Determination of essential biomarkers in lung cancer: a real-world data study in Spain with demographic, clinical, epidemiological and pathological characteristics

Artículo escrito por un elevado número de autores, sólo se referencia el que aparece en primer lugar y los autores pertenecientes a la UAMThe survival of patients with lung cancer has substantially increased in the last decade by about 15%. This increase is, basically, due to targeted therapies available for advanced stages and the emergence of immunotherapy itself. This work aims to study the situation of biomarker testing in Spain. The Thoracic Tumours Registry (TTR) is an observational, prospective, registry-based study that included patients diagnosed with lung cancer and other thoracic tumours, from September 2016 to 2020. This TTR study was sponsored by the Spanish Lung Cancer Group (GECP) Foundation, an independent, scientific, multidisciplinary oncology society that coordinates more than 550 experts and 182 hospitals across the Spanish territory. Nine thousand two hundred thirty-nine patients diagnosed with stage IV non-small cell lung cancer (NSCLC) between 2106 and 2020 were analysed. 7,467 (80.8%) were non-squamous and 1,772 (19.2%) were squamous. Tumour marker testing was performed in 85.0% of patients with non-squamous tumours vs 56.3% in those with squamous tumours (p-value < 0.001). The global testing of EGFR, ALK, and ROS1 was 78.9, 64.7, 35.6% respectively, in non-squamous histology. PDL1 was determined globally in the same period (46.9%), although if we focus on the last 3 years it exceeds 85%. There has been a significant increase in the last few years of all determinations and there are even close to 10% of molecular determinations that do not yet have targeted drug approval but will have it in the near future. 4,115 cases had a positive result (44.5%) for either EGFR, ALK, KRAS, BRAF, ROS1, or high PDL1. Despite the lack of a national project and standard protocol in Spain that regulates the determination of biomarkers, the situation is similar to other European countries. Given the growing number of different determinations and their high positivity, national strategies are urgently needed to implement next-generation sequencing (NGS) in an integrated and cost-effective way in lung cancerThis study was supported by the European Union Horizon 2020 Research and Innovation Program under grant agreement n° 875160 CLARIFY projec

Liquid fuels from biomass: An energy self-sustained process integrating H2 recovery and liquid refining

[EN] In the last years the research activities on biomass valorisation (mainly residues from urban and agricultural activities) have been intensified. Biomass is an abundant resource for energy generation and its extensive utilization may make possible to fulfil the goals determined by the national and international regulations about renewable sources and greenhouse gas emissions. In this work, simulations are carried out using ASPEN PLUS for an integrated process to produce liquid fuels from biomass in a self-sustainable energetic regime (thermal and electric) and several process factors have been considered. The process initially combines a primary pyrolysis reactor associated to a (char + gases) gasification unit in order to optimize the biomass use, followed by downstream processes to enhance the quality of final liquid fuel. The factors studied were the composition of the biomass, the primary (or pyrolytic) liquid yield, the composition of the liquid fuel, as well as the amount of the oxidant and steam used in the primary char-gasifier reactor. The use of a simplified model for liquid fuel composition let us to stablish a range of operational conditions in which both thermal and electric balance of the process are favourable. In this sense, the maximum extraction of liquid fuel was found around 20-25% by working at 10-25% of O-2 (as pure oxygen or air) and 15-45% of steam in the gasifier and fulfilling self-sustainable process condition, while biomass should possess C/O weight ratios >= 1.Financial support by the Spanish Government (ENE2014-57651, CTQ2015-67592, and SEV-2016-0683 grants) is gratefully acknowledged.D. Catalán-Martínez; Domine ., ME.; Serra Alfaro, JM. (2018). Liquid fuels from biomass: An energy self-sustained process integrating H2 recovery and liquid refining. Fuel. 212:353-363. https://doi.org/10.1016/j.fuel.2017.10.014S35336321

Characterization and Distillation of Pyrolysis Liquids Coming from Polyolefins Segregated of MSW for Their Use as Automotive Diesel Fuel

This document is the Accepted Manuscript version of a Published Work that appeared in final form in Energy & Fuels, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://doi.org/10.1021/acs.energyfuels.0c00403.[EN] The liquids resulting from pyrolysis of industrial plastic waste (IPW) and postconsumer colored and white plastic film waste (PCPW and PWPW, respectively) at the pilot scale (80 kg/h) were widely characterized by different techniques to assess their potential as both petrochemical raw material and automotive diesel fuel. It was found that pyrolysis liquids mainly consisted of hydrocarbons in the diesel boiling point range (180-380 degrees C), amounting to approximately 50-55 vol %. Therefore, the results were further contrasted with limits established by the EN 590:2014 + A1:2017 standard for automotive diesel fuel. Although pyrolysis liquids showed good properties, they do not conform to some key fuel parameters for diesel engines, such as density, distillation curve, kinematic viscosity, flash point, and cold filter plugging point. To improve these properties, PWPW pyrolysis liquids were distilled in the diesel range and the liquid fractions were characterized according to automotive diesel standards. It was found that the diesel fraction met all specifications with the exception of the cold filter plugging point (-10 to 4 degrees C vs -10 degrees C winter/0 degrees C summer) and density (800-807 vs 820 kg/m(3)). To accomplish these standards, a blend of diesel obtained from PWPW pyrolysis liquids and commercial diesel (50/50 wt %) was also prepared and analyzed. Results revealed that the blend met the requirements of the 21 parameters demanded by the standard for a product to be marketed and used as automotive fuel in diesel engine vehicles.The authors acknowledge the financial support of the Centre for the Development of Industrial Technology (grant number IDI-20150730) and the Ministerio de Ciencia, Innovacion y Universidades (Spain) (grant number DI-16-08700).Gala, A.; Guerrero, M.; Guirao, B.; Domine, ME.; Serra Alfaro, JM. (2020). Characterization and Distillation of Pyrolysis Liquids Coming from Polyolefins Segregated of MSW for Their Use as Automotive Diesel Fuel. Energy & Fuels. 34(5):5969-5982. https://doi.org/10.1021/acs.energyfuels.0c00403S59695982345Al-Salem, S. M., Lettieri, P., & Baeyens, J. (2009). Recycling and recovery routes of plastic solid waste (PSW): A review. Waste Management, 29(10), 2625-2643. doi:10.1016/j.wasman.2009.06.004Hestin, M.; Faninger, T.; Milios, L. 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Real Decreto 61/2006 de 31 de enero de 2006, por el que se determinan las especificaciones de gasolinas, gasóleos, fuelóleos y gases licuados del petróleo y se regula el uso de determinados biocarburantes. BOE núm. 41. Reference: BOE-A-2006-2779, 2006. https://www.boe.es/buscar/act.php?id=BOE-A-2006-2779 (accessed July 18, 2019).Spain. Real Decreto 1088/2010, de 3 de septiembre, por el que se modifica el Real Decreto 61/2006, de 31 de enero, en lo relativo a las especificaciones de gasolinas, gasóleos, utilización de biocarburantes y contenido en azufre de los combustibles para uso marítimo. BOE núm. 215. Reference: BOE-A-2010-13704, 2010. https://www.boe.es/buscar/doc.php?id=BOE-A-2010-13704 (accessed July 18, 2019).Min, K., Valco, D. J., Oldani, A., Kim, K., Temme, J., Kweon, C.-B. M., & Lee, T. (2019). Autoignition of varied cetane number fuels at low temperatures. 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Addition of Immune Checkpoint Inhibitors to Chemotherapy vs Chemotherapy Alone as First-Line Treatment in Extensive-Stage Small-Cell Lung Carcinoma: A Systematic Review and Meta-Analysis

Introduction The addition of immune checkpoint inhibitors (ICIs) to conventional chemotherapy (CT) as first-line treatment improves survival in extensive-stage small-cell lung cancer (ES-SCLC). The aim of this meta-analysis was to determine the relative efficacy of first-line ICIs compared with CT in patients with ES-SCLC. Methods Two independent reviewers extracted relevant data according to PRISMA guidelines and assessed the risk of bias using the Cochrane Collaboration's risk-of-bias tool. Meta-analysis was conducted using random-effects models to calculate an average effect size for overall survival (OS), progression-free survival (PFS), and safety outcomes in the overall populations and clinically relevant subgroups. Results A literature search of PubMed and Embase was performed. Six randomized controlled clinical trials (IMpower133, CHECKMATE-451, CASPIAN, KEYNOTE-604, and phase II and III ipilimumab plus CT trials) with a total of 3757 patients were included. Compared with CT alone, ICIs plus CT showed a favourable effect on OS (hazard ratio [HR] 0.85; 95% confidence intervals [CI] 0.79–0.96) and PFS (HR 0.78; 95% CI 0.72–0.83) but a non-significant increase in the risk of experiencing any adverse event (relative risk, 1.05; 95% CI 0.99–1.11). The estimated HR for OS favoured ICI combinations in all planned subgroups according to age (< 65 years/≥ 65 years), sex (men/women), and ECOG performance status (0/1). Analysis by specific ICI revealed significant improvements in OS only for atezolizumab + CT (HR 1.36; 95% CI 1.09–1.69) and durvalumab + CT (HR 1.35; 95% CI 1.12–1.62) compared with CT alone. Conclusion Combining anti-programmed cell death ligand 1 antibodies with platinum/etoposide is a superior therapeutic approach compared to CT alone for the first-line treatment of patients with ES-SCLC

Upgrading of oxygenated compounds present in aqueous biomass-derived feedstocks over NbOx-based catalysts

[EN] The influence of synthesis and post-synthesis procedures of different niobium oxides on their catalytic performance in the aqueous phase condensation of oxygenated compounds is studied. Hydrothermally synthesized niobium oxide with a pseudo-crystalline structure shows enhanced acid properties, surface area and consequently better catalytic activity than Nb2O5 prepared by other synthesis methods. The optimized NbOx-based catalyst also demonstrates higher stability after several reuses compared to the Ce-Zr mixed oxide reference catalyst.Financial support by the Spanish Government (CTQ-2015-67592, CTQ-2015-68951-C3-1, and SEV-2012-0267) is gratefully acknowledged. A. F.-A. and D. D. thank the "La Caixa-Severo Ochoa" Foundation and the Severo Ochoa Excellence Program (SVP-2014-068669), respectively, for their fellowships. Authors also thank the Electron Microscopy Service of Universitat Politecnica de Valencia for their supportFernandez-Arroyo, A.; Delgado-Muñoz, D.; Domine, ME.; López Nieto, JM. (2017). Upgrading of oxygenated compounds present in aqueous biomass-derived feedstocks over NbOx-based catalysts. Catalysis Science & Technology. 7(23):5495-5499. https://doi.org/10.1039/c7cy00916jS54955499723Huber, G. W., Iborra, S., & Corma, A. (2006). Synthesis of Transportation Fuels from Biomass:  Chemistry, Catalysts, and Engineering. Chemical Reviews, 106(9), 4044-4098. doi:10.1021/cr068360dTuck, C. O., Perez, E., Horvath, I. T., Sheldon, R. A., & Poliakoff, M. (2012). Valorization of Biomass: Deriving More Value from Waste. Science, 337(6095), 695-699. doi:10.1126/science.1218930Huber, G. W., & Corma, A. (2007). Synergies between Bio- and Oil Refineries for the Production of Fuels from Biomass. Angewandte Chemie International Edition, 46(38), 7184-7201. doi:10.1002/anie.200604504Alonso, D. M., Bond, J. Q., & Dumesic, J. A. (2010). Catalytic conversion of biomass to biofuels. Green Chemistry, 12(9), 1493. doi:10.1039/c004654jPinheiro, A., Hudebine, D., Dupassieux, N., & Geantet, C. (2009). Impact of Oxygenated Compounds from Lignocellulosic Biomass Pyrolysis Oils on Gas Oil Hydrotreatment. Energy & Fuels, 23(2), 1007-1014. doi:10.1021/ef800507zBui, V. N., Toussaint, G., Laurenti, D., Mirodatos, C., & Geantet, C. (2009). Co-processing of pyrolisis bio oils and gas oil for new generation of bio-fuels: Hydrodeoxygenation of guaïacol and SRGO mixed feed. Catalysis Today, 143(1-2), 172-178. doi:10.1016/j.cattod.2008.11.024Asadieraghi, M., Wan Daud, W. M. A., & Abbas, H. F. (2014). Model compound approach to design process and select catalysts for in-situ bio-oil upgrading. Renewable and Sustainable Energy Reviews, 36, 286-303. doi:10.1016/j.rser.2014.04.050Cherubini, F., Jungmeier, G., Wellisch, M., Willke, T., Skiadas, I., Van Ree, R., & de Jong, E. (2009). Toward a common classification approach for biorefinery systems. Biofuels, Bioproducts and Biorefining, 3(5), 534-546. doi:10.1002/bbb.172Gaertner, C. A., Serrano-Ruiz, J. C., Braden, D. J., & Dumesic, J. A. (2009). Catalytic coupling of carboxylic acids by ketonization as a processing step in biomass conversion. Journal of Catalysis, 266(1), 71-78. doi:10.1016/j.jcat.2009.05.015Omata, K., Matsumoto, K., Murayama, T., & Ueda, W. (2016). Direct oxidative transformation of glycerol to acrylic acid over Nb-based complex metal oxide catalysts. Catalysis Today, 259, 205-212. doi:10.1016/j.cattod.2015.07.01

Reflux-synthesized bulk and diluted W-Nb-O mixed oxide bronzes for the valorization of short-chain oxygenates aqueous mixtures

[EN] This work reports the preparation of bulk and KIT-6-diluted W-Nb-O mixed oxide bronzes by a reflux method. The influence of the incorporation of Nb and a mesoporous silica on the physicochemical features of the catalysts is studied. The addition of Nb favors the formation of single-phase oxide bronze structure, with improved Lewis acidity; while the incorporation of KIT-6 gives rise to well-dispersed mixed metal oxide particles on the diluter. These diluted W-Nb-O catalysts present enhanced surface areas and mesopore volumes. The materials have been tested in the valorization of an aqueous model mixture (acetol/propanal/ethanol/acetic acid/water weight ratio of 5/25/10/30/30), through C-C bond formation reactions. The increase in the Lewis nature of surface acid sites stands as the key point to maximize the total organic yield during the reaction (Cs-Cio products). The best catalysts maintain their catalytic behavior after five consecutive uses.Financial support by the Spanish Government (RT12018-099668-B-C21, PGC2018-097277-B-100, and SEV-2016-0683) is gratefully acknowledged. DD and AF-A thank the Severo Ochoa Excellence Program (SVP-2014-068669) and the "La Caixa-Severo Ochoa" Foundation, respectively, for their fellowships. NS thanks "Conselho Nacional de Desenvolvimento Cientifico y Tecnologico (CNPq)" in Brasil. Authors are also grateful to the Electron Microscopy Service (Universitat Politecnica de Valencia) for facilities.Delgado-Muñoz, D.; Fernández-Arroyo, A.; La Salvia, N.; Domine, ME.; López Nieto, JM. (2019). Reflux-synthesized bulk and diluted W-Nb-O mixed oxide bronzes for the valorization of short-chain oxygenates aqueous mixtures. Chinese Journal of Catalysis. 40(11):1778-1787. https://doi.org/10.1016/S1872-2067(19)63419-4S17781787401

The specific surface area and chemical composition of diamond dust near Barrow, Alaska

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/95687/1/jgrd17349.pd

Prospective Exploratory Analysis of Angiogenic Biomarkers in Peripheral Blood in Advanced NSCLC Patients Treated With Bevacizumab Plus Chemotherapy: The ANGIOMET Study

[EN] Finding angiogenic prognostic markers in advanced non-small-cell lung cancer is still an unmet medical need. We explored a set of genetic variants in the VEGF-pathway as potential biomarkers to predict clinical outcomes of patients with non-small-cell lung cancer treated with chemotherapy plus bevacizumab. We prospectively analyzed the relationship between VEGF-pathway components with both pathological and prognostic variables in response to chemotherapy plus bevacizumab in 168 patients with non-squamous non-small-cell lung cancer. Circulating levels of VEGF and VEGFR2 and expression of specific endothelial surface markers and single-nucleotide polymorphisms in VEGF-pathway genes were analyzed. The primary clinical endpoint was progression-free survival. Secondary endpoints included overall survival and objective tumor response. VEGFR-1 rs9582036 variants AA/AC were associated with increased progression-free survival (p = 0.012 and p = 0.035, respectively), and with improved overall survival (p = 0.019) with respect to CC allele. Patients with VEGF-A rs3025039 harboring allele TT had also reduced mortality risk (p = 0.049) compared with the CC allele. The VEGF-A rs833061 variant was found to be related with response to treatment, with 61.1% of patients harboring the CC allele achieving partial treatment response. High pre-treatment circulating levels of VEGF-A were associated with shorter progression-free survival (p = 0.036). In conclusion, in this prospective study, genetic variants in VEGFR-1 and VEGF-A and plasma levels of VEGF-A were associated with clinical benefit, progression-free survival, or overall survival in a cohort of advanced non-squamous non-small-cell lung cancer patients receiving chemotherapy plus antiangiogenic therapy.The authors thank Drs. Blanca Piedrafita and Vanessa Marfil at Medical Statistics Consulting for medial writing services. RR also wish to acknowledge the support by the Asociacion Espanola Contra el Cancer (AECC).Jantus-Lewintre, E.; Massuti Sureda, B.; Gonzalez Larriba, JL.; Rodríguez-Abreu, D.; Juan, O.; Blasco, A.; Domine, M.... (2021). Prospective Exploratory Analysis of Angiogenic Biomarkers in Peripheral Blood in Advanced NSCLC Patients Treated With Bevacizumab Plus Chemotherapy: The ANGIOMET Study. Frontiers in Oncology. 11:1-11. https://doi.org/10.3389/fonc.2021.695038S1111

Nivolumab versus docetaxel in previously treated advanced non-small-cell lung cancer (CheckMate 017 and CheckMate 057): 3-year update and outcomes in patients with liver metastases

Abstract Background Long-term data with immune checkpoint inhibitors in non-small-cell lung cancer (NSCLC) are limited. Two phase III trials demonstrated improved overall survival (OS) and a favorable safety profile with the anti-programmed death-1 antibody nivolumab versus docetaxel in patients with previously treated advanced squamous (CheckMate 017) and nonsquamous (CheckMate 057) NSCLC. We report results from ≥3 years' follow-up, including subgroup analyses of patients with liver metastases, who historically have poorer prognosis among patients with NSCLC. Patients and methods Patients were randomized 1 : 1 to nivolumab (3 mg/kg every 2 weeks) or docetaxel (75 mg/m2 every 3 weeks) until progression or discontinuation. The primary end point of each study was OS. Patients with baseline liver metastases were pooled across studies by treatment for subgroup analyses. Results After 40.3 months' minimum follow-up in CheckMate 017 and 057, nivolumab continued to show an OS benefit versus docetaxel: estimated 3-year OS rates were 17% [95% confidence interval (CI), 14% to 21%] versus 8% (95% CI, 6% to 11%) in the pooled population with squamous or nonsquamous NSCLC. Nivolumab was generally well tolerated, with no new safety concerns identified. Of 854 randomized patients across both studies, 193 had baseline liver metastases. Nivolumab resulted in improved OS compared with docetaxel in patients with liver metastases (hazard ratio, 0.68; 95% CI, 0.50–0.91), consistent with findings from the overall pooled study population (hazard ratio, 0.70; 95% CI, 0.61–0.81). Rates of treatment-related hepatic adverse events (primarily grade 1–2 liver enzyme elevations) were slightly higher in nivolumab-treated patients with liver metastases (10%) than in the overall pooled population (6%). Conclusions After 3 years' minimum follow-up, nivolumab continued to demonstrate an OS benefit versus docetaxel in patients with advanced NSCLC. Similarly, nivolumab demonstrated an OS benefit versus docetaxel in patients with liver metastases, and remained well tolerated. Clinical trial registration CheckMate 017: NCT01642004; CheckMate 057: NCT01673867