Retrospective Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 14, 2020; 26(6): 657-669
Published online Feb 14, 2020. doi: 10.3748/wjg.v26.i6.657
Validation and evaluation of clinical prediction systems for first and repeated transarterial chemoembolization in unresectable hepatocellular carcinoma: A Chinese multicenter retrospective study
Zhe-Xuan Wang, En-Xin Wang, Wei Bai, Dong-Dong Xia, Wei Mu, Jing Li, Qiao-Yi Yang, Ming Huang, Guo-Hui Xu, Jun-Hui Sun, Hai-Liang Li, Hui Zhao, Jian-Bing Wu, Shu-Fa Yang, Jia-Ping Li, Zi-Xiang Li, Chun-Qing Zhang, Xiao-Li Zhu, Yan-Bo Zheng, Qiu-He Wang, Jing Li, Jie Yuan, Xiao-Mei Li, Jing Niu, Zhan-Xin Yin, Jie-Lai Xia, Dai-Ming Fan, Guo-Hong Han, on behalf of China HCC-TACE Study Group
Zhe-Xuan Wang, En-Xin Wang, Wei Bai, Dong-Dong Xia, Jing Li, Qiao-Yi Yang, Qiu-He Wang, Jing Li, Jie Yuan, Xiao-Mei Li, Jing Niu, Zhan-Xin Yin, Dai-Ming Fan, Guo-Hong Han, Department of Liver Disease and Digestive Interventional Radiology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an 710032, Shaanxi Province, China
Wei Mu, Department of Radiology, the Southwest Hospital, Third Military Medical University, Chongqing 400037, China
Jing Li, Jing Li, Department of Hepatobiliary Surgery, the Second Affiliated Hospital of Third Military Medical University, Chongqing 400037, China
Ming Huang, Department of Minimally Invasive International Therapy, the Third Affiliated Hospital of Kunming University, Tumor Hospital of Yunnan Province, Kunming 650000, Yunnan Province, China
Guo-Hui Xu, Department of Interventional Radiology, Tumor Hospital of Sichuan Province, Chengdu 610000, Sichuan Province, China
Jun-Hui Sun, Department of Hepatobiliary and Pancreatic Interventional Cancer, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China
Hai-Liang Li, Department of Interventional Radiology, Henan Cancer Hospital, the Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou 450008, Henan Province, China
Hui Zhao, Department of Interventional Radiology, the Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China
Jian-Bing Wu, Department of Oncology, the Second Affiliated Hospital of Nanchang University, Nanchang 330000, Jiangxi Province, China
Shu-Fa Yang, Department of Interventional Radiology, the Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi 830001, Xinjiang Uygur Autonomous Region, China
Jia-Ping Li, Department of Interventional Radiology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, Guangdong Province, China
Zi-Xiang Li, Department of Interventional Medical Center, the Affiliated Hospital of Qingdao University, Qingdao 266000, Shandong Province, China
Chun-Qing Zhang, Department of Gastroenterology and Hepatology, Shandong Province Hospital affiliated to Shandong University, Jinan 250021, Shandong Province, China
Xiao-Li Zhu, Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China
Yan-Bo Zheng, Department of Interventional Radiology, Yantai Yuhuangding Hospital, Yantai 264000, Shandong Province, China
Jie-Lai Xia, Department of Health Statistics, Fourth Military Medical University, Xi’an, Xi’an 710032, Shaanxi Province, China
Author contributions: Wang ZX and Wang EX contributed equally to this work; Wang ZX, Wang EX and Han GH designed the research; Wang ZX, Wang EX, Xia DD and Bai W performed the research and collected data; Wang ZX, Wang EX analyzed the data; Xia DD and Xia JL contributed to statistical support; Wang ZX, Wang EX, Xia DD, Bai W, Mu W, Li J, Yang QY, Huang M, Xu GH, Sun JH, Li HL, Zhao H, Wu JB, Yang SF, Li JP, Li ZX, Zhang CQ, Zhu XL, Zheng YB, Wang QH, Li J, Yuan J, Li XM, Niu J, Yin ZX, Xia JL, Fan DM and Han GH contributed to administrative, technical, or material support; Wang ZX, Wang EX and Han GH wrote the paper.
Institutional review board statement: The study protocol was reviewed and approved by the institutional Ethics Committees of the First Affiliated Hospital of the Fourth Military Medical University.
Informed consent statement: Patients were not required to give informed consent for this study because the analysis used anonymous clinical data that were obtained after each patient agreed to treatment by written consent.
Conflict-of-interest statement: The authors have no conflict of interest to disclose.
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 NonCommercial (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: Guo-Hong Han, MD, PhD, Professor, Department of Liver Disease and Digestive Interventional Radiology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 15 West Changle Road, Xi’an 710032, Shaanxi Province, China. hangh@fmmu.edu.cn
Received: November 19, 2019
Peer-review started: November 19, 2019
First decision: December 7, 2019
Revised: January 8, 2020
Accepted: January 15, 2020
Article in press: January 15, 2020
Published online: February 14, 2020
Processing time: 87 Days and 2.7 Hours
Abstract
BACKGROUND

The treatment outcome of transarterial chemoembolization (TACE) in unresectable hepatocellular carcinoma (HCC) varies greatly due to the clinical heterogeneity of the patients. Therefore, several prognostic systems have been proposed for risk stratification and candidate identification for first TACE and repeated TACE (re-TACE).

AIM

To investigate the correlations between prognostic systems and radiological response, compare the predictive abilities, and integrate them in sequence for outcome prediction.

METHODS

This nationwide multicenter retrospective cohort consisted of 1107 unresectable HCC patients in 15 Chinese tertiary hospitals from January 2010 to May 2016. The Hepatoma Arterial-embolization Prognostic (HAP) score system and its modified versions (mHAP, mHAP2 and mHAP3), as well as the six-and-twelve criteria were compared in terms of their correlations with radiological response and overall survival (OS) prediction for first TACE. The same analyses were conducted in 912 patients receiving re-TACE to evaluate the ART (assessment for re-treatment with TACE) and ABCR (alpha-fetoprotein, Barcelona Clinic Liver Cancer, Child-Pugh and Response) systems for post re-TACE survival (PRTS).

RESULTS

All the prognostic systems were correlated with radiological response achieved by first TACE, and the six-and-twelve criteria exhibited the highest correlation (Spearman R = 0.39, P = 0.026) and consistency (Kappa = 0.14, P = 0.019), with optimal performance by area under the receiver operating characteristic curve of 0.71 [95% confidence interval (CI): 0.68-0.74]. With regard to the prediction of OS, the mHAP3 system identified patients with a favorable outcome with the highest concordance (C)-index of 0.60 (95%CI: 0.57-0.62) and the best area under the receiver operating characteristic curve at any time point during follow-up; whereas, PRTS was well-predicted by the ABCR system with a C-index of 0.61 (95%CI: 0.59-0.63), rather than ART. Finally, combining the mHAP3 and ABCR systems identified candidates suitable for TACE with an improved median PRTS of 36.6 mo, compared with non-candidates with a median PRTS of 20.0 mo (log-rank test P < 0.001).

CONCLUSION

Radiological response to TACE is closely associated with tumor burden, but superior prognostic prediction could be achieved with the combination of mHAP3 and ABCR in patients with unresectable liver-confined HCC.

Keywords: Transarterial chemoembolization; Hepatocellular carcinoma; Prognostic system; Radiological response; Overall survival; Predictive ability

Core tip: There are several prognostic systems for the prediction of treatment outcome following transarterial chemoembolization for hepatocellular carcinoma; however, their discriminatory abilities in real-world patients need to be validated and compared to select the optimal system for clinical decision-making. We found that the six-and-twelve criteria were closely correlated with radiological response, modified Hepatoma Arterial-embolization Prognostic version 3 predicted overall survival best, and ABCR (alpha-fetoprotein, Barcelona Clinic Liver Cancer, Child-Pugh and Response) was a reliable predictive system for post repeated transarterial chemoembolization survival. The sequential combination of these systems performed well in outcome prediction.