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Survival benefit of second line therapies for recurrent hepatocellular carcinoma: repeated hepatectomy, thermoablation and second-line transplant referral in a real life national scenario |
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HPB (Oxford). 2023 Oct;25(10):1223-1234. doi: 10.1016/j.hpb.2023.06.004. Epub 2023 Jun 12.
Simone Famularo 1, Umberto Cillo 2, Andrea Lauterio 3, Matteo Donadon 4, Alessandro Vitale 2, Matteo Serenari 5, Federica Cipriani 6, Federico Fazio 7, Mario Giuffrida 8, Francesco Ardito 9, Tommaso Dominioni 10, Mattia Garancini 11, Quirino Lai 12, Daniele Nicolini 13, Sarah Molfino 14, Pasquale Perri 15, Enrico Pinotti 16, Simone Conci 17, Cecilia Ferrari 18, Matteo Zanello 19, Stefan Patauner 20, Giuseppe Zimmitti 21, Paola Germani 22, Marco Chiarelli 23, Maurizio Romano 24, Michela De Angelis 25, Giuliano La Barba 26, Albert Troci 27, Valentina Ferraro 28, Francesco Izzo 29, Adelmo Antonucci 30, Andrea Belli 29, Riccardo Memeo 28, Michele Crespi 27, Giorgio Ercolani 26, Luigi Boccia 25, Giacomo Zanus 24, Paola Tarchi 22, Moh'd Abu Hilal 21, Antonio Frena 20, Elio Jovine 19, Guido Griseri 18, Andrea Ruzzenente 17, Mauro Zago 31, Gianluca Grazi 15, Gian L Baiocchi 14, Marco Vivarelli 13, Massimo Rossi 12, Fabrizio Romano 11, Marcello Maestri 10, Felice Giuliante 9, Raffaele D Valle 8, Alessandro Ferrero 7, Luca Aldrighetti 6, Luciano De Carlis 3, Matteo Cescon 5, Guido Torzilli 32; HE.RC.O.LE.S. Group Contributors
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Author information
Collaborators
- HE.RC.O.LE.S. Group Contributors:
Flavio Milana 4, Alessandra Bertacco 2, Riccardo De Carlis 33, Francesca Ratti 6, Nadia Russolillo 7, Maurizio Iaria 8, Francesco Razionale 9, Giuseppe Tartaglia 10, Cristina Ciulli 11, Francesca Carissimi 11, Zoe L Laureiro 12, Laura Marinelli 13, Valerio DePeppo 15, Mauro Montuori 16, Ivan Marchitelli 17, Angelo Franceschi 18, Francesca Notte 20, Alberto Manzoni 21, Davide Cosola 22, Pio Corleone 22, Luca Fumagalli 23, Luca Salvador 34, Guido Mantovani 25, Alessandro Cucchetti 26, Francesco Cammarata 27, Maria Conticchio 28, Renato Patrone 29, Davide P Bernasconi 35
Affiliations
- 1Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy; Department of Hepatobiliary and General Surgery, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy; Surgical Data Science Team, Research Institute Against Digestive Cancer (IRCAD), Strasbourg, France. Electronic address: simone.famularo@gmail.com.
- 2Department of Surgical, Oncological and Gastroenterological Sciences (DiSCOG), University of Padova, Second General Surgical Unit, Padova Teaching Hospital, Padua, Italy.
- 3Department of General and Transplant Surgery, Grande Ospedale Metropolitano Niguarda, School of Medicine and Surgery, University of Milan-Bicocca, Milan, Italy.
- 4Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy; Department of Hepatobiliary and General Surgery, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy.
- 5Hepato-biliary Surgery and Transplant Unit, Policlinico Sant'Orsola IRCCS, Department of Medical and Surgical Sciences, University of Bologna, Italy.
- 6Hepatobiliary Surgery Division, "Vita e Salute" University, Ospedale San Raffaele IRCCS, Milano, Italy.
- 7Department of General and Oncological Surgery, Mauriziano Hospital "Umberto I", Turin, Italy.
- 8Department of Medicine and Surgery, University of Parma, Parma, Italy.
- 9Hepatobiliary Surgery Unit, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Catholic University of the Sacred Heart, Rome, Italy.
- 10Unit of General Surgery 1, University of Pavia and Foundation IRCCS Policlinico San Matteo, Pavia, Italy.
- 11School of Medicine and Surgery, University of Milano-Bicocca, San Gerardo Hospital, Monza, Italy.
- 12General Surgery and Organ Transplantation Unit, Sapienza University of Rome, Umberto I Polyclinic of Rome, Rome, Italy.
- 13HPB Surgery and Transplantation Unit, Department of Clinical and Experimental Medicine, Polytechnic University of Marche, Ancona, Italy.
- 14Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.
- 15Division of Hepatobiliarypancreatic Unit, IRCCS - Regina Elena National Cancer Institute, Rome, Italy.
- 16Department of Surgery, Ponte San Pietro Hospital, Bergamo, Italy.
- 17Division of General and Hepatobiliary Surgery, Department of Surgical Sciences, Dentistry, Gynecology and Pediatrics, University of Verona, Verona, Italy.
- 18HPB Surgical Unit, San Paolo Hospital, Savona, Italy.
- 19Alma Mater Studiorum, University of Bologna, AOU Sant'Orsola Malpighi, IRCCS at Maggiore Hospital, Bologna, Italy.
- 20Department of General and Pediatric Surgery, Bolzano Central Hospital, Bolzano, Italy.
- 21Department of General Surgery, Poliambulanza Foundation Hospital, Brescia, Italy.
- 22Division of General Surgery, Department of Medical and Surgical Sciences, ASUGI, Trieste, Italy.
- 23Department of Emergency and Robotic Surgery, ASST Lecco, Lecco, Italy.
- 24Department of Surgical, Oncological and Gastroenterological Science (DISCOG), University of Padua, Hepatobiliary and Pancreatic Surgery Unit - Treviso Hospital, Italy.
- 25Department of General Surgery, Ospedale Carlo Poma, Mantua, Italy.
- 26General and Oncologic Surgery, Morgagni-Pierantoni Hospital, Department of Medical and Surgical Sciences - University of Bologna Forlì, Italy.
- 27Department of Surgery, L. Sacco Hospital, Milan, Italy.
- 28Department of Hepato-Pancreatic-Biliary Surgery, Miulli Hospital, Bari, Italy.
- 29Division of Epatobiliary Surgical Oncology, Istituto Nazionale Tumori IRCCS Fondazione Pascale-IRCCS di Napoli, Naples, Italy.
- 30Department of Surgery, Monza Policlinic, Monza, Italy.
- 31Department of Surgery, Ponte San Pietro Hospital, Bergamo, Italy; Department of Emergency and Robotic Surgery, ASST Lecco, Lecco, Italy.
- 32Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy; Department of Hepatobiliary and General Surgery, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy. Electronic address: guido.torzilli@hunimed.eu.
- 33Department of General and Transplant Surgery, Grande Ospedale Metropolitano Niguarda School of Medicine and Surgery, University of Milan-Bicocca, Milan, Italy; Clinical and Experimental Sciences, University of Padua, Padua, Italy.
- 34Department of Surgical, Oncological and Gastroenterological Science (DISCOG), University of Padua Hepatobiliary and Pancreatic Surgery Unit - Treviso Hospital, Italy.
- 35Bicocca Bioinformatics Biostatistics and Bioimaging Centre - B4, School of Medicine and Surgery, University of Milan - Bicocca, Monza, Italy.
Abstract
Background: Despite second-line transplant(SLT) for recurrent hepatocellular carcinoma(rHCC) leads to the longest survival after recurrence(SAR), its real applicability has never been reported. The aim was to compare the SAR of SLT versus repeated hepatectomy and thermoablation(CUR group).
Methods: Patients were enrolled from the Italian register HE.RC.O.LE.S. between 2008 and 2021. Two groups were created: CUR versus SLT. A propensity score matching (PSM) was run to balance the groups.
Results: 743 patients were enrolled, CUR = 611 and SLT = 132. Median age at recurrence was 71(IQR 6575) years old and 60(IQR 53-64, p < 0.001) for CUR and SLT respectively. After PSM, median SAR for CUR was 43 months(95%CI = 37 - 93) and not reached for SLT(p < 0.001). SLT patients gained a survival benefit of 9.4 months if compared with CUR. MilanCriteria(MC)-In patients were 82.7% of the CUR group. SLT(HR 0.386, 95%CI = 0.23 - 0.63, p < 0.001) and the MELD score(HR 1.169, 95%CI = 1.07 - 1.27, p < 0.001) were the only predictors of mortality. In case of MC-Out, the only predictor of mortality was the number of nodules at recurrence(HR 1.45, 95%CI= 1.09 - 1.93, p = 0.011).
Conclusion: It emerged an important transplant under referral in favour of repeated hepatectomy or thermoablation. In patients with MC-Out relapse, the benefit of SLT over CUR was not observed.
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