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142 results on '"Mazzaschi G."'

3. Prognostic Impact of Blood Lipid Profile in Patients With Advanced Solid Tumors Treated With Immune Checkpoint Inhibitors:A Multicenter Cohort Study

Author

Pecci, F, Cantini, L, Cognigni, V, Perrone, F, Mazzaschi, G, Agostinelli, V, Mentrasti, G, Favari, E, Maffezzoli, M, Cortellini, A, Rossi, F, Chiariotti, R, Venanzi, FM, Lo Russo, G, Galli, G, Proto, C, Ganzinelli, M, Tronconi, F, Morgese, F, Campolucci, C, Moretti, M, Vignini, A, Tiseo, M, Minari, R, Rocchi, MLB, Buti, S, Berardi, Rossana, Pecci, F, Cantini, L, Cognigni, V, Perrone, F, Mazzaschi, G, Agostinelli, V, Mentrasti, G, Favari, E, Maffezzoli, M, Cortellini, A, Rossi, F, Chiariotti, R, Venanzi, FM, Lo Russo, G, Galli, G, Proto, C, Ganzinelli, M, Tronconi, F, Morgese, F, Campolucci, C, Moretti, M, Vignini, A, Tiseo, M, Minari, R, Rocchi, MLB, Buti, S, and Berardi, Rossana

Abstract

Background: Specific components of lipid profile seem to differently impact on immune activity against cancer and unraveling their prognostic role in patients with solid cancer treated with immune checkpoint inhibitors (ICIs) is needed. Materials and Methods: We retrospectively collected baseline clinicopathological characteristics including circulating lipid profile (total cholesterol [TC], triglycerides [TG], low-density lipoproteins [LDL], high-density lipoproteins [HDL]) of patients with consecutive solid cancer treated with ICIs, and we investigated their role in predicting clinical outcomes. Results: At a median follow-up of 32.9 months, among 430 enrolled patients, those with TC ≥ 200 mg/dl showed longer median progression-free survival (mPFS; 6.6 vs. 4.7 months, P = .4), although not reaching statistical significance, and significantly longer median overall survival (mOS; 19.4 vs. 10.8 months, P = .02) compared to those with TC < 200 mg/dl. Conversely, patients with TG ≥150 mg/dl displayed shorter PFS (3.4 vs. 5.1 months, P = .02) and OS (7.1 vs. 12.9 months, P = .009) compared to those with TG <150 mg/dl. TC and TG were then combined in a “LIPID score” identifying three subgroups: good-risk (GR) (TC ≥200 mg/dl and TG <150 mg/dl), intermediate-risk (IR) (TC <200 mg/dl and TG <150 mg/dl or TC ≥200 mg/dl and TG ≥150 mg/dl) and poor-risk (PR) (TC <200 mg/dl and TG ≥150 mg/dl). The mPFS of GR, IR, and PR groups was 7.8, 4.3, and 2.5 months, respectively (P = .005); mOS of GR, IR, and PR was 20.4, 12.4, and 5.3 months, respectively (P < .001). At multivariable analysis, the PR profile represented an independent poor prognostic factor for both PFS and OS. Conclusions: We developed a lipid score that defined subgroups of patients with cancer who differently benefit from ICIs. Further mechanistic insights are warranted to clarify the prognostic and predictive role of lipid profile components in patients treated with ICIs.

Published
2024

5. Resistance to osimertinib in advanced EGFR-mutated NSCLC: a prospective study of molecular genotyping on tissue and liquid biopsies

Author

Leonetti, A., primary, Verzè, M., additional, Minari, R., additional, Perrone, F., additional, Gnetti, L., additional, Bordi, P., additional, Pluchino, M., additional, Nizzoli, R., additional, Azzoni, C., additional, Bottarelli, L., additional, Lagrasta, C. A. M., additional, Mazzaschi, G., additional, Buti, S., additional, Gasparro, D., additional, Cosenza, A., additional, Ferri, L., additional, Majori, M., additional, De Filippo, M., additional, Ampollini, L., additional, La Monica, S., additional, Alfieri, R., additional, Silini, E. M., additional, and Tiseo, M., additional

Published
2023
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6. PO-2243 Development of a µCT radiomic platform to identify radio-immune signatures in murine tumor models

Author

Mazzaschi, G., primary, Dos Santos, M., additional, Bergeron, P., additional, Sitterle, L., additional, Gerbé De Thoré, M., additional, Liu, W., additional, Clémenson, C., additional, Meziani, L., additional, Gonnelli, A., additional, Bawa, O., additional, Leroy, A., additional, Sun, R., additional, Henry, T., additional, Laurent, P., additional, Moron Dalla Tor, L., additional, Quaini, F., additional, Tiseo, M., additional, Milliat, F., additional, Robert, C., additional, Mondini, M., additional, and Deutsch, E., additional

Published
2023
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7. 238P Exploring blood immune cell dynamics to unravel the immunomodulatory effect of radiotherapy in NSCLC patients undergoing immune checkpoint inhibitors

Author

Mazzaschi, G., primary, Tamarozzi, P., additional, Lorusso, B., additional, Verzè, M., additional, Pluchino, M., additional, Trentini, F., additional, Dalla Valle, B., additional, Minari, R., additional, Perrone, F., additional, Bordi, P., additional, Leonetti, A., additional, Moron Dalla Tor, L., additional, Leo, L., additional, Milanese, G., additional, Balbi, M., additional, Buti, S., additional, Roti, G., additional, Quaini, F., additional, Sverzellati, N., additional, and Tiseo, M., additional

Published
2022
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8. Predictive ability of a drug-based score in patients with advanced non-small-cell lung cancer receiving first-line immunotherapy

Author

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

9. 1061P Static and dynamic tracking of radiomic and immunophenotypic features predicts the benefit of immune checkpoint inhibitors in advanced NSCLC

Author

Mazzaschi, G., primary, Moron Dalla Tor, L., additional, Balbi, M., additional, Milanese, G., additional, Tognazzi, D., additional, Lorusso, B., additional, Trentini, F., additional, Di Rienzo, G., additional, Verzè, M., additional, Pluchino, M., additional, Minari, R., additional, Leo, L., additional, Gnetti, L., additional, Bordi, P., additional, Leonetti, A., additional, Ampollini, L., additional, Roti, G., additional, Quaini, F., additional, Sverzellati, N., additional, and Tiseo, M., additional

Published
2022
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10. P1.15-04 Dynamic Profiling of Blood Immunophenotypes and Radiomic Features to Predict Immunotherapy Response in Advanced Non-small Cell Lung Cancer

Author

Mazzaschi, G., primary, Moron Dalla Tor, L., additional, Milanese, G., additional, Balbi, M., additional, Tognazzi, D., additional, Lorusso, B., additional, Verzè, M., additional, Pluchino, M., additional, Minari, R., additional, Leo, L., additional, Ledda, R.E., additional, Bordi, P., additional, Leonetti, A., additional, Buti, S., additional, Roti, G., additional, Quaini, F., additional, Sverzellati, N., additional, and Tiseo, M., additional

Published
2022
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13. 165P Dynamic evolution of blood immune-inflammatory descriptors in advanced non-small cell lung cancer undergoing first-line immunotherapy-based regimens

Author

Mazzaschi, G., primary, Verzè, M., additional, Tognazzi, D., additional, Lorusso, B., additional, Minari, R., additional, Pluchino, M., additional, Trentini, F., additional, Manini, M., additional, Bordi, P., additional, Leonetti, A., additional, Perrone, F., additional, Corianò, M., additional, Casali, M., additional, Toscani, I., additional, Cosenza, A., additional, Ferri, L., additional, Buti, S., additional, Sverzellati, N., additional, Quaini, F., additional, and Tiseo, M., additional

Published
2022
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14. 17P Dynamic changes of CT-radiomic and systemic immune-inflammatory features predict the response to immune checkpoint inhibitors in advanced NSCLC patients

Author

Mazzaschi, G., primary, Milanese, G., additional, Moron Dalla Tor, L., additional, Leo, L., additional, Balbi, M., additional, Trentini, F., additional, Manini, M., additional, Pavone, C., additional, Silva, M., additional, Ledda, R.E., additional, Minari, R., additional, Bordi, P., additional, Buti, S., additional, Leonetti, A., additional, Roti, G., additional, Quaini, F., additional, Sverzellati, N., additional, and Tiseo, M., additional

Published
2021
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15. P57.08 High Performance Radiomic Classifier to Predict the Response to Immunotherapy in Advanced NSCLC

Author

Mazzaschi, G., primary, Scandino, R., additional, Milanese, G., additional, Pavone, C., additional, Balbi, M., additional, Ledda, R., additional, Minari, R., additional, Trentini, F., additional, Bordi, P., additional, Buti, S., additional, Leonetti, A., additional, Quaini, F., additional, Sverzellati, N., additional, Romanel, A., additional, and Tiseo, M., additional

Published
2021
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16. 1352P A highly predictive blood-radiomics classifier in advanced NSCLC treated with immunotherapy

Author

Mazzaschi, G., primary, Scandino, R., additional, Milanese, G., additional, Pavone, C., additional, Maurizio, B., additional, Silva, M., additional, Ledda, R., additional, Minari, R., additional, Trentini, F., additional, Buti, S., additional, Bordi, P., additional, Leonetti, A., additional, Quaini, F., additional, Sverzellati, N., additional, Romanel, A., additional, and Tiseo, M., additional

Published
2021
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21. 192TiP Radiological morphological (MF) and radiomic features (RF) of brain metastases in oncogene-addicted advanced non-small cell lung cancer (NSCLC) patients: Diagnostic implications and prognostic role (BRAIN Lung study)

Author

Rebuzzi, S.E., primary, Barletta, L., additional, Rosso, E., additional, Maddalo, M., additional, Signori, A., additional, Catalano, F., additional, Grassi, M., additional, Tagliamento, M., additional, Rossi, G., additional, Dal Bello, M.G., additional, Mazzaschi, G., additional, Barabino, E., additional, Fedeli, A., additional, Doni, M., additional, Tiseo, M., additional, and Genova, C., additional

Published
2021
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24. 1929O Soluble PD-L1 and circulating CD8+PD1+ and NK cells enclose a highly prognostic and predictive immune effector score in immunotherapy treated NSCLC patients

Author

Mazzaschi, G., primary, Minari, R., additional, Ferri, V., additional, Bordi, P., additional, Gnetti, L., additional, Bersanelli, M., additional, Cavazzoni, A., additional, Buti, S., additional, Leonetti, A., additional, Zecca, A., additional, Cosenza, A., additional, Ferri, L., additional, Rapacchi, E., additional, Mori, C., additional, Petronini, P.G., additional, Missale, G., additional, Quaini, F., additional, and Tiseo, M., additional

Published
2020
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25. 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

26. Genetic, tissue and circulating PD-L1 profiling to predict the response to immuno-checkpoint inhibitors in advanced NSCLC

Author

Mazzaschi, G., primary, Minari, R., additional, Ferri, V., additional, Gnetti, L., additional, Bersanelli, M., additional, Cavazzoni, A., additional, Bordi, P., additional, Squadrilli, A., additional, Buti, S., additional, Cosenza, A., additional, Ferri, L., additional, Rapacchi, E., additional, Petronini, P.G., additional, Missale, G., additional, Quaini, F., additional, and Tiseo, M., additional

Published
2019
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28. Differentially regulated high-throughput CT imaging features correlate to distinct tumor immune contextures portraying a radiomic signature with prognostic impact on surgically resected NSCLC

Author

Mazzaschi, G., primary, Quaini, F., additional, Milanese, G., additional, Madeddu, D., additional, Bocchialini, G., additional, Ampollini, L., additional, Gnetti, L., additional, Lagrasta, C., additional, Silva, M., additional, Roti, G., additional, Sverzellati, N., additional, and Tiseo, M., additional

Published
2019
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29. Advanced CT imaging features reflect distinct tissue immune profiles and exhibit high prognostic impact on NSCLC

Author

Mazzaschi, G., primary, Pagano, P., additional, Milanese, G., additional, Madeddu, D., additional, Falco, A., additional, Armani, G., additional, Bocchialini, G., additional, Marturano, D., additional, Ampollini, L., additional, Lorusso, B., additional, Lagrasta, C., additional, Sverzellati, N., additional, Silva, M., additional, Tiseo, M., additional, Quaini, F., additional, and Roti, G., additional

Published
2018
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31. Divergent PD-1 expression in tissue and circulating CD8 lymphocytes defines an immune profile predictive of the response to nivolumab in advanced NSCLC

Author

Mazzaschi, G., primary, Madeddu, D., additional, Veneziani, M., additional, Sogni, F., additional, Armani, G., additional, Frati, C., additional, Lagrasta, C., additional, Falco, A., additional, Lorusso, B., additional, Vilella, R., additional, Mangiaracina, C., additional, Bocchialini, G., additional, Silini, E.M., additional, Facchinetti, F., additional, Ardizzoni, A., additional, Missale, G., additional, Tiseo, M., additional, and Quaini, F., additional

Published
2017
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33. F-066BLOOD AND LYMPHATIC VESSELS CONSTITUTE AN ESSENTIAL COMPONENT OF THE IMMUNE MICROENVIRONMENT AND ITS IMPACT ON NON-SMALL CELL LUNG CANCER CLINICAL OUTCOME

Author

Quaini, Federico, primary, Armani, G, additional, Madeddu, D, additional, Mazzaschi, G, additional, Bocchialini, G, additional, Sogni, F, additional, Frati, C, additional, Urbanek, K, additional, Lorusso, B, additional, Falco, A, additional, Lagrasta, C A, additional, Quaini, E, additional, Carbognani, P, additional, and Ampollini, L, additional

Published
2017
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34. Circulating immune-profile as predictor of outcome in advanced NSCLC patients treated with Nivolumab

Author

Tiseo, M., primary, Facchinetti, F., additional, Buti, S., additional, Gelsomino, F., additional, Veneziani, M., additional, Squadrilli, A., additional, Bordi, P., additional, Bersanelli, M., additional, Cosenza, A., additional, Ferri, L., additional, Rapacchi, E., additional, Mazzaschi, G., additional, Leonardi, F., additional, Quaini, F., additional, Ardizzoni, A., additional, and Missale, G., additional

Published
2017
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44. A1033 - Evaluation of PBRM1, PD-L1, CD31 and CD4/CD8 ratio as predictive biomarkers of response to VEGFR-TKI-based therapy in metastatic renal cell carcinoma (mRCC) patients with IMDC intermediate prognosis: Results from the APAChE-I study.

Author

Ciccarese, C., Buti, S., Roberto, M., Calabrò, F., Masini, C., Massari, F., Cannella, M., Mazzaschi, G., Astore, S., Di Girolamo, S., Panebianco, M., Mollica, V., Granitto, A., Fiorentino, V., Pierconti, F., Martini, M., Porta, C., Tortora, G., and Iacovelli, R.

Subjects
*RENAL cell carcinoma, *PROGRAMMED death-ligand 1, *TREATMENT effectiveness, *BIOMARKERS, *PROGNOSIS
Published
2023
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45. PD-L1 SNPs as biomarkers to define benefit in patients with advanced NSCLC treated with immune checkpoint inhibitors

Author

Melissa Bersanelli, Francesco Bonatti, Sebastiano Buti, Agnese Cosenza, Paola Bordi, Roberta Minari, Marcello Tiseo, Francesco Facchinetti, Gloria Cinquegrani, Andrea Ardizzoni, Elena Rapacchi, Leonarda Ferri, Alessandro Leonetti, Federico Quaini, Alessandra Dodi, Giulia Mazzaschi, Anna Squadrilli, Francesco Gelsomino, Minari R., Bonatti F., Mazzaschi G., Dodi A., Facchinetti F., Gelsomino F., Cinquegrani G., Squadrilli A., Bordi P., Buti S., Bersanelli M., Leonetti A., Cosenza A., Ferri L., Rapacchi E., Quaini F., Ardizzoni A., and Tiseo M.

Subjects
Oncology, PD-L1, Adult, Male, Cancer Research, medicine.medical_specialty, medicine.medical_treatment, Immune checkpoint inhibitors, Programmed Cell Death 1 Receptor, Single-nucleotide polymorphism, NSCLC, Polymorphism, Single Nucleotide, B7-H1 Antigen, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Carcinoma, Non-Small-Cell Lung, Biomarkers, Tumor, Medicine, Humans, In patient, CTLA-4 Antigen, 030212 general & internal medicine, Immune Checkpoint Inhibitors, Aged, Neoplasm Staging, Aged, 80 and over, biology, business.industry, General Medicine, Immunotherapy, Middle Aged, Progression-Free Survival, Treatment Outcome, 030220 oncology & carcinogenesis, biology.protein, Biomarker (medicine), biomarker, Female, immunotherapy, business, SNPs
Abstract

Objective: To investigate the role of CTLA-4, PD-1 (programmed death-1), and PD-L1 (programmed death-ligand 1) single nucleotide polymorphisms (SNPs) in predicting clinical outcome of patients with advanced non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs). Methods: A total of 166 consecutive patients were included. We correlated SNPs with clinical benefit, progression-free survival, time to treatment failure, and overall survival and evaluated the incidence of SNPs in nonresponder and long clinical benefit groups. Results: Considering the entire cohort, no correlation was found between SNPs and clinical outcome; however, PD-L1 rs4143815 SNP and the long clinical benefit group showed a statistically significant association ( p = 0.02). The nonresponder cohort displayed distinctive PD-L1 haplotype ( p = 0.05). Conclusion: PD-L1 SNPs seem to be marginally involved in predicting clinical outcome of NSCLC treated with ICI, but further investigations are required.

Published
2021

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

Author

Alessandra Bearz, Antonio Rossi, Roberta Camisa, Chiara Bennati, Francesca Mazzoni, Diego Cortinovis, Silvia Novello, Lorenza Landi, Marina Chiara Garassino, Elio Gregory Pizzutilo, Emilio Bria, Emanuele Vita, Giorgia Guaitoli, Giulio Rossi, Giulia Mazzaschi, Massimo Di Maio, Cinzia Baldessari, Giuseppe Luigi Banna, Fabiana Letizia Cecere, L.P. Ciccone, Giulia Sartori, Francesco Passiglia, Gabriele Bartoli, Luca Toschi, Marcello Tiseo, Andrea Camerini, F. Zanelli, Francesco Facchinetti, Elisa Sala, Giulio Cerea, Alessandro Del Conte, Filippo Gustavo Dall'Olio, Vieri Scotti, Elisa De Carlo, Maria Rita Migliorino, Claudia Proto, Fausto Barbieri, Sara Pilotto, Rossana Berardi, Andrea Ardizzoni, Sabrina Rossi, Facchinetti F., Mazzaschi G., Barbieri F., Passiglia F., Mazzoni F., Berardi R., Proto C., Cecere F.L., Pilotto S., Scotti V., Rossi S., Del Conte A., Vita E., Bennati C., Ardizzoni A., Cerea G., Migliorino M.R., Sala E., Camerini A., Bearz A., De Carlo E., Zanelli F., Guaitoli G., Garassino M.C., Ciccone L.P., Sartori G., Toschi L., Dall'Olio F.G., Landi L., Pizzutilo E.G., Bartoli G., Baldessari C., Novello S., Bria E., Cortinovis D.L., Rossi G., Rossi A., Banna G.L., Camisa R., Di Maio M., and Tiseo M.

Subjects
0301 basic medicine, Oncology, Male, Cancer Research, medicine.medical_specialty, Lung Neoplasms, Programmed Cell Death 1 Receptor, Pembrolizumab, Immune checkpoint inhibitor, Antibodies, Monoclonal, Humanized, NSCLC, 03 medical and health sciences, Immune checkpoint inhibitors, 0302 clinical medicine, Internal medicine, Carcinoma, Non-Small-Cell Lung, PD-1, medicine, Humans, Progression-free survival, Adverse effect, Lung cancer, Survival rate, Survival analysis, Aged, Retrospective Studies, ECOG PS 2, Immunotherapy, business.industry, Retrospective cohort study, medicine.disease, Confidence interval, 030104 developmental biology, 030220 oncology & carcinogenesis, Female, business
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

47. Imatinib mesylate-induced cardiomyopathy involves resident cardiac progenitors

Author

Gallia Graiani, Emilia Corradini, Serena Galati, Donato Cappetta, Federica Galaverna, Costanza Lagrasta, Giulia Mazzaschi, Liberato Berrino, Caterina Frati, Lucia Prezioso, Angela Falco, Annamaria Buschini, Denise Madeddu, Franco Aversa, Monia Savi, Antonella De Angelis, Federico Quaini, Stefano Cavalli, Konrad Urbanek, Savi, M, Frati, C, Cavalli, S, Graiani, G, Galati, S, Buschini, A, Madeddu, D, Falco, A, Prezioso, L, Mazzaschi, G, Galaverna, F, Lagrasta, Cam, Corradini, E, De Angelis, A, Cappetta, D, Berrino, L, Aversa, F, Quaini, F, Urbanek, K, Savi, Monia, Frati, Caterina, Cavalli, Stefano, Graiani, Gallia, Galati, Serena, Buschini, Annamaria, Madeddu, Denise, Falco, Angela, Prezioso, Lucia, Mazzaschi, Giulia, Galaverna, Federica, Lagrasta, Costanza Anna Maria, Corradini, Emilia, De Angelis, Antonella, Cappetta, Donato, Berrino, Liberato, Aversa, Franco, Quaini, Federico, and Urbanek, Konrad

Subjects
0301 basic medicine, Male, Programmed cell death, medicine.drug_class, Cardiomyopathy, Hemodynamics, 030204 cardiovascular system & hematology, Pharmacology, Tyrosine-kinase inhibitor, Cardiac progenitor cell, 03 medical and health sciences, 0302 clinical medicine, medicine, Animals, Humans, Cells, Cultured, Cardiotoxicity, Cell Death, Dose-Response Relationship, Drug, business.industry, Myocardium, Stem Cells, Kit, medicine.disease, Rats, 030104 developmental biology, Imatinib mesylate, Imatinib Mesylate, Myocardial fibrosis, business, Cardiomyopathies, Tyrosine kinase
Abstract

Cardiovascular complications are included among the systemic effects of tyrosine kinase inhibitor (TKI)-based therapeutic strategies. To test the hypothesis that inhibition of Kit tyrosine kinase that promotes cardiac progenitor cell (CPC) survival and function may be one of the triggering mechanisms of imatinib mesylate (IM)-related cardiovascular effects, the anatomical, structural and ultrastructural changes in the heart of IM-treated rats were evaluated. Cardiac anatomy in IM-exposed rats showed a dose-dependent, restrictive type of remodeling and depressed hemodynamic performance in the absence of remarkable myocardial fibrosis. The effects of IM on rat and human CPCs were also assessed. IM induced rat CPC depletion, reduced growth and increased cell death. Similar effects were observed in CPCs isolated from human hearts. These results extend the notion that cardiovascular side effects are driven by multiple actions of IM. The identification of cellular mechanisms responsible for cardiovascular complications due to TKIs will enable future strategies aimed at preserving concomitantly cardiac integrity and anti-tumor activity of advanced cancer treatment.

Published
2018

48. Longitudinal Changes of CT-radiomic and Systemic Inflammatory Features Predict Survival in Advanced Non-Small Cell Lung Cancer Patients Treated With Immune Checkpoint Inhibitors.

Author

Balbi M, Mazzaschi G, Leo L, Moron Dalla Tor L, Milanese G, Marrocchio C, Silva M, Mura R, Favia P, Bocchialini G, Trentini F, Minari R, Ampollini L, Quaini F, Roti G, Tiseo M, and Sverzellati N

Subjects
Humans, Male, Female, Aged, Retrospective Studies, Middle Aged, Aged, 80 and over, Adult, Inflammation diagnostic imaging, Inflammation blood, Prognosis, Lung diagnostic imaging, Predictive Value of Tests, Radiomics, Carcinoma, Non-Small-Cell Lung diagnostic imaging, Carcinoma, Non-Small-Cell Lung drug therapy, Lung Neoplasms diagnostic imaging, Lung Neoplasms drug therapy, Immune Checkpoint Inhibitors therapeutic use, Tomography, X-Ray Computed methods
Abstract

Purpose: This study aims to determine whether longitudinal changes in CT radiomic features (RFs) and systemic inflammatory indices outperform single-time-point assessment in predicting survival in advanced non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs)., Materials and Methods: We retrospectively acquired pretreatment (T0) and first disease assessment (T1) RFs and systemic inflammatory indices from a single-center cohort of stage IV NSCLC patients and computed their delta (Δ) variation as [(T1-T0)/T0]. RFs from the primary tumor were selected for building baseline-radiomic (RAD) and Δ-RAD scores using the linear combination of standardized predictors detected by LASSO Cox regression models. Cox models were generated using clinical features alone or combined with baseline and Δ blood parameters and integrated with baseline-RAD and Δ-RAD. All models were 3-fold cross-validated. A prognostic index (PI) of each model was tested to stratify overall survival (OS) through Kaplan-Meier analysis., Results: We included 90 ICI-treated NSCLC patients (median age 70 y [IQR=42 to 85], 63 males). Δ-RAD outperformed baseline-RAD for predicting OS [c-index: 0.632 (95%CI: 0.628 to 0.636) vs. 0.605 (95%CI: 0.601 to 0.608) in the test splits]. Integrating longitudinal changes of systemic inflammatory indices and Δ-RAD with clinical data led to the best model performance [Integrated-Δ model, c-index: 0.750 (95% CI: 0.749 to 0.751) in training and 0.718 (95% CI: 0.715 to 0.721) in testing splits]. PI enabled significant OS stratification within all the models ( P -value <0.01), reaching the greatest discriminative ability in Δ models (high-risk group HR up to 7.37, 95% CI: 3.9 to 13.94, P <0.01)., Conclusion: Δ-RAD improved OS prediction compared with single-time-point radiomic in advanced ICI-treated NSCLC. Integrating Δ-RAD with a longitudinal assessment of clinical and laboratory data further improved the prognostic performance., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Published
2025
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49. Longitudinal blood immune-inflammatory and radiomic profiling to decode different patterns of acquired resistance to immunotherapy in patients with NSCLC.

Author

Mazzaschi G, Marrocchio C, Moron Dalla Tor L, Leo L, Balbi M, Milanese G, Adebanjo GAR, Lorusso B, Monica G, Pluchino M, Minari R, D'Agnelli S, Cardinale E, Perrone F, Bordi P, Leonetti A, Ledda RE, Silva M, Buti S, Roti G, Bettati S, Quaini F, Tiseo M, and Sverzellati N

Abstract

Purpose: To uncover the underpinnings of acquired resistance (AR) to immunotherapy (IO), we determined whether distinctive clinico-pathological, radiomic and peripheral blood (PB) immune-inflammatory features reflect oligo- and systemic (sys)-AR in advanced NSCLC patients undergoing immune checkpoints inhibitors., Experimental Design: On 105 consecutive IO-treated advanced NSCLC, PB immunophenotypes, cytokines and CT-derived radiomic features (RFs), extracted from primary and merged metastatic lesions, were prospectively collected at baseline (T0) and first disease assessment (T1, 9-12 weeks), and their delta (Δ) variation [(T1-T0)/T0] computed. AR, defined as progression after initial response (complete/partial) or stable disease ≥ 6 months, was subdivided according to the number of new and/or progressive lesions in oligoAR (≤3) and sysAR (>3). Clinico-pathological, PB and radiomic parameters and survival outcome were statistically correlated to AR patterns., Results: OligoAR and sysAR involved 24% and 12.4% of cases, respectively. While baseline PB immune profiles were comparable, a Δpos cytotoxic (NK, CD8+GnzB+) and Δneg immunosuppressive (CD14+ monocytes) dynamic coupled with different modulation of IL-6, TGF-β1, TNFα and sPD-L1 represented distinctive features of oligoAR vs sysAR (P<0.05). Significantly longer post-progression survival characterized oligoAR vs sysAR (median 20.3 vs 5.6 months;HR:0.22,P<0.001). The number and sites of oligoAR involvement appeared to condition blood immune background (P<0.05) and survival. Delta radiomic outperformed baseline RFs, with 15 ΔRFs sharply discriminating oligoAR from sysAR (P range:<0.001-0.04). ROC analysis confirmed the optimal performance of top-ranked ΔRFs (AUC range:0.88-0.99)., Conclusions: Longitudinal analysis of blood immune hallmarks and radiomic descriptors may decipher distinct patterns of AR to IO in advanced NSCLC patients.

Published
2024
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50. Liquid Biopsy and 18F-FDG PET/CT Derived Parameters as Predictive Factors of Osimertinib Treatment in Advanced EGFR-Mutated NSCLC.

Author

Leonetti A, Cervati V, Minari R, Scarlattei M, Verzè M, Peroni M, Pluchino M, Bonatti F, Perrone F, Mazzaschi G, Cosenza A, Gnetti L, Bordi P, Ruffini L, and Tiseo M

Subjects
Humans, Male, Female, Middle Aged, Aged, Prospective Studies, Liquid Biopsy methods, Adult, Aged, 80 and over, Prognosis, Radiopharmaceuticals, Antineoplastic Agents therapeutic use, Indoles, Pyrimidines, Carcinoma, Non-Small-Cell Lung drug therapy, Carcinoma, Non-Small-Cell Lung genetics, Carcinoma, Non-Small-Cell Lung pathology, Carcinoma, Non-Small-Cell Lung diagnostic imaging, Acrylamides therapeutic use, Aniline Compounds therapeutic use, Lung Neoplasms drug therapy, Lung Neoplasms genetics, Lung Neoplasms pathology, Lung Neoplasms diagnostic imaging, ErbB Receptors genetics, Positron Emission Tomography Computed Tomography methods, Fluorodeoxyglucose F18, Mutation
Abstract

Objectives: Despite the outstanding results achieved by osimertinib for the treatment of advanced EGFR-mutated NSCLC, the development of resistance is almost inevitable. While molecular mechanism responsible for osimertinib resistance are being mostly revealed, the definition of predictive biomarkers is crucial in order to identify patients at higher risk of progression and optimize treatment strategy., Materials and Methods: This is a prospective single-center study aimed to assess the potential role of liquid biopsy and 18F-FDG PET/CT derived metabolic parameters as noninvasive predictive biomarkers of osimertinib outcomes in advanced EGFR-mutated NSCLC patients. Patients underwent blood samples for ctDNA analysis at baseline, after 15 days and 1 month (t1) of osimertinib. 18F-FDG PET/CT was performed at baseline and after 1 month of osimertinib., Results: Seventy-two advanced EGFR-mutated NSCLC patients treated with osimertinib in first (n = 63) and in second-line (n = 9) were prospectively enrolled. Baseline positive shedding status was significantly associated with a shorter progression-free survival (PFS) (9.5 vs. 29.2 months, P = .031). Early metabolic response (MR) led to improved PFS (16.8 vs. 5.5 months, P = .038) and OS (35.2 vs. 15.3 months, P = .047). Early MR was significantly correlated with subsequent radiologic response (P = .010). All 18F-FDG PET/CT baseline parameters were significantly related to baseline EGFR activating mutation allele frequency. Both clearance and no detection of EGFR at t1 were significantly associated with MR (P = .001 and P = .004, respectively)., Conclusion: Molecular and 18F-FDG PET/CT derived metabolic parameters might represent a useful tool to predict osimertinib outcome in advanced EGFR-mutated NSCLC patients., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Published
2024
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