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1. Randomized open-label controlled study of cancer vaccine OSE2101 versus chemotherapy in HLA-A2-positive patients with advanced non-small-cell lung cancer with resistance to immunotherapy: ATALANTE-1

Author

Zemanová, M., Besse, B., Bonnet, C., Cadranel, J., Chouaid, C., Cortot, A., Debieuvre, D., Delclaux, B., Denis, F., Duchemann, B., El Kouri, C., Ferrand, F.R., Ginoux, M., Hilgers, W., Madroszyk, A., Masson, P., Mazieres, J., Molinier, O., Moro-Sibilot, D., Pichon, E., Mascaux, C., Robinet, G., Roch, B., Zalcman, G., Schmidtke-Schrezenmeier, G., Schuette, W., Urban, L., Gottfried, M., Nechushtan, H., Peled, N., Wollner, M., Zer, A., Baldini, E., Bonanno, L., Bonetti, A., Cappuzzo, F., Delmonte, A., Galetta, D., Maio, M., Minotti, V., Rea, A., Romano, G., Tassinari, D., Tonini, G., Dziadziuszko, R., Karaszewska, B., Szczęsna, A., Cobo, M., De Castro, J., Felip, E., Garcia Campelo, M.R., Hernández, A., Moran, T., Provencio, M., Viteri, S., Dasgupta, A., Gabrail, N., Giaccone, G., Harshad, A., Liu, S., Oubre, D., Panikkar, R., Razaq, M., Sanborn, R., Garcia Campelo, R., Remon, J., Costantini, D., and Vasseur, B.

Published
2023
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5. Nanotechnology boosts the production of clean energy via nanoparticle addition in anaerobic digestion

Author

de Castro, J. Cunha, Resende, E., Taveira, Igor, Enrich Prast, Alex, Abreu, F., de Castro, J. Cunha, Resende, E., Taveira, Igor, Enrich Prast, Alex, and Abreu, F.

Abstract

Biogas production via anaerobic digestion is an established and robust technology that produces energy and recycles nutrients. Several biotechnological attempts have been applied to this process to increase biogas production, including adding nanoparticles, but several discrepancies have been reported. To elucidate the contradictory results, we performed a literature review followed by a meta-analysis to evaluate the effect of adding natural nanoparticles to biogas sludge. Our results showed that adding nanoparticles can increase biogas production by up to two orders of magnitude. Considering that, we attribute these results to variability in the nanoparticles applied, leading to less reliable, consistent, and even contradictory results. We observed that the magnetite nanoparticles are the most tested ones with the most promising positive effects. In addition, we observed that concentrations of nanoparticles higher than 100 mg/L can have adverse effects, with an overall decrease in biogas production. The findings in this study highlight the need for a proper characterization of the nanomaterials type and concentration applied to the process to understand the interactions and effects on the microbial communities and dynamics that lead to an overall increase or decrease in biogas yield., Funding Agencies|Linkpings Universitet10.13039/501100003945; CNPq; CAPES; FAPERJ

Published
2024
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6. Cumulative Distribution Functions as Hysteresis Models.

Author

DE CAMPOS, M. F. and DE CASTRO, J. A.

Subjects
*CUMULATIVE distribution function, *DISTRIBUTION (Probability theory), *MAGNETIC noise, *SYMMETRIC functions, *GAUSSIAN function
Abstract

The cumulative distribution functions can be used as the basis for hysteresis models. Here it is de- scribed how, using only 3 parameters, including one representing the shape, hysteresis curves can be constructed using symmetric distribution functions. The model is useful in the interpretation of magnetic Barkhausen noise data. The model also has a clear physical meaning because it represents the distribution of coercivity inside the sample. An isotropic Stoner-Wohlfarth hysteresis was partially modelled by a three-parameter cumulative distribution function of Gaussian hysteresis for the 1st and 3rd quadrants. Asymmetric distributions will provide better hysteresis adjustment, but these are four- parameter models. [ABSTRACT FROM AUTHOR]

Published
2024
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7. Clinical utility of plasma-based digital next-generation sequencing in patients with advance-stage lung adenocarcinomas with insufficient tumor samples for tissue genotyping

Author

Zugazagoitia, J., Ramos, I., Trigo, J.M., Palka, M., Gómez-Rueda, A., Jantus-Lewintre, E., Camps, C., Isla, D., Iranzo, P., Ponce-Aix, S., García-Campelo, R., Provencio, M., Franco, F., Bernabé, R., Juan-Vidal, O., Felip, E., de Castro, J., Sanchez-Torres, J.M., Faul, I., Lanman, R.B., Garrido, P., and Paz-Ares, L.

Published
2019
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8. Effects of Resistance Training with Blood Flow Restriction on Muscle Strength and Biomarkers in Older People: A Systematic Review of Randomized Clinical Trials

Author

Gama Linhares, D., primary, de Souza Alves, A., additional, Almeida Barreto, Y., additional, Brito Narciso, O., additional, de Souza Filho, A.V., additional, Gonçalves Cardozo, G., additional, Gomes da Costa, M., additional, Brandão Pinto de Castro, J., additional, and Gomes de Souza Vale, R., additional

Published
2023
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9. P2.14-01 Patient-Reported Outcomes from IMfirst: Chemotherapy Plus Atezolizumab in a Real-World Setting of Extensive-Stage SCLC

Author

Dómine Gómez, M., primary, Cobo Dols, M., additional, de Castro, J., additional, Moreno Vega, A., additional, Ponce Aix, S., additional, Arriola, E., additional, Carcereny, E., additional, Majem Tarruella, M., additional, Huidobro Vence, G., additional, Esteban González, E., additional, Fuentes Pradera, J., additional, Ortega Granados, A.L., additional, Guillot Morales, M., additional, Massuti Sureda, B., additional, Vilà, L., additional, Blasco Cordellat, A., additional, Fajardo, C.A., additional, Crama, L., additional, Lerones, N., additional, and García Campelo, R., additional

Published
2023
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10. P2.14-04 Treatment Beyond Progression with Atezolizumab in Extensive-Stage SCLC: Exploratory Analysis from the IMfirst Study

Author

García-Campelo, R., primary, Dómine Gómez, M., additional, de Castro, J., additional, Moreno Vega, A., additional, Ponce Aix, S., additional, Arriola, E., additional, Carcereny, E., additional, Majem Tarruella, M., additional, Huidobro Vence, G., additional, Esteban González, E., additional, Fuentes Pradera, J., additional, Ortega Granados, A.L., additional, Guillot Morales, M., additional, Massuti Sureda, B., additional, Vilà, L., additional, Blasco Cordellat, A., additional, Fajardo, C.A., additional, Crama, L., additional, Lerones, N., additional, and Cobo Dols, M., additional

Published
2023
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11. P1.27-07 BRAF Mutations Identify Non-small-Cell Lung Cancer Patients Who Benefit from Neoadjuvant Chemo-Immunotherapy

Author

Robado de Lope, L., primary, Nadal, E., additional, Calvo, V., additional, González-Larriba, J.L., additional, Insa, A., additional, Martinez-Marti, A., additional, Massutí, B., additional, González, C., additional, Serna Blasco, R., additional, Bosch-Barrera, J., additional, Garcia-Campelo, M.R., additional, Ponce, S., additional, Reguart, N., additional, Bernabé, R., additional, Cobo, M., additional, De Castro, J., additional, Dómine, M., additional, Camps, C., additional, Barneto, I., additional, López-Vivanco, G., additional, Majem, M., additional, Rodríguez-Abreu, D., additional, Palmero, R., additional, Cruz-Bermudez, A., additional, Romero, A., additional, and Provencio, M., additional

Published
2023
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12. Risk of detecting prostate cancer based on the PSAD and PIRADS lesions in MRI in patients with a negative previous biopsy.

Author

Gonzalez De Gor Garcia Herrera, V., primary, Aragón Chamizo, J., additional, Herranz Del Amo, F., additional, Barbas Bernardo, G., additional, Luis Cardo, A., additional, Cancho Gil, M.J, additional, Sánchez Ochoa, M.A., additional, Bataller Monfort, V., additional, Moreno Cortés, J.C., additional, Cano Velasco, J., additional, Mayor De Castro, J., additional, and Hernández Fernández, C., additional

Published
2023
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13. Quality of life in patients with Non-Muscle Invasive Bladder Cancer (NMIBC) subjected to intravesical instillations with BCG induction

Author

Cano Velasco, J., primary, Moreno Cortés, J.C., additional, Lafuente Puentedura, A., additional, Polanco Pujol, L., additional, Subiela Henriquez, J.D., additional, Aragón Chamizo, J., additional, Mayor de Castro, J., additional, Pastor Cordero, A., additional, Herranz Amo, F., additional, and Hernández Fernández, C., additional

Published
2023
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14. Randomized open-label controlled study of cancer vaccine OSE2101 versus chemotherapy in HLA-A2-positive patients with advanced non-small-cell lung cancer with resistance to immunotherapy: ATALANTE-1

Author

Besse, B., primary, Felip, E., additional, Garcia Campelo, R., additional, Cobo, M., additional, Mascaux, C., additional, Madroszyk, A., additional, Cappuzzo, F., additional, Hilgers, W., additional, Romano, G., additional, Denis, F., additional, Viteri, S., additional, Debieuvre, D., additional, Galetta, D., additional, Baldini, E., additional, Razaq, M., additional, Robinet, G., additional, Maio, M., additional, Delmonte, A., additional, Roch, B., additional, Masson, P., additional, Schuette, W., additional, Zer, A., additional, Remon, J., additional, Costantini, D., additional, Vasseur, B., additional, Dziadziuszko, R., additional, Giaccone, G., additional, Zemanová, M., additional, Besse, B., additional, Bonnet, C., additional, Cadranel, J., additional, Chouaid, C., additional, Cortot, A., additional, Delclaux, B., additional, Duchemann, B., additional, El Kouri, C., additional, Ferrand, F.R., additional, Ginoux, M., additional, Mazieres, J., additional, Molinier, O., additional, Moro-Sibilot, D., additional, Pichon, E., additional, Zalcman, G., additional, Schmidtke-Schrezenmeier, G., additional, Urban, L., additional, Gottfried, M., additional, Nechushtan, H., additional, Peled, N., additional, Wollner, M., additional, Bonanno, L., additional, Bonetti, A., additional, Minotti, V., additional, Rea, A., additional, Tassinari, D., additional, Tonini, G., additional, Karaszewska, B., additional, Szczęsna, A., additional, De Castro, J., additional, Garcia Campelo, M.R., additional, Hernández, A., additional, Moran, T., additional, Provencio, M., additional, Dasgupta, A., additional, Gabrail, N., additional, Harshad, A., additional, Liu, S., additional, Oubre, D., additional, Panikkar, R., additional, and Sanborn, R., additional

Published
2023
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18. Ovidian verses in El licenciado Vidriera

Author

Castro de Castro, J. David and Castro de Castro, J. David

Abstract

In El licenciado Vidriera we find three Latin quotations from Ovid. From the editio princeps (1613) onwards, those verses have appeared in editions up to the present day with different formulations. We explain those verses’ textual history in the Latin editions of Ovid. We also review the history of the textual conformations of these verses in the editions of El licenciado Vidriera from the princeps to our days, explaining the strategies used by the different editors. Finally, we offer our own proposal and explain that Cervantes takes these texts from a work by Tomaso Garzoni entitled Piazza Universale di tutte le professioni del mondo., En El licenciado Vidriera encontramos tres citas en latín de Ovidio. Desde la editio princeps (1613) hasta nuestros días esos versos han aparecido en las ediciones con distintas formulaciones. Explicamos la historia textual de esos versos en las ediciones latinas de Ovidio. Repasamos también la historia de las conformaciones textuales de estos versos en las ediciones de El licenciado Vidriera desde la princeps a nuestros días, explicando las estrategias utilizadas por los distintos editores. Ofrecemos, finalmente, nuestra propia propuesta y explicamos que Cervantes toma estos textos de una obra de Tomaso Garzoni titulada Piazza Universale di tutte le professioni del mondo.

Published
2023

21. PP01.17 Sotorasib in Advanced KRAS p.G12C–Mutated NSCLC with Treated or Untreated Brain Metastases: Safety and Efficacy Data from the Global Expanded Access Program (EAP)

Author

Awad, M.M., primary, Pelizzari, G., additional, Stevenson, J., additional, Majem, M., additional, Gil Ferreira, C., additional, Petty, W., additional, Arriola, E., additional, De Castro, J., additional, Morbeck, I., additional, Bauman, J., additional, Toschi, L., additional, Zer, A., additional, Metro, G., additional, Kalmadi, S., additional, Azkárate, A., additional, Xia, C., additional, Meloni, A., additional, Obiozor, C., additional, Hsu, H., additional, Varrieur, T., additional, Ardito-Abraham, C., additional, Maimon, N., additional, and Novello, S., additional

Published
2023
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23. Costs of adverse events associated with erlotinib or afatinib in first-line treatment of advanced EGFR-positive non-small cell lung cancer

Author

Isla D, De Castro J, Juan O, Grau S, Orofino J, Gordo R, Rubio-Terrés C, and Rubio-Rodríguez D

Subjects
adverse event, afatinib, cost-analysis, erlotinib, non-small-cell lung cancer., Medicine (General), R5-920, Therapeutics. Pharmacology, RM1-950
Abstract

Dolores Isla,1 Javier De Castro,2 Oscar Juan,3 Santiago Grau,4 Javier Orofino,5 Rocío Gordo,5 Carlos Rubio-Terrés,6 Darío Rubio-Rodríguez6 1Medical Oncology Department, Clinical Universitary Hospital Lozano Blesa, Zaragoza, 2Medical Oncology Department, Universitary Hospital La Paz, Madrid, 3Medical Oncology Department, Universitary and Polytechnic Hospital La Fe, Valencia, 4Pharmacy Department, Del Mar Hospital, Barcelona, 5Roche Farma, S.A., Health Economics, 6Health Value, Health Economics, Madrid, Spain Objectives: Epidermal growth factor receptor–tyrosine kinase inhibitors (EGFR-TKIs) are an established treatment for advanced non-small cell lung cancer (NSCLC) with EGFR mutation. According to published meta-analyses, no significant efficacy differences have been demonstrated between erlotinib and afatinib. However, the incidence of EGFR–TKI-related adverse events (AEs) was lower with erlotinib. This study compares the cost of management of the AEs associated with these two drugs from the perspective of the Spanish National Health System (NHS).Methods: The frequency of AEs was established from a recently published meta-analysis. In Spain, the daily cost of both drugs can be considered similar; as a result, only the costs of management of the AEs were considered. Costs and resource utilization in the management of the AEs were estimated by a panel of Spanish oncologists and from studies previously carried out in Spain. A probabilistic analysis was performed based on a Monte Carlo simulation.Results: The model generated 1,000 simulations. The total cost per patient treated with erlotinib and afatinib was €657.44 and €1,272.15, respectively. With erlotinib, the cost per patient and per AE of grades ≤2 and ≥3 was €550.86 and €106.58, respectively, whereas the cost with afatinib was €980.63 and €291.52, respectively. The reduction in the number of AEs with erlotinib could avoid a mean cost for the NHS of €614.71 (95% CI: €342.57–881.29) per patient.Conclusion: In advanced EGFR mutation-positive NSCLC patients, first-line treatment with erlotinib could reduce health care costs for the NHS, due to a decrease in the AE rate compared with afatinib. In long-term treatments, the avoidance of complications and the lowering of costs associated with the management of AEs are relevant factors that contribute to the sustainability of the health system. Keywords: adverse event, afatinib, cost analysis, erlotinib, non-small cell lung cancer

Published
2016

24. EE495 Cost-Effectiveness Analysis of Adjuvant Atezolizumab Versus Best Supportive Care in the Treatment of Patients With Resectable Early-Stage Non-Small Cell Lung Cancer and PD-L1≥50% Expression

Author

Escudero, V, primary, Collado, R, additional, de Castro, J, additional, Insa, A, additional, Martínez, A, additional, Fernández, E, additional, Sullivan, I, additional, Flores, A, additional, Arrabal, N, additional, Carcedo, D, additional, and Manzaneque, A, additional

Published
2022
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26. Basal characteristics of the prospective spanish immunotherapy registry of cardiovascular toxicity: SIR-CVT

Author

Zatarain-Nicolas, E, primary, Perez-Ramirez, S, additional, De Castro, J, additional, Martin-Garcia, A, additional, Del Barco, E, additional, Mesa Rubio, D, additional, De La Haba, J, additional, Martinez Monzonis, M A, additional, Aguin Losada, S, additional, Lozano Palencia, T, additional, Martinez-Banaclocha, N, additional, Gomez-Rubin, M C, additional, Cortez-Castedo, P, additional, Martin, P, additional, and Lopez-Fernandez, T, additional

Published
2022
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27. Design of a Competitive and Collaborative Learning Strategy in a Communication Networks Course

Author

Regueras, L. M., Verdu, E., Verdu, M. J., and de Castro, J. P.

Abstract

In this paper, an educational methodology based on collaborative and competitive learning is proposed. The suggested approach has been successfully applied to an undergraduate communication networks course, which is part of the core curriculum of the three-year degree in telecommunications engineering at the University of Valladolid in Spain. This methodology is supported by two tools: the Moodle wiki for the collaborative part and a competitive learning tool called QUESTOURnament, which has been created by the authors to encourage the development of students' inquiry, documentation, and critical analysis skills while raising the level of involvement and communication between students and teachers. This paper describes how the collaborative and competitive approaches were combined and how the activities were ordered in phases. This educational proposal has been validated with academic outcomes and students' feedback. (Contains 6 tables and 2 figures.)

Published
2011
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28. PL03.12 Progression Free Survival and Overall Survival in NADIM II Study

Author

Provencio, M., primary, Serna, R., additional, Nadal, E., additional, Glez Larriba, J.L., additional, Martínez-Martí, A., additional, Bernabé, R., additional, Bosch-Barrera, J., additional, Garcia Benito, C., additional, Calvo, V., additional, Insa, A., additional, Ponce, S., additional, Reguart, N., additional, De Castro, J., additional, Massutí, B., additional, Palmero, R., additional, Aguado de la Rosa, C., additional, Mosquera, J., additional, Cobo, M., additional, Aguilar, A., additional, López Vivanco, G., additional, Camps, C., additional, Hernando Trancho, F., additional, López Castro, R., additional, Moran, T., additional, Barneto, I., additional, Rodríguez-Abreu, D., additional, and Romero, A., additional

Published
2022
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29. EP08.02-131 Alectinib after Crizotinib Failure in Patients with Advanced ALK-Positive NSCLC: Results from the Spanish Early Access Program

Author

Bernabé-Caro, R., primary, García-Campelo, R., additional, Garrido, P., additional, Palmero, R., additional, Artal, Á., additional, Bayona, C., additional, Rodríguez-Abreu, D., additional, López-Brea, M., additional, Paredes, A., additional, Vicente, D., additional, Sánchez Torres, J.M., additional, Majem, M., additional, Diz, P., additional, Gordo, R., additional, Coca, M., additional, and de Castro, J., additional

Published
2022
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30. MA06.03 Pre-treatment ctDNA Levels Significantly Predicts of OS and PFS in NADIM II Trial

Author

Romero, A., primary, Serna, R., additional, Nadal, E., additional, Larriba, J.L. Glez, additional, Martínez-Martí, A., additional, Bernabé, R., additional, Bosch-Barrera, J., additional, Fernandez, A. Garrido, additional, Calvo, V., additional, Insa, A., additional, Ponce, S., additional, Reguart, N., additional, De Castro, J., additional, Massutí, B., additional, Palmero, R., additional, Aguado de la Rosa, C., additional, Mosquera, J., additional, Cobo, M., additional, Aguilar, A., additional, Vivanco, G. López, additional, Camps, C., additional, Trancho, F. Hernando, additional, Castro, R. Lopez, additional, Moran, T., additional, Barneto, I., additional, Rodríguez-Abreu, D., additional, Cruz, A., additional, and Provencio, M., additional

Published
2022
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31. 989P Sotorasib in advanced KRAS p.G12C-mutated non-small cell lung cancer (NSCLC): Safety and efficacy data from the global expanded access program (EAP)

Author

Awad, M., primary, Pelizzari, G., additional, Stevenson, J.P., additional, Majem Tarruella, M., additional, Ferreira, C.G.M., additional, Petty, W.J., additional, Arriola, E., additional, de Castro, J., additional, Morbeck, I., additional, Bauman, J.R., additional, Toschi, L., additional, Zer, A., additional, Metro, G., additional, Kalmadi, S., additional, Azkárate Martínez, A., additional, Xia, C., additional, Meloni, A., additional, Obiozor, C., additional, Maimon, N., additional, and Novello, S., additional

Published
2022
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32. P2.07-02 RET Fusion Testing with FISH and Real-Time PCR: a Comparison with RNA-Based Next-Generation Sequencing in RET Positive NSCLC

Author

Hernandez, S., primary, Rodriguez Carrillo, J.L., additional, Caminoa, A., additional, Benito, A., additional, Martinez, R., additional, Alonso, M., additional, Clave, S., additional, Arriola, E., additional, Esteban-Rodriguez, I., additional, De Castro, J., additional, Sansano, I., additional, Felip, E., additional, Abdulkader, I., additional, Garcia, J., additional, Rojo, F., additional, Domine, M., additional, Teixido, C., additional, Reguart, N., additional, Compañ, D., additional, Insa, A., additional, Mancheño, N., additional, Palanca, S., additional, Juan, O., additional, Baixeras, N., additional, Nadal, E., additional, Cebollero, M., additional, Calles, A., additional, Martin, P., additional, Salas, C., additional, Provencio, M., additional, Aranda, I., additional, Massuti, B., additional, Lopez-Vilaro, L., additional, Majem, M., additional, Garrido, P., additional, Paz-Ares, L., additional, Lopez-Rios, F., additional, and Conde, E., additional

Published
2022
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34. Revision of TD1 and TD2 stratigraphic sequence of Gran Dolina cave (Sierra de Atapuerca, Spain)

Author

Universitat Rovira i Virgili, Campana, I; Benito-Calvo, A.; Perez-Gonzalez, A.; Alvaro-Gallo, A.; Miguens-Rodriguez, L.; Iglesias-Cibanal, J.; Bermudez de Castro, J. M.; Carbonell, E., Universitat Rovira i Virgili, and Campana, I; Benito-Calvo, A.; Perez-Gonzalez, A.; Alvaro-Gallo, A.; Miguens-Rodriguez, L.; Iglesias-Cibanal, J.; Bermudez de Castro, J. M.; Carbonell, E.

Abstract

Gran Dolina is a cavity infilled by at least 25 m of Pleistocene sediments divided into 12 lithostratigraphic units and 19 sedimentary facies. These sedimentary facies have been divided into allochthonous facies, defined as sediment inputs from the outside, and autochthonous facies, defined as sediments generated within the karst; but this division has been challenged in recent works. In this study, TD1 and TD2 units of Gran Dolina have been detailed studied and the use of autochthonous facies has been assessed. For that purpose, we have studied the stratigraphic excavation profile, combining field observation with laboratory sedimentary analysis (sieving, laser diffraction, and XRD) to characterize the texture and structure of the sediments. Based on these studies, a total of 8 sedimentary facies have been identified. Consequently, TD1 unit has been separated into two sub-units and 13 layers, while the TD2 unit has been divided into three sub-units. The facies associations indicate a succession of phreatic and vadose phases that would define together epiphreatic conditions inside the cave, related to the transition between Arlanzon valley terraces T3 and T4. Interior facies (and entrance facies for allochthonous facies) is proposed to define Gran Dolina's sediments since the facies analyses indicate transport by underground flows.

Published
2022

35. 32P Impact of smoking status on the relative efficacy of the EGFR TKI/angiogenesis inhibitor combination therapy in advanced NSCLC: A systematic review and meta-analysis

Author

Dafni, U., primary, Soo, R.A., additional, Peters, S., additional, Tsourti, Z., additional, Vervita, K., additional, Han, J-Y., additional, De Castro, J., additional, Coate, L., additional, Früh, M., additional, Hashemi, S.M.S., additional, Nadal, E., additional, Carcereny, E., additional, Angeles Sala González, M., additional, Bernabé Caro, R., additional, Provencio Pulla, M., additional, Cuffe, S., additional, Ruepp, B., additional, Roschitzki-Voser, H., additional, Rosell, R., additional, and Stahel, R.A., additional

Published
2022
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36. A Reply to Otterbein

Author

Carbonell, E., Cáceres, I., Lozano, M., Saladié, P., Rosell, J., Lorenzo, C., Vallverdú, J., Huguet, R., Canals, A., and Bermúdez de Castro, J. M.

Published
2011
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37. A randomised phase II study of osimertinib and bevacizumab versus osimertinib alone as second-line targeted treatment in advanced NSCLC with confirmed EGFR and acquired T790M mutations: the European Thoracic Oncology Platform (ETOP 10-16) BOOSTER trial

Author

Sooy, R. A. Han, J. -Y. Dafni, U. Cho, B. C. Yeo, C. M. and Nadal, E. Carcereny, E. de Castro, J. Sala, M. A. and Bernabe, R. Coate, L. Provencio Pulla, M. Campelo, R. Garcia and Cuffe, S. Hashemi, S. M. S. Fruh, M. Massuti, B. and Garcia-Sanchez, J. Domine, M. Majem, M. Sanchez-Torres, J. -M. Britschgi, C. Pless, M. Dimopoulou, G. and Roschitzki-Voser, H. Ruepp, B. Rosell, R. Stahel, R. A. and Peters, S. ETOP 10-16 BOOSTER Collaborators

Abstract

Background: While osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) is the standard treatment in patients with advanced non-small-cell lung cancer (NSCLC) with sensitising EGFR and acquired T790M mutations, progression inevitably occurs. The angiogenic pathway is implicated in EGFR TKI resistance. Patients and methods: BOOSTER is an open-label randomised phase II trial investigating the efficacy and safety of combined osimertinib 80 mg daily and bevacizumab 15 mg/kg every 3 weeks, versus osimertinib alone, in patients with EGFR-mutant advanced NSCLC and acquired T790M mutations after failure on previous EGFR TKI therapy. Primary endpoint was investigator-assessed progression-free survival (PFS). Secondary endpoints were overall survival (OS), objective response rate (ORR) and adverse events (AEs). Results: Between May 2017 and February 2019, 155 patients were randomised (combination: 78; osimertinib: 77). At data cut-off of 22 February 2021, median follow-up was 33.8 months [interquartile range (IQR): 26.5-37.6 months] and 129 (83.2%) PFS events were reported in the intention-to-treat population. There was no difference in median PFS between the combination [15.4 months; 95% confidence interval (CI) 9.2-18.0 months] and osimertinib arm (12.3 months; 95% CI 6.2-17.2 months; stratified log-rank P = 0.83), [hazard ratio (HR) = 0.96; 95% CI 0.68-1.37]. Median OS was 24.0 months (95% CI 17.8- 32.1 months) in the combination arm and 24.3 months (95% CI 16.9-37.0 months) in the osimertinib arm (stratified log-rank P = 0.91), (HR = 1.03; 95% CI 0.67-1.56). Exploratory analysis revealed a significant interaction of smoking history with treatment for PFS (adjusted P = 0.0052) with a HR of 0.52 (95% CI 0.30-0.90) for smokers, and 1.47 (95% CI 0.92-2.33) for never smokers. ORR was 55% in both arms and the median time to treatment failure was significantly shorter in the combination than in the osimertinib arm, 8.2 months versus 10.8 months, respectively (P = 0.0074). Safety of osimertinib and bevacizumab was consistent with previous reports with grade >= 3 treatment-related AEs (TRAEs) reported in 47% and 18% of patients on combination and osimertinib alone, respectively. Conclusions: No difference in PFS was observed between osimertinib plus bevacizumab and osimertinib alone. Grade >= 3 TRAEs were more common in patients on combination.

Published
2022

39. A randomised phase II study of osimertinib and bevacizumab versus osimertinib alone as second-line targeted treatment in advanced NSCLC with confirmed EGFR and acquired T790M mutations: the European Thoracic Oncology Platform (ETOP 10-16) BOOSTER trial

Author

Soo, R.A., primary, Han, J.-Y., additional, Dafni, U., additional, Cho, B.C., additional, Yeo, C.M., additional, Nadal, E., additional, Carcereny, E., additional, de Castro, J., additional, Sala, M.A., additional, Bernabé, R., additional, Coate, L., additional, Provencio Pulla, M., additional, Garcia Campelo, R., additional, Cuffe, S., additional, Hashemi, S.M.S., additional, Früh, M., additional, Massuti, B., additional, Garcia-Sanchez, J., additional, Dómine, M., additional, Majem, M., additional, Sanchez-Torres, J.-M., additional, Britschgi, C., additional, Pless, M., additional, Dimopoulou, G., additional, Roschitzki-Voser, H., additional, Ruepp, B., additional, Rosell, R., additional, Stahel, R.A., additional, Peters, S., additional, Stahel, Rolf, additional, Peters, Solange, additional, Soo, Ross, additional, Han, Ji-Youn, additional, Früh, Martin, additional, Provencio, Mariano, additional, Coate, Linda, additional, Dafni, Urania, additional, Hiltbrunner, Anita, additional, Ruepp, Barbara, additional, Roschitzki-Voser, Heidi, additional, Gasca-Ruchti, Adriana, additional, Giacomelli, Nino, additional, Kammler, Rosita, additional, Marti, Nesa, additional, Nobs, Lionel, additional, Pardo-Contreras, Mariana, additional, Pfister, Rita, additional, Piguet, Anne-Christine, additional, Ribeli-Hofmann, Sabrina, additional, Martinez, Virginia Rodriguez, additional, Roux, Susanne, additional, Sanchez-Hohl, Magdalena, additional, Schneider, Mirjam, additional, Schweri, Robin, additional, Troesch, Sandra, additional, Zigomo, Isabel, additional, Tsourti, Zoi, additional, Zygoura, Panagiota, additional, Kassapian, Marie, additional, Vervita, Katerina, additional, Dimopoulou, Georgia, additional, Andriakopoulou, Charitini, additional, Fernandez, Maria, additional, Pereira, Eva, additional, Simona, Carolina, additional, Tucker, Lisa, additional, Burnes, Jillian, additional, Barrett, Aisling, additional, McGrillen, Meghan, additional, Berset, Catherine, additional, Biaggi, Christine, additional, Reist, Martin, additional, Rentsch, Priska, additional, Cuffe, Sinead, additional, Hashemi, Sayed, additional, Nadal, Ernest, additional, Carcereny, Enric, additional, de Castro, Javier, additional, Sala, Maria Angeles, additional, Reyes, Bernabé, additional, Pulla, Mariano Provencio, additional, Campelo, Rosario Garcia, additional, Massutí, Bartomeu, additional, Garcia, Jose, additional, Dómine, Manuel, additional, Majem, Margarita, additional, Sanchez, Jose Miguel, additional, Britschgi, Christian, additional, Pless, Miklos, additional, Yeo, Chong Ming, additional, and Cho, Byoung Chul, additional

Published
2022
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41. VP3-2021: A randomized phase II study of second-line osimertinib (Osi) and bevacizumab (Bev) versus Osi in advanced non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) and T790M mutations (mt): Results from the ETOP BOOSTER trial

Author

Soo, R., Han, J-Y., Dimopoulou, G., Cho, B.C., Yeo, C.M., Nadal, E., Carcereny, E., de Castro, J., Sala, M.A., Bernabe, R., Coate, L., Provencio, M., Campelo, R. Garcia, Cuffe, S., Hashemi, S., Früh, M., Ruepp, B., Roschitzki-Voser, H., Stahel, R., and Peters, S.

Published
2021
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44. OA20.02 Pre-Treatment Levels of ctDNA for Long-Term Survival Prediction in Stage IIIA NSCLC Treated With Neoadjuvant Chemo-Immunotherapy

Author

Romero, A., primary, Nadal, E., additional, Serna, R., additional, Insa, A., additional, Campelo, M.R. García, additional, Benito, C., additional, Domine, M., additional, Majem, M., additional, Abreu, D. Rodriguez, additional, Martinez-Marti, A., additional, De Castro, J., additional, Cobo, M., additional, Vivanco, G. López, additional, Del Barco, E., additional, Bernabé, R., additional, Viñolas, N., additional, Barneto, I., additional, Viteri, S., additional, Pereira, E., additional, Royuela, A., additional, Casarrubios, M., additional, Calvo, V., additional, Laza - Briviesca, R., additional, Massuti, B., additional, Cruz, A., additional, Sánchez-Herrero, E., additional, and Provencio, M., additional

Published
2021
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45. MA14.02 RET Fusion Testing in Advanced Non-Small Cell Lung Carcinoma Patients: the RETING Study

Author

Conde, E., primary, Hernandez, S., additional, Caminoa, A., additional, Benito, A., additional, Martinez, R., additional, Alonso, M., additional, Jimenez, B., additional, Boni, V., additional, Remon, J., additional, Pijuan, L., additional, Clave, S., additional, Arriola, E., additional, Esteban, I., additional, De Castro, J., additional, Sansano, I., additional, Felip, E., additional, Abdulkader, I., additional, Garcia, J., additional, Rojo, F., additional, Domine, M., additional, Teixido, C., additional, Reguart, N., additional, Compañ, D., additional, Insa, A., additional, Mancheño, N., additional, Palanca, S., additional, Juan, O., additional, Baixeras, N., additional, Nadal, E., additional, Cebollero, M., additional, Calles, A., additional, Martin, P., additional, Salas, C., additional, Provencio, M., additional, Aranda, I., additional, Massuti, B., additional, Lopez-Vilaro, L., additional, Majem, M., additional, Enguita, A.B., additional, Paz-Ares, L., additional, Garrido, P., additional, and Lopez-Rios, F., additional

Published
2021
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46. OA20.01 Long Term Survival in Operable Stage Iiia Nsclc Patients Treated With Neoadjuvant Nivolumab Plus Chemotherapy - Nadim Study

Author

Provencio, M., primary, Nadal, E., additional, Insa, A., additional, Campelo, M.R. García, additional, Pereiro, D., additional, Domine, M., additional, Majem, M., additional, Abreu, D. Rodriguez, additional, Martinez-Marti, A., additional, De Castro, J., additional, Cobo, M., additional, Vivanco, G. López, additional, Del Barco, E., additional, Bernabé, R., additional, Viñolas, N., additional, Barneto, I., additional, Viteri, S., additional, Pereira, E., additional, Royuela, A., additional, Casarrubios, M., additional, Salas, C., additional, Parra, E.R., additional, Wistuba, I., additional, Calvo, V., additional, Laza - Briviesca, R., additional, Romero, A., additional, Massuti, B., additional, and Cruz, A., additional

Published
2021
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47. LETTERS

Author

Lott, John R., Kundrat, Frank, Yu, Cristina, Harris, Richard K., Short, J. Lindsey, Reynolds, Glenn Harlan, Mencher, Bruce S., McPherson, Bob, Ludden, Karen Libertiny, Foster, Wilson Jerry, de Castro, J. Edmund, and Woolery, Benjamin J.

Published
1998

48. The role of Food Safety Agencies in the evaluation, communication and management of risks associated with microplastics in food

Author

Rubio-Armendáriz, C., Daschner, A., González Fandos, E., González Muñoz, M.J., Moreno-Arribas, V., Talens Oliag, P., and Bustos García de Castro, J.

Abstract

A scientific report based on solid scientific data has been published by AESAN Identifying the most relevant dietary sources of microplastics, knowing the occurrence of the different molecules and polymers and their relevance in terms of exposure will contribute to focus future research projects, regulatory initiatives and monitoring programs. It is the interest of AESAN to promote research on MP and NP in the food supply and contribute to fill the identified knowledge gaps. Toxicokinetic; biomarkers of exposure; toxicity in experimental animals/models like acute toxicity, repeat dose and chronic toxicity; mode of action of the different MP and the observations in humans (Acute and Chronic effects); health based guidance values (dose response models and selection of critical reference points) Assessing the Spanish population dietary exposure to MP should be a challenge for our Food Safety experts and networking among the research groups should be promoted through our national food agencies and EFSA.

Published
2021

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

Author

Jantus-Lewintre, E, Sureda, BM, Larriba, JLG, Rodriguez-Abreu, D, Juan, O, Blasco, A, Domine, M, Pulla, MP, Garde, J, Alvarez, R, Maestu, I, de Carrion, RP, Artal, A, Rolfo, C, de Castro, J, Guillot, M, Oramas, J, de las Penas, R, Ferrera, L, Martinez, N, Serra, O, Rosell, R, Camps, C, and Grp Espanol Canc Pulmon GECP

Subjects
0301 basic medicine, Oncology, Cancer Research, Prognostic variable, medicine.medical_specialty, Bevacizumab, medicine.medical_treatment, Vasodilatadors, BIOLOGIA CELULAR, NSCLC, 03 medical and health sciences, angiogenesis, 0302 clinical medicine, Internal medicine, medicine, Clinical endpoint, Allele, Liquid biopsy, Lung cancer, Prospective cohort study, RC254-282, Original Research, Chemotherapy, liquid biopsy, business.industry, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Vasodilators, biomarkers, medicine.disease, VEGF, 030104 developmental biology, 030220 oncology & carcinogenesis, Càncer de pulmó, business, medicine.drug
Abstract

[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).

Published
2021

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