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Start Over Author "Gardini, Andrea Casadei" Topic hepatocellular carcinoma
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2. Circulating microRNAs as biomarkers for stratifying different phases of liver cancer progression and response to therapy.

Author

D'Abundo, Lucilla, Bassi, Cristian, Callegari, Elisa, Moshiri, Farzaneh, Guerriero, Paola, Michilli, Angelo, Mora, Fernanda, Gardini, Andrea Casadei, Sangiovanni, Angelo, Piscaglia, Fabio, Sabbioni, Silvia, Gramantieri, Laura, and Negrini, Massimo

Subjects
NUCLEOTIDE sequencing, LIVER cancer, HEPATOCELLULAR carcinoma, BLOOD serum analysis, LIVER diseases
Abstract

Hepatocellular carcinoma (HCC) is the most common liver cancer and is among the leading causes of cancer-related death worldwide. There is no reliable biomarker for the early diagnosis of HCC. Circulating microRNAs (miRNAs) have attracted attention as potential biomarkers of disease. By small-RNA next-generation sequencing, the analysis of serum miRNAs led to the identification of molecular signatures able to discriminate advanced HCC from early HCC (n = 246); advanced HCC from CIRRHOSIS (n = 299); advanced HCC from HEALTHY (n = 320); HEALTHY from early HCC (n = 343); and HEALTHY from CIRRHOSIS (n = 414). Cirrhotic patients and early HCC patients exhibited similar serum miRNA profiles, yet a small number of miRNAs (n = 57) were able to distinguish these two classes of patients. A second objective of the study was to identify serum miRNAs capable of predicting the response to therapy in patients with advanced HCC. All patients were treated with sorafenib as first-line therapy: 24 were nonresponsive and 24 responsive. Analysis of circulating miRNAs revealed a 54 miRNAs signature able to separate the two subgroups. This study suggested that circulating miRNAs could be useful biomarkers for monitoring patients with liver diseases ranging from cirrhosis to advanced HCC and possibly predicting susceptibility to first-line treatment based on sorafenib. [ABSTRACT FROM AUTHOR]

Published
2024
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3. Recalibrating survival prediction among patients receiving trans‐arterial chemoembolization for hepatocellular carcinoma

Author

Cucchetti, Alessandro, Giannini, Edoardo G., Mosconi, Cristina, Plaz Torres, Maria Corina, Pieri, Giulia, Farinati, Fabio, Rapaccini, Gian Ludovico, Di Marco, Maria, Caturelli, Eugenio, Sacco, Rodolfo, Cabibbo, Giuseppe, Campani, Claudia, Mega, Andrea, Guarino, Maria, Gasbarrini, Antonio, Svegliati‐Baroni, Gianluca, Foschi, Francesco Giuseppe, Missale, Gabriele, Masotto, Alberto, Nardone, Gerardo, Raimondo, Giovanni, Vidili, Gianpaolo, Brunetto, Maurizia Rossana, Sansone, Vito, Zoli, Marco, Azzaroli, Francesco, Trevisani, Franco, Biselli, Maurizio, Caraceni, Paolo, Gramenzi, Annagiulia, Rampoldi, Davide, Reggidori, Nicola, Santi, Valentina, Stefanini, Benedetta, Granito, Alessandro, Muratori, Luca, Piscaglia, Fabio, Tovoli, Francesco, Magalotti, Donatella, Dajti, Elton, Marasco, Giovanni, Ravaioli, Federico, Cappelli, Alberta, Golfieri, Rita, Renzulli, Matteo, Pelizzaro, Filippo, Penzo, Barbara, Marina Cela, Ester, Facciorusso, Antonio, Cacciato, Valentina, Casagrande, Edoardo, de Matthaeis, Nicoletta, Allegrini, Gloria, Lauria, Valentina, Ghittoni, Giorgia, Pelecca, Giorgio, Chegai, Fabrizio, Coratella, Fabio, Ortenzi, Mariano, Dell'Isola, Serena, Biasini, Elisabetta, Olivani, Andrea, Inno, Alessandro, Marchetti, Fabiana, Celsa, Ciro, Grova, Mauro, Stornello, Caterina, Busacca, Anita, Cammà, Calogero, Maria Rizzo, Giacomo Emanuele, Franzè, Maria Stella, Saitta, Carlo, Sauchella, Assunta, Napoli, Lucia, Bevilacqua, Vittoria, Berardinelli, Dante, Borghi, Alberto, Gardini, Andrea Casadei, Conti, Fabio, Dall'Aglio, Anna Chiara, Ercolani, Giorgio, Marra, Fabio, Di Bonaventura, Chiara, Gitto, Stefano, Adotti, Valentina, Coccoli, Pietro, Malerba, Antonio, Capasso, Mario, Morisco, Filomena, Oliveri, Filippo, Romagnoli, Veronica, Cucchetti, Alessandro, Giannini, Edoardo G., Mosconi, Cristina, Plaz Torres, Maria Corina, Pieri, Giulia, Farinati, Fabio, Rapaccini, Gian Ludovico, Di Marco, Maria, Caturelli, Eugenio, Sacco, Rodolfo, Cabibbo, Giuseppe, Campani, Claudia, Mega, Andrea, Guarino, Maria, Gasbarrini, Antonio, Svegliati‐Baroni, Gianluca, Foschi, Francesco Giuseppe, Missale, Gabriele, Masotto, Alberto, Nardone, Gerardo, Raimondo, Giovanni, Vidili, Gianpaolo, Brunetto, Maurizia Rossana, Sansone, Vito, Zoli, Marco, Azzaroli, Francesco, Trevisani, Franco, Biselli, Maurizio, Caraceni, Paolo, Gramenzi, Annagiulia, Rampoldi, Davide, Reggidori, Nicola, Santi, Valentina, Stefanini, Benedetta, Granito, Alessandro, Muratori, Luca, Piscaglia, Fabio, Tovoli, Francesco, Magalotti, Donatella, Dajti, Elton, Marasco, Giovanni, Ravaioli, Federico, Cappelli, Alberta, Golfieri, Rita, Renzulli, Matteo, Pelizzaro, Filippo, Penzo, Barbara, Marina Cela, Ester, Facciorusso, Antonio, Cacciato, Valentina, Casagrande, Edoardo, de Matthaeis, Nicoletta, Allegrini, Gloria, Lauria, Valentina, Ghittoni, Giorgia, Pelecca, Giorgio, Chegai, Fabrizio, Coratella, Fabio, Ortenzi, Mariano, Dell'Isola, Serena, Biasini, Elisabetta, Olivani, Andrea, Inno, Alessandro, Marchetti, Fabiana, Celsa, Ciro, Grova, Mauro, Stornello, Caterina, Busacca, Anita, Cammà, Calogero, Maria Rizzo, Giacomo Emanuele, Franzè, Maria Stella, Saitta, Carlo, Sauchella, Assunta, Napoli, Lucia, Bevilacqua, Vittoria, Berardinelli, Dante, Borghi, Alberto, Gardini, Andrea Casadei, Conti, Fabio, Dall'Aglio, Anna Chiara, Ercolani, Giorgio, Marra, Fabio, Di Bonaventura, Chiara, Gitto, Stefano, Adotti, Valentina, Coccoli, Pietro, Malerba, Antonio, Capasso, Mario, Morisco, Filomena, Oliveri, Filippo, and Romagnoli, Veronica

Subjects
Liver Cancer, Pre-TACE-Predict model, medicine.medical_specialty, business.industry, Trans-arterial chemoembolization, Pharmaceutical Science, hepatocellular carcinoma, medicine.disease, Gastroenterology, Complementary and alternative medicine, Internal medicine, Hepatocellular carcinoma, medicine, Pharmacology (medical), Trans arterial chemoembolization, business
Abstract

Background & Aims The Pre-TACE-Predict model was devised to assess prognosis of patients treated with trans-arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC). However, before entering clinical practice, a model should demonstrate that it performs a useful role. Methods We performed an independent external validation of the Pre-TACE model in a cohort that differs in setting and time period from the one that generated the original model. Data from 826 patients treated with TACE for naïve HCC (2008-2018) were used to assess calibration and discrimination of the Pre-TACE-Predict model. Results The four risk-categories identified by the Pre-TACE-Predict model had gradient monotonicity, with median survivals of 52.0, 36.2, 29.9, and 14.1 months respectively. However, predicted survivals systematically underestimated observed survivals (R2: 0.667). A recalibration was adopted maintaining fixed the prognostic index and modifying the baseline survival function. This resulted in an almost perfect calibration (R2: 0.995) in all the four risk categories. Cox regressions showed that aetiology and macrovascular invasion, included in the Pre-TACE-Predict model, had no prognostic impact in the present study population, and that coefficients for tumour size and multiplicity were overestimated. The c-index was similar to that of the m-HAP-III, but higher than those of HAP, m-HAP-II and the six-and-twelve models. Conclusions The recalibration of Pre-TACE-Predict model improved the estimation of survival probabilities of HCC patients treated with TACE. The highest discriminatory ability of the Pre-TACE-model in comparison to other available models, together with risk stratification and recalibration, makes it the best prognostic tool currently available for these patients.

Published
2021
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4. Effect of direct-acting antivirals on future occurrence of hepatocellular carcinoma in compensated cirrhotic patients

Author

Cucchetti, Alessandro, D’Amico, Gennaro, Trevisani, Franco, Morelli, Maria Cristina, Vitale, Alessandro, Pinna, Antonio Daniele, Cescon, Matteo, Cillo, Umberto, Burra, Patrizia, Russo, Francesco P., Mescoli, Claudia, Rendina, Maria, Lupo, Luigi G., Losito, Francesco, Fucilli, Fabio, Brancaccio, Giusep-Pina, Persico, Marcello, Viganò, Luca, Iavarone, Massimo, D’Ambrosio, Roberta, Sangiovanni, Angelo, Renzulli, Matteo, Galati, Giovanni, Ponziani, Francesca Romana, Pompili, Maurizio, Miele, Luca, Grieco, Antonio, Rapaccini, Gianlodovico, Gasbarrini, Antonio, Sandri, Giovanni Battisa Levi, Lai, Quirino, Melandro, Fabio, Rossi, Massimo, Lenci, Ilaria, Manzia, Tommaso Maria, Tortora, Raffaella, Di Costanzo, Giovan Giuseppe, Sacco, Rodolfo, Simonetti, Natalia, Morisco, Filomena, Guarino, Maria, Cabibbo, Giuseppe, Bhoori, Carlo Sposito Sherrie, Di Sandro, Stefano, Foschi, Francesco Giuseppe, Gardini, Andrea Casadei, Nicolini, Daniele, Mazzocato, Susanna, Alba, Kostandini, Violi, Paola, Baccarani, Umberto, Pravisani, Riccardo, A. Cucchetti, G. D'Amico, F. Trevisani, M.C. Morelli, A. Vitale, A.D.Pinna, M. Cescon, Cucchetti, Alessandro, D’Amico, Gennaro, Trevisani, Franco, Morelli, Maria Cristina, Vitale, Alessandro, Pinna, Antonio Daniele, Cescon, Matteo, Cillo, Umberto, Burra, Patrizia, Russo, Francesco P., Mescoli, Claudia, Rendina, Maria, Lupo, Luigi G., Losito, Francesco, Fucilli, Fabio, Brancaccio, Giusep-Pina, Persico, Marcello, Viganò, Luca, Iavarone, Massimo, D’Ambrosio, Roberta, Sangiovanni, Angelo, Renzulli, Matteo, Galati, Giovanni, Ponziani, Francesca Romana, Pompili, Maurizio, Miele, Luca, Grieco, Antonio, Rapaccini, Gianlodovico, Gasbarrini, Antonio, Sandri, Giovanni Battisa Levi, Lai, Quirino, Melandro, Fabio, Rossi, Massimo, Lenci, Ilaria, Manzia, Tommaso Maria, Tortora, Raffaella, Di Costanzo, Giovan Giuseppe, Sacco, Rodolfo, Simonetti, Natalia, Morisco, Filomena, Guarino, Maria, Cabibbo, Giuseppe, Bhoori, Carlo Sposito Sherrie, Di Sandro, Stefano, Foschi, Francesco Giuseppe, Gardini, Andrea Casadei, Nicolini, Daniele, Mazzocato, Susanna, Alba, Kostandini, Violi, Paola, Baccarani, Umberto, and Pravisani, Riccardo

Subjects
Male, Time Factors, Sustained Virologic Response, Hepatocellular carcinoma, Hepacivirus, Direct-acting antiviral, Direct-acting antivirals, medicine.disease_cause, Gastroenterology, Competing risk, Hepatitis C, Markov model, Survival benefit, Sustained virological response, Hepatology, 0302 clinical medicine, Risk Factors, 030212 general & internal medicine, biology, Incidence, Incidence (epidemiology), Liver Neoplasms, Middle Aged, Markov Chains, Competing risk Direct-acting antivirals Hepatitis C Hepatocellular carcinoma Markov model Survival benefit Sustained virological response, Italy, Liver Neoplasm, Female, 030211 gastroenterology & hepatology, Human, Adult, medicine.medical_specialty, Carcinoma, Hepatocellular, Time Factor, Hepatitis C virus, Antiviral Agents, 03 medical and health sciences, Internal medicine, medicine, Humans, Antiviral Agent, Hepaciviru, business.industry, Risk Factor, Carcinoma, Hepatocellular, Markov Chain, medicine.disease, biology.organism_classification, digestive system diseases, Settore MED/18 - Chirurgia Generale, Liver function, Varices, business
Abstract

Background: The achievement of high rates of sustained virological response (SVR) with direct-acting antivirals (DAAs) in hepatitis C virus (HCV) infected patients will reduce decompensating terminal events. Aims: To investigate whether hepatocellular carcinoma (HCC) occurrence could change due to the DAA-induced increase in life-expectancy. Methods: A Markov model was built on clinical data of 494 cirrhotic patients and available literature to estimate probabilities of “death before HCC” and of “HCC occurrence” without and with DAA. Results: In comparison to untreated patients, DAA therapy reduced the 20-year mortality before HCC by 21.9% in patients without varices and by 21.5% in those with varices, considering an SVR of 95% and no direct effect on hepatocarcinogenesis. Tumour occurrence increased by 5%–8.2% and the proportion of HCCs diagnosed in compensated stages increased to >98%. If we consider DAA as having “anti-tumoral” effects, the benefit becomes greater, achieving a 20-year survival of 81.5% in patients without varices, and 52.2% in patients with varices. Instead, if we consider DAA as having a “pro-tumoral” effect, then, the increased incidence of HCC nullifies the survival benefits. Conclusion: DAAs drastically reduce the mortality caused by the liver function worsening, increasing the proportion of HCCs diagnosed in compensated stages. Knowledge of the DAA effect on hepatocarcinogenesis remains pivotal. © 2017 Editrice Gastroenterologica Italiana S.r.l.

Published
2018
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5. Direct-acting antivirals and hepatocellular carcinoma in chronic hepatitis C: A few lights and many shadows

Author

Guarino, Maria, Sessa, Anna, Cossiga, Valentina, Morando, Federica, Caporaso, Nicola, Morisco, Filomena, Luca, Viganó, Romana, Ponziani Francesca, Maurizio, Pompili, Cillo, Umberto, Burra, Patrizia, Mescoli, Claudia, Gambato, Martina, Russo, FRANCESCO PAOLO, Vitale, Alessandro, Giuseppe, Cabibbo, Mauro, Vigano', Giovanni, Galati, Erica, Villa, Lupo, Luigi G., Maria, Rendina, Losito, Francesco, Fucilli, Fabio, Persico, Marcello, D'Ambrosio, Roberta, Sangiovanni, Angelo, Massimo, Iavarone, Brancaccio, Giuseppina, Cucchetti, Alessandro, Renzulli, Matteo, Franco, Trevisani, Miele, Luca, Grieco, Antonio, Rapaccini, Gianlodovico, Gasbarrini, Antonio, Sandri, Giovanni Battisa Levi, Melandro, Fabio, Rossi, Massimo, Quirino, Lai, Lenci, Ilaria, Manzia, Tommaso Maria, Tortora, Raffaella, Di Costanzo, Giovan Giuseppe, Ghinolfi, Davide, Rreka, Erion, Carrai, Paola, Simonetti, Natalia, Rodolfo, Sacco, Sposito, Carlo, Bhoori, Sherrie, Di Sandro, Stefano, Foschi, Francesco Giuseppe, Gardini, Andrea Casadei, Nicolini, Daniele, Mazzocato, Susanna, Alba, Kostandini, Violi, Paola, Baccarani, Umberto, Pravisani, Riccardo, Vincenzi, Valter, Maria, Guarino, Anna, Sessa, Valentina, Cossiga, Federica, Morando, Nicola, Caporaso, Filomena, Morisco, Viganó, Luca, Ponziani Francesca, Romana, Pompili, Maurizio, Umberto, Cillo, Patrizia, Burra, Claudia, Mescoli, Martina, Gambato, Russo Francesco, Paolo, Vitale, Alessandro, Cabibbo, Giuseppe, Vigano', Mauro, Galati, Giovanni, Villa, Erica, Luigi G., Lupo, Rendina, Maria, Francesco, Losito, Fabio, Fucilli, Marcello, Persico, Roberta, D'Ambrosio, Angelo, Sangiovanni, Iavarone, Massimo, Brancaccio, Giuseppina, Alessandro, Cucchetti, Matteo, Renzulli, Trevisani, Franco, Luca, Miele, Antonio, Grieco, Gianlodovico, Rapaccini, Antonio, Gasbarrini, Giovanni Battisa Levi, Sandri, Fabio, Melandro, Massimo, Rossi, Lai, Quirino, Ilaria, Lenci, Tommaso Maria, Manzia, Raffaella, Tortora, Giovan Giuseppe, Di Costanzo, Davide, Ghinolfi, Erion, Rreka, Paola, Carrai, Natalia, Simonetti, Sacco, Rodolfo, Carlo, Sposito, Sherrie, Bhoori, Stefano, Di Sandro, Francesco Giuseppe, Foschi, Andrea Casadei, Gardini, Daniele, Nicolini, Susanna, Mazzocato, Kostandini, Alba, Paola, Violi, Umberto, Baccarani, Riccardo, Pravisani, Valter, Vincenzi, Guarino, Maria, Sessa, Anna, Cossiga, Valentina, Morando, Federica, Caporaso, Nicola, Morisco, Filomena, Luca, Viganó, Romana, Ponziani Francesca, Maurizio, Pompili, Cillo, Umberto, Burra, Patrizia, Mescoli, Claudia, Gambato, Martina, Paolo, Russo Francesco, Alessandro, Vitale, Giuseppe, Cabibbo, Mauro, Vigano', Giovanni, Galati, Erica, Villa, Lupo, Luigi G., Maria, Rendina, Losito, Francesco, Fucilli, Fabio, Persico, Marcello, D'Ambrosio, Roberta, Sangiovanni, Angelo, Massimo, Iavarone, Giuseppina, Brancaccio, Cucchetti, Alessandro, Renzulli, Matteo, Franco, Trevisani, Miele, Luca, Grieco, Antonio, Rapaccini, Gianlodovico, Gasbarrini, Antonio, Sandri, Giovanni Battisa Levi, Melandro, Fabio, Rossi, Massimo, Quirino, Lai, Lenci, Ilaria, Manzia, Tommaso Maria, Tortora, Raffaella, Di Costanzo, Giovan Giuseppe, Ghinolfi, Davide, Rreka, Erion, Carrai, Paola, Simonetti, Natalia, Rodolfo, Sacco, Sposito, Carlo, Bhoori, Sherrie, Di Sandro, Stefano, Foschi, Francesco Giuseppe, Gardini, Andrea Casadei, Nicolini, Daniele, Mazzocato, Susanna, Alba, Kostandini, Violi, Paola, Baccarani, Umberto, Pravisani, Riccardo, and Vincenzi, Valter

Subjects
Oncology, Cirrhosis, Direct-acting antiviral agent, Sustained Virologic Response, Direct-acting antiviral agents, Hepatitis C virus, Hepatocellular carcinoma, Occurrence, Recurrence, Antiviral Agents, Carcinoma, Hepatocellular, Disease Progression, Hepacivirus, Hepatitis C, Chronic, Humans, Incidence, Liver, Liver Neoplasms, Neoplasm Recurrence, Local, Risk Factors, Treatment Outcome, Gastroenterology, medicine.disease_cause, DIRECT ACTING ANTIVIRALS, 0302 clinical medicine, Chronic, biology, Incidence (epidemiology), Minireviews, General Medicine, Hepatitis C, Local, Liver Neoplasm, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Human, medicine.medical_specialty, Interferon therapy, 03 medical and health sciences, Chronic hepatitis, Internal medicine, medicine, Antiviral Agent, Hepaciviru, business.industry, Risk Factor, Carcinoma, Hepatocellular, medicine.disease, biology.organism_classification, digestive system diseases, Settore MED/18 - Chirurgia Generale, Neoplasm Recurrence, business, Hepatitis C viru
Abstract

With the introduction of direct-acting antiviral agents (DAA), the rate of sustained virological response (SVR) in the treatment of hepatitis C virus (HCV) has radically improved to over 95%. Robust scientific evidence supports a beneficial role of SVR after interferon therapy in the progression of cirrhosis, resulting in a decreased incidence of hepatocellular carcinoma (HCC). However, a debate on the impact of DAAs on the development of HCC is ongoing. This review aimed to analyse the scientific literature regarding the risk of HCC in terms of its recurrence and occurrence after the use of DAAs to eradicate HCV infection. Among 11 studies examining HCC occurrence, the de novo incidence rate ranged from 0 to 7.4% (maximum follow-up: 18 mo). Among 18 studies regarding HCC recurrence, the rate ranged from 0 to 54.4% (maximum "not well-defined" followup: 32 mo). This review highlights the major difficulties in interpreting data and reconciling the results of the included studies. These difficulties include heterogeneous cohorts, potential misclassifications of HCC prior to DAA therapy, the absence of an adequate control group, short follow-up times and different kinds of follow-up. Moreover, no clinical feature-based scoring system accounts for the molecular characteristics and pathobiology of the tumours. Nonetheless, this review does not suggest that there is a higher rate of de novo HCC occurrence or recurrence after DAA therapy in patients with previous HCV infection. © 2018 The Author(s). Published by Baishideng Publishing Group Inc. All rights reserved.

Published
2018

6. Efficacy of sorafenib in BRAF-mutated non-small-cell lung cancer (NSCLC) and no response in synchronous BRAF wild type-hepatocellular carcinoma: a case report.

Author

Gardini, Andrea Casadei, Chiadini, Elisa, Faloppi, Luca, Marisi, Giorgia, Delmonte, Angelo, Scartozzi, Mario, Loretelli, Cristian, Lucchesi, Alessandro, Oboldi, Devil, Dubini, Alessandra, Frassineti, Giovanni Luca, Ulivi, Paola, and Casadei Gardini, Andrea

Subjects
*SORAFENIB, *LUNG cancer, *CARCINOGENS, *LIVER cancer, *TUMORS, *HEPATOCELLULAR carcinoma, *LIVER tumors, *LUNG tumors, *MULTIPLE tumors, *GENETIC mutation, *TRANSFERASES, *UREA, *TREATMENT effectiveness, *VITAMIN B complex, *VITAMIN therapy, *THERAPEUTICS
Abstract

Background: Sorafenib is a multi-targeted kinase inhibitor with a demonstrated activity in renal cell carcinoma (RCC) and hepatocellular carcinoma (HCC), and it is currently used for the treatment of these pathologies. Ongoing clinical trials are studying its activity in other malignancies, such as non-small-cell lung cancer (NSCLC). However, no biological marker is known to define either the sensitivity or resistance to the drug.Case Presentation: Here we report a case of a patient with two synchronous tumors, HCC and NSCLC, with metastases in the contralateral lung and bone. The patient was treated with gemcitabine as first line, with a resulting progressive disease after two months, and then with sorafenib at standard dosage in the second line setting. After 6 months of treatment CT scan showed a partial response in the primary lesion of the lung, complete response of the metastasis in the contralateral lung, and stability of HCC. The patient had progression in the lung, liver and bone after 13 months of therapy. A molecular characterization of NSCLC and HCC lesions was performed, revealing a BRAF exon 11 mutation (G469V) only in NSCLC. We hypothesize that the response observed in NSCLC lesions could be due to the presence of BRAF mutation, and that this alteration could be responsible in determining sorafenib sensitivity.Conclusions: Results observed in this case encourage further research on the activity of sorafenib in both HCC and NSCLC, based on the presence of BRAF mutation. This could lead to a selection of HCC patients to be treated with this drug, and could help identify a novel treatment strategy for BRAF-mutated NSCLC patients. [ABSTRACT FROM AUTHOR]

Published
2016
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7. Minimization of Immunosuppressive Therapy Is Associated with Improved Survival of Liver Transplant Patients with Recurrent Hepatocellular Carcinoma.

Author

Ossami Saidy, Ramin Raul, Postel, Maximilian Paul, Pflüger, Michael Johannes, Schoening, Wenzel, Öllinger, Robert, Gül-Klein, Safak, Schmelzle, Moritz, Tacke, Frank, Pratschke, Johann, Eurich, Dennis, Foschi, Francesco G., Gardini, Andrea Casadei, and Conti, Fabio

Subjects
GRAFT rejection, CANCER relapse, IMMUNOSUPPRESSION, CHEMOEMBOLIZATION, CANCER patients, SURVIVAL analysis (Biometry), DESCRIPTIVE statistics, LIVER transplantation, HEPATOCELLULAR carcinoma, TRANSPLANTATION of organs, tissues, etc., PALLIATIVE treatment
Abstract

Simple Summary: Liver transplantation is a curative treatment option for a subset of patients with hepatocellular carcinoma (HCC). However, about twenty percent of patients develop recurrence in the graft or at extrahepatic sites, which is associated with limited therapeutic options and poor survival. To date, management of the immunosuppressive regimen after recurrence and its impact on survival are unknown. In this retrospective study, we analyzed a cohort of liver recipients with HCC recurrence. Our findings indicate that reduction of immunosuppressive therapy after diagnosis of recurrence has a beneficial impact on patient survival. Therefore, we propose further investigation into the management of immunosuppressive therapy following recurrence. Introduction: Recurrence of hepatocellular carcinoma (rHCC) after liver transplantation (LT) is associated with limited survival. Therefore, identification of factors that prolong survival in these patients is of great interest. Surgical resection, radiotherapy, and transarterial chemoembolization (TACE) are established interventions to improve outcomes in these patients; however, the impact of immunosuppression is unknown. Methods: All patients diagnosed with rHCC in the follow-up after LT were identified from a database of liver recipients transplanted between 1988 and 2019 at our institution (Charité Universitätsmedizin Berlin, Germany). Based on the immunosuppressive regimen following diagnosis of rHCC and the oncological treatment approach, survival analysis was performed. Results: Among 484 patients transplanted for HCC, 112 (23.1%) developed rHCC in the follow-up. Recurrent HCC was diagnosed at a median interval of 16.0 months (range 1.0–203.0), with the majority presenting early after transplantation (63.0%, <2 years). Median survival after rHCC diagnosis was 10.6 months (0.3–228.7). Reduction of immunosuppression was associated with improved survival, particularly in patients with palliative treatment (8.4 versus 3.0 months). In addition, greater reduction of immunosuppression seemed to be associated with greater prolongation of survival. Graft rejection after reduction was uncommon (n = 7, 6.8%) and did not result in any graft loss. Patients that underwent surgical resection showed improved survival rates (median 19.5 vs. 8.7 months). Conclusion: Reduction of immunosuppressive therapy after rHCC diagnosis is associated with prolonged survival in LT patients. Therefore, reduction of immunosuppression should be an early intervention following diagnosis. In addition, surgical resection should be attempted, if technically feasible and oncologically meaningful. [ABSTRACT FROM AUTHOR]

Published
2021
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8. THU-448-Multicentric prospettive study of validation of angiogenesis-related gene polymorphisms in hepatocellular carcinoma patients treated with sorafenib: Interim analysis of INNOVATE study.

Author

Gardini, Andrea Casadei, Marisi, Giorgia, Faloppi, Luca, Dadduzio, Vincenzo, Scarpi, Emanuela, Ielasi, Luca, Foschi, Francesco, Vivaldi, Caterina, Cardellino, Giovanni, Tamburini, Emiliano, Siletta, Marianna, Negri, Francesca, Ulivi, Paola, Rizzato, Mario Domenico, Gramantieri, Laura, Conti, Fabio, Fornaro, Lorenzo, Porfiello, Annamaria, Rudnas, Britt, and Santini, Daniele

Subjects
*HEPATOCELLULAR carcinoma, *PROGRESSION-free survival
Published
2019
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10. Radiofrequency ablation of hepatocellular carcinoma: a meta-analysis of overall survival and recurrence-free survival

Author

Francesco Giuseppe Foschi, Giovanni Luca Frassineti, Giorgio Ercolani, Gabriele Donati, Matteo Canale, Emanuela Scarpi, Alessandro Passardi, Martina Valgiusti, Andrea Casadei Gardini, Giorgia Marisi, Gardini, Andrea Casadei, Marisi, Giorgia, Canale, Matteo, Foschi, Francesco Giuseppe, Donati, Gabriele, Ercolani, Giorgio, Valgiusti, Martina, Passardi, Alessandro, Frassineti, Giovanni Luca, Scarpi, Emanuela, and Casadei Gardini, Andrea

Subjects
medicine.medical_specialty, Radiofrequency ablation, Gastroenterology, OncoTargets and Therapy, law.invention, NLR, immune-inflammation index, 03 medical and health sciences, alpha-fetoprotein, 0302 clinical medicine, radiofrequency, Randomized controlled trial, law, neutrophil-to-lymphocyte ratio, Internal medicine, Recurrence free survival, chilpugh, medicine, Overall survival, platelet-lymphocyte ratio, Pharmacology (medical), Neutrophil to lymphocyte ratio, Neutrophil-to-lymphocyte ratio, Outcome, Original Research, marker, business.industry, Immune-inflammation index, ALBI score, Marker, medicine.disease, Oncology, 030220 oncology & carcinogenesis, Meta-analysis, Hepatocellular carcinoma, Alpha-fetoprotein, Radiofrequency, outcome, 030211 gastroenterology & hepatology, business, Chil-pugh, Platelet-lymphocyte ratio
Abstract

Andrea Casadei Gardini,1 Giorgia Marisi,2 Matteo Canale,2 Francesco Giuseppe Foschi,3 Gabriele Donati,4 Giorgio Ercolani,5,6 Martina Valgiusti,1 Alessandro Passardi,1 Giovanni Luca Frassineti,1 Emanuela Scarpi7 1Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy; 2Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy; 3Department of Internal Medicine, Degli Infermi Hospital, Faenza, Italy; 4Internal Medicine, Infermi Hospital, AUSL Romagna, Rimini, Italy; 5Department of General Surgery, Morgagni-Pierantoni Hospital, Forlì, Italy; 6Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy; 7Unit of Biostatistics and Clinical Trials, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy Background and aims: So far, no randomized trial or meta-analysis has been conducted on overall survival (OS) and recurrence-free survival (RFS) factors in patients treated with radiofrequency ablation (RFA) alone. The purpose of this meta-analysis was to evaluate prognostic factors of OS and RFS in patients treated with RFA.Methods: A primary analysis was planned to evaluate the clinical prognostic factor of OS. RFS was the secondary aim. Thirty-four studies published from 2003 to 2017 were analyzed. They included 11,216 hepatocellular carcinoma patients.Results: The results showed that Child–Pugh B vs Child–Pugh A (HR =2.32; 95% CI: 2.201–2.69; P2 cm vs 3 cm vs 1 nodule (HR =1.59; 95% CI: 1.46–1.74; P20 ng/mL (HR =1.46; 95% CI: 1.25–1.70; P

Published
2018

11. Ten years of sorafenib in hepatocellular carcinoma: Are there any predictive and/or prognostic markers?

Author

Matteo Canale, Giorgia Marisi, Giovanni Luca Frassineti, Giorgio Ercolani, Paola Ulivi, Mario Scartozzi, Francesco Giuseppe Foschi, Martina Valgiusti, Andrea Casadei Gardini, Leonardo Solaini, Alessandro Cucchetti, Serena De Matteis, Giuseppe Cabibbo, Marisi, Giorgia, Cucchetti, Alessandro, Ulivi, Paola, Canale, Matteo, Cabibbo, Giuseppe, Solaini, Leonardo, Foschi, Francesco G, De Matteis, Serena, Ercolani, Giorgio, Valgiusti, Martina, Frassineti, Giovanni L, Scartozzi, Mario, Gardini, Andrea Casadei, and Marisi G, Cucchetti A, Ulivi P, Canale M, Cabibbo G, Solaini L, Foschi FG, De Matteis S, Ercolani G, Valgiusti M, Frassineti GL, Scartozzi M, Casadei Gardini A.

Subjects
Oncology, Hepatocellular carcinoma, law.invention, Leukocyte Count, 0302 clinical medicine, Randomized controlled trial, Neutrophil-tolymphocyte ratio, law, Medicine, Neutrophil-to-lymphocyte ratio, Liver Neoplasms, Gastroenterology, MicroRNA, General Medicine, Sorafenib, Prognosis, Treatment Outcome, Liver, 030220 oncology & carcinogenesis, Biomarker (medicine), 030211 gastroenterology & hepatology, Adverse events, Angiopoietin, Biomarker, Polymorphisms, Vascular endothelial growth factor, medicine.drug, Adverse event, medicine.medical_specialty, Carcinoma, Hepatocellular, Antineoplastic Agents, Single-nucleotide polymorphism, 03 medical and health sciences, Internal medicine, Biomarkers, Tumor, Humans, Neoplasm Invasiveness, Polymorphism, Neutrophil to lymphocyte ratio, Adverse effect, business.industry, medicine.disease, digestive system diseases, Clinical Trials, Phase III as Topic, Drug Resistance, Neoplasm, Etiology, business
Abstract

Sorafenib has been considered the standard of care for patients with advanced unresectable hepatocellular carcinoma (HCC) since 2007 and numerous studies have investigated the role of markers involved in the angiogenesis process at both the expression and genetic level and clinical aspect. What results have ten years of research produced? Several clinical and biological markers are associated with prognosis. The most interesting clinical parameters are adverse events, Barcelona Clinic Liver Cancer stage, and macroscopic vascular invasion, while several single nucleotide polymorphisms and plasma angiopoietin-2 levels represent the most promising biological biomarkers. A recent pooled analysis of two phase III randomized trials showed that the neutrophil-to-lymphocyte ratio, etiology and extra-hepatic spread are predictive factors of response to sorafenib, but did not identify any predictive biological markers. After 10 years of research into sorafenib there are still no validated prognostic or predictive factors of response to the drug in HCC. The aim of the present review was to summarize 10 years of research into sorafenib, looking in particular at the potential of associated clinical and biological markers to predict its efficacy in patients with advanced HCC.

Published
2018
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12. Metronomic capecitabine versus best supportive care as second-line treatment in hepatocellular carcinoma: a retrospective study

Author

Giorgia Marisi, Martina Valgiusti, Emiliano Tamburini, Andrea Casadei Gardini, Britt Rudnas, Francesco Giuseppe Foschi, Oronzo Brunetti, Flavia Foca, Davide Tassinari, Stefano Cascinu, Luca Faloppi, Salvatore Pisconti, Giovanni Luca Frassineti, Giorgio Ercolani, Mario Scartozzi, Nicola Silvestris, Andrea Casadei Gardini, Flavia Foca, Mario Scartozzi, Nicola Silvestri, Emiliano Tamburini, Luca Faloppi, Oronzo Brunetti, Britt Rudna, Salvatore Pisconti, Martina Valgiusti, Giorgia Marisi, Francesco Giuseppe Foschi, Giorgio Ercolani, Davide Tassinari, Stefano Cascinu, Giovanni Luca Frassineti, Gardini, Andrea Casadei, Foca, Flavia, Scartozzi, Mario, Silvestris, Nicola, Tamburini, Emiliano, Faloppi, Luca, Brunetti, Oronzo, Rudnas, Britt, Pisconti, Salvatore, Valgiusti, Martina, Marisi, Giorgia, Foschi, Francesco Giuseppe, Ercolani, Giorgio, Tassinari, Davide, Cascinu, Stefano, and Frassineti, Giovanni Luca

Subjects
Oncology, Adult, Male, medicine.medical_specialty, Antimetabolites, Antineoplastic, Carcinoma, Hepatocellular, Article, Capecitabine, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Carcinoma, medicine, Combined Modality Therapy, Humans, Progression-free survival, Adverse effect, Aged, Neoplasm Staging, Proportional Hazards Models, Retrospective Studies, Aged, 80 and over, Multidisciplinary, Proportional hazards model, business.industry, Liver Neoplasms, capecitabina, hepatocellular carcinoma, best supportive care, Retrospective cohort study, Middle Aged, medicine.disease, Treatment Outcome, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, Administration, Metronomic, Retreatment, 030211 gastroenterology & hepatology, Female, business, medicine.drug
Abstract

Preliminary studies suggest that capecitabine may be safe and effective in HCC patients. The aim of this study was to retrospectively evaluate the safety and efficacy of metronomic capecitabine as second-line treatment. This multicentric study retrospectively analyzed data of HCC patients unresponsive or intolerant to sorafenib treatment with metronomic capecitabine or best supportive care (BSC).Median progression free survival was 3.1 months in patients treated with capecitabine (95%CI: 2.7–3.5). Median overall survival was 12.0 months (95% CI: 10.7–15.8) in patients receiving capecitabine, while 9.0 months (95% CI: 6.5–13.9) in patients receiving BSC. The result of univariate unweighted Cox regression model shows a 46% reduction in death risk for patients on capecitabine (95%CI: 0.357–0.829; p =0.005) compared to patients receiving BSC alone. After weighting for potential confounders, death risk remained essentially unaltered (45%; 95%CI: 0.354–0.883; p = 0.013). Metronomic capecitabine seems a safe second-line treatment for HCC patients in terms of management of adverse events, showing a potential anti-tumour activity which needs further evaluation in phase III studies.

Published
2017

13. Immune inflammation indicators and implication for immune modulation strategies in advanced hepatocellular carcinoma patients receiving sorafenib

Author

Luca Faloppi, Nicola Silvestris, Giorgio de Stefano, Daniele Santini, Giorgio Ercolani, Francesco Giuseppe Foschi, Francesca Negri, Mario Scartozzi, Emanuela Scarpi, Giorgia Marisi, Giovanni Luca Frassineti, Andrea Casadei Gardini, Martina Valgiusti, Gardini, Andrea Casadei, Scarpi, Emanuela, Faloppi, Luca, Scartozzi, Mario, Silvestris, Nicola, Santini, Daniele, de Stefano, Giorgio, Marisi, Giorgia, Negri, Francesca V., Foschi, Francesco Giuseppe, Valgiusti, Martina, Ercolani, Giorgio, Frassineti, Giovanni Luca, Casadei Gardini, Andrea, and Negri, Francesca V

Subjects
Male, 0301 basic medicine, Hepatocellular carcinoma, Kaplan-Meier Estimate, 0302 clinical medicine, systemic immune-inflammation index, Biomarker, Inflammation, Neutrophil-to-lymphocyte ratio, Systemic immune-inflammation index, Oncology, Liver Neoplasms, hepatocellular carcinoma, Middle Aged, Sorafenib, Prognosis, University hospital, 030220 oncology & carcinogenesis, biomarker, Female, Research Paper, medicine.drug, Immune inflammation, Adult, Niacinamide, medicine.medical_specialty, Carcinoma, Hepatocellular, Antineoplastic Agents, Disease-Free Survival, 03 medical and health sciences, neutrophil-to-lymphocyte ratio, Internal medicine, Biomarkers, Tumor, medicine, Humans, In patient, Neutrophil to lymphocyte ratio, neoplasms, Aged, Proportional Hazards Models, Retrospective Studies, Interventional Ultrasound, business.industry, Phenylurea Compounds, fungi, Immune modulation, medicine.disease, digestive system diseases, Surgery, 030104 developmental biology, inflammation, business
Abstract

// Andrea Casadei Gardini 1 , Emanuela Scarpi 2 , Luca Faloppi 3, 4 , Mario Scartozzi 4 , Nicola Silvestris 5 , Daniele Santini 6 , Giorgio de Stefano 7 , Giorgia Marisi 8 , Francesca V. Negri 9 , Francesco Giuseppe Foschi 10 , Martina Valgiusti 1 , Giorgio Ercolani 11, 12 , Giovanni Luca Frassineti 1 1 Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e Cura dei Tumori (IRST) IRCCS, Meldola, Italy 2 Unit of Biostatistics and Clinical Trials, IRST IRCCS, Meldola, Italy 3 Department of Medical Oncology, Ospedale Generale Provinciale di Macerata ASUR Marche AV3, Macerata, Italy 4 Department of Medical Oncology, University Hospital Cagliari, Cagliari, Italy 5 Medical Oncology Unit, Cancer Institute “Giovanni Paolo II”, Bari, Italy 6 Medical Oncology Department, University Campus Bio-Medico, Via Alvaro del Portillo, Rome, Italy 7 Infectious Diseases and Interventional Ultrasound Unit, D. Cotugno Hospital, Naples, Italy 8 Biosciences Laboratory, IRST IRCCS, Meldola, Italy 9 Medical Oncology Unit, University Hospital, Parma, Italy 10 DPT Internal Medicine, Faenza Hospital, Faenza, AUSL Romagna, Forli, Italy 11 Department of General Surgery, Morgagni-Pierantoni Hospiatal, AUSL Romagna, Forli, Italy 12 Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy Correspondence to: Andrea Casadei Gardini, email: andrea.casadei@irst.emr.it Keywords: systemic immune-inflammation index, inflammation, biomarker, hepatocellular carcinoma, neutrophil-to-lymphocyte ratio Received: June 21, 2016 Accepted: August 15, 2016 Published: August 24, 2016 ABSTRACT We evalueted a systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) with the aim to explored their prognostic value in patients with advanced hepatocellular carcinoma (HCC) treated with sorafenib. 56 advanced HCC patients receiving sorafenib were available for our analysis. Lymphocyte, neutrophil and platelet were measured before beginning of treatment and after one month. Patient with SII ≥ 360 showed lower median PFS (2.6 vs. 3.9 months, P < 0.026) and OS (5.6 vs. 13.9 months, P = 0.027) with respect to patients with SII < 360. NLR ≥ 3 had a lower median PFS (2.6 vs. 3.3 months, P < 0.049) but not OS (5.6 vs. 13.9 months, P = 0.062) than those with NLR < 3. After adjusting for clinical covariates SII and NLR remained an independent prognostic factor for OS. The SII and NLR represent potential prognostic indicator in patients with advanced HCC treated with sorafenib.

Published
2016

14. FRI-474-AGT gene polymorphisms predict early dose modification of sorafenib for dermatological adverse events: towards tailored medicine for patients with hepatocellular carcinoma.

Author

Iavarone, Massimo, Galmozzi, Enrico, Silvestri, Annalisa De, Gardini, Andrea Casadei, Piscaglia, Fabio, Marisi, Giorgia, Facchetti, Floriana, Faloppi, Luca, Ielasi, Luca, Benevento, Francesca, Scartozzi, Mario, Cascinu, Stefano, Sangiovanni, Angelo, Tinelli, Carmine, and Lampertico, Pietro

Subjects
*HEPATOCELLULAR carcinoma, *GENES, *GENETIC polymorphisms, *SORAFENIB, *REDUCTION of drug dosage, *DRUG side effects, *SKIN diseases
Published
2019
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