Long term results of down-staging and liver transplantation for patients with hepatocellular carcinoma beyond the conventional criteria

Matteo Ravaioli, Federica Odaldi, Alessandro Cucchetti, Franco Trevisani, Fabio Piscaglia, Vanessa De Pace, Valentina Rosa Bertuzzo, Flavia Neri, Rita Golfieri, Alberta Cappelli, Antonietta D’Errico, Matteo Cescon, Massimo Del Gaudio, Guido Fallani, Antonio Siniscalchi, Maria Cristina Morelli, Francesca Ciccarese, Maria Di Marco, Fabio Farinati, Edoardo Giovanni Giannini & 1 others Antonio Daniele Pinna

Research output: Contribution to journalArticle

Abstract

The objective of the study is to evaluate 10 years of down-staging strategy for liver transplantation (LT) with a median follow-up of 5 years. Data on long-term results are poor and less information is available for hepatocellular carcinoma (HCC) non-responder patients or those ineligible for down-staging. The outcome of 308 HCC candidates and the long-term results of 231 LTs for HCC performed between 2003 and 2013 were analyzed. HCCs were divided according to tumor stage and response to therapy: 145 patients were T2 (metering Milan Criteria, MC), 43 were T3 successfully down-staged to T2 (Down-Achieved), 20 were T3 not fully down-staged to T2 (Down-not Achieved), and 23 patients were T3 not receiving down-staging treatments (No-Down). The average treatment effect (ATE) of LT for T3 tumors was estimated using the outcome of 535 T3 patients undergoing non-LT therapies, using inverse probability weighting regression adjustment. The 24-month drop-out rate during waiting time was significantly higher in the down-staging groups: 27.6% vs. 9.2%, p < 0.005. After LT, the tumor recurrence rate was significantly different: MC 7.6%, Down-Achieved 20.9%, Down-not Achieved 31.6%, and No-Down 30.4% (p < 0.001). The survival rates at 5 years were: 63% in Down-Achieved, 62% in Down-not Achieved, 63% in No-Down, and 77% in MC (p = n.s.). The only variable related to a better outcome was the effective down-staging to T2 at the histological evaluation of the explanted liver: recurrence rate = 7.8% vs. 26% (p < 0.001) and 5-year patient survival = 76% vs. 67% (p < 0.05). The ATE estimation showed that the mean survival of T3-LT candidates was significantly better than that of T3 patients ineligible for LT [83.3 vs 39.2 months (+44.6 months); p < 0.001]. Long term outcome of T3 down-staged candidates was poorer than that of MC candidates, particularly for cases not achieving down-staging. However, their survival outcome was significantly better than that achieved with non-transplant therapies.

Original languageEnglish
Article number3781
JournalScientific Reports
Volume9
Issue number1
DOIs
Publication statusPublished - Dec 1 2019

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Liver Transplantation
Hepatocellular Carcinoma
Survival
Therapeutics
Recurrence
Neoplasms
Survival Rate
Transplantation
Liver

ASJC Scopus subject areas

  • General

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Long term results of down-staging and liver transplantation for patients with hepatocellular carcinoma beyond the conventional criteria. / Ravaioli, Matteo; Odaldi, Federica; Cucchetti, Alessandro; Trevisani, Franco; Piscaglia, Fabio; De Pace, Vanessa; Bertuzzo, Valentina Rosa; Neri, Flavia; Golfieri, Rita; Cappelli, Alberta; D’Errico, Antonietta; Cescon, Matteo; Del Gaudio, Massimo; Fallani, Guido; Siniscalchi, Antonio; Morelli, Maria Cristina; Ciccarese, Francesca; Di Marco, Maria; Farinati, Fabio; Giannini, Edoardo Giovanni; Pinna, Antonio Daniele.

In: Scientific Reports, Vol. 9, No. 1, 3781, 01.12.2019.

Research output: Contribution to journalArticle

Ravaioli, M, Odaldi, F, Cucchetti, A, Trevisani, F, Piscaglia, F, De Pace, V, Bertuzzo, VR, Neri, F, Golfieri, R, Cappelli, A, D’Errico, A, Cescon, M, Del Gaudio, M, Fallani, G, Siniscalchi, A, Morelli, MC, Ciccarese, F, Di Marco, M, Farinati, F, Giannini, EG & Pinna, AD 2019, 'Long term results of down-staging and liver transplantation for patients with hepatocellular carcinoma beyond the conventional criteria', Scientific Reports, vol. 9, no. 1, 3781. https://doi.org/10.1038/s41598-019-40543-4
Ravaioli, Matteo ; Odaldi, Federica ; Cucchetti, Alessandro ; Trevisani, Franco ; Piscaglia, Fabio ; De Pace, Vanessa ; Bertuzzo, Valentina Rosa ; Neri, Flavia ; Golfieri, Rita ; Cappelli, Alberta ; D’Errico, Antonietta ; Cescon, Matteo ; Del Gaudio, Massimo ; Fallani, Guido ; Siniscalchi, Antonio ; Morelli, Maria Cristina ; Ciccarese, Francesca ; Di Marco, Maria ; Farinati, Fabio ; Giannini, Edoardo Giovanni ; Pinna, Antonio Daniele. / Long term results of down-staging and liver transplantation for patients with hepatocellular carcinoma beyond the conventional criteria. In: Scientific Reports. 2019 ; Vol. 9, No. 1.
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abstract = "The objective of the study is to evaluate 10 years of down-staging strategy for liver transplantation (LT) with a median follow-up of 5 years. Data on long-term results are poor and less information is available for hepatocellular carcinoma (HCC) non-responder patients or those ineligible for down-staging. The outcome of 308 HCC candidates and the long-term results of 231 LTs for HCC performed between 2003 and 2013 were analyzed. HCCs were divided according to tumor stage and response to therapy: 145 patients were T2 (metering Milan Criteria, MC), 43 were T3 successfully down-staged to T2 (Down-Achieved), 20 were T3 not fully down-staged to T2 (Down-not Achieved), and 23 patients were T3 not receiving down-staging treatments (No-Down). The average treatment effect (ATE) of LT for T3 tumors was estimated using the outcome of 535 T3 patients undergoing non-LT therapies, using inverse probability weighting regression adjustment. The 24-month drop-out rate during waiting time was significantly higher in the down-staging groups: 27.6{\%} vs. 9.2{\%}, p < 0.005. After LT, the tumor recurrence rate was significantly different: MC 7.6{\%}, Down-Achieved 20.9{\%}, Down-not Achieved 31.6{\%}, and No-Down 30.4{\%} (p < 0.001). The survival rates at 5 years were: 63{\%} in Down-Achieved, 62{\%} in Down-not Achieved, 63{\%} in No-Down, and 77{\%} in MC (p = n.s.). The only variable related to a better outcome was the effective down-staging to T2 at the histological evaluation of the explanted liver: recurrence rate = 7.8{\%} vs. 26{\%} (p < 0.001) and 5-year patient survival = 76{\%} vs. 67{\%} (p < 0.05). The ATE estimation showed that the mean survival of T3-LT candidates was significantly better than that of T3 patients ineligible for LT [83.3 vs 39.2 months (+44.6 months); p < 0.001]. Long term outcome of T3 down-staged candidates was poorer than that of MC candidates, particularly for cases not achieving down-staging. However, their survival outcome was significantly better than that achieved with non-transplant therapies.",
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AU - Ravaioli, Matteo

AU - Odaldi, Federica

AU - Cucchetti, Alessandro

AU - Trevisani, Franco

AU - Piscaglia, Fabio

AU - De Pace, Vanessa

AU - Bertuzzo, Valentina Rosa

AU - Neri, Flavia

AU - Golfieri, Rita

AU - Cappelli, Alberta

AU - D’Errico, Antonietta

AU - Cescon, Matteo

AU - Del Gaudio, Massimo

AU - Fallani, Guido

AU - Siniscalchi, Antonio

AU - Morelli, Maria Cristina

AU - Ciccarese, Francesca

AU - Di Marco, Maria

AU - Farinati, Fabio

AU - Giannini, Edoardo Giovanni

AU - Pinna, Antonio Daniele

PY - 2019/12/1

Y1 - 2019/12/1

N2 - The objective of the study is to evaluate 10 years of down-staging strategy for liver transplantation (LT) with a median follow-up of 5 years. Data on long-term results are poor and less information is available for hepatocellular carcinoma (HCC) non-responder patients or those ineligible for down-staging. The outcome of 308 HCC candidates and the long-term results of 231 LTs for HCC performed between 2003 and 2013 were analyzed. HCCs were divided according to tumor stage and response to therapy: 145 patients were T2 (metering Milan Criteria, MC), 43 were T3 successfully down-staged to T2 (Down-Achieved), 20 were T3 not fully down-staged to T2 (Down-not Achieved), and 23 patients were T3 not receiving down-staging treatments (No-Down). The average treatment effect (ATE) of LT for T3 tumors was estimated using the outcome of 535 T3 patients undergoing non-LT therapies, using inverse probability weighting regression adjustment. The 24-month drop-out rate during waiting time was significantly higher in the down-staging groups: 27.6% vs. 9.2%, p < 0.005. After LT, the tumor recurrence rate was significantly different: MC 7.6%, Down-Achieved 20.9%, Down-not Achieved 31.6%, and No-Down 30.4% (p < 0.001). The survival rates at 5 years were: 63% in Down-Achieved, 62% in Down-not Achieved, 63% in No-Down, and 77% in MC (p = n.s.). The only variable related to a better outcome was the effective down-staging to T2 at the histological evaluation of the explanted liver: recurrence rate = 7.8% vs. 26% (p < 0.001) and 5-year patient survival = 76% vs. 67% (p < 0.05). The ATE estimation showed that the mean survival of T3-LT candidates was significantly better than that of T3 patients ineligible for LT [83.3 vs 39.2 months (+44.6 months); p < 0.001]. Long term outcome of T3 down-staged candidates was poorer than that of MC candidates, particularly for cases not achieving down-staging. However, their survival outcome was significantly better than that achieved with non-transplant therapies.

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