Prospective Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Oct 7, 2019; 25(37): 5687-5701
Published online Oct 7, 2019. doi: 10.3748/wjg.v25.i37.5687
Long-term outcomes of hepatocellular carcinoma that underwent chemoembolization for bridging or downstaging
Breno Boueri Affonso, Francisco Leonardo Galastri, Joaquim Mauricio da Motta Leal Filho, Felipe Nasser, Priscila Mina Falsarella, Rafael Noronha Cavalcante, Marcio Dias de Almeida, Guilherme Eduardo Gonçalves Felga, Leonardo Guedes Moreira Valle, Nelson Wolosker
Breno Boueri Affonso, Francisco Leonardo Galastri, Joaquim Mauricio da Motta Leal Filho, Felipe Nasser, Priscila Mina Falsarella, Rafael Noronha Cavalcante, Leonardo Guedes Moreira Valle, Department of Interventional Radiology, Hospital Israelita Albert Einstein, São Paulo 05651-901, São Paulo, Brazil
Marcio Dias de Almeida, Guilherme Eduardo Gonçalves Felga, Department of Liver Transplant, Hospital Israelita Albert Einstein, São Paulo 05651-901, São Paulo, Brazil
Nelson Wolosker, Department of Vascular Surgery, Hospital Israelita Albert Einstein, São Paulo 05651-901, São Paulo, Brazil
Author contributions: da Motta Leal Filho JM and Nasser F designed research/study; Affonso BB, Galastri FL, da Motta Leal Filho JM, Nasser F, Falsarella PM, Cavalcante RN, and Wolosker N performed research/study; Affonso BB, Galastri FL, Falsarella PM, de Almeida MD, Felga GEG, Valle LGM, and Wolosker N contributed important reagents; Affonso BB, Galastri FL, Nasser F, da Motta Leal Filho JM, Falsarella PM, de Almeida MD, and Valle LGM collected data; Affonso BB, Galastri FL, da Motta Leal Filho JM, Cavalcante RN and Falsarella PM analyzed data; Affonso BB and Valle LGM submit a manuscript; da Motta Leal Filho JM and Cavalcante RN wrote the paper.
Institutional review board statement: Process CEP/Einstein nº11/1704.
Informed consent statement: All study participants, or their legal guardian, provided written consent prior to study enrollment.
Conflict-of-interest statement: Breno Affonso has no conflict of interest.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Breno Boueri Affonso, PhD, Medical Assistant, Research Scientist, Staff Physician, Surgeon, Teacher, Interventional Radiologist, Department of Interventional Radiology, Hospital Israelita Albert Einstein, Av. Albert Einstein, 627/701, São Paulo 05651-901, São Paulo, Brazil. breno.affonso@einstein.br
Telephone: +55-11-982625115 Fax: +55-11-21510434
Received: June 1, 2019
Peer-review started: June 3, 2019
First decision: July 21, 2019
Revised: August 30, 2019
Accepted: September 11, 2019
Article in press: September 11, 2019
Published online: October 7, 2019
Processing time: 121 Days and 7.2 Hours
Abstract
BACKGROUND

Prospective study of 200 patients with hepatocellular carcinoma (HCC) that underwent liver transplant (LT) after drug-eluting beads transarterial chemoembolization (DEB-TACE) for downstaging versus bridging. Overall survival and tumor recurrence rates were calculated, eligibility for LT, time on the waiting list and radiological response were compared. After TACE, only patients within Milan Criteria (MC) were transplanted. More patients underwent LT in bridging group. Five-year post-transplant overall survival, recurrence-free survival has no difference between the groups. Complete response was observed more frequently in bridging group. Patients in DS group can achieve post-transplant survival and HCC recurrence-free probability, at five years, just like patients within MC in patients undergoing DEB-TACE.

AIM

To determine long-term outcomes of patients with HCC that underwent LT after DEB-TACE for downstaging vs bridging.

METHODS

Prospective cohort study of 200 patients included from April 2011 through June 2014. Bridging group included patients within MC. Downstaging group (out of MC) was divided in 5 subgroups (G1 to G5). Total tumor diameter was ≤ 8 cm for G1, 2, 3, 4 (n = 42) and was > 8 cm for G5 (n = 22). Downstaging (n = 64) and bridging (n = 136) populations were not significantly different. Overall survival and tumor recurrence rates were calculated by the Kaplan-Meier method. Additionally, eligibility for LT, time on the waiting list until LT and radiological response were compared.

RESULTS

After TACE, only patients within MC were transplanted. More patients underwent LT in bridging group 65.9% (P = 0.001). Downstaging population presented: higher number of nodules 2.81 (P = 0.001); larger total tumor diameter 8.09 (P = 0.001); multifocal HCC 78% (P = 0.001); more post-transplantation recurrence 25% (P = 0.02). Patients with maximal tumor diameter up to 7.05 cm were more likely to receive LT (P = 0.005). Median time on the waiting list was significantly longer in downstaging group 10.6 mo (P = 0.028). Five-year post-transplant overall survival was 73.5% in downstaging and 72.3% bridging groups (P = 0.31), and recurrence-free survival was 62.1% in downstaging and 74.8% bridging groups (P = 0.93). Radiological response: complete response was observed more frequently in bridging group (P = 0.004).

CONCLUSION

Tumors initially exceeding the MC down-staged after DEB-TACE, can achieve post-transplant survival and HCC recurrence-free probability, at five years, just like patients within MC in patients undergoing DEB-TACE.

Keywords: Hepatocellular carcinoma; Down-staging; Liver transplantation; Local regional therapy; Bridging

Core tip: The great finding of this work was that through a homogeneous technique of hepatic chemoembolization with drug eluting beads, it was possible to perform the procedures controlling the drug delivery and end point. In conclusion, as far as the degree of tumor necrosis as well as in relation to survival, there was no difference between the group within the Milan criteria (bridging) and the group outside the criteria (downstaging). Therefore, it is worth investing in the treatment of patients out of the Milan criteria so that they have a survival with the same expectations of the patients in criterion.