R3-AFP score is a new composite tool to refine prediction of hepatocellular carcinoma recurrence after liver transplantation
Charlotte Costentin, Federico Piñero, Helena Degroote, Andrea Notarpaolo, Ilka de Fátima Santana Ferreira Boin, Karim Boudjéma, Cinzia Baccaro, Luis G. Podestá, Philippe Bachellier, Giuseppe Maria Ettorre, Jaime Poníachik, Fabrice Muscari, Fabrizio Di Benedetto, Sergio Hoyos Duque, Ephrem Salamé, Umberto Cillo, Sebastián Marciano, Claire Vanlemmens, S. Fagiuoli, Patrizia Burra, Hans Van Vlierberghe, Daniel Cherqui, Quirino Lai, Marcelo Silva, Fernando Rubinstein, Christophe Duvoux, Karim Boudjéma, Philippe Bachellier, Filoména Conti, Olivier Scatton, Fabrice Muscari, Ephrem Salamé, Pierre Bernard, Claire Francoz, François 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, L. Chiche, V DELEDINGHEN, Jean Hardwigsen, J. Gugenheim, Mario Altieri, Marie Noelle Hilleret, Thomas Decaens, Christophe Duvoux, Federico Piñero, Aline Lopes Chagas, Paulo Everton Garcia Costa, Elaine Cristina de Ataíde, Emilio Quiñones, Sergio Hoyos Duque, Sebastián Marciano, Margarita Anders, Adriana Varón, Alina Zerega, Jaime Poníachik, Alejandro Soza, Martín Padilla, Diego Arufe, Josemaría Menéndez, Rodrigo Zapata, Mario Vilatobá, Linda E. Muñoz‐Espinosa, Ricardo Chong Menéndez, Martín Maraschio, Luis G. Podestá, Lucas McCormack, Juan Mattera, Adrián Gadano, Ilka S.F. Fatima Boin, Jose Huygens Parente García, Flair José Carrilho, Marcelo Silva, Andrea Notarpaolo, Giulia Magini, L. Miglioresi, Martina Gambato, Fabrizio Di Benedetto, C. D’Ambrosio, Giuseppe Maria Ettorre, Alessandro Vitale, Patrizia Burra, S. Fagiuoli, Umberto Cillo, M. Colledan, D. Pinelli, Paolo Magistri, Giovanni Vennarecci, Marco Colasanti, V. Giannelli, Adriano Pellicelli
Abstract
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: = 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.