 25.5%, P<0.05), although there was no statistical difference in the disease control rate with either first- or second-line treatment. In conclusion, chemotherapy plus bevacizumab as the first-line and maintenance treatment, led to better curative rates and tolerable adverse reactions compared with chemotherapy alone in advanced NSCLC patients. Bevacizumab combined with cytotoxic drugs was suitable as the second-line treatment for such patients. PMID:27536131

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

    PubMed Central

    Nishino, Mizuki; Cardarella, Stephanie; Dahlberg, Suzanne E.; Araki, Tetsuro; Lydon, Christine; Jackman, David M.; Rabin, Michael S.; Hatabu, Hiroto; Johnson, Bruce E.

    2015-01-01

    Objective Interstitial lung diseases are associated with increased risk of lung cancer. The prevalence of ILA at diagnosis of advanced non-small-cell lung cancer (NSCLC) and its impact on overall survival (OS) remain to be investigated. Materials and Method The study included 120 treatment-naïve stage IV NSCLC patients (53 males, 67 females). ILA was scored on CT prior to any systemic therapy using a 4-point scale [0=no evidence of ILA, 1=equivocal for ILA, 2=suspicious for ILA, 3=ILA] by a sequential reading method previously reported. ILA scores of 2 or 3 indicated the presence of ILA. Results ILA was present in 17 patients (14%) with advanced NSCLC prior to any treatment (score3:n=2, score2:n=15). These 17 patients were significantly older (median age: 69 vs. 63, p=0.04) and had a heavier smoking history (median: 40 vs. 15.5 pack-year, p=0.003) than those with ILA score 0 or 1. Higher ILA scores were associated with shorter OS (p=0.001). Median OS of the 17 patients with ILA was 7.2 months [95%CI: 2.9-9.4] compared to 14.8 months [95%CI: 11.1-18.4] in patients with ILA score 0 or 1 (p=0.002). In a multivariate model, the presence of ILA remained significant for increased risk for death (HR=2.09, p=0.028) after adjusting for first-line systemic therapy (chemotherapy, p<0.001; TKI, p<0.001; each compared to no therapy) and pack years of smoking (p=0.40). Conclusion Radiographic ILA was present in 14% of treatment-naïve advanced NSCLC patients. Higher ILA scores were associated with shorter OS, indicating that ILA could be a marker of shorter survival in advanced NSCLC. PMID:25726730

  14. Prognostic factors for long term survival in patients with advanced non-small cell lung cancer

    PubMed Central

    Moumtzi, Despoina; Lampaki, Sofia; Porpodis, Konstantinos; Lagoudi, Kalliopi; Hohenforst-Schmidt, Wolfgang; Pataka, Athanasia; Tsiouda, Theodora; Zissimopoulos, Athanasios; Lazaridis, George; Karavasilis, Vasilis; Timotheadou, Helen; Barbetakis, Nikolaos; Pavlidis, Pavlos; Kontakiotis, Theodoros; Zarogoulidis, Konstantinos

    2016-01-01

    Background Non-small cell lung cancer (NSCLC) represents 85% of all lung cancers. It is estimated that 60% of patients with NSCLC at time of diagnosis have advanced disease. The aim of this study was to investigate clinical and demographic prognostic factors of long term survival in patients with unresectable NSCLC. Methods We retrospectively reviewed data of 1,156 patients with NSCLC stage IIIB or IV who survived more than 60 days from the time of diagnosis and treated from August 1987 until March 2013 in the Oncology Department of Pulmonary Clinic of the General Hospital Papanikolaou. Initially univariate analysis using the log-rank test was conducted and then multivariate analysis using the proportional hazards model of Cox. Also Kaplan Meier curves were used to describe the distribution of survival times of patients. The level of significance was set at 0.05. Results The mean age at diagnosis was 62 years. About 11.9% of patients were women and 88.1% were male. The majority of cases were adenocarcinomas (42.2%), followed squamous (33%) and finally the large cell (6%). Unlike men, most common histological type among women was adenocarcinoma rather than squamous (63% vs. 10.9%). In univariate analysis statistically significant factors in the progression free survival (PFS) and overall survival (OS) were: weight loss ≥5%, histological type, line 1 drugs, line 1 combination, line 1 cycles and radio lung. Specifically radio lung gives clear survival benefit in the PFS and OS in stage IIIB (P=0.002) and IV (P<0.001). On the other hand, the number of distant metastases in stage IV patients did not affect OS, neither PFS. In addition patients who received platinum and taxane had better PFS (P=0.001) and OS (P<0.001) than those who received platinum without taxane. Also the third drug administration proved futile, since survival (682.06±34.9) (P=0.023) and PFS (434.93±26.93) (P=0.012) of patients who received less than three drugs was significantly larger. Finally

  15. Achievement of Cure with Gefitinib in Advanced Lung Adenocarcinoma Harboring an Activating EGFR Mutation: A Case Report

    PubMed Central

    Kuwata, Taiji; Yoneda, Kazue; Kobayashi, Kenichi; Oyama, Rintarou; Matumiya, Hiroki; Shinohara, Shuichi; Takenaka, Masaru; Oka, Soichi; Chikaishi, Yasuhiro; Imanishi, Naoko; Kuroda, Koji; Tanaka, Fumihiro

    2016-01-01

    Tyrosine kinase inhibitors (TKIs) of the epidermal growth factor receptor (EGFR) may achieve long-term survival in selected cases with advanced non-small cell lung cancer harboring activating mutations in the EGFR gene, but a cured case has not been reported yet. Here, we present the first case of EGFR-mutated lung adenocarcinoma cured with an EGFR-TKI, as the 75-year-old Japanese man has achieved complete response with gefitinib treatment and has survived without tumor 10 years after termination of gefitinib treatment.

  16. Rapid Response to High-Dose, Pulsatile Erlotinib in Afatinib-Refractory Leptomeningeal Carcinomatosis from Adenocarcinoma of the Lung: A Case Report

    PubMed Central

    Fan, Frank S.

    2016-01-01

    Leptomeningeal carcinomatosis occurred in an old female patient who was on a standard dose of afatinib for the treatment of her non-small cell lung cancer harboring an epidermal growth factor receptor gene mutation sensitive to tyrosine kinase inhibitors when extracranial lesions were still under control. Shifting to high-dose, pulsatile erlotinib dramatically saved her from the devastating condition in a very short period of time. Inadequate afatinib concentration in cerebrospinal fluid is reasonably suspected, and there is a call for clinical trials testing high-dose afatinib in leptomeningeal carcinomatosis. PMID:27790117

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

    PubMed Central

    ZHANG, WEI; WANG, JIEZHONG; TANG, MINGDENG; PAN, JIANJI; BAI, PENGGANG; LIN, DUANYU; QIAN, FEIYU; LIN, FENGJIE; YANG, XUEQIN; ZHANG, SHENGLI

    2012-01-01

    Radiation lung injury is a common side-effect of pulmonary radiotherapy. The aim of this study was to quantitatively assess early changes in lung perfusion single photon emission computed tomography (SPECT) scanning and pulmonary function testing (PFT) prior to and after intensity modulated radiotherapy (IMRT) for patients suffering from locally advanced non-small cell lung cancer (LANSCLC). Twenty patients with LANSCLC received lung perfusion SPECT scanning and PFT prior to IMRT and immediately after IMRT. Lung perfusion index (LPI) was calculated after the quantification of perfusion SPECT images. The LPI of the two groups was analyzed by matched t-test. The radioactive count of each layer of single lung was added to obtain the sum of the irradiated area. The percentage of the irradiated area of single lung was calculated. Linear correlation analysis was carried out between the percentage of the irradiated area and LPI in order to verify the validity of LPI. In this study, LPI and the percentage of the irradiated area of single lung exhibited an excellent correlation either prior to or after IMRT (r=0.820 and r=0.823, respectively; p<0.001). There was no statistically significant difference between pre-IMRT LPI and post-IMRT LPI (p=0.135). LPI in the group receiving a radical dose had no statistically significant difference (p=0.993), however, it showed a statistically significant difference in the group receiving a non-radical dose (p=0.025). In the non-radical dose group, the post-IMRT LPI was larger compared to pre-IMRT. None of the parameters of PFT exhibited a statistically significant difference prior to and after IMRT (p>0.05). The quantitative method of lung perfusion SPECT scanning can be used to evaluate changes in perfusion early in patients receiving a non-radical dose (BED ≤126,500 cGy) IMRT. Evaluating early changes in global lung function using the current method of PFT is difficult, since time can be a contributing factor for radiation

  18. 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

  19. Efficacy of combined gemcitabine, oxaliplatin and pegaspargase (P-gemox regimen) in patients with newly diagnosed advanced-stage or relapsed/refractory extranodal NK/T-cell lymphoma

    PubMed Central

    Xia, Zhong-jun; Huang, Hui-qiang; Lin, Tong-yu; Jiang, Wen-qi; Lu, Yue

    2016-01-01

    Extranodal natural killer/T-cell lymphoma (ENKTL) is an aggressive neoplasm with a poor outcome. Asparaginase-based regimens are recommended for patients with advanced-stage or relapsed/refractory ENKTL. We retrospectively investigated the efficacy and toxicity of combined gemcitabine, oxaliplatin, and pegaspargase (P-gemox) in these patients. A total of 35 patients with newly diagnosed stage III–IV, relapsed or refractory ENKTL were treated with 2 to 8 cycles of P-gemox: gemcitabine (1250 mg/m2) and oxaliplatin (85 mg/m2) injected intravenously and pegaspargase (2500 IU/m2) injected intramuscularly on day 1 and repeated every 2 weeks. Upon completion of treatment, the overall response rate was 80.0%, with a complete response in 51.4% of patients. The 1-, 2- and 3- year progression-free survival rates were 45.0%, 38.6% and 38.6%, and overall survival rates were 76.8%, 64.7% and 64.7%, respectively. Patients who attained a complete response showed better progression-free survival than those without a complete response (p = 0.01). The major adverse effects were hematologic toxicity and liver dysfunction. Grade 3/4 leucopenia and neutropenia occurred in 40.0% of patients. No treatment-related deaths occurred. These results indicate the P-gemox regimen is a safe and effective treatment for patients with newly diagnosed advanced-stage or relapsed/refractory ENKTL. We anticipate future prospective trials will confirm the efficacy. PMID:27093153

  20. Dose escalation for unresectable locally advanced non-small cell lung cancer: end of the line?

    PubMed Central

    Hong, Julian C.

    2016-01-01

    Radiation Therapy Oncology Group (RTOG) 0617 was a randomized trial that investigated both the impact of radiation dose-escalation and the addition of cetuximab on the treatment of non-small cell lung cancer (NSCLC). The results of RTOG 0617 were surprising, with the dose escalation randomization being closed prematurely due to futility stopping rules, and cetuximab ultimately showing no overall survival benefit. Locally advanced unresectable NSCLC has conventionally been treated with concurrent chemoradiation. Though advances in treatment technology have improved the ability to deliver adequate treatment dose, the foundation for radiotherapy (RT) has remained the same since the 1980s. Since then, progressive studies have sought to establish the safety and efficacy of escalating radiation dose to loco-regional disease. Though RTOG 0617 did not produce the anticipated result, much interest remains in dose escalation and establishing an explanation for the findings of this study. Cetuximab was also not found to provide a survival benefit when applied to an unselected population. However, planned retrospective analysis suggests that those patients with high epidermal growth factor receptor (EGFR) expression may benefit, suggesting that cetuximab should be applied in a targeted fashion. We discuss the results of RTOG 0617 and additional findings from post-hoc analysis that suggest that dose escalation may be limited by normal tissue toxicity. We also present ongoing studies that aim to address potential causes for mortality in the dose escalation arm through adaptive or proton therapy, and are also leveraging additional concurrent systemic agents such as tyrosine kinase inhibitors (TKIs) for EGFR-activating mutations or EML4-ALK rearrangements, and poly (ADP-ribose) polymerase (PARP) inhibitors. PMID:26958507

  1. Dose escalation for unresectable locally advanced non-small cell lung cancer: end of the line?

    PubMed

    Hong, Julian C; Salama, Joseph K

    2016-02-01

    Radiation Therapy Oncology Group (RTOG) 0617 was a randomized trial that investigated both the impact of radiation dose-escalation and the addition of cetuximab on the treatment of non-small cell lung cancer (NSCLC). The results of RTOG 0617 were surprising, with the dose escalation randomization being closed prematurely due to futility stopping rules, and cetuximab ultimately showing no overall survival benefit. Locally advanced unresectable NSCLC has conventionally been treated with concurrent chemoradiation. Though advances in treatment technology have improved the ability to deliver adequate treatment dose, the foundation for radiotherapy (RT) has remained the same since the 1980s. Since then, progressive studies have sought to establish the safety and efficacy of escalating radiation dose to loco-regional disease. Though RTOG 0617 did not produce the anticipated result, much interest remains in dose escalation and establishing an explanation for the findings of this study. Cetuximab was also not found to provide a survival benefit when applied to an unselected population. However, planned retrospective analysis suggests that those patients with high epidermal growth factor receptor (EGFR) expression may benefit, suggesting that cetuximab should be applied in a targeted fashion. We discuss the results of RTOG 0617 and additional findings from post-hoc analysis that suggest that dose escalation may be limited by normal tissue toxicity. We also present ongoing studies that aim to address potential causes for mortality in the dose escalation arm through adaptive or proton therapy, and are also leveraging additional concurrent systemic agents such as tyrosine kinase inhibitors (TKIs) for EGFR-activating mutations or EML4-ALK rearrangements, and poly (ADP-ribose) polymerase (PARP) inhibitors.

  2. 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

  3. Advanced Glycation End-Products Enhance Lung Cancer Cell Invasion and Migration.

    PubMed

    Hsia, Te-Chun; Yin, Mei-Chin; Mong, Mei-Chin

    2016-01-01

    Effects of carboxymethyllysine (CML) and pentosidine, two advanced glycation end-products (AGEs), upon invasion and migration in A549 and Calu-6 cells, two non-small cell lung cancer (NSCLC) cell lines were examined. CML or pentosidine at 1, 2, 4, 8 or 16 μmol/L were added into cells. Proliferation, invasion and migration were measured. CML or pentosidine at 4-16 μmol/L promoted invasion and migration in both cell lines, and increased the production of reactive oxygen species, tumor necrosis factor-α, interleukin-6 and transforming growth factor-β1. CML or pentosidine at 2-16 μmol/L up-regulated the protein expression of AGE receptor, p47(phox), intercellular adhesion molecule-1 and fibronectin in test NSCLC cells. Matrix metalloproteinase-2 protein expression in A549 and Calu-6 cells was increased by CML or pentosidine at 4-16 μmol/L. These two AGEs at 2-16 μmol/L enhanced nuclear factor κ-B (NF-κ B) p65 protein expression and p38 phosphorylation in A549 cells. However, CML or pentosidine at 4-16 μmol/L up-regulated NF-κB p65 and p-p38 protein expression in Calu-6 cells. These findings suggest that CML and pentosidine, by promoting the invasion, migration and production of associated factors, benefit NSCLC metastasis. PMID:27517907

  4. Advanced Glycation End-Products Enhance Lung Cancer Cell Invasion and Migration

    PubMed Central

    Hsia, Te-Chun; Yin, Mei-Chin; Mong, Mei-Chin

    2016-01-01

    Effects of carboxymethyllysine (CML) and pentosidine, two advanced glycation end-products (AGEs), upon invasion and migration in A549 and Calu-6 cells, two non-small cell lung cancer (NSCLC) cell lines were examined. CML or pentosidine at 1, 2, 4, 8 or 16 μmol/L were added into cells. Proliferation, invasion and migration were measured. CML or pentosidine at 4–16 μmol/L promoted invasion and migration in both cell lines, and increased the production of reactive oxygen species, tumor necrosis factor-α, interleukin-6 and transforming growth factor-β1. CML or pentosidine at 2–16 μmol/L up-regulated the protein expression of AGE receptor, p47phox, intercellular adhesion molecule-1 and fibronectin in test NSCLC cells. Matrix metalloproteinase-2 protein expression in A549 and Calu-6 cells was increased by CML or pentosidine at 4–16 μmol/L. These two AGEs at 2–16 μmol/L enhanced nuclear factor κ-B (NF-κ B) p65 protein expression and p38 phosphorylation in A549 cells. However, CML or pentosidine at 4–16 μmol/L up-regulated NF-κB p65 and p-p38 protein expression in Calu-6 cells. These findings suggest that CML and pentosidine, by promoting the invasion, migration and production of associated factors, benefit NSCLC metastasis. PMID:27517907

  5. New drugs in the palliative chemotherapy of advanced non-small-cell lung cancer.

    PubMed

    Malayeri, R; Pirker, R; Huber, H

    2001-10-01

    In inoperable advanced non-small-cell lung cancer (NSCLC), palliative chemotherapy is established and aims at palliation of symptoms, improvement of quality of life and prolongation of survival. In the last years, several new drugs with enhanced activity towards NSCLC and improved toxicity profile have been characterised, for example vinorelbine, gemcitabine, paclitaxel and docetaxel. Data from randomised trials suggest that regimens containing new drugs are more active than older combinations. Platin-based combinations of either vinorelbine, gemcitabine or paclitaxel have resulted in better outcome than cisplatin alone and new drugs in combination with platins are more active than the corresponding single agent. Non-platin-based combinations must be considered investigational until their non-inferiority to platin-based protocols has been proven in randomised trials on large patient populations. Patients with good performance status and adequate organ function should receive platin-based chemotherapy that includes the new drugs (vinorelbine, gemcitabine, paclitaxel or docetaxel). New drugs without platins are suitable for elderly patients and patients with poor performance status. Second-line chemotherapy prolongs survival in selected patients and should be particularly offered to patients with good performance status. PMID:11694767

  6. The 2015 World Health Organization Classification of Lung Tumors: Impact of Genetic, Clinical and Radiologic Advances Since the 2004 Classification.

    PubMed

    Travis, William D; Brambilla, Elisabeth; Nicholson, Andrew G; Yatabe, Yasushi; Austin, John H M; Beasley, Mary Beth; Chirieac, Lucian R; Dacic, Sanja; Duhig, Edwina; Flieder, Douglas B; Geisinger, Kim; Hirsch, Fred R; Ishikawa, Yuichi; Kerr, Keith M; Noguchi, Masayuki; Pelosi, Giuseppe; Powell, Charles A; Tsao, Ming Sound; Wistuba, Ignacio

    2015-09-01

    The 2015 World Health Organization (WHO) Classification of Tumors of the Lung, Pleura, Thymus and Heart has just been published with numerous important changes from the 2004 WHO classification. The most significant changes in this edition involve (1) use of immunohistochemistry throughout the classification, (2) a new emphasis on genetic studies, in particular, integration of molecular testing to help personalize treatment strategies for advanced lung cancer patients, (3) a new classification for small biopsies and cytology similar to that proposed in the 2011 Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification, (4) a completely different approach to lung adenocarcinoma as proposed by the 2011 Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification, (5) restricting the diagnosis of large cell carcinoma only to resected tumors that lack any clear morphologic or immunohistochemical differentiation with reclassification of the remaining former large cell carcinoma subtypes into different categories, (6) reclassifying squamous cell carcinomas into keratinizing, nonkeratinizing, and basaloid subtypes with the nonkeratinizing tumors requiring immunohistochemistry proof of squamous differentiation, (7) grouping of neuroendocrine tumors together in one category, (8) adding NUT carcinoma, (9) changing the term sclerosing hemangioma to sclerosing pneumocytoma, (10) changing the name hamartoma to "pulmonary hamartoma," (11) creating a group of PEComatous tumors that include (a) lymphangioleiomyomatosis, (b) PEComa, benign (with clear cell tumor as a variant) and PMID:26291008

  7. 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.

  8. Pembrolizumab for the treatment of PD-L1 positive advanced or metastatic non-small cell lung cancer.

    PubMed

    Dang, Thu Oanh; Ogunniyi, Adebayo; Barbee, Meagan S; Drilon, Alexander

    2016-01-01

    The emergence of immune checkpoint inhibitors marked an important advancement in the development of cancer therapeutics. Pembrolizumab is a selective humanized IgG4 kappa monoclonal antibody that inhibits the programmed death-1 (PD-1) receptor, an integral component of immune checkpoint regulation in the tumor microenvironment. The drug is currently approved by the Food and Drug Administration for the treatment of advanced melanoma and metastatic squamous and nonsquamous non-small cell lung cancer (NSCLC). Several published studies demonstrate that single-agent pembrolizumab is safe and has efficacy in patients with NSCLC. Many ongoing protocols are investigating the role of pembrolizumab in combination with other agents in lung cancer and various other cancer types. We review the available data on pembrolizumab in NSCLC and examine the role of potential predictive biomarkers of response to therapy.

  9. S0536: Cetuximab, Paclitaxel, Carboplatin, and Bevacizumab in Treating Patients With Advanced Non-Small Cell Lung Cancer

    ClinicalTrials.gov

    2015-08-11

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

  10. Rapid Response of Advanced Squamous Non-Small Cell Lung Cancer with Thrombocytopenia after First-Line Treatment with Pembrolizumab Plus Autologous Cytokine-Induced Killer Cells.

    PubMed

    Hui, Zhenzhen; Zhang, Xinwei; Ren, Baozhu; Li, Runmei; Ren, Xiubao

    2015-01-01

    We present the first clinical evidence of advanced squamous non-small cell lung cancer with severe thrombocytopenia showing dramatic improvement after first-line treatment with pembrolizumab plus autologous cytokine-induced killer cells.

  11. 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.

  12. 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.

  13. 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

  14. A Dose Escalation and Cohort Expansion Study of Anti-CD27 (Varlilumab) and Anti-PD-1 (Nivolumab) in Advanced Refractory Solid Tumors

    ClinicalTrials.gov

    2016-07-21

    Non-small Cell Lung Cancer (NSCLC); Squamous Cell Carcinoma of the Head and Neck (SCCHN); Ovarian Carcinoma; Colorectal Cancer (CRC); Renal Cell Carcinoma (RCC) (Phase ll Only); Glioblastoma (GBM) (Phase ll Only); Melanoma (Phase 1 Only)

  15. Intensity-Modulated Radiotherapy for Locally Advanced Non-Small-Cell Lung Cancer: A Dose-Escalation Planning Study

    SciTech Connect

    Lievens, Yolande; Nulens, An; Gaber, Mousa Amr; Defraene, Gilles; De Wever, Walter; Stroobants, Sigrid; Van den Heuvel, Frank

    2011-05-01

    Purpose: To evaluate the potential for dose escalation with intensity-modulated radiotherapy (IMRT) in positron emission tomography-based radiotherapy planning for locally advanced non-small-cell lung cancer (LA-NSCLC). Methods and Materials: For 35 LA-NSCLC patients, three-dimensional conformal radiotherapy and IMRT plans were made to a prescription dose (PD) of 66 Gy in 2-Gy fractions. Dose escalation was performed toward the maximal PD using secondary endpoint constraints for the lung, spinal cord, and heart, with de-escalation according to defined esophageal tolerance. Dose calculation was performed using the Eclipse pencil beam algorithm, and all plans were recalculated using a collapsed cone algorithm. The normal tissue complication probabilities were calculated for the lung (Grade 2 pneumonitis) and esophagus (acute toxicity, grade 2 or greater, and late toxicity). Results: IMRT resulted in statistically significant decreases in the mean lung (p <.0001) and maximal spinal cord (p = .002 and 0005) doses, allowing an average increase in the PD of 8.6-14.2 Gy (p {<=}.0001). This advantage was lost after de-escalation within the defined esophageal dose limits. The lung normal tissue complication probabilities were significantly lower for IMRT (p <.0001), even after dose escalation. For esophageal toxicity, IMRT significantly decreased the acute NTCP values at the low dose levels (p = .0009 and p <.0001). After maximal dose escalation, late esophageal tolerance became critical (p <.0001), especially when using IMRT, owing to the parallel increases in the esophageal dose and PD. Conclusion: In LA-NSCLC, IMRT offers the potential to significantly escalate the PD, dependent on the lung and spinal cord tolerance. However, parallel increases in the esophageal dose abolished the advantage, even when using collapsed cone algorithms. This is important to consider in the context of concomitant chemoradiotherapy schedules using IMRT.

  16. 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.

  17. Biomarkers and targeted systemic therapies in advanced non-small cell lung cancer.

    PubMed

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

    2015-11-01

    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.

  18. 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

  19. 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.

  20. Gabapentin for Chronic Refractory Cancer Cough.

    PubMed

    Atreya, Shrikant; Kumar, Gaurav; Datta, Soumitra Shankar

    2016-01-01

    Vagal sensory neuropathy or vagal hypersensitivity has been implicated in the pathophysiology of chronic cough. Earlier reports have shown gabapentin to be effective in sensory laryngeal neuropathy and symptom conditions that have a proven neural origin. We present a case report of a patient with chronic refractory cough due to a soft tissue mass in the lung that caused compression of the mediastinal structures. The patient was successfully treated with gabapentin with reduction in the cough intensity, duration, and frequency. PMID:26962287

  1. Gabapentin for Chronic Refractory Cancer Cough

    PubMed Central

    Atreya, Shrikant; Kumar, Gaurav; Datta, Soumitra Shankar

    2016-01-01

    Vagal sensory neuropathy or vagal hypersensitivity has been implicated in the pathophysiology of chronic cough. Earlier reports have shown gabapentin to be effective in sensory laryngeal neuropathy and symptom conditions that have a proven neural origin. We present a case report of a patient with chronic refractory cough due to a soft tissue mass in the lung that caused compression of the mediastinal structures. The patient was successfully treated with gabapentin with reduction in the cough intensity, duration, and frequency. PMID:26962287

  2. The evidence base for oxygen for chronic refractory breathlessness: issues, gaps, and a future work plan.

    PubMed

    Johnson, Miriam J; Abernethy, Amy P; Currow, David C

    2013-04-01

    Breathlessness or "shortness of breath," medically termed dyspnea, is a common and distressing symptom featuring strongly in advanced lung, cardiac, and neuromuscular diseases; its prevalence and intensity increase as death approaches. However, despite the increasing understanding in the genesis of breathlessness, as well as an increasing portfolio of treatment options, breathlessness is still difficult to manage and engenders helplessness in caregivers and health care professionals and fear for patients. Although hypoxemia does not appear to be the dominant driver for breathlessness in advanced disease, the belief that oxygen is important for the relief of acute, chronic, and acute-on-chronic shortness of breath is firmly embedded in the minds of patients, caregivers, and health care professionals. This article presents current understanding of the use of oxygen for treating refractory breathlessness in advanced disease. The objective is to highlight what is still unknown, set a research agenda to resolve these questions, and highlight methodological issues for consideration in planned studies.

  3. [Advances in Bevacizumab Therapy for Non-small Cell Lung Cancer 
with Brain Metastases].

    PubMed

    Qu, Liyan; Geng, Rui; Song, Xia

    2016-08-20

    Brain metastases are frequently encountered in patients with non-small cell lung cancer (NSCLC) and are a significant cause of morbidity and mortality. Antiangiogenesis therapy plays a major role in the management of brain metastases in lung cancer. Bevacizumab have become the novel method for the treatment of lung cancer with brain metastases beyond the whole brain radiation therapy, stereotactic radiosurgery and chemotherapy. Recently, more and more studies and trials laid emphasis on the bevacizumab for NSCLC with brain metastases treatment. The key point is the efficacy and safety. In this review, bevacizumab therapy of NSCLC with brain metastases were summarized. PMID:27561800

  4. 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

  5. Long noncoding and circular RNAs in lung cancer: advances and perspectives.

    PubMed

    Xie, Weijia; Yuan, Shuai; Sun, Zhifu; Li, Yafei

    2016-09-01

    Better understanding and management of lung cancer are needed. Although much has been learned from known protein coding genes, long noncoding RNAs (lncRNAs), a relatively new and fast evolving large family of transcripts, have recently generated much attention for new discoveries. LncRNAs play critical regulatory functions and are emerging as new players in tumorigenesis and phenotypic determinators of lung cancer. In this review, we highlight the latest development of lncRNAs, including circular RNAs in lung cancer. We start with well-characterized lncRNAs and circular RNAs as an oncogene or tumor suppressor and then extend our discussion on the impact of SNPs in lncRNA on its functions and lung cancer risk and the clinical applications of lncRNAs as biomarkers and therapeutic targets. PMID:27585562

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

    PubMed

    Vincent, M D

    2009-08-01

    The management of advanced non-small-cell lung cancer (a-nsclc) is currently undergoing one of its rare paradigm shifts. Just as the nihilism of the 1970s gave way to the empiricism of the 1980s and 1990s, so the current decade has seen the first truly rational therapies based on informed design. In addition, molecular markers and traditional parameters can now be combined to provide a framework of knowledge that will guide the application of not just the new therapies, but also the older ones that remain effective. This framework-as important a component of the rational paradigm as the new drugs themselves are-is necessary to decide who should and, crucially, who should not receive the various components of this rapidly expanding armamentarium. Here, I have provided a historical overview of the drug treatment of a-nsclc, a mini-review of important new data, and an integrative approach that tries to ensure that patients receive the optimal treatment choice at the appropriate time.The speed at which new knowledge now arrives, coupled with the persistent high level of unmet medical need, suggests that the traditional pace of evidence-based review needs to be accelerated. Indeed, the increased scope for personalized management constitutes something of a challenge to "business as usual" evidence-based medicine. As a result, substantial investment on the part of payers, which may or may not be possible, will be required. In the meantime, some patients may wish and may be financially able to take advantage of modern developments before they have been fully digested by the public-payer system. Responsive clinicians face difficult tradeoffs as they try to balance the pros and cons of early adoption versus excessive conservatism.The present article is my personal view of how to navigate these waters, and although it is written especially for patients who like to be the captain of their own ship, there is good reason to believe that all patients will eventually be managed by

  7. 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

  8. 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

  9. Effect of trifluoperazine on Tc-99m sestamibi uptake in patients with advanced nonsmall cell lung cancer

    PubMed Central

    Abdülrezzak, Ümmühan; Erdoğan, Zeynep; Silov, Güler; Özdal, Ayşegül; Turhal, Özgül

    2016-01-01

    Objective: The aim of this study was to investigate whether there is an effect of trifluoperazine on Tc-99m  methoxyisobutylisonitrile (MIBI) uptake in patients with advanced nonsmall cell lung cancer (NCLC). Materials and Methods: A total of 23 patients with biopsy-proven advanced NCLC who had no previous history of chemo-radiotherapy, underwent baseline dual phase planar, single photon emission computed tomography and whole body Tc-99m MIBI scintigraphy performed at 20 and 120 min. After oral administration of trifluoperazine (5 mg, 2 times a day, for 5 days), dual phase Tc-99m MIBI scintigraphy was repeated. For each patient, and for both studies, regions of interest were drawn over the tumor area (T) and over the normal lung area (L) on the contralateral side in transverse slices where tumor was visualized clearly. Then, early and delayed T/L ratios and washout rate (WR) were calculated. Results: Tc-99m MIBI was accumulated in the cancer tissue in all of the patients. Delayed ratio after the oral administration of trifluoperazine (DR2) was significantly higher (P = 0.039) than delayed ratio before trifluoperazine (DR1). We found no significant differences of early ratio before trifluoperazine (ER1) and early ratio after trifluoperazine (ER2), and washout rate before (WR1) and washout rate after trifluoperazine (WR2). Conclusion: In patients with advanced NCLC, trifluoperazine treatment in addition to chemotherapy might be useful. However, our results need to be confirmed in larger series of patients. PMID:27095857

  10. 18F-FDG PET/CT Reveals Disease Remission in a Patient With Ipilimumab-Refractory Advanced Melanoma Treated With Pembrolizumab.

    PubMed

    Sachpekidis, Christos; Hassel, Jessica C; Dimitrakopoulou-Strauss, Antonia

    2016-02-01

    Pembrolizumab is an anti-programmed cell death receptor 1 (anti-PD-1) antibody, recently approved for the treatment of ipilimumab-refractory metastatic melanoma. We report on a 49-year-old patient with unresectable metastatic melanoma initially treated with 4 cycles of ipilimumab. Because of demonstration of progressive disease on PET/CT, the patient was enrolled into a clinical trial of pembrolizumab. After completion of 4 cycles of pembrolizumab, the follow-up PET/CT scans performed early after and 7 months after the end of treatment exhibited complete disease remission, reflecting the potential role of the modality in treatment response evaluation of melanoma patients receiving anti-PD-1 therapy.

  11. CFB refractory repair

    SciTech Connect

    Sur, C.; Nagar, A.; Singh, D.K.; Chakraborty, I.N.

    2006-01-15

    ACC Refractories has provided the refractories of 13 of the 20 circulating fluidized-bed combustion (CFBC) plants in India. If high levels of sulfur oxide gases are generated in India's coal, lignite or pet coke fuelled power plants they can wreak havoc on furnace liners. Calcium sulfate was the most common denominator in failed castable matrices analysed by ACC. To solve the problem, Accplast 80, a phosphate-bonded aluminous plastic has been used successfully. The article gives advice on installation of plastic refractories and on steps to prevent erosion. 10 figs., 1 tab., 4 photos.

  12. 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

  13. The role of maintenance treatment in advanced non-small-cell lung cancer: reality or early second line?

    PubMed

    Gridelli, Cesare; Rossi, Antonio; Maione, Paolo; Ambrosio, Rita; Barbato, Valentina; Bareschino, Maria Anna; Schettino, Clorinda; Palazzolo, Giovanni; Sacco, Paola Claudia

    2010-11-01

    First-line platinum-based chemotherapy has reached a plateau of effectiveness for the treatment of patients with advanced non-small-cell lung cancer (NSCLC). In patients who reported a stable disease, no more than 4 cycles of chemotherapy are recommended while a maximum of 6 cycles is recommended in patients who are responding to therapy. A potential strategy with the aim of improving outcomes for NSCLC patients is to administer more therapy. This term includes different approaches: duration of therapy, sequential therapy, consolidation therapy, and maintenance therapy. Here, we attempt to define the different approaches that fall under the rubric of maintenance strategy, and discuss the results available to date.

  14. 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

  15. 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.

  16. Recent advances and clinical implications of the micropapillary histological subtype in lung adenocarcinomas.

    PubMed

    Lee, Ming-Ching; Buitrago, Daniel H; Kadota, Kyuichi; Jones, David R; Adusumilli, Prasad S

    2014-06-01

    Micropapillary (MIP) histologic subtype included in the classification of lung adenocarcinomas (ADCs) is associated with both size- and stage-independent poor prognoses. MIP pattern in lung ADCs, even at small, early stages, correlates with high lymphovascular invasion, visceral pleural invasion and lymph node metastases. Recently, we reported that patients with a MIP component are at a higher risk of locoregional recurrence after limited resection. Identification of a MIP pattern is only possible with permanent pathologic sections; preoperative imaging, cytology or intraoperative frozen section specimens remain unreliable. The intermixed, heterogenous morphology of lung ADC presents a technical challenge in investigating the molecular biology of cells with MIP morphology. A comprehensive understanding of the biology of MIP morphology is vital for therapeutic interventions.

  17. Challenges in molecular testing in non-small-cell lung cancer patients with advanced disease.

    PubMed

    Hiley, Crispin T; Le Quesne, John; Santis, George; Sharpe, Rowena; de Castro, David Gonzalez; Middleton, Gary; Swanton, Charles

    2016-09-01

    Lung cancer diagnostics have progressed greatly in the previous decade. Development of molecular testing to identify an increasing number of potentially clinically actionable genetic variants, using smaller samples obtained via minimally invasive techniques, is a huge challenge. Tumour heterogeneity and cancer evolution in response to therapy means that repeat biopsies or circulating biomarkers are likely to be increasingly useful to adapt treatment as resistance develops. We highlight some of the current challenges faced in clinical practice for molecular testing of EGFR, ALK, and new biomarkers such as PDL1. Implementation of next generation sequencing platforms for molecular diagnostics in non-small-cell lung cancer is increasingly common, allowing testing of multiple genetic variants from a single sample. The use of next generation sequencing to recruit for molecularly stratified clinical trials is discussed in the context of the UK Stratified Medicine Programme and The UK National Lung Matrix Trial. PMID:27598680

  18. [Advances in the study of the relationship between autophagy and sepsis-induced lung injury].

    PubMed

    Wang, Xingtong; Li, Hengyu; Xia, Zhaofan

    2014-08-01

    Sepsis is one of the most common pathogenetic causes of acute lung injury (ALI), and at present there is still a lack of effective targeted techniques and methods for its prevention and treatment. Autophagy is a homeostatic mecha- nism common to all eukaryotic cells, including adaption to environment, defense against invasion of pathogens, and maintenance of cellular homeostasis. Autophagy is also involved in a variety of lung-related diseases. In septic lung injury, autophagy not only serves to dissipate dysfunctional organelles, but also inhibits the release of inflammatory cytokines. This review aims at eliciting the role of autophagy in sepsis-induced ALI and further exploring the potential targets of autophagy in inhibiting inflammation, in an effort to provide a new perspective for clinical treatment of sepsis-induced ALI.

  19. Metachronous primary uterine cancer surgically resected during Crizotinib treatment in a ALK-rearranged advanced lung adenocarcinoma

    PubMed Central

    Misino, Andrea; Scattone, Anna; Caldarola, Lucia; Petroni, Stella; Logroscino, Antonio; Montagna, Elisabetta Sara; Serio, Gabriella; Simone, Giovanni; Galetta, Domenico

    2016-01-01

    Rearrangements of the anaplastic lymphoma kinase (ALK) gene are present in 3% to 7% of non-small-cell lung cancers (NSCLCs). Patients harboring ALK rearrangements show very favourable outcomes if treated with targeted agents, among which crizotinib is the first and best studied. Crizotinib, an oral small-molecule tyrosine kinase inhibitor of ALK, MET, and ROS1 kinases, is a very active and well tolerated drug. Nevertheless, the optimal therapy management with this new drug is still partially unknown, especially with regard to the safety of combined treatments. Recently, the integration of locoregional treatments has been proposed as a feasible multimodality strategy in selected patients with good clinical conditions and slow-growing or oligoprogressive disease. In this report, a case of advanced lung adenocarcinoma, progressed after first line chemotherapy and re-biopsied detecting ALK rearrangement, is described. During crizotinib treatment the primary lung tumor showed an excellent regression; meanwhile a major surgery for a metachronous uterine cancer was safely and successfully carried out. PMID:26958511

  20. Advanced lung ventilation system (ALVS) with linear respiratory mechanics assumption for waveform optimization of dual-controlled ventilation.

    PubMed

    Montecchia, F; Guerrisi, M; Canichella, A

    2007-03-01

    The present paper describes the functional features of an advanced lung ventilation system (ALVS) properly designed for the optimization of conventional dual-controlled ventilation (DCV), i.e. with pressure-controlled ventilation with ensured tidal or minute volume. Considering the particular clinical conditions of patients treated with controlled ventilation the analysis and synthesis of ALVS control have been performed assuming a linear respiratory mechanics. Moreover, new airways pressure waveforms with more physiological shape can be tested on simulators of respiratory system in order to evaluate their clinical application. This is obtained through the implementation of a compensation procedure making the desired airways pressure waveform independent on patient airways resistance and lung compliance variations along with a complete real-time monitoring of respiratory system parameters leading the ventilator setting. The experimental results obtained with a lung simulator agree with the theoretical ones and show that ALVS performance is useful for the research activity aiming at the improvement of both diagnostic evaluation and therapeutic outcome relative to mechanical ventilation treatments.

  1. 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

  2. Prognostic impact of serum CYFRA 21–1 in patients with advanced lung adenocarcinoma: a retrospective study

    PubMed Central

    2013-01-01

    Background Serum CYFRA 21–1 is one of the most important serum markers in the diagnosis of non-small cell lung cancer (NSCLC), especially squamous-cell carcinoma. However, it remains unknown whether pretreatment serum CYFRA 21–1 values (PCV) may also have prognostic implications in patients with advanced lung adenocarcinoma. Methods We retrospectively reviewed the data of 284 patients (pts) who were diagnosed as having advanced lung adenocarcinoma and had received initial therapy. Results Of the study subjects, 121 pts (43%) had activating epidermal growth factor receptor (EGFR) mutations (Mt+), while the remaining 163 pts (57%) had wild-type EGFR (Mt-). Univariate analysis identified gender (male/ female), ECOG performance status (PS) (0-1/ ≥2), PCV (<2.2 ng/ml/ ≥2.2 ng/ml), EGFR mutation status (Mt+/ Mt-), pretreatment serum CEA values (<5.0 ng/ml/ ≥5.0 ng/ml), smoking history (yes/ no) and EGFR-TKI treatment (yes/ no) as prognostic factors (p = .008, p < .0001, p < .0001, p < .0001, p = .036, p = .0012, p < .0001 respectively). Cox's multivariate regression analysis identified PCV < 2.2ng/ml as the only factor significantly associated with prolonged survival (p < .0001, hazard ratio: 0.43, 95% CI 0.31-0.59), after adjustments for PS (p < .0001), EGFR mutation status (p = .0069), date of start of initial therapy (p = .07), gender (p = .75), serum CEA level (p = .63), smoking history (p = .39) and EGFR-TKI treatment (p = .20). Furthermore, pts with Mt+ and PCV of <2.2 ng/ml had a more favorable prognosis than those with Mt+ and PCV of ≥2.2 ng/ml (MST: 67.0 vs. 21.0 months, p < .0001), and patients with Mt- and PCV of <2.2 ng/ml had a more favorable prognosis than those with Mt- and PCV of ≥2.2 ng/ml (MST: 24.1 vs. 10.2 months, p < .0001). Conclusion PCV may be a potential independent prognostic factor in both Mt+ and Mt- patients with advanced lung adenocarcinoma. PMID:23879483

  3. 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.

  4. 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

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

    PubMed

    Bigelow, Mary Emma Gorham; 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

  6. Gradual versus abrupt weaning from respiratory support in acute respiratory failure and advanced chronic obstructive lung disease.

    PubMed

    Ashutosh, K

    1983-10-01

    Two methods of weaning from mechanical ventilation were compared in 18 instances of acute respiratory failure requiring mechanical ventilation for more than 30 days in patients with advanced chronic obstructive lung disease. All patients were ventilated using intermittent mandatory ventilation. Abrupt weaning (AW) consisted of abruptly discontinuing mechanical ventilation when the patients were considered ready for unassisted breathing. Gradual weaning (GW) involved a gradual reduction in the rate of intermittent mandatory ventilation before starting unassisted breathing. Gradual or abrupt weaning alone was used for weaning in five and four instances, respectively. Both methods were used in nine other instances. In the 14 instances when GW was tried, weaning was successful in three. In the 13 instances when AW was tried, weaning was successful in nine. The time in which mechanical ventilation was required was 64 +/- 31 (SD) days with GW and 42 +/- 12 (SD) days with AW. There was no difference in age, pulmonary function, or arterial blood gas results between the patients being weaned by the different methods. I conclude that GW offers no advantage over AW in weaning patients with advanced chronic obstructive lung disease requiring prolonged mechanical ventilation.

  7. 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.

  8. Is uniportal thoracoscopic surgery a feasible approach for advanced stages of non-small cell lung cancer?

    PubMed Central

    Fieira, Eva; Delgado, Maria; Mendez, Lucía; Fernandez, Ricardo; de la Torre, Mercedes

    2014-01-01

    Objectives Conventional video-assisted thoracoscopic (VATS) lobectomy for advanced lung cancer is a feasible and safe surgery in experienced centers. The aim of this study is to assess the feasibility of uniportal VATS approach in the treatment of advanced non-small cell lung cancer (NSCLC) and compare the perioperative outcomes and survival with those in early-stage tumors operated through the uniportal approach. Methods From June 2010 to December 2012, we performed 163 uniportal VATS major pulmonary resections. Only NSCLC cases were included in this study (130 cases). Patients were divided into two groups: (A) early stage and (B) advanced cases (>5 cm, T3 or T4, or tumors requiring neoadjuvant treatment). A descriptive and retrospective study was performed, comparing perioperative outcomes and survival obtained in both groups. A survival analysis was performed with Kaplan-Meier curves and the log-rank test was used to compare survival between patients with early and advanced stages. Results A total of 130 cases were included in the study: 87 (A) vs. 43 (B) patients (conversion rate 1.1 vs. 6.5%, P=0.119). Mean global age was 64.9 years and 73.8% were men. The patient demographic data was similar in both groups. Upper lobectomies (A, 52 vs. B, 21 patients) and anatomic segmentectomies (A, 4 vs. B, 0) were more frequent in group A while pneumonectomy was more frequent in B (A, 1 vs. B, 6 patients). Surgical time was longer (144.9±41.3 vs. 183.2±48.9, P<0.001), and median number of lymph nodes (14 vs. 16, P=0.004) were statistically higher in advanced cases. Median number of nodal stations (5 vs. 5, P=0.165), days of chest tube (2 vs. 2, P=0.098), HOS (3 vs. 3, P=0.072), and rate of complications (17.2% vs. 14%, P=0.075) were similar in both groups. One patient died on the 58th postoperative day. The 30-month survival rate was 90% for the early stage group and 74% for advanced cases Conclusions Uniportal VATS lobectomy for advanced cases of NSCLC is a safe and

  9. 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

  10. 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

  11. 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.

  12. 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

  13. Tetrandrine Combined with Gemcitabine and Cisplatin for Patients with Advanced Non-Small Cell Lung Cancer Improve Efficacy

    PubMed Central

    Liu, Wenchao; Zhang, Ju; Ying, Cheng; Wang, Qianrong; Yan, Chen; Jingyue, Yang; Zhaocai, Yu; Yan, Xue; Heng-jun, Shi; Lin, Jiang

    2012-01-01

    Lung cancer has the highest morbidity and mortality of any malignant tumor. To improve efficacy and reduce toxicity in patients with advanced non-small cell lung cancer (NSCLC), it is important to integrate traditional and conventional medicine. Two hundred and forty patients with advanced NSCLC were randomized to tetrandrine plus GP or GP only. We infused gemcitabine on days 1 and 8; cisplatin on day 1. The tetrandrine group received continuous i.v. infusion for 10 days, with treatment repeated every 21 days. After 2 consecutive treatment cycles, we used RECIST criteria to evaluate short-term efficacy. Quality of life (QOL) was assessed according to Karnofsky score (KPS) and body weight change. We used NCI CTC 3.0 to evaluate treatment toxicity. The short-term objective response rate was 36.1% in the tetrandrine group and 24.3% in the controls (P=0.057). The short-term disease control rate was 63.9% in the tetrandrine group and 52.3% in the controls (P=0.081). The 1-year survival rates were 45.7% and 31.3%, respectively (P=0.059). KPS scores improved by 49.1% and 32.4%, respectively (P=0.012). Body weight increased by 28.7% in the tetrandrine group and 16.2% in the controls (P=0.027). The incidence of grade 2-4 leukopenia, thrombocytopenia, nausea, and vomiting in the tetrandrine group was 38.0%, 19.4%, 46.3%, and 16.7%, respectively; the control group figures were 53.2%, 34.2%, 63.0% and 27.9% (P<0.05). Tetrandrine may improve short-term efficacy and survival in patients with advanced NSCLC. Tetrandrine may also mitigate adverse reactions to chemotherapy and improve QOL for patients with NSCLC. PMID:23675254

  14. Erlotinib-associated interstitial lung disease in advanced pancreatic carcinoma: a case report and literature review.

    PubMed

    Macerelli, Marianna; Mazzer, Micol; Foltran, Luisa; Cardellino, Giovanni Gerardo; Aprile, Giuseppe

    2015-07-24

    The combination of erlotinib and gemcitabine is a recognized option for patients with metastatic pancreatic cancer whose common adverse events such as skin rash, diarrhea, or fatigue are usually easily manageable. Interstitial lung disease (ILD) is a life-threatening toxicity reported in patients with non-small-cell lung cancers treated with epidermal growth factor receptor-tyrosine kinase inhibitors or gemcitabine. This side effect is extremely rare in patients with pancreatic cancer. We report fatal treatment-related ILD that occurred in a 67-year-old patient with metastatic pancreatic cancer. Risk factors and pathophysiology of ILD need further investigation but caution is highly recommended for patients with an underlying pulmonary disease when using erlotinib in monotherapy or combination therapy.

  15. 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. PMID:27565914

  16. Local and systemic effects of an allogeneic tumor cell vaccine combining transgenic human lymphotactin with interleukin-2 in patients with advanced or refractory neuroblastoma.

    PubMed

    Rousseau, Raphaël F; Haight, Ann E; Hirschmann-Jax, Charlotte; Yvon, Eric S; Rill, Donna R; Mei, Zhuyong; Smith, Susan C; Inman, Shannon; Cooper, Kristine; Alcoser, Pat; Grilley, Bambi; Gee, Adrian; Popek, Edwina; Davidoff, Andrew; Bowman, Laura C; Brenner, Malcolm K; Strother, Douglas

    2003-03-01

    In murine models, transgenic chemokine-cytokine tumor vaccines overcome many of the limitations of single-agent immunotherapy by producing the sequence of T-cell attraction followed by proliferation. The safety and immunologic effects of this approach in humans were tested in 21 patients with relapsed or refractory neuroblastoma. They received up to 8 subcutaneous injections of a vaccine combining lymphotactin (Lptn)- and interleukin-2 (IL-2)-secreting allogeneic neuroblastoma cells in a dose-escalating scheme. Severe adverse reactions were limited to reversible panniculitis in 5 patients and bone pain in 1 patient. Injection-site biopsies revealed increased cellularity caused by infiltration of CD4+ and CD8+ lymphocytes, eosinophils, and Langerhans cells. Systemically, the vaccine produced a 2-fold (P =.035) expansion of CD4+ T cells, a 3.5-fold (P =.039) expansion of natural killer (NK) cells, a 2.1-fold (P =.014) expansion of eosinophils, and a 1.6-fold (P =.049) increase in serum IL-5. When restimulated in vitro by the immunizing cell line, T cells collected after vaccination showed a 2.3-fold increase (P =.02) of T-helper (TH2)-type CD3+IL-4+ cells. Supernatant collected from restimulated cells showed increased amounts of IL-4 (11.4-fold; P =.021) and IL-5 (8.7-fold; P =.002). Six patients had significant increases in NK cytolytic activity. Fifteen patients made immunoglobulin G (IgG) antibodies that bound to the immunizing cell line. Measurable tumor responses included complete remission in 2 patients and partial response in 1 patient. Hence, allogeneic tumor cell vaccines combining transgenic Lptn with IL-2 appear to have little toxicity in humans and can induce an antitumor immune response.

  17. 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

  18. An advanced stochastic model for mucociliary particle clearance in cystic fibrosis lungs

    PubMed Central

    Sturm, Robert

    2012-01-01

    Background A mathematical model describing mucociliary clearance in cystic fibrosis (CF) patients and its development with progressing course of the disease was developed. The approach should support the prediction of the disease state on the basis of measured bronchial clearance efficiencies. Methods The approach is based on the assumption of a steady-state steady-flow mucus transport through the tracheobronchial tree which enables the determination of airway generation-specific mucus velocities by using a measured tracheal mucus velocity and a realistic morphometric dataset of the human lung. Architecture of the tracheobronchial tree was approximated by a stochastic model, reflecting the intra-subject variability of geometric parameters within a given lung generation. Results As predicted by the appropriately validated mathematical approach, mucociliary clearance efficiency in CF patients is partly significantly decreased with respect to healthy controls. 24-h retention of patients with mild CF (FEV1 >70% of predicted) is reduced by 10% compared to healthy subjects, whilst 24-h retention of patients with moderate to severe CF (FEV1 <70% of predicted) differs by 25% from that of the healthy controls. These discrepancies are further enhanced with continuation of the clearance process. Conclusions The theoretical results lead to the conclusion that CF patients have a higher risk of inhaled particle accumulation and related particle overload in specific lung compartments than healthy subjects. PMID:22295167

  19. Vivekananda Yoga Program for Patients with Advanced Lung Cancer and their Family Caregivers

    PubMed Central

    Milbury, Kathrin; Mallaiah, Smitha; Lopez, Gabriel; Liao, Zhongxing; Yang, Chunyi; Carmack, Cindy; Chaoul, Alejandro; Spelman, Amy; Cohen, Lorenzo

    2015-01-01

    BACKGROUND Although yoga practice may improve quality of life (QOL) in cancer patients, feasibility in patients with lung cancer is largely unknown. Moreover, previous research has excluded patients’ family caregivers. Because caregivers are vulnerable to caregiver burden, a dyadic approach targeting QOL in both patient and caregiver may be particularly beneficial. Thus, the purpose of this study was to establish the feasibility of a couple-based Vivekananda Yoga (VKC) intervention in lung cancer patients and caregivers. Vivekananda Yoga may be suitable for a dyadic approach and address the multifaceted needs (e.g., emotional, physical, spiritual, and social) common among families coping with lung cancer. METHOD In this single-arm feasibility trial, patients with lung cancer undergoing radiotherapy and their caregivers participated in a 15-session VKC program focused on the interconnectedness of the dyad. The program consisted of four main components: 1) joint loosening with breath synchronization; 2) postures (asanas) and a deep relaxation technique; 3) breath energization (pranayama) with sound resonance; and 4) meditation. We assessed pre/post-intervention levels of fatigue (BFI), sleep disturbances (PSQI), psychological distress (BSI), overall mental and physical QOL (SF-36), spirituality (FACT-Sp) and relational closeness. We also tracked feasibility data, and participants completed program evaluations. RESULTS We approached 28 eligible dyads of which 15 (53%) consented and 9 (60%) completed the intervention. No adverse events were reported. Patients (mean age: 73 years, 63% female, all stage III) and caregivers (mean age: 62 years, 38% female, 63% spouses) completed a mean of 10 sessions (range: 4–14) and 95.5% of them rated the program as very useful. Paired t-tests revealed a significant increase in patients’ mental health (d=.84, P=.04) and a significant decrease in caregivers’ sleep disturbances (d=1.44, P=.02). Although not statistically

  20. [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.

  1. 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

  2. Angiogenesis inhibitors rechallenge in patients with advanced non-small-cell lung cancer: a pooled analysis of randomized controlled trials

    PubMed Central

    Zhao, Lingdi; Li, Wei; Zhang, Huiying; Hou, Nan; Guo, Lanwei; Gao, Quanli

    2015-01-01

    Purpose Data on the role of angiogenesis inhibitors (AIs) rechallenge in the treatment of advanced non-small-cell lung cancer (NSCLC) patients who previously received bevacizumab remain limited. We aim to investigate the efficacy of AIs in the treatment of advanced NSCLC in this setting. Methods Studies from PubMed, Web of Science, and abstracts presented at American Society of Clinical Oncology meeting up to December 1, 2014 were searched to identify relevant studies. Eligible studies included prospective randomized controlled trials evaluating AIs in advanced NSCLC, with survival data on patients who previously received bevacizumab. The end points were overall survival and progression-free survival. Statistical analyses were conducted by using either random effects or fixed effect models according to the heterogeneity of included studies. Results A total of 452 patients with advanced NSCLC who previously received bevacizumab were identified for analysis. The meta-analysis results demonstrated that AI rechallenge significantly improved progression-free survival (hazard ratio: 0.72, 95% confidence interval: 0.58–0.89, P=0.002) when compared to non-AI containing regimens. Additionally, a nonsignificant improvement in overall survival was also observed in advanced NSCLC in this setting (hazard ratio: 0.82, 95% confidence interval: 0.65–1.03, P=0.087). Similar results were also observed in subgroup analysis according to treatment regimens. Conclusion The findings of this study suggest that NSCLC patients who relapsed after a first-line bevacizumab-containing chemotherapy obtain improved clinical benefits from AI rechallenge. Prospective clinical trials investigating the role of AI rechallenge in this setting are recommended. PMID:26491352

  3. 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.

  4. Are VEGFR-TKIs effective or safe for patients with advanced non-small cell lung cancer?

    PubMed Central

    Wang, Shuai; Yang, Zhe; Wang, Zhou

    2015-01-01

    Vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) might be new therapeutic strategies for advanced non-small cell lung cancer (NSCLC). Here a total of 12,520 patients from 23 randomized controlled trials (RCTs) were enrolled to evaluate the efficacy and safety of VEGFR-TKIs quantitatively in advanced NSCLC. Compared with non-VEGFR-TKIs, VEGFR-TKIs regimen significantly improved progression-free survival (PFS) [hazard ratio (HR): 0.839, 95% confidence interval (CI): 0.805-0.874, P < 0.001], objective response rates (ORR) [relative risk (RR): 1.374, 95% CI: 1.193-1.583, P < 0.001] and disease control rates (DCR) (RR: 1.113, 95% CI: 1.027-1.206, P = 0.009), but not overall survival (OS) (HR: 0.960, 95% CI: 0.921-1.002, P = 0.060) for NSCLC patients. The RR of all-grade neutropenia, thrombocytopenia, hypertension, hemorrhage, fatigue, anorexia, stomatitis, diarrhea, rash, hand-foot skin reaction (HFSR) were increased in patients received VEGFR-TKIs. As for high-grade (≥ 3) adverse events (AEs), VEGFR-TKIs were associated with higher RR of neutropenia, thrombocytopenia, hypertension, fatigue, stomatitis, diarrhea, rash and HFSR. This study demonstrates VEGFR-TKIs improve PFS, ORR and DCR, but not OS in advanced NSCLC patients. VEGFR-TKIs induce more frequent and serious AEs compared with control therapies. PMID:26156021

  5. Role of erlotinib in first-line and maintenance treatment of advanced non-small-cell lung cancer

    PubMed Central

    Reguart, Noemí; Cardona, Andrés Felipe; Rosell, Rafael

    2010-01-01

    Erlotinib hydrochloride (Tarceva®) is a member of a class of small molecule inhibitors that targets the tyrosine kinase domain of the epidermal growth factor receptor (EGFR), with anti-tumor activity in preclinical models. Erlotinib represents a new-generation of agents known as “targeted therapies” designed to act upon cancer cells by interfering with aberrant specific activated pathways needed for tumor growth, angiogenesis and cell survival. Since its approval in November 2004 for the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) after the failure of at least one prior chemotherapy regimen and with a view to improving patients’ outcomes and prevent symptoms, the scientific community has evaluated the potential role of erlotinib in other scenarios such as in maintenance therapy and, in first-line setting for a selected population based on biological markers of response such as mutations of the EGFR. The convenient once-a-day pill administration and the good toxicity profile of erlotinib make it a reasonable candidate for testing in this context. This report provides a review of the role of erlotinib therapy in advanced NSCLC. It summarizes current data and perspectives of erlotinib in upfront treatment and maintenance for advanced NSCLC as well as looking at candidate biomarkers of response to these new targeted-agents. PMID:21188105

  6. 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

  7. 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.

  8. Dose Escalation for Locally Advanced Lung Cancer using Adaptive Radiotherapy with Simultaneous Integrated Volume-Adapted Boost

    PubMed Central

    Weiss, Elisabeth; Fatyga, Mirek; Wu, Yan; Dogan, Nesrin; Balik, Salim; Sleeman, William; Hugo, Geoffrey

    2013-01-01

    Purpose Test the feasibility of a planned phase I study of image-guided adaptive radiotherapy in locally advanced lung cancer. Methods and Materials Weekly 4D FBCTs of ten lung cancer patients undergoing concurrent radiochemotherapy were used to simulate adaptive radiotherapy: After an initial IMRT plan (0–30 Gy/2 Gy), adaptive replanning was performed on week 2 (30 to 50 Gy/2 Gy) and week 4 scans (50 to 66 Gy/2 Gy) to adjust for volume and shape changes of primary tumors and lymph nodes. Week 2 and 4 clinical target volumes (CTV) were deformably warped from the initial planning scan to adjust for anatomical changes. On week 4 scan a simultaneous integrated volume-adapted boost was created to the shrunken PT with dose increases in five 0.4 Gy steps from 66 Gy to 82 Gy in two scenarios: Plan A. lung isotoxicity and B. normal tissue tolerance. Cumulative dose was assessed by deformably mapping and accumulating biologically equivalent dose normalized to 2 Gy-fractions (EQD2). Results The 82 Gy level was achieved in 1/10 patients in scenario A resulting in a 13.4 Gy EQD2 increase and a 22.1% increase in tumor control probability (TCP) compared to the 66 Gy plan. In scenario B, 2 patients reached the 82 Gy level with a 13.9 Gy EQD2 and 23.4% TCP increase. Conclusions The tested IGART strategy enabled relevant increases in EQD2 and TCP. Normal tissue was often dose limiting, indicating a need to modify the present study design prior to clinical implementation. PMID:23523321

  9. Dose Escalation for Locally Advanced Lung Cancer Using Adaptive Radiation Therapy With Simultaneous Integrated Volume-Adapted Boost

    SciTech Connect

    Weiss, Elisabeth; Fatyga, Mirek; Wu, Yan; Dogan, Nesrin; Balik, Salim; Sleeman, William; Hugo, Geoffrey

    2013-07-01

    Purpose: To test the feasibility of a planned phase 1 study of image-guided adaptive radiation therapy in locally advanced lung cancer. Methods and Materials: Weekly 4-dimensional fan beam computed tomographs (4D FBCT) of 10 lung cancer patients undergoing concurrent chemoradiation therapy were used to simulate adaptive radiation therapy: After an initial intensity modulated radiation therapy plan (0-30 Gy/2 Gy), adaptive replanning was performed on week 2 (30-50 Gy/2 Gy) and week 4 scans (50-66 Gy/2 Gy) to adjust for volume and shape changes of primary tumors and lymph nodes. Week 2 and 4 clinical target volumes (CTV) were deformably warped from the initial planning scan to adjust for anatomical changes. On the week 4 scan, a simultaneous integrated volume-adapted boost was created to the shrunken primary tumor with dose increases in 5 0.4-Gy steps from 66 Gy to 82 Gy in 2 scenarios: plan A, lung isotoxicity; plan B, normal tissue tolerance. Cumulative dose was assessed by deformably mapping and accumulating biologically equivalent dose normalized to 2 Gy-fractions (EQD2). Results: The 82-Gy level was achieved in 1 in 10 patients in scenario A, resulting in a 13.4-Gy EQD2 increase and a 22.1% increase in tumor control probability (TCP) compared to the 66-Gy plan. In scenario B, 2 patients reached the 82-Gy level with a 13.9 Gy EQD2 and 23.4% TCP increase. Conclusions: The tested image-guided adaptive radiation therapy strategy enabled relevant increases in EQD2 and TCP. Normal tissue was often dose limiting, indicating a need to modify the present study design before clinical implementation.

  10. 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

  11. 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

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

    PubMed

    Meko, J; Rusch, V W

    2000-10-01

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

  13. Selection of chemotherapy for patients with advanced non-small cell lung cancer.

    PubMed

    Pennell, Nathan A

    2012-05-01

    Chemotherapy remains the first-line treatment for most patients with stage IV non-small cell lung cancer (NSCLC), but optimal regimens are now defined by histology. Platinum-based regimens with pemetrexed, bevacizumab, or both are reasonable first-line options for patients with nonsquamous NSCLC. The standard treatment for squamous NSCLC remains a platinum doublet with a drug other than pemetrexed. Maintenance therapy is emerging as a treatment strategy for patients who do not progress after four cycles of first-line chemotherapy. In the maintenance setting, pemetrexed and erlotinib significantly prolong overall survival compared with placebo after the completion of first-line chemotherapy.

  14. [The effect of extrapleural thoracoplasty on the mechanical properties of lungs and ventilation indices in advanced fibrous-cavernous tuberculosis].

    PubMed

    Strelis, A K; Lenskaia, L G

    1994-01-01

    Basing on clinical data obtained on 42 patients, the authors prove the existence of changes in all the respiratory biomechanical parameters, primarily viscosity, in response to development of advanced fibrous-cavernous tuberculosis in the lungs. Disorders in the bronchopulmonary mechanics depend on the terms of collapsosurgical intervention and its efficacy. The viscosity-induced resistance to respiration results basically from inflammation of the tracheobronchial tree and bronchospasm. An increase in the bronchial resistance in the early postoperative period occurs both in effective and uneffective extrapleural thoracoplasty, while later on it is observed only after uneffective and corrective collapsosurgical interventions. Basic biomechanical parameters of respiration (total performance, extensibility, bronchial resistance) together with spirographic and clinicoroentgenological evidence can be of help in predicting the effect of the surgery itself. A positive response of collapsosurgical interventions on respiratory biomechanics can be judged from a persistent fall in total respiratory performance irrespective of surgical effectivity.

  15. 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.

  16. 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.

  17. 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

  18. Pemetrexed/cisplatin as first-line chemotherapy for advanced lung cancer with brain metastases

    PubMed Central

    He, Guangzhao; Xiao, Xiaoguang; Zou, Man; Zhang, Chengliang; Xia, Shu

    2016-01-01

    Abstract Background: Brain metastases (BMs) are a common and serious complication of non-small cell lung cancer (NSCLC). Whole-brain radiotherapy (WBRT), surgery, and molecular targeted therapy are usually used to treat NSCLC with BM. Chemotherapeutic options for BM are limited by tumor resistance, ineffective agents, and the blood–brain barrier. Pemetrexed/cisplatin is the preferred chemotherapy in nonsquamous NSCLC, but the efficacy of this treatment for nonsquamous NSCLC with BM is uncertain. Methods: We present a case of nonsquamous NSCLC with asymptomatic BM presenting with irritating cough and right shoulder back pain (unknown sensitizing epidermal growth factor receptor mutations or anaplastic lymphoma kinase). Results: He benefited from administration of first-line chemotherapy of pemetrexed/cisplatin. Partial remission was achieved in the primary lesion of the lungs and BM lesion. He was further given 3 cycles of pemetrexed monotherapy and WBRT. Complete remission was further achieved in BM lesion. Conclusion: The findings of clinical trials and theoretical studies about the current pemetrexed/cisplatin in the treatment of nonsquamous NSCLC with BM are also summarized to provide a reference for the application of pemetrexed/cisplatin in nonsquamous NSCLC with BM. Whether or not pemetrexed/cisplatin is definitely effective in nonsquamous NSCLC with BM must be proven by subsequent phase III clinical trials. PMID:27512852

  19. Clinical development of nintedanib for advanced non-small-cell lung cancer

    PubMed Central

    Takeda, Masayuki; Okamoto, Isamu; Nakagawa, Kazuhiko

    2015-01-01

    Angiogenesis is an essential process in the development, growth, and metastasis of malignant tumors including lung cancer. Several angiogenesis inhibitors have been developed as potential therapies for non-small-cell lung cancer (NSCLC). Nintedanib is a small-molecule tyrosine kinase inhibitor that targets receptors for vascular endothelial growth factor, platelet-derived growth factor, and fibroblast growth factor as well as RET (rearranged during transfection) and Flt3. When administered as monotherapy, nintedanib was well tolerated at doses up to 250 mg or 200 mg twice daily in European and Japanese patients, respectively, with liver toxicity featuring prominently among dose-limiting toxicities in both populations. A recent Phase III trial demonstrated that treatment with the combination of nintedanib and docetaxel resulted in a significant and clinically meaningful improvement in both progression-free survival and overall survival compared with docetaxel alone in predefined NSCLC patients with adenocarcinoma tumor histology. Although the incidence of elevated alanine aminotransferase or aspartate aminotransferase as well as of diarrhea was higher in patients treated with nintedanib plus docetaxel, most of these adverse events were manageable with supportive treatment or dose reduction. The results of completed and ongoing clinical trials of nintedanib monotherapy and combination therapy for the treatment of NSCLC are summarized in this study. PMID:26622180

  20. 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

  1. 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.

  2. 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

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

    PubMed Central

    Rothschild, Sacha I

    2016-01-01

    Rearrangements in ALK gene and EML4 gene were first described in 2007. This genomic aberration is found in about 2%–8% of non-small-cell lung cancer (NSCLC) patients. Crizotinib was the first ALK tyrosine kinase inhibitor licensed for the treatment of metastatic ALK-positive NSCLC based on a randomized Phase III trial. Despite the initial treatment response of crizotinib, disease progression inevitably develops after approximately 10 months of therapy. Different resistance mechanisms have recently been described. One relevant mechanism of resistance is the development of mutations in ALK. Novel ALK tyrosine kinase inhibitors have been developed to overcome these mutations. Ceritinib is an oral second-generation ALK inhibitor showing clinical activity not only in crizotinib-resistant ALK-positive NSCLC but also in treatment-naïve ALK-positive disease. In this paper, preclinical and clinical data of ceritinib are reviewed, and its role in the clinical setting is put into perspective. PMID:27217763

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

    ClinicalTrials.gov

    2016-07-29

    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

  5. Robotic-assisted thoracoscopic sleeve lobectomy for locally advanced lung cancer

    PubMed Central

    Lin, Mong-Wei; Kuo, Shuenn-Wen; Yang, Shun-Mao

    2016-01-01

    Background The Da Vinci robotic system has been used to enhance the surgeon’s visualization and agility in lung cancer surgery, and thus facilitate refined dissection, knot tying and suturing. However, only a few case reports exist on performing a sleeve lobectomy with a robotic-assisted thoracoscopic surgery (RATS) technique. Here we describe our early experience performing RATS sleeve lobectomies. To our knowledge, this is the first study reporting a series of RATS sleeve lobectomies. Methods The six consecutive NSCLC patients who underwent a RATS sleeve lobectomy between November 2013 and July 2015 at the National Taiwan University Hospital were enrolled in this study. The lobectomies were all performed by the same surgeon using a three-arm robotic system with an additional utility incision made for assistance and specimen retrieval. Results Five patients were diagnosed with squamous cell carcinoma, while the sixth was diagnosed with a carcinoid tumor. The mean operation time was 436.7 [255–745] minutes. The mean postoperative intensive care unit (ICU) stay and hospital stay were 3.7 [1–11] and 11.3 [3–26] days, respectively. Two (33.3%; 2/6) morbidities were noted, including one pneumonia and one anastomosis stricture. There were no cases of mortality or of conversion to thoracotomy. Conclusions Our experience performing a RATS sleeve lobectomy in the six patients demonstrated the feasibility of RATS in complex lung cancer surgeries. The three-dimensional vision and articulated joint instruments made robotic-assisted bronchial anastomosis easier under the endoscopic setting. Our experience suggests that RATS offers specific advantages with regard to accuracy and safety when performing sleeve lobectomies. PMID:27499965

  6. 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

  7. 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

  8. 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.

  9. Continuous infusion cisplatin and 5-fluorouracil with bolus vinorelbine in the treatment of advanced nonsmall cell carcinoma of the lung.

    PubMed

    Beuzeboc, P; Livartowski, A; Dierick, A; Paraiso, D; Pouillart, P

    1995-01-01

    Thirty-three patients, with histologically proven advanced nonsmall cell lung cancer (NSCLC) were treated at Institut Curie with a three-drug combination chemotherapy. The regimen consisted of cisplatin 25 mg/m2 per day continuous infusion (CI) and 5-fluorouracil (5-FU) CI 600 mg/m2 on 5 consecutive days with 30 minutes infusion navelbine 25 mg/m2 on days 1 and 5 only. Cycles were repeated every 28 days. Response was evaluated after three cycles. One patient died of an ischemic cerebrovascular stroke after the third cycle. Thirty-two pts were evaluable. Partial response was achieved in 11/20 patients with stage III disease (55%) and in 7/12 patients with stage IV disease (58%). WHO grade 4 toxicities were leucopenia 31%, thrombocytopenia 4%, and mucositis 4%. The tolerance was acceptable. Median survival was 19 months for stage III and 9.5 months for stage IV. We conclude that the combination of 5-FU, navelbine, and cisplatin is an effective chemotherapy regimen for patients with advanced stage NSCLC.

  10. Improved refractories for slagging gasifiers in IGCC power systems

    SciTech Connect

    Bennett, James P.; Kwong, Kyei-Sing; Powell, Cynthia A.; Chinn, Richard E.

    2004-01-01

    Most gasifiers are operated for refining, chemical production, and power generation. They are also considered a possible future source of H2 for future power systems under consideration. A gasifier fulfills these roles by acting as a containment vessel to react carbon-containing raw materials with oxygen and water using fluidized-bed, moving-bed, or entrained-flow systems to produce CO and H2, along with other gaseous by-products including CO2, CH4, SOx, HS, and/or NOx. The gasification process provides the opportunity to produce energy more efficiently and with less environmental impact than more conventional combustion processes. Because of these advantages, gasification is viewed as one of the key processes in the U.S. Department of Energy?s vision of an advanced power system for the 21st Century. However, issues with both the reliability and the economics of gasifier operation will have to be resolved before gasification will be widely adopted by the power industry. Central to both enhanced reliability and economics is the development of materials with longer service lives in gasifier systems that can provide extended periods of continuous, trouble-free gasifier operation. The focus of the Advanced Refractories for Gasification project at the Albany Research Center (ARC) is to develop improved refractory liner materials capable of withstanding the harsh, high-temperature environment created by the gasification reaction. Current generation refractory liners in slagging gasifiers are typically replaced every 3 to 18 months at costs ranging up to $1,000,000 or more, depending upon the size of the gasification vessel. Compounding materials and installation costs are the lost-opportunity costs for the time that the gasifier is off-line for refractory repair/exchange. The goal of this project is to develop new refractory materials or to extend the service life of refractory liner materials currently used to at least 3 years. Post-mortem analyses of refractory brick

  11. Adenosine triphosphate infusion increases liver energy status in advanced lung cancer patients: an in vivo 31P magnetic resonance spectroscopy study.

    PubMed

    Leij-Halfwerk, Susanne; Agteresch, Hendrik J; Sijens, Paul E; Dagnelie, Pieter C

    2002-02-01

    We recently observed inhibition of weight loss in patients with advanced nonsmall-cell lung cancer after intravenous infusion of ATP. Because liver ATP levels were found to be decreased in lung cancer patients with weight loss, the present 31P magnetic resonance spectroscopy (MRS) study was aimed at investigating whether ATP infusion restores liver energy status in these patients. Nine patients with advanced nonsmall-cell lung cancer (stage IIIB/IV) were studied 1 week before (baseline) and at 22 to 24 hours of continuous ATP infusion (37-75 microg/kg/min). Localized hepatic 31P MR spectra (repetition time 15 seconds), obtained in the overnight-fasted state, were analyzed for ATP and P(i) content. Ten healthy subjects (without ATP infusion) served as control. Liver ATP levels in lung cancer patients increased from 8.8 +/- 0.7% (relative to total MR-detectable phosphate; mean +/- SE) at baseline to 12.2 +/- 0.9% during ATP infusion (P <.05), i.e., a level similar to that in healthy subjects (11.9 +/- 0.9%). The increase in ATP level during ATP infusion was most prominent in patients with > or = 5% weight loss (baseline: 7.9 +/- 0.7%, during ATP infusion: 12.8 +/- 1.0%, P < 0.01). In conclusion, ATP infusion restores hepatic energy levels in patients with advanced lung cancer, especially in weight-losing patients. These changes may contribute to the previously reported beneficial effects of ATP infusion on the nutritional status of lung cancer patients. PMID:11826418

  12. 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.

  13. Refractory status epilepticus

    PubMed Central

    Singh, Sanjay P; Agarwal, Shubhi; Faulkner, M

    2014-01-01

    Refractory status epilepticus is a potentially life-threatening medical emergency. It requires early diagnosis and treatment. There is a lack of consensus upon its semantic definition of whether it is status epilepticus that continues despite treatment with benzodiazepine and one antiepileptic medication (AED), i.e., Lorazepam + phenytoin. Others regard refractory status epilepticus as failure of benzodiazepine and 2 antiepileptic medications, i.e., Lorazepam + phenytoin + phenobarb. Up to 30% patients in SE fail to respond to two antiepileptic drugs (AEDs) and 15% continue to have seizure activity despite use of three drugs. Mechanisms that have made the treatment even more challenging are GABA-R that is internalized during status epilepticus and upregulation of multidrug transporter proteins. All patients of refractory status epilepticus require continuous EEG monitoring. There are three main agents used in the treatment of RSE. These include pentobarbital or thiopental, midazolam and propofol. RSE was shown to result in mortality in 35% cases, 39.13% of patients were left with severe neurological deficits, while another 13% had mild neurological deficits. PMID:24791086

  14. Refractory plasmonics (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Guler, Urcan; Boltasseva, Alexandra; Shalaev, Vladimir M.

    2016-04-01

    The use of plasmonic effects over a broad range of electromagnetic spectrum has been a challenge over the first few decades of research due to limited number of available materials. Recently, the efforts in the area has been concentrated on identifying and examining new material classes as the building blocks for optical technologies over a broader electromagnetic spectrum. Transition metal nitrides attract attention as plasmonic materials in the visible and infrared spectral regions with optical properties resembling gold. As refractory materials, nitrides can withstand heat induced physical phenomena as well as aggressive chemical environment. Adjustable dielectric permittivity of plasmonic nitrides allow fine tuning of optical properties for selected applications. In addition to favorable optical, physical and chemical properties; transition metal nitrides provide CMOS- and bio-compatibility. In this talk, novel designs and concepts based on refractory plasmonic materials for infrared applications will be presented. Additionally, light confinement at the nanoscale with refractory plasmonic antennas, spectral engineering of absorption and emission with metamaterials, and the use of colloidal solutions for a variety of applications will be discussed.

  15. Effects of ATP infusion on glucose turnover and gluconeogenesis in patients with advanced non-small-cell lung cancer.

    PubMed

    Agteresch, H J; Leij-Halfwerk, S; Van Den Berg, J W; Hordijk-Luijk, C H; Wilson, J H; Dagnelie, P C

    2000-06-01

    Cancer cachexia is associated with elevated lipolysis, proteolysis and gluconeogenesis. ATP infusion has been found to significantly inhibit loss of body weight, fat mass and fat-free mass in patients with advanced lung cancer. The present study was aimed at exploring the effects of ATP on whole-body glucose turnover, alanine turnover and gluconeogenesis from alanine. Twelve patients with advanced non-small-cell lung cancer (NSCLC) were studied 1 week before and during 22-24 h of continuous ATP infusion. After an overnight fast, turnover rates of glucose and alanine, and gluconeogenesis from alanine, were determined using primed constant infusions of ¿6, 6-(2)H(2)ğlucose and ¿3-(13)Călanine. Thirteen NSCLC patients and eleven healthy subjects were studied as control groups without ATP infusion. During high-dose ATP infusion (75 microg.min(-1).kg(-1)), glucose turnover was 0.62+/-0.07 mmol.h(-1).kg(-1), compared with 0. 44+/-0.13 mmol.h(-1).kg(-1) at baseline (P=0.04). For gluconeogenesis a similar, but non-significant, trend was observed ¿baseline, 0.30+/-0.16 mmol.h(-1).kg(-1); during ATP, 0.37+/-0.13 mmol.h(-1).kg(-1) (P=0.08). At lower ATP doses (37-50 microg. min(-1).kg(-1)) these effects were not detected. The relative increase in glucose turnover during ATP infusion compared with baseline showed a significant correlation with the ATP dose (r=0.58, P=0.02). No change in alanine turnover was observed at any ATP dose. The results of this study indicate an increase in glucose turnover during high-dose ATP infusion compared with baseline levels. During high-dose ATP infusion, glucose turnover was similar to that during low-dose ATP infusion and to that in control NSCLC patients. Between ATP infusions, however, glucose turnover in patients treated with high-dose ATP was significantly lower than that in the low-dose and control NSCLC patients (P=0.04 and P=0.03 respectively), and similar to that in healthy subjects. This would suggest that repeated high

  16. Combined treatment with everolimus and fulvestrant reversed anti-HER2 resistance in a patient with refractory advanced breast cancer: a case report

    PubMed Central

    Sun, Bing; Ding, Lijuan; Wu, Shikai; Meng, Xiangying; Song, Santai

    2016-01-01

    Background Everolimus, an inhibitor of the mammalian target of rapamycin, shows promising antitumor activity when combined with trastuzumab and chemotherapy for human epidermal growth factor receptor-2 (HER2)-positive breast cancer or when combined with endocrine agents for hormone receptor (HR)-positive tumors. However, data are limited regarding the effect of everolimus in combination with endocrine drugs in HER2-positive advanced breast cancer regardless of the HR status. Case presentation A 44-year-old female was diagnosed with recurrent HER2-positive breast cancer. The primary tumor was HR positive; however, the metastatic tumor was HR negative. The patient was resistant to classical chemotherapeutic agents and anti-HER2 treatment. Thus, the combination of everolimus and fulvestrant, a selective estrogen receptor downregulator, was chosen to reverse the resistance to anti-HER2 therapy. Indeed, the patient experienced long-term disease stabilization. Adverse events associated with the treatment were manageable by dose adjustments. We performed genetic testing of the metastatic tumor, which harbored a PIK3CA gene mutation but was positive for phosphatase and tensin homologue expression, which might result in resistance to the mammalian target of rapamycin inhibitor. Conclusion This case study indicates that combined treatment with everolimus and fulvestrant might be a viable option for the treatment of metastatic breast cancer patients who are HER2 positive and carry a PIK3CA gene mutation but are resistant to anti-HER2 therapy and classical chemotherapeutic agents. Further prospective randomized trials are needed to confirm this finding. PMID:27445490

  17. Phase I Study of BIIB028, a selective heat shock protein 90 inhibitor, in patients with refractory metastatic or locally advanced solid tumors

    PubMed Central

    Hong, David; Said, Rabih; Falchook, Gerald; Naing, Aung; Moulder, Stacy; Tsimberidou, Apostolia-Maria; Galluppi, Gerald; Dakappagari, Naveen; Storgard, Chris; Kurzrock, Razelle; Rosen, Lee S.

    2014-01-01

    Purpose Heat shock protein 90 (Hsp90) is a ubiquitous molecular chaperone involved in protein folding, activation, and assembly, including key mediators of signal transduction, cell cycle control, and transcriptional regulation. We conducted a phase I dose-finding and pharmacokinetic/pharmacodynamic study of BIIB028, a prodrug designed to inhibit Hsp90 activity. Patients and Methods Patients with advanced solid tumors were enrolled and received escalating doses of BIIB028 intravenously twice a week in 21-day cycles (3+3 design). Response was evaluated after 2 cycles. Results Forty-one patients received doses of 6 to 192 mg/m2. The maximum tolerated dose was 144 mg/m2. Dose-limiting toxicities were syncope (n=1) and fatigue (n=1). Common toxicities at least possibly related to drug were grade 1–2, including fatigue (46%), diarrhea (44%), nausea (44%), vomiting (29%), hot flushes (29%) and abnormal dreams (17%). The concentration-time curves for Day 1 and Day 18 for both prodrug and active metabolite (CF2772) showed a negligible difference. There was a dose-dependent increase in plasma exposure for BIIB028 (CF3647) and CF2772 with plasma half-life of 0.5 and 2.1 hours, respectively. Pharmacodynamic analyses demonstrated significant increases in Hsp70 in peripheral blood mononuclear cells and significantly decreased circulating human epidermal growth factor receptor 2- extracellular domain in all patients who received BIIB028 at dose levels ≥48mg/m2. Stable disease for at least 8 cycles (24 weeks) was achieved in 5 (12%) patients (6, 6, 8, 12.5 and 19 months). Conclusion BIIB028 is a well-tolerated molecule that demonstrated target impact and was associated with prolonged stable disease in 2 patients. PMID:23873691

  18. Agents for refractory/relapsed acute lymphocytic leukemia in adults.

    PubMed

    Qian, L-R; Fu, W; Shen, J-L

    2014-01-01

    Although treatment results for adult acute lymphoblastic leukemia (ALL) have improved considerably in the past decades, treating adult patients with relapsed/refractory acute lymphocytic leukemia (ALL) is still difficult. Adults with refractory/relapsed acute lymphocytic leukemia (ALL) processed to death rapidly associated with chemotherapy resistance, high mortality by reinduction, etc. Only 20% to 30% of those patients acquired complete remission (CR). Those patients are always of short duration unless an allogeneic stem cell transplant is feasible. Median survival is only ranging from 2 to 12 months. Therapeutic strategy on relapsed/refractory acute lymphocytic leukemia (ALL) is always a major therapeutic challenge bothering hematological researchers. Novel agents and unique therapeutic strategies have been developed in recent years. This review focuses on major clinical advances in the agents for refractory/relapsed ALL.

  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. 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. PMID:25336937

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

    PubMed Central

    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. PMID:25336937

  2. 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.

  3. 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. PMID:25464271

  4. Potential Therapeutic Benefit of Combining Gefitinib and Tamoxifen for Treating Advanced Lung Adenocarcinoma

    PubMed Central

    Chiu, Kuo-Liang; Chen, Tzu-Sheng; Chang, Shang-Miao; Yang, Shu-Yun; Chen, Li-Hsiou; Ni, Yung-Lun

    2015-01-01

    Introduction. Epidermal growth factor receptor (EGFR) mutations are known as oncogene driver mutations and with EGFR mutations exhibit good response to the EGFR tyrosine kinase inhibitor Gefitinib. Some studies have shown that activation of estrogen and estrogen receptor α or β (ERα/β) promote adenocarcinoma. We evaluated the relationship between the two receptors and the potential therapeutic benefit with Gefitinib and Tamoxifen. Methods. We assessed the association between EGFR mutations as well as ERα/β expression/location and overall survival in a cohort of 55 patients with LAC from a single hospital. PC9 (EGFR exon 19 deletion mutant; Gefitinib-vulnerable cells) and A549 (EGFR wild type; Gefitinib-resistant cells) cancer cells were used to evaluate the in vitro therapeutic benefits of combining Gefitinib and Tamoxifen. Results. We found that the cytosolic but not the nuclear expression of ERβ was associated with better OS in LAC tumors but not associated with EGFR mutation. The in vitro study showed that combined Gefitinib and Tamoxifen resulted in increased apoptosis and cytosolic expression of ERβ. In addition, combining both medications resulted in reduced cell growth and increased the cytotoxic effect of Gefitinib. Conclusion. Tamoxifen enhanced advanced LAC cytotoxic effect induced by Gefitinib by arresting ERβ in cytosol. PMID:25692143

  5. Refractory composites structural materials

    NASA Astrophysics Data System (ADS)

    Sanzero, G. V.

    1990-10-01

    This paper presents the latest available data for the NASP Refractory Composites Materials and Structures Augmentation Program. The program's main goal is to provide the necessary information for a positive phase II to phase III plan for the X-30 to be built. After a brief overview of the program, the state-of-the-art fabrication of carbon/carbon subelements is presented. Material data packages for screening data, characterization data, damage and durability tolerance and actively-cooled airframe and engine program development are also presented.

  6. Third generation FCCU refractories

    SciTech Connect

    Caprio, J.A.

    1986-03-01

    After four years of research and field installations, it has now been shown that the most reasonable solution to heat, abrasion and cracking problems associated with cat cracker components can best be reached using amorphous silica aggregate castables. Incorporating the traditional cement-based system established in 50% and 90% alumina refractory castables, low K-factor amorphous silica castables provide abrasion-resistant one-component linings while reducing heat loss by 20 to 25%. Above-average shock and crack resistance, which can minimize coke penetration, will also result from linings cast or gunned with this latest generation of amorphous silica castables.

  7. 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.

  8. [The refractory glaucomas].

    PubMed

    Valtot, F

    2003-10-01

    Refractory types of glaucoma continue to present a therapeutic challenge to ophthalmologists. Approaches toward the management of these difficult glaucomas are addressed in this paper. The first part devotes special attention to understand the cause(s) of the failure of previous filtering surgery(ies). The next part emphasizes filtration surgery with intraoperative application of antimetabolites: 5-fluorouracil or mitomycin C and the surgical and pharmacological management of failing filtration. In case of failure of multiple filtering surgery with application of antimetabolites, surgeons have to consider cyclodestructive procedures (transscleral diode laser or endoscopic cyclophotocoagulation) to reduce aqueous production, or fistulizing procedures with tube implants or other drainage devices (valves). PMID:14646834

  9. 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

  10. 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

  11. 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.

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

    PubMed Central

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

    2016-01-01

    Nicotinic acetylcholine receptors (nAChRs) play a key role in carcinogenesis and progression of lung cancer; and polymorphisms in CHRNA5-A3 and CHRNB3-A6, two gene clusters encoding nAChR subunits, have been associated with lung cancer risk. In this study, we investigated whether variants in the two gene clusters were associated with prognosis of advanced non-small cell lung cancer (NSCLC). A total of 165 stage IIIB–IV NSCLC patients were enrolled in this study. Three polymorphisms (rs667282 and rs3743073 in CHRNA5-A3 and rs13280604 in CHRNB3-A6) were genotyped using the TaqMan method. Overall survival (OS) was estimated using the log-rank test and the Cox models. Our results showed that patients with CHRNA5-A3 rs667282 TT or TC genotypes had a significantly shorter OS than those carrying the CC genotype (Log-rank, P = 0.043). Furthermore, multivariate Cox regression analysis showed that rs667282 TT/TC genotypes are significantly associated with increased risk of overall deaths (adjusted hazard ratio, 1.7; 95% CI, 1.1–2.7). However, the similar results were not observed for other two polymorphisms. Furthermore, no evident association was found between these variants and clinicopathologic features of advanced NSCLC. Our present study suggested that rs667282 in CHRNA5-A3 may modify the prognosis of patients with advanced NSCLC. PMID:27050379

  13. Efficacy of erlotinib in patients with advanced non-small cell lung cancer: a pooled analysis of randomized trials.

    PubMed

    Gao, Hui; Ding, Xin; Wei, Dong; Cheng, Peng; Su, Xiaomei; Liu, Huanyi; Aziz, Fahad; Wang, Daoyuan; Zhang, Tao

    2011-10-01

    Erlotinib is a potent reversible HER1/epidermal growth factor receptor tyrosine kinase inhibitor with single-agent activity in patients with non-small cell lung cancer. The aim of this study was to evaluate the efficacy of erlotinib for treating advanced non-small cell lung cancer by carrying out a pooled analysis of randomized controlled trials that compared erlotinib-based regimens with other agent-based regimens between January 1997 and 2011. Outcomes analyzed were objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and adverse events. Fourteen trials including 7974 patients were identified. As first-line therapy was compared with chemotherapy, there was a similar ORR [OR: 0.33; 95% confidence interval (CI): 0.64-17.36; P=0.15], but decreased PFS [hazard ratio (HR): 1.55; 95% CI: 1.24-1.93; P<0.01] and OS (HR: 1.39; 95% CI: 0.99-1.94; P=0.05). As maintenance therapy was compared with placebo, erlotinib-based regimens significantly increased ORR (OR: 0.47; 95% CI: 0.31-0.70; P<0.01), prolonged PFS (HR: 0.71; 95% CI: 0.60-0.83; P<0.01), but did not improve OS (HR: 0.87; 95% CI: 0.68-1.11; P=0.22). As second/third-line therapy was compared with placebo, erlotinib-based regimens also significantly increased ORR (OR: 0.10; 95% CI: 0.02-0.41; P<0.01), prolonged PFS (HR: 0.61; 95% CI: 0.51-0.73; P<0.01), and improved OS (HR: 0.70; 95% CI: 0.58-0.84; P<0.01). However, as second/third-line therapy was compared with chemotherapy, the outcomes were similar between the two arms. When compared with PF299804, there was a decreased ORR (OR: 3.87; 95% CI: 1.27-11.81; P=0.02), and shortened PFS (HR: 0.58; 95% CI: 0.49-0.95; P=0.02). Meanwhile, erlotinib-based regimens showed no significant difference in adverse events, except for diarrhea, rash, and anemia. Erlotinib-based regimens significantly increased ORR and improved PFS as a first-line maintenance therapy or as a second/third-line therapy when compared with placebo. PMID:21808188

  14. 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.

  15. Next generation sequencing analysis of platinum refractory advanced germ cell tumor sensitive to Sunitinib (Sutent®) a VEGFR2/PDGFRβ/c-kit/ FLT3/RET/CSF1R inhibitor in a phase II trial

    PubMed Central

    2014-01-01

    Background Germ cell tumors (GCT) are the most common solid tumors in adolescent and young adult males (age 15 and 35 years) and remain one of the most curable of all solid malignancies. However a subset of patients will have tumors that are refractory to standard chemotherapy agents. The management of this refractory population remains challenging and approximately 400 patients continue to die every year of this refractory disease in the United States. Methods Given the preclinical evidence implicating vascular endothelial growth factor (VEGF) signaling in the biology of germ cell tumors, we hypothesized that the vascular endothelial growth factor receptor (VEGFR) inhibitor sunitinib (Sutent) may possess important clinical activity in the treatment of this refractory disease. We proposed a Phase II efficacy study of sunitinib in seminomatous and non-seminomatous metastatic GCT’s refractory to first line chemotherapy treatment (ClinicalTrials.gov Identifier: NCT00912912). Next generation targeted exome sequencing using HiSeq 2000 (Illumina Inc., San Diego, CA, USA) was performed on the tumor sample of the unusual responder. Results Five patients are enrolled into this Phase II study. Among them we report here the clinical course of a patient (Patient # 5) who had an exceptional response to sunitinib. Next generation sequencing to understand this patient’s response to sunitinib revealed RET amplification, EGFR and KRAS amplification as relevant aberrations. Oncoscan MIP array were employed to validate the copy number analysis that confirmed RET gene amplification. Conclusion Sunitinib conferred clinical benefit to this heavily pre-treated patient. Next generation sequencing of this ‘exceptional responder’ identified the first reported case of a RET amplification as a potential basis of sensitivity to sunitinib (VEGFR2/PDGFRβ/c-kit/ FLT3/RET/CSF1R inhibitor) in a patient with refractory germ cell tumor. Further characterization of GCT patients using

  16. Management of refractory angina pectoris.

    PubMed

    Manchanda, Aarush; Aggarwal, Ashim; Aggarwal, Nupur; Soran, Ozlem

    2011-01-01

    Despite significant advances in revascularization techniques and medical therapy, there remains a significant population of patients who continue to have intractable angina symptoms. This review aims to define the patients with refractory angina pectoris (RAP) and to present the therapeutic options currently available for this condition. RAP itself is defined and the pharmacological treatment options other than traditional medical therapies are discussed. The latest therapeutic options for this patient population are extensively reviewed. Among the multitude of pharmacological and non-invasive therapeutic options for patients with RAP, ranolazine is a new drug indicated for the treatment of chronic angina, in combination with amlodipine, beta-blockers or nitrates. Enhanced external counterpulsation has not only been shown to improve symptoms, but also to improve long-term ventricular function in these patients. In randomized trials, neurostimulation has been shown to be effective in reducing angina symptoms. Transmyocardial laser revascularization has emerged as an invasive treatment for RAP over the last two decades. Extracorporeal shockwave myocardial revascularization gene therapy and percutaneous in situ coronary venous arterialization are still under investigation.

  17. Large fraction radiotherapy plus misonidazole for treatment of advanced lung cancer: report of a phase I/II trial

    SciTech Connect

    Simpson, J.R.; Perez, C.A.; Phillips, T.L.; Concannon, J.P.; Carella, R.J.

    1982-02-01

    From August 1978 through December 1979, 51 patients with advanced non-oat cell carcinoma of the lung were enrolled in a Phase I/II trial sponsored by the Radiation Therapy Oncology Group (RTOG) employing misonidazole (a 2-nitroimidazole) as a hypoxic cell sensitizer and radiation. The purpose of this study was to test drug and radiation tolerance and to assess the short term efficacy of this unconventional treatment. Tumor doses of 600 rad were given twice weekly for three weeks for a total of 3600 rad, preceded four to six hours by misonidazole in a dose of 2 gm/m/sup 2/ or 1.75 gm/m/sup 2/, administered orally. Forty-nine patients were evaluable. Serious toxicity from this treatment was rare. Grade 2 or 3 peripheral neuro-toxicity occurred in eight of 24 patients (33%) with drug doses of 2 gm/m/sup 2/ and in four of 26 patients (15%) who received 1.75 gm/m/sup 2/. Grade 3 or 4 central nervous system toxicity occurred in two patients. Two patients developed serious late radiation complications: one patient had a transverse myelitis that appeared one year following delivery of 3600 rad to the spinal cord; a second patient developed a tracheoesophageal fistula and pericarditis eight months following treatment. Objective responses were reported in 67% of patients (complete in 18%); 70% of the patients died with a median survival time of nine months. Of 32 patients eligible for 12 month follow-up, 34% survived more than one year. Patterns of relapse after initial treatment and comparison with results from other RTOG trials using conventional fractionation are discussed.

  18. 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.

  19. A phase I study of dexosome immunotherapy in patients with advanced non-small cell lung cancer

    PubMed Central

    Morse, Michael A; Garst, Jennifer; Osada, Takuya; Khan, Shubi; Hobeika, Amy; Clay, Timothy M; Valente, Nancy; Shreeniwas, Revati; Sutton, Mary Ann; Delcayre, Alain; Hsu, Di-Hwei; Le Pecq, Jean-Bernard; Lyerly, H Kim

    2005-01-01

    Background There is a continued need to develop more effective cancer immunotherapy strategies. Exosomes, cell-derived lipid vesicles that express high levels of a narrow spectrum of cell proteins represent a novel platform for delivering high levels of antigen in conjunction with costimulatory molecules. We performed this study to test the safety, feasibility and efficacy of autologous dendritic cell (DC)-derived exosomes (DEX) loaded with the MAGE tumor antigens in patients with non-small cell lung cancer (NSCLC). Methods This Phase I study enrolled HLA A2+ patients with pre-treated Stage IIIb (N = 4) and IV (N = 9) NSCLC with tumor expression of MAGE-A3 or A4. Patients underwent leukapheresis to generate DC from which DEX were produced and loaded with MAGE-A3, -A4, -A10, and MAGE-3DPO4 peptides. Patients received 4 doses of DEX at weekly intervals. Results Thirteen patients were enrolled and 9 completed therapy. Three formulations of DEX were evaluated; all were well tolerated with only grade 1–2 adverse events related to the use of DEX (injection site reactions (N = 8), flu like illness (N = 1), and peripheral arm pain (N = 1)). The time from the first dose of DEX until disease progression was 30 to 429+ days. Three patients had disease progression before the first DEX dose. Survival of patients after the first DEX dose was 52–665+ days. DTH reactivity against MAGE peptides was detected in 3/9 patients. Immune responses were detected in patients as follows: MAGE-specific T cell responses in 1/3, increased NK lytic activity in 2/4. Conclusion Production of the DEX vaccine was feasible and DEX therapy was well tolerated in patients with advanced NSCLC. Some patients experienced long term stability of disease and activation of immune effectors PMID:15723705

  20. Systemic inflammatory status at baseline predicts bevacizumab benefit in advanced non-small cell lung cancer patients

    PubMed Central

    Botta, Cirino; Barbieri, Vito; Ciliberto, Domenico; Rossi, Antonio; Rocco, Danilo; Addeo, Raffaele; Staropoli, Nicoletta; Pastina, Pierpaolo; Marvaso, Giulia; Martellucci, Ignazio; Guglielmo, Annamaria; Pirtoli, Luigi; Sperlongano, Pasquale; Gridelli, Cesare; Caraglia, Michele; Tassone, Pierfrancesco; Tagliaferri, Pierosandro; Correale, Pierpaolo

    2013-01-01

    Bevacizumab is a humanized anti-VEGF monoclonal antibody able to produce clinical benefit in advanced non-squamous non-small-cell lung cancer (NSCLC) patients when combined to chemotherapy. At present, while there is a rising attention to bevacizumab-related adverse events and costs, no clinical or biological markers have been identified and validated for baseline patient selection. Preclinical findings suggest an important role for myeloid-derived inflammatory cells, such as neutrophils and monocytes, in the development of VEGF-independent angiogenesis. We conducted a retrospective analysis to investigate the role of peripheral blood cells count and of an inflammatory index, the neutrophil-to-lymphocyte ratio (NLR), as predictors of clinical outcome in NSCLC patients treated with bevacizumab plus chemotherapy. One hundred twelve NSCLC patients treated with chemotherapy ± bevacizumab were retrospectively evaluated for the predictive value of clinical or laboratory parameters correlated with inflammatory status. Univariate analysis revealed that a high number of circulating neutrophils and monocytes as well as a high NLR were associated with shorter progression-free survival (PFS) and overall survival (OS) in bevacizumab-treated patients only. We have thus developed a model based on the absence or the presence of at least one of the above-mentioned inflammatory parameters. We found that the absence of all variables strongly correlated with longer PFS and OS (9.0 vs. 7.0 mo, HR: 0.39, p = 0.002; and 20.0 vs. 12.0 mo, HR: 0.29, p < 0.001 respectively) only in NSCLC patients treated with bevacizumab plus chemotherapy. Our results suggest that a baseline systemic inflammatory status is marker of resistance to bevacizumab treatment in NSCLC patients. PMID:23760488

  1. Comparison of dose–volume histograms between proton beam and X-ray conformal radiotherapy for locally advanced non-small-cell lung cancer

    PubMed Central

    Ohno, Toshiki; Oshiro, Yoshiko; Mizumoto, Masashi; Numajiri, Haruko; Ishikawa, Hitoshi; Okumura, Toshiyuki; Terunuma, Toshiyuki; Sakae, Takeji; Sakurai, Hideyuki

    2015-01-01

    The purpose of this study was to compare the parameters of the dose–volume histogram (DVH) between proton beam therapy (PBT) and X-ray conformal radiotherapy (XCRT) for locally advanced non-small-cell lung cancer (NSCLC), according to the tumor conditions. A total of 35 patients having NSCLC treated with PBT were enrolled in this analysis. The numbers of TNM stage and lymph node status were IIB (n = 3), IIIA (n = 15) and IIIB (n = 17), and N0 (n = 2), N1 (n = 4), N2 (n = 17) and N3 (n = 12), respectively. Plans for XCRT were simulated based on the same CT, and the same clinical target volume (CTV) was used based on the actual PBT plan. The treatment dose was 74 Gy-equivalent dose (GyE) for the primary site and 66 GyE for positive lymph nodes. The parameters were then calculated according to the normal lung dose, and the irradiation volumes of the doses (Vx) were compared. We also evaluated the feasibility of both plans according to criteria: V5 ≥ 42%, V20 ≥ 25%, mean lung dose ≥ 20 Gy. The mean normal lung dose and V5 to V50 were significantly lower in PBT than in XCRT. The differences were greater with the more advanced nodal status and with the larger CTV. Furthermore, 45.7% of the X-ray plans were classified as inadequate according to the criteria, whereas 17.1% of the proton plans were considered unsuitable. The number of inadequate X-ray plans increased in cases with advanced nodal stage. This study indicated that some patients who cannot receive photon radiotherapy may be able to be treated using PBT. PMID:25368341

  2. Efficacy of Addition of Antiangiogenic Agents to Taxanes-Containing Chemotherapy in Advanced Nonsmall-Cell Lung Cancer

    PubMed Central

    Sheng, Jin; Yang, Yun-Peng; Yang, Bi-Jun; Zhao, Yuan-Yuan; Ma, Yu-Xiang; Hong, Shao-Dong; Zhang, Ya-Xiong; Zhao, Hong-Yun; Huang, Yan; Zhang, Li

    2015-01-01

    Abstract Preclinical researches indicated a potential synergistic effect of taxanes-containing chemotherapy (TCC) and antiangiogenic agents (AAs) on the treatment of advanced nonsmall-cell lung cancer (NSCLC). The advantage of adding AA to TCC in the real world remains confusing. We summarized the current evidences from relevant phase II/III randomized controlled trials (RCTs) by performing this meta-analyses. Electronic databases were searched for eligible literatures. The primary endpoint was overall survival (OS). Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) for outcomes were calculated using RevMan 5.2. A total of 14 phase II/III RCTs involving 9703 participants were included. Compared to standard TCC, the addition of AA was associated with the significant better OS (HR 0.92, 95% CI 0.87–0.97, P = 0.002), prolonged progression-free survival (HR 0.79, 95% CI 0.71–0.87, P < 0.00001), superior response rate (risk ratio [RR] 1.69, 95% CI 1.47–1.95, P < 0.0001), and disease control rate (RR 1.19, 95% CI 1.08–1.32, P < 0.00001). Subgroup analyses indicated that patient treated with monoclonal antibodies (HR 0.89, 95% CI 0.82–0.96, P = 0.02) as well as application in second-line (HR 0.91, 95% CI 0.85–0.96, P = 0.02) acquired significant OS improvement. Other clinical factors directing significant OS improvement by the combination strategy included nonsquamous cancer (P = 0.002), nonsmokers (P = 0.0005), and female (P = 0.02). Toxicities were greater but generally mild or moderate in the combination group, and were mostly manageable. In summary, the addition of AAs to TCC could improve prognosis of advanced NSCLC. Furthermore, proper selection of patient population and AAs is crucial for clinical trials design and clinical practice in the future. PMID:26252298

  3. Targeted drugs for unselected patients with advanced non-small-cell lung cancer: a network meta-analysis

    PubMed Central

    Zhao, Yueguang; Wang, Fang; Li, Shanshan; Wang, Xiaojie; Shou, Tao; Luo, Ying

    2016-01-01

    Background Currently, targeted therapy has shown encouraging treatment benefits in selected patients with advanced non-small cell lung cancer (NSCLC). However, the comparative benefits of targeted drugs and chemotherapy (CT) treatments in unselected patients are not clear. We therefore conduct a network meta-analysis to assess the relative efficacy and safety of these regimens. Methods PubMed, EMBASE, Cochrane Library and abstracts from major scientific meetings were searched for eligible literatures. The odds ratio (OR) for objective response rate (ORR) and safety was used for pooling effect sizes. Bayesian network meta-analysis was conducted to calculate the efficacy and safety of all included treatments. All tests of statistical significance were two sided. Results A total of 13,060 patients from 24 randomized controlled trials (RCT) were assessed. The targeted agents included bevacizumab (Bev), gefitinib (Gef), erlotinib (Erl) and cetuximab (Cet). Network meta-analysis showed that Bev + CT had a statistically significantly higher incidence of ORR relative to the other six different treatments, including placebo (OR =6.47; 95% CI, 3.85–10.29), Erl (OR =2.81; 95% CI, 2.08–3.70), CT (OR =1.92; 95% CI, 1.61–2.28), Gef (OR =1.40; 95% CI, 1.10–1.75), Erl + CT (OR =1.46; 95% CI, 1.17–1.80) and Gef + CT (OR =1.75; 95% CI, 1.36–2.22), whereas placebo and Erl were associated with statistically significantly lower incidence of ORR. Trend analyses of rank probability revealed that Bev + CT had the highest probability of being the best treatment arm in term of ORR, followed by Cet + CT. Meanwhile, Cet + CT showed significant severer rash and thrombocytopenia compared with Bev + CT. Gef was probable to be the rank 3 for ORR but was associated with relatively low risk for grade ≥3 toxicities. Conclusions Our study suggested that Bev + CT may offer better ORR in the treatment of unselected patients with advanced NSCLC. Future studies will be needed to investigate

  4. Refractory gastroesophageal reflux disease

    PubMed Central

    Subramanian, Charumathi Raghu; Triadafilopoulos, George

    2015-01-01

    Gastroesophageal reflux disease (GERD) is a condition that develops when the reflux of stomach contents into the esophagus causes troublesome symptoms, esophageal injury, and/or complications. Use of proton pump inhibitors (PPI) remains the standard therapy for GERD and is effective in most patients. Those whose symptoms are refractory to PPIs should be evaluated further and other treatment options should be considered, according to individual patient characteristics. Response to PPIs could be total (no symptoms), partial (residual breakthrough symptoms), or absent (no change in symptoms). Patients experiencing complete response do not usually need further management. Patients with partial response can be treated surgically or by using emerging endoscopic therapies. Patients who exhibit no response to PPI need further evaluation to rule out other causes. PMID:25274499

  5. 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 Central

    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. PMID:26317340

  6. Intensity-modulated radiotherapy, not 3D conformal, is the preferred technique for treating locally advanced lung cancer

    PubMed Central

    Chang, Joe Y.

    2015-01-01

    When used to treat lung cancer, intensity-modulated radiotherapy (IMRT) can deliver higher dose to the targets and spare more critical organs in lung cancer than can 3D conformal radiotherapy (3DCRT). However, tumor-motion management and optimized radiotherapy planning based on four-dimensional computed tomography (4D CT) scanning are crucial to maximize the benefit of IMRT and to eliminate or minimize potential uncertainties. This article summarizes these strategies and reviews published findings supporting the safety and efficacy of IMRT for lung cancer. PMID:25771415

  7. Critical appraisal of the role of gefitinib in the management of locally advanced or metastatic non-small cell lung cancer.

    PubMed

    Yuan, Ying; Li, Xiao-Fen; Chen, Jia-Qi; Dong, Cai-Xia; Weng, Shan-Shan; Huang, Jian-Jin

    2014-01-01

    Past studies have demonstrated that epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors can significantly improve clinical outcomes in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) and sensitive EGFR gene mutations. Gefitinib (Iressa(®)), the first oral EGFR tyrosine kinase inhibitor, has been shown to be more effective and better tolerated than chemotherapy either in first-line or second-line treatment for patients with advanced NSCLC harboring sensitive EGFR mutations. Conversely, among patients with wild-type EGFR, gefitinib is inferior to standard chemotherapy in both the first-line and second-line settings. Further, gefitinib is effective in patients with brain metastases because of its low molecular weight and excellent penetration of the blood-brain barrier. In this review, we summarize the current data from clinical trials with gefitinib and appraise its role in the management of locally advanced or metastatic NSCLC.

  8. [Locally Advanced Breast Cancer Treated with Halsted's Operation Because of Drug-Induced Lung Injury Caused by Neoadjuvant Chemotherapy--A Case Report].

    PubMed

    Moro, Kazuki; Nagahashi, Masayuki; Tsuchida, Junko; Tatsuda, Kumiko; Toshikawa, Chie; Hasegawa, Miki; Ishikawa, Takashi; Shimada, Yoshifumi; Sakata, Jun; Kameyama, Hitoshi; Kobayashi, Takashi; Minagawa, Masahiro; Kosugi, Shin-ichi; Koyama, Yu; Wakai, Toshifumi

    2015-11-01

    A 64-year-old woman discovered a mass in her left breast and visited our hospital. A thorough examination resulted in a diagnosis of left, locally advanced breast cancer (cT4bN3, M0, cStage Ⅲc) with muscle invasion and Level Ⅲ lymph node metastases. Because of drug-induced lung disease following 4 courses of adriamycin and cyclophosphamide, the chemotherapy had to be stopped. Halsted's operation and postoperative radiotherapy (50 Gy) were performed. The patient was alive with no evidence of recurrence 9 months after surgery. Although multidisciplinary therapy is recommended in locally advanced breast cancer, chemotherapy sometimes cannot be performed due to factors such as age and physical status. Halsted's operation could be considered as a treatment of choice in patients with locally advanced breast cancer. It is important to choose the treatment strategy based on the condition of the patient. PMID:26805178

  9. Pharmacological approaches of refractory angina.

    PubMed

    Giannopoulos, Andreas A; Giannoglou, George D; Chatzizisis, Yiannis S

    2016-07-01

    Refractory angina refers to a group of patients with stable coronary atherosclerotic disease and angina symptoms, unresponsive to traditional medical management, while considered to be suboptimal candidates for revascularization procedures. Up to 15% of angina patients are considered to have refractory angina and, taking into account the aging population and the improvements in the treatment of stable coronary artery disease, the incidence of this entity is expected to increase. This review describes traditional and novel pharmacotherapies for symptoms relief and for long-term management of refractory angina. Mechanisms of action and relevant clinical trials are discussed and current recommendations from major European and US cardiovascular societies are reported.

  10. Successful Management of a Patient with Refractory Ventricular Fibrillation (VF) due to Acute Myocardial Infarction (AMI) and Lung Injury by Transition from Percutaneous Cardiopulmonary Support (PCPS) to Veno-Venous Extracorporeal Membrane Oxygenation (ECMO).

    PubMed

    Sato, Atsushi; Isoda, Kikuo; Gatate, Yodo; Akita, Koji; Daida, Hiroyuki

    2016-01-01

    A 69-year-old man was admitted to our hospital with cardiopulmonary arrest. Percutaneous cardio-pulmonary support (PCPS) using the right femoral artery and vein was initiated, because ventricular fibrillation continued. Although we succeeded in defibrillation after percutaneous coronary intervention (PCI), a chest radiograph indicated a pneumothorax in the right lung and a pulmonic contusion in the left lung caused by cardiopulmonary resuscitation. Two days after PCI, partial pressure of arterial oxygen (PaO2) from the right radial artery suddenly decreased, and his cardiac function showed improvement on an echocardiogram. To avoid additional brain damage, we converted the treatment to veno-venous extracorporeal membrane oxygenation by changing the blood returning site of PCPS from the right femoral artery to the right jugular vein. Thereafter, the patient's PaO2 level gradually improved. PMID:27432096

  11. Tocilizumab for refractory organising pneumonia associated with Sjögren's disease.

    PubMed

    Justet, Aurelien; Ottaviani, Sebastien; Dieudé, Philippe; Taillé, Camille

    2015-05-14

    Lung involvement in primary Sjögren syndrome occurs in approximately 10-20% of patients. Tocilizumab, an anti-interleukin-6 receptor antibody, has demonstrated efficacy and safety in small series of systemic sclerosis, and systemic lupus erythematosus, but its effect on interstitial lung manifestations of connective tissue diseases is not well known. We report the use of tocilizumab in a refractory organising pneumonia associated with Sjögren's disease. Our observation suggests that tocilizumab could be an alternative therapeutic in refractory organising pneumonia.

  12. 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

  13. 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 Central

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

    2011-01-01

    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. PMID:22263071

  14. Sequential measurements of serum matrix metalloproteinase 9 to monitor chemotherapy responses in patients with advanced non-small-cell lung cancer

    PubMed Central

    Qiao, Xiaojuan; Zhai, Xiaoran; Wang, Jinghui; Zhao, Xiaoting; Yang, Xinjie; Lv, Jialin; Ma, Li; Zhang, Lina; Wang, Yue; Zhang, Shucai; Yue, Wentao

    2016-01-01

    Background Matrix metalloproteinase 9 (MMP-9) plays an important role in tumor invasion and metastasis, including lung cancer. However, whether variations in serum MMP-9 levels can serve as a biomarker for monitoring chemotherapy curative effect remains unclear. This study was designed to investigate the association between variations in serum MMP-9 levels and chemotherapy curative effect in patients with lung cancer. Patients and methods A total of 82 patients with advanced lung cancer were included. All newly diagnosed patients were treated with platinum-based doublet chemotherapy. Serial measurements of serum MMP-9 levels were performed by enzyme-linked immunosorbent assay. In this manner, we chose four time points to examine the association, including before chemotherapy, and 3 weeks after the beginning of the first, second, and fourth cycles of chemotherapy. Results Compared with the serum level of MMP-9 before progressive disease, patients with progressive disease had elevated serum levels of MMP-9. Compared with the previous time point of collecting specimens, the serum levels of MMP-9 in the patients with a complete response/partial response/stable disease decreased or were maintained stable. The differences of variation in serum MMP-9 levels in patients with different chemotherapy curative effects were all statistically significant after one cycle, two cycles, and four cycles (after one cycle: P<0.001; after two cycles: P<0.001; after four cycles: P=0.01). However, patients with small-cell lung cancer did not exhibit similar test results. Conclusion The variation in serum MMP-9 levels in patients with non-small-cell lung cancer during chemotherapy was closely related to chemotherapy curative effect and could be useful to monitor chemotherapy curative effect for a small portion of patients. PMID:27330309

  15. 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

  16. 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.

  17. Contemporary management of refractory hypertension.

    PubMed

    Alper, A B; Calhoun, D A

    1999-10-01

    Refractory or resistant hypertension is conventionally defined as systolic or diastolic blood pressure that remains uncontrolled despite sustained therapy with at least three different classes of antihypertensive agents. Refractory hypertension is estimated to affect less than 5% of the general population with hypertension; however, its prevalence increases with increasing severity of blood pressure. Patients presenting with refractory hypertension usually have progressed from mild, to moderate, to severe hypertension because of lack of or inadequate treatment. Other common contributing factors include obesity, medical nonadherence, suboptimal medical regimens, excessive dietary salt ingestion, secondary forms of hypertension, sleep apnea, and ingestion of substances that interfere with treatment. Combination therapy that includes appropriate doses of a diuretic is recommended for treatment of refractory hypertension. Use of fixed-dose combinations enhances compliance through cost savings, more convenient dosing, and reduced pill burdens. PMID:10981097

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

    ClinicalTrials.gov

    2016-04-12

    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. 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.

  20. 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.

  1. 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

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

    PubMed

    Jotte, Robert M; Spigel, David R

    2015-11-01

    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

  3. Comparison of an advanced minimally invasive cardiac output monitoring with a continuous invasive cardiac output monitoring during lung transplantation.

    PubMed

    Tomasi, Roland; Prueckner, Stephan; Czerner, Stephan; Schramm, Renè; Preissler, Gerhard; Zwißler, Bernhard; von Dossow-Hanfstingl, Vera

    2016-08-01

    The aim of this study was to compare a continuous non-calibrated left heart cardiac index (CI) measurement by arterial waveform analysis (FloTrac(®)/Vigileo(®)) with a continuous calibrated right heart CI measurement by pulmonary artery thermodilution (CCOmbo-PAC(®)/Vigilance II(®)) for hemodynamic monitoring during lung transplantation. CI was measured simultaneously by both techniques in 13 consecutive lung transplants (n = 4 single-lung transplants, n = 9 sequential double-lung transplants) at distinct time points perioperatively. Linear regression analysis and Bland-Altman analysis with percentage error calculation were used for statistical comparison of CI measurements by both techniques. In this study the FloTrac(®) system underestimated the CI in comparison with the continuous pulmonary arterial thermodilution (p < 0.000). For all measurement pairs we calculated a bias of -0.55 l/min/m(2) with limits of agreement between -2.31 and 1.21 l/min/m(2) and a percentage error of 55 %. The overall correlations before clamping a branch oft the pulmonary artery (percentage error 41 %) and during the clamping periods of a branch oft the pulmonary artery (percentage error 66 %) failed to reached the required percentage error of less than 30 %. We found good agreement of both CI measurements techniques only during the measurement point "15 min after starting the second one-lung ventilation period" (percentage error 30 %). No agreement was found during all other measurement points. This pilot study shows for the first time that the CI of the FloTrac(®) system is not comparable with the continuous pulmonary-artery thermodilution during lung transplantation including the time periods without clamping a branch of the pulmonary artery. Arterial waveform and continuous pulmonary artery thermodilution are, therefore, not interchangeable during these complex operations.

  4. Overview of Clinical Lung Transplantation

    PubMed Central

    Yeung, Jonathan C.; Keshavjee, Shaf

    2014-01-01

    Since the first successful lung transplant 30 years ago, lung transplantation has rapidly become an established standard of care to treat end-stage lung disease in selected patients. Advances in lung preservation, surgical technique, and immunosuppression regimens have resulted in the routine performance of lung transplantation around the world for an increasing number of patients, with wider indications. Despite this, donor shortages and chronic lung allograft dysfunction continue to prevent lung transplantation from reaching its full potential. With research into the underlying mechanisms of acute and chronic lung graft dysfunction and advances in personalized diagnostic and therapeutic approaches to both the donor lung and the lung transplant recipient, there is increasing confidence that we will improve short- and long-term outcomes in the near future. PMID:24384816

  5. Overcoming resistance to first/second generation epidermal growth factor receptor tyrosine kinase inhibitors and ALK inhibitors in oncogene-addicted advanced non-small cell lung cancer

    PubMed Central

    Romanidou, Ourania; Landi, Lorenza; Cappuzzo, Federico; Califano, Raffaele

    2016-01-01

    Epidermal growth factor receptor (EGFR) activating mutations and anaplastic lymphoma kinase (ALK) gene rearrangement in advanced non-small cell lung cancer (NSCLC) represent the two oncogenic events with an impact on current clinical practice. EGFR tyrosine kinase inhibitors (TKIs) and crizotinib are the standard of care for the treatment of EGFR mutant and ALK gene rearranged advanced NSCLC patients. Unfortunately, despite initial clinical benefit, acquired resistance to EGFR-TKIs or crizotinib usually develops after an average of 10–12 months of treatment. The aim of this review is to describe the mechanisms of resistance to first/second generation EGFR-TKIs and crizotinib. In particular, we focus on strategies to overcome resistance due to secondary EGFR T790M mutation and mutations of the ALK domain. PMID:27239236

  6. 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.

  7. 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

  8. Atypical skin reaction in a patient treated with gefitinib for advanced lung cancer: A case report and review of the literature

    PubMed Central

    FERRAZZI, ANNA; RUSSO, IRENE; PASELLO, GIULIA; ALAIBAC, MAURO

    2016-01-01

    Gefitinib is a selective epidermal growth factor receptor tyrosine kinase inhibitor utilized for the treatment of advanced non-small cell lung carcinoma. The most commonly reported adverse event during gefitinib therapy is skin rash, particularly a papulopustular acne-like eruption. Cutaneous toxicities can affect treatment compliance and the quality of life of the patient. The present study reports a case of gefitinib-induced atypical skin reaction in a 73-year-old woman with advanced non-small cell lung cancer, who developed a squamous-crusted eruption on her face after 4 weeks of oral treatment with gefitinib at a dose of 250 mg/day. The patient was treated with 100 mg minocyclin (2 tablets/day, orally) and with ryfamicin topically. A complete resolution of the lesions was observed 2 weeks later. The present case report explored the pathogenesis of this skin manifestation, focusing on the underlying immunological mechanisms. A review of the literature concerning skin reactions to gefitinib was also conducted. PMID:26889239

  9. [Bronchoscopic lung volume reduction (BLVR) in advanced pulmonary emphysema: dreams of the future or much ado about nothing?].

    PubMed

    Stanzel, F

    2012-01-01

    Bronchoscopic lung volume reduction (BLVR) is a rapidly developing area and at present it is being intensively evaluated and discussed. There is a great interest in developing new treatment modalities that can reduce lung volume and air trapping without the risk of a surgical intervention. The different techniques of BLVR are characterised by lower morbidity and mortality, but by a more limited effect too. The placement of valves leads to blockade of the airway and sometimes to absorption atelectasis. The valves have been most intensively evaluated and are frequently applied. Beside the blocking devices there are partially blocking or deforming devices available as coils that are introduced in heterogeneous emphysema. Irreversible procedures such as polymeric lung volume reduction or thermal vapour ablation are used too. The creation of airway bypasses to allow trapped air to escape is mainly employed in homogenous emphysema. Following such by-pass creation there is an increase of lung function tests and a reduction of dyspnea, but only for a limited time. The bypass procedure has disappeared from bronchoscopy units completely. We give a review of the recent developments regarding BLVR and the state of the art.

  10. 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

  11. Dynamic Testing of Gasifier Refractory

    SciTech Connect

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

    2004-09-27

    The University of North Dakota (UND) Chemical Engineering Department in conjunction with the UND Energy & Environmental Research Center (EERC) have initiated a program to thoroughly examine the combined chemical (reaction and phase change) and physical (erosion) effects experienced by a variety of refractory materials during both normal operation and thermal cycling 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) is being 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. Shakedown testing of the CADCAF has been completed. Samples of slag and refractory from the Tampa Electric Polk Power Station have been obtained for testing in the CADCAF. The slag has been dried and sieved to the size needed for our flowing slag corrosion tests. Screening tests are in currently in progress. Detailed analysis of corrosion rates from the first tests is in progress.

  12. Dynamic Testing of Gasifier Refractory

    SciTech Connect

    Michael D. Mann; Devdutt Shukla; John P. Hurley

    2003-09-27

    The University of North Dakota (UND) Chemical Engineering Department in conjunction with the UND Energy & Environmental Research Center (EERC) have initiated a program to thoroughly examine the combined chemical (reaction and phase change) and physical (erosion) effects experienced by a variety of refractory materials during both normal operation and thermal cycling 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) is being 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. Shakedown testing of the CADCAF is in progress. Samples of slag and refractory from the Tampa Electric Polk Power Station have been obtained for testing in the CADCAF. The slag has been dried and sieved to the size needed for our flowing slag corrosion tests. Testing is expected to begin in October.

  13. 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.

  14. 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.

  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.

    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.

  16. Long-term benefit of PD-L1 blockade in lung cancer associated with JAK3 activation

    PubMed Central

    Van Allen, Eliezer M.; Golay, Hadrien G.; Liu, Yan; Koyama, Shohei; Wong, Karrie; Taylor-Weiner, Amaro; Giannakis, Marios; Harden, Maegan; Rojas-Rudilla, Vanesa; Chevalier, Aaron; Thai, Tran; Lydon, Christine; Mach, Stacy; Wong, Joshua A.; Rabin, Alexandra R.; Helmkamp, Joshua; Sholl, Lynette; Carter, Scott L.; Oxnard, Geoffrey; Janne, Pasi; Getz, Gad; Lindeman, Neal; Hammerman, Peter S.; Garraway, Levi A.; Hodi, F. Stephen; Rodig, Scott; Dranoff, Glenn; Wong, Kwok-Kin; Barbie, David A.

    2015-01-01

    PD-1 immune checkpoint blockade occasionally results in durable clinical responses in advanced metastatic cancers. However, mechanism-based predictors of response to this immunotherapy remain incompletely characterized. We performed comprehensive genomic profiling on a tumor and germline sample from a patient with refractory lung adenocarcinoma who achieved marked long-term clinical benefit from anti-PD-L1 therapy. We discovered activating somatic and germline amino acid variants in JAK3 that promoted PD-L1 induction in lung cancer cells and in the tumor immune microenvironment. These findings suggest that genomic alterations that deregulate cytokine receptor signal transduction could contribute to PD-L1 activation and engagement of the PD-1 immune checkpoint in lung cancer. PMID:26014096

  17. Efficacy of cisplatin/pemetrexed with bevacizumab to treat advanced lung adenocarcinoma with different drive genes: case report and literature review

    PubMed Central

    Wang, Haiyong; Zhu, Hui; Kong, Li; Yu, Jinming

    2016-01-01

    Background Bevacizumab combined with chemotherapy has become the first-line therapy in advanced nonsquamous non-small-cell lung cancer (NSCLC). However, few studies have focused on cisplatin/pemetrexed with bevacizumab as the first-line therapy to treat advanced nonsquamous NSCLC. Importantly, whether the epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements can influence the efficacy of bevacizumab in combination with chemotherapy is very interesting. Herein, we report three cases with different types of gene drives in advanced nonsquamous NSCLC. Case presentation In the first case, a patient presented with wild-type EGFR and negative ALK rearrangement. In the second case, a patient presented with wild-type EGFR and positive ALK rearrangement. In the third case, a patient presented with negative ALK rearrangement and mutated EGFR in exon 19. Conclusion We speculate that bevacizumab in combination with cisplatin/pemetrexed as the first-line therapy is well tolerated and results in a clinically meaningful treatment benefit, irrespective of the gene drive type in advanced nonsquamous NSCLC. However, more data are needed to confirm the relationship. PMID:27555784

  18. 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.

  19. The genetic variations in DNA repair genes ERCC2 and XRCC1 were associated with the overall survival of advanced non-small-cell lung cancer patients.

    PubMed

    Wang, Suhan; Wang, Jianzhong; Bai, Yansen; Wang, Qing; Liu, Li; Zhang, Kai; Hong, Xiaohua; Deng, Qifei; Zhang, Xiaomin; He, Meian; Wu, Tangchun; Xu, Ping; Guo, Huan

    2016-09-01

    It was reported that DNA repair can confer cancer cell resistance to therapeutic treatments by activating antiapoptotic cellular defense. We hypothesized that genetic variants of DNA repair genes may be associated with lung cancer prognosis. Seventeen tagging single-nucleotide polymorphism (tagSNPs) selected from 12 DNA repair genes were genotyped in 280 advanced non-small-cell lung cancer (NSCLC) patients by TaqMan assay. The associations of these SNPs and overall survival of advanced NSCLC patients were investigated. Advanced NSCLC patients carrying ERCC2 rs50872 CT+TT genotypes had significantly longer median survival time (MST) and decreased death risk than patients with rs50872 CC genotype [log-rank P = 0.031; adjusted HR(95% CI) = 0.73 (0.55-0.98), P = 0.033]. These effects were mainly seen among younger patients (≤65 years old) [HR(95% CI) = 0.57 (0.37-0.87), P = 0.010], patients without surgery [HR(95% CI) = 0.68 (0.47-0.98), P = 0.036] but with chemotherapy [HR(95% CI) = 0.64 (0.46-0.91), P = 0.012] or radiotherapy [HR(95% CI) = 0.58 (0.38-0.89), P = 0.013]. Meanwhile, compared to advanced NSCLC patients with rs25487 GG genotype, patients carrying XRCC1 rs25487 GA+AA genotypes had significantly shorter MST (MST = 11.7 vs. 16.7, log-rank P = 0.048). In addition, advanced NSCLC patients carrying the ERCC2 rs50872 CC in combination with XRCC1 rs25487 GA+AA genotype had the shortest MST (11.2 month) and highest death risk [HR(95% CI) = 1.70 (1.15-2.52), P = 0.008] when compared with those carrying rs50872 CT+TT and rs25487 GG genotype (MST = 22.0 month). The ERCC2 rs50872 T allele was associated with favorable but XRCC1 rs25487 A allele with bad survival for advanced NSCLC in Chinese population, which may offer novel biomarkers for predicting clinical outcomes.

  20. Treatment-refractory Tourette Syndrome.

    PubMed

    Kious, Brent M; Jimenez-Shahed, Joohi; Shprecher, David R

    2016-10-01

    Tourette Syndrome (TS) is a complex neurodevelopmental condition marked by tics and frequently associated with psychiatric comorbidities. While most cases are mild and improve with age, some are treatment-refractory. Here, we review strategies for the management of this population. We begin by examining the diagnosis of TS and routine management strategies. We then consider emerging treatments for refractory cases, including deep brain stimulation (DBS), electroconvulsive therapy (ECT), repetitive transcranial magnetic stimulation (rTMS), and novel pharmacological approaches such as new vesicular monoamine transporter type 2 inhibitors, cannabinoids, and anti-glutamatergic drugs. PMID:26875502

  1. 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

  2. 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.

  3. Beneficiation of aluminosilicate and magnesia secondary refractories

    SciTech Connect

    Baranovskii, N.I.; Klyachin, V.V.; Rogozina, V.G.; Bortnikova, N.V.

    1987-09-01

    This article provides a comprehensive description of the recycling, magnetic separation, and utilization of waste refractories comprised of aluminosilicate and magnesia refractories along with data on the properties pertinent to the efficiency of the recycling process.

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

    PubMed Central

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

    2012-01-01

    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 (GTVP) and involved lymph nodes (GTVLN) 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 GTVP and GTVLN, respectively. Compared to bony alignment, transitive-based and seeded registrations significantly reduced GTVP centroid LE to 4.7 ± 3.7 mm (p = 0.011) and 4.3 ± 2.5 mm (p < 1 × 10−3), respectively, but the smallest GTVP LE of 2.4 ± 2.1 mm was provided by rereferenced registration (p < 1 × 10−6). Standard registration significantly reduced GTVLN centroid LE to 3.2 ± 2.5 mm (p < 1 × 10−3) compared to bony alignment, with little additional gain offered by the other registration techniques. For simultaneous target alignment, centroid LE as low as 3

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

    PubMed

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

    2016-05-01

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

  6. 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

  7. 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.

  8. Comparison of the efficacy and tolerability of gefitinib with pemetrexed maintenance after first-line platinum-based doublet chemotherapy in advanced lung adenocarcinoma: single-center experience

    PubMed Central

    Lin, Liping; Zhao, Juanjuan; Hu, Jiazhu; Huang, Fuxi; Han, Jianjun; He, Yan; Cao, Xiaolong

    2016-01-01

    Purpose Both gefitinib and pemetrexed maintenance were effective therapies for advanced lung adenocarcinoma, but which is better is unclear. For patients with advanced lung adenocarcinoma, we have no idea whether we should choose gefitinib or pemetrexed maintenance in clinical practice. Here, we assessed the efficacy and tolerability of gefitinib versus pemetrexed maintenance in these patients. Patients and methods A total of 101 patients were identified and divided into gefitinib (n=53) or pemetrexed (n=48) maintenance. Epidermal growth factor receptor (EGFR) status of tumors was analyzed in 67 patients. Disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) were compared between the two groups. Results The results showed that DCR (79.2% vs 75%, P=0.642) was similar between gefitinib and pemetrexed groups. The PFS of gefitinib was significantly longer than that of pemetrexed (8 months vs 5.4 months, hazard ratio [HR]: 0.520, 95% confidence interval [CI]: 0.341–0.791, P=0.002); however, the OS was similar (19.9 months vs 18.8 months, HR: 1.006, 95% CI: 0.664–1.525, P=0.977). In EGFR mutation-positive patients, PFS was significantly longer in gefitinib (12 months vs 5.4 months; HR: 0.158, 95% CI: 0.074–0.333, P<0.001), whereas in EGFR wild-type subgroup gefitinib had a significantly shorter PFS than that by pemetrexed (2.5 months vs 5 months; HR: 2.822, 95% CI: 1.137–7.005, P=0.025). Cox multivariate regression analysis of PFS for overall population showed that smoking status (P=0.001) and maintenance regimens (P=0.013) were independent prognostic factors for PFS. Both gefitinib and pemetrexed were well tolerated. Conclusion Gefitinib compared with pemetrexed as maintenance therapy had a significantly longer PFS and a similar OS with good tolerability in patients with advanced lung adenocarcinoma. Moreover, for EGFR mutation-positive patients, gefitinib maintenance had a significantly longer PFS; however, pemetrexed

  9. The eelectrochemical processing of refractory metals

    NASA Astrophysics Data System (ADS)

    Sadoway, Donald R.

    1991-07-01

    Electrochemical processing is used extensively in the primary extraction of metals (electrowinning), the purification and recycling of metals (electrorefining), and the formation of metal coatings (electroplating). With respect to the refractory metals, electrochemical processing is conducted almost exclusively in nonaqueous media, predominantly in molten salts. Electrolysis infused salts as well as other nonaqueous media has enormous potential for materials processing. First, because of the special attributes of nonaqueous electrolytes, electrochemical processing in these media has an important role to play in the generation of advanced materials—materials with specialized chemistries or tailored microstructures (electrosynthesis). Second,as environmental quality standards rise beyond the capabilities of classical metals extraction technologies to comply, electrochemical processing may prove to be the only acceptable route from ore to metal.

  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. Refractory shield for superheater tubes

    SciTech Connect

    Green, K.E.; Johnson, D.K.; Woodruff, R.W.

    1987-07-28

    A refractory shield is described for protecting superheater tubes against attack by the products of combustion comprising: a pair of elongated molded and fired refractory half shields of predetermined identical interchangeable interlocking size and shape adapted when one of the half shields is rotated 180/sup 0/ and extends longitudinally relative to the other half shields to be slid axially together and interlocked together solely without additional fastening means, surround and shield the superheater tube. Each half shield has: an elongated refractory sidewall portion of predetermined axial length and thickness between opposite ends extending circumferentially between and to diametrically opposite refractory tongue and grooved side wall portions of predetermined axially engageable interlocking shape. An elongated tongue of predetermined shape, width and radial length projects radially outwardly from the tongue sidewall portion; and an elongated internal groove projects radially outward in the grooved side wall portion and of predetermined interlocking shape. Sufficient width and radial depth accept an elongated tongue of the other one of the pair of half shields assembled and locked together against relative rotation solely by axially inserting the tongues into the grooves.

  12. 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.

  13. MicroRNA expression profiling of sputum for the detection of early and locally advanced non-small-cell lung cancer: a prospective case–control study

    PubMed Central

    Razzak, R.; Bédard, E.L.R.; Kim, J.O.; Gazala, S.; Guo, L.; Ghosh, S.; Joy, A.; Nijjar, T.; Wong, E.; Roa, W.H.

    2016-01-01

    Background Non-small-cell lung cancer (nsclc) is associated with very poor overall survival because 70% of patients present with locally advanced or metastatic disease at the time of diagnosis. Micrornas (mirnas) are a class of short, noncoding rna molecules whose presence in samples of biologic fluids such as sputum has demonstrated promise as a potential means of detecting nsclc. We investigated the stage-specific nsclc detection potential of an efficient panel of 3 mirnas (mir-21, mir-210, mir-372) using a single sputum sample. Methods A single spontaneously expectorated sputum sample was prospectively collected from 21 early nsclc (≤stage ii) patients, 22 advanced nsclc (≥stage iii) patients, and 10 control subjects. Mirna expression profiles were determined by quantitative real-time polymerase chain reaction and were analyzed by unsupervised hierarchical cluster analysis. Results Mean tumour size (±95% confidence interval) in the early and advanced nsclc patients was 3.3 cm ± 0.9 cm and 4.8 cm ± 0.7 cm respectively. Adenocarcinoma constituted 61.9% of the early and 45.5% of the advanced nsclc cases respectively. In comparing the early nsclc group with the control group, the mirna panel yielded a diagnostic sensitivity of 67% and a specificity of 90.0%. For the advanced nsclc group, the mirna panel detected nsclc with a sensitivity and specificity of 64% and 100% respectively. Conclusions A sputum mir-21, mir-210, and mir-372 expression profile might provide a sensitive and highly specific means for detecting nsclc. Sputum mirna analysis demonstrates promise as a potential complementary screening tool. PMID:27122989

  14. Risk of venous and arterial thromboembolic events associated with anti-VEGF agents in advanced non-small-cell lung cancer: a meta-analysis and systematic review

    PubMed Central

    Zhang, Dianbao; Zhang, Xianfen; Zhao, Chunling

    2016-01-01

    Aims To assess the incidence and risk of arterial and venous thromboembolic events (ATEs and VTEs) associated with antivascular endothelial growth factor (VEGF) agents, including VEGF receptor-tyrosine kinase inhibitors and VEGF monoclonal antibodies, in advanced non-small-cell lung cancer (NSCLC) patients. Methods We performed a broad search of PubMed for relevant trials. Prospective randomized trials evaluating therapy with or without anti-VEGF agents in patients with advanced NSCLC were included for analysis. Data on VTEs and ATEs were extracted. The overall incidence, Peto odds ratio (Peto OR), and 95% confidence intervals (CIs) were pooled according to the heterogeneity of included trials. Results A total of 13,436 patients from 23 trials were included for analysis. Our results showed that anti-VEGF agents significantly increased the risk of developing high-grade ATEs (Peto OR: 1.44, 95% CI: 1.00–2.07, P=0.048), but not for all-grade ATEs (Peto OR: 0.94, 95% CI: 0.56–1.59, P=0.82) compared with controls. Additionally, no increased risk of all-grade and high-grade VTEs (Peto OR: 0.94, 95% CI: 0.67–1.31, P=0.71 and Peto OR: 0.95, 95% CI: 0.73–1.22, P=0.67, respectively) was observed in advanced NSCLC patients receiving anti-VEGF agents. Conclusion The use of anti-VEGF agents in advanced NSCLC patients significantly increased the risk of high-grade ATEs, but not for VTEs. Clinicians should be aware of the risk of severe ATEs with administration of these drugs in advanced NSCLC patients. PMID:27382307

  15. First-line systemic treatment of advanced stage non-small-cell lung cancer in Asia: consensus statement from the Asian Oncology Summit 2009.

    PubMed

    Soo, Ross A; Anderson, Benjamin O; Cho, Byoung Chul; Yang, Chih-Hsin; Liao, Meilin; Lim, Wan-Teck; Goldstraw, Peter; Mok, Tony S

    2009-11-01

    Non-small-cell lung cancer (NSCLC) is an increasing global challenge, especially in low-income countries. Most guidelines for the management of advanced-stage NSCLC have limited effect in countries with resource constraints. Following a systematic literature search, we present an overview of the management of advanced-stage NSCLC in the first-line setting, discuss resources required for systemic therapy, and provide treatment recommendations stratified to four resources levels. Treatment guidelines appropriate for different resource levels offer a realistic approach to management of advanced-stage NSCLC, by recognising the limitations of a particular health-care system. Although there are many barriers to cancer control in low-resource countries, these can be overcome by using measures that are culturally appropriate, economically feasible, and evidence-based. Initiatives include strategic planning, tobacco control, training of health-care workers, access to therapeutic agents, acquisition of information, public education, and alliances with established institutions and international organisations. PMID:19880064

  16. 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. PMID:26387039

  17. [Analysis of the risk factors for severe neutropenia in advanced non-small cell lung cancer after the first course of chemotherapy with third-generation agents].

    PubMed

    Shibuya, Midori; Kogo, Mari; Kurihara, Tatsuya; Shikama, Yusuke; Nakajima, Hiroaki; Yoneyama, Keiichiro; Kiuchi, Yuji

    2013-01-01

      We retrospectively evaluated clinical data before therapy to determine the risk factors for severe neutropenia in advanced non-small-cell lung cancer (NSCLC) patients treated with third-generation agents. We analyzed 100 patients who received such agents (paclitaxel, docetaxel, gemcitabine, irinotecan, or vinorelbine) for advanced NSCLC. The endpoint of the survey was the occurrence of severe neutropenia (grade 4). Risk factors significantly related to severe neutropenia were identified using logistic regression analysis. Of the 100 patients studied, the median age was 62.0 (32-81 years), and 77 (77.0%) were male. CEA 6.6 (0-2220) ng/dL and cytokeratin 19 fragment 21-1 (CYFRA) 4.8 (0.2-173.8) ng/dL before chemotherapy were higher than normal range. Severe neutropenia occurred in 36.0%, the incidence being highest in the first cycle (61.1%). In the univariate analysis, variables associated with severe neutropenia were sex, chest pain, absolute neutrophil count (ANC), Cr, CRP, and CYFRA. In the multivariate analysis, low CYFRA level was identified as a significant risk factor that contributed independently to chemotherapy-induced severe neutropenia (p<0.05). Our analysis suggests that low CYFRA level is the most important risk factor for severe neutropenia in advanced NSCLC patients after the first course of chemotherapy with third-generation agents. PMID:23728094

  18. 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.

  19. 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.

  20. A phase II study of cisplatin, vindesine and continuously infused 5-fluorouracil in the treatment of advanced non-small-cell lung cancer. Osaka Lung Cancer Chemotherapy Study Group.

    PubMed Central

    Nakano, T.; Ikegami, H.; Nakamura, S.; Kawase, T.; Nishikawa, H.; Yokota, S.; Yoshida, M.; Tachibana, T.; Igarashi, T.; Komuta, K.; Higashino, K.

    1996-01-01

    Fifty-two previously untreated patients with advanced non-small-cell lung cancer (NSCLC) were treated on a 14 day cycle with cisplatin (60 mg m-2 i.v.) and vindesine (3 mg m-2 i.v.) on day 1, followed by a 3 day continuous infusion of 5-fluorouracil (800 mg m-2 day-1) starting on day 8. An overall response rate of 40.4% was observed in 47 evaluable patients, which included one complete response and 18 partial responses. Responses were achieved in 61.1% of stage 3 patients and 27.6% of stage 4 patients. The median progression-free interval was 19.3 weeks, and median survival time was 41.6 weeks (47.1 weeks for patients with stage 3 disease and 38.7 weeks for those with stage 4 disease). Toxicity was well tolerated. Gastrointestinal and renal toxicities did not exceed WHO grade 2. Grade 3 or 4 leucopenia and anaemia occurred in nine (19%) and four (9%) patients respectively, but only grade 2 thrombocytopenia was observed. Phlebitis at the infusion site was observed in 24 patients (53%). This treatment programme achieved a response rate similar to other active combination regimens for the treatment of advanced NSCLC, and was less toxic. PMID:8624270

  1. New developments in gasifier refractories

    SciTech Connect

    Dogan, Cynthia P.; Kwong, Kyei-Sing; Bennet, James P.; Chinn, Richard E.; Dahlin, Cheryl L.

    2002-01-01

    For Integrated Gasification Combined Cycle (IGCC) systems, operational reliability depends in part upon the ability of the materials of construction to tolerate harsh, high-temperature environments for extended periods of time. The harshest conditions within an IGCC system occur inside the gasifier itself, where for slagging systems the environment includes elevated temperature and pressure, as well as the presence of corrosive slags and gases. Attempts to enhance gasifier performance by operating at higher temperatures, with higher throughputs, and/or with variable feedstocks, put additional stress on the materials exposed to the operating environment, often resulting in a corresponding decrease in their useful service life. Current generation refractory materials commonly used at the hot face of commercial slagging systems will typically last from four to 18 months, depending on the operating conditions of the specific gasifier. However, as gasification technology matures, the need for new and improved materials will increase as the time between required maintenance shutdowns, and hence the economics and reliability of operation, are defined more and more by the service life of the materials from which the system is built. To address this need for materials development, the U.S. Department of Energy's Office of Fossil Energy and the Albany Research Center are exploring ways to extend the service life of the refractory liner that contains the gasification reaction in slagging gasifiers. In this paper, we examine how refractory materials fail in the gasifier environment, and introduce a new refractory designed specifically to resist such failures. Based on laboratory exposure tests, this new refractory is predicted to significantly enhance gasifier reliability and availability through increased service life.

  2. Improved Refractories for Slagging Gasifiers in IGCC Power Systems

    SciTech Connect

    Dogan, Cynthia P.; Kwong, Kyei-Sing; Bennett, James P.; Chinn, Richard E.

    2003-04-24

    The gasification of coal and other carbon-containing fuels provides the opportunity to produce energy more efficiently, and with significantly less environmental impact, than more-conventional combustion-based processes. In addition, the synthesis gas that is the product of the gasification process offers the option of ''polygeneration,'' i.e., the production of alternative products instead of power should it be economically favorable to do so. Because of these advantages, gasification is viewed as one of the key processes in the U.S. Department of Energy's Vision 21 power system. However, issues with both the reliability and the economics of gasifier operation will have to be resolved before gasification will be widely adopted by the power industry. Central to both enhanced reliability and economics is the development of materials with longer service lives in gasifier systems that can provide extended periods of continuous, trouble-free gasifier operation. The focus of the Advanced Refractories for Gasification project at the Albany Research Center is to develop improved refractory materials capable of withstanding the harsh, high-temperature environment created by the gasification reaction, and includes both the refractory lining that protects and insulates the slagging gasifier, as well as the thermocouple assemblies that are utilized to monitor gasifier operating temperatures. Current generation refractory liners in slagging gasifiers are typically replaced every four to 18 months, at costs ranging up to $2,000,000, depending upon the size of the gasification vessel. Compounding materials and installation costs are the lost-opportunity costs for the time that the gasifier is off-line for the refractory exchange. Current generation thermocouple devices rarely survive the gasifier start-up process, leaving the operator with no real means of temperature measurement during routine operation. Reliable, efficient, and economical gasifier operation that includes the

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

    PubMed

    Gupta, Neha; Hatoum, Hassan; Dy, Grace K

    2014-01-01

    Lung cancer is the leading cause of cancer mortality worldwide in both men and women. Non-small-cell lung cancer (NSCLC) is the most common type of lung cancer, accounting for more than 80% of cases. Paclitaxel has a broad spectrum of activity against various malignancies, including NSCLC. Paclitaxel is poorly soluble in water and thus, until recently, its commercially available preparations contained a non-ionic solvent Cremophor EL®. Cremophor EL® improves the solubility of paclitaxel and allows its intravenous administration. However, certain side-effects associated with paclitaxel, such as hypersensitivity reactions, myelosuppression, and peripheral neuropathy, are known to be worsened by Cremophor®. Nanoparticle albumin-bound paclitaxel ([nab-paclitaxel] ABRAXANE® ABI-007) is a new generation formulation of paclitaxel that obviates the need for Cremophor®, resulting in a safer and faster infusion without requiring the use of premedications to avoid hypersensitivity. Albumin-binding receptor-mediated delivery and lack of sequestering Cremophor® micelles allow higher intratumoral concentration of pharmacologically active paclitaxel. Multiple clinical trials have demonstrated a superior tolerability profile of nab-paclitaxel in comparison to solvent-bound paclitaxel (sb-paclitaxel). A recent Phase III trial compared the effects of weekly nab-paclitaxel in combination with carboplatin versus sb-paclitaxel in combination with carboplatin given every 3 weeks for first line treatment of NSCLC. This trial highlights the weekly nab-paclitaxel combination as an alternate treatment option for NSCLC, with higher response rate in squamous cell NSCLC and longer survival in elderly patients. This review will focus on the properties of nab-paclitaxel and its use in the first line treatment of NSCLC.

  4. Activity of pemetrexed-based regimen as first-line chemotherapy for advanced non-small cell lung cancer with asymptomatic inoperable brain metastasis: a retrospective study.

    PubMed

    Zhu, Weiyou; Røe, Oluf Dimitri; Wu, Chen; Li, Wei; Guo, Renhua; Gu, Yanhong; Liu, Yiqian; Shu, Yongqian; Chen, Xiaofeng

    2015-08-01

    This retrospective study was conducted to assess the efficacy of combination of pemetrexed and cisplatin/carboplatin as first-line treatment in inoperable and asymptomatic brain metastasis (BM) from non-small cell lung cancer (NSCLC). A total of 30 patients with adenocarcinoma were included. Nine patients had solitary, and 21 patients had multiple BM. At evaluation after two cycles, the complete response (CR) rate, partial response (PR) rate, and stable disease (SD) for brain lesions was 0, 33.3, and 46.7%, respectively. The overall CR, PR, and SD were 0, 23.3, and 46.7%, respectively. The median time to tumour progression of BM (TTP-BM) was 6.0 months (95% CI 4.068-7.932). The median progression-free survival (PFS) and overall survival (OS) were 5.0 months (95% CI 4.197-5.803) and 11.0 months (95% CI 7.398-14.602), respectively. Pemetrexed has comparable activity on brain lesions as on extracranial tumours in advanced lung adenocarcinoma patients with inoperable and asymptomatic BM.

  5. 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.

  6. 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.

  7. 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

  8. 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

  9. Initial Evaluation of Treatment-Related Pneumonitis in Advanced-Stage Non-Small-Cell Lung Cancer Patients Treated With Concurrent Chemotherapy and Intensity-Modulated Radiotherapy

    SciTech Connect

    Yom, Sue S.; Liao Zhongxing . E-mail: zliao@mdanderson.org; Liu, H. Helen; Tucker, Susan L.; Hu, C.-S.; Wei Xiong; Wang Xuanming; Wang Shulian; Mohan, Radhe; Cox, James D.; Komaki, Ritsuko

    2007-05-01

    Purpose: To investigate the rate of high-grade treatment-related pneumonitis (TRP) in patients with advanced non-small-cell lung cancer (NSCLC) treated with concurrent chemotherapy and intensity-modulated radiotherapy (IMRT). Methods and Materials: From August 2002 to August 2005, 151 NSCLC patients were treated with IMRT. We excluded patients who did not receive concurrent chemotherapy or who had early-stage cancers, a history of major lung surgery, prior chest RT, a dose <50 Gy, or IMRT combined with three-dimensional conformal RT (3D-CRT). Toxicities were graded by Common Terminology Criteria for Adverse Events version 3.0. Grade {>=}3 TRP for 68 eligible IMRT patients was compared with TRP among 222 similar patients treated with 3D-CRT. Results: The median follow-up durations for the IMRT and 3D-CRT patients were 8 months (range, 0-27 months) and 9 months (range, 0-56 months), respectively. The median IMRT and 3D-CRT doses were 63 Gy. The median gross tumor volume was 194 mL (range, 21-911 mL) for IMRT, compared with 142 mL (range, 1.5-1,186 mL) for 3D-CRT (p = 0.002). Despite the IMRT group's larger gross tumor volume, the rate of Grade {>=}3 TRP at 12 months was 8% (95% confidence interval 4%-19%), compared with 32% (95% confidence interval 26%-40%) for 3D-CRT (p = 0.002). Conclusions: In advanced NSCLC patients treated with chemoradiation, IMRT resulted in significantly lower levels of Grade {>=}3 TRP compared with 3D-CRT. Clinical, dosimetric, and patient selection factors that may have influenced rates of TRP require continuing investigation. A randomized trial comparing IMRT with 3D-CRT has been initiated.

  10. Functional design of refractories for slagging gasifiers

    SciTech Connect

    Kwong, Kyei-Sing; Dogan, Cynthia P.; Bennett, James P.; Chinn, Richard E.; Dahlin, Cheryl L.

    2002-09-01

    Refractories are used in coal slagging gasifiers to protect the outer steel shell from coal slag attack and to insulate it from heat. Corrosion by the aggressive coal slags and unexpected temperature shock severely shorten the service life of these refractories. Currently, the best refractories available for the slagging coal gasifiers last from 6 to 18 months. The down time for the installation of new refractory lining reduces on-line availability of the gasifier. Researchers at the Albany Research Center (ARC) have found that structural spalling by slag penetration into the refractory is responsible for the early failure of refractories in some gasifiers. The low melting point of coal slags, the low thermal gradient in the refractory, and the improper design of refractory microstructure contribute to promote slag penetration. Work at ARC has demonstrated that refractories with an improved functional design are more resistant to slag penetration. Cooperation with commercial refractory companies and gasifier designers/operators is underway to produce and test improved refractories.

  11. Cardiogenic syncope possibly related to bevacizumab-containing combination chemotherapy for advanced non-small cell lung cancer

    PubMed Central

    Amano, Yosuke; Yamauchi, Yasuhiro; Matsuda, Jun; Takeda, Norihiko; Tanaka, Goh; Takai, Daiya; Nagase, Takahide

    2016-01-01

    We report the case of a 55-year-old man with stage IV lung adenocarcinoma who received carboplatin-paclitaxel-bevacizumab chemotherapy as second-line therapy. After four cycles of chemotherapy, he experienced syncope with a decrease in blood pressure. Electrocardiography (ECG) revealed atrial fibrillation. Cardiac ultrasonography showed a markedly reduced ejection fraction (45%), with moderate decrease in comparison to that before chemotherapy (66%). Bisoprolol fumarate was initiated, and the conversion to sinus rhythm was detected by ECG 4 days after the syncope. At that time, no improvement in the ejection fraction was detected. Bevacizumab-associated cardiotoxicity was suspected, and bevacizumab maintenance therapy was discontinued, although the chemotherapy achieved a stable disease status based on the Response Evaluation Criteria in Solid Tumors. Two months after bevacizumab cessation, the ejection fraction improved to pretreatment level (62%). To the best of our knowledge, this is the first report on cardiogenic syncope due to left ventricular dysfunction that is most consistent with bevacizumab-associated cardiotoxicity in non-small cell lung cancer (NSCLC). Our results indicate that bevacizumab could lead to cardiotoxicity in patients with NSCLC and suggest the importance of the follow-up cardiac ultrasonography. PMID:27747019

  12. The prognostic value of whole blood SOX2, NANOG and OCT4 mRNA expression in advanced small-cell lung cancer

    PubMed Central

    Rijavec, Matija; Koren, Ana; Sadikov, Aleksander; Korošec, Peter; Cufer, Tanja

    2016-01-01

    Abstract Background The data on expression and clinical impact of cancer stem cell markers SOX2, NANOG and OCT4 in lung cancer is still lacking. The aim of our study was to compare SOX2, NANOG and OCT4 mRNA expression levels in whole blood between advanced small-cell lung cancer (SCLC) patients and healthy controls, and to correlate mRNA expression with progression-free survival (PFS) after first-line chemotherapy and overall survival (OS) in advanced SCLC patients. Patients and methods 50 advanced SCLC patients treated with standard chemotherapy and followed at University Clinic Golnik, Slovenia, between 2009 and 2013 were prospectively included. SOX2, NANOG and OCT4 mRNA expression levels were determined using TaqMan qPCR in whole blood collected prior to chemotherapy. Whole blood of 34 matched healthy individuals with no cancerous disease was also tested. Results SOX2 mRNA expression was significantly higher in whole blood of SCLC patients compared to healthy controls (p = 0.006). Significant correlation between SOX2 mRNA expression levels and the number of distant metastatic sites was established (p = 0.027). In survival analysis, patients with high SOX2 expression had shorter OS (p = 0.017) and PFS (p = 0.046). In multivariate Cox analysis, an independent value of high SOX2 expression for shorter OS (p = 0.002), but not PFS was confirmed. No significant differences were observed for NANOG or OCT4 expression levels when comparing SCLC patients and healthy controls neither when analysing survival outcomes in SCLC patients. Conclusions SOX2 mRNA expression in whole blood might be a promising non-invasive marker for molecular screening of SCLC and important prognostic marker in advanced chemotherapy-treated SCLC patients, altogether indicating important role of cancer stem-like cell (CSC) regulators in cancer spread. Further evaluation of SOX2 as a possible screening/prognostic marker and a therapeutic target of SCLC is warranted. PMID:27247551

  13. Donor management and lung preservation for lung transplantation.

    PubMed

    Munshi, Laveena; Keshavjee, Shaf; Cypel, Marcelo

    2013-06-01

    Although lung transplantation has become a life-saving option for patients with end-stage lung disease, this intervention is hampered by a shortage of lungs in view of the growing number of people on the waiting list. Lungs are retrieved from only a small percentage of multiorgan donors, and the transplantation and intensive-care communities have recognised the need to develop innovative methods to expand the donor pool. Advancements in lung-preservation techniques in the preretrieval and postretrieval periods have increased the pool of available donors, and novel research and discoveries in this area have steadily improved post-transplantation adverse events. This Review summarises current best practice and the latest research on intensive-care management of a potential lung donor. We also discuss lung-preservation techniques, including advancements in normothermic ex-vivo lung perfusion, and the potential for a personalised medicine approach to the organ. PMID:24429157

  14. Efficacy of targeted agents in the treatment of elderly patients with advanced non-small-cell lung cancer: a systematic review and meta-analysis

    PubMed Central

    Chen, Jianqing; Chen, Jianbo; Wu, Xiaoan; Shi, Tao; Kang, Meiling

    2016-01-01

    Purpose The efficacy of targeted agents (TAs) in the treatment of elderly patients with advanced non-small-cell lung cancer (NSCLC) remains controversial. We aimed to assess the efficacy of TAs in the treatment of advanced NSCLC in this setting. Materials and methods Relevant trials were identified by searching electronic databases and conference meetings. Prospective randomized controlled trials assessing chemotherapies with or without TAs in elderly patients with advanced NSCLC were included. Outcomes of interest included overall survival (OS) and progression-free survival (PFS) in elderly patients with advanced NSCLC. Results A total of 4,093 elderly patients from 17 randomized controlled trials were included for analysis. The addition of TAs to chemotherapy significantly improved PFS (hazard ratio [HR] 0.85, 95% confidence interval [CI]: 0.75–0.96, P=0.01) when compared to chemotherapy alone. There was also a tendency to improve OS in the combination groups (HR 0.92, 95% CI: 0.85–1.01, P=0.064). Subgroup analysis based on treatment line indicated that TAs plus chemotherapy as first-line chemotherapy in elderly patients with advanced NSCLC significantly improved PFS (HR 0.80, 95% CI: 0.68–0.95, P=0.01) and OS (HR 0.91, 95% CI: 0.83–0.99, P=0.037), while the use of TA-containing regimens as second-line therapy in these patients did not significantly improve PFS (HR 0.91, 95% CI: 0.75–1.10, P=0.33) and OS (HR 1.04, 95% CI: 0.81–1.33, P=0.77) in comparison with chemotherapy alone. No publication bias was detected by Begg’s and Egger’s tests for OS. Conclusion The findings of this study suggest that the addition of TAs to first-line chemotherapy in elderly patients with advanced NSCLC offers an improved PFS and OS. Further trials are recommended to clearly investigate the efficacy of adding specific TAs to first-line chemotherapy for advanced NSCLC in this setting. PMID:27536143

  15. 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. PMID:24978055

  16. Efficacy of tamoxifen in combination with docetaxel in patients with advanced non-small-cell lung cancer pretreated with platinum-based chemotherapy.

    PubMed

    Wen, Shimin; Fu, Xi; Li, Guangming; He, Lang; Zhao, Caixia; Hu, Xin; Pan, Rongqiang; Guo, Cuihua; Zhang, Xinping; Hu, Xingsheng

    2016-06-01

    The aim of this study was to evaluate the efficacy and safety of the combination of docetaxel (TXT) plus tamoxifen (TAM) in advanced non-small-cell lung cancer (NSCLC) patients who had received platinum-based first-line chemotherapy. A total of 120 advanced NSCLC patients pretreated with platinum-based chemotherapy were randomized into two treatment groups (the TXT and TXT+TAM groups) in a 1 : 1 ratio. Reversal of P-glycoprotein (P-gp) expression, tumor response, progression-free survival, overall survival, and safety were evaluated on an intention-to-treat basis. The median number of cycles of allocated chemotherapy was four in each treatment group (range: 2-6 cycles). The overall response rate and disease control rate in the TXT+TAM group were significantly higher than those in the TXT group (36.7 vs. 15.0% for overall response rate, P=0.007; 85.0 vs. 68.3% for disease control rate, P=0.031). The combination of TXT and TAM could effectively reverse P-gp expression in tumor tissues and provide a significant survival benefit for advanced NSCLC patients compared with TXT alone (11.6 vs. 9.1 months, P=0.030). In addition, in the TXT+TAM group, patients achieving P-gp reversal had a significantly greater median progression-free survival and overall survival than nonreversal patients. Furthermore, the combined therapy showed a safety profile comparable to that of TXT. The combination of TXT and TAM may be an effective and safe treatment option for advanced NSCLC patients who have already developed P-gp-mediated multidrug resistance. PMID:26882453

  17. 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 ...

  18. Lung Cancer

    MedlinePlus

    ... version of this page please turn Javascript on. Lung Cancer What is Lung Cancer? How Tumors Form The body is made ... button on your keyboard.) Two Major Types of Lung Cancer There are two major types of lung ...

  19. Lung metastases

    MedlinePlus

    Metastases to the lung; Metastatic cancer to the lung ... Metastatic tumors in the lungs are cancers that developed at other places in the body (or other parts of the lungs) and spread through the ...

  20. Endobronchial valve placement as destination therapy for recurrent pneumothorax in the setting of advanced malignancy.

    PubMed

    Gilbert, Christopher R; Toth, Jennifer W; Osman, Umar; Reed, Michael F

    2015-03-01

    The development of a persistent air leak after pneumothorax can be encountered in patients with underlying structural lung disease. In those with advanced malignancy or other comorbidities, the ability to tolerate general anesthesia and thoracoscopic procedures may limit definitive management. We describe the case of a 68-y-old male with refractory acute myelogenous leukemia presenting with recurrent secondary spontaneous pneumothorax and persistent air leak related to an underlying fungal pneumonia. Endobronchial valve placement allowed for timely chest tube removal and discharge from the hospital, as well as avoidance of a thoracoscopic procedure and pleurodesis.

  1. 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

  2. Bone marrow immunophenotyping by flow cytometry in refractory cytopenia of childhood.

    PubMed

    Aalbers, Anna M; van den Heuvel-Eibrink, Marry M; Baumann, Irith; Dworzak, Michael; Hasle, Henrik; Locatelli, Franco; De Moerloose, Barbara; Schmugge, Markus; Mejstrikova, Ester; Nováková, Michaela; Zecca, Marco; Zwaan, C Michel; Te Marvelde, Jeroen G; Langerak, Anton W; van Dongen, Jacques J M; Pieters, Rob; Niemeyer, Charlotte M; van der Velden, Vincent H J

    2015-03-01

    Refractory cytopenia of childhood is the most common type of childhood myelodysplastic syndrome. Because the majority of children with refractory cytopenia have a normal karyotype and a hypocellular bone marrow, differentiating refractory cytopenia from the immune-mediated bone marrow failure syndrome (very) severe aplastic anemia can be challenging. Flow cytometric immunophenotyping of bone marrow has been shown to be a valuable diagnostic tool in differentiating myelodysplastic syndrome from non-clonal cytopenias in adults. Here, we performed the first comprehensive flow cytometric analysis of immature myeloid, lymphoid cells and erythroid cells, and granulocytes, monocytes, and lymphoid cells in bone marrow obtained from a large prospective cohort of 81 children with refractory cytopenia. Children with refractory cyotopenia had a strongly reduced myeloid compartment, but not as severe as children with aplastic anemia. Furthermore, the number of flow cytometric abnormalities was significantly higher in children with refractory cytopenia than in healthy controls and in children with aplastic anemia, but lower than in advanced myelodysplastic syndrome. We conclude that flow cytometric immunophenotyping could be a relevant addition to histopathology in the diagnosis of refractory cytopenia of childhood. (The multi-center studies EWOG-MDS RC06 and EWOG-MDS 2006 are registered at clinicaltrials.gov identifiers 00499070 and 00662090, respectively).

  3. 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.

  4. 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.

  5. Genetic Association of Curative and Adverse Reactions to Tyrosine Kinase Inhibitors in Chinese advanced Non-Small Cell Lung Cancer patients

    PubMed Central

    Ruan, Yunfeng; Jiang, Jie; Guo, Liang; Li, Yan; Huang, Hailiang; Shen, Lu; Luan, Mengqi; Li, Mo; Du, Huihui; Ma, Cheng; He, Lin; Zhang, Xiaoqing; Qin, Shengying

    2016-01-01

    Epidermal growth factor receptor (EGFR) Tyrosine kinase inhibitor (TKI) is an effective targeted therapy for advanced non-small cell lung cancer (NSCLC) but also causes adverse drug reactions (ADRs) e.g., skin rash and diarrhea. SNPs in the EGFR signal pathway, drug metabolism/ transport pathways and miRNA might contribute to the interpersonal difference in ADRs but biomarkers for therapeutic responses and ADRs to TKIs in Chinese population are yet to be fully investigated. We recruited 226 Chinese advanced NSCLC patients who received TKIs erlotinib, gefitinib and icotinib hydrochloride and systematically studied the genetic factors associated with therapeutic responses and ADRs. Rs884225 (T > C) in EGFR 3′ UTR was significantly associated with lower risk of ADRs to erlotinib (p value = 0.0010, adjusted p value = 0.042). A multivariant interaction four-SNP model (rs884225 in EGFR 3′UTR, rs7787082 in ABCB1 intron, rs38845 in MET intron and rs3803300 in AKT1 5′UTR) was associated with ADRs in general and the more specific drug induced skin injury. The SNPs associated with both therapeutic responses and ADRs indicates they might share a common genetic basis. Our study provided potential biomarkers and clues for further research of biomarkers for therapeutic responses and ADRs in Chinese NSCLC patients. PMID:26988277

  6. Refractory materials from lunar resources

    NASA Astrophysics Data System (ADS)

    Fabes, B. D.; Poisl, W. H.

    Refractories - materials which are able to withstand extremely high temperatures - are sure to be an important part of any processing facility or human outpost which is built on Mars. Containers for processing lunar oxygen will need high temperature components. Fabrication of structural material from lunar resources need both containment vessels to hold high temperature melts and molds in which to form the final shapes. Certainly, it would be desirable to fabricate such vessels and molds on the Moon, rather than carrying them up from the Earth. At first glance, this might appear to be a trivial task, since the Moon's surface consists of a variety of refractory compositions. To turn the regolith into a useful fire brick or mold, however, will require water or other binders and additives which are likely to be in extremely short supply on the Moon. The steps needed to make fire bricks and molds for lunar-derived structural materials are examined, pointing out the critical steps and resources which will be needed. While these processes and applications may seem somewhat mundane, it is emphasized that it is precisely these rudimentary processes which must be mastered before discussing making aerobrakes, and other fancier refractories from lunar resources.

  7. Understanding and treating refractory constipation

    PubMed Central

    Bassotti, Gabrio; Blandizzi, Corrado

    2014-01-01

    Chronic constipation is a frequently encountered disorder in clinical practice. Most constipated patients benefit from standard medical approaches. However, current therapies may fail in a proportion of patients. These patients deserve better evaluation and thorough investigations before their labeling as refractory to treatment. Indeed, several cases of apparent refractoriness are actually due to misconceptions about constipation, poor basal evaluation (inability to recognize secondary causes of constipation, use of constipating drugs) or inadequate therapeutic regimens. After a careful re-evaluation that takes into account the above factors, a certain percentage of patients can be defined as being actually resistant to first-line medical treatments. These subjects should firstly undergo specific diagnostic examination to ascertain the subtype of constipation. The subsequent therapeutic approach should be then tailored according to their underlying dysfunction. Slow transit patients could benefit from a more robust medical treatment, based on stimulant laxatives (or their combination with osmotic laxatives, particularly over the short-term), enterokinetics (such as prucalopride) or secretagogues (such as lubiprostone or linaclotide). Patients complaining of obstructed defecation are less likely to show a response to medical treatment and might benefit from biofeedback, when available. When all medical treatments prove to be unsatisfactory, other approaches may be attempted in selected patients (sacral neuromodulation, local injection of botulinum toxin, anterograde continence enemas), although with largely unpredictable outcomes. A further although irreversible step is surgery (subtotal colectomy with ileorectal anastomosis or stapled transanal rectal resection), which may confer some benefit to a few patients with refractoriness to medical treatments. PMID:24868488

  8. Association of CHEK2 polymorphisms with the efficacy of platinum-based chemotherapy for advanced non-small-cell lung cancer in Chinese never-smoking women

    PubMed Central

    Xu, Wen; Liu, Di; Yang, Yang; Ding, Xi; Sun, Yifeng; Zhang, Baohong

    2016-01-01

    Background Cell cycle checkpoint kinase 2 (CHEK2) plays an essential role in the repair of DNA damage. Single nucleotide polymorphisms (SNPs) in DNA repair genes are thought to influence treatment effects and survival of cancer patients. This study aimed to investigate the relationship between polymorphisms in the CHEK2 gene and efficacy of platinum-based doublet chemotherapy in never-smoking Chinese female patients with advanced non-small-cell lung cancer (NSCLC). Methods Using DNA from blood samples of 272 Chinese advanced NSCLC non-smoking female patients treated with first-line platinum-based chemotherapy, we have analyzed the relationships between four SNPs in the CHEK2 gene and clinical outcomes. Results We found that overall survival (OS) was significantly associated with CHEK2 rs4035540 (Log-Rank P=0.020), as well as the CHEK2 rs4035540 dominant model (Log-Rank P=0.026), especially in the lung adenocarcinoma group. After multivariate analysis, patients with rs4035540 A/G genotype had a significantly better OS than those with the G/G genotype (HR =0.67, 95% CI, 0.48–0.93; P=0.016). In the toxicity analysis, it was observed that patients with the CHEK2 rs4035540 A/A genotype had a higher risk of gastrointestinal toxicity than the G/G genotype group (P=0.009). However, there are no significant associations between chemotherapy treatments and genetic variations. Conclusions Our findings indicate that SNPs in CHEK2 are related to Chinese advanced NSCLC never-smoking female patients receiving platinum-based doublet chemotherapy in China. Patients with rs4035540 A/G genotype have a better OS. And patients with rs4035540 A/A genotype have a higher risk of gastrointestinal toxicity. These results point to a direction for predicting the prognosis for Chinese never-smoking NSCLC female patients. However, there are no significant associations between chemotherapy treatments and SNPs in CHEK2, which need more samples to the further study. PMID:27747004

  9. Interfraction Displacement of Primary Tumor and Involved Lymph Nodes Relative to Anatomical Landmarks in Image–guided Radiotherapy of Locally Advanced Lung Cancer

    PubMed Central

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

    2014-01-01

    Purpose Image-guided radiotherapy for patients with locally advanced lung cancer relies on bony landmarks and carina or - if visible - the primary tumor (PT) for daily patient alignment, neglecting potential variations in the relative position of PT and involved lymph nodes (LN). This study analyzes PT and LN position changes relative to each other and relative to anatomical landmarks during conventionally fractionated radiotherapy. Methods and Materials In 12 patients with locally advanced non-small cell lung cancer PT, LN, carina and one thoracic vertebra were manually contoured on weekly 4D fan beam CTs. Systematic and random interfraction displacements of all contoured structures were identified in the three cardinal directions, 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 vertebra both for PT and LN. For PT, mean 3D displacement vectors with carina-based alignment were 7 mm/SD 4 mm versus 9 mm/SD 5 mm with bony anatomy (p<0.0001). For LN, smaller displacements were found with carina- (5 mm/SD 3 mm, p<0.0001) and vertebra-based (6 mm/SD 3 mm, p=0.002) alignment compared to using PT for setup (8 mm/SD 5 mm). Primary tumor and LN displacements relative to bone and carina were independent (p>0.05). Displacements between PT and bone (p=0.04), and between PT and LN (p=0.01) were significantly correlated with PT volume regression. Displacements between LN and carina were correlated with LN volume change (p=0.03). 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 primary tumorbased alignment is recommended in locally advanced disease. PMID:24239387

  10. [Ultra high-dose chemotherapy with peripheral blood stem cell autotransplantation for refractory testicular cancer].

    PubMed

    Sugimoto, K; Nakagawa, S; Mikami, K; Watanabe, H; Sonoda, Y; Abe, T; Fujii, H

    1994-02-01

    This is a report of 45-year-old man with advanced nonseminomatous germ cell tumor (stage IIIB2: embryonal carcinoma, yolk sac tumor, seminoma), who had relapse after PVB (cisplatin, vinblastine, bleomycin) chemotherapy. Peripheral blood stem cells (PBSCs) were taken by two consecutive apheresis using a CS-3000 blood separator after high-dose chemotherapy of cytarabine and mitoxantrone. In total, 6.4 x 10(5)/kg of granulocytic cells (CFU-GM) was collected. He was treated with ultra high-dose chemotherapy consisting of carboplatin (800 mg/m2), etoposide (1,000 mg/m2) and cyclophosphamide (100 mg/kg) from day 1, followed by peripheral blood stem cell autotransplantation (PBSCT) on day 9. We transfused 2.4 x 10(5)/kg CFU-GM, which was enough number of stem cells for safe PBSCT. No serious side effects or complications were encountered. The patient achieved partial remission for more than two months. However, he died of respiratory dysfunction caused by metastatic lung cancer 5 months later. It was thought that ultra high-dose chemotherapy with PBSCT might be a new therapy for refractory testicular cancer.

  11. Refractory sea salt CCN spectra

    NASA Astrophysics Data System (ADS)

    Noble, S.; Hudson, J. G.

    2012-12-01

    Hudson et al. (2011; H11) showed a substantial sea salt (NaCl) CCN contribution for low critical supersaturation (Sc) CCN (< 0.1%), which was a positive function of horizontal wind speed (U) at the ocean surface in the RICO project in the Caribbean. Somewhat similar results were found over the Pacific near California in spite of a factor of 3 higher average CCN concentrations. Results were obscured over the mid Pacific in PASE because of the lack of cloud scavenging (H11). The results were obtained by CCN spectral volatility measurements, which remove all but the refractory CCN that survive heating to 300 degrees C, which are only NaCl. Fig. 1 shows that ambient CCN concentrations were uncorrelated with U but that refractory CCN were correlated with U in RICO and POST. Fig. 2 compares low altitude average refractory CCN spectra during flights with various noted mean U. The two POST flights and the RICO flights displayed here show the same dependence on U that was quantified by H11. The higher concentrations for PASE in relation to U are due to the lack of cloud scavenging, which allowed higher concentrations to build up that are thus not related to the simultaneously measured U. The abundant clouds of RICO and POST provided enough removal of CCN that sea salt CCN were correlated with simultaneously measured U. These measurements have begun the quantification of this most definite natural CCN source. This is needed in order to assess the impact of anthropogenic CCN on clouds; i.e., the indirect aerosol effect. Hudson, J.G., S. Noble, and V. Jha, 2011: On the relative role of sea salt cloud condensation nuclei (CCN). J. Atmos. Chem. Volume 68, Number 1, Pages 71-88, DOI: 10.1007/s10874-011-9210-5. Fig. 1. Correlation coefficients (R) between CCN concentrations at various S and wind speed for ambient CCN (all) and refractory CCN. Fig. 2. Flight averaged refractory CCN spectra.

  12. 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.

  13. Chemotherapy versus supportive care in advanced non-small cell lung cancer: improved survival without detriment to quality of life

    PubMed Central

    Spiro, S; Rudd, R; Souhami, R; Brown, J; Fairlamb, D; Gower, N; Maslove, L; Milroy, R; Napp, V; Parmar, M; Peake, M; Stephens, R; Thorpe, H; Waller, D; West, P

    2004-01-01

    Background: In 1995 a meta-analysis of randomised trials investigating the value of adding chemotherapy to primary treatment for non-small cell lung cancer (NSCLC) suggested a small survival benefit for cisplatin-based chemotherapy in each of the primary treatment settings. However, the meta-analysis included many small trials and trials with differing eligibility criteria and chemotherapy regimens. Methods: The aim of the Big Lung Trial was to confirm the survival benefits seen in the meta-analysis and to assess quality of life and cost in the supportive care setting. A total of 725 patients were randomised to receive supportive care alone (n = 361) or supportive care plus cisplatin-based chemotherapy (n = 364). Results: 65% of patients allocated chemotherapy (C) received all three cycles of treatment and a further 27% received one or two cycles. 74% of patients allocated no chemotherapy (NoC) received thoracic radiotherapy compared with 47% of the C group. Patients allocated C had a significantly better survival than those allocated NoC: HR 0.77 (95% CI 0.66 to 0.89, p = 0.0006), median survival 8.0 months for the C group v 5.7 months for the NoC group, a difference of 9 weeks. There were 19 (5%) treatment related deaths in the C group. There was no evidence that any subgroup benefited more or less from chemotherapy. No significant differences were observed between the two groups in terms of the pre-defined primary and secondary quality of life end points, although large negative effects of chemotherapy were ruled out. The regimens used proved to be cost effective, the extra cost of chemotherapy being offset by longer survival. Conclusions: The survival benefit seen in this trial was entirely consistent with the NSCLC meta-analysis and subsequent similarly designed large trials. The information on quality of life and cost should enable patients and their clinicians to make more informed treatment choices. PMID:15454647

  14. Optimized selection of three major EGFR-TKIs in advanced EGFR-positive non-small cell lung cancer: a network metaanalysis

    PubMed Central

    Fang, Wenfeng; Kang, Shiyang; He, Yang; Hong, Shaodong; Zhan, Jianhua; Zhao, Yuanyuan; Xue, Cong; Ma, Yuxiang; Zhou, Ting; Ma, Shuxiang; Gao, Fangfang; Qin, Tao; Hu, Zhihuang; Tian, Ying; Hou, Xue; Huang, Yan; Zhou, Ningning; Zhao, Hongyun; Zhang, Li

    2016-01-01

    Background: To answer which epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) is the best choice for advanced non-small cell lung cancer (NSCLC) EGFR mutants. Results: 16 phase III randomized trials involving 2962 advanced NSCLC EGFR mutants were enrolled. Multiple treatment comparisons showed different EGFR-TKIs shared equivalent curative effect in terms of all outcome measures among the overall, chemo-naïve and previously treated patients. Rank probabilities showed that erlotinib and afatinib had potentially better efficacy compared with gefitinib in both of the overall and chemo-naïve patients. Potentially survival benefit of erlotinib was also observed in previously treated patients compared with gefitinib. Additionally, EGFR-TKI showed numerically greater survival benefit in 19 Del compared with chemotherapy, while it was opposite in 21 L858R. Furthermore, afatinib, erlotinib and gefitinib had high, moderate and low risk of rash & diarrhea, respectively, while the occurrence of elevated liver transaminase was more common in gefitinib. Methods: Data of objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and adverse events were extracted from included studies. Efficacy and toxicity of all included treatments were integrated by network meta-analyses. Conclusion: Our study indicated a high efficacy-high toxicity pattern of afatinib, a high efficacy-moderate toxicity pattern of erlotinib and a medium efficacy-moderate toxicity pattern of gefitinib. Recommended EGFR-TKI should be suggested according to patients' tolerability and therapeutic efficacy in clinical practice. Moreover, the treatment for advanced EGFR-positive NSCLC might be different between 19 Del and 21 L858R. PMID:26933807

  15. 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

  16. Prognostic models to predict survival in patients with advanced non-small cell lung cancer treated with first-line chemo- or targeted therapy

    PubMed Central

    Berardi, Rossana; Rinaldi, Silvia; Santoni, Matteo; Newsom-Davis, Thomas; Tiberi, Michela; Morgese, Francesca; Caramanti, Miriam; Savini, Agnese; Ferrini, Consuelo; Torniai, Mariangela; Fiordoliva, Ilaria; Bower, Marc; Cascinu, Stefano

    2016-01-01

    Background We aimed to assess the prognostic role of neutrophilia, lymphocytopenia and the neutrophil-to-lymphocyte ratio (NLR), and to design models to define the prognosis of patients receiving first-line chemo- or targeted therapy for advanced non-small cell lung cancer (NSCLC). Materials and Methods We retrospectively analysed 401 consecutive patients with advanced NSCLC treated with first line chemo- or targeted therapy. Patients were stratified into two groups with pre-treatment NLR ≥ 3.7 (Group A) vs. < 3.7 (Group B). The best NLR cut-off was identified by ROC curve analysis. Results At baseline 264 patients had NLR≥3.7 (Group A), whilst 137 had lower NLR (Group B). Median OS was 10.8 months and 19.4 months in the two groups (p < 0.001), while median PFS was 3.6 months and 5.6 months, respectively (p = 0.012). At multivariate analysis, ECOG-PS≥2, stage IV cancer, non-adenocarcinoma histology, EGFR wild-type status and NLR were predictors of worse OS. Stage IV cancer, wild type EGFR status and NLR≥3.7 were independent prognostic factors for worse PFS. Patients were stratified according to the presence of 0-1 prognostic factors (8%), 2-3 factors (73%) and 4-5 factors (19%) and median OS in these groups was 33.7 months, 14.6 months and 6.6 months, respectively (p < 0.001). Similarly, patients were stratified for PFS based on the presence of 0-1 prognostic factor (15%), 2 factors (41%) and 3 factors (44%). The median PFS was 8.3 months, 4.6 months and 3.3 months respectively (p < 0.001). Conclusion Pre-treatment NLR is an independent prognostic factor for patients with advanced NSCLC treated with first-line therapies. PMID:27029035

  17. Comprehensive geriatric assessment and traditional Chinese medicine intervention benefit symptom control in elderly patients with advanced non-small cell lung cancer.

    PubMed

    Xue, Dong; Han, Shuyan; Jiang, Shantong; Sun, Hong; Chen, Yanzhi; Li, Yuanqing; Wang, Wei; Feng, Ye; Wang, Ke; Li, Pingping

    2015-04-01

    The aim of this study was to observe the symptom improvement and clinical benefit in elderly patients with advanced non-small cell lung cancer (NSCLC) stratified on the basis of CGA findings after treatment with a combination of traditional Chinese medicine and Western medicine. Twenty-four elderly advanced NSCLC patients with a mean age of 73.0 ± 5.3 (65-83) years were categorized into three stratifications according to CGA results, namely function independent, mildly function impaired, and function dependent. They received standardized therapy, individualized therapy, and best supportive care, respectively. The patients receiving standardized therapy and individualized therapy were randomized into two groups, with or without traditional Chinese medicine for symptom control, while for all the patients receiving best supportive care, traditional Chinese medicine was administered. Nine non-elderly NSCLC patients (<65 years old) were enrolled as control and treated in accordance with NCCN NSCLC treatment guidelines. EORTC QLQ-C30 core scale, LC13 scale, and MDASI-TCM scale were used to assess relevant symptoms before and after treatment. After treatment for 3 weeks, it was shown by QLQ-C30+LC13 scales, for function-dependent patients, that the physical and role performances and the global health status were improved and the symptoms of fatigue and cough were alleviated; by MDASI-TCM scale, the symptoms of fatigue, cough, and expectoration were improved. In function-independent and mildly function-impaired elderly patients, there were no significant changes in functional status and symptoms. But in non-elderly patients, the physical and social performances were lowered, and the symptoms of fatigue, constipation, and poor appetite were aggravated. The elderly patients with advanced NSCLC were categorized on the basis of CGA findings, and traditional Chinese medicine may be beneficial to symptom control of function-dependent patients.

  18. 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

  19. Minimally invasive (robotic assisted thoracic surgery and video-assisted thoracic surgery) lobectomy for the treatment of locally advanced non-small cell lung cancer

    PubMed Central

    Yang, Hao-Xian; Woo, Kaitlin M.; Sima, Camelia S.

    2016-01-01

    Background Insufficient data exist on the results of minimally invasive surgery (MIS) for locally advanced non-small cell lung cancer (NSCLC) traditionally approached by thoracotomy. The use of telerobotic surgical systems may allow for greater utilization of MIS approaches to locally advanced disease. We will review the existing literature on MIS for locally advanced disease and briefly report on the results of a recent study conducted at our institution. Methods We performed a retrospective review of a prospective single institution database to identify patients with clinical stage II and IIIA NSCLC who underwent lobectomy following induction chemotherapy. The patients were classified into two groups (MIS and thoracotomy) and were compared for differences in outcomes and survival. Results From January 2002 to December 2013, 428 patients {397 thoracotomy, 31 MIS [17 robotic and 14 video-assisted thoracic surgery (VATS)]} underwent induction chemotherapy followed by lobectomy. The conversion rate in the MIS group was 26% (8/31) The R0 resection rate was similar between the groups (97% for MIS vs. 94% for thoracotomy; P=0.71), as was postoperative morbidity (32% for MIS vs. 33% for thoracotomy; P=0.99). The median length of hospital stay was shorter in the MIS group (4 vs. 5 days; P<0.001). The 3-year overall survival (OS) was 48.3% in the MIS group and 56.6% in the thoracotomy group (P=0.84); the corresponding 3-year DFS were 49.0% and 42.1% (P=0.19). Conclusions In appropriately selected patients with NSCLC, MIS approaches to lobectomy following induction therapy are feasible and associated with similar disease-free and OS to those following thoracotomy. PMID:27195138

  20. Treatment and prognosis after progression in long-term responders to EGFR-tyrosine kinase inhibitor in advanced non-small cell lung cancer

    PubMed Central

    Song, Zhengbo

    2016-01-01

    Introduction The aim of this study was to investigate the treatment and prognosis of advanced non-small cell lung cancer (NSCLC) patients after failure of long-term treatment with epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI). Material and methods We retrospectively analyzed all NSCLC patients with EGFR-TKI (gefitinib or erlotinib) treatment at our institution between 2011 and 2013 who progressed after at least stable disease on erlotinib or gefitinib for more than 6 months. Survival curves were plotted using the Kaplan-Meier method. The Cox proportional hazard model was used for multivariate analysis. Results In total, 521 patients were administered EGFR-TKI. Of these, 298 patients received EGFR-TKI with progression-free survival less than 6 months (group A), and the other 223 patients more than 6 months (group B). There was a significant difference in overall survival (OS) between group A and group B (7.2 months vs. 5.0 months, p < 0.0001). The median OS for group B patients was 5.0 months. Among the 223 patients in group B, 38 patients received chemotherapy with continued EGFR-TKI after failure of prior gefitinib or erlotinib treatment, 92 with chemotherapy alone and 93 with best supportive care. Patients who continued gefitinib or erlotinib had a significantly longer OS (median: 7.5 months), followed by chemotherapy (5.5 months) and best supportive care (4.0 months) (p < 0.001). Conclusions The prognosis of advanced NSCLC patients after failure of long-term treatment with EGFR-TKI was poor. Chemotherapy with continued EGFR-TKI beyond progression of long-term responders was feasible and led to prolonged OS in advanced NSCLC patients. PMID:26925125

  1. 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

  2. Improving outcomes of refractory celiac disease - current and emerging treatment strategies.

    PubMed

    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

  3. Surgical treatment for medically refractory myasthenic blepharoptosis

    PubMed Central

    Shimizu, Yusuke; Suzuki, Shigeaki; Nagasao, Tomohisa; Ogata, Hisao; Yazawa, Masaki; Suzuki, Norihiro; Kishi, Kazuo

    2014-01-01

    Purpose Currently, only a few reports have recommended surgery as a suitable treatment for blepharoptosis associated with myasthenia gravis. The present study aims to introduce our surgical criteria, surgical options, outcomes, and precautions for medically refractory myasthenic blepharoptosis. Patients and methods Eight patients who failed to respond to at least 2 years of medical treatment and who underwent blepharoptosis surgery, from January 2008 to December 2011, were enrolled in this study. Medical records, photographs, and questionnaire results regarding postoperative status were evaluated. Of the eleven procedures performed, four involved frontal suspension, four involved external levator advancement, one involved nonincisional transconjunctival levator advancement, and two involved subbrow blepharoplasty with orbicularis oculi muscle tucking. The margin reflex distance improved postoperatively in seven patients. Results Seven patients had very minimal scarring, and one had minimal scarring. Five patients showed no eyelid asymmetry, one had subtle asymmetry, and two had obvious asymmetry. Seven patients were very satisfied, and one patient was satisfied with the overall result. Postoperative complications included mild lid lag with incomplete eyelid closure, prolonged scar redness, and worsened heterophoria. No patient experienced postoperative exposure keratitis or recurrent blepharoptosis during the study period. Conclusion Our results indicate that blepharoptosis surgery is effective for patients with myasthenia gravis, especially those with residual blepharoptosis despite multiple sessions of medical treatments. We recommend that neurologists and surgeons collaborate more systematically and discuss comprehensive treatment plans to increase the quality of life for patients with myasthenia gravis. PMID:25278744

  4. Refractories for vacuum degassing of steel

    SciTech Connect

    Sokolov, A.N.; Kuznetsov, G.I.

    1988-07-01

    New equipment for outside-the-furnace vacuum degassing of steel includes argon-oxygen refining units, circulation flow vacuum degassing units, and units for steel degassing in the ladle with electric arc heating. The refractories developed for use in this equipment include magnesia, periclase-carbon, corundum, alumina, periclase-lime, magnesia-dolomite, forsterite, and unformed and vibrocompacted refractories. The refractories were selected for heat resisting and thermal insulation applications. This paper reviews at length the raw material base, production processes, and applicable properties of these refractories under degassing conditions, including slag and silicate resistance, temperature and phase behavior, permeability, compression strength, service life, and wear behavior. In addition, specifications are given for a wide range of refractories and their applications in specific pieces of equipment. Savings in refractory and power consumption are discussed.

  5. Clinical effect of pemetrexed as the first‐line treatment in Chinese patients with advanced anaplastic lymphoma kinase‐positive non‐small cell lung cancer

    PubMed Central

    Ma, Di; Hao, Xuezhi; Wang, Yan; Xing, Puyuan

    2016-01-01

    Background The efficacy of pemetrexed‐based first‐line chemotherapy in anaplastic lymphoma kinase (ALK)‐positive non‐small cell lung cancer (NSCLC) has been demonstrated in several studies; however, there is a lack of data from Chinese populations. Methods The clinicopathological characteristics and treatment outcomes of 52 patients with ALK‐positive advanced NSCLC who received pemetrexed as first‐line chemotherapy at the Department of Medical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences were retrospectively reviewed. The primary end points were response rate and progression‐free survival (PFS). Results The gender proportion was balanced and the median age was 51 years (range 26–76). Of the 52 patients, 46 (88.5%) had stage IV disease, predominantly adenocarcinoma (98.1%). Sixteen patients were current/former smokers and 36 were never/light smokers. The most common sites of metastasis were the pleura (36.5%), bone (30.8%), lung (26.9%), and brain (17.3%). The median PFS was 9.5 months (95% confidence interval 7.454–11.536). At the time of analysis, partial remission was achieved in 18 (34.6%) patients, stable disease in 26 (50.0%), and progressive disease in eight (15.4%); none of the patients achieved complete remission. The objective response rate was 34.6% and the disease control rate was 84.6%. Common adverse events with pemetrexed were neutropenia (53.8%), nausea and vomiting (51.9%), leukopenia (32.7%), and fatigue (25.0%), mainly at grades 1 or 2. Conclusions Pemetrexed is efficient and tolerated as first‐line treatment for ALK‐positive NSCLC in a cohort of Chinese patients and may prove to be an alternative option for the treatment of ALK‐positive NSCLC. PMID:27385988

  6. Flexible modeling improves assessment of prognostic value of C-reactive protein in advanced non-small cell lung cancer

    PubMed Central

    Gagnon, B; Abrahamowicz, M; Xiao, Y; Beauchamp, M-E; MacDonald, N; Kasymjanova, G; Kreisman, H; Small, D

    2010-01-01

    Background: C-reactive protein (CRP) is gaining credibility as a prognostic factor in different cancers. Cox's proportional hazard (PH) model is usually used to assess prognostic factors. However, this model imposes a priori assumptions, which are rarely tested, that (1) the hazard ratio associated with each prognostic factor remains constant across the follow-up (PH assumption) and (2) the relationship between a continuous predictor and the logarithm of the mortality hazard is linear (linearity assumption). Methods: We tested these two assumptions of the Cox's PH model for CRP, using a flexible statistical model, while adjusting for other known prognostic factors, in a cohort of 269 patients newly diagnosed with non-small cell lung cancer (NSCLC). Results: In the Cox's PH model, high CRP increased the risk of death (HR=1.11 per each doubling of CRP value, 95% CI: 1.03–1.20, P=0.008). However, both the PH assumption (P=0.033) and the linearity assumption (P=0.015) were rejected for CRP, measured at the initiation of chemotherapy, which kept its prognostic value for approximately 18 months. Conclusion: Our analysis shows that flexible modeling provides new insights regarding the value of CRP as a prognostic factor in NSCLC and that Cox's PH model underestimates early risks associated with high CRP. PMID:20234363

  7. [Advances in the Research of Autophagy in EGFR-TKI Treatment and Resistance 
in Lung Cancer].

    PubMed

    Zhang, Qicheng; Xu, Ke

    2016-09-20

    Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) is a group of targeted-drugs which effectively inhibits the growth of tumor cells with sensitive mutations in EGFR. However, the innate and acquired resistance are major obstacles of the efficiency. Autophagy is a highly conserved self-digesting process in cells, which is considered to be associated with cancer development andchemoresistance. The activation of EGFR may regulate autophagy through multiple signal pathways. EGFR-TKIs can induce autophagy, however, the function of the inducted autophagy remains biphasic. On one hand, autophagy induced by EGFR-TKI acts as a cytoprotective response in cancer cells, and autophagy inhibitors can enhance the cytotoxic effects of EGFR-TKI. On the other hand, a high level of autophagy after treatment of EGFR-TKI can also result in autophagic cell death lacking features of apoptosis, and the combination of EGFR-TKI with autophagy inducer might be beneficial. Thus, autophagy regulation represents a promising approach for improving the efficiency of EGFR-TKI in the treatment of cancer patients. Here we summarized the signaling pathways involved in EGFR-TKI induced autophagy, and reviewed the roles of autophagy in the treatment and chemoresistance of EGFR-TKI treatment in lung cancer. PMID:27666552

  8. Feasibility Study for Casting of High Temperature Refractory Superalloy Composites

    NASA Technical Reports Server (NTRS)

    Lee, Jonathan A.

    1998-01-01

    Abstract This study investigated the feasibility of using conventional casting technique to fabricate refractory wires reinforced superalloy composites. These composites were being developed for advanced rocket engine turbine blades and other high temperature applications operating up to 2000 F. Several types of refractory metal wires such as W- Th, W-Re, Mo-Hf-C and W-HF-C reinforced waspaloy were experimentally cast and heat treated at 2000 F up to 48 hrs. Scanning electron microscope analysis was conducted in regions adjacent to the wire-matrix interface to determine the reaction zone and chemical compatibility resulting from material interdiffusion. It was concluded that fabrication using conventional casting may be feasible because the wire-matrix reaction zone thickness was comparable to similar composites produced by arc-sprayed monotape with hot isostatic pressing technique, Moreover, it was also found that the chemical compatibility could be improved significantly through a slight modification of the superalloy matrix compositions.

  9. 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

  10. 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.

  11. Refractory liner materials used in slagging gasifiers

    SciTech Connect

    Bennett, James P.

    2004-09-01

    Refractory liners are used on the working face of entrained flow slagging gasifiers that react coal, petroleum coke, or other carbon feedstock with oxygen and water. The refractory liners protect the gasifier shell from elevated temperatures, corrosive slags, and thermal cycling during gasification. Refractory failure is primarily by two means, corrosive dissolution and spalling. High chrome oxide refractory materials have evolved as the material of choice to line the hot face of gasifiers, yet the performance of these materials does not meet the service requirements of industry. A review of gasifier liner materials, their evolution, issues impacting their performance, and future research direction are discussed.

  12. Refractories for dry ash coal gasifiers

    SciTech Connect

    Sadler, L.Y. III; Heystek, H.; Raymon, N.S.; Clancy, T.A.

    1984-01-01

    This report summarizes the findings of a 9-yr research program, sponsored by the US Department of Energy and conducted by the Bureau of Mines, to evaluate refractory liner materials for coal gasifier reactors. Commercially available refractories were exposed to coal gasifier reactor environments, reproduced in the laboratory with a high-temperature, high-pressure test facility, followed by extensive postexposure evaluation. Thirty-six castable or gunnable refractories and cements and 24 refractory brick were evaluated. The behavior of castable refractories reinforced with stainless steel fibers was also examined. Gas environments that were evaluated included steam, H/sub 2/, CO/sub 2/, CO, and typical high- and low-Btu gas mixtures. Exposure pressures ranged from 100 to 1,000 psig, temperatures from 500/sup 0/ to 1100/sup 0/C, for periods from 50 h to 2000 h. In some exposures, sodium and/or potassium hydroxide were introduced in order to simulate a high-alkali environment. It was found that intermediate- and low-alumina refractories produced from domestically available raw materials, rather than high-alumina refractories produced from imported raw materials, gave the best service as liner materials and that alkali attack was probably not a serious problem with most refractories. Based on the results of this program, good choices of refractory liner materials for gasifier reactors can be made. 7 references, 25 figures, 30 tables.

  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. A Phase II First-Line Study of Gemcitabine, Carboplatin, and Bevacizumab in Advanced Stage Non-squamous Non-small Cell Lung Cancer

    PubMed Central

    Clément-Duchêne, Christelle; Krupitskaya, Yelena; Ganjoo, Kristen; Lavori, Philip; McMillan, Alex; Kumar, Atul; Zhao, Gary; Padda, Sukhmani; Zhou, Lisa; Pedro-Salcedo, Melanie San; Colevas, A. Dimitrios; Wakelee, Heather A.

    2014-01-01

    Background Bevacizumab improves responses and progression-free survival when added to first-line paclitaxel/carboplatin or cisplatin/gemcitabine for patients with advanced nonsquamous non-small cell lung cancer. This study was designed to evaluate toxicities and efficacy of gemcitabine/carboplatin/bevacizumab. Methods Patients with untreated advanced nonsquamous non-small cell lung cancer, with no evidence of brain metastases and not on anticoagulation were eligible. Patients received gemcitabine 1000 mg/m2 on days 1 and 8; carboplatin area under the curve 5 day 1; and bevacizumab 15 mg/kg day 1 every 3 weeks for up to six cycles. Bevacizumab was then continued every 3 weeks until disease progression or unacceptable toxicity. Results From July 2006 to December 2008, 48 patients were enrolled: 23 (48%) men, 25 (52%) women, and 19 (40%) never smokers. One patient never received therapy and is not included in the analysis. Median cycle number was 8 (1– 42) with 37 patients (78.7%) completing ≥4 cycles of three drugs. Dose reductions occurred in 34 (72.3%) patients. Grade 3/4 toxicities included neutropenia (47%/15%), thrombocytopenia (11%/15%), anemia (6%/0%), dyspnea (6%/2%), bacterial pneumonia (4%/0%), and hypertension (4%/2%). No neutropenic fevers occurred. One patient died of hemoptysis. Grade 3 bleeding occurred in three other patients. There were seven (14.9%) partial responses. Median time to first event (progression/death/toxicity requiring discontinuation) was 6.4 months (95% confidence interval: 4.8 –7.9 months). The median overall survival (OS) was 12.8 months (95% confidence interval: 10.0 –16.5). The OS is 57% at 1 year and 10% at 2 years. Conclusions Although perhaps skewed by a high proportion of nonsmokers and women, treatment with gemcitabine/carboplatin/bevacizumab has an acceptable toxicity profile with promising median OS despite a low response rate. PMID:20881641

  15. 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.

  16. 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

  17. 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

  18. Indirect comparison of the efficacy and safety of gefitinib and cetuximab-based therapy in patients with advanced non-small-cell lung cancer

    PubMed Central

    TANG, JIFENG; ZHANG, HENA; YAN, JIANZHOU; SHAO, RONG

    2015-01-01

    The aim of this study was to systematically evaluate the efficacy and safety of gefitinib and cetuximab-based therapies in patients with advanced non-small-cell lung cancer (NSCLC). The studies to be used for the comparisons were selected from the available literature on gefitinib and cetuximab-based therapies compared to conventional chemotherapy in patients with advanced NSCLC. The meta-analysis was performed with RevMan 5.0 software and the Bucher approach was applied to conduct the indirect comparisons. A total of 4 studies, including 935 patients, on gefitinib therapy vs. conventional chemotherapy and 4 studies, including 1,015 patients, on cetuximab-based therapy vs. conventional chemotherapy, were used for indirect comparisons. As regards efficacy, the risk ratio (RR) of objective response rate and 1-year survival rate between gefitinib and cetuximab-based therapies in patients with advanced NSCLC were 0.99 [95% confidence interval (CI): 0.75–1.32; P=0.9584] and 0.85 (95% CI: 0.71–1.01; P=0.0696), respectively, and the mean difference of progression-free survival and overall survival (OS) were −0.15 (95% CI: −0.90 to 0.60; P=0.6946) and −1.84 (95% CI: −3.53 to −0.15; P=0.0331), respectively. As regards safety, the RR of grade 3/4 adverse events (AEs) was 0.29 (95% CI: 0.19–0.44; P=0.0001). The results demonstrated that cetuximab-based therapy was superior to gefitinib therapy in terms of OS and inferior to gefitinib therapy in terms of AEs, whereas there were no significant differences in terms of efficacy and safety between the two therapies on other endpoints adopted for advanced NSCLC. However, further well-designed randomized controlled trials and continuous studies are required to confirm our findings. PMID:25469285

  19. The efficacy and safety of nivolumab in previously treated advanced non-small-cell lung cancer: a meta-analysis of prospective clinical trials

    PubMed Central

    Huang, Jiaxing; Zhang, Yaxiong; Sheng, Jin; Zhang, Hongyu; Fang, Wenfeng; Zhan, Jianhua; Zhou, Ting; Chen, Ying; Liu, Lin; Zhang, Li

    2016-01-01

    Background Nivolumab (BMS-936558/ONO-4538) was the first monoclonal antibody targeting programmed death (PD)-1. So far, a number of clinical trials on nivolumab have showed satisfactory efficacy in treating non-small-cell lung cancer (NSCLC). Herein, we present a meta-analysis evaluating the efficacy and safety of nivolumab for previously treated advanced NSCLC patients. Methods Electronic databases were searched for eligible literature. Data of objective response rate (ORR), disease control rate, overall survival, progression-free survival, and adverse effects (AEs) were extracted and pooled. Outcomes analyzed and presented in this study were according to the original data from nivolumab 3 mg/kg. Results In general, nine trials with 817 patients were included in this meta-analysis. The pooled ORR, disease control rate, 1-year overall survival rate, and 1-year progression-free survival rate were 20% (95% confidence interval [CI]: 17%–23%), 36% (95% CI: 22%–51%), 47% (95% CI: 40%–53%), 21% (95% CI: 18%–24%), respectively. In addition, the rate of grade 3–4 AEs was only 8% (95% CI: 6%–12%). Subgroup analysis showed no significant difference in terms of ORR between squamous and non-squamous NSCLC (odds ratio 1.23, 95% CI: 0.63–2.39, P=0.51). However, significantly greater ORR was presented in programmed cell death ligand 1 (PD-L1) positive cohort (ORR 31%, 95% CI: 24%–38%), compared to PD-L1 negative cohort (ORR 12%, 95% CI: 9%–17%). The odds ratio for objective response to nivolumab in PD-L1 positive cases relative to negative cases was 3.08 (95% CI: 1.87–5.08, P<0.0001). Conclusion In conclusion, nivolumab is a promising second-line agent for previously treated advanced NSCLC with manageable AEs. Both squamous and non-squamous NSCLC patients showed similar efficacy. In addition, patients with positive PD-L1 expression had better response from nivolumab. Microabstract We present a meta-analysis evaluating the efficacy and safety of nivolumab for

  20. 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 ...

  1. Planning analysis for locally advanced lung cancer: dosimetric and efficiency comparisons between intensity-modulated radiotherapy (IMRT), single-arc/partial-arc volumetric modulated arc therapy (SA/PA-VMAT)

    PubMed Central

    2011-01-01

    Purpose To analyze the differences between the intensity-modulated radiotherapy (IMRT), single/partial-arc volumetric modulated arc therapy (SA/PA-VMAT) techniques in treatment planning for locally advanced lung cancer. Materials and methods 12 patients were retrospectively studied. In each patient's case, several parameters were analyzed based on the dose-volume histograms (DVH) of the IMRT, SA/PA-VMAT plans respectively. Also, each plan was delivered to a phantom for time comparison. Results The SA-VMAT plans showed the superior target dose coverage, although the minimum/mean/maximum doses to the target were similar. For the total and contralateral lungs, the higher V5/10, lower V20/30 and mean lung dose (MLD) were observed in the SA/PA-VMAT plans (p < 0.05, respectively). The PA-VMAT technique improves the dose sparing (V20, V30 and MLD) of the controlateral lung more notably, comparing to those parameters of the IMRT and SA-VMAT plans respectively. The delivered monitor units (MUs) and treatment times were reduced significantly with VMAT plans, especially PA-VMAT plans (for MUs: mean 458.3 vs. 439.2 vs. 435.7 MUs, p < 0.05 and for treatment time: mean 13.7 vs. 10.6 vs. 6.4 minutes, p < 0.01). Conclusions The SA-VMAT technique achieves highly conformal dose distribution to the target. Comparing to the IMRT plans, the higher V5/10, lower V20/30 and MLD were observed in the total and contralateral lungs in the VMAT plans, especially in the PA-VMAT plans. The SA/PA-VMAT plans also reduced treatment time with more efficient dose delivering. But the clinical benefit of the VMAT technique for locally advanced lung cancer needs further investigations. PMID:22014217

  2. Hydration with magnesium and mannitol without furosemide prevents the nephrotoxicity induced by cisplatin and pemetrexed in patients with advanced non-small cell lung cancer

    PubMed Central

    Muraki, Keiko; Koyama, Ryo; Honma, Yuichiro; Yagishita, Shigehiro; Shukuya, Takehito; Ohashi, Rina; Takahashi, Fumiyuki; Kido, Kenji; Iwakami, Shin-ichiro; Sasaki, Shinichi; Iwase, Akihiko

    2012-01-01

    Background The aim of this study was to examine the effect of hydration with magnesium and mannitol without furosemide on the nephrotoxocity accompanying combination chemotherapy using cisplatin and pemetrexed in patients with advanced non-small cell lung cancer (NSCLC). Methods Fifty patients with NSCLC who received cisplatin plus pemetrexed, using either old hydration protocol including normal saline with mannitol and furosemide, or a new one including normal saline with magnesium and mannitol without furosemide were retrospectively analyzed. Nephrotoxicity was compared between patients treated using the old protocol and those treated with the new protocol. Univariate and multivariate analyses were performed to identify the independent factors associated with protection against nephrotoxicity in patients with NSCLC who received cisplatin plus pemetrexed. Results Thirty patients received the old hydration protocol, while 20 patients were treated using the new hydration protocol. The patients treated using the new hydration protocol showed a significantly greater increase in creatinine clearance (P=0.0004) and a decrease in the serum creatinine level (P=0.0148) after one course of chemotherapy compared with those treated using the old hydration protocol. There were no differences in the chemotherapeutic response or overall survival between the groups (P=0.572). The new hydration protocol with supplemented magnesium with mannitol without furosemide was an independent factor for the protection against nephrotoxicity induced by cisplatin and pemetrexed in patients with advanced NSCLC [HR 0.232 (95% CI: 0.055-0.986), P=0.039]. Conclusions These results demonstrate that the new hydration protocol comprising supplementation with magnesium without furosemide could prevent the nephrotoxicity induced by cisplatin and pemetrexed without affecting the treatment outcome. PMID:23205279

  3. 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

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

    PubMed Central

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

    2016-01-01

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

  5. Relationship between quality of life and clinical outcomes in advanced non-small cell lung cancer: best supportive care (BSC) versus BSC plus chemotherapy.

    PubMed

    Thongprasert, S; Sanguanmitra, P; Juthapan, W; Clinch, J

    1999-04-01

    In a prospective randomized study, 287 patients with advanced non-small cell lung cancer (NSCLC) stage IIIb or IV with ECOG performance status (PS) 0-1 or 2 were randomly assigned to receive either best supportive care (BSC) or supportive care plus combination chemotherapy (IEP regimen: ifosfamide 3 gm/m2 IV with mesna uroprotection, epirubicin 60 mg/m2 IV on day 1 and cisplatin 60 mg/m2 IV on day 2; or MVP regimen: mitomycin-C 8 mg/m2, cisplatin 100 mg/m2 IV on day 1, vinblastine 4 mg/m2 IV on days 1 and 15). Serial assessment of Karnofsky performance status (KPS), modified Functional Living Index-Cancer (T-FLIC) and modified Quality of Life-Index (T-QLI) were used to estimate the quality of life. Interviews were done at entry, at the third month and at 2 months post complete treatment. At least two courses of chemotherapy were considered to be adequate for response evaluation. Patients were treated for a total of four to six courses or until progression of disease. Partial response rates were 40 and 41.7% in IEP and MVP arms. Median survival durations were 5.9 and 8.1 months for the IEP and MVP chemotherapy arms, and 4.1 months for BSC (log-rank test: P = 0.0003). One year survival was 13, 29.8 and 39.3% for the BSC, IEP and MVP regimens, respectively. Two years survival was 7.8, 6.4 and 13.1% for the BSC, IEP and MVP regimens, respectively. Improvement in quality of life (QOL) scores at the first, second and third interview were seen in chemotherapy arms only, not in the BSC arm. We conclude that combination chemotherapy improves the quality of life as well as prolonging the survival of patients with advanced NSCLC.

  6. 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. PMID:17382431

  7. Randomized Phase II Trial of Erlotinib Alone or With Carboplatin and Paclitaxel in Patients Who Were Never or Light Former Smokers With Advanced Lung Adenocarcinoma: CALGB 30406 Trial

    PubMed Central

    Jänne, Pasi A.; Wang, Xiaofei; Socinski, Mark A.; Crawford, Jeffrey; Stinchcombe, Thomas E.; Gu, Lin; Capelletti, Marzia; Edelman, Martin J.; Villalona-Calero, Miguel A.; Kratzke, Robert; Vokes, Everett E.; Miller, Vincent A.

    2012-01-01

    Purpose Erlotinib is clinically effective in patients with non–small-cell lung cancer (NSCLC) who have adenocarcinoma, are never or limited former smokers, or have EGFR mutant tumors. We investigated the efficacy of erlotinib alone or in combination with chemotherapy in patients with these characteristics. Patients and Methods Patients with advanced NSCLC (adenocarcinoma) who were epidermal growth factor receptor tyrosine kinase inhibitor and chemotherapy naive never or light former smokers (smokers of > 100 cigarettes and ≤ 10 pack years and quit ≥ 1 year ago) were randomly assigned to continuous erlotinib or in combination with carboplatin and paclitaxel (ECP) for six cycles followed by erlotinib alone. The primary end point was progression-free survival (PFS). Tissue collection was mandatory. Results PFS was similar (5.0 v 6.6 months; P = .1988) in patients randomly assigned to erlotinib alone (arm A; n = 81) or to ECP (arm B; n = 100). EGFR mutation analysis was possible in 91% (164 of 181) of patients, and EGFR mutations were detected in 40% (51 of 128) of never smokers and in 42% (15 of 36) of light former smokers. In arm A, response rate (70% v 9%), PFS (14.1 v 2.6 months), and overall survival (OS; 31.3 v 18.1 month) favored EGFR-mutant patients. In arm B, response rate (73% v 30%), PFS (17.2 v 4.8 months), and OS (38.1 v 14.4 months) favored EGFR-mutant patients. Incidence of grades 3 to 4 hematologic (2% v 49%; P < .001) and nonhematologic (24% v 52%; P < .001) toxicity was greater in patients treated with ECP. Conclusion Erlotinib and erlotinib plus chemotherapy have similar efficacy in clinically selected populations of patients with advanced NSCLC. EGFR mutations identify patients most likely to benefit. PMID:22547605

  8. Gemcitabine plus paclitaxel versus carboplatin plus either gemcitabine or paclitaxel in advanced non-small-cell lung cancer: a literature-based meta-analysis.

    PubMed

    Li, Chenguang; Sun, Yihua; Pan, Yunjian; Wang, Qifeng; Yang, Shu; Chen, Haiquan

    2010-10-01

    The combination of gemcitabine plus paclitaxel has been proposed as an alternative to the platinum-based combinations for treatment of advanced non-small-cell lung cancer (NSCLC). However, conflicting results have been reported. This meta-analysis was performed to compare the activity, efficacy, and toxicity of gemcitabine plus paclitaxel versus carboplatin plus either gemcitabine or paclitaxel in patients with untreated advanced NSCLC. Randomized phase II and phase III clinical trials comparing gemcitabine plus paclitaxel with carboplatin plus gemcitabine or paclitaxel were collected from electronic databases (Medline, EMBASE, and the Cochrane Central Register of Controlled Trials), relevant reference lists, and abstract books. The published languages and years were not limited. Pooled odds ratios (ORs) were calculated for the 1-year survival rate (1-year SR), the overall response rate (ORR), and grade 3 and grade 4 toxicities. Four randomized controlled trials (2186 patients) were identified from 2051 reports. They were all published as full-text articles. No significant heterogeneity was detected in these studies. A significant difference in ORR favoring gemcitabine plus paclitaxel over carboplatin-based doublets was observed [OR = 1.20; 95% confidence interval (95% CI) = 1.02-1.42; P = 0.03], whereas the trend toward an improved 1-year SR was not significant (OR = 1.07; 95% CI = 0.91-1.26; P = 0.41). An increased risk of grade 3-4 toxicities for patients receiving carboplatin-based chemotherapy was statistically demonstrated. The gemcitabine plus paclitaxel combination showed an improved ORR and a better toxicity profile but a similar 1-year SR compared to carboplatin-based doublets. For nonplatinum-based chemotherapy, gemcitabine plus paclitaxel is a useful alternative. PMID:20703493

  9. 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.

  10. 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.

  11. Prognostic significance of the absolute monocyte counts in lung cancer patients with venous thromboembolism.

    PubMed

    Go, Se-Il; Kim, Rock Bum; Song, Haa-Na; Kang, Myoung Hee; Lee, Un Seok; Choi, Hye Jung; Jo, Wonyong; Lee, Seung Jun; Cho, Yu Ji; Jeong, Yi Yeong; Kim, Ho Cheol; Lee, Jong Deog; Kim, Seok-Hyun; Kang, Jung-Hun; Lee, Gyeong-Won

    2015-09-01

    We investigated the clinical significance of the absolute monocyte count (AMC) as a predictor of the response to anticoagulation and survival in lung cancer patients with venous thromboembolism (VTE). We retrospectively reviewed 1707 patients with pathologically proven lung cancer who visited the hospital between July 2008 and May 2014. Among them, the clinical data of patients newly diagnosed with VTE and treated with anticoagulation were compared between the low and high AMC groups according to the median value of AMC (640/μL) at the time of VTE diagnosis. The incidence of VTE was 7.9 % during the study period. Most of the patients had non-small-cell lung cancer (82.1 %), stage IV (64.2 %), and pulmonary thromboembolism (76.1 %) and were incidentally diagnosed with VTE (76.9 %). The patients' characteristics and laboratory values were not significantly different between the low and high AMC groups. Among patients available for evaluation of the response to anticoagulation, the high AMC group was significantly more refractory to anticoagulation than the low AMC group (no response to anticoagulation, 21.7 vs. 6.8 %, respectively; p = 0.044). Additionally, the high AMC group showed worse overall survival (OS) than the low AMC group (median, 9.6 vs. 5.9 months; p = 0.038). On multivariate analysis, high AMC, low albumin, and advanced stage were independent poor prognostic factors for OS. High AMC is associated with refractoriness to anticoagulation and poor prognosis in lung cancer patients with VTE.

  12. Prognostic Potential and Tumor Growth–Inhibiting Effect of Plasma Advanced Glycation End Products in Non–Small Cell Lung Carcinoma

    PubMed Central

    Bartling, Babett; Hofmann, Hans-Stefan; Sohst, Antonia; Hatzky, Yvonne; Somoza, Veronika; Silber, Rolf-Edgar; Simm, Andreas

    2011-01-01

    The plasma fluorescence related to the standard fluorescence of advanced glycation end products (AGEs) is a simple measurable blood parameter for distinct diseases but its importance in human cancer, including non–small cell lung carcinoma (NSCLC), is unknown. Plasma samples of 70 NSCLC patients who underwent resection surgery of the tumor were analyzed for the distinct AGE-related fluorescence at 370 nm excitation/440 nm emission. In a retrospective study, we tested the prognostic relevance of this AGE-related plasma fluorescence. The effect of circulating AGEs on the NSCLC growth was studied experimentally in vitro and in vivo. NSCLC patients with high (> median) AGE-related plasma fluorescence were characterized by a later reoccurrence of the tumor after curative surgery and a higher survival rate compared with patients with low plasma fluorescence (25% versus 47% 5-y survival, P = 0.011). Treating NSCLC cell spheroids with patients’ plasma showed an inverse correlation between the growth of spheroids in vitro and the individual AGE-related fluorescence of each plasma sample. To confirm the impact of circulating AGEs on the NSCLC progression, we studied the NSCLC growth in mice whose circulating AGE level was elevated by AGE-rich diet. In vivo tumorigenicity assays demonstrated that mice with higher levels of circulating AGEs developed smaller tumors than mice with normal AGE levels. The AGE-related plasma fluorescence has prognostic relevance for NSCLC patients in whom the tumor growth-inhibiting effect of circulating AGEs might play a critical role. PMID:21629968

  13. Management of refractory cardiogenic shock.

    PubMed

    Reyentovich, Alex; Barghash, Maya H; Hochman, Judith S

    2016-08-01

    Cardiogenic shock is a life-threatening condition that occurs in response to reduced cardiac output in the presence of adequate intravascular volume and results in tissue hypoxia. Cardiogenic shock has several underlying aetiologies, with the most common being acute myocardial infarction (AMI). Refractory cardiogenic shock presents as persistent tissue hypoperfusion despite administration of adequate doses of two vasoactive medications and treatment of the underlying aetiology. Investigators of the SHOCK trial reported a long-term mortality benefit of emergency revascularization for shock complicating AMI. Since the publication of the SHOCK trial and subsequent guideline recommendations, the increase in community-based use of percutaneous coronary intervention for this condition has resulted in a significant decline in mortality. Despite these successes in the past 15 years, mortality still remains exceptionally high, particularly in patients with refractory cardiogenic shock. In this Review, we discuss the aetiology and pathophysiology of cardiogenic shock and summarize the data on the available therapeutics and their limitations. Although new mechanical circulatory support devices have been shown to improve haemodynamic variables in patients with shock complicating AMI, they did not improve clinical outcomes and are associated with high costs and complications. PMID:27356877

  14. 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.

  15. 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

  16. Management of refractory cardiogenic shock.

    PubMed

    Reyentovich, Alex; Barghash, Maya H; Hochman, Judith S

    2016-08-01

    Cardiogenic shock is a life-threatening condition that occurs in response to reduced cardiac output in the presence of adequate intravascular volume and results in tissue hypoxia. Cardiogenic shock has several underlying aetiologies, with the most common being acute myocardial infarction (AMI). Refractory cardiogenic shock presents as persistent tissue hypoperfusion despite administration of adequate doses of two vasoactive medications and treatment of the underlying aetiology. Investigators of the SHOCK trial reported a long-term mortality benefit of emergency revascularization for shock complicating AMI. Since the publication of the SHOCK trial and subsequent guideline recommendations, the increase in community-based use of percutaneous coronary intervention for this condition has resulted in a significant decline in mortality. Despite these successes in the past 15 years, mortality still remains exceptionally high, particularly in patients with refractory cardiogenic shock. In this Review, we discuss the aetiology and pathophysiology of cardiogenic shock and summarize the data on the available therapeutics and their limitations. Although new mechanical circulatory support devices have been shown to improve haemodynamic variables in patients with shock complicating AMI, they did not improve clinical outcomes and are associated with high costs and complications.

  17. Lung disease

    MedlinePlus

    ... the lungs to take in oxygen and release carbon dioxide. People with this type of lung disorder often ... the lungs to take up oxygen and release carbon dioxide. These diseases may also affect heart function. An ...

  18. Collapsed Lung

    MedlinePlus

    A collapsed lung happens when air enters the pleural space, the area between the lung and the chest wall. If it is a ... is called pneumothorax. If only part of the lung is affected, it is called atelectasis. Causes of ...

  19. Refractory metal particles in refractory inclusions in the Allende meteorite

    SciTech Connect

    Fuchs, L. H.; Blander, M.

    1980-01-01

    An examination of refractory metal particles in five calcium-aluminum-rich inclusions in the Allende meteorite indicates a complex variety of compositions and large departures from equilibrium. These particles appear to 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 perhaps ordered phases) and the formation of metastable condensates appears to have been involved in the modification of these materials to their present state. Only a small fraction of our observations cannot be reconciled with this picture because of a lack of knowledge of some of the phase equilibria which might have bee involved.

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

    PubMed Central

    Ou-Yang, Chen Sheng; Wang, Xi-Xin; Yang, Zhen-Jiang; Tong, Yao; Cho, William C.S.

    2013-01-01

    Many published studies reflect the growing application of complementary and alternative medicine, particularly Chinese herbal medicine (CHM) use in combination with conventional cancer therapy for advanced non-small cell lung cancer (NSCLC), but its efficacy remains largely unexplored. The purpose of this study is to evaluate the efficacy of CHM combined with conventional chemotherapy (CT) in the treatment of advanced NSCLC. Publications in 11 electronic databases were extensively searched, and 24 trials were included for analysis. A sum of 2,109 patients was enrolled in these studies, at which 1,064 patients participated in CT combined CHM and 1,039 in CT (six patients dropped out and were not reported the group enrolled). Compared to using CT alone, CHM combined with CT significantly increase one-year survival rate (RR = 1.36, 95% CI = 1.15–1.60, p = 0.0003). Besides, the combined therapy significantly increased immediate tumor response (RR = 1.36, 95% CI = 1.19–1.56, p<1.0E−5) and improved Karnofsky performance score (KPS) (RR = 2.90, 95% CI = 1.62–5.18, p = 0.0003). Combined therapy remarkably reduced the nausea and vomiting at toxicity grade of III–IV (RR = 0.24, 95% CI = 0.12–0.50, p = 0.0001) and prevented the decline of hemoglobin and platelet in patients under CT at toxicity grade of I–IV (RR = 0.64, 95% CI = 0.51–0.80, p<0.0001). Moreover, the herbs that are frequently used in NSCLC patients were identified. This systematic review suggests that CHM as an adjuvant therapy can reduce CT toxicity, prolong survival rate, enhance immediate tumor response, and improve KPS in advanced NSCLC patients. However, due to the lack of large-scale randomized clinical trials in the included studies, further larger scale trials are needed. PMID:23469033

  1. 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

  2. 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.

  3. Pazopanib, a multikinase angiogenesis inhibitor, in patients with relapsed or refractory advanced soft tissue sarcoma: a phase II study from the European organisation for research and treatment of cancer-soft tissue and bone sarcoma group (EORTC study 62043).

    PubMed

    Sleijfer, Stefan; Ray-Coquard, Isabelle; Papai, Zsuzsa; Le Cesne, Axel; Scurr, Michelle; Schöffski, Patrick; Collin, Françoise; Pandite, Lini; Marreaud, Sandrine; De Brauwer, Annick; van Glabbeke, Martine; Verweij, Jaap; Blay, Jean-Yves

    2009-07-01

    PURPOSE Given the importance of angiogenesis in soft tissue sarcoma (STS), pazopanib, an oral angiogenesis inhibitor that targets vascular endothelial growth factor receptor and platelet-derived growth factor receptor, was explored in patients with advanced STS. PATIENTS AND METHODS Patients with intermediate- or high-grade advanced STS who were ineligible for chemotherapy or who had received no more than two prior cytotoxic agents for advanced disease, who had documented progression, who had adequate performance status, and who had good organ function were eligible. Pazopanib 800 mg was given daily. The primary end point was progression-free rate at 12 weeks (PFR(12 weeks)). Secondary end points were response, safety, and overall survival. Four different strata were studied: adipocytic STS, leiomyosarcomas, synovial sarcomas, and other STS types. A Simon two-stage design was applied (P1 = 40%; P0 = 20%; alpha = beta = .1) for each stratum. Results One hundred forty-two patients were enrolled. The adipocytic STS stratum was closed after the first stage, given insufficient activity (PFR(12 weeks), five [26%] of19). PFR(12 weeks) was 18 (44%) of 41 patients in the leiomyosarcoma cohort, 18 (49%) of 37 in the synovial sarcomas, and 16 (39%) of 41 in the other STS types. Compared with historical controls who were treated with second-line chemotherapy, progression-free and overall survivals were prolonged in the three cohorts in which the primary end point was reached. The most frequent drug-related toxicities were hypertension, fatigue, hypopigmentation, and nausea. Other toxicities included liver enzyme elevations, myelosuppression, and proteinuria, all of which were mostly grades 1 to 2. The most frequent grades 3 to 4 toxicities were hyperbilirubinemia (6.3%), hypertension (7.7%), and fatigue (7.7%). CONCLUSION Pazopanib is well tolerated in patients with relapsed, advanced STS and demonstrates interesting activity that warrants additional study in patients with

  4. 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

  5. Dabrafenib in BRAF V600E–Mutant Advanced Non-Small Cell Lung Cancer: an Open-label, Single arm, Multicenter, Phase 2 Trial

    PubMed Central

    Planchard, David; Kim, Tae Min; Mazieres, Julien; Quoix, Elisabeth; Riely, Gregory; Barlesi, Fabrice; Souquet, Pierre-John; Smit, Egbert F.; Groen, Harry J. M.; Kelly, Ronan J.; Cho, B. C.; Socinski, Mark A.; Pandite, Lini; Nase, Christine; Ma, Bo; D’Amelio, Anthony; Mookerjee, Bijoyesh; Curtis, C. Martin; Johnson, Bruce E.

    2016-01-01

    Background Activating BRAF V600E mutations are found in approximately 1–2% of adenocarcinomas of the lung offering an opportunity to test targeted therapy for this disease. Dabrafenib is an oral selective inhibitor of the BRAF kinase. The aim of this study was to assess the clinical activity of dabrafenib in patients with advanced BRAF V600E-mutant non-small cell lung cancer (NSCLC). Methods In this phase 2, multicenter, nonrandomized, open-label study of previously treated and untreated patients with stage IV, metastatic NSCLC and BRAF V600E mutation, we evaluated the antitumor activity and safety of oral dabrafenib (150 mg twice daily). The primary endpoint was investigator-assessed overall response rate (ORR) in patients receiving ≥ 1 dose of study drug. Safety analysis was performed on the all-treated population (all previously treated and untreated patients receiving ≥ 1 dose of study drug). The study is ongoing but not enrolling participants in this cohort. This trial is registered with ClinicalTrials.gov, number NCT01336634. Findings Between August 2011 and February 2014 a total of 84 previously treated and untreated patients were enrolled. Investigator-assessed ORR for 78 pretreated patients was 33% (95% confidence interval [CI], 23·1 to 44·9). Independent review committee assessment of ORR was consistent with investigator-based assessment. Four of the six previously untreated patients had an objective response. One patient died on study due to intracranial hemorrhage that was considered by the investigator to be due to study drug. Serious adverse events were reported in 35 (42%) of 84 patients. The most frequent grade 3 or higher adverse events were cutaneous squamous cell carcinoma (10 [12%] of 84 patients), asthenia (4 [5%] of 84 patients), and basal cell carcinoma (4 [5%] of 84 patients). Interpretation This is, to our knowledge, the first prospective trial focusing on BRAF V600E-mutant NSCLC to show clinical activity of a BRAF inhibitor. The

  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

    2016-01-01

    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. 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

  8. 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

  9. 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

  10. 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

  11. 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.

  12. 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.

  13. Inhaled Amikacin for Treatment of Refractory Pulmonary Nontuberculous Mycobacterial Disease

    PubMed Central

    Shaw, Pamela A.; Glaser, Tanya S.; Bhattacharyya, Darshana; Fleshner, Michelle; Brewer, Carmen C.; Zalewski, Christopher K.; Folio, Les R.; Siegelman, Jenifer R.; Shallom, Shamira; Park, In Kwon; Sampaio, Elizabeth P.; Zelazny, Adrian M.; Holland, Steven M.; Prevots, D. Rebecca

    2014-01-01

    Rationale: Treatment of pulmonary nontuberculous mycobacteria, especially Mycobacterium abscessus, requires prolonged, multidrug regimens with high toxicity and suboptimal efficacy. Options for refractory disease are limited. Objectives: We reviewed the efficacy and toxicity of inhaled amikacin in patients with treatment-refractory nontuberculous mycobacterial lung disease. Methods: Records were queried to identify patients who had inhaled amikacin added to failing regimens. Lower airway microbiology, symptoms, and computed tomography scan changes were assessed together with reported toxicity. Measurements and Main Results: The majority (80%) of the 20 patients who met entry criteria were women; all had bronchiectasis, two had cystic fibrosis and one had primary ciliary dyskinesia. At initiation of inhaled amikacin, 15 were culture positive for M. abscessus and 5 for Mycobacterium avium complex and had received a median (range) of 60 (6, 190) months of mycobacterial treatment. Patients were followed for a median of 19 (1, 50) months. Eight (40%) patients had at least one negative culture and 5 (25%) had persistently negative cultures. A decrease in smear quantity was noted in 9 of 20 (45%) and in mycobacterial culture growth for 10 of 19 (53%). Symptom scores improved in nine (45%), were unchanged in seven (35%), and worsened in four (20%). Improvement on computed tomography scans was noted in 6 (30%), unchanged in 3 (15%), and worsened in 11 (55%). Seven (35%) stopped amikacin due to: ototoxicity in two (10%), hemoptysis in two (10%), and nephrotoxicity, persistent dysphonia, and vertigo in one each. Conclusions: In some patients with treatment-refractory pulmonary nontuberculous mycobacterial disease, the addition of inhaled amikacin was associated with microbiologic and/or symptomatic improvement; however, toxicity was common. Prospective evaluation of inhaled amikacin for mycobacterial disease is warranted. PMID:24460437

  14. 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

  15. 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

  16. REFRACTORY FOR BLACK LIQUOR GASIFIERS

    SciTech Connect

    William L. Headrick Jr; Musa Karakus; Xiaoting Liang; Alireza Rezaie

    2004-07-01

    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

  17. Refractory for Black Liquor Gasifiers

    SciTech Connect

    William L. Headrick; Musa Karakus; Alireza Rezaie

    2004-03-30

    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

  18. NASA research on refractory compounds.

    NASA Technical Reports Server (NTRS)

    Gangler, J. J.

    1971-01-01

    The behavior and properties of the refractory carbides, nitrides, and borides are being investigated by NASA as part of its research aimed at developing superior heat resistant materials for aerospace applications. Fundamental studies on the electronic and defect structures of the carbides indicate that there is promise for improving the strength and ductility of these materials. Studies of the zirconium-carbon-oxygen system show that zirconium oxycarbides of different compositions and lattice parameters can be formed between 1500 and 1900 C and are stable below 1500 C. More applied studies show that hot working generally improves the microstructure and therefore the strength of TiC and NbC. Sintering studies on UN indicate that very high densities can be achieved. Hot pressing of cermets of HfN and HfC produces good mechanical properties for high temperature bearing applications.

  19. NASA research on refractory compounds.

    NASA Technical Reports Server (NTRS)

    Gangler, J. J.

    1971-01-01

    The behavior and properties of the refractory carbides, nitrides, and borides are being investigated by NASA as part of its research aimed at developing superior heat resistant materials for aerospace applications. Studies of the zirconium-carbon-oxygen system show that zirconium oxycarbides of different compositions and lattice parameters can be formed between 1500 C and 1900 C and are stable below 1500 C. More applied studies show that hot working generally improves the microstructure and therefore the strength of TiC and NbC. Sintering studies on UN indicate that very high densities can be achieved. Hot pressing of cermets of HfN and HfC produces good mechanical properties for high temperature bearing applications. Attempts to improve the impact resistance of boride composites by the addition of a nickel or carbon yarn were not overly successful.

  20. REFRACTORY FOR BLACK LIQUOR GASIFIERS

    SciTech Connect

    William L. Headrick Jr; Musa Karakus; Xiaoting Liang; Alireza Rezaie

    2004-10-01

    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

  1. 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

  2. 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 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

  3. 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

  4. REFRACTORY FOR BLACK LIQUOR GASIFIERS

    SciTech Connect

    William L. Headrick Jr.; Alireza Rezaie

    2004-04-01

    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 materials 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. 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

  6. Refractory for Black Liquor Gasifiers

    SciTech Connect

    William L. Headrick Jr; Musa Karakus; Xiaoting Liang

    2005-10-01

    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/developed that either react with the gasifier environment to form protective surfaces in-situ; and

  7. 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

  8. REFRACTORY FOR BLACK LIQUOR GASIFIERS

    SciTech Connect

    William L. Headrick Jr; Musa Karakus; Xiaoting Liang

    2005-07-01

    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

  9. Primordial Compositions of Refractory Inclusions

    SciTech Connect

    Grossman, L; Simon, S B; Rai, V K; Thiemens, M H; Hutcheon, I D; Williams, R W; Galy, A; Ding, T; Fedkin, A V; Clayton, R N; Mayeda, T K

    2008-02-20

    Bulk chemical and oxygen, magnesium and silicon isotopic compositions were measured for each of 17 Types A and B refractory inclusions from CV3 chondrites. After bulk chemical compositions were corrected for non-representative sampling in the laboratory, the Mg and Si isotopic compositions of each inclusion were used to calculate its original chemical composition assuming that the heavy-isotope enrichments of these elements are due to Rayleigh fractionation that accompanied their evaporation from CMAS liquids. The resulting pre-evaporation chemical compositions are consistent with those predicted by equilibrium thermodynamic calculations for high-temperature nebular condensates but only if different inclusions condensed from nebular regions that ranged in total pressure from 10{sup -6} to 10{sup -1} bar, regardless of whether they formed in a system of solar composition or in one enriched in OC dust relative to gas by a factor of ten relative to solar composition. This is similar to the range of total pressures predicted by dynamic models of the solar nebula for regions whose temperatures are in the range of silicate condensation temperatures. Alternatively, if departure from equilibrium condensation and/or non-representative sampling of condensates in the nebula occurred, the inferred range of total pressure could be smaller. Simple kinetic modeling of evaporation successfully reproduces observed chemical compositions of most inclusions from their inferred pre-evaporation compositions, suggesting that closed-system isotopic exchange processes did not have a significant effect on their isotopic compositions. Comparison of pre-evaporation compositions with observed ones indicates that 80% of the enrichment in refractory CaO + Al{sub 2}O{sub 3} relative to more volatile MgO + SiO{sub 2} is due to initial condensation and 20% due to subsequent evaporation for both Type A and Type B inclusions.

  10. Primordial compositions of refractory inclusions

    NASA Astrophysics Data System (ADS)

    Grossman, L.; Simon, S. B.; Rai, V. K.; Thiemens, M. H.; Hutcheon, I. D.; Williams, R. W.; Galy, A.; Ding, T.; Fedkin, A. V.; Clayton, R. N.; Mayeda, T. K.

    2008-06-01

    Bulk chemical and O-, Mg- and Si-isotopic compositions were measured for each of 17 Types A and B refractory inclusions from CV3 chondrites. After bulk chemical compositions were corrected for non-representative sampling in the laboratory, the Mg- and Si-isotopic compositions of each inclusion were used to calculate its original chemical composition assuming that the heavy-isotope enrichments of these elements are due to Rayleigh fractionation that accompanied their evaporation from CMAS liquids. The resulting pre-evaporation chemical compositions are consistent with those predicted by equilibrium thermodynamic calculations for high-temperature nebular condensates, but only if different inclusions condensed from nebular regions that ranged in total pressure from 10-6 to 10-1 bar, regardless of whether they formed in a system of solar composition or in one enriched in dust of ordinary chondrite composition relative to gas by a factor of 10 compared to solar composition. This is similar to the range of total pressures predicted by dynamic models of the solar nebula for regions whose temperatures are in the range of silicate condensation temperatures. Alternatively, if departure from equilibrium condensation and/or non-representative sampling of condensates in the nebula occurred, the inferred range of total pressure could be smaller. Simple kinetic modeling of evaporation successfully reproduces observed chemical compositions of most inclusions from their inferred pre-evaporation compositions, suggesting that closed-system isotopic exchange processes did not have a significant effect on their isotopic compositions. Comparison of pre-evaporation compositions with observed ones indicates that 80% of the enrichment in refractory CaO + Al2O3 relative to more volatile MgO + SiO2 is due to initial condensation and 20% due to subsequent evaporation for both Types A and B inclusions.

  11. Optimal tumor shrinkage predicts long-term outcome in advanced nonsmall cell lung cancer (NSCLC) treated with target therapy: Result from 3 clinical trials of advanced NSCLC by 1 institution.

    PubMed

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

    2016-08-01

    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 (HR, 2.36, 95

  12. [Postoperative refractory chylothorax which was improved by octreotide acetate].

    PubMed

    Gabe, Atsushi; Seki, Masahiro; Taira, Naohiro; Katsura, Morihiro; Ishida, Tomoki; Kang, Yukijya; Kubota, Tadao; Yamashiro, Toshimitsu; Uehara, Tetsuo; Sunagawa, Tohru; Ohkubo, Kazuaki

    2012-03-01

    A 77-year-old male with chronic hepatitis and liver cirrhosis underwent a right middle-lower lobectomy and lymph node dissection because of non-small cell carcinoma of the lung. On the 1st post-operative day (POD1), a large quantity of chylous pleural effusion was recognized after he initiated oral intake. The diagnosis was postoperative chylothorax. Conservative therapy including a medium chain tryglyceride diet and total parental nutrition were not effective. Considering of the patient's past history, we decided to continue conservative therapy using octreotide acetate on POD7. After administration of the octreotide acetate, the volume of chylous pleural effusion gradually decreased. The chest tube was removed on POD19. Octeotide acetate should be a choice for the conservative treatment of postoperative refractory chylothorax.

  13. Diagnostic and therapeutic issues for patients with advanced non‑small cell lung cancer harboring anaplastic lymphoma kinase rearrangement: European vs. US perspective (review).

    PubMed

    Di Maio, Massimo; De Marinis, Filippo; Hirsch, Fred R; Gridelli, Cesare

    2014-08-01

    The recent availability of crizotinib in clinical practice, for the treatment of patients with advanced non-small cell lung cancer (NSCLC) selected by the presence of anaplastic lymphoma kinase (ALK) rearrangement, has relevant implications for both the diagnostic phase and the treatment choices. In the United States, crizotinib was approved by the Food and Drug Administration (FDA) in 2011 for patients with ALK positivity detected by FDA-approved companion diagnostic test. As of January, 2014, the only FDA-approved diagnostic test is Vysis ALK Break-Apart FISH Probe Kit. In Europe, European Medicines Agency (EMA) approved crizotinib for ALK-positive patients in 2012, without specifying the type of test used for determining the positivity. FISH remains the reference technique for ALK determination, but, if fully validated, immunohistochemistry could challenge the current ALK screening practice. Given the robust evidence of activity of crizotinib in ALK-positive patients both pretreated and chemotherapy-naïve, and the favourable tolerability profile of the drug, many oncologists would prefer to administer the drug as early as possible. This is technically feasible in the United States, where crizotinib was approved well before the availability of the results of the randomized phase III trial comparing the drug with standard second-line chemotherapy, and the use of crizotinib in ALK-positive patients is not restricted to a specific line of treatment. On the contrary, in Europe, differently from the FDA decision, crizotinib cannot be used in chemotherapy-naïve patients. In both realities, a deeper knowledge of mechanisms of resistance, the role of repeated biopsies, the treatment strategy for patients experiencing disease progression with crizotinib, the choice of the best chemotherapy regimen are challenging topics for the management of ALK-positive patients in clinical practice.

  14. Mutation status concordance between primary lesions and metastatic sites of advanced non-small-cell lung cancer and the impact of mutation testing methodologies: a literature review.

    PubMed

    Sherwood, James; Dearden, Simon; Ratcliffe, Marianne; Walker, Jill

    2015-01-01

    Increased understanding of the genetic aetiology of advanced non-small-cell lung cancer (aNSCLC) has facilitated personalised therapies that target specific molecular aberrations associated with the disease. Biopsy samples for mutation testing may be taken from primary or metastatic sites, depending on which sample is most accessible, and upon differing diagnostic practices between territories. However, the mutation status concordance between primary tumours and corresponding metastases is the subject of debate. This review aims to ascertain whether molecular diagnostic testing of either the primary or metastatic tumours is equally suitable to determine patient eligibility for targeted therapies. A literature search was performed to identify articles reporting studies of mutations in matched primary and metastatic aNSCLC tumour samples. Clinical results of mutation status concordance between matched primary and metastatic tumour samples from patients with aNSCLC were collated. Articles included in this review (N =26) all reported mutation status data from matched primary and metastatic tumour samples obtained from adult patients with aNSCLC. Generally, substantial concordance was observed between primary and metastatic tumours in terms of EGFR, KRAS, BRAF, p16 and p53 mutations. However, some level of discordance was seen in most studies; mutation testing methodologies appeared to play a key role in this, along with underlying tumour heterogeneity. Substantial concordance in mutation status observed between primary and metastatic tumour sites suggests that diagnostic testing of either tumour type may be suitable to determine a patient's eligibility for personalised therapies. As with all diagnostic testing, highly sensitive and appropriately validated mutation analysis methodologies are desirable to ensure accuracy. Additional work is also required to define how much discordance is clinically significant given natural tumour heterogeneity. The ability of both

  15. 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

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

    PubMed Central

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

    2014-01-01

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

  17. Chemotherapy With Erlotinib or Chemotherapy Alone in Advanced Non-Small Cell Lung Cancer With Acquired Resistance to EGFR Tyrosine Kinase Inhibitors

    PubMed Central

    Oxnard, Geoffrey R.; Digumarthy, Subba; Muzikansky, Alona; Jackman, David M.; Lennes, Inga T.; Sequist, Lecia V.

    2013-01-01

    Purpose. Epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer has an oncogene-addicted biology that confers sensitivity to EGFR tyrosine kinase inhibitors (TKIs). Published data suggest that EGFR addiction persists after development of TKI acquired resistance, leading many clinicians to continue TKI with subsequent chemotherapy; however, this strategy has not been formally evaluated. Methods. We retrospectively reviewed an institutional database to identify patients with advanced EGFR mutation with acquired resistance who subsequently received chemotherapy. Patients were classified as receiving chemotherapy with continued erlotinib or chemotherapy alone. We assessed differences in outcomes between the two strategies. Results. Seventy-eight patients were included, 34 treated with chemotherapy and erlotinib and 44 treated with chemotherapy alone. Objective response rate was evaluable in 57 patients and was 41% for those treated with chemotherapy and erlotinib and 18% for those treated with chemotherapy alone. After adjusting for chemotherapy regimen and length of initial TKI course, the odds ratio for the response rate was 0.20 (95% confidence interval: 0.05–0.78; p = .02) favoring treatment with chemotherapy and erlotinib. The median progression-free survival was 4.4 months on chemotherapy and erlotinib and 4.2 months on chemotherapy alone (adjusted hazard ratio = 0.79; 95% confidence interval: 0.48–1.29; p = .34). There was no difference in overall survival. Conclusion. This is the first study, to our knowledge, to demonstrate that continuation of EGFR TKI with chemotherapy in patients with acquired resistance improves outcomes compared with chemotherapy alone. We observed an improved response rate but no difference in progression-free survival or overall survival. A larger prospective clinical trial is needed to evaluate this promising strategy further. PMID:24072220

  18. Thymidylate synthase polymorphisms in genomic DNA as clinical outcome predictors in a European population of advanced non-small cell lung cancer patients receiving pemetrexed

    PubMed Central

    2014-01-01

    Background We studied whether thymidylate synthase (TS) genotype has an independent prognostic/predictive impact on a European population of advanced non-small cell lung cancer (NSCLC) patients receiving pemetrexed. Methods Twenty-five patients treated with pemetrexed-based regimens were included. Genomic DNA was isolated prior to treatment. The variable number of tandem repeat (VNTR) polymorphisms, the G > C single nucleotide polymorphisms (SNP) and the TS 6-bp insertion/deletion (6/6) in the 3′ untranslated region (UTR) polymorphisms were analyzed and correlated with overall response rate (ORR), progression-free survival (PFS), overall-survival (OS) and toxicity. Results The genotype +6/+6 predicted a higher ORR among active/former smokers compared to +6/-6 genotype (100% vs. 50%; p = 0.085). Overall, the 3R/3R genotype predicted a higher ORR (100%) over the rest VNTR polymorphisms (p = 0.055). The presence of 3R/3R genotype significantly correlated with a superior ORR in patients without EGFR activating mutations (100%) compared to 2R/2R, 2R/3R and 3R/4R genotype (77.8%, 33.3% and 0% respectively; p = 0.017). After a median follow-up of 21 months, a trend towards a better PFS, although not significant, was found among subjects showing 3R/3R polymorphisms (p = 0.089). A significantly superior OS was found in patients showing 3R/3R genotype rather than other VNTR polymorphisms (p = 0.019). No significant correlation with the toxicity was observed. Conclusion In our series, 3R/3R polymorphism correlated with a superior OS. Also, this polymorphism, when associated to wild type EGFR, was related to a higher ORR to pemetrexed. Toxicity was not significantly correlated with a specific TS genotype. PMID:24726028

  19. 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

  20. Second- and Further-Line Therapy with Erlotinib in Patients with Advanced Non-Small-Cell Lung Cancer in Daily Clinical Practice

    PubMed Central

    Krainhöfer, Josephine; Steinert, Matthias; Reissig, Angelika

    2014-01-01

    Introduction. The aim of this retrospective study was to examine effect of erlotinib in patients with advanced non-small cell lung cancer (NSCLC) in second-line and further therapy in daily clinical practice. Methods. Patients with histologically or cytologically proven NSCLC (n = 84) treated with erlotinib in second-line (n = 34), third-line (n = 36), and more-line therapy (n = 14) were examined for progression-free survival (PFS), overall survival (OS), disease control rate (DCR), duration of therapy, and adverse effects. Results. Median PFS of all lines was 83 days (CI 70.0–96.0), OS was 7 months (CI 4.7–9.3), DCR was 66.2% (CI 55–77%), and 1-year survival rate was 33% (CI 22–43%), with no significant difference between therapy lines. Median duration of treatment was 76 days (IQR 39–139.5). Patients with epidermal growth factor receptor mutation (EGFR-M) reached the highest PFS (204 days), as did patients with good performance status (ECOG 0-1: 94 versus ECOG 2-3: 65 days, P = 0.035). Patients with EGFR-M also revealed a DCR of 100%. The most frequent side effects were rash (69%) and diarrhoea (41%), without any significant difference between therapy lines. In 24 patients, the treatment dose was reduced and in 18, the therapy was paused. Conclusion. Erlotinib works in all therapy lines without any significant differences in efficacy and side effects. PMID:25028671

  1. Behavior of refractory materials in vacuum ladles

    SciTech Connect

    Haile, O.; Lauri, H.

    1998-12-31

    The use of vacuum treatment has strongly increased during the last decade the main purposes being to lower gas contents (H, N), to improve steel cleanliness and to achieve ultra low carbon contents. Tank degasing, DH, RH and RH-OB degassers are the main techniques for modern vacuum treatment. The purpose of this work was to study the behavior of refractory materials in vacuum ladles and vessels. Earlier common materials like silica, shamotte and alumina bricks have been replaced by high alumina and basic refractory materials, doloma and magnesia as well as spinel type refractories. Monolithic lining instead of bricks has become common practice for ladles.

  2. Efficacy and safety of maintenance erlotinib in Asian patients with advanced non-small-cell lung cancer: a subanalysis of the phase III, randomized SATURN study.

    PubMed

    Wu, Yi-Long; Kim, Joo-Hang; Park, Keunchil; Zaatar, Adel; Klingelschmitt, Gaëlle; Ng, Christina

    2012-08-01

    Maintenance therapy, commenced immediately after the completion of first-line chemotherapy, is a promising strategy for improving treatment outcomes in patients with non-small-cell lung cancer (NSCLC). The global phase III SequentiAl Tarceva in UnResectable NSCLC (SATURN) study evaluated the efficacy and safety of the epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitor erlotinib as maintenance treatment in NSCLC patients without progression after first-line chemotherapy. We report a retrospective subanalysis of Asian patients enrolled in SATURN. Patients with advanced NSCLC with no evidence of progression after four cycles of chemotherapy were randomized to receive erlotinib 150 mg/day or placebo, until progressive disease or limiting toxicity. The co-primary endpoints of SATURN were progression-free survival (PFS) in all patients and in those with positive EGFR immunohistochemistry (IHC) status. Secondary endpoints included overall survival (OS), disease control rate, safety, quality of life (QoL) and biomarker analyses. In total, 126 patients from East and South-East Asian centers were randomized (14% of the intent-to-treat population): 88 from Korea, 28 from China and 10 from Malaysia; one patient was excluded from this analysis due to Indian ethnicity. PFS was significantly prolonged in the erlotinib treatment arm, both overall (hazard ratio [HR]: 0.57; p=0.0067) and in patients with EGFR IHC-positive disease (HR=0.50; p=0.0057). There was a trend towards an increase in OS, which reached statistical significance in the EGFR IHC-positive subgroup (p=0.0233). The overall response rate was significantly higher with erlotinib compared with placebo (24% versus 5%; p=0.0025). Erlotinib was generally well tolerated and had no negative impact on QoL in this subpopulation. The most common treatment-related adverse events were rash, diarrhea and pruritus. Erlotinib was effective and well tolerated in Asian patients, producing benefits consistent with those

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

    PubMed Central

    Bonanno, Laura; Zago, Giulia; Marulli, Giuseppe; Del Bianco, Paola; Schiavon, Marco; Pasello, Giulia; Polo, Valentina; Canova, Fabio; Tonetto, Fabrizio; Loreggian, Lucio; Rea, Federico; Conte, PierFranco; Favaretto, Adolfo

    2016-01-01

    Objectives If concurrent chemoradiotherapy cannot be performed, induction chemotherapy followed by radical-intent surgical treatment is an acceptable option for non primarily resectable non-small-cell lung cancers (NSCLCs). No markers are available to predict which patients may benefit from local treatment after induction. This exploratory study aims to assess the feasibility and the activity of multimodality treatment, including triple-agent chemotherapy followed by radical surgery and/or radiotherapy in locally advanced NSCLCs. Methods We retrospectively collected data from locally advanced NSCLCs treated with induction chemotherapy with carboplatin (area under the curve 6, d [day]1), paclitaxel (200 mg/m2, d1), and gemcitabine (1,000 mg/m2 d1, 8) for three to four courses, followed by radical surgery and/or radiotherapy. We analyzed radiological response and toxicity. Estimated progression-free survival (PFS) and overall survival (OS) were correlated to response, surgery, and clinical features. Results In all, 58 NSCLCs were included in the study: 40 staged as IIIA, 18 as IIIB (according to TNM Classification of Malignant Tumors–7th edition staging system). A total of 36 (62%) patients achieved partial response (PR), and six (10%) progressions were recorded. Grade 3–4 hematological toxicity was observed in 36 (62%) cases. After chemotherapy, 37 (64%) patients underwent surgery followed by adjuvant radiotherapy, and two patients received radical-intent radiotherapy. The median PFS and OS were 11 months and 23 months, respectively. Both PFS and OS were significantly correlated to objective response (P<0.0001) and surgery (P<0.0001 and P=0.002). Patients obtaining PR and receiving local treatment achieved a median PFS and OS of 35 and 48 months, respectively. Median PFS and OS of patients not achieving PR or not receiving local treatment were 5–7 and 11–15 months, respectively. The extension of surgery did not affect the outcome. Conclusion The

  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. Refractories for Industrial Processing. Opportunities for Improved Energy Efficiency

    SciTech Connect

    Hemrick, James G.; Hayden, H. Wayne; Angelini, Peter; Moore, Robert E.; Headrick, William L.

    2005-01-01

    Refractories are a class of materials of critical importance to manufacturing industries with high-temperature unit processes. This study describes industrial refractory applications and identifies refractory performance barriers to energy efficiency for processing. The report provides recommendations for R&D pathways leading to improved refractories for energy-efficient manufacturing and processing.

  6. Refractories for high-alkali environments

    SciTech Connect

    Rau, A.W.; Cloer, F.

    1996-01-01

    There are two reliable and cost-effective tests for evaluating refractory materials. They are used to determine which refractory products allow greater variance in fuel type with respect to alkali environment for coal-fired applications. Preselection of a particular refractory is important because of down-time cost for premature failure. One test is a variation of the standard alkali cup test. The second involves reacting test specimens with the contaminant, followed by physical properties testing to determine degree of degradation and properties affected. The alkali cup test rates products using a relative numerical scale based upon visual appearance. This test indicates the presence and relative degree of chemical attack to the refractory. The physical properties test determines the specific properties affected by the given contaminant.

  7. Refractory thermal insulation for smooth metal surfaces

    NASA Technical Reports Server (NTRS)

    1964-01-01

    To protect rocket metal surfaces from engine exhaust heat, a refractory thermal insulation mixture, which adheres to smooth metals, has been developed. Insulation protection over a wide temperature range can be controlled by thickness of the applied mixture.

  8. Mipsagargin, a novel thapsigargin-based PSMA-activated prodrug: results of a first-in-man phase I clinical trial in patients with refractory, advanced or metastatic solid tumours

    PubMed Central

    Mahalingam, D; Wilding, G; Denmeade, S; Sarantopoulas, J; Cosgrove, D; Cetnar, J; Azad, N; Bruce, J; Kurman, M; Allgood, V E; Carducci, M

    2016-01-01

    Background: Mipsagargin (G-202; (8-O-(12-aminododecanoyl)-8-O-debutanoyl thapsigargin)-Asp-γ-Glu-γ-Glu-γ-GluGluOH)) is a novel thapsigargin-based targeted prodrug that is activated by PSMA-mediated cleavage of an inert masking peptide. The active moiety is an inhibitor of the sarcoplasmic/endoplasmic reticulum calcium adenosine triphosphatase (SERCA) pump protein that is necessary for cellular viability. We evaluated the safety of mipsagargin in patients with advanced solid tumours and established a recommended phase II dosing (RP2D) regimen. Methods: Patients with advanced solid tumours received mipsagargin by intravenous infusion on days 1, 2 and 3 of 28-day cycles and were allowed to continue participation in the absence of disease progression or unacceptable toxicity. The dosing began at 1.2 mg m−2 and was escalated using a modified Fibonacci schema to determine maximally tolerated dose (MTD) with an expansion cohort at the RP2D. Plasma was analysed for mipsagargin pharmacokinetics and response was assessed using RECIST criteria. Results: A total of 44 patients were treated at doses ranging from 1.2 to 88 mg m−2, including 28 patients in the dose escalation phase and 16 patients in an expansion cohort. One dose-limiting toxicity (DLT; Grade 3 rash) was observed in the dose escalation portion of the study. At 88 mg m−2, observations of Grade 2 infusion-related reaction (IRR, 2 patients) and Grade 2 creatinine elevation (1 patient) led to declaration of 66.8 mg m−2 as the recommended phase II dose (RP2D). Across the study, the most common treatment-related adverse events (AEs) were fatigue, rash, nausea, pyrexia and IRR. Two patients developed treatment-related Grade 3 acute renal failure that was reversible during the treatment-free portion of the cycle. To help ameliorate the IRR and creatinine elevations, a RP2D of 40 mg m−2 on day 1 and 66.8 mg m−2 on days 2 and 3 with prophylactic premedications and hydration on each

  9. Method of making a composite refractory material

    DOEpatents

    Morrow, Marvin S.; Holcombe, Cressie E.

    1995-01-01

    A composite refractory material is prepared by combining boron carbide with furan resin to form a mixture containing about 8 wt. % furan resin. The mixture is formed into a pellet which is placed into a grit pack comprising an oxide of an element such as yttrium to form a sinterable body. The sinterable body is sintered under vacuum with microwave energy at a temperature no greater than 2000.degree. C. to form a composite refractory material.

  10. Refractory hypertension: definition, prevalence, and patient characteristics.

    PubMed

    Acelajado, Maria Czarina; Pisoni, Roberto; Dudenbostel, Tanja; Dell'Italia, Louis J; Cartmill, Falynn; Zhang, Bin; Cofield, Stacey S; Oparil, Suzanne; Calhoun, David A

    2012-01-01

    Among patients with resistant hypertension (RHTN), there are those whose blood pressure (BP) remains uncontrolled in spite of maximal medical therapy. This retrospective analysis aims to characterize these patients with refractory hypertension. Refractory hypertension was defined as BP that remained uncontrolled after ≥3 visits to a hypertension clinic within a minimum 6-month follow-up period. Of the 304 patients referred for RHTN, 29 (9.5%) remained refractory to treatment. Patients with refractory hypertension and those with controlled RHTN had similar aldosterone levels and plasma renin activity (PRA). Patients with refractory hypertension had higher baseline BP (175±23/97±15 mm Hg vs 158±25/89±15 mm Hg; P=.001/.005) and heart rate, and higher rates of prior stroke and congestive heart failure. During follow-up, the BP of patients with refractory hypertension remained uncontrolled (168.4±14.8/93.8±17.7 mm Hg) in spite of use of an average of 6 antihypertensive medications, while those of patients with controlled RHTN decreased to 129.3±11.2/77.6±10.8 mm Hg. Spironolactone reduced the BP by 12.9±17.8/6.6±13.7 mm Hg in patients with refractory hypertension and by 24.1±16.7/9.2±12.0 mm Hg in patients with controlled RHTN. In patients with RHTN, approximately 10% remain refractory to treatment. Similar aldosterone and PRA levels and a diminished response to spironolactone suggest that aldosterone excess does not explain the treatment failure.

  11. The modified atkins diet in refractory epilepsy.

    PubMed

    Sharma, Suvasini; Jain, Puneet

    2014-01-01

    The modified Atkins diet is a less restrictive variation of the ketogenic diet. This diet is started on an outpatient basis without a fast, allows unlimited protein and fat, and does not restrict calories or fluids. Recent studies have shown good efficacy and tolerability of this diet in refractory epilepsy. In this review, we discuss the use of the modified Atkins diet in refractory epilepsy.

  12. [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.

  13. Refractory Thrombocytopenia and Neutropenia: a Diagnostic Challenge

    PubMed Central

    Gyan, Emmanuel; Dreyfus, François; Fenaux, Pierre

    2015-01-01

    The 2008 WHO classification identified refractory cytopenia with unilineage dysplasia (RCUD) as a composite entity encompassing refractory anemia, refractory thrombocytopenia (RT), and refractory neutropenia (RN), characterized by 10% or more dysplastic cells in the bone marrow respective lineage. The diagnosis of RT and RN is complicated by several factors. Diagnosing RT first requires exclusion of familial thrombocytopenia, chronic auto-immune thrombocytopenia, concomitant medications, viral infections, or hypersplenism. Diagnosis of RN should also be made after ruling out differential diagnoses such as ethnic or familial neutropenia, as well as acquired, drug-induced, infection-related or malignancy-related neutropenia. An accurate quantification of dysplasia should be performed in order to distinguish RT or RN from the provisional entity named idiopathic cytopenia of unknown significance (ICUS). Cytogenetic analysis, and possibly in the future somatic mutation analysis (of genes most frequently mutated in MDS), and flow cytometry analysis aberrant antigen expression on myeloid cells may help in this differential diagnosis. Importantly, we and others found that, while isolated neutropenia and thrombocytopenia are not rare in MDS, those patients can generally be classified (according to WHO 2008 classification) as refractory cytopenia with multilineage dysplasia or refractory anemia with excess blasts, while RT and RN (according to WHO 2008) are quite rare. These results suggest in particular that identification of RT and RN as distinct entities could be reconsidered in future WHO classification updates. PMID:25745545

  14. Management of medically refractory prolactinoma.

    PubMed

    Molitch, Mark E

    2014-05-01

    Resistance to dopamine agonists is defined here as failure to normalize prolactin levels and failure to decrease macroprolactinoma size by ≥50 %. Failure to normalize prolactin levels is found in about 25 % of patients treated with bromocriptine and 10-15 % of those treated with cabergoline. Failure to achieve at least a 50 % reduction in tumor size occurs in about one-third of those treated with bromocriptine and 10-15 % of those treated with cabergoline. Treatment approaches for patients resistant to dopamine agonists include changing to another dopamine agonist and increasing the dose of the drug as long as there is continued response to the dose increases and no adverse effects with higher doses. Transsphenoidal surgery is also an option. Clomiphene, gonadotropins, and GnRH can be used if fertility is desired. For those not desiring fertility, estrogen replacement may be used unless there is a macroadenoma, in which case control of tumor growth is also an issue and dopamine agonists are generally necessary. In many patients modest or even no reduction in tumor size may be acceptable as long as there is not tumor growth. Hormone replacement [estrogen or testosterone] may cause a decrease in efficacy of the dopamine agonist. Reduction of endogenous estrogen, use of selective estrogen receptor modulators, and aromatase inhibitors are potential experimental approaches. Temozolomide may be useful as a last resort for aggressive, invasive tumors refractory to other medical and ablative therapies.

  15. Refractory Materials for Flame Deflector Protection System Corrosion Control: Flame Deflector Protection System Life Cycle Cost Analysis Report

    NASA Technical Reports Server (NTRS)

    Calle, Luz Marina; Hintze, Paul E.; Parlier, Christopher R.; Coffman, Brekke E.; Kolody, Mark R.; Curran, Jerome P.; Trejo, David; Reinschmidt, Ken; Kim, Hyung-Jin

    2009-01-01

    A 20-year life cycle cost analysis was performed to compare the operational life cycle cost, processing/turnaround timelines, and operations manpower inspection/repair/refurbishment requirements for corrosion protection of the Kennedy Space Center launch pad flame deflector associated with the existing cast-in-place materials and a newer advanced refractory ceramic material. The analysis compared the estimated costs of(1) continuing to use of the current refractory material without any changes; (2) completely reconstructing the flame trench using the current refractory material; and (3) completely reconstructing the flame trench with a new high-performance refractory material. Cost estimates were based on an analysis of the amount of damage that occurs after each launch and an estimate of the average repair cost. Alternative 3 was found to save $32M compared to alternative 1 and $17M compared to alternative 2 over a 20-year life cycle.

  16. Adaptive/non-adaptive proton radiation planning and outcome in a phase II trial for locally advanced non-small cell lung cancer

    PubMed Central

    Koay, Eugene J.; Lege, David; Mohan, Radhe; Komaki, Ritsuko; Cox, James D.; Chang, Joe Y.

    2012-01-01

    Purpose To analyze dosimetric variables and outcomes after adaptive replanning of radiotherapy during concurrent high-dose protons and chemotherapy for locally advanced non-small cell lung cancer (NSCLC). Methods and Materials Nine of 44 patients with stage III NSCLC in a prospective phase II trial of concurrent paclitaxel/carboplatin with proton radiation [74 Gy(RBE) in 37 fractions] had modifications to their original treatment plans after re-evaluation revealed changes that would compromise coverage of the target volume or violate dose constraints; plans for the other 35 patients were not changed. We compared patients with adaptive plans with those with nonadaptive plans in terms of dosimetry and outcomes. Results At a median follow-up of 21.2 months (median overall survival, 29.6 months), no differences were found in local, regional, or distant failure or overall survival between groups. Adaptive planning was used more often for large tumors that shrank to a greater extent (median, 107.1 cm3 adaptive and 86.4 cm3 non-adaptive; median changes in volume, 25.3% adaptive and 1.2% non-adaptive; p<0.01). The median number of fractions delivered using adaptive planning was 13 (range, 4–22). Adaptive planning generally improved sparing of the esophagus (median absolute decrease in V70, 1.8%; range, 0–22.9%) and spinal cord (median absolute change in maximum dose, 3.7 Gy; range, 0–13.8 Gy). Without adaptive replanning, target coverage would have been compromised in 2 cases (57% and 82% coverage without adaptation vs. 100% for both with adaptation); neither patient experienced local failure. Radiation-related grade 3 toxicity rates were similar between groups. Conclusions Adaptive planning can reduce normal tissue doses and prevent target misses, particularly for patients with large tumors that shrink substantially during therapy. Adaptive plans seem to have acceptable toxicity and achieve similar local, regional, and distant control and overall survival, even in

  17. Mesenchymal stromal cells, colony-forming unit fibroblasts, from bone marrow of untreated advanced breast and lung cancer patients suppress fibroblast colony formation from healthy marrow.

    PubMed

    Hofer, Erica Leonor; Labovsky, Vivian; La Russa, Vincent; Vallone, Valeria Fernández; Honegger, Alba Elizabeth; Belloc, Carlos Gabriel; Wen, Huei Chi; Bordenave, Raúl Horacio; Bullorsky, Eduardo Oscar; Feldman, Leonardo; Chasseing, Norma Alejandra

    2010-03-01

    We have shown that bone marrow (BM) from untreated advanced lung and breast cancer patients (LCP and BCP) have a reduced number of colony-forming unit fibroblasts (CFU-Fs) or mesenchymal stem cells (MSCs). Factors that regulate the proliferation and differentiation of CFU-F are produced by the patients' BM microenvironment. We have now examined whether conditioned media (CM) from patients' CFU-F-derived stromal cells also inhibits the colony-forming efficiency (CFE) of CFU-F in primary cultures from healthy volunteers (HV)-BM. Thus the number and proliferation potential of HV-CFU-F were also found to be decreased and similar to colony numbers and colony size of patients' CFU-F. Stromal cells from both of these types of colonies appeared relatively larger and lacked the characteristic spindle morphology typically seen in healthy stromal cells. We developed an arbitrary mesenchymal stromal cell maturational index by taking three measures consisting of stromal cell surface area, longitudinal and horizontal axis. All stromal indices derived from HV-CFU-F grown in patients' CM were similar to those from stromal elements derived from patients' CFU-F. These indices were markedly higher than stromal indices typical of HV-CFU-F cultured in healthy CM or standard medium [alpha-medium plus 20% heat-inactivated fetal bovine serum (FBS)]. Patients' CM had increased concentrations of the CFU-F inhibitor, GM-CSF, and low levels of bFGF and Dkk-1, strong promoters of self-renewal of MSCs, compared to the levels quantified in CM from HV-CFU-F. Moreover, the majority of patients' MSCs were unresponsive in standard medium and healthy CM to give CFU-F, indicating that the majority of mesenchymal stromal cells from patients' CFU-F are locked in maturational arrest. These results show that alterations of GM-CSF, bFGF, and Dkk-1 are associated with deficient cloning and maturation arrest of CFU-F. Defective autocrine and paracrine mechanisms may be involved in the BM microenvironments of

  18. 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

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

    SciTech Connect

    Koay, Eugene J.; Lege, David; Mohan, Radhe; Komaki, Ritsuko; Cox, James D.; Chang, Joe Y.

    2012-12-01

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

  20. Mortality of workers occupationally exposed to refractory ceramic fibers.

    PubMed

    LeMasters, Grace Kawas; Lockey, James E; Yiin, James H; Hilbert, Timothy J; Levin, Linda S; Rice, Carol H

    2003-04-01

    This study was prompted by refractory ceramic fibers (RCF) inhalation studies at high dose levels in animals that demonstrated positive effects for lung fibrosis, mesothelioma, and lung cancer. Current and former male workers employed between 1952 and 2000 at two RCF manufacturing facilities were followed to investigate a possible excess in mortality. The mortality analytic methods included: (1) standardized mortality ratios comparing this cohort to the general and state populations, and (2) a proportional hazards model that relates risk of death to the lifetime cumulative fiber-months/cc exposure among the RCF cohort, adjusted for age at hire and for race. There was no excess mortality related to all deaths, all cancers, or malignancies or diseases of the respiratory system including mesothelioma, but there was a statistically significant association with cancers of the urinary organs SMR = 344.8 (95% CL of 111.6, 805.4). The quality of the data for job history, exposure, and smoking history were very high. Although the cohort was relatively small and young with an average age of 51, the mean latency period was over 21 years. Because of these limitations, the preliminary findings warrant the continuation of this mortality registry for future analyses.

  1. Lung transplant

    MedlinePlus

    Solid organ transplant - lung ... the new lung Have severe disease of other organs Cannot reliably take their medicines Are unable to ... medicines Damage to your kidneys, liver, or other organs from anti-rejection medicines Future risk of certain ...

  2. Lung surgery

    MedlinePlus

    ... Pneumonectomy; Lobectomy; Lung biopsy; Thoracoscopy; Video-assisted thoracoscopic surgery; VATS ... You will have general anesthesia before surgery. You will be asleep and unable to feel pain. Two common ways to do surgery on your lungs are thoracotomy and video- ...

  3. ALK positivity on pleuroscopic pleural biopsy in lung adenocarcinoma.

    PubMed

    Vaidya, Preyas J; Kate, Arvind H; Mehta, Deval; Dhabar, Boman N; Chhajed, Prashant N

    2016-01-01

    Lung cancer is the leading cause of cancer deaths worldwide, and around 75% to 80% of lung cancers are detected in advanced stage. Multiple genetic mutations are identified and reported in adenocarcinoma of the lung. Various pulmonary samples can be tested for molecular mutations in lung cancer. However, feasibility of molecular profiling of pleuroscopic pleural biopsies in lung adenocarcinoma is not reported. We describe a case of advanced adenocarcinoma of lung with positive anaplastic lymphoma tyrosine kinase mutation on pleuroscopic pleural biopsy and improved with oral crizotinib. The current case highlights the feasibility of pleuroscopy.-guided pleural biopsies in molecular profiling of lung adenocarcinoma. PMID:27461706

  4. The microbiome and the lung.

    PubMed

    Cui, Lijia; Morris, Alison; Huang, Laurence; Beck, James M; Twigg, Homer L; von Mutius, Erika; Ghedin, Elodie

    2014-08-01

    Investigation of the human microbiome has become an important field of research facilitated by advances in sequencing technologies. The lung, which is one of the latest body sites being explored for the characterization of human-associated microbial communities, has a microbiome that is suspected to play a substantial role in health and disease. In this review, we provide an overview of the basics of microbiome studies. Challenges in the study of the lung microbiome are highlighted, and further attention is called to the optimization and standardization of methodologies to explore the role of the lung microbiome in health and disease. We also provide examples of lung microbial communities associated with disease or infection status and discuss the role of fungal species in the lung. Finally, we review studies demonstrating that the environmental microbiome can influence lung health and disease, such as the finding that the diversity of microbial exposure correlates inversely with the development of childhood asthma.

  5. Development and Evaluation of a Lung Cancer Screening Decision Aid.

    PubMed

    Hart, Katelyn; Tofthagen, Cindy; Wang, Hsiao-Lan

    2016-10-01

    Lung cancer is the second most common cancer; however, it often is not diagnosed until the advanced stages. Early-stage lung cancer is curable, but screening tools are not usually implemented in practice because of a lack of provider awareness. A lung cancer screening decision aid may increase screening use and, ultimately, reduce lung cancer deaths.
. PMID:27668377

  6. Rational use of refractories in regenerator checkers

    SciTech Connect

    Popov, O.N.; Borovkova, L.B.; Izosenkova, A.V.; Shatova, N.P.

    1985-09-01

    The thermal efficiency of regenerators in glass furnaces depends on the rational choice of the checker system and the refractory materials used in their construction. In order to develop practical recommendations for the rational use of refractories in checkers for sheet glass, container, and medical-glass furnaces, the authors carried out an all-around investigation of the resistance of aluminosilicate and magnesia refractories in laboratory conditions, modelling the actual service conditions of the material in the checkers. Magnesite, ordinary MO-89, compressed magnesite MU-91, magnesitechromite ordinary, MKhSO, periclase-spinel ordinary, PShSO, forsterite F, unfired magnesite-chromite BMKh, chamotte ShN-38, and highalumina DV-12 were selected as refractories. The use in checkers of magnesia refractories, bearing in mind their corrosion resistance, and with the elimination of the factors in the damaging action, will enable one to ensure prolonged service for the checkers without carrying out hot repairs during the campaign of furnaces producing sheet, container, and medical glasses.

  7. Identification of platelet refractoriness in oncohematologic patients

    PubMed Central

    Ferreira, Aline Aparecida; Zulli, Roberto; Soares, Sheila; de Castro, Vagner; Moraes-Souza, Helio

    2011-01-01

    OBJECTIVES: To identify the occurrence and the causes of platelet refractoriness in oncohematologic patients. INTRODUCTION: Platelet refractoriness (unsatisfactory post-transfusion platelet increment) is a severe problem that impairs the treatment of oncohematologic patients and is not routinely investigated in most Brazilian services. METHODS: Forty-four episodes of platelet concentrate transfusion were evaluated in 16 patients according to the following parameters: corrected count increment, clinical conditions and detection of anti-platelet antibodies by the platelet immunofluorescence test (PIFT) and panel reactive antibodies against human leukocyte antigen class I (PRA-HLA). RESULTS: Of the 16 patients evaluated (median age: 53 years), nine (56%) were women, seven of them with a history of pregnancy. An unsatisfactory increment was observed in 43% of the transfusion events, being more frequent in transfusions of random platelet concentrates (54%). Platelet refractoriness was confirmed in three patients (19%), who presented immunologic and non-immunologic causes. Alloantibodies were identified in eight patients (50%) by the PIFT and in three (19%) by the PRA-HLA. Among alloimmunized patients, nine (64%) had a history of transfusion, and three as a result of pregnancy (43%). Of the former, two were refractory (29%). No significant differences were observed, probably as a result of the small sample size. CONCLUSION: The high rate of unsatisfactory platelet increment, refractoriness and alloimmunization observed support the need to set up protocols for the investigation of this complication in all chronically transfused patients, a fundamental requirement for the guarantee of adequate management. PMID:21437433

  8. Fecal Microbiota Transplantation for Refractory Clostridium difficile Colitis in Solid Organ Transplant Recipients

    PubMed Central

    Friedman-Moraco, R. J.; Mehta, A. K.; Lyon, G. M.; Kraft, C. S.

    2015-01-01

    Fecal microbiota transplantation (FMT) has been shown to be safe and efficacious in individuals with refractory Clostridium difficile . It has not been widely studied in individuals with immunosuppression due to concerns about infectious complications. We describe two solid organ transplant recipients, one lung and one renal, in this case report that both had resolution of their diarrhea caused by C. difficile after FMT. Both recipients required two FMTs to achieve resolution of their symptoms and neither had infectious complications. Immunosuppressed individuals are at high risk for acquisition of C. difficile and close monitoring for infectious complications after FMT is necessary, but should not preclude its use in patients with refractory disease due to C. difficile . Sequential FMT may be used to achieve cure in these patients with damaged microbiota from antibiotic use and immunosuppression. PMID:24433460

  9. Fecal microbiota transplantation for refractory Clostridium difficile colitis in solid organ transplant recipients.

    PubMed

    Friedman-Moraco, R J; Mehta, A K; Lyon, G M; Kraft, C S

    2014-02-01

    Fecal microbiota transplantation (FMT) has been shown to be safe and efficacious in individuals with refractory Clostridium difficile. It has not been widely studied in individuals with immunosuppression due to concerns about infectious complications. We describe two solid organ transplant recipients, one lung and one renal, in this case report that both had resolution of their diarrhea caused by C. difficile after FMT. Both recipients required two FMTs to achieve resolution of their symptoms and neither had infectious complications. Immunosuppressed individuals are at high risk for acquisition of C. difficile and close monitoring for infectious complications after FMT is necessary, but should not preclude its use in patients with refractory disease due to C. difficile. Sequential FMT may be used to achieve cure in these patients with damaged microbiota from antibiotic use and immunosuppression.

  10. MicroRNA-related single-nucleotide polymorphism of XPO5 is strongly correlated with the prognosis and chemotherapy response in advanced non-small-cell lung cancer patients.

    PubMed

    Geng, Ji-Qun; Wang, Xiao-Chen; Li, Long-Fei; Zhao, Jun; Wu, Song; Yu, Gui-Ping; Zhu, Kou-Jun

    2016-02-01

    This study was performed to investigate if the microRNA-related single-nucleotide polymorphisms (miR-SNPs) of XPO5 gene predicted the prognosis and pathological features of advanced non-small-cell lung cancer patients receiving chemotherapy. A total of 131 advanced non-small-cell lung cancer (NSCLC) patients were recruited. MicroRNA (miRNA) binding site prediction software was adopted for the prediction and screening of SNPs in XPO5 and miRNA binding regions. Polymerase chain reaction (PCR) amplification was further performed. Time-dependent survival-free curves were constructed using the Kaplan-Meier technique. Univariate and the multivariate survival analyses were conducted for confirmation of prognostic factor for advanced NSCLC patients receiving chemotherapy. There were no significant differences of SNP distribution frequencies between groups, without statistical significance (P > 0.05). Included clinical pathological features and chemotherapy regimens showed no apparent statistical significance in influencing the curative effect of chemotherapy in advanced NSCLC patients (all P > 0.05). While the objective response rate (ORR) in patients who carried AA and AC genotype was 35.48 and 51.22 %, respectively, with statistically significant difference (P < 0.05). Univariate survival analysis indicated that patients who carried AA genotype showed a significantly lower 5-year survival rate to those who carried AC genotype (P < 0.05). And, considering pathological features, statistical significance was found in patients with different pathological types, lymph node metastasis, differentiation degree, T staging, and pathological staging (all P < 0.05). Multivariate analysis results indicated that the SNP sites of rs11077 might be an independent prognostic factor of advanced NSCLC patients receiving chemotherapy (risk ratio [RR] = 0.346; 95 % confidence interval [95 % CI] = 0.174-0.685, P = 0.002). Other clinical features were all

  11. Refractory Behaviors of Magnetite-Kaolin Bricks

    NASA Astrophysics Data System (ADS)

    Adeosun, S. O.; Akpan, E. I.; Gbenebor, O. P.; Taiwo, O. O.; Eke, I. J.

    2016-09-01

    In this work, the suitability of using kaolin-magnetite-plastic clay to produce refractory bricks has been experimentally explored. Thirty bricks of different compositions were produced and fired at 1200°C. The density, shrinkage moisture content, loss on ignition, porosity and permeability of the bricks were examined. Results show that the bricks remained stable during firing and thus possess good insulating characteristics. The highest (2.23 g/cm3) and lowest (2.00 g/cm3) bulk densities obtained in this study are higher than the highest bulk density reported for Al dross-filled refractories (1.23 g/cm3). The bricks also possessed very low effective moisture content (10-23%) and very high compression modulus (16-100 MPa) desirable in insulating refractory bricks with high resistance to abrasion.

  12. Lenalidomide in Treating Young Patients With Relapsed or Refractory Solid Tumors or Myelodysplastic Syndromes

    ClinicalTrials.gov

    2014-06-10

    Childhood Myelodysplastic Syndromes; de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Refractory Anemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Ringed Sideroblasts; Refractory Cytopenia With Multilineage Dysplasia; Secondary Myelodysplastic Syndromes; Unspecified Childhood Solid Tumor, Protocol Specific

  13. Fluoxetine in tricyclic refractory major depressive disorder.

    PubMed

    Beasley, C M; Sayler, M E; Cunningham, G E; Weiss, A M; Masica, D N

    1990-11-01

    Data regarding open-label treatment with fluoxetine following failure to respond to tricyclic antidepressants (TCAs) or intolerance of TCA side effects, suggest a response rate between 51.4% and 62.1%, depending on the definition of TCA refractoriness employed. Double-blind study of this issue would extend these findings. Fluoxetine is well tolerated in patients unable to tolerate TCAs. Within this population, more than 80% of patients unable to tolerate TCAs found fluoxetine acceptable. Fluoxetine, as an alternative to polypharmaceutical augmentation, may represent a logical choice as the next step in therapy for a patient who has initially been treated with a TCA and has proven refractory or intolerant.