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1. 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](S2059702922000278)(10.1016/j.esmoop.2022.100406)

Author

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

Abstract

The publisher regrets that at the time the article was published the name of the author N. La Verde was mistakenly abbreviated as N.L. Verde. This has now been corrected. The publisher would like to apologise for any inconvenience caused.

Published
2022

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

Author

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

Subjects
Pulmonary and Respiratory Medicine, Oncology
Published
2022
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3. Efficacy and Safety of Anti-PD-1 Immunotherapy in Patients Aged ≥ 75 Years With Non–small-cell Lung Cancer (NSCLC): An Italian, Multicenter, Retrospective Study

Author

Luciani, A, Marra, A, Toschi, L, Cortinovis, D, Fava, S, Filipazzi, V, Tuzi, A, Cerea, G, Rossi, S, Perfetti, V, Rossi, A, Giannetta, L, Sala, L, Finocchiaro, G, Pizzutilo, E, Carelli, S, Agustoni, F, Cergnul, M, Zonato, S, Siena, S, Bidoli, P, Ferrari, D, Luciani A., Marra A., Toschi L., Cortinovis D., Fava S., Filipazzi V., Tuzi A., Cerea G., Rossi S., Perfetti V., Rossi A., Giannetta L., Sala L., Finocchiaro G., Pizzutilo E. G., Carelli S., Agustoni F., Cergnul M., Zonato S., Siena S., Bidoli P., Ferrari D., Luciani, A, Marra, A, Toschi, L, Cortinovis, D, Fava, S, Filipazzi, V, Tuzi, A, Cerea, G, Rossi, S, Perfetti, V, Rossi, A, Giannetta, L, Sala, L, Finocchiaro, G, Pizzutilo, E, Carelli, S, Agustoni, F, Cergnul, M, Zonato, S, Siena, S, Bidoli, P, Ferrari, D, Luciani A., Marra A., Toschi L., Cortinovis D., Fava S., Filipazzi V., Tuzi A., Cerea G., Rossi S., Perfetti V., Rossi A., Giannetta L., Sala L., Finocchiaro G., Pizzutilo E. G., Carelli S., Agustoni F., Cergnul M., Zonato S., Siena S., Bidoli P., and Ferrari D.

Abstract

This study was conducted in the setting of advanced non–small-cell lung cancer in older patients. It is a multicenter retrospective analysis on very old persons that explores the efficacy and the safety of anti-programmed cell death protein 1 therapy. Older patients seem to tolerate immunotherapy as well as younger patients with comparable efficacy. This is a relevant message for everyday clinical practice.

Published
2020

4. Chemotherapy in non-small cell lung cancer patients after prior immunotherapy: The multicenter retrospective CLARITY study

Author

Bersanelli, M, Buti, S, Giannarelli, D, Leonetti, A, Cortellini, A, Russo, G, Signorelli, D, Toschi, L, Milella, M, Pilotto, S, Bria, E, Proto, C, Marinello, A, Randon, G, Rossi, S, Vita, E, Sartori, G, D'Argento, E, Qako, E, Giaiacopi, E, Ghilardi, L, Bettini, A, Rapacchi, E, Mazzoni, F, Lavacchi, D, Scotti, V, Ciccone, L, De Tursi, M, Di Marino, P, Santini, D, Russano, M, Bordi, P, Di Maio, M, Audisio, M, Filetti, M, Giusti, R, Berardi, R, Fiordoliva, I, Cerea, G, Pizzutilo, E, Bearz, A, De Carlo, E, Cecere, F, Renna, D, Camisa, R, Caruso, G, Ficorella, C, Banna, G, Cortinovis, D, Brighenti, M, Garassino, M, Tiseo, M, Bersanelli M., Buti S., Giannarelli D., Leonetti A., Cortellini A., Russo G. L., Signorelli D., Toschi L., Milella M., Pilotto S., Bria E., Proto C., Marinello A., Randon G., Rossi S., Vita E., Sartori G., D'Argento E., Qako E., Giaiacopi E., Ghilardi L., Bettini A. C., Rapacchi E., Mazzoni F., Lavacchi D., Scotti V., Ciccone L. P., De Tursi M., Di Marino P., Santini D., Russano M., Bordi P., Di Maio M., Audisio M., Filetti M., Giusti R., Berardi R., Fiordoliva I., Cerea G., Pizzutilo E. G., Bearz A., De Carlo E., Cecere F., Renna D., Camisa R., Caruso G., Ficorella C., Banna G. L., Cortinovis D., Brighenti M., Garassino M. C., Tiseo M., Bersanelli, M, Buti, S, Giannarelli, D, Leonetti, A, Cortellini, A, Russo, G, Signorelli, D, Toschi, L, Milella, M, Pilotto, S, Bria, E, Proto, C, Marinello, A, Randon, G, Rossi, S, Vita, E, Sartori, G, D'Argento, E, Qako, E, Giaiacopi, E, Ghilardi, L, Bettini, A, Rapacchi, E, Mazzoni, F, Lavacchi, D, Scotti, V, Ciccone, L, De Tursi, M, Di Marino, P, Santini, D, Russano, M, Bordi, P, Di Maio, M, Audisio, M, Filetti, M, Giusti, R, Berardi, R, Fiordoliva, I, Cerea, G, Pizzutilo, E, Bearz, A, De Carlo, E, Cecere, F, Renna, D, Camisa, R, Caruso, G, Ficorella, C, Banna, G, Cortinovis, D, Brighenti, M, Garassino, M, Tiseo, M, Bersanelli M., Buti S., Giannarelli D., Leonetti A., Cortellini A., Russo G. L., Signorelli D., Toschi L., Milella M., Pilotto S., Bria E., Proto C., Marinello A., Randon G., Rossi S., Vita E., Sartori G., D'Argento E., Qako E., Giaiacopi E., Ghilardi L., Bettini A. C., Rapacchi E., Mazzoni F., Lavacchi D., Scotti V., Ciccone L. P., De Tursi M., Di Marino P., Santini D., Russano M., Bordi P., Di Maio M., Audisio M., Filetti M., Giusti R., Berardi R., Fiordoliva I., Cerea G., Pizzutilo E. G., Bearz A., De Carlo E., Cecere F., Renna D., Camisa R., Caruso G., Ficorella C., Banna G. L., Cortinovis D., Brighenti M., Garassino M. C., and Tiseo M.

Abstract

Objectives: In the most of cases, for non-small cell lung cancer (NSCLC) patients who progressed to previous immune checkpoint inhibitors (CKI) administered as first- or as second-line therapy, chemotherapy (CT) remains the only viable options in the absence of “druggable” mutations. We aimed to explore the efficacy of salvage chemotherapy after immunotherapy (SCAI) in advanced NSCLC patients. Materials and Methods: We designed a retrospective, multicenter study, involving 20 Italian centers, with the primary objective of describing the clinical outcome of advanced NSCLC patients treated with SCAI at the participating institutions from November 2013 to July 2019. The primary endpoint of the study was represented by overall survival (OS), defined as the time from CT initiation to death. Secondary outcome endpoints of the SCAI (progression free survival, PFS, objective response rate, ORR and toxicity) and explorative biomarkers (lactate dehydrogenase, LDH, and neutrophil-to-lymphocyte ratio, NLR during immunotherapy) were also analyzed. Results: In our study population of 342 NSCLC patients, SCAI obtained a median OS of 6.8 months (95 % confidence interval, CI 5.5–8.1), median PFS of 4.1 months (95 % CI 3.4−4.8) and ORR of 22.8 %. A “Post-CKI score” was constructed by combining significant predictors of OS at the multivariate analyses (sex, ECOG PS, disease control with prior immunotherapy), Harrell'C was 0.65, (95 % CI:0.59−0.71). Conclusions: Despite the late-line settings, our findings support the hypothesis that previous immunotherapy might increase the sensitivity of the tumor to the subsequent chemotherapy. The “Post-CKI score” was clinically effective in successfully discriminating three distinct prognostic subgroups of patients after the failure of CKI, representing a possibly useful tool for the tailored decision-making process of advanced treatment-line settings in NSCLC.

Published
2020

5. First-line pembrolizumab in advanced non-small cell lung cancer patients with poor performance status

Author

Facchinetti, F, Mazzaschi, G, Barbieri, F, Passiglia, F, Mazzoni, F, Berardi, R, Proto, C, Cecere, F, Pilotto, S, Scotti, V, Rossi, S, Del Conte, A, Vita, E, Bennati, C, Ardizzoni, A, Cerea, G, Migliorino, M, Sala, E, Camerini, A, Bearz, A, De Carlo, E, Zanelli, F, Guaitoli, G, Garassino, M, Ciccone, L, Sartori, G, Toschi, L, Dall'Olio, F, Landi, L, Pizzutilo, E, Bartoli, G, Baldessari, C, Novello, S, Bria, E, Cortinovis, D, Rossi, G, Rossi, A, Banna, G, Camisa, R, Di Maio, M, Tiseo, M, Cecere, FL, Migliorino, MR, Garassino, MC, Ciccone, LP, Dall'Olio, FG, Pizzutilo, EG, Banna, GL, Facchinetti, F, Mazzaschi, G, Barbieri, F, Passiglia, F, Mazzoni, F, Berardi, R, Proto, C, Cecere, F, Pilotto, S, Scotti, V, Rossi, S, Del Conte, A, Vita, E, Bennati, C, Ardizzoni, A, Cerea, G, Migliorino, M, Sala, E, Camerini, A, Bearz, A, De Carlo, E, Zanelli, F, Guaitoli, G, Garassino, M, Ciccone, L, Sartori, G, Toschi, L, Dall'Olio, F, Landi, L, Pizzutilo, E, Bartoli, G, Baldessari, C, Novello, S, Bria, E, Cortinovis, D, Rossi, G, Rossi, A, Banna, G, Camisa, R, Di Maio, M, Tiseo, M, Cecere, FL, Migliorino, MR, Garassino, MC, Ciccone, LP, Dall'Olio, FG, Pizzutilo, EG, and Banna, GL

Abstract

Background: Pembrolizumab is the first-line standard of care for advanced non–small cell lung cancer (NSCLC) with a PD-L1 tumour proportion score (TPS) ≥ 50%. Eastern Cooperative Oncology Group performance status (PS) 2 patients may receive pembrolizumab, despite the absence of sustaining evidence. Patients and methods: GOIRC-2018-01 is a multicentre, retrospective, observational study. PS 2 NSCLC patients with a PD-L1 TPS ≥50% receiving first-line pembrolizumab from June 2017 to December 2018 at 21 Italian institutions were included. Clinical-pathological characteristics were correlated with disease response and survival outcomes; adverse events were recorded. The primary objective was 6-months progression-free rate (6-months PFR). Results: One hundred fifty-three patients (median age 70 years) were enrolled. At a median follow-up of 18.2 months, median progression-free survival (PFS) and overall survival (OS) were 2.4 (95% confidence interval, 95% CI, 1.6–2.5) and 3.0 months (95% CI 2.4–3.5), respectively. 6-months PFR was 27% (95% CI 21–35%). Patients with a PS 2 determined by comorbidities (n = 41) had significantly better outcomes compared with disease burden-induced PS 2 (n = 112). Indeed, 6-months PFR was 49% versus 19%, median PFS 5.6 versus 1.8 months and OS 11.8 versus 2.8 months, respectively. Additional potential prognostic factors (radiotherapy, antibiotics, steroids received before pembrolizumab) correlated with clinical outcomes. The determinant of PS 2 resulted the only factor independently impacting on both PFS and OS. No toxicity issues emerged. Conclusions: Outcomes of PS 2 NSCLC patients with PD-L1 TPS ≥50% receiving first-line pembrolizumab were globally dismal but strongly dependent on the reason conditioning the poor PS itself.

Published
2020

8. On the need of improved Accelerated Degradation Protocols (ADPs):examination of platinum dissolution and carbon corrosion in half-cell tests

Author

Pizzutilo, E., Geiger, S., Grote, J. P., Mingers, A., Mayrhofer, K. J. J., Arenz, Matthias, Cherevko, S., Pizzutilo, E., Geiger, S., Grote, J. P., Mingers, A., Mayrhofer, K. J. J., Arenz, Matthias, and Cherevko, S.

Abstract

In this work we employ the advanced scanning flow cell based analytical techniques, viz. inductively coupled plasma mass spectrometry (SFC-ICP-MS) and on-line electrochemical mass-spectrometry (SFC-OLEMS) to directly detect the amounts of dissolved platinum and evolved carbon dioxide in two protocols that are commonly used in the fuel cell community to simulate load cycle and start-stop conditions in proton exchange membrane fuel cells (PEMFCs). In contrast to previous assumptions, claiming a separation between carbon corrosion and platinum dissolution, in both standard protocols platinum dissolution and carbon corrosion are present at low rates, which is also reflected by a comparably low ECSA decrease. On the other hand, a huge increase in rate of both processes is observed during transitions from low to high potential regimes experienced by a PEMFC in operation, here studied in a third protocol covering the whole potential range from 0.6 to 1.5 VRHE. The latter is typically not addressed in literature. This finding is explained by taking into account platinum catalyzed carbon corrosion and transient platinum dissolution. Based on the obtained results, the question is raised on the practical adequacy of the standard protocols for differentiation of degradation processes and simulation of the degradation processes occurring in PEMFCs.

Published
2016

12. Tropomyosin receptor kinase (TRK) biology and the role of NTRK gene fusions in cancer.

Author

Amatu, A, Sartore-Bianchi, A, Bencardino, K, Pizzutilo, E G, Tosi, F, and Siena, S

Subjects
*GENE fusion, *TROPOMYOSINS, *CANCER genes, *BIOLOGY, *COLON cancer
Abstract

The tropomyosin receptor kinase (TRK) family of receptor tyrosine kinases are encoded by NTRK genes and have a role in the development and normal functioning of the nervous system. Since the discovery of an oncogenic NTRK gene fusion in colorectal cancer in 1986, over 80 different fusion partner genes have been identified in a wide array of adult and paediatric tumours, providing actionable targets for targeted therapy. This review describes the normal function and physiology of TRK receptors and the biology behind NTRK gene fusions and how they act as oncogenic drivers in cancer. Finally, an overview of the incidence and prevalence of NTRK gene fusions in various types of cancers is discussed. [ABSTRACT FROM AUTHOR]

Published
2019
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13. 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

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

14. Efficacy and Safety of Anti-PD-1 Immunotherapy in Patients Aged ≥ 75 Years With Non-small-cell Lung Cancer (NSCLC): An Italian, Multicenter, Retrospective Study

Author

Francesco Agustoni, Massimiliano Cergnul, V. Filipazzi, Andrea Luciani, Sabrina Rossi, Antonio Marra, Elio Gregory Pizzutilo, Alessandro Tuzi, Paolo Bidoli, Diego Cortinovis, Salvatore Siena, Sergio Fava, Luca Toschi, Giovanna Finocchiaro, Antonio Rossi, Stephana Carelli, S. Zonato, Daris Ferrari, Giulio Cerea, Vittorio Perfetti, Luca Sala, Laura Giannetta, Luciani, A, Marra, A, Toschi, L, Cortinovis, D, Fava, S, Filipazzi, V, Tuzi, A, Cerea, G, Rossi, S, Perfetti, V, Rossi, A, Giannetta, L, Sala, L, Finocchiaro, G, Pizzutilo, E, Carelli, S, Agustoni, F, Cergnul, M, Zonato, S, Siena, S, Bidoli, P, and Ferrari, D

Subjects
0301 basic medicine, Pulmonary and Respiratory Medicine, Oncology, Male, Cancer Research, medicine.medical_specialty, Lung Neoplasms, non-small cell lung cancer (NSCLC), Adenocarcinoma of Lung, B7-H1 Antigen, 03 medical and health sciences, Elderly, 0302 clinical medicine, Antineoplastic Agents, Immunological, Internal medicine, Carcinoma, Non-Small-Cell Lung, PD-1, medicine, Humans, Lung cancer, Aged, Retrospective Studies, Aged, 80 and over, Performance status, business.industry, Proportional hazards model, Incidence (epidemiology), Cancer, Retrospective cohort study, medicine.disease, Prognosis, Clinical trial, Survival Rate, 030104 developmental biology, Italy, 030220 oncology & carcinogenesis, Carcinoma, Squamous Cell, Female, Immunotherapy, business, Follow-Up Studies
Abstract

Introduction Non–small-cell lung cancer (NSCLC) is predominantly a disease of the elderly population. Over the past few years, immunotherapy with monoclonal antibodies named checkpoint inhibitors (ICIs) greatly improved the clinical management of a significant proportion of patients with metastatic NSCLC. However, pivotal trials excluded older patients, although, given the favorable clinical profile of ICIs, this treatment may be revealed to be a most valuable option also for these patients. To this aim, a multicenter retrospective analysis was performed on patients aged ≥ 75 years with NSCLC treated with anti-programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) immunotherapy. Material and Methods Inclusion criteria were: diagnosis of locally advanced or metastatic NSCLC (stage IIIB or IV, according to the American Joint Committee on Cancer (AJCC) classification system, version 8.0); age ≥ 75 years; treatment with anti-PD-1/PD-L1 monoclonal antibodies in first or subsequent lines of treatment; absence of epidermal growth factor receptor-activating mutations or anaplastic lymphoma kinase and ROS-1 rearrangements. The primary endpoints of the study were the efficacy, in terms of overall response rate, progression-free survival, and overall survival, and safety, by means of evaluations of the incidence of immune-related adverse events. Results Eighty-six patients were considered for the final analysis; 71 (82.6%) were male. The mean age was 78.5 years (range, 75-86 years; SD, 3.12 years). Of the 86 patients, 69 (80.2%) of patients had a performance status of 0 or 1. The overall median progression-free survival was 5.6 months (range 1-36 months; SD, 7.5 months,) whereas the median overall survival was 10.1 months (range, 1.7-34.8 months; SD, 8 months). At the Cox regression analysis, the only parameter significantly associated with survival was the smoking status (P = .008). No difference in survival was found between patients younger and older than 80 years. Conclusions In the present real-world retrospective cohort, efficacy and toxicity profiles of ICIs in older patients with advanced NSCLC were comparable with those observed in younger patients enrolled in clinical trials.

Published
2019

15. Novel electrical conduction properties obtained in few-layer graphene/epoxy nanocomposites

Author

Davide Fabiani, Enrico Pizzutilo, L. Da Gama Fernandes Vieira, J.-Y. Chane Ching, Z. Valdez Nava, Sombel Diaham, Emmanuel Flahaut, Diaham, S., Pizzutilo, E., Vieira, L. Da Gama Fernande, Nava, Z. Valdez, Chane Ching, J.-Y., Flahaut, E., and Fabiani, D.

Subjects
Materials science, Nanocomposite, Graphene, Process Chemistry and Technology, Electronic, Optical and Magnetic Material, Graphene foam, Multi-layer graphene, Insulator (electricity), Ceramics and Composite, Epoxy, law.invention, Surfaces, Coatings and Films, Epoxy Nanocomposite, law, Electrical resistivity and conductivity, visual_art, Few-layer graphene, visual_art.visual_art_medium, Electrical conductivity, Exfoliation, Composite material, Electrical and Electronic Engineering, Graphene nanoribbons, Graphene oxide paper
Abstract

In this paper, we propose to study the impact of very low filler content (0.005 wt.%) of graphite nanoflakes (80 nm), multi-layer (5–20 nm) and few-layer (1–2 nm) graphene on the electrical conductivity of an epoxy nanocomposite. The results highlight that an improvement of the quality of the exfoliation process of graphene, particularly in few-layer graphene/epoxy, allows decreasing the DC electrical conductivity (by a factor 100 compared to neat epoxy) in a large range of electric field from 1 to 10 kV/mm. This novel property could allow decreasing space charge trapping within the insulator bulk at the origin of long-term electrical ageing.

Published
2015

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

Author

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

Subjects
Humans, Retrospective Studies, Male, Female, Middle Aged, Aged, Adult, Aged, 80 and over, Antineoplastic Agents therapeutic use, Antineoplastic Agents pharmacology, Protein Kinase Inhibitors therapeutic use, Protein Kinase Inhibitors pharmacology, Indoles, Pyrimidines, Carcinoma, Non-Small-Cell Lung drug therapy, Carcinoma, Non-Small-Cell Lung genetics, Carcinoma, Non-Small-Cell Lung pathology, Acrylamides therapeutic use, Acrylamides pharmacology, Lung Neoplasms drug therapy, Lung Neoplasms genetics, Lung Neoplasms pathology, ErbB Receptors genetics, Aniline Compounds therapeutic use, Aniline Compounds pharmacology, Mutation
Abstract

Background: Osimertinib represents the standard of care for the treatment of advanced non-small-cell lung cancer (NSCLC) harboring classical epidermal growth factor receptor (EGFR) mutations, constituting 80%-90% of all EGFR alterations. In the remaining cases, an assorted group of uncommon alterations of EGFR (uEGFR) can be detected, which confer variable sensitivity to previous generations of EGFR inhibitors, overall with lower therapeutic activity. Data on osimertinib in this setting are limited and strongly warranted., Patients and Methods: The ARTICUNO study retrospectively evaluated data on osimertinib activity from patients with advanced NSCLC harboring uEGFR treated in 21 clinical centers between August 2017 and March 2023. Data analysis was carried out with a descriptive aim. Investigators collected response data according to RECIST version 1.1 criteria. The median duration of response, progression-free survival (mPFS), and overall survival were estimated by the Kaplan-Meier method., Results: Eighty-six patients harboring uEGFR and treated with osimertinib were identified. Patients with 'major' uEGFR, that is, G719X, L861X, and S768I mutations (n = 51), had an overall response rate (ORR) and mPFS of 50% and 9 months, respectively. Variable outcomes were registered in cases with rarer 'minor' mutations (n = 27), with ORR and mPFS of 31% and 4 months, respectively. Among seven patients with exon 20 insertions, ORR was 14%, while the best outcome was registered among patients with compound mutations including at least one classical EGFR mutation (n = 13). Thirty patients presented brain metastases (BMs) and intracranial ORR and mPFS were 58% and 9 months, respectively. Amplification of EGFR or MET, TP53 mutations, and EGFR E709K emerged after osimertinib failure in a dataset of 18 patients with available rebiopsy., Conclusion: The ARTICUNO study confirms the activity of osimertinib in patients with uEGFR, especially in those with compound uncommon-common mutations, or major uEGFR, even in the presence of BMs. Alterations at the E709 residue of EGFR are associated with resistance to osimertinib., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Published
2024
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18. Erratum to 'Evaluation of COVID-19 impact on DELAYing diagnostic-therapeutic pathways of lung cancer patients in Italy (COVID-DELAY study): fewer cases and higher stages from a real-world scenario': [ESMO Open Volume 7, Issue 2, April 2022, 100406].

Author

Cantini L, Mentrasti G, Lo Russo G, Signorelli D, Pasello G, Rijavec E, Russano M, Antonuzzo L, Rocco D, Giusti R, Adamo V, Genova C, Tuzi A, Morabito A, Gori S, La Verde N, Chiari R, Cortellini A, Cognigni V, Pecci F, Indini A, De Toma A, Zattarin E, Oresti S, Pizzutilo EG, 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 MS, Guida A, Caglio A, Salerno F, Spinelli GP, Bennati C, Morgillo F, Russo A, Dellepiane C, Vallini I, Sforza V, Inno A, Rastelli F, Tassi V, Nicolardi L, Pensieri MV, Emili R, Roca E, Migliore A, Galassi T, Rocchi MBL, and Berardi R

Published
2022
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19. Evaluation of COVID-19 impact on DELAYing diagnostic-therapeutic pathways of lung cancer patients in Italy (COVID-DELAY study): fewer cases and higher stages from a real-world scenario.

Author

Cantini L, Mentrasti G, Russo GL, 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, Chiari R, Cortellini A, Cognigni V, Pecci F, Indini A, De Toma A, Zattarin E, Oresti S, Pizzutilo EG, 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 MS, 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 MLB, and Berardi R

Subjects
Communicable Disease Control, Humans, Italy epidemiology, Pandemics, COVID-19, Lung Neoplasms diagnosis, Lung Neoplasms epidemiology, Lung Neoplasms therapy
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., Competing Interests: Disclosure DS received personal fees from AstraZeneca, Merck Sharp & Dohme (MSD), Boehringer Ingelheim and received travel grants from Roche, AstraZeneca, Bristol Myers Squibb (BMS), MSD. AMo received honoraria from Roche, AstraZeneca, Boehringer, Pfizer, MSD, BMS, Novartis, Lilly, Takeda. RC received fees for speaker's bureau and advisory boards participation in BMS, MSD, Roche, Pfizer, AstraZeneca, Takeda, Amgen, Boehringer, Novartis. FM received founding from AstraZeneca, Incyte and served as consultant for MSD. RB is a consultant/advisory board member for AstraZeneca, Boehringer Ingelheim, Novartis, MSD, Otsuka, Eli Lilly, Roche. All other authors have declared no conflicts of interest., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Published
2022
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20. Shape-Controlled Nanoparticles in Pore-Confined Space.

Author

Knossalla J, Paciok P, Göhl D, Jalalpoor D, Pizzutilo E, Mingers AM, Heggen M, Dunin-Borkowski RE, Mayrhofer KJJ, Schüth F, and Ledendecker M

Abstract

Increasing the catalyst's stability and activity are one of the main quests in catalysis. Tailoring crystal surfaces to a specific reaction has demonstrated to be a very effective way in increasing the catalyst's specific activity. Shape controlled nanoparticles with specific crystal facets are usually grown kinetically and are highly susceptible to morphological changes during the reaction due to agglomeration, metal dissolution, or Ostwald ripening. A strong interaction of the catalytic material to the support is thus crucial for successful stabilization. Taken both points into account, a general catalyst design is proposed, combining the enhanced activity of shape-controlled nanoparticles with a pore-confinement approach for high stability. Hollow graphitic spheres with narrow and uniform bimodal mesopores serve as model system and were used as support material. As catalyst, different kinds of particles, such as pure platinum (Pt), platinum/nickel (Pt 3 Ni) and Pt 3 Ni doped with molybdenum (Pt 3 Ni-Mo), have exemplarily been synthesized. The advantages, limits and challenges of the proposed concept are discussed and elaborated by means of time-resolved, in and ex situ measurements. It will be shown that during catalysis, the potential boundaries are crucial especially for the proposed catalyst design, resulting in either retention of the initial activity or drastic loss in shape, size and elemental composition. The synthesis and catalyst design can be adapted to a wide range of catalytic reactions where stabilization of shape-controlled particles is a focus.

Published
2018
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