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101 results on '"Zampino, M. G."'

1. Validation of the ONKOTEV Risk Prediction Model for Venous Thromboembolism in Outpatients with Cancer

Author

Cella, C, Knoedler, M, Hall, M, Arcopinto, M, Bagnardi, V, Gervaso, L, Pellicori, S, Spada, F, Zampino, M, Ravenda, P, Frassoni, S, Passaro, A, Milano, M, Laffi, A, Fazio, N, Lordick, F, Cella C. A., Knoedler M., Hall M., Arcopinto M., Bagnardi V., Gervaso L., Pellicori S., Spada F., Zampino M. G., Ravenda P. S., Frassoni S., Passaro A., Milano M., Laffi A., Fazio N., Lordick F., Cella, C, Knoedler, M, Hall, M, Arcopinto, M, Bagnardi, V, Gervaso, L, Pellicori, S, Spada, F, Zampino, M, Ravenda, P, Frassoni, S, Passaro, A, Milano, M, Laffi, A, Fazio, N, Lordick, F, Cella C. A., Knoedler M., Hall M., Arcopinto M., Bagnardi V., Gervaso L., Pellicori S., Spada F., Zampino M. G., Ravenda P. S., Frassoni S., Passaro A., Milano M., Laffi A., Fazio N., and Lordick F.

Abstract

Importance: The assessment of the risk of venous thromboembolism (VTE) among outpatients with cancer represents an unsolved topic. Current international guidelines recommend primary prophylaxis for patients at intermediate to high risk of VTE, indicated by a Khorana score of 2 or more. A previous prospective study developed the ONKOTEV score, a 4-variable risk assessment model (RAM) consisting of a Khorana score of more than 2, metastatic disease, vascular or lymphatic compression, and previous VTE event. Objective: To validate the ONKOTEV score as a novel RAM to assess the risk of VTE among outpatients with cancer. Design, Setting, and Participants: ONKOTEV-2 is a noninterventional prognostic study conducted in 3 European centers located in Italy, Germany, and the United Kingdom among a prospective cohort of 425 ambulatory patients with a histologically confirmed diagnosis of a solid tumor who were receiving active treatments. The total study duration was 52 months, with an accrual period of 28 months (from May 1, 2015, to September 30, 2017) and an overall follow up-period of 24 months (data were censored September 30, 2019). Statistical analysis was performed in October 2019. Exposures: The ONKOTEV score was calculated for each patient at baseline by collecting clinical, laboratory, and imaging data from tests performed for routine practice. Each patient was then observed to detect any thromboembolic event throughout the study period. Main Outcomes and Measures: The primary outcome of the study was the incidence of VTE, including deep vein thrombosis and pulmonary embolism. Results: A total of 425 patients (242 women [56.9%]; median age, 61 years [range, 20-92 years]) were included in the validation cohort of the study. The cumulative incidences for the risk of developing VTE at 6 months were 2.6% (95% CI, 0.7%-6.9%), 9.1% (95% CI, 5.8%-13.2%), 32.3% (95% CI, 21.0%-44.1%), and 19.3% (95% CI, 2.5%-48.0%), respectively, among 425 patients with an ONKOTEV score of 0

Published
2023

2. Clinical efficacy of sequential treatments in KRASG12C-mutant metastatic colorectal cancer: findings from a real-life multicenter Italian study (CRC-KR GOIM)

Author

Ciardiello, D, Chiarazzo, C, Famiglietti, V, Damato, A, Pinto, C, Zampino, M G, Castellano, G, Gervaso, L, Zaniboni, A, Oneda, E, Rapisardi, S, Bordonaro, R, Zichi, C, De Vita, F, Di Maio, M, Parisi, A, Giampieri, R, Berardi, R, Lavacchi, D, Antonuzzo, L, Tamburini, E, Maiorano, B A, Parrella, P, Latiano, T P, Normanno, N, De Stefano, A, Avallone, A, Martini, G, Napolitano, S, Troiani, T, Martinelli, E, Ciardiello, F, Maiello, E, Ciardiello, D, Chiarazzo, C, Famiglietti, V, Damato, A, Pinto, C, Zampino, M G, Castellano, G, Gervaso, L, Zaniboni, A, Oneda, E, Rapisardi, S, Bordonaro, R, Zichi, C, De Vita, F, Di Maio, M, Parisi, A, Giampieri, R, Berardi, R, Lavacchi, D, Antonuzzo, L, Tamburini, E, Maiorano, B A, Parrella, P, Latiano, T P, Normanno, N, De Stefano, A, Avallone, A, Martini, G, Napolitano, S, Troiani, T, Martinelli, E, Ciardiello, F, and Maiello, E

Subjects
KRASG12C mutation, Cancer Research, real-world data, Irinotecan, chemotherapy, first line treatment, Oxaliplatin, Treatment Outcome, Oncology, mCRC, Antineoplastic Combined Chemotherapy Protocols, Colonic Neoplasms, Humans, Fluorouracil, Colorectal Neoplasms, Retrospective Studies
Abstract

Background: The presence of KRASG12C mutation in metastatic colorectal cancer (mCRC) correlates with poor outcome. Although different selective inhibitors are under clinical development, the optimal treatment remains uncertain. Thus, we conducted a retrospective analysis in a large cohort of patients with KRASG12C mCRC treated in 12 Italian oncology units. Patients and methods: Patients with unresectable mCRC harboring KRASG12C mutation receiving a first-line chemotherapy doublet or triplet between 2011 and 2021 were included in the study. Evaluation of overall response rate (ORR), progression-free survival (PFS) and overall survival (OS) analysis was carried out. Results: A total of 256/6952 (3.7%) patients with mCRC displayed KRASG12C mutation; of these, 111 met the inclusion criteria. The ORR of first-line therapy was 38.7% (43/111). Median PFS (mPFS) was 9 months [95% confidence interval (CI) 7.5-10.5 months]. After progression, only 62% and 36% of the patients are fit to receive second or third lines of treatment, with limited clinical benefit. Median OS (mOS) was 21 months (95% CI 17.4-24.6 months). In patients receiving first-line triplet chemotherapy, ORR was 56.3% (9/16), mPFS was 13 months (95% CI 10.3-15.7 months) and mOS was 32 months (95% CI 7.7-56.3 months). For irinotecan-based doublets, ORR was 34.5 (10/29), mPFS was 9 months (95% CI 6.4-11.6 months) and mOS was 22 months (95% CI 16.0-28.0 months). With oxaliplatin-based doublets ORR was 36.4% (24/62), mPFS was 7 months (95% CI 4.6-9.4 months) and mOS was 18 months (95% CI, 13.6-22.4 months). Conclusion: Patients with KRASG12C-mutant mCRC had a disappointing response to standard treatments. Within the limitations of a retrospective study, these results suggest that first-line chemotherapy intensification with FOLFOXIRI is a valid option in fit patients.

Published
2022

4. Genital marginal failures after intensity-modulated radiation therapy (IMRT) in squamous cell anal cancer: no higher risk with IMRT when compared to 3DCRT

Author

Dell’Acqua, V., Kobiela, J., Kraja, F., Leonardi, M. C., Surgo, A., Zerella, M. A., Arculeo, S., Fodor, C., Ricotti, R., Zampino, M. G., Ravenda, S., Spinoglio, G., Biffi, R., Bazani, A., Luraschi, R., Vigorito, S., Spychalski, P., Orecchia, R., Glynne-Jones, R., and Jereczek-Fossa, B. A.

Published
2018
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5. Colorectal cancer, Vitamin D and microbiota: A double-blind Phase II randomized trial (ColoViD) in colorectal cancer patients

Author

Bellerba, F, Serrano, D, Harriet, J, Pozzi, C, Segata, N, Nabinejad, A, Piperni, E, Gnagnarella, P, Macis, D, Aristarco, V, Accornero, C, Manghi, P, Gonzaga, A, Biffi, R, Bottiglieri, L, Trovato, C, Zampino, M, Corso, F, Bellocco, R, Raimondi, S, Rescigno, M, Gandini, S, Bellerba F., Serrano D., Harriet J., Pozzi C., Segata N., NabiNejad A., Piperni E., Gnagnarella P., Macis D., Aristarco V., Accornero C. A., Manghi P., Gonzaga A. G., Biffi R., Bottiglieri L., Trovato C., Zampino M. G., Corso F., Bellocco R., Raimondi S., Rescigno M., Gandini S., Bellerba, F, Serrano, D, Harriet, J, Pozzi, C, Segata, N, Nabinejad, A, Piperni, E, Gnagnarella, P, Macis, D, Aristarco, V, Accornero, C, Manghi, P, Gonzaga, A, Biffi, R, Bottiglieri, L, Trovato, C, Zampino, M, Corso, F, Bellocco, R, Raimondi, S, Rescigno, M, Gandini, S, Bellerba F., Serrano D., Harriet J., Pozzi C., Segata N., NabiNejad A., Piperni E., Gnagnarella P., Macis D., Aristarco V., Accornero C. A., Manghi P., Gonzaga A. G., Biffi R., Bottiglieri L., Trovato C., Zampino M. G., Corso F., Bellocco R., Raimondi S., Rescigno M., and Gandini S.

Abstract

Background: Several studies suggest a role of gut microbiota in colorectal cancer (CRC) initiation and progression. Vitamin D (vitD) blood levels are also inversely correlated with CRC risk and prognosis. However, these factors’ interplay remains unknown. Methods: 74 CRC patients after standard treatment were randomized to 1-year 2000 IU/day vitD or placebo. Baseline and post-treatment fecal microbiota for shotgun metagenomics sequencing was collected. Coda-lasso and Principal Component Analysis were used to select and summarize treatment-associated taxa and pathways. Associations between vitD and taxa/pathways were investigated with logistic regression. Mediation analysis was performed to study if treatment-associated taxa mediated the effect of supplementation on 25(OH)D levels. Cox proportional-hazards model was used for disease-free survival (DFS). Results: 60 patients were analyzed. Change in alpha diversity (Shannon: p = 0.77; Simpson: p = 0.63) and post-treatment beta diversity (p = 0.70) were comparable between arms. Post-treatment abundances of 63 taxa and 32 pathways differed between arms. The 63 taxa also mediated the effect of supplementation on 25(OH)D (p = 0.02). There were sex differences in vitD levels, microbiota and pathways. Pathways of essential amino acids’ biosynthesis were more abundant in supplemented women. Fusobacterium nucleatum presence at baseline was associated with worse DFS (p = 0.02). Those achieving vitD sufficiency (25(OH)D≥30 ng/ml) had lower post-treatment abundances (p = 0.05). Women were more likely to have F. nucleatum post-treatment (p = 0.02). Conclusions: VitD supplementation may contribute shaping the gut microbiota and the microbiota may partially mediate the effect of supplementation on 25(OH)D. The observed sex-specific differences highlight the necessity of including sex/gender as a variable in microbiome studies.

Published
2022

6. PD-1/PD-L1 blockade, a novel strategy for targeting metastatic colorectal cancer: A systematic review and meta-analysis of randomized trials

Author

Rotundo, M, Bagnardi, V, Comande, M, Zampino, M, Rotundo M. S., Bagnardi V., Rotundo M., Comande M., Zampino M. G., Rotundo, M, Bagnardi, V, Comande, M, Zampino, M, Rotundo M. S., Bagnardi V., Rotundo M., Comande M., and Zampino M. G.

Abstract

Currently, standard treatment of patients with metastatic colorectal cancer (mCRC) comprises chemotherapy (CT) and/or biological therapy (BT) and/or best supportive care (BSC). The present study performed a meta-analysis on five phase II-III randomized clinical trials, which compared CT/BT/BSC as the control arm with the immune checkpoint inhibitors (ICIs) anti-programmed cell death protein 1 (PD-1) or its ligand (PD-L1) alone or in combination with cytotoxic T lymphocyte antigen 4 or mitogen activated protein kinase kinase inhibitors as the experimental arm, to evaluate whether a standard approach could be overcome using the novel target therapy strategy. Pooled hazard ratio (HR) for progression-free survival was 0.95 in favor of the experimental arm [95% confi- dence interval (CI), 0.74-1.22; P=0.68]. Heterogeneity was significant: Cochran's Q, 21.0; P=0.0082; I2 index, 76%. Pooled HR for overall survival was 0.88 in favor of the experimental arm (95% CI, 0.75-1.02; P=0.08). Heterogeneity was not significant (Cochran's Q, 6.0; P=0.31; I2 index, 16%). The present meta-analysis demonstrated a trend toward the improvement of survival by PD-1/PD-L1 blockade in mCRC. Further homogeneous studies are necessary to strengthen these results, beyond the known benefits of ICIs in deficient mismatch repair/high microsatellite instability tumors.

Published
2022

7. Preoperative versus postoperative docetaxel–cisplatin–fluorouracil (TCF) chemotherapy in locally advanced resectable gastric carcinoma: 10-year follow-up of the SAKK 43/99 phase III trial†

Author

Fazio, N., Biffi, R., Maibach, R., Hayoz, S., Thierstein, S., Brauchli, P., Bernhard, J., Stupp, R., Andreoni, B., Renne, G., Crosta, C., Morant, R., Chiappa, A., Luca, F., Zampino, M. G., Huber, O., Goldhirsch, A., de Braud, F., Roth, A. D., Pace, U., Cenciarelli, S., Pozzi, S., Bertani, E., Mura, S., Lorizzo, K., Di Meglio, G., Ravizza, D., Boselli, S., Matter, M., Richter, M., Monfardini, S., Dittrich, C., Häfner, M., and Clemens, M.

Published
2016
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8. Oxaliplatin plus fluoropyrimidines as adjuvant therapy for colon cancer in older patients: A subgroup analysis from the TOSCA trial

Author

Rosati, G, Lonardi, S, Galli, F, Di Bartolomeo, M, Ronzoni, M, Zampino, M, Banzi, M, Zaniboni, A, Pasini, F, Bozzarelli, S, Garattini, S, Ferrari, D, Montesarchio, V, Mambrini, A, Ciuffreda, L, Pusceddu, V, Carlomagno, C, Bidoli, P, Amoroso, D, Bochicchio, A, Frassineti, L, Corsi, D, Bilancia, D, Pastorino, A, De Stefano, A, Labianca, R, Iaffaioli, R, Nasti, G, Daniele, B, Zagonel, V, Pella, N, Aprile, G, Marchetti, R, Romiti, A, Foa, P, Mosconi, S, Sobrero, A, Cazzaniga, M, Beretta, G, Cortesi, E, Barni, S, Petrelli, F, Allione, P, D'Arco, A, Valmadre, G, Piazza, E, Veltri, E, Ramus, G, Giustini, L, Tumulo, S, Cascinu, S, Granetto, C, Testore, F, Giordano, M, Moroni, M, Di Seri, M, Nuzzo, A, Angelelli, L, Gori, S, Farina, G, Aglietta, M, Franchi, R, Comande, M, Giordani, P, Tonini, G, Bucci, E, Ballestrero, A, Benasso, M, Graiff, C, Bravi, S, Caffo, O, Silva, R, Frontini, L, Rota, S, Cozzi, L, Cantore, M, Maiello, E, Cinieri, S, Silvestris, N, Romito, S, Gebbia, V, Santoro, A, Artioli, F, Mattioli, R, Contu, A, Di Costanzo, F, Leonardi, F, Cavanna, L, Passalacqua, R, Sozzi, P, D'Amico, M, Amadori, D, Turci, D, Ravaioli, A, Pasquini, E, Gambi, A, Faedi, M, Cruciani, G, Bajetta, E, Gianni, L, Ionta, M, Massidda, B, Scartozzi, M, Ciarlo, A, Di Leo, A, Frustaci, S, Rangoni, G, Arizzoia, A, Pavesi, L, Verusio, C, Pinotti, G, Iop, A, De Placido, S, Adamo, V, Ficorella, C, Natale, D, Greco, E, Rulli, E, Poli, D, Porcu, L, Torri, V, Rosati G., Lonardi S., Galli F., Di Bartolomeo M., Ronzoni M., Zampino M. G., Banzi M., Zaniboni A., Pasini F., Bozzarelli S., Garattini S. K., Ferrari D., Montesarchio V., Mambrini A., Ciuffreda L., Pusceddu V., Carlomagno C., Bidoli P., Amoroso D., Bochicchio A. M., Frassineti L., Corsi D., Bilancia D., Pastorino A., De Stefano A., Labianca R., Iaffaioli R. V., Nasti G., Daniele B., Zagonel V., Pella N., Aprile G., Marchetti R. P., Romiti A., Foa P., Mosconi S., Sobrero A., Cazzaniga M., Beretta G. D., Cortesi E., Barni S., Petrelli F., Allione P., D'Arco A. M., Valmadre G., Piazza E., Veltri E., Ramus G. V., Giustini L., Tumulo S., Cascinu S., Granetto C., Testore F., Giordano M., Moroni M., Di Seri M., Nuzzo A., Angelelli L., Gori S., Farina G., Aglietta M., Franchi R., Comande M., Giordani P., Tonini G., Bucci E., Ballestrero A., Benasso M., Graiff C., Bravi S., Caffo O., Silva R. R., Frontini L., Rota S., Cozzi L., Cantore M., Maiello E., Cinieri S., Silvestris N., Romito S., Gebbia V., Santoro A., Artioli F., Mattioli R., Contu A., Di Costanzo F., Leonardi F., Cavanna L., Passalacqua R., Sozzi P., D'Amico M., Amadori D., Turci D., Ravaioli A., Pasquini E., Gambi A., Faedi M., Cruciani G., Bajetta E., Gianni L., Ionta M. T., Massidda B., Scartozzi M., Ciarlo A., Di Leo A., Frustaci S., Rangoni G., Arizzoia A., Pavesi L., Verusio C., Pinotti G., Iop A., De Placido S., Adamo V., Ficorella C., Natale D., Greco E., Rulli E., Poli D., Porcu L., Torri V., Rosati, G, Lonardi, S, Galli, F, Di Bartolomeo, M, Ronzoni, M, Zampino, M, Banzi, M, Zaniboni, A, Pasini, F, Bozzarelli, S, Garattini, S, Ferrari, D, Montesarchio, V, Mambrini, A, Ciuffreda, L, Pusceddu, V, Carlomagno, C, Bidoli, P, Amoroso, D, Bochicchio, A, Frassineti, L, Corsi, D, Bilancia, D, Pastorino, A, De Stefano, A, Labianca, R, Iaffaioli, R, Nasti, G, Daniele, B, Zagonel, V, Pella, N, Aprile, G, Marchetti, R, Romiti, A, Foa, P, Mosconi, S, Sobrero, A, Cazzaniga, M, Beretta, G, Cortesi, E, Barni, S, Petrelli, F, Allione, P, D'Arco, A, Valmadre, G, Piazza, E, Veltri, E, Ramus, G, Giustini, L, Tumulo, S, Cascinu, S, Granetto, C, Testore, F, Giordano, M, Moroni, M, Di Seri, M, Nuzzo, A, Angelelli, L, Gori, S, Farina, G, Aglietta, M, Franchi, R, Comande, M, Giordani, P, Tonini, G, Bucci, E, Ballestrero, A, Benasso, M, Graiff, C, Bravi, S, Caffo, O, Silva, R, Frontini, L, Rota, S, Cozzi, L, Cantore, M, Maiello, E, Cinieri, S, Silvestris, N, Romito, S, Gebbia, V, Santoro, A, Artioli, F, Mattioli, R, Contu, A, Di Costanzo, F, Leonardi, F, Cavanna, L, Passalacqua, R, Sozzi, P, D'Amico, M, Amadori, D, Turci, D, Ravaioli, A, Pasquini, E, Gambi, A, Faedi, M, Cruciani, G, Bajetta, E, Gianni, L, Ionta, M, Massidda, B, Scartozzi, M, Ciarlo, A, Di Leo, A, Frustaci, S, Rangoni, G, Arizzoia, A, Pavesi, L, Verusio, C, Pinotti, G, Iop, A, De Placido, S, Adamo, V, Ficorella, C, Natale, D, Greco, E, Rulli, E, Poli, D, Porcu, L, Torri, V, Rosati G., Lonardi S., Galli F., Di Bartolomeo M., Ronzoni M., Zampino M. G., Banzi M., Zaniboni A., Pasini F., Bozzarelli S., Garattini S. K., Ferrari D., Montesarchio V., Mambrini A., Ciuffreda L., Pusceddu V., Carlomagno C., Bidoli P., Amoroso D., Bochicchio A. M., Frassineti L., Corsi D., Bilancia D., Pastorino A., De Stefano A., Labianca R., Iaffaioli R. V., Nasti G., Daniele B., Zagonel V., Pella N., Aprile G., Marchetti R. P., Romiti A., Foa P., Mosconi S., Sobrero A., Cazzaniga M., Beretta G. D., Cortesi E., Barni S., Petrelli F., Allione P., D'Arco A. M., Valmadre G., Piazza E., Veltri E., Ramus G. V., Giustini L., Tumulo S., Cascinu S., Granetto C., Testore F., Giordano M., Moroni M., Di Seri M., Nuzzo A., Angelelli L., Gori S., Farina G., Aglietta M., Franchi R., Comande M., Giordani P., Tonini G., Bucci E., Ballestrero A., Benasso M., Graiff C., Bravi S., Caffo O., Silva R. R., Frontini L., Rota S., Cozzi L., Cantore M., Maiello E., Cinieri S., Silvestris N., Romito S., Gebbia V., Santoro A., Artioli F., Mattioli R., Contu A., Di Costanzo F., Leonardi F., Cavanna L., Passalacqua R., Sozzi P., D'Amico M., Amadori D., Turci D., Ravaioli A., Pasquini E., Gambi A., Faedi M., Cruciani G., Bajetta E., Gianni L., Ionta M. T., Massidda B., Scartozzi M., Ciarlo A., Di Leo A., Frustaci S., Rangoni G., Arizzoia A., Pavesi L., Verusio C., Pinotti G., Iop A., De Placido S., Adamo V., Ficorella C., Natale D., Greco E., Rulli E., Poli D., Porcu L., and Torri V.

Abstract

Background: Previous studies on oxaliplatin and fluoropyrimidines as adjuvant therapy in older patients with stage III colon cancer (CC) produced conflicting results. Patients and methods: We assessed the impact of age on time to tumour recurrence (TTR), disease-free survival (DFS), cancer-specific survival (CSS), and overall survival (OS) in 2360 patients with stage III CC (1667 aged <70 years and 693 ≥ 70 years) randomised to receive 3 or 6 months of FOLFOX or CAPOX within the frame of the phase III, TOSCA study. Results: Older patients compared with younger ones presented more frequently an Eastern Cooperative Oncology Group performance status equal to 1 (10.5% vs 3.3%, p < 0.001), a greater number of right-sided tumours (40.9% vs 26.6%, p < 0.001), and were at higher clinical risk (37.2% vs 33.2%, p = 0.062). The treatments were almost identical in the two cohorts (p = 0.965). We found a greater proportion of dose reductions (46.7% vs 41.4%, p = 0.018), treatment interruptions (26.1% vs 19.3%, p < 0.001) and a higher proportion of recurrences (24.2% vs 20.3%, p = 0.033) in the older patients. The multivariable analysis of the TTR did not indicate a statistically significant effect of age (hazard ratio [HR]: 1.19; 95% confidence interval [CI]: 0.98–1.44; p = 0.082). The HR comparing older with younger patients was 1.34 (95% CI: 1.12–1.59; p = 0.001) for DFS, 1.58 (95% CI: 1.26–1.99; p < 0.001) for OS, and 1.28 (95% CI: 0.96–1.70; p = 0.089) for CSS. Conclusions: Worse prognostic factors and reduced treatment compliance have a negative impact on the efficacy of oxaliplatin-based adjuvant therapy in older patients.

Published
2021

12. Khorana score and thromboembolic risk in stage II–III colorectal cancer patients: a post hoc analysis from the adjuvant TOSCA trial

Author

Barni, S, Rosati, G, Lonardi, S, Pella, N, Banzi, M, Zampino, M, Dotti, K, Rimassa, L, Marchetti, P, Maiello, E, Artioli, F, Ferrari, D, Labianca, R, Bidoli, P, Zaniboni, A, Sobrero, A, Iaffaioli, V, De Placido, S, Frassineti, G, Ciarlo, A, Buonadonna, A, Silvestris, N, Piazza, E, Pavesi, L, Moroni, M, Clerico, M, Aglietta, M, Giordani, P, Galli, F, Petrelli, F, Barni S., Rosati G., Lonardi S., Pella N., Banzi M., Zampino M. G., Dotti K. F., Rimassa L., Marchetti P., Maiello E., Artioli F., Ferrari D., Labianca R., Bidoli P., Zaniboni A., Sobrero A., Iaffaioli V., De Placido S., Frassineti G. L., Ciarlo A., Buonadonna A., Silvestris N., Piazza E., Pavesi L., Moroni M., Clerico M., Aglietta M., Giordani P., Galli F., Petrelli F., Barni, S, Rosati, G, Lonardi, S, Pella, N, Banzi, M, Zampino, M, Dotti, K, Rimassa, L, Marchetti, P, Maiello, E, Artioli, F, Ferrari, D, Labianca, R, Bidoli, P, Zaniboni, A, Sobrero, A, Iaffaioli, V, De Placido, S, Frassineti, G, Ciarlo, A, Buonadonna, A, Silvestris, N, Piazza, E, Pavesi, L, Moroni, M, Clerico, M, Aglietta, M, Giordani, P, Galli, F, Petrelli, F, Barni S., Rosati G., Lonardi S., Pella N., Banzi M., Zampino M. G., Dotti K. F., Rimassa L., Marchetti P., Maiello E., Artioli F., Ferrari D., Labianca R., Bidoli P., Zaniboni A., Sobrero A., Iaffaioli V., De Placido S., Frassineti G. L., Ciarlo A., Buonadonna A., Silvestris N., Piazza E., Pavesi L., Moroni M., Clerico M., Aglietta M., Giordani P., Galli F., and Petrelli F.

Abstract

Background: The risk of venous thromboembolic events (VTE) during adjuvant chemotherapy for colorectal cancer (CRC) is unknown. We aim to evaluate if the Khorana score (KS) can predict this risk, and if it represents a prognostic factor for overall survival (OS) through a post hoc analysis of the phase III TOSCA trial of different durations (3- versus 6-months) of adjuvant chemotherapy. Methods: A logistic regression model was used to test the associations between the risk of VTE and the KS. The results are expressed as odds ratios (OR) with 95% confidence intervals (95% CI). To assess the effect of the KS on OS, multivariable analyses using Cox regression models were performed. The results are expressed as hazard ratios (HR) with 95% CI. Results: Among 1380 CRC patients with available data, the VTE risk (n = 72 events: 5.2%) was similar in the two duration arms (5.5% versus 4.9%), with 0.2% of patients belonging to the high-risk KS group. Rates of VTE were similar in the low- and intermediate-risk groups (4.8% versus 6.4%). KS did not represent an independent predictive factor for VTE occurrence. Chemotherapy duration was not associated with VTE risk. In addition, KS was not prognostic for OS in multivariate analysis (HR: 0.92, 95% CI, 0.63–1.36; p = 0.6835). Conclusions: The use of the KS did not predict VTEs in a low–moderate thromboembolic risk population as CRC. These data did not support the use of KS to predict VTE during adjuvant chemotherapy, and suggest that other risk assessment models should be researched.

Published
2020

13. Cisplatin plus capecitabine concomitant with intensity-modulated radiation therapy in non-metastatic anal squamous cell carcinoma: the experience of a single research cancer center

Author

Rotundo, M, Zampino, M, Ravenda, P, Bagnardi, V, Peveri, G, Dell'Acqua, V, Surgo, A, Trovato, C, Bottiglieri, L, Bertani, E, Petz, W, Fumagalli Romario, U, Fazio, N, Rotundo M. S., Zampino M. G., Ravenda P. S., Bagnardi V., Peveri G., Dell'Acqua V., Surgo A., Trovato C., Bottiglieri L., Bertani E., Petz W. L., Fumagalli Romario U., Fazio N., Rotundo, M, Zampino, M, Ravenda, P, Bagnardi, V, Peveri, G, Dell'Acqua, V, Surgo, A, Trovato, C, Bottiglieri, L, Bertani, E, Petz, W, Fumagalli Romario, U, Fazio, N, Rotundo M. S., Zampino M. G., Ravenda P. S., Bagnardi V., Peveri G., Dell'Acqua V., Surgo A., Trovato C., Bottiglieri L., Bertani E., Petz W. L., Fumagalli Romario U., and Fazio N.

Abstract

Background and Aims: The standard treatment of non-metastatic anal squamous cell carcinoma (ASCC) consists of chemotherapy with mitomycin (MMC) plus 5-fluorouracil (5FU) for 1–2 cycles concomitant with pelvic radiotherapy. Subsequent studies introduced cisplatin (CDDP) combined with 5FU, with unclear results. We evaluated the doublet capecitabine (C) and CDDP as a possible alternative to MMC-5FU regimen concomitant with intensity-modulated radiation therapy (IMRT). Patients and Methods: We carried out a retrospective study on 67 patients affected by stage I–III ASCC, treated with CDDP (60–70 mg/m2 every 21 days for two courses) plus C (825 mg/m2 twice daily for 5 days/week) chemotherapy concomitant with IMRT for curative intent. Results: At a median follow up of 41 months, the clinical complete response calculated at the 6-month time-point (6-moCR), the 6-month objective response rate and the 6-month disease control rate were 93%, 94%, and 99%, respectively. Disease-free survival rates at 1, 2, and 3 years were 89%, 87%, and 85%, while the overall survival rates at 1 and 2 years were 100% and 95%. The colostomy-free survival rates were 90% at 1 year and 88% at 2 years. Grade 3–4 acute adverse events were reported in 61% of patients; predominantly skin toxicity (46%) and limited hematological toxicity (12%). Conclusion: In this retrospective study, chemotherapy with C plus CDDP concomitant with IMRT proved safe and effective, and may represent a possible alternative option to standard MMC-containing regimen for curative intent.

Published
2020

19. Oxaliplatin combined with 5-fluorouracil and methotrexate in advanced colorectal cancer

Author

Zampino, M. G., Lorizzo, K., Rocca, A., Locatelli, M., Zorzino, L., Manzoni, S., Mazzetta, C., nicola fazio, Biffi, R., and Braud, F.

Subjects
Adult, Male, Vascular Endothelial Growth Factor A, Organoplatinum Compounds, Middle Aged, Drug Administration Schedule, Oxaliplatin, Methotrexate, Antineoplastic Combined Chemotherapy Protocols, Humans, Female, Fluorouracil, Colorectal Neoplasms, Infusions, Intravenous, Aged
Abstract

A promising regimen including 5-Fluorouracil, methotrexate and oxaliplatin is reported.Patients with untreated measurable metastatic disease received bolus 5-Fluorouracil (600 mg/m2) on days 2 and 16, modulated by methotrexate (200 mg/m2) 24 h earlier, alternated with 4 weeks of continuous infusion of 5-Fluorouracil (200 mg/m2/daily) plus oxaliplatin (130 mg/m2) on days 29 and 56, followed by 2 weeks of rest. Serum vascular endothelial growth factor (VEGF) was analyzed at baseline and before every cycle.Fifty-eight patients were enrolled. Objective remissions were reported in 45.6% (95% CI=34.3%, 57.3%). The median progression-free survival was 7.8 months and the median overall survival was 19.4 months. No grade 4 toxicity was reported, except for one case of diarrhea. The serum VEGF evaluated in 23 patients showed a decreasing trend during therapy.The regimen was active, well tolerated and may be a possible option in patients not suitable for radical surgery.

Published
2006

21. Factors predicting worse prognosis in patients affected by pT3 N0 colon cancer. Long-term results of a monocentric series of 137 radically resected patients in a 5-year period

Author

Biffi, R., primary, Botteri, E., additional, Bertani, E., additional, Zampino, M. G., additional, Cenciarelli, S., additional, Luca, F., additional, Pozzi, S., additional, Cossu, M. L., additional, Chiappa, A., additional, Rotmensz, N., additional, Bazolli, B., additional, Magni, E., additional, Sonzogni, A., additional, and Andreoni, B., additional

Published
2012
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22. First-line therapy with metronomic capecitabine (mC) plus docetaxel (D) followed by mC as maintenance for patients with HER2-negative metastatic breast cancer (MBC): Preliminary analysis of a monocentric phase II trial.

Author

Aurilio, G., primary, Sciandivasci, A., additional, Munzone, E., additional, Riva, D. F., additional, Radice, D., additional, Bertolini, F., additional, Minchella, I., additional, Cullura, D., additional, Curigliano, G., additional, Zampino, M. G., additional, Goldhirsch, A., additional, and Nole, F., additional

Published
2011
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27. An effective chemotherapy regimen for patients with heavily pretreated metastatic breast cancer (MBC) using vinorelbine (V) administered with weekly epirubicin (E) and continuous infusion of 5- fluorouracil (CIFU

Author

Sanna, G., primary, Balduzzi, A., additional, Franceschelli, L., additional, Corsetto, L., additional, Zampino, M. G., additional, Minchella, I., additional, Catania, C., additional, Lorizzo, K., additional, Rocca, A., additional, and Nolè, F., additional

Published
2004
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31. Effects of Anthracycline Therapy on Intestinal Absorption in Patients with Advanced Breast Cancer

Author

Parrilli, G., Iaffaioli, R. V., Martorano, M., Rosario Cuomo, Tafuto, S., Zampino, M. G., Budillon, G., Bianco, A. R., Parrilli, G., Iaffaioli, R. V., Martorano, M., Cuomo, Rosario, Tafuto, S., Zampino, M. G., Budillon, G., and Bianco, A. R.

Subjects
Xylose, Intestinal Absorption, Doxorubicin, Breast Cancer, 3-O-Methylglucose, Carbohydrate Metabolism, Humans, Methylglucosides, Breast Neoplasms, Female, Anthracycline, Rhamnose, Lactulose
Abstract

Although cytotoxic chemotherapy for human cancer has been reported to induce alterations in intestinal permeability, its effects on the absorptive process are still controversial. We have studied mediated and nonmediated absorption in 10 patients with metastatic breast cancer before and after treatment with Adriamycin by the use of specific test sugars given orally and their subsequent urinary recovery, as measured by chromatography. Mediated absorption was investigated by the use of D-xylose and 3-O-methylglucose, while lactulose and L-rhamnose were used to study nonmediated permeation. Lactulose is considered a marker of unmediated paracellular (tight junction) permeation, while L-rhamnose explores passage across cell membranes. The test was performed on patients before and on the second and the eighth days after Adriamycin administration, and only once in 22 age-matched healthy women. Under basal conditions, as well as 2 and 8 days after chemotherapy, D-xylose and 3-O-methylglucose absorption was 35% lower in patients than in controls (P less than 0.001). Lactulose absorption was significantly higher in patients than in controls under basal conditions (P less than 0.001); it reached levels three times higher the second day after chemotherapy, and returned to basal levels by the eighth day. The data suggest an early reversible effect of Adriamycin on cellular tight junctions with resulting increased permeabilization. This effect seems of a toxic nature rather than due to increased cell loss. It is interesting that both nonmediated absorption and mediated absorption were already altered before chemotherapy in cancer patients, suggesting a preexisting functional damage of the intestine. The significance of this alteration as a potential mechanism of cancer cachexia is discussed.

37. Institutional guidelines and ongoing studies in management of liver tumours: the experience of the European Institute of Oncology.

Author

Biffi, R., Orsi, F., Zampino, M. G., Chiappa, A., Fazio, N., De Braud, F., Bonomo, G., Monfardini, L., Vigna, P. D., Luca, F., Bodei, L., Bartolomei, M., Catalano, G., Leonardi, M. C., Ferrari, M., Andreoni, B., Goldhirsch, A., Paganelli, G., and Orecchia, R.

Subjects
*MEDICAL research, *LIVER tumors, *MEDICAL care, *ONCOLOGIC surgery, *RADIOLOGY, *THERAPEUTICS, EUROPEAN Institute of Oncology (Milan, Italy)
Abstract

Background: An institutional task force on upper gastrointestinal tumours is active at the European Institute of Oncology (EIO). Members decided to collate the institutional guidelines on management of liver tumours (primary and metastatic) into a document. This article is aimed at presenting the current treatment guidelines as well as ongoing research protocols and trials in this field at the EIO. Methods: A steering committee convened to assign tasks to individual members. Contributions from experts in each treatment area were collated in a single document, in order to produce a draft for subsequent review from the aforementioned committee. Six drafts have been discussed and the final version approved. Results: Surgical, medical oncology, interventional radiology, nuclear medicine and radiation therapy approaches, their roles in management of liver tumours and ongoing research trials are presented and discussed in this article. Conclusions: At the EIO a multi-disciplinary integrated approach to liver tumours is standard and several ongoing research projects are currently active in this field. [ABSTRACT FROM AUTHOR]

Published
2008
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38. Phase III trial comparing 3-6 months of adjuvant FOLFOX4/XELOX in stage II-III colon cancer: safety and compliance in the TOSCA trial.

Author

Lonardi, S., Sobrero, A., Rosati, G., Di Bartolomeo, M., Ronzoni, M., Aprile, G., Scartozzi, M., Banzi, M., Zampino, M. G., Pasini, F., Marchetti, P., Cantore, M., Zaniboni, A., Rimassa, L., Ciuffreda, L., Ferrari, D., Barni, S., Zagonel, V., Maiello, E., and Rulli, E.

Subjects
*COLON cancer treatment, *ADJUVANT treatment of cancer, *CLINICAL trials, *OXALIPLATIN, *CANCER chemotherapy
Abstract

Background: Six months of oxaliplatin-based adjuvant chemotherapy is standard of care for radically resected stage III colon cancer and an accepted option for high-risk stage II. A shorter duration of therapy, if equally efficacious, would be advantageous for patients and Health-Care Systems. Patients and methods: TOSCA ['Randomized trial investigating the role of FOLFOX-4 or XELOX (3 versus 6 months) regimen duration and bevacizumab as adjuvant therapy for patients with stage II/III colon cancer] is an open-label, phase III, multicenter, noninferiority trial randomizing patients with high-risk stage II or stage III radically resected colon cancer to receive 3 months (arm 3 m) versus 6 months (arm 6 m) of FOLFOX4/XELOX. Primary end-point was relapse-free survival. We present here safety and compliance data. Results: From June 2007 to March 2013, 3759 patients were accrued from 130 Italian sites, 64% receiving FOLFOX4 and 36% XELOX in either arm. Treatment completion rate without any modification was 35% versus 12% and with delays or dose reduction 52% versus 44% in arm 3 and 6 m. Treatment was permanently discontinued in 8% (arm 3 m) and 33% (arm 6 m). In arm 6 m, 50% of patients discontinuing treatment did so after completing 80% of planned program. Grade 3+ toxicities were higher in arm 6 m than that in 3 m. Grade 2+ neuropathy was 31.2% versus 8.8% (P < 0.0001) while grade 3+ was 8.4 versus 1.3 (P < 0.0001), in arm 3 and 6 m. Seven deaths within 30 days from last treatment administration in arm 6 m and three deaths in arm 3 m were observed (0.3% versus 0.1%, P = 0.34). [ABSTRACT FROM AUTHOR]

Published
2016
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39. The prognostic value of the new combined hemo-eosinophil inflammation index (Hei index): A multicenter analysis of anal cancer patients treated with concurrent chemo-radiation

Author

Berardino De Bari, Andrea Casadei-Gardini, Almalina Bacigalupo, Giulia Bartolini, Stefano Vagge, Maria Giulia Zampino, Pierfrancesco Franco, Giovanni Luca Frassinetti, Renzo Corvò, Francesca Arcadipane, Stefano Cascinu, Martina Valgiusti, Lorenzo Gervaso, D. Aloi, Margherita Rimini, Marianna Alessandra Gerardi, Rimini, M., Franco, P., De Bari, B., Zampino, M. G., Vagge, S., Frassinetti, G. L., Arcadipane, F., Bacigalupo, A., Valgiusti, M., Aloi, D., Gervaso, L., Corvo, R., Bartolini, G., Gerardi, M. A., Cascinu, S., and Casadei-Gardini, A.

Subjects
0301 basic medicine, squamous cell anal cancer, Cancer Research, medicine.medical_specialty, Multivariate analysis, Inflammation, Prognostic factors, lcsh:RC254-282, Gastroenterology, Prognostic index, Article, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Anal cancer, Squamous cell anal cancer, Univariate analysis, business.industry, Proportional hazards model, prognostic index, Hazard ratio, Anal Squamous Cell Carcinoma, prognostic factors, Eosinophil, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, 030104 developmental biology, medicine.anatomical_structure, Oncology, inflammation, 030220 oncology & carcinogenesis, medicine.symptom, business
Abstract

Anal squamous cell carcinoma (SCC) is a rare tumor, and bio-humoral predictors of response to chemo-radiation (CT-RT) are lacking. We developed a prognostic score system based on laboratory inflammation parameters. We investigated the correlation between baseline clinical and laboratory variables and disease-free (DFS) and overall (OS) survival in anal SCC patients treated with CT-RT in five institutions. The bio-humoral parameters of significance were included in a new scoring system, which was tested with other significant variables in a Cox’s proportional hazard model. A total of 308 patients was included. We devised a prognostic model by combining baseline hemoglobin level, SII, and eosinophil count: the Hemo-Eosinophils Inflammation (HEI) Index. We stratified patients according to the HEI index into low- and high-risk groups. Median DFS for low-risk patients was not reached, and it was found to be 79.5 months for high-risk cases (Hazard Ratio 3.22, 95% CI: 2.04–5.10, p &lt, 0.0001). Following adjustment for clinical covariates found significant at univariate analysis, multivariate analysis confirmed the HEI index as an independent prognostic factor for DFS and OS. The HEI index was shown to be a prognostic parameter for DFS and OS in anal cancer patients treated with CT-RT. An external validation of the HEI index is mandatory for its use in clinical practice.

Published
2021

40. Oxaliplatin plus fluoropyrimidines as adjuvant therapy for colon cancer in older patients: A subgroup analysis from the TOSCA trial

Author

Gerardo Rosati, Sara Lonardi, Fabio Galli, Maria Di Bartolomeo, Monica Ronzoni, Maria G. Zampino, Maria Banzi, Alberto Zaniboni, Felice Pasini, Silvia Bozzarelli, Silvio K. Garattini, Daris Ferrari, Vincenzo Montesarchio, Andrea Mambrini, Libero Ciuffreda, Francesca Galli, Valeria Pusceddu, Chiara Carlomagno, Paolo Bidoli, Domenico Amoroso, Anna M. Bochicchio, Luca Frassineti, Domenico Corsi, Domenico Bilancia, Alessandro Pastorino, Alfonso De Stefano, Roberto Labianca, D. Bilancia, G. Rosati, V. Montesarchio, R.V. Iaffaioli, G. Nasti, B. Daniele, V. Zagonel, S. Lonardi, N. Pella, G. Aprile, F. Pasini, Roma P. Marchetti, A. Romiti, L. Ciuffreda, D. Ferrari, P. Foa, A. Zaniboni, R. Labianca, S. Mosconi, A. Sobrero, P. Bidoli, M. Cazzaniga, G.D. Beretta, D.C. Corsi, E. Cortesi, S. Barni, F. Petrelli, P. Allione, A.M. D'Arco, G. Valmadre, E. Piazza, E. Veltri, G. Vietti Ramus, L. Giustini, S. Tumulo, S. Cascinu, C. Granetto, F. Testore, M. Giordano, M. Moroni, M. Di Seri, A. Nuzzo, L. Angelelli, S. Gori, G. Farina, M. Aglietta, R. Franchi, M. Comandé, P. Giordani, G. Tonini, E. Bucci, A. Ballestrero, M. Benasso, C. Graiff, S. Bravi, O. Caffo, R.R. Silva, L. Frontini, S. Rota, L. Cozzi, M. Cantore, E. Maiello, S. Cinieri, N. Silvestris, S. Romito, V. Gebbia, M. Banzi, A. Santoro, F. Artioli, R. Mattioli, A. Contu, F. Di Costanzo, F. Leonardi, L. Cavanna, R. Passalacqua, D. Amoroso, P. Sozzi, M. D'Amico, D. Amadori, L. Frassineti, D. Turci, A. Ravaioli, E. Pasquini, A. Gambi, M. Faedi, G. Cruciani, E. Bajetta, M. Di Bartolomeo, L. Gianni, M. Ronzoni, M.T. Ionta, B. Massidda, M. Scartozzi, M.G. Zampino, A.M. Bochicchio, A. Ciarlo, A. Di Leo, S. Frustaci, G. Rangoni, A. Arizzoia, L. Pavesi, C. Verusio, G. Pinotti, A. Iop, S. De Placido, C. Carlomagno, V. Adamo, C. Ficorella, D. Natale, E. Greco, E. Rulli, F. Galli, D. Poli, L. Porcu, V. Torri, Rosati, G, Lonardi, S, Galli, F, Di Bartolomeo, M, Ronzoni, M, Zampino, M, Banzi, M, Zaniboni, A, Pasini, F, Bozzarelli, S, Garattini, S, Ferrari, D, Montesarchio, V, Mambrini, A, Ciuffreda, L, Pusceddu, V, Carlomagno, C, Bidoli, P, Amoroso, D, Bochicchio, A, Frassineti, L, Corsi, D, Bilancia, D, Pastorino, A, De Stefano, A, Labianca, R, Iaffaioli, R, Nasti, G, Daniele, B, Zagonel, V, Pella, N, Aprile, G, Marchetti, R, Romiti, A, Foa, P, Mosconi, S, Sobrero, A, Cazzaniga, M, Beretta, G, Cortesi, E, Barni, S, Petrelli, F, Allione, P, D'Arco, A, Valmadre, G, Piazza, E, Veltri, E, Ramus, G, Giustini, L, Tumulo, S, Cascinu, S, Granetto, C, Testore, F, Giordano, M, Moroni, M, Di Seri, M, Nuzzo, A, Angelelli, L, Gori, S, Farina, G, Aglietta, M, Franchi, R, Comande, M, Giordani, P, Tonini, G, Bucci, E, Ballestrero, A, Benasso, M, Graiff, C, Bravi, S, Caffo, O, Silva, R, Frontini, L, Rota, S, Cozzi, L, Cantore, M, Maiello, E, Cinieri, S, Silvestris, N, Romito, S, Gebbia, V, Santoro, A, Artioli, F, Mattioli, R, Contu, A, Di Costanzo, F, Leonardi, F, Cavanna, L, Passalacqua, R, Sozzi, P, D'Amico, M, Amadori, D, Turci, D, Ravaioli, A, Pasquini, E, Gambi, A, Faedi, M, Cruciani, G, Bajetta, E, Gianni, L, Ionta, M, Massidda, B, Scartozzi, M, Ciarlo, A, Di Leo, A, Frustaci, S, Rangoni, G, Arizzoia, A, Pavesi, L, Verusio, C, Pinotti, G, Iop, A, De Placido, S, Adamo, V, Ficorella, C, Natale, D, Greco, E, Rulli, E, Poli, D, Porcu, L, Torri, V, Rosati, G., Lonardi, S., Galli, F., Di Bartolomeo, M., Ronzoni, M., Zampino, M. G., Banzi, M., Zaniboni, A., Pasini, F., Bozzarelli, S., Garattini, S. K., Ferrari, D., Montesarchio, V., Mambrini, A., Ciuffreda, L., Pusceddu, V., Carlomagno, C., Bidoli, P., Amoroso, D., Bochicchio, A. M., Frassineti, L., Corsi, D., Bilancia, D., Pastorino, A., De Stefano, A., Labianca, R., Iaffaioli, R. V., Nasti, G., Daniele, B., Zagonel, V., Pella, N., Aprile, G., Marchetti, R. P., Romiti, A., Foa, P., Mosconi, S., Sobrero, A., Cazzaniga, M., Beretta, G. D., Cortesi, E., Barni, S., Petrelli, F., Allione, P., D'Arco, A. M., Valmadre, G., Piazza, E., Veltri, E., Ramus, G. V., Giustini, L., Tumulo, S., Cascinu, S., Granetto, C., Testore, F., Giordano, M., Moroni, M., Di Seri, M., Nuzzo, A., Angelelli, L., Gori, S., Farina, G., Aglietta, M., Franchi, R., Comande, M., Giordani, P., Tonini, G., Bucci, E., Ballestrero, A., Benasso, M., Graiff, C., Bravi, S., Caffo, O., Silva, R. R., Frontini, L., Rota, S., Cozzi, L., Cantore, M., Maiello, E., Cinieri, S., Silvestris, N., Romito, S., Gebbia, V., Santoro, A., Artioli, F., Mattioli, R., Contu, A., Di Costanzo, F., Leonardi, F., Cavanna, L., Passalacqua, R., Sozzi, P., D'Amico, M., Amadori, D., Turci, D., Ravaioli, A., Pasquini, E., Gambi, A., Faedi, M., Cruciani, G., Bajetta, E., Gianni, L., Ionta, M. T., Massidda, B., Scartozzi, M., Ciarlo, A., Di Leo, A., Frustaci, S., Rangoni, G., Arizzoia, A., Pavesi, L., Verusio, C., Pinotti, G., Iop, A., De Placido, S., Adamo, V., Ficorella, C., Natale, D., Greco, E., Rulli, E., Poli, D., Porcu, L., Torri, V., and Corsi, D. C.

Subjects
0301 basic medicine, Oncology, Male, Cancer Research, Colorectal cancer, Leucovorin, Efficacy, Older patient, 0302 clinical medicine, Antineoplastic Combined Chemotherapy Protocols, Stage (cooking), Aged, 80 and over, Colonic Neoplasm, Prognostic factor, Middle Aged, Prognosis, Colon cancer, Survival Rate, Oxaliplatin, Chemotherapy, Adjuvant, 030220 oncology & carcinogenesis, Colonic Neoplasms, Female, Fluorouracil, medicine.drug, Human, Compliance, Adult, medicine.medical_specialty, Prognosi, Adjuvant chemotherapy, Older patients, Prognostic factors, Subgroup analysis, Follow-Up Studie, 03 medical and health sciences, Internal medicine, Post-hoc analysis, medicine, Adjuvant therapy, Humans, Capecitabine, Cancer staging, Aged, Antineoplastic Combined Chemotherapy Protocol, business.industry, medicine.disease, 030104 developmental biology, Neoplasm Recurrence, Local, business, Follow-Up Studies
Abstract

Background: Previous studies on oxaliplatin and fluoropyrimidines as adjuvant therapy in older patients with stage III colon cancer (CC) produced conflicting results. Patients and methods: We assessed the impact of age on time to tumour recurrence (TTR), disease-free survival (DFS), cancer-specific survival (CSS), and overall survival (OS) in 2360 patients with stage III CC (1667 aged

Published
2021

41. From CENTRAL to SENTRAL (SErum aNgiogenesis cenTRAL): Circulating Predictive Biomarkers to Anti-VEGFR Therapy

Author

Vittorina Zagonel, Maria Giulia Zampino, Carla Codecà, Pina Ziranu, Nicoletta Pella, Gerardo Rosati, M. Libertini, Domenico Germano, Bruno Daniele, Pietro Sozzi, Luigi Cavanna, Mariaelena Casagrande, Antonio Zizzi, Roberto Labianca, Alberto Zaniboni, Sara Lonardi, Mario Scartozzi, Stefano Cascinu, Riccardo Giampieri, Eleonora Lai, Marco Puzzoni, Daris Ferrari, Laura Demurtas, Valeria Pusceddu, Giampieri, R., Ziranu, P., Daniele, B., Zizzi, A., Ferrari, D., Lonardi, S., Zaniboni, A., Cavanna, L., Rosati, G., Casagrande, M., Pella, N., Demurtas, L., Zampino, M. G., Sozzi, P., Pusceddu, V., Germano, D., Lai, E., Zagonel, V., Codeca, C., Libertini, M., Puzzoni, M., Labianca, R., Cascinu, S., and Scartozzi, M.

Subjects
0301 basic medicine, Oncology, Placental growth factor, Cancer Research, medicine.medical_specialty, Bevacizumab, Circulating biomarkers, Colorectal cancer, FGF2, bevacizumab, lcsh:RC254-282, Article, 03 medical and health sciences, Folinic acid, angiogenesis, 0302 clinical medicine, Internal medicine, medicine, Progression-free survival, business.industry, circulating biomarkers, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, VEGF, Colon cancer, Irinotecan, Regimen, 030104 developmental biology, colon cancer, PlGF, 030220 oncology & carcinogenesis, FOLFIRI, Angiogenesis, business, medicine.drug
Abstract

Background: In the last decade, a series of analyses failed to identify predictive biomarkers of resistance/susceptibility for anti-angiogenic drugs in metastatic colorectal cancer (mCRC). We conducted an exploratory preplanned analysis of serum pro-angiogenic factors (SErum aNgiogenesis-cenTRAL) in 72 mCRC patients enrolled in the phase II CENTRAL (ColorEctalavastiNTRiAlLdh) trial, with the aim to identify potential predictive factors for sensitivity/resistance to first line folinic acid-fluorouracil-irinotecan regimen (FOLFIRI) plus bevacizumab. Methods: First-line FOLFIRI/bevacizumab patients were prospectively assessed for the following circulating pro-angiogenic factors, evaluated with ELISA (enzyme-linked immunosorbent assay)-based technique at baseline and at every cycle: Vascular endothelial growth factor A (VEGF-A), hepatocyte growth factor (HGF), stromal derived factor-1 (SDF-1), placental derived growth factor (PlGF), fibroblast growth factor-2 (FGF-2), monocyte chemotactic protein-3 (MCP-3), interleukin-8 (IL-8). Results: Changes in circulating FGF-2 levels among different blood samples seemed to correlate with clinical outcome. Patients who experienced an increase in FGF-2 levels at the second cycle of chemotherapy compared to baseline, had a median Progression Free Survival (mPFS) of 12.85 vs. 7.57 months (Hazard Ratio&mdash, HR: 0.73, 95% Confidence Interval&mdash, CI: 0.43-1.27, p = 0.23). Similar results were seen when comparing FGF-2 concentrations between baseline and eight-week time point (mPFS 12.98 vs. 8.00 months, HR: 0.78, 95% CI: 0.46&ndash, 1.33, p = 0.35). Conclusions: Our pre-planned, prospective analysis suggests that circulating FGF-2 levels&rsquo, early increase could be used as a marker to identify patients who are more likely to gain benefit from FOLFIRI/bevacizumab first-line therapy.

Published
2020

42. Impact of Metformin Use and Diabetic Status During Adjuvant Fluoropyrimidine-Oxaliplatin Chemotherapy on the Outcome of Patients with Resected Colon Cancer: A TOSCA Study Subanalysis

Author

Vincenzo Adamo, Sabino De Placido, Luigi Cavanna, Evaristo Maiello, Sandro Barni, Francesca Galli, Claudio Vernieri, M. Nicolini, Massimo Aglietta, Sara Lonardi, Maria Di Bartolomeo, Laura Ferrari, Emiliano Tamburini, Azzurra Damiani, Maria Giulia Zampino, Rosario Vincenzo Iaffaioli, Francesco Leonardi, Gerardo Rosati, Katia Fiorella Dotti, F. Galli, Paolo Marchetti, Paolo Giordani, Giovanni Lo Re, Alberto Zaniboni, Roberto Labianca, Maria Antista, Tosca Investigators, A. Ciarlo, Maria Banzi, Lorenzo Pavesi, Paolo Bidoli, Giovanni Luca Frassineti, Maria Chiara Tronconi, S. Ferrario, Stefania Gori, Daris Ferrari, Marina Faedi, Mario Clerico, Angela Buonadonna, Saverio Cinieri, Vernieri, C., Galli, F., Ferrari, L., Marchetti, P., Lonardi, S., Maiello, E., Iaffaioli, R. V., Zampino, M. G., Zaniboni, A., De Placido, S., Banzi, M., Damiani, A., Ferrari, D., Rosati, G., Labianca, R. F., Bidoli, P., Frassineti, G. L., Nicolini, M., Pavesi, L., Tronconi, M. C., Buonadonna, A., Ferrario, S., Re, G. L., Adamo, V., Tamburini, E., Clerico, M., Giordani, P., Leonardi, F., Barni, S., Ciarlo, A., Cavanna, L., Gori, S., Cinieri, S., Faedi, M., Aglietta, M., Antista, M., Dotti, K. F., Di Bartolomeo, M., Vernieri, C, Galli, F, Ferrari, L, Marchetti, P, Lonardi, S, Maiello, E, Iaffaioli, R, Zampino, M, Zaniboni, A, De Placido, S, Banzi, M, Damiani, A, Ferrari, D, Rosati, G, Labianca, R, Bidoli, P, Frassineti, G, Nicolini, M, Pavesi, L, Tronconi, M, Buonadonna, A, Ferrario, S, Re, G, Adamo, V, Tamburini, E, Clerico, M, Giordani, P, Leonardi, F, Barni, S, Ciarlo, A, Cavanna, L, Gori, S, Cinieri, S, Faedi, M, Aglietta, M, Antista, M, Dotti, K, and Di Bartolomeo, M

Subjects
Aged, Antineoplastic Agents, Chemotherapy, Adjuvant, Colonic Neoplasms, Diabetes Mellitus, Type 2, Female, Fluorouracil, Humans, Hypoglycemic Agents, Male, Metformin, Middle Aged, Oxaliplatin, Risk Factors, 0301 basic medicine, Oncology, Male, Cancer Research, medicine.medical_specialty, endocrine system diseases, Colorectal cancer, colon cancer (CC), radical surgery, Antineoplastic Agents, 03 medical and health sciences, 0302 clinical medicine, Type 2 diabetes mellitus (T2DM), colon cancer (CC), metformin, radical surgery, TOSCA study, Risk Factors, Diabetes mellitus, Internal medicine, Gastrointestinal Cancer, medicine, Adjuvant therapy, Humans, Hypoglycemic Agents, Prospective cohort study, Cancer staging, business.industry, Hazard ratio, nutritional and metabolic diseases, Middle Aged, medicine.disease, Metformin, Oxaliplatin, Type 2 diabetes mellitus (T2DM), 030104 developmental biology, TOSCA study, colon cancer, Diabetes Mellitus, Type 2, Chemotherapy, Adjuvant, 030220 oncology & carcinogenesis, Colonic Neoplasms, Female, Fluorouracil, business, medicine.drug
Abstract

Background Type 2 diabetes mellitus (T2DM) is associated with increased risk of colon cancer (CC), whereas metformin use seems to be protective. However, the impact of metformin use on the risk of death or disease recurrence after radical surgery for CC remains uncertain. Materials and Methods This is a substudy conducted in patients with high-risk stage II or stage III CC randomized in the TOSCA trial, which compared 3 versus 6 months of fluoropyrimidine-oxaliplatin adjuvant chemotherapy. Objective of the study was to investigate the impact of metformin exposure during adjuvant chemotherapy on overall survival (OS) and relapse-free survival (RFS). We also evaluated the impact of T2DM or metformin dosage on clinical outcomes. Results Out of 3,759 patients enrolled in the TOSCA trial, 133 patients with diabetes (9.2%) and 1,319 without diabetes (90.8%) were recruited in this study. After excluding 13 patients with diabetes without information on metformin exposure, 76 patients with T2DM (63.3%) were defined as metformin users and 44 (36.7%) as metformin nonusers. After a median follow-up of 60.4 months, 26 (21.7%) patients relapsed and 16 (13.3%) died. Metformin use was neither associated with OS (adjusted hazard ratio [HR], 1.51; 95% confidence interval [CI], 0.48–4.77; p = .4781) nor with RFS (HR, 1.56; 95% CI, 0.69–3.54; p = .2881). Similarly, we found no association between T2DM or metformin dosage and OS or RFS. Conclusions Metformin use and T2DM did not impact on OS or RFS in patients with resected CC treated with adjuvant fluoropyrimidine-oxaliplatin chemotherapy. Larger studies and longer follow-up are required to clarify the potential efficacy of metformin in improving the prognosis of patients with CC. Implications for Practice The role of the antidiabetic drug metformin in colon cancer prevention and treatment is highly debated. While low-dose metformin reduced the incidence of colorectal adenomas in two prospective studies, its effect in patients with already established colon cancer remains unclear. In this study, the potential impact of metformin on the survival of resected colon cancer patients who received adjuvant chemotherapy was investigated in the context of the TOSCA study. We did not find any association between metformin use or dosages and patient survival. Prospective studies are required to draw definitive conclusions about metformin impact on colon cancer recurrence and survival.

Published
2018

44. Carcinoid heart disease in patients with advanced small-intestinal neuroendocrine tumors and carcinoid syndrome: a retrospective experience from two European referral centers.

Author

Algeri L, Falkman L, Spada F, Frassoni S, Bagnardi V, Boselli S, Cardinale D, Zanobini M, Crona J, Benini L, Tamayo D, Mazzon C, Gervaso L, Cella CA, Zampino MG, Ciardiello D, Russo A, Badalamenti G, Welin S, and Fazio N

Abstract

Background: Up to 50% of patients with advanced small-intestinal neuroendocrine tumors (SI-NETs) and carcinoid syndrome (CS) develop carcinoid heart disease (CHD). However, the true frequency and prognostic markers for CHD in CS are lacking. We described the real-world management of patients in two NET referral centers in this clinical context and relationships between clinical features, including CHD and overall survival (OS)., Patients and Methods: This is a retrospective analysis of patients with stage IV SI-NET and CS, treated at the European Institute of Oncology in Milan and Uppsala University in Sweden between 2015 and 2021. CHD was defined as at least one moderate right-sided heart valve defect. Median OS and cumulative incidence of CHD were estimated from the diagnosis of metastatic disease, and the association between clinical parameters with both OS and occurrence of CHD was evaluated., Results: We included 165 patients, with 97% having low-intermediate-grade SI-NETs and 86% having synchronous liver metastases. Ninety-eight patients (59%) became refractory to full label dose of somatostatin analogues and 25% developed a CHD. At CHD diagnosis, baseline urine 5-hydroxyindoleacetic acid (24-h u5-HIAA) value and plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) value were known in 76% of patients. Moderate-to-severe tricuspid insufficiency was the most common alteration of CHD. Prognosis was significantly impaired by CHD (multivariable hazard ratio for OS = 2.85, P < 0.001). The median OS from the CHD diagnosis was 4.5 years [95% confidence interval (CI) 2.1-7.2 years], and the 5-year survival rate was 34% (95% CI 13% to 57%)., Conclusions: In our study population of SI-NET patients with CS, more than half had a refractory carcinoid syndrome (RCS) and one-quarter developed a CHD, with a negative impact on OS. Therefore, it is recommended to screen and monitor patients with CS for CHD, ideally with a combination of u5-HIAA, NT-proBNP values, and echocardiography at CS baseline, preferably in NET referral centers., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Published
2024
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45. Comprehensive genomic profiling by liquid biopsy captures tumor heterogeneity and identifies cancer vulnerabilities in patients with RAS/BRAF V600E wild-type metastatic colorectal cancer in the CAPRI 2-GOIM trial.

Author

Ciardiello D, Boscolo Bielo L, Napolitano S, Martinelli E, Troiani T, Nicastro A, Latiano TP, Parente P, Maiello E, Avallone A, Normanno N, Pisconti S, Nisi C, Bordonaro R, Russo AE, Tamburini E, Toma I, Lotesoriere C, Vallarelli S, Zampino MG, Fazio N, Curigliano G, De Vita F, Ciardiello F, and Martini G

Abstract

Background: Emerging evidence supports tumor tissue-based comprehensive genomic profiling (CGP) in metastatic colorectal cancer (mCRC). Data on liquid biopsy-based circulating tumor DNA (ctDNA) CGP are scarce and mainly retrospective. Prospective comparison between the two tests is not currently available., Materials and Methods: The CAPRI 2-GOIM trial investigates efficacy and safety of ctDNA-driven, cetuximab-based sequence of three treatment lines in patients with RAS/BRAF V600E wild-type (WT) mCRC, as determined by the local laboratory. Before first-line therapy, CGP is carried out with FoundationOne (F1) CDx and F1 Liquid (F1L) CDx (324 genes) on tumor tissue DNA and plasma ctDNA, respectively., Results: For 2/207 (0.96%) patients, no ctDNA was detected by F1L CDx. No patient displayed tumor fraction (TF) below 1%, whereas elevated ctDNA (TF ≥ 10%) was detected among 140/205 (68.3%) patients. One thousand and thirteen genomic variants were identified. F1L CDx found KRAS, NRAS, or BRAF V600E alterations in 19 patients, whose tumors were classified as RAS/BRAF V600E WT by the local laboratory. Both F1 CDx and F1L CDx were available for 164/205 (80%) patients. A concordance of 61.4% between the two tests was observed. The concordance increased to 72.7% for F1L CDx with TF ≥ 10%. Concordance for genes potentially involved in anti-epidermal growth factor receptor resistance was found in 137/164 (83%) patients, increasing to 91.5% for F1L CDx with TF ≥ 10%. A higher number of genomic alterations was detected by F1L CDx compared with F1 CDx, including six cases with KRAS and NRAS alterations. Overall, 109/205 (53.2%) patients displayed at least one actionable genomic alteration (I to IIIB), according to the European Society for Medical Oncology Scale for Clinical Actionability of Molecular Targets (ESCAT)., Conclusion: Baseline liquid biopsy-based CGP is feasible, has high concordance with tumor tissue-based CGP, could better recapitulate tumor heterogeneity, and is clinically informative by identifying additional actionable genomic alterations in approximately half of RAS/BRAF V600E WT mCRC patients., (Copyright © 2024 European Society for Medical Oncology. Published by Elsevier Ltd. All rights reserved.)

Published
2024
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46. Unfavorable carcinoma of unknown primary with a gastrointestinal profile: a retrospective study.

Author

Guidi L, Valenza C, Battaiotto E, Trapani D, Ghioni MC, Crimini E, Boscolo Bielo L, Venetis K, Belli C, Bottiglieri L, Gervaso L, Cella CA, Ciardiello D, Spada F, Benini L, Adorisio R, Mane E, Fazio N, Guerini Rocco E, Curigliano G, and Zampino MG

Subjects
Humans, Retrospective Studies, Male, Female, Middle Aged, Aged, Adult, Aged, 80 and over, Prognosis, Gastrointestinal Neoplasms pathology, Neoplasms, Unknown Primary
Abstract

Background: Carcinoma of unknown primary (CUP) with a gastrointestinal profile is categorized by the European Society of Medical Oncology (ESMO) guidelines into favorable and unfavorable subsets. Favorable CUPs benefit from site-specific chemotherapy (CT), while the optimal treatment for unfavorable CUPs is still undefined., Materials and Methods: We conducted a single-center retrospective study to describe outcomes of patients with CUP with a gastrointestinal profile referred to our center from January 2000 to August 2023. Favorable CUPs were defined as CK7-/CK20+/CDX2+ by immunohistochemistry, according to the ESMO definition; all other cases were considered unfavorable. The main endpoint was the progression-free survival (PFS) of first-line CT for advanced disease in all patients and in the unfavorable group., Results: A total of 56 patients were included, of whom 46 (82%) had unfavorable CUPs. After a median follow-up of 43.9 months, the median overall survival (mOS) was 11.8 months [95% confidence interval (CI) 8.3-15.3 months]. At univariate analysis, the presence of peritoneal metastases and residual tumor after primary surgery were associated with a shorter OS. The median PFS (mPFS) was 6.1 months (95% CI 3.6-8.7 months). In the unfavorable CUP subgroup, the mOS was 12.6 months (95% CI 8.7-16.5 months), the mPFS was 6.1 months (95% CI 3.5-8.9 months) and none of the CT regimens used showed to portend better PFS. The most relevant altered genes included: KRAS (9/29; 31%), BRAF (1/26; 4%), NRAS (1/25; 4%), TP53 (9/23; 39%)., Conclusions: CUPs with a gastrointestinal profile are characterized by poor prognosis and the absence of biomarker for treatment personalization. No CT regimen was superior in terms of PFS in patients with unfavorable CUPs., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Published
2024
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47. Promising targetable biomarkers in pancreatic neuroendocrine tumours.

Author

Borghesani M, Gervaso L, Cella CA, Benini L, Ciardiello D, Algeri L, Ferrero A, Valenza C, Guidi L, Zampino MG, Spada F, and Fazio N

Subjects
Humans, Treatment Outcome, Biomarkers, Tumor, Patient Selection, Pancreatic Neoplasms drug therapy, Pancreatic Neoplasms pathology, Neuroendocrine Tumors drug therapy, Neuroendocrine Tumors pathology
Abstract

Introduction: In the treatment scenario of PanNETs-targeted therapies are desired but limited, as rarity and heterogeneity on PanNETs pose limitations to their development., Areas Covered: We performed a literature review searching for promising druggable biomarkers and potential treatments to be implemented in the next future. We focused on treatments which have already reached clinical experimentation, although in early phases. Six targets were identified, namely Hsp90, HIFa, HDACs, CDKs, uPAR, and DDR. Even though biological rational is strong, so far reported efficacy outcomes are quite disappointing. The reason of that should be searched in the patients' heterogeneity, lack of biomarker selection, poor knowledge of interfering mechanisms as well as difficulties in patients accrual. Moreover, different ways to assess treatment efficacy should be considered, other than response rate, in light of the more indolent nature of NETs., Expert Opinion: Development of targeted treatments in PanNETs is still an uncovered area, far behind other more frequent cancers. Rarity of NETs led to accrual of unselected populations, possibly jeopardizing the drug efficacy. Better patients' selection, both in terms of topography, grading and biomarkers is crucial and will help understanding which role targeted therapies can really play in these tumors.

Published
2023
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48. Clinical efficacy of sequential treatments in KRASG12C-mutant metastatic colorectal cancer: findings from a real-life multicenter Italian study (CRC-KR GOIM).

Author

Ciardiello D, Chiarazzo C, Famiglietti V, Damato A, Pinto C, Zampino MG, Castellano G, Gervaso L, Zaniboni A, Oneda E, Rapisardi S, Bordonaro R, Zichi C, De Vita F, Di Maio M, Parisi A, Giampieri R, Berardi R, Lavacchi D, Antonuzzo L, Tamburini E, Maiorano BA, Parrella P, Latiano TP, Normanno N, De Stefano A, Avallone A, Martini G, Napolitano S, Troiani T, Martinelli E, Ciardiello F, De Vita F, and Maiello E

Subjects
Humans, Oxaliplatin pharmacology, Oxaliplatin therapeutic use, Irinotecan pharmacology, Irinotecan therapeutic use, Retrospective Studies, Fluorouracil adverse effects, Antineoplastic Combined Chemotherapy Protocols pharmacology, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Treatment Outcome, Colorectal Neoplasms drug therapy, Colorectal Neoplasms genetics, Colorectal Neoplasms pathology, Colonic Neoplasms drug therapy
Abstract

Background: The presence of KRASG12C mutation in metastatic colorectal cancer (mCRC) correlates with poor outcome. Although different selective inhibitors are under clinical development, the optimal treatment remains uncertain. Thus, we conducted a retrospective analysis in a large cohort of patients with KRASG12C mCRC treated in 12 Italian oncology units., Patients and Methods: Patients with unresectable mCRC harboring KRASG12C mutation receiving a first-line chemotherapy doublet or triplet between 2011 and 2021 were included in the study. Evaluation of overall response rate (ORR), progression-free survival (PFS) and overall survival (OS) analysis was carried out., Results: A total of 256/6952 (3.7%) patients with mCRC displayed KRASG12C mutation; of these, 111 met the inclusion criteria. The ORR of first-line therapy was 38.7% (43/111). Median PFS (mPFS) was 9 months [95% confidence interval (CI) 7.5-10.5 months]. After progression, only 62% and 36% of the patients are fit to receive second or third lines of treatment, with limited clinical benefit. Median OS (mOS) was 21 months (95% CI 17.4-24.6 months). In patients receiving first-line triplet chemotherapy, ORR was 56.3% (9/16), mPFS was 13 months (95% CI 10.3-15.7 months) and mOS was 32 months (95% CI 7.7-56.3 months). For irinotecan-based doublets, ORR was 34.5 (10/29), mPFS was 9 months (95% CI 6.4-11.6 months) and mOS was 22 months (95% CI 16.0-28.0 months). With oxaliplatin-based doublets ORR was 36.4% (24/62), mPFS was 7 months (95% CI 4.6-9.4 months) and mOS was 18 months (95% CI, 13.6-22.4 months)., Conclusion: Patients with KRASG12C-mutant mCRC had a disappointing response to standard treatments. Within the limitations of a retrospective study, these results suggest that first-line chemotherapy intensification with FOLFOXIRI is a valid option in fit patients., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Published
2022
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49. Overall survival with 3 or 6 months of adjuvant chemotherapy in Italian TOSCA phase 3 randomised trial.

Author

Petrelli F, Rulli E, Labianca R, Lonardi S, Rosati G, Dotti K, Ronzoni M, Pella N, Pusceddu V, Banzi M, Zampino MG, Yasmina M, Marchetti P, Cantore M, Zaniboni A, Rimassa L, Ciuffreda L, Ferrari D, Zagonel V, Maiello E, and Sobrero A

Subjects
Antineoplastic Combined Chemotherapy Protocols adverse effects, Capecitabine therapeutic use, Chemotherapy, Adjuvant, Disease-Free Survival, Humans, Italy, Neoplasm Staging, Fluorouracil adverse effects, Neoplasm Recurrence, Local pathology
Abstract

Background: Oxaliplatin-based adjuvant chemotherapy is the standard treatment of high-risk colon cancer (CC). A shorter duration (3 months) can achieve a similar outcome [in terms of relapse-free survival (RFS)] to a longer duration. This study reports the overall survival (OS) analysis of the three or six colon adjuvant (TOSCA) phase III study. It assessed different adjuvant chemotherapy durations in patients with resected high-risk stage II and stage III CC., Material and Methods: TOSCA was an open-label, phase III, multicentre, non-inferiority trial conducted in 130 Italian centres. Patients were randomly assigned, in a 1 : 1 ratio, to receive 3 months of standard doses of FOLFOX/CAPOX, or 6 months of FOLFOX/CAPOX. Patients with histologically confirmed high-risk stage II and III CC were included, with RFS being the primary end point. OS was a secondary end point., Results: From June 2007 to March 2013, 3759 patients were accrued. At a median follow-up of 7 years, the hazard ratio (HR) for RFS of the 3-month versus 6-month arms was 1.13; 95% confidence interval (CI) 0.99-1.29, P for non-inferiority = 0.380, P for superiority = 0.068, crossing the non-inferiority limit of 1.20. This result did not allow us to reject the null hypothesis of the inferiority of the 3-month arm. The HR for OS of the 3-month versus 6-month arms was 1.09 (95% CI 0.93-1.26, P for superiority = 0.288). At the last follow-up analysis, the absolute OS difference between arms was <1%., Conclusions: The present analysis of the TOSCA trial does not indicate any significant difference in OS between the treatment groups. The extra benefit provided by the longer treatment should be balanced against the extra toxicity of more prolonged therapy. The trial is registered with ClinicalTrials.gov, registration number: NCT0064660., Competing Interests: Disclosure LR reports receiving consulting fees from Amgen, ArQule, AstraZeneca, Basilea, Bayer, Celgene, Eisai, Exelixis, Hengrui, Incyte, Ipsen, Lilly, MSD, Nerviano Medical Sciences, Roche, Sanofi; lectures fees from AbbVie, Amgen, Eisai, Gilead, Incyte, Ipsen, Lilly, Roche, Sanofi; travel fees from Ipsen; and institutional research funding from Agios, ARMO BioSciences, AstraZeneca, BeiGene, Eisai, Exelixis, FibroGen, Incyte, Ipsen, Lilly, MSD, Roche. All other authors declared no conflict of interest., (Copyright © 2020 European Society for Medical Oncology. Published by Elsevier Ltd. All rights reserved.)

Published
2021
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50. Genital marginal failures after intensity-modulated radiation therapy (IMRT) in squamous cell anal cancer: no higher risk with IMRT when compared to 3DCRT.

Author

Dell'Acqua V, Kobiela J, Kraja F, Leonardi MC, Surgo A, Zerella MA, Arculeo S, Fodor C, Ricotti R, Zampino MG, Ravenda S, Spinoglio G, Biffi R, Bazani A, Luraschi R, Vigorito S, Spychalski P, Orecchia R, Glynne-Jones R, and Jereczek-Fossa BA

Subjects
Adult, Aged, Aged, 80 and over, Anus Neoplasms drug therapy, Carcinoma, Squamous Cell drug therapy, Chemoradiotherapy, Cohort Studies, Female, Humans, Male, Middle Aged, Neoplasm Staging, Radiotherapy Planning, Computer-Assisted, Radiotherapy, Conformal, Radiotherapy, Intensity-Modulated, Retrospective Studies, Treatment Failure, Anus Neoplasms pathology, Anus Neoplasms radiotherapy, Carcinoma, Squamous Cell pathology, Carcinoma, Squamous Cell radiotherapy, Genitalia pathology
Abstract

Intensity-modulated radiotherapy (IMRT) is considered the preferred option in squamous cell canal cancer (SCAC), delivering high doses to tumor volumes while minimizing dose to surrounding normal tissues. IMRT has steep dose gradients, but the technique is more demanding as deep understanding of target structures is required. To evaluate genital marginal failure in a cohort of patients with non-metastatic SCAC treated either with IMRT or 3DCRT and concurrent chemotherapy, 117 patients with SCAC were evaluated: 64 and 53 patients were treated with IMRT and 3DCRT techniques, respectively. All patients underwent clinical and radiological examination during their follow-up. Tumor response was evaluated with response evaluation criteria in solid tumors v1.1 guideline on regular basis. All patients' data were analyzed, and patients with marginal failure were identified. Concomitant chemotherapy was administered in 97 and 77.4% of patients in the IMRT and 3DCRT groups, respectively. In the IMRT group, the median follow-up was 25 months (range 6-78). Progressive disease was registered in 15.6% of patients; infield recurrence, distant recurrence and both infield recurrence and distant recurrence were identified in 5, 4 and 1 patient, respectively. Two out of 64 patients (3.1%) had marginal failures, localized at vagina/recto-vaginal septum and left perineal region. In the 3DCRT group, the median follow-up was 71.3 months (range 6-194 months). Two out of 53 patients (3.8%) had marginal failures, localized at recto-vaginal septum and perigenital structures. The rate of marginal failures was comparable in IMRT and 3DCRT groups (χ 2 test p = 0.85). In this series, the use of IMRT for the treatment of SCAC did not increase the rate of marginal failures offering improved dose conformity to the target. Dose constraints should be applied with caution-particularly in females with involvement of the vagina or the vaginal septum.

Published
2018
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