R3-AFP score is a new composite tool to refine prediction of hepatocellular carcinoma recurrence after liver transplantation
Background & Aims: Patients with hepatocellular carcinoma (HCC) are selected for liver transplantation (LT) based on pre-LT imaging ± alpha-foetoprotein (AFP) level, but discrepancies between pre-LT tumour assessment and explant are frequent. Our aim was to design an explant-based recurrence...
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2022-05-01
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| Series: | JHEP Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589555922000179 |
| _version_ | 1818023509995028480 |
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| author | Charlotte Costentin Federico Piñero Helena Degroote Andrea Notarpaolo Ilka F. Boin Karim Boudjema Cinzia Baccaro Luis G. Podestá Philippe Bachellier Giuseppe Maria Ettorre Jaime Poniachik Fabrice Muscari Fabrizio Dibenedetto Sergio Hoyos Duque Ephrem Salame Umberto Cillo Sebastian Marciano Claire Vanlemmens Stefano Fagiuoli Patrizia Burra Hans Van Vlierberghe Daniel Cherqui Quirino Lai Marcelo Silva Fernando Rubinstein Christophe Duvoux Karim Boudjema Philippe Bachellier Filomena Conti Olivier Scatton Fabrice Muscari Ephrem Salame Pierre Henri Bernard Claire Francoz Francois Durand Sébastien Dharancy Marie-lorraine Woehl Claire Vanlemmens Alexis Laurent Sylvie Radenne Jérôme Dumortier Armand Abergel Daniel Cherqui Louise Barbier Pauline Houssel-Debry Georges Philippe Pageaux Laurence Chiche Victor Deledinghen Jean Hardwigsen J. Gugenheim M. Altieri Marie Noelle Hilleret Thomas Decaens Christophe Duvoux Federico Piñero Aline Chagas Paulo Costa Elaine Cristina de Ataide Emilio Quiñones Sergio Hoyos Duque Sebastián Marciano Margarita Anders Adriana Varón Alina Zerega Jaime Poniachik Alejandro Soza Martín Padilla Machaca Diego Arufe Josemaría Menéndez Rodrigo Zapata Mario Vilatoba Linda Muñoz Ricardo Chong Menéndez Martín Maraschio Luis G. Podestá Lucas McCormack Juan Mattera Adrian Gadano Ilka S.F. Fatima Boin Jose Huygens Parente García Flair Carrilho Marcelo Silva Andrea Notarpaolo Giulia Magini Lucia Miglioresi Martina Gambato Fabrizio Di Benedetto Cecilia D’Ambrosio Giuseppe Maria Ettorre Alessandro Vitale Patrizia Burra Stefano Fagiuoli Umberto Cillo Michele Colledan Domenico Pinelli Paolo Magistri Giovanni Vennarecci Marco Colasanti Valerio Giannelli Adriano Pellicelli Cizia Baccaro Quirino Lai Helena Degroote Hans Van Vlierberghe Callebout Eduard Iesari Samuele Dekervel Jeroen Schreiber Jonas Pirenne Jacques Verslype Chris Ysebaert Dirk Michielsen Peter Lucidi Valerio Moreno Christophe Detry Olivier Delwaide Jean Troisi Roberto Lerut Jan Paul |
| author_facet | Charlotte Costentin Federico Piñero Helena Degroote Andrea Notarpaolo Ilka F. Boin Karim Boudjema Cinzia Baccaro Luis G. Podestá Philippe Bachellier Giuseppe Maria Ettorre Jaime Poniachik Fabrice Muscari Fabrizio Dibenedetto Sergio Hoyos Duque Ephrem Salame Umberto Cillo Sebastian Marciano Claire Vanlemmens Stefano Fagiuoli Patrizia Burra Hans Van Vlierberghe Daniel Cherqui Quirino Lai Marcelo Silva Fernando Rubinstein Christophe Duvoux Karim Boudjema Philippe Bachellier Filomena Conti Olivier Scatton Fabrice Muscari Ephrem Salame Pierre Henri Bernard Claire Francoz Francois Durand Sébastien Dharancy Marie-lorraine Woehl Claire Vanlemmens Alexis Laurent Sylvie Radenne Jérôme Dumortier Armand Abergel Daniel Cherqui Louise Barbier Pauline Houssel-Debry Georges Philippe Pageaux Laurence Chiche Victor Deledinghen Jean Hardwigsen J. Gugenheim M. Altieri Marie Noelle Hilleret Thomas Decaens Christophe Duvoux Federico Piñero Aline Chagas Paulo Costa Elaine Cristina de Ataide Emilio Quiñones Sergio Hoyos Duque Sebastián Marciano Margarita Anders Adriana Varón Alina Zerega Jaime Poniachik Alejandro Soza Martín Padilla Machaca Diego Arufe Josemaría Menéndez Rodrigo Zapata Mario Vilatoba Linda Muñoz Ricardo Chong Menéndez Martín Maraschio Luis G. Podestá Lucas McCormack Juan Mattera Adrian Gadano Ilka S.F. Fatima Boin Jose Huygens Parente García Flair Carrilho Marcelo Silva Andrea Notarpaolo Giulia Magini Lucia Miglioresi Martina Gambato Fabrizio Di Benedetto Cecilia D’Ambrosio Giuseppe Maria Ettorre Alessandro Vitale Patrizia Burra Stefano Fagiuoli Umberto Cillo Michele Colledan Domenico Pinelli Paolo Magistri Giovanni Vennarecci Marco Colasanti Valerio Giannelli Adriano Pellicelli Cizia Baccaro Quirino Lai Helena Degroote Hans Van Vlierberghe Callebout Eduard Iesari Samuele Dekervel Jeroen Schreiber Jonas Pirenne Jacques Verslype Chris Ysebaert Dirk Michielsen Peter Lucidi Valerio Moreno Christophe Detry Olivier Delwaide Jean Troisi Roberto Lerut Jan Paul |
| author_sort | Charlotte Costentin |
| collection | DOAJ |
| description | Background & Aims: Patients with hepatocellular carcinoma (HCC) are selected for liver transplantation (LT) based on pre-LT imaging ± alpha-foetoprotein (AFP) level, but discrepancies between pre-LT tumour assessment and explant are frequent. Our aim was to design an explant-based recurrence risk reassessment score to refine prediction of recurrence after LT and provide a framework to guide post-LT management. Methods: Adult patients who underwent transplantation between 2000 and 2018 for HCC in 47 centres were included. A prediction model for recurrence was developed using competing-risk regression analysis in a European training cohort (TC; n = 1,359) and tested in a Latin American validation cohort (VC; n=1,085). Results: In the TC, 76.4% of patients with HCC met the Milan criteria, and 89.9% had an AFP score of ≤2 points. The recurrence risk reassessment (R3)-AFP model was designed based on variables independently associated with recurrence in the TC (with associated weights): ≥4 nodules (sub-distribution of hazard ratio [SHR] = 1.88, 1 point), size of largest nodule (3–6 cm: SHR = 1.83, 1 point; >6 cm: SHR = 5.82, 5 points), presence of microvascular invasion (MVI; SHR = 2.69, 2 points), nuclear grade >II (SHR = 1.20, 1 point), and last pre-LT AFP value (101–1,000 ng/ml: SHR = 1.57, 1 point; >1,000 ng/ml: SHR = 2.83, 2 points). Wolber’s c-index was 0.76 (95% CI 0.72–0.80), significantly superior to an R3 model without AFP (0.75; 95% CI 0.72–0.79; p = 0.01). Four 5-year recurrence risk categories were identified: very low (score = 0; 5.5%), low (1–2 points; 15.1%), high (3–6 points; 39.1%), and very high (>6 points; 73.9%). The R3-AFP score performed well in the VC (Wolber’s c-index of 0.78; 95% CI 0.73–0.83). Conclusions: The R3 score including the last pre-LT AFP value (R3-AFP score) provides a user-friendly, standardised framework to design post-LT surveillance strategies, protocols, or adjuvant therapy trials for HCC not limited to the Milan criteria. Clinical Trials Registration: NCT03775863. Lay summary: Considering discrepancies between pre-LT tumour assessment and explant are frequent, reassessing the risk of recurrence after LT is critical to further refine the management of patients with HCC. In a large and international cohort of patients who underwent transplantation for HCC, we designed and validated the R3-AFP model based on variables independently associated with recurrence post-LT (number of nodules, size of largest nodule, presence of MVI, nuclear grade, and last pre-LT AFP value). The R3-AFP model including last available pre-LT AFP value outperformed the original R3 model only based on explant features. The final R3-AFP scoring system provides a robust framework to design post-LT surveillance strategies, protocols, or adjuvant therapy trials, irrespective of criteria used to select patients with HCC for LT. |
| first_indexed | 2024-12-10T03:45:28Z |
| format | Article |
| id | doaj.art-29c9d741bd394d8280fcb30803332d94 |
| institution | Directory Open Access Journal |
| issn | 2589-5559 |
| language | English |
| last_indexed | 2024-12-10T03:45:28Z |
| publishDate | 2022-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | JHEP Reports |
| spelling | doaj.art-29c9d741bd394d8280fcb30803332d942022-12-22T02:03:26ZengElsevierJHEP Reports2589-55592022-05-0145100445R3-AFP score is a new composite tool to refine prediction of hepatocellular carcinoma recurrence after liver transplantationCharlotte Costentin0Federico Piñero1Helena Degroote2Andrea Notarpaolo3Ilka F. Boin4Karim Boudjema5Cinzia Baccaro6Luis G. Podestá7Philippe Bachellier8Giuseppe Maria Ettorre9Jaime Poniachik10Fabrice Muscari11Fabrizio Dibenedetto12Sergio Hoyos Duque13Ephrem Salame14Umberto Cillo15Sebastian Marciano16Claire Vanlemmens17Stefano Fagiuoli18Patrizia Burra19Hans Van Vlierberghe20Daniel Cherqui21Quirino Lai22Marcelo Silva23Fernando Rubinstein24Christophe Duvoux25Karim BoudjemaPhilippe BachellierFilomena ContiOlivier ScattonFabrice MuscariEphrem SalamePierre Henri BernardClaire FrancozFrancois DurandSébastien DharancyMarie-lorraine WoehlClaire VanlemmensAlexis LaurentSylvie RadenneJérôme DumortierArmand AbergelDaniel CherquiLouise BarbierPauline Houssel-DebryGeorges Philippe PageauxLaurence ChicheVictor DeledinghenJean HardwigsenJ. GugenheimM. AltieriMarie Noelle HilleretThomas DecaensChristophe DuvouxFederico PiñeroAline ChagasPaulo CostaElaine Cristina de AtaideEmilio QuiñonesSergio Hoyos DuqueSebastián MarcianoMargarita AndersAdriana VarónAlina ZeregaJaime PoniachikAlejandro SozaMartín Padilla MachacaDiego ArufeJosemaría MenéndezRodrigo ZapataMario VilatobaLinda MuñozRicardo Chong MenéndezMartín MaraschioLuis G. PodestáLucas McCormackJuan MatteraAdrian GadanoIlka S.F. Fatima BoinJose Huygens Parente GarcíaFlair CarrilhoMarcelo SilvaAndrea NotarpaoloGiulia MaginiLucia MiglioresiMartina GambatoFabrizio Di BenedettoCecilia D’AmbrosioGiuseppe Maria EttorreAlessandro VitalePatrizia BurraStefano FagiuoliUmberto CilloMichele ColledanDomenico PinelliPaolo MagistriGiovanni VennarecciMarco ColasantiValerio GiannelliAdriano PellicelliCizia BaccaroQuirino LaiHelena DegrooteHans Van VlierbergheCallebout EduardIesari SamueleDekervel JeroenSchreiber JonasPirenne JacquesVerslype ChrisYsebaert DirkMichielsen PeterLucidi ValerioMoreno ChristopheDetry OlivierDelwaide JeanTroisi RobertoLerut Jan PaulGrenoble Alpes University, Institute for Advanced Biosciences, Research Center UGA/Inserm U 1209/CNRS 5309, Grenoble, France; Gastroenterology, Hepatology and GI Oncology Department, Digidune, Grenoble Alpes University Hospital, La Tronche, France; Corresponding author. Address: Gastroenterology, Hepatology and Transplant Unit, CHU Grenoble-Alpes, Avenue Maquis du Grésivaudan, 38700 La Tronche, France. Tel.: +33-4-76-76-75-75; Fax: +33-4-76-76-51-79.Hospital Universitario Austral, School of Medicine, Austral University, Buenos Aires, Argentina; Latin American Liver Research Educational and Awareness Network (LALREAN), Buenos Aires, ArgentinaDepartment of Hepatology and Gastroenterology, Ghent University Hospital, Ghent, BelgiumArcispedale Santa Maria Nuova, Reggio Emilia, ItalyHospital das Clinicas UNICAMP, Campiñas, BrazilDepartment of Hepatobiliary and Digestive Surgery, Pontchaillou Hospital Rennes 1 University, Rennes, FranceLanciano’s Hospital, Chieti, Rome, ItalyHospital Universitario Austral, School of Medicine, Austral University, Buenos Aires, Argentina; Latin American Liver Research Educational and Awareness Network (LALREAN), Buenos Aires, ArgentinaDigestive Surgery Unit, CHU de Strasbourg, Strasbourg, FranceOspedale San Camillo di Roma, Rome, ItalyHospital Clínico de la Universidad de Chile, Santiago, ChileDigestive Surgery and Transplant Unit, Hôpital Rangueil, Toulouse, FranceHepato-Pancreato-Biliary Surgery and Liver Transplantation Unit, Department of General Surgery, University of Modena and Reggio Emilia, Modena, ItalyHospital Pablo Tobón Uribe y Grupo de Gastrohepatología de la Universidad de Antioquía, Medellín, ColombiaDigestive Surgery Unit, CHU de Tours, Tours, FranceHepatobiliary Surgery and Liver Transplant Unit, Padova University Hospital, Padua, ItalyHospital Italiano de Buenos Aires, Buenos Aires, ArgentinaHepatology Unit, Hôpital Jean Minjoz, Besançon, FranceGastroenterology, Hepatology and Transplantation, Papa Giovanni XXIII Hospital, Bergamo, ItalyMultivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padova University Hospital, Padua, ItalyDepartment of Hepatology and Gastroenterology, Ghent University Hospital, Ghent, BelgiumHospital Paul Brousse, University of Paris, Paris, FranceGeneral Surgery and Organ Transplantation Unit, Sapienza University of Rome, Rome, ItalyHospital Universitario Austral, School of Medicine, Austral University, Buenos Aires, Argentina; Latin American Liver Research Educational and Awareness Network (LALREAN), Buenos Aires, ArgentinaInstituto de Efectividad Clínica y Sanitaria (IECS), Buenos Aires, ArgentinaHospital Henri Mondor, University of Paris-Est, Creteil, FranceBackground & Aims: Patients with hepatocellular carcinoma (HCC) are selected for liver transplantation (LT) based on pre-LT imaging ± alpha-foetoprotein (AFP) level, but discrepancies between pre-LT tumour assessment and explant are frequent. Our aim was to design an explant-based recurrence risk reassessment score to refine prediction of recurrence after LT and provide a framework to guide post-LT management. Methods: Adult patients who underwent transplantation between 2000 and 2018 for HCC in 47 centres were included. A prediction model for recurrence was developed using competing-risk regression analysis in a European training cohort (TC; n = 1,359) and tested in a Latin American validation cohort (VC; n=1,085). Results: In the TC, 76.4% of patients with HCC met the Milan criteria, and 89.9% had an AFP score of ≤2 points. The recurrence risk reassessment (R3)-AFP model was designed based on variables independently associated with recurrence in the TC (with associated weights): ≥4 nodules (sub-distribution of hazard ratio [SHR] = 1.88, 1 point), size of largest nodule (3–6 cm: SHR = 1.83, 1 point; >6 cm: SHR = 5.82, 5 points), presence of microvascular invasion (MVI; SHR = 2.69, 2 points), nuclear grade >II (SHR = 1.20, 1 point), and last pre-LT AFP value (101–1,000 ng/ml: SHR = 1.57, 1 point; >1,000 ng/ml: SHR = 2.83, 2 points). Wolber’s c-index was 0.76 (95% CI 0.72–0.80), significantly superior to an R3 model without AFP (0.75; 95% CI 0.72–0.79; p = 0.01). Four 5-year recurrence risk categories were identified: very low (score = 0; 5.5%), low (1–2 points; 15.1%), high (3–6 points; 39.1%), and very high (>6 points; 73.9%). The R3-AFP score performed well in the VC (Wolber’s c-index of 0.78; 95% CI 0.73–0.83). Conclusions: The R3 score including the last pre-LT AFP value (R3-AFP score) provides a user-friendly, standardised framework to design post-LT surveillance strategies, protocols, or adjuvant therapy trials for HCC not limited to the Milan criteria. Clinical Trials Registration: NCT03775863. Lay summary: Considering discrepancies between pre-LT tumour assessment and explant are frequent, reassessing the risk of recurrence after LT is critical to further refine the management of patients with HCC. In a large and international cohort of patients who underwent transplantation for HCC, we designed and validated the R3-AFP model based on variables independently associated with recurrence post-LT (number of nodules, size of largest nodule, presence of MVI, nuclear grade, and last pre-LT AFP value). The R3-AFP model including last available pre-LT AFP value outperformed the original R3 model only based on explant features. The final R3-AFP scoring system provides a robust framework to design post-LT surveillance strategies, protocols, or adjuvant therapy trials, irrespective of criteria used to select patients with HCC for LT.http://www.sciencedirect.com/science/article/pii/S2589555922000179Liver transplantationLiver cancerRecurrenceExplants pathologyPrediction |
| spellingShingle | Charlotte Costentin Federico Piñero Helena Degroote Andrea Notarpaolo Ilka F. Boin Karim Boudjema Cinzia Baccaro Luis G. Podestá Philippe Bachellier Giuseppe Maria Ettorre Jaime Poniachik Fabrice Muscari Fabrizio Dibenedetto Sergio Hoyos Duque Ephrem Salame Umberto Cillo Sebastian Marciano Claire Vanlemmens Stefano Fagiuoli Patrizia Burra Hans Van Vlierberghe Daniel Cherqui Quirino Lai Marcelo Silva Fernando Rubinstein Christophe Duvoux Karim Boudjema Philippe Bachellier Filomena Conti Olivier Scatton Fabrice Muscari Ephrem Salame Pierre Henri Bernard Claire Francoz Francois Durand Sébastien Dharancy Marie-lorraine Woehl Claire Vanlemmens Alexis Laurent Sylvie Radenne Jérôme Dumortier Armand Abergel Daniel Cherqui Louise Barbier Pauline Houssel-Debry Georges Philippe Pageaux Laurence Chiche Victor Deledinghen Jean Hardwigsen J. Gugenheim M. Altieri Marie Noelle Hilleret Thomas Decaens Christophe Duvoux Federico Piñero Aline Chagas Paulo Costa Elaine Cristina de Ataide Emilio Quiñones Sergio Hoyos Duque Sebastián Marciano Margarita Anders Adriana Varón Alina Zerega Jaime Poniachik Alejandro Soza Martín Padilla Machaca Diego Arufe Josemaría Menéndez Rodrigo Zapata Mario Vilatoba Linda Muñoz Ricardo Chong Menéndez Martín Maraschio Luis G. Podestá Lucas McCormack Juan Mattera Adrian Gadano Ilka S.F. Fatima Boin Jose Huygens Parente García Flair Carrilho Marcelo Silva Andrea Notarpaolo Giulia Magini Lucia Miglioresi Martina Gambato Fabrizio Di Benedetto Cecilia D’Ambrosio Giuseppe Maria Ettorre Alessandro Vitale Patrizia Burra Stefano Fagiuoli Umberto Cillo Michele Colledan Domenico Pinelli Paolo Magistri Giovanni Vennarecci Marco Colasanti Valerio Giannelli Adriano Pellicelli Cizia Baccaro Quirino Lai Helena Degroote Hans Van Vlierberghe Callebout Eduard Iesari Samuele Dekervel Jeroen Schreiber Jonas Pirenne Jacques Verslype Chris Ysebaert Dirk Michielsen Peter Lucidi Valerio Moreno Christophe Detry Olivier Delwaide Jean Troisi Roberto Lerut Jan Paul R3-AFP score is a new composite tool to refine prediction of hepatocellular carcinoma recurrence after liver transplantation JHEP Reports Liver transplantation Liver cancer Recurrence Explants pathology Prediction |
| title | R3-AFP score is a new composite tool to refine prediction of hepatocellular carcinoma recurrence after liver transplantation |
| title_full | R3-AFP score is a new composite tool to refine prediction of hepatocellular carcinoma recurrence after liver transplantation |
| title_fullStr | R3-AFP score is a new composite tool to refine prediction of hepatocellular carcinoma recurrence after liver transplantation |
| title_full_unstemmed | R3-AFP score is a new composite tool to refine prediction of hepatocellular carcinoma recurrence after liver transplantation |
| title_short | R3-AFP score is a new composite tool to refine prediction of hepatocellular carcinoma recurrence after liver transplantation |
| title_sort | r3 afp score is a new composite tool to refine prediction of hepatocellular carcinoma recurrence after liver transplantation |
| topic | Liver transplantation Liver cancer Recurrence Explants pathology Prediction |
| url | http://www.sciencedirect.com/science/article/pii/S2589555922000179 |
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