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Sangro B, Argemi J, Ronot M, Paradis V, Meyer T, Mazzaferro V, Jepsen P, Golfieri R, Galle P, Dawson L, Reig M. EASL Clinical Practice Guidelines on the management of hepatocellular carcinoma. J Hepatol 2025; 82:315-374. [PMID: 39690085 DOI: 10.1016/j.jhep.2024.08.028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2024] [Accepted: 08/29/2024] [Indexed: 12/19/2024]
Abstract
Liver cancer is the third leading cause of cancer-related deaths worldwide, with hepatocellular carcinoma (HCC) accounting for approximately 90% of primary liver cancers. Advances in diagnostic and therapeutic tools, along with improved understanding of their application, are transforming patient treatment. Integrating these innovations into clinical practice presents challenges and necessitates guidance. These clinical practice guidelines offer updated advice for managing patients with HCC and provide a comprehensive review of pertinent data. Key updates from the 2018 EASL guidelines include personalised surveillance based on individual risk assessment and the use of new tools, standardisation of liver imaging procedures and diagnostic criteria, use of minimally invasive surgery in complex cases together with updates on the integrated role of liver transplantation, transitions between surgical, locoregional, and systemic therapies, the role of radiation therapies, and the use of combination immunotherapies at various stages of disease. Above all, there is an absolute need for a multiparametric assessment of individual risks and benefits, considering the patient's perspective, by a multidisciplinary team encompassing various specialties.
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Xia D, Bai W, Wang Q, Chung JW, Adhoute X, Kloeckner R, Zhang H, Zeng Y, Sripongpun P, Nie C, Kim SU, Huang M, Hu W, Ding X, Yin G, Li H, Zhao H, Bronowicki JP, Li J, Li J, Zhu X, Wu J, Zhang C, Gong W, Li Z, Lin Z, Xu T, Yin T, Anty R, Song J, Shi H, Shao G, Ren W, Zhang Y, Yang S, Zheng Y, Xu J, Wang W, Zhu X, Fu Y, Liu C, Kaewdech A, Ding R, Zheng J, Liu S, Yu H, Zheng L, You N, Fan W, Zhang S, Feng L, Wang G, Zhang P, Li X, Chen J, Zhang F, Shao W, Zhou W, Zeng H, Cao G, Huang W, Jiang W, Zhang W, Li L, Feng A, Wang E, Wang Z, Han D, Lv Y, Sun J, Ren B, Xia L, Li X, Yuan J, Wang Z, Luo B, Li K, Guo W, Yin Z, Zhao Y, Xia J, Fan D, Wu K, Bettinger D, Vogel A, Han G. Tumor burden with AFP improves survival prediction for TACE-treated patients with HCC: An international observational study ☆. JHEP Rep 2025; 7:101216. [PMID: 39758510 PMCID: PMC11699734 DOI: 10.1016/j.jhepr.2024.101216] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/15/2023] [Revised: 08/30/2024] [Accepted: 09/05/2024] [Indexed: 01/04/2025] Open
Abstract
BACKGROUND & AIMS Current prognostic models for patients with hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE) are not extensively validated and widely accepted. We aimed to develop and validate a continuous model incorporating tumor burden and biology for individual survival prediction and risk stratification. METHODS Overall, 4,377 treatment-naive candidates for whom TACE was recommended, from 39 centers in five countries, were enrolled and divided into training, internal validation, and two external validation datasets. The novel model was developed using a Cox multivariable regression analysis and compared with our original 6-and-12 model (the largest tumor size [ts, centimetres] + tumor number [tn]) and other available models in terms of predictive accuracy. RESULTS The proposed model, named the '6-and-12 model 2.0', was generated as 'ts + tn + 1.5×log10 alpha-fetoprotein (AFP)', showed good discrimination (C-index 0.674) and calibration (Hosmer-Lemeshow test p = 0.147), and outperformed current existing models. An easy-to-use stratification was proposed according to the different AFP levels (≤100, 100-400, 400-2,000, 2,000-10,000, 10,000-40,000, and >40,000 ng/ml) along with the corresponding tumor burden cutoffs (8/14, 7/13, 6/12, 5/11, 4/10, and any tumor burden); that is, if the AFP level was 400-2,000 ng/ml, the stratification should be low-(≤6)/intermediate-(6-12)/high-risk (>12) strata. Hence, it could divide the patients into three distinct risk categories with a median overall survival of 45.0 (95% CI, 40.1-49.9), 30.0 (95% CI, 26.1-33.9), and 15.4 (95% CI, 13.4-17.4) months (p <0.001) from low-risk to high-risk strata, respectively. These findings were confirmed in validation and subgroup analyses. CONCLUSIONS The 6-and-12 model 2.0 significantly improved individual outcome predictions and better stratified the candidates recommended for TACE; thus, this model could be used in both clinical practice and trial design. IMPACT AND IMPLICATIONS In this international multicentre study, we developed and internally and externally validated a novel outcome prediction model for candidates with HCC who would be ideal for TACE. The model, called the 6-and-12 model 2.0, was based on 4,377 patients from 39 centers in five countries. The model offers individualized outcome prediction, outperforming the original 6-and-12 model score and other existing metrics across all datasets and subsets. Based on different levels of alpha-fetoprotein (AFP) and corresponding cut-offs of tumor burden, patients could be stratified into three risk strata with significantly different survival prognoses, which could provide a referential framework to control study heterogeneity and define the target population in future trial designs.
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Affiliation(s)
- Dongdong Xia
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, China
- Department of Liver Diseases and Interventional Radiology, National Clinical Research Centre for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, China
- Department of Liver Diseases and Interventional Radiology, Digestive Diseases Hospital, Xi’an International Medical Center Hospital, Northwest University, Xi’an, China
| | - Wei Bai
- Department of Liver Diseases and Interventional Radiology, National Clinical Research Centre for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, China
- Department of Liver Diseases and Interventional Radiology, Digestive Diseases Hospital, Xi’an International Medical Center Hospital, Northwest University, Xi’an, China
| | - Qiuhe Wang
- Department of Liver Diseases and Interventional Radiology, National Clinical Research Centre for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, China
- Department of Cardiology, Tangdu Hospital, Fourth Military Medical University, Xi’an, China
| | - Jin Wook Chung
- Department of Radiology, Seoul National University Hospital, Seoul, Korea
| | - Xavier Adhoute
- Department of Gastroenterology and Hepatology, Hôpital Saint-Joseph, Marseille, France
| | - Roman Kloeckner
- Department of Diagnostic and Interventional Radiology, University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckst, Mainz, Germany
- Department for Interventional Radiology, University Hospital of Lübeck, Ratzeburger Allee 160, Lübeck, Germany
| | - Hui Zhang
- Department of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing, China
| | - Yong Zeng
- Department of Liver Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Pimsiri Sripongpun
- Gastroenterology and Hepatology Unit, Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Songkhla, Thailand
| | - Chunhui Nie
- Department of Hepatobiliary and Pancreatic Interventional Cancer, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Seung Up Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Ming Huang
- Department of Minimally Invasive International Therapy, The Third Affiliated Hospital of Kunming University, Tumor Hospital of Yunnan Province, Kunming, China
| | - Wenhao Hu
- Department of Interventional Radiology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Xiangchun Ding
- Department of Infectious Disease, General Hospital of Ningxia Medical University, Yinchuan, China
| | - Guowen Yin
- Department of Interventional Radiology, Jiangsu Provincial Cancer Hospital, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China
| | - Hailiang Li
- Department of Interventional Radiology, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China
| | - Hui Zhao
- Department of Interventional Radiology, The Affiliated Hospital of Nantong University, Nantong, China
| | - Jean-Pierre Bronowicki
- Department of Gastroenterology and Hepatology, Centre Hospitalo-Universitaire de Nancy, France
| | - Jing Li
- Department of Hepatobiliary Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing, China
| | - Jiaping Li
- Department of Interventional Radiology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Xiaoli Zhu
- Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Jianbing Wu
- Department of Oncology, The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Chunqing Zhang
- Department of Gastroenterology and Hepatology, Shandong Province Hospital Affiliated to Shandong University, Jinan, China
| | - Weidong Gong
- Department of Interventional Radiology, Tangdu Hospital, Fourth Military Medical University, Xi’an, China
| | - Zixiang Li
- Interventional Medical Centre of the Affiliated Hospital of Qingdao University, Qingdao, China
| | - Zhengyu Lin
- Department of Interventional Radiology, the First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Tao Xu
- Department of Infectious Diseases, the 910 Hospital of the Chinese People’s Liberation Army Joint Logistic Support Force, Quanzhou, China
| | - Tao Yin
- Department of Hepatic & Biliary & Pancreatic Surgery, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Rodolphe Anty
- Department of Gastroenterology and Hepatology, Hôpital Universitaire de l’Archet Nice, France
| | - Jinlong Song
- Department of Interventional Therapy, Shandong Tumor Hospital, Jinan, China
| | - Haibin Shi
- Department of Interventional Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Guoliang Shao
- Department of Radiology, Zhejiang Cancer Hospital, Hangzhou, China
| | - Weixin Ren
- Department of Interventional Radiology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
| | - Yongjin Zhang
- Department of Interventional Radiology and Vascular Surgery, Hunan Provincial People’s Hospital, Changsha, China
| | - Shufa Yang
- Department of Interventional Radiology, The Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi, China
| | - Yanbo Zheng
- Department of Interventional Radiology, Yantai Yuhuangding Hospital, Yantai, China
| | - Jian Xu
- Department of Medical Imaging, Nanjing General Hospital of the Nanjing Military Command, Nanjing, China
| | - Wenhui Wang
- Department of Interventional Medicine, The First Affiliated Hospital of Lanzhou University, Lanzhou, China
| | - Xu Zhu
- Department of Interventional Radiology, Peking University Cancer Hospital, Beijing, China
| | - Ying Fu
- Department of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing, China
| | - Chang Liu
- Department of Liver Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Apichat Kaewdech
- Gastroenterology and Hepatology Unit, Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Songkhla, Thailand
| | - Rong Ding
- Department of Minimally Invasive International Therapy, The Third Affiliated Hospital of Kunming University, Tumor Hospital of Yunnan Province, Kunming, China
| | - Jie Zheng
- Department of Interventional Radiology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Shuaiwei Liu
- Department of Infectious Disease, General Hospital of Ningxia Medical University, Yinchuan, China
| | - Hui Yu
- Department of Interventional Radiology, Jiangsu Provincial Cancer Hospital, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China
| | - Lin Zheng
- Department of Interventional Radiology, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China
| | - Nan You
- Department of Hepatobiliary Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing, China
| | - Wenzhe Fan
- Department of Interventional Radiology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Shuai Zhang
- Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Long Feng
- Department of Oncology, The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Guangchuan Wang
- Department of Gastroenterology and Hepatology, Shandong Province Hospital Affiliated to Shandong University, Jinan, China
| | - Peng Zhang
- Department of Interventional Radiology, Tangdu Hospital, Fourth Military Medical University, Xi’an, China
- Department of Digestive Medicine, Xi’an No.3 Hospital, Xi’an, China
| | - Xueda Li
- Interventional Medical Centre of the Affiliated Hospital of Qingdao University, Qingdao, China
| | - Jian Chen
- Department of Interventional Radiology, the First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Feng Zhang
- Department of Hepatic & Biliary & Pancreatic Surgery, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Wenbo Shao
- Department of Interventional Therapy, Shandong Tumor Hospital, Jinan, China
| | - Weizhong Zhou
- Department of Interventional Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Hui Zeng
- Department of Radiology, Zhejiang Cancer Hospital, Hangzhou, China
| | - Gengfei Cao
- Department of Interventional Radiology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
| | - Wukui Huang
- Department of Interventional Radiology, The Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi, China
| | - Wenjin Jiang
- Department of Interventional Radiology, Yantai Yuhuangding Hospital, Yantai, China
| | - Wen Zhang
- Department of Medical Imaging, Nanjing General Hospital of the Nanjing Military Command, Nanjing, China
| | - Lei Li
- Department of Interventional Medicine, The First Affiliated Hospital of Lanzhou University, Lanzhou, China
| | - Aiwei Feng
- Department of Interventional Radiology, Peking University Cancer Hospital, Beijing, China
| | - Enxin Wang
- Department of Liver Diseases and Interventional Radiology, National Clinical Research Centre for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, China
- Department of Medical Affairs, Air Force Hospital of Western Theater Command, Chengdu, China
| | - Zhexuan Wang
- Department of Liver Diseases and Interventional Radiology, National Clinical Research Centre for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, China
| | - Dandan Han
- Department of Liver Diseases and Interventional Radiology, National Clinical Research Centre for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, China
- Department of General Surgery, The Southern Theater Air Force Hospital, Guangzhou, China
| | - Yong Lv
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, China
- Department of Liver Diseases and Interventional Radiology, National Clinical Research Centre for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, China
| | - Jun Sun
- Department of Liver Diseases and Interventional Radiology, National Clinical Research Centre for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, China
| | - Bincheng Ren
- Department of Rheumatology and Immunology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Linying Xia
- Department of Cardiology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China
| | - Xiaomei Li
- Department of Liver Diseases and Interventional Radiology, National Clinical Research Centre for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, China
- Department of Liver Diseases and Interventional Radiology, Digestive Diseases Hospital, Xi’an International Medical Center Hospital, Northwest University, Xi’an, China
| | - Jie Yuan
- Department of Liver Diseases and Interventional Radiology, National Clinical Research Centre for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, China
- Department of Liver Diseases and Interventional Radiology, Digestive Diseases Hospital, Xi’an International Medical Center Hospital, Northwest University, Xi’an, China
| | - Zhengyu Wang
- Department of Liver Diseases and Interventional Radiology, National Clinical Research Centre for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, China
- Department of Liver Diseases and Interventional Radiology, Digestive Diseases Hospital, Xi’an International Medical Center Hospital, Northwest University, Xi’an, China
| | - Bohan Luo
- Department of Liver Diseases and Interventional Radiology, National Clinical Research Centre for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, China
- Department of Liver Diseases and Interventional Radiology, Digestive Diseases Hospital, Xi’an International Medical Center Hospital, Northwest University, Xi’an, China
| | - Kai Li
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, China
- Department of Liver Diseases and Interventional Radiology, National Clinical Research Centre for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, China
| | - Wengang Guo
- Department of Liver Diseases and Interventional Radiology, National Clinical Research Centre for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, China
- Department of Liver Diseases and Interventional Radiology, Digestive Diseases Hospital, Xi’an International Medical Center Hospital, Northwest University, Xi’an, China
| | - Zhanxin Yin
- Department of Liver Diseases and Interventional Radiology, National Clinical Research Centre for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, China
- Department of Liver Diseases and Interventional Radiology, Digestive Diseases Hospital, Xi’an International Medical Center Hospital, Northwest University, Xi’an, China
| | - Yan Zhao
- Department of Liver Diseases and Interventional Radiology, Digestive Diseases Hospital, Xi’an International Medical Center Hospital, Northwest University, Xi’an, China
| | - Jielai Xia
- Department of Health Statistics, Fourth Military Medical University, Xi’an, China
| | - Daiming Fan
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, China
| | - Kaichun Wu
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, China
| | - Dominik Bettinger
- Department of Medicine II, University Medical Center Freiburg, Freiburg, Germany
| | - Arndt Vogel
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
- Division of Gastroenterology and Hepatology, Toronto General Hospital Medical Oncology, Princess Margaret Cancer Centre, Schwartz Reisman Liver Research Centre, Toronto, Canada
| | - Guohong Han
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, China
- Department of Liver Diseases and Interventional Radiology, National Clinical Research Centre for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, China
- Department of Liver Diseases and Interventional Radiology, Digestive Diseases Hospital, Xi’an International Medical Center Hospital, Northwest University, Xi’an, China
| | - China HCC-TACE study group
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, China
- Department of Liver Diseases and Interventional Radiology, National Clinical Research Centre for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, China
- Department of Liver Diseases and Interventional Radiology, Digestive Diseases Hospital, Xi’an International Medical Center Hospital, Northwest University, Xi’an, China
- Department of Cardiology, Tangdu Hospital, Fourth Military Medical University, Xi’an, China
- Department of Radiology, Seoul National University Hospital, Seoul, Korea
- Department of Gastroenterology and Hepatology, Hôpital Saint-Joseph, Marseille, France
- Department of Diagnostic and Interventional Radiology, University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckst, Mainz, Germany
- Department for Interventional Radiology, University Hospital of Lübeck, Ratzeburger Allee 160, Lübeck, Germany
- Department of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing, China
- Department of Liver Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China
- Gastroenterology and Hepatology Unit, Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Songkhla, Thailand
- Department of Hepatobiliary and Pancreatic Interventional Cancer, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Department of Minimally Invasive International Therapy, The Third Affiliated Hospital of Kunming University, Tumor Hospital of Yunnan Province, Kunming, China
- Department of Interventional Radiology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
- Department of Infectious Disease, General Hospital of Ningxia Medical University, Yinchuan, China
- Department of Interventional Radiology, Jiangsu Provincial Cancer Hospital, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China
- Department of Interventional Radiology, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China
- Department of Interventional Radiology, The Affiliated Hospital of Nantong University, Nantong, China
- Department of Gastroenterology and Hepatology, Centre Hospitalo-Universitaire de Nancy, France
- Department of Hepatobiliary Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing, China
- Department of Interventional Radiology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, Suzhou, China
- Department of Oncology, The Second Affiliated Hospital of Nanchang University, Nanchang, China
- Department of Gastroenterology and Hepatology, Shandong Province Hospital Affiliated to Shandong University, Jinan, China
- Department of Interventional Radiology, Tangdu Hospital, Fourth Military Medical University, Xi’an, China
- Interventional Medical Centre of the Affiliated Hospital of Qingdao University, Qingdao, China
- Department of Interventional Radiology, the First Affiliated Hospital of Fujian Medical University, Fuzhou, China
- Department of Infectious Diseases, the 910 Hospital of the Chinese People’s Liberation Army Joint Logistic Support Force, Quanzhou, China
- Department of Hepatic & Biliary & Pancreatic Surgery, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Department of Gastroenterology and Hepatology, Hôpital Universitaire de l’Archet Nice, France
- Department of Interventional Therapy, Shandong Tumor Hospital, Jinan, China
- Department of Interventional Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Department of Radiology, Zhejiang Cancer Hospital, Hangzhou, China
- Department of Interventional Radiology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
- Department of Interventional Radiology and Vascular Surgery, Hunan Provincial People’s Hospital, Changsha, China
- Department of Interventional Radiology, The Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi, China
- Department of Interventional Radiology, Yantai Yuhuangding Hospital, Yantai, China
- Department of Medical Imaging, Nanjing General Hospital of the Nanjing Military Command, Nanjing, China
- Department of Interventional Medicine, The First Affiliated Hospital of Lanzhou University, Lanzhou, China
- Department of Interventional Radiology, Peking University Cancer Hospital, Beijing, China
- Department of Digestive Medicine, Xi’an No.3 Hospital, Xi’an, China
- Department of Medical Affairs, Air Force Hospital of Western Theater Command, Chengdu, China
- Department of General Surgery, The Southern Theater Air Force Hospital, Guangzhou, China
- Department of Rheumatology and Immunology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- Department of Cardiology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China
- Department of Health Statistics, Fourth Military Medical University, Xi’an, China
- Department of Medicine II, University Medical Center Freiburg, Freiburg, Germany
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
- Division of Gastroenterology and Hepatology, Toronto General Hospital Medical Oncology, Princess Margaret Cancer Centre, Schwartz Reisman Liver Research Centre, Toronto, Canada
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Wang X, Fan B, Liu S. Comprehensive treatment focusing on transarterial chemoembolization for postoperative liver metastasis in gastric cancer patients. Am J Transl Res 2024; 16:7330-7342. [PMID: 39822559 PMCID: PMC11733346 DOI: 10.62347/kwbt3893] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2024] [Accepted: 11/11/2024] [Indexed: 01/19/2025]
Abstract
OBJECTIVE To investigate the clinical efficacy of comprehensive treatment focusing on transarterial chemoembolization (TACE) for postoperative liver metastasis in patients with gastric cancer and analyze the factors influencing prognosis. METHODS A retrospective study was conducted on 116 patients who developed liver metastasis after gastric cancer surgery and were admitted to Gansu Provincial Cancer Hospital between January 2018 and February 2020. The observation group, consisting of 62 patients, received TACE with fluorouracil (FU) + irinotecan (CPT-11) + oxaliplatin (OXA) and moderate lipiodol embolization. The control group, consisting of 54 patients, received systemic S-1 and Oxaliplatin regimen (SOX) alone. The clinical efficacy and incidence of adverse reactions were compared between the two groups. Liver function indicators, tumor markers, and immunoglobulin changes were analyzed in both groups. The 2-year survival rate of patients was analyzed using the Kaplan-Meier (K-M) curve. Lasso-Cox regression was used to identify independent prognostic factors affecting the 2-year survival rate. A Nomogram model was constructed to predict outcomes. RESULTS The overall clinical efficacy (P = 0.001) and objective response rate (ORR) (P = 0.001) were significantly lower in the control group compared to the observation group. No significant differences were found in ALT and AST changes between the two groups (P > 0.05). Post-treatment, CEA and CA19-9 levels were significantly lower, and IgG and IgM levels were significantly higher in the observation group (P < 0.001). There was no significant difference in the incidence of adverse reactions (P > 0.05). Lasso-Cox regression identified treatment plan, pathological differentiation, degree of liver metastasis, and pre-treatment CEA as independent prognostic factors for 2-year survival. Based on these, a Nomogram model was constructed. In the training group, the model had AUC values over 0.8 for 1- and 2-year survival rates, and in the validation group, the AUC was 0.765 and 0.687, respectively, indicating good predictive performance. CONCLUSION Compared to the conventional SOX regimen, comprehensive treatment focusing on TACE embolization for postoperative liver metastasis in gastric cancer is more effective and can improve survival rates.
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Affiliation(s)
- Xingdong Wang
- Department of Interventional Therapy, Gansu Provincial Cancer HospitalNo. 2 Xiaoxihu East Street, Qilihe District, Lanzhou 730050, Gansu, China
| | - Bin Fan
- Drug Research Institute, Gansu Province Academic Institute For Medical ResearchNo. 2 Xiaoxihu East Street, Qilihe District, Lanzhou 730050, Gansu, China
| | - Shuwen Liu
- Department of Gastric Tumor Surgery, Gansu Provincial Cancer HospitalNo. 2 Xiaoxihu East Street, Qilihe District, Lanzhou 730050, Gansu, China
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Alhaddad O, Gomaa A, Shamandy ME, Kohla M, Edrees A, Ashour R. Evaluation of different scoring systems for repeating Transarterial Chemoembolization in Egyptian patients with Hepatocellular Carcinoma. ROMANIAN JOURNAL OF INTERNAL MEDICINE = REVUE ROUMAINE DE MEDECINE INTERNE 2024; 62:430-439. [PMID: 39217454 DOI: 10.2478/rjim-2024-0028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/13/2024] [Indexed: 09/04/2024]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) patients undergoing transarterial chemoembolization (TACE) have a diverse range of outcomes due to their high degree of heterogeneity. Therefore, different predictive scoring systems have been created to assist in decision-making regarding retreatment with TACE. We compared the predictive capabilities of different scoring systems, such as ART, ABCR, and SNACOR, for prediction of the outcome of subsequent TACE in HCC patients. METHOD In this retrospective study, the three scoring systems were compared for their capability of predicting the outcome of repeating TACE in 149 HCC patients treated at the National Liver Institute, Egypt, between January 2017 and December 2019. We used the likelihood ratio to select the model with the highest predictive capability for overall survival (OS). RESULTS According to our data, the amount of tumor, the change in Barcelona Clinic Liver Cancer (BCLC) stage following TACE, and the SNACOR score (with a 95% confidence range for HR 1.0305-1.256 and p-value = 0.0106) were the most predictive variables. It was also shown that the ABCR score was a good predictor of survival (90 patients had an ABCR score ≤ 0 with a P- value <0.0001, 56 patients had 0 < ABCR < 4 with a P-value <0.0001, and the ART score was not useful in predicting OS (P-value = 0.18). CONCLUSION The SNACOR score is the most predictive score for OS and would be the most helpful scoring system in decision-making regarding retreatment with TACE.
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Affiliation(s)
- Omkolsoum Alhaddad
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebin El-Kom, 32511, Egypt
| | - Asmaa Gomaa
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebin El-Kom, 32511, Egypt
| | - Merhan El Shamandy
- Department of Hepatology and Gastroenterology, Ahmad Maher Teaching Hospital, Cairo 11511, Egypt
| | - Mohamed Kohla
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebin El-Kom, 32511, Egypt
| | - Ahmed Edrees
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebin El-Kom, 32511, Egypt
| | - Reham Ashour
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebin El-Kom, 32511, Egypt
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Feng J, Bin JL, Liao XW, Wu Y, Tang Y, Lu PZ, Zhu GZ, Cui QR, Dan YY, Yang GH, Li LX, Deng JH, Peng T, Hooi SC, Zhou J, Lu GD. The prognostic role of ACSL4 in postoperative adjuvant TACE-treated HCC: implications for therapeutic response and mechanistic insights. J Exp Clin Cancer Res 2024; 43:306. [PMID: 39563427 PMCID: PMC11575417 DOI: 10.1186/s13046-024-03222-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2024] [Accepted: 11/01/2024] [Indexed: 11/21/2024] Open
Abstract
BACKGROUND The response of hepatocellular carcinoma (HCC) to transarterial chemoembolization (TACE) treatment and its underlying mechanisms remain elusive. This study investigates the role of enzymes involved in fatty acid activation, specifically Acyl-CoA synthetase long chain 4 (ACSL4), in HCC patients treated with postoperative adjuvant TACE (PA-TACE) and in nutrient-deprived HCC cells. METHODS We examined the expression of ACSL4 and its family members in HCC clinical samples and cell lines. The clinical significance of ACSL4, particularly regarding the prognosis of patients treated with PA-TACE, was assessed using two independent HCC cohorts. We further explored the role of ACSL4 in glucose starvation-induced cell death in HCC cells and xenograft mouse models. RESULTS Among the family members, ACSL4 is the most up-regulated enzyme, associated with poor survival in HCC patients, particularly in post-recurrent TACE-treated patients in a Singapore cohort. ACSL4 is essential for HCC cell survival in response to glucose starvation, rather than to hypoxia or to the combination of hypoxia with doxorubicin or cisplatin. ACSL4-mediated arachidonic acid (AA) metabolism supports mitochondrial β-oxidation and energy production. CCAAT/enhancer binding protein α (CEBPA) transcriptionally regulates ACSL4 by binding 3 motifs (-623 to -613, -1197 to -1187 and -1745 to -1735) of ACSL4 upstream promoter region, enhancing its pro-survival effects. Furthermore, canagliflozin (Cana), a clinical-approved drug for type 2 diabetes, mimics glucose starvation and inhibits the growth of ACSL4-low xenograft tumors. Moreover, high ACSL4 or CEBPA expressions correlate with increased recurrence susceptibility after PA-TACE in the China-Guangxi HCC cohort. CONCLUSIONS The CEBPA-ACSL4 pathway is critical in protecting HCC cells from glucose starvation-induced cell death, suggesting that ACSL4 and CEBPA could serve as valuable prognostic indicators and potential therapeutic targets in the context of PA-TACE treatment for HCC.
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Affiliation(s)
- Ji Feng
- School of Public Health, Fudan University, 130 Dong-An Road, Shanghai, 200032, China
- Department of Toxicology, School of Public Health, Guangxi Medical University, Nanning, Guangxi, 530021, China
- Key Laboratory of Basic Research On Regional Diseases (Guangxi Medical University), Education Department of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, 530021, China
| | - Jin-Lian Bin
- Department of Toxicology, School of Public Health, Guangxi Medical University, Nanning, Guangxi, 530021, China
| | - Xi-Wen Liao
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning, Guangxi, 530021, China
| | - Yong Wu
- Department of Toxicology, School of Public Health, Guangxi Medical University, Nanning, Guangxi, 530021, China
| | - Yue Tang
- Department of Toxicology, School of Public Health, Guangxi Medical University, Nanning, Guangxi, 530021, China
| | - Pei-Zhi Lu
- Department of Toxicology, School of Public Health, Guangxi Medical University, Nanning, Guangxi, 530021, China
| | - Guang-Zhi Zhu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning, Guangxi, 530021, China
| | - Qian-Ru Cui
- Department of Physiology, School of Preclinical Medicine, Guangxi Medical University, 22 Shuangyong Road, Nanning, Guangxi, 530021, China
| | - Yock Young Dan
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 119228, Singapore
| | - Guo-Huan Yang
- Department of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
| | - Li-Xin Li
- Department of Hepato-Oncology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
| | - Jing-Huan Deng
- Department of Toxicology, School of Public Health, Guangxi Medical University, Nanning, Guangxi, 530021, China
| | - Tao Peng
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning, Guangxi, 530021, China.
- Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor (Guangxi Medical University), Ministry of Education; Guangxi Key Laboratory of High-Incidence-Tumor Prevention & Treatment, (Guangxi Medical University), Nanning, Guangxi, 530021, China.
| | - Shing Chuan Hooi
- Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, 2 Medical Drive MD9, Singapore, 117593, Singapore.
| | - Jing Zhou
- Department of Physiology, School of Preclinical Medicine, Guangxi Medical University, 22 Shuangyong Road, Nanning, Guangxi, 530021, China.
| | - Guo-Dong Lu
- School of Public Health, Fudan University, 130 Dong-An Road, Shanghai, 200032, China.
- Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor (Guangxi Medical University), Ministry of Education; Guangxi Key Laboratory of High-Incidence-Tumor Prevention & Treatment, (Guangxi Medical University), Nanning, Guangxi, 530021, China.
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Lu SY, Sun HY, Zhou Y, Luo X, Liu S, Zhou WZ, Shi HB, Yang W, Tian W. Prognosis of Patients with Hepatocellular Carcinoma Treated with TACE: A New Score Combining Alpha-Fetoprotein and Des-γ-Carboxy Prothrombin. J Hepatocell Carcinoma 2024; 11:1979-1992. [PMID: 39465043 PMCID: PMC11512524 DOI: 10.2147/jhc.s481393] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2024] [Accepted: 10/15/2024] [Indexed: 10/29/2024] Open
Abstract
Purpose Hepatocellular carcinoma (HCC) represents a significant global health problem, requiring precise prognostic tools for optimal treatment stratification. This study aimed to develop a new risk prediction score, called AD score, based on the serum markers alpha-fetoprotein (AFP) and des-γ-carboxy prothrombin (DCP), to offer an objective and accurate preoperative assessment of HCC in patients undergoing transarterial chemoembolization (TACE). Patients and Methods This was a retrospective study that included 295 HCC patients who were subjected to TACE (training set, n=147; testing set, n=148). Serum AFP and DCP levels were log-transformed to construct the AD score. Multivariate Cox regression analysis on cirrhosis subgroups validated the objectivity of the model. Performance comparison of established models (Child Pugh, BCLC, ALBI, Up-to-seven, Six-and-twelve, Four and seven, HAP score, mHAP-II, FAIL-T score), was assessed through time-dependent receiver operating characteristic (ROC) curves and risk stratification. Results The AD score, incorporating lgAFP and lgDCP, demonstrated superior predictive accuracy than the existing models. Time-dependent ROC curve revealed the consistent superiority of the AD score over a 5-year period. The risk stratification into low, intermediate, and high group based on the AD score showed a significant survival difference in both training and testing set. Conclusion For HCC patients undergoing TACE, the AD score serves as an objective and straightforward prognostic tool, enhancing predictive accuracy and showcasing its clinical utility. It demonstrates potential significance as a crucial addition to preoperative risk assessment for TACE.
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Affiliation(s)
- Shang-Yu Lu
- Department of Interventional Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China
| | - Han-Yao Sun
- Department of Interventional Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China
| | - Yan Zhou
- Department of Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China
| | - Xi Luo
- The First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China
| | - Sheng Liu
- Department of Interventional Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China
| | - Wei-Zhong Zhou
- Department of Interventional Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China
| | - Hai-Bin Shi
- Department of Interventional Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China
| | - Wei Yang
- Department of Interventional Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China
| | - Wei Tian
- Department of Interventional Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China
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Yang C, Yang HC, Luo YG, Li FT, Cong TH, Li YJ, Ye F, Li X. Predicting Survival Using Whole-Liver MRI Radiomics in Patients with Hepatocellular Carcinoma After TACE Refractoriness. Cardiovasc Intervent Radiol 2024; 47:964-977. [PMID: 38750156 DOI: 10.1007/s00270-024-03730-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2023] [Accepted: 04/07/2024] [Indexed: 07/12/2024]
Abstract
PURPOSE To develop a model based on whole-liver radiomics features of pre-treatment enhanced MRI for predicting the prognosis of hepatocellular carcinoma (HCC) patients undergoing continued transarterial chemoembolization (TACE) after TACE-resistance. MATERIALS AND METHODS Data from 111 TACE-resistant HCC patients between January 2014 and March 2018 were retrospectively collected. At a ratio of 7:3, patients were randomly assigned to developing and validation cohorts. The whole-liver were manually segmented, and the radiomics signature was extracted. The tumor and liver radiomics score (TLrad-score) was calculated. Models were trained by machine learning algorithms and their predictive efficacies were compared. RESULTS Tumor stage, tumor burden, body mass index, alpha-fetoprotein, and vascular invasion were revealed as independent risk factors for survival. The model trained by Random Forest algorithms based on tumor burden, whole-liver radiomics signature, and clinical features had the highest predictive efficacy, with c-index values of 0.85 and 0.80 and areas under the ROC curve of 0.96 and 0.83 in the developing cohort and validation cohort, respectively. In the high-rad-score group (TLrad-score > - 0.34), the median overall survival (mOS) was significantly shorter than in the low-rad-score group (17 m vs. 37 m, p < 0.001). A shorter mOS was observed in patients with high tumor burden compared to those with low tumor burden (14 m vs. 29 m, p = 0.007). CONCLUSION The combined radiomics model from whole-liver signatures may effectively predict survival for HCC patients continuing TACE after TACE refractoriness. The TLrad-score and tumor burden are potential prognostic markers for TACE therapy following TACE-resistance.
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Affiliation(s)
- Chao Yang
- Department of Radiology, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, China
| | - Hong-Cai Yang
- Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17 Panjiayuan Nanli, Chaoyang District, Beijing, 100021, China
| | - Yin-Gen Luo
- Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17 Panjiayuan Nanli, Chaoyang District, Beijing, 100021, China
| | - Fu-Tian Li
- Huiying Medical Technology (Beijing) Co., Ltd, Beijing, 100192, China
| | - Tian-Hao Cong
- Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17 Panjiayuan Nanli, Chaoyang District, Beijing, 100021, China
| | - Yu-Jie Li
- Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17 Panjiayuan Nanli, Chaoyang District, Beijing, 100021, China
| | - Feng Ye
- Department of Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
| | - Xiao Li
- Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17 Panjiayuan Nanli, Chaoyang District, Beijing, 100021, China.
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Pan X, Hu E, Zhou Y, Li L, Huang X, Cai Z. The prognostic nutritional index as a predictor of efficacy and early recurrence for adjuvant transarterial chemoembolization in hepatocellular carcinoma. Clin Res Hepatol Gastroenterol 2024; 48:102344. [PMID: 38641249 DOI: 10.1016/j.clinre.2024.102344] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2024] [Revised: 04/06/2024] [Accepted: 04/17/2024] [Indexed: 04/21/2024]
Abstract
BACKGROUND AND AIMS Postoperative adjuvant transcatheter arterial chemoembolization (TACE) can prevent recurrence of hepatocellular carcinoma (HCC) in certain patients. This study aimed to identify the potential beneficiaries of adjuvant TACE. METHODS 477 patients who underwent curative resection for HCC were enrolled in this retrospectively cohort study. The trajectory of the prognostic nutritional index (PNI) during the perioperative period was fitted using a latent-class growth mixed model. The association between adjuvant TACE and recurrence-free survival in each PNI group was assessed using the Kaplan-Meier curve. Furthermore, Cox regression analysis was conducted to identify the risk factors for early recurrence after adjuvant TACE and develop a nomogram model. RESULTS Patients in the PNI group III had a high risk of recurrence and could benefit from adjuvant TACE (P = 0.009). The prognostic prediction model for adjuvant TACE (PAT) incorporated eight variables (PNI, tumor size, tumor number, microvascular invasion, sex, aspartate aminotransferase, gamma-glutamyl transferase, and degree of differentiation). Patients with PAT score >330 and 235-330 had significantly higher recurrence rates than those with PAT score <235 (P < 0.001). CONCLUSION PNI may help guide the selection of adjuvant TACE beneficiaries. PAT demonstrated a high accuracy in predicting the prognosis of patients who underwent postoperative TACE.
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Affiliation(s)
- Xinting Pan
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, China
| | - En Hu
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, China
| | - Yang Zhou
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, China
| | - Ling Li
- Department of Interventional Radiology, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, China
| | - Xinhui Huang
- Department of Interventional Radiology, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, China.
| | - Zhixiong Cai
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, China.
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Lin J, Li J, Kong Y, Yang J, Zhang Y, Zhu G, Yu Z, Xia J. Construction of a prognostic model for hepatocellular carcinoma patients receiving transarterial chemoembolization treatment based on the Tumor Burden Score. BMC Cancer 2024; 24:306. [PMID: 38448905 PMCID: PMC10916036 DOI: 10.1186/s12885-024-12049-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2023] [Accepted: 02/23/2024] [Indexed: 03/08/2024] Open
Abstract
BACKGROUND Patients with hepatocellular carcinoma (HCC) who undergo transarterial chemoembolization (TACE) may have varied outcomes based on their liver function and tumor burden diversity. This study aims to assess the prognostic significance of the tumor burden score (TBS) in these patients and develop a prognostic model for their overall survival. METHODS The study involved a retrospective analysis of 644 newly diagnosed HCC patients undergoing TACE treatment. The individuals were assigned randomly to a training cohort (n = 452) and a validation cohort (n = 192). We utilized a multivariate Cox proportional risk model to identify independent preoperative predictive factors. We then evaluated model performance using the area under the curve (AUC), consistency index (c-index), calibration curve, and decision curve analysis (DCA) methods. RESULTS The multivariate analysis revealed four prognostic factors associated with overall survival: Tumor Burden Score, Tumor Extent, Types of portal vein invasion (PVI), and Child-Pugh score. The total score was calculated based on these factors. The model demonstrated strong discriminative ability with high AUC values and c-index, providing high net clinical benefits for patients. Based on the model's scoring results, patients were categorized into high, medium, and low-risk groups. These results were validated in the validation cohort. CONCLUSIONS The tumor burden score shows promise as a viable alternative prognostic indicator for assessing tumor burden in cases of HCC. The new prognostic model can place patients in one of three groups, which will estimate their individual outcomes. For high-risk patients, it is suggested to consider alternative treatment options or provide the best supportive care, as they may not benefit significantly from TACE treatment.
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Affiliation(s)
- Jiawei Lin
- Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Jie Li
- Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
- Liver Cancer Institute, Zhongshan Hospital of Fudan University, Shanghai, China
| | - Yifan Kong
- Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Junhui Yang
- Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Yunjie Zhang
- Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Guoqing Zhu
- Department of Interventional Radiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Zhijie Yu
- Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Jinglin Xia
- Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
- Liver Cancer Institute, Zhongshan Hospital of Fudan University, Shanghai, China.
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Lee HA, Lee M, Yoo JJ, Chun HS, Park Y, Kim HY, Kim TH, Seo YS, Sinn DH. Identification of patients with favorable prognosis after resection in intermediate-stage-hepatocellular carcinoma. Int J Surg 2024; 110:1008-1018. [PMID: 38016294 PMCID: PMC10871631 DOI: 10.1097/js9.0000000000000941] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2023] [Accepted: 11/11/2023] [Indexed: 11/30/2023]
Abstract
BACKGROUNDS It is unclear which patients benefit from resection in intermediate-stage-hepatocellular carcinoma (HCC). The authors aimed to identify high-risk patients for early recurrence among patients with resectable intermediate-stage HCC. METHODS This multicenter retrospective study included patients who underwent resection or trans-arterial chemoembolization (TACE) for intermediate-stage HCC (2008-2019). Multivariable Cox proportional analysis was performed to identify high-risk patients when treated with resection. A prediction score for 2-year recurrence-free survival (RFS) was developed using the training cohort and validated. The 2-year RFS in each risk group was compared with that in TACE group, after propensity score matching (PSM). RESULTS A total of 1686 patients were included (480 and 1206 patients in the resection and TACE groups). During a median follow-up of 31.4 months, the 2-year RFS was significantly higher in the resection (47.7%) than in the TACE group (19.8%) [adjusted hazard ratio (aHR)=1.471, 95% CI: 1.199-1.803, P <0.001). On multivariate analysis, alpha-fetoprotein ≥5.0 ng/ml (aHR=0.202), ALBI grade ≥2 (aHR=0.709), tumor number ≥3 (aHR=0.404), and maximal tumor size ≥5 cm (aHR=0.323) were significantly associated with the lower risk of 2-year RFS in the resection group. The newly developed Surgery Risk score in BCLC-B (SR-B score) with four significant risk factors showed an area under the curve of 0.801 for the 2-year RFS and was validated. Based on the SR-B score, low-risk patients had a significantly higher 2-year RFS (training: aHR=5.834; validation: aHR=5.675) than high-risk patients (all P <0.001) did. In a PSM cohort, a low-risk resection group had a significantly higher (aHR=3.891); a high-risk resection group had a comparable 2-year RFS to those treated with TACE (aHR=0.816). CONCLUSIONS Resection may be beneficial for resectable intermediate-stage HCC based on the SR-B score.
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Affiliation(s)
- Han Ah Lee
- Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Ewha Womans University Medical Center
- The Korean Liver Cancer Association
| | - Minjong Lee
- Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Ewha Womans University Medical Center
- The Korean Liver Cancer Association
| | - Jeong-Ju Yoo
- Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea
| | - Ho Soo Chun
- Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Ewha Womans University Medical Center
| | - Yewan Park
- Department of Internal Medicine, Kyung Hee University Hospital
| | - Hwi Young Kim
- Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Ewha Womans University Medical Center
| | - Tae Hun Kim
- Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Ewha Womans University Medical Center
| | - Yeon Seok Seo
- Department of Internal Medicine, Korea University College of Medicine, Seoul
| | - Dong Hyun Sinn
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine
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Sun J, Qi C, Liu Y, Gao F, Fu X, Tian Y. Evaluation of Multiple Liver Cancer Scoring Systems. Adv Biol (Weinh) 2024; 8:e2300301. [PMID: 37863815 DOI: 10.1002/adbi.202300301] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2023] [Revised: 09/17/2023] [Indexed: 10/22/2023]
Abstract
Liver cancer is one of the most common malignant tumors in the world, and its incidence and mortality are increasing year by year. The prognosis of liver cancer depends on the stage of liver cancer, the treatment method, the liver function, and individual differences. The prognosis of liver cancer mainly worsens with the progression of the stage. The prediction and staging system of liver cancer prognosis plays a very important role in the outcome of liver cancer prognosis, providing some guidance for clinical practice and bringing benefits for patients. This article reports on the prediction models and staging systems that have been applied in the field of liver cancer in the past 5 years, objectively analyzes the advantages and disadvantages, applicable population of each model and staging system, and searches for other patient and clinical characteristics that need to be considered for successfully establishing a prediction model, aiming to improve the specificity, sensitivity, and accuracy of liver cancer prediction and increase the overall survival rate of liver cancer.
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Affiliation(s)
- Jingchao Sun
- Department of Biliary and Pancreatic Surgery, Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, 030032, China
| | - Chao Qi
- Department of Biliary and Pancreatic Surgery, Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, 030032, China
| | - Ya Liu
- Department of Biliary and Pancreatic Surgery, Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, 030032, China
| | - Fei Gao
- Department of Biliary and Pancreatic Surgery, Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, 030032, China
| | - Xifeng Fu
- Department of Biliary and Pancreatic Surgery, Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, 030032, China
| | - Yanzhang Tian
- Department of Biliary and Pancreatic Surgery, Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, 030032, China
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Asano K, Kageyama K, Yamamoto A, Jogo A, Uchida-Kobayashi S, Sohgawa E, Murai K, Kawada N, Miki Y. Transcatheter Arterial Chemoembolization for Treatment-Naive Hepatocellular Carcinoma Has Different Treatment Effects Depending on Central or Peripheral Tumor Location. Liver Cancer 2023; 12:576-589. [PMID: 38058422 PMCID: PMC10697731 DOI: 10.1159/000530441] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2022] [Accepted: 03/27/2023] [Indexed: 12/08/2023] Open
Abstract
Introduction The purpose of this study was to evaluate the treatment efficacy of transcatheter arterial chemoembolization (TACE) for treatment-naive hepatocellular carcinoma (HCC) according to tumor location and burden. Methods Between 2010 and 2019, consecutive patients who underwent TACE as the first treatment were enrolled. Tumors were classified into two categories based on their location, as central or peripheral tumors. Tumors in the central zone, which is within 1 cm of the main trunk or the first branch of the portal vein, were classified as central tumors, while those located in the peripheral zone were classified as peripheral tumors. Patients were grouped according to the HCC location and up-to-7 criteria. Patients with central tumors were classified into the central arm and those with only peripheral tumors were classified into the peripheral arm. Patients within and beyond the up-to-7 criteria were classified into the up-to-7 in and up-to-7 out-groups, respectively. Local recurrence-free survival (LRFS) and progression-free survival (PFS) were compared per nodule (central tumor vs. peripheral tumor) and per patient (central arm vs. peripheral arm), respectively. The prognostic factors of LRFS and PFS were analyzed by univariate and multivariate analyses. Results A total of 174 treatment-naive patients with 352 HCCs were retrospectively enrolled. Ninety-six patients and 130 lesions were selected by propensity score matching. Median LRFS was longer for peripheral tumors than central tumors (not reached vs. 3.3 months, p < 0.001). Median PFS was 17.1 months (8.3-24.9) in the peripheral arm and up-to-7 in, 7.0 months (3.3-12.7) in the peripheral arm and up-to-7 out, 8.4 months (4.0-12.6) in the central arm and up-to-7 in, and 3.0 months (1.2-4.9) in the central arm and up-to-7 out-groups. The peripheral arm and up-to-7 in-groups had significantly longer PFS than the other three groups (p = 0.013, p = 0.015, p < 0.001, respectively). Multivariate analysis confirmed that the central zone and central arm were associated with high adjusted hazard ratios for tumor recurrence or death (2.87, p < 0.001; 2.89, p < 0.001, respectively). Conclusion Treatment-naive HCCs in the peripheral zone had a longer LRFS and PFS following TACE compared to those in the central zone.
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Affiliation(s)
- Kazuo Asano
- Department of Diagnostic and Interventional Radiology, Graduate School of Medicine, Osaka City University, Osaka, Japan
| | - Ken Kageyama
- Department of Diagnostic and Interventional Radiology, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan
| | - Akira Yamamoto
- Department of Diagnostic and Interventional Radiology, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan
| | - Atsushi Jogo
- Department of Diagnostic and Interventional Radiology, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan
| | - Sawako Uchida-Kobayashi
- Department of Premier Preventive Medicine, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan
| | - Etsuji Sohgawa
- Department of Diagnostic and Interventional Radiology, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan
| | - Kazuki Murai
- Department of Diagnostic and Interventional Radiology, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan
| | - Norifumi Kawada
- Department of Hepatology, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan
| | - Yukio Miki
- Department of Diagnostic and Interventional Radiology, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan
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Jia KF, Wang H, Yu CL, Yin WL, Zhang XD, Wang F, Sun C, Shen W. ASARA, a prediction model based on Child-Pugh class in hepatocellular carcinoma patients undergoing transarterial chemoembolization. Hepatobiliary Pancreat Dis Int 2023; 22:490-497. [PMID: 35260337 DOI: 10.1016/j.hbpd.2022.02.007] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/26/2021] [Accepted: 02/21/2022] [Indexed: 02/05/2023]
Abstract
BACKGROUND Due to the high heterogeneity among hepatocellular carcinoma (HCC) patients receiving transarterial chemoembolization (TACE), the prognosis of patients varies significantly. The decision-making on the initiation and/or repetition of TACE under different liver functions is a matter of concern in clinical practice. Thus, we aimed to develop a prediction model for TACE candidates using risk stratification based on varied liver function. METHODS A total of 222 unresectable HCC patients who underwent TACE as their only treatment were included in this study. Cox proportional hazards regression was performed to select the independent risk factors and establish a predictive model for the overall survival (OS). The model was validated in patients with different Child-Pugh class and compared to previous TACE scoring systems. RESULTS The five independent risk factors, including alpha-fetoprotein (AFP) level, maximal tumor size, the increase of albumin-bilirubin (ALBI) grade score, tumor response, and the increase of aspartate aminotransferase (AST), were used to build a prognostic model (ASARA). In the training and validation cohorts, the OS of patients with ASARA score ≤ 2 was significantly higher than that of patients with ASARA score > 2 (P < 0.001, P = 0.006, respectively). The ASARA model and its modified version "AS(ARA)" can effectively distinguish the OS (P < 0.001, P = 0.004) between patients with Child-Pugh class A and B, and the C-index was 0.687 and 0.706, respectively. For repeated TACE, the ASARA model was superior to Assessment for Retreatment with TACE (ART) and ALBI grade, maximal tumor size, AFP, and tumor response (ASAR) among Child-Pugh class A patients. For the first TACE, the performance of AS(ARA) was better than that of modified hepatoma arterial-embolization prognostic (mHAP), mHAP3, and ASA(R) models among Child-Pugh class B patients. CONCLUSIONS The ASARA scoring system is valuable in the decision-making of TACE repetition for HCC patients, especially Child-Pugh class A patients. The modified AS(ARA) can be used to screen the ideal candidate for TACE initiation in Child-Pugh class B patients with poor liver function.
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Affiliation(s)
- Ke-Feng Jia
- Department of Radiology, First Central Clinical College, Tianjin Medical University, Tianjin 300192, China; Department of Radiology, Tianjin Third Central Hospital, Tianjin 300170, China
| | - Hao Wang
- Department of Radiology, First Central Clinical College, Tianjin Medical University, Tianjin 300192, China; Department of Radiology, Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin 300192, China
| | - Chang-Lu Yu
- Department of Radiology, Tianjin Third Central Hospital, Tianjin 300170, China
| | - Wei-Li Yin
- Department of Gastroenterology and Hepatology, Tianjin Third Central Hospital, Tianjin 300170, China
| | - Xiao-Dong Zhang
- Department of Radiology, Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin 300192, China
| | - Fang Wang
- Department of Gastroenterology and Hepatology, Tianjin Third Central Hospital, Tianjin 300170, China
| | - Cheng Sun
- Department of Radiology, Tianjin Third Central Hospital, Tianjin 300170, China
| | - Wen Shen
- Department of Radiology, Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin 300192, China.
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Di Sandro S, Sposito C, Ravaioli M, Lauterio A, Magistri P, Bongini M, Odaldi F, De Carlis R, Botta F, Centonze L, Maroni L, Citterio D, Guidetti C, Bagnardi V, De Carlis L, Cescon M, Mazzaferro V, Di Benedetto F. Surgical Treatment of Hepatocellular Carcinoma: Multicenter Competing-risk Analysis of Tumor-related Death Following Liver Resection and Transplantation Under an Intention-to-treat Perspective. Transplantation 2023; 107:1965-1975. [PMID: 37022089 DOI: 10.1097/tp.0000000000004593] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/07/2023]
Abstract
BACKGROUND Early-stage hepatocellular carcinoma could benefit from upfront liver resection (LR) or liver transplantation (LT), but the optimal strategy in terms of tumor-related outcomes is still debated. We compared the oncological outcomes of LR and LT for hepatocellular carcinoma, stratifying the study population into a low-, intermediate-, and high-risk class according to the risk of death at 5-y predicted by a previously developed prognostic model. The impact of tumor pathology on oncological outcomes of low- and intermediate-risk patients undergoing LR was investigated as a secondary outcome. METHODS We performed a retrospective multicentric cohort study involving 2640 patients consecutively treated by LR or LT from 4 tertiary hepatobiliary and transplant centers between 2005 and 2015, focusing on patients amenable to both treatments upfront. Tumor-related survival and overall survival were compared under an intention-to-treat perspective. RESULTS We identified 468 LR and 579 LT candidates: 512 LT candidates underwent LT, whereas 68 (11.7%) dropped-out for tumor progression. Ninety-nine high-risk patients were selected from each treatment cohort after propensity score matching. Three and 5-y cumulative incidence of tumor-related death were 29.7% and 39.5% versus 17.2% and 18.3% for LR and LT group ( P = 0.039), respectively. Low-risk and intermediate-risk patients treated by LR and presenting satellite nodules and microvascular invasion had a significantly higher 5-y incidence of tumor-related death (29.2% versus 12.5%; P < 0.001). CONCLUSIONS High-risk patients showed significantly better intention-to-treat tumor-related survival after upfront LT rather than LR. Cancer-specific survival of low- and intermediate-risk LR patients was significantly impaired by unfavorable pathology, suggesting the application of ab-initio salvage LT in such scenarios.
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Affiliation(s)
- Stefano Di Sandro
- Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit, University of Modena and Reggio Emilia, Modena, Italy
| | - Carlo Sposito
- HPB Surgery, Hepatology and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori di Milano, Milan, Italy
- Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy
| | - Matteo Ravaioli
- Department of General Surgery and Transplantation, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy
| | - Andrea Lauterio
- Department of General Surgery and Transplantation, Niguarda Ca' Granda Hospital, Milan, Italy
- School of Medicine and Surgery, University of Milan-Bicocca, Milan, Italy
| | - Paolo Magistri
- Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit, University of Modena and Reggio Emilia, Modena, Italy
| | - Marco Bongini
- HPB Surgery, Hepatology and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori di Milano, Milan, Italy
| | - Federica Odaldi
- Department of General Surgery and Transplantation, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Riccardo De Carlis
- Department of General Surgery and Transplantation, Niguarda Ca' Granda Hospital, Milan, Italy
- PhD Course in Clinical and Experimental Sciences, Univeristy of Padua, Padua, Italy
| | - Francesca Botta
- Department of Statistics and Quantitative Methods, University of Milan-Bicocca, Milan, Italy
| | - Leonardo Centonze
- Department of General Surgery and Transplantation, Niguarda Ca' Granda Hospital, Milan, Italy
- Clinical and Experimental Medicine PhD Program, University of Modena and Reggio Emilia, Modena, Italy
| | - Lorenzo Maroni
- Department of General Surgery and Transplantation, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Davide Citterio
- HPB Surgery, Hepatology and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori di Milano, Milan, Italy
| | - Cristiano Guidetti
- Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit, University of Modena and Reggio Emilia, Modena, Italy
| | - Vincenzo Bagnardi
- Department of Statistics and Quantitative Methods, University of Milan-Bicocca, Milan, Italy
| | - Luciano De Carlis
- Department of General Surgery and Transplantation, Niguarda Ca' Granda Hospital, Milan, Italy
- School of Medicine and Surgery, University of Milan-Bicocca, Milan, Italy
| | - Matteo Cescon
- Department of General Surgery and Transplantation, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy
| | - Vincenzo Mazzaferro
- HPB Surgery, Hepatology and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori di Milano, Milan, Italy
- Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy
| | - Fabrizio Di Benedetto
- Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit, University of Modena and Reggio Emilia, Modena, Italy
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Recommendation of mHAP and ABCR scoring systems for the decision-making of the first and subsequent TACE session in HCC patients. Eur J Gastroenterol Hepatol 2023; 35:461-470. [PMID: 36827534 PMCID: PMC9981324 DOI: 10.1097/meg.0000000000002515] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/26/2023]
Abstract
BACKGROUND Due to the high heterogeneity among hepatocellular carcinoma (HCC) patients receiving transarterial chemoembolization (TACE), the prognosis of patients varies significantly. Various predictive scoring systems have been developed to identify the patients who could benefit from TACE. However, there is no consensus on which is better. This study aims to validate and compare the predictive capabilities of scoring systems for first and subsequent TACE. MATERIALS A total of 524 HCC patients were treated with TACE, and 222 patients who met the inclusion criteria were included. Log-rank test was used to verify the predictive value of six scoring systems for the first TACE and four TACE retreatment scoring systems. Harrell's concordance (C)-index, likelihood ratio and integrated Brier score (IBS) were used to compare the predictive performance. RESULTS For the scoring systems of TACE, the overall survival (OS) of candidates screened by Hepatoma Arterial-embolization Prognostic (HAP), modified HAP (mHAP), mHAP3, alpha-fetoprotein, Barcelona Clinic Liver Cancer, Child-Pugh and Response (ABCR), albumin-bilirubin grade (ALBI), tumor size, alpha-fetoprotein, first TACE response and pre-/post-TACE was significantly longer than that of the noncandidates (all P < 0.05), whereas the mHAP2 and assessment for retreatment with TACE did not distinguish the candidates from noncandidates (P = 0.206, 0.115, respectively). The predictive and calibration performances of mHAP and ABCR were the highest for the first TACE and TACE retreatment, respectively. CONCLUSION mHAP identifies the patients who could benefit from the first TACE, whereas ABCR distinguishes patients who could benefit from subsequent TACE sessions.
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Identifying optimal candidates for post-TIPS patients with HCC undergoing TACE: a multicenter observational study. Eur Radiol 2023; 33:2809-2820. [PMID: 36562786 PMCID: PMC10017639 DOI: 10.1007/s00330-022-09249-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2022] [Revised: 09/19/2022] [Accepted: 10/19/2022] [Indexed: 12/24/2022]
Abstract
OBJECTIVE To develop a prognostic model for post-transjugular intrahepatic portosystemic shunt (TIPS) patients with hepatocellular carcinoma (HCC) beyond the Milan criteria treated by transarterial chemoembolization (TACE). DESIGN Between January 2013 and January 2020, 512 patients with HCC beyond the Milan criteria who underwent TACE after TIPS were retrospectively recruited from 15 tertiary centers. Patients were randomly sorted into a training set (n = 382) and a validation set (n = 130). Medical data and overall survival were assessed. A prediction model was developed using multivariate Cox regression analyses. Predictive performance and discrimination were evaluated and compared with other prognostic models. RESULTS Vascular invasion, log10(AFP), 1/creatinine, extrahepatic spread, and log10(ALT) were the most significant prognostic factors of survival. These five parameters were included in a new VACEA score. This score was able to stratify patients in the training set into four distinct risk grades whose median overall survival were 25.2, 15.1, 8.9, and 6.2 months, respectively. The 6-month, 1-year, 2-year, and 3-year AUROC values and C-index of the VACEA model were 0.819, 0.806, 0.779, 0.825, and 0.735, respectively, and higher than those of other seven currently available models in both the training and validation sets, as well as in different subgroups. CONCLUSION The VACEA score could stratify post-TIPS patients with HCC beyond the Milan criteria treated by TACE and help to identify candidates who benefit from this treatment. KEY POINTS • Vascular invasion, AFP, creatinine, extrahepatic spread, and ALT were independent significant prognostic factors of survival for HCC patients who underwent TACE after TIPS. • Our new model, named VACEA score, can accurately predict prognosis at the individual level and stratify patients into four distinct risk grades. • The VACEA model showed better prognostic discrimination and calibration than other current TACE-/TIPS-specific models Graphical abstract.
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Zhu Y, Wang E, Zhao S, Han D, Zhao Y, Chen H, Zhu J, Han T, Bai Y, Lou Y, Zhang Y, Yang M, Zuo L, Fan J, Chen X, Jia J, Wu W, Ren W, Bai T, Ma S, Xu F, Tang Y, Han Y, Zhao J, Qi X, Li J, Du X, Chen D, Liu L. Identify optimal HAP series scores for unresectable HCC patients undergoing TACE plus sorafenib: A Chinese multicenter observational study. Front Oncol 2023; 12:983554. [PMID: 36776366 PMCID: PMC9911813 DOI: 10.3389/fonc.2022.983554] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2022] [Accepted: 12/15/2022] [Indexed: 01/28/2023] Open
Abstract
BACKGROUND Hepatoma arterial-embolization prognostic (HAP) series scores have been proposed for prognostic prediction in patients with unresectable hepatocellular carcinoma (uHCC) undergoing transarterial chemoembolization (TACE). However, their prognostic value in TACE plus sorafenib (TACE-S) remains unknown. Here, we aim to evaluate their prognostic performance in such conditions and identify the best model for this combination therapy. METHODS Between January 2012 and December 2018, consecutive patients with uHCC receiving TACE-S were recruited from 15 tertiary hospitals in China. Cox regression analyses were used to investigate the prognostic values of baseline factors and every scoring system. Their prognostic performance and discriminatory performance were evaluated and confirmed in subgroup analyses. RESULTS A total of 404 patients were enrolled. In the whole cohort, the median follow-up period was 44.2 (interquartile range (IQR), 33.2-60.7) months, the median overall survival (OS) time was 13.2 months, and 336 (83.2%) patients died at the end of the follow-up period. According to multivariate analyses, HAP series scores were independent prognostic indicators of OS. In addition, the C-index, Akaike information criterion (AIC) values, and time-dependent area under the receiver operating characteristic (ROC) curve (AUC) indicated that modified HAP (mHAP)-III had the best predictive performance. Furthermore, the results remained consistent in most subsets of patients. CONCLUSION HAP series scores exhibited good predictive ability in uHCC patients accepting TACE-S, and the mHAP-III score was found to be superior to the other HAP series scores in predicting OS. Future prospective high-quality studies should be conducted to confirm our results and help with treatment decision-making.
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Affiliation(s)
- Yejing Zhu
- Department of General Surgery, Tangdu Hospital, Air Force Medical University (Fourth Military Medical University), Xi'an, China
| | - Enxin Wang
- Department of Digestive Diseases, Air Force Hospital of Western Theater Command, Chengdu, China
| | - Shoujie Zhao
- Department of General Surgery, Tangdu Hospital, Air Force Medical University (Fourth Military Medical University), Xi'an, China
| | - Dandan Han
- Department of General Surgery, The Air Force Hospital of Southern Theater Command, Guangzhou, China
| | - Yan Zhao
- Department of Digestive Diseases, The First Affiliated Hospital of Xi'an Jiao Tong University, Xi’an, China
| | - Hui Chen
- Xijing Hospital of Digestive Diseases, Air Force Medical University (Fourth Military Medical University), Xi’an, China
| | - Jun Zhu
- Department of General Surgery, The Air Force Hospital of Southern Theater Command, Guangzhou, China
| | - Tenghui Han
- Department of Internal Medicine, Air Force Medical University (Fourth Military Medical University), Xi’an, China
| | - Yang Bai
- Department of Neurosurgery, General Hospital of Northern Theater Command, Shenyang, China
| | - Yanju Lou
- Department of Orthopedic Surgery, Air Force Hospital of Western Theater Command, Chengdu, China
| | - Yongchao Zhang
- Department of Medical Affairs, Air Force Hospital of Western Theater Command, Chengdu, China
| | - Man Yang
- Center for Digestive Disease, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
| | - Luo Zuo
- Department of Digestive Diseases, the Second Affiliated Hospital of Chengdu Medical College, Chengdu, China
| | - Jiahao Fan
- Department of Digestive Diseases, the Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Xing Chen
- Department of Oncology, Qingdao Women and Children's Hospital, Qingdao, China
| | - Jia Jia
- Department of Emergency, Shaanxi Provincial People's Hospital, Xi’an, China
| | - Wenbin Wu
- Department of Digestive Diseases, Xi'an First Hospital, Xi’an, China
| | - Weirong Ren
- Department of Digestive Diseases, Sanmenxia Central Hospital, Henan University of Science and Technology, Sanmenxia, China
| | - Tingting Bai
- Department of Digestive Diseases, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Shouzheng Ma
- Department of Surgery, Tangdu Hospital, Air Force Medical University (Fourth Military Medical University), Xi’an, China
| | - Fenghua Xu
- Department of Digestive Diseases, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Yuxin Tang
- Department of Digestive Diseases, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Ying Han
- Xijing Hospital of Digestive Diseases, Air Force Medical University (Fourth Military Medical University), Xi’an, China
| | - Junlong Zhao
- State Key Laboratory of Cancer Biology, Medical Genetics and Development Biology, Fourth Military Medical University, Xi’an, China
| | - Xingshun Qi
- Department of Digestive Diseases, General Hospital of Northern Theater Command, Shenyang, China
| | - Jing Li
- Department of Digestive Diseases, Shanxi Bethune Hospital, Shanxi Academy of Medical Science, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, China
- Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xilin Du
- Department of General Surgery, Tangdu Hospital, Air Force Medical University (Fourth Military Medical University), Xi'an, China
| | - Dongfeng Chen
- Department of Digestive Diseases, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Lei Liu
- Department of Digestive Diseases, Tangdu Hospital, Air Force Medical University (Fourth Military Medical University), Xi’an, China
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Cappelli A, Golfieri R, Mulas V, De Cinque A, Cocozza MA, Mosconi C. The Current Situation Regarding TACE-Specific Scores. TRANSARTERIAL CHEMOEMBOLIZATION (TACE) 2023:83-88. [DOI: 10.1007/978-3-031-36261-3_10] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Preoperative estimation of the survival of patients with unresectable hepatocellular carcinoma achieving complete response after conventional transcatheter arterial chemoembolization: assessments of clinical and LI-RADS MR features. Radiol Med 2022; 127:939-949. [DOI: 10.1007/s11547-022-01517-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2022] [Accepted: 06/13/2022] [Indexed: 10/15/2022]
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Hatzidakis A, Müller L, Krokidis M, Kloeckner R. Local and Regional Therapies for Hepatocellular Carcinoma and Future Combinations. Cancers (Basel) 2022; 14:cancers14102469. [PMID: 35626073 PMCID: PMC9139740 DOI: 10.3390/cancers14102469] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2022] [Revised: 05/10/2022] [Accepted: 05/11/2022] [Indexed: 02/08/2023] Open
Abstract
Simple Summary Percutaneous interventional radiological techniques offer many alternatives for treatment of Hepatocellular Carcinoma (HCC) using local anesthesia and sedation. These methods aim to destroy the malignant tumors locally without affecting the non-malignant liver. In this way, complications are kept low and patient recovery is quick. Indications depend on tumor size, type and stage, as well as patient’s condition, liver function and co-morbidities. In recent years, a lot of research has been made in combining such approaches with immune therapy, but there is still much work to be done. This manuscript tries to analyze where we stand today and explain, using a comprehensive algorithm, the treatment options for each different clinical condition. Abstract Background: Hepatocellular carcinoma (HCC) can be treated by local and regional methods of percutaneous interventional radiological techniques. Indications depend on tumor size, type and stage, as well as patient’s condition, liver function and co-morbidities. According to international classification systems such as Barcelona Clinic Liver Cancer (BCLC) classification, very early, early or intermediate staged tumors can be treated either with ablative methods or with transarterial chemoembolization (TACE), depending on tumor characteristics. The combination of both allows for individualized forms of treatment with the ultimate goal of improving response and survival. In recent years, a lot of research has been carried out in combining locoregional approaches with immune therapy. Although recent developments in systemic treatment, especially immunotherapy, seem quite promising and have expanded possible combined treatment options, there is still not enough evidence in their favor. The aim of this review is to provide a comprehensive up-to-date overview of all these techniques, explaining indications, contraindications, technical problems, outcomes, results and complications. Moreover, combinations of percutaneous treatment with each other or with immunotherapy and future options will be discussed. Use of all those methods as down-staging or bridging solutions until surgery or transplantation are taken into consideration will also be reviewed. Conclusion: Local and regional therapies remain a mainstay of curative and palliative treatment of patients with HCC. Currently, evidence on potential combination of the local and regional treatment options with each other as well as with other treatment modalities is growing and has the potential to further individualize HCC therapy. To identify the most suitable treatment option out of these new various options, a repeated interdisciplinary discussion of each case by the tumor board is of utmost importance.
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Affiliation(s)
- Adam Hatzidakis
- Department of Radiology, AHEPA University Hospital of Thessaloniki, Faculty of Health Sciences, School of Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece
- Correspondence:
| | - Lukas Müller
- Department of Diagnostic and Interventional Radiology, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany; (L.M.); (R.K.)
| | - Miltiadis Krokidis
- 1st Department of Radiology, Areteion Hospital, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, Greece;
| | - Roman Kloeckner
- Department of Diagnostic and Interventional Radiology, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany; (L.M.); (R.K.)
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Hepatitis B Virus-Associated Hepatocellular Carcinoma. Viruses 2022; 14:v14050986. [PMID: 35632728 PMCID: PMC9146458 DOI: 10.3390/v14050986] [Citation(s) in RCA: 89] [Impact Index Per Article: 29.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2022] [Revised: 05/02/2022] [Accepted: 05/03/2022] [Indexed: 02/06/2023] Open
Abstract
Hepatitis B virus (HBV) is DNA-based virus, member of the Hepadnaviridae family, which can cause liver disease and increased risk of hepatocellular carcinoma (HCC) in infected individuals, replicating within the hepatocytes and interacting with several cellular proteins. Chronic hepatitis B can progressively lead to liver cirrhosis, which is an independent risk factor for HCC. Complications as liver decompensation or HCC impact the survival of HBV patients and concurrent HDV infection worsens the disease. The available data provide evidence that HBV infection is associated with the risk of developing HCC with or without an underlying liver cirrhosis, due to various direct and indirect mechanisms promoting hepatocarcinogenesis. The molecular profile of HBV-HCC is extensively and continuously under study, and it is the result of altered molecular pathways, which modify the microenvironment and lead to DNA damage. HBV produces the protein HBx, which has a central role in the oncogenetic process. Furthermore, the molecular profile of HBV-HCC was recently discerned from that of HDV-HCC, despite the obligatory dependence of HDV on HBV. Proper management of the underlying HBV-related liver disease is fundamental, including HCC surveillance, viral suppression, and application of adequate predictive models. When HBV-HCC occurs, liver function and HCC characteristics guide the physician among treatment strategies but always considering the viral etiology in the treatment choice.
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22
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D'Avola D, Granito A, Torre-Aláez MDL, Piscaglia F. The importance of liver functional reserve in the non-surgical treatment of hepatocellular carcinoma. J Hepatol 2022; 76:1185-1198. [PMID: 34793869 DOI: 10.1016/j.jhep.2021.11.013] [Citation(s) in RCA: 54] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2020] [Revised: 11/02/2021] [Accepted: 11/05/2021] [Indexed: 02/08/2023]
Abstract
The aim of any oncological treatment is not just to eliminate the tumour, but to maximise patient survival and quality of life. Since the liver has a vital function, any radical treatment that severely compromises liver function will result in a shortening of life expectancy, rather than a prolongation. Furthermore, even non-severe liver damage may prevent the delivery of further effective therapies. This is particularly important in the case of hepatocellular carcinoma (HCC), as it is associated with underlying cirrhosis in most patients - cirrhosis itself is not only a potentially lethal disease and independent prognostic factor in HCC, but it also makes liver function fragile. Accordingly, some information about liver dysfunction is included in most staging systems for HCC and can be used to guide the selection of treatments that the functional liver reserve can tolerate. Unfortunately, the prediction of functional damage to the liver in the case of antitumor treatments is very challenging and still suboptimal in any given patient. Moreover, while the assessment of functional reserve can now be used to avoid postoperative liver failure in the surgical setting, its use has been less well clarified for non-surgical therapies, which is of particular relevance today, as several lines of effective non-surgical treatments, including systemic therapies, have become available. The present article will a) critically review the implications of the assessment of liver functional reserve in patients with HCC, b) illustrate the available tools to assess liver functional reserve and c) discuss the role of functional assessment for each type of non-surgical therapy for HCC.
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Affiliation(s)
- Delia D'Avola
- Liver Unit, Internal Medicine Department, Clinica Universidad de Navarra, Pamplona and Madrid, Spain; Centro de Investigación Bio Medica en Red de Enfermedades Hepáticas y Digestivas (Ciberehd), Pamplona, Spain
| | - Alessandro Granito
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Italy; Department of Medical and Surgical Sciences, University of Bologna, Italy
| | - Manuel de la Torre-Aláez
- Liver Unit, Internal Medicine Department, Clinica Universidad de Navarra, Pamplona and Madrid, Spain
| | - Fabio Piscaglia
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Italy; Department of Medical and Surgical Sciences, University of Bologna, Italy.
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A 10-Gene Signature Identified by Machine Learning for Predicting the Response to Transarterial Chemoembolization in Patients with Hepatocellular Carcinoma. JOURNAL OF ONCOLOGY 2022; 2022:3822773. [PMID: 35111225 PMCID: PMC8803430 DOI: 10.1155/2022/3822773] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/08/2021] [Revised: 12/28/2021] [Accepted: 12/29/2021] [Indexed: 12/15/2022]
Abstract
Background Transarterial chemoembolization (TACE) is recommended for intermediate-stage HCC patients. Owing to substantial variation in its efficacy, indicators of patient responses to TACE need to be determined. Methods A Gene Expression Omnibus (GEO) dataset consisting of patients of different TACE-response status was retrieved. Differentially expressed genes (DEGs) were calculated and variable gene ontology analyses were conducted. Potential drugs and response to immunotherapy were predicted using multiple bioinformatic algorithms. We built and compared 5 machine-learning models with finite genes to predict patients' response to TACE. The model was also externally validated to discern different survival outcomes after TACE. Tumor-infiltrating lymphocytes (TILs) and tumor stemness index were evaluated to explore potential mechanism of our model. Results The gene set variation analysis revealed enhanced pathways related to G2/M checkpoint, E2F, mTORC1, and myc in TACE nonresponders. TACE responders had better immunotherapy response too. 373 DEGs were detected and the upregulated DEGs in nonresponders were enriched in IL-17 signal pathway. 5 machine-learning models were constructed and evaluated, and a linear support vector machine (SVM)-based model with 10 genes was selected (AQP1, FABP4, HERC6, LOX, PEG10, S100A8, SPARCL1, TIAM1, TSPAN8, and TYRO3). The model achieved an AUC and accuracy of 0.944 and 0.844, respectively, in the development cohort. In the external validation cohort comprised of patients receiving adjuvant TACE and postrecurrence TACE treatment, the predicted response group significantly outlived the predicted nonresponse counterparts. TACE nonresponders tend to have more macrophage M0 cells and lower resting mast cells in the tumor tissue and the stemness index is also higher than responders. Those characteristics were successfully captured by our model. Conclusion The model based on expression data of 10 genes could potentially predict HCC patients' response and prognosis after TACE treatment. The discriminating power was TACE-specific.
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Cheng S, Yu X, Liu S, Jin Z, Xue H, Wang Z, Xie P. Development of a Prognostic Nomogram in Hepatocellular Carcinoma with Portal Vein Tumor Thrombus Following Trans-Arterial Chemoembolization with Drug-Eluting Beads. Cancer Manag Res 2022; 13:9367-9377. [PMID: 34992462 PMCID: PMC8713724 DOI: 10.2147/cmar.s341672] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2021] [Accepted: 12/10/2021] [Indexed: 12/16/2022] Open
Abstract
Objective To develop and validate a prognostic nomogram in eastern patients with hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT) receiving trans-arterial chemoembolization with drug-eluting beads (DEB-TACE). Methods This retrospective study included 200 patients with training cohort (n = 118) from institution 1 and test cohort (n = 82) from institution 2. All these patients received first-line DEB-TACE between October 2016 and October 2018. Multivariate Cox proportional hazard regression analysis was performed on the training cohort to reveal the independent prognostic factors, and then prognostic nomograms were developed. In order to evaluate the performance of the nomogram comprehensively in both the training and test cohorts, C-index, Kaplan–Meier curve with Log rank test, receiver operating characteristic curve (ROC), calibration plot, and decision curve analysis (DCA) were performed. Results Tumor number, serum γ-glutamyl transferase (GGT) level, and level of PVTT were independent risk factors of prognosis. A nomogram was constructed to predict 6-, 12- and 18-month overall survival (OS) based on these identified prognostic factors. C-indexes of the nomogram were 0.88 (95% confidence interval [CI], 0.79–0.97) in the training cohort and 0.87 (95% CI, 0.75–0.99) in the test cohort. The Kaplan–Meier curve analysis showed that the nomogram was able to separate patients into low- and high-risk subgroups. ROC curves for the nomogram at 6-, 12- and 18-month showed satisfied discrimination, with an AUC of 0.765, 0.803 and 0.809 in the training cohort, respectively, and 0.772, 0.724 and 0.746 in the test cohort, respectively. The calibration curve demonstrated good agreement between predicted and actual survival rates in the training and test cohorts. The decision curve showed good performance of the nomogram in terms of clinical application. Conclusion We developed and validated a nomogram that was accurate and clinically useful in eastern patients with HBV-associated HCC with PVTT who underwent DEB-TACE.
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Affiliation(s)
- Sihang Cheng
- Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, People's Republic of China.,Department of Radiology, Sichuan Provincial People's Hospital, Sichuan Academy of Medical Sciences, Chengdu, People's Republic of China
| | - Xiang Yu
- Department of Radiology, Sichuan Provincial People's Hospital, Sichuan Academy of Medical Sciences, Chengdu, People's Republic of China
| | - Siyun Liu
- Pharmaceutical Diagnostics, GE Healthcare, Beijing, People's Republic of China
| | - Zhengyu Jin
- Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, People's Republic of China
| | - Huadan Xue
- Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, People's Republic of China
| | - Zhiwei Wang
- Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, People's Republic of China
| | - Ping Xie
- Department of Radiology, Sichuan Provincial People's Hospital, Sichuan Academy of Medical Sciences, Chengdu, People's Republic of China
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Dong Z, Lin Y, Lin F, Luo X, Lin Z, Zhang Y, Li L, Li ZP, Feng ST, Cai H, Peng Z. Prediction of Early Treatment Response to Initial Conventional Transarterial Chemoembolization Therapy for Hepatocellular Carcinoma by Machine-Learning Model Based on Computed Tomography. J Hepatocell Carcinoma 2021; 8:1473-1484. [PMID: 34877267 PMCID: PMC8643205 DOI: 10.2147/jhc.s334674] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2021] [Accepted: 11/05/2021] [Indexed: 12/20/2022] Open
Abstract
Purpose The treatment response to initial conventional transarterial chemoembolization (cTACE) is essential for the prognosis of patients with hepatocellular carcinoma (HCC). This study explored and verified the feasibility of machine-learning models based on clinical data and contrast-enhanced computed tomography (CT) image findings to predict early responses of HCC patients after initial cTACE treatment. Patients and Methods Overall, 110 consecutive unresectable HCC patients who were treated with cTACE for the first time were retrospectively enrolled. Clinical data and imaging features based on contrast-enhanced CT were collected for the selection of characteristics. Treatment responses were evaluated based on the modified Response Evaluation Criteria in Solid Tumors (mRECIST) by postoperative CT examination within 2 months after the procedure. Python (version 3.70) was used to develop machine learning models. Least absolute shrinkage and selection operator (LASSO) algorithm was applied to select features with the impact on predicting treatment response after the first TACE procedure. Six machine learning algorithms were used to build predictive models, including XGBoost, decision tree, support vector machine, random forest, k-nearest neighbor, and fully convolutional networks, and their performances were compared using receiver operator characteristic (ROC) curves to determine the best performing model. Results Following TACE, 31 patients (28.2%) were described as responsive to TACE, while 72 patients (71.8%) were nonresponsive to TACE. Portal vein tumor thrombosis type, albumin level, and distribution of tumors within the liver were selected for predictive model building. Among the models, the RF model showed the best performance, with area under the curve (AUC), accuracy, sensitivity, and specificity of 0.802, 0.784, 0.904, and 0.480, respectively. Conclusion Machine learning models can provide an accurate prediction of the early response of initial TACE treatment for HCC, which can help in individualizing clinical decision-making and modification of further treatment strategies for patients with unresectable HCC.
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Affiliation(s)
- Zhi Dong
- Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, 510080, People's Republic of China
| | - Yingyu Lin
- Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, 510080, People's Republic of China
| | - Fangzeng Lin
- Department of Interventional Radiology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, 510080, People's Republic of China
| | - Xuyi Luo
- Department of Emergency, Guangzhou First People's Hospital, Guangzhou, Guangdong, 510180, People's Republic of China
| | - Zhi Lin
- Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, 510080, People's Republic of China
| | - Yinhong Zhang
- Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, 510080, People's Republic of China
| | - Lujie Li
- Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, 510080, People's Republic of China
| | - Zi-Ping Li
- Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, 510080, People's Republic of China
| | - Shi-Ting Feng
- Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, 510080, People's Republic of China
| | - Huasong Cai
- Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, 510080, People's Republic of China
| | - Zhenpeng Peng
- Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, 510080, People's Republic of China
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Adhoute X, Larrey E, Anty R, Chevallier P, Penaranda G, Tran A, Bronowicki JP, Raoul JL, Castellani P, Perrier H, Bayle O, Monnet O, Pol B, Bourliere M. Expected outcomes and patients’ selection before chemoembolization—“Six-and-Twelve or Pre-TACE-Predict” scores may help clinicians: Real-life French cohorts results. World J Clin Cases 2021; 9:4559-4572. [PMID: 34222423 PMCID: PMC8223847 DOI: 10.12998/wjcc.v9.i18.4559] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2020] [Revised: 12/26/2020] [Accepted: 02/04/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Careful selection of hepatocellular carcinoma (HCC) patients prior to chemoembolization treatment is a daily reality, and is even more necessary with new available therapeutic options in HCC.
AIM To propose two new models to better stratify patients and maximize clinical benefit: “6 and 12” and “pre/post-TACE-predict” (TACE, transarterial chemoembolization).
METHODS We evaluated and compared their performance in predicting overall survival with other systems {Barcelona Clinic Liver Cancer (BCLC), Albumin-Bilirubin (ALBI) and NIACE [Number of tumor(s), Infiltrative HCC, alpha-fetoprotein, Child-Pugh (CP), and performance status]} in two HCC French cohorts of different stages enrolled between 2010 and 2018.
RESULTS The cohorts included 324 patients classified as BCLC stages A/B (cohort 1) and 137 patients classified as BCLC stages B/C (cohort 2). The majority of the patients had cirrhosis with preserved liver function. “Pre-TACE-predict” and “6 and 12” models identified three distinct categories of patients exhibiting different prognosis in cohort 1. However, their prognostic value was no better than the BCLC system or NIACE score. Liver function based on CP and ALBI grades significantly impacted patient survival. Conversely, the “post-TACE-predict” model had a higher predictive value than other models. The stratification ability as well as predictive performance of these new models in an intermediate/advanced stage population was less efficient (cohort 2).
CONCLUSION The newly proposed “Pre-TACE-predict” and “6 and 12” models offer an interesting stratification into three categories in a recommended TACE population, as they identify poor candidates, those with partial control and durable response. The models' contribution was reduced in a population with advanced stage HCCs.
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Affiliation(s)
- Xavier Adhoute
- Department of Gastroenterology and Hepatology, Hôpital Saint-Joseph, Marseille 13008, France
| | - Edouard Larrey
- Department of Gastroenterology and Hepatology, Hôpital Universitaire de l’Archet, Nice 06000, France
| | - Rodolphe Anty
- Department of Gastroenterology and Hepatology, Hôpital Universitaire de l’Archet, Nice 06000, France
| | - Patrick Chevallier
- Department of Radiology, Hôpital Universitaire de l’Archet, Nice 06000, France
| | | | - Albert Tran
- Department of Gastroenterology and Hepatology, Hôpital Universitaire de l’Archet, Nice 06000, France
| | - Jean-Pierre Bronowicki
- Department of Gastroenterology and Hepatology, Centre Hospitalo-Universitaire de Nancy, Vandoeuvre les Nancy 54511, France
| | - Jean-Luc Raoul
- Department of Medical Oncology, Institut de Cancérologie de l’Ouest, Site de Nantes, Nantes 44805, France
| | - Paul Castellani
- Department of Gastroenterology and Hepatology, Hôpital Saint-Joseph, Marseille 13008, France
| | - Hervé Perrier
- Department of Gastroenterology and Hepatology, Hôpital Saint-Joseph, Marseille 13008, France
| | - Olivier Bayle
- Department of Radiology, Hôpital Saint-Joseph, Marseille 13008, France
| | - Olivier Monnet
- Department of Radiology, Hôpital Saint-Joseph, Marseille 13008, France
| | - Bernard Pol
- Department of Hepatobiliary Surgery, Hôpital Saint-Joseph, Marseille 13008, France
| | - Marc Bourliere
- Department of Gastroenterology and Hepatology, Hôpital Saint-Joseph, Marseille 13008, France
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Sheen H, Kim JS, Lee JK, Choi SY, Baek SY, Kim JY. A radiomics nomogram for predicting transcatheter arterial chemoembolization refractoriness of hepatocellular carcinoma without extrahepatic metastasis or macrovascular invasion. Abdom Radiol (NY) 2021; 46:2839-2849. [PMID: 33388805 DOI: 10.1007/s00261-020-02884-x] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2020] [Revised: 11/19/2020] [Accepted: 11/25/2020] [Indexed: 12/12/2022]
Abstract
OBJECTIVE A radiomics nomogram for pretreatment prediction of TACE refractoriness was developed and validated for hepatocellular carcinoma (HCC) without extrahepatic metastasis or macrovascular invasion. MATERIALS AND METHODS This study included 80 patients with HCC without extrahepatic metastasis or macrovascular involvement treated with TACE between July 2016 and November 2018. The datasets were divided into a training set (80%) and a test set (20%) for feature selection and tenfold cross-validation. Forty radiomic features were extracted from arterial-phase computed tomography (CT) using the Local Image Features Extraction software. The Lasso regression model was used for radiomics signature selection. The Lasso regression model was used for radiomics signature selection and the selected signatures were validated using the Mann-Whitney U-test. The radiomics nomogram was developed based on a multivariate logistic regression model incorporating the Rad-score, CT imaging factors, and clinical factors, and it was validated. RESULTS The Rad-score, which consists of the Gray-Level Zone Length Matrix (GLZLM)-Long-Zone Low Gray-Level Emphasis (LZLGE) and GLZLM-Gray-Level Non-Uniformity (GLNU), T-stage, log α-fetoprotein (AFP), and bilobar distribution were significantly associated with TACE refractoriness (p < 0.05). Predictors in the radiomics nomogram were the Rad-score and T-stage (Rad-score + T-stage), Rad-score and bilobar distribution (Rad-score + bilobar distribution), or Rad-score and logAFP (Rad-score + logAFP). The multivariate logistic regression model showed a good predictive performance (Rad-score + T-stage, AUC, 0.95; Rad-score + bilobar distribution, AUC 0.91; and Rad-score + logAFP, AUC, 0.91). CONCLUSION The radiomics nomogram could be used for the pretreatment prediction of TACE refractoriness.
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Affiliation(s)
- Heesoon Sheen
- Department of Radiation Oncology, Samsung Medical Center, #81, Irwon-ro Gangnam-gu, Seoul, 06351, Republic of Korea
- RI Translational Research Team, Division of Applied RI, Korea Institute of Radiological & Medical Sciences, Seoul, 01812, Republic of Korea
| | - Jin Sil Kim
- Department of Radiology and Medical Research Institute, College of Medicine, Ewha Womans University, Anyangcheon-Ro, 1071, Yangcheon-gu, Seoul, 07985, Republic of Korea.
| | - Jeong Kyong Lee
- Department of Radiology and Medical Research Institute, College of Medicine, Ewha Womans University, Anyangcheon-Ro, 1071, Yangcheon-gu, Seoul, 07985, Republic of Korea
| | - Sun Young Choi
- Department of Radiology and Medical Research Institute, College of Medicine, Ewha Womans University, Anyangcheon-Ro, 1071, Yangcheon-gu, Seoul, 07985, Republic of Korea
| | - Seung Yon Baek
- Department of Radiology and Medical Research Institute, College of Medicine, Ewha Womans University, Anyangcheon-Ro, 1071, Yangcheon-gu, Seoul, 07985, Republic of Korea
| | - Jung Young Kim
- RI Translational Research Team, Division of Applied RI, Korea Institute of Radiological & Medical Sciences, Seoul, 01812, Republic of Korea
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Müller L, Stoehr F, Mähringer-Kunz A, Hahn F, Weinmann A, Kloeckner R. Current Strategies to Identify Patients That Will Benefit from TACE Treatment and Future Directions a Practical Step-by-Step Guide. J Hepatocell Carcinoma 2021; 8:403-419. [PMID: 34012930 PMCID: PMC8128497 DOI: 10.2147/jhc.s285735] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2021] [Accepted: 04/21/2021] [Indexed: 12/11/2022] Open
Abstract
Treatment of hepatocellular carcinoma (HCC) depends on the stage of disease. In the Western Hemisphere, the Barcelona Clinic Liver Cancer classification (BCLC) is the preferred staging system. Approximately one-third of patients initially present with intermediate-stage disease. For these patients, transarterial chemoembolization (TACE) is the treatment of choice. However, the intermediate-stage comprises a heterogeneous subgroup of patients with considerable differences in tumor burden and liver function. In addition, differences in individual factors that are not captured by the BCLC framework, such as the tumor growth pattern, degree of hypervascularity, and vascular supply, complicate further evaluation of these patients. Due to these differences, not all patients benefit equally from TACE. Several tools and scoring systems have been devised to provide decision-making support. All of these have shown promising initial results but failed external evaluation and have not been translated to the clinic. Nevertheless, criteria for objectifying treatment decisions in daily clinical practice are needed in all stages of disease. Therefore, this review provides a concise practical step-by-step guide on current strategies for patient selection and decision-making, with a focus on TACE, to critically evaluate the existing decision-support tools and provide a summary of the latest updates in the field.
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Affiliation(s)
- Lukas Müller
- Department of Diagnostic and Interventional Radiology, University Medical Centre of the Johannes Gutenberg-University Mainz, Mainz, Germany
| | - Fabian Stoehr
- Department of Diagnostic and Interventional Radiology, University Medical Centre of the Johannes Gutenberg-University Mainz, Mainz, Germany
| | - Aline Mähringer-Kunz
- Department of Diagnostic and Interventional Radiology, University Medical Centre of the Johannes Gutenberg-University Mainz, Mainz, Germany
| | - Felix Hahn
- Department of Diagnostic and Interventional Radiology, University Medical Centre of the Johannes Gutenberg-University Mainz, Mainz, Germany
| | - Arndt Weinmann
- Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
| | - Roman Kloeckner
- Department of Diagnostic and Interventional Radiology, University Medical Centre of the Johannes Gutenberg-University Mainz, Mainz, Germany
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Chang K, Chi C, Lee R, Hou M, Huang Y, Lee I. Efficacy and predictors of survival in patients with solitary hepatocellular carcinoma larger than 5 cm undergoing transarterial chemoembolization. ADVANCES IN DIGESTIVE MEDICINE 2021. [DOI: 10.1002/aid2.13278] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Affiliation(s)
- Ke‐Bin Chang
- Division of Gastroenterology and Hepatology, Department of Medicine Keelung Hospital, Ministry of Health and Welfare Keelung Taiwan
- Division of Gastroenterology and Hepatology, Department of Medicine Taipei Veterans General Hospital Taipei Taiwan
- Faculty of Medicine National Yang Ming Chiao Tung University School of Medicine Taipei Taiwan
| | - Chen‐Ta Chi
- Division of Gastroenterology and Hepatology, Department of Medicine Taipei Veterans General Hospital Taipei Taiwan
- Faculty of Medicine National Yang Ming Chiao Tung University School of Medicine Taipei Taiwan
| | - Rheun‐Chuan Lee
- Department of Radiology Taipei Veterans General Hospital Taipei Taiwan
| | - Ming‐Chih Hou
- Division of Gastroenterology and Hepatology, Department of Medicine Taipei Veterans General Hospital Taipei Taiwan
- Faculty of Medicine National Yang Ming Chiao Tung University School of Medicine Taipei Taiwan
| | - Yi‐Hsiang Huang
- Division of Gastroenterology and Hepatology, Department of Medicine Taipei Veterans General Hospital Taipei Taiwan
- Faculty of Medicine National Yang Ming Chiao Tung University School of Medicine Taipei Taiwan
- Institute of Clinical Medicine National Yang Ming Chiao Tung University Taipei Taiwan
| | - I‐Cheng Lee
- Division of Gastroenterology and Hepatology, Department of Medicine Taipei Veterans General Hospital Taipei Taiwan
- Faculty of Medicine National Yang Ming Chiao Tung University School of Medicine Taipei Taiwan
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Vogel A, Bathon M, Saborowski A. Advances in systemic therapy for the first-line treatment of unresectable HCC. Expert Rev Anticancer Ther 2021; 21:621-628. [PMID: 33499684 DOI: 10.1080/14737140.2021.1882855] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Introduction: Hepatocellular carcinoma (HCC) is one of the most common and deadliest cancers worldwide. In recent years, several drugs have been approved in first- and second-line setting. Currently, several phase-III trials are ongoing with combinations of checkpoint inhibitors, tyrosine kinase inhibitors (TKI) and anti-angiogenic antibodies, which will most likely increase therapeutic options in frontline therapy in the near future.Areas covered: This review summarizes the standard of care in first-line systemic therapy for patients with advanced HCC and provides an outlook on the most promising combinations currently tested in prospective trials.Expert opinion: The recent approval of novel substances has substantially changed the field of palliative treatment strategies in patients with advanced HCC. Immuno-oncology (IO)-based combination therapies will become the next standard of care in frontline HCC. The potent anti-tumor efficacy and good tolerability of these therapies will increase the use of upfront systemic therapy in patients with intermediate stage HCC.
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Affiliation(s)
- Arndt Vogel
- Department of Gastroenterology, Hepatology & Endokrinologie, Medizinische Hochschule Hannover, Hannover, Germany
| | - Melanie Bathon
- Department of Gastroenterology, Hepatology & Endokrinologie, Medizinische Hochschule Hannover, Hannover, Germany
| | - Anna Saborowski
- Department of Gastroenterology, Hepatology & Endokrinologie, Medizinische Hochschule Hannover, Hannover, Germany
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Campani C, Vitale A, Dragoni G, Arena U, Laffi G, Cillo U, Giannini EG, Tovoli F, Rapaccini GL, Di Marco M, Caturelli E, Zoli M, Sacco R, Cabibbo G, Mega A, Guarino M, Gasbarrini A, Svegliati-Baroni G, Foschi FG, Biasini E, Masotto A, Nardone G, Raimondo G, Azzaroli F, Vidili G, Brunetto MR, Farinati F, Trevisani F, Marra F. Time-Varying mHAP-III Is the Most Accurate Predictor of Survival in Patients with Hepatocellular Carcinoma Undergoing Transarterial Chemoembolization. Liver Cancer 2021; 10:126-136. [PMID: 33977089 PMCID: PMC8077424 DOI: 10.1159/000513404] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2020] [Accepted: 10/31/2020] [Indexed: 02/05/2023] Open
Abstract
INTRODUCTION The prognosis of patients undergoing transarterial chemoembolization (TACE) is extremely variable, and a confounding factor is that TACE is often repeated several times. We retrospectively evaluated the accuracy of different prognostic scores and staging systems in estimating overall survival (OS) in patients with hepatocellular carcinoma (HCC). METHODS An analysis considering prognostic models as time-varying variables was performed, calculating OS from the time of TACE to the time of the subsequent treatment. Total follow-up time for each patient was therefore split into several observation times accounting for each TACE procedure. Values of the likelihood ratio test (LRT) and Akaike information criterion (AIC) were used to compare different systems. Univariable and multivariable analyses were conducted to identify additional factors predictive of OS. We analyzed 1,610 TACE performed in 1,058 patients recorded in the Italian Liver Cancer database from 2008 through 2016. RESULTS The median OS of the enrolled patients was 41 months. According to LRT χ2 and AIC values based on the time-varying analysis, mHAP-III achieved the best values (41.72 and 4,625.49, respectively, p < 0.0001), indicating the highest predictive performance compared with all other scores (HAP, mHAP-II, ALBI, and pALBI) and staging systems (MELD, ITALICA, CLIP, MESH, MESIAH, JIS, HKLC, and BCLC). In the multivariable Cox proportional hazards model, mHAP-III maintained an independent effect on OS (hazard ratio 1.31, 95% CI: 1.10-1.55, p < 0.0001). Time-varying age, alcoholic etiology, radiologic response to TACE, and performing ablation or surgery after TACE were additional significant variables resulting from the multivariable model. CONCLUSION An innovative time-varying analysis revealed that mHAP-III was the most accurate model in predicting OS in patients with HCC undergoing TACE. Other clinical pre- and post-TACE variables were also found to be relevant for this prediction.
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Affiliation(s)
- Claudia Campani
- Internal Medicine and Hepatology Unit, Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Alessandro Vitale
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - Gabriele Dragoni
- Internal Medicine and Hepatology Unit, Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Umberto Arena
- Internal Medicine and Hepatology Unit, Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Giacomo Laffi
- Internal Medicine and Hepatology Unit, Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Umberto Cillo
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - Edoardo G. Giannini
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, IRCCS Policlinico San Martino, Genoa, Italy
| | - Francesco Tovoli
- Internal Medicine-Piscaglia Unit, Azienda Ospedaliero-Universitaria S. Orsola-Malpighi, University of Bologna, Bologna, Italy
| | | | | | | | - Marco Zoli
- Internal Medicine-Zoli Unit, Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Rodolfo Sacco
- Gastroenterology and Digestive Endoscopy Unit, Foggia University Hospital, Foggia, Italy
| | - Giuseppe Cabibbo
- Gastroenterology & Hepatology Unit, Department of Health Promotion, Mother & Child Care, Internal Medicine & Medical Specialties, PROMISE, University of Palermo, Palermo, Italy
| | - Andrea Mega
- Gastroenterology Unit, Bolzano Regional Hospital, Bolzano, Italy
| | - Maria Guarino
- Gastroenterology Unit, Department of Clinical Medicine and Surgery, University of Naples “Federico II”, Naples, Italy
| | - Antonio Gasbarrini
- Internal Medicine and Gastroenterology Unit, Policlinico Gemelli, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Gianluca Svegliati-Baroni
- Liver Injury and Transplant Unit, and Obesity Center, Polytechnic University of Marche, Ancona, Italy
| | | | - Elisabetta Biasini
- Infectious Diseases and Hepatology Unit, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy
| | - Alberto Masotto
- Gastroenterology Unit, Ospedale Sacro Cuore Don Calabria, Negrar, Italy
| | - Gerardo Nardone
- Hepato-Gastroenterology Unit, Department of Clinical Medicine and Surgery, University of Naples “Federico II”, Naples, Italy
| | - Giovanni Raimondo
- Clinical and Molecular Hepatology Unit, Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
| | - Francesco Azzaroli
- Gastroenterology Unit, Department of Surgical and Medical Sciences, Alma Mater Studiorum − Università of Bologna, Bologna, Italy
| | - Gianpaolo Vidili
- Department of Medical, Surgical and Experimental Sciences, Sassari, Italy
- Clinica Medica Unit, University of Sassari, Azienda Ospedaliero-Universitaria di Sassari, Sassari, Italy
| | - Maurizia Rossana Brunetto
- Hepatology and Liver Physiopathology Laboratory and Internal Medicine, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Fabio Farinati
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - Franco Trevisani
- Department of Medical and Surgical Sciences, Semeiotics Unit, Alma Mater Studiorum-University of Bologna, Bologna, Italy
| | - Fabio Marra
- Internal Medicine and Hepatology Unit, Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
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Ji J, Gu J, Wu JZ, Yang W, Shi HB, Liu S, Zhou WZ. The "Six-and-Twelve" Score for Recurrent HCC Patients Receiving TACE: Does it Still Work? Cardiovasc Intervent Radiol 2021; 44:720-727. [PMID: 33655358 DOI: 10.1007/s00270-021-02791-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2020] [Accepted: 01/30/2021] [Indexed: 01/10/2023]
Abstract
BACKGROUND A new prognostic model, the "six-and-twelve" (SAT) score, was suggested to be effective in selecting ideal transarterial chemoembolization (TACE) candidates from treatment naïve hepatocellular carcinoma (HCC) patients. However, whether the SAT score could also be applied in recurrent HCC patients with prior curative-intent treatments remains unknown. We aimed to validate and compare SAT focussing on these patients. METHODS From January 2014 to May 2019, 121 unresectable HCC patients with recurrence in Barcelona Clinic Liver Cancer (BCLC) A/B receiving TACE were enrolled. Survival distribution was evaluated by the Kaplan-Meier method compared by the log-rank test. Discriminatory ability was compared with the concordance index (C-index) to rank six prognostic systems (SAT, Four-and-seven, HAP, mHAP, mHAP2, mHAP3). The area under the curve (AUC) was performed to assess the mortality prediction at 1, 2, and 3 years. RESULTS In recurrent HCC patients receiving TACE, SAT had better performances in survival distribution. Due to the highest C-index, SAT was deemed the first ranking prognostic score. In terms of mortality prediction at 1, 2 and 3 years, SAT had the best mortality prediction at 2 and 3 years and mHAP3 had the best mortality prediction at 1 year. CONCLUSIONS Among the six prognostic systems analysed in ideal TACE patients with recurrences after curative-intent treatments, SAT was proven to be superior to other systems, suggesting that it could also be used in these patients.
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Affiliation(s)
- Jie Ji
- Department of Interventional Radiology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Gulou District, Nanjing, 210029, China
| | - Jie Gu
- Department of Interventional Radiology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Gulou District, Nanjing, 210029, China
| | - Jun-Zheng Wu
- Department of Interventional Radiology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Gulou District, Nanjing, 210029, China
| | - Wei Yang
- Department of Interventional Radiology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Gulou District, Nanjing, 210029, China
| | - Hai-Bin Shi
- Department of Interventional Radiology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Gulou District, Nanjing, 210029, China
| | - Sheng Liu
- Department of Interventional Radiology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Gulou District, Nanjing, 210029, China
| | - Wei- Zhong Zhou
- Department of Interventional Radiology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Gulou District, Nanjing, 210029, China.
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Chen M, Cao J, Hu J, Topatana W, Li S, Juengpanich S, Lin J, Tong C, Shen J, Zhang B, Wu J, Pocha C, Kudo M, Amedei A, Trevisani F, Sung PS, Zaydfudim VM, Kanda T, Cai X. Clinical-Radiomic Analysis for Pretreatment Prediction of Objective Response to First Transarterial Chemoembolization in Hepatocellular Carcinoma. Liver Cancer 2021; 10:38-51. [PMID: 33708638 PMCID: PMC7923935 DOI: 10.1159/000512028] [Citation(s) in RCA: 73] [Impact Index Per Article: 18.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2020] [Accepted: 09/23/2020] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND The preoperative selection of patients with intermediate-stage hepatocellular carcinoma (HCC) who are likely to have an objective response to first transarterial chemoembolization (TACE) remains challenging. OBJECTIVE To develop and validate a clinical-radiomic model (CR model) for preoperatively predicting treatment response to first TACE in patients with intermediate-stage HCC. METHODS A total of 595 patients with intermediate-stage HCC were included in this retrospective study. A tumoral and peritumoral (10 mm) radiomic signature (TPR-signature) was constructed based on 3,404 radiomic features from 4 regions of interest. A predictive CR model based on TPR-signature and clinical factors was developed using multivariate logistic regression. Calibration curves and area under the receiver operating characteristic curves (AUCs) were used to evaluate the model's performance. RESULTS The final CR model consisted of 5 independent predictors, including TPR-signature (p < 0.001), AFP (p = 0.004), Barcelona Clinic Liver Cancer System Stage B (BCLC B) subclassification (p = 0.01), tumor location (p = 0.039), and arterial hyperenhancement (p = 0.050). The internal and external validation results demonstrated the high-performance level of this model, with internal and external AUCs of 0.94 and 0.90, respectively. In addition, the predicted objective response via the CR model was associated with improved survival in the external validation cohort (hazard ratio: 2.43; 95% confidence interval: 1.60-3.69; p < 0.001). The predicted treatment response also allowed for significant discrimination between the Kaplan-Meier curves of each BCLC B subclassification. CONCLUSIONS The CR model had an excellent performance in predicting the first TACE response in patients with intermediate-stage HCC and could provide a robust predictive tool to assist with the selection of patients for TACE.
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Affiliation(s)
- Mingyu Chen
- Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University, Hangzhou, China
- Engineering Research Center of Cognitive Healthcare of Zhejiang Province, Hangzhou, China
- Zhejiang University School of Medicine, Hangzhou, China
| | - Jiasheng Cao
- Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University, Hangzhou, China
| | - Jiahao Hu
- Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University, Hangzhou, China
| | - Win Topatana
- Zhejiang University School of Medicine, Hangzhou, China
| | - Shijie Li
- Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University, Hangzhou, China
| | | | - Jian Lin
- General Surgery, Longyou People's Hospital, Quzhou, China
| | - Chenhao Tong
- General Surgery, Shaoxing People's Hospital, Shaoxing, China
| | - Jiliang Shen
- Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University, Hangzhou, China
| | - Bin Zhang
- Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University, Hangzhou, China
| | - Jennifer Wu
- Perlmutter Cancer Center, NYU Langone Health, New York, New York, USA
| | - Christine Pocha
- Avera McKennnan Hospital and University Medical Center, Sanford School of Medicine, University of South Dakota, Sioux Falls, South Dakota, USA
| | - Masatoshi Kudo
- Department of Gastroenterology and Hepatology, Kindai University School of Medicine, Osaka, Japan
| | - Amedeo Amedei
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Franco Trevisani
- Department of Medical and Surgical Sciences, Semeiotica Medica, Alma Mater Studiorum, University of Bologna, Bologna, Italy
| | - Pil Soo Sung
- Department of Internal Medicine, College of Medicine, Eunpyeong St. Mary's Hospital, Seoul, Republic of Korea
| | - Victor M. Zaydfudim
- Department of Surgery, Section of Hepatobiliary and Pancreatic Surgery, University of Virginia, Charlottesville, Virginia, USA
| | - Tatsuo Kanda
- Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan
| | - Xiujun Cai
- Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University, Hangzhou, China
- Engineering Research Center of Cognitive Healthcare of Zhejiang Province, Hangzhou, China
- Zhejiang Research and Development Engineering Laboratory of Minimally Invasive Technology and Equipment, Hangzhou, China
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Prince D, Liu K, Xu W, Chen M, Sun JY, Lu XJ, Ji J. Management of patients with intermediate stage hepatocellular carcinoma. Ther Adv Med Oncol 2020; 12:1758835920970840. [PMID: 33224278 PMCID: PMC7649909 DOI: 10.1177/1758835920970840] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2020] [Accepted: 10/08/2020] [Indexed: 12/12/2022] Open
Abstract
Hepatocellular carcinoma (HCC) causes a significant health burden globally and its impact is expected to increase in the coming years. Intermediate stage HCC, as defined by the Barcelona Clinic Liver Cancer (BCLC) system stage B, represents up to 30% of patients at diagnosis and encompasses a broad spectrum of tumor burden. Several attempts have been made to further subclassify this heterogenous group. The current standard of care recommended by BCLC for intermediate stage HCC patients is transarterial chemoembolization (TACE), with modest outcomes reported. While refinements have been made to TACE technique and patient selection, it remains non-curative. In the real-world setting, only 60% of patients with intermediate stage HCC receive TACE, with the remainder deviating to a range of other therapies that have shown promise in select patient subgroups. These include curative treatments (resection, ablation, and liver transplantation), radiotherapy (stereotactic and radioembolization), systemic therapies, and their combination. In this review, we summarize the classifications and current management for patients with intermediate stage HCC as well as highlight recent key developments in this space.
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Affiliation(s)
- David Prince
- AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Sydney, NSW, Australia
| | - Ken Liu
- AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Sydney, NSW, Australia
- Sydney Medical School, The University of Sydney, Sydney, NSW, Australia
- Liver Injury and Cancer Program, The Centenary Institute, Sydney, NSW, Australia
| | - Weiqi Xu
- Department of Hepatic Surgery, Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Minjiang Chen
- Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, The Fifth Affiliated Hospital of Wenzhou Medical University/Affiliated Lishui Hospital of Zhejiang University/The Central Hospital of Zhejiang Lishui, Lishui, China
- Department of Radiology, the Fifth Affiliated Hospital of Wenzhou Medical University/Affiliated Lishui Hospital of Zhejiang University/The Central Hospital of Zhejiang Lishui, Lishui, China
| | - Jin-Yu Sun
- Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Sparkfire Scientific Research Group, Nanjing Medical University, Nanjing, China
| | - Xiao-Jie Lu
- Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Jiansong Ji
- Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, The Fifth Affiliated Hospital of Wenzhou Medical University/Affiliated Lishui Hospital of Zhejiang University/The Central Hospital of Zhejiang Lishui, Lishui 323000, China
- Department of Radiology, the Fifth Affiliated Hospital of Wenzhou Medical University/Affiliated Lishui Hospital of Zhejiang University/The Central Hospital of Zhejiang Lishui, Lishui, 323000, China
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Chang Y, Jeong SW, Young Jang J, Jae Kim Y. Recent Updates of Transarterial Chemoembolilzation in Hepatocellular Carcinoma. Int J Mol Sci 2020; 21:E8165. [PMID: 33142892 PMCID: PMC7662786 DOI: 10.3390/ijms21218165] [Citation(s) in RCA: 185] [Impact Index Per Article: 37.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2020] [Revised: 10/28/2020] [Accepted: 10/28/2020] [Indexed: 12/24/2022] Open
Abstract
Transarterial chemoembolization (TACE) is a standard treatment for intermediate-stage hepatocellular carcinoma (HCC). In this review, we summarize recent updates on the use of TACE for HCC. TACE can be performed using two techniques; conventional TACE (cTACE) and drug-eluting beads using TACE (DEB-TACE). The anti-tumor effect of the two has been reported to be similar; however, DEB-TACE carries a higher risk of hepatic artery and biliary injuries and a relatively lower risk of post-procedural pain than cTACE. TACE can be used for early stage HCC if other curative treatments are not feasible or as a neoadjuvant treatment before liver transplantation. TACE can also be considered for selected patients with limited portal vein thrombosis and preserved liver function. When deciding to repeat TACE, the ART (Assessment for Retreatment with TACE) score and ABCR (AFP, BCLC, Child-Pugh, and Response) score can guide the decision process, and TACE refractoriness needs to be considered. Studies on the combination therapy of TACE with other treatment modalities, such as local ablation, radiation therapy, or systemic therapy, have been actively conducted and are still ongoing. Recently, new prognostic models, including analysis of the neutrophil-lymphocyte ratio, radiomics, and deep learning, have been developed to help predict survival after TACE.
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Affiliation(s)
- Young Chang
- Department of Internal Medicine, Digestive Disease Center, Institute for Digestive Research, Soonchunhyang University College of Medicine, Seoul 04401, Korea; (Y.C.); (J.Y.J.)
| | - Soung Won Jeong
- Department of Internal Medicine, Digestive Disease Center, Institute for Digestive Research, Soonchunhyang University College of Medicine, Seoul 04401, Korea; (Y.C.); (J.Y.J.)
| | - Jae Young Jang
- Department of Internal Medicine, Digestive Disease Center, Institute for Digestive Research, Soonchunhyang University College of Medicine, Seoul 04401, Korea; (Y.C.); (J.Y.J.)
| | - Yong Jae Kim
- Department of Radiology, Soonchunhyang University College of Medicine, Seoul 04401, Korea;
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Adhoute X, Pénaranda G, Raoul JL, Bronowicki JP, Anty R, Bourlière M. “Six-and-twelve” score for outcome prediction of hepatocellular carcinoma following transarterial chemoembolization. In-depth analysis from a multicenter French cohort. World J Hepatol 2020; 12:525-532. [PMID: 32952879 PMCID: PMC7475776 DOI: 10.4254/wjh.v12.i8.525] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2020] [Revised: 07/05/2020] [Accepted: 07/19/2020] [Indexed: 02/06/2023] Open
Abstract
The “six-and-twelve” (6&12) score is a new hepatocellular carcinoma (HCC) prognostic index designed for recommended transarterial chemoembolization (TACE) candidates. Quick and easy to use by the sum of tumor size (cm) and number, this model identifies three groups with different survival time (the sum is ≤ 6; or > 6 but ≤ 12; or > 12); a survival benefit with TACE can be expected for HCC patients with a score not exceeding twelve. Recently, Wang ZW et al showed that the “6&12” model was the best system correlated with radiological response after the first TACE. Thus, we wanted to assess its survival prediction ability as well as its prognostic value and compared it to other systems (Barcelona Clinic Liver Cancer, Hong Kong Liver Cancer (HKLC) staging, Albumin-Bilirubin grade, tumor nodularity, infiltrative nature of the tumor, alpha-fetoprotein, Child-Pugh class, and Performance Status score, Cancer of the Liver Italian Program, Model to Estimate Survival for HCC scores, up-to-seven criteria) different from Wang ZW et al study in a multicenter French cohort of HCC including only recommended TACE candidates retrospectively enrolled. As previously demonstrated, we show that the "6&12” score can classify survival within this French cohort, with a prognostic value comparable to that of other systems, except HKLC staging. More importantly, the “6&12” score simplicity and ability in patients’ stratification outperform other systems for a routine clinical practice.
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Affiliation(s)
- Xavier Adhoute
- Department of Gastroenterology and Hepatology, Hôpital Saint-Joseph, Marseille 13008, France
| | | | - Jean-Luc Raoul
- Department of Medical Oncology, Institut de Cancérologie de l'Ouest, Nantes 44805, France
| | - Jean-Pierre Bronowicki
- Department of Gastroenterology and Hepatology, Centre Hospitalo-Universitaire de, Nancy 54511, France
| | - Rodolphe Anty
- Department of Gastroenterology and Hepatology, Hôpital Universitaire de l’Archet, Nice 06200, France
| | - Marc Bourlière
- Department of Gastroenterology and Hepatology, Hôpital Saint-Joseph, Marseille 13008, France
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Meng XP, Wang YC, Ju S, Lu CQ, Zhong BY, Ni CF, Zhang Q, Yu Q, Xu J, Ji J, Zhang XM, Tang TY, Yang G, Zhao Z. Radiomics Analysis on Multiphase Contrast-Enhanced CT: A Survival Prediction Tool in Patients With Hepatocellular Carcinoma Undergoing Transarterial Chemoembolization. Front Oncol 2020; 10:1196. [PMID: 32850345 PMCID: PMC7396545 DOI: 10.3389/fonc.2020.01196] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2020] [Accepted: 06/12/2020] [Indexed: 12/12/2022] Open
Abstract
Patients with HCC receiving TACE have various clinical outcomes. Several prognostic models have been proposed to predict clinical outcomes for patients with hepatocellular carcinomas (HCC) undergoing transarterial chemoembolization (TACE), but establishing an accurate prognostic model remains necessary. We aimed to develop a radiomics signature from pretreatment CT to establish a combined radiomics-clinic (CRC) model to predict survival for these patients. We compared this CRC model to the existing prognostic models in predicting patient survival. This retrospective study included multicenter data from 162 treatment-naïve patients with unresectable HCC undergoing TACE as an initial treatment from January 2007 and March 2017. We randomly allocated patients to a training cohort (n = 108) and a testing cohort (n = 54). Radiomics features were extracted from intra- and peritumoral regions on both the arterial phase and portal venous phase CT images. A radiomics signature (Rad-signature) for survival was constructed using the least absolute shrinkage and selection operator method in the training cohort. We used univariate and multivariate Cox regressions to identify associations between the Rad- signature and clinical factors of survival. From these, a CRC model was developed, validated, and further compared with previously published prognostic models including four-and-seven criteria, six-and-twelve score, hepatoma arterial-embolization prognostic scores, and albumin-bilirubin grade. The CRC model incorporated two variables: The Rad-signature (composed of features extracted from intra- and peritumoral regions on the arterial phase and portal venous phase) and tumor number. The CRC model performed better than the other seven well-recognized prognostic models, with concordance indices of 0.73 [95% confidence interval (CI) 0.68–0.79] and 0.70 [95% CI 0.62–0.82] in the training and testing cohorts, respectively. Among the seven models tested, the six-and-12 score and four-and-seven criteria performed better than the other models, with C-indices of 0.64 [95% CI 0.58–0.70] and 0.65 [95% CI 0.55–0.75] in the testing cohort, respectively. The CT radiomics signature represents an independent biomarker of survival in patients with HCC undergoing TACE, and the CRC model displayed improved predictive performance.
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Affiliation(s)
- Xiang-Pan Meng
- Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School of Southeast University, Nanjing, China
| | - Yuan-Cheng Wang
- Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School of Southeast University, Nanjing, China
| | - Shenghong Ju
- Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School of Southeast University, Nanjing, China
| | - Chun-Qiang Lu
- Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School of Southeast University, Nanjing, China
| | - Bin-Yan Zhong
- Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Cai-Fang Ni
- Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Qi Zhang
- Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School of Southeast University, Nanjing, China
| | - Qian Yu
- Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School of Southeast University, Nanjing, China
| | - Jian Xu
- Department of Interventional Radiology, Jinling Hospital, Medical School of Nanjing University, Nanjing, China
| | - JianSong Ji
- Department of Radiology, Affiliated Lishui Hospital of Zhejiang University, The Central Hospital of Zhejiang Lishui, Lishui, China
| | - Xiu-Ming Zhang
- Department of Radiology, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Nanjing, China
| | - Tian-Yu Tang
- Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School of Southeast University, Nanjing, China
| | - Guanyu Yang
- LIST, Key Laboratory of Computer Network and Information Integration, Southeast University, Ministry of Education, Nanjing, China
| | - Ziteng Zhao
- LIST, Key Laboratory of Computer Network and Information Integration, Southeast University, Ministry of Education, Nanjing, China
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Han G, Berhane S, Toyoda H, Bettinger D, Elshaarawy O, Chan AWH, Kirstein M, Mosconi C, Hucke F, Palmer D, Pinato DJ, Sharma R, Ottaviani D, Jang JW, Labeur TA, van Delden OM, Pirisi M, Stern N, Sangro B, Meyer T, Fateen W, García‐Fiñana M, Gomaa A, Waked I, Rewisha E, Aithal GP, Travis S, Kudo M, Cucchetti A, Peck‐Radosavljevic M, Takkenberg R, Chan SL, Vogel A, Johnson PJ. Prediction of Survival Among Patients Receiving Transarterial Chemoembolization for Hepatocellular Carcinoma: A Response-Based Approach. Hepatology 2020; 72:198-212. [PMID: 31698504 PMCID: PMC7496334 DOI: 10.1002/hep.31022] [Citation(s) in RCA: 95] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2019] [Accepted: 10/28/2019] [Indexed: 01/27/2023]
Abstract
BACKGROUND AND AIMS The heterogeneity of intermediate-stage hepatocellular carcinoma (HCC) and the widespread use of transarterial chemoembolization (TACE) outside recommended guidelines have encouraged the development of scoring systems that predict patient survival. The aim of this study was to build and validate statistical models that offer individualized patient survival prediction using response to TACE as a variable. APPROACH AND RESULTS Clinically relevant baseline parameters were collected for 4,621 patients with HCC treated with TACE at 19 centers in 11 countries. In some of the centers, radiological responses (as assessed by modified Response Evaluation Criteria in Solid Tumors [mRECIST]) were also accrued. The data set was divided into a training set, an internal validation set, and two external validation sets. A pre-TACE model ("Pre-TACE-Predict") and a post-TACE model ("Post-TACE-Predict") that included response were built. The performance of the models in predicting overall survival (OS) was compared with existing ones. The median OS was 19.9 months. The factors influencing survival were tumor number and size, alpha-fetoprotein, albumin, bilirubin, vascular invasion, cause, and response as assessed by mRECIST. The proposed models showed superior predictive accuracy compared with existing models (the hepatoma arterial embolization prognostic score and its various modifications) and allowed for patient stratification into four distinct risk categories whose median OS ranged from 7 months to more than 4 years. CONCLUSIONS A TACE-specific and extensively validated model based on routinely available clinical features and response after first TACE permitted patient-level prognostication.
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Affiliation(s)
- Guohong Han
- Department of Liver Disease and Digestive Interventional RadiologyXijing Hospital of Digestive DiseaseFourth Military Medical UniversityXi’anChina
| | - Sarah Berhane
- Department of BiostatisticsUniversity of LiverpoolLiverpoolUnited Kingdom
| | - Hidenori Toyoda
- Department of Gastroenterology and HepatologyOgaki Municipal HospitalOgakiJapan
| | - Dominik Bettinger
- Department of Medicine IIFaculty of MedicineMedical Center University of FreiburgUniversity of FreiburgFreiburgGermany
| | - Omar Elshaarawy
- National Liver InstituteMenoufia UniversityShebeen El‐KomEgypt
| | | | - Martha Kirstein
- Department of Gastroenterology, Hepatology and EndocrinologyHannover Medical SchoolHannoverGermany
| | - Cristina Mosconi
- Radiology UnitDepartment of SpecializedDiagnostic and Experimental MedicineAlma Mater Studiorum ‐ University of BolognaItaly University Hospital of Bologna Sant'Orsola‐Malpighi PolyclinicBolognaItaly
| | - Florian Hucke
- Department of Internal Medicine and GastroenterologyKlinikum Klagenfurt am WörtherseeKlagenfurtAustria
| | - Daniel Palmer
- Department of Molecular and Clinical Cancer MedicineUniversity of LiverpoolLiverpoolUnited Kingdom
| | - David J. Pinato
- Department of Surgery and CancerImperial College LondonLondonUnited Kingdom
| | - Rohini Sharma
- Department of Surgery and CancerImperial College LondonLondonUnited Kingdom
| | - Diego Ottaviani
- UCL Cancer InstituteUniversity College LondonLondonUnited Kingdom
| | - Jeong W. Jang
- Department of Internal MedicineThe Catholic University of KoreaSeoul St. Mary’s HospitalSeoulRepublic of Korea
| | - Tim A. Labeur
- Department of Gastroenterology and HepatologyAmsterdam University Medical CenterAmsterdamthe Netherlands
| | - Otto M. van Delden
- Department of RadiologyAmsterdam University Medical CentersAmsterdamthe Netherlands
| | - Mario Pirisi
- Department of Translational MedicineUniversità del Piemonte OrientaleNovaraItaly
| | - Nick Stern
- Department of Gastroenterology and HepatologyAintree University HospitalLiverpoolUnited Kingdom
| | - Bruno Sangro
- Liver UnitClínica Universidad de Navarra IDISNA and CIBEREHDPamplonaSpain
| | - Tim Meyer
- Research Department of OncologyUCL Cancer InstituteUniversity College LondonLondonUnited Kingdom
| | - Waleed Fateen
- National Institute for Health Research Nottingham Biomedical Research CentreNottingham University Hospitals National Health Service Trust and the University of NottinghamNottinghamUnited Kingdom
- Nottingham Digestive Diseases CentreSchool of MedicineUniversity of NottinghamNottinghamUnited Kingdom
| | | | - Asmaa Gomaa
- National Liver InstituteMenoufia UniversityShebeen El‐KomEgypt
| | - Imam Waked
- National Liver InstituteMenoufia UniversityShebeen El‐KomEgypt
| | - Eman Rewisha
- National Liver InstituteMenoufia UniversityShebeen El‐KomEgypt
| | - Guru P. Aithal
- National Institute for Health Research Nottingham Biomedical Research CentreNottingham University Hospitals National Health Service Trust and the University of NottinghamNottinghamUnited Kingdom
- Nottingham Digestive Diseases CentreSchool of MedicineUniversity of NottinghamNottinghamUnited Kingdom
| | - Simon Travis
- Department of RadiologyNottingham University Hospitals National Health Service TrustNottinghamUnited Kingdom
| | - Masatoshi Kudo
- Department of Gastroenterology and HepatologyKinki University School of MedicineOsaka‐SayamaOsakaJapan
| | | | - Markus Peck‐Radosavljevic
- Department of Internal Medicine and GastroenterologyKlinikum Klagenfurt am WörtherseeKlagenfurtAustria
| | - R.B. Takkenberg
- Department of Gastroenterology and HepatologyAmsterdam University Medical CenterAmsterdamthe Netherlands
| | - Stephen L. Chan
- Department of Clinical OncologyChinese University of Hong KongShatinHong Kong
| | - Arndt Vogel
- Department of Gastroenterology, Hepatology and EndocrinologyHannover Medical SchoolHannoverGermany
| | - Philip J. Johnson
- Department of Molecular and Clinical Cancer MedicineUniversity of LiverpoolLiverpoolUnited Kingdom
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Hu K, Lu S, Li M, Zhang F, Tang B, Yuan J, Shan Y, Xu P, Chen R, Ren Z, Yin X. A Novel Pre-treatment Model Predicting Risk of Developing Refractoriness to Transarterial Chemoembolization in Unresectable Hepatocellular Carcinoma. J Cancer 2020; 11:4589-4596. [PMID: 32489476 PMCID: PMC7255373 DOI: 10.7150/jca.44847] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2020] [Accepted: 05/02/2020] [Indexed: 12/16/2022] Open
Abstract
Background and aim: Refractoriness to transarterial chemoembolization is common during the therapeutic process of hepatocellular carcinoma, which is an intractable issue and may compromise the prognosis. We aim to establish a pre-treatment model to identify patients with high risks of refractoriness. Methods: From 2010 to 2016, 824 treatment-naive patients who had initially underwent at least two sessions of transarterial chemoembolization in Zhongshan Hospital, Fudan University were retrospectively enrolled. These patients were randomly allocated into a training cohort and a validation cohort. The pre-treatment scoring model was established based on the clinical and radiological variables using logistic regression and nomogram. The discrimination and calibration of the model were also evaluated. Results: Logistic regression identified vascularization pattern, ALBI grade, serum alpha-fetoprotein level, serum γ-glutamyl transpeptidase level and major tumor size as the key parameters related to refractoriness. The p-TACE model was established using these variables (risk score range: 0-19.5). Patients were divided into six risk subgroups based on their scores (<4, ≥4, ≥7, ≥10, ≥13, ≥16). The discriminative ability, as determined by the area under receiver operating characteristic curve was 0.784 (95% confidence interval: 0.741-0.827) in the training cohort and 0.743 (95% confidence interval: 0.696-0.789) in the validation cohort. Moreover, satisfactory calibration was confirmed by Hosmer-Lemeshow test with P values of 0.767 and 0.913 in the training cohort and validation cohort. Conclusions: This study presents a pre-treatment model to identify patients with high risks of refractoriness after transarterial chemoembolization and shed light on clinical decision making.
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Affiliation(s)
- Keshu Hu
- Liver Cancer Institute & Zhongshan Hospital, Fudan University, Shanghai, China; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education
| | - Shenxin Lu
- Liver Cancer Institute & Zhongshan Hospital, Fudan University, Shanghai, China; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education
| | - Miao Li
- Liver Cancer Institute & Zhongshan Hospital, Fudan University, Shanghai, China; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education
| | - Feng Zhang
- Liver Cancer Institute & Zhongshan Hospital, Fudan University, Shanghai, China; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education
| | - Bei Tang
- Liver Cancer Institute & Zhongshan Hospital, Fudan University, Shanghai, China; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education
| | - Jia Yuan
- Liver Cancer Institute & Zhongshan Hospital, Fudan University, Shanghai, China; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education
| | - Yan Shan
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Pengju Xu
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Rongxin Chen
- Liver Cancer Institute & Zhongshan Hospital, Fudan University, Shanghai, China; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education
| | - Zhenggang Ren
- Liver Cancer Institute & Zhongshan Hospital, Fudan University, Shanghai, China; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education
| | - Xin Yin
- Liver Cancer Institute & Zhongshan Hospital, Fudan University, Shanghai, China; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education
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Predictive performance of the mHAP-II score in a real-life western cohort with hepatocellular carcinoma following trans-arterial chemoembolisation with drug-eluting beads (DEB-TACE). Eur Radiol 2020; 30:3782-3792. [PMID: 32125515 PMCID: PMC7305077 DOI: 10.1007/s00330-020-06734-8] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2019] [Revised: 02/05/2020] [Accepted: 02/07/2020] [Indexed: 12/26/2022]
Abstract
Objectives To evaluate the predictive performance of the modified hepatoma arterial embolisation prognostic II (mHAP-II) score in a real-life western hepatocellular carcinoma (HCC) cohort treated with drug-eluting bead-TACE and compare the mHAP-II with other scores in this cohort. Methods One hundred seventy-nine HCC patients (mean age 77 (± 9) years, 87% male) with one or more drug-eluting bead (DEB)-TACE sessions using 100–300 μm microspheres were retrospectively analysed. Performance analysis of the mHAP-II score was based on Mann-Whitney U tests, the Kaplan-Meier method, log-rank tests, receiver operating characteristics, Akaike’s information criterion and Cox regression models. Results In this population, HCC risk factors were mainly alcohol abuse (31%) and hepatitis C (28%). The median survival of the entire cohort was 29.4 months. mHAP-II classification of the cohort was mHAP-II B (30%), C (41%) and D (23%) respectively. Survival of all subgroups differed significantly from each other (each p < 0.05). Area under the curve for receiver operating characteristic was 0.60 and Akaike’s information criterion was 21.8 (p = 0.03), indicating a superior performance of mHAP-II score compared with HAP score and BCLC. Tumour number ≥ two (HR 1.54), alpha-fetoprotein > 400 μg/l (HR 1.14), serum albumin < 3.6 g/dl (HR 1.63) and total bilirubin > 0.9 mg/dl (HR 1.58) contributed significantly in Cox proportional hazards regression (each p < 0.05). Conclusion The mHAP-II score can predict survival outcomes of western HCC patients undergoing DEB-TACE and further subdivide this heterogeneous group; however, certain limitations concerning the predictive power of mHAP-II score must be taken into account. Key Points • This retrospective study evaluated the predictive performance of the modified hepatoma arterial embolisation prognostic II (mHAP-II) score in a real-life western HCC cohort treated with drug-eluting bead-TACE. • Survival of all mHAP-II subgroups differed significantly, area under the curve for mHAP-II was 0.60 and Akaike’s information criterion was 21.8. • The mHAP-II score can predict survival outcomes of western HCC patients undergoing DEB-TACE and further subdivide this heterogeneous group. However, because the study is underpowered, true survival prediction may be more difficult to infer.
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Wang ZX, Wang EX, Bai W, Xia DD, 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, Han GH, on behalf of China HCC-TACE Study Group. Validation and evaluation of clinical prediction systems for first and repeated transarterial chemoembolization in unresectable hepatocellular carcinoma: A Chinese multicenter retrospective study. World J Gastroenterol 2020; 26:657-669. [PMID: 32103874 PMCID: PMC7029354 DOI: 10.3748/wjg.v26.i6.657] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2019] [Revised: 01/09/2020] [Accepted: 01/14/2020] [Indexed: 02/06/2023] Open
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.
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Affiliation(s)
- Zhe-Xuan Wang
- 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
| | - En-Xin Wang
- 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 Bai
- 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
| | - Dong-Dong Xia
- 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
- 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
- Department of Hepatobiliary Surgery, the Second Affiliated Hospital of Third Military Medical University, Chongqing 400037, China
| | - Qiao-Yi Yang
- 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
| | - 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
| | - Qiu-He Wang
- 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
| | - Jing Li
- 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
- Department of Hepatobiliary Surgery, the Second Affiliated Hospital of Third Military Medical University, Chongqing 400037, China
| | - Jie Yuan
- 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
| | - Xiao-Mei Li
- 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
| | - Jing Niu
- 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
| | - Zhan-Xin Yin
- 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
| | - Jie-Lai Xia
- Department of Health Statistics, Fourth Military Medical University, Xi’an, Xi’an 710032, Shaanxi Province, China
| | - Dai-Ming Fan
- 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
| | - 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
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Marquardt JU, Saborowski A, Czauderna C, Vogel A. The Changing Landscape of Systemic Treatment of Advanced Hepatocellular Carcinoma: New Targeted Agents and Immunotherapies. Target Oncol 2020; 14:115-123. [PMID: 30805831 DOI: 10.1007/s11523-019-00624-w] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Hepatocellular carcinoma (HCC) is one of the most common and deadliest cancers worldwide with a rising incidence in the Western world. HCCs are characterized by high resistance to systemic therapies induced by phenotypic and molecular heterogeneity. For almost 10 years, the tyrosine kinase inhibitor sorafenib was the only approved treatment for advanced HCCs in patients with preserved liver function, and until 2016, no new compounds tested in large phase III studies have led to a survival benefit. The tyrosine kinase inhibitor regorafenib, a fluorinated sorafenib analog, was the first substance that showed a significant improvement in overall survival after failure of sorafenib treatment, which subsequently led to its regulatory approval in a second-line setting in 2017. In addition, the non-inferiority of lenvatinib in comparison with sorafenib opened another therapeutic first-line option in the same year. Furthermore, several other compounds showed promising results in recent phase III studies, including ramucirumab in patients with elevated alpha-fetoprotein (AFP) levels as well as cabozantinib in second- and third-line settings. In addition, promising early reports of the immune checkpoint inhibitors nivolumab and pembrolizumab, with objective response rates of 15-20%, paved the way for immuno-oncological interventions for HCC and these will probably gain increasing attention as mono- and combination therapies. In summary, following the approval of sorafenib in 2007 and almost 10 years of therapeutic stagnation, results from recent clinical trials in first- and further-line settings for the first time demonstrated efficacy of several active compounds in advanced HCCs. Thus, a sequential approach should now be implemented in HCC treatment and will improve the survival of HCC patients.
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Affiliation(s)
- Jens U Marquardt
- Department of Medicine, Lichtenberg Research Group for Molecular Hepatocarcinogenesis, University of Mainz, Mainz, Germany
| | - Anna Saborowski
- Department of Gastroenterology, Hepatology and Endocrinology, Medizinische Hochschule, Hannover, Germany
| | - Carolin Czauderna
- Department of Medicine, Lichtenberg Research Group for Molecular Hepatocarcinogenesis, University of Mainz, Mainz, Germany
| | - Arndt Vogel
- Department of Gastroenterology, Hepatology and Endocrinology, Medizinische Hochschule, Hannover, Germany.
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Adhoute X, Pénaranda G, Raoul JL, Pietri O, Bronowicki JP, Castellani P, Perrier H, Monnet O, Bayle O, Oules V, Pol B, Beaurain P, Muller C, Cassagneau P, Bourlière M. Hepatocellular carcinoma macroscopic gross appearance on imaging: predictor of outcome after transarterial chemoembolization in a real-life multicenter French cohort. Eur J Gastroenterol Hepatol 2019; 31:1414-1423. [PMID: 31045613 DOI: 10.1097/meg.0000000000001420] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
BACKGROUND Conventional transarterial chemoembolization (cTACE) with lipiodol is widely performed in patients with hepatocellular carcinoma (HCC) unsuitable for curative treatment. Additional tumor parameters such as HCC macroscopic appearance based on imaging might be helpful for transarterial chemoembolization prognostication and management. PATIENTS AND METHODS A total of 405 patients with HCC who underwent cTACE between 2008 and 2016 from a real-life multicenter French cohort were retrospectively reviewed. Tumors were classified into two macroscopic types according to HCC gross appearance on imaging: nodular versus non-nodular. The study population was stratified into two groups: derivation and validation cohorts. Independent prognostic factors of survival based on multivariate cox regression models were determined and then assessed in the validation set. Thereafter, time to progression (TTP) and radiological response rate were investigated for each prognostic factors of survival. RESULTS Median overall survival (OS) was 35 months for Barcelona Clinic Liver Cancer (BCLC) stage A, 22 months for BCLC stage B and 12 months for BCLC stage C patients (P < 0.0001). The corresponding TTP for these patients was 12 (7-17) months, 5 (3-6) months and 1.2 (1.2-3) months (P < 0.0001). Multivariate analysis revealed that tumors size and number, non-nodular type, alpha-fetoprotein, aspartate aminotransferase serum levels and impairment of performance status-1 were independent predictors of survival among the study groups. Non-nodular type was the most powerful factor that influences OS, TTP and radiological response rate for the recommended transarterial chemoembolization candidates. TTP was consistent with OS within each stage. CONCLUSION HCC macroscopic appearance on imaging is a determinant predictor of outcome after cTACE in a real-life multicenter cohort.
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Affiliation(s)
| | | | - Jean-Luc Raoul
- Department of Medical Oncology, Institut de Cancérologie de l'Ouest Nantes, Saint-Herblain
| | | | - Jean-Pierre Bronowicki
- Department of Gastroenterology and Hepatology, Centre Hospitalo-Universitaire de Nancy, Nancy, France
| | | | | | - Olivier Monnet
- Department of Interventional Radiology and Medical Imaging
| | - Olivier Bayle
- Department of Interventional Radiology and Medical Imaging
| | | | - Bernard Pol
- Department of Hepatobiliary Surgery, Hôpital Saint-Joseph Marseille
| | | | - Cyrille Muller
- Department of Interventional Radiology and Medical Imaging
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Reply to: "The "six-and-twelve score" for TACE treatment: Does it really help us?". J Hepatol 2019; 71:1053-1054. [PMID: 31500855 DOI: 10.1016/j.jhep.2019.07.009] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2019] [Revised: 07/08/2019] [Accepted: 07/11/2019] [Indexed: 01/22/2023]
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Lee IC, Hung YW, Liu CA, Lee RC, Su CW, Huo TI, Li CP, Chao Y, Lin HC, Hou MC, Huang YH. A new ALBI-based model to predict survival after transarterial chemoembolization for BCLC stage B hepatocellular carcinoma. Liver Int 2019; 39:1704-1712. [PMID: 31319016 DOI: 10.1111/liv.14194] [Citation(s) in RCA: 69] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2019] [Revised: 06/29/2019] [Accepted: 07/07/2019] [Indexed: 12/13/2022]
Abstract
BACKGROUND & AIMS Transarterial chemoembolization (TACE) is a standard treatment for Barcelona Clinic Liver Cancer (BCLC) stage B hepatocellular carcinoma (HCC), but the outcome varied. This study aimed to develop a model to predict the outcome of TACE in HCC patients. METHODS Consecutive 570 treatment-naïve BCLC stage B HCC patients undergoing TACE as the initial treatment from 2007 to 2016 were retrospectively enrolled. Factors associated with survival were analysed. Patients undergoing TACE from 2007 to 2011 constituted the training cohort (n = 293), while patients undergoing TACE from 2012 to 2016 constituted the validation cohort (n = 277). Homogeneity and corrected Akaike information criterion (AICc) were compared between each prognostic model. RESULTS A total of 1796 TACE sessions were performed for the 570 patients during the median follow-up period of 18.3 months. By multivariate analysis, beyond up-to-11 criteria (hazard ratio [HR] = 1.694, P < .001), alpha-foetoprotein >200 ng/mL (HR = 1.771, P < .001) and albumin-bilirubin (ALBI) grade 2 or 3 (HR = 1.817, P < .001) were independent predictors of overall survival (OS) in the training cohort. An ALBI-TAE model based on the three independent predictors of OS from the training cohort was developed to classify HCC patients into four subgroups. The performance of the ALBI-TAE model was superior to other prognostic models with lowest AICc values and highest homogeneity in both the training and validation datasets as well as the overall cohort. CONCLUSIONS Albumin-bilirubin grade is an important factor associated with survival in BCLC stage B HCC patients undergoing TACE. ALBI-TAE model can be applied to select patients who can get most benefit from TACE.
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Affiliation(s)
- I-Cheng Lee
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.,Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
| | - Ya-Wen Hung
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Chien-An Liu
- Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan.,Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Rheun-Chuan Lee
- Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Chien-Wei Su
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.,Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
| | - Teh-Ia Huo
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.,Institute of Pharmacology, National Yang-Ming University School of Medicine, Taipei, Taiwan
| | - Chung-Pin Li
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.,Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
| | - Yee Chao
- Cancer Center, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Han-Chieh Lin
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.,Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
| | - Ming-Chih Hou
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.,Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
| | - Yi-Hsiang Huang
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.,Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan.,Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan
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Elshaarawy O, Gomaa A, Omar H, Rewisha E, Waked I. Intermediate stage hepatocellular carcinoma: a summary review. J Hepatocell Carcinoma 2019; 6:105-117. [PMID: 31372364 PMCID: PMC6628956 DOI: 10.2147/jhc.s168682] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2019] [Accepted: 06/14/2019] [Indexed: 12/12/2022] Open
Abstract
It is well known that intermediate stage hepatocellular carcinoma (HCC) encompasses the widest class of patients with this disease. The main characteristic of this special sub-group of patients is that it is extensively heterogenous. This substantial heterogeneity is due to the wide range of liver functions of such patients and variable tumor numbers and sizes. Real world clinical data show huge support for transarterial chemo-embolization (TACE) as a therapeutic modality for intermediate stage HCC, applied in 50%-60% of those class of patients. There are special considerations in various international guidelines regarding treatment allocation in intermediate stage HCC. There is an epidemiological difference in HCC in eastern and western cohorts, and various guidelines have been proposed. In patients with HCC, it has frequently been reported that there is poor correlation between the clinical benefit and real gain in patient condition and the conventional way of tumor response assessment after locoregional treatments. This is due to the evaluation criteria in addition to the scoring systems used for treatment allocation in those patients. It became clear that intermediate stage HCC patients receiving TACE need a proper prognostic score that offers valid clinical prediction and supports proper decision-making. Also, it is the proper time to study more treatment options beyond TACE, such as multimodal regimens for this class of patients. In this review, we tried to provide a summary of the challenges and future directions in managing patients with intermediate stage HCC.
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Affiliation(s)
- Omar Elshaarawy
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebeen El-Kom, Egypt
| | - Asmaa Gomaa
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebeen El-Kom, Egypt
| | - Hazem Omar
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebeen El-Kom, Egypt
| | - Eman Rewisha
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebeen El-Kom, Egypt
| | - Imam Waked
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebeen El-Kom, Egypt
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Development of a prognostic score for recommended TACE candidates with hepatocellular carcinoma: A multicentre observational study. J Hepatol 2019; 70:893-903. [PMID: 30660709 DOI: 10.1016/j.jhep.2019.01.013] [Citation(s) in RCA: 160] [Impact Index Per Article: 26.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2018] [Revised: 12/27/2018] [Accepted: 01/04/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Previous prognostic scores for transarterial chemoembolization (TACE) were mainly derived from real-world settings, which are beyond guideline recommendations. A robust model for outcome prediction and risk stratification of recommended TACE candidates is lacking. We aimed to develop an easy-to-use tool specifically for these patients. METHODS Between January 2010 and May 2016, 1,604 treatment-naïve patients with unresectable hepatocellular carcinoma (HCC), Child-Pugh A5-B7 and performance status 0 undergoing TACE were included from 24 tertiary centres. Patients were randomly divided into training (n = 807) and validation (n = 797) cohorts. A prognostic model was developed and subsequently validated. Predictive performance and discrimination were further evaluated and compared with other prognostic models. RESULTS The final presentation of the model was "linear predictor = largest tumour diameter (cm) + tumour number", which consistently outperformed other currently available models in both training and validation datasets as well as in different subgroups. The thirtieth percentile and the third quartile of the linear predictor, namely 6 and 12, were further selected as cut-off values, leading to the "six-and-twelve" score which could divide patients into 3 strata with the sum of tumour size and number ≤6, >6 but ≤12, and >12 presenting significantly different median survival of 49.1 (95% CI 43.7-59.4) months, 32.0 (95% CI 29.9-37.5) months, and 15.8 (95% CI 14.1-17.7) months, respectively. CONCLUSIONS The six-and-twelve score may prove an easy-to-use tool to stratify recommended TACE candidates (Barcelona Clinic Liver Cancer stage-A/B) and predict individual survival with favourable performance and discrimination. Moreover, the score could stratify these patients in clinical practice as well as help design clinical trials with comparable criteria involving these patients. Further external validation of the score is required. LAY SUMMARY There is currently no prognostic model specifically developed for recommended or ideal transarterial chemoembolization (TACE) candidates with hepatocellular carcinoma, despite these patients being frequently identified as the best target population in pivotal randomized controlled trials. The six-and-twelve score provides patient survival prediction, especially in ideal candidates of TACE, outperforming other currently available models in both training and validation sets, as well as different subgroups. With cut-off values of 6 and 12, the score can stratify ideal TACE candidates into 3 strata with significantly different outcomes and may shed light on risk stratification of these patients in clinical practice as well as in clinical trials.
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Park Y, Kim BK, Park JY, Kim DY, Ahn SH, Han KH, Yeon JE, Byun KS, Kim HS, Kim JH, Kim SU. Feasibility of dynamic risk assessment for patients with repeated trans-arterial chemoembolization for hepatocellular carcinoma. BMC Cancer 2019; 19:363. [PMID: 30991968 PMCID: PMC6469056 DOI: 10.1186/s12885-019-5495-6] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2018] [Accepted: 03/20/2019] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND Hepatoma arterial-embolization prognostic (HAP) score and its modifications (modified HAP [mHAP] and mHAP-II), consisting of some or all of the following factors of tumor size, number, alpha-fetoprotein, bilirubin, and serum albumin, have been found to predict outcomes after trans-arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC). We investigated the feasibility of using HAP-related risk scores for dynamic risk assessment during repeated TACE. METHODS A total of 619 HCC patients treated with TACE from two institutions between 2003 and 2010 were included. RESULTS Patients with A-B class risk scores showed significantly better survival than those with C-D class risk scores at the first (median 43.7 vs. 21.5 months for mHAP-II, 35.2 vs. 10.2 months for mHAP, and 39.8 vs. 18.6 months for HAP; all P < 0.001) and the second rounds of TACE (38.6 vs. 17.2 months for mHAP-II, 30.0 vs. 8.5 months for mHAP, and 32.6 vs. 17.3 months for HAP; all P < 0.001). Sequential assessment of risk scores at the second TACE round was applied for patients with A-B class risk scores at the first TACE round, which further identified two subgroups of A-B and C-D class risk scores with different outcomes (median survival 40.6 vs. 19.6 months for mHAP-II, 31.2 vs. 16.9 months for mHAP, and 35.8 vs. 21.0 months for HAP; all P < 0.001). Compared with mHAP and HAP, mHAP-II showed the highest likelihood ratio (22.61 vs. 14.67 and 13.97, respectively), highest linear trend (24.43 vs. 19.67 and 14.19, respectively), and lowest Akaike information criteria value (1432.51 vs. 3412.29 and 2296.98, respectively). CONCLUSIONS All HAP-related risk scores dynamically predicted outcomes during repeated TACE. Sequential risk assessment using mHAP-II best identified optimal candidates for repeated TACE.
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Affiliation(s)
- Yehyun Park
- Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun–gu, Seoul, 120–752 South Korea
| | - Beom Kyung Kim
- Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun–gu, Seoul, 120–752 South Korea
- Liver Cirrhosis Clinical Research Center, Seoul, South Korea
| | - Jun Yong Park
- Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun–gu, Seoul, 120–752 South Korea
- Liver Cirrhosis Clinical Research Center, Seoul, South Korea
| | - Do Young Kim
- Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun–gu, Seoul, 120–752 South Korea
- Liver Cirrhosis Clinical Research Center, Seoul, South Korea
| | - Sang Hoon Ahn
- Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun–gu, Seoul, 120–752 South Korea
- Liver Cirrhosis Clinical Research Center, Seoul, South Korea
| | - Kwang-Hyub Han
- Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun–gu, Seoul, 120–752 South Korea
- Liver Cirrhosis Clinical Research Center, Seoul, South Korea
| | - Jong Eun Yeon
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University College of Medicine, 148, Gurodong-ro, Guro-gu, Seoul, 08308 South Korea
| | - Kwan Soo Byun
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University College of Medicine, 148, Gurodong-ro, Guro-gu, Seoul, 08308 South Korea
| | - Hye Soo Kim
- Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun–gu, Seoul, 120–752 South Korea
| | - Ji Hoon Kim
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University College of Medicine, 148, Gurodong-ro, Guro-gu, Seoul, 08308 South Korea
| | - Seung Up Kim
- Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun–gu, Seoul, 120–752 South Korea
- Liver Cirrhosis Clinical Research Center, Seoul, South Korea
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Mähringer-Kunz A, Weinmann A, Schmidtmann I, Koch S, Schotten S, Pinto Dos Santos D, Pitton MB, Dueber C, Galle PR, Kloeckner R. Validation of the SNACOR clinical scoring system after transarterial chemoembolisation in patients with hepatocellular carcinoma. BMC Cancer 2018; 18:489. [PMID: 29703174 PMCID: PMC5923193 DOI: 10.1186/s12885-018-4407-5] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2017] [Accepted: 04/18/2018] [Indexed: 02/06/2023] Open
Abstract
Background Transarterial chemoembolisation is the standard of care for intermediate stage (BCLC B) hepatocellular carcinoma, but it is challenging to decide when to repeat or stop treatment. Here we performed the first external validation of the SNACOR (tumour Size and Number, baseline Alpha-fetoprotein, Child-Pugh and Objective radiological Response) risk prediction model. Methods A total of 1030 patients with hepatocellular carcinoma underwent transarterial chemoembolisation at our tertiary referral centre from January 2000 to December 2016. We determined the following variables that were needed to calculate the SNACOR at baseline: tumour size and number, alpha-fetoprotein level, Child-Pugh class, and objective radiological response after the first transarterial chemoembolisation. Overall survival, time-dependent area under receiver-operating characteristic curves, Harrell’s C-index, and the integrated Brier score were calculated to assess predictive ability. Finally, multivariate analysis was performed to identify independent predictors of survival. Results The study included 268 patients. Low, intermediate, and high SNACOR scores predicted a median survival of 31.5, 19.9, and 9.2 months, respectively. The areas under the receiver-operating characteristic curve for overall survival were 0.641, 0.633, and 0.609 at 1, 3, and 6 years, respectively. Harrell’s C-index was 0.59, and the integrated Brier Score was 0.175. Independent predictors of survival included tumour size (P < 0.001), baseline alpha-fetoprotein level (P < 0.001) and Child-Pugh class (P < 0.004). Objective radiological response (P = 0.821) and tumour number (P = 0.127) were not additional independent predictors of survival. Conclusions The SNACOR risk prediction model can be used to identify patients with a dismal prognosis after the first transarterial chemoembolisation who are unlikely to benefit from further transarterial chemoembolisation. However, Harrell’s C-index showed only moderate performance. Accordingly, this risk prediction model can only serve as one of several components used to make the decision about whether to repeat treatment.
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Affiliation(s)
- Aline Mähringer-Kunz
- Department of Diagnostic and Interventional Radiology, Johannes Gutenberg-University Medical Center Mainz, Langenbeckst. 1, 55131, Mainz, Germany
| | - Arndt Weinmann
- Department of Internal Medicine, Johannes Gutenberg-University Medical Center Mainz, Mainz, Germany.,Clinical Registry Unit (CRU), Johannes Gutenberg-University Medical Center Mainz, Mainz, Germany
| | - Irene Schmidtmann
- Institute of Medical Biostatistics, Epidemiology and Informatics, Johannes Gutenberg-University Mainz, Mainz, Germany
| | - Sandra Koch
- Clinical Registry Unit (CRU), Johannes Gutenberg-University Medical Center Mainz, Mainz, Germany
| | - Sebastian Schotten
- Department of Diagnostic and Interventional Radiology, Johannes Gutenberg-University Medical Center Mainz, Langenbeckst. 1, 55131, Mainz, Germany
| | | | - Michael Bernhard Pitton
- Department of Diagnostic and Interventional Radiology, Johannes Gutenberg-University Medical Center Mainz, Langenbeckst. 1, 55131, Mainz, Germany
| | - Christoph Dueber
- Department of Diagnostic and Interventional Radiology, Johannes Gutenberg-University Medical Center Mainz, Langenbeckst. 1, 55131, Mainz, Germany
| | - Peter Robert Galle
- Department of Internal Medicine, Johannes Gutenberg-University Medical Center Mainz, Mainz, Germany
| | - Roman Kloeckner
- Department of Diagnostic and Interventional Radiology, Johannes Gutenberg-University Medical Center Mainz, Langenbeckst. 1, 55131, Mainz, Germany.
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Cucchetti A, Mazzaferro V, Pinna AD, Sposito C, Golfieri R, Serra C, Spreafico C, Piscaglia F, Cappelli A, Bongini M, Cucchi M, Cescon M. Average treatment effect of hepatic resection versus locoregional therapies for hepatocellular carcinoma. Br J Surg 2017; 104:1704-1712. [DOI: 10.1002/bjs.10613] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2016] [Revised: 04/19/2017] [Accepted: 05/09/2017] [Indexed: 12/12/2022]
Abstract
Abstract
Background
When comparing the efficacy of surgical and non-surgical therapies for hepatocellular carcinoma (HCC), a major limitation is the causal inference problem. This concerns the impossibility of seeing both outcomes of two different treatments for the same individual at the same time because one is inevitably missing. This aspect can be addressed methodologically by estimating the so-called average treatment effect (ATE).
Methods
To estimate the ATE of hepatic resection over locoregional therapies for HCC, data from patients treated in two tertiary care settings between August 2000 and December 2014 were used to obtain counterfactual outcomes using an inverse probability weight survival adjustment.
Results
A total of 1585 patients were enrolled: 815 underwent hepatic resection, 337 radiofrequency ablation (RFA) and 433 transarterial chemoembolization (TACE). The option of operating on all patients who had tumour ablation returned an ATE of +9·8 months for resection (effect size 0·111; adjusted P = 0·064). The option of operating on all patients who had TACE returned an ATE of +27·9 months (effect size 0·383; adjusted P < 0·001). The ATE of surgery was negligible in patients undergoing ablation for very early HCCs (effect size 0·027; adjusted P = 0·627), independently of albumin–bilirubin (ALBI) grade; or in patients with ALBI liver function grade 2 (effect size 0·083; adjusted P = 0·213), independently of tumour stage. In all other instances, the ATE of surgery was notably greater. Operating on patients who had TACE with multinodular HCC beyond the Milan criteria resulted in a mild ATE (effect size 0·140; adjusted P = 0·037).
Conclusion
ATE estimation suggests that hepatic resection is a better treatment option than ablation and TACE in patients with HCC.
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Affiliation(s)
- A Cucchetti
- Department of Medical and Surgical Sciences, S. Orsola-Malpighi Hospital, Alma Mater Studiorum – University of Bologna, Bologna, Italy
| | - V Mazzaferro
- Gastrointestinal Surgery and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
| | - A D Pinna
- Department of Medical and Surgical Sciences, S. Orsola-Malpighi Hospital, Alma Mater Studiorum – University of Bologna, Bologna, Italy
| | - C Sposito
- Gastrointestinal Surgery and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
| | - R Golfieri
- Radiology Unit, Department of Diagnostic and Preventive Medicine, S. Orsola-Malpighi Hospital, Bologna, Italy
| | - C Serra
- Department of Organ Insufficiency and Transplantation, S. Orsola-Malpighi Hospital, Bologna, Italy
| | - C Spreafico
- Interventional Radiology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
| | - F Piscaglia
- Department of Medical and Surgical Sciences, S. Orsola-Malpighi Hospital, Alma Mater Studiorum – University of Bologna, Bologna, Italy
| | - A Cappelli
- Radiology Unit, Department of Diagnostic and Preventive Medicine, S. Orsola-Malpighi Hospital, Bologna, Italy
| | - M Bongini
- Gastrointestinal Surgery and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
| | - M Cucchi
- Department of Medical and Surgical Sciences, S. Orsola-Malpighi Hospital, Alma Mater Studiorum – University of Bologna, Bologna, Italy
| | - M Cescon
- Department of Medical and Surgical Sciences, S. Orsola-Malpighi Hospital, Alma Mater Studiorum – University of Bologna, Bologna, Italy
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