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1. Atezolizumab and chemotherapy for advanced or recurrent endometrial cancer (AtTEnd): a randomised, double-blind, placebo-controlled, phase 3 trial

Author

Zola, Paolo, Casanova, Claudia, Arcangeli, Valentina, Antonuzzo, Lorenzo, Gadducci, Angiolo, Cosio, Stefania, Clamp, Andrew, Persic, Mojca, McNeish, Ian, Tookman, Laura, Redondo Sanchez, Andrés, Choi, Chel Hun, Baldini, Editta, Palaia, Innocenza, Benedetti Panici, Pierluigi, Takahashi, Nobutaka, Lombard, Janine, Ardizzoia, Antonio, Bologna, Alessandra, Herrero Ibáñez, Ana Maria, Musolino, Antonino, Márquez Vázquez, Raúl, Pietzner, Klaus, Braicu, Elena, Heinzelmann-Schwarz, Viola A., Powell, Melanie, Yokoyama, Yoshihito, Baron-Hay, Sally, Abeni, Chiara, Martin Lorente, Cristina, Cueva, Juan Fernando, Trillsch, Fabian, Heitz, Florian, Ataseven, Beyhan, Petru, Edgar, Heubner, MartinLeonhard, Sadozye, Azmat Hassanq, Dubey, Sidharth, Tazbirkova, Andrea, Tiley, Susan, Chrystal, Kathryn, Kim, Sang Wun, Fehr, Mathias, Scatchard, Kate, Anand, Anjana, Taylor, Alexandra, Watary, Hidemichi, Enomoto, Takayuki, Yoshihara, Kosuke, Selva-Nayagam, Sudarsha, Karki, Bhaskar, Harrison, Michelle, Wilkinson, Kate, Goh, Jeffrey, Glasgow, Amanda, Chantrill, Lorraine, Lee, Chulmin, Bertolini, Alessandro, Narducci, Filomena, Bellotti, Giovanna, Fusco, Vittorio, Aebi, Stefan, Del Grande, Maria, Colombo, Ilaria, Tokunaga, Hideki, Shigeta, Shogo, Goss, Geraldine, Siow, Zhen Rong, Steer, Christopher, Lin, Hao, Lee, Kwang-Beom, Di Meglio, Giovanni, Massa, Elena, De Marino, Elvira, Tortora, Vincenzo, Palacio Vazquez, Isabel, Tsuji, Kosuke, Tominaga, Eiichiro, Black, Allison, So, Kyeong A, Suh, Dong Hoon, Lee, Keun Ho, Kim, Yong Man, Fossati, Roldano, Carlucci, Luciano, Barberis, Massimo, Torri, Valter, Santoni, Anna, Colombo, Nicoletta, Biagioli, Elena, Harano, Kenichi, Galli, Francesca, Hudson, Emma, Antill, Yoland, Rabaglio, Manuela, Marmé, Frederic, Marth, Christian, Parma, Gabriella, Fariñas-Madrid, Lorena, Nishio, Shin, Allan, Karen, Lee, Yeh Chen, Piovano, Elisa, Pardo, Beatriz, Nakagawa, Satoshi, McQueen, John, Zamagni, Claudio, Manso, Luis, Takehara, Kazuhiro, Tasca, Giulia, Ferrero, Annamaria, Tognon, Germana, Lissoni, Andrea Alberto, Petrella, Mariacristina, Laudani, Maria Elena, Rulli, Eliana, Uggeri, Sara, and Barretina Ginesta, M Pilar

Published
2024
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3. Long-Alkyl Chain Functionalized Imidazo[1,5-a]pyridine Derivatives as Blue Emissive Dyes

Author

Gioele Colombo, Anita Cinco, G. Attilio Ardizzoia, and Stefano Brenna

Subjects
boron difluoride, imidazo[1,5-a]pyridine, blue emission, fluorescence, TD-DFT, Chemistry, QD1-999
Abstract

A series of boron difluoride compounds with 2-(imidazo[1,5-a]pyridin-3-yl)phenols bearing alkylic chains at the 1-position has been synthesized and characterized both with 1H and 13C NMR and infrared spectroscopy. This series of compounds displayed blue emission in solution and in thin polymeric films, with interesting features like large Stokes shifts and good fluorescence quantum yields. Time-Dependent Density Functional Theory (TD-DFT) calculations allowed for the identification of the main electronic transitions as intra ligand transitions (1ILT), as corroborated by the Natural Transition Orbitals (NTOs) shapes.

Published
2023
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5. Low RNA disruption during neoadjuvant chemotherapy predicts pathologic complete response absence in patients with breast cancer

Author

Cazzaniga, M, Ademuyiwa, F, Petit, T, Tio, J, Generali, D, Ciruelos, E, Califaretti, N, Poirier, B, Ardizzoia, A, Dr Med, A, Dr Med, B, Mouret-Reynier, M, Dr Med, D, Isambert, N, Masetti, R, Pitre, L, Augereau, P, Milani, M, Rask, S, Dr Med, C, Pritzker, L, Noubir, S, Parissenti, A, Trudeau, M, Cazzaniga M. E., Ademuyiwa F., Petit T., Tio J., Generali D., Ciruelos E. M., Califaretti N., Poirier B., Ardizzoia A., Dr Med A. H., Dr Med B. L., Mouret-Reynier M. -A., Dr Med D. G., Isambert N., Masetti R., Pitre L., Dr Med D. W., Augereau P., Milani M., Rask S., Dr Med C. S., Pritzker L., Noubir S., Parissenti A., Trudeau M. E., Cazzaniga, M, Ademuyiwa, F, Petit, T, Tio, J, Generali, D, Ciruelos, E, Califaretti, N, Poirier, B, Ardizzoia, A, Dr Med, A, Dr Med, B, Mouret-Reynier, M, Dr Med, D, Isambert, N, Masetti, R, Pitre, L, Augereau, P, Milani, M, Rask, S, Dr Med, C, Pritzker, L, Noubir, S, Parissenti, A, Trudeau, M, Cazzaniga M. E., Ademuyiwa F., Petit T., Tio J., Generali D., Ciruelos E. M., Califaretti N., Poirier B., Ardizzoia A., Dr Med A. H., Dr Med B. L., Mouret-Reynier M. -A., Dr Med D. G., Isambert N., Masetti R., Pitre L., Dr Med D. W., Augereau P., Milani M., Rask S., Dr Med C. S., Pritzker L., Noubir S., Parissenti A., and Trudeau M. E.

Abstract

In previously reported retrospective studies, high tumor RNA disruption during neoadjuvant chemotherapy predicted for post-treatment pathologic complete response (pCR) and improved disease-free survival at definitive surgery for primary early breast cancer. The BREVITY (Breast Cancer Response Evaluation for Individualized Therapy) prospective clinical trial (NCT03524430) seeks to validate these prior findings. Here we report training set (Phase I) findings, including determination of RNA disruption index (RDI) cut points for outcome prediction in the subsequent validation set (Phase II; 454 patients). In 80 patients of the training set, maximum tumor RDI values for biopsies obtained during neoadjuvant chemotherapy were significantly higher in pCR responders than in patients without pCR post-treatment (P 1⁄4 .008). Moreover, maximum tumor RDI values ≤3.7 during treatment predicted for a lack of pCR at surgery (negative predictive value 1⁄4 93.3%). These findings support the prospect that on-treatment tumor RNA disruption assessments may effectively predict post-surgery outcome, possibly permitting treatment optimization.

Published
2024

6. Atezolizumab and chemotherapy for advanced or recurrent endometrial cancer (AtTEnd): a randomised, double-blind, placebo-controlled, phase 3 trial

Author

Colombo, N, Biagioli, E, Harano, K, Galli, F, Hudson, E, Antill, Y, Choi, C, Rabaglio, M, Marmé, F, Marth, C, Parma, G, Fariñas-Madrid, L, Nishio, S, Allan, K, Lee, Y, Piovano, E, Pardo, B, Nakagawa, S, Mcqueen, J, Zamagni, C, Manso, L, Takehara, K, Tasca, G, Ferrero, A, Tognon, G, Lissoni, A, Petrella, M, Laudani, M, Rulli, E, Uggeri, S, Barretina Ginesta, M, Zola, P, Casanova, C, Arcangeli, V, Antonuzzo, L, Gadducci, A, Cosio, S, Clamp, A, Persic, M, Mcneish, I, Tookman, L, Redondo Sanchez, A, Baldini, E, Palaia, I, Benedetti Panici, P, Takahashi, N, Lombard, J, Ardizzoia, A, Bologna, A, Herrero Ibáñez, A, Musolino, A, Márquez Vázquez, R, Pietzner, K, Braicu, E, Heinzelmann-Schwarz, V, Powell, M, Yokoyama, Y, Baron-Hay, S, Abeni, C, Martin Lorente, C, Cueva, J, Trillsch, F, Heitz, F, Ataseven, B, Petru, E, Heubner, M, Sadozye, A, Dubey, S, Tazbirkova, A, Tiley, S, Chrystal, K, Kim, S, Fehr, M, Scatchard, K, Anand, A, Taylor, A, Watary, H, Enomoto, T, Yoshihara, K, Selva-Nayagam, S, Karki, B, Harrison, M, Wilkinson, K, Goh, J, Glasgow, A, Chantrill, L, Lee, C, Bertolini, A, Narducci, F, Bellotti, G, Fusco, V, Aebi, S, Del Grande, M, Colombo, I, Tokunaga, H, Shigeta, S, Goss, G, Siow, Z, Steer, C, Lin, H, Colombo N., Biagioli E., Harano K., Galli F., Hudson E., Antill Y., Choi C. H., Rabaglio M., Marmé F., Marth C., Parma G., Fariñas-Madrid L., Nishio S., Allan K., Lee Y. C., Piovano E., Pardo B., Nakagawa S., McQueen J., Zamagni C., Manso L., Takehara K., Tasca G., Ferrero A., Tognon G., Lissoni A. A., Petrella M., Laudani M. E., Rulli E., Uggeri S., Barretina Ginesta M. P., Zola P., Casanova C., Arcangeli V., Antonuzzo L., Gadducci A., Cosio S., Clamp A., Persic M., McNeish I., Tookman L., Redondo Sanchez A., Baldini E., Palaia I., Benedetti Panici P., Takahashi N., Lombard J., Ardizzoia A., Bologna A., Herrero Ibáñez A. M., Musolino A., Márquez Vázquez R., Pietzner K., Braicu E., Heinzelmann-Schwarz V. A., Powell M., Yokoyama Y., Baron-Hay S., Abeni C., Martin Lorente C., Cueva J. F., Trillsch F., Heitz F., Ataseven B., Petru E., Heubner M. L., Sadozye A. H., Dubey S., Tazbirkova A., Tiley S., Chrystal K., Kim S. W., Fehr M., Scatchard K., Anand A., Taylor A., Watary H., Enomoto T., Yoshihara K., Selva-Nayagam S., Karki B., Harrison M., Wilkinson K., Goh J., Glasgow A., Chantrill L., Lee C., Bertolini A., Narducci F., Bellotti G., Fusco V., Aebi S., Del Grande M., Colombo I., Tokunaga H., Shigeta S., Goss G., Siow Z. R., Steer C., Lin H., Colombo, N, Biagioli, E, Harano, K, Galli, F, Hudson, E, Antill, Y, Choi, C, Rabaglio, M, Marmé, F, Marth, C, Parma, G, Fariñas-Madrid, L, Nishio, S, Allan, K, Lee, Y, Piovano, E, Pardo, B, Nakagawa, S, Mcqueen, J, Zamagni, C, Manso, L, Takehara, K, Tasca, G, Ferrero, A, Tognon, G, Lissoni, A, Petrella, M, Laudani, M, Rulli, E, Uggeri, S, Barretina Ginesta, M, Zola, P, Casanova, C, Arcangeli, V, Antonuzzo, L, Gadducci, A, Cosio, S, Clamp, A, Persic, M, Mcneish, I, Tookman, L, Redondo Sanchez, A, Baldini, E, Palaia, I, Benedetti Panici, P, Takahashi, N, Lombard, J, Ardizzoia, A, Bologna, A, Herrero Ibáñez, A, Musolino, A, Márquez Vázquez, R, Pietzner, K, Braicu, E, Heinzelmann-Schwarz, V, Powell, M, Yokoyama, Y, Baron-Hay, S, Abeni, C, Martin Lorente, C, Cueva, J, Trillsch, F, Heitz, F, Ataseven, B, Petru, E, Heubner, M, Sadozye, A, Dubey, S, Tazbirkova, A, Tiley, S, Chrystal, K, Kim, S, Fehr, M, Scatchard, K, Anand, A, Taylor, A, Watary, H, Enomoto, T, Yoshihara, K, Selva-Nayagam, S, Karki, B, Harrison, M, Wilkinson, K, Goh, J, Glasgow, A, Chantrill, L, Lee, C, Bertolini, A, Narducci, F, Bellotti, G, Fusco, V, Aebi, S, Del Grande, M, Colombo, I, Tokunaga, H, Shigeta, S, Goss, G, Siow, Z, Steer, C, Lin, H, Colombo N., Biagioli E., Harano K., Galli F., Hudson E., Antill Y., Choi C. H., Rabaglio M., Marmé F., Marth C., Parma G., Fariñas-Madrid L., Nishio S., Allan K., Lee Y. C., Piovano E., Pardo B., Nakagawa S., McQueen J., Zamagni C., Manso L., Takehara K., Tasca G., Ferrero A., Tognon G., Lissoni A. A., Petrella M., Laudani M. E., Rulli E., Uggeri S., Barretina Ginesta M. P., Zola P., Casanova C., Arcangeli V., Antonuzzo L., Gadducci A., Cosio S., Clamp A., Persic M., McNeish I., Tookman L., Redondo Sanchez A., Baldini E., Palaia I., Benedetti Panici P., Takahashi N., Lombard J., Ardizzoia A., Bologna A., Herrero Ibáñez A. M., Musolino A., Márquez Vázquez R., Pietzner K., Braicu E., Heinzelmann-Schwarz V. A., Powell M., Yokoyama Y., Baron-Hay S., Abeni C., Martin Lorente C., Cueva J. F., Trillsch F., Heitz F., Ataseven B., Petru E., Heubner M. L., Sadozye A. H., Dubey S., Tazbirkova A., Tiley S., Chrystal K., Kim S. W., Fehr M., Scatchard K., Anand A., Taylor A., Watary H., Enomoto T., Yoshihara K., Selva-Nayagam S., Karki B., Harrison M., Wilkinson K., Goh J., Glasgow A., Chantrill L., Lee C., Bertolini A., Narducci F., Bellotti G., Fusco V., Aebi S., Del Grande M., Colombo I., Tokunaga H., Shigeta S., Goss G., Siow Z. R., Steer C., and Lin H.

Abstract

Background: At the time of AtTEnd trial design, standard treatment for advanced or recurrent endometrial cancer included carboplatin and paclitaxel chemotherapy. This trial assessed whether combining atezolizumab with chemotherapy might improve outcomes in this population. Methods: AtTEnd was a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial done in 89 hospitals in 11 countries across Europe, Australia, New Zealand, and Asia. Enrolled patients were aged 18 years or older, and had advanced or recurrent endometrial carcinoma or carcinosarcoma, an Eastern Cooperative Oncology Group performance status of 0–2, and received no previous systemic chemotherapy for recurrence. Patients were randomly assigned (2:1) using an interactive web response system (block size of six) to either atezolizumab 1200 mg or placebo given intravenously with chemotherapy (carboplatin at area under the curve of 5 or 6 and paclitaxel 175 mg/m2 intravenously on day 1 every 21 days) for 6–8 cycles, then continued until progression. Stratification factors were country, histological subtype, advanced or recurrent status, and mismatch repair (MMR) status. Participants and treating clinicians were masked to group allocation. The hierarchically tested co-primary endpoints were progression-free survival (in patients with MMR-deficient [dMMR] tumours, and in the overall population) and overall survival (in the overall population). Primary analyses were done in the intention-to-treat population, defined as all randomly assigned patients who gave their full consent to participation in the study and data processing. Safety was assessed in all patients included in the intention-to-treat population who received at least one dose of study treatment. Here, we report the primary progression-free survival and the interim overall survival results. This study is ongoing and is registered with ClinicalTrials.gov, NCT03603184. Findings: Between Oct 3, 2018, and Jan 7, 2022, 551 patients were r

Published
2024

7. Carboplatin-based doublet plus bevacizumab beyond progression versus carboplatin-based doublet alone in patients with platinum-sensitive ovarian cancer: a randomised, phase 3 trial

Author

Pignata, S, Lorusso, D, Joly, F, Gallo, C, Colombo, N, Sessa, C, Bamias, A, Salutari, V, Selle, F, Frezzini, S, De Giorgi, U, Pautier, P, Bologna, A, Orditura, M, Dubot, C, Gadducci, A, Mammoliti, S, Ray-Coquard, I, Zafarana, E, Breda, E, Favier, L, Ardizzoia, A, Cinieri, S, Largillier, R, Sambataro, D, Guardiola, E, Lauria, R, Pisano, C, Raspagliesi, F, Scambia, G, Daniele, G, Perrone, F, Pignata, Sandro, Lorusso, Domenica, Joly, Florence, Gallo, Ciro, Colombo, Nicoletta, Sessa, Cristiana, Bamias, Aristotelis, Salutari, Vanda, Selle, Frédèric, Frezzini, Simona, De Giorgi, Ugo, Pautier, Patricia, Bologna, Alessandra, Orditura, Michele, Dubot, Coraline, Gadducci, Angiolo, Mammoliti, Serafina, Ray-Coquard, Isabelle, Zafarana, Elena, Breda, Enrico, Favier, Laure, Ardizzoia, Antonio, Cinieri, Saverio, Largillier, Rémy, Sambataro, Daniela, Guardiola, Emmanuel, Lauria, Rossella, Pisano, Carmela, Raspagliesi, Francesco, Scambia, Giovanni, Daniele, Gennaro, and Perrone, Francesco

Published
2021
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9. Real-world experience of abiraterone acetate plus prednisone in chemotherapy-naive patients with metastatic castration-resistant prostate cancer: long-term results of the prospective ABItude study

Author

Procopio, Giuseppe, Chiuri, Vincenzo, Mantini, Giovanna, Roberto Bordonaro, Roberto Maisano., Cinieri, Saverio, Rossetti, Sabrina, De Placido, Sabino, Airoldi, Mario, Galli, Luca, Gasparro, Donatello, Ludovico, Giuseppe Mario, Guglielmini, Pamela Francesca, Santini, Daniele, Naglieri, Emanuele, Fagnani, Daniele, Aglietta, Massimo, Livi, Lorenzo, Schips, Luigi, Passalacqua, Rodolfo, Fiore, Michele, D'Angelillo, Rolando Maria, Ceresoli, Giovanni Luca, Magrini, Stefano, Rondonotti, David, Mirone, Vincenzo, Ferriero, Maria Consiglia, Sciarra, Alessandro, Acquati, Mirko, Boccardo, Francesco, Scagliotti, Giorgio Vittorio, Mencoboni, Manlio, De Giorgi, Ugo, Micheletti, Gennaro, Lanzetta, Gaetano, Sartori, Donata, Carlini, Paolo, Soto Parra, Hector Josè, Battaglia, Michele, Uricchio, Francesco, Bernardo, Antonio, De Lisa, Antonello, Carrieri, Giuseppe, Ardizzoia, Antonio, Aieta, Michele, Pisconti, Salvatore, Marchetti, Paolo, Paiar, Fabiola, Procopio, G., Chiuri, V.E., Giordano, M., Alitto, A.R., Maisano, R., Bordonaro, R., Cinieri, S., Rossetti, S., De Placido, S., Airoldi, M., Galli, L., Gasparro, D., Ludovico, G.M., Guglielmini, P.F., Carella, C., Nova, P., Aglietta, M., Schips, L., Beccaglia, P., Sciarra, A., Livi, L., and Santini, D.

Published
2022
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10. Prognostic Relevance of Copy Number Losses in Ovarian Cancer.

Author

Jemma, Andrea, Ardizzoia, Alessandra, Redaelli, Serena, Bentivegna, Angela, Lavitrano, Marialuisa, and Conconi, Donatella

Abstract

Background/Objectives: Aneuploidy is a prevalent cancer feature that occurs in many solid tumors. For example, high-grade serous ovarian cancer shows a high level of copy number alterations and genomic rearrangements. This makes genomic variants appealing as diagnostic or prognostic biomarkers, as well as for their easy detection. In this study, we focused on copy number (CN) losses shared by ovarian cancer stem cells (CSCs) to identify chromosomal regions that may be important for CSC features and, in turn, for patients' prognosis. Methods: Array-CGH and bioinformatic analyses on three CSCs subpopulations were performed. Results: Pathway and gene ontology analyses on genes involved in copy number loss in all CSCs revealed a significant decrease in mRNA surveillance pathway, as well as miRNA-mediated gene silencing. Then, starting from these CN losses, we validated their potential prognostic relevance by analyzing the TCGA cohort. Notably, losses of 4q34.3-q35.2, 8p21.2-p21.1, and 18q12.2-q23 were linked to increased genomic instability. Loss of 18q12.2-q23 was also related to a higher tumor stage and poor prognosis. Finally, specific genes mapping in these regions, such as PPP2R2A and TPGS2A, emerged as potential biomarkers. Conclusions: Our findings highlight the importance of genomic alterations in ovarian cancer and their impact on tumor progression and patients' prognosis, offering advance in understanding of the application of numerical aberrations as prognostic ovarian cancer biomarkers. [ABSTRACT FROM AUTHOR]

Published
2024
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11. Blue‐Emissive Fluorescent Zinc(II) Complexes with Bis(imidazo[1,5‐a]pyridine)methane Ligands.

Author

Colombo, Gioele, Cinco, Anita, Vola, Chiara, Therrien, Bruno, Ardizzoia, G. Attilio, and Brenna, Stefano

Subjects
FRONTIER orbitals, METHANE derivatives, PYRIDINE, ZINC, METHANE
Abstract

Three bis(imidazo[1,5‐a]pyridine)methane derivatives (bis(1‐methylimidazo[1,5‐a]pyridin‐3‐yl)methane, LH; 3,3'‐(ethane‐1,1‐diyl)bis(1‐methylimidazo[1,5‐a]pyridine) LMe; 3,3'‐(2‐phenylethane‐1,1‐diyl)bis(1‐methylimidazo[1,5‐a]pyridine), LBz) have been synthesized, and fully characterized in solution (1H and 13C NMR spectra) and in the solid state (X‐ray). In particular, LH has been prepared in high yield (75 %) under very mild conditions (water, 60 °C), offering an alternative route to those reported in the literature. LMe and LBz have been obtained from LH by functionalization of the methylene bridge. The bis(imidazo[1,5‐a]pyridine)methane compounds have been coordinated to a zinc(II) center, leading to tetrahedral complexes of general formula [Zn(LR)2](ClO4)2 (R=H, Me, Bz), which showed a bright fluorescent emission with (x,y) color coordinates very close to standard blue. TD‐DFT have been employed to describe the Frontier Molecular Orbitals (FMOs) participating in electronic transitions, highlighting the main transition as 1(π‐π*) transition in the bis(imidazo[1,5‐a]pyridine)methane and a mixed intra‐ligand (1ILT) and ligand‐to‐ligand (1LLT) transition in the complexes. [ABSTRACT FROM AUTHOR]

Published
2024
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12. Minnesota acute graft-versus-host disease risk score predicts survival at onset of graft-versus-host disease after post-transplant cyclophosphamide prophylaxis

Author

Federica Ardizzoia, Francesca Lorentino, Alessandro Bruno, Sarah Marktel, Fabio Giglio, Daniela Clerici, Francesca Farina, Sara Mastaglio, Simona Piemontese, Andrea A. Assanelli, Matteo G. Carrabba, Massimo Bernardi, Consuelo Corti, Jacopo Peccatori, Fabio Ciceri, Raffaella Greco, and Maria Teresa Lupo-Stanghellini

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Published
2022
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14. Upfront FOLFOXIRI plus bevacizumab and reintroduction after progression versus mFOLFOX6 plus bevacizumab followed by FOLFIRI plus bevacizumab in the treatment of patients with metastatic colorectal cancer (TRIBE2): a multicentre, open-label, phase 3, randomised, controlled trial

Author

Falcone, Alfredo, Lonardi, Sara, De Braud, Filippo Guglielmo Maria, Bordonaro, Roberto, Maiello, Evaristo, Tamburini, Emiliano, Santini, Daniele, Frassineti, Giovanni Luca, Gamucci, Teresa, Aprile, Giuseppe, Zaniboni, Alberto, Granetto, Cristina, Buonadonna, Angela, Di Costanzo, Francesco, Tomasello, Gianluca, Gianni, Luca, Di Donato, Samantha, Carlomagno, Chiara, Clavarezza, Matteo, Racca, Patrizia, Mambrini, Andrea, Roselli, Mario, Allegrini, Giacomo, Sobrero, Alberto, Aglietta, Massimo, Corgna, Enrichetta, Cortesi, Enrico, Corsi, Domenico Cristiano, Ballestrero, Alberto, Bonetti, Andrea, Di Clemente, Francesco, Ruggeri, Enzo, Ciardiello, Fortunato, Benasso, Marco, Vitello, Stefano, Cinieri, Saverio, Mosconi, Stefania, Silvestris, Nicola, Frassoldati, Antonio, Cupini, Samantha, Bertolini, Alessandro, Tortora, Giampaolo, Bengala, Carmelo, Ferrari, Daris, Ardizzoia, Antonia, Milandri, Carlo, Chiara, Silvana, Romano, Gianpiero, Miraglia, Stefania, Scaltriti, Laura, Pucci, Francesca, Blasi, Livio, Brugnatelli, Silvia, Fioretto, Luisa, Ribecco, Angela Stefania, Longarini, Raffaella, Frisinghelli, Michela, Banzi, Maria, Cremolini, Chiara, Antoniotti, Carlotta, Rossini, Daniele, Loupakis, Fotios, Pietrantonio, Filippo, Latiano, Tiziana Pia, Passardi, Alessandro, Marmorino, Federica, Grande, Roberta, Murgioni, Sabina, Moretto, Roberto, Corallo, Salvatore, Cordio, Stefano, Antonuzzo, Lorenzo, Masi, Gianluca, Ronzoni, Monica, Ritorto, Giuliana, Cupini, Samanta, Mammoliti, Serafina, Fenocchio, Elisabetta, Zagonel, Vittorina, Fontanini, Gabriella, Ugolini, Clara, and Boni, Luca

Published
2020
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15. High-dose-rate brachytherapy as monotherapy for localized prostate cancer using three different doses – 14 years of single-centre experience

Author

Carlo Pietro Soatti, Durim Delishaj, Romerai D’Amico, Cristina Frigerio, Ilaria Costanza Fumagalli, Francesco Bonsignore, Giulia Sangalli, Fausto Declich, Stefano Arcangeli, Antonio Ardizzoia, and Alessandro Colombo

Subjects
high-dose-rate, brachytherapy, prostate cancer, prostate-specific antigen, psa, Medicine
Published
2020
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16. AhRR and PPP1R3C: Potential Prognostic Biomarkers for Serous Ovarian Cancer

Author

Ardizzoia, A, Jemma, A, Redaelli, S, Silva, M, Bentivegna, A, Lavitrano, M, Conconi, D, Ardizzoia, Alessandra, Jemma, Andrea, Redaelli, Serena, Silva, Marco, Bentivegna, Angela, Lavitrano, Marialuisa, Conconi, Donatella, Ardizzoia, A, Jemma, A, Redaelli, S, Silva, M, Bentivegna, A, Lavitrano, M, Conconi, D, Ardizzoia, Alessandra, Jemma, Andrea, Redaelli, Serena, Silva, Marco, Bentivegna, Angela, Lavitrano, Marialuisa, and Conconi, Donatella

Abstract

The lack of effective screening and successful treatment contributes to high ovarian cancer mortality, making it the second most common cause of gynecologic cancer death. Development of chemoresistance in up to 75% of patients is the cause of a poor treatment response and reduced survival. Therefore, identifying potential and effective biomarkers for its diagnosis and prognosis is a strong critical need. Copy number alterations are frequent in cancer, and relevant for molecular tumor stratification and patients’ prognoses. In this study, array-CGH analysis was performed in three cell lines and derived cancer stem cells (CSCs) to identify genes potentially predictive for ovarian cancer patients’ prognoses. Bioinformatic analyses of genes involved in copy number gains revealed that AhRR and PPP1R3C expression negatively correlated with ovarian cancer patients’ overall and progression-free survival. These results, together with a significant association between AhRR and PPP1R3C expression and ovarian cancer stemness markers, suggested their potential role in CSCs. Furthermore, AhRR and PPP1R3C’s increased expression was maintained in some CSC subpopulations, reinforcing their potential role in ovarian cancer. In conclusion, we reported for the first time, to the best of our knowledge, a prognostic role of AhRR and PPP1R3C expression in serous ovarian cancer.

Published
2023

19. Low RNA disruption during neoadjuvant chemotherapy predicts pCR absence in patients with breast cancer

Author

Cazzaniga, Marina Elena, primary, Ademuyiwa, Foluso, additional, Petit, Thierry, additional, Tio, Joke, additional, Generali, Daniele, additional, Ciruelos, Eva M, additional, Califaretti, Nadia, additional, Poirier, Brigitte, additional, Ardizzoia, Antonio, additional, Hoenig, Arnd, additional, Lex, Benno, additional, Mouret-Reynier, Marie-Ange, additional, Giesecke, Dagmar, additional, Isambert, Nicolas, additional, Masetti, Ricardo, additional, Pitre, Lacey, additional, Wrobel, Denise, additional, Augereau, Paule, additional, Milani, Manuela, additional, Rask, Sara, additional, Solbach, Christine, additional, Pritzker, Laura, additional, Noubir, Sanaa, additional, Parissenti, Amadeo, additional, and Trudeau, Maureen, additional

Published
2023
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20. Multiple Myeloma Treatment in Real-world Clinical Practice: Results of a Prospective, Multinational, Noninterventional Study

Author

Bekadja, Mohamed, Hamladji, Rose-Marie, Ali, Hocine Ait, Hamdi, Selma, Touhami, Hadj, Mansour, Nourredine Sidi, Willenbacher, Wolfgang, Linkesch, Werner, Nemet, Damir, Pedersen, Robert Shou, Abildgaard, Niels, Laane, Edward, Hein, Marju, Mohty, Mohamad, Eveillard, Jean Richard, Yamani, Abderrazak el, Moreau, Philippe, Sanhes, Laurence, Lepeu, Gérard, Laribi, Kamel, Jourdan, Eric, Fitoussi, Olivier, Allangba, Olivier, Fleury, Joël, Escoffre, Martine, Benramdane, Riad, Cartron, Guillaume, Dine, Gérard, Legouffe, Eric, Harich, Hanns-Detlev, Illmer, Thomas, Dörfel, Steffen, Hannig, Carla Verena, Koenigsmann, Michael, Prange-Krex, Gabriele, Salwender, Hans, Tamm, Ingo, Zeller, Wolfgang, Maasberg, Michael, Schlag, Rudolf, Klausmann, Martine, Uhlig, Jens, Alkemper, Burkhard, Schütz, Stefan, Tessen, Hans-Werner, Mohr, Benno, Schmidt, Peter, Heinrich, Bernhard, Hebart, Holger, Seipelt, Gernot, Zoeller, Thomas, Heits, Frank, Müller-Naendrup, Clemens, Hansen, Richard, Repp, Roland, Von Weikersthal, Ludwig Fischer, Schmits, Rudolf, Heßling, Jörg, Krammer-Steiner, B., Janzen, Viktor, Schauer, Michael, Grüner, Marcus W., Kisro, Jens, Denzlinger, Claudio, Freier, Werner, Junghanss, Christian, Görner, Martin, Laichinger, Katharina, Ostermann, Helmut, Dürk, Heinz, Hess, Georg, Reich, Gernot, Terpos, Evangelos, Dimopoulos, Meletios, Matsouka, Panagiota, Pouli, Anastasia, Anagnostopoulos, Achilles, Masszi, Tamas, Borbényi, Zita, Ivanyi, Janos, Szomor, Arpad, Abadi, Uri, Nagler, Arnon, Magen, Hila, Avivi, Irit, Quitt, Miriam, Palumbo, Antonio, Boccadoro, Mario, De Stefano, Valerio, Za, Tommaso, Vallisa, Daniele, Foa, Roberto, Corso, Alessandro, Bosi, Alberto, Vacca, Angelo, Lanza, Francesco, Palazzo, Giulia, Avvisati, Giuseppe, Cavo, Michele, Ferrara, Felicetto, Consoli, Ugo, Cantonetti, Maria, Angelucci, Emanuele, Califano, Catello, Di Raimondo, Francesco, Guarini, Attilio, Musso, Maurizio, Pizzuti, Michele, Giuliani, Nicola, Ardizzoia, Antonio, Di Renzo, Nicola, Gaidano, Gianluca, Gozzetti, Alessandro, Pitini, Vincenzo, Farina, Gabriella, Centurioni, Riccardo, De Fabritiis, Paolo, Iuliano, Francesco, La Nasa, Giorgio, La Verde, Giacinto, Pane, Fabrizio, Recine, Umberto, La Targia, Maria, Mineo, Giuseppe, Cangialosi, Clotilde, Fagnani, Daniele, Federici, Augusto, Romano, Atelda, Specchia, Giorgina, Storti, Sergio, Bongarzoni, Velia, Bacigalupo, Andrea, Gobbi, Marco, Latte, Giancarlo, Mannina, Donato, Capalbo, Silvana, Lejniece, Sandra, Pečeliūnas, Valdas, Jurgutis, Mindaugas, Stankovic, Svetlana, Legiec, Wojciech, Woszczyk, Dariusz, Hołojda, Jadwiga, Gornik, Slawomir, Pluta, Andrzej, Morawiec-Szymonik, Elzbieta, Kyrcz-Krzemien, Slawomira, Homenda, Wojciech, Grosicki, Sebastian, Sulek, Kazimierz, Lange, Andrzej, Kloczko, Janusz, Starzak-Gwozdz, Jolanta, Hellmann, Andrzej, Komarnicki, Mieczyslaw, Kuliczkowski, Kazimierz, Viveiros, Carolina, Gonçalves, Cristina, Esefyeva, Natalia, Kochkareva, Julia, Kaplanov, Kamil, Volodicheva, Elena, Laricheva, Elena, Dergacheva, Valentina, Chukavina, Marina, Volchenko, Natalia, Nazarova, Irina, Anchukova, Ludmila, Ovanesova, Elena, Gritsenko, Taras, Salogub, Galina, Magomedova, Ludmila, Kuznetsova, Irina, Osyunikhina, Svetlana, Serdyuk, Olga, Karyagina, Elena, Ivanova, Valentina, Černelč, Slovenia Peter, Louw, Vernon, Coetzee, Corlia, Gunther, Karen, Moodley, Dhayanithi, Duran, Soledad, Gutiérrez, Asunción Echeveste, De Oteyza, Jaime Perez, Capote, Francisco Javier, Casanova, Maria, Sanchez, Jesus Martin, Rios-Herranz, Eduardo, Ibañez-Garcia, Jeronima, Herranz, Maria Jose, Hernandez, Belen, Sanchez, Sara Sanchez, Escalante, Fernando, Carnicero, Fernando, Lleonart, Joan Bargay, Gironella, Mercedes, Martínez, Rafael, De La Guia, Ana Lopez, Palomera, Luis, Iglesias, Rebeca, Ramos, Fernando Solano, De La Serna, Javier, Sanchez, Pedro Garcia, Vidal, Juan Besalduch, Mateos, Maria-Victoria, Morfa, Miguel Diaz, Beksac, Turkey – Meral, Vural, Filiz, Aydin, Yildiz, Unal, Ali, Goker, Hakan, Bilgir, Oktay, Guvenc, Birol, Turgut, Mehmet, Ozet, Gulsum Gulistan, Ali, Ridvan, Masliak, Zvenyslava, Kyselyova, Maryna, Glushko, Nataliia, Vybyrana, Renata, Skrypnyk, Igor, Tretyak, Natalya, Kharchevska, Tetiana, Dyagil, Iryna, Popovs'ka, Tetiana, Shimanskiy, Vadim, Lysa, Tamila, Oliynyk, Hanna, Vilchevskaya, Kateryna, Kryachok, Iryna, Popovych, Yuriy, Romanyuk, Natalia, Yushchenko, Natalia, Kaplan, Polina, Rekhtman, Grygoriy, Pylypenko, Halyna, Kozlov, Viktor, Drach, Johannes, Harousseau, Jean-Luc, Einsele, Hermann, Goldschmidt, Hartmut, Facon, Thierry, Michalet, Mauricette, Savchenko, Valery G., De la Rubia, Javier, Cook, Gordon, Mellqvist, Ulf-Henrik, Ludwig, Heinz, Beksac, Meral, Bekadja, Mohamed Amine, Durán, Maria Soledad, Kochkareva, Yulia, Berthou, Christian, Silva, João, Pedersen, Robert Schou, Černelč, Peter, Potamianou, Anna, Couturier, Catherine, Feys, Caroline, and Thoret-Bauchet, Florence

Published
2018
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22. Outcomes of First-Generation EGFR-TKIs Against Non-Small-Cell Lung Cancer Harboring Uncommon EGFR Mutations: A Post Hoc Analysis of the BE-POSITIVE Study

Author

Pilotto, Sara, Rossi, Antonio, Vavalà, Tiziana, Follador, Alessandro, Tiseo, Marcello, Galetta, Domenico, Morabito, Alessandro, Di Maio, Massimo, Martelli, Olga, Caffo, Orazio, Piovano, Pier Luigi, Cortinovis, Diego, Zilembo, Nicoletta, Casartelli, Clelia, Banna, Giuseppe Luigi, Ardizzoia, Antonio, Barzelloni, Maria Luisa, Bearz, Alessandra, Genestreti, Giovenzio, Mucciarini, Claudia, Filipazzi, Virginio, Menis, Jessica, Rizzo, Elisa, Barbieri, Fausto, Rijavec, Erika, Cecere, Fabiana, Spitaleri, Gianluca, Bria, Emilio, and Novello, Silvia

Published
2018
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24. Tas-102 for Refractory Metastatic Colorectal Cancer: A Multicenter Retrospective Cohort Study

Author

Conti, Matteo, primary, Bolzacchini, Elena, additional, Luchena, Giovanna, additional, Bertu’, Lorenza, additional, Tagliabue, Paola, additional, Aglione, Stefania, additional, Ardizzoia, Antonio, additional, Arnoffi, Jessica, additional, Guida, Francesco Maria, additional, Bertolini, Alessandro, additional, Pastorini, Alessandro, additional, Duro, Maria, additional, Bettega, Donato, additional, Roda’, Giovambattista, additional, Artale, Salvatore, additional, Squizzato, Alessandro, additional, and Giordano, Monica, additional

Published
2023
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25. Low RNA disruption during neoadjuvant chemotherapy predicts pathologic complete response absence in patients with breast cancer.

Author

Cazzaniga, Marina Elena, Ademuyiwa, Foluso, Petit, Thierry, Tio, Joke, Generali, Daniele, Ciruelos, Eva M, Califaretti, Nadia, Poirier, Brigitte, Ardizzoia, Antonio, Hoenig, Arnd, Lex, Benno, Mouret-Reynier, Marie-Ange, Giesecke, Dagmar, Isambert, Nicolas, Masetti, Ricardo, Pitre, Lacey, Wrobel, Denise, Augereau, Paule, Milani, Manuela, and Rask, Sara

Subjects
NUCLEOTIDE sequence, GENETICS of breast cancer, CANCER chemotherapy
Abstract

In previously reported retrospective studies, high tumor RNA disruption during neoadjuvant chemotherapy predicted for post-treatment pathologic complete response (pCR) and improved disease-free survival at definitive surgery for primary early breast cancer. The BREVITY (Breast Cancer Response Evaluation for Individualized Therapy) prospective clinical trial (NCT03524430) seeks to validate these prior findings. Here we report training set (Phase I) findings, including determination of RNA disruption index (RDI) cut points for outcome prediction in the subsequent validation set (Phase II; 454 patients). In 80 patients of the training set, maximum tumor RDI values for biopsies obtained during neoadjuvant chemotherapy were significantly higher in pCR responders than in patients without pCR post-treatment (P  = .008). Moreover, maximum tumor RDI values ≤3.7 during treatment predicted for a lack of pCR at surgery (negative predictive value = 93.3%). These findings support the prospect that on-treatment tumor RNA disruption assessments may effectively predict post-surgery outcome, possibly permitting treatment optimization. [ABSTRACT FROM AUTHOR]

Published
2024
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26. Tas-102 for Refractory Metastatic Colorectal Cancer: A Multicenter Retrospective Cohort Study

Author

Giordano, Matteo Conti, Elena Bolzacchini, Giovanna Luchena, Lorenza Bertu’, Paola Tagliabue, Stefania Aglione, Antonio Ardizzoia, Jessica Arnoffi, Francesco Maria Guida, Alessandro Bertolini, Alessandro Pastorini, Maria Duro, Donato Bettega, Giovambattista Roda’, Salvatore Artale, Alessandro Squizzato, and Monica

Subjects
TAS-102, mCRC, DPYD, HIV, elderly
Abstract

Trifluridine/tipiracil (TAS-102) is an oral chemotherapy approved for the treatment of metastatic colorectal cancer. The efficacy and tolerability of TAS-102 were shown in phase II-III clinical trials and in several real-life studies. The elderly and other special subgroups are underrepresented in published literature. We conducted a retrospective multicenter study to assess the effectiveness and safety of TAS-102 in consecutive patients with pretreated mCRC. In particular, we estimated the effectiveness and safety of TAS-102 in elderly patients (aged ≥70, ≥75 and ≥80 years) and in special subgroups, e.g., patients with concomitant heart disease. One hundred and sixty patients were enrolled. In particular, 71 patients (44%) were 70 years of age or older, 50 (31%) were 75 years of age or older, and 23 (14%) were 80 years of age or older. 19 patients (12%) had a concomitant chronic heart disease, three (2%) patients were HIV positive, and one (

Published
2023
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27. Response to chemotherapy and Clinical Outcome of Patients with recurrent epithelial ovarian cancer after PARP inhibitor maintenance treatment: a Multicenter retrospective italina Study

Author

Gadducci, A, Cosio, S, Landoni, F, Lissoni, A, Zola, P, Elena Laudani, M, Ardizzoia, A, Gambino and Enrico Sartori, A, Angiolo Gadducci, Stefania Cosio, Fabio Landoni, Andrea Alberto Lissoni, Paolo Zola, Maria Elena Laudani, Antonio Ardizzoia, Angela Gambino and Enrico Sartori, Gadducci, A, Cosio, S, Landoni, F, Lissoni, A, Zola, P, Elena Laudani, M, Ardizzoia, A, Gambino and Enrico Sartori, A, Angiolo Gadducci, Stefania Cosio, Fabio Landoni, Andrea Alberto Lissoni, Paolo Zola, Maria Elena Laudani, Antonio Ardizzoia, and Angela Gambino and Enrico Sartori

Abstract

Background/Aim: To assess response rates and survival in patients with recurrent platinum-sensitive epithelial ovarian cancer (EOC) who received PARP inhibitor (PARP-i) maintenance and who subsequently underwent salvage chemotherapy for disease progression after PARPi. Patients and Methods: This retrospective investigation analyzed 103 patients who were treated in five Italian Gynecologic centers. The PARPi used was olaparib in 46 patients, niraparib in 55, and rucaparib in 2. The interval time between the last cycle of pre- PARPi platinum–based chemotherapy and the diagnosis of progression during PARPi maintenance was defined as platinum–free interval (PFI). Results: Of the 28 patients with PFI [removed]12 months received chemotherapy (platinum-based chemotherapy, 23; trabectedin + PLD, 3; non platinum – single agent, 5). An objective response was found in 13.0%, 26.2% and 41.9 % of the patients with PFI [removed]12 months (p= 0.03), respectively, and the corresponding median survivals after PARPi were 8.9 months, 17.5 months and 24.1 months (p= 0.002), respectively. Conclusion: Before the PARPi era, some randomized trials on platinum rechallenge in patients with recurrent EOC after more than 6 months from the last platinum cycle have shown response rates ranging from 47.2% to 66%. Response rates to chemotherapy for progression after PARPi appear to be lower than those expected according to PFI.

Published
2022

30. Specific Expression of a New Bruton Tyrosine Kinase Isoform (p65BTK) in the Glioblastoma Gemistocytic Histotype

Author

Luca Sala, Giovanni Cirillo, Gabriele Riva, Gabriele Romano, Carlo Giussani, Annamaria Cialdella, Antonio Todisco, Assunta Virtuoso, Maria Grazia Cerrito, Angela Bentivegna, Emanuela Grassilli, Antonio Ardizzoia, Emanuela Bonoldi, Roberto Giovannoni, Michele Papa, and Marialuisa Lavitrano

Subjects
Bruton’s tyrosine kinase, p65BTK, gemistocytes, glioblastoma, biomarker, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Bruton’s tyrosine-kinase (BTK) is a non-receptor tyrosine kinase recently associated with glioma tumorigenesis and a novel prognostic marker for poor survival in patients with glioma. The p65BTK is a novel BTK isoform involved in different pathways of drug resistance of solid tumors, thus we aimed to investigate the expression and the putative role of p65BTK in tumors of the central nervous system (CNS). We selected a large cohort of patients with glial tumors (n = 71) and analyzed the expression of p65BTK in different histotypes and correlation with clinical parameters. Sections were stained with glial fibrillary acidic protein (GFAP), p53, epidermal growth factor receptor (EGFR), S100, vimentin, and epithelial membrane antigen (EMA) antibodies. Glioma stem cell (GSC) lines, isolated from glioblastoma multiforme (GBM), were treated with different concentrations of ibrutinib, a specific inhibitor of BTK, in order to evaluate their metabolic activity, mitotic index and mortality. Moreover, an orthotopic xenotransplant of GSC from human GBM was used to evaluate the expression of p65BTK in the brain of immunodeficient mice. p65BTK was expressed in GSC and in gemistocytes in human gliomas at different histological grade. We found a significant correlation between BTK expression and low-grade (LG) tumors (p ≤ 0.05) and overall survival (OS) of patients with grade III gliomas (p ≤ 0.05), suggestive of worst prognosis. Interestingly, the expression of p65BTK remained restricted exclusively to gemistocytic cells in the xenograft mouse model. Ibrutinib administration significantly reduced metabolic activity and mitotic index and increased mortality in GSC, highlighting the specific role of p65BTK in cell proliferation and survival. In conclusion, our data demonstrated that p65BTK is expressed in glioma tumors, restricted to gemistocytic cells, has a key role in GSC and has a bad prognostic value, thus highlighting the importance of future research for targeted therapy of human gliomas.

Published
2019
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32. First-line treatment of metastatic castration-resistant prostate cancer: the real-world Italian cohort of the Prostate Cancer Registry

Author

Luca Galli, Vincenzo Emanuele Chiuri, Giuseppe Di Lorenzo, Salvatore Pisconti, Sabrina Rossetti, Zuzana Sirotova, Andrea Muto, Roberto Petrioli, Michele De Tursi, Andrea Sbrana, Giulio Francolini, Antonio Ardizzoia, Claudio Scavelli, Francesco Satta, Silvia Quadrini, Mario Airoldi, Carmine D’Aniello, Andrea Bonetti, Serafino Conforti, Michele Aieta, Patrizia Beccaglia, Antonio Maestri, and Lucia Fratino

Subjects
Cancer Research, Oncology, General Medicine
Abstract

Background: With the availability of multiple treatment options for metastatic castration-resistant prostate cancer (mCRPC), new real-world data on disease management and drugs’ performance are needed. Methods: We described characteristics, management and clinical outcomes of patients receiving first-line mCRPC treatment within the Italian cohort of the real-world, prospective, international Prostate Cancer Registry. Patients were enrolled consecutively (2013-2016) in 32 Italian sites and followed for 3 years. Results: 238 patients were included: 157 received first-line abiraterone acetate plus prednisone (“abiraterone” thereafter) and 70 first-line docetaxel; 11 patients receiving other treatments were not considered. Compared with docetaxel-treated patients, those receiving abiraterone were significantly older (age ⩾75: 63.7% vs 38.6%), less frequently had a Gleason score >8 (48.2% vs 67.6%, pConclusion: This investigation provided valuable information on the overall mCRPC treatment pattern and the effectiveness of first-line abiraterone and docetaxel in a population representative of everyday practice.

Published
2022
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35. Carboplatin-based doublet plus bevacizumab beyond progression versus carboplatin-based doublet alone in patients with platinum-sensitive ovarian cancer: a randomised, phase 3 trial

Author

Giovanni Scambia, Daniela Sambataro, Coraline Dubot, Rossella Lauria, Francesco Raspagliesi, Patricia Pautier, Simona Frezzini, S Mammoliti, U De Giorgi, Ugo De Giorgi, C Sessa, Angiolo Gadducci, Isabelle Ray-Coquard, A Gadducci, Rémy Largillier, Francesco Perrone, Alessandra Bologna, Sandro Pignata, G Scambia, Elena Zafarana, E Breda, Florence Joly, R Largillier, Saverio Cinieri, C Pisano, Carmela Pisano, C Gallo, Frédéric Selle, Vanda Salutari, Cristiana Sessa, Aristotelis Bamias, F Joly, R Lauria, A Ardizzoia, Laure Favier, Nicoletta Colombo, D Sambataro, F Perrone, Domenica Lorusso, C Dubot, G Daniele, Emmanuel Guardiola, A Bamias, Gennaro Daniele, V Salutari, F Selle, S. Mammoliti, E Zafarana, P Pautier, M Orditura, Enrico Breda, A Bologna, E Guardiola, Michele Orditura, Ciro Gallo, L Favier, S Cinieri, N Colombo, I Ray-Coquard, S Frezzini, S Pignata, F Raspagliesi, Antonio Ardizzoia, Pignata, S., Lorusso, D., Joly, F., Gallo, C., Colombo, N., Sessa, C., Bamias, A., Salutari, V., Selle, F., Frezzini, S., De Giorgi, U., Pautier, P., Bologna, A., Orditura, M., Dubot, C., Gadducci, A., Mammoliti, S., Ray-Coquard, I., Zafarana, E., Breda, E., Favier, L., Ardizzoia, A., Cinieri, S., Largillier, R., Sambataro, D., Guardiola, E., Lauria, R., Pisano, C., Raspagliesi, F., Scambia, G., Daniele, G., Perrone, F., Pignata, S, Lorusso, D, Joly, F, Gallo, C, Colombo, N, Sessa, C, Bamias, A, Salutari, V, Selle, F, Frezzini, S, De Giorgi, U, Pautier, P, Bologna, A, Orditura, M, Dubot, C, Gadducci, A, Mammoliti, S, Ray-Coquard, I, Zafarana, E, Breda, E, Favier, L, Ardizzoia, A, Cinieri, S, Largillier, R, Sambataro, D, Guardiola, E, Lauria, R, Pisano, C, Raspagliesi, F, Scambia, G, Daniele, G, and Perrone, F

Subjects
Oncology, Adult, medicine.medical_specialty, Bevacizumab, Paclitaxel, Phases of clinical research, Disease-Free Survival, Carboplatin, Polyethylene Glycols, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Maintenance therapy, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Pelvic inflammatory disease, medicine, Humans, 030212 general & internal medicine, Progression-free survival, Aged, Ovarian Neoplasms, Antineoplastic Combined Chemotherapy Protocol, Performance status, business.industry, Ovarian Neoplasm, Middle Aged, Gemcitabine, chemistry, Doxorubicin, Drug Resistance, Neoplasm, 030220 oncology & carcinogenesis, Disease Progression, Female, Neoplasm Recurrence, Local, business, medicine.drug, Human
Abstract

Background: Bevacizumab is approved in combination with chemotherapy for the treatment of ovarian cancer, either in first-line therapy or for patients with recurrent disease not previously treated with the same drug. We aimed to test the value of continuing bevacizumab beyond progression after first-line treatment with the same drug. Methods: In our open-label, randomised, phase 3 trial done at 82 sites in four countries, we enrolled women (aged ≥18 years) who had previously received first-line platinum-based therapy including bevacizumab, and had recurrent (≥6 months since last platinum dose), International Federation of Gynaecology and Obstetrics stage IIIB–IV ovarian cancer with an Eastern Cooperative Oncology Group performance status 0–2. Patients were randomly assigned (1:1) to receive a carboplatin-based doublet intravenously (carboplatin area under the concentration curve [AUC] 5 on day 1 plus paclitaxel 175 mg/m2 on day 1, every 21 days; carboplatin AUC 4 on day 1 plus gemcitabine 1000 mg/m2 on days 1 and 8, every 21 days; or carboplatin AUC 5 on day 1 plus pegylated liposomal doxorubicin 30 mg/m2 on day 1, every 28 days), or a carboplatin-based doublet plus bevacizumab (10 mg/kg intravenous every 14 days combined with pegylated liposomal doxorubicin–carboplatin, or 15 mg/kg every 21 days combined with gemcitabine–carboplatin or paclitaxel–carboplatin). Evaluable disease according to RECIST 1.1 guidelines was required before randomisation. Randomisation was done through the trial website with a minimisation procedure, stratified by centre, time of recurrence, performance status, and type of second-line chemotherapy. The primary endpoint was investigator-assessed progression-free survival, analysed on an intention-to-treat basis. Safety was assessed in all participants who received at least one dose. This trial is registered with ClinicalTrials.gov, NCT01802749 and EudraCT 2012-004362-17. Findings: Between Dec 6, 2013, and Nov 11, 2016, 406 patients were recruited (203 [50%] assigned to the bevacizumab group and 203 [50%] to the standard chemotherapy group). 130 patients (64%) in the bevacizumab group and 131 (65%) in the standard chemotherapy group had progressed after receiving a last dose of platinum more than 12 months before, and 146 patients (72%) in the bevacizumab group and 147 (72%) in the standard chemotherapy group had progressed after completion of first-line bevacizumab maintenance. 161 participants (79%) progressed in the standard chemotherapy group, as did 143 (70%) in the bevacizumab group. Median progression-free survival was 8·8 months (95% CI 8·4–9·3) in the standard chemotherapy group and 11·8 months (10·8–12·9) in the bevacizumab group (hazard ratio 0·51, 95% CI 0·41–0·65; log-rank p

Published
2021

36. Neoadjuvant radiotherapy dose escalation for locally advanced rectal cancers in the new era of radiotherapy: A review of literature

Author

Francesco Colangelo, Antonio Stefanelli, Agostino Cristaudo, Alessandro Alghisi, Antonio Ardizzoia, A. Cocchi, Stefano Ursino, Ilaria Costanza Fumagalli, Romerai D’Amico, Giuseppe De Nobili, Carlo Pietro Soatti, and Durim Delishaj

Subjects
Neoadjuvant radiotherapy, medicine.medical_specialty, Systematic Reviews, Radiotherapy, Intensity-modulated radiotherapy, business.industry, Colorectal cancer, medicine.medical_treatment, Rectal cancer, Radiotherapy, Volumetric Modulated Arc Therapy, Image-guided radiotherapy, Intensity-modulated radiotherapy, Neoadjuvant radiotherapy, Locally advanced, Image-guided radiotherapy, General Medicine, Volumetric Modulated Arc Therapy, medicine.disease, Image guided radiotherapy, Volumetric modulated arc therapy, Radiation therapy, Radiotherapy dose, Medicine, Radiology, Intensity modulated radiotherapy, Rectal cancer, business
Abstract

BACKGROUND The standard treatment of locally advanced rectal cancers (LARC) consists on neoadjuvant chemoradiotherapy followed by total mesorectal excision. Different data in literature showed a benefit on tumor downstaging and pathological complete response (pCR) rate using radiotherapy dose escalation, however there is shortage of studies regarding dose escalation using the innovative techniques for LARC (T3-4 or N1-2). AIM To analyze the role of neoadjuvant radiotherapy dose escalation for LARC using innovative radiotherapy techniques. METHODS In December 2020, we conducted a comprehensive literature search of the following electronic databases: PubMed, Web of Science, Scopus and Cochrane library. The limit period of research included articles published from January 2009 to December 2020. Screening by title and abstract was carried out to identify only studies using radiation doses equivalent dose 2 Gy fraction (EQD2) ≥ 54 Gy and Volumetric Modulated Arc Therapy (VMAT), intensity-modulated radiotherapy or image-guided radiotherapy (IGRT) techniques. The authors’ searches generated a total of 2287 results and, according to PRISMA Group (2009) screening process, 21 publications fulfil selection criteria and were included for the review. RESULTS The main radiotherapy technique used consisted in VMAT and IGRT modality. The mainly dose prescription was 55 Gy to high risk volume and 45 Gy as prophylactic volume in 25 fractions given with simultaneous integrated boosts technique (42.85%). The mean pCR was 28.2% with no correlation between dose prescribed and response rates (P value ≥ 0.5). The R0 margins and sphincter preservation rates were 98.88% and 76.03%, respectively. After a mean follow-up of 35 months local control was 92.29%. G3 or higher toxicity was 11.06% with no correlation between dose prescription and toxicities. Patients receiving EQD2 dose > 58.9 Gy and BED > 70.7 Gy had higher surgical complications rates compared to other group (P value = 0.047). CONCLUSION Dose escalation neoadjuvant radiotherapy using innovative techniques is safe for LARC achieving higher rates of pCR. EQD2 doses > 58.9 Gy is associated with higher rate of surgical complications.

Published
2021
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37. Breast cancer management with CDK4/6 inhibitors as first line treatment: a single institution retrospective review

Author

Villa, F., primary, Corbetta, C., additional, Crippa, A., additional, Pelizzoni, D., additional, Vittimberga, I., additional, Sansi, C., additional, Arnoffi, J., additional, Guida, F.M., additional, Cuomo, O., additional, Tafuni, M., additional, Sassone, M.C., additional, Viganò, C.V., additional, Anghilieri, M., additional, and Ardizzoia, A., additional

Published
2022
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38. Randomized trial on adjuvant treatment with FOLFIRI followed by docetaxel and cisplatin versus 5-fluorouracil and folinic acid for radically resected gastric cancer

Author

Floriani, I., Rulli, E., Cropalato Di Tullio, M., Poli, D., Galli, F., Biagioli, E., De Simone, I., Mangano, S., Tonato, M., Zucca, E., Valsecchi, M.G., Bajetta, E., Di Bartolomeo, M., Labianca, R., Amadori, D., Falcone, A., Di Costanzo, F., Daniele, B., Pinto, C., Comella, G., Nitti, D., Mini, E., De Placido, S., Marchet, A., Catena, L., Schiavo, M., Pinotti, G., Proserpio, I., Rosati, G., Bordonaro, R., Cordio, S., Burrafato, G., Bochicchio, A.M., Aieta, M., Fazio, N., Spada, F., Amoroso, V., Marini, G., Soto Parra, H., Novello, G., Massidda, B., Ionta, M.T., Comandè, M., Venezia, R., Bertolini, A., Menatti, E., Zanlorenzi, L., Colombo, A., Iop, A., Bonura, S., Mazza, E., Viganò, M., Ardizzoia, A., Dell'Oro, S., Lo Re, G., Santeufemia, D., Buonadonna, A., Luisi, D., Ucci, G., Di Lucca, G., Bonetti, A., Bergamo, F., Alù, M., Vastola, F., Marchetti, P., Corsi, D.C., Massa, E., Di Pinto, G., Duro, M., Oliani, C., Franchini, M., Inzoli, A., Gebbia, N., Repetto, L., Rota, S., Frontini, L., Mosconi, S., Quadri, A., De Grossi, S., Bidoli, P., Cazzaniga, M.E., Villa, F., Foa, P., Ferrari, D., Aitini, E., Rabbi, C., Barni, S., Petrelli, F., Giordano, M., Luchena, G., Pirovano, M., Nasisi, A., Catalano, V., Giordani, P., Zaniboni, A., Leone, F., Ferrario, S., Beretta, G.D., Menichetti, E.T., Conte, D., Mari, D., Giannicola, R., Pierantoni, C., Luporini, A.G., Ravaioli, A., Tassinari, D., Nicolini, M., Frassineti, G.L., Turci, D., Zumaglini, F., Tamberi, S., Piancastelli, A., Cruciani, G., Landi, L., Minuti, G., Cantore, M., Orlandi, M., Mambrini, A., Ciarlo, A., Cavaciocchi, D., Del Monte, F., Ricci, S., Brunetti, M.I., Lencioni, M., Sisani, M., Sozzi, P., Granetto, C., Chiara, S., Galetto, A.S., Ribecco, A.S., DeCensi, A., Ciuffreda, L., Baldini, E.E., Camisa, R., Todeschini, R., Santoro, A., Rimassa, L., Carnaghi, C., Pressiani, T., Boni, C., Rondini, E., Gnoni, R., Gasperoni, S., Cavanna, L., Palladino, M.A., Mattioli, R., Laici, G., Pucci, F., Alessio, M.D., Bernardini, I., Tomasello, G., Baldino, G., Rossetti, R., Giaquinta, S., Di Fabio, F., Rijas Llimpe, F.L., Brandes, A.A., Marzola, M., Montesarchio, V., Rea, A., Genua, G., Casaretti, R., Silvestro, L., Montano, M., Sarobba, M.G., Sanna, G., Filippelli, G., Dima, G., Greco, E., Roselli, M., Natale, D., Condemi, G., Fumi, G., Tafuto, S., Masullo, P., Tiberio, G., de Manzoni, G., Fiorentini, G., Mazzanti, R., Carlomagno, C., De Stefano, A., Cartenì, G., and Otero, M.

Published
2014
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39. Upfront FOLFOXIRI plus bevacizumab and reintroduction after progression versus mFOLFOX6 plus bevacizumab followed by FOLFIRI plus bevacizumab in the treatment of patients with metastatic colorectal cancer (TRIBE2): a multicentre, open-label, phase 3, randomised, controlled trial

Author

Chiara Cremolini, Carlotta Antoniotti, Daniele Rossini, Sara Lonardi, Fotios Loupakis, Filippo Pietrantonio, Roberto Bordonaro, Tiziana Pia Latiano, Emiliano Tamburini, Daniele Santini, Alessandro Passardi, Federica Marmorino, Roberta Grande, Giuseppe Aprile, Alberto Zaniboni, Sabina Murgioni, Cristina Granetto, Angela Buonadonna, Roberto Moretto, Salvatore Corallo, Stefano Cordio, Lorenzo Antonuzzo, Gianluca Tomasello, Gianluca Masi, Monica Ronzoni, Samantha Di Donato, Chiara Carlomagno, Matteo Clavarezza, Giuliana Ritorto, Andrea Mambrini, Mario Roselli, Samanta Cupini, Serafina Mammoliti, Elisabetta Fenocchio, Enrichetta Corgna, Vittorina Zagonel, Gabriella Fontanini, Clara Ugolini, Luca Boni, Alfredo Falcone, Filippo Guglielmo Maria De Braud, Evaristo Maiello, Giovanni Luca Frassineti, Teresa Gamucci, Francesco Di Costanzo, Luca Gianni, Patrizia Racca, Giacomo Allegrini, Alberto Sobrero, Massimo Aglietta, Enrico Cortesi, Domenico Cristiano Corsi, Alberto Ballestrero, Andrea Bonetti, Francesco Di Clemente, Enzo Ruggeri, Fortunato Ciardiello, Marco Benasso, Stefano Vitello, Saverio Cinieri, Stefania Mosconi, Nicola Silvestris, Antonio Frassoldati, Samantha Cupini, Alessandro Bertolini, Giampaolo Tortora, Carmelo Bengala, Daris Ferrari, Antonia Ardizzoia, Carlo Milandri, Silvana Chiara, Gianpiero Romano, Stefania Miraglia, Laura Scaltriti, Francesca Pucci, Livio Blasi, Silvia Brugnatelli, Luisa Fioretto, Angela Stefania Ribecco, Raffaella Longarini, Michela Frisinghelli, Maria Banzi, Cremolini, C., Antoniotti, C., Rossini, D., Lonardi, S., Loupakis, F., Pietrantonio, F., Bordonaro, R., Latiano, T. P., Tamburini, E., Santini, D., Passardi, A., Marmorino, F., Grande, R., Aprile, G., Zaniboni, A., Murgioni, S., Granetto, C., Buonadonna, A., Moretto, R., Corallo, S., Cordio, S., Antonuzzo, L., Tomasello, G., Masi, G., Ronzoni, M., Di Donato, S., Carlomagno, C., Clavarezza, M., Ritorto, G., Mambrini, A., Roselli, M., Cupini, S., Mammoliti, S., Fenocchio, E., Corgna, E., Zagonel, V., Fontanini, G., Ugolini, C., Boni, L., Falcone, A., De Braud, F. G. M., Maiello, E., Frassineti, G. L., Gamucci, T., Di Costanzo, F., Gianni, L., Racca, P., Allegrini, G., Sobrero, A., Aglietta, M., Cortesi, E., Corsi, D. C., Ballestrero, A., Bonetti, A., Di Clemente, F., Ruggeri, E., Ciardiello, F., Benasso, M., Vitello, S., Cinieri, S., Mosconi, S., Silvestris, N., Frassoldati, A., Bertolini, A., Tortora, G., Bengala, C., Ferrari, D., Ardizzoia, A., Milandri, C., Chiara, S., Romano, G., Miraglia, S., Scaltriti, L., Pucci, F., Blasi, L., Brugnatelli, S., Fioretto, L., Ribecco, A. S., Longarini, R., Frisinghelli, M., and Banzi, M.

Subjects
Male, 0301 basic medicine, GONO, Organoplatinum Compounds, multicentre, Leucovorin, Colorectal Neoplasm, Gastroenterology, Settore MED/06, Antineoplastic Agents, Immunological, 0302 clinical medicine, Antineoplastic Combined Chemotherapy Protocols, Neoplasm Metastasis, FOLFOXIRI, progression versus mFOLFOX6 plus bevacizumab, mFOLFOX6, metastatic colorectal cancer, Middle Aged, TRIBE2 trial, FOLFIRI plus bevacizumab, Neoplasm Metastasi, Bevacizumab, FOLFOXIRI plus bevacizumab, triplet FOLFOXIRI, Oncology, Fluorouracil, 030220 oncology & carcinogenesis, Disease Progression, FOLFIRI, Female, metastatic colorectal cancer, triplet FOLFOXIRI , FOLFOXIRI plus bevacizumab, FOLFIRI plus bevacizumab, progression versus mFOLFOX6 plus bevacizumab, TRIBE2, Colorectal Neoplasms, Human, medicine.drug, Adult, medicine.medical_specialty, Adolescent, Analogs & derivatives, open-label, NO, Young Adult, 03 medical and health sciences, Folinic acid, Internal medicine, medicine, cancer, Humans, neoplasms, Aged, Antineoplastic Combined Chemotherapy Protocol, Performance status, business.industry, Organoplatinum Compound, randomised controlled, FOLFOXIRI, bevacizumab, mFOLFOX6, FOLFIRI, metastatic colorectal cancer, TRIBE2 trial, multicentre, open-label, phase 3, randomised controlled, GONO, Irinotecan, 030104 developmental biology, phase 3, TRIBE2, Camptothecin, business
Abstract

Summary Background The triplet FOLFOXIRI (fluorouracil, leucovorin, oxaliplatin, and irinotecan) plus bevacizumab showed improved outcomes for patients with metastatic colorectal cancer, compared with FOLFIRI (fluorouracil, leucovorin, and irinotecan) plus bevacizumab. However, the actual benefit of the upfront exposure to the three cytotoxic drugs compared with a preplanned sequential strategy of doublets was not clear, and neither was the feasibility or efficacy of therapies after disease progression. We aimed to compare a preplanned strategy of upfront FOLFOXIRI followed by the reintroduction of the same regimen after disease progression versus a sequence of mFOLFOX6 (fluorouracil, leucovorin, and oxaliplatin) and FOLFIRI doublets, in combination with bevacizumab. Methods TRIBE2 was an open-label, phase 3, randomised study of patients aged 18–75 years with an Eastern Cooperative Oncology Group (ECOG) performance status of 2, with unresectable, previously untreated metastatic colorectal cancer, recruited from 58 Italian oncology units. Patients were stratified according to centre, ECOG performance status, primary tumour location, and previous adjuvant chemotherapy. A randomisation system incorporating a minimisation algorithm was used to randomly assign patients (1:1) via a masked web-based allocation procedure to two different treatment strategies. In the control group, patients received first-line mFOLFOX6 (85 mg/m2 of intravenous oxaliplatin concurrently with 200 mg/m2 of leucovorin over 120 min; 400 mg/m2 intravenous bolus of fluorouracil; 2400 mg/m2 continuous infusion of fluorouracil for 48 h) plus bevacizumab (5 mg/kg intravenously over 30 min) followed by FOLFIRI (180 mg/m2 of intravenous irinotecan over 120 min concurrently with 200 mg/m2 of leucovorin; 400 mg/m2 intravenous bolus of fluorouracil; 2400 mg/m2 continuous infusion of fluorouracil for 48 h) plus bevacizumab after disease progression. In the experimental group, patients received FOLFOXIRI (165 mg/m2 of intravenous irinotecan over 60 min; 85 mg/m2 intravenous oxaliplatin concurrently with 200 mg/m2 of leucovorin over 120 min; 3200 mg/m2 continuous infusion of fluorouracil for 48 h) plus bevacizumab followed by the reintroduction of the same regimen after disease progression. Combination treatments were repeated every 14 days for up to eight cycles followed by fluorouracil and leucovorin (at the same dose administered at the last induction cycle) plus bevacizumab maintenance until disease progression, unacceptable adverse events, or consent withdrawal. Patients and investigators were not masked. The primary endpoint was progression-free survival 2, defined as the time from randomisation to disease progression on any treatment given after first disease progression, or death, analysed by intention to treat. Safety was assessed in patients who received at least one dose of their assigned treatment. Study recruitment is complete and follow-up is ongoing. This trial is registered with Clinicaltrials.gov , NCT02339116 . Findings Between Feb 26, 2015, and May 15, 2017, 679 patients were randomly assigned and received treatment (340 in the control group and 339 in the experimental group). At data cut-off (July 30, 2019) median follow-up was 35·9 months (IQR 30·1–41·4). Median progression-free survival 2 was 19·2 months (95% CI 17·3–21·4) in the experimental group and 16·4 months (15·1–17·5) in the control group (hazard ratio [HR] 0·74, 95% CI 0·63–0·88; p=0·0005). During the first-line treatment, the most frequent of all-cause grade 3–4 events were diarrhoea (57 [17%] vs 18 [5%]), neutropenia (168 [50%] vs 71 [21%]), and arterial hypertension (25 [7%] vs 35 [10%]) in the experimental group compared with the control group. Serious adverse events occurred in 84 (25%) patients in the experimental group and in 56 (17%) patients in the control group. Eight treatment-related deaths were reported in the experimental group (two intestinal occlusions, two intestinal perforations, two sepsis, one myocardial infarction, and one bleeding) and four in the control group (two occlusions, one perforation, and one pulmonary embolism). After first disease progression, no substantial differences in the incidence of grade 3 or 4 adverse events were reported between the control and experimental groups, with the exception of neurotoxicity, which was only reported in the experimental group (six [5%] of 132 patients). Serious adverse events after disease progression occurred in 20 (15%) patients in the experimental group and 25 (12%) in the control group. Three treatment-related deaths after first disease progression were reported in the experimental group (two intestinal occlusions and one sepsis) and four in the control group (one intestinal occlusion, one intestinal perforation, one cerebrovascular event, and one sepsis). Interpretation Upfront FOLFOXIRI plus bevacizumab followed by the reintroduction of the same regimen after disease progression seems to be a preferable therapeutic strategy to sequential administration of chemotherapy doublets, in combination with bevacizumab, for patients with metastatic colorectal cancer selected according to the study criteria. Funding The GONO Cooperative Group, the ARCO Foundation, and F Hoffmann–La Roche.

Published
2020
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40. Response to Chemotherapy and Clinical Outcome of Patients With Recurrent Epithelial Ovarian Cancer After PARP Inhibitor Maintenance Treatment: A Multicenter Retrospective Italian Study

Author

ANGIOLO GADDUCCI, STEFANIA COSIO, FABIO LANDONI, ANDREA ALBERTO LISSONI, PAOLO ZOLA, MARIA ELENA LAUDANI, ANTONIO ARDIZZOIA, ANGELA GAMBINO, ENRICO SARTORI, Gadducci, A, Cosio, S, Landoni, F, Lissoni, A, Zola, P, Elena Laudani, M, Ardizzoia, A, and Gambino and Enrico Sartori, A

Subjects
epithelial ovarian cancer, Ovarian Neoplasms, Cancer Research, recurrence, General Medicine, Carcinoma, Ovarian Epithelial, Poly(ADP-ribose) Polymerase Inhibitors, chemotherapy, PARP inhibitor, Oncology, Antineoplastic Combined Chemotherapy Protocols, Humans, Female, Homologous recombination, Neoplasm Recurrence, Local, Retrospective Studies
Abstract

To assess response rates and survival in patients with recurrent platinum-sensitive epithelial ovarian cancer (EOC) who received PARP inhibitor (PARP-i) maintenance and who subsequently underwent salvage chemotherapy for disease progression after PARPi.This retrospective investigation analyzed 103 patients who were treated in five Italian Gynecologic centers. The PARPi used was olaparib in 46 patients, niraparib in 55, and rucaparib in 2. The interval time between the last cycle of pre- PARPi platinum-based chemotherapy and the diagnosis of progression during PARPi maintenance was defined as platinum-free interval (PFI).Of the 28 patients with PFI6 months, 23 received chemotherapy (non-platinum single agent, 20; trabectedin + pegylated liposomal doxorubicin (PLD), 3). Forty-two of the 43 patients with PFI 6-12 months underwent chemotherapy (platinum-based chemotherapy,11; trabectedin + PLD, 10; non platinum-single agent, 21). Thirty-one of the 32 patients with PFI12 months received chemotherapy (platinum-based chemotherapy, 23; trabectedin + PLD, 3; non platinum - single agent, 5). An objective response was found in 13.0%, 26.2% and 41.9 % of the patients with PFI6 months, 6-12 months, and12 months (p= 0.03), respectively, and the corresponding median survivals after PARPi were 8.9 months, 17.5 months and 24.1 months (p= 0.002), respectively.Before the PARPi era, some randomized trials on platinum rechallenge in patients with recurrent EOC after more than 6 months from the last platinum cycle have shown response rates ranging from 47.2% to 66%. Response rates to chemotherapy for progression after PARPi appear to be lower than those expected according to PFI.

Published
2022

41. High-dose-rate brachytherapy as monotherapy for localized prostate cancer using three different doses - 14 years of single-centre experience

Author

Soatti, C, Delishaj, D, D'Amico, R, Frigerio, C, Fumagalli, I, Bonsignore, F, Sangalli, G, Declich, F, Arcangeli, S, Ardizzoia, A, Colombo, A, Soatti C. P., Delishaj D., D'Amico R., Frigerio C., Fumagalli I. C., Bonsignore F., Sangalli G., Declich F., Arcangeli S., Ardizzoia A., Colombo A., Soatti, C, Delishaj, D, D'Amico, R, Frigerio, C, Fumagalli, I, Bonsignore, F, Sangalli, G, Declich, F, Arcangeli, S, Ardizzoia, A, Colombo, A, Soatti C. P., Delishaj D., D'Amico R., Frigerio C., Fumagalli I. C., Bonsignore F., Sangalli G., Declich F., Arcangeli S., Ardizzoia A., and Colombo A.

Abstract

Purpose: To evaluate clinical outcomes in patients with localized prostate cancer (LPC) treated with 3D conformal high-dose-rate (HDR) brachytherapy (BT) as monotherapy. Material and methods: From March 2004 to November 2017, 277 men with LPC underwent 3D conformal HDR-BT as monotherapy, with a temporary implant. The dose prescription was: 38 Gy in 4 fractions (149 patients), 27 Gy in 2 fractions (41 patients), and 19-20 Gy in a single fraction (87 patients). Biochemical progression-free survival (bPFS), progression- free survival (PFS), and cancer-specific survival (CSS) were calculated. Acute and late genitourinary (GU) and gastrointestinal (GI) toxicity assessment were performed using Common Terminology Criteria for Adverse Events v5.0. Results: The mean age was 67 (range, 47-81) years. Overall, 145 patients were low-risk, 116 intermediate-risk, and 16 high-risk prostate cancer. After a median follow-up of six years (range, 6-160 months), bPFS, PFS, and CSS were 81%, 96%, and 97%, respectively. Dose prescription, initial prostate specific antigen (iPSA) ≥ 9,5 ng/ml, and high-risk disease resulted in prognostic factors regarding bPFS. Only G2-G3 acute or late GI and GU toxicities were observed. Conclusions: HDR-BT as monotherapy is a valid and safe treatment modality for localized prostate cancer. After a long follow-up, patients receiving 19-20 Gy in a single fraction had a lower biochemical control rate compared to patients receiving 38 Gy in 4 fractions or 27 Gy in 2 fractions. Randomized prospective trials with a longer follow-up are necessary to confirm our results, and define total doses and dose per fraction for HDR-BT in patients with LPC.

Published
2021

42. Indicators of guideline-concordant care in lung cancer defined with a modified Delphi method and piloted in a cohort of over 5,800 cases

Author

Andreano, A, Valsecchi, M, Russo, A, Siena, S, Andruccioli, M, Ardizzoia, A, Assi, A, Baisi, A, Bedini, A, Beretta, G, Bersani, M, Bertagna, F, Berti, E, Bertolini, A, Bettini, A, Bignardi, M, Bini, F, Bna, C, Bono, F, Ottoni, D, Borghesi, A, Borghetti, P, Brunelli, A, Buffoli, A, Cacioppo, C, Calati, A, Calcagno, A, Casagrande, S, Casartelli, C, Castellani, M, Castro, A, Catalano, G, Catena, L, Ceresoli, G, Cergnul, M, Ciocia, G, Colombo, A, Conti, B, Corti, D, Cortinovis, D, Cozzi, C, Crippa, F, De Monte, A, Candis, D, De Toma, D, De Marinis, F, Dimarco, B, Di Nuovo, F, Doglioni, C, Fabbris, V, Faccioli, P, Fagnani, D, Farina, G, Fariselli, L, Filipazzi, V, Franzi, F, Frata, P, Gajate, A, Gardani, G, Gasparini, M, Giordano, M, Grignani, F, Landoni, C, Lombardi, C, Lombardi, F, Luciani, A, Maffioli, L, Marchione, R, Mariani, P, Maspero, A, Meriggi, F, Miedico, A, Morbini, P, Muriana, G, Orlandoni, G, Paris, E, Pedrazzoli, P, Pepe, G, Pezzica, E, Piccoli, F, Pinotti, G, Quadri, A, Ravasio, A, Ravenna, F, Ricchiuti, E, Rinaldo, D, Roda, G, Rossi, G, Santoro, A, Soatti, C, Stiglich, F, Tagliabue, L, Tirelli, V, Tironi, A, Tomirotti, M, Travaini, L, Ucci, G, Vaghi, A, Vanzulli, A, Veronesi, G, Vittimberga, I, Zambelli, C, Andreano A., Valsecchi M. G., Russo A. G., Siena S., Andruccioli M., Ardizzoia A., Assi A., Baisi A., Bedini A. V., Beretta G., Bersani M., Bertagna F., Berti E., Bertolini A., Bettini A., Bignardi M., Bini F., Bna C., Bono F., Ottoni D. B., Borghesi A., Borghetti P., Brunelli A., Buffoli A., Cacioppo C., Calati A., Calcagno A., Casagrande S., Casartelli C., Castellani M., Castro A., Catalano G., Catena L., Ceresoli G. L., Cergnul M., Ciocia G., Colombo A., Conti B., Corti D., Cortinovis D., Cozzi C., Crippa F., De Monte A., Candis D. D., De Toma D., De Marinis F., DiMarco B., Di Nuovo F., Doglioni C., Fabbris V., Faccioli P., Fagnani D., Farina G., Fariselli L., Filipazzi V., Franzi F., Frata P., Gajate A. M. S., Gardani G., Gasparini M., Giordano M., Grignani F., Landoni C., Lombardi C., Lombardi F., Luciani A., Maffioli L. S., Marchione R., Mariani P., Maspero A., Meriggi F., Miedico A., Morbini P., Muriana G., Orlandoni G., Paris E., Pedrazzoli P., Pepe G., Pezzica E., Piccoli F., Pinotti G., Quadri A., Ravasio A., Ravenna F., Ricchiuti E., Rinaldo D., Roda G., Rossi G., Santoro A., Soatti C. P., Stiglich F., Tagliabue L., Tirelli V., Tironi A., Tomirotti M., Travaini L. L., Ucci G., Vaghi A., Vanzulli A., Veronesi G., Vittimberga I., Zambelli C., Andreano, A, Valsecchi, M, Russo, A, Siena, S, Andruccioli, M, Ardizzoia, A, Assi, A, Baisi, A, Bedini, A, Beretta, G, Bersani, M, Bertagna, F, Berti, E, Bertolini, A, Bettini, A, Bignardi, M, Bini, F, Bna, C, Bono, F, Ottoni, D, Borghesi, A, Borghetti, P, Brunelli, A, Buffoli, A, Cacioppo, C, Calati, A, Calcagno, A, Casagrande, S, Casartelli, C, Castellani, M, Castro, A, Catalano, G, Catena, L, Ceresoli, G, Cergnul, M, Ciocia, G, Colombo, A, Conti, B, Corti, D, Cortinovis, D, Cozzi, C, Crippa, F, De Monte, A, Candis, D, De Toma, D, De Marinis, F, Dimarco, B, Di Nuovo, F, Doglioni, C, Fabbris, V, Faccioli, P, Fagnani, D, Farina, G, Fariselli, L, Filipazzi, V, Franzi, F, Frata, P, Gajate, A, Gardani, G, Gasparini, M, Giordano, M, Grignani, F, Landoni, C, Lombardi, C, Lombardi, F, Luciani, A, Maffioli, L, Marchione, R, Mariani, P, Maspero, A, Meriggi, F, Miedico, A, Morbini, P, Muriana, G, Orlandoni, G, Paris, E, Pedrazzoli, P, Pepe, G, Pezzica, E, Piccoli, F, Pinotti, G, Quadri, A, Ravasio, A, Ravenna, F, Ricchiuti, E, Rinaldo, D, Roda, G, Rossi, G, Santoro, A, Soatti, C, Stiglich, F, Tagliabue, L, Tirelli, V, Tironi, A, Tomirotti, M, Travaini, L, Ucci, G, Vaghi, A, Vanzulli, A, Veronesi, G, Vittimberga, I, Zambelli, C, Andreano A., Valsecchi M. G., Russo A. G., Siena S., Andruccioli M., Ardizzoia A., Assi A., Baisi A., Bedini A. V., Beretta G., Bersani M., Bertagna F., Berti E., Bertolini A., Bettini A., Bignardi M., Bini F., Bna C., Bono F., Ottoni D. B., Borghesi A., Borghetti P., Brunelli A., Buffoli A., Cacioppo C., Calati A., Calcagno A., Casagrande S., Casartelli C., Castellani M., Castro A., Catalano G., Catena L., Ceresoli G. L., Cergnul M., Ciocia G., Colombo A., Conti B., Corti D., Cortinovis D., Cozzi C., Crippa F., De Monte A., Candis D. D., De Toma D., De Marinis F., DiMarco B., Di Nuovo F., Doglioni C., Fabbris V., Faccioli P., Fagnani D., Farina G., Fariselli L., Filipazzi V., Franzi F., Frata P., Gajate A. M. S., Gardani G., Gasparini M., Giordano M., Grignani F., Landoni C., Lombardi C., Lombardi F., Luciani A., Maffioli L. S., Marchione R., Mariani P., Maspero A., Meriggi F., Miedico A., Morbini P., Muriana G., Orlandoni G., Paris E., Pedrazzoli P., Pepe G., Pezzica E., Piccoli F., Pinotti G., Quadri A., Ravasio A., Ravenna F., Ricchiuti E., Rinaldo D., Roda G., Rossi G., Santoro A., Soatti C. P., Stiglich F., Tagliabue L., Tirelli V., Tironi A., Tomirotti M., Travaini L. L., Ucci G., Vaghi A., Vanzulli A., Veronesi G., Vittimberga I., and Zambelli C.

Abstract

Background: To identify indicators of guideline-concordant care in lung cancer, to implement such indicators with cancer registry data linked to health databases, and to pilot them in a cohort of patients from the cancer registry of the Milan Province. Methods: Thirty-four indicators were selected by revision of main guidelines by cancer epidemiologists, and then evaluated by a multidisciplinary panel of clinicians involved in lung cancer care and working on the pathway of lung cancer diagnosis and treatment in the Lombardy region, Italy. With a modified Delphi method, they assessed for each indicator the content validity as a quality measure of the care pathway, the degree of modifiability from the health professional, and the relevance to the health professional. Feasibility was assessed using the cancer registry and the routine health records of the Lombardy region. Feasible indicators were then calculated in the cohort of lung cancer patients diagnosed in 2007–2012 derived from the cancer registry of the Milan Province. Criterion validity was assessed reviewing clinical records of a random sample of 114 patients (threshold for acceptable discordance ≤20%). Finally, reliability was evaluated at the provider level. Results: Initially, 34 indicators were proposed for evaluation in the first Delphi round. Of the finally 22 selected indicators, 3 were not feasible because the required information was actually not available. The remaining 19 were calculated on the pilot cohort. After assessment of criterion validity (3 eliminated), 16 indicators were retained in the final set and evaluated for reliability. Conclusion: The developed and piloted set of indicators is now available to implement and monitor, over time, quality initiatives for lung cancer care in the studied health system.

Published
2021

44. Driving the Emission Towards Blue by Controlling the HOMO‐LUMO Energy Gap in BF 2 ‐Functionalized 2‐(Imidazo[1,5‐ a ]pyridin‐3‐yl)phenols

Author

Colombo, Gioele, Attilio Ardizzoia, G., Furrer, Julien, Therrien, Bruno, and Brenna, Stefano

Subjects
Boron Compounds, Models, Molecular, Band gap, Substituent, Catalysis, chemistry.chemical_compound, symbols.namesake, Phenols, Stokes shift, 540 Chemistry, HOMO/LUMO, Density Functional Theory, blue emission, Full Paper, HOMO-LUMO gap, Ligand, Chemistry, Organic Chemistry, boron, fluorescence, TD-DFT, General Chemistry, Full Papers, Fluorescence, Crystallography, Atomic electron transition, symbols, Quantum Theory, Density functional theory
Abstract

Several boron compounds with 2‐(imidazo[1,5‐a]pyridin‐3‐yl)phenols, differentiated by the nature of the substituent (R) in the para position of the hydroxy group, have been synthesized and thoroughly characterized both in solution (1H, 13C, 11B, 19F NMR) and in the solid state (X‐ray). All derivatives displayed attractive photophysical properties like very high Stokes shift, high fluorescence quantum yields and a good photostability in solution. Time‐Dependent Density Functional Theory (TD‐DFT) calculations allowed to define the main electronic transitions as intra ligand transitions (1ILT), which was corroborated by the Natural Transition Orbitals (NTOs) shapes. The homo‐lumo energy gap was correlated to the electronic properties of the substituent R on the phenolic ring, as quantified by its σp Hammett constant., Blue emissive materials: boron containing fluorescent compounds have been prepared starting from imidazo[1,5‐a]pyridine phenols. Large Stokes shift, high absolute quantum yields and good photostability are observed in solution. TD‐DFT calculations allowed to find a linear correlation between the HOMO‐LUMO energy gap of these compounds and the Hammett constants of substituents R para to the hydroxyl group of the phenols.

Published
2021
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45. Metronomic chemotherapy with oral vinorelbine (mVNR) and capecitabine (mCAPE) in advanced HER2-negative breast cancer patients: is it a way to optimize disease control? Final results of the VICTOR-2 study

Author

Cazzaniga, M. E., Cortesi, L., Ferzi, A., Scaltriti, L., Cicchiello, F., Ciccarese, M., Della Torre, S., Villa, F., Giordano, M., Verusio, C., Nicolini, M., Gambaro, A. R., Zanlorenzi, L., Biraghi, E., Legramandi, L., Rulli, E., Riva, Francesca, Davide, Pelizzoni, Marchi, Isabella, Collovà, Elena, Prati, Giuseppe, Ardizzoia, Antonio, Toniolo, Davide, Pugliese, Palma, Pogliani, Claudia, Gambino, Abbondanza, Stocchi, Lucia, Colombo, Andrea, Fasola, Cinzia, Venezia, Raffaele, Galli, Fabio, Torri, Valter, and On behalf of VICTOR Study Group

Published
2016
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46. Minnesota acute graft-versus-host disease risk score predicts survival at onset of graft-versus-host disease after post-transplant cyclophosphamide prophylaxis

Author

Ardizzoia, Federica, primary, Lorentino, Francesca, additional, Bruno, Alessandro, additional, Marktel, Sarah, additional, Giglio, Fabio, additional, Clerici, Daniela, additional, Farina, Francesca, additional, Mastaglio, Sara, additional, Piemontese, Simona, additional, Assanelli, Andrea A., additional, Carrabba, Matteo G., additional, Bernardi, Massimo, additional, Corti, Consuelo, additional, Peccatori, Jacopo, additional, Ciceri, Fabio, additional, Greco, Raffaella, additional, and Lupo-Stanghellini, Maria Teresa, additional

Published
2022
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49. Minnesota acute graft

Author

Federica, Ardizzoia, Francesca, Lorentino, Alessandro, Bruno, Sarah, Marktel, Fabio, Giglio, Daniela, Clerici, Francesca, Farina, Sara, Mastaglio, Simona, Piemontese, Andrea A, Assanelli, Matteo G, Carrabba, Massimo, Bernardi, Consuelo, Corti, Jacopo, Peccatori, Fabio, Ciceri, Raffaella, Greco, and Maria Teresa, Lupo-Stanghellini

Subjects
Risk Factors, Minnesota, Hematopoietic Stem Cell Transplantation, Humans, Graft vs Host Disease, Cyclophosphamide
Published
2022

50. Long-Alkyl Chain Functionalized Imidazo[1,5- a ]pyridine Derivatives as Blue Emissive Dyes.

Author

Colombo, Gioele, Cinco, Anita, Ardizzoia, G. Attilio, and Brenna, Stefano

Subjects
PYRIDINE derivatives, DENSITY functional theory, SELECTION rules (Nuclear physics), INFRARED spectroscopy, FLUORESCENCE
Abstract

A series of boron difluoride compounds with 2-(imidazo[1,5-a]pyridin-3-yl)phenols bearing alkylic chains at the 1-position has been synthesized and characterized both with 1H and 13C NMR and infrared spectroscopy. This series of compounds displayed blue emission in solution and in thin polymeric films, with interesting features like large Stokes shifts and good fluorescence quantum yields. Time-Dependent Density Functional Theory (TD-DFT) calculations allowed for the identification of the main electronic transitions as intra ligand transitions (1ILT), as corroborated by the Natural Transition Orbitals (NTOs) shapes. [ABSTRACT FROM AUTHOR]

Published
2023
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