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1. MET exon 14 skipping mutations in non-small-cell lung cancer: real-world data from the Italian biomarker ATLAS database

Author

Reale, M.L., Passiglia, F., Cappuzzo, F., Minuti, G., Occhipinti, M., Bulotta, A., Delmonte, A., Sini, C., Galetta, D., Roca, E., Pelizzari, G., Cortinovis, D., Gariazzo, E., Pilotto, S., Citarella, F., Bria, E., Muscolino, P., Pozzessere, D., Carta, A., Pignataro, D., Calvetti, L., Leone, F., Banini, M., Di Micco, C., Baldini, E., Favaretto, A., Malapelle, U., Novello, S., Pasello, G., and Tiseo, M.

Published
2024
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2. Activity of osimeRTInib in non-small-cell lung Cancer with UNcommon epidermal growth factor receptor mutations: retrospective Observational multicenter study (ARTICUNO)

Author

Pizzutilo, E.G., Agostara, A.G., Oresti, S., Signorelli, D., Stabile, S., Lauricella, C., Motta, V., Amatu, A., Ruggieri, L., Brambilla, M., Occhipinti, M., Proto, C., Giusti, R., Filetti, M., Genova, C., Barletta, G., Gelsomino, F., Bennati, C., Siringo, M., Di Fazio, G.R., Russano, M., Montrone, M., Gariazzo, E., Roca, E., Bordi, P., Delmonte, A., Scimone, A., Belluomini, L., Mazzoni, F., Carta, A., Pelizzari, G., Viscardi, G., Morgillo, F., Gelibter, A., Gori, S., Berardi, R., Cortinovis, D., Ardizzoni, A., Veronese, S.M., Sartore-Bianchi, A., Giannetta, L.G., Cerea, G., and Siena, S.

Published
2024
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4. Evaluation of COVID-19 impact on DELAYing diagnostic-therapeutic pathways of lung cancer patients in Italy (COVID-DELAY study): fewer cases and higher stages from a real-world scenario

Author

Cantini, L., Mentrasti, G., Russo, G.L., Signorelli, D., Pasello, G., Rijavec, E., Russano, M., Antonuzzo, L., Rocco, D., Giusti, R., Adamo, V., Genova, C., Tuzi, A., Morabito, A., Gori, S., Verde, N. La, Chiari, R., Cortellini, A., Cognigni, V., Pecci, F., Indini, A., De Toma, A., Zattarin, E., Oresti, S., Pizzutilo, E.G., Frega, S., Erbetta, E., Galletti, A., Citarella, F., Fancelli, S., Caliman, E., Della Gravara, L., Malapelle, U., Filetti, M., Piras, M., Toscano, G., Zullo, L., De Tursi, M., Di Marino, P., D’Emilio, V., Cona, M.S., Guida, A., Caglio, A., Salerno, F., Spinelli, G., Bennati, C., Morgillo, F., Russo, A., Dellepiane, C., Vallini, I., Sforza, V., Inno, A., Rastelli, F., Tassi, V., Nicolardi, L., Pensieri, V., Emili, R., Roca, E., Migliore, A., Galassi, T., Rocchi, M. L. Bruno, and Berardi, R.

Published
2022
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5. Sotorasib in KRASp.G12C mutated advanced NSCLC: Real-world data from the Italian expanded access program

Author

Passiglia, F, Lucia Reale, M, Lo Russo, G, Pasello, G, Minuti, G, Bulotta, A, Galetta, D, Pelizzari, G, Sini, C, Bria, E, Roca, E, Pilotto, S, Genova, C, Metro, G, Citarella, F, Chiari, R, Cortinovis, D, Delmonte, A, Russo, A, Tiseo, M, Cerea, G, Carta, A, Scotti, V, Vavalà, T, Brambilla, M, Buffoni, L, Buosi, R, Catania, C, Gori, S, Grisanti, S, Agustoni, F, Garbo, E, Malapelle, U, Novello, S, Passiglia, Francesco, Lucia Reale, Maria, Lo Russo, Giuseppe, Pasello, Giulia, Minuti, Gabriele, Bulotta, Alessandra, Galetta, Domenico, Pelizzari, Giacomo, Sini, Claudio, Bria, Emilio, Roca, Elisa, Pilotto, Sara, Genova, Carlo, Metro, Giulio, Citarella, Fabrizio, Chiari, Rita, Cortinovis, Diego, Delmonte, Angelo, Russo, Alessandro, Tiseo, Marcello, Cerea, Giulio, Carta, Annamaria, Scotti, Vieri, Vavalà, Tiziana, Brambilla, Marta, Buffoni, Lucio, Buosi, Roberta, Catania, Chiara, Gori, Stefania, Grisanti, Salvatore, Agustoni, Francesco, Garbo, Edoardo, Malapelle, Umberto, Novello, Silvia, Passiglia, F, Lucia Reale, M, Lo Russo, G, Pasello, G, Minuti, G, Bulotta, A, Galetta, D, Pelizzari, G, Sini, C, Bria, E, Roca, E, Pilotto, S, Genova, C, Metro, G, Citarella, F, Chiari, R, Cortinovis, D, Delmonte, A, Russo, A, Tiseo, M, Cerea, G, Carta, A, Scotti, V, Vavalà, T, Brambilla, M, Buffoni, L, Buosi, R, Catania, C, Gori, S, Grisanti, S, Agustoni, F, Garbo, E, Malapelle, U, Novello, S, Passiglia, Francesco, Lucia Reale, Maria, Lo Russo, Giuseppe, Pasello, Giulia, Minuti, Gabriele, Bulotta, Alessandra, Galetta, Domenico, Pelizzari, Giacomo, Sini, Claudio, Bria, Emilio, Roca, Elisa, Pilotto, Sara, Genova, Carlo, Metro, Giulio, Citarella, Fabrizio, Chiari, Rita, Cortinovis, Diego, Delmonte, Angelo, Russo, Alessandro, Tiseo, Marcello, Cerea, Giulio, Carta, Annamaria, Scotti, Vieri, Vavalà, Tiziana, Brambilla, Marta, Buffoni, Lucio, Buosi, Roberta, Catania, Chiara, Gori, Stefania, Grisanti, Salvatore, Agustoni, Francesco, Garbo, Edoardo, Malapelle, Umberto, and Novello, Silvia

Abstract

Background: Sotorasib showed a significant improvement of progression free survival (PFS), safety and quality of life over docetaxel in patients with KRASp.G12C-mutated advanced non-small-cell lung cancer (NSCLC) within the CodeBreak-200 study. Here we report real-world efficacy and tolerability data from NSCLC patients who received sotorasib within the Italian expanded access program (EAP). Methods: Sotorasib (960 mg, orally, once daily) was available on physician request for KRASp.G12C mutant advanced NSCLC patients. Clinical-pathological and molecular data were collected from the Italian ATLAS real-world registry. Patients underwent CT-scan and responses were evaluated by RECIST criteria. Efficacy and tolerability outcomes have been assessed. Results: A total of 196 advanced NSCLC patients were treated across 30 Italian centers. Median age was 69 years old (range 33-86). Most patients were male (61 %), former (49 %) or current smokers (43 %), with ECOG-PS 0/1 (84 %) and adenocarcinoma subtype (90 %). 45 % and 32 % of patients received sotorasib in 2nd and 3rd line, respectively. Overall, response rate was 26 % and the median duration of response was 5.7 months (95 % CI: 4.4-7.0). Median PFS and OS were 5.8 months (95 % CI: 5 - 6.5) and 8.2 months (95 % CI: 6.3 - 9.9). Grade 3-4 TRAEs occurred in 16.5 % of patients, with Grade >= 3 liver enzyme increase and TRAEs-related discontinuation reported in 12 % and 4.6 % of cases. Conclusion: Real-world data from the Italian EAP confirm the tolerability and effectiveness of sotorasib in patients with KRASp.G12C-mutated advanced NSCLC and highlight the value of the national ATLAS network as source of real-world evidence driving the clinical management of NSCLC patients.

Published
2024

6. Real-world outcomes of Italian patients with advanced non-squamous lung cancer treated with first-line pembrolizumab plus platinum-pemetrexed

Author

Leonetti, A, Perrone, F, Puntoni, M, Maglietta, G, Bordi, P, Bria, E, Vita, E, Gelsomino, F, De Giglio, A, Gelibter, A, Siringo, M, Mazzoni, F, Caliman, E, Genova, C, Bertolini, F, Guaitoli, G, Passiglia, F, Delcuratolo, M, Montrone, M, Cerea, G, Pasello, G, Roca, E, Belluomini, L, Cecere, F, Guida, A, Manzo, A, Adamo, V, Rastelli, F, Bulotta, A, Citarella, F, Toschi, L, Zoratto, F, Cortinovis, D, Berardi, R, Follador, A, Carta, A, Camerini, A, Salerno, F, Silva, R, Baldini, E, Cortellini, A, Brighenti, M, Santoni, M, Malorgio, F, Caminiti, C, Tiseo, M, Leonetti, Alessandro, Perrone, Fabiana, Puntoni, Matteo, Maglietta, Giuseppe, Bordi, Paola, Bria, Emilio, Vita, Emanuele, Gelsomino, Francesco, De Giglio, Andrea, Gelibter, Alain, Siringo, Marco, Mazzoni, Francesca, Caliman, Enrico, Genova, Carlo, Bertolini, Federica, Guaitoli, Giorgia, Passiglia, Francesco, Delcuratolo, Marco Donatello, Montrone, Michele, Cerea, Giulio, Pasello, Giulia, Roca, Elisa, Belluomini, Lorenzo, Cecere, Fabiana Letizia, Guida, Annalisa, Manzo, Anna, Adamo, Vincenzo, Rastelli, Francesca, Bulotta, Alessandra, Citarella, Fabrizio, Toschi, Luca, Zoratto, Federica, Cortinovis, Diego Luigi, Berardi, Rossana, Follador, Alessandro, Carta, Annamaria, Camerini, Andrea, Salerno, Flavio, Silva, Rosa Rita, Baldini, Editta, Cortellini, Alessio, Brighenti, Matteo, Santoni, Matteo, Malorgio, Francesco, Caminiti, Caterina, Tiseo, Marcello, Leonetti, A, Perrone, F, Puntoni, M, Maglietta, G, Bordi, P, Bria, E, Vita, E, Gelsomino, F, De Giglio, A, Gelibter, A, Siringo, M, Mazzoni, F, Caliman, E, Genova, C, Bertolini, F, Guaitoli, G, Passiglia, F, Delcuratolo, M, Montrone, M, Cerea, G, Pasello, G, Roca, E, Belluomini, L, Cecere, F, Guida, A, Manzo, A, Adamo, V, Rastelli, F, Bulotta, A, Citarella, F, Toschi, L, Zoratto, F, Cortinovis, D, Berardi, R, Follador, A, Carta, A, Camerini, A, Salerno, F, Silva, R, Baldini, E, Cortellini, A, Brighenti, M, Santoni, M, Malorgio, F, Caminiti, C, Tiseo, M, Leonetti, Alessandro, Perrone, Fabiana, Puntoni, Matteo, Maglietta, Giuseppe, Bordi, Paola, Bria, Emilio, Vita, Emanuele, Gelsomino, Francesco, De Giglio, Andrea, Gelibter, Alain, Siringo, Marco, Mazzoni, Francesca, Caliman, Enrico, Genova, Carlo, Bertolini, Federica, Guaitoli, Giorgia, Passiglia, Francesco, Delcuratolo, Marco Donatello, Montrone, Michele, Cerea, Giulio, Pasello, Giulia, Roca, Elisa, Belluomini, Lorenzo, Cecere, Fabiana Letizia, Guida, Annalisa, Manzo, Anna, Adamo, Vincenzo, Rastelli, Francesca, Bulotta, Alessandra, Citarella, Fabrizio, Toschi, Luca, Zoratto, Federica, Cortinovis, Diego Luigi, Berardi, Rossana, Follador, Alessandro, Carta, Annamaria, Camerini, Andrea, Salerno, Flavio, Silva, Rosa Rita, Baldini, Editta, Cortellini, Alessio, Brighenti, Matteo, Santoni, Matteo, Malorgio, Francesco, Caminiti, Caterina, and Tiseo, Marcello

Abstract

Purpose: The aim of this multi-center, retrospective/prospective cohort observational study was to evaluate outcomes in routine clinical practice of first-line chemo-immunotherapy with cis/carboplatin, pemetrexed and pembrolizumab in patients with advanced non-squamous non-small cell lung cancer (NSCLC) in 33 Italian centers. Methods: The outcome measure was to evaluate overall survival (OS) in a real-world patient population. Secondary endpoints were: progression-free survival (PFS), objective response rate (ORR), duration of response (DoR) and incidence of treatment-related adverse events (AEs). Results: 1068 patients were enrolled at the time of data cut-off (January 31st, 2023), and 812 (76.0%) belonged to the retrospective cohort. Median age was 66 years (27−85), ECOG PS was ≥ 2 in 91 (8.6%) patients; 254 (23.8%) patients had brain metastases at baseline; 38 (3.6%) patients had tumor with PD-L1 expression ≥ 50%. After a median follow-up of 17.0 months (95% CI, 16.1–17.9), median OS was 16.1 months (95% CI, 14.4–18.8) and PFS was 9.9 months (95% CI, 8.8–11.2). Median DoR (n = 493) was 14.7 months (95% CI, 13.6–17.1). ORR was 43.4% (95% CI, 40.4–46.4). Any-grade AEs occurred in 636 (59.6%) patients and grade ≥ 3 in 253 (23.7%) patients. Most common grade ≥ 3 AEs were neutropenia (6.3%) and anemia (6.3%). Conclusions: First-line chemo-immunotherapy was effective and tolerable in this large, real-world Italian study of patients with advanced non-squamous NSCLC. Our results were in line with the KEYNOTE-189 registration study, also considering the low number of PD-L1 ≥ 50% patients included in our study.

Published
2024

7. Reliability improvement of SRAM PUFs based on a detailed experimental study into the stochastic effects of aging

Author

Universidad de Sevilla. Departamento de Electrónica y Electromagnetismo, Ministerio de Ciencia e Innovación (MICIN). España, Agencia Estatal de Investigación. España, European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER), Santana-Andreo, Andrés, Saraza Canflanca, Pablo, Castro López, R., Roca, E., Fernández Fernández, Francisco Vidal, Universidad de Sevilla. Departamento de Electrónica y Electromagnetismo, Ministerio de Ciencia e Innovación (MICIN). España, Agencia Estatal de Investigación. España, European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER), Santana-Andreo, Andrés, Saraza Canflanca, Pablo, Castro López, R., Roca, E., and Fernández Fernández, Francisco Vidal

Abstract

Physical Unclonable Functions (PUFs) have gained attention as a lightweight hardware security primitive. In particular, the SRAM-based PUF uses the unpredictable power-up value of the cells within an SRAM. Although these values should ideally be always the same within each SRAM to accomplish a correct PUF operation, this is often not the case, especially when factors like circuit aging are considered. While certain studies explore the effects of aging on SRAM PUFs, they often simplify the analysis. For instance, some studies assume that only Bias Temperature Instability (BTI) contributes to circuit degradation while others evaluate the overall degradation without accounting for the stochastic effects of aging on each individual cell. In this work, we first perform a detailed characterization of the nature of aging in SRAM PUFs, demonstrating that the impact of Non-Conductive Hot-Carrier Injection cannot be neglected. We also show that different cells degrade differently, highlighting the importance of accounting for the stochasticity of aging. After that, a method based on the Data Retention Voltage metric to select the cells with the most stable power-up response is introduced. Using these cells to generate the PUF identifier will result in a more stable response, and thus a better PUF performance.

Published
2024

9. EP11.01-01 Final Analysis of First-Line Chemo-Immunotherapy in Patients with Advanced Lung Adenocarcinoma: An Italian Real-World Study

Author

Leonetti, A., primary, Perrone, F., additional, Puntoni, M., additional, Bordi, P., additional, Maglietta, G., additional, Bria, E., additional, Gelsomino, F., additional, Gelibter, A., additional, Caliman, E., additional, Genova, C., additional, Guaitoli, G., additional, Passiglia, F., additional, Montrone, M., additional, Oresti, S., additional, Pasello, G., additional, Roca, E., additional, Pilotto, S., additional, Cecere, F.L., additional, Guida, A., additional, Manzo, A., additional, Russo, A., additional, Rastelli, F., additional, Bulotta, A., additional, Citarella, F., additional, Toschi, L., additional, Zoratto, F., additional, Cortinovis, D.L., additional, Paoloni, F., additional, Follador, A., additional, Carta, A., additional, Camerini, A., additional, Di Maio, M., additional, and Tiseo, M., additional

Published
2023
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15. Ancient DNA of Guinea Pigs (Cavia spp.) Indicates a Probable New Center of Domestication and Pathways of Global Distribution

Author

Lord, E., Collins, C., deFrance, S., LeFebvre, M. J., Pigière, F., Eeckhout, P., Erauw, C., Fitzpatrick, S. M., Healy, P. F., Martínez-Polanco, M. F., Garcia, J. L., Ramos Roca, E., Delgado, M., Sánchez Urriago, A., Peña Léon, G. A., Toyne, J. M., Dahlstedt, A., Moore, K. M., Laguer Diaz, C., Zori, C., and Matisoo-Smith, E.

Published
2020
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16. Aneurismal subarachnoid hemorrhage during the COVID-19 outbreak in a Hub and Spoke system: observational multicenter cohort study in Lombardy, Italy

Author

Fiorindi, A, Vezzoli, M, Doglietto, F, Zanin, L, Saraceno, G, Agosti, E, Barbieri, A, Bellocchi, S, Bernucci, C, Bongetta, D, Cardia, A, Costi, E, Egidi, M, Fioravanti, A, Gasparotti, R, Giussani, C, Grimod, G, Latronico, N, Locatelli, D, Mardighian, D, Nodari, G, Poli, J, Rasulo, F, Roca, E, Sicuri, G, Spena, G, Stefini, R, Vivaldi, O, Zoia, C, Calza, S, Fontanella, M, Cenzato, M, Fiorindi A., Vezzoli M., Doglietto F., Zanin L., Saraceno G., Agosti E., Barbieri A., Bellocchi S., Bernucci C., Bongetta D., Cardia A., Costi E., Egidi M., Fioravanti A., Gasparotti R., Giussani C., Grimod G., Latronico N., Locatelli D., Mardighian D., Nodari G., Poli J. C., Rasulo F., Roca E., Sicuri G. M., Spena G., Stefini R., Vivaldi O., Zoia C., Calza S., Fontanella M. M., Cenzato M., Fiorindi, A, Vezzoli, M, Doglietto, F, Zanin, L, Saraceno, G, Agosti, E, Barbieri, A, Bellocchi, S, Bernucci, C, Bongetta, D, Cardia, A, Costi, E, Egidi, M, Fioravanti, A, Gasparotti, R, Giussani, C, Grimod, G, Latronico, N, Locatelli, D, Mardighian, D, Nodari, G, Poli, J, Rasulo, F, Roca, E, Sicuri, G, Spena, G, Stefini, R, Vivaldi, O, Zoia, C, Calza, S, Fontanella, M, Cenzato, M, Fiorindi A., Vezzoli M., Doglietto F., Zanin L., Saraceno G., Agosti E., Barbieri A., Bellocchi S., Bernucci C., Bongetta D., Cardia A., Costi E., Egidi M., Fioravanti A., Gasparotti R., Giussani C., Grimod G., Latronico N., Locatelli D., Mardighian D., Nodari G., Poli J. C., Rasulo F., Roca E., Sicuri G. M., Spena G., Stefini R., Vivaldi O., Zoia C., Calza S., Fontanella M. M., and Cenzato M.

Abstract

Background: Lombardy was the most affected Italian region by the first phase of the COVID-19 pandemic and underwent urgent reorganization for the management of emergencies, including subarachnoid hemorrhage from a ruptured cerebral aneurysm (aSAH). The aim of the study was to define demographics, clinical, and therapeutic features of aSAH during the COVID-19 outbreak and compare these with a historical cohort. Methods: In this observational multicenter cohort study, patients aged 18 years or older, who were diagnosed with aSAH at the participating centers in Lombardy from March 9 to May 10, 2020, were included (COVID-19 group). In order to minimize bias related to possible SAH seasonality, the control group was composed of patients diagnosed with aSAH from March 9 to May 10 of the three previous years, 2017–2018-2019 (pre-pandemic group). Twenty-three demographic, clinical, and therapeutic features were collected. Statistical analysis was performed. Results: Seventy-two patients during the COVID-19 period and 179 in the control group were enrolled at 14 centers. Only 4 patients were positive for SARS-CoV-2. The “diagnostic delay” was significantly increased (+ 68%) in the COVID-19 group vs. pre-pandemic (1.06 vs. 0.63 days, respectively, p-value = 0.030), while “therapeutic delay” did not differ significantly between the two periods (0.89 vs. 0.74 days, p-value = 0.183). Patients with poor outcome (GOS at discharge from 1 to 3) were higher during the COVID-19 period (54.2%) compared to pre-pandemic (40.2%, p = 0.044). In logistic regression analysis, in which outcome was the dichotomized Glasgow Outcome Scale (GOS), five variables showed p-values < 0.05: age at admission, WFNS grade, treatment (none), days in ICU, and ischemia. Conclusions: We documented a significantly increased “diagnostic delay” for subarachnoid hemorrhages during the first COVID-19 outbreak in Lombardy. However, despite the dramatic situation that the healthcare system was expe

Published
2022

17. PACOSYT: A Passive Component Synthesis Tool Based on Machine Learning and Tailored Modeling Strategies Towards Optimal RF and mm-Wave Circuit Designs

Author

Universidad de Sevilla. Departamento de Electrónica y Electromagnetismo, European Union (UE). H2020, Instituto de Telecomunicações. Portugal, Ministerio de Ciencia e Innovación (MICIN). España, Fundação para a Ciência e a Tecnologia. Portugal, Moreira de Passos, Fabio, Lourenço, N., Roca, E., Martins, R., Castro López, R., Horta, N., Fernández Fernández, Francisco Vidal, Universidad de Sevilla. Departamento de Electrónica y Electromagnetismo, European Union (UE). H2020, Instituto de Telecomunicações. Portugal, Ministerio de Ciencia e Innovación (MICIN). España, Fundação para a Ciência e a Tecnologia. Portugal, Moreira de Passos, Fabio, Lourenço, N., Roca, E., Martins, R., Castro López, R., Horta, N., and Fernández Fernández, Francisco Vidal

Abstract

In this paper, the application of regression-based supervised machine learning (ML) methods to the modeling of integrated inductors and transformers is examined. Different ML techniques are used and compared to improve accuracy. However, it is demonstrated that none of the ML techniques considered provided good results unless a smart modeling strategy, tailored to the specific design problem, is used. Taking advantage of these modeling strategies, high accuracy can be obtained when compared to full-wave electromagnetic (EM) simulations (less than 2% error) and experimental measurements (less than 5% error). The most accurate model, obtained by the appropriate combination of an ML technique and modeling strategy, has been integrated into a tool called PACOSYT. The tool uses optimization algorithms to allow the designer to obtain an inductor/transformer with optimal performances in just seconds while keeping the accuracy of EM simulations. Furthermore, the tool provides the passive component S parameter description file for seamless use in circuit simulations. The tool can be used standalone or integrated with design frameworks, like Cadence Virtuoso or AIDASoft, a framework for circuit optimization. To illustrate the different usages of the tool, several passive devices are synthesized, and hundreds of millimeter-wave power amplifiers are synthesized using AIDASoft together with PACOSYT. The tool has been developed using open-source Python frameworks and does not use any closed-source licenses. PACOSYT, which also allows other designers to create their models for different technologies, is made publicly available.

Published
2023

18. Perioperative Pembrolizumab for Early-Stage Non-Small-Cell Lung Cancer

Author

Heather, W, Moishe, L, Terufumi, K, Masahiro, T, Se-Hoon, L, Shugeng, G, Ke-Neng, C, Christophe, D, Margarita, M, Ekkehard, E, Gastón L, M, Olivier, B, Delvys, R, Jamie E, C, Silvia, N, Jing, Y, Steven M, K, Ayman, S, Spicer, D Marcelo Tatangelo, J, Flores, M, Pastor, A, Puig, J, Martinengo, G, Varela, M, Brocca, C, Wong, M, Hui, R, Dooms, C, Vansteenkiste, J, Demedts, I, Sibille, A, Surmont, V, Deschepper, K, Lambrechts, M, Dias, J, Rafael Martins De Marchi, P, Alves, G, Henrique Araujo, L, Matias, D, Chaves, F, Franke, F, Teixeira, C, Tabacof, J, Faria, L, Morbeck, I, Henrique Cronemberger, E, Lima, I, Sardenberg, R, de Paiva Junior, T, Dutra, C, Luiz Guimaraes, J, Begin, P, Langleben, A, Liu, G, Liberman, M, Spicer, J, Gao, S, Zhao, G, Jiang, T, Yan, X, Hu, J, Chen, J, Tan, L, Wang, Q, Li, S, Chen, K, Yang, Y, Bai, J, Ma, S, Chen, H, Chen, Q, Wang, W, Zhang, L, Zhu, Y, Vanakesa, T, Zasadny, X, Duchemann, B, Girard, N, Bylicki, O, Berard, H, Thiberville, L, Mennecier, B, Mazieres, J, Eigendorff, E, Bonnet, R, Fix, P, Reck, M, Rittmeyer, A, Reinacher-Schick, A, Wehler, T, Lehmann, M, Serke, M, Wesseler, C, Täuscher, D, Lang, S, Wermke, M, Grohe, C, Wirtz, H, Kollmeier, J, Ritgen, M, Mueller, A, Frohling, K, Vogel, G, Faehling, M, Cuffe, S, Collins, D, Delmonte, A, Gilli, M, Piantedosi, F, Ogliari, F, Bulotta, A, Gregorc, V, Gianni, L, Grisanti, S, Intagliata, S, Roca, E, Ferrari, V, Berruti, A, Cortinovis, D, Lo Russo, G, Ferrara, R, Garassino, M, Rita Migliorino, M, Novello, S, Santoro, A, Signorelli, D, Tsuboi, M, Okada, M, Kato, T, Nishio, W, Kuroda, H, Shimizu, J, Sakao, Y, Sugio, K, Horinouchi, H, Takamochi, K, Saji, H, Tanaka, F, Ikeda, N, Muto, S, Shio, Y, Suzuki, H, Hegmane, A, Cicenas, S, Zemaitis, M, Kek Pang, Y, Yew Heng, F, Leong Yu, K, Lowczak, A, Makles, K, Bryl, M, Zurawski, B, Pawlak, I, Han, J, Lee, S, Kim, J, Yong Shim, B, Cebotaru, C, Ganea, D, Scheusan, R, Ciurescu, I, Mazilu, L, Ungureanu, A, Gal, C, Ciubotaru, E, Iordan, I, Berceanu-Ion, R, Ciuleanu, T, Laktionov, K, Karaseva, N, Smagina, M, Luft, A, Afanasyev, S, Nesterova, A, Levchenko, E, Arkhipov, A, Fedenko, A, Ruff, P, Jacobs, C, Fourie, S, Carcereny, E, Calles Blanco, A, Rodriguez Abreu, D, Majem Tarruella, M, Bosch Barrera, J, Bernabe Caro, R, Nadal Alforja, E, Martnez Marti, A, Liao, B, Huang, H, Chiu, C, Wang, C, Tsai, C, Voitko, N, Kryzhanivska, A, Kolesnik, O, Levenko, O, Bondarenko, I, Trukhin, D, Ursol, G, Paramonov, V, Sokur, I, Khan, S, Arora, A, Goranov, B, Greystoke, A, Ahmed, S, Pope, T, O'Brien, M, Charu, V, Cobb, P, Costin, D, Weksler, B, Schumacher, L, Finley, G, Furqan, M, Gentzler, R, Misleh, J, Guarino, M, Halmos, B, Keresztes, R, Jain, K, Yan Lou, Y, Molina, J, Liu-Dumlao, T, Zhao, Q, Niu, J, Taysir Hammoud, Z, Rybkin, I, Cuevo, R, Fernando, H, Schiller, J, Srkalovic, G, Koontz, M, Stampleman, L, Anderson, I, Villaruz, L, Wang, S, Komiya, T, Jain, S, Starodub, A, Wakelee, H, Kishor Ganti, A, Ernani, V, Kristedja, T, O'Day, S, Radhi, S, Sangal, A, Duvivier, H, Rich, P, Kazmi, S, Pollock, T, Chaft, J, Rathnasabapathy, C, Savvides, P, Costas, K, Kaywin, P, Villalona-Calero, M, Alekshun, T, Rao, S, Siegel, R, Wakelee, Heather, Liberman, Moishe, Kato, Terufumi, Tsuboi, Masahiro, Lee, Se-Hoon, Gao, Shugeng, Chen, Ke-Neng, Dooms, Christophe, Majem, Margarita, Eigendorff, Ekkehard, Martinengo, Gastón L, Bylicki, Olivier, Rodríguez-Abreu, Delvys, Chaft, Jamie E, Novello, Silvia, Yang, Jing, Keller, Steven M, Samkari, Ayman, Jonathan D Marcelo Tatangelo, Marcos Flores, Andrea Pastor, Juan Puig, Gaston Martinengo, Mirta Varela, Carlos Brocca, Mark Wong, Rina Hui, Christophe Dooms, Johan Vansteenkiste, Ingel Demedts, Anne Sibille, Veerle Surmont, Koenraad Deschepper, Marc Lambrechts, Josiane Dias, Pedro Rafael Martins De Marchi, Gustavo Alves, Luiz Henrique Araujo, Danielli Matias, Fabio Chaves, Fabio Franke, Carlos Teixeira, Jacques Tabacof, Luiza Faria, Igor Morbeck, Eduardo Henrique Cronemberger, Iane Lima, Rodrigo Sardenberg, Tadeu de Paiva Junior, Carolina Dutra, Jose Luiz Guimaraes, Paul Begin, Adrian Langleben, Geoffrey Liu, Moishe Liberman, Jonathan Spicer, Shugeng Gao, Guofang Zhao, Tao Jiang, Xiaolong Yan, Jian Hu, Jun Chen, Lijie Tan, Qun Wang, Shanqing Li, Keneng Chen, Yue Yang, Jie Bai, Shaohua Ma, Haiquan Chen, Qixun Chen, Wenxiang Wang, Lanjun Zhang, Yuming Zhu, Tonu Vanakesa, Xavier Zasadny, Boris Duchemann, Nicolas Girard, Olivier Bylicki, Henri Berard, Luc Thiberville, Bertrand Mennecier, Julien Mazieres, Ekkehard Eigendorff, Reiner Bonnet, Peter Fix, Martin Reck, Achim Rittmeyer, Anke Reinacher-Schick, Thomas Wehler, Markus Lehmann, Monika Serke, Claas Wesseler, Dagmar Täuscher, Susanne Lang, Martin Wermke, Christian Grohe, Hubert Wirtz, Jens Kollmeier, Mathias Ritgen, Annette Mueller, Klaus-Peter Frohling, Gunther Vogel, Martin Faehling, Sinead Cuffe, Dearbhaile Collins, Angelo Delmonte, Marina Gilli, Francovito Piantedosi, Francesca Ogliari, Alessandra Bulotta, Vanesa Gregorc, Luca Gianni, Salvatore Grisanti, Salvatore Intagliata, Elisa Roca, Vittorio Ferrari, Alfredo Berruti, Diego Cortinovis, Giuseppe Lo Russo, Roberto Ferrara, Marina Garassino, Maria Rita Migliorino, Silvia Novello, Armando Santoro, Diego Signorelli, Masahiro Tsuboi, Morihito Okada, Terufumi Kato, Wataru Nishio, Hiroaki Kuroda, Junichi Shimizu, Yukinori Sakao, Kenji Sugio, Hidehito Horinouchi, Kazuya Takamochi, Hisashi Saji, Fumihiro Tanaka, Norihiko Ikeda, Satoshi Muto, Yutaka Shio, Hiroyuki Suzuki, Alinta Hegmane, Saulius Cicenas, Marius Zemaitis, Yong Kek Pang, Fook Yew Heng, Kong Leong Yu, Anna Lowczak, Krytsyna Makles, Maciej Bryl, Bogdan Zurawski, Ireneusz Pawlak, Ji-Youn Han, Se-Hoon Lee, Jhingook Kim, Byoung Yong Shim, Cristina Cebotaru, Doina Ganea, Roxana Scheusan, Ioana Ciurescu, Laura Mazilu, Andrei Ungureanu, Cristian Gal, Elena Ciubotaru, Ingrid Iordan, Radu Berceanu-Ion, Tudor Ciuleanu, Konstantin Laktionov, Nina Karaseva, Maria Smagina, Alexander Luft, Sergey Afanasyev, Alfiya Nesterova, Evgeny Levchenko, Alexander Arkhipov, Alexander Fedenko, Paul Ruff, Conrad Jacobs, Samuel Fourie, Enric Carcereny, Antonio Calles Blanco, Delvys Rodriguez Abreu, Margarita Majem Tarruella, Joaquim Bosch Barrera, Reyes Bernabe Caro, Ernest Nadal Alforja, Alex Martnez Marti, Bin-Chi Liao, Hsu-Ching Huang, Chao-Hua Chiu, Chin-Chou Wang, Chen-Liang Tsai, Nataliia Voitko, Anna Kryzhanivska, Olena Kolesnik, Oleh Levenko, Oleksii Kolesnik, Igor Bondarenko, Dmytro Trukhin, Grygorii Ursol, Viktor Paramonov, Iryna Sokur, Sarah Khan, Arvind Arora, Bojidar Goranov, Alastair Greystoke, Samreen Ahmed, Tony Pope, Mary O'Brien, Veena Charu, Patrick Cobb, Dan Costin, Benny Weksler, Lana Schumacher, Gene Finley, Muhammad Furqan, Ryan Gentzler, Jamal Misleh, Michael Guarino, Balazs Halmos, Roger Keresztes, Kirti Jain, Yan Yan Lou, Julian Molina, Theresa Liu-Dumlao, Qing Zhao, Jiaxin Niu, Zane Taysir Hammoud, Igor Rybkin, Raymund Cuevo, Hiran Fernando, Joan Schiller, Gordan Srkalovic, Michael Koontz, Laura Stampleman, Ian Anderson, Liza Villaruz, Sarah Wang, Takefumi Komiya, Sushil Jain, Alexander Starodub, Heather Wakelee, Apar Kishor Ganti, Vinicius Ernani, Timothy Kristedja, Steven O'Day, Saba Radhi, Ashish Sangal, Herbert Duvivier, Patricia Rich, Shayma Kazmi, Theodore Pollock, Jamie Chaft, Chenthilmurugan Rathnasabapathy, Panayiotis Savvides, Kimberly Costas, Paul Kaywin, Miguel Villalona-Calero, Todd Alekshun, Kevin Chen, Suman Rao, Robert Siegel, Heather, W, Moishe, L, Terufumi, K, Masahiro, T, Se-Hoon, L, Shugeng, G, Ke-Neng, C, Christophe, D, Margarita, M, Ekkehard, E, Gastón L, M, Olivier, B, Delvys, R, Jamie E, C, Silvia, N, Jing, Y, Steven M, K, Ayman, S, Spicer, D Marcelo Tatangelo, J, Flores, M, Pastor, A, Puig, J, Martinengo, G, Varela, M, Brocca, C, Wong, M, Hui, R, Dooms, C, Vansteenkiste, J, Demedts, I, Sibille, A, Surmont, V, Deschepper, K, Lambrechts, M, Dias, J, Rafael Martins De Marchi, P, Alves, G, Henrique Araujo, L, Matias, D, Chaves, F, Franke, F, Teixeira, C, Tabacof, J, Faria, L, Morbeck, I, Henrique Cronemberger, E, Lima, I, Sardenberg, R, de Paiva Junior, T, Dutra, C, Luiz Guimaraes, J, Begin, P, Langleben, A, Liu, G, Liberman, M, Spicer, J, Gao, S, Zhao, G, Jiang, T, Yan, X, Hu, J, Chen, J, Tan, L, Wang, Q, Li, S, Chen, K, Yang, Y, Bai, J, Ma, S, Chen, H, Chen, Q, Wang, W, Zhang, L, Zhu, Y, Vanakesa, T, Zasadny, X, Duchemann, B, Girard, N, Bylicki, O, Berard, H, Thiberville, L, Mennecier, B, Mazieres, J, Eigendorff, E, Bonnet, R, Fix, P, Reck, M, Rittmeyer, A, Reinacher-Schick, A, Wehler, T, Lehmann, M, Serke, M, Wesseler, C, Täuscher, D, Lang, S, Wermke, M, Grohe, C, Wirtz, H, Kollmeier, J, Ritgen, M, Mueller, A, Frohling, K, Vogel, G, Faehling, M, Cuffe, S, Collins, D, Delmonte, A, Gilli, M, Piantedosi, F, Ogliari, F, Bulotta, A, Gregorc, V, Gianni, L, Grisanti, S, Intagliata, S, Roca, E, Ferrari, V, Berruti, A, Cortinovis, D, Lo Russo, G, Ferrara, R, Garassino, M, Rita Migliorino, M, Novello, S, Santoro, A, Signorelli, D, Tsuboi, M, Okada, M, Kato, T, Nishio, W, Kuroda, H, Shimizu, J, Sakao, Y, Sugio, K, Horinouchi, H, Takamochi, K, Saji, H, Tanaka, F, Ikeda, N, Muto, S, Shio, Y, Suzuki, H, Hegmane, A, Cicenas, S, Zemaitis, M, Kek Pang, Y, Yew Heng, F, Leong Yu, K, Lowczak, A, Makles, K, Bryl, M, Zurawski, B, Pawlak, I, Han, J, Lee, S, Kim, J, Yong Shim, B, Cebotaru, C, Ganea, D, Scheusan, R, Ciurescu, I, Mazilu, L, Ungureanu, A, Gal, C, Ciubotaru, E, Iordan, I, Berceanu-Ion, R, Ciuleanu, T, Laktionov, K, Karaseva, N, Smagina, M, Luft, A, Afanasyev, S, Nesterova, A, Levchenko, E, Arkhipov, A, Fedenko, A, Ruff, P, Jacobs, C, Fourie, S, Carcereny, E, Calles Blanco, A, Rodriguez Abreu, D, Majem Tarruella, M, Bosch Barrera, J, Bernabe Caro, R, Nadal Alforja, E, Martnez Marti, A, Liao, B, Huang, H, Chiu, C, Wang, C, Tsai, C, Voitko, N, Kryzhanivska, A, Kolesnik, O, Levenko, O, Bondarenko, I, Trukhin, D, Ursol, G, Paramonov, V, Sokur, I, Khan, S, Arora, A, Goranov, B, Greystoke, A, Ahmed, S, Pope, T, O'Brien, M, Charu, V, Cobb, P, Costin, D, Weksler, B, Schumacher, L, Finley, G, Furqan, M, Gentzler, R, Misleh, J, Guarino, M, Halmos, B, Keresztes, R, Jain, K, Yan Lou, Y, Molina, J, Liu-Dumlao, T, Zhao, Q, Niu, J, Taysir Hammoud, Z, Rybkin, I, Cuevo, R, Fernando, H, Schiller, J, Srkalovic, G, Koontz, M, Stampleman, L, Anderson, I, Villaruz, L, Wang, S, Komiya, T, Jain, S, Starodub, A, Wakelee, H, Kishor Ganti, A, Ernani, V, Kristedja, T, O'Day, S, Radhi, S, Sangal, A, Duvivier, H, Rich, P, Kazmi, S, Pollock, T, Chaft, J, Rathnasabapathy, C, Savvides, P, Costas, K, Kaywin, P, Villalona-Calero, M, Alekshun, T, Rao, S, Siegel, R, Wakelee, Heather, Liberman, Moishe, Kato, Terufumi, Tsuboi, Masahiro, Lee, Se-Hoon, Gao, Shugeng, Chen, Ke-Neng, Dooms, Christophe, Majem, Margarita, Eigendorff, Ekkehard, Martinengo, Gastón L, Bylicki, Olivier, Rodríguez-Abreu, Delvys, Chaft, Jamie E, Novello, Silvia, Yang, Jing, Keller, Steven M, Samkari, Ayman, Jonathan D Marcelo Tatangelo, Marcos Flores, Andrea Pastor, Juan Puig, Gaston Martinengo, Mirta Varela, Carlos Brocca, Mark Wong, Rina Hui, Christophe Dooms, Johan Vansteenkiste, Ingel Demedts, Anne Sibille, Veerle Surmont, Koenraad Deschepper, Marc Lambrechts, Josiane Dias, Pedro Rafael Martins De Marchi, Gustavo Alves, Luiz Henrique Araujo, Danielli Matias, Fabio Chaves, Fabio Franke, Carlos Teixeira, Jacques Tabacof, Luiza Faria, Igor Morbeck, Eduardo Henrique Cronemberger, Iane Lima, Rodrigo Sardenberg, Tadeu de Paiva Junior, Carolina Dutra, Jose Luiz Guimaraes, Paul Begin, Adrian Langleben, Geoffrey Liu, Moishe Liberman, Jonathan Spicer, Shugeng Gao, Guofang Zhao, Tao Jiang, Xiaolong Yan, Jian Hu, Jun Chen, Lijie Tan, Qun Wang, Shanqing Li, Keneng Chen, Yue Yang, Jie Bai, Shaohua Ma, Haiquan Chen, Qixun Chen, Wenxiang Wang, Lanjun Zhang, Yuming Zhu, Tonu Vanakesa, Xavier Zasadny, Boris Duchemann, Nicolas Girard, Olivier Bylicki, Henri Berard, Luc Thiberville, Bertrand Mennecier, Julien Mazieres, Ekkehard Eigendorff, Reiner Bonnet, Peter Fix, Martin Reck, Achim Rittmeyer, Anke Reinacher-Schick, Thomas Wehler, Markus Lehmann, Monika Serke, Claas Wesseler, Dagmar Täuscher, Susanne Lang, Martin Wermke, Christian Grohe, Hubert Wirtz, Jens Kollmeier, Mathias Ritgen, Annette Mueller, Klaus-Peter Frohling, Gunther Vogel, Martin Faehling, Sinead Cuffe, Dearbhaile Collins, Angelo Delmonte, Marina Gilli, Francovito Piantedosi, Francesca Ogliari, Alessandra Bulotta, Vanesa Gregorc, Luca Gianni, Salvatore Grisanti, Salvatore Intagliata, Elisa Roca, Vittorio Ferrari, Alfredo Berruti, Diego Cortinovis, Giuseppe Lo Russo, Roberto Ferrara, Marina Garassino, Maria Rita Migliorino, Silvia Novello, Armando Santoro, Diego Signorelli, Masahiro Tsuboi, Morihito Okada, Terufumi Kato, Wataru Nishio, Hiroaki Kuroda, Junichi Shimizu, Yukinori Sakao, Kenji Sugio, Hidehito Horinouchi, Kazuya Takamochi, Hisashi Saji, Fumihiro Tanaka, Norihiko Ikeda, Satoshi Muto, Yutaka Shio, Hiroyuki Suzuki, Alinta Hegmane, Saulius Cicenas, Marius Zemaitis, Yong Kek Pang, Fook Yew Heng, Kong Leong Yu, Anna Lowczak, Krytsyna Makles, Maciej Bryl, Bogdan Zurawski, Ireneusz Pawlak, Ji-Youn Han, Se-Hoon Lee, Jhingook Kim, Byoung Yong Shim, Cristina Cebotaru, Doina Ganea, Roxana Scheusan, Ioana Ciurescu, Laura Mazilu, Andrei Ungureanu, Cristian Gal, Elena Ciubotaru, Ingrid Iordan, Radu Berceanu-Ion, Tudor Ciuleanu, Konstantin Laktionov, Nina Karaseva, Maria Smagina, Alexander Luft, Sergey Afanasyev, Alfiya Nesterova, Evgeny Levchenko, Alexander Arkhipov, Alexander Fedenko, Paul Ruff, Conrad Jacobs, Samuel Fourie, Enric Carcereny, Antonio Calles Blanco, Delvys Rodriguez Abreu, Margarita Majem Tarruella, Joaquim Bosch Barrera, Reyes Bernabe Caro, Ernest Nadal Alforja, Alex Martnez Marti, Bin-Chi Liao, Hsu-Ching Huang, Chao-Hua Chiu, Chin-Chou Wang, Chen-Liang Tsai, Nataliia Voitko, Anna Kryzhanivska, Olena Kolesnik, Oleh Levenko, Oleksii Kolesnik, Igor Bondarenko, Dmytro Trukhin, Grygorii Ursol, Viktor Paramonov, Iryna Sokur, Sarah Khan, Arvind Arora, Bojidar Goranov, Alastair Greystoke, Samreen Ahmed, Tony Pope, Mary O'Brien, Veena Charu, Patrick Cobb, Dan Costin, Benny Weksler, Lana Schumacher, Gene Finley, Muhammad Furqan, Ryan Gentzler, Jamal Misleh, Michael Guarino, Balazs Halmos, Roger Keresztes, Kirti Jain, Yan Yan Lou, Julian Molina, Theresa Liu-Dumlao, Qing Zhao, Jiaxin Niu, Zane Taysir Hammoud, Igor Rybkin, Raymund Cuevo, Hiran Fernando, Joan Schiller, Gordan Srkalovic, Michael Koontz, Laura Stampleman, Ian Anderson, Liza Villaruz, Sarah Wang, Takefumi Komiya, Sushil Jain, Alexander Starodub, Heather Wakelee, Apar Kishor Ganti, Vinicius Ernani, Timothy Kristedja, Steven O'Day, Saba Radhi, Ashish Sangal, Herbert Duvivier, Patricia Rich, Shayma Kazmi, Theodore Pollock, Jamie Chaft, Chenthilmurugan Rathnasabapathy, Panayiotis Savvides, Kimberly Costas, Paul Kaywin, Miguel Villalona-Calero, Todd Alekshun, Kevin Chen, Suman Rao, and Robert Siegel

Abstract

BACKGROUND Among patients with resectable early-stage non-small-cell lung cancer (NSCLC), a perioperative approach that includes both neoadjuvant and adjuvant immune checkpoint inhibition may provide benefit beyond either approach alone. METHODS We conducted a randomized, double-blind, phase 3 trial to evaluate perioperative pembrolizumab in patients with early-stage NSCLC. Participants with resectable stage II, IIIA, or IIIB (N2 stage) NSCLC were assigned in a 1:1 ratio to receive neoadjuvant pembrolizumab (200 mg) or placebo once every 3 weeks, each of which was given with cisplatin-based chemotherapy for 4 cycles, followed by surgery and adjuvant pembrolizumab (200 mg) or placebo once every 3 weeks for up to 13 cycles. The dual primary end points were event-free survival (the time from randomization to the first occurrence of local progression that precluded the planned surgery, unresectable tumor, progression or recurrence, or death) and overall survival. Secondary end points included major pathological response, pathological complete response, and safety. RESULTS A total of 397 participants were assigned to the pembrolizumab group, and 400 to the placebo group. At the prespecified first interim analysis, the median follow-up was 25.2 months. Event-free survival at 24 months was 62.4% in the pembrolizumab group and 40.6% in the placebo group (hazard ratio for progression, recurrence, or death, 0.58; 95% confidence interval [CI], 0.46 to 0.72; P<0.001). The estimated 24-month overall survival was 80.9% in the pembrolizumab group and 77.6% in the placebo group (P = 0.02, which did not meet the significance criterion). A major pathological response occurred in 30.2% of the participants in the pembrolizumab group and in 11.0% of those in the placebo group (difference, 19.2 percentage points; 95% CI, 13.9 to 24.7; P<0.0001; threshold, P = 0.0001), and a pathological complete response occurred in 18.1% and 4.0%, respectively (difference, 14.2 percentage points

Published
2023

21. EP16.03-011 The European Program for ROutine Testing of Patients with Advanced Lung Cancer (EPROPA) 1 Year Activity

Author

Passiglia, F., primary, Righi, L., additional, Listì, A., additional, Tabbò, F., additional, Bironzo, P., additional, Reale, M.L., additional, Sini, C., additional, Vallone, S., additional, Arizio, F., additional, Parravicini, M.V. Pacchiana, additional, Mazilu, L., additional, Linardou, H., additional, Roca, E., additional, Buffoni, L., additional, Mohorcic, K., additional, Barbieri, V., additional, Pignataro, D., additional, Araujo, A., additional, Ares, L. Paz, additional, Felip, E., additional, Secen, N., additional, Comanescu, A., additional, Szmytke, E., additional, Scagliotti, G., additional, and Novello, S., additional

Published
2022
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22. EP14.01-005 Weekly Sequential ACOCEV Chemotherapy (ADR, CTX, CBDCA, VP16, VCR) for Elderly - Poor PS SCLC Patients: An Observational Study

Author

Santo, A., primary, Lombardo, F., additional, Roca, E., additional, Cucinella, A., additional, Comel, A., additional, Benato, C., additional, Stefanizzi, L., additional, Divis, P., additional, Sposito, M., additional, Vaccari, S., additional, Fedrigo, E., additional, Tosoni, E., additional, and Milella, M., additional

Published
2022
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23. EP08.02-046 Activity of OsimeRTInib in NSCLC with Uncommon EGFR Mutations: Retrospective Observational Multicenter Study (ARTICUNO)

Author

Pizzutilo, E.G., primary, Agostara, A.G., additional, Oresti, S., additional, Signorelli, D., additional, Giannetta, L.G., additional, Stabile, S., additional, Lauricella, C., additional, Amatu, A., additional, Brambilla, M., additional, Lo Russo, G., additional, Proto, C., additional, Mazzeo, L., additional, Beninato, T., additional, Siringo, M., additional, Giusti, R., additional, Filetti, M., additional, Genova, C., additional, Barletta, G., additional, Russano, M., additional, Di Fazio, G.R., additional, Tosoni, E., additional, Metro, G., additional, Pilotto, S., additional, Carta, A., additional, Mazzoni, F., additional, Roca, E., additional, Gelibter, A.J., additional, Gori, S., additional, Berardi, R., additional, Cerea, G., additional, Sartore-Bianchi, A., additional, and Siena, S., additional

Published
2022
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24. 996P Activity of OsimeRTInib in NSCLC with UNcommon EGFR Mutations: Retrospective observational multicenter study (ARTICUNO)

Author

Pizzutilo, E.G., primary, Cerea, G., additional, Oresti, S., additional, Agostara, A.G., additional, Signorelli, D., additional, Stabile, S., additional, Lauricella, C., additional, Brambilla, M., additional, Mazzeo, L., additional, Giusti, R., additional, Montrone, M., additional, Russano, M., additional, Bennati, C., additional, Russo, A., additional, Viscardi, G., additional, Roca, E., additional, Gelibter, A.J., additional, Cortinovis, D.L., additional, Sartore Bianchi, A., additional, and Siena, S., additional

Published
2022
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25. Homozygous R136S mutation in PRNP gene causes inherited early onset prion disease

Author

Ximelis, Teresa, Marín-Moreno, Alba, Espinosa, J. C., Eraña, H., Charco, J. M., Hernández, I., Riveira, C., Alcolea, Daniel, González-Roca, E., Aldecoa, Iban, Molina-Porcel, L., Parchi, P., Rossi, M., Castilla, Joaquín, Ruiz-García, R., Gelpi, E., Torres, J. M., Sánchez-Valle, Raquel, Universitat Autònoma de Barcelona, Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación (España), Fundació La Marató de TV3, CSIC - Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), Ximelis, Teresa, Marín-Moreno, Alba, Espinosa, Juan Carlos, Eraña, Hasier, Charco, Jorge M, Alcolea, Daniel, González-Roca, Eva, Aldecoa, Iban, Molina-Porcel, Laura, Parchi, Piero, Rossi, Marcello, Castilla, Joaquín, Ruiz-García, Raquel, Gelpi, Ellen, Torres, Juan María, Sánchez-Valle, Raquel, Ximelis, Teresa [0000-0002-9634-1496], Marín-Moreno, Alba [0000-0002-4023-6398], Espinosa, Juan Carlos [0000-0002-6719-9902], Eraña, Hasier [0000-0001-8776-4211], Charco, Jorge M [0000-0003-3476-1855], Alcolea, Daniel [0000-0002-3819-3245], González-Roca, Eva [0000-0002-1126-0321], Aldecoa, Iban [0000-0001-5774-7453], Molina-Porcel, Laura [0000-0003-4068-8578], Parchi, Piero [0000-0002-9444-9524], Rossi, Marcello [0000-0002-8125-6571], Castilla, Joaquín [0000-0002-2216-1361], Ruiz-García, Raquel [0000-0002-8403-3613], Gelpi, Ellen [0000-0003-2948-4187], Torres, Juan María [0000-0003-0443-9232], Sánchez-Valle, Raquel [0000-0001-7750-896X], Ximelis T., Marin-Moreno A., Espinosa J.C., Erana H., Charco J.M., Hernandez I., Riveira C., Alcolea D., Gonzalez-Roca E., Aldecoa I., Molina-Porcel L., Parchi P., Rossi M., Castilla J., Ruiz-Garcia R., Gelpi E., Torres J.M., and Sanchez-Valle R.

Subjects
Proband, Prions, Cognitive Neuroscience, animal diseases, Neurosciences. Biological psychiatry. Neuropsychiatry, Neuropathology, Biology, medicine.disease_cause, Prion Protein, Genetic analysis, Prion Proteins, Prion Diseases, PRNP, Mice, Gene PRNP, medicine, Animals, Humans, Gerstmann-Straussler-Scheinker Disease, GSS, Homozygous, RC346-429, Index case, Genetics, Mutation, Animal, Research, Brain, Homozygou, Recombinant Protein, Recombinant Proteins, Prion Disease, nervous system diseases, Neurology, Prion, Protein Misfolding Cyclic Amplification, Female, Neurology (clinical), Neurology. Diseases of the nervous system, medicine.symptom, Myoclonus, Human, RC321-571
Abstract

13 Pág. Centro de Investigación en Sanidad Animal (CISA), More than 40 pathogenic heterozygous PRNP mutations causing inherited prion diseases have been identified to date. Recessive inherited prion disease has not been described to date., This work was funded by the Instituto de Salud Carlos III (grant no. PI20/00448 to RSV), Spanish Ministerio de Ciencia e Innovación (grant no. PDI2019-105837RB-I00 to J.M.T. and J.C.E., and RTI2018-098515-B-I00 to J.C.), Fundació La Marató de TV3 (grant no. 201821-31 to J.C.E.), Instituto Nacional de Investigación y Tecnología Agraria y Agroalimentaria (fellowship INIA-FPI-SGIT-2015-02 to A.M.M.) and Dr Baselga funds for CJD research. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Published
2021

26. Caracterización química de pigmentos cerámicos a base de sulfoseleniuro de cadmio

Author

Gazulla Barreda, M. F., Rodrigo Edo, M., Blasco Roca, E., and Orduña Cordero, M.

Subjects
zircon-cadmium sulfoselenide pigment, chemical properties, spectroscopy (WD-XRF), elemental analysis (combustion infrared detection), pigmentos de sulfoseleniuro de cadmio, propiedades químicas, espectroscopía (WD-FRX), análisis elemental (combustión y detección mediante IR), Clay industries. Ceramics. Glass, TP785-869
Abstract

The present paper addresses the development of a methodology that allows the complete chemical characterisation of zirconcadmium sulfoselenide ceramic pigments including minor and major elements. To develop the methodology, five zircon-cadmium sulfoselenide pigments with different hues were selected, studying the different measurement process steps, from sample preparation to the optimisation of the measurement of the different components of the pigments by spectroscopic techniques (WD-XRF and elemental analysis by combustion and IR detection). The chemical characterisation method developed was validated with synthetic standards prepared from the mixture of certified reference materials and pure oxides because no certified referenced materials of this type of pigments were commercially available. The developed method can be used for a complete chemical characterization of zircon-cadmium sulfoselenide ceramic pigments with a very low uncertainty for all the elements analysed.El objetivo del presente trabajo es el desarrollo de una metodología que permita la caracterización química completa de pigmentos cerámicos a base de sulfoseleniuro de cadmio, incluyendo elementos mayoritarios y minoritarios. Para desarrollar la metodología, se seleccionaron cinco pigmentos a base de sulfoseleniuro de cadmio, estudiando las distintas fases del proceso de medida, desde la preparación de la muestra hasta la optimización de la medida de los distintos componentes de los pigmentos por técnicas espectroscópicas (WD-FRX y análisis elemental por combustión y detección mediante IR). El método de caracterización química desarrollado se validó con patrones sintéticos preparados a partir de la mezcla de materiales de referencia certificados y óxidos puros debido a que no existen comercialmente materiales de referencia certificados de este tipo de pigmentos. Este método se puede utilizar para la caracterización química completa de pigmentos a base de sulfoseleniuro de cadmio con incertidumbres muy bajas para todos los elementos analizados.

Published
2013
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28. High Prevalence and Early Occurrence of Skeletal Complications in EGFR Mutated NSCLC Patients With Bone Metastases

Author

Lagana, M, Gurizzan, C, Roca, E, Cortinovis, D, Signorelli, D, Pagani, F, Bettini, A, Bonomi, L, Rinaldi, S, Berardi, R, Filetti, M, Giusti, R, Pilotto, S, Milella, M, Intagliata, S, Baggi, A, Cortellini, A, Soto Parra, H, Brighenti, M, Petrelli, F, Bennati, C, Bidoli, P, Garassino, M, Berruti, A, Lagana M., Gurizzan C., Roca E., Cortinovis D., Signorelli D., Pagani F., Bettini A., Bonomi L., Rinaldi S., Berardi R., Filetti M., Giusti R., Pilotto S., Milella M., Intagliata S., Baggi A., Cortellini A., Soto Parra H., Brighenti M., Petrelli F., Bennati C., Bidoli P., Garassino M. C., Berruti A., Lagana, M, Gurizzan, C, Roca, E, Cortinovis, D, Signorelli, D, Pagani, F, Bettini, A, Bonomi, L, Rinaldi, S, Berardi, R, Filetti, M, Giusti, R, Pilotto, S, Milella, M, Intagliata, S, Baggi, A, Cortellini, A, Soto Parra, H, Brighenti, M, Petrelli, F, Bennati, C, Bidoli, P, Garassino, M, Berruti, A, Lagana M., Gurizzan C., Roca E., Cortinovis D., Signorelli D., Pagani F., Bettini A., Bonomi L., Rinaldi S., Berardi R., Filetti M., Giusti R., Pilotto S., Milella M., Intagliata S., Baggi A., Cortellini A., Soto Parra H., Brighenti M., Petrelli F., Bennati C., Bidoli P., Garassino M. C., and Berruti A.

Abstract

Objectives: The prevalence of Skeletal Related Adverse Events (SREs) in EGFR mutated non-small cell lung cancer (NSCLC) patients with bone metastases, treated with modern tyrosine kinase inhibitors (TKIs), has been scarcely investigated. Materials and Methods: We retrospectively evaluated the data of EGFR mutated NSCLC patients with bone metastases treated with TKIs in 12 Italian centers from 2014 to 2019, with the primary aim to explore type and frequency of SREs. Results: Seventy-seven out of 274 patients enrolled (28%) developed at least one major SRE: 55/274 (20%) bone fractures, 30/274 (11%) spinal cord compression, 5/274 (2%) hypercalcemia. Median time to the onset of SRE was 3.63 months. Nine patients (3%) underwent bone surgery and 150 (55%) radiation therapy on bone. SREs were more frequently observed within the 12 months from TKI start than afterwards (71 vs 29%, p 0.000). Patient Performance Status and liver metastases where independently associated with the risk of developing SREs. Median TKI exposure and overall survival were 11 and 28 months, respectively. Bone resorption inhibitors were associated with a lower risk of death (HR 0.722, 95% CI: 0.504–1.033, p = 0.075) although not statistically significant at multivariate analysis. Conclusion: Bone metastatic NSCLC patients with EGFR mutated disease, treated with EGFR TKIs, have a relatively long survival expectancy and are at high risk to develop SREs. The early SRE occurrence after the TKI start provides the rationale to administer bone resorption inhibitors.

Published
2020

29. Addressing a New Class of Multi-Objective Passive Device Optimization for Radiofrequency Circuit Design

Author

Universidad de Sevilla. Departamento de Electrónica y Electromagnetismo, Ministerio de Ciencia e Innovación (MICIN). España, European Union (UE). H2020, Moreira de Passos, Fabio, Roca, E., Castro López, R., Fernández Fernández, Francisco Vidal, Universidad de Sevilla. Departamento de Electrónica y Electromagnetismo, Ministerio de Ciencia e Innovación (MICIN). España, European Union (UE). H2020, Moreira de Passos, Fabio, Roca, E., Castro López, R., and Fernández Fernández, Francisco Vidal

Abstract

The design of radiofrequency circuits and systems lends itself to multi-objective optimization and the bottom-up composition of Pareto-optimal fronts. Conventional multi-objective optimization algorithms can effectively attain these fronts, which maximize or minimize a set of competing objective functions of interest. However, some of these real-life optimization problems reveal a non-conventional feature: there is one objective function that calls neither for minimization nor maximization. Instead, using the Pareto front demands this objective function to be swept across so that all its feasible values are available. Such a non-conventional feature, as shown here, emerges in the case of inductor optimization. The problem thus turns into a non-conventional one: determining how to find uniformly distributed feasible values of this function over the broadest possible range (typically unknown) while minimizing or maximizing the remaining competing objective functions. An NSGA-II-inspired algorithm is proposed that, based on the dynamic allocation of objective function slots and a modified dominance definition, can successfully return sets of solutions for inductor optimization problems with one sweeping objective. Furthermore, a mathematical benchmark function modeling this kind of problem is presented, which is also used to exhaustively test the proposed algorithm and obtain insight into its parameter settings.

Published
2022

30. A Definitive Prognostication System for Patients With Thoracic Malignancies Diagnosed With Coronavirus Disease 2019: An Update From the TERAVOLT Registry

Author

Whisenant, J. G., Baena, J., Cortellini, A., Huang, L. C., Lo Russo, G., Porcu, L., Wong, S. K., Bestvina, C. M., Hellmann, M. D., Roca, E., Rizvi, H., Monnet, I., Boudjemaa, A., Rogado, J., Pasello, G., Leighl, N. B., Arrieta, O., Aujayeb, A., Batra, U., Azzam, A. Y., Unk, M., Azab, M. A., Zhumagaliyeva, A. N., Gomez-Martin, C., Blaquier, J. B., Geraedts, E., Mountzios, G., Serrano-Montero, G., Reinmuth, N., Coate, L., Marmarelis, M., Presley, C. J., Hirsch, F. R., Garrido, P., Khan, H., Baggi, A., Mascaux, C., Halmos, B., Ceresoli, G. L., Fidler, M. J., Scotti, V., Métivier, A. C., Falchero, L., Felip, E., Genova, C., Mazieres, J., Tapan, U., Brahmer, J., Dingemans, A. M., Peters, S., Whisenant, J. G., Baena, J., Cortellini, A., Huang, L. C., Lo Russo, G., Porcu, L., Wong, S. K., Bestvina, C. M., Hellmann, M. D., Roca, E., Rizvi, H., Monnet, I., Boudjemaa, A., Rogado, J., Pasello, G., Leighl, N. B., Arrieta, O., Aujayeb, A., Batra, U., Azzam, A. Y., Unk, M., Azab, M. A., Zhumagaliyeva, A. N., Gomez-Martin, C., Blaquier, J. B., Geraedts, E., Mountzios, G., Serrano-Montero, G., Reinmuth, N., Coate, L., Marmarelis, M., Presley, C. J., Hirsch, F. R., Garrido, P., Khan, H., Baggi, A., Mascaux, C., Halmos, B., Ceresoli, G. L., Fidler, M. J., Scotti, V., Métivier, A. C., Falchero, L., Felip, E., Genova, C., Mazieres, J., Tapan, U., Brahmer, J., Dingemans, A. M., and Peters, S.

Abstract

Introduction: Patients with thoracic malignancies are at increased risk for mortality from coronavirus disease 2019 (COVID-19), and a large number of intertwined prognostic variables have been identified so far. Methods: Capitalizing data from the Thoracic Cancers International COVID-19 Collaboration (TERAVOLT) registry, a global study created with the aim of describing the impact of COVID-19 in patients with thoracic malignancies, we used a clustering approach, a fast-backward step-down selection procedure, and a tree-based model to screen and optimize a broad panel of demographics and clinical COVID-19 and cancer characteristics. Results: As of April 15, 2021, a total of 1491 consecutive eligible patients from 18 countries were included in the analysis. With a mean observation period of 42 days, 361 events were reported with an all-cause case fatality rate of 24.2%. The clustering procedure screened 73 covariates in 13 clusters. A further multivariable logistic regression for the association between clusters and death was performed, resulting in five clusters significantly associated with the outcome. The fast-backward step-down selection procedure then identified the following seven major determinants of death: Eastern Cooperative Oncology Group—performance status (ECOG-PS) (OR = 2.47, 1.87–3.26), neutrophil count (OR = 2.46, 1.76–3.44), serum procalcitonin (OR = 2.37, 1.64–3.43), development of pneumonia (OR = 1.95, 1.48–2.58), C-reactive protein (OR = 1.90, 1.43–2.51), tumor stage at COVID-19 diagnosis (OR = 1.97, 1.46–2.66), and age (OR = 1.71, 1.29–2.26). The receiver operating characteristic analysis for death of the selected model confirmed its diagnostic ability (area under the receiver operating curve = 0.78, 95% confidence interval: 0.75–0.81). The nomogram was able to classify the COVID-19 mortality in an interval ranging from 8% to 90%, and the tree-based model recognized ECOG-PS, neutrophil count, and c-reactive protein as the major determinants of

Published
2022

31. Preliminary Validation of FoRCaSco: A New Grading System for Cerebral and Cerebellar Cavernomas

Author

Fontanella, Marco Maria, Zanin, L., Panciani, P., Belotti, F., Doglietto, Francesco, Cremonesi, A., Migliorati, K., Roca, E., De Maria, L., Franzin, A., Vivaldi, O., Griva, F., Narducci, A., Draghi, R., Calbucci, F., Borghesi, I., Crobeddu, E., Cossandi, C., Fioravanti, A., Arias, J. A., Scerrati, A., De Bonis, P., Locatelli, D., Agosti, E., Veiceschi, P., Ceraudo, M., Zona, G., Gasparotti, R., Terzi di Bergamo, L., Rigamonti, D., Fontanella M. M., Doglietto F. (ORCID:0000-0002-7438-0734), Fontanella, Marco Maria, Zanin, L., Panciani, P., Belotti, F., Doglietto, Francesco, Cremonesi, A., Migliorati, K., Roca, E., De Maria, L., Franzin, A., Vivaldi, O., Griva, F., Narducci, A., Draghi, R., Calbucci, F., Borghesi, I., Crobeddu, E., Cossandi, C., Fioravanti, A., Arias, J. A., Scerrati, A., De Bonis, P., Locatelli, D., Agosti, E., Veiceschi, P., Ceraudo, M., Zona, G., Gasparotti, R., Terzi di Bergamo, L., Rigamonti, D., Fontanella M. M., and Doglietto F. (ORCID:0000-0002-7438-0734)

Abstract

Objective: Surgical indications for cerebral cavernous malformations (CCMs) remain significantly center- and surgeon-dependent; available grading systems are potentially limited, as they do not include epileptologic and radiologic data. Several experienced authors proposed a new grading system for CCM and the first group of patients capable of providing its statistical validation was analyzed. Methods: A retrospective series of 289 CCMs diagnosed between 2008 and 2021 was collected in a shared anonymous database among 9 centers. The new grading system ranges from –1 to 10. For each patient with cortical and cerebellar cavernous malformations the grading system was applied, and a retrospective outcome analysis was performed. We proposed a score of 4 as a cutoff for surgical indication. Results: Operated patients with a score ≥4 were grouped with non-operated patients with a score <4, as they constituted the group that received correct treatment according to the new grading system. Patients with a score ≥4, who underwent surgery and had an improved outcome, were compared to patients with a score ≥4 who were not operated (P = 0.04), and to patients with a score <4 who underwent surgery (P < 0.001). Conclusions: This preliminary statistical analysis demonstrated that this new grading would be applicable in surgical reality. The cutoff score of 4 correctly separated the patients who could benefit from surgical intervention from those who would not. The outcome analysis showed that the treated patients in whom the grading system has been correctly applied have a better outcome than those in whom the grading system has not been applied.

Published
2022

32. Robotics in Neuroendoscopy

Author

Mohammed Maan Al-Salihi, R. Shane Tubbs, Ali Ayyad, Tetsuya Goto, Mohammad Maarouf, Madoglio, A., Roca, E., Tampalini, F., Fontanella, Marco Maria, Doglietto, Francesco, Fontanella M. M., Doglietto F. (ORCID:0000-0002-7438-0734), Mohammed Maan Al-Salihi, R. Shane Tubbs, Ali Ayyad, Tetsuya Goto, Mohammad Maarouf, Madoglio, A., Roca, E., Tampalini, F., Fontanella, Marco Maria, Doglietto, Francesco, Fontanella M. M., and Doglietto F. (ORCID:0000-0002-7438-0734)

Abstract

Robotics is routinely used in several surgical fields. Different robots have been applied in neurosurgery, but only a few of them are relevant to neuroendoscopy. This chapter provides an overview of robotics applied to the different fields of cranial neuroendoscopy. It describes the advantages and disadvantages of reported preclinical prototypes and reviews the few clinical studies that have described robotics as applied to neuroendoscopic cranial surgery. Robotics in neurosurgical practice is a growing field of interest. As it stands, more research is needed to develop systems that are conceived specifically for cranial neuroendoscopy. Further preclinical and clinical studies are required to evaluate the benefits and limits of current commercially available systems.

Published
2022

33. Aneurismal subarachnoid hemorrhage during the COVID-19 outbreak in a Hub and Spoke system: observational multicenter cohort study in Lombardy, Italy

Author

Fiorindi, A., Vezzoli, M., Doglietto, Francesco, Zanin, L., Saraceno, G., Agosti, E., Barbieri, A., Bellocchi, S., Bernucci, C., Bongetta, D., Cardia, A., Costi, E., Egidi, M., Fioravanti, A., Gasparotti, R., Giussani, C., Grimod, G., Latronico, N., Locatelli, D., Mardighian, D., Nodari, G., Poli, J. C., Rasulo, F., Roca, E., Sicuri, G. M., Spena, G., Stefini, R., Vivaldi, O., Zoia, C., Calza, S., Fontanella, Marco Maria, Cenzato, M., Doglietto F. (ORCID:0000-0002-7438-0734), Fontanella M. M., Fiorindi, A., Vezzoli, M., Doglietto, Francesco, Zanin, L., Saraceno, G., Agosti, E., Barbieri, A., Bellocchi, S., Bernucci, C., Bongetta, D., Cardia, A., Costi, E., Egidi, M., Fioravanti, A., Gasparotti, R., Giussani, C., Grimod, G., Latronico, N., Locatelli, D., Mardighian, D., Nodari, G., Poli, J. C., Rasulo, F., Roca, E., Sicuri, G. M., Spena, G., Stefini, R., Vivaldi, O., Zoia, C., Calza, S., Fontanella, Marco Maria, Cenzato, M., Doglietto F. (ORCID:0000-0002-7438-0734), and Fontanella M. M.

Abstract

Background: Lombardy was the most affected Italian region by the first phase of the COVID-19 pandemic and underwent urgent reorganization for the management of emergencies, including subarachnoid hemorrhage from a ruptured cerebral aneurysm (aSAH). The aim of the study was to define demographics, clinical, and therapeutic features of aSAH during the COVID-19 outbreak and compare these with a historical cohort. Methods: In this observational multicenter cohort study, patients aged 18 years or older, who were diagnosed with aSAH at the participating centers in Lombardy from March 9 to May 10, 2020, were included (COVID-19 group). In order to minimize bias related to possible SAH seasonality, the control group was composed of patients diagnosed with aSAH from March 9 to May 10 of the three previous years, 2017–2018-2019 (pre-pandemic group). Twenty-three demographic, clinical, and therapeutic features were collected. Statistical analysis was performed. Results: Seventy-two patients during the COVID-19 period and 179 in the control group were enrolled at 14 centers. Only 4 patients were positive for SARS-CoV-2. The “diagnostic delay” was significantly increased (+ 68%) in the COVID-19 group vs. pre-pandemic (1.06 vs. 0.63 days, respectively, p-value = 0.030), while “therapeutic delay” did not differ significantly between the two periods (0.89 vs. 0.74 days, p-value = 0.183). Patients with poor outcome (GOS at discharge from 1 to 3) were higher during the COVID-19 period (54.2%) compared to pre-pandemic (40.2%, p = 0.044). In logistic regression analysis, in which outcome was the dichotomized Glasgow Outcome Scale (GOS), five variables showed p-values < 0.05: age at admission, WFNS grade, treatment (none), days in ICU, and ischemia. Conclusions: We documented a significantly increased “diagnostic delay” for subarachnoid hemorrhages during the first COVID-19 outbreak in Lombardy. However, despite the dramatic situation that the healthcare system was expe

Published
2022

34. Erratum to ‘Evaluation of COVID-19 impact on DELAYing diagnostic-therapeutic pathways of lung cancer patients in Italy (COVID-DELAY study): fewer cases and higher stages from a real-world scenario’: [ESMO Open Volume 7, Issue 2, April 2022, 100406]

Author

Cantini, L., Mentrasti, G., Lo Russo, G., Signorelli, D., Pasello, G., Rijavec, E., Russano, M., Antonuzzo, L., Rocco, D., Giusti, R., Adamo, V., Genova, C., Tuzi, A., Morabito, A., Gori, S., La Verde, N., Chiari, R., Cortellini, A., Cognigni, V., Pecci, F., Indini, A., De Toma, A., Zattarin, E., Oresti, S., Pizzutilo, E.G., Frega, S., Erbetta, E., Galletti, A., Citarella, F., Fancelli, S., Caliman, E., Della Gravara, L., Malapelle, U., Filetti, M., Piras, M., Toscano, G., Zullo, L., De Tursi, M., Di Marino, P., D’Emilio, V., Cona, M.S., Guida, A., Caglio, A., Salerno, F., Spinelli, G.P., Bennati, C., Morgillo, F., Russo, A., Dellepiane, C., Vallini, I., Sforza, V., Inno, A., Rastelli, F., Tassi, V., Nicolardi, L., Pensieri, M.V., Emili, R., Roca, E., Migliore, A., Galassi, T., Rocchi, M.B.L., and Berardi, R.

Published
2022
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39. Efficacy of nivolumab in pre-treated non-small-cell lung cancer patients harbouring KRAS mutations

Author

Passiglia, F, Cappuzzo, F, Alabiso, O, Bettini, A, Bidoli, P, Chiari, R, Defferrari, C, Delmonte, A, Finocchiaro, G, Francini, G, Gelsomino, F, Giannarelli, D, Giordano, M, Illiano, A, Livi, L, Martelli, O, Natoli, C, Puppo, G, Ricevuto, E, Roca, E, Turci, D, Galetta, D, Passiglia F, Cappuzzo F, Alabiso O, Bettini AC, Bidoli P, Chiari R, Defferrari C, Delmonte A, Finocchiaro G, Francini G, Gelsomino F, Giannarelli D, Giordano M, Illiano A, Livi L, Martelli O, Natoli C, Puppo G, Ricevuto E, Roca E, Turci D, Galetta D., Passiglia, F, Cappuzzo, F, Alabiso, O, Bettini, A, Bidoli, P, Chiari, R, Defferrari, C, Delmonte, A, Finocchiaro, G, Francini, G, Gelsomino, F, Giannarelli, D, Giordano, M, Illiano, A, Livi, L, Martelli, O, Natoli, C, Puppo, G, Ricevuto, E, Roca, E, Turci, D, Galetta, D, Passiglia F, Cappuzzo F, Alabiso O, Bettini AC, Bidoli P, Chiari R, Defferrari C, Delmonte A, Finocchiaro G, Francini G, Gelsomino F, Giannarelli D, Giordano M, Illiano A, Livi L, Martelli O, Natoli C, Puppo G, Ricevuto E, Roca E, Turci D, and Galetta D.

Abstract

Background: The present study investigated the efficacy and safety of nivolumab in pre-treated patients with advanced NSCLC harbouring KRAS mutations. Methods: Clinical data and KRAS mutational status were analysed in patients treated with nivolumab within the Italian Expanded Access Program. Objective response rate, progression-free survival and overall survival were evaluated. Patients were monitored for adverse events using the National Cancer Institute Common Terminology Criteria for Adverse Events. Results: Among 530 patients evaluated for KRAS mutations, 206 (39%) were positive while 324 (61%) were KRAS wild-type mutations. KRAS status did not influence nivolumab efficacy in terms of ORR (20% vs 17%, P = 0.39) and DCR (47% vs 41%, P = 0.23). The median PFS and OS were 4 vs 3 months (P = 0.5) and 11.2 vs 10 months (P = 0.8) in the KRAS-positive vs the KRAS-negative group. The 3-months PFS rate was significantly higher in the KRAS-positive group as compared to the KRAS-negative group (53% vs 42%, P = 0.01). The percentage of any grade and grade 3–4 AEs were 45% vs 33% (P = 0.003) and 11% vs 6% (P = 0.03) in KRAS-positive and KRAS-negative groups, respectively. Conclusions: Nivolumab is an effective and safe treatment option for patients with previously treated, advanced non-squamous NSCLC regardless of KRAS mutations.

Published
2019

40. Preparación de secciones estratigráficas: aspectos prácticos del análisis de estratos en obras del Patrimonio Cultural (pigmentos y soportes)

Author

Jiménez Roca, E., Ruiz-Conde, A., and Sánchez-Soto, P. J.

Subjects
Stratigraphic section (cross-section), Cultural Heritage, analysis of strates, pigments, supports, Sección estratigráfica, Patrimonio Cultural, análisis de estratos, pigmentos, soportes, Clay industries. Ceramics. Glass, TP785-869
Abstract

The stratigraphic sections (cross-sections) are of valuable utility for scientific studies concerning samples coming from Cultural Heritage materials. This paper aims to show several indications and orientations as a working methodology that allows an easy, economic and versatile procedure of simultaneous preparation concerning these stratigraphic sections. Several steps must be followed: a) initial preparation of samples using (poly)metacrylate bars; b) consolidation using a polymer; c) cutting; d) polishing; e) observation using optical microscopy and photography. The main practical aspects involved in the stratigraphic analysis are described. In particular, pigments and supports are used as illustrative examples. It is pointed out the importante of stratigraphic preparations, which must be representative of the material if a diagnosis or approximation to the conservation-degradation state of the original artwork piece is being pursued. This is very important prior to a second step of restauration and conservation by other specialists. Moreover, the preparation of stratigraphic sections open the possibility of further studies using several techniques applied in materials science analysis, obtaining relevant results concerning texture, chemical and phase composition of these samples of Cultural Heritage.Las secciones estratigráficas (estratigrafías) son de suma utilidad para los estudios científicos de muestras pertenecientes al Patrimonio Cultural. En este artículo se pretende dar una serie de consejos y orientaciones útiles como metodología de trabajo que permite un fácil, económico y versátil procedimiento de preparación de dichas secciones estratigráficas, con posibilidad de realización simultánea. En concreto, las distintas etapas a seguir son: a) preparación inicial utilizando tiras de (poli)metacrilato; b) embutido de las muestras; c) corte de las preparaciones; d) lijado y pulido; e) observación al microscopio óptico y fotografiado. Se describen los aspectos prácticos más destacados en el análisis de estratos que se pueden realizar; en particular, los pigmentos y soportes como ejemplos más ilustrativos. Se destaca la importancia de la obtención de estratigrafías representativas si lo que se pretende es llegar a un diagnóstico o aproximación al estado de alteración-degradación de la obra de arte con objeto de una fase siguiente de restauración y conservación de la misma, a cargo de otros especialistas. Asimismo, la preparación de estratigrafías abre la posibilidad de estudios posteriores por distintas técnicas instrumentales de análisis de materiales, obteniendo datos de relevancia sobre textura, composición química y de fases de muestras del Patrimonio Cultural.

Published
2005

41. Control paleomagnético de la cinemática de márgenes pasivos invertidos con estructuras salinas diapíricas. Resultados preliminares en sedimentos sindiapíricos del margen norte de la cuenca extensional Vasco-Cantábrica

Author

Beamud, Elisabet, Roca, E., Soto, R., Peigney, Charlotte, Pueyo, E. L., Generalitat de Catalunya, and Agencia Estatal de Investigación (España)

Subjects
Basque-Cantabrian extensional Basin, salt diapiric structures, Salt tectonics, Basque-Cantabrian Basin, vetical axis rotation, remagnetization, Paleomagnetic
Abstract

X Congreso Geológico de España, 5-7 Julio 2021, Vitoria - Gasteiz, Los niveles salinos depositados antes de la deformación, tanto en márgenes pasivos como en contextos orogénicos, producen una deformación diferencial en los niveles por encima y por debajo del despegue salino. La distribución de los despegues salinos controla el acortamiento diferencial y la formación de arcos orogénicos y el diapirismo puede generar minicuencas asociadas a rotaciones de ejes vertical durante su desarrollo. Nuestro estudio, con 65 estaciones paleomagnéticas, pretende deducir la cinemática de estructuras salinas mediante el estudio de una porción del Arco Vasco, en el margen norte de la Cuenca extensiva Vasco-Cantábrica, donde la cobertera de la sal está compartimentada por varias paredes salinas (diapiros de Bakio, Bermeo, Guernica y Mungia). Los resultados muestran rotaciones antihorarias predominantes y rotaciones horarias y antihorarias en flancos opuestos de los diapiros. Los test del pliegue revelan que algunas estaciones están remagnetizadas mientras otras muestran magnetizaciones ¿prefolding¿. Los experimentos de magnetismo de rocas en parte de las muestras estudiadas confirman estas observaciones. A pesar de que son necesarios más análisis para entender el origen y la distribución de las remagnetizaciones, es posible establecer un modelo cinemático preliminar de la deformación suprasal junto a los materiales despegados infrayacentes., This work has been supported by the project SALTCON- BELT-CGL2017-85532-P funded by Agencia Estatal de Investigación (AEI) and FEDER. Some of the authors are members of the consolidated research group of Geodynamics and Basin Analysis 2017SGR596 of the Generalitat de Catalunya.

Published
2021

42. OA01.02 Impact of COVID-19 Outbreak on Lung Cancer Diagnosis and Continuum of Care: Data From an Italian Multicenter Study

Author

Cantini, L., primary, Mentrasti, G., additional, Siena, S., additional, Pasello, G., additional, Galetti, A., additional, Caliman, E., additional, Rocco, D., additional, Adamo, V., additional, Genova, C., additional, Morabito, A., additional, Gori, S., additional, Rijavec, E., additional, Chiari, R., additional, Oldani, S., additional, Caglio, A., additional, De Tursi, M., additional, Cortellini, A., additional, Morgillo, F., additional, Bennati, C., additional, Guida, A., additional, Spinelli, G.P., additional, Emili, R., additional, Roca, E., additional, Indini, A., additional, De Toma, A., additional, Vallini, I., additional, D'Emilio, V., additional, Cognigni, V., additional, Pecci, F., additional, Migliore, A., additional, Della Gravara, L., additional, Frega, S., additional, Zullo, L., additional, Zattarin, E., additional, Citarella, F., additional, Russo, A., additional, Fancelli, S., additional, Oresti, S., additional, and Berardi, R., additional

Published
2021
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43. Protective effect of Chuquiraga spinosa Lessing associated with simvastatin on N-Nitroso-N-methylurea (NMU)-induced prostate cancer in rats

Author

Arroyo-Acevedo JL, Rojas-Armas JP, Herrera-Calderón O, Chávez-Asmat R, Justil-Guerrero HJ, Aguilar-Carranza C, Enciso-Roca E, Tinco-Jayo JA, Yuli-Posadas RÁ, Franco-Quino C, and Chumpitaz-Cerrate V

Subjects
Prostate cancer, Chuquiraga spinosa, simvastatin, anti-tumor, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, lcsh:RC254-282
Abstract

Jorge Luis Arroyo-Acevedo,1 Juan Pedro Rojas-Armas,1 Oscar Herrera-Calderón,2 Roberto Chávez-Asmat,3 Hugo Jesús Justil-Guerrero,1 Cristian Aguilar-Carranza,4 Edwin Enciso-Roca,5 Johnny Aldo Tinco-Jayo,5 Ricardo Ángel Yuli-Posadas,6 Cesar Franco-Quino,7 Victor Chumpitaz-Cerrate81Laboratory of Pharmacology, Faculty of Medicine, Universidad Nacional Mayor De San Marcos, Lima, Peru; 2Laboratory of Pharmacognosy and Traditional Medicine, Faculty of Pharmacy and Biochemistry, Universidad Nacional Mayor De San Marcos, Lima, Peru; 3Association for the Development of Student Research in Health Sciences (ADIECS), Lima, Peru; 4Department of Pathology, National Cardiovascular Institute, Lima, Peru; 5Faculty of Health Sciences, Universidad Nacional De San Cristóbal De Huamanga, Ayacucho, Peru; 6Universidad Continental, Huancayo, Peru; 7Faculty of Public Health and Administration, Universidad Peruana Cayetano Heredia, Lima, Peru; 8Laboratory of Pharmacology, Universidad Científica Del Sur, Lima, PeruBackground and objective: Chuquiraga spinosa Lessing (ChS) has shown protective effect on N-Nitroso-N-methylurea (NMU)-induced prostate cancer in rats. Currently, statins are being studied for their pro-apoptotic and antimetastatic effects. The main objective of this research was to determine the protective effect associated withthe oral administration of simvastatin and ethanolic extract of the aerial parts of ChSin the prevention of prostate cancer.Methods: Fifty-six albino male rats were randomized into seven groups: I) negative control: physiological serum: 2 mL/kg; II) TCN: testosterone 100 mg/kg + cyproterone 50 mg/kg + NMU 50 mg/kg; III) TCN + S40 (simvastatin 40 mg/kg); IV) TCN + ChS250 (ChS 250 mg/kg); V) TCN + ChS50 (ChS 50 mg/kg) + S40; VI) TCN + ChS250 (ChS 250 mg/kg) + S40; and VII) TCN + ChS500 (ChS 500 mg/kg) + S40. The antioxidant activity was tested by using (2,2-diphenyl-1-picrylhydrazyl) (DPPH) assay. Hematology, toxicological biochemical parameters, prostate-specific antigen (PSA), histology and prostate size were evaluated as main indicators of protective effect.Results: Triglyceride values were decreased in the groups receiving ChS, being significant (P=0.02) in IV and VII group compared to cancer-inducing group (TCN). In groups that received ChS, PSA levels (P=0.71) were significant compared with TCN group. The VII group had the lowest prostate volume by sonography. The TCN group showed multiple foci of high-grade prostatic intraepithelial neoplasia (HG-PIN) with the presence of cells in mitosis; whilst, groups V and VI had few areas of HG-PIN.Conclusion: In experimental conditions, the ethanolic extract of C. spinosa in association with simvastatin showed a protective effect on prostate cancer through hypolipidemic and antioxidant activity.Keywords: prostate cancer, anti-tumor, Chuquiraga spinosa, simvastatin

Published
2019

47. El proyecto DIGNITY: hacia un sistema de movilidad digital inclusivo en el Área Metropolitana de Barcelona

Author

Roca, E., Bartosz W., Lazzarini, B., Villares, M., ALVAR GAROLA, Universitat Politècnica de Catalunya. Departament d'Enginyeria Civil i Ambiental, Universitat Politècnica de Catalunya. Institut Universitari de Recerca en Ciència i Tecnologies de la Sostenibilitat, Universitat Politècnica de Catalunya. LESEC - Laboratori d'Estudis Socials de l'Enginyeria Civil, and Universitat Politècnica de Catalunya. EXIT - Enginyeria, Xarxes, Infraestructures, Territori

Subjects
Àrea metropolitana) [Transport urbà -- Barcelona (Catalunya], Urban transportation--Spain--Catalonia, Enginyeria civil::Infraestructures i modelització dels transports::Transport urbà [Àrees temàtiques de la UPC]
Abstract

Los recientes desarrollos en el sector del transporte y la movilidad, tal como la digitalización, las aplicaciones inteligentes y los servicios digitales de ámbito local, están alterando radicalmente los patrones de movilidad, ofreciendo una amplia gama de innovaciones que se adaptan a los estilos de vida en rápida evolución. Sin embargo, en este contexto, la falta de una alfabetización digital adecuada, así como competencias/habilidades específicas, puede generar situaciones de exclusión, ya que muchos servicios se ofrecen actualmente en modalidad ‘en línea’ o incorporan elementos digitales. El proyecto DIGNITY (https://www.dignity-project.eu/), una iniciativa europea en el marco H2020, tiene como objetivo promover un ecosistema de servicios digitales de movilidad que sea sostenible, integrado y fácil de usar, que mejore la accesibilidad y la inclusión social, la experiencia de viaje y la vida diaria de todos los ciudadanos. Los desafíos clave del proyecto son: i) integrar las necesidades y características de todos los usuarios finales en el diseño de soluciones de movilidad digital y ii) apoyar a los responsables políticos en la planificación de estrategias a largo plazo para reducir la brecha digital en el transporte, teniendo en cuenta todos los grupos vulnerables (ancianos, pobres, inmigrantes, etc.) y las cuestiones de género. El proyecto ha seleccionado cuatro estudios piloto en cinco países de la UE (España, Italia, Bélgica, los Países Bajos y Alemania) por sus propuestas innovadoras en movilidad sostenible e inclusiva. Los estudios de caso aplicarán el enfoque DIGNITY, llevando a cabo talleres, entrevistas y encuestas. Esta contribución quiere abordar específicamente el estudio basado en Barcelona, que lidera una transformación urbana ‘inteligente’. La brecha digital en movilidad del Área Metropolitana de Barcelona (AMB) se ha evaluado mediante un enfoque mixto: combina una encuesta cuantitativa con un enfoque cualitativo basado en entrevistas en profundidad y una revisión de la literatura. Los resultados discuten las necesidades y actitudes de los usuarios en la movilidad local, así como las brechas en el uso de productos tecnológicos. Objectius de Desenvolupament Sostenible::11 - Ciutats i Comunitats Sostenibles

Published
2021

48. Origin and kinematics of the South Pyrenean front salient from the paleomagnetic study of its eastwards flanking synorogenic materials

Author

Peigney, Charlotte, Beamud, Elisabet, Gratacos, Óscar, Valero Montesa, Luis, Soto, R., Roca, E., and Muñoz, J. A.

Subjects
Paleomagnetisme, Paleomagnetism, vertical-axis rotations, Structural geology, Pyrenees, rotaciones de eje vertical, central South Pyrenean front, frente surpirenaico cen tral, Geologia estructural, Pirineus
Abstract

X Congreso Geológico de España, 5-7 Julio 2021, Vitoria - Gasteiz, Los mantos de cabalgamiento de Bóixols, Montsec y Sierras Marginales constituyen la principal curvatura orogénica del frente surpirenaico central. La parte frontal de este saliente se caracteriza por unos antiformes con núcleo salino de orientación oblicua y despegados en los niveles evaporíticos sinorogénicos de la cuenca de antepaís del Ebro. Estas estructuras deforman los depósitos paleógenos de la cuenca de antepaís. Con la finalidad de explicar la evolución cinemática de estas estructuras y el papel de los niveles evaporíticos en la geometría del saliente, se llevó a cabo el estudio de las rotaciones de eje vertical (VAR) en el sector de Artesa de Segre-Cardona. Se muestrearon 80 estaciones de paleomagnetismo en los materiales detríticos del Eoceno superior-Oligoceno del sector. Su análisis muestra principalmente unas rotaciones antihorarias, relacionadas con el emplazamiento hacia el sur de los mantos de corrimiento surpirenaicos. Adicionalmente, el estudio magnetoestratigráfico de las series del Eoceno superior-Oligoceno permite acotar la edad de las rotaciones observadas., The Bóixols, Montsec and Sierras Marginales thrust sheets make up the principal orogenic curvature of the central South Pyrenean front. The frontal part of this thrust salient is characterized by a series of oblique salt-cored antiforms, which are detached above the synorogenic evaporitic layers of the Ebro forealnd basin. These structures deform the Paleogene deposits of the foreland basin. A study of vertical-axis rotations (VAR) was carried in the Artesa de Segre-Cardona area, aiming to explain the evolution of the kinematics of these structures and the role of the evaporitic detachment levels in the geometry of the salient. 80 paleomagnetic sites were sampled on the Eocene-Oligocene detritic levels in the area. Their analysis shows predominant anti-clockwise rotations, related to the southwards emplacement of the South-Pyrenean thrust sheets. Additionally, a magnetostratigraphic study of the upper Eocene-Oligocene succession add constraints to the age of the observed VAR.

Published
2021

49. Statistical characterization of time-dependent variability defects using the maximum current fluctuation

Author

Universidad de Sevilla. Departamento de Electrónica y Electromagnetismo, Agencia Estatal de Investigación. España, Saraza Canflanca, Pablo, Martín Martínez, J., Castro-López, Rubén, Roca, E., Rodríguez, R., Fernández Fernández, Francisco Vidal, Nafria, Montserrat, Universidad de Sevilla. Departamento de Electrónica y Electromagnetismo, Agencia Estatal de Investigación. España, Saraza Canflanca, Pablo, Martín Martínez, J., Castro-López, Rubén, Roca, E., Rodríguez, R., Fernández Fernández, Francisco Vidal, and Nafria, Montserrat

Abstract

This article presents a new methodology to extract, at a given operation condition, the statistical distribution of the number of active defects that contribute to the observed device time-dependent variability, as well as their amplitude distribution. Unlike traditional approaches based on complex and time-consuming individual analysis of thousands of current traces, the proposed approach uses a simpler trace processing, since only the maximum and minimum values of the drain current during a given time interval are needed. Moreover, this extraction method can also estimate defects causing small current shifts, which can be very complex to identify by traditional means. Experimental data in a wide range of gate voltages, from near-threshold up to nominal operation conditions, are analyzed with the proposed methodology.

Published
2021

50. Origen y cinemática del saliente del frente surpirenaico central a partir del estudio paleomagnético de los materiales sinorogénicos de su margen este

Author

Peigney, Charlotte, Beamud, Elisabet, Gratacos, Óscar, Valero Montesa, Luis, Soto, R., Roca, E., Muñoz, J. A., Peigney, Charlotte, Beamud, Elisabet, Gratacos, Óscar, Valero Montesa, Luis, Soto, R., Roca, E., and Muñoz, J. A.

Abstract

Los mantos de cabalgamiento de Bóixols, Montsec y Sierras Marginales constituyen la principal curvatura orogénica del frente surpirenaico central. La parte frontal de este saliente se caracteriza por unos antiformes con núcleo salino de orientación oblicua y despegados en los niveles evaporíticos sinorogénicos de la cuenca de antepaís del Ebro. Estas estructuras deforman los depósitos paleógenos de la cuenca de antepaís. Con la finalidad de explicar la evolución cinemática de estas estructuras y el papel de los niveles evaporíticos en la geometría del saliente, se llevó a cabo el estudio de las rotaciones de eje vertical (VAR) en el sector de Artesa de Segre-Cardona. Se muestrearon 80 estaciones de paleomagnetismo en los materiales detríticos del Eoceno superior-Oligoceno del sector. Su análisis muestra principalmente unas rotaciones antihorarias, relacionadas con el emplazamiento hacia el sur de los mantos de corrimiento surpirenaicos. Adicionalmente, el estudio magnetoestratigráfico de las series del Eoceno superior-Oligoceno permite acotar la edad de las rotaciones observadas., The Bóixols, Montsec and Sierras Marginales thrust sheets make up the principal orogenic curvature of the central South Pyrenean front. The frontal part of this thrust salient is characterized by a series of oblique salt-cored antiforms, which are detached above the synorogenic evaporitic layers of the Ebro forealnd basin. These structures deform the Paleogene deposits of the foreland basin. A study of vertical-axis rotations (VAR) was carried in the Artesa de Segre-Cardona area, aiming to explain the evolution of the kinematics of these structures and the role of the evaporitic detachment levels in the geometry of the salient. 80 paleomagnetic sites were sampled on the Eocene-Oligocene detritic levels in the area. Their analysis shows predominant anti-clockwise rotations, related to the southwards emplacement of the South-Pyrenean thrust sheets. Additionally, a magnetostratigraphic study of the upper Eocene-Oligocene succession add constraints to the age of the observed VAR.

Published
2021

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