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.

Costentin, C., Piñero, F., Degroote, H., Notarpaolo, A., Boin, I., Boudjema, K., et al. (2022). R3-AFP score is a new composite tool to refine prediction of hepatocellular carcinoma recurrence after liver transplantation. JHEP REPORTS, 4(5) [10.1016/j.jhepr.2022.100445].

R3-AFP score is a new composite tool to refine prediction of hepatocellular carcinoma recurrence after liver transplantation

Fagiuoli, Stefano;Colledan, Michele;
2022

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: 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.
Articolo in rivista - Articolo scientifico
Explants pathology; Liver cancer; Liver transplantation; Prediction; Recurrence;
English
Costentin, C., Piñero, F., Degroote, H., Notarpaolo, A., Boin, I., Boudjema, K., et al. (2022). R3-AFP score is a new composite tool to refine prediction of hepatocellular carcinoma recurrence after liver transplantation. JHEP REPORTS, 4(5) [10.1016/j.jhepr.2022.100445].
Costentin, C; Piñero, F; Degroote, H; Notarpaolo, A; Boin, I; Boudjema, K; Baccaro, C; Podestá, L; Bachellier, P; Ettorre, G; Poniachik, J; Muscari, F; Dibenedetto, F; Hoyos Duque, S; Salame, E; Cillo, U; Marciano, S; Vanlemmens, C; Fagiuoli, S; Burra, P; Van Vlierberghe, H; Cherqui, D; Lai, Q; Silva, M; Rubinstein, F; Duvoux, C; Boudjema, K; Bachellier, P; Conti, F; Scatton, O; Muscari, F; Salame, E; Bernard, P; Francoz, C; Durand, F; Dharancy, S; Woehl, M; Vanlemmens, C; Laurent, A; Radenne, S; Dumortier, J; Abergel, A; Cherqui, D; Barbier, L; Houssel-Debry, P; Pageaux, G; Chiche, L; Deledinghen, V; Hardwigsen, J; Gugenheim, J; Altieri, M; Hilleret, M; Decaens, T; Duvoux, C; Piñero, F; Chagas, A; Costa, P; Cristina de Ataide, E; Quiñones, E; Duque, S; Marciano, S; Anders, M; Varón, A; Zerega, A; Poniachik, J; Soza, A; Machaca, M; Arufe, D; Menéndez, J; Zapata, R; Vilatoba, M; Muñoz, L; Menéndez, R; Maraschio, M; Podestá, L; Mccormack, L; Mattera, J; Gadano, A; Fatima Boin, I; Parente García, J; Carrilho, F; Silva, M; Notarpaolo, A; Magini, G; Miglioresi, L; Gambato, M; Benedetto, F; D’Ambrosio, C; Ettorre, G; Vitale, A; Burra, P; Fagiuoli, S; Cillo, U; Colledan, M; Pinelli, D; Magistri, P; Vennarecci, G; Colasanti, M; Giannelli, V; Pellicelli, A; Baccaro, C; Lai, Q; Degroote, H; Vlierberghe, H; Eduard, C; Samuele, I; Jeroen, D; Jonas, S; Jacques, P; Chris, V; Dirk, Y; Peter, M; Valerio, L; Christophe, M; Olivier, D; Jean, D; Roberto, T; Paul, L
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/354380
Citazioni
  • Scopus 1
  • ???jsp.display-item.citation.isi??? 1
Social impact