Retrospective Cohort Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 28, 2017; 23(20): 3690-3701
Published online May 28, 2017. doi: 10.3748/wjg.v23.i20.3690
Radiological response and inflammation scores predict tumour recurrence in patients treated with transarterial chemoembolization before liver transplantation
Daniele Nicolini, Andrea Agostini, Roberto Montalti, Federico Mocchegiani, Cinzia Mincarelli, Alessandra Mandolesi, Nicola L Robertson, Roberto Candelari, Andrea Giovagnoni, Marco Vivarelli
Daniele Nicolini, Roberto Montalti, Federico Mocchegiani, Marco Vivarelli, Division of Hepatobiliary and Transplant Surgery, Department of Experimental and Clinical Medicine, Polytechnic University of Marche, 60126 Ancona, Italy
Andrea Agostini, Andrea Giovagnoni, Division of General and Pediatric Radiology, Department of Radiological Sciences, Polytechnic University of Marche, 60126 Ancona, Italy
Cinzia Mincarelli, Roberto Candelari, Division of Interventional Radiology, Department of Radiological Sciences, Polytechnic University of Marche, 60126 Ancona, Italy
Alessandra Mandolesi, Division of Pathology, Department of Pathology, Polytechnic University of Marche, 60126 Ancona, Italy
Nicola L Robertson, Division of Radiology, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, United States
Author contributions: Nicolini D and Agostini A designed the research; Nicolini D collected and analysed the data, and drafted the manuscript; Agostini A evaluated the radiological response after the TACE procedures; Montalti R interpreted the data and revised the statistical analysis; Mincarelli C and Candelari R performed the TACE procedures and collected the radiological data; Mandolesi A revised the histological specimens; Mocchegiani F and Robertson NL revised the article; Robertson NL also performed the language editing of the manuscript; Giovagnoni A and Vivarelli M revised the manuscript for important intellectual content; all authors have read and approved the final version to be published.
Institutional review board statement: The study was reviewed and approved by the Ethics Committee of Marche Region.
Informed consent statement: All patients provided informed written consent prior to the TACE procedures and transplant waiting list inclusion.
Conflict-of-interest statement: None of the listed authors has conflicts of interest to declare.
Data sharing statement: The dataset is available from the corresponding author at nicolini_daniele@yahoo.it.
Open-Access: This article is an open-access article which 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/
Correspondence to: Daniele Nicolini, MD, PhD, Division of Hepatobiliary and Transplant Surgery, Department of Experimental and Clinical Medicine, Polytechnic University of Marche, via Tronto n°10/a, 60126 Ancona, Italy. daniele.nicolini@ospedaliriuniti.marche.it
Telephone: +39-71-5965051 Fax: +39-71-5965100
Received: January 18, 2017
Peer-review started: January 19, 2017
First decision: February 9, 2017
Revised: March 7, 2017
Accepted: May 4, 2017
Article in press: May 4, 2017
Published online: May 28, 2017
Processing time: 128 Days and 23.2 Hours
Abstract
AIM

To investigate the prognostic value of the radiological response after transarterial chemoembolization (TACE) and inflammatory markers in patients affected by hepatocellular carcinoma (HCC) awaiting liver transplantation (LT).

METHODS

We retrospectively evaluated the preoperative predictors of HCC recurrence in 70 patients treated with conventional (n = 16) or doxorubicin-eluting bead TACE (n = 54) before LT. The patient and tumour characteristics, including the static and dynamic alpha-fetoprotein, neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio (PLR) measurements, were recorded. Treatment response was classified according to the modified Response Evaluation Criteria in Solid Tumours (mRECIST) and the European Association for the Study of the Liver (EASL) criteria as complete response (CR), partial response (PR), stable disease or progressive disease. After examination of the explanted livers, histological necrosis was classified as complete (100% of the cumulative tumour area), partial (50%-99%) or minimal (< 50%) and was correlated with the preoperative radiological findings.

RESULTS

According to the pre-TACE radiological evaluation, 22/70 (31.4%) and 12/70 (17.1%) patients were beyond Milan and University of San Francisco (UCSF) criteria, respectively. After TACE procedures, the objective response (CR + PR) rates were 71.4% and 70.0% according to mRECIST and EASL criteria, respectively. The agreement between the two guidelines in defining the radiological response was rated as very good both for the overall and target lesion response (weighted k-value: 0.98 and 0.93, respectively). Complete and partial histological necrosis were achieved in 14/70 (20.0%) and 28/70 (40.0%) patients, respectively. Using histopathology as the reference standard, mRECIST criteria correctly classified necrosis in 72.9% (51/70) of patients and EASL criteria in 68.6% (48/70) of cases. The mRECIST non-response to TACE [Exp(b) = 9.2, p = 0.012], exceeding UCSF criteria before TACE [Exp(b) = 4.7, p = 0.033] and a preoperative PLR > 150 [Exp(b) = 5.9, p = 0.046] were independent predictors of tumour recurrence.

CONCLUSION

The radiological response and inflammatory markers are predictive of tumour recurrence and allow the proper selection of TACE-treated candidates for LT.

Keywords: Liver transplantation; Recurrence-free survival; Hepatocellular carcinoma; Radiological response; Locoregional therapies; Inflammatory markers; Selection criteria

Core tip: The response to loco-regional therapy and biological markers appear to stratify the prognosis of hepatocellular carcinoma patients awaiting liver transplantation (LT) better than morphological criteria; however, their role in the selection scheme still needs validation. We analysed a homogeneous cohort of 70 patients treated exclusively by transarterial chemoembolization (TACE) prior to LT; the radiological response was assessed by two different enhancing methods (mRECIST and EASL criteria) that provided an accurate preoperative estimation of histological necrosis. We also demonstrated that a lack of response to TACE and a high platelet-to-lymphocyte ratio before surgery are strongly predictive of tumour recurrence, independently of the Milan criteria status at referral.