138 results on '"Citarella, F."'
Search Results
2. Bone metastases are associated with worse prognosis in patients affected by metastatic colorectal cancer treated with doublet or triplet chemotherapy plus bevacizumab: a subanalysis of the TRIBE and TRIBE2 trials
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Dell’Aquila, E., Rossini, D., Fulgenzi, C.A.M., Passardi, A., Tamburini, E., Vetere, G., Carullo, M., Citarella, F., Antoniotti, C., Zaniboni, A., Pietrantonio, F., Spagnoletti, A., Marmorino, F., Borelli, B., Allegrini, G., Lonardi, S., Nappo, F., Masi, G., Cremolini, C., and Santini, D.
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- 2022
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3. 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
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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.
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- 2022
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4. The lung immuno-oncology prognostic score (LIPS-3): a prognostic classification of patients receiving first-line pembrolizumab for PD-L1 ≥ 50% advanced non-small-cell lung cancer
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Banna, G.L., Cortellini, A., Cortinovis, D.L., Tiseo, M., Aerts, J.G.J.V., Barbieri, F., Giusti, R., Bria, E., Grossi, F., Pizzutilo, P., Berardi, R., Morabito, A., Genova, C., Mazzoni, F., Di Noia, V., Signorelli, D., Gelibter, A., Macerelli, M., Rastelli, F., Chiari, R., Rocco, D., Gori, S., De Tursi, M., Di Marino, P., Mansueto, G., Zoratto, F., Filetti, M., Montrone, M., Citarella, F., Marco, R., Cantini, L., Nigro, O., D'Argento, E., Buti, S., Minuti, G., Landi, L., Guaitoli, G., Lo Russo, G., De Toma, A., Donisi, C., Friedlaender, A., De Giglio, A., Metro, G., Porzio, G., Ficorella, C., and Addeo, A.
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- 2021
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5. Sotorasib in KRASp.G12C mutated advanced NSCLC: Real-world data from the Italian expanded access program
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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.
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- 2024
6. Real-world outcomes of Italian patients with advanced non-squamous lung cancer treated with first-line pembrolizumab plus platinum-pemetrexed
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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.
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- 2024
7. EP17.06-01 COVID-19 Long-Lasting Effect on Lung Cancer Diagnoses in Italy: Update of the Real-World Multicenter COVID-DELAY Study
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Mentrasti, G., primary, Cognigni, V., additional, Galassi, T., additional, Signorelli, D., additional, Pizzutilo, E.G., additional, Martinelli, F., additional, Lo Russo, G., additional, Leporati, R., additional, Ambrosini, P., additional, Giusti, R., additional, D'Amuri, S., additional, Rocco, D., additional, Della Gravara, L., additional, Antonuzzo, L., additional, Fancelli, S., additional, Gori, S., additional, Sernia, S., additional, Ferrari, M., additional, De Tursi, M., additional, Di Marino, P., additional, Di Maio, M., additional, Salerno, F., additional, Zumstein, L., additional, Russano, M., additional, Citarella, F., additional, Adamo, V., additional, Russo, A., additional, Scimone, C., additional, Sforza, V., additional, Morabito, A., additional, La Verde, N., additional, Cona, M.S., additional, Catalano, V., additional, Emili, R., additional, Sarti, D., additional, Morgillo, F., additional, Di Guida, G., additional, Rocchi, M.B.L., additional, Parisi, A., additional, and Berardi, R., additional
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- 2023
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8. EP11.01-01 Final Analysis of First-Line Chemo-Immunotherapy in Patients with Advanced Lung Adenocarcinoma: An Italian Real-World Study
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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
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- 2023
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9. Host immune-inflammatory markers to unravel the heterogeneous outcome and assessment of patients with PD-L1 ≥50% metastatic non-small cell lung cancer and poor performance status receiving first-line immunotherapy
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Banna, G, Tiseo, M, Cortinovis, D, Facchinetti, F, Aerts, J, Baldessari, C, Giusti, R, Bria, E, Grossi, F, Berardi, R, Morabito, A, Catino, A, Genova, C, Mazzoni, F, Gelibter, A, Rastelli, F, Macerelli, M, Chiari, R, Gori, S, Mansueto, G, Citarella, F, Cantini, L, Rijavec, E, Bertolini, F, Cappuzzo, F, De Toma, A, Friedlaender, A, Metro, G, Pensieri, M, Porzio, G, Ficorella, C, Pinato, D, Cortellini, A, Addeo, A, Banna GL, Tiseo M, Cortinovis D, Facchinetti F, Aerts JGJV, Baldessari C, Giusti R, Bria E, Grossi F, Berardi R, Morabito A, Catino A, Genova C, Mazzoni F, Gelibter A, Rastelli F, Macerelli M, Chiari R, Gori S, Mansueto G, Citarella F, Cantini L, Rijavec E, Bertolini F, Cappuzzo F, De Toma A, Friedlaender A, Metro G, Pensieri MV, Porzio G, Ficorella C, Pinato DJ, Cortellini A, Addeo A, Banna, G, Tiseo, M, Cortinovis, D, Facchinetti, F, Aerts, J, Baldessari, C, Giusti, R, Bria, E, Grossi, F, Berardi, R, Morabito, A, Catino, A, Genova, C, Mazzoni, F, Gelibter, A, Rastelli, F, Macerelli, M, Chiari, R, Gori, S, Mansueto, G, Citarella, F, Cantini, L, Rijavec, E, Bertolini, F, Cappuzzo, F, De Toma, A, Friedlaender, A, Metro, G, Pensieri, M, Porzio, G, Ficorella, C, Pinato, D, Cortellini, A, Addeo, A, Banna GL, Tiseo M, Cortinovis D, Facchinetti F, Aerts JGJV, Baldessari C, Giusti R, Bria E, Grossi F, Berardi R, Morabito A, Catino A, Genova C, Mazzoni F, Gelibter A, Rastelli F, Macerelli M, Chiari R, Gori S, Mansueto G, Citarella F, Cantini L, Rijavec E, Bertolini F, Cappuzzo F, De Toma A, Friedlaender A, Metro G, Pensieri MV, Porzio G, Ficorella C, Pinato DJ, Cortellini A, and Addeo A
- Abstract
Background: Patients with programmed cell death-ligand 1 (PD-L1) ≥50% metastatic non-small cell lung cancer (mNSCLC) and ECOG performance status (PS) of 2 treated with first-line immunotherapy have heterogeneous clinical assessment and outcomes. Methods: To explore the role of immune-inflammatory surrogates by the validated lung immuno-oncology prognostic score (LIPS) score, including the neutrophil-to-lymphocyte ratio (NLR) and the pretreatment use of steroids, alongside other prognostic variables. A retrospective analysis of 128 patients with PS2 and PD-L1 ≥50% mNSCLC treated between April 2018 and September 2019 with first-line pembrolizumab in a real-world setting was performed. Results: With a median follow-up of 15.3 months, the 1-year overall survival (OS) and median progression-free survival (PFS) were 32.3% (95% CI: 30.9–33.9) and 3.3 months (95% CI: 1.8–4.7), respectively. The NLR, lactate dehydrogenase (LDH) and pretreatment steroids results were the only significant prognostic factors on the univariate analysis and independent prognostic factors by the multivariate analysis on both OS and PFS. The LIPS score, including the NLR and pretreatment steroids, identified 29 (23%) favourable-risk patients, with 0 factors, 1-year OS of 67.6% and median PFS of 8.2 months; 57 (45%) intermediate-risk patients, with 1 factor, 1-year OS 32.1% and median PFS 2.7 months; 42 (33%) poor-risk patients, with both factors, 1-year OS of 10.7% and median PFS of 1.2 months. Conclusions: The assessment of pre-existing imbalance of the host immune response by combined blood and clinical immune-inflammatory markers may represent a way to unravel the heterogeneous outcome and assessment of patients with mNSCLC and poor PS in the immune-oncology setting.
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- 2022
10. EP08.01-007 Real-World Outcomes of Patients with Advanced Lung Adenocarcinoma Treated with First-Line Chemo-Immunotherapy in Italy
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F. Perrone, A. Leonetti, primary, Puntoni, M., additional, Bordi, P., additional, Maglietta, G., additional, Carpana, C., additional, Gelsomino, F., additional, Passiglia, F., additional, Genova, C., additional, Montrone, M., additional, Caliman, E., additional, Cerea, G., additional, Pasello, G., additional, Cecere, F., additional, Manzo, A., additional, Adamo, V., additional, Citarella, F., additional, Toschi, L., additional, Gelibter, A., additional, Rastelli, F., additional, Carta, A., additional, Guida, A., additional, Camerini, A., additional, Paoloni, F., additional, Bertolini, F., additional, and Tiseo, M., additional
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- 2022
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11. 1007P Mechanisms of primary and secondary resistance to RET inhibitors in patients with RET-positive advanced NSCLC
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Marinello, A., primary, Vasseur, D., additional, Conci, N., additional, Fallet, V., additional, Audigier-Valette, C., additional, Cousin, S., additional, Tabbò, F., additional, Guisier, F., additional, Russo, A., additional, Calles Blanco, A., additional, Metro, G., additional, Massa, G., additional, Citarella, F., additional, Eisert, A.K., additional, Iranzo Gomez, P., additional, Tagliamento, M., additional, Mezquita, L., additional, Lindsay, C., additional, Ponce, S., additional, and Aldea, M., additional
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- 2022
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12. Predictive ability of a drug-based score in patients with advanced non-small-cell lung cancer receiving first-line immunotherapy
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Buti, S, Bersanelli, M, Perrone, F, Bracarda, S, Di Maio, M, Giusti, R, Nigro, O, Cortinovis, D, Aerts, J, Guaitoli, G, Barbieri, F, Ferrara, M, Bria, E, Grossi, F, Bareggi, C, Berardi, R, Torniai, M, Cantini, L, Sforza, V, Genova, C, Chiari, R, Rocco, D, Della Gravara, L, Gori, S, De Tursi, M, Di Marino, P, Mansueto, G, Zoratto, F, Filetti, M, Citarella, F, Russano, M, Mazzoni, F, Garassino, M, De Toma, A, Signorelli, D, Gelibter, A, Siringo, M, Follador, A, Bisonni, R, Tuzi, A, Minuti, G, Landi, L, Ricciardi, S, Migliorino, M, Tabbò, F, Olmetto, E, Metro, G, Adamo, V, Russo, A, Spinelli, G, Banna, G, Addeo, A, Friedlaender, A, Cannita, K, Porzio, G, Ficorella, C, Carmisciano, L, Pinato, D, Mazzaschi, G, Tiseo, M, Cortellini, A, Buti S, Bersanelli M, Perrone F, Bracarda S, Di Maio M, Giusti R, Nigro O, Cortinovis D, Aerts JGJV, Guaitoli G, Barbieri F, Ferrara MG, Bria E, Grossi F, Bareggi C, Berardi R, Torniai M, Cantini L, Sforza V, Genova C, Chiari R, Rocco D, Della Gravara L, Gori S, De Tursi M, Di Marino P, Mansueto G, Zoratto F, Filetti M, Citarella F, Russano M, Mazzoni F, Garassino MC, De Toma A, Signorelli D, Gelibter A, Siringo M, Follador A, Bisonni R, Tuzi A, Minuti G, Landi L, Ricciardi S, Migliorino MR, Tabbò F, Olmetto E, Metro G, Adamo V, Russo A, Spinelli GP, Banna GL, Addeo A, Friedlaender A, Cannita K, Porzio G, Ficorella C, Carmisciano L, Pinato DJ, Mazzaschi G, Tiseo M, Cortellini A, Buti, S, Bersanelli, M, Perrone, F, Bracarda, S, Di Maio, M, Giusti, R, Nigro, O, Cortinovis, D, Aerts, J, Guaitoli, G, Barbieri, F, Ferrara, M, Bria, E, Grossi, F, Bareggi, C, Berardi, R, Torniai, M, Cantini, L, Sforza, V, Genova, C, Chiari, R, Rocco, D, Della Gravara, L, Gori, S, De Tursi, M, Di Marino, P, Mansueto, G, Zoratto, F, Filetti, M, Citarella, F, Russano, M, Mazzoni, F, Garassino, M, De Toma, A, Signorelli, D, Gelibter, A, Siringo, M, Follador, A, Bisonni, R, Tuzi, A, Minuti, G, Landi, L, Ricciardi, S, Migliorino, M, Tabbò, F, Olmetto, E, Metro, G, Adamo, V, Russo, A, Spinelli, G, Banna, G, Addeo, A, Friedlaender, A, Cannita, K, Porzio, G, Ficorella, C, Carmisciano, L, Pinato, D, Mazzaschi, G, Tiseo, M, Cortellini, A, Buti S, Bersanelli M, Perrone F, Bracarda S, Di Maio M, Giusti R, Nigro O, Cortinovis D, Aerts JGJV, Guaitoli G, Barbieri F, Ferrara MG, Bria E, Grossi F, Bareggi C, Berardi R, Torniai M, Cantini L, Sforza V, Genova C, Chiari R, Rocco D, Della Gravara L, Gori S, De Tursi M, Di Marino P, Mansueto G, Zoratto F, Filetti M, Citarella F, Russano M, Mazzoni F, Garassino MC, De Toma A, Signorelli D, Gelibter A, Siringo M, Follador A, Bisonni R, Tuzi A, Minuti G, Landi L, Ricciardi S, Migliorino MR, Tabbò F, Olmetto E, Metro G, Adamo V, Russo A, Spinelli GP, Banna GL, Addeo A, Friedlaender A, Cannita K, Porzio G, Ficorella C, Carmisciano L, Pinato DJ, Mazzaschi G, Tiseo M, and Cortellini A
- Abstract
Background: We previously demonstrated the cumulative poor prognostic role of concomitant medications on the clinical outcome of patients with advanced cancer treated with immune checkpoint inhibitors, creating and validating a drug-based prognostic score to be calculated before immunotherapy initiation in patients with advanced solid tumours. This ‘drug score’ was calculated assigning score 1 for each between proton-pump inhibitor and antibiotic administration until a month before cancer therapy initiation and score 2 in case of corticosteroid intake. The good risk group included patients with score 0, intermediate risk with score 1–2 and poor risk with score 3–4. Methods: Aiming at validating the prognostic and putative predictive ability depending on the anticancer therapy, we performed the present comparative analysis in two cohorts of advanced non–small-cell lung cancer (NSCLC), respectively, receiving first-line pembrolizumab or chemotherapy through a random case-control matching and through a pooled multivariable analysis including the interaction between the computed score and the therapeutic modality (pembrolizumab vs chemotherapy). Results: Nine hundred fifty and 595 patients were included in the pembrolizumab and chemotherapy cohorts, respectively. After the case-control random matching, 589 patients from the pembrolizumab cohort and 589 from the chemotherapy cohort were paired, with no statistically significant differences between the characteristics of the matched subjects. Among the pembrolizumab-treated group, good, intermediate and poor risk evaluable patients achieved an objective response rate (ORR) of 50.0%, 37.7% and 23.4%, respectively, (p < 0.0001), whereas among the chemotherapy-treated group, patients achieved an ORR of 37.0%, 40.0% and 32.4%, respectively (p = 0.4346). The median progression-free survival (PFS) of good, intermediate and poor risk groups was 13.9 months, 6.3 months and 2.8 months, respectively, within the pembrolizumab coh
- Published
- 2021
13. Differential influence of antibiotic therapy and other medications on oncological outcomes of patients with non-small cell lung cancer treated with first-line pembrolizumab versus cytotoxic chemotherapy
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Cortellini, A, Di Maio, M, Nigro, O, Leonetti, A, Cortinovis, D, Aerts, J, Guaitoli, G, Barbieri, F, Giusti, R, Ferrara, M, Bria, E, D'Argento, E, Grossi, F, Rijavec, E, Guida, A, Berardi, R, Torniai, M, Sforza, V, Genova, C, Mazzoni, F, Garassino, M, De Toma, A, Signorelli, D, Gelibter, A, Siringo, M, Marchetti, P, Macerelli, M, Rastelli, F, Chiari, R, Rocco, D, Della Gravara, L, Inno, A, Michele, T, Grassadonia, A, Di Marino, P, Mansueto, G, Zoratto, F, Filetti, M, Santini, D, Citarella, F, Russano, M, Cantini, L, Tuzi, A, Bordi, P, Minuti, G, Landi, L, Ricciardi, S, Migliorino, M, Passiglia, F, Bironzo, P, Metro, G, Adamo, V, Russo, A, Spinelli, G, Banna, G, Friedlaender, A, Addeo, A, Cannita, K, Ficorella, C, Porzio, G, Pinato, D, Cortellini A, Di Maio M, Nigro O, Leonetti A, Cortinovis D, Aerts JG, Guaitoli G, Barbieri F, Giusti R, Ferrara MG, Bria E, D'Argento E, Grossi F, Rijavec E, Guida A, Berardi R, Torniai M, Sforza V, Genova C, Mazzoni F, Garassino MC, De Toma A, Signorelli D, Gelibter A, Siringo M, Marchetti P, Macerelli M, Rastelli F, Chiari R, Rocco D, Della Gravara L, Inno A, Michele T, Grassadonia A, Di Marino P, Mansueto G, Zoratto F, Filetti M, Santini D, Citarella F, Russano M, Cantini L, Tuzi A, Bordi P, Minuti G, Landi L, Ricciardi S, Migliorino MR, Passiglia F, Bironzo P, Metro G, Adamo V, Russo A, Spinelli GP, Banna GL, Friedlaender A, Addeo A, Cannita K, Ficorella C, Porzio G, Pinato DJ, Cortellini, A, Di Maio, M, Nigro, O, Leonetti, A, Cortinovis, D, Aerts, J, Guaitoli, G, Barbieri, F, Giusti, R, Ferrara, M, Bria, E, D'Argento, E, Grossi, F, Rijavec, E, Guida, A, Berardi, R, Torniai, M, Sforza, V, Genova, C, Mazzoni, F, Garassino, M, De Toma, A, Signorelli, D, Gelibter, A, Siringo, M, Marchetti, P, Macerelli, M, Rastelli, F, Chiari, R, Rocco, D, Della Gravara, L, Inno, A, Michele, T, Grassadonia, A, Di Marino, P, Mansueto, G, Zoratto, F, Filetti, M, Santini, D, Citarella, F, Russano, M, Cantini, L, Tuzi, A, Bordi, P, Minuti, G, Landi, L, Ricciardi, S, Migliorino, M, Passiglia, F, Bironzo, P, Metro, G, Adamo, V, Russo, A, Spinelli, G, Banna, G, Friedlaender, A, Addeo, A, Cannita, K, Ficorella, C, Porzio, G, Pinato, D, Cortellini A, Di Maio M, Nigro O, Leonetti A, Cortinovis D, Aerts JG, Guaitoli G, Barbieri F, Giusti R, Ferrara MG, Bria E, D'Argento E, Grossi F, Rijavec E, Guida A, Berardi R, Torniai M, Sforza V, Genova C, Mazzoni F, Garassino MC, De Toma A, Signorelli D, Gelibter A, Siringo M, Marchetti P, Macerelli M, Rastelli F, Chiari R, Rocco D, Della Gravara L, Inno A, Michele T, Grassadonia A, Di Marino P, Mansueto G, Zoratto F, Filetti M, Santini D, Citarella F, Russano M, Cantini L, Tuzi A, Bordi P, Minuti G, Landi L, Ricciardi S, Migliorino MR, Passiglia F, Bironzo P, Metro G, Adamo V, Russo A, Spinelli GP, Banna GL, Friedlaender A, Addeo A, Cannita K, Ficorella C, Porzio G, and Pinato DJ
- Abstract
Background Some concomitant medications including antibiotics (ATB) have been reproducibly associated with worse survival following immune checkpoint inhibitors (ICIs) in unselected patients with non-small cell lung cancer (NSCLC) (according to programmed death-ligand 1 (PD-L1) expression and treatment line). Whether such relationship is causative or associative is matter of debate. Methods We present the outcomes analysis according to concomitant baseline medications (prior to ICI initiation) with putative immune-modulatory effects in a large cohort of patients with metastatic NSCLC with a PD-L1 expression >= 50%, receiving first-line pembrolizumab monotherapy. We also evaluated a control cohort of patients with metastatic NSCLC treated with first-line chemotherapy. The interaction between key medications and therapeutic modality (pembrolizumab vs chemotherapy) was validated in pooled multivariable analyses. Results 950 and 595 patients were included in the pembrolizumab and chemotherapy cohorts, respectively. Corticosteroid and proton pump inhibitor (PPI) therapy but not ATB therapy was associated with poorer performance status at baseline in both the cohorts. No association with clinical outcomes was found according to baseline statin, aspirin, beta-blocker and metformin within the pembrolizumab cohort. On the multivariable analysis, ATB emerged as a strong predictor of worse overall survival (OS) (HR=1.42 (95% CI 1.13 to 1.79); p=0.0024), and progression free survival (PFS) (HR=1.29 (95% CI 1.04 to 1.59); p=0.0192) in the pembrolizumab but not in the chemotherapy cohort. Corticosteroids were associated with shorter PFS (HR=1.69 (95% CI 1.42 to 2.03); p<0.0001), and OS (HR=1.93 (95% CI 1.59 to 2.35); p<0.0001) following pembrolizumab, and shorter PFS (HR=1.30 (95% CI 1.08 to 1.56), p=0.0046) and OS (HR=1.58 (95% CI 1.29 to 1.94), p<0.0001), following chemotherapy. PPIs were associated with worse OS (HR=1.49 (95% CI 1.26 to 1.77); p<0.0001) with pem
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- 2021
14. Smoking status during first-line immunotherapy and chemotherapy in NSCLC patients: A case-control matched analysis from a large multicenter study
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Cortellini, A, De Giglio, A, Cannita, K, Cortinovis, D, Cornelissen, R, Baldessari, C, Giusti, R, D'Argento, E, Grossi, F, Santoni, M, Catino, A, Berardi, R, Sforza, V, Rossi, G, Antonuzzo, L, Di Noia, V, Signorelli, D, Gelibter, A, Occhipinti, M, Follador, A, Rastelli, F, Chiari, R, Gravara, L, Inno, A, De Tursi, M, Di Marino, P, Mansueto, G, Zoratto, F, Filetti, M, Montrone, M, Citarella, F, Pensieri, M, Russano, M, Cantini, L, Nigro, O, Leonetti, A, Bordi, P, Minuti, G, Landi, L, De Toma, A, Donisi, C, Ricciardi, S, Migliorino, M, Napoli, V, Leone, G, Metro, G, Banna, G, Friedlaender, A, Addeo, A, Ficorella, C, Porzio, G, Cortellini A, De Giglio A, Cannita K, Cortinovis D, Cornelissen R, Baldessari C, Giusti R, D'Argento E, Grossi F, Santoni M, Catino A, Berardi R, Sforza V, Rossi G, Antonuzzo L, Di Noia V, Signorelli D, Gelibter A, Occhipinti MA, Follador A, Rastelli F, Chiari R, Gravara LD, Inno A, De Tursi M, Di Marino P, Mansueto G, Zoratto F, Filetti M, Montrone M, Citarella F, Pensieri MV, Russano M, Cantini L, Nigro O, Leonetti A, Bordi P, Minuti G, Landi L, De Toma A, Donisi C, Ricciardi S, Migliorino MR, Napoli VM, Leone G, Metro G, Banna GL, Friedlaender A, Addeo A, Ficorella C, Porzio G, Cortellini, A, De Giglio, A, Cannita, K, Cortinovis, D, Cornelissen, R, Baldessari, C, Giusti, R, D'Argento, E, Grossi, F, Santoni, M, Catino, A, Berardi, R, Sforza, V, Rossi, G, Antonuzzo, L, Di Noia, V, Signorelli, D, Gelibter, A, Occhipinti, M, Follador, A, Rastelli, F, Chiari, R, Gravara, L, Inno, A, De Tursi, M, Di Marino, P, Mansueto, G, Zoratto, F, Filetti, M, Montrone, M, Citarella, F, Pensieri, M, Russano, M, Cantini, L, Nigro, O, Leonetti, A, Bordi, P, Minuti, G, Landi, L, De Toma, A, Donisi, C, Ricciardi, S, Migliorino, M, Napoli, V, Leone, G, Metro, G, Banna, G, Friedlaender, A, Addeo, A, Ficorella, C, Porzio, G, Cortellini A, De Giglio A, Cannita K, Cortinovis D, Cornelissen R, Baldessari C, Giusti R, D'Argento E, Grossi F, Santoni M, Catino A, Berardi R, Sforza V, Rossi G, Antonuzzo L, Di Noia V, Signorelli D, Gelibter A, Occhipinti MA, Follador A, Rastelli F, Chiari R, Gravara LD, Inno A, De Tursi M, Di Marino P, Mansueto G, Zoratto F, Filetti M, Montrone M, Citarella F, Pensieri MV, Russano M, Cantini L, Nigro O, Leonetti A, Bordi P, Minuti G, Landi L, De Toma A, Donisi C, Ricciardi S, Migliorino MR, Napoli VM, Leone G, Metro G, Banna GL, Friedlaender A, Addeo A, Ficorella C, and Porzio G
- Abstract
Background: Improved outcome in tobacco smoking patients with non-small cell lung cancer (NSCLC) following immunotherapy has previously been reported. However, little is known regarding this association during first-line immunotherapy in patients with high PD-L1 expression. In this study we compared clinical outcomes according to the smoking status of two large multicenter cohorts. Methods: We compared clinical outcomes according to the smoking status (never smokers vs. current/former smokers) of two retrospective multicenter cohorts of metastatic NSCLC patients, treated with first-line pembrolizumab and platinum-based chemotherapy. Results: A total of 962 NSCLC patients with PD-L1 expression ≥50% who received first-line pembrolizumab and 462 NSCLC patients who received first-line platinum-based chemotherapy were included in the study. Never smokers were confirmed to have a significantly higher risk of disease progression (hazard ratio [HR] = 1.49 [95% CI: 1.15–1.92], p = 0.0022) and death (HR = 1.38 [95% CI: 1.02–1.87], p = 0.0348) within the pembrolizumab cohort. On the contrary, a nonsignificant trend towards a reduced risk of disease progression (HR = 0.74 [95% CI: 0.52–1.05], p = 0.1003) and death (HR = 0.67 [95% CI: 0.45–1.01], p = 0.0593) were reported for never smokers within the chemotherapy cohort. After a random case–control matching, 424 patients from both cohorts were paired. Within the matched pembrolizumab cohort, never smokers had a significantly shorter progression-free survival (PFS) (HR = 1.68 [95% CI: 1.17–2.40], p = 0.0045) and a nonsignificant trend towards a shortened overall survival (OS) (HR = 1.32 [95% CI: 0.84–2.07], p = 0.2205). On the contrary, never smokers had a significantly longer PFS (HR = 0.68 [95% CI: 0.49–0.95], p = 0.0255) and OS (HR = 0.66 [95% CI: 0.45–0.97], p = 0,0356) compared to current/former smoker patients within the matched chemotherapy cohort. On pooled multivariable analysis, the interaction term between smoking stat
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- 2021
15. The lung immuno-oncology prognostic score (LIPS-3): a prognostic classification of patients receiving first-line pembrolizumab for PD-L1 ≥ 50% advanced non-small-cell lung cancer
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Banna, G, Cortellini, A, Cortinovis, D, Tiseo, M, Aerts, J, Barbieri, F, Giusti, R, Bria, E, Grossi, F, Pizzutilo, P, Berardi, R, Morabito, A, Genova, C, Mazzoni, F, Di Noia, V, Signorelli, D, Gelibter, A, Macerelli, M, Rastelli, F, Chiari, R, Rocco, D, Gori, S, De Tursi, M, Di Marino, P, Mansueto, G, Zoratto, F, Filetti, M, Montrone, M, Citarella, F, Marco, R, Cantini, L, Nigro, O, D'Argento, E, Buti, S, Minuti, G, Landi, L, Guaitoli, G, Lo Russo, G, De Toma, A, Donisi, C, Friedlaender, A, De Giglio, A, Metro, G, Porzio, G, Ficorella, C, Addeo, A, Banna GL, Cortellini A, Cortinovis D, Tiseo M, Aerts JGJV, Barbieri F, Giusti R, Bria E, Grossi F, Pizzutilo P, Berardi R, Morabito A, Genova C, Mazzoni F, Di Noia V, Signorelli D, Gelibter A, Macerelli M, Rastelli F, Chiari R, Rocco D, Gori S, De Tursi M, Di Marino P, Mansueto G, Zoratto F, Filetti M, Montrone M, Citarella F, Marco R, Cantini L, Nigro O, D'Argento E, Buti S, Minuti G, Landi L, Guaitoli G, Lo Russo G, De Toma A, Donisi C, Friedlaender A, De Giglio A, Metro G, Porzio G, Ficorella C, Addeo A., Banna, G, Cortellini, A, Cortinovis, D, Tiseo, M, Aerts, J, Barbieri, F, Giusti, R, Bria, E, Grossi, F, Pizzutilo, P, Berardi, R, Morabito, A, Genova, C, Mazzoni, F, Di Noia, V, Signorelli, D, Gelibter, A, Macerelli, M, Rastelli, F, Chiari, R, Rocco, D, Gori, S, De Tursi, M, Di Marino, P, Mansueto, G, Zoratto, F, Filetti, M, Montrone, M, Citarella, F, Marco, R, Cantini, L, Nigro, O, D'Argento, E, Buti, S, Minuti, G, Landi, L, Guaitoli, G, Lo Russo, G, De Toma, A, Donisi, C, Friedlaender, A, De Giglio, A, Metro, G, Porzio, G, Ficorella, C, Addeo, A, Banna GL, Cortellini A, Cortinovis D, Tiseo M, Aerts JGJV, Barbieri F, Giusti R, Bria E, Grossi F, Pizzutilo P, Berardi R, Morabito A, Genova C, Mazzoni F, Di Noia V, Signorelli D, Gelibter A, Macerelli M, Rastelli F, Chiari R, Rocco D, Gori S, De Tursi M, Di Marino P, Mansueto G, Zoratto F, Filetti M, Montrone M, Citarella F, Marco R, Cantini L, Nigro O, D'Argento E, Buti S, Minuti G, Landi L, Guaitoli G, Lo Russo G, De Toma A, Donisi C, Friedlaender A, De Giglio A, Metro G, Porzio G, Ficorella C, and Addeo A.
- Abstract
Background: To stratify the prognosis of patients with programmed cell death-ligand 1 (PD-L1) ≥ 50% advanced non-small-cell lung cancer (aNSCLC) treated with first-line immunotherapy. Methods: Baseline clinical prognostic factors, the neutrophil-to-lymphocyte ratio (NLR), PD-L1 tumour cell expression level, lactate dehydrogenase (LDH) and their combination were investigated by a retrospective analysis of 784 patients divided between statistically powered training (n = 201) and validation (n = 583) cohorts. Cut-offs were explored by receiver operating characteristic (ROC) curves and a risk model built with validated independent factors by multivariate analysis. Results: NLR < 4 was a significant prognostic factor in both cohorts (P < 0.001). It represented 53% of patients in the validation cohort, with 1-year overall survival (OS) of 76.6% versus 44.8% with NLR > 4, in the validation series. The addition of PD-L1 ≥ 80% (21% of patients) or LDH < 252 U/l (25%) to NLR < 4 did not result in better 1-year OS (of 72.6% and 74.1%, respectively, in the validation cohort). Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 2 [P < 0.001, hazard ratio (HR) 2.04], pretreatment steroids (P < 0.001, HR 1.67) and NLR < 4 (P < 0.001, HR 2.29) resulted in independent prognostic factors. A risk model with these three factors, namely, the lung immuno-oncology prognostic score (LIPS)-3, accurately stratified three OS risk-validated categories of patients: favourable (0 risk factors, 40%, 1-year OS of 78.2% in the whole series), intermediate (1 or 2 risk factors, 54%, 1-year OS 53.8%) and poor (>2 risk factors, 5%, 1-year OS 10.7%) prognosis. Conclusions: We advocate the use of LIPS-3 as an easy-to-assess and inexpensive adjuvant prognostic tool for patients with PD-L1 ≥ 50% aNSCLC.
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- 2021
16. Post-progression outcomes of NSCLC patients with PD-L1 expression ≥ 50% receiving first-line single-agent pembrolizumab in a large multicentre real-world study
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Cortellini, A, Cannita, K, Tiseo, M, Cortinovis, D, Aerts, J, Baldessari, C, Giusti, R, Ferrara, M, D'Argento, E, Grossi, F, Guida, A, Berardi, R, Morabito, A, Genova, C, Antonuzzo, L, Mazzoni, F, De Toma, A, Signorelli, D, Gelibter, A, Targato, G, Rastelli, F, Chiari, R, Rocco, D, Gori, S, De Tursi, M, Mansueto, G, Zoratto, F, Filetti, M, Bracarda, S, Citarella, F, Russano, M, Cantini, L, Nigro, O, Buti, S, Minuti, G, Landi, L, Ricciardi, S, Migliorino, M, Natalizio, S, Simona, C, De Filippis, M, Metro, G, Adamo, V, Russo, A, Spinelli, G, Di Maio, M, Banna, G, Friedlaender, A, Addeo, A, Pinato, D, Ficorella, C, Porzio, G, Cortellini A, Cannita K, Tiseo M, Cortinovis D, Aerts JGJV, Baldessari C, Giusti R, Ferrara MG, D'Argento E, Grossi F, Guida A, Berardi R, Morabito A, Genova C, Antonuzzo L, Mazzoni F, De Toma A, Signorelli D, Gelibter A, Targato G, Rastelli F, Chiari R, Rocco D, Gori S, De Tursi M, Mansueto G, Zoratto F, Filetti M, Bracarda S, Citarella F, Russano M, Cantini L, Nigro O, Buti S, Minuti G, Landi L, Ricciardi S, Migliorino MR, Natalizio S, Simona C, De Filippis M, Metro G, Adamo V, Russo A, Spinelli GP, Di Maio M, Banna GL, Friedlaender A, Addeo A, Pinato DJ, Ficorella C, Porzio G, Cortellini, A, Cannita, K, Tiseo, M, Cortinovis, D, Aerts, J, Baldessari, C, Giusti, R, Ferrara, M, D'Argento, E, Grossi, F, Guida, A, Berardi, R, Morabito, A, Genova, C, Antonuzzo, L, Mazzoni, F, De Toma, A, Signorelli, D, Gelibter, A, Targato, G, Rastelli, F, Chiari, R, Rocco, D, Gori, S, De Tursi, M, Mansueto, G, Zoratto, F, Filetti, M, Bracarda, S, Citarella, F, Russano, M, Cantini, L, Nigro, O, Buti, S, Minuti, G, Landi, L, Ricciardi, S, Migliorino, M, Natalizio, S, Simona, C, De Filippis, M, Metro, G, Adamo, V, Russo, A, Spinelli, G, Di Maio, M, Banna, G, Friedlaender, A, Addeo, A, Pinato, D, Ficorella, C, Porzio, G, Cortellini A, Cannita K, Tiseo M, Cortinovis D, Aerts JGJV, Baldessari C, Giusti R, Ferrara MG, D'Argento E, Grossi F, Guida A, Berardi R, Morabito A, Genova C, Antonuzzo L, Mazzoni F, De Toma A, Signorelli D, Gelibter A, Targato G, Rastelli F, Chiari R, Rocco D, Gori S, De Tursi M, Mansueto G, Zoratto F, Filetti M, Bracarda S, Citarella F, Russano M, Cantini L, Nigro O, Buti S, Minuti G, Landi L, Ricciardi S, Migliorino MR, Natalizio S, Simona C, De Filippis M, Metro G, Adamo V, Russo A, Spinelli GP, Di Maio M, Banna GL, Friedlaender A, Addeo A, Pinato DJ, Ficorella C, and Porzio G
- Abstract
Background: Treatment sequencing with first-line immunotherapy, followed by second-line chemotherapy, is still a viable option for NSCLC patients with PD-L1 expression ≥50%. Methods: We evaluated post-progression treatment pathways in a large real-world cohort of metastatic NSCLC patients with PD-L1 expression ≥ 50% treated with first-line pembrolizumab monotherapy. Results: Overall, 974 patients were included. With a median follow-up of 22.7 months (95%CI: 21.6–38.2), the median overall survival (OS) of the entire population was 15.8 months (95%CI: 13.5–17.5; 548 events). At the data cutoff, among the 678 patients who experienced disease progression, 379 (55.9%) had not received any further treatment, and 359 patients (52.9%) had died. Patients who did not receive post-progression therapies were older (p = 0.0011), with a worse ECOG-PS (p < 0.0001) and were on corticosteroids prior to pembrolizumab (p = 0.0024). At disease progression, 198 patients (29.2%) received a switched approach and 101 (14.9%) received pembrolizumab ByPD either alone (64 [9.4%]) or in combination with local ablative treatments (37 [5.5%]) (LATs). After a random-case control matching according to ECOG-PS, CNS metastases, bone metastases, and (previous) best response to pembrolizumab, patients receiving pembrolizumab ByPD plus LATs were confirmed to have a significantly longer post-progression OS compared to patients receiving pembrolizumab ByPD alone 13.9 months versus 7.8 months (p = 0.0179) 241 patients (35.5%) among the 678 who had experienced PD, received a second-line systemic treatment (regardless of previous treatment beyond PD). As compared to first-line treatment commencement, patients’ features at the moment of second-line initiation showed a significantly higher proportion of patients aged under 70 years (p = 0.0244), with a poorer ECOG-PS (p < 0.0001) and having CNS (p = 0.0001), bone (p = 0.0266) and liver metastases (p = 0.0148). Conclusions: In the real-world scenario NSC
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- 2021
17. Osimertinib beyond disease progression in T790M EGFR-positive NSCLC patients: a multicenter study of clinicians' attitudes
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Cortellini, A, Leonetti, A, Catino, A, Pizzutillo, P, Ricciuti, B, De Giglio, A, Chiari, R, Bordi, P, Santini, D, Giusti, R, De Tursi, M, Brocco, D, Zoratto, F, Rastelli, F, Citarella, F, Russano, M, Filetti, M, Marchetti, P, Berardi, R, Torniai, M, Cortinovis, D, Sala, E, Maggioni, C, Follador, A, Macerelli, M, Nigro, O, Tuzi, A, Iacono, D, Migliorino, M, Banna, G, Porzio, G, Cannita, K, Ferrara, M, Bria, E, Galetta, D, Ficorella, C, Tiseo, M, Cortellini A, Leonetti A, Catino A, Pizzutillo P, Ricciuti B, De Giglio A, Chiari R, Bordi P, Santini D, Giusti R, De Tursi M, Brocco D, Zoratto F, Rastelli F, Citarella F, Russano M, Filetti M, Marchetti P, Berardi R, Torniai M, Cortinovis D, Sala E, Maggioni C, Follador A, Macerelli M, Nigro O, Tuzi A, Iacono D, Migliorino MR, Banna G, Porzio G, Cannita K, Ferrara MG, Bria E, Galetta D, Ficorella C, Tiseo M., Cortellini, A, Leonetti, A, Catino, A, Pizzutillo, P, Ricciuti, B, De Giglio, A, Chiari, R, Bordi, P, Santini, D, Giusti, R, De Tursi, M, Brocco, D, Zoratto, F, Rastelli, F, Citarella, F, Russano, M, Filetti, M, Marchetti, P, Berardi, R, Torniai, M, Cortinovis, D, Sala, E, Maggioni, C, Follador, A, Macerelli, M, Nigro, O, Tuzi, A, Iacono, D, Migliorino, M, Banna, G, Porzio, G, Cannita, K, Ferrara, M, Bria, E, Galetta, D, Ficorella, C, Tiseo, M, Cortellini A, Leonetti A, Catino A, Pizzutillo P, Ricciuti B, De Giglio A, Chiari R, Bordi P, Santini D, Giusti R, De Tursi M, Brocco D, Zoratto F, Rastelli F, Citarella F, Russano M, Filetti M, Marchetti P, Berardi R, Torniai M, Cortinovis D, Sala E, Maggioni C, Follador A, Macerelli M, Nigro O, Tuzi A, Iacono D, Migliorino MR, Banna G, Porzio G, Cannita K, Ferrara MG, Bria E, Galetta D, Ficorella C, and Tiseo M.
- Abstract
Background: In most cases, T790M EGFR-positive NSCLC patients receiving osimertinib developed “non-drugable” progression, as the patients with common EGFR-sensitizing mutations were treated with first-line osimertinib. In both settings, chemotherapy represents the standard treatment and local ablative treatments (LATs) are potential useful options in the case of oligo-progression. Methods: We conducted a study on “post-progression” (pp) outcomes of T790M EGFR-positive NSCLC patients treated with osimertinib, according to the therapeutic strategy applied: osimertinib beyond progression (± LATs), “switched therapies” or best supportive care only (BSC). Results: 144 consecutive patients were evaluated: 53 (36.8%) did not received post-progression treatments (BSC), while 91 (63.2%) patients received at least 1 subsequent treatment; 50 patients (54.9%) received osimertinib beyond disease progression [19 (20.9%) of them with adjunctive LATs] and 41 (45.1%) a switched therapy. Median ppPFS (progression-free survival) and median ppOS (overall survival) of patients who received osimertinib beyond progression vs. switched therapies were 6.4 months vs. 4.7 months, respectively [HR 0.57 (95% CI 0.35–0.92), p = 0.0239] and 11.3 months vs 7.8 months, respectively [HR 0.57 (95% CI 0.33–0.98), p = 0.0446]. Among patients who received osimertinib beyond progression with and without LATs median ppPFS was 6.4 months and 5.7 months, respectively [HR 0.90 (95% CI 0.68–1.18), p = 0.4560], while median ppOS was 20.2 months and 9.9 months, respectively [HR 0.73 (95% CI 0.52–1.03), p = 0.0748]. At the univariate analysis, the only factor significantly related to the ppPFS was the therapeutic strategy in favor of osimertinib beyond progression (± LATs). Moreover, the only variable which was significantly related to ppOS at the multivariate analysis was osimertinib beyond progression (± LATs). Conclusion: Our study confirmed that in clinical practice, in case of “non-druggable” disease progre
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- 2020
18. Immune-related Adverse Events of Pembrolizumab in a Large Real-world Cohort of Patients With NSCLC With a PD-L1 Expression ≥ 50% and Their Relationship With Clinical Outcomes
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Cortellini, A, Friedlaender, A, Banna, G, Porzio, G, Bersanelli, M, Cappuzzo, F, Aerts, J, Giusti, R, Bria, E, Cortinovis, D, Grossi, F, Migliorino, M, Galetta, D, Passiglia, F, Berardi, R, Mazzoni, F, Di Noia, V, Signorelli, D, Tuzi, A, Gelibter, A, Marchetti, P, Macerelli, M, Rastelli, F, Chiari, R, Rocco, D, Inno, A, Di Marino, P, Mansueto, G, Zoratto, F, Santoni, M, Tudini, M, Ghidini, M, Filetti, M, Catino, A, Pizzutilo, P, Sala, L, Occhipinti, M, Citarella, F, Marco, R, Torniai, M, Cantini, L, Follador, A, Sforza, V, Nigro, O, Ferrara, M, D'Argento, E, Leonetti, A, Pettoruti, L, Antonuzzo, L, Scodes, S, Landi, L, Guaitoli, G, Baldessari, C, Bertolini, F, Della Gravara, L, Dal Bello, M, Belderbos, R, De Filippis, M, Cecchi, C, Ricciardi, S, Donisi, C, De Toma, A, Proto, C, Addeo, A, Cantale, O, Ricciuti, B, Genova, C, Morabito, A, Santini, D, Ficorella, C, Cannita, K, Cortellini A, Friedlaender A, Banna GL, Porzio G, Bersanelli M, Cappuzzo F, Aerts JGJV, Giusti R, Bria E, Cortinovis D, Grossi F, Migliorino MR, Galetta D, Passiglia F, Berardi R, Mazzoni F, Di Noia V, Signorelli D, Tuzi A, Gelibter A, Marchetti P, Macerelli M, Rastelli F, Chiari R, Rocco D, Inno A, Di Marino P, Mansueto G, Zoratto F, Santoni M, Tudini M, Ghidini M, Filetti M, Catino A, Pizzutilo P, Sala L, Occhipinti MA, Citarella F, Marco R, Torniai M, Cantini L, Follador A, Sforza V, Nigro O, Ferrara MG, D'Argento E, Leonetti A, Pettoruti L, Antonuzzo L, Scodes S, Landi L, Guaitoli G, Baldessari C, Bertolini F, Della Gravara L, Dal Bello MG, Belderbos RA, De Filippis M, Cecchi C, Ricciardi S, Donisi C, De Toma A, Proto C, Addeo A, Cantale O, Ricciuti B, Genova C, Morabito A, Santini D, Ficorella C, Cannita K., Cortellini, A, Friedlaender, A, Banna, G, Porzio, G, Bersanelli, M, Cappuzzo, F, Aerts, J, Giusti, R, Bria, E, Cortinovis, D, Grossi, F, Migliorino, M, Galetta, D, Passiglia, F, Berardi, R, Mazzoni, F, Di Noia, V, Signorelli, D, Tuzi, A, Gelibter, A, Marchetti, P, Macerelli, M, Rastelli, F, Chiari, R, Rocco, D, Inno, A, Di Marino, P, Mansueto, G, Zoratto, F, Santoni, M, Tudini, M, Ghidini, M, Filetti, M, Catino, A, Pizzutilo, P, Sala, L, Occhipinti, M, Citarella, F, Marco, R, Torniai, M, Cantini, L, Follador, A, Sforza, V, Nigro, O, Ferrara, M, D'Argento, E, Leonetti, A, Pettoruti, L, Antonuzzo, L, Scodes, S, Landi, L, Guaitoli, G, Baldessari, C, Bertolini, F, Della Gravara, L, Dal Bello, M, Belderbos, R, De Filippis, M, Cecchi, C, Ricciardi, S, Donisi, C, De Toma, A, Proto, C, Addeo, A, Cantale, O, Ricciuti, B, Genova, C, Morabito, A, Santini, D, Ficorella, C, Cannita, K, Cortellini A, Friedlaender A, Banna GL, Porzio G, Bersanelli M, Cappuzzo F, Aerts JGJV, Giusti R, Bria E, Cortinovis D, Grossi F, Migliorino MR, Galetta D, Passiglia F, Berardi R, Mazzoni F, Di Noia V, Signorelli D, Tuzi A, Gelibter A, Marchetti P, Macerelli M, Rastelli F, Chiari R, Rocco D, Inno A, Di Marino P, Mansueto G, Zoratto F, Santoni M, Tudini M, Ghidini M, Filetti M, Catino A, Pizzutilo P, Sala L, Occhipinti MA, Citarella F, Marco R, Torniai M, Cantini L, Follador A, Sforza V, Nigro O, Ferrara MG, D'Argento E, Leonetti A, Pettoruti L, Antonuzzo L, Scodes S, Landi L, Guaitoli G, Baldessari C, Bertolini F, Della Gravara L, Dal Bello MG, Belderbos RA, De Filippis M, Cecchi C, Ricciardi S, Donisi C, De Toma A, Proto C, Addeo A, Cantale O, Ricciuti B, Genova C, Morabito A, Santini D, Ficorella C, and Cannita K.
- Abstract
Background: The role of immune-related adverse events (irAEs), as a surrogate predictor of the efficacy of checkpoint inhibitors, has not yet been described in the setting of first-line, single-agent pembrolizumab for patients with metastatic non-small-cell lung-cancer (NSCLC) with a programmed death-ligand 1 (PD-L1) expression of ≥ 50%. Patients and methods: We previously conducted a multicenter retrospective analysis in patients with treatment-naive metastatic NSCLC and a PD-L1 expression of ≥ 50% receiving first-line pembrolizumab. Here, we report the results of the irAE analysis and the potential correlation between irAEs and clinical outcomes. Results: A total of 1010 patients were included in this analysis; after a 6-week landmark selection, 877 (86.8%) patients were included in the efficacy analysis. Any grade irAEs (P < .0001), grade 3/4 irAEs (P = .0025), leading to discontinuation irAEs (P = .0144), multiple-site and single-site irAEs (P < .0001), cutaneous irAEs (P = .0001), endocrine irAEs (P = .0227), pulmonary irAEs (P = .0479), and rheumatologic irAEs (P = .0018) were significantly related to a higher objective response rate. Any grade irAEs (P < .0001), single-site irAEs (P < .0001), multiple-site irAEs (P = .0005), cutaneous irAEs (P = .0042), endocrine irAEs (P < .0001), gastrointestinal irAEs (P = .0391), and rheumatologic irAEs (P = .0086) were significantly related to progression-free survival. Any grade irAEs (P < .0001), single-site irAEs (P < .0001), multiple-site irAEs (P = .0003), cutaneous irAEs (P = .0002), endocrine irAEs (P = .0001), and rheumatologic irAEs (P = .0214) were significantly related to overall survival. Conclusions: This study confirms the feasibility and the safety of first-line, single-agent pembrolizumab, in a large, real-world cohort of patients with NSCLC with PD-L1 expression ≥ 50%. The occurrence of irAEs may be a surrogate of clinical activity and improved outcomes in this setting.
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- 2020
19. Baseline BMI and BMI variation during first line pembrolizumab in NSCLC patients with a PD-L1 expression ≥ 50%: a multicenter study with external validation
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Cortellini, A, Ricciuti, B, Tiseo, M, Bria, E, Banna, G, Aerts, J, Barbieri, F, Giusti, R, Cortinovis, D, Migliorino, M, Catino, A, Passiglia, F, Torniai, M, Morabito, A, Genova, C, Mazzoni, F, Di Noia, V, Signorelli, D, Gelibter, A, Occhipinti, M, Rastelli, F, Chiari, R, Rocco, D, Inno, A, De Tursi, M, Di Marino, P, Mansueto, G, Zoratto, F, Grossi, F, Filetti, M, Pizzutilo, P, Russano, M, Citarella, F, Cantini, L, Targato, G, Nigro, O, Ferrara, M, Buti, S, Scodes, S, Landi, L, Guaitoli, G, Della Gravara, L, Tabbò, F, Ricciardi, S, De Toma, A, Friedlaender, A, Petrelli, F, Addeo, A, Porzio, G, Ficorella, C, Cortellini A, Ricciuti B, Tiseo M, Bria E, Banna GL, Aerts JG, Barbieri F, Giusti R, Cortinovis D, Migliorino MR, Catino A, Passiglia F, Torniai M, Morabito A, Genova C, Mazzoni F, Di Noia V, Signorelli D, Gelibter A, Occhipinti MA, Rastelli F, Chiari R, Rocco D, Inno A, De Tursi M, Di Marino P, Mansueto G, Zoratto F, Grossi F, Filetti M, Pizzutilo P, Russano M, Citarella F, Cantini L, Targato G, Nigro O, Ferrara MG, Buti S, Scodes S, Landi L, Guaitoli G, Della Gravara L, Tabbò F, Ricciardi S, De Toma A, Friedlaender A, Petrelli F, Addeo A, Porzio G, Ficorella C., Cortellini, A, Ricciuti, B, Tiseo, M, Bria, E, Banna, G, Aerts, J, Barbieri, F, Giusti, R, Cortinovis, D, Migliorino, M, Catino, A, Passiglia, F, Torniai, M, Morabito, A, Genova, C, Mazzoni, F, Di Noia, V, Signorelli, D, Gelibter, A, Occhipinti, M, Rastelli, F, Chiari, R, Rocco, D, Inno, A, De Tursi, M, Di Marino, P, Mansueto, G, Zoratto, F, Grossi, F, Filetti, M, Pizzutilo, P, Russano, M, Citarella, F, Cantini, L, Targato, G, Nigro, O, Ferrara, M, Buti, S, Scodes, S, Landi, L, Guaitoli, G, Della Gravara, L, Tabbò, F, Ricciardi, S, De Toma, A, Friedlaender, A, Petrelli, F, Addeo, A, Porzio, G, Ficorella, C, Cortellini A, Ricciuti B, Tiseo M, Bria E, Banna GL, Aerts JG, Barbieri F, Giusti R, Cortinovis D, Migliorino MR, Catino A, Passiglia F, Torniai M, Morabito A, Genova C, Mazzoni F, Di Noia V, Signorelli D, Gelibter A, Occhipinti MA, Rastelli F, Chiari R, Rocco D, Inno A, De Tursi M, Di Marino P, Mansueto G, Zoratto F, Grossi F, Filetti M, Pizzutilo P, Russano M, Citarella F, Cantini L, Targato G, Nigro O, Ferrara MG, Buti S, Scodes S, Landi L, Guaitoli G, Della Gravara L, Tabbò F, Ricciardi S, De Toma A, Friedlaender A, Petrelli F, Addeo A, Porzio G, and Ficorella C.
- Abstract
Background The association between obesity and outcomes in patients receiving programmed death-1/programmed death ligand-1 (PD-L1) checkpoint inhibitors has already been confirmed in pre-treated non-small cell lung cancer (NSCLC) patients, regardless of PD-L1 tumor expression. Methods We present the outcomes analysis according to baseline body mass index (BMI) and BMI variation in a large cohort of metastatic NSCLC patients with a PD-L1 expression ≥50%, receiving first line pembrolizumab. We also evaluated a control cohort of metastatic NSCLC patients treated with first line platinum-based chemotherapy. Normal weight was set as control group. Results 962 patients and 426 patients were included in the pembrolizumab and chemotherapy cohorts, respectively. Obese patients had a significantly higher objective response rate (ORR) (OR=1.61 (95% CI: 1.04-2.50)) in the pembrolizumab cohort, while overweight patients had a significantly lower ORR (OR=0.59 (95% CI: 0.37-0.92)) within the chemotherapy cohort. Obese patients had a significantly longer progression-free survival (PFS) (HR=0.61 (95% CI: 0.45-0.82)) in the pembrolizumab cohort. Conversely, they had a significantly shorter PFS in the chemotherapy cohort (HR=1.27 (95% CI: 1.01-1.60)). Obese patients had a significantly longer overall survival (OS) within the pembrolizumab cohort (HR=0.70 (95% CI: 0.49-0.99)), while no significant differences according to baseline BMI were found in the chemotherapy cohort. BMI variation significantly affected ORR, PFS and OS in both the pembrolizumab and the chemotherapy cohorts. Conclusions Baseline obesity is associated to significantly improved ORR, PFS and OS in metastatic NSCLC patients with a PD-L1 expression of ≥50%, receiving first line pembrolizumab, but not among patients treated with chemotherapy. BMI variation is also significantly related to clinical outcomes.
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- 2020
20. Clinicopathologic correlates of first-line pembrolizumab effectiveness in patients with advanced NSCLC and a PD-L1 expression of ≥ 50
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Cortellini, A, Tiseo, M, Banna, G, Cappuzzo, F, Aerts, J, Barbieri, F, Giusti, R, Bria, E, Cortinovis, D, Grossi, F, Migliorino, M, Galetta, D, Passiglia, F, Santini, D, Berardi, R, Morabito, A, Genova, C, Mazzoni, F, Di Noia, V, Signorelli, D, Tuzi, A, Gelibter, A, Marchetti, P, Macerelli, M, Rastelli, F, Chiari, R, Rocco, D, Gori, S, De Tursi, M, Mansueto, G, Zoratto, F, Santoni, M, Tudini, M, Rijavec, E, Filetti, M, Catino, A, Pizzutilo, P, Sala, L, Citarella, F, Marco, R, Torniai, M, Cantini, L, Targato, G, Sforza, V, Nigro, O, Ferrara, M, D'Argento, E, Buti, S, Bordi, P, Antonuzzo, L, Scodes, S, Landi, L, Guaitoli, G, Baldessari, C, Della Gravara, L, Dal Bello, M, Belderbos, R, Bironzo, P, Carnio, S, Ricciardi, S, Grieco, A, De Toma, A, Proto, C, Friedlaender, A, Cantale, O, Ricciuti, B, Addeo, A, Metro, G, Ficorella, C, Porzio, G, Cortellini A, Tiseo M, Banna GL, Cappuzzo F, Aerts JGJV, Barbieri F, Giusti R, Bria E, Cortinovis D, Grossi F, Migliorino MR, Galetta D, Passiglia F, Santini D, Berardi R, Morabito A, Genova C, Mazzoni F, Di Noia V, Signorelli D, Tuzi A, Gelibter A, Marchetti P, Macerelli M, Rastelli F, Chiari R, Rocco D, Gori S, De Tursi M, Mansueto G, Zoratto F, Santoni M, Tudini M, Rijavec E, Filetti M, Catino A, Pizzutilo P, Sala L, Citarella F, Marco R, Torniai M, Cantini L, Targato G, Sforza V, Nigro O, Ferrara MG, D'Argento E, Buti S, Bordi P, Antonuzzo L, Scodes S, Landi L, Guaitoli G, Baldessari C, Della Gravara L, Dal Bello MG, Belderbos RA, Bironzo P, Carnio S, Ricciardi S, Grieco A, De Toma A, Proto C, Friedlaender A, Cantale O, Ricciuti B, Addeo A, Metro G, Ficorella C, Porzio G., Cortellini, A, Tiseo, M, Banna, G, Cappuzzo, F, Aerts, J, Barbieri, F, Giusti, R, Bria, E, Cortinovis, D, Grossi, F, Migliorino, M, Galetta, D, Passiglia, F, Santini, D, Berardi, R, Morabito, A, Genova, C, Mazzoni, F, Di Noia, V, Signorelli, D, Tuzi, A, Gelibter, A, Marchetti, P, Macerelli, M, Rastelli, F, Chiari, R, Rocco, D, Gori, S, De Tursi, M, Mansueto, G, Zoratto, F, Santoni, M, Tudini, M, Rijavec, E, Filetti, M, Catino, A, Pizzutilo, P, Sala, L, Citarella, F, Marco, R, Torniai, M, Cantini, L, Targato, G, Sforza, V, Nigro, O, Ferrara, M, D'Argento, E, Buti, S, Bordi, P, Antonuzzo, L, Scodes, S, Landi, L, Guaitoli, G, Baldessari, C, Della Gravara, L, Dal Bello, M, Belderbos, R, Bironzo, P, Carnio, S, Ricciardi, S, Grieco, A, De Toma, A, Proto, C, Friedlaender, A, Cantale, O, Ricciuti, B, Addeo, A, Metro, G, Ficorella, C, Porzio, G, Cortellini A, Tiseo M, Banna GL, Cappuzzo F, Aerts JGJV, Barbieri F, Giusti R, Bria E, Cortinovis D, Grossi F, Migliorino MR, Galetta D, Passiglia F, Santini D, Berardi R, Morabito A, Genova C, Mazzoni F, Di Noia V, Signorelli D, Tuzi A, Gelibter A, Marchetti P, Macerelli M, Rastelli F, Chiari R, Rocco D, Gori S, De Tursi M, Mansueto G, Zoratto F, Santoni M, Tudini M, Rijavec E, Filetti M, Catino A, Pizzutilo P, Sala L, Citarella F, Marco R, Torniai M, Cantini L, Targato G, Sforza V, Nigro O, Ferrara MG, D'Argento E, Buti S, Bordi P, Antonuzzo L, Scodes S, Landi L, Guaitoli G, Baldessari C, Della Gravara L, Dal Bello MG, Belderbos RA, Bironzo P, Carnio S, Ricciardi S, Grieco A, De Toma A, Proto C, Friedlaender A, Cantale O, Ricciuti B, Addeo A, Metro G, Ficorella C, and Porzio G.
- Abstract
Background: Single-agent pembrolizumab represents the standard first-line option for metastatic non-small-cell lung cancer (NSCLC) patients with a PD-L1 (programmed death-ligand 1) expression of ≥ 50%. Methods: We conducted a multicenter retrospective study aimed at evaluating the clinicopathologic correlates of pembrolizumab effectiveness in patients with treatment-naïve NSCLC and a PD-L1 expression of ≥ 50%. Results: One thousand and twenty-six consecutive patients were included. The objective response rate (ORR) was 44.5% (95% CI 40.2–49.1), while the median progression free survival (PFS) and overall survival (OS) were 7.9 months (95% CI 6.9–9.5; 599 events) and 17.2 months (95% CI 15.3–22.3; 598 censored patients), respectively. ECOG-PS ≥ 2 (p < 0.0001) and bone metastases (p = 0.0003) were confirmed to be independent predictors of a worse ORR. Former smokers (p = 0.0002), but not current smokers (p = 0.0532) were confirmed to have a significantly prolonged PFS compared to never smokers at multivariate analysis. ECOG-PS (p < 0.0001), bone metastases (p < 0.0001) and liver metastases (p < 0.0001) were also confirmed to be independent predictors of a worse PFS. Previous palliative RT was significantly related to a shortened OS (p = 0.0104), while previous non-palliative RT was significantly related to a prolonged OS (p = 0.0033). Former smokers (p = 0.0131), but not current smokers (p = 0.3433) were confirmed to have a significantly prolonged OS compared to never smokers. ECOG-PS (p < 0.0001), bone metastases (p < 0.0001) and liver metastases (p < 0.0001) were also confirmed to be independent predictors of a shortened OS. A PD-L1 expression of ≥ 90%, as assessed by recursive partitioning, was associated with significantly higher ORR (p = 0.0204), and longer and OS (p = 0.0346) at multivariable analysis. Conclusion: Pembrolizumab was effective in a large cohort of NSCLC patients treated outside of clinical trials. Questions regarding the effe
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- 2020
21. Mechanisms of primary and secondary resistance to RET inhibitors in patients with RET-positive advanced NSCLC
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Marinello, A., Vasseur, D., Conci, N., Fallet, V., Audigier-Valette, C., Cousin, S., Tabbo, F., Guisier, F., Russo, A., Blanco, A. Calles, Metro, G., Massa, G., Citarella, F., Eisert, A. K., Gomez, P. Iranzo, Tagliamento, M., Mezquita, L., Lindsay, C., Ponce, S., Aldea, M., Marinello, A., Vasseur, D., Conci, N., Fallet, V., Audigier-Valette, C., Cousin, S., Tabbo, F., Guisier, F., Russo, A., Blanco, A. Calles, Metro, G., Massa, G., Citarella, F., Eisert, A. K., Gomez, P. Iranzo, Tagliamento, M., Mezquita, L., Lindsay, C., Ponce, S., and Aldea, M.
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- 2022
22. 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]
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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.
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- 2022
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23. 10P Family history of cancer correlates with improved outcome from immunotherapy in NSCLC independent of somatic DNA damage response gene status
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Cortellini, A., primary, Filetti, M., additional, Citarella, F., additional, Giusti, R., additional, Russano, M., additional, Grossi, F., additional, Gelibter, A.J., additional, Pecci, F., additional, De Tursi, M., additional, Macerelli, M., additional, Nigro, O., additional, Ferrara, M.G., additional, Buti, S., additional, Mazzoni, F., additional, Cantini, L., additional, Migliorino, M.R., additional, Addeo, A., additional, Adamo, V., additional, Russo, A., additional, and Pinato, D.J., additional
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- 2021
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24. Novel drugs, familiar interactions: ciprofloxacin may increase exposure to the RET inhibitor pralsetinib
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Citarella, F., Russano, M., Galletti, A., Vincenzi, B., Tonini, G., and Santini, D.
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- 2021
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25. Corrigendum to ‘The lung immuno-oncology prognostic score (LIPS-3): a prognostic classification of patients receiving first-line pembrolizumab for PD-L1 ≥ 50% advanced non-small-cell lung cancer’: [ESMO Open Volume 6, Issue 2, April 2021, 100078]
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Banna, G.L., Cortellini, A., Cortinovis, D.L., Tiseo, M., Aerts, J.G.J.V., Barbieri, F., Giusti, R., Bria, E., Grossi, F., Pizzutilo, P., Berardi, R., Morabito, A., Genova, C., Mazzoni, F., Di Noia, V., Signorelli, D., Gelibter, A., Macerelli, M., Rastelli, F., Chiari, R., Rocco, D., Gori, S., De Tursi, M., Di Marino, P., Mansueto, G., Zoratto, F., Filetti, M., Montrone, M., Citarella, F., Marco, R., Cantini, L., Nigro, O., D'Argento, E., Buti, S., Minuti, G., Landi, L., Guaitoli, G., Lo Russo, G., De Toma, A., Donisi, C., Friedlaender, A., De Giglio, A., Metro, G., Porzio, G., Ficorella, C., and Addeo, A.
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- 2021
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26. Corrigendum to 'The lung immuno-oncology prognostic score (LIPS-3): a prognostic classification of patients receiving first-line pembrolizumab for PD-L1 ≥ 50% advanced non-small-cell lung cancer': [ESMO Open Volume 6, Issue 2, April 2021, 100078]
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Banna, GL, Cortellini, A, Cortinovis, DL, Tiseo, M, Aerts, JGJV, Barbieri, F, Giusti, R, Bria, E, Grossi, F, Pizzutilo, P, Berardi, R, Morabito, A, Genova, C, Mazzoni, F, Di Noia, V, Signorelli, D, Gelibter, A, Macerelli, M, Rastelli, F, Chiari, R, Rocco, D, Gori, S, De Tursi, M, Di Marino, P, Mansueto, G, Zoratto, F, Filetti, M, Montrone, M, Citarella, F, Marco, R, Cantini, L, Nigro, O, D'Argento, E, Buti, S, Minuti, G, Landi, L, Guaitoli, G, Lo Russo, G, De Toma, A, Donisi, C, Friedlaender, A, De Giglio, A, Metro, G, Porzio, G, Ficorella, C, and Addeo, A
- Abstract
ispartof: ESMO Open vol:6 issue:3 pages:100137- ispartof: location:England status: published
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- 2021
27. OA01.02 Impact of COVID-19 Outbreak on Lung Cancer Diagnosis and Continuum of Care: Data From an Italian Multicenter Study
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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
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- 2021
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28. Smoking status during first-line immunotherapy and chemotherapy in NSCLC patients: A case–control matched analysis from a large multicenter study
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Cortellini, A. (Alessio), De Giglio, A. (Andrea), Cannita, K. (Katia), Cortinovis, D.L. (Diego L.), Cornelissen, R. (Robin), Baldesarri, C. (Cinzia), Giusti, R. (Raffaele), D'Argento, E. (Ettore), Grossi, F. (Francesco), Santoni, M. (Matteo), Catino, A. (Annamaria), Berardi, R. (Rossana), Sforza, V. (Vincenzo), Rossi, G. (Giovanni), Antonuzzo, L. (Lorenzo), Di Noia, V. (Vincenzo), Signorelli, D. (Diego), Gelibter, A. (Alain), Occhipinti, M.A. (Mario Alberto), Follador, A. (Alessandro), Rastelli, F. (Francesca), Chiari, R. (Rita), Gravara, L.D. (Luigi Della), Inno, A. (Alessandro), De Tursi, M. (Michele), Di Marino, P. (Pietro), Mansueto, G. (Giovanni), Zoratto, F. (Federica), Filetti, M. (Marco), Montrone, M. (Michele), Citarella, F. (Fabrizio), Pensieri, M.V. (Maria Vittoria), Russano, M. (Marco), Cantini, L. (Luca), Nigro, O. (Olga), Leonetti, A. (Alessandro), Bordi, P. (Paola), Minuti, G. (Gabriele), Landi, L. (Lorenza), De Toma, A. (Alessandro), Donisi, C. (Clelia), Ricciardi, S. (Serena), Migliorino, M.R. (Maria Rita), Napoli, V.M. (Valerio Maria), Leone, G. (Gianmarco), Metro, G. (Giulio), Banna, G.L. (Giuseppe L.), Friedlaender, A. (Alex), Addeo, A. (Alfredo), Ficorella, C. (Corrado), Porzio, G. (Giampiero), Cortellini, A. (Alessio), De Giglio, A. (Andrea), Cannita, K. (Katia), Cortinovis, D.L. (Diego L.), Cornelissen, R. (Robin), Baldesarri, C. (Cinzia), Giusti, R. (Raffaele), D'Argento, E. (Ettore), Grossi, F. (Francesco), Santoni, M. (Matteo), Catino, A. (Annamaria), Berardi, R. (Rossana), Sforza, V. (Vincenzo), Rossi, G. (Giovanni), Antonuzzo, L. (Lorenzo), Di Noia, V. (Vincenzo), Signorelli, D. (Diego), Gelibter, A. (Alain), Occhipinti, M.A. (Mario Alberto), Follador, A. (Alessandro), Rastelli, F. (Francesca), Chiari, R. (Rita), Gravara, L.D. (Luigi Della), Inno, A. (Alessandro), De Tursi, M. (Michele), Di Marino, P. (Pietro), Mansueto, G. (Giovanni), Zoratto, F. (Federica), Filetti, M. (Marco), Montrone, M. (Michele), Citarella, F. (Fabrizio), Pensieri, M.V. (Maria Vittoria), Russano, M. (Marco), Cantini, L. (Luca), Nigro, O. (Olga), Leonetti, A. (Alessandro), Bordi, P. (Paola), Minuti, G. (Gabriele), Landi, L. (Lorenza), De Toma, A. (Alessandro), Donisi, C. (Clelia), Ricciardi, S. (Serena), Migliorino, M.R. (Maria Rita), Napoli, V.M. (Valerio Maria), Leone, G. (Gianmarco), Metro, G. (Giulio), Banna, G.L. (Giuseppe L.), Friedlaender, A. (Alex), Addeo, A. (Alfredo), Ficorella, C. (Corrado), and Porzio, G. (Giampiero)
- Abstract
Background: Improved outcome in tobacco smoking patients with non-small cell lung cancer (NSCLC) following immunotherapy has previously been reported. However, little is known regarding this association during first-line immunotherapy in patients with high PD-L1 expression. In this study we compared clinical outcomes according to the smoking status of two large multicenter cohorts. Methods: We compared clinical outcomes according to the smoking status (never smokers vs. current/former smokers) of two retrospective multicenter cohorts of metastatic NSCLC patients, treated with first-line pembrolizumab and platinum-based chemotherapy. Results: A total of 962 NSCLC patients with PD-L1 expression ≥50% who received first-line pembrolizumab and 462 NSCLC patients who received first-line platinum-based chemotherapy were included in the study. Never smokers were confirmed to have a significantly higher risk of disease progression (hazard ratio [HR] = 1.49 [95% CI: 1.15–1.92], p = 0.0022) and death (HR = 1.38 [95% CI: 1.02–1.87], p = 0.0348) within the pembrolizumab cohort. On the contrary, a nonsignificant trend towards a reduced risk of disease progression (HR = 0.74 [95% CI: 0.52–1.05], p = 0.1003) and death (HR = 0.67 [95% CI: 0.45–1.01], p = 0.0593) were reported for never smokers within the chemotherapy cohort. After a random case–control matching, 424 patients from both cohorts were paired. Within the matched pembrolizumab cohort, never smokers had a significantly shorter progression-free survival (PFS) (HR = 1.68 [95% CI: 1.17–2.40], p = 0.0045) and a nonsignificant trend towards a shortened overall survival (OS) (HR = 1.32 [95% CI: 0.84–2.07], p = 0.2205). On the contrary, never smokers had a significantly longer PFS (HR = 0.68 [95% CI: 0.49–0.95], p = 0.0255) and OS (HR = 0.66 [95% CI: 0.45–0.97], p = 0,0356) compared to current/former smoker patients within the matched chemotherapy cohort. On pooled multivariable analysis, the interaction term between smoking stat
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- 2021
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29. Corrigendum to 'The lung immuno-oncology prognostic score (LIPS-3):a prognostic classification of patients receiving first-line pembrolizumab for PD-L1 ≥ 50% advanced non-small-cell lung cancer': [ESMO Open Volume 6, Issue 2, April 2021, 100078
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Banna, G. L., Cortellini, A., Cortinovis, D. L., Tiseo, M., Aerts, J. G.J.V., Barbieri, F., Giusti, R., Bria, E., Grossi, F., Pizzutilo, P., Berardi, R., Morabito, A., Genova, C., Mazzoni, F., Di Noia, V., Signorelli, D., Gelibter, A., Macerelli, M., Rastelli, F., Chiari, R., Rocco, D., Gori, S., De Tursi, M., Di Marino, P., Mansueto, G., Zoratto, F., Filetti, M., Montrone, M., Citarella, F., Marco, R., Cantini, L., Nigro, O., D'Argento, E., Buti, S., Minuti, G., Landi, L., Guaitoli, G., Lo Russo, G., De Toma, A., Donisi, C., Friedlaender, A., De Giglio, A., Metro, G., Porzio, G., Ficorella, C., Addeo, A., Banna, G. L., Cortellini, A., Cortinovis, D. L., Tiseo, M., Aerts, J. G.J.V., Barbieri, F., Giusti, R., Bria, E., Grossi, F., Pizzutilo, P., Berardi, R., Morabito, A., Genova, C., Mazzoni, F., Di Noia, V., Signorelli, D., Gelibter, A., Macerelli, M., Rastelli, F., Chiari, R., Rocco, D., Gori, S., De Tursi, M., Di Marino, P., Mansueto, G., Zoratto, F., Filetti, M., Montrone, M., Citarella, F., Marco, R., Cantini, L., Nigro, O., D'Argento, E., Buti, S., Minuti, G., Landi, L., Guaitoli, G., Lo Russo, G., De Toma, A., Donisi, C., Friedlaender, A., De Giglio, A., Metro, G., Porzio, G., Ficorella, C., and Addeo, A.
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- 2021
30. The lung immuno-oncology prognostic score (LIPS-3):a prognostic classification of patients receiving first-line pembrolizumab for PD-L1 ≥ 50% advanced non-small-cell lung cancer
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Banna, G. L., Cortellini, A., Cortinovis, D. L., Tiseo, M., Aerts, J. G.J.V., Barbieri, F., Giusti, R., Bria, E., Grossi, F., Pizzutilo, P., Berardi, R., Morabito, A., Genova, C., Mazzoni, F., Di Noia, V., Signorelli, D., Gelibter, A., Macerelli, M., Rastelli, F., Chiari, R., Rocco, D., Gori, S., De Tursi, M., Di Marino, P., Mansueto, G., Zoratto, F., Filetti, M., Montrone, M., Citarella, F., Marco, R., Cantini, L., Nigro, O., D'Argento, E., Buti, S., Minuti, G., Landi, L., Guaitoli, G., Lo Russo, G., De Toma, A., Donisi, C., Friedlaender, A., De Giglio, A., Metro, G., Porzio, G., Ficorella, C., Addeo, A., Banna, G. L., Cortellini, A., Cortinovis, D. L., Tiseo, M., Aerts, J. G.J.V., Barbieri, F., Giusti, R., Bria, E., Grossi, F., Pizzutilo, P., Berardi, R., Morabito, A., Genova, C., Mazzoni, F., Di Noia, V., Signorelli, D., Gelibter, A., Macerelli, M., Rastelli, F., Chiari, R., Rocco, D., Gori, S., De Tursi, M., Di Marino, P., Mansueto, G., Zoratto, F., Filetti, M., Montrone, M., Citarella, F., Marco, R., Cantini, L., Nigro, O., D'Argento, E., Buti, S., Minuti, G., Landi, L., Guaitoli, G., Lo Russo, G., De Toma, A., Donisi, C., Friedlaender, A., De Giglio, A., Metro, G., Porzio, G., Ficorella, C., and Addeo, A.
- Abstract
Background: To stratify the prognosis of patients with programmed cell death-ligand 1 (PD-L1) ≥ 50% advanced non-small-cell lung cancer (aNSCLC) treated with first-line immunotherapy. Methods: Baseline clinical prognostic factors, the neutrophil-to-lymphocyte ratio (NLR), PD-L1 tumour cell expression level, lactate dehydrogenase (LDH) and their combination were investigated by a retrospective analysis of 784 patients divided between statistically powered training (n = 201) and validation (n = 583) cohorts. Cut-offs were explored by receiver operating characteristic (ROC) curves and a risk model built with validated independent factors by multivariate analysis. Results: NLR < 4 was a significant prognostic factor in both cohorts (P < 0.001). It represented 53% of patients in the validation cohort, with 1-year overall survival (OS) of 76.6% versus 44.8% with NLR > 4, in the validation series. The addition of PD-L1 ≥ 80% (21% of patients) or LDH < 252 U/l (25%) to NLR < 4 did not result in better 1-year OS (of 72.6% and 74.1%, respectively, in the validation cohort). Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 2 [P < 0.001, hazard ratio (HR) 2.04], pretreatment steroids (P < 0.001, HR 1.67) and NLR < 4 (P < 0.001, HR 2.29) resulted in independent prognostic factors. A risk model with these three factors, namely, the lung immuno-oncology prognostic score (LIPS)-3, accurately stratified three OS risk-validated categories of patients: favourable (0 risk factors, 40%, 1-year OS of 78.2% in the whole series), intermediate (1 or 2 risk factors, 54%, 1-year OS 53.8%) and poor (>2 risk factors, 5%, 1-year OS 10.7%) prognosis. Conclusions: We advocate the use of LIPS-3 as an easy-to-assess and inexpensive adjuvant prognostic tool for patients with PD-L1 ≥ 50% aNSCLC.
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- 2021
31. 1403P Sotorasib in KRAS p.G12C mutated advanced NSCLC: Real-word data from the Italian Expanded Access Program
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Reale, M.L., Passiglia, F., Brambilla, M., Pasello, G., Minuti, G., Bulotta, A., Pizzutilo, P., Sini, C., Costa, J., Roca, E., Bria, E., Pilotto, S., Genova, C., Metro, G., Citarella, F., Bordi, P., Russo, A., Chiari, R., Andrikou, K., and Novello, S.
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- 2023
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32. 117P Family history of cancer and improved outcomes with first-line immunotherapy in NSCLC patients
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Cortellini, A., primary, Buti, S., additional, Di Maio, M., additional, Giusti, R., additional, Nigro, O., additional, Cantini, L., additional, Bria, E., additional, Grossi, F., additional, Torniai, M., additional, De Tursi, M., additional, Citarella, F., additional, Mazzoni, F., additional, Gelibter, A.J., additional, Macerelli, M., additional, Migliorino, M.R., additional, Russo, A., additional, Addeo, A., additional, Porzio, G., additional, Ficorella, C., additional, and Pinato, D.J., additional
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- 2021
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33. Baseline BMI and BMI variation during first line pembrolizumab in NSCLC patients with a PD-L1 expression >= 50%: a multicenter study with external validation
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Cortellini, A., Ricciuti, B., Tiseo, M., Bria, E., Banna, G.L., Aerts, J.G.J.V. (Joachim), Barbieri, F. (Federica), Giusti, R., Cortinovis, D.L., Migliorino, M.R., Catino, A., Passiglia, F., Torniai, M., Morabito, A., Genova, C., Mazzoni, F., Di Noia, V., Signorelli, D., Gelibter, A., Occhipinti, M.A., Rastelli, F., Chiari, R., Rocco, D. (Daniela) de, Inno, A., De Tursi, M., Di Marino, P., Mansueto, G., Zoratto, F., Grossi, F., Filetti, M., Pizzutilo, P., Russano, M., Citarella, F., Cantini, L., Targato, G., Nigro, O., Ferrara, M.G., Buti, S., Scodes, S., Landi, L., Guaitoli, G., Della Gravara, L., Tabbo, F., Ricciardi, S., De Toma, A., Friedlaender, A., Petrelli, F., Addeo, A., Porzio, G., Ficorella, C., Cortellini, A., Ricciuti, B., Tiseo, M., Bria, E., Banna, G.L., Aerts, J.G.J.V. (Joachim), Barbieri, F. (Federica), Giusti, R., Cortinovis, D.L., Migliorino, M.R., Catino, A., Passiglia, F., Torniai, M., Morabito, A., Genova, C., Mazzoni, F., Di Noia, V., Signorelli, D., Gelibter, A., Occhipinti, M.A., Rastelli, F., Chiari, R., Rocco, D. (Daniela) de, Inno, A., De Tursi, M., Di Marino, P., Mansueto, G., Zoratto, F., Grossi, F., Filetti, M., Pizzutilo, P., Russano, M., Citarella, F., Cantini, L., Targato, G., Nigro, O., Ferrara, M.G., Buti, S., Scodes, S., Landi, L., Guaitoli, G., Della Gravara, L., Tabbo, F., Ricciardi, S., De Toma, A., Friedlaender, A., Petrelli, F., Addeo, A., Porzio, G., and Ficorella, C.
- Abstract
Background The association between obesity and outcomes in patients receiving programmed death-1/ programmed death ligand-1 (PD-L1) checkpoint inhibitors has already been confirmed in pre-treated non-small cell lung cancer (NSCLC) patients, regardless of PD-L1 tumor expression. Methods We present the outcomes analysis according to baseline body mass index (BMI) and BMI variation in a large cohort of metastatic NSCLC patients with a PD-L1 expression ≥50%, receiving first line pembrolizumab. We also evaluated a control cohort of metastatic NSCLC patients treated with first line platinum-based chemotherapy. Normal weight was set as control group. Results 962 patients and 426 patients were included in the pembrolizumab and chemotherapy cohorts, respectively. Obese patients had a significantly higher objective response rate (ORR) (OR=1.61 (95% CI: 1.04– 2.50)) in the pembrolizumab cohort, while overweight patients had a significantly lower ORR (OR=0.59 (95% CI: 0.37–0.92)) within the chemotherapy cohort. Obese patients had a significantly longer progression-free survival (PFS) (HR=0.61 (95% CI: 0.45–0.82)) in the pembrolizumab cohort. Conversely, they had a significantly shorter PFS in the chemotherapy cohort (HR=1.27 (95% CI: 1.01–1.60)). Obese patients had a significantly longer overall survival (OS) within the pembrolizumab cohort (HR=0.70 (95% CI: 0.49–0.99)), while no significant differences according to baseline BMI were found in the chemotherapy cohort. BMI variation significantly affected ORR, PFS and OS in both the pembrolizumab and the chemotherapy cohorts. Conclusions Baseline obesity is associated to significantly improved ORR, PFS and OS in metastatic NSCLC patients with a PD-L1 expression of ≥50%, receiving first line pembrolizumab, but not among patients treated with chemotherapy. BMI variation is also significantly related to clinical outcomes.
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- 2020
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34. Baseline BMI and BMI variation during first line pembrolizumab in NSCLC patients with a PD-L1 expression >= 50%: a multicenter study with external validation
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Cortellini, A, Ricciuti, B, Tiseo, M, Bria, E, Banna, GL, Aerts, Joachim, Barbieri, F, Giusti, R, Cortinovis, DL, Migliorino, MR, Catino, A, Passiglia, F, Torniai, M, Morabito, A, Genova, C, Mazzoni, F, Di Noia, V, Signorelli, D, Gelibter, A, Occhipinti, MA, Rastelli, F, Chiari, R, De Rocco, D, Inno, A, De Tursi, M, Di Marino, P, Mansueto, G, Zoratto, F, Grossi, F, Filetti, M, Pizzutilo, P, Russano, M, Citarella, F, Cantini, Luca, Targato, G, Nigro, O, Ferrara, MG, Buti, S, Scodes, S, Landi, L, Guaitoli, G, Della Gravara, L, Tabbo, F, Ricciardi, S, De Toma, A, Friedlaender, A, Petrelli, F, Addeo, A, Porzio, G, Ficorella, C, Cortellini, A, Ricciuti, B, Tiseo, M, Bria, E, Banna, GL, Aerts, Joachim, Barbieri, F, Giusti, R, Cortinovis, DL, Migliorino, MR, Catino, A, Passiglia, F, Torniai, M, Morabito, A, Genova, C, Mazzoni, F, Di Noia, V, Signorelli, D, Gelibter, A, Occhipinti, MA, Rastelli, F, Chiari, R, De Rocco, D, Inno, A, De Tursi, M, Di Marino, P, Mansueto, G, Zoratto, F, Grossi, F, Filetti, M, Pizzutilo, P, Russano, M, Citarella, F, Cantini, Luca, Targato, G, Nigro, O, Ferrara, MG, Buti, S, Scodes, S, Landi, L, Guaitoli, G, Della Gravara, L, Tabbo, F, Ricciardi, S, De Toma, A, Friedlaender, A, Petrelli, F, Addeo, A, Porzio, G, and Ficorella, C
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- 2020
35. P-161 Efficacy of third-line anti-EGFR-based treatment versus regorafenib/TAS-102 (R/T) according to primary tumor site in RAS/BRAF wild-type metastatic colorectal cancer patients
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Vivolo, R., primary, Bria, E., additional, Zurlo, I., additional, Bensi, M., additional, Dell'Aquila, E., additional, Anghelone, A., additional, Corsi, D., additional, Caira, G., additional, Santini, D., additional, Ingrosso, D., additional, Emiliani, A., additional, Calegari, M., additional, Citarella, F., additional, Pozzo, C., additional, Grande, R., additional, Basso, M., additional, Tortora, G., additional, and Salvatore, L., additional
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- 2020
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36. An Emerging Player in the Adaptive Immune Response: MicroRNA-146a is a modulator of IL-2 expression and AICD in T lymphocytes
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Curtale, G., Citarella, F., Carissimi, C., Carucci, N., valerio fulci, Franceschini, D., Meloni, F., Barnaba, V., and Macino, G.
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- 2010
37. Identification of a putative binding site for negatively charged surfaces in the fibronectin type II domain of human factor XII-an immunochemical and homology modeling approach
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Citarella F, te Velthuis H, Manuela Helmer-Citterich, Ce, Hack, and VU University medical center
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Protein Structure ,Binding Sites ,Settore BIO/11 ,Static Electricity ,Molecular Sequence Data ,Antibodies, Monoclonal ,Factor XIIa ,Antibodies ,Protein Structure, Tertiary ,Fibronectins ,Structure-Activity Relationship ,Epitopes ,Humans ,Factor XII ,Kaolin ,Sequence Alignment ,Amino Acid Sequence ,Protein Binding ,Monoclonal ,Tertiary - Abstract
Monoclonal antibodies directed against functional sites of proteins provide useful tools for structure-function studies. Here we describe a mAb, KOK5, directed against the heavy chain region of human coagulation factor XII (FXII), which inhibits kaolin-induced clotting activity by preventing the binding of FXII to kaolin. Furthermore, mAb KOK5 enhances FXII susceptibility for cleavage by kallikrein and supports FXII autoactivation. Hence, mAb KOK5 likely is directed against the binding site of FXII for negatively charged surfaces. Screening of two phage-displayed random peptide libraries with mAb KOK5 selected phages that could be grouped on the basis of two amino acid consensus sequences: A) FXFQTPXW and B) HQ/LCTHR/KKC. Sequence A contains two motifs: one shares homology with FXII amino acid residues 30-33 (FPFQ), the second one with residues 57-60 (TPNF); both amino acid stretches belonging to the fibronectin type II domain of FXII. Sequence B also reveals homology with part of the fibronectin type II domain, i.e. the stretch 40-47 (HKCTHKGR). A three-dimensional model of FXII residues 28-65, obtained by homology modeling, indicated that the three amino acid stretches 30-33, 40-47 and 57-60 are close to each other and accessible for the solvent, i.e. in a form available for interaction with the monoclonal antibody, suggesting that mAb KOK5 recognizes a discontinuous epitope on the fibronectin type III domain of FXII. Peptides corresponding to FXII sequences 29-37 (FXII29-37) or 39-47 (FXII39-47), were synthesized and tested for the capability to inhibit FXII binding to negatively charged surfaces. Peptide FXII39-47 inhibited the binding of labeled FXII to kaolin and effectively prevented both dextran sulfate- and kaolin-induced activation of the contact system in plasma. Hence, we suggest that the fibronectin type II domain of FXII, in particular residues 39 to 47, contribute to the binding site of FXII for negatively charged surfaces.
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- 2000
38. Monoclonal antibody F1 binds to the kringle domain of factor XII and induces enhanced susceptibility for cleavage by kallikrein
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Dm, Ravon, Citarella F, Yt, Lubbers, BARBARA PASCUCCI, and Ce, Hack
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DNA, Complementary ,Base Sequence ,Molecular Sequence Data ,Antibodies, Monoclonal ,Epitopes ,Kinetics ,Chromogenic Compounds ,Kringles ,Factor XII ,Animals ,Humans ,Kallikreins ,Amino Acid Sequence ,Oligopeptides - Abstract
In a previous study we have shown that monoclonal antibody F1 (MoAb F1), directed against an epitope on the heavy chain of factor XII distinct from the binding site for anionic surfaces, is able to activate factor XII in plasma (Nuijens JH, et al: J Biol Chem 264; 12941, 1989). Here, we studied in detail the mechanism underlying the activation of factor XII by MoAb F1 using purified proteins. Formation of factor XIIa was assessed by measuring its amidolytic activity towards the chromogenic substrate H-D-Pro-Phe-Arg-pNA (S-2302) in the presence of soybean trypsin inhibitor and by assessing cleavage on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Upon incubation with MoAb F1 alone, factor XII was auto-activated in a time-dependent fashion, activation being maximal after 30 hours. Factor XII incubated in the absence of MoAb F1 was hardly activated by kallikrein, whereas in the presence of MoAb F1, but not in that of a control MoAb, the rate of factor XII activation by kallikrein was promoted at least 60-fold. Maximal activation of factor XII with kallikrein in the presence of MoAb F1 was reached within 1 hour. This effect of kallikrein on the cleavage of factor XII bound to MoAb F1 was specific because the fibrinolytic enzymes plasmin, urokinase, and tissue-type plasminogen activator could not substitute for kallikrein. Also, trypsin could easily activate factor XII, but in contrast to kallikrein, this activation was independent of MoAb F1. SDS-PAGE analysis showed that the appearance of amidolytic activity correlated well with cleavage of factor XII. MoAb F1-induced activation of factor XII in this purified system was not dependent on the presence of high-molecular-weight kininogen (HK), in contrast to the activation of the contact system in plasma by MoAb F1. Experiments with deletion mutants revealed that the epitopic region for MoAb F1 on factor XII is located on the kringle domain. Thus, this study shows that binding of ligands to the kringle domain, which does not contribute to the proposed binding site for negatively charged surfaces, may induce activation of factor XII. Therefore, these findings point to the existence of multiple mechanisms of activation of factor XII.
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- 1995
39. Assignment of human coagulation factor XII (fXII) to chromosome 5 by cDNA hybridization to DNA from somatic cell hybrids
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Citarella, F., Tripodi, M., Fantoni, A., Bernardi, F., Romeo, G., and Rocchi, M.
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- 1988
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40. Estrogen induction and contact phase activation of human factor XII
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Citarella, F, Misiti, S, Felici, A, Farsetti, Antonella, Pontecorvi, Alfredo, Fantoni, A., Pontecorvi, Alfredo (ORCID:0000-0003-0570-6865), Citarella, F, Misiti, S, Felici, A, Farsetti, Antonella, Pontecorvi, Alfredo, Fantoni, A., and Pontecorvi, Alfredo (ORCID:0000-0003-0570-6865)
- Abstract
This paper reviews data reported in the literature and results of our experiments on the transcriptional control of Factor XII by estrogens and on the activation of Factor XII in the plasma. Coagulation Factor XII (Hageman factor, FXII) is a serine protease secreted by the liver and activated by negative charged surfaces to play roles in fibrinolysis, coagulation, and inflammation. Multiple effects on hemostasis involving these processes via Hageman factor have been reported in relation to estrogen therapy. The nucleotide sequence of 3,174 base pair (bp) DNA at the 5' end of the Factor XII gene indicates that the Factor XII promoter is typical of TATA-less, liver-specific, and serine protease-type eukaryotic genes involved in clotting. In addition the Factor XII promoter contains at position -44/-31 a palindrome similar, but not identical, to an estrogen-responsive element (ERE) together with four hemisite EREs between positions -1314 and -608. These promoter regions may underlie the mechanism by which estrogens enhance Factor XII concentrations in plasma. In vivo, a 6-fold stimulation of FXII gene transcription by 17 beta-estradiol was observed in ovariectomized rats. In vitro a 230-bp promoter fragment of Factor XII (-181/+49) confers a strong 17 beta-estradiol responsiveness onto a chlorampenicol acetyltransferase reporter when transiently co-transfected with the human estrogen receptor. The domain structure of Factor XII allows identification of those parts of the protein with particular functions. cDNA constructs, in which sequences coding for selected domains were deleted, were used to produce recombinant deleted Factor XII proteins in a vacinia virus expression system. To identify the domain(s) responsible for contact phase activation, these recombinant proteins were tested for their capacity to bind to negatively charged substrates, to become activated by kallikrein, and to sustain blood clotting and amidolytic activity. In addition to the N-terminal domain
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- 1996
41. Molecular basis of estrogen regulation of Hageman factor XII gene expression
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Farsetti, Antonella, Misiti, S, Citarella, F, Felici, A, Andreoli, M, Fantoni, A, Sacchi, A, Pontecorvi, Alfredo, Pontecorvi, Alfredo (ORCID:0000-0003-0570-6865), Farsetti, Antonella, Misiti, S, Citarella, F, Felici, A, Andreoli, M, Fantoni, A, Sacchi, A, Pontecorvi, Alfredo, and Pontecorvi, Alfredo (ORCID:0000-0003-0570-6865)
- Abstract
Estrogen therapy has been reported to cause multiple alterations in hemostasis and to increase blood levels of several procoagulants, including Hageman factor [factor XII (FXII)]. Liver FXII gene expression has been investigated in ovariectomized rats, treated or not with 17 beta-estradiol. A 6-fold stimulation of FXII gene transcription was observed in treated compared to untreated animals, indicating that 17 beta-estradiol is able to induce FXII gene expression in vivo. We have recently shown that human FXII promoter contains an imperfect palindrome, 5'-GGGCAnnnTGACC-3', at position -43/-31 resembling the consensus estrogen-responsive element (ERE). Portions of different length of the FXII promoter were fused to the chloramphenicol acetyltransferase (CAT) coding sequence and transiently cotransfected with human estrogen receptor (ER) into NIH3T3 and HepG2 cells in the presence or absence of 17 beta-estradiol. A 230-base pair fragment of FXII promoter, spanning nucleotides - 181/49, conferred a strong estrogen responsiveness to the CAT reporter gene, suggesting that a functional ERE resides in this region. Cognate receptors, such as those for thyroid hormone or retinoic acid, did not stimulate CAT activity. Gel mobility assays demonstrated a specific interaction between ER and the 230-bp FXII promoter fragment containing the putative ERE palindrome. Similar results were obtained when an oligonucleotide spanning the consensus ERE was used; the complex between ER and FXII promoter sequences was supershifted after the addition of an anti-ER monoclonal antibody. Insertion of FXII-ERE into the heterologous thymidine kinase promoter conferred a strong estrogen responsiveness that was abolished by mutations of the 5'-half of the palindrome. These results represent the first demonstration at the molecular level of the regulation of a blood coagulation factor gene by 17 beta-estradiol as well as the first identification of a functional ERE within this class of genes.
- Published
- 1995
42. Monoclonal antibody F1 binds to the kringle domain of factor XII and induces enhanced susceptibility for cleavage by kallikrein
- Author
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Ravon, DM, primary, Citarella, F, additional, Lubbers, YT, additional, Pascucci, B, additional, and Hack, CE, additional
- Published
- 1995
- Full Text
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43. Expression of human recombinant granzyme A zymogen and its activation by the cysteine proteinase cathepsin C.
- Author
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Kummer, J A, Kamp, A M, Citarella, F, Horrevoets, A J, and Hack, C E
- Abstract
Human granzyme A is one of the serine proteinases present in the granules of cytotoxic T lymphocytes and natural killer cells. Granzymes are synthesized as inactive proenzymes with an amino-terminal prodipeptide, which is processed during transport of granzymes to the cytotoxic granules, where they are stored as active proteinases. In this study, we explored the possibility of producing recombinant granzymes. Recombinant human granzyme A zymogen was expressed in several eukaryotic cell lines (HepG2, Jurkat, and COS-1) after infection with a recombinant vaccinia virus containing full-length granzyme A cDNA. Immunoblot analysis of cell lysates showed that all infected cells produced a disulfide-linked homodimer of identical molecular weight as natural granzyme A. Infected HepG2 cells produced the largest amount of this protease (approximately 160 times more than lymphokine activated killer (LAK) cells). The recombinant protein only had high mannose type oligosaccharides as did the natural protein. Although infected HepG2 and COS cells contained high granzyme A antigen levels, lysates from these cells did not show any granzyme A proteolytic activity. However, the inactive proenzyme could be converted into active granzyme A by incubation with the thiol proteinase cathepsin C (dipeptidyl peptidase I). This study is the first to demonstrate expression of an active recombinant human cytotoxic lymphocyte proteinase and conversion of inactive progranzyme A into an active enzyme by cathepsin C. We suggest that a similar approach can be used for the production of other granzymes and related proteinases.
- Published
- 1996
44. Modulation of contact system proteases by glycosaminoglycans. Selective enhancement of the inhibition of factor XIa.
- Author
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Wuillemin, W A, Eldering, E, Citarella, F, de Ruig, C P, ten Cate, H, and Hack, C E
- Abstract
We investigated the influence of dextran sulfate, heparin, heparan sulfate, and dermatan sulfate on the inhibition of FXIa (where FXIa is activated factor XI, for example), FXIIa, and kallikrein by C1 inhibitor, alpha1-antitrypsin, alpha2-antiplasmin, and antithrombin III. The second-order rate constants for the inhibition of FXIa by C1 inhibitor, alpha1-antitrypsin, alpha2-antiplasmin, and antithrombin III, in the absence of glycosaminoglycans, were 1.8, 0.1, 0.43, and 0.32 x 10(3) M-1 s-1, respectively. The rate constants of the inactivation of FXIa by C1 inhibitor and by antithrombin III increased up to 117-fold in the presence of glycosaminoglycans. These data predicted that considering the plasma concentration of the inhibitors, C1 inhibitor would be the main inhibitor of FXIa in plasma in the presence of glycosaminoglycans. Results of experiments in which the formation of complexes between serine protease inhibitors and FXIa was studied in plasma agreed with this prediction. Glycosaminoglycans did not enhance the inhibition of alpha-FXIIa, beta-FXIIa, or kallikrein by C1 inhibitor. Thus, physiological glycosaminoglycans selectively enhance inhibition of FXIa without affecting the activity of FXIIa and kallikrein, suggesting that glycosaminoglycans may modulate the biological effects of contact activation, by inhibiting intrinsic coagulation without affecting the fibrinolytic potential of FXIIa/kallikrein.
- Published
- 1996
45. The second exon-encoded factor XII region is involved in the interaction of factor XII with factor XI and does not contribute to the binding site for negatively charged surfaces
- Author
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Citarella, F., GIORGIO FEDELE, Roem, D., Fantoni, A., and Hack, C. E.
- Subjects
Immunology ,Cell Membrane ,Factor XII ,Static Electricity ,Humans ,Cell Biology ,Hematology ,Exons ,Biochemistry ,Blood Coagulation ,Factor XI ,Recombinant Proteins ,Protein Binding - Abstract
Contact system activation, in vitro, is triggered by activation of factor XII (FXII) on binding to an activator, such as negatively charged surfaces. A putative surface-binding site of FXII has been located within the amino acid residues 1-28 by identifying the epitope recognized by a monoclonal antibody (MoAb), B7C9, which inhibits kaolin-induced clotting activity. To further elucidate the role of the amino terminal binding site in the regulation of FXII activation, we have characterized a FXII recombinant protein (rFXII-triangle up19) deleted of the amino acid residues 3-19, which are encoded by the second exon of FXII gene. A plasmid encoding for rFXII-triangle up19 was constructed and expressed in HepG2 cells by using vaccinia virus. Purified rFXII-triangle up19 migrated as a single band of Mr 77,000 on sodium dodecyl sulfate (SDS)-polyacrylamide gel, did not bind to MoAb B7C9 immobilized on Protein A-Sepharose, thus confirming that it lacked the epitope for this MoAb, and had no amidolytic activity towards the chromogenic substrate S-2302 in the absence of activator. rFXII-triangle up19 specific clotting activity was lower (44%) than that of native FXII. The activation rate of rFXII-triangle up19 by kallikrein in the absence of dextran sulfate was about four times higher than that of full-length FXII and was increased in the presence of dextran sulfate. However, rFXII-triangle up19 underwent autoactivation in the presence of dextran sulfate. Labeled rFXII-triangle up19 bound to kaolin, which binding was equally well inhibited by either, rFXII-triangle up19 or full-length FXII (IC50 = 7.2 +/- 2.2 nmol/L for both proteins). Accordingly, a synthetic peptide corresponding to FXII amino acid residues 3-19 did not inhibit the binding of labeled full-length FXII to kaolin. rFXII-triangle up19 generated a similar amount of FXIIa- and kallikrein-C1-inhibitor complexes in FXII-deficient plasma in the presence of kaolin, as did full-length FXII; but generated less factor XIa-C1-inhibitor complexes (50%) than full-length FXII. This impaired factor XI activation by rFXII-triangle up19a was also observed in a purified system and was independent of the presence of high molecular weight kininogen. Furthermore, the synthetic peptide 3-19, preincubated with factor XI, inhibited up to 30% activation of factor XI both in the purified system as well as in plasma. These results together indicate that amino acid residues 3-19 of FXII are involved in the activation of factor XI and do not contribute to the binding of FXII to negatively charged surfaces.
46. Recettori per il Testosterone e la Prolattina nel Tegumento e nella Pinna Caudale del Tritone Crestate Tiroidectomizzato o Ipofisectomizzato
- Author
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D'istria, M., primary, Peyrot, A., additional, Citarella, F., additional, Vellano, C., additional, and Delrio, G., additional
- Published
- 1978
- Full Text
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47. Smoking status during first-line immunotherapy and chemotherapy in NSCLC patients: A case-control matched analysis from a large multicenter study
- Author
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Maria Vittoria Pensieri, Ettore D'Argento, Giovanni Mansueto, Lorenza Landi, Mario Occhipinti, Diego Cortinovis, Robin Cornelissen, Diego Signorelli, Lorenzo Antonuzzo, Gabriele Minuti, Valerio Maria Napoli, Corrado Ficorella, Francesco Grossi, Raffaele Giusti, Cinzia Baldesarri, Vincenzo Di Noia, Giampiero Porzio, Alfredo Addeo, Luigi Della Gravara, Vincenzo Sforza, Serena Ricciardi, Paola Bordi, Francesca Rastelli, Alessandro Inno, Giuseppe Luigi Banna, Giovanni Rossi, Michele De Tursi, Matteo Santoni, Rita Chiari, Alessandro De Toma, Olga Nigro, Andrea De Giglio, Clelia Donisi, Luca Cantini, Fabrizio Citarella, Alessio Cortellini, Michele Montrone, Alain Gelibter, Gianmarco Leone, Alessandro Follador, Annamaria Catino, Federica Zoratto, Marco Filetti, Pietro Di Marino, Giulio Metro, Alex Friedlaender, Alessandro Leonetti, Rossana Berardi, Maria Rita Migliorino, Marco Russano, Katia Cannita, Pulmonary Medicine, Cortellini A., De Giglio A., Cannita K., Cortinovis D.L., Cornelissen R., Baldessari C., Giusti R., D'Argento E., Grossi F., Santoni M., Catino A., Berardi R., Sforza V., Rossi G., Antonuzzo L., Di Noia V., Signorelli D., Gelibter A., Occhipinti M.A., Follador A., Rastelli F., Chiari R., Gravara L.D., Inno A., De Tursi M., Di Marino P., Mansueto G., Zoratto F., Filetti M., Montrone M., Citarella F., Pensieri M.V., Russano M., Cantini L., Nigro O., Leonetti A., Bordi P., Minuti G., Landi L., De Toma A., Donisi C., Ricciardi S., Migliorino M.R., Napoli V.M., Leone G., Metro G., Banna G.L., Friedlaender A., Addeo A., Ficorella C., and Porzio G.
- Subjects
Male ,non‐small cell lung cancer ,0301 basic medicine ,Pulmonary and Respiratory Medicine ,Oncology ,medicine.medical_specialty ,Lung Neoplasms ,medicine.medical_treatment ,First line ,Respiratory System ,Pembrolizumab ,immunotherapy ,non-small cell lung cancer ,pembrolizumab ,smoking ,tobacco ,lcsh:RC254-282 ,03 medical and health sciences ,0302 clinical medicine ,SDG 3 - Good Health and Well-being ,Carcinoma, Non-Small-Cell Lung ,Internal medicine ,medicine ,Humans ,Chemotherapy ,Science & Technology ,business.industry ,Hazard ratio ,Original Articles ,General Medicine ,Immunotherapy ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Former Smoker ,Survival Analysis ,Lung Neoplasm ,030104 developmental biology ,Case-Control Studies ,030220 oncology & carcinogenesis ,Cohort ,Female ,Original Article ,Smoking status ,Case-Control Studie ,business ,Life Sciences & Biomedicine ,Human - Abstract
Background Improved outcome in tobacco smoking patients with non‐small cell lung cancer (NSCLC) following immunotherapy has previously been reported. However, little is known regarding this association during first‐line immunotherapy in patients with high PD‐L1 expression. In this study we compared clinical outcomes according to the smoking status of two large multicenter cohorts. Methods We compared clinical outcomes according to the smoking status (never smokers vs. current/former smokers) of two retrospective multicenter cohorts of metastatic NSCLC patients, treated with first‐line pembrolizumab and platinum‐based chemotherapy. Results A total of 962 NSCLC patients with PD‐L1 expression ≥50% who received first‐line pembrolizumab and 462 NSCLC patients who received first‐line platinum‐based chemotherapy were included in the study. Never smokers were confirmed to have a significantly higher risk of disease progression (hazard ratio [HR] = 1.49 [95% CI: 1.15–1.92], p = 0.0022) and death (HR = 1.38 [95% CI: 1.02–1.87], p = 0.0348) within the pembrolizumab cohort. On the contrary, a nonsignificant trend towards a reduced risk of disease progression (HR = 0.74 [95% CI: 0.52–1.05], p = 0.1003) and death (HR = 0.67 [95% CI: 0.45–1.01], p = 0.0593) were reported for never smokers within the chemotherapy cohort. After a random case–control matching, 424 patients from both cohorts were paired. Within the matched pembrolizumab cohort, never smokers had a significantly shorter progression‐free survival (PFS) (HR = 1.68 [95% CI: 1.17–2.40], p = 0.0045) and a nonsignificant trend towards a shortened overall survival (OS) (HR = 1.32 [95% CI: 0.84–2.07], p = 0.2205). On the contrary, never smokers had a significantly longer PFS (HR = 0.68 [95% CI: 0.49–0.95], p = 0.0255) and OS (HR = 0.66 [95% CI: 0.45–0.97], p = 0,0356) compared to current/former smoker patients within the matched chemotherapy cohort. On pooled multivariable analysis, the interaction term between smoking status and treatment modality was concordantly statistically significant with respect to ORR (p = 0.0074), PFS (p = 0.0001) and OS (p = 0.0020), confirming the significantly different impact of smoking status across the two cohorts. Conclusions Among metastatic NSCLC patients with PD‐L1 expression ≥50% receiving first‐line pembrolizumab, current/former smokers experienced improved PFS and OS. On the contrary, worse outcomes were reported among current/former smokers receiving first‐line chemotherapy., Improved outcome in tobacco smoking NSCLC patients following treatment with immune checkpoint inhibitors (ICIs) has previously been reported. Little is known regarding this association during first‐line immunotherapy in patients with high PD‐L1 expression. Clinical outcomes according to the smoking status of two large multicenter cohorts were compared in this study. Smokers with high PD‐L1 expression ≥ 50% experienced improved progression‐free survival (PFS) and overall survival (OS) with first‐line pembrolizumab. The opposite trend was found in NSCLC patients treated with first‐line platinum‐based chemotherapy.
- Published
- 2021
- Full Text
- View/download PDF
48. Nutritional intervention in a hemodialysis pregnant woman: a case report
- Author
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Brunella Guida, Annamaria Nastasi, Rossella Trio, Bruno Memoli, Fabrizio Pollio, Roberta Laccetti, A. Di Lieto, F. Citarella, Guida, B., Pollio, F., Nastasi, A., Trio, R., Laccetti, R., DI LIETO, Andrea, Citarella, F., Memoli, B., Guida, Bruna, Pollio, Fabrizio, Nastasi, Annamaria, Trio, R, Laccetti, Roberta, Citarella, F, and Memoli, Bruno
- Subjects
Adult ,Pediatrics ,medicine.medical_specialty ,medicine.medical_treatment ,Pregnancy, High-Risk ,Abortion ,Critical Care and Intensive Care Medicine ,Dialysis patients ,Pregnancy ,Renal Dialysis ,Risk Factors ,Intervention (counseling) ,medicine ,Humans ,Nutritional Physiological Phenomena ,Intensive care medicine ,Dialysis ,Nutrition and Dietetics ,business.industry ,Pregnancy Outcome ,medicine.disease ,Pregnancy Complications ,Nutritionist ,nutrition ,hemodialysi ,Chronic renal failure ,Kidney Failure, Chronic ,Female ,Hemodialysis ,business - Abstract
Pregnancy in dialysis patients is a rare occurrence. When pregnancy does occur, the risk of spontaneous abortion, stillbirth and neonatal complications, such as prematurity and growth retardation, are fairly high. The authors describe their experience in the follow-up of a patient with chronic renal failure who became pregnant during regular dialysis treatment and followed nutritional care. The outcomes were successful and she gave birth to a healthy baby. It is emphasized that special dedication to the nutritional control enabled a good outcome of the pregnancy. The importance of the nutritionist intervention in the follow-up of dialysis patients with the integration of a multidisciplinary staff is stressed.
- Published
- 2003
49. 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
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L. Cantini, G. Mentrasti, G.L. Russo, D. Signorelli, G. Pasello, E. Rijavec, M. Russano, L. Antonuzzo, D. Rocco, R. Giusti, V. Adamo, C. Genova, A. Tuzi, A. Morabito, S. Gori, N. La Verde, R. Chiari, A. Cortellini, V. Cognigni, F. Pecci, A. Indini, A. De Toma, E. Zattarin, S. Oresti, E.G. Pizzutilo, S. Frega, E. Erbetta, A. Galletti, F. Citarella, S. Fancelli, E. Caliman, L. Della Gravara, U. Malapelle, M. Filetti, M. Piras, G. Toscano, L. Zullo, M. De Tursi, P. Di Marino, V. D’Emilio, M.S. Cona, A. Guida, A. Caglio, F. Salerno, G. Spinelli, C. Bennati, F. Morgillo, A. Russo, C. Dellepiane, I. Vallini, V. Sforza, A. Inno, F. Rastelli, V. Tassi, L. Nicolardi, V. Pensieri, R. Emili, E. Roca, A. Migliore, T. Galassi, M. L. Bruno Rocchi, R. Berardi, 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. L., 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. B., and Berardi, R.
- Subjects
Cancer Research ,ECOG PS, Eastern Cooperative Oncology Group Performance Status ,Lung Neoplasms ,Settore MED/06 - Oncologia Medica ,PD-(L)1, programmed death-(ligand) 1 ,COVID-19 ,diagnostic delay ,lung cancer ,staging ,therapeutic delay ,LC, lung cancer ,SCLC, small cell lung cancer ,NSCLC, non-small cell lung cancer ,Humans ,COVID-19, Coronavirus Disease 19 ,Pandemics ,IQR, interquartile range ,Original Research ,pts, patients ,CI, confidence interval ,Oncology ,Communicable Disease Control ,Italy ,SD, standard deviation - Abstract
Introduction: COVID-19 has disrupted the global health care system since March 2020. Lung cancer (LC) patients (pts) represent a vulnerable population highly affected by the pandemic. This multicenter Italian study aimed to evaluate whether the COVID-19 outbreak had an impact on access to cancer diagnosis and treatment of LC pts compared with pre-pandemic time. Methods: Consecutive newly diagnosed LC pts referred to 25 Italian Oncology Departments between March and December 2020 were included. Access rate and temporal intervals between date of symptoms onset and diagnostic and therapeutic services were compared with the same period in 2019. Differences between the 2 years were analyzed using the chi-square test for categorical variables and the Mann–Whitney U test for continuous variables. Results: A slight reduction (−6.9%) in newly diagnosed LC cases was observed in 2020 compared with 2019 (1523 versus 1637, P = 0.09). Newly diagnosed LC pts in 2020 were more likely to be diagnosed with stage IV disease (P < 0.01) and to be current smokers (someone who has smoked more than 100 cigarettes, including hand-rolled cigarettes, cigars, cigarillos, in their lifetime and has smoked in the last 28 days) (P < 0.01). The drop in terms of new diagnoses was greater in the lockdown period (percentage drop −12% versus −3.2%) compared with the other months included. More LC pts were referred to a low/medium volume hospital in 2020 compared with 2019 (P = 0.01). No differences emerged in terms of interval between symptoms onset and radiological diagnosis (P = 0.94), symptoms onset and cytohistological diagnosis (P = 0.92), symptoms onset and treatment start (P = 0.40), and treatment start and first radiological revaluation (P = 0.36). Conclusions: Our study pointed out a reduction of new diagnoses with a shift towards higher stage at diagnosis for LC pts in 2020. Despite this, the measures adopted by Italian Oncology Departments ensured the maintenance of the diagnostic-therapeutic pathways of LC pts.
- Published
- 2022
50. Control of human coagulation by recombinant serine proteases. Blood clotting is activated by recombinant factor XII deleted of five regulatory domains
- Author
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Antonio Fantoni, Giulia Russo, Monica Rinaldi, Alessandro Aiuti, Concetta Pietropaolo, Franca Citarella, Claudia La Porta, Citarella, F, Aiuti, Alessandro, LA PORTA, C, Russo, G, Pietropaolo, C, Rinaldi, M, Fantoni, A., Citarella, F., Aiuti, A., LA PORTA, C., Russo, G., Pietropaolo, Concetta, and Rinaldi, M.
- Subjects
Proteases ,animal structures ,Carcinoma, Hepatocellular ,medicine.medical_treatment ,Molecular Sequence Data ,Restriction Mapping ,Coagulation Factor XII ,Biology ,Protein Engineering ,Biochemistry ,law.invention ,Cell Line ,law ,Complementary DNA ,medicine ,Humans ,cardiovascular diseases ,Cloning, Molecular ,Blood Coagulation ,Gene Library ,Factor XII ,Protease ,Binding Sites ,Base Sequence ,Liver Neoplasms ,Serine Endopeptidases ,Protein engineering ,DNA ,Recombinant Proteins ,Kinetics ,Coagulation ,Oligodeoxyribonucleotides ,Recombinant DNA ,Chromosome Deletion ,circulatory and respiratory physiology - Abstract
The availability of engineered serine proteases allows one to study the activation, substrate specificity and regulation of human coagulation and fibrinolytic activities. Human coagulation factor XII is composed of the protease catalytic region at the C-terminus, a hinge proline-rich region and regulatory domains at the N-terminus. From cDNA clones coding for factor XII, two DNA molecules were constructed, one being full length and the other being deleted of exons coding for the regulatory domains. Engineered factor-XII cDNA species were inserted by a homologous recombination technique into vaccinia viruses, which were used to infect the human hepatoma cell line HepG2. Two recombinant proteins were prepared from the culture media and identified by their antigenic properties and electrophoretic mobilities. The recombinant protein of larger size was identified as the full-length factor XII of 80 kDa and its specific activities and activation patterns, determined both by the coagulation and the amidolytic assays, are very similar to these of native human factor XII. The recombinant protein of smaller size was identified as a 319-amino-acid-deleted factor-XII protein of 32 kDa, containing only the entire protease region and part of the proline-rich hinge. This protein was expected to be the ‘minimal’ portion of factor XII able to sustain protease activity, but unable to recognize substrates and surfaces necessary to activate the contact phase of coagulation. However, this ‘minimal’ factor-XII protein displays a marked protease activity and, although lacking five regulatory domains of factor XII, is bound and activated by negative charges and promotes coagulation with high efficiency.
- Published
- 1992
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