132 results on '"Francesco Atzori"'
Search Results
2. Data from Dasatinib plus Capecitabine for Advanced Breast Cancer: Safety and Efficacy in Phase I Study CA180004
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Javier Cortes, Linda T. Vahdat, Oumar Sy, Alissa Rybicki, William J. Gradishar, Jennifer M. Specht, William J. Geese, Lewis C. Strauss, Francesco Atzori, and George Somlo
- Abstract
Purpose: Dasatinib is an Src family kinase inhibitor with modest activity in advanced breast cancer. We aimed to assess toxicity and maximum tolerated dose (MTD) for dasatinib plus capecitabine, estimate efficacy, and explore effects on angiogenesis.Experimental Design: Dose levels (DL) were dasatinib 50 mg twice daily (DL1), 70 mg twice daily (DL2 and DL3), or 100 mg daily (DL3a); plus capecitabine on days 1 to 14 of a 21-day cycle, at 825 mg/m2 twice daily (DL1 and DL2) or 1,000 mg/m2 twice daily [DL3 and DL3a (MTD)]. DL3a was expanded to evaluate safety/efficacy. Plasma samples were collected for biomarker analysis.Results: Thirty-one and 21 patients were treated in the escalation and expansion phases. Sixty percent of tumors were hormone receptor–positive. Most common adverse events (AE) were any grade nausea (58%), hand–foot syndrome (44%), diarrhea (33%), fatigue (33%), vomiting (31%), and asthenia (31%). Most common grade 3/4 AEs were hand–foot syndrome (12%), diarrhea (8%), fatigue (8%), pleural effusion (8%), and vomiting (6%). The MTD was defined at DL3a (capecitabine 1,000 mg/m2 twice daily and dasatinib 100 mg daily). Of 25 response-evaluable patients treated at DL3a, confirmed partial response was noted in 24% and stable disease in an additional 32%; median progression-free survival was 14.4 weeks. Significant decreases in plasma VEGF-A and increases in VEGFR-2 and collagen-IV were observed.Conclusions: Dasatinib 100 mg once daily plus capecitabine 1,000 mg/m2 twice daily were tolerable and were associated with clinical benefit in 56% of response-evaluable patients. Biomarker changes were consistent with an antiangiogenic effect. Clin Cancer Res; 19(7); 1884–93. ©2013 AACR.
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- 2023
3. Data from A Phase I Pharmacokinetic and Pharmacodynamic Study of Dalotuzumab (MK-0646), an Anti-Insulin-like Growth Factor-1 Receptor Monoclonal Antibody, in Patients with Advanced Solid Tumors
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José Baselga, Ronald B. Langdon, Susana Roselló, Emiliano Calvo, Karl Hsu, William D. Hanley, Robert A. Beckman, James S. Hardwick, Jason Clark, Holly Brown, Serena Di Cosimo, Jordi Rodon, Cristina Gamez, Jorge Guijarro, Amparo Domingo, Edith Rodríguez-Braun, Jordi Andreu, Ludmila Prudkin, Andrés Cervantes, Josep Tabernero, and Francesco Atzori
- Abstract
Purpose: Insulin-like growth factor-1 receptor (IGF-1R) mediates cellular processes in cancer and has been proposed as a therapeutic target. Dalotuzumab (MK-0646) is a humanized IgG1 monoclonal antibody that binds to IGF-1R preventing receptor activation. This study was designed to evaluate the safety and tolerability of dalotuzumab, determine the pharmacokinetic (PK) and pharmacodynamic (PD) profiles, and identify a recommended phase II dose.Experimental Design: Patients with tumors expressing IGF-1R protein were allocated to dose-escalating cohorts of three or more patients each and received intravenous dalotuzumab weekly, every 2 or 3 weeks. Plasma was collected for PK analysis. Paired baseline and on-treatment skin and tumor biopsy samples were collected for PD analyses.Results: Eighty patients with chemotherapy-refractory solid tumors were enrolled. One dose-limiting toxicity was noted, but a maximum-tolerated dose was not identified. Grade 1 to 3 hyperglycemia, responsive to metformin, occurred in 15 (19%) patients. At dose levels or more than 5 mg/kg, dalotuzumab mean terminal half-life was 95 hours or more, mean Cmin was more than 25 μg/mL, clearance was constant, and serum exposures were approximately dose proportional. Decreases in tumor IGF-1R, downstream receptor signaling, and Ki67 expression were observed. 18F-Fluorodeoxy-glucose positron emission tomography metabolic responses occurred in three patients. One patient with Ewing's sarcoma showed a mixed radiologic response. The recommended phase II doses were 10, 20, and 30 mg/kg for the weekly, every other week, and every third week schedules, respectively.Conclusions: Dalotuzumab was generally well-tolerated, exhibited dose-proportional PK, inhibited IGF-1R pathway signaling and cell proliferation in treated tumors, and showed clinical activity. The low clearance rate and long terminal half-life support more extended dosing intervals. Clin Cancer Res; 17(19); 6304–12. ©2011 AACR.
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- 2023
4. Supplementary Figure 1 from A Phase I Pharmacokinetic and Pharmacodynamic Study of Dalotuzumab (MK-0646), an Anti-Insulin-like Growth Factor-1 Receptor Monoclonal Antibody, in Patients with Advanced Solid Tumors
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José Baselga, Ronald B. Langdon, Susana Roselló, Emiliano Calvo, Karl Hsu, William D. Hanley, Robert A. Beckman, James S. Hardwick, Jason Clark, Holly Brown, Serena Di Cosimo, Jordi Rodon, Cristina Gamez, Jorge Guijarro, Amparo Domingo, Edith Rodríguez-Braun, Jordi Andreu, Ludmila Prudkin, Andrés Cervantes, Josep Tabernero, and Francesco Atzori
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PDF file - 85K
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- 2023
5. Supplementary Figure 3 from A Phase I Pharmacokinetic and Pharmacodynamic Study of Dalotuzumab (MK-0646), an Anti-Insulin-like Growth Factor-1 Receptor Monoclonal Antibody, in Patients with Advanced Solid Tumors
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José Baselga, Ronald B. Langdon, Susana Roselló, Emiliano Calvo, Karl Hsu, William D. Hanley, Robert A. Beckman, James S. Hardwick, Jason Clark, Holly Brown, Serena Di Cosimo, Jordi Rodon, Cristina Gamez, Jorge Guijarro, Amparo Domingo, Edith Rodríguez-Braun, Jordi Andreu, Ludmila Prudkin, Andrés Cervantes, Josep Tabernero, and Francesco Atzori
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PDF file - 301K
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- 2023
6. Supplementary Figure Legends from Dasatinib plus Capecitabine for Advanced Breast Cancer: Safety and Efficacy in Phase I Study CA180004
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Javier Cortes, Linda T. Vahdat, Oumar Sy, Alissa Rybicki, William J. Gradishar, Jennifer M. Specht, William J. Geese, Lewis C. Strauss, Francesco Atzori, and George Somlo
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PDF file - 97 KB
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- 2023
7. Supplementary Figure S1 and S3 from Dasatinib plus Capecitabine for Advanced Breast Cancer: Safety and Efficacy in Phase I Study CA180004
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Javier Cortes, Linda T. Vahdat, Oumar Sy, Alissa Rybicki, William J. Gradishar, Jennifer M. Specht, William J. Geese, Lewis C. Strauss, Francesco Atzori, and George Somlo
- Abstract
PDF file - 212 KB, Figure S1A. Proportion of cell growth inhibition with the combination of dasatinib and 5- fluorouracil (5FU) in KPL4 breast cancer carcinoma cells in vitro Figure S1B. Proportion of cell growth inhibition with the combination of Dasatinib and 5- FU in HCC70 breast carcinoma cells in vitro Figure S3A. VEGFA changes by patients over baseline who were treated with Dasatinib and 5-FU (current study: CA18004; NCT00452673) Figure S3B. VEGFR2 changes by patients over baseline who were treated with Dasatinib and 5-FU (current study: CA18004; NCT00452673) Figure S3C. Collagen IV (Col-IV ) changes by patients over baseline who were treated with Dasatinib and 5-FU (current study: CA18004; NCT00452673) Figure S3D. VEGFR2 changes in value by patients over baseline (prior single dasatinib studies: CA180059 / NCT00371254 and CA180088/NCT00371345) Figure S3E. Collagen IV (Col-IV ) changes in value by patients over baseline (prior single dasatinib studies: CA180059 / NCT00371254 and CA180088/NCT00371345) Figure S3F. VEGFR2 changes in percentage over baseline (prior single dasatinib studies: CA180059 / NCT00371254 and CA180088/NCT00371345) Figure S3G. Collagen IV (Col-IV ) changes in percentage over baseline (prior single dasatinib studies: CA180059 / NCT00371254 and CA180088/NCT00371345)
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- 2023
8. Supplementary Table S3A from Dasatinib plus Capecitabine for Advanced Breast Cancer: Safety and Efficacy in Phase I Study CA180004
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Javier Cortes, Linda T. Vahdat, Oumar Sy, Alissa Rybicki, William J. Gradishar, Jennifer M. Specht, William J. Geese, Lewis C. Strauss, Francesco Atzori, and George Somlo
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PDF file - 25 KB, Table S3C . Changes in biomarkers in patients treated with single agent dasatinib on trials CA180059 + CA180088
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- 2023
9. Data from NVP-BEZ235, a Dual PI3K/mTOR Inhibitor, Prevents PI3K Signaling and Inhibits the Growth of Cancer Cells with Activating PI3K Mutations
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José Baselga, Joaquin Arribas, Josep Lluis Parra, Carlos Garcia-Echeverria, Michel Maira, Serena Di Cosimo, Francesco Atzori, Elisabeth Llonch, Maria Luisa Botero, Marta Guzman, Vanesa Valero, Pieter J.A. Eichhorn, Maurizio Scaltriti, Ben Markman, and Violeta Serra
- Abstract
Phosphatidylinositol-3-kinase (PI3K) pathway deregulation is a common event in human cancer, either through inactivation of the tumor suppressor phosphatase and tensin homologue deleted from chromosome 10 or activating mutations of p110-α. These hotspot mutations result in oncogenic activity of the enzyme and contribute to therapeutic resistance to the anti-HER2 antibody trastuzumab. The PI3K pathway is, therefore, an attractive target for cancer therapy. We have studied NVP-BEZ235, a dual inhibitor of the PI3K and the downstream mammalian target of rapamycin (mTOR). NVP-BEZ235 inhibited the activation of the downstream effectors Akt, S6 ribosomal protein, and 4EBP1 in breast cancer cells. The antiproliferative activity of NVP-BEZ235 was superior to the allosteric selective mTOR complex inhibitor everolimus in a panel of 21 cancer cell lines of different origin and mutation status. The described Akt activation due to mTOR inhibition was prevented by higher doses of NVP-BEZ235. NVP-BEZ235 reversed the hyperactivation of the PI3K/mTOR pathway caused by the oncogenic mutations of p110-α, E545K, and H1047R, and inhibited the proliferation of HER2-amplified BT474 cells exogenously expressing these mutations that render them resistant to trastuzumab. In trastuzumab-resistant BT474 H1047R breast cancer xenografts, NVP-BEZ235 inhibited PI3K signaling and had potent antitumor activity. In treated animals, there was complete inhibition of PI3K signaling in the skin at pharmacologically active doses, suggesting that skin may serve as surrogate tissue for pharmacodynamic studies. In summary, NVP-BEZ235 inhibits the PI3K/mTOR axis and results in antiproliferative and antitumoral activity in cancer cells with both wild-type and mutated p110-α. [Cancer Res 2008;68(19):8022–30]
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- 2023
10. Supplementary Figure 3 from NVP-BEZ235, a Dual PI3K/mTOR Inhibitor, Prevents PI3K Signaling and Inhibits the Growth of Cancer Cells with Activating PI3K Mutations
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José Baselga, Joaquin Arribas, Josep Lluis Parra, Carlos Garcia-Echeverria, Michel Maira, Serena Di Cosimo, Francesco Atzori, Elisabeth Llonch, Maria Luisa Botero, Marta Guzman, Vanesa Valero, Pieter J.A. Eichhorn, Maurizio Scaltriti, Ben Markman, and Violeta Serra
- Abstract
Supplementary Figure 3 from NVP-BEZ235, a Dual PI3K/mTOR Inhibitor, Prevents PI3K Signaling and Inhibits the Growth of Cancer Cells with Activating PI3K Mutations
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- 2023
11. Supplementary Figure 1 from NVP-BEZ235, a Dual PI3K/mTOR Inhibitor, Prevents PI3K Signaling and Inhibits the Growth of Cancer Cells with Activating PI3K Mutations
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José Baselga, Joaquin Arribas, Josep Lluis Parra, Carlos Garcia-Echeverria, Michel Maira, Serena Di Cosimo, Francesco Atzori, Elisabeth Llonch, Maria Luisa Botero, Marta Guzman, Vanesa Valero, Pieter J.A. Eichhorn, Maurizio Scaltriti, Ben Markman, and Violeta Serra
- Abstract
Supplementary Figure 1 from NVP-BEZ235, a Dual PI3K/mTOR Inhibitor, Prevents PI3K Signaling and Inhibits the Growth of Cancer Cells with Activating PI3K Mutations
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- 2023
12. Supplementary Legends 1-4 from NVP-BEZ235, a Dual PI3K/mTOR Inhibitor, Prevents PI3K Signaling and Inhibits the Growth of Cancer Cells with Activating PI3K Mutations
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José Baselga, Joaquin Arribas, Josep Lluis Parra, Carlos Garcia-Echeverria, Michel Maira, Serena Di Cosimo, Francesco Atzori, Elisabeth Llonch, Maria Luisa Botero, Marta Guzman, Vanesa Valero, Pieter J.A. Eichhorn, Maurizio Scaltriti, Ben Markman, and Violeta Serra
- Abstract
Supplementary Legends 1-4 from NVP-BEZ235, a Dual PI3K/mTOR Inhibitor, Prevents PI3K Signaling and Inhibits the Growth of Cancer Cells with Activating PI3K Mutations
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- 2023
13. Supplementary Figure 2 from NVP-BEZ235, a Dual PI3K/mTOR Inhibitor, Prevents PI3K Signaling and Inhibits the Growth of Cancer Cells with Activating PI3K Mutations
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José Baselga, Joaquin Arribas, Josep Lluis Parra, Carlos Garcia-Echeverria, Michel Maira, Serena Di Cosimo, Francesco Atzori, Elisabeth Llonch, Maria Luisa Botero, Marta Guzman, Vanesa Valero, Pieter J.A. Eichhorn, Maurizio Scaltriti, Ben Markman, and Violeta Serra
- Abstract
Supplementary Figure 2 from NVP-BEZ235, a Dual PI3K/mTOR Inhibitor, Prevents PI3K Signaling and Inhibits the Growth of Cancer Cells with Activating PI3K Mutations
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- 2023
14. Supplementary Figure 4 from NVP-BEZ235, a Dual PI3K/mTOR Inhibitor, Prevents PI3K Signaling and Inhibits the Growth of Cancer Cells with Activating PI3K Mutations
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José Baselga, Joaquin Arribas, Josep Lluis Parra, Carlos Garcia-Echeverria, Michel Maira, Serena Di Cosimo, Francesco Atzori, Elisabeth Llonch, Maria Luisa Botero, Marta Guzman, Vanesa Valero, Pieter J.A. Eichhorn, Maurizio Scaltriti, Ben Markman, and Violeta Serra
- Abstract
Supplementary Figure 4 from NVP-BEZ235, a Dual PI3K/mTOR Inhibitor, Prevents PI3K Signaling and Inhibits the Growth of Cancer Cells with Activating PI3K Mutations
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- 2023
15. Clinico-Pathological Features Influencing the Prognostic Role of Body Mass Index in Patients With Advanced Renal Cell Carcinoma Treated by Immuno-Oncology Combinations (ARON-1)
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Matteo Santoni, Francesco Massari, Zin W. Myint, Roberto Iacovelli, Martin Pichler, Umberto Basso, Jindrich Kopecky, Jakub Kucharz, Sebastiano Buti, Alessia Salfi, Thomas Büttner, Ugo De Giorgi, Ravindran Kanesvaran, Ondřej Fiala, Enrique Grande, Paolo Andrea Zucali, Giuseppe Fornarini, Maria T Bourlon, Sarah Scagliarini, Javier Molina-Cerrillo, Gaetano Aurilio, Marc R Matrana, Renate Pichler, Carlo Cattrini, Tomas Büchler, Emmanuel Seront, Fabio Calabrò, Alvaro Pinto, Rossana Berardi, Anca Zgura, Giulia Mammone, Jawaher Ansari, Francesco Atzori, Rita Chiari, Roubini Zakopoulou, Orazio Caffo, Giuseppe Procopio, Maria Bassanelli, Ilaria Zampiva, Carlo Messina, Zsófia Küronya, Alessandra Mosca, Dipen Bhuva, Nuno Vau, Lorena Incorvaia, Sara Elena Rebuzzi, Giandomenico Roviello, Ignacio Ortego Zabalza, Alessandro Rizzo, Veronica Mollica, Ilaria Catalini, Fernando Sabino M. Monteiro, Rodolfo Montironi, Nicola Battelli, Mimma Rizzo, Camillo Porta, Santoni, Matteo, Massari, Francesco, Myint, Zin W, Iacovelli, Roberto, Pichler, Martin, Basso, Umberto, Kopecky, Jindrich, Kucharz, Jakub, Buti, Sebastiano, Salfi, Alessia, Büttner, Thoma, De Giorgi, Ugo, Kanesvaran, Ravindran, Fiala, Ondřej, Grande, Enrique, Zucali, Paolo Andrea, Fornarini, Giuseppe, Bourlon, Maria T, Scagliarini, Sarah, Molina-Cerrillo, Javier, Aurilio, Gaetano, Matrana, Marc R, Pichler, Renate, Cattrini, Carlo, Büchler, Toma, Seront, Emmanuel, Calabrò, Fabio, Pinto, Alvaro, Berardi, Rossana, Zgura, Anca, Mammone, Giulia, Ansari, Jawaher, Atzori, Francesco, Chiari, Rita, Zakopoulou, Roubini, Caffo, Orazio, Procopio, Giuseppe, Bassanelli, Maria, Zampiva, Ilaria, Messina, Carlo, Küronya, Zsófia, Mosca, Alessandra, Bhuva, Dipen, Vau, Nuno, Incorvaia, Lorena, Rebuzzi, Sara Elena, Roviello, Giandomenico, Zabalza, Ignacio Ortego, Rizzo, Alessandro, Mollica, Veronica, Catalini, Ilaria, Monteiro, Fernando Sabino M, Montironi, Rodolfo, Battelli, Nicola, Rizzo, Mimma, and Porta, Camillo
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Tumor Response ,Oncology ,Survival ,Urology ,Immunocombo ,NCT05287464 ,Immunotherapy ,Obesity ,mRCC - Abstract
Background: Obesity has been associated with improved response to immunotherapy in cancer patients. We investigated the role of body mass index (BMI) in patients from the ARON-1 study (NCT05287464) treated by dual immuno-oncology agents (IO+IO) or a combination of immuno-oncology drug and a tyrosine kinase inhibitors (TKI) as first-line therapy for metastatic renal cell carcinoma (mRCC). Patients and methods: Medical records of patients with documented mRCC treated by immuno-oncology combinations were reviewed at 47 institutions from 16 countries. Patients were assessed for overall survival (OS), progression-free survival (OS), and overall clinical benefit (OCB), defined as the sum of the rate of partial/complete responses and stable disease. Univariate and multivariate analyses were used to explore the association of variables of interest with survival. Results: A total of 675 patients were included; BMI was >25 kg/m2 in 345 patients (51%) and was associated with improved OS (55.7 vs. 28.4 months, P < .001). The OCB of patients with BMI >25 kg/m2 versus those with BMI ≤25 kg/m2 was significantly higher only in patients with nonclear cell histology (81% vs. 65%, P = .011), and patients with liver metastases (76% vs. 58%, P = .007), Neutrophil to lymphocyte ratio >4 (77% vs 62%, P = .022) or treated by nivolumab plus ipilimumab (77% vs. 64%, P=.044). In the BMI ≤25 kg/m2 subgroup, significant differences were found between patients with NLR >4 versus ≤4 (62% vs. 82%, P = .002) and patients treated by IO+IO versus IO+TKIs combinations (64% vs. 83%, P = .002). Conclusion: Our study suggests that the prognostic significance and the association of BMI with treatment outcome varies across clinico-pathological mRCC subgroups.
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- 2023
16. Addition of Niraparib to Best Supportive Care as Maintenance Treatment in Patients with Advanced Urothelial Carcinoma Whose Disease Did Not Progress After First-line Platinum-based Chemotherapy: The Meet-URO12 Randomized Phase 2 Trial
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Francesca Vignani, Rosa Tambaro, Ugo De Giorgi, Patrizia Giannatempo, Davide Bimbatti, Claudia Carella, Marco Stellato, Francesco Atzori, Michele Aieta, Cristina Masini, Alketa Hamzaj, Paola Ermacora, Antonello Veccia, Giuseppa Scandurra, Teresa Gamba, Gianluca Ignazzi, Sandro Pignata, Marilena Di Napoli, Cristian Lolli, Giuseppe Procopio, Francesco Pierantoni, Antonia Zonno, Daniele Santini, and Massimo Di Maio
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Maintenance treatment ,Urology ,Urothelial carcinoma ,Niraparib - Abstract
Platinum-based chemotherapy (PBCT) is the standard first-line treatment for advanced urothelial carcinoma (UC). Potential cross-sensitivity can be hypothesized between platinum drugs and poly-ADP ribose-polymerase (PARP) inhibitors.To compare maintenance treatment with the PARP inhibitor niraparib plus best supportive care (BSC) versus BSC alone in patients with advanced UC without disease progression after first-line PBCT.Meet-URO12 is a randomized, multicenter, open-label phase 2 trial. Patients with advanced UC, without disease progression after four to six cycles of PBCT, with Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1, were enrolled between August 2019 and March 2021. Randomization was stratified by ECOG performance status (0/1) and response to PBCT (objective response/stable disease).Patients were randomized (2:1) to experimental arm A (niraparib 300 or 200 mg daily according to body weight and baseline platelets, plus BSC) or control arm B (BSC alone).The primary endpoint was progression-free survival (PFS). The analysis was performed on an intention-to-treat basis. The secondary endpoints reported in this primary analysis are progression-free rate at 6 mo and safety (adverse event rate).Fifty-eight patients were randomized (39 in arm A and 19 in arm B). The median age was 69 yr, ECOG performance status was 0 in 66% and 1 in 34%; and the best response with chemotherapy was objective response in 55% and stable disease in 45%. The median PFS was 2.1 mo in arm A and 2.4 mo in arm B (hazard ratio 0.92; 95% confidence interval 0.49-1.75, p = 0.81). The 6-mo progression-free rates were 28.2% and 26.3%, respectively. The most common adverse events with niraparib were anemia (50%, grade [G]3 11%), thrombocytopenia (37%, G3-4 16%), neutropenia (21%, G3 5%), fatigue (32%, G3 16%), constipation (32%, G3 3%), mucositis (13%, G3 3%), and nausea (13%, G3 3%). The main limitation of the study is the small sample size: in March 2021, approval of maintenance avelumab for the same setting rendered randomization of patients in the control arm to BSC alone unethical, and accrual was stopped prematurely.Addition of maintenance niraparib to BSC after first-line PBCT did not demonstrate a significant improvement in PFS in patients with UC. These results do not support the conduction of a phase 3 trial with single agent niraparib in this population.In this trial, we tested the efficacy of niraparib as maintenance treatment in patients affected by advanced urothelial cancer after the completion of first-line chemotherapy. We could not demonstrate a significant improvement in progression-free survival with maintenance niraparib.
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- 2023
17. The prognostic value of the previous nephrectomy in pretreated metastatic renal cell carcinoma receiving immunotherapy: a sub-analysis of the Meet-URO 15 study
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Sara Elena Rebuzzi, Alessio Signori, Giuseppe Luigi Banna, Annalice Gandini, Giuseppe Fornarini, Alessandra Damassi, Marco Maruzzo, Ugo De Giorgi, Umberto Basso, Silvia Chiellino, Luca Galli, Paolo Andrea Zucali, Emanuela Fantinel, Emanuele Naglieri, Giuseppe Procopio, Michele Milella, Francesco Boccardo, Lucia Fratino, Stefania Pipitone, Riccardo Ricotta, Stefano Panni, Veronica Mollica, Mariella Sorarù, Matteo Santoni, Alessio Cortellini, Veronica Prati, Hector Josè Soto Parra, Daniele Santini, Francesco Atzori, Marilena Di Napoli, Orazio Caffo, Marco Messina, Franco Morelli, Giuseppe Prati, Franco Nolè, Francesca Vignani, Alessia Cavo, Giandomenico Roviello, Pasquale Rescigno, and Sebastiano Buti
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Nivolumab ,Cytokines ,Humans ,Immunotherapy ,General Medicine ,Prognosis ,Carcinoma, Renal Cell ,Nephrectomy ,Kidney Neoplasms ,General Biochemistry, Genetics and Molecular Biology ,Retrospective Studies - Abstract
Background Nephrectomy is considered the backbone of managing patients with localized and selected metastatic renal cell carcinoma (mRCC). The prognostic role of nephrectomy has been widely investigated with cytokines and targeted therapy, but it is still unclear in the immunotherapy era. Methods We investigated the Meet-URO-15 study dataset of 571 pretreated mRCC patients receiving nivolumab as second or further lines about the prognostic role of the previous nephrectomy (received in either the localized or metastatic setting) in the overall population and according to the Meet-URO score groups. Results Patients who underwent nephrectomy showed a significantly reduced risk of death (HR 0.44, 95% CI 0.32–0.60, p p = 0.17). It was statistically significant when merging group 1 with 2 and 3 and group 4 with 5 (p = 0.038) and associated with a longer OS for the first three prognostic groups (p p = 0.54). Conclusions Our study suggests an overall positive impact of the previous nephrectomy on the outcome of pretreated mRCC patients receiving immunotherapy. The clinical relevance of cytoreductive nephrectomy, optimal timing and patient selection deserves further investigation, especially for patients with Meet-URO scores of 1 to 3, who are the once deriving benefit in our analyses. However, that benefit is not evident for IMDC poor-risk patients (including the Meet-URO score groups 4 and 5) and a subgroup of IMDC intermediate-risk patients defined as group 4 by the Meet-URO score.
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- 2022
18. Compassionate Use Program of Ipilimumab and Nivolumab in Intermediate or Poor Risk Metastatic Renal Cell Carcinoma: A Large Multicenter Italian Study
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Tortora, Umberto Basso, Federico Paolieri, Mimma Rizzo, Ugo De Giorgi, Sergio Bracarda, Lorenzo Antonuzzo, Francesco Atzori, Giacomo Cartenì, Giuseppe Procopio, Lucia Fratino, Manolo D’Arcangelo, Giuseppe Fornarini, Paolo Zucali, Antonio Cusmai, Matteo Santoni, Stefania Pipitone, Claudia Carella, Stefano Panni, Filippo Deppieri, Vittorina Zagonel, and Giampaolo
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ipilimumab ,nivolumab ,metastatic Renal Cell Carcinoma ,toxicity ,progression ,survival ,retrospective ,immune-related adverse events - Abstract
This is a retrospective analysis on the safety and activity of compassionate Ipilimumab and Nivolumab (IPI-NIVO) administered to patients with metastatic Renal Cell Carcinoma (mRCC) with intermediate or poor International Metastatic RCC Database Consortium (IMDC) score as a first-line regimen. IPI was infused at 1 mg/kg in combination with Nivolumab 3 mg/kg every three weeks for four doses, followed by maintenance Nivolumab (240 or 480 mg flat dose every two or four weeks, respectively) until disease progression or unacceptable toxicity. A total of 324 patients started IPI-NIVO at 86 Italian centers. Median age was 62 years, 68.2% IMDC intermediate risk. Primary tumor had been removed in 65.1% of patients. Two hundred and twenty patients (67.9%) completed the four IPI-NIVO doses. Investigator-assessed overall response rate was 37.6% (2.8% complete). Twelve-month survival rate was 66.8%, median progression-free survival was 8.3 months. Grade 3 or 4 treatment-related adverse events occurred in 67 patients (26.9%). IMDC intermediate risk, nephrectomy, BMI ≥ 25 kg/m2, and steroid use for toxicities correlated with improved survival, while age < 70 years did not. IPI-NIVO combination is a feasible and effective regimen for the first-line treatment of intermediate-poor IMDC risk mRCC patients in routine clinical practice.
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- 2022
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19. The Endolog technique for moderate to severe hallux valgus treatment: Clinical and radiographic analysis of 194 patients
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Daniela Invernizzi, Federico Bertolo, Francesco Atzori, Claudio Cuocolo, and Andrea Pautasso
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Adult ,Male ,Moderate to severe ,medicine.medical_specialty ,Radiography ,Severity of Illness Index ,03 medical and health sciences ,0302 clinical medicine ,Recurrence ,Deformity ,medicine ,Humans ,Orthopedics and Sports Medicine ,Hallux Valgus ,Aged ,Retrospective Studies ,Aged, 80 and over ,Aofas score ,030222 orthopedics ,biology ,business.industry ,Retrospective cohort study ,030229 sport sciences ,Middle Aged ,biology.organism_classification ,Osteotomy ,Surgery ,Valgus ,Treatment Outcome ,Associated procedure ,Radiological weapon ,Female ,medicine.symptom ,business - Abstract
Background Endolog is an intra-medullary titanium device used for a minimally-invasive hallux valgus correction. The aim of this study was to evaluate clinical and radiographic outcomes of this device. Methods A retrospective study with a prospective data collection was conducted. Patients underwent to Endolog procedures from September 2009 to April 2017 were enrolled. Mild HV deformity (HVA ≤ 19° and IMA ≤ 13°) or associated procedure to Endolog technique were excluded. The radiological (HVA, IMA and PASA) and clinical (AOFAS score) pre and post-operative data were compared through Wilcoxon Signed-Rank test. Results 194 feet (144 moderate and 50 severe HV) underwent HV correction respecting study’s criteria. AOFAS scores significantly improved from 31.0 ± 12.7 points preoperatively to 88.5 ± 8.0 at 24 months. Even all radiographic measurements significantly improved during 2 years’ follow-up. Only 6 patients experienced complications: 4 cases of HV recurrence and 2 cases of intolerance device-related pain. Conclusions Endolog technique proved to be a valid option in the moderate-to-severe hallux valgus treatment, comparable to other surgical techniques described in literature.
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- 2021
20. Cabozantinib in the elderly with metastatic renal cell carcinoma undergoing geriatric G8 screening test: A prospective multicenter observational study (ZEBRA/MEET-URO 9)
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Umberto Basso, Sebastiano Buti, Elena Verzoni, Mariella Sorarù, Marilena Di Napoli, Lucia Fratino, Daniele Santini, Francesco Grillone, Vincenzo Emanuele Emanuele Chiuri, Claudia Carella, Francesco Atzori, Giandomenico Roviello, Donata Sartori, Marco Maruzzo, Francesco Pierantoni, Melissa Bersanelli, Melissa Ballestrin, Chiara De Toni, Alvise Mattana, and Vittorina Zagonel
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Cancer Research ,Oncology - Abstract
647 Background: Cabozantinib (CABO) is an oral tyrosine kinase inhibitor registered for the treatment of metastatic renal cell carcinoma (mRCC) for the first or subsequent lines. Tolerability in real world elderly patients is poorly documented. G8 is a short test for vulnerability gaining increased interest as a screening tool for trials in geriatric oncology. Methods: ZEBRA/MEET-URO 9 was a prospective multicenter study of safety and activity of CABO administered to pts ≥70 years with mRCC, either in the first or subsequent lines of treatment, until progression or unacceptable toxicity. All pts underwent G8 score at baseline, with a cut-off for vulnerability of 14 or below. Data on tolerability and activity were collected prospectively after signature of informed consent. Results: A total of 104 pts started CABO at 13 Italian Centers, 38,5% as first line. Median age was 75.8 yrs (range 70.2-87.4 yrs, 26 pts ≥80 yrs), 73.1% males. IMDC score was good 19.2%, intermediate 53.9%, poor 26.9%. Primary tumor had been removed in 82.7% of pts, histology was clear cell 78.8%, papillary 8.7%, chromophobe 5.8%, unclassified 6.7%. G8 score was ≤14 in 65.4% of pts. Up-front dose reduction of CABO was more frequent in pts with low G8 score (79.4 vs 41.7%, p=0.003), but eventually the majority of pts (91.4%) underwent dose reductions of CABO. After a median treatment of 6.4 months (0.5-26.1 months), 38.4% of pts developed G3-4 toxicities, 22.1% interrupted treatment due to adverse events, 2.8% (3 pts) died due to cardiovascular or thromboembolic events. Median PFS was 7.6 months (95% CI=5.8-12.6 months) in first line, 10.0 months (5.8-15.6) in second or further lines, median OS was 20.1 months (11.1-not reached) and 15.6 months (12.5-not reached), respectively. G8 score ≤14 did not correlate with rate of temporary interruptions >7 days, hospitalization, incidence of G3-5 toxicities, as well as with PFS. Pts with G8 score ≤14 had a trend for reduced OS, but difference was not statistically significant both in the first and further lines of treatment. Conclusions: Screening G8 test was positive in more than a half of pts, underlying the need for detailed geriatric assessment and increased clinical monitoring of such patients. A G8 score ≤14 correlated with up-front dose reduction of CABO but not with G3-5 toxicities probably due to the high rates of dose reductions in the whole cohort. Correlation between low G8 score and OS could not be demonstrated in this population.
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- 2023
21. Validation of a Novel Three-Dimensional (3D Fusion) Gross Sampling Protocol for Clear Cell Renal Cell Carcinoma to Overcome Intratumoral Heterogeneity: The Meet-Uro 18 Study
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Matteo Brunelli, Guido Martignoni, Giorgio Malpeli, Alessandro Volpe, Luca Cima, Maria Rosaria Raspollini, Mattia Barbareschi, Alessandro Tafuri, Giulia Masi, Luisa Barzon, Serena Ammendola, Manuela Villanova, Maria Angela Cerruto, Michele Milella, Sebastiano Buti, Melissa Bersanelli, Giuseppe Fornarini, Sara Elena Rebuzzi, Valerio Gaetano Vellone, Gabriele Gaggero, Giuseppe Procopio, Elena Verzoni, Sergio Bracarda, Martina Fanelli, Roberto Sabbatini, Rodolfo Passalacqua, Bruno Perrucci, Maria Olga Giganti, Maddalena Donini, Stefano Panni, Marcello Tucci, Veronica Prati, Cinzia Ortega, Anna Caliò, Albino Eccher, Filippo Alongi, Giovanni Pappagallo, Roberto Iacovelli, Alessandra Mosca, Paolo Umari, Ilaria Montagnani, Stefano Gobbo, Francesco Atzori, Enrico Munari, Marco Maruzzo, Umberto Basso, Francesco Pierconti, Carlo Patriarca, Piergiuseppe Colombo, Alberto Lapini, Giario Conti, Roberto Salvioni, Enrico Bollito, Andrea Cossarizza, Francesco Massari, Mimma Rizzo, Renato Franco, Federica Zito-Marino, Yoseba Aberasturi Plata, Francesca Galuppini, Marta Sbaraglia, Matteo Fassan, Angelo Paolo Dei Tos, Maurizio Colecchia, Holger Moch, Maurizio Scaltriti, Camillo Porta, Brett Delahunt, Gianluca Giannarini, Roberto Bortolus, Pasquale Rescigno, Giuseppe Luigi Banna, Alessio Signori, Miguel Angel Llaja Obispo, Roberto Perris, Alessandro Antonelli, Brunelli, Matteo, Martignoni, Guido, Malpeli, Giorgio, Volpe, Alessandro, Cima, Luca, Raspollini, Maria Rosaria, Barbareschi, Mattia, Tafuri, Alessandro, Masi, Giulia, Barzon, Luisa, Ammendola, Serena, Villanova, Manuela, Cerruto, Maria Angela, Milella, Michele, Buti, Sebastiano, Bersanelli, Melissa, Fornarini, Giuseppe, Rebuzzi, Sara Elena, Vellone, Valerio Gaetano, Gaggero, Gabriele, Procopio, Giuseppe, Verzoni, Elena, Bracarda, Sergio, Fanelli, Martina, Sabbatini, Roberto, Passalacqua, Rodolfo, Perrucci, Bruno, Giganti, Maria Olga, Donini, Maddalena, Panni, Stefano, Tucci, Marcello, Prati, Veronica, Ortega, Cinzia, Caliò, Anna, Eccher, Albino, Alongi, Filippo, Pappagallo, Giovanni, Iacovelli, Roberto, Mosca, Alessandra, Umari, Paolo, Montagnani, Ilaria, Gobbo, Stefano, Atzori, Francesco, Munari, Enrico, Maruzzo, Marco, Basso, Umberto, Pierconti, Francesco, Patriarca, Carlo, Colombo, Piergiuseppe, Lapini, Alberto, Conti, Giario, Salvioni, Roberto, Bollito, Enrico, Cossarizza, Andrea, Massari, Francesco, Rizzo, Mimma, Franco, Renato, Zito-Marino, Federica, Aberasturi Plata, Yoseba, Galuppini, Francesca, Sbaraglia, Marta, Fassan, Matteo, Dei Tos, Angelo Paolo, Colecchia, Maurizio, Moch, Holger, Scaltriti, Maurizio, Porta, Camillo, Delahunt, Brett, Giannarini, Gianluca, Bortolus, Roberto, Rescigno, Pasquale, Banna, Giuseppe Luigi, Signori, Alessio, Obispo, Miguel Angel Llaja, Perris, Roberto, Antonelli, Alessandro, Brunelli M., Martignoni G., Malpeli G., Volpe A., Cima L., Raspollini M.R., Barbareschi M., Tafuri A., Masi G., Barzon L., Ammendola S., Villanova M., Cerruto M.A., Milella M., Buti S., Bersanelli M., Fornarini G., Rebuzzi S.E., Vellone V.G., Gaggero G., Procopio G., Verzoni E., Bracarda S., Fanelli M., Sabbatini R., Passalacqua R., Perrucci B., Giganti M.O., Donini M., Panni S., Tucci M., Prati V., Ortega C., Calio A., Eccher A., Alongi F., Pappagallo G., Iacovelli R., Mosca A., Umari P., Montagnani I., Gobbo S., Atzori F., Munari E., Maruzzo M., Basso U., Pierconti F., Patriarca C., Colombo P., Lapini A., Conti G., Salvioni R., Bollito E., Cossarizza A., Massari F., Rizzo M., Franco R., Zito-Marino F., Plata Y.A., Galuppini F., Sbaraglia M., Fassan M., Dei Tos A.P., Colecchia M., Moch H., Scaltriti M., Porta C., Delahunt B., Giannarini G., Bortolus R., Rescigno P., Banna G.L., Signori A., Obispo M.A.L., Perris R., and Antonelli A.
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angiogenesis ,clear cell renal cell carcinoma ,tumor sampling ,intratumoral heterogeneity ,immunity ,immunohistochemistry ,Medicine (miscellaneous) ,angiogenesi - Abstract
We aimed to overcome intratumoral heterogeneity in clear cell renal cell carcinoma (clearRCC). One hundred cases of clearRCC were sampled. First, usual standard sampling was applied (1 block/cm of tumor); second, the whole tumor was sampled, and 0.6 mm cores were taken from each block to construct a tissue microarray; third, the residual tissue, mapped by taking pieces 0.5 × 0.5 cm, reconstructed the entire tumor mass. Precisely, six randomly derived pieces of tissues were placed in each cassette, with the number of cassettes being based on the diameter of the tumor (called multisite 3D fusion). Angiogenic and immune markers were tested. Routine 5231 tissue blocks were obtained. Multisite 3D fusion sections showed pattern A, homogeneous high vascular density (10%), pattern B, homogeneous low vascular density (8%) and pattern C, heterogeneous angiogenic signatures (82%). PD-L1 expression was seen as diffuse (7%), low (33%) and absent (60%). Tumor-infiltrating CD8 scored high in 25% (pattern hot), low in 65% (pattern weak) and zero in 10% of cases (pattern desert). Grading was upgraded in 26% of cases (G3–G4), necrosis and sarcomatoid/rhabdoid characters were observed in, respectively, 11 and 7% of cases after 3D fusion (p = 0.03). CD8 and PD-L1 immune expressions were higher in the undifferentiated G4/rhabdoid/sarcomatoid clearRCC subtypes (p = 0.03). Again, 22% of cases were set to intermediate to high risk of clinical recurrence due to new morphological findings of all aggressive G4, sarcomatoid/rhabdoid features by using 3D fusion compared to standard methods (p = 0.04). In conclusion, we propose an easy-to-apply multisite 3D fusion sampling that negates bias due to tumor heterogeneity.
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- 2022
22. Another side of the association between body mass index (BMI) and clinical outcomes of cancer patients receiving programmed cell death protein-1 (PD-1)/ Programmed cell death-ligand 1 (PD-L1) checkpoint inhibitors: A multicentre analysis of immune-related adverse events
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Giampiero Porzio, Michele De Tursi, Paolo A. Ascierto, Tea Zeppola, Marcello Tiseo, Daniele Santini, Sebastiano Buti, Francesca Rastelli, Sergio Bracarda, Rossana Berardi, Riccardo Marconcini, Clara Natoli, Andrea De Giglio, Rita Chiari, Cecilia Anesi, Marco Filetti, Federica Zoratto, Rosa Rita Silva, Melissa Bersanelli, Alessio Cortellini, Paolo Marchetti, Raffaele Giusti, Andrea Botticelli, Federica De Galitiis, Alain Gelibter, Corrado Ficorella, Claudia Mosillo, Vito Vanella, Maria Rita Migliorino, Marianna Tudini, Fabiana Perrone, Francesco Atzori, Marco Russano, Biagio Ricciuti, Katia Cannita, Silvia Rinaldi, Domenico Mallardo, and Maria Giuseppa Vitale
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Male ,0301 basic medicine ,Oncology ,Cancer Research ,Programmed Cell Death 1 Receptor ,Overweight ,Severity of Illness Index ,B7-H1 Antigen ,Body Mass Index ,Antineoplastic Agents, Immunological ,0302 clinical medicine ,Risk Factors ,Immune-related adverse events ,Renal cell carcinoma ,Neoplasms ,80 and over ,Cancer ,Aged, 80 and over ,Incidence ,Middle Aged ,Immunological ,BMI ,Checkpoint inhibitors ,Immunotherapy ,Obesity ,PD-1/PD-L1 ,030220 oncology & carcinogenesis ,Female ,medicine.symptom ,Underweight ,Adult ,medicine.medical_specialty ,Drug-Related Side Effects and Adverse Reactions ,Aged ,Humans ,Retrospective Studies ,Young Adult ,Antineoplastic Agents ,03 medical and health sciences ,Internal medicine ,medicine ,Carcinoma ,Adverse effect ,business.industry ,Retrospective cohort study ,medicine.disease ,030104 developmental biology ,business ,Body mass index - Abstract
Several studies have found an association between higher body mass index (BMI) and improved clinical outcomes in cancer patients receiving programmed cell death protein-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) checkpoint inhibitors. In a previous study, we found that overweight/obese patients were significantly more likely to experience any grade immune-related adverse events (irAEs) compared to non-overweight patients.We conducted a 'real-life', multi centre, retrospective observational study aimed at comparing the incidence of irAEs among cancer patients treated with PD-1/PD-L1 inhibitors according to baseline BMI.One thousand and seventy advanced cancer patients were evaluated. The median age was 68 years (range: 21-92), male/female ratio was 724/346. Primary tumours were: non-small-cell lung carcinoma (NSCLC) (653 patients), melanoma (233 patients), renal cell carcinoma (RCC) (152 patients) and others (29 patients). Median BMI was 25 (13.6-46.6); according to World Health Organisation (WHO) classification, 44 patients (4.1%) were defined as underweight, 480 patients (44.9%) as having a normal weight, 416 patients (38.9%) as overweight and 130 patients (12.1%) as obese. Higher BMI was significantly related to higher occurrence of any grade immune-related adverse events [irAEs] (p 0.0001), G3/G4 irAEs (p 0.0001) and irAEs leading to discontinuation (LTD) (p 0.0001). Overweight and obesity were confirmed predictors for irAEs of any grade at both univariate and multivariate analysis. The adjusted odds ratios (ORs) (compared to normal-weight) were 10.6; 95% confidence interval (95%CI): 7.5-14.9 for overweight, and 16.6 (95%CI: 10.3-26.7) for obese patients. Obesity was the only factor significantly related to a higher incidence of G3/G4 irAEs (OR = 11.9 [95%CI: 6.4-22.3], p 0.0001) and LTD irAEs (OR = 8.8 [95%CI: 4.3-18.2], p 0.0001). Overweight and obese patients experienced a significantly higher occurrence of cutaneous, endocrine, gastro-intestinal (GI), hepatic and 'others' irAEs, compared to normal-weight patients. Only obese patients experienced a significantly higher occurrence of pulmonary and rheumatic irAEs, compared to normal-weight patients.Considering the previously evidenced association between higher BMI and better outcome, the current finding about the relationship between BMI and irAEs occurrence can contribute to consideration of these findings as the upside of the downside, which underlies an 'immunogenic phenotype'.
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- 2020
23. GU-CA-COVID: a clinical audit among Italian genitourinary oncologists during the first COVID-19 outbreak
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Sergio Bracarda, Sebastiano Buti, Marco Stellato, Maria Giuseppa Vitale, Giuseppe Procopio, Alessio Cortellini, Ilaria Toscani, Francesco Massari, Carlo Cattrini, Francesco Atzori, Orazio Caffo, Paolo Andrea Zucali, D. Zara, Alessandra Gennari, Mimma Rizzo, Luca Galli, Francesca Corti, Cinzia Baldessari, Melissa Bersanelli, Alberto Dalla Volta, Martina Fanelli, Claudia Mucciarini, Leonardo La Torre, Serena Macrini, Giuseppe Fornarini, Camillo Porta, Angela Gernone, Franco Morelli, Cristina Masini, Alice Gatti, Bersanelli M., Buti S., Rizzo M., Cortellini A., Cattrini C., Massari F., Masini C., Vitale M.G., Fornarini G., Caffo O., Atzori F., Gatti A., Macrini S., Mucciarini C., Galli L., Morelli F., Stellato M., Fanelli M., Corti F., Zucali P.A., Toscani I., Dalla Volta A., Gernone A., Baldessari C., La Torre L., Zara D., Gennari A., Bracarda S., Procopio G., and Porta C.
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Clinical audit ,cancer patient ,medicine.medical_specialty ,Urology ,Population ,Context (language use) ,genitourinary cancer ,Renal cell carcinoma ,Internal medicine ,medicine ,education ,Original Research ,education.field_of_study ,Bladder cancer ,business.industry ,SARS-CoV-2 ,Incidence (epidemiology) ,Cancer ,COVID-19 ,medicine.disease ,genitourinary cancers ,Diseases of the genitourinary system. Urology ,Discontinuation ,renal cancer: urothelial cancer ,bladder cancer ,RC870-923 ,Corrigendum ,business ,cancer patients - Abstract
Background: Considering the growing genitourinary (GU) cancer population undergoing systemic treatment with immune checkpoint inhibitors (ICIs) in the context of the COVID-19 pandemic, we planned a clinical audit in 24 Italian institutions treating GU malignancies. Objective: The primary objective was investigating the clinical impact of COVID-19 in GU cancer patients undergoing ICI-based therapy during the first outbreak of SARS-CoV-2 contagion in Italy. Design, setting, and participants: The included centers were 24 Oncology Departments. Two online forms were completed by the responsible Oncology Consultants, respectively, for metastatic renal cell carcinoma (mRCC) and metastatic urothelial carcinoma (mUC) patients receiving at least one administration of ICIs between 31 January 2020 and 30 June 2020. Results and limitation: In total, 287 mRCC patients and 130 mUC patients were included. The COVID-19 incidence was, respectively, 3.5%, with mortality 1%, in mRCC patients and 7.7%, with mortality 3.1%, in mUC patients. In both groups, 40% of patients developing COVID-19 permanently discontinued anticancer treatment. The pre-test SARS-CoV-2 probability in the subgroup of patients who underwent nasal/pharyngeal swab ranged from 14% in mRCC to 26% in mUC. The main limitation of the work was its nature of audit: data were not recorded at the single-patient level. Conclusion: GU cancer patients undergoing active treatment with ICIs have meaningful risk factors for developing severe events from COVID-19 and permanent discontinuation of therapy after the infection. Treatment delays due to organizational issues during the pandemic were unlikely to affect the treatment outcome in this population.
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- 2021
24. Primary Tumor Shrinkage and the Effect on Metastatic Disease and Outcomes in Patients With Advanced Kidney Cancer With Intermediate or Poor Prognosis Treated With Nivolumab Plus Ipilimumab or Cabozantinib
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Roberto Iacovelli, Chiara Ciccarese, Marco Maruzzo, Francesco Atzori, Luca Galli, Sarah Scagliarini, Francesco Massari, Elena Verzoni, Antonella Cannella, Maria Grazia Maratta, Claudia Caserta, Davide Bimbatti, Filippo Maria Deppieri, Mariele Dessi, Federico Paolieri, Ferdinando Riccardi, Sergio Bracarda, Ugo De Giorgi, Umberto Basso, Giampaolo Tortora, and Giuseppe Procopio
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Nivolumab ,Oncology ,Pyridines ,Urology ,Antineoplastic Combined Chemotherapy Protocols ,Humans ,Anilides ,Prognosis ,Carcinoma, Renal Cell ,Immune Checkpoint Inhibitors ,Ipilimumab ,Kidney Neoplasms - Abstract
Immune checkpoint inhibitor (ICI)-based combinations have become the first-line standard of care in metastatic renal cell carcinoma (mRCC), but their activity on the primary tumor is still one of the most debated issues.The aim of our analysis was to evaluate the primary tumor's response to first-line therapy with cabozantinib or nivolumab+ipilimumab, and its correlation with metastatic response and with patient outcomes.Sixty-seven mRCC patients met the criteria for inclusion in the final analysis (30 treated with cabozantinib and 37 with nivolumab+ipilimumab). In the overall population, the primary tumor control rate (PTCR) was 90.9%; no complete responses (CR) were achieved. A significant correlation was found between the baseline size of the primary tumor's longest diameter and its response according to RECIST v1.1 criteria at the time of the second radiological assessment (rs = -0.351; P = .049). Moreover, a significant correlation between the type of primary tumor response and the response of the metastases was observed in the overall population (rs = 0.50; two-sided P 0.001). There was also a significant correlation between primary tumor response and 1-year survival rate (P = .002), even when adjusted for the IMDC prognostic group and type of therapy (HR = 8.70; 95%CI, 2.52-30.05; P = .001).Extension of the primary tumor did not affect patient survival, while its response was significantly related to the response on metastatic disease and survival. No significant differences in terms of primary tumor shrinkage were identified between treatment with nivolumab+ipilimumab or cabozantinib in this cohort.
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- 2022
25. Histological analysis of the anterolateral ligament of the knee
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Pier Francesco Indelli, Marco Volante, Luigi Sabatini, Alessandro Aprato, Francesco Atzori, Alessandro Massè, and Salvatore Risitano
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musculoskeletal diseases ,Anterolateral ligament ,Anterior cruciate ligament ,Total knee arthroplasty ,Article ,03 medical and health sciences ,0302 clinical medicine ,ALL histology ,Joint capsule ,medicine ,Knee ,Orthopedics and Sports Medicine ,030222 orthopedics ,Articular capsule of the knee joint ,business.industry ,Knee joint capsule ,Capsule ,030229 sport sciences ,Anatomy ,musculoskeletal system ,medicine.anatomical_structure ,ALL ,business ,human activities - Abstract
Anterolateral ligament (ALL) was recently described as an important structure to control the pivot-shift phenomenon in the knee. Doubts remain regarding its origin and histological properties. The purpose of this study was to identify the ALL histological structure comparing its characteristics with those of the anterior cruciate ligament (ACL) and joint capsule. ALL was harvested in 25 knees during a total knee arthroplasty (TKA) and histologically evaluated investigating for orientation of fibers, adipose tissue, presence of proprioceptors and synovial like coating. Analysis showed significant differences in several aspects between capsule and ALL; analogies were found comparing the ALL with ACL.
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- 2019
26. Drug-related toxicity in breast cancer patients: a new path towards tailored treatment?—a narrative review
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Eleonora Lai, Mara Persano, Marco Dubois, Dario Spanu, Clelia Donisi, Marta Pozzari, Giulia Deias, Giorgio Saba, Marco Migliari, Nicole Liscia, Mariele Dessì, Mario Scartozzi, and Francesco Atzori
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Cancer Research ,Anesthesiology and Pain Medicine ,Oncology ,Oncology (nursing) ,Pharmacology (medical) ,Surgery - Published
- 2022
27. Extended interval dosing in patients with cancer receiving immune checkpoint inhibitors: Safety analysis from the EDICI study
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Luca Cantini, Francesco Paoloni, Federica Pecci, Francesco Spagnolo, Sophie Aerts, Alice Indini, Sara Fancelli, Fabrizio Citarella, Mattia Garutti, Maria Chiara Sergi, Raffaele Giusti, Anna Maria Di Giacomo, Antonello Veccia, Diego Luigi Cortinovis, Rita Leporati, Ilaria Mariangela Scaglione, Francesco Atzori, Lucia Festino, Joachim Aerts, and Rossana Berardi
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Cancer Research ,Oncology - Abstract
2595 Background: Healthcare costs and need of frequent patients' (pts) access to oncology departments led to an increasing interest in alternative immune check-point inhibitors (ICIs) administration schedules able to offer longer dose intervals. The extended interval dosing (ED) of nivolumab and pembrolizumab was approved based on pharmacokinetic data, the relationship of exposure to efficacy, and the relationship of exposure to safety. We aimed to investigate real-life immune-related adverse events (irAEs) incidence in pts treated with ED-ICIs. Methods: Clinicopathological and treatment characteristics of all consecutive solid cancer pts treated with ICIs (pembrolizumab, nivolumab) monotherapy who received at least one cycle of the ED (pembrolizumab 400 every 6 weeks or nivolumab 480 mg every 4 weeks) were identified from patient electronic records of 37 oncology departments across Europe and entered into a prospectively maintained database. Results: Among 756 pts enrolled in the EDICI study, 733 pts (229 treated with pembrolizumab, and 504 with nivolumab) were included in the final safety analysis (median follow up time: 24.7 months). 476 pts were males, with melanoma (441, 60%) and non-small cell lung cancer (151, 20%) being the prevalent tumor types. Median age was 67 years old, and 589 (80%) pts received ICIs in the advanced setting. 501 (68%) of the enrolled pts started ICIs with canonical interval dosing (CD, median number of cycles administered: 13) and subsequently switched to ED after a median time interval of 210 days. During CD-ICI, 197 pts (39%) developed irAEs of any grade and 14 patients (3%) G3/G4 events; after switching to ED-ICI treatment, which was administered for a median of 7 cycles and 336 days, irAEs of any grade and G3/G4 events were experienced by 155 (36%) and 20 (5%) pts, respectively; 73 (47%) cases of any grade-toxicity and 12 (60%) of G3/G4-toxicity were de novo. 33 (7%) pts switched back to CD, in 45% of the cases due to toxicity. Pts who started upfront with ED (n = 232, 32%) were exposed to the drug for a median of 7 cycles; 56 of them (25%) developed irAEs of any grade and 9 (6%) G3/G4 irAEs. Skin (12% of patients), endocrine (11%), rheumatic (10%) and gastrointestinal (9%) were the most common irAEs during ED; 42% were “multiple-site” irAEs, showing no difference with CD (p = 0.21). Lower creatinine values before switch to ED (adjusted odds ratio [aOR], 1.24; 95%CI, 1.03-1.48; P = 0.02) and previous toxicity during CD (aOR, 1.20; 95%CI, 1.08-1.33; P < 0.01) were independent risk factors for development of irAEs during ED. Conclusions: Despite similar exposure time, the safety profile of ED treatment did not differ from CD, confirming that ED-ICI administration is a safe and feasible option also in cancer pts outside of clinical trials. Future investigations are needed to explore efficacy data and economic impact of this strategy.
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- 2022
28. Fulvestrant-Palbociclib vs Letrozole-Palbociclib as Initial Therapy for Endocrine-Sensitive, Hormone Receptor-Positive, ERBB2-Negative Advanced Breast Cancer. A Randomized Clinical Trial
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Miguel Sampayo-Cordero, Trial Investigators, Duncan Wheatley, Marco Colleoni, Petra Tesarova, Pilar Zamora, Kepa Amillano, Steven Chan, Gianfilippo Bertelli, Jacques Medioni, Thierry Petit, Juan de la Haba, Vicente Caranyana, Joan Albanell, Peter Schmid, Mark Beresford, Andrea Malfettone, Francesco Atzori, Joaquín Gavilá, Saverio Cinieri, Vladimir Moiseyenko, Luigi Cavanna, Gemma Viñas, Vladimir Vladimirov, Maria Luque-Cabal, Mario Airoldi, Sonia Servitja, Elena Aguirre, Florence Dalenc, Jose Perez-Garcia, Santiago González, Purificación Martínez, Daniele Generali, Meritxell Bellet, Antonio Antón, Andreas Schneeweiss, Manuel Ruíz-Borrego, Antonio Llombart-Cussac, Serena Di Cosimo, Eduardo Martínez-de Dueñas, Laura Cortesi, Juan Cueva Bañuelos, Joseph Gligorov, Guzel Mukhametsina, Bohuslav Melichar, Javier Cortes, Joachim Bischoff, Maria Cazzaniga, Raquel Andres, Tatiana Barannikova, Juan Bayo, Andrew Wardley, Paul Cottu, Frederik Marmé, Miguel Gil-Gil, Llombart-Cussac, A., Perez-Garcia, J. M., Bellet, M., Dalenc, F., Gil-Gil, M., Ruiz-Borrego, M., Gavila, J., Sampayo-Cordero, M., Aguirre, E., Schmid, P., Marme, F., Di Cosimo, S., Gligorov, J., Schneeweiss, A., Albanell, J., Zamora, P., Wheatley, D., Martinez-De Duenas, E., Amillano, K., Malfettone, A., Cortes, J., and Generali, D.
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Oncology ,Cancer Research ,medicine.medical_specialty ,Receptor, ErbB-2 ,Pyridines ,Pyridine ,Anastrozole ,Breast Neoplasms ,Palbociclib ,Piperazines ,Breast cancer ,ErbB-2 ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Clinical endpoint ,Humans ,Female ,Fulvestrant ,Letrozole ,Middle Aged ,Piperazine ,Original Investigation ,Antineoplastic Combined Chemotherapy Protocol ,business.industry ,Hazard ratio ,Correction ,medicine.disease ,Response Evaluation Criteria in Solid Tumors ,business ,Human ,medicine.drug ,Receptor - Abstract
Question Which is the optimal endocrine partner (fulvestrant vs letrozole) for cyclin-dependent kinase 4 and 6 inhibitor palbociclib in previously untreated, endocrine-sensitive, hormone receptor-positive, ERBB2-negative advanced breast cancer? Findings In this randomized, open-label, phase 2 trial, 486 patients were assigned in equal numbers to receive palbociclib plus fulvestrant or letrozole. Median investigator-assessed progression-free survival was 27.9 months for fulvestrant-palbociclib vs 32.8 months for letrozole-palbociclib, a difference that was not statistically significant. Meaning Fulvestrant-palbociclib demonstrated no improvement in progression-free survival over letrozole-palbociclib, confirming letrozole as the preferred palbociclib partner in this patient population. This randomized clinical trial investigates fulvestrant-palbociclib vs letrozole-palbociclib as initial therapy for endocrine-sensitive, hormone receptor-positive, ERBB2-negative breast cancer. IMPORTANCE The cyclin-dependent kinase 4 and 6 inhibitor palbociclib in combination with letrozole has become a standard first-line treatment for patients with endocrine-sensitive, hormone receptor-positive, ERBB2-negative advanced breast cancer. Meanwhile, the antiestrogen fulvestrant was shown to be superior to anastrozole in the absence of cyclin-dependent kinase 4 and 6 inhibition for this patient population. OBJECTIVE To assess whether fulvestrant is superior to letrozole when combined with palbociclib in the first-line scenario. DESIGN, SETTING, AND PARTICIPANTS In this international, randomized, open-label, phase 2 clinical study conducted from July 30, 2015, to January 8, 2018, patients with hormone receptor-positive, ERBB2-negative advanced breast cancer with no prior therapy in the metastatic setting and endocrine-sensitive criteria were recruited from 47 centers in 7 countries. Data were analyzed from February 11 to May 15, 2020. INTERVENTIONS Patients were randomly assigned (1:1 ratio) to receive palbociclib with either fulvestrant or letrozole. Stratification factors were type of disease presentation (de novo vs recurrent) and the presence of visceral involvement (yes vs no). MAIN OUTCOMES AND MEASURES The primary end point was investigator-assessed progression-free survival determined by Response Evaluation Criteria in Solid Tumors, version 1.1. RESULTS A total of 486 women (median age, 63 years [range, 25-90 years]; 3 Asian women [0.6%]; 4 Black women [0.8%]; 461 White women [94.9%]; 18 women of unknown race [3.7%]) were randomized (243 to fulvestrant-palbociclib and 243 to letrozole-palbociclib). Median investigator-assessed progression-free survival was 27.9 months (95% CI, 24.2-33.1 months) in the fulvestrant-palbociclib group vs 32.8 months (95% CI, 25.8-35.9 months) in the letrozole-palbociclib group (hazard ratio, 1.13; 95% CI, 0.89-1.45; P = .32). This result was consistent across the stratification factors. No significant differences were observed in objective response rate (46.5% vs 50.2%) and 3-year overall survival rate (79.4% vs 77.1%) for fulvestrant-palbociclib and letrozole-palbociclib, respectively. Grade 3-4 adverse events were comparable among treatment groups, and no new safety signals were identified. No treatment-related deaths were reported. CONCLUSIONS AND RELEVANCE Although fulvestrant-palbociclib demonstrated significant antitumor activity, this randomized clinical trial failed to identify an improvement in progression-free survival with this regimen over letrozole-palbociclib in patients with endocrine-sensitive, hormone receptor-positive, ERBB2-negative advanced breast cancer.
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- 2021
29. Radical metastasectomy followed by sorafenib versus observation in patients withclear cell renal cell carcinoma: extended follow -up of efficacy results from the randomized phase II RESORT trial
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Franco Morelli, Francesco Atzori, Melanie Claps, Maddalena Donini, Alessandra Mosca, Vera Cappelletti, Alessandra Bearz, Rosalba Miceli, Elena Verzoni, Cinzia Ortega, Francesco Cognetti, M. Milella, Valentina Guadalupi, Pierangela Sepe, V.E. Chiuri, Alessia Mennitto, F. de Braud, and Giuseppe Procopio
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Sorafenib ,Oncology ,medicine.medical_specialty ,relapse-free survival ,medicine.medical_treatment ,Cell ,Metastatic renal cell carcinoma ,adjuvant treatment ,Antineoplastic Agents ,urologic and male genital diseases ,030226 pharmacology & pharmacy ,Relapse free survival ,Disease-Free Survival ,Targeted therapy ,03 medical and health sciences ,0302 clinical medicine ,Renal cell carcinoma ,Internal medicine ,surgical metastasectomy ,Medicine ,Humans ,Pharmacology (medical) ,In patient ,General Pharmacology, Toxicology and Pharmaceutics ,Carcinoma, Renal Cell ,Probability ,business.industry ,Carcinoma ,Metastasectomy ,Renal Cell ,General Medicine ,medicine.disease ,targeted therapy ,Kidney Neoplasms ,medicine.anatomical_structure ,Neoplasm Recurrence ,Local ,030220 oncology & carcinogenesis ,Neoplasm Recurrence, Local ,business ,medicine.drug ,Follow-Up Studies - Abstract
Background: The RESORT trial showed no longer relapse free survival (RFS) with sorafenib following radical metastasectomy in metastatic renal cell carcinoma. We present the updated 42-month follow-...
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- 2021
30. Inflammatory indices and clinical factors in metastatic renal cell carcinoma patients treated with nivolumab: the development of a novel prognostic score (Meet-URO 15 study)
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Matteo Santoni, Sara Elena Rebuzzi, Francesca Vignani, Silvia Chiellino, Sebastiano Buti, Alessio Cortellini, Paolo Andrea Zucali, Hector Soto Parra, Franco Morelli, Cristina Masini, Melissa Bersanelli, Emanuele Naglieri, Giandomenico Roviello, Laura Tomasello, Franco Nolè, Paolo Pedrazzoli, Veronica Prati, Marco Messina, Alessio Signori, Giuseppe Fornarini, Francesco Pierantoni, Francesco Atzori, Federico Paolieri, Giuseppe Procopio, Roberto Iacovelli, Lucia Fratino, Andrea Sbrana, Sara Merler, Giuseppe Luigi Banna, Sandro Pignata, Alessia Cavo, Chiara Casadei, Matteo Brunelli, Mariella Sorarù, Ugo De Giorgi, Camillo Porta, Giuseppe Prati, Marco Maruzzo, Riccardo Ricotta, Marco Stellato, Matteo Perrino, Veronica Mollica, Carlo Messina, Cinzia Baldessari, and Stefano Panni
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0301 basic medicine ,Oncology ,medicine.medical_specialty ,biomarkers ,clinical factors ,immune checkpoint inhibitor ,immunotherapy ,prognostic score ,renal cell carcinoma ,medicine.medical_treatment ,Immune checkpoint inhibitors ,Article ,Prognostic score ,03 medical and health sciences ,0302 clinical medicine ,Renal cell carcinoma ,Internal medicine ,medicine ,Survival advantage ,RC254-282 ,Original Research ,business.industry ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Immunotherapy ,medicine.disease ,030104 developmental biology ,030220 oncology & carcinogenesis ,Nivolumab ,business - Abstract
Background: Despite the survival advantage, not all metastatic renal cell carcinoma (mRCC) patients achieve a long-term benefit from immunotherapy. Moreover, the identification of prognostic biomarkers is still an unmet clinical need. Methods: This multicenter retrospective study investigated the prognostic role of peripheral-blood inflammatory indices and clinical factors to develop a novel prognostic score in mRCC patients receiving at least second-line nivolumab. The complete blood count before the first cycle of therapy was assessed by calculating neutrophil-to-lymphocyte ratio (NLR), derived NLR (dNLR), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), systemic inflammation index (SII), and systemic inflammation response index (SIRI). Clinical factors included pre-treatment International Metastatic RCC Database Consortium (IMDC) score, line of therapy, and metastatic sites. Results: From October 2015 to November 2019, 571 mRCC patients received nivolumab as second- and further-line treatment in 69% and 31% of cases. In univariable and multivariable analyses all inflammatory indices, IMDC score, and bone metastases significantly correlated with overall survival (OS). The multivariable model with NLR, IMDC score, and bone metastases had the highest c-index (0.697) and was chosen for the developing of the score (Schneeweiss scoring system). After internal validation (bootstrap re-sampling), the final index (Meet-URO score) composed by NLR, IMDC score, and bone metastases had a c-index of 0.691. It identified five categories with distinctive OSs: group 1 (median OS – mOS = not reached), group 2 (mOS = 43.9 months), group 3 (mOS = 22.4 months), group 4 (mOS = 10.3 months), and group 5 (mOS = 3.2 months). Moreover, the Meet-URO score allowed for a fine risk-stratification across all three IMDC groups. Conclusion: The Meet-URO score allowed for the accurate stratification of pretreated mRCC patients receiving nivolumab and is easily applicable for clinical practice at no additional cost. Future steps include its external validation, the assessment of its predictivity, and its application to first-line combinations.
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- 2021
31. Defining the metabolomic profile associated with early cardiotoxicity in patients with breast cancer treated with anthracyclines
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Antonio Noto, S Ricci, Clelia Madeddu, Christian Cadeddu Dessalvi, Martino Deidda, Mario Scartozzi, Francesco Atzori, Daniele Cocco, Giuseppe Mercuro, and Enrico G. Ferro
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Oncology ,Cardiotoxicity ,medicine.medical_specialty ,Breast cancer ,Metabolomics ,business.industry ,Internal medicine ,Medicine ,In patient ,Cardiology and Cardiovascular Medicine ,business ,medicine.disease - Abstract
Background Anthracycline (ANT) therapy has dramatically improved clinical outcomes for patients with breast cancer, but it causes cardiotoxicity (CTX) in a dose-dependent manner. Current cardiac biomarkers (troponin, brain natriuretic peptide) and 2D echocardiography only detect CTX in advanced and often irreversible stages. Metabolomic analysis may allow early diagnosis of CTX, and prompt initiation of cardio protective therapies. Purpose To diagnose early CTX via speckle tracking echocardiography (STE), and to characterize the metabolomic fingerprint of patients affected by ANT-mediated CTX. Methods In 2019, patients with breast cancer and normal baseline ejection fraction (EF) were enrolled and longitudinally monitored through clinical assessment, blood sample collection and echocardiography, before initiation of ANT therapy and at 180, 270 and 360 mg/m2 of ANT. CTX, defined as >15% reduction in Global Longitudinal Strain (GLS), was monitored at each ANT dose increment. Unsupervised Principal Component Analysis, supervised Partial Least Square and Partial Least-Square Discriminant Analyses were used to compare the metabolomic profiles of patients who did and did not develop CTX during the study period. Results In the study sample (n=33), no patient developed clinical heart failure, but 8 patients (25%) developed CTX by GLS criteria. Patients with CTX had a significant decrease in GLS compared to patients without CTX at 270 mg/m2 (GLS 20.5 vs 17.9, p=0.01) and 360 mg/m2 ANT (GLS 21.6 vs 17.7, p Conclusions For the first time in a human population of breast cancer patients, we show that early ANT-induced CTX (diagnosed via asymptomatic GLS reduction) is associated with a unique metabolomic profile, which affects molecular pathways of energy production. Notably, CTX damage upregulates similar metabolites to those previously identified in clinical heart failure and in mouse CTX models. Our results suggest that a metabolomic fingerprint can be leveraged to create prediction models to identify patients at higher risk of developing cardiovascular complications from ANT therapy. This, in turn, will allow to personalize both chemotherapy and cardioprotective treatments. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): University of Cagliari
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- 2020
32. Early primary tumor response in metastatic RCC patients treated with immune checkpoint inhibitors-based combinations
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Chiara Ciccarese, Davide Bimbatti, Francesco Atzori, Adele Bonato, Sarah Scagliarini, Ilaria Pellegrini, Sergio Bracarda, Ugo De Giorgi, Cristina Masini, Matteo Santoni, Francesco Massari, Sebastiano Buti, Alessandra Damassi, Ilaria Zampiva, Alessandro Strusi, Ileana Sparagna, Sara Elena Rebuzzi, Giampaolo Tortora, and Roberto Iacovelli
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Cancer Research ,Oncology - Abstract
349 Background: 25-30% of renal cell carcinoma presents with metastases (mRCC) at diagnosis. The activity of immune checkpoint inhibitor (ICI)-combinations on the primary tumor (PT) is debated. Patients and Methods: mRCC patients (pts) with PT who received first-line nivolumab plus ipilimumab (N/I) or pembrolizumab plus axitinib (P/A) were included. We investigated the early primary tumor response (EPTR) at the first radiological assessment. Results: 73 pts were included. The median early reduction of the PT longest diameter was 12.4% with P/A versus 6.2% with N/I (p = 0.42). We evaluated if the type of EPTR could affect the metastases response. Among pts with PT stable disease (SD), 8.3% had metastatic disease progression (PD) with P/A and 34.8% with N/I. Early PT partial response (PR) was associated with no metastatic PD with both N/I and P/A. The 2 pts with PT PD had also metastatic PD to P/A. Of the 3 PT with PD to N/I, 1 had metastatic SD and 2 PD. In the overall population, of the 94.1% without PT progression (PR+SD), 47.5% had metastatic PR, 35.6% SD, 16.9% PD. Conclusions: ICIs-combinations achieved an early PT PR in about 10-20%, without any complete responses. Only a small percentage of PT had an early PD, mainly associated with metastatic PD. However, among those PT without an early progression, metastatic PR can be achieved in approximately 50% of cases.[Table: see text]
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- 2022
33. Histologic subtyping affecting outcome of triple negative breast cancer: a large Sardinian population-based analysis
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Luisa Canu, Maria Giuseppina Sarobba, Dolores Palmas, Vincenzo Marras, Ricardo Medda, Paolo Cossu-Rocca, Tiziana Moi, Elisabetta Sollai, Maria Rosaria Muroni, Anna Asunis, Francesco Atzori, Angelo Zinellu, Enrichetta Valle, Renata Barrocu, Maria Rosaria De Miglio, Sergio Cossu, F. Cambosu, Cristina Bosetti, Alessandra Manca, Maria Gabriela Uras, Giovanna Pira, Daniela Onnis, Maurizio D'Incalci, Silvana Anna Maria Urru, Maria Cristina Santona, Silvano Gallus, Sandra Orrù, Matteo Floris, Francesca Sanges, Alma Murgia, and Massimo Ghiani
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0301 basic medicine ,Oncology ,Adult ,Cancer Research ,medicine.medical_specialty ,Adenoid cystic carcinoma ,Metaplastic carcinoma ,Lobular carcinoma ,Clinical Decision-Making ,Metastatic lymph node ,Triple Negative Breast Neoplasms ,Histologic special type ,Kaplan-Meier Estimate ,lcsh:RC254-282 ,Disease-Free Survival ,Clinico-pathological features ,03 medical and health sciences ,0302 clinical medicine ,Surgical oncology ,Internal medicine ,Genetics ,medicine ,Carcinoma ,Humans ,Triple negative breast cancer ,Breast ,Triple-negative breast cancer ,Aged ,Neoplasm Staging ,Retrospective Studies ,business.industry ,Apocrine ,Tumor size ,Middle Aged ,medicine.disease ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Prognosis ,Tumor Burden ,030104 developmental biology ,Medullary carcinoma ,Italy ,030220 oncology & carcinogenesis ,Lymphatic Metastasis ,Female ,Lymph Nodes ,business ,Research Article ,Follow-Up Studies - Abstract
Background Triple Negative breast cancer (TNBC) includes a heterogeneous group of tumors with different clinico-pathological features, molecular alterations and treatment responsivity. Our aim was to evaluate the clinico-pathological heterogeneity and prognostic significance of TNBC histologic variants, comparing “special types” to high-grade invasive breast carcinomas of no special type (IBC-NST). Methods This study was performed on data obtained from TNBC Database, including pathological features and clinical records of 1009 TNBCs patients diagnosed between 1994 and 2015 in the four most important Oncology Units located in different hospitals in Sardinia, Italy. Kaplan-Meier analysis, log-rank test and multivariate Cox proportional-hazards regression were applied for overall survival (OS) and disease free survival (DFS) according to TNBC histologic types. Results TNBC “special types” showed significant differences for several clinico-pathological features when compared to IBC-NST. We observed that in apocrine carcinomas as tumor size increased, the number of metastatic lymph nodes manifestly increased. Adenoid cystic carcinoma showed the smallest tumor size relative to IBC-NST. At five-year follow-up, OS was 92.1, 100.0, and 94.5% for patients with apocrine, adenoid cystic and medullary carcinoma, respectively; patients with lobular and metaplastic carcinoma showed the worst OS, with 79.7 and 84.3%, respectively. At ten-years, patients with adenoid cystic (100.0%) and medullary (94.5%) carcinoma showed a favourable prognosis, whereas patients with lobular carcinoma showed the worst prognosis (73.8%). TNBC medullary type was an independent prognostic factor for DFS compared to IBC-NST. Conclusions Our study confirms that an accurate and reliable histopathologic definition of TNBC subtypes has a significant clinical utility and is effective in the therapeutic decision-making process, with the aim to develop innovative and personalized treatments.
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- 2020
34. Impact of influenza syndrome and flu vaccine on survival of cancer patients during immunotherapy in the INVIDIa study
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Emmanuele De Luca, Francesca Mazzoni, Maria Giuseppa Vitale, Massimo Di Maio, Alessio Cortellini, Corrado Ficorella, Ugo De Giorgi, Francesco Atzori, Giuseppe Fornarini, Antonio Maestri, Sara Elena Rebuzzi, Melissa Bersanelli, Diana Giannarelli, Elena Verzoni, Silverio Tomao, Pietro Di Marino, Veronica Mollica, Roberto Sabbatini, Giovanni Schinzari, Sebastiano Buti, Mariella Sorarù, Michele De Tursi, Giuseppe Procopio, Sabrina Rossetti, Claudia Mucciarini, Pierangela Sepe, Teodoro Sava, Leonardo La Torre, Francesco Massari, Marcello Tiseo, Ernesto Rossi, Giuseppe Luigi Banna, Vanja Vaccaro, Stefano Panni, and Valentino Martelli
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0301 basic medicine ,Oncology ,Male ,medicine.medical_specialty ,Multivariate analysis ,Influenza vaccine ,influenza syndrome ,medicine.medical_treatment ,overall survival ,Immunology ,Population ,flu vaccine ,immune checkpoint inhibitors ,immunotherapy ,influenza vaccination ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Neoplasms ,Influenza, Human ,medicine ,Overall survival ,Immunology and Allergy ,Humans ,Immunologic Factors ,Lung cancer ,education ,Aged ,Retrospective Studies ,education.field_of_study ,business.industry ,Cancer ,Immunotherapy ,Syndrome ,medicine.disease ,Survival Analysis ,030104 developmental biology ,Italy ,Influenza Vaccines ,030220 oncology & carcinogenesis ,Population study ,Female ,business ,Follow-Up Studies - Abstract
Aim: INVIDIa was a retrospective, multicenter study, exploring the clinical efficacy of influenza vaccine in 300 cancer patients undergoing immunotherapy. Overall survival (OS) was immature at the initial report. Methods: We reported the final OS analysis from the original study population and within subgroups. Results: Both at the univariate and multivariate analysis, the occurrence of influenza syndrome (IS) was significantly related to better OS in the overall population (OR: 0.53 [95% CI: 0.32–0.88]; p = 0.01). In the lung cancer subgroup, receiving flu vaccine and/or developing IS was related to better OS (p = 0.04). Within elderly patients, the flu vaccine was the main variable for the relative OS advantage (p = 0.05). Conclusion: Receiving the flu vaccine and/or developing IS was related to better OS within the INVIDIa population.
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- 2020
35. Evaluating the role of FAMIly history of cancer and diagnosis of multiple neoplasms in cancer patients receiving PD-1/PD-L1 checkpoint inhibitors. the multicenter FAMI-L1 study
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Fabiana Perrone, Rosa Rita Silva, Cristina Zannori, Paolo Marchetti, Francesco Atzori, Giampiero Porzio, Raffaele Giusti, Domenico Mallardo, Nicola Tinari, Enzo Veltri, Tea Zeppola, Federica De Galitiis, Marcello Tiseo, Alessio Cortellini, Cecilia Anesi, Claudia Mosillo, Alessandro Inno, Marianna Tudini, Stefania Gori, Alain Gelibter, Marco Filetti, Corrado Ficorella, Alessandra Tessitore, Melissa Bersanelli, Andrea Botticelli, Mario Occhipinti, Antonino Grassadonia, Marco Russano, Maria Giuseppa Vitale, Annagrazia Pireddu, Maria Concetta Fargnoli, Francesco Malorgio, Katia Cannita, Federica Pergolesi, Silvia Rinaldi, Michele De Tursi, Maria Rita Migliorino, Francesca Rastelli, Daniela Iacono, Gian Carlo Antonini Cappellini, Rossana Berardi, Pietro Di Marino, Alessandro Parisi, Sergio Bracarda, Paolo A. Ascierto, Daniele Santini, Sebastiano Buti, Federica Zoratto, and Francesco Martella
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0301 basic medicine ,Oncology ,multiple neoplasms ,medicine.medical_specialty ,Multivariate analysis ,medicine.medical_treatment ,Immunology ,Programmed Cell Death 1 Receptor ,ddr genes ,B7-H1 Antigen ,family history of cancer ,immune checkpoint inhibitors ,03 medical and health sciences ,0302 clinical medicine ,Antineoplastic Agents, Immunological ,Internal medicine ,Neoplasms ,medicine ,Immunology and Allergy ,Humans ,cardiovascular diseases ,Family history ,Adverse effect ,RC254-282 ,Retrospective Studies ,Original Research ,business.industry ,Incidence (epidemiology) ,Hazard ratio ,pd-1 ,Cancer ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Retrospective cohort study ,Immunotherapy ,RC581-607 ,medicine.disease ,immunotherapy ,030104 developmental biology ,030220 oncology & carcinogenesis ,Immunologic diseases. Allergy ,business - Abstract
Background: We investigate the role of family history of cancer (FHC) and diagnosis of metachronous and/or synchronous multiple neoplasms (MN), during anti-PD-1/PD-L1 immunotherapy. Design: This was a multicenter retrospective study of advanced cancer patients treated with anti-PD-1/PD-L1 immunotherapy. FHC was collected in lineal and collateral lines, and patients were categorized as follows: FHC-high (in case of cancer diagnoses in both the lineal and collateral family lines), FHC-low (in case of cancer diagnoses in only one family line), and FHC-negative. Patients were also categorized according to the diagnosis of MN as follows: MN-high (>2 malignancies), MN-low (two malignancies), and MN-negative. Objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and incidence of immune-related adverse events (irAEs) of any grade were evaluated. Results: 822 consecutive patients were evaluated. 458 patients (55.7%) were FHC-negative, 289 (35.2%) were FHC-low, and 75 (9.1%) FHC-high, respectively. 29 (3.5%) had a diagnosis of synchronous MN and 94 (11.4%) of metachronous MN. 108 (13.2%) and 15 (1.8%) patients were MN-low and MN-high, respectively. The median follow-up was 15.6 months. No significant differences were found regarding ORR among subgroups. FHC-high patients had a significantly longer PFS (hazard ratio [HR] = 0.69 [95% CI: 0.48–0.97], p = .0379) and OS (HR = 0.61 [95% CI: 0.39–0.93], p = .0210), when compared to FHC-negative patients. FHC-high was confirmed as an independent predictor for PFS and OS at multivariate analysis. No significant differences were found according to MN categories. FHC-high patients had a significantly higher incidence of irAEs of any grade, compared to FHC-negative patients (p = .0012). Conclusions: FHC-high patients seem to benefit more than FHC-negative patients from anti-PD-1/PD-L1 checkpoint inhibitors.
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- 2020
36. Symptomatic COVID-19 in advanced-cancer patients treated with immune-checkpoint inhibitors. Prospective analysis from a multicentre observational trial by FICOG
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Vanja Vaccaro, Alessio Cortellini, Francesca Mazzoni, Carmine Pinto, Elena Verzoni, Vieri Scotti, Cinzia Baldessari, Ugo De Giorgi, Lucia Fratino, Sebastiano Buti, Francesco Verderame, Fausto Meriggi, Valentina Guadalupi, Francesco Di Costanzo, Saverio Cinieri, Giorgia Negrini, Stefania Gori, Pamela Guglielmini, Pasqualina Giordano, Mariella Sorarù, Davide Tassinari, Debora Pezzuolo, Francesco Carrozza, Lorenzo Calvetti, Claudia Mucciarini, Chiara Casadei, Sara Pilotto, Vincenzo Montesarchio, Massimo Di Maio, Evaristo Maiello, Nicola Battelli, Fable Zustovich, Alberto Clemente, Raffaele Giusti, Roberto Labianca, Simona Carnio, Giuseppe Fornarini, Mauro Iannopollo, Francesco Atzori, Paola Ermacora, Elisabetta Garzoli, Maria Banzi, Diana Giannarelli, Gaetano Lacidogna, Marco Filetti, Manlio Mencoboni, Lucia Longo, Angela Maria Dicorato, Diego Zara, Sandro Pignata, Claudio Verusio, Andrea Bonetti, Marcello Tiseo, Ernesto Rossi, Michele Tognetto, Marilena Di Napoli, Donata Sartori, Antonino Castro, Sergio Bracarda, Angela Gernone, Marco Maruzzo, Antonio Russo, Veronica Prati, Mimma Rizzo, Claudia Corbo, Alessandro Cappetta, Francesco Grossi, Paolo Andrea Zucali, Diego Signorelli, Fausto Barbieri, Antonello Veccia, Luigi Cavanna, and Melissa Bersanelli
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0301 basic medicine ,medicine.medical_specialty ,medicine.medical_treatment ,immune-checkpoint inhibitors ,influenza-like illness ,lcsh:RC254-282 ,03 medical and health sciences ,0302 clinical medicine ,Cancer immunotherapy ,Internal medicine ,Medicine ,Prospective cohort study ,Cancer staging ,Original Research ,Influenza-like illness ,business.industry ,SARS-CoV-2 ,virus diseases ,COVID-19 ,Immunotherapy ,cancer patients ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,Comorbidity ,Vaccination ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Observational study ,business - Abstract
Background:This prospective, multicentre, observational INVIDIa-2 study is investigating the clinical efficacy of influenza vaccination in advanced-cancer patients receiving immune-checkpoint inhibitors (ICIs), enrolled in 82 Italian centres, from October 2019 to January 2020. The primary endpoint was the incidence of influenza-like illness (ILI) until 30 April 2020. All the ILI episodes, laboratory tests, complications, hospitalizations and pneumonitis were recorded. Therefore, the study prospectively recorded all the COVID-19 ILI events.Patients and methods:Patients were included in this non-prespecified COVID-19 analysis, if alive on 31 January 2020, when the Italian government declared the national emergency. The prevalence of confirmed COVID-19 cases was detected as ILI episode with laboratory confirmation of SARS-CoV-2. Cases with clinical-radiological diagnosis of COVID-19 (COVID-like ILIs), were also reported.Results:Out of 1257 enrolled patients, 955 matched the inclusion criteria for this unplanned analysis. From 31 January to 30 April 2020, 66 patients had ILI: 9 of 955 cases were confirmed COVID-19 ILIs, with prevalence of 0.9% [95% confidence interval (CI): 0.3–2.4], a hospitalization rate of 100% and a mortality rate of 77.8%. Including 5 COVID-like ILIs, the overall COVID-19 prevalence was 1.5% (95% CI: 0.5–3.1), with 100% hospitalization and 64% mortality. The presence of elderly, males and comorbidities was significantly higher among patients vaccinated against influenza versus unvaccinated ( p = 0.009, p Conclusion:COVID-19 has a meaningful clinical impact on the cancer-patient population receiving ICIs, with high prevalence, hospitalization and an alarming mortality rate among symptomatic cases. Influenza vaccination does not protect from SARS-CoV-2 infection.
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- 2020
37. Real-World Data on Cabozantinib in Previously Treated Patients with Metastatic Renal Cell Carcinoma: Focus on Sequences and Prognostic Factors
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Alessia Cimadamore, Camillo Porta, Giacomo Cartenì, Paolo Andrea Zucali, Cinzia Ortega, Roberto Iacovelli, Matteo Santoni, Daniele Santini, Alessandra Mosca, Erin Pierce, Marc R. Matrana, Elena Verzoni, Orazio Caffo, Michele Milella, Rodolfo Montironi, Sebastiano Buti, Jeffrey Graham, Sara Merler, Francesco Carrozza, Sergio Bracarda, Marina Scarpelli, Umberto Basso, Francesco Massari, Francesco Piva, Liang Cheng, Vittorio Paolucci, Angelo Martignetti, Franco Morelli, Cristina Masini, Fabio Calabrò, Giuseppe Fornarini, Sarah Scagliarini, Lorena Incorvaia, Nuno Vau, Mimma Rizzo, Francesco Atzori, Alain Gelibter, Riccardo Ricotta, Antonio Lopez-Beltran, Maria Giuseppa Vitale, Ugo De Giorgi, Simon J. Crabb, Giulia Sorgentoni, Pierangela Sepe, Luca Galli, Giuseppe Procopio, Daniel Y. Heng, Alessandro Conti, Nicola Battelli, Santoni M., Heng D.Y., Bracarda S., Procopio G., Milella M., Porta C., Matrana M.R., Carteni G., Crabb S.J., De Giorgi U., Basso U., Masini C., Calabro F., Vitale M.G., Santini D., Massari F., Galli L., Fornarini G., Ricotta R., Buti S., Zucali P., Caffo O., Morelli F., Carrozza F., Martignetti A., Gelibter A., Iacovelli R., Mosca A., Atzori F., Vau N., Incorvaia L., Ortega C., Scarpelli M., Lopez-Beltran A., Cheng L., Paolucci V., Graham J., Pierce E., Scagliarini S., Sepe P., Verzoni E., Merler S., Rizzo M., Sorgentoni G., Conti A., Piva F., Cimadamore A., Montironi R., and Battelli N.
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0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,renal cell carcinoma ,Cabozantinib ,Prognosi ,Context (language use) ,urologic and male genital diseases ,lcsh:RC254-282 ,Article ,Pazopanib ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Renal cell carcinoma ,cabozantinib ,Internal medicine ,medicine ,Progression-free survival ,Nivolumab ,Prognosis ,Real-world data ,Targeted therapy ,nivolumab ,real-world data ,business.industry ,Sunitinib ,Retrospective cohort study ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,targeted therapy ,Axitinib ,030104 developmental biology ,chemistry ,030220 oncology & carcinogenesis ,prognosis ,business ,medicine.drug - Abstract
Cabozantinib is approved for the treatment of renal cell carcinoma (RCC). However, prognostic factors are still lacking in this context. The aim of this study was to evaluate prognostic factors in RCC patients treated with second- or third-line cabozantinib. A multicenter retrospective real-world study was conducted, involving 32 worldwide centers. A total of 237 patients with histologically confirmed clear-cell and non-clear-cell RCC who received cabozantinib as second- or third-line therapy for metastatic disease were included. We analyzed overall survival (OS), progression-free survival (PFS) and time-to-strategy failure (TTSF) using Kaplan&ndash, Meier curves. Cox proportional models were used at univariate and multivariate analyses.The median PFS and OS of cabozantinib were 7.76 months (95% CI 6.51&ndash, 10.88) and 11.57 months (95% CI 10.90&ndash, not reached (NR)) as second-line and 11.38 months (95% CI 5.79&ndash, NR) and NR (95% CI 11.51&ndash, NR) as third-line therapy. The median TTSF and OS were 11.57 and 15.52 months with the sequence of cabozantinib&ndash, nivolumab and 25.64 months and NR with nivolumab&ndash, cabozantinib, respectively. The difference between these two sequences was statistically significant only in good-risk patients. In the second-line setting, hemoglobin (Hb) levels (HR= 2.39, 95% CI 1.24&ndash, 4.60, p = 0.009) and IMDC (International Metastatic Renal Cell Carcinoma Database Consortium) group (HR = 1.72, 95% CI 1.04&ndash, 2.87, p = 0.037) were associated with PFS while ECOG-PS (HR = 2.33, 95%CI, 1.16&ndash, 4.69, p = 0.018) and Hb levels (HR = 3.12, 95%CI 1.18&ndash, 8.26, p = 0.023) correlated with OS at multivariate analysis, while in the third-line setting, only Hb levels (HR = 2.72, 95%CI 1.04&ndash, 7.09, p = 0.042) were associated with OS. Results are limited by the retrospective nature of the study.This real-world study provides evidence on the presence of prognostic factors in RCC patients receiving cabozantinib.
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- 2019
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38. Static antibiotic spacers augmented by calcium sulphate impregnated beads in revision TKA: Surgical technique and review of literature
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Luigi Sabatini, Alessandro Massè, Francesco Atzori, Pier Francesco Indelli, and Salvatore Risitano
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musculoskeletal diseases ,Antibiotic release ,030222 orthopedics ,medicine.medical_specialty ,medicine.drug_class ,business.industry ,Antibiotics ,Total knee arthroplasty ,Periprosthetic ,chemistry.chemical_element ,Calcium ,Article ,Surgery ,03 medical and health sciences ,0302 clinical medicine ,chemistry ,Surgical removal ,medicine ,Orthopedics and Sports Medicine ,030212 general & internal medicine ,business ,Surgical interventions - Abstract
Periprosthetic joint infection (PJI) is a serious complication in total knee arthroplasty (TKA) and represents one of the most common causes of revision. The challenge for surgeons treating an infected TKA is to quickly obtain an infection-free joint in order to re-implant, when possible, a new TKA. Recent literature confirms the role of local antibiotic-loaded beads as a strong bactericidal, allowing higher antibiotic elution when compared with antibiotic loaded spacers only. Unfortunately, classical Polymethylmethacrylate (PMMA) beads might allow bacteria adhesion, secondary development of antibiotic resistance and eventually surgical removal once antibiotics have eluted. This article describes a novel surgical technique using static, custom-made antibiotic loaded spacers augmented by calcium sulphate antibiotic-impregnated beads to improve the success rate of revision TKA in a setting of PJI. The use of calcium sulphate beads has several potential benefits, including a longer sustained local antibiotic release when compared with classical PMMA beads and, being resorbable, not requiring accessory surgical interventions.
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- 2018
39. 696P Is it possible to improve the prognostic ability of the IMDC score? Validation of the Meet-URO score in metastatic renal cell carcinoma (mRCC) patients (pts) receiving first-line nivolumab plus ipilimumab in the Italian Expanded Access Program (EAP)
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Mino Rizzo, A. Astone, U. De Giorgi, Sebastiano Buti, Sergio Bracarda, Fabio Calabrò, Giacomo Cartenì, L. Fratino, Giuseppe Fornarini, Giampaolo Tortora, Cinzia Baldessari, Matteo Santoni, Sara Elena Rebuzzi, Francesco Atzori, Alessio Signori, Lorenzo Antonuzzo, Laura Galli, Stefano Tamberi, Marco Maruzzo, and G. Procopio
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Oncology ,medicine.medical_specialty ,business.industry ,First line ,Ipilimumab ,Hematology ,medicine.disease ,Renal cell carcinoma ,Internal medicine ,Expanded access ,Medicine ,Nivolumab ,business ,medicine.drug - Published
- 2021
40. Effective combinatorial immunotherapy for castration-resistant prostate cancer: new future chance?
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Pina Ziranu, Francesco Atzori, Marco Puzzoni, Laura Demurtas, Giorgio Astara, and Mario Scartozzi
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Cancer Research ,Oncology ,Radiology, Nuclear Medicine and imaging - Published
- 2017
41. 736P Updated data on patients (pts) with metastatic renal cell carcinoma (mRCC) treated with sorafenib (SOR) vs observation (obs) after radical metastasectomy in the RESORT trial
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Rodolfo Passalacqua, Francesco Atzori, R. Montone, Giulia Apollonio, Franco Morelli, Alessandra Bearz, Michele Milella, Rosalba Miceli, Giuseppe Procopio, Pierangela Sepe, Valentina Guadalupi, Cinzia Ortega, Melanie Claps, Maddalena Donini, V.E. Chiuri, Francesco Cognetti, Alessia Mennitto, Alessandra Mosca, Elena Verzoni, and A. Martinetti
- Subjects
Sorafenib ,medicine.medical_specialty ,Oncology ,Renal cell carcinoma ,business.industry ,medicine ,Urology ,Hematology ,Metastasectomy ,medicine.disease ,business ,medicine.drug - Published
- 2020
42. Patellofemoral Joint Arthroplasty: Our Experience in Isolated Patellofemoral and Bicompartmental Arthritic Knees
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Luigi Sabatini, M. Schirò, Giovanni Battista Ferrero, Francesco Atzori, and Alessandro Massè
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medicine.medical_specialty ,total knee arthroplasty ,lcsh:Diseases of the musculoskeletal system ,medicine.medical_treatment ,Total knee arthroplasty ,Arthritis ,Patellofemoral joint ,Osteoarthritis ,Bioinformatics ,03 medical and health sciences ,0302 clinical medicine ,Rheumatology ,Immunology and Allergy ,Medicine ,Unicompartmental knee arthroplasty ,030222 orthopedics ,Bone preservation ,business.industry ,patellofemoral arthritis ,030229 sport sciences ,medicine.disease ,Arthroplasty ,patellofemoral joint arthroplasty ,Surgery ,bicompartmental knee arthroplasty ,Implant ,lcsh:RC925-935 ,business ,Rapid Communication - Abstract
Introduction Isolated patellofemoral (PF) arthritis is rare, and there is no complete agreement about the best surgical treatment. The operative treatments are total knee arthroplasty and patellofemoral replacement (PFR). The incidence of many early complications of PF arthroplasty has decreased with the introduction of newer designs. Nowadays, the main cause of revision surgery is the progression of tibiofemoral osteoarthritis. In the past, PF arthroplasty was contraindicated in patients with evidence of osteoarthritis or pain in medial or lateral tibiofemoral compartments. The improvement in implant designs and surgical techniques has allowed the addition of a monocompartmental arthroplasty for the medial or lateral tibiofemoral compartment. In this work, we evaluate our first experience with PF arthroplasty and its combination with unicompartmental knee arthroplasty. Materials and Methods From May 2014 to March 2016, we treated 14 patients. An isolated PF arthroplasty was performed in six knees (five patients), and a combined PF and unicompartmental knee arthroplasty was performed in nine cases. We observed a significant improvement in the clinical and functional Knee Society Scores (KSSs) after surgery in our patients. Results We obtained good results in our cases both for clinical and functional KSSs. Patellar clunk was recorded in one case. Discussion and Conclusion We are going toward a new attitude in which partial osteoarthritic changes could be treated with partial resurfacing prosthetic solutions such as unicompartmental, bi–unicompartmental or PFR alone, or unicompartmental combined, which respects the cruciates and achieves maximal bone preservation, which is vital, particularly, for young patients.
- Published
- 2016
43. Sorafenib Versus Observation Following Radical Metastasectomy for Clear-cell Renal Cell Carcinoma: Results from the Phase 2 Randomized Open-label RESORT Study
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Elena Verzoni, Giuseppe Procopio, Vincenzo Emanuele Chiuri, Alessandra Raimondi, Cinzia Ortega, Vera Cappelletti, Francesco Cognetti, Antonia Martinetti, Filippo de Braud, Raffaele Ratta, Alessandra Mosca, Michele Milella, Umberto Capitanio, Giulia Apollonio, Alessandra Bearz, Franco Morelli, Rosalba Miceli, Melanie Claps, Maddalena Donini, and Francesco Atzori
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Sorafenib ,Adult ,Male ,medicine.medical_specialty ,Urology ,medicine.medical_treatment ,Population ,030232 urology & nephrology ,Phases of clinical research ,Antineoplastic Agents ,urologic and male genital diseases ,03 medical and health sciences ,0302 clinical medicine ,Renal cell carcinoma ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Radical surgery ,education ,Carcinoma, Renal Cell ,Aged ,education.field_of_study ,business.industry ,Metastasectomy ,Middle Aged ,medicine.disease ,Nephrectomy ,Clear cell renal cell carcinoma ,Oncology ,030220 oncology & carcinogenesis ,Surgery ,Female ,business ,medicine.drug - Abstract
Background In selected metastatic renal cell carcinoma (mRCC) patients, radical metastasectomy followed by observation is a potential strategy. It is still to be defined whether systemic therapy should be administered following metastasectomy. Objective To assess the potential benefit of postoperative treatment with sorafenib compared with observation alone after radical metastasectomy in mRCC patients. Design, setting, and participants The RESORT trial was a multicenter, randomized, open-label, phase 2 study conducted between November 2012 and November 2017 in Italy. Patients with clear-cell mRCC pretreated with nephrectomy and undergoing radical metastasectomy (three or fewer lesions) were eligible for the study. Patients were randomized (1:1) within 12 wk from metastasectomy to sorafenib (standard dose 400 mg twice daily) or observation for a maximum of 52 wk. Stratification factors were interval from nephrectomy, site, and number of lesions. Overall, 76 patients were screened and 69 were randomized: 33 were assigned to sorafenib and 36 to observation. The primary endpoint was recurrence-free survival (RFS). Secondary endpoints were overall survival and the safety profile. Outcome measurements and statistical analysis RFS curves were estimated with the Kaplan-Meier method, and the log-rank test was used to statistically compare the curves. Results and limitations At a median follow-up of 38 mo, median RFS was 37 mo (95% confidence interval [CI] 20–not available [NA]) in the observation arm versus 21 mo (95% CI 11–NA) in the sorafenib arm (log-rank test p = 0.404), with 12-, 24-, and 36-mo RFS probability of 74% versus 63%, 59% versus 49%, and 50% versus 41%, respectively, in the observation versus the sorafenib arm. Any-grade adverse event (AE) rates were 84% in the sorafenib arm and 31% in the observation arm; grade ≥3 AE rates were 22% and 3% in the sorafenib and the observation arm, respectively, with a rate of treatment discontinuation for AEs of 19% in the sorafenib arm. Conclusions This prospective study showed that systemic treatment with sorafenib did not increase RFS as compared with observation in mRCC patients following radical metastasectomy. Patient summary This article reports the clinical outcome of patients with metastatic renal cell carcinoma treated with sorafenib or managed with an observation-alone strategy after the radical surgery of metastases. We found that sorafenib did not improve the patient outcome in terms of relapse-free survival in this selected population.
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- 2019
44. Is There Still a Role for Endocrine Therapy Alone in HR+/HER2- Advanced Breast Cancer Patients? Results from the Analysis of Two Data Sets of Patients Treated with High-Dose Fulvestrant as First-Line Therapy in the Real-World Setting: The EVA and GIM-13 AMBRA Studies
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Michela Maur, A. Frassoldati, Alberto Zambelli, Antonio Febbraro, L. Livi, Raffaella Palumbo, Luca Clivio, Alessandra Fabi, D Sartori, Salvatore Artale, Ornella Garrone, A. Ferzi, N. La Verde, Marina Elena Cazzaniga, M. De Laurentiis, Lucia Mentuccia, Mariangela Ciccarese, M. Donadio, Piero Marchetti, Clara Natoli, A. Turletti, Mirco Pistelli, Claudio Scavelli, Luca Gianni, E. Romagnoli, Giancarlo Bisagni, G. Mustacchi, A. Schirone, Patrizia Vici, M. Porpiglia, M. Giordano, Daniele Generali, Livio Blasi, Andrea Michelotti, Valter Torri, Filippo Montemurro, Claudio Verusio, Giulia Bianchi, Paolo Pronzato, Corrado Ficorella, Laura Biganzoli, Ferdinando Riccardi, Francesco Atzori, L. Del Mastro, Daniele Santini, G. Moretti, A. Fumagalli, Vittorio Gebbia, Antonino Musolino, Maria Rosaria Valerio, Marta Airoldi, Cazzaniga, M. E., Verusio, C., Ciccarese, M., Fumagalli, A., Sartori, D., Valerio, M. R., Airoldi, M., Moretti, G., Ficorella, C., Gianni, L., Michelotti, A., Zambelli, A., Febbraro, A., Generali, D., Pistelli, M., Garrone, O., Musolino, A., Vici, P., Maur, M., Mentuccia, L., La Verde, N., Bianchi, G. V., Artale, S., Blasi, L., De Laurentiis, M., Atzori, F., Turletti, A., Porpiglia, M., Santini, D., Fabi, A., Gebbia, V., Schirone, A., Palumbo, R., Ferzi, A., Frassoldati, A., Scavelli, C., Clivio, L., Giordano, M., Donadio, M., Biganzoli, L., Del Mastro, L., Bisagni, G., Livi, L., Natoli, C., Montemurro, F., Riccardi, F., Romagnoli, E., Marchetti, P., Torri, V., Pronzato, P., Mustacchi, G., Cazzaniga M.E., Verusio C., Ciccarese M., Fumagalli A., Sartori D., Valerio M.R., Airoldi M., Moretti G., Ficorella C., Gianni L., Michelotti A., Zambelli A., Febbraro A., Generali D., Pistelli M., Garrone O., Musolino A., Vici P., Maur M., Mentuccia L., La Verde N., Bianchi G.V., Artale S., Blasi L., De Laurentiis M., Atzori F., Turletti A., Porpiglia M., Santini D., Fabi A., Gebbia V., Schirone A., Palumbo R., Ferzi A., Frassoldati A., Scavelli C., Clivio L., Giordano M., Donadio M., Biganzoli L., Del Mastro L., Bisagni G., Livi L., Natoli C., Montemurro F., Riccardi F., Romagnoli E., Marchetti P., Torri V., Pronzato P., Mustacchi G., Cazzaniga, M, Verusio, C, Ciccarese, M, Fumagalli, A, Sartori, D, Valerio, M, Airoldi, M, Moretti, G, Ficorella, C, Gianni, L, Michelotti, A, Zambelli, A, Febbraro, A, Generali, D, Pistelli, M, Garrone, O, Musolino, A, Vici, P, Maur, M, Mentuccia, L, La Verde, N, Bianchi, G, Artale, S, Blasi, L, De Laurentiis, M, Atzori, F, Turletti, A, Porpiglia, M, Santini, D, Fabi, A, Gebbia, V, Schirone, A, Palumbo, R, Ferzi, A, Frassoldati, A, Scavelli, C, Clivio, L, Giordano, M, Donadio, M, Biganzoli, L, Del Mastro, L, Bisagni, G, Livi, L, Natoli, C, Montemurro, F, Riccardi, F, Romagnoli, E, Marchetti, P, Torri, V, Pronzato, P, and Mustacchi, G
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Oncology ,medicine.medical_specialty ,medicine.drug_class ,Population ,Anastrozole ,NO ,Internal medicine ,Fulvestrant · First-line setting · Hormone receptor positive, Advanced breast cancer ,medicine ,Adjuvant therapy ,Progression-free survival ,education ,Fulvestrant ,First-Line setting ,education.field_of_study ,Hormone receptor positive ,Aromatase inhibitor ,EVA ,business.industry ,trials ,Cancer ,Endocrine Therapy ,GIM-13 ,medicine.disease ,Endocrine Therapy, HR+/HER2–, Advanced Breast Cancer, High-Dose, Fulvestrant, First-Line setting, EVA, GIM-13, AMBRA, trials ,Advanced breast cancer ,First-line setting ,HR+/HER2– ,Advanced Breast Cancer ,Surgery ,AMBRA ,business ,High-Dose ,Tamoxifen ,Research Article ,medicine.drug - Abstract
Background: Different studies suggest that fulvestrant 500 mg every 28 days (HD-FUL) could be an active treatment in HR+ advanced breast cancer (ABC) patients even treated with aromatase inhibitors in the adjuvant setting. The aim of this analysis is to describe the outcome of ABC patients treated with HD-FUL as first-line treatment in terms of median duration of treatment and the overall response rate in a real-world setting. Methods: For the purpose of the present analysis, we considered two data sets of HR+ ABC patients collected in Italy between 2012 and 2015 (EVA and GIM-13 AMBRA studies). Results: Eighty-one and 91 patients have been identified from the two data sets. The median age was 63 years (range 35–82) for the EVA and 57.8 years (range 35.0–82.3) for the AMBRA patients. ORRs were 23.5 and 24.3% in the whole population, 26.9% in the patients with bone only, and 21.8 and 21.4% in those with visceral metastases. The median duration of HD-FUL was 11.6 months (range 1–48) and 12.4 months (range 2.9–70.0) in the two data sets, respectively. Conclusion: These data suggest that HD-FUL should still continue to play a significant role as first-line therapy in HR+ ABC patients.
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- 2019
45. Correlations Between the Immune-related Adverse Events Spectrum and Efficacy of Anti-PD1 Immunotherapy in NSCLC Patients
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Rosa Rita Silva, Antonino Grassadonia, Marco Russano, Michele De Tursi, Biagio Ricciuti, Raffaele Giusti, Rita Chiari, Katia Cannita, Sebastiano Buti, Daniele Santini, Corrado Ficorella, Federica Zoratto, Paolo Marchetti, Melissa Bersanelli, Maria Rita Migliorino, Paola Bordi, Giampiero Porzio, N. Tinari, Fabiana Perrone, Francesco Atzori, Enzo Veltri, Pietro Di Marino, Cecilia Anesi, Marco Filetti, Tea Zeppola, Rossana Berardi, Alessio Cortellini, Giulio Metro, Marcello Tiseo, Silvia Rinaldi, Marianna Tudini, Francesco Malorgio, Daniela Iacono, Annagrazia Pireddu, and Carlo Garufi
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0301 basic medicine ,Oncology ,Cancer Research ,Multivariate analysis ,medicine.medical_treatment ,Pembrolizumab ,carcinoma ,NSCLC ,survival analysis ,0302 clinical medicine ,Immune-related adverse events ,Carcinoma, Non-Small-Cell Lung ,italy ,middle aged ,80 and over ,antibodies ,humans ,Aged, 80 and over ,humanized ,adult ,aged ,retrospective studies ,female ,Nivolumab ,030220 oncology & carcinogenesis ,young adult ,Immunotherapy ,Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,immune system diseases ,monoclonal ,lung neoplasms ,Antibodies, Monoclonal, Humanized ,programmed cell death 1 receptor ,03 medical and health sciences ,Immune system ,male ,Internal medicine ,medicine ,Adverse effect ,Lung cancer ,business.industry ,Surrogate endpoint ,medicine.disease ,non-small-cell lung ,030104 developmental biology ,drug-related side effects and adverse reactions ,treatment outcome ,immune-related adverse events ,immunotherapy ,nivolumab ,nsclc ,pembrolizumab ,business - Abstract
Immune-related adverse events (irAEs) developed during immunotherapy with anti-PD-1 agents, could be a predictive surrogate marker of clinical benefit in patients with advanced non-small-cell lung cancer (NSCLC).Patients with NSCLC, treated with anti-PD-1 agents, were retrospectively evaluated. Univariate and multivariate analyses were performed to evaluate the relationships between types of irAEs (differentiated according to system/organ involved and to single-site/multiple-site), overall response rate (ORR), progression-free survival (PFS) and overall survival (OS). We further performed a 6-week landmark analysis.A total of 559 patients were enrolled; 231 patients (41.3%) developed irAEs of any grade and 50 patients (8.9%) G3/G4 events; 191 of them (82.6%) developed "single-site" irAEs and 40 (17.4%) "multiple-site" irAEs. At multivariate analysis, higher ORR was related to irAEs of any grade (P .0001), "single-site" irAEs (P .0001), endocrine (P = .0043) and skin irAEs (P = .0005). Longer PFS was related to irAEs of any grade (P .0001), "single-site" irAEs (P .0001), "multiple-site" irAEs (P = .0374), endocrine irAEs (P = .0084) and skin irAEs (P = .0001). Longer OS was related to irAEs of any grade (P .0001), "single-site" irAEs (P .0001), endocrine irAEs (P = .0044), gastrointestinal irAEs (P = .0437), skin irAEs (P = .0006), and others irAEs (P = .0378). At the 6-week landmark analysis, irAEs of any grade was confirmed an independent predictor of higher ORR, longer PFS, and longer OS.Our study confirmed that irAEs are concordantly related to higher ORR, longer PFS, and longer OS with anti-PD-1 immunotherapy in patients with NSCLC.
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- 2019
46. Clinical Outcomes of Patients with Advanced Cancer and Pre-Existing Autoimmune Diseases Treated with Anti-Programmed Death-1 Immunotherapy: A Real-World Transverse Study
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Carlo Garufi, Antonino Grassadonia, Maria Giuseppa Vitale, Sergio Bracarda, Roberto Sabbatini, Tea Zeppola, Paolo A. Ascierto, Riccardo Marconcini, Andrea Botticelli, Marcello Tiseo, Cecilia Anesi, Giampiero Porzio, Raffaele Giusti, Gian Carlo Antonini Cappellini, Fabiana Perrone, Valeria Ciciarelli, Maria Concetta Fargnoli, Francesco Atzori, Sebastiano Buti, Enzo Veltri, Marco Filetti, Alessio Cortellini, Paolo Marchetti, Daniela Iacono, Michele De Tursi, Federica De Galitiis, Rossana Berardi, Annagrazia Pireddu, Davide Brocco, Melissa Bersanelli, Marianna Tudini, Rosa Rita Silva, Silvia Rinaldi, Federica Zoratto, Maria Rita Migliorino, Marco Russano, Antonio Rossi, Biagio Ricciuti, Katia Cannita, Francesco Malorgio, Maria Michiara, Rita Chiari, Daniele Santini, Nicola Tinari, and Corrado Ficorella
- Subjects
Adult ,Male ,0301 basic medicine ,Cancer Research ,medicine.medical_specialty ,Drug-Related Side Effects and Adverse Reactions ,medicine.medical_treatment ,Programmed Cell Death 1 Receptor ,Severity of Illness Index ,Autoimmune Diseases ,Young Adult ,03 medical and health sciences ,Immune checkpoint inhibitors ,Antineoplastic Agents, Immunological ,0302 clinical medicine ,Acquired immunodeficiency syndrome (AIDS) ,Neoplasms ,Internal medicine ,Autoimmune disease ,medicine ,Humans ,Anti-programmed death-1 ,Immunotherapy ,Performance status ,Sex ,Oncology ,Adverse effect ,Aged ,Retrospective Studies ,Aged, 80 and over ,business.industry ,Incidence ,Incidence (epidemiology) ,Middle Aged ,medicine.disease ,Immuno‐Oncology ,Progression-Free Survival ,Clinical trial ,030104 developmental biology ,030220 oncology & carcinogenesis ,Female ,business ,Kidney cancer - Abstract
BACKGROUND. Patients with a history of autoimmune diseases (AIDs) have not usually been included in clinical trials with immune checkpoint inhibitors. MATERIALS AND METHODS. Consecutive patients with advanced cancer, treated with anti‐programmed death‐1 (PD‐1) agents, were evaluated according to the presence of pre‐existing AIDs. The incidence of immune‐related adverse events (irAEs) and clinical outcomes were compared among subgroups. RESULTS. A total of 751 patients were enrolled; median age was 69 years. Primary tumors were as follows: non‐small cell lung cancer, 492 (65.5%); melanoma, 159 (21.2%); kidney cancer, 94 (12.5%); and others, 6 (0.8%). Male/female ratio was 499/252. Eighty‐five patients (11.3%) had pre‐existing AIDs, further differentiated in clinically active (17.6%) and inactive (82.4%). Among patients with pre‐existing AIDs, incidence of irAEs of any grade was significantly higher when compared with patients without AIDs (65.9% vs. 39.9%). At multivariate analysis, both inactive (p = .0005) and active pre‐existing AIDs (p = .0162), female sex (p = .0004), and Eastern Cooperative Oncology Group Performance Status
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- 2019
47. Efficacy and safety of neoadjuvant chemotherapy plus trastuzumab and pertuzumab in non-metastatic HER2-positive breast cancer in real life: NEOPEARL study
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A. Vaccaro, Enzo Maria Ruggeri, Elisabetta Cretella, Daniele Alesini, Armando Orlandi, G. Piesco, M. Persano, Luca Moscetti, A. Botticelli, R. Ceccherini, Maria Agnese Fabbri, Federico Piacentini, A. Mercanti, Valentina Sini, Francesco Atzori, Claudia Omarini, A. Fabi, Laura Pizzuti, and M.L. Framarino
- Subjects
Oncology ,medicine.medical_specialty ,Chemotherapy ,business.industry ,medicine.medical_treatment ,macromolecular substances ,Hematology ,Loading dose ,Chemotherapy regimen ,Carboplatin ,chemistry.chemical_compound ,chemistry ,Docetaxel ,Trastuzumab ,Internal medicine ,medicine ,Pertuzumab ,business ,Neoadjuvant therapy ,medicine.drug - Abstract
Background In HER2+ breast cancer (BC) patients (pts) the pathological complete response (pCR) is associated with improved survival. With regimens based on the combination of trastuzumab (T), pertuzumab (P) and chemotherapy, pCR rates are slightly over 48%. We conducted a retrospective analysis on HER2+ BC pts to describe the outcomes of neoadjuvant combination of P+T and chemotherapy in the real-life setting. Methods Our cohort included 64 pts treated between Sept 2015 and Mar 2018 in 15 Italian Cancer Centers. Treatment outcomes were analyzed in terms of pCR (defined as ypT0/Tis, ypN0i-) and toxicities, recorded according to National Cancer Institute Common Toxicity Criteria. Statistical analysis was performed with T di Student test and χ2 test. Results Overall, in the 55 evaluable pts median age was 50 (range 28-77) and 29 pts (53%) were pre-menopausal. 24 pts (45%) were ER-/PgR-, 12 (21%) ER+/PgR-, 16 (29%) ER+/PgR+, median ki67 was 40. 9% of pts were cT1, 73% cT2, 13% cT3 and 5% cT4; 42 pts (76%) were cN+. All pts received 4 cycles of T (8 mg/kg loading dose, followed by 6 mg/kg every 3 weeks) and P (loading dose 840 mg, followed by 420 mg every 3 weeks). In 42 pts T+P were administered with docetaxel (75 mg/mq every 3 weeks), in 8 pts with paclitaxel (80 mg/mq) and 5 pts received docetaxel and carboplatin (AUC5). In 13 pts also 3 cycles of anthracyclines, according to the FEC scheme, were administered. A pCR was achieved in 29 pts (53%). No significant associations were found between pCR and baseline characteristics or treatments schedule. Seven out of 55 (13%) pts reported G3-G4 toxicities (5 pts neutropenia G3-G4, 1 pt vomiting G3, 1 pt diarrhoea G3, 1 pt anemia G3). Three out of 4 pts treated with docetaxel, carboplatin and P+T reported G3/G4 toxicities. A significant association was found between chemotherapy schedule and toxicities (p = 0.004). Conclusions The association of P+T+chemotherapy improved pCR rate in HER2+ BC pts treated in the real-life setting. Our results showed that the selection of chemotherapy that will be associated with the dual blockade of HER2 is of paramount importance in order to avoid severe toxicities and increase the compliance with treatment. Legal entity responsible for the study Department of Oncology, Belcolle Hospital. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.
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- 2019
48. A multicenter study of body mass index in cancer patients treated with anti-PD-1/PD-L1 immune checkpoint inhibitors: When overweight becomes favorable
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Mario Occhipinti, Gian Carlo Antonini Cappellini, Marco Filetti, Giampiero Porzio, Clara Natoli, Andrea De Giglio, Francesca Rastelli, Federica Zoratto, Silvia Rinaldi, Cecilia Anesi, Sebastiano Buti, Rita Chiari, Fabiana Perrone, Francesco Atzori, Pietro Di Marino, Andrea Botticelli, Enzo Veltri, Melissa Bersanelli, Federica Pergolesi, Nicola Tinari, Alessio Cortellini, Paolo A. Ascierto, Corrado Ficorella, Daniele Santini, Alain Gelibter, Marianna Tudini, Rossana Berardi, Maria Concetta Fargnoli, Tea Zeppola, Rosa Rita Silva, Marcello Tiseo, Riccardo Marconcini, Daniela Iacono, Raffaele Giusti, Federica De Galitiis, Annagrazia Pireddu, Paolo Marchetti, Alessandro Parisi, Francesco Malorgio, Maria Giuseppa Vitale, Michele De Tursi, Maria Michiara, Marco Russano, Biagio Ricciuti, Katia Cannita, Cortellini A., Bersanelli M., Buti S., Cannita K., Santini D., Perrone F., Giusti R., Tiseo M., Michiara M., Di Marino P., Tinari N., De Tursi M., Zoratto F., Veltri E., Marconcini R., Malorgio F., Russano M., Anesi C., Zeppola T., Filetti M., Marchetti P., Botticelli A., Antonini Cappellini G.C., De Galitiis F., Vitale M.G., Rastelli F., Pergolesi F., Berardi R., Rinaldi S., Tudini M., Silva R.R., Pireddu A., Atzori F., Chiari R., Ricciuti B., De Giglio A., Iacono D., Gelibter A., Occhipinti M.A., Parisi A., Porzio G., Fargnoli M.C., Ascierto P.A., Ficorella C., and Natoli C.
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Male ,0301 basic medicine ,Cancer Research ,Programmed Cell Death 1 Receptor ,Kaplan-Meier Estimate ,Anti-PD-1/PD-L1 ,Overweight ,Gastroenterology ,B7-H1 Antigen ,Body Mass Index ,Antineoplastic Agents, Immunological ,0302 clinical medicine ,BMI ,Cancer ,Immunotherapy ,Obesity ,Immunology and Allergy ,Immunology ,Molecular Medicine ,Oncology ,Pharmacology ,Renal cell carcinoma ,Neoplasms ,Molecular Targeted Therapy ,Aged, 80 and over ,Middle Aged ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Treatment Outcome ,030220 oncology & carcinogenesis ,Female ,Underweight ,medicine.symptom ,Research Article ,Adult ,medicine.medical_specialty ,lcsh:RC254-282 ,Young Adult ,03 medical and health sciences ,Internal medicine ,Biomarkers, Tumor ,medicine ,Humans ,Aged ,Neoplasm Staging ,Proportional Hazards Models ,business.industry ,nutritional and metabolic diseases ,Retrospective cohort study ,medicine.disease ,Clinical trial ,030104 developmental biology ,business ,Body mass index - Abstract
Background Recent evidence suggested a potential correlation between overweight and the efficacy of immune checkpoint inhibitors (ICIs) in cancer patients. Patients and methods We conducted a retrospective study of advanced cancer patients consecutively treated with anti-PD-1/PD-L1 inhibitors, in order to compare clinical outcomes according to baseline BMI levels as primary analysis. Based on their BMI, patients were categorized into overweight/obese (≥ 25) and non-overweight (
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- 2019
49. The effect of a treatment delay on outcome in metastatic renal cell carcinoma
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Francesco Atzori, Roberto Sabbatini, Ugo De Giorgi, Elisa Biasco, Riccardo Ricotta, Luca Galli, Paolo Andrea Zucali, Giuseppe Fornarini, Francesco Massari, Nicole Gri, Elena Verri, Sebastiano Buti, Alessandra Mosca, Camillo Porta, Roberto Iacovelli, Chiara Miggiano, Franco Nolè, Cristina Masini, Cristian Lolli, Gaetano Facchini, Giampaolo Tortora, Daniele Santini, and Maria Giuseppa Vitale
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Male ,medicine.medical_specialty ,Urology ,medicine.medical_treatment ,030232 urology & nephrology ,Gastroenterology ,Time-to-Treatment ,03 medical and health sciences ,0302 clinical medicine ,Renal cell carcinoma ,Internal medicine ,medicine ,Humans ,Progression-free survival ,Neoplasm Metastasis ,Carcinoma, Renal Cell ,Survival analysis ,business.industry ,Hazard ratio ,Bone metastasis ,Middle Aged ,medicine.disease ,Survival Analysis ,Confidence interval ,Nephrectomy ,Editorial Commentary ,Oncology ,030220 oncology & carcinogenesis ,Localized disease ,Female ,business - Abstract
Objectives To investigate if a first-line treatment delay (TD) can negatively affect the outcomes of patients affected by metastatic renal cancer. Patients and methods Patients with a diagnosis of metastatic renal cancer who were ineligible for active surveillance were included in the sample. A TD was defined as the time from the diagnosis of metastatic disease to the start of first-line therapy with tyrosine kinase inhibitors. Results A total of 835 patients were assessed and 635 were included in the final analysis. The median TD was 6.3 weeks. No significant differences were found in baseline characteristics between patients experiencing a TD below/equal to or above the median value, with the exceptions being the rate of bone metastases (25.3% vs. 35.9%) and advanced disease at diagnosis (34.7% vs. 54.9%). In patients who had received a previous nephrectomy for localized disease, the TD was 5.3 compared to 8.0 weeks for those with metastatic disease at diagnosis (P = 0.001). Among this latter group, 68.7% had received a cytoreductive nephrectomy. In patients with a TD below/equal to and above the median value, the median progression-free survival was 10.3 and 11.2 months, respectively (hazard ratio = 1.03; 95% confidence intervals, 0.86–1.22; P = 0.78); the median overall survival was 27.3 and 28.2 months, respectively (hazard ratio = 1.04; 95% confidence intervals, 0.86–1.27; P = 0.68). The lack of differences was confirmed when adjusted for prognostic factors and baseline characteristics. Conclusions This study reports that patients with bone metastases and advanced disease at diagnosis have a significant probability of experiencing delayed first-line therapy of more than 6 weeks from the time of diagnosis. However, a TD does not significantly affect outcomes and survival.
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- 2018
50. Baseline and early change of systemic inflammation index (bSII and ΔSII) as prognostic factors in metastatic renal cell carcinoma (mRCC) patients treated with Nivolumab: Final results of the Meet-URO 15 (I-BIO-REC) study
- Author
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Marco Messina, Giuseppe Fornarini, Francesca Vignani, Francesco Atzori, Ugo De Giorgi, Silvia Chiellino, Sara Elena Rebuzzi, Paolo Andrea Zucali, Federico Paolieri, Giandomenico Roviello, Veronica Prati, Alessio Signori, Emanuela Fantinel, Melissa Bersanelli, Alessia Cavo, Giuseppe Procopio, Hector Soto Parra, Davide Bimbatti, Marco Stellato, and Marilena Di Napoli
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Immunotherapy ,Systemic inflammation ,medicine.disease ,Renal cell carcinoma ,Internal medicine ,medicine ,Nivolumab ,medicine.symptom ,business - Abstract
5072 Background: Biomarkers to select mRCC patients most likely to benefit to immunotherapy are still needed. The retrospective multicentre Meet-URO-15 study evaluated the prognostic role of peripheral blood cells in mRCC patients treated with Nivolumab. Methods: Complete blood count was collected at the first four cycles of Nivolumab. The primary endpoint was median overall survival (mOS) according to baseline neutrophil-to-lymphocyte ratio. Secondary analyses included bSII defined as platelet x NLR (cutoff = 1375) and ΔSII defined as the difference between SII at 2ndcycle and bSII (median used as cutoff = 383). Results: From October 2015 to October 2019, 470 patients started Nivolumab as 2nd(67%), 3rd(22%) and > 3rd(11%) line. Median age was 66 years, 71% were male and 83% had clear cell histology. Baseline IMDC group was favorable in 25%, intermediate in 63% and poor in 12%. Lymph-nodes, visceral and bone metastases were present in 54%, 91% and 36%. mOS and progression-free survival (PFS) were 34.8 and 7.5 months. Overall response rate (ORR) and disease control rate (DCR) were 30% and 61%. SII was available in 404 patients: SII < 1375 (82%) correlated with statistically significant improvement of PFS [10.2 vs 4.1 months, HR 2.06 (1.54-2.76), p< 0.001], OS [46.2 vs 9.5 months, HR 3.16 (2.23-4.49), p< 0.001], ORR (35% vs 21%, p= 0.035) and DCR (67% vs 40%, p< 0.001). ΔSII was available in 360 patients: ΔSII < 383 (75%) correlated with statistically significant improvement of PFS [11.3 vs 4.7 months; HR 1.64 (1.23-2.18), p= 0.001] and OS [NR vs 21.1 months; HR 1.76 (1.21-2.56), p= 0.003], ORR (37% vs 24%, p= 0.023) and DCR (68% vs 53%, p= 0.01). Multivariate analyses adjusted for IMDC group, line of therapy and metastatic sites, confirmed the statistically significant correlation of bSII and ΔSII with OS, PFS and DCR. Conclusions: Our study showed the statistically significant correlation of lower bSII and early ΔSII with longer OS, PFS and higher DCR in mRCC patients treated with Nivolumab.
- Published
- 2020
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