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.

R3-AFP score is a new composite tool to refine prediction of hepatocellular carcinoma recurrence after liver transplantation / Costentin, C.; Pinero, F.; Degroote, H.; Notarpaolo, A.; Boin, I. F.; Boudjema, K.; Baccaro, C.; Podesta, L. G.; Bachellier, P.; Ettorre, G. M.; Poniachik, J.; Muscari, F.; Dibenedetto, F.; Duque, S. H.; 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.; Conti, F.; Scatton, O.; Bernard, P. H.; Francoz, C.; Durand, F.; Dharancy, S.; Woehl, M. -L.; Laurent, A.; Radenne, S.; Dumortier, J.; Abergel, A.; Barbier, L.; Houssel-Debry, P.; Pageaux, G. P.; Chiche, L.; Deledinghen, V.; Hardwigsen, J.; Gugenheim, J.; Altieri, M.; Hilleret, M. N.; Decaens, T.; Chagas, A.; Costa, P.; Cristina de Ataide, E.; Quinones, E.; Marciano, S.; Anders, M.; Varon, A.; Zerega, A.; Soza, A.; Machaca, M. P.; Arufe, D.; Menendez, J.; Zapata, R.; Vilatoba, M.; Munoz, L.; Menendez, R. C.; Maraschio, M.; Mccormack, L.; Mattera, J.; Gadano, A.; Fatima Boin, I. S. F.; Parente Garcia, J. H.; Carrilho, F.; Magini, G.; Miglioresi, L.; Gambato, M.; Di Benedetto, F.; D'Ambrosio, C.; Vitale, A.; Colledan, M.; Pinelli, D.; Magistri, P.; Vennarecci, G.; Colasanti, M.; Giannelli, V.; Pellicelli, A.; Baccaro, C.; 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. J.. - In: JHEP REPORTS. - ISSN 2589-5559. - 4:5(2022), pp. N/A-N/A. [10.1016/j.jhepr.2022.100445]

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

Di Benedetto F.;Magistri P.;
2022-01-01

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.
4
5
N/A
N/A
R3-AFP score is a new composite tool to refine prediction of hepatocellular carcinoma recurrence after liver transplantation / Costentin, C.; Pinero, F.; Degroote, H.; Notarpaolo, A.; Boin, I. F.; Boudjema, K.; Baccaro, C.; Podesta, L. G.; Bachellier, P.; Ettorre, G. M.; Poniachik, J.; Muscari, F.; Dibenedetto, F.; Duque, S. H.; 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.; Conti, F.; Scatton, O.; Bernard, P. H.; Francoz, C.; Durand, F.; Dharancy, S.; Woehl, M. -L.; Laurent, A.; Radenne, S.; Dumortier, J.; Abergel, A.; Barbier, L.; Houssel-Debry, P.; Pageaux, G. P.; Chiche, L.; Deledinghen, V.; Hardwigsen, J.; Gugenheim, J.; Altieri, M.; Hilleret, M. N.; Decaens, T.; Chagas, A.; Costa, P.; Cristina de Ataide, E.; Quinones, E.; Marciano, S.; Anders, M.; Varon, A.; Zerega, A.; Soza, A.; Machaca, M. P.; Arufe, D.; Menendez, J.; Zapata, R.; Vilatoba, M.; Munoz, L.; Menendez, R. C.; Maraschio, M.; Mccormack, L.; Mattera, J.; Gadano, A.; Fatima Boin, I. S. F.; Parente Garcia, J. H.; Carrilho, F.; Magini, G.; Miglioresi, L.; Gambato, M.; Di Benedetto, F.; D'Ambrosio, C.; Vitale, A.; Colledan, M.; Pinelli, D.; Magistri, P.; Vennarecci, G.; Colasanti, M.; Giannelli, V.; Pellicelli, A.; Baccaro, C.; 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. J.. - In: JHEP REPORTS. - ISSN 2589-5559. - 4:5(2022), pp. N/A-N/A. [10.1016/j.jhepr.2022.100445]
Costentin, C.; Pinero, F.; Degroote, H.; Notarpaolo, A.; Boin, I. F.; Boudjema, K.; Baccaro, C.; Podesta, L. G.; Bachellier, P.; Ettorre, G. M.; Poniachik, J.; Muscari, F.; Dibenedetto, F.; Duque, S. H.; 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.; Conti, F.; Scatton, O.; Bernard, P. H.; Francoz, C.; Durand, F.; Dharancy, S.; Woehl, M. -L.; Laurent, A.; Radenne, S.; Dumortier, J.; Abergel, A.; Barbier, L.; Houssel-Debry, P.; Pageaux, G. P.; Chiche, L.; Deledinghen, V.; Hardwigsen, J.; Gugenheim, J.; Altieri, M.; Hilleret, M. N.; Decaens, T.; Chagas, A.; Costa, P.; Cristina de Ataide, E.; Quinones, E.; Marciano, S.; Anders, M.; Varon, A.; Zerega, A.; Soza, A.; Machaca, M. P.; Arufe, D.; Menendez, J.; Zapata, R.; Vilatoba, M.; Munoz, L.; Menendez, R. C.; Maraschio, M.; Mccormack, L.; Mattera, J.; Gadano, A.; Fatima Boin, I. S. F.; Parente Garcia, J. H.; Carrilho, F.; Magini, G.; Miglioresi, L.; Gambato, M.; Di Benedetto, F.; D'Ambrosio, C.; Vitale, A.; Colledan, M.; Pinelli, D.; Magistri, P.; Vennarecci, G.; Colasanti, M.; Giannelli, V.; Pellicelli, A.; Baccaro, C.; 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. J.
File in questo prodotto:
File Dimensione Formato  
1-s2.0-S2589555922000179-main.pdf

Open access

Tipologia: Versione pubblicata dall'editore
Dimensione 784.98 kB
Formato Adobe PDF
784.98 kB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

Licenza Creative Commons
I metadati presenti in IRIS UNIMORE sono rilasciati con licenza Creative Commons CC0 1.0 Universal, mentre i file delle pubblicazioni sono rilasciati con licenza Attribuzione 4.0 Internazionale (CC BY 4.0), salvo diversa indicazione.
In caso di violazione di copyright, contattare Supporto Iris

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/1286472
Citazioni
  • ???jsp.display-item.citation.pmc??? 1
  • Scopus 1
  • ???jsp.display-item.citation.isi??? ND
social impact