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Li J, Liu Y, Qiu Y, Qu C, Li J. Comparison of adjuvant treatment regimens for high-risk hepatocellular carcinoma: a Bayesian network meta analysis and systematic review. Front Immunol 2024; 15:1487353. [PMID: 39588371 PMCID: PMC11586331 DOI: 10.3389/fimmu.2024.1487353] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2024] [Accepted: 10/17/2024] [Indexed: 11/27/2024] Open
Abstract
Background The five-year recurrence rate for patients with hepatocellular carcinoma (HCC) is as high as 70%. Patients with high-risk recurrence factors experience significantly poorer prognosis. Local regional therapies, including transarterial chemoembolisation (TACE), hepatic arterial infusion chemotherapy (HAIC), radiotherapy, and emerging immunotherapy, are commonly used adjuvant treatment options. We conducted an indirect comparison of these adjuvant therapies for such patients. Methods We conducted a systematic search in public databases for relevant studies and assessed the efficacy and safety of the corresponding therapies by consolidating disease-free survival (DFS), overall survival (OS), and adverse events (AEs). Results A total of eight randomised controlled trials were ultimately included. The Gelman-Rubin plot and kernel density estimation indicate that the stability of the combined model is satisfactory. Conclusion immunotherapy is not inferior to local regional therapies in delaying tumour recurrence, however, the higher incidence of AEs remains a significant concern. Adjuvant radiotherapy demonstrated superior efficacy in delaying tumour recurrence compared to adjuvant TACE, although further support from phase III clinical trial evidence is required. Systematic review registration https://www.crd.york.ac.uk/prospero/, identifier CRD42024576316.
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Affiliation(s)
- Jiahao Li
- Department of Interventional Therapy, The First Hospital of Jilin University, Changchun, Jilin, China
| | - Yingnan Liu
- Department of Radiology, The First Hospital of Jilin University, Changchun, Jilin, China
| | - Yuqi Qiu
- Department of Interventional Therapy, The First Hospital of Jilin University, Changchun, Jilin, China
| | - Chao Qu
- Department of Interventional Therapy, The First Hospital of Jilin University, Changchun, Jilin, China
| | - Jiarui Li
- Department of Interventional Therapy, The First Hospital of Jilin University, Changchun, Jilin, China
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Huang K, Qian T, Chen W, Lao M, Li H, Lin WC, Chen BW, Bai X, Gao S, Ma T, Liang T. The role of adjuvant transcatheter arterial chemoembolization following repeated curative resection/ablation for hepatocellular carcinoma with early recurrence: a propensity score matching analysis. BMC Cancer 2024; 24:620. [PMID: 38773564 PMCID: PMC11110442 DOI: 10.1186/s12885-024-12396-2] [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: 01/30/2024] [Accepted: 05/16/2024] [Indexed: 05/24/2024] Open
Abstract
BACKGROUND The role of adjuvant transcatheter arterial chemoembolization (TACE) following repeated resection/ablation for recurrent hepatocellular carcinoma (HCC) remains uncertain. The aim of this study was to assess the effectiveness of adjuvant TACE following repeated resection or ablation in patients with early recurrent HCC. METHODS Information for patients who underwent repeated surgery or radiofrequency ablation (RFA) for early recurrent HCCs (< 2 years) at our institution from January 2017 to December 2020 were collected. Patients were divided into adjuvant TACE and observation groups according to whether they received adjuvant TACE or not. The recurrence-free survival (RFS) and overall survival (OS) were compared between the two groups before and after propensity score matching (PSM). RESULTS Of the 225 patients enrolled, the median time of HCC recurrence was 11 months (IQR, 6-16 months). After repeated surgery or radiofrequency ablation (RFA) for recurrent tumors, 45 patients (20%) received adjuvant TACE while the remaining 180 (80%) didn't. There were no significant differences in RFS (P = 0.325) and OS (P = 0.072) between adjuvant TACE and observation groups before PSM. There were also no significant differences in RFS (P = 0.897) and OS (P = 0.090) between the two groups after PSM. Multivariable analysis suggested that multiple tumors, liver cirrhosis, and RFA were independent risk factors for the re-recurrence of HCC. CONCLUSION Adjuvant TACE after repeated resection or ablation for early recurrent HCCs was not associated with a long-term survival benefit in this single-center cohort.
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Affiliation(s)
- Kaiquan Huang
- Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital of Zhejiang University School of Medicine, 79 Qingchun Rd., Hangzhou, 310003, China
| | - Tao Qian
- Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital of Zhejiang University School of Medicine, 79 Qingchun Rd., Hangzhou, 310003, China
| | - Wen Chen
- Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital of Zhejiang University School of Medicine, 79 Qingchun Rd., Hangzhou, 310003, China
| | - Mengyi Lao
- Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital of Zhejiang University School of Medicine, 79 Qingchun Rd., Hangzhou, 310003, China
| | - Huiliang Li
- Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital of Zhejiang University School of Medicine, 79 Qingchun Rd., Hangzhou, 310003, China
| | - Wei-Chiao Lin
- Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital of Zhejiang University School of Medicine, 79 Qingchun Rd., Hangzhou, 310003, China
| | - Bryan Wei Chen
- Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital of Zhejiang University School of Medicine, 79 Qingchun Rd., Hangzhou, 310003, China
| | - Xueli Bai
- Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital of Zhejiang University School of Medicine, 79 Qingchun Rd., Hangzhou, 310003, China
| | - Shunliang Gao
- Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital of Zhejiang University School of Medicine, 79 Qingchun Rd., Hangzhou, 310003, China
| | - Tao Ma
- Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital of Zhejiang University School of Medicine, 79 Qingchun Rd., Hangzhou, 310003, China.
| | - Tingbo Liang
- Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital of Zhejiang University School of Medicine, 79 Qingchun Rd., Hangzhou, 310003, China.
- Innovation Center for the Study of Pancreatic Diseases of Zhejiang Province, Hangzhou, China.
- Zhejiang Clinical Research Center of Hepatobiliary and Pancreatic Diseases, Hangzhou, China.
- Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou, China.
- Cancer Center, Zhejiang University, Hangzhou, China.
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Kim SJ, Cummins KC, Tsung A. Immunotherapy as a Complement to Surgical Management of Hepatocellular Carcinoma. Cancers (Basel) 2024; 16:1852. [PMID: 38791931 PMCID: PMC11120323 DOI: 10.3390/cancers16101852] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2024] [Revised: 03/29/2024] [Accepted: 05/10/2024] [Indexed: 05/26/2024] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common primary liver tumor in adults, and the fourth leading cause of cancer-related deaths worldwide. While surgical and ablative therapies remain the standard of care in early localized disease, late presentation with advanced stages of disease, impaired hepatic function, or local recurrence following surgical resection preclude operative management as the sole treatment modality in a subgroup of patients. As such, systemic therapies, namely immunotherapy, have become an integral part of the HCC treatment algorithm over the past decade. While agents, such as atezolizumab/bevacizumab, have well-established roles as first-line systemic therapy in intermediate- and advanced-stage HCC, the role of immunotherapy in disease amenable to surgical management continues to evolve. In this review, we will discuss the current evidence and aggregate impact of immunotherapy in the context of HCC amenable to surgical management, including its application in the neoadjuvant and adjuvant settings.
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Affiliation(s)
| | | | - Allan Tsung
- Department of Surgery, University of Virginia, Charlottesville, VA 22908, USA
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Liang Y, Yang R, Shang J, Zhong D, Yang Q, Su Y, Shi Y, Huang X. Lung immune prognostic index‑based nomogram for recurrence of hepatocellular carcinoma after postoperative adjuvant TACE. J Cancer Res Clin Oncol 2023; 149:16461-16471. [PMID: 37707573 DOI: 10.1007/s00432-023-05413-7] [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: 08/06/2023] [Accepted: 09/06/2023] [Indexed: 09/15/2023]
Abstract
BACKGROUND Transarterial chemoembolization (TACE), one of the most commonly used postoperative adjuvant therapy for HCC, has achieved satisfactory outcomes. This study aimed to explore the prognostic value of lung immune prognostic index (LIPI) and develop a novel nomogram for recurrence-free survival (RFS) of HCC patients received postoperative adjuvant TACE (PA-TACE). METHODS The prognostic value of LIPI was evaluated by C-index, receiver operating characteristic (ROC) analysis, and Kaplan-Meier survival curve. An effective nomogram based on preoperative prognostic factors was established from multivariate analysis and validated in the validation cohort. RESULTS The ROC and survival analysis demonstrated that the LIPI exhibited better prediction performance of HCC recurrence than other inflammatory biomarkers. According to univariate and multivariate analysis, LIPI, followed by AFP, MVI and age, were significant independent predictors for HCC recurrence and were utilized to construct the nomogram. The C-indexes of the nomogram were 0.746 (95% CI 0.721-0.770) and 0.738 (95% CI 0.701-0.775) in the training and validation cohort, respectively. The AUCs for the 1-, 2-, and 3-year RFS were 0.799, 0.867 and 0.884 in the training cohort and 0.798, 0.779 and 0.770 in the validation cohort, respectively. The calibration curves presented good consistencies. Moreover, compared with the LIPI and other clinical staging system, the established nomogram presented better prognostic performance. CONCLUSION Preoperative LIPI might be a powerful predictor for RFS in HCC patients received PA-TACE. The LIPI-based nomogram could further effectively predict the risk of recurrence and help clinicians formulate personalized follow-up strategies and adjuvant therapy to improve patient outcomes.
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Affiliation(s)
- Yuxin Liang
- Liver Transplantation Center and HBP Surgery, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Ruoyi Yang
- School of Stomatology, Guizhou Medical University, Guiyang, China
- Department of Head and Neck Surgery, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Jin Shang
- Liver Transplantation Center and HBP Surgery, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Deyuan Zhong
- Liver Transplantation Center and HBP Surgery, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Qinyan Yang
- Liver Transplantation Center and HBP Surgery, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Yuhao Su
- Liver Transplantation Center and HBP Surgery, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Ying Shi
- Liver Transplantation Center and HBP Surgery, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
| | - Xiaolun Huang
- Liver Transplantation Center and HBP Surgery, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
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Zeng JS, Zeng JX, Huang Y, Liu JF, Zeng JH. The effect of adjuvant transarterial chemoembolization for hepatocellular carcinoma after liver resection based on risk stratification. Hepatobiliary Pancreat Dis Int 2023; 22:482-489. [PMID: 35934610 DOI: 10.1016/j.hbpd.2022.07.007] [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: 08/01/2021] [Accepted: 07/25/2022] [Indexed: 02/05/2023]
Abstract
BACKGROUND There is currently no standard adjuvant treatment proven to prevent hepatocellular carcinoma (HCC) recurrence. Recent studies suggest that postoperative adjuvant transarterial chemoembolization (PA-TACE) is beneficial for patients at high risk of tumor recurrence. However, it is difficult to select the patients. The present study aimed to develop an easy-to-use score to identify these patients. METHODS A total of 4530 patients undergoing liver resection were recruited. Independent risk factors were identified by Cox regression model in the training cohort and the Primary liver cancer big data transarterial chemoembolization (PDTE) scoring system was established. RESULTS The scoring system was composed of ten risk factors including alpha-fetoprotein (AFP), albumin-bilirubin (ALBI) grade, operative bleeding loss, resection margin, tumor capsular, satellite nodules, tumor size and number, and microvascular and macrovascular invasion. Using 5 points as risk stratification, the patients with PA-TACE had higher recurrence-free survival (RFS) compared with non-TACE in > 5 points group (P < 0.001), whereas PA-TACE patients had lower RFS compared with non-TACE in ≤ 5 points group (P = 0.013). In the training and validation cohorts, the C-indexes of PDTE scoring system were 0.714 [standard errors (SE) = 0.010] and 0.716 (SE = 0.018), respectively. CONCLUSIONS The model is a simple tool to identify PA-TACE for HCC patients after liver resection with a favorable performance. Patients with > 5 points may benefit from PA-TACE.
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Affiliation(s)
- Jin-Shu Zeng
- Department of Ultrasonic Medical, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, China; The Liver Center of Fujian Province, Fujian Medical University, Fuzhou 350025, China
| | - Jian-Xing Zeng
- The Liver Center of Fujian Province, Fujian Medical University, Fuzhou 350025, China; Department of Hepatobiliary Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, China; Department of Hepatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350005, China
| | - Yao Huang
- The Liver Center of Fujian Province, Fujian Medical University, Fuzhou 350025, China; Department of Hepatobiliary Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, China; Department of Hepatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350005, China
| | - Jing-Feng Liu
- The Liver Center of Fujian Province, Fujian Medical University, Fuzhou 350025, China; Department of Hepatobiliary Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, China; Department of Hepatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350005, China
| | - Jin-Hua Zeng
- The Liver Center of Fujian Province, Fujian Medical University, Fuzhou 350025, China; Department of Hepatobiliary Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, China; Department of Hepatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350005, China.
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Ye Y, Wang Y, Xu H, Yi F. Network meta-analysis of adjuvant treatments for patients with hepatocellular carcinoma after curative resection. BMC Gastroenterol 2023; 23:320. [PMID: 37730533 PMCID: PMC10510134 DOI: 10.1186/s12876-023-02955-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2023] [Accepted: 09/10/2023] [Indexed: 09/22/2023] Open
Abstract
PURPOSE The prevention of recurrence for patients with hepatocellular carcinoma after curative resection is still a great challenge in clinical practice. There are numerous studies that trying to search for favorable strategies to decrease the recurrence and prolong life span for these patients, whereas no consensus is reached till now. Herein, we aim to compare the efficacy between different reported treatments by network meta-analysis(NMA). METHODS We searched Pubmed, Web of Science and Cochrane Library for abstracts and full-text articles published from database inception through February 2023. All of the random controlled trials(RCTs) were evaluated and collected as eligible studies. The primary outcome was the prevention of recurrence between different procedures. The second outcomes were one-year survival, three-year survival and five-year survival. RESULTS Thirty-two RCTs including 5783 patients were selected, and 12 treatments were classified. Most of the studies were high quality with low bias. Thirty-one studies including 5629 patients were recruited for recurrence analysis. The network meta-analysis showed benefits from transarterial chemoembolization(TACE) + portal vein chemotherapy(PVC)[OR, 2.84 (1.15,6.99)] and internal radiotherapy(IRT) [OR, 2.63 (1.41,4.91)] compared to non-adjuvant(NA) treatment when considering prevention of recurrence. Seventeen studies including 2047 patients were collected for one-year survival analysis. The network meta-analysis showed benefit from TACE[OR, 0.33 (0.14,0.75)] when considering one-year survival. Twenty-one studies including 2463 patients were collected for three-year survival analysis. The network meta-analysis showed TACE [OR, 0.51 (0.30,0.86)], IRT[OR, 0.41 (0.20,0.83)] and dendritic cell(DC) [OR, 0.09 (0.01,0.98)] were better than NA when considering three-year survival. Sixteen studies including 1915 patients were collected for five-year survival analysis. The network meta-analysis didn't show any benefit from different treatments when considering five-year survival. Other strategies including external radiotherapy(ERT), branched-chain amino acids(BCAA), hepatic artery infusion chemotherapy(HAIC), cytokine-induced killer(CIK), adoptive immunotherapy(AIT), Huaier, interferon(IFN), oral chemotherapy(OCT) and sorafenib(SOR) didn't show significant benefit regardless of prevention of recurrence or short-, long- time survival. CONCLUSION This NMA found that TACE + PVC and IRT were considered as the procedures to decrease HCC recurrence rate. TACE, IRT and DC were preferred when considering the extending of life span for post-operative patients with HCC. Large scale of RCTs are needed to verify it.
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Affiliation(s)
- Yanyan Ye
- Department of Ultrasound, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, P.R. of China
| | - Ying Wang
- Department of Oncology, Second Affiliated Hospital of Nanchang University, Nanchang, 330006, P.R. of China
- JiangXi Key Laboratory of Clinical and Translational Cancer Research, Nanchang, 330006, P.R. of China
| | - Haoqian Xu
- Department of Oncology, Second Affiliated Hospital of Nanchang University, Nanchang, 330006, P.R. of China
- JiangXi Key Laboratory of Clinical and Translational Cancer Research, Nanchang, 330006, P.R. of China
| | - Fengming Yi
- Department of Oncology, Second Affiliated Hospital of Nanchang University, Nanchang, 330006, P.R. of China.
- JiangXi Key Laboratory of Clinical and Translational Cancer Research, Nanchang, 330006, P.R. of China.
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Mo A, Lin B, Chen D. Efficacy of sequential TACE on primary hepatocellular carcinoma with microvascular invasion after radical resection: a systematic review and meta-analysis. World J Surg Oncol 2023; 21:277. [PMID: 37667375 PMCID: PMC10478229 DOI: 10.1186/s12957-023-03160-0] [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: 05/29/2023] [Accepted: 08/24/2023] [Indexed: 09/06/2023] Open
Abstract
OBJECTIVES The purpose of this study is to examine the impact of sequential transcatheter arterial chemoembolization (TACE) on the prognosis of patients with hepatocellular carcinoma (HCC) and microvascular invasion (MVI) following radical resection. METHODS Five databases were searched for studies on the efficacy of TACE after radical hepatectomy resection (HR) for treating HCC with MVI. Depending on the heterogeneity between included studies, the relative risk (RR) and 95% confidence interval (CI) were computed using a random or fixed effect model. RESULTS Thirteen articles were included in this study. There were 1378 cases in the HR-TACE group (cases undergoing TACE after HR) and 1636 cases in the HR group (cases only undergoing HR). The recurrence-free survival (RFS) at 1 year, 2 years, 3 years, and 5 years after radical HCC resection was statistically significantly greater in the HR-TACE group than in the HR group. The HR-TACE group exhibited statistically significant advantages at 1-year, 2-year, 3-year, and 5-year overall survival (OS) after radical HCC resection when compared with the HR group. CONCLUSION Postoperative sequential TACE treatment can improve the RFS and OS rates at 1 year, 2 years, 3 years, and 5 years following radical HR in patients with HCC and MVI. These findings will guide clinicians in selecting appropriate cases for adjuvant TACE treatment during clinical diagnosis and treatment to maximize patient benefit. TRIAL REGISTRATION PROSPERO CRD42023449238.
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Affiliation(s)
- Anwei Mo
- Department of Medical Oncology, Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University), Haikou, Hainan, China
| | - Biquan Lin
- Intervention Clinic, Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University), No. 19 Xiuhua Road, Haikou, Hainan, 570000, China.
| | - Denglin Chen
- Department of Medical Oncology, Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University), Haikou, Hainan, China
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Liang Y, Wang Z, Peng Y, Dai Z, Lai C, Qiu Y, Yao Y, Shi Y, Shang J, Huang X. Development of ensemble learning models for prognosis of hepatocellular carcinoma patients underwent postoperative adjuvant transarterial chemoembolization. Front Oncol 2023; 13:1169102. [PMID: 37305570 PMCID: PMC10254793 DOI: 10.3389/fonc.2023.1169102] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2023] [Accepted: 05/09/2023] [Indexed: 06/13/2023] Open
Abstract
Background Postoperative adjuvant transarterial chemoembolization (PA-TACE) has been increasing widely used to improve the prognosis of hepatocellular carcinoma (HCC) patients. However, clinical outcomes vary from patient to patient, which calls for individualized prognostic prediction and early management. Methods A total of 274 HCC patients who underwent PA-TACE were enrolled in this study. The prediction performance of five machine learning models was compared and the prognostic variables of postoperative outcomes were identified. Results Compared with other machine learning models, the risk prediction model based on ensemble learning strategies, including Boosting, Bagging, and Stacking algorithms, presented better prediction performance for overall mortality and HCC recurrence. Moreover, the results showed that the Stacking algorithm had relatively low time consumption, good discriminative ability, and the best prediction performance. In addition, according to time-dependent ROC analysis, the ensemble learning strategies were found to perform well in predicting both OS and RFS for the patients. Our study also found that BCLC Stage, hsCRP/ALB and frequency of PA-TACE were relatively important variables in both overall mortality and recurrence, while MVI contributed more to the recurrence of the patients. Conclusion Among the five machine learning models, the ensemble learning strategies, especially the Stacking algorithm, could better predict the prognosis of HCC patients following PA-TACE. Machine learning models could also help clinicians identify the important prognostic factors that are clinically useful in individualized patient monitoring and management.
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Affiliation(s)
- Yuxin Liang
- Liver Transplantation Center and Hepatobiliary and Pancreatic Surgery, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
- Department of Hepatobiliary-Pancreatic Surgery, Cell Transplantation Center, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, China
| | - Zirui Wang
- School of Computer Science and Engineering, University of Electronic Science and Technology of China, Chengdu, China
| | - Yujiao Peng
- Liver Transplantation Center and Hepatobiliary and Pancreatic Surgery, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Zonglin Dai
- Liver Transplantation Center and Hepatobiliary and Pancreatic Surgery, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
- Department of Hepatobiliary-Pancreatic Surgery, Cell Transplantation Center, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, China
| | - Chunyou Lai
- Liver Transplantation Center and Hepatobiliary and Pancreatic Surgery, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
- Department of Hepatobiliary-Pancreatic Surgery, Cell Transplantation Center, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, China
| | - Yuqin Qiu
- Liver Transplantation Center and Hepatobiliary and Pancreatic Surgery, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Yutong Yao
- Liver Transplantation Center and Hepatobiliary and Pancreatic Surgery, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
- Department of Hepatobiliary-Pancreatic Surgery, Cell Transplantation Center, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, China
| | - Ying Shi
- Liver Transplantation Center and Hepatobiliary and Pancreatic Surgery, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
- Department of Hepatobiliary-Pancreatic Surgery, Cell Transplantation Center, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, China
| | - Jin Shang
- Liver Transplantation Center and Hepatobiliary and Pancreatic Surgery, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
- Department of Hepatobiliary-Pancreatic Surgery, Cell Transplantation Center, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, China
| | - Xiaolun Huang
- Liver Transplantation Center and Hepatobiliary and Pancreatic Surgery, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
- Department of Hepatobiliary-Pancreatic Surgery, Cell Transplantation Center, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, China
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Feng LH, Zhu YY, Zhou JM, Wang M, Xu WQ, Zhang T, Mao AR, Cong WM, Dong H, Wang L. Adjuvant TACE may not improve recurrence-free or overall survival in HCC patients with low risk of recurrence after hepatectomy. Front Oncol 2023; 13:1104492. [PMID: 37293583 PMCID: PMC10244569 DOI: 10.3389/fonc.2023.1104492] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2022] [Accepted: 05/10/2023] [Indexed: 06/10/2023] Open
Abstract
Background To identify whether adjuvant transarterial chemoembolization (TACE) can improve prognosis in HCC patients with a low risk of recurrence (tumor size ≤ 5 cm, single nodule, no satellites, and no microvascular or macrovascular invasions) after hepatectomy. Methods The data of 489 HCC patients with a low risk of recurrence after hepatectomy from Shanghai Cancer Center (SHCC) and Eastern Hepatobiliary Surgery Hospital (EHBH) were retrospectively reviewed. Recurrence-free survival (RFS) and overall survival (OS) were analyzed with Kaplan-Meier curves and Cox proportional hazards regression models. The effects of selection bias and confounding factors were balanced using propensity score matching (PSM). Results In the SHCC cohort, 40 patients (19.9%, 40/201) received adjuvant TACE, and in the EHBH cohort, 113 patients (46.2%, 133/288) received adjuvant TACE. Compared to the patients without adjuvant TACE after hepatectomy, patients receiving adjuvant TACE had significantly shorter RFS (P=0.022; P=0.014) in both cohorts before PSM. However, no significant difference existed in OS (P=0.568; P=0.082). Multivariate analysis revealed that serum alkaline phosphatase and adjuvant TACE were independent prognostic factors for recurrence in both cohorts. Furthermore, significant differences existed in tumor size between the adjuvant TACE and non-adjuvant TACE groups in the SHCC cohort. There were differences in transfusion, Barcelona Clinic Liver Cancer stage and tumor-node-metastasis stage in the EHBH cohort. These factors were balanced by PSM. After PSM, patients with adjuvant TACE after hepatectomy still had significantly shorter RFS than those without (P=0.035; P=0.035) in both cohorts, but there was no difference in OS (P=0.638; P=0.159). Adjuvant TACE was the only independent prognostic factor for recurrence in multivariate analysis, with hazard ratios of 1.95 and 1.57. Conclusions Adjuvant TACE may not improve long-term survival and might promote postoperative recurrence in HCC patients with a low risk of recurrence after hepatectomy.
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Affiliation(s)
- Long-Hai Feng
- Department of Hepatic Surgery, Shanghai Cancer Center, Fudan University, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Yu-Yao Zhu
- Department of Pathology, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China
| | - Jia-Min Zhou
- Department of Hepatic Surgery, Shanghai Cancer Center, Fudan University, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Miao Wang
- Department of Hepatic Surgery, Shanghai Cancer Center, Fudan University, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Wei-Qi Xu
- Department of Hepatic Surgery, Shanghai Cancer Center, Fudan University, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Ti Zhang
- Department of Hepatic Surgery, Shanghai Cancer Center, Fudan University, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - An-Rong Mao
- Department of Hepatic Surgery, Shanghai Cancer Center, Fudan University, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Wen-Ming Cong
- Department of Pathology, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China
| | - Hui Dong
- Department of Pathology, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China
| | - Lu Wang
- Department of Hepatic Surgery, Shanghai Cancer Center, Fudan University, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
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10
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Yang YQ, Wen ZY, Liu XY, Ma ZH, Liu YE, Cao XY, Hou L, Xie H. Current status and prospect of treatments for recurrent hepatocellular carcinoma. World J Hepatol 2023; 15:129-150. [PMID: 36926237 PMCID: PMC10011906 DOI: 10.4254/wjh.v15.i2.129] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2022] [Revised: 11/13/2022] [Accepted: 01/23/2023] [Indexed: 02/24/2023] Open
Abstract
Owing to its heterogeneous and highly aggressive nature, hepatocellular carcinoma (HCC) has a high recurrence rate, which is a non-negligible problem despite the increasing number of available treatment options. Recent clinical trials have attempted to reduce the recurrence and develop innovative treatment options for patients with recurrent HCC. In the event of liver remnant recurrence, the currently available treatment options include repeat hepatectomy, salvage liver transplantation, tumor ablation, transcatheter arterial chemoembolization, stereotactic body radiotherapy, systemic therapies, and combination therapy. In this review, we summarize the strategies to reduce the recurrence of high-risk tumors and aggressive therapies for recurrent HCC. Additionally, we discuss methods to prevent HCC recurrence and prognostic models constructed based on predictors of recurrence to develop an appropriate surveillance program.
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Affiliation(s)
- Yu-Qing Yang
- Department of Epidemiology and Biostatistics, Jilin University, Changchun 130021, Jilin Province, China
| | - Zhen-Yu Wen
- Department of Occupational and Environmental Health, Jilin University, Changchun 130021, Jilin Province, China
| | - Xiao-Yan Liu
- Senior Department of Hepatology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China
| | - Zhen-Hu Ma
- Senior Department of Oncology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China
| | - Yan-E Liu
- Department of Epidemiology and Biostatistics, Jilin University, Changchun 130021, Jilin Province, China
| | - Xue-Ying Cao
- Senior Department of Oncology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China
| | - Li Hou
- Senior Department of Oncology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China
| | - Hui Xie
- Senior Department of Oncology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China
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11
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Guo B, Chen Q, Liu Z, Chen X, Zhu P. Adjuvant therapy following curative treatments for hepatocellular carcinoma: current dilemmas and prospects. Front Oncol 2023; 13:1098958. [PMID: 37139151 PMCID: PMC10149944 DOI: 10.3389/fonc.2023.1098958] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2022] [Accepted: 04/04/2023] [Indexed: 05/05/2023] Open
Abstract
Curative surgical treatments, mainly liver resection, are still one of the optimal options for patients with early-, mid-, and even progression-stage hepatocellular carcinoma (HCC). However, the recurrence rate within 5 years after surgery is as high as 70%, especially in patients with high risk factors for recurrence, most of whom experience early recurrence within 2 years. Effective adjuvant therapy may improve prognosis, previous studies found that adjuvant transarterial chemoembolization, antiviral, and traditional Chinese medicine et al. were helpful in preventing HCC recurrence. Nevertheless, due to controversial results or lack of high-level evidence, there is no standardized postoperative management protocol worldwide at present. Continued exploration of effective postoperative adjuvant treatments to improve surgical prognosis is necessary.
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Affiliation(s)
- Bin Guo
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Qian Chen
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
- Hepatobiliary Surgery Department, The First Affiliated Hospital of Shihezi University, Shihezi, Xinjiang, China
| | - Zhicheng Liu
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Xiaoping Chen
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Peng Zhu
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
- *Correspondence: Peng Zhu,
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12
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Nevarez NM, Chang GY, Yopp AC. An Overview of Clinical Trials in the Treatment of Resectable Hepatocellular Carcinoma. Surg Oncol Clin N Am 2023; 32:101-117. [PMID: 36410911 DOI: 10.1016/j.soc.2022.07.008] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related death worldwide. Partial hepatectomy, one of a few curative therapeutic modalities, is plagued by high recurrence rate of up to 70% at 5 years. Throughout the past 3 decades, many clinical trials have attempted to improve HCC recurrence rate following partial hepatectomy using adjuvant and neoadjuvant treatment modalities such as antiviral therapy, brachytherapy, systemic chemotherapy, immunotherapy, transarterial chemoembolization and radioembolization, and radiotherapy. The goal of this review is to discuss the clinical trials pertaining to resectable HCC including surgical technique considerations, adjuvant, and neoadjuvant treatment modalities.
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Affiliation(s)
- Nicole M Nevarez
- Department of Surgery, Division of Surgical Oncology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA.
| | - Gloria Y Chang
- Department of Surgery, Division of Surgical Oncology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA
| | - Adam C Yopp
- Department of Surgery, Division of Surgical Oncology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA
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13
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Mo A, Zhang Q, Xia F, Huang Z, Peng S, Cao W, Mei H, Ren L, Su Y, Gao H, Chen W. Preoperative transcatheter arterial chemoembolization and prognosis of patients with solitary large hepatocellular carcinomas (≥5 cm): Multicenter retrospective study. Cancer Med 2022; 12:7734-7747. [PMID: 36540041 PMCID: PMC10134378 DOI: 10.1002/cam4.5529] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2022] [Revised: 10/24/2022] [Accepted: 11/25/2022] [Indexed: 12/24/2022] Open
Abstract
OBJECTIVES Large hepatocellular carcinoma (LHCC) is prone to short-term recurrence and poor long-term survival after hepatectomy, and there is still a lack of effective neoadjuvant treatments to improve recurrence-free survival (RFS) and overall survival (OS). We retrospectively analyzed the efficacy of preoperative transcatheter arterial chemoembolization (TACE) in solitary LHCC (≥5 cm). MATERIALS AND METHODS A multicenter medical database was used to analyze preoperative TACE's effects on RFS, OS, and perioperative complications in patients with solitary LHCC who received surgical treatment from January 2005 to December 2015. The patients were divided into Group A (5.0-9.9 cm) and Group B (≥10 cm), with 10 cm as the critical value, and the effect of preoperative TACE on RFS, OS and perioperative complications was assessed in each subgroup. RESULTS In the overall population, patients with preoperative TACE had better RFS and OS than those without preoperative TACE. However, after stratifying the patients into the two HCC groups, preoperative TACE only improved the survival outcomes of patients with Group B (≥10 cm). Multivariate Cox-regression analysis showed that lack of preoperative TACE was an independent risk factor for RFS and OS in the overall population and in Group B but not in Group A. CONCLUSIONS Preoperative TACE is beneficial for patients with solitary HCC (≥10 cm).
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Affiliation(s)
- Ali Mo
- Guangdong Medical University Guangdong China
- Department of Hepatobiliary Surgery Zhongshan People's Hospital Zhongshan City China
| | - Qiao Zhang
- Guangdong Medical University Guangdong China
- Department of Hepatobiliary Surgery Zhongshan People's Hospital Zhongshan City China
| | - Feng Xia
- Department of Hepatic Surgery Center Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology Wuhan China
| | - Zhiyuan Huang
- Department of Hepatic Surgery Center Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology Wuhan China
| | - Shasha Peng
- Department of Hepatobiliary and Pancreatic Surgery,Huangshi Central Hospital of Edong Healthcare Group Hubei Polytechnic University Huangshi China
| | - Wenjing Cao
- Southern Medical University Graduate School Guangzhou City China
| | - Hongliang Mei
- General Surgery General Hospital of Central Theater Wuhan China
| | - Li Ren
- Hepatobiliary Pancreatic Surgery Qinghai University Affiliated Hospital Xining China
| | - Yang Su
- Department of Hepatobiliary Surgery Renmin Hospital of Wuhan University Wuhan China
| | - Hengyi Gao
- Department of Hepatobiliary and Pancreatic Surgery Shenzhen Longhua District People's Hospital Shenzhen City China
| | - Weiqiang Chen
- Guangdong Medical University Guangdong China
- Department of Hepatobiliary Surgery Zhongshan People's Hospital Zhongshan City China
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14
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Zeng ZM, Mo N, Zeng J, Ma FC, Jiang YF, Huang HS, Liao XW, Zhu GZ, Ma J, Peng T. Advances in postoperative adjuvant therapy for primary liver cancer. World J Gastrointest Oncol 2022; 14:1604-1621. [PMID: 36187393 PMCID: PMC9516643 DOI: 10.4251/wjgo.v14.i9.1604] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2021] [Revised: 05/13/2022] [Accepted: 07/26/2022] [Indexed: 02/05/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is a highly heterogeneous, invasive, and conventional chemotherapy-insensitive tumor with unique biological characteristics. The main methods for the radical treatment of HCC are surgical resection or liver transplantation. However, recurrence rates are as high as 50% and 70% at 3 and 5 years after liver resection, respectively, and even in Milan-eligible recipients, the recurrence rate is approximately 20% at 5 years after liver transplantation. Therefore, reducing the postoperative recurrence rate is key to improving the overall outcome of liver cancer. This review discusses the risk factors for recurrence in patients with HCC radical surgical resection and adjuvant treatment options that may reduce the risk of recurrence and improve overall survival, including local adjuvant therapy (e.g., transcatheter arterial chemoembolization), adjuvant systemic therapy (e.g., molecular targeted agents and immunotherapy), and other adjuvant therapies (e.g., antiviral and herbal therapy). Finally, potential research directions that may change the paradigm of adjuvant therapy for HCC are analyzed.
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Affiliation(s)
- Zhi-Ming Zeng
- Department of Medical Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Ning Mo
- Department of Medical Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Jie Zeng
- Department of Medical Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Fu-Chao Ma
- Department of Medical Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Yan-Feng Jiang
- Department of Medical Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Hua-Sheng Huang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Xi-Wen Liao
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Guang-Zhi Zhu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Jie Ma
- Department of Medical Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Tao Peng
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
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15
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Qiu Y, Yang Y, Wang T, Shen S, Wang W. Efficacy of Postoperative Adjuvant Transcatheter Arterial Chemoembolization in Hepatocellular Carcinoma Patients With Microscopic Portal Vein Invasion. Front Oncol 2022; 12:831614. [PMID: 35795039 PMCID: PMC9252591 DOI: 10.3389/fonc.2022.831614] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2021] [Accepted: 05/24/2022] [Indexed: 12/04/2022] Open
Abstract
Background Microscopic portal vein invasion (MPVI) strongly predicts poor prognosis in patients with hepatocellular carcinoma (HCC). This study aims to investigate the impact of MPVI on the efficacy of postoperative adjuvant transcatheter arterial chemoembolization (PA-TACE). Methods From April 2014 to July 2019, a total of 512 HCC patients who underwent curative liver resection (LR) with microscopic vascular invasion (MVI) confirmed by histopathological examination were enrolled and divided into LR alone and PA-TACE groups. They were subsequently stratified into subgroups according to the presence of MPVI. Recurrence-free survival (RFS) and overall survival (OS) were compared using Kaplan–Meier curves and the log-rank test. The efficacy of PA-TACE was tested using univariate and multivariate Cox regression analyses. Sensitivity analysis was conducted after propensity score matching (PSM). Results Among all patients, 165 (32.3%) patients underwent PA-TACE, and 196 (38.2%) patients presented MPVI. In the entire cohort, PA-TACE and the presence of MPVI were identified as independent predictors for RFS and OS (all p<0.05). In the subgroup analysis, patients without MPVI who received PA-TACE had significantly better outcomes than those who underwent LR alone before and after PSM (all p<0.05). For patients with MPVI, PA-TACE displayed no significant benefit in terms of improving either RFS or OS, which was consistent with the results from the PSM cohort. Conclusion Among the HCC patients without MPVI who underwent curative liver resection, those who received PA-TACE had better RFS and OS outcomes than those who underwent LR alone. For patients with MPVI, PA-TACE had no significant effect on either RFS or OS outcomes.
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16
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Zhang Q, Xia F, Mo A, He W, Chen J, Zhang W, Chen W. Guiding Value of Circulating Tumor Cells for Preoperative Transcatheter Arterial Embolization in Solitary Large Hepatocellular Carcinoma: A Single-Center Retrospective Clinical Study. Front Oncol 2022; 12:839597. [PMID: 35664772 PMCID: PMC9159764 DOI: 10.3389/fonc.2022.839597] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2021] [Accepted: 04/15/2022] [Indexed: 12/07/2022] Open
Abstract
Background Large hepatocellular carcinoma (LHCC) is highly malignant and prone to recurrence, leading to a poor long-term prognosis for patients. There is an urgent need for measures to intervene in postoperative recurrence. Preoperative Transcatheter Arterial Embolization (TACE) is an effective treatment. However, there is a lack of reliable preoperative indicators to guide the application of preoperative TACE. We, therefore, investigated whether the preoperative status of circulating tumor cells (CTCs) could be used to guide preoperative TACE for HCC treatment. Methods This study recruited 361 HCC patients and compared recurrence-free survival (RFS) and overall survival (OS) in patients treated with TACE prior to surgery and those not treated with TACE. Patients were divided into CTC-positive group and CTC-negative group according to CTC status, and the effect of preoperative TACE on RFS and OS was compared in each subgroup. Results In CTC-positive patients, preoperative TACE reduces early recurrence and improves long-term survival. However, HCC patients did not benefit from preoperative TACE for the overall population and CTC-negative patients. Conclusions Preoperative CTC testing is a reliable indicator of whether HCC patients received TACE preoperatively. CTC positivity was associated with early tumor recurrence, and preoperative TACE could reduce early recurrence and long-term prognosis in CTC-positive patients.
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Affiliation(s)
- Qiao Zhang
- Zhongshan People's Hospital, Guangdong Medical University, Zhongshan, China
| | - Feng Xia
- Department of Hepatic Surgery Center, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China
| | - Ali Mo
- Zhongshan People's Hospital, Guangdong Medical University, Zhongshan, China
| | - Weiming He
- Zhongshan People's Hospital, Guangdong Medical University, Zhongshan, China
| | - Jiazhen Chen
- Zhongshan People's Hospital, Guangdong Medical University, Zhongshan, China
| | - Weiqiao Zhang
- Zhongshan People's Hospital, Guangdong Medical University, Zhongshan, China
| | - Weiqiang Chen
- Zhongshan People's Hospital, Guangdong Medical University, Zhongshan, China
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17
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Postoperative adjuvant transarterial chemoembolization improves outcomes of hepatocellular carcinoma associated with bile duct tumor thrombus: a propensity score matching analysis. HPB (Oxford) 2022; 24:547-557. [PMID: 34635434 DOI: 10.1016/j.hpb.2021.09.005] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2021] [Revised: 07/13/2021] [Accepted: 09/06/2021] [Indexed: 02/08/2023]
Abstract
BACKGROUND Surgical resection is the primary treatment for hepatocellular carcinoma (HCC) with bile duct tumor thrombus (BDTT). This study was conducted to investigate the efficacy of postoperative adjuvant TACE (PA-TACE) in patients with HCC and BDTT. METHODS Data from patients who underwent surgery for HCC with BDTT at two medical centers were retrospectively analyzed. The survival outcomes of patients who were treated by hepatic resection followed by PA-TACE were compared with those of patients who underwent surgery alone. Propensity score matching (PSM) analysis was performed with a 1:1 ratio. RESULTS Of the 308 consecutively enrolled HCC patients with BDTT who underwent surgical resection, 134 underwent PA-TACE whereas 174 underwent surgery alone. From the initial cohort, PSM matched 106 pairs of patients. The OS and DFS rates were significantly better for the PA-TACE group than the surgery alone group (for OS: before PSM, P = 0.026; after PSM, P = 0.039; for DFS: before PSM, P = 0.010; after PSM, P = 0.013). CONCLUSION PA-TACE was associated with better survival outcomes than surgery alone for patients with HCC and BDTT. Prospective clinical trials are warranted to validate the beneficial effect of PA-TACE on HCC patients associated with BDTT.
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18
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Chen B, Wu J, Cheng S, Wang L, Rong W, Wu F, Wang S, Jin J, Liu Y, Song Y, Ren H, Fang H, Tang Y, Li N, Li Y, Wang W. Phase 2 Study of Adjuvant Radiotherapy Following Narrow-Margin Hepatectomy in Patients With HCC. Hepatology 2021; 74:2595-2604. [PMID: 34097307 PMCID: PMC8672362 DOI: 10.1002/hep.31993] [Citation(s) in RCA: 52] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2021] [Revised: 05/06/2021] [Accepted: 05/30/2021] [Indexed: 01/27/2023]
Abstract
BACKGROUND AND AIMS Surgical resection is the primary treatment for HCC; however, it is associated with a high rate of recurrence and death. We conducted this phase 2 study to investigate the efficacy and safety of postoperative intensity-modulated radiotherapy (IMRT) for HCC after narrow-margin hepatectomy. APPROACH AND RESULTS We designed a single-arm, prospective phase 2 trial to evaluate overall survival (OS), disease-free survival (DFS), recurrence patterns, and toxicity in patients receiving adjuvant radiotherapy. The eligibility criteria included the following: pathological diagnosis of HCC after hepatectomy, with narrow pathological margins (< 1 cm); age > 18 years; and Eastern Cooperative Oncology Group performance status score of 0 or 1. Patients received IMRT within 4-6 weeks after surgical resection. This trial was registered at ClinicalTrials.gov (NCT01456156). Between 2008 and 2016, a total of 76 eligible patients who underwent narrow-margin resection were enrolled. The median follow-up duration was 70 months; the 3-year OS and DFS rates were 88.2% and 68.1%, respectively; and the 5-year OS and DFS rates were 72.2% and 51.6%, respectively. Intrahepatic recurrence was the primary recurrence pattern. No marginal recurrence was found. Intrahepatic, extrahepatic, and combined recurrences at the first relapse were found in 33, 5, and 1 patient, respectively. The most common radiation-related grade-3 toxicities were leukopenia (7.9%), elevated alanine aminotransferase (3.9%) and aspartate aminotransferase (2.6%) levels, and thrombocytopenia (1.3%). Classical or nonclassical radiation-induced liver disease was not noted. CONCLUSIONS Adjuvant radiotherapy is an effective, well-tolerated, and promising adjuvant regimen in patients with HCC who have undergone narrow-margin hepatectomy. Our trial provides evidence and a rationale for planning a future phase 3 trial.
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Affiliation(s)
- Bo Chen
- State Key Laboratory of Molecular OncologyDepartment of Radiation OncologyNational Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences, and Peking Union Medical CollegeBeijingP. R. China
| | - Jian‐Xiong Wu
- Department of Hepatobiliary SurgeryNational Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences, and Peking Union Medical CollegeBeijingP. R. China
| | - Shu‐Hui Cheng
- State Key Laboratory of Molecular OncologyDepartment of Radiation OncologyNational Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences, and Peking Union Medical CollegeBeijingP. R. China
| | - Li‐Ming Wang
- Department of Hepatobiliary SurgeryNational Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences, and Peking Union Medical CollegeBeijingP. R. China
| | - Wei‐Qi Rong
- Department of Hepatobiliary SurgeryNational Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences, and Peking Union Medical CollegeBeijingP. R. China
| | - Fan Wu
- Department of Hepatobiliary SurgeryNational Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences, and Peking Union Medical CollegeBeijingP. R. China
| | - Shu‐Lian Wang
- State Key Laboratory of Molecular OncologyDepartment of Radiation OncologyNational Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences, and Peking Union Medical CollegeBeijingP. R. China
| | - Jing Jin
- State Key Laboratory of Molecular OncologyDepartment of Radiation OncologyNational Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences, and Peking Union Medical CollegeBeijingP. R. China
| | - Yue‐Ping Liu
- State Key Laboratory of Molecular OncologyDepartment of Radiation OncologyNational Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences, and Peking Union Medical CollegeBeijingP. R. China
| | - Yong‐Wen Song
- State Key Laboratory of Molecular OncologyDepartment of Radiation OncologyNational Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences, and Peking Union Medical CollegeBeijingP. R. China
| | - Hua Ren
- State Key Laboratory of Molecular OncologyDepartment of Radiation OncologyNational Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences, and Peking Union Medical CollegeBeijingP. R. China
| | - Hui Fang
- State Key Laboratory of Molecular OncologyDepartment of Radiation OncologyNational Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences, and Peking Union Medical CollegeBeijingP. R. China
| | - Yuan Tang
- State Key Laboratory of Molecular OncologyDepartment of Radiation OncologyNational Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences, and Peking Union Medical CollegeBeijingP. R. China
| | - Ning Li
- State Key Laboratory of Molecular OncologyDepartment of Radiation OncologyNational Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences, and Peking Union Medical CollegeBeijingP. R. China
| | - Ye‐Xiong Li
- State Key Laboratory of Molecular OncologyDepartment of Radiation OncologyNational Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences, and Peking Union Medical CollegeBeijingP. R. China
| | - Wei‐Hu Wang
- State Key Laboratory of Molecular OncologyDepartment of Radiation OncologyNational Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences, and Peking Union Medical CollegeBeijingP. R. China,Key Laboratory of Carcinogenesis and Translational ResearchDepartment of Radiation OncologyPeking University Cancer Hospital & InstituteBeijingP. R. China
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Shehta A, Farouk A, Elghawalby AN, Elshobary M, Aboelenin A, Fouad A, Ali MA. Outcomes of Hepatic Resection for Hepatocellular Carcinoma Associated with Portal Vein Invasion. J Surg Res 2021; 266:269-283. [PMID: 34038849 DOI: 10.1016/j.jss.2021.04.011] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2020] [Revised: 04/02/2021] [Accepted: 04/10/2021] [Indexed: 01/27/2023]
Abstract
BACKGROUND To evaluate our experience of liver resection for hepatocellular carcinoma (HCC) patients associated with macroscopic portal vein invasion (PVI). METHODS Consecutive HCC patients who underwent liver resection for HCC between November 2009 & June 2019 were included. To overcome selection bias between patients with and without macroscopic PVI, we performed 1:1 match using propensity score matching (PSM). RESULTS Macroscopic PVI was detected in 37 patients (12.8%). We divided our patients into two groups according to the presence of macroscopic PVI. After PSM, 36 patients of PVI group were matched with 36 patients from Non-PVI group. After PSM, both groups were well balanced regarding tumor site, number, liver resection extent and type. Longer operation time and more blood loss were noted in PVI group. Higher incidence of post-operative morbidities occurred in PVI group especially, post-hepatectomy liver dysfunction. The 1-, 2-, and 3-y overall survival rates for Non-PVI group were 85.3%, 64.6%, and 64.6% & 69.8%, 42%, and 0% for PVI group, respectively (P = 0.009). There were no significant differences regarding the recurrence rate, site, and its management. The 1-, 2-, and 3-y disease-free survival (DFS) rates for Non-PVI group were 81.7%, 72.3%, and 21.7% & 67.7%, 42.3%, and 0% for PVI group, respectively (P = 0.172). CONCLUSION Surgical management of advanced HCCs with macroscopic PVI is feasible, and associated with comparable DFS but poorer overall survival, compared to patients without PVI.
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Affiliation(s)
- Ahmed Shehta
- Gastrointestinal Surgery Center, Department of Surgery, College of Medicine, Mansoura University, Mansoura, Egypt.
| | - Ahmed Farouk
- Gastrointestinal Surgery Center, Department of Surgery, College of Medicine, Mansoura University, Mansoura, Egypt
| | - Ahmed Nabieh Elghawalby
- Gastrointestinal Surgery Center, Department of Surgery, College of Medicine, Mansoura University, Mansoura, Egypt
| | - Mohamed Elshobary
- Gastrointestinal Surgery Center, Department of Surgery, College of Medicine, Mansoura University, Mansoura, Egypt
| | - Ahmed Aboelenin
- Gastrointestinal Surgery Center, Department of Surgery, College of Medicine, Mansoura University, Mansoura, Egypt
| | - Amgad Fouad
- Gastrointestinal Surgery Center, Department of Surgery, College of Medicine, Mansoura University, Mansoura, Egypt
| | - Mahmoud Abdelwahab Ali
- Gastrointestinal Surgery Center, Department of Surgery, College of Medicine, Mansoura University, Mansoura, Egypt
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20
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Shao Z, Liu X, Peng C, Wang L, Xu D. Combination of transcatheter arterial chemoembolization and portal vein embolization for patients with hepatocellular carcinoma: a review. World J Surg Oncol 2021; 19:293. [PMID: 34598689 PMCID: PMC8487116 DOI: 10.1186/s12957-021-02401-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2021] [Accepted: 09/15/2021] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Transcatheter arterial chemoembolization has been widely used in patients with hepatocellular carcinoma. However, double blood supply and the existence of portal vein tumor thrombus influence the efficacy of transcatheter arterial chemoembolization. MAIN BODY Theoretically, portal vein embolization combined with transcatheter arterial chemoembolization may bring a breakthrough in the therapeutic effect of hepatocellular carcinoma. The feasibility, efficacy, long-term survival benefits, and side effects of the combined treatment have been explored in previous studies. Chemotherapeutic agents may also be added in the portal vein embolization procedure to further improve the treatment response. CONCLUSION In this study, we review the existing data and studies on the combined treatment in patients with hepatocellular carcinoma and provide an overall view of the strategy.
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Affiliation(s)
- Zhiying Shao
- Department of Interventional Ultrasound, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences , No. 1 East Banshan Road, Gongshu District, Hangzhou, 310022, People's Republic of China
| | - Xin Liu
- Department of Interventional Ultrasound, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences , No. 1 East Banshan Road, Gongshu District, Hangzhou, 310022, People's Republic of China
| | - Chanjuan Peng
- Department of Interventional Ultrasound, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences , No. 1 East Banshan Road, Gongshu District, Hangzhou, 310022, People's Republic of China
| | - Liping Wang
- Department of Interventional Ultrasound, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences , No. 1 East Banshan Road, Gongshu District, Hangzhou, 310022, People's Republic of China
| | - Dong Xu
- Department of Interventional Ultrasound, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences , No. 1 East Banshan Road, Gongshu District, Hangzhou, 310022, People's Republic of China.
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21
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Transcatheter arterial chemoembolization followed by surgical resection for hepatocellular carcinoma: a focus on its controversies and screening of patients most likely to benefit. Chin Med J (Engl) 2021; 134:2275-2286. [PMID: 34593696 PMCID: PMC8509936 DOI: 10.1097/cm9.0000000000001767] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Surgical resection (SR) is recommended as a radical procedure in the treatment of hepatocellular carcinoma (HCC). However, postoperative recurrence negatively affects the long-term efficacy of SR, and preoperative adjuvant therapy has therefore become a research hotspot. Some clinicians adopt transcatheter arterial chemoembolization (TACE) as a preoperative adjuvant therapy in patients undergoing SR to increase the resection rate, reduce tumor recurrence, and improve the prognosis. However, the findings of the most relevant studies remain controversial. Some studies have confirmed that preoperative TACE cannot improve the long-term survival rate of patients with HCC and might even negatively affect the resection rate. Which factors influence the efficacy of preoperative TACE combined with SR is a topic worthy of investigation. In this review, existing clinical studies were analyzed with a particular focus on several topics: screening of the subgroups of patients most likely to benefit from preoperative TACE, exploration of the optimal treatment regimen of preoperative TACE, and determination of the extent of tumor necrosis as the deciding prognostic factor.
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22
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Liu Y, Wang Y, Guo X, He Y, Zhou J, Lv Q, Huang X, Li X. Comparative Effectiveness of Adjuvant Treatment for Resected Hepatocellular Carcinoma: A Systematic Review and Network Meta-Analysis. Front Oncol 2021; 11:709278. [PMID: 34540675 PMCID: PMC8445365 DOI: 10.3389/fonc.2021.709278] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2021] [Accepted: 08/09/2021] [Indexed: 12/24/2022] Open
Abstract
Background It is controversial whether adjuvant treatment could be recommended for hepatocellular carcinoma (HCC) after curative hepatectomy. Thus, we performed a network meta-analysis (NMA) to assess adjuvant treatment’s benefit and determine the optimal adjuvant regimen. Methods We systematically searched PubMed, Embase, and Cochrane Library for randomized controlled trials comparing adjuvant therapy versus no active treatment after curative hepatectomy among patients with HCC. Pooled data on recurrence and overall survival (OS) were analyzed within pairwise meta-analysis and NMA. Results Twenty-three eligible trials (3,940 patients) reporting eight treatments were included. The direct meta-analysis showed that adjuvant therapy prevented the recurrence (OR = 0.65; 95% CI: 0.55, 0.77; P = 0.177; I2 = 21.7%) and contributed to OS (HR = 0.63; 95% CI: 0.54, 0.73; P = 0.087; I2 = 31.1%) in comparison to the observation. In the NMA, internal radiotherapy (IRT; OR = 0.55; 95% CI: 0.39, 0.77; SUCRA = 87.7%) followed by hepatic artery infusion chemotherapy (HAIC; OR = 0.6; 95% CI: 0.36, 0.97; SUCRA = 77.8%), and HAIC (HR = 0.44; 95% CI: 0.21, 0.87; SUCRA = 82.6%) followed by IRT (HR 0.54; 95% CI:0.36, 0.81; SUCRA = 69.7%) were ranked superior to other treatments in terms of preventing recurrence and providing survival benefit, respectively. Conclusions The addition of adjuvant therapy lowers the risk of recurrence and provide survival benefit after surgical resection for HCC. HAIC and IRT are likely to be the two most effective adjuvant regimens. Systematic Review Registration https://inplasy.com/inplasy-2020-11-0039/.
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Affiliation(s)
- Ying Liu
- Department of Pharmacy, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yuzhu Wang
- Department of Pharmacy, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Xinkun Guo
- Deparment of Hepatic Oncology, Zhongshan Hospital, Fudan University, Xiamen, China
| | - Yifeng He
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China.,Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China
| | - Jian Zhou
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China.,Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China
| | - Qianzhou Lv
- Department of Pharmacy, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Xiaowu Huang
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China.,Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China
| | - Xiaoyu Li
- Department of Pharmacy, Zhongshan Hospital, Fudan University, Shanghai, China
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23
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Esagian SM, Kakos CD, Giorgakis E, Burdine L, Barreto JC, Mavros MN. Adjuvant Transarterial Chemoembolization Following Curative-Intent Hepatectomy Versus Hepatectomy Alone for Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Cancers (Basel) 2021; 13:2984. [PMID: 34203692 PMCID: PMC8232114 DOI: 10.3390/cancers13122984] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2021] [Revised: 06/07/2021] [Accepted: 06/09/2021] [Indexed: 02/07/2023] Open
Abstract
The role of adjuvant transarterial chemoembolization (TACE) for patients with resectable hepatocellular carcinoma (HCC) undergoing hepatectomy is currently unclear. We performed a systematic review of the literature using the MEDLINE, Embase, and Cochrane Library databases. Random-effects meta-analysis was carried out to compare the overall survival (OS) and recurrence-free survival (RFS) of patients with resectable HCC undergoing hepatectomy followed by adjuvant TACE vs. hepatectomy alone in randomized controlled trials (RCTs). The risk of bias was assessed using the Risk of Bias 2.0 tool. Meta-regression analyses were performed to explore the effect of hepatitis B viral status, microvascular invasion, type of resection (anatomic vs. parenchymal-sparing), and tumor size on the outcomes. Ten eligible RCTs, reporting on 1216 patients in total, were identified. The combination of hepatectomy and adjuvant TACE was associated with superior OS (hazard ratio (HR): 0.66, 95% confidence interval (CI): 0.52 to 0.85; p < 0.001) and RFS (HR: 0.70, 95% CI: 0.56 to 0.88; p < 0.001) compared to hepatectomy alone. There were significant concerns regarding the risk of bias in most of the included studies. Overall, adjuvant TACE may be associated with an oncologic benefit in select HCC patients. However, the applicability of these findings may be limited to Eastern Asian populations, due to the geographically restricted sample. High-quality multinational RCTs, as well as predictive tools to optimize patient selection, are necessary before adjuvant TACE can be routinely implemented into standard practice. PROSPERO Registration ID: CRD42021245758.
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Affiliation(s)
- Stepan M. Esagian
- Oncology Working Group, Society of Junior Doctors, 15123 Athens, Greece;
| | - Christos D. Kakos
- Surgery Working Group, Society of Junior Doctors, 15123 Athens, Greece;
| | - Emmanouil Giorgakis
- Department of Surgery, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA; (E.G.); (L.B.); (J.C.B.)
| | - Lyle Burdine
- Department of Surgery, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA; (E.G.); (L.B.); (J.C.B.)
| | - J. Camilo Barreto
- Department of Surgery, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA; (E.G.); (L.B.); (J.C.B.)
| | - Michail N. Mavros
- Surgery Working Group, Society of Junior Doctors, 15123 Athens, Greece;
- Department of Surgery, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA; (E.G.); (L.B.); (J.C.B.)
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24
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Zhang W, Zhang B, Chen XP. Adjuvant treatment strategy after curative resection for hepatocellular carcinoma. Front Med 2021; 15:155-169. [PMID: 33754281 DOI: 10.1007/s11684-021-0848-3] [Citation(s) in RCA: 60] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2020] [Accepted: 02/20/2021] [Indexed: 01/27/2023]
Abstract
Hepatic resection represents the first-line treatment for patients with resectable hepatocellular carcinoma (HCC). However, the 5-year recurrence rates of HCC after surgery have been reported to range from 50% to 70%. In this review, we evaluated the available evidence for the efficiency of adjuvant treatments to prevent HCC recurrence after curative liver resection. Antiviral therapy has potential advantages in terms of reducing the recurrence rate and improving the overall survival (OS) and/or disease-free survival of patients with hepatitis-related HCC. Postoperative adjuvant transarterial chemoembolization can significantly reduce the intrahepatic recurrence rate and improve OS, especially for patients with a high risk of recurrence. The efficacy of molecular targeted drugs as an adjuvant therapy deserves further study. Adjuvant adoptive immunotherapy can significantly improve the clinical prognosis in the early stage. Randomized controlled trial (RCT) studies evaluating adjuvant immune checkpoint inhibitors are ongoing, and the results are highly expected. Adjuvant hepatic artery infusion chemotherapy might be beneficial in patients with vascular invasion. Huaier granule, a traditional Chinese medicine, has been proved to be effective in prolonging the recurrence-free survival and reducing extrahepatic recurrence. The efficiency of other adjuvant treatments needs to be further confirmed by large RCT studies.
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Affiliation(s)
- Wei Zhang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Bixiang Zhang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
| | - Xiao-Ping Chen
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
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25
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Wang W, Guo Y, Zhong J, Wang Q, Wang X, Wei H, Li J, Xiu P. The clinical significance of microvascular invasion in the surgical planning and postoperative sequential treatment in hepatocellular carcinoma. Sci Rep 2021; 11:2415. [PMID: 33510294 PMCID: PMC7843639 DOI: 10.1038/s41598-021-82058-x] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2020] [Accepted: 01/12/2021] [Indexed: 02/07/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the most common and most lethal malignant tumors in the world. Microvascular invasion (MVI) is a major risk factor for survival outcomes and intrahepatic metastasis after resection in patients with HCC. Relevant English literatures retrieved using PubMed on the research progress of MVI in patients with HCC were reviewed. For HCC patients, especially those with MVI, it is very important to develop a comprehensive and sequential treatment plan to support the long-term survival of patients. This manuscript reviewed and analyzed the risk factors for MVI; the preoperative prediction of MVI, which informs the selection of surgical strategies; and the current situation and future direction of comprehensive postoperative treatment strategies; to provide a basis for the comprehensive treatment of HCC patients with MVI. For HCC patients with MVI, the preoperative prediction of MVI may play a certain guiding role in planning procedures, and the comprehensive sequential postoperative pathological detection of HCC MVI may provide a basis for treatment decisions.
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Affiliation(s)
- Wentao Wang
- Department of General Surgery, Shandong Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250014, Shandong, China
- Department of General Surgery, Shandong Provincial Qianfoshan Hospital, the First Hospital Affiliated With Shandong First Medical University, Jinan, China
| | - Yaxun Guo
- Department of General Surgery, Shandong Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250014, Shandong, China
- Department of General Surgery, Shandong Provincial Qianfoshan Hospital, the First Hospital Affiliated With Shandong First Medical University, Jinan, China
| | - Jingtao Zhong
- Department of Hepatobiliary Surgery, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China
| | - Qi Wang
- Department of General Surgery, Shandong Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250014, Shandong, China
| | - Xin Wang
- Department of General Surgery, Shandong Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250014, Shandong, China
- Department of General Surgery, Shandong Provincial Qianfoshan Hospital, the First Hospital Affiliated With Shandong First Medical University, Jinan, China
| | - Honglong Wei
- Department of General Surgery, Shandong Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250014, Shandong, China
- Department of General Surgery, Shandong Provincial Qianfoshan Hospital, the First Hospital Affiliated With Shandong First Medical University, Jinan, China
| | - Jie Li
- Department of General Surgery, Shandong Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250014, Shandong, China
- Department of General Surgery, Shandong Provincial Qianfoshan Hospital, the First Hospital Affiliated With Shandong First Medical University, Jinan, China
| | - Peng Xiu
- Department of General Surgery, Shandong Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250014, Shandong, China.
- Department of General Surgery, Shandong Provincial Qianfoshan Hospital, the First Hospital Affiliated With Shandong First Medical University, Jinan, China.
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26
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Liang L, Li C, Diao YK, Jia HD, Xing H, Pawlik TM, Lau WY, Shen F, Huang DS, Zhang CW, Yang T. Survival benefits from adjuvant transcatheter arterial chemoembolization in patients undergoing liver resection for hepatocellular carcinoma: a systematic review and meta-analysis. Therap Adv Gastroenterol 2020; 13:1756284820977693. [PMID: 33329759 PMCID: PMC7720303 DOI: 10.1177/1756284820977693] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2020] [Accepted: 11/10/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Although adjuvant transcatheter arterial chemoembolization (TACE) has been used to prevent recurrence after surgery in patients with hepatocellular carcinoma (HCC), the survival benefits from adjuvant TACE remain controversial. We sought to systematically evaluate the data on the effectiveness of adjuvant TACE for HCC, as well as identify patient populations that might benefit from adjuvant TACE. METHODS The PubMed, Embase, Medline and Cochrane library were systematically searched for studies published before July 2019 that compared adjuvant TACE versus surgery alone for HCC. The study endpoints were overall survival (OS) and disease-free survival (DFS). Patients with large HCC (⩾5 cm), multinodular HCC, microvascular invasion (MVI), or portal vein tumor thrombosis (PVTT) were analyzed in subgroup analyses. RESULTS Twenty-four studies with 6977 patients were included in the analytic cohort. The pooled analysis demonstrated that adjuvant TACE was associated with a better OS and DFS [hazard ratio (HR): 0.67 and 0.67, both p < 0.01]. In subgroup analyses, pooled results revealed that adjuvant TACE was associated with an improved OS and DFS in patients with multinodular HCC (HR: 0.79 and 0.31, both p < 0.01), MVI (HR: 0.62 and 0.67, both p < 0.01), or PVTT (HR: 0.49 and 0.58, both p < 0.01), but not among patients with large HCC (⩾5 cm). CONCLUSION Postoperative adjuvant TACE may be effective to improve OS and DFS in patients with multinodular HCC, or HCC with MVI or PVTT. Future randomized controlled trials are needed to better define the benefit of adjuvant TACE in subset patients with HCC.
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Affiliation(s)
- Lei Liang
- Department of Hepatobiliary, Pancreatic and Minimal Invasive Surgery, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, China
- Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Hangzhou, China
| | - Chao Li
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China
| | - Yong-Kang Diao
- Department of Hepatobiliary, Pancreatic and Minimal Invasive Surgery, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, China
- Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Hangzhou, China
| | - Hang-Dong Jia
- Department of Hepatobiliary, Pancreatic and Minimal Invasive Surgery, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, China
- Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Hangzhou, China
| | - Hao Xing
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China
| | - Timothy M. Pawlik
- Department of Surgery, Ohio State University, Wexner Medical Center, Columbus, OH, USA
| | - Wan Yee Lau
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China Faculty of Medicine, the Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, N.T., Hong Kong SAR, China
| | - Feng Shen
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China
| | - Dong-Sheng Huang
- School of Clinical Medicine, Hangzhou Medical College, Hangzhou, Zhejiang, China
| | - Cheng-Wu Zhang
- Department of Hepatobiliary, Pancreatic and Minimal Invasive Surgery, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, No. 158, Shangtang Road, Hangzhou, Zhejiang, China
| | - Tian Yang
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, No. 225, Changhai Road, Shanghai, 200438, China
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27
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Zhang YL, Nie CH, Chen F, Zhou TY, Zhou GH, Zhu TY, Chen SQ, Chen XH, Wang HL, Wang BQ, Yu ZN, Jing L, He ZM, Sun JH. Adjuvant Transarterial Chemoembolization for Barcelona Clinic Liver Cancer Stage A Hepatocellular Carcinoma After Hepatectomy. Front Oncol 2020; 10:1754. [PMID: 32984060 PMCID: PMC7492616 DOI: 10.3389/fonc.2020.01754] [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: 04/09/2020] [Accepted: 08/05/2020] [Indexed: 11/24/2022] Open
Abstract
Introduction The care for patients with hepatocellular carcinoma (HCC) is challenging. This study is to evaluate the effect of adjuvant transarterial chemoembolization (TACE) for Barcelona Clinic Liver Cancer (BCLC) stage A HCC patients after hepatectomy. Methods Consecutive HCC patients with BCLC stage A, treated by hepatectomy alone (HA) or hepatectomy with TACE (HT), were retrospectively enrolled. Propensity score matching (PSM) was used to balance baseline differences. The recurrence-free survival (RFS) and overall survival (OS) were evaluated using the Kaplan-Meier. The impact of TACE on survival outcome was determined by Cox hazard regression. Results After PSM, 230 patients (115 HT and 115 HA) were enrolled in the analysis. The 1-, 3-, and 5-year RFS rates were 87.0, 63.5, and 50.4%, respectively, for the HT group, and 87.8, 67.0, and 58.3% for the HA group. The OS rates at 1-, 3-, and 5-year were 99.1, 93.9, and 87%, respectively, for the HT group, and 100, 92.2, and 88.7% for the HA group. No significant differences were seen in either the RFS (log-rank test, χ2 = 0.891, p = 0.345) or OS (log-rank test, χ2 = 0.146, p = 0.702) between the specific pairs of two groups. Cox regression identified that TACE was not the factor affecting RFS or OS (p = 0.399; HR 0.847; 95% CI 0.576–1.245 for RFS vs. p = 0.989; HR 0.995; 95% CI 0.471–2.100 for OS). Conclusion Our data indicate that TACE is not an effective intervention in the adjuvant setting for BCLC stage A HCC after hepatectomy.
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Affiliation(s)
- Yue-Lin Zhang
- Hepatobiliary and Pancreatic Interventional Treatment Center, Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Zhejiang Clinical Research Center of Hepatobiliary and Pancreatic Diseases, Hangzhou, China
| | - Chun-Hui Nie
- Hepatobiliary and Pancreatic Interventional Treatment Center, Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Zhejiang Provincial Research Center for Diagnosis and Treatment of Hepatobiliary Diseases, Hangzhou, China
| | - Feng Chen
- Department of Radiology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Tan-Yang Zhou
- Hepatobiliary and Pancreatic Interventional Treatment Center, Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Zhejiang Clinical Research Center of Hepatobiliary and Pancreatic Diseases, Hangzhou, China
| | - Guan-Hui Zhou
- Hepatobiliary and Pancreatic Interventional Treatment Center, Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Zhejiang Clinical Research Center of Hepatobiliary and Pancreatic Diseases, Hangzhou, China
| | - Tong-Yin Zhu
- Hepatobiliary and Pancreatic Interventional Treatment Center, Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Zhejiang Clinical Research Center of Hepatobiliary and Pancreatic Diseases, Hangzhou, China
| | - Sheng-Qun Chen
- Hepatobiliary and Pancreatic Interventional Treatment Center, Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Zhejiang Provincial Research Center for Diagnosis and Treatment of Hepatobiliary Diseases, Hangzhou, China
| | - Xin-Hua Chen
- Hepatobiliary and Pancreatic Interventional Treatment Center, Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Zhejiang Clinical Research Center of Hepatobiliary and Pancreatic Diseases, Hangzhou, China
| | - Hong-Liang Wang
- Hepatobiliary and Pancreatic Interventional Treatment Center, Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Zhejiang Provincial Research Center for Diagnosis and Treatment of Hepatobiliary Diseases, Hangzhou, China
| | - Bao-Quan Wang
- Hepatobiliary and Pancreatic Interventional Treatment Center, Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Zhejiang Clinical Research Center of Hepatobiliary and Pancreatic Diseases, Hangzhou, China
| | - Zi-Niu Yu
- Hepatobiliary and Pancreatic Interventional Treatment Center, Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Zhejiang Clinical Research Center of Hepatobiliary and Pancreatic Diseases, Hangzhou, China
| | - Li Jing
- Hepatobiliary and Pancreatic Interventional Treatment Center, Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Zhejiang Clinical Research Center of Hepatobiliary and Pancreatic Diseases, Hangzhou, China
| | - Zhi-Min He
- Hepatobiliary and Pancreatic Interventional Treatment Center, Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Zhejiang Provincial Research Center for Diagnosis and Treatment of Hepatobiliary Diseases, Hangzhou, China
| | - Jun-Hui Sun
- Hepatobiliary and Pancreatic Interventional Treatment Center, Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Zhejiang Clinical Research Center of Hepatobiliary and Pancreatic Diseases, Hangzhou, China.,Zhejiang Provincial Research Center for Diagnosis and Treatment of Hepatobiliary Diseases, Hangzhou, China
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28
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Huang Q, Lin K, Wang L, Zeng J, Liu H, Ding Z, Zeng Y, Liu J. Postoperative Adjuvant Transarterial Chemoembolization Improves Short-Term Prognosis of Hepatocellular Carcinoma with Bile Duct Tumor Thrombus: A Propensity-Score Matching Study. Cancer Manag Res 2020; 12:9183-9195. [PMID: 33061610 PMCID: PMC7535114 DOI: 10.2147/cmar.s270467] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2020] [Accepted: 08/29/2020] [Indexed: 12/14/2022] Open
Abstract
PURPOSE To evaluate the effect of postoperative adjuvant transarterial chemoembolization (PA-TACE) on the prognosis of hepatocellular carcinoma (HCC) with macroscopic bile duct tumor thrombus (BDTT). PATIENTS AND METHODS This study included 109 patients who underwent R0 resection for HCC with BDTT between January 2008 and December 2017: non-TACE (48) and PA-TACE (61). Propensity-score matching (PSM) was conducted in a 1:1 ratio. Recurrence and overall survival (OS) rates were analyzed using the Kaplan-Meier method. Independent risk factors were identified by univariate and multivariate Cox regression analyses. Subgroup analysis was performed by risk-factor stratification. RESULTS The recurrence rates in the non-TACE and PA-TACE groups were different at 6 months (50.9% vs 26.9%, P=0.03) before PSM and at 6 months (59.3% vs 26.5%, P=0.02) and 12 months (81.4% vs 37.5%, P=0.022) after PSM. OS rates of the non-TACE and PA-TACE groups were different at 6 months (74.0% vs 91.6%, P<0.001) and 12 months (61.1% vs 77.6%, P=0.01) before PSM and at 6 months (73.0% vs 96.8%, P=0.01), 12 months (52.1% vs 89.6%, P=0.001), and 18 months (33.8% vs 64.4%, P=0.034) after PSM. PA-TACE was an independent prognostic factor for both recurrence and OS before and after PSM. Subgroup analysis showed that patients with no HBV infection, tumors >5 cm, macrovascular invasion, alpha-fetoprotein (AFP) >400 ng/mL, or gamma-glutamyl transferase (GGT) >150 U/L benefited significantly from PA-TACE in terms of recurrence rates (all P<0.05). Patients with no HBV infection, multiple tumors, tumors >5 cm, macrovascular invasion, or AFP >400 ng/mL benefited significantly from PA-TACE in terms of OS (all P<0.05). CONCLUSION PA-TACE could prolong the short-term prognosis of HCC with macroscopic BDTT and should be recommended for patients with no HBV infection, multiple tumors, tumors >5 cm, poor differentiation, macrovascular invasion, AFP >400 ng/mL, or GGT >150 U/L.
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Affiliation(s)
- Qizhen Huang
- Department of Radiation Oncology, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, People’s Republic of China
| | - Kongying Lin
- Department of Hepatopancreatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, People’s Republic of China
| | - Lei Wang
- Department of Radiation Oncology, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, People’s Republic of China
| | - Jianxing Zeng
- Department of Hepatopancreatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, People’s Republic of China
| | - Hongzhi Liu
- Department of Hepatopancreatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, People’s Republic of China
| | - Zongren Ding
- Department of Hepatopancreatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, People’s Republic of China
| | - Yongyi Zeng
- Department of Hepatopancreatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, People’s Republic of China
| | - Jingfeng Liu
- Department of Hepatopancreatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, People’s Republic of China
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Zhu XD, Li KS, Sun HC. Adjuvant therapies after curative treatments for hepatocellular carcinoma: Current status and prospects. Genes Dis 2020; 7:359-369. [PMID: 32884990 PMCID: PMC7452398 DOI: 10.1016/j.gendis.2020.02.002] [Citation(s) in RCA: 37] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2019] [Accepted: 02/20/2020] [Indexed: 02/07/2023] Open
Abstract
Tumor recurrence rate after surgery or ablation of hepatocellular carcinoma (HCC) is as high as 70%. However, there are no widely accepted adjuvant therapies; therefore, no treatment has been recommended by guidelines from the American Association for the Study of Liver Disease or the European Association for the Study of the Liver. All the registered trials failed to find any treatment to prolong recurrence-free survival, which is the primary outcome in most studies, including sorafenib. Some investigator-initiated studies revealed that anti-hepatitis B virus agents, interferon-α, transcatheter chemoembolization, chemokine-induced killer cells, and other treatments prolonged patient recurrence-free survival or overall survival after curative therapies. In this review, we summarize the current status of adjuvant treatments for HCC and explain the challenges associated with designing a clinical trial for adjuvant therapy. Promising new treatments being used as adjuvant therapy, especially anti-PD-1 antibodies, are also discussed.
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Key Words
- Adjuvant therapy
- Anti-PD-1 antibody
- CIK, chemokine-induced killer cells
- CR, complete response
- Clinical trial
- HCC, hepatocellular carcinoma
- Hepatocellular carcinoma
- ICI, immune checkpoint inhibitor
- Molecular targeted therapy
- ORR, objective response rate
- OS, overall survival
- PD-1, program death-1
- PD-L1, program death-1 ligand
- PR, partial response
- RCT, randomized clinical trial
- RECIST, Response Evaluation Criteria in Solid Tumors
- RFS, recurrence-free survival
- Recurrence-free survival
- TACE, transcatheter chemoembolization
- TKI, tyrosine kinase inhibitor
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Affiliation(s)
- Xiao-Dong Zhu
- Department of Liver Surgery and Transplantation, Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, 200032, China
| | - Kang-Shuai Li
- Department of Liver Surgery and Transplantation, Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, 200032, China
| | - Hui-Chuan Sun
- Department of Liver Surgery and Transplantation, Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, 200032, China
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Neutrophil-lymphocyte ratio predicts the therapeutic benefit of neoadjuvant transarterial chemoembolization in patients with resectable hepatocellular carcinoma. Eur J Gastroenterol Hepatol 2020; 32:1186-1191. [PMID: 31851089 DOI: 10.1097/meg.0000000000001629] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND AIMS All published meta-analyses failed to demonstrate that preoperative transarterial chemoembolization improves the clinical outcomes of patients with resectable hepatocellular carcinoma. The present study aimed to investigate the utility of systemic inflammatory cells as a tumor biology marker predicting therapeutic benefit of neoadjuvant transarterial chemoembolization in patients with resectable hepatocellular carcinoma. MATERIALS AND METHODS We retrospectively investigated 441 hepatocellular carcinoma patients who underwent curative resection. Among 441 patients, 73 patients underwent preoperative transarterial chemoembolization, and 368 patients did not. We compared recurrence-free survival and overall survival between transarterial chemoembolization plus sequential resection group and resection only group. We analyzed whether pretreatment neutrophil-lymphocyte ratio demonstrates survival benefit in each groups. RESULTS No significant difference was observed in recurrence-free or overall survival between both groups. In the transarterial chemoembolization plus sequential resection group, the 5-year overall survival in patients with high neutrophil-lymphocyte ratio (≥1.6) was significantly lower than that in patients with low neutrophil-lymphocyte ratio (78.4% and 100%, P = 0.027). High neutrophil-lymphocyte ratio was associated with vascular invasion (P = 0.033). CONCLUSION Neutrophil-lymphocyte ratio can be considered as a predictive factor of long-term survival and used to identify patients with resectable hepatocellular carcinoma who benefit from neoadjuvant transarterial chemoembolization.
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Hirokawa F, Komeda K, Taniguchi K, Asakuma M, Shimizu T, Inoue Y, Kagota S, Tomioka A, Yamamoto K, Uchiyama K. Is Postoperative Adjuvant Transcatheter Arterial Infusion Therapy Effective for Patients with Hepatocellular Carcinoma who Underwent Hepatectomy? A Prospective Randomized Controlled Trial. Ann Surg Oncol 2020; 27:4143-4152. [PMID: 32500344 DOI: 10.1245/s10434-020-08699-w] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2020] [Indexed: 12/15/2022]
Abstract
BACKGROUND The effectiveness of adjuvant transcatheter arterial chemo- or/and chemoembolization therapy after curative hepatectomy of initial hepatocellular carcinoma (HCC) is controversial. This study aimed to evaluate whether hepatectomy combined with adjuvant transcatheter arterial infusion therapy (TAI) for initial HCC has better long-term survival outcomes than hepatectomy alone. METHODS From January 2012 to December 2014, a prospective randomized controlled trial of patients with initial HCC was conducted. Then, 114 initial HCC patients were recruited to undergo hepatectomy with adjuvant TAI (TAI group, n = 55) or hepatectomy alone (control group, n = 59) at our institution. The TAI therapy was performed twice, at 3 and 6 months after curative hepatectomy (UMIN 000011900). RESULTS The patients treated with TAI had no serious side effects, and operative outcomes did not differ between the two groups. No significant differences were found in the pattern of intrahepatic recurrence or time until recurrence between the two groups. Moreover, no significant differences were found in the relapse-free survival or overall survival. Low cholinesterase level (< 200) had been identified as a risk factor affecting relapse-free survival. Furthermore, compared with surgery alone, adjuvant TAI with hepatectomy improved the overall survival for lower-cholinesterase patients. CONCLUSIONS Adjuvant TAI is safe and feasible, but it cannot reduce the incidence of postoperative recurrence or prolong survival for patients who underwent curative hepatectomy for initial HCC.
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Affiliation(s)
- Fumitoshi Hirokawa
- Department of General and Gastroenterological Surgery, Osaka Medical College, Takatsuki City, Osaka, Japan.
| | - Koji Komeda
- Department of General and Gastroenterological Surgery, Osaka Medical College, Takatsuki City, Osaka, Japan
| | - Kohei Taniguchi
- Department of General and Gastroenterological Surgery, Osaka Medical College, Takatsuki City, Osaka, Japan.,Translational Research Program, Osaka Medical College, Osaka, Japan
| | - Mitsuhiro Asakuma
- Department of General and Gastroenterological Surgery, Osaka Medical College, Takatsuki City, Osaka, Japan
| | - Tetsunosuke Shimizu
- Department of General and Gastroenterological Surgery, Osaka Medical College, Takatsuki City, Osaka, Japan
| | - Yoshihiro Inoue
- Department of General and Gastroenterological Surgery, Osaka Medical College, Takatsuki City, Osaka, Japan
| | - Shuji Kagota
- Department of General and Gastroenterological Surgery, Osaka Medical College, Takatsuki City, Osaka, Japan
| | - Atsushi Tomioka
- Department of General and Gastroenterological Surgery, Osaka Medical College, Takatsuki City, Osaka, Japan
| | | | - Kazuhisa Uchiyama
- Department of General and Gastroenterological Surgery, Osaka Medical College, Takatsuki City, Osaka, Japan
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Chen W, Ma T, Zhang J, Zhang X, Chen W, Shen Y, Bai X, Liang T. A systematic review and meta-analysis of adjuvant transarterial chemoembolization after curative resection for patients with hepatocellular carcinoma. HPB (Oxford) 2020; 22:795-808. [PMID: 31980307 DOI: 10.1016/j.hpb.2019.12.013] [Citation(s) in RCA: 45] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2019] [Revised: 12/15/2019] [Accepted: 12/20/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND The aim of this study was to systematically evaluate and determine those patients with hepatocellular carcinoma (HCC) that would benefit from the administration of postoperative adjuvant transarterial chemoembolization (PA-TACE). METHODS PubMed, Embase and Cochrane Library were searched for randomized controlled trials (RCTs) and observational studies up to July 30, 2019. The outcome of Overall survival (OS) and disease-free survival (DFS) were extracted and converted to hazard ratios (HRs) with 95% confidence intervals (95%CIs). RESULTS A total of 40 studies (10 RCTs and 30 non-RCTs) involving 11,165 patients were included. Overall, PA-TACE was associated with an increased OS [HR, 0.71 (95% CI, 0.65-0.77); P < 0.001] and DFS [HR, 0.73 (95% CI, 0.66-0.80); P < 0.001]. Subgroup analysis in patients with microvascular invasion (MVI), tumor diameter >5 cm or multinodular tumors demonstrated that PA-TACE improved OS and DFS. In patients without MVI, PA-TACE showed no improvement in OS [HR, 1.14 (95% CI, 0.85-1.53); P = 0.370], and resulted in worse DFS than curative resection alone [HR, 1.20 (95% CI, 1.03-1.39); P = 0.002]. CONCLUSION This meta-analysis indicated that PA-TACE was beneficial in patients with HCC who were at high risk of postoperative recurrence including tumor diameter >5 cm, multinodular tumors and MVI-positive. In patients with tumor diameter ≤5 cm, single tumor or MVI-negative. PA-TACE does not appear to improve outcomes and may potentially promote postoperative recurrence in certain patients.
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Affiliation(s)
- Wen Chen
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, China; Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou 310009, China; Innovation Center for the Study of Pancreatic Diseases, Zhejiang Province, China
| | - Tao Ma
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, China; Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou 310009, China; Innovation Center for the Study of Pancreatic Diseases, Zhejiang Province, China
| | - Jian Zhang
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, China; Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou 310009, China; Innovation Center for the Study of Pancreatic Diseases, Zhejiang Province, China
| | - Xiaozhen Zhang
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, China; Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou 310009, China; Innovation Center for the Study of Pancreatic Diseases, Zhejiang Province, China
| | - Wei Chen
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, China; Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou 310009, China; Innovation Center for the Study of Pancreatic Diseases, Zhejiang Province, China
| | - Yinan Shen
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, China; Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou 310009, China; Innovation Center for the Study of Pancreatic Diseases, Zhejiang Province, China
| | - Xueli Bai
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, China; Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou 310009, China; Innovation Center for the Study of Pancreatic Diseases, Zhejiang Province, China
| | - Tingbo Liang
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, China; Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou 310009, China; Innovation Center for the Study of Pancreatic Diseases, Zhejiang Province, China.
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Shen A, Liu M, Zheng D, Chen Q, Wu Z. Adjuvant transarterial chemoembolization after curative hepatectomy for hepatocellular carcinoma with microvascular invasion: A systematic review and meta-analysis. Clin Res Hepatol Gastroenterol 2020; 44:142-154. [PMID: 31303533 DOI: 10.1016/j.clinre.2019.06.012] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2019] [Revised: 05/30/2019] [Accepted: 06/05/2019] [Indexed: 02/07/2023]
Abstract
OBJECTIVE Microvascular invasion (MVI) has been associated with a poor prognosis for hepatocellular carcinoma (HCC) patients. This study aimed to evaluate the efficacy and safety of adjuvant transarterial chemoembolization (TACE) after curative hepatectomy for HCC with MVI. METHODS An online search on Embase and Ovid MEDLINE(R) was conducted to identify the appropriate articles published prior to March 11, 2019. The primary endpoint was the overall survival (OS) of patients treated using adjuvant TACE after hepatectomy (HTAT) versus hepatectomy (HT) alone for HCC with MVI. The secondary endpoints were disease-free survival (DFS) and safety. RESULTS Seven studies with 1869 patients were included in this analysis. Meta-analyses demonstrated that HTAT was superior to HT in OS (Hazard Ratio [HR]: 0.67, 95%CI: 0.58-0.77, P<0.001) and DFS (HR: 0.71, 95%CI: 0.62-0.81, P<0.001) for treating HCC with MVI. Subgroup analysis revealed that for early-stage HCC, HTAT was associated with longer OS (P=0.009) and DFS (P=0.066) as compared with HT. For HCC larger than 5cm, HTAT also prolonged the DFS (P=0.008) of patients, but the difference in OS was not statistically significant (P=0.266). Adjuvant TACE commonly caused nausea and vomiting, liver dysfunction, leucopenia, pain, and fever. CONCLUSIONS Adjuvant TACE after hepatectomy is effective and safe for patients with HCC accompanied by MVI. However, the benefit of adjuvant TACE in patients who have HCC with a diameter >5cm is not clear. Further randomized controlled studies are warranted to test these conclusions.
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Affiliation(s)
- Ai Shen
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; Hepatobiliary and Pancreatic Tumor Center, Chongqing University Cancer Hospital, Chongqing, China.
| | - Miao Liu
- Gastrointestinal Tumor Center, Chongqing University Cancer Hospital, Chongqing, China.
| | - Daofeng Zheng
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
| | - Qingsong Chen
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
| | - Zhongjun Wu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
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Resection Plus Post-operative Adjuvant Transcatheter Arterial Chemoembolization (TACE) Compared with Resection Alone for Hepatocellular Carcinoma: A Systematic Review and Meta-analysis. Cardiovasc Intervent Radiol 2020; 43:572-586. [PMID: 31897617 DOI: 10.1007/s00270-019-02392-6] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2019] [Accepted: 12/03/2019] [Indexed: 02/08/2023]
Abstract
PURPOSE Multiple studies have demonstrated adjuvant transcatheter arterial chemoembolization (aTACE) after resection improved outcomes compared to resection alone for patients with hepatocellular carcinoma (HCC). Unlike pre-operative TACE which targets a lesion, aTACE is administered in the proximal hepatic artery to destroy cancer cells within the remaining liver. This systematic review and meta-analysis aims to quantify this survival and disease-free survival (DFS) benefit. METHODS A search of five databases was performed from inception to 20 August 2019. RESULTS A total of 26 studies (six randomized controlled trials) involving 7817 patients were included. Patients treated with resection plus aTACE had significantly better 1-year survival (OR, 2.53 [95% CI, 1.70-3.76, p < 0.001) and 1-year DFS (OR, 1.91 [95% CI, 1.60-2.28, p < 0.001) compared to resection alone. The survival benefit remained significant for 2- to 5-year survival (OR 2.39, 1.83, 2.12, 1.87, respectively) and 2- to 4-year DFS (OR 1.85, 1.24, 1.67, respectively). Subgroup analysis showed significant survival benefit with aTACE in microvascular invasion (MVI)-positive HCC, portal venous tumour thrombus (PVTT) that does not involve the main trunk, PVTT-negative, satellite nodules, with and without resection margin < 1 cm. No mortalities were reported with aTACE. CONCLUSION Post-operative aTACE is safe and improves overall and disease-free survival, with the greatest benefit in MVI-positive patients. The current evidence weakly supports the use of adjuvant TACE for patients without PVTT, with PVTT that does not involve the main trunk, with and without a resection margin < 1 cm, and patients with satellite nodules. LEVEL OF EVIDENCE Level 1.
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Lu SD, Li L, Liang XM, Chen W, Chen FL, Fan LL, Ahir BK, Zhang WG, Zhong JH. Updates and advancements in the management of hepatocellular carcinoma patients after hepatectomy. Expert Rev Gastroenterol Hepatol 2019; 13:1077-1088. [PMID: 31648568 DOI: 10.1080/17474124.2019.1684898] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2019] [Accepted: 10/21/2019] [Indexed: 02/07/2023]
Abstract
Introduction: The 5-year recurrence rate of hepatocellular carcinoma (HCC) after hepatic resection or local ablation is up to 70%. Adjuvant therapies to prevent HCC recurrence have been reported but are not currently recommended by EASL or AASLD guidelines. This review examined evidence from randomized controlled trials, meta-analyses and systematic reviews on the safety and efficacy of adjuvant therapies and chemotherapies in HCC patients after resection or local ablation.Areas covered: PubMed was searched through 15 June 2019. Available evidence was assessed based on the GRADE system.Expert commentary: Transarterial chemoembolization is the best adjuvant therapy for HCC patients at high risk of recurrence, antiviral therapy with nucleoside analogs is effective for preventing recurrence of HBV-related HCC, and interferon-α is effective for preventing recurrence of HCV-related HCC. Further studies are needed to clarify the efficacy of adjuvant immune checkpoint inhibitors. Adjuvant sorafenib appears to offer negligible clinical benefit and high risk of adverse effects.
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Affiliation(s)
- Shi-Dong Lu
- Department of Hepatobiliary Surgery, the Third Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Lin Li
- Department of Hepatobiliary Surgery, the Third Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Xin-Min Liang
- Grade 2016, Basic medical college of Guangxi Medical University, Nanning, China
| | - Wu Chen
- Grade 2016, Basic medical college of Guangxi Medical University, Nanning, China
| | - Fu-Li Chen
- Grade 2016, Basic medical college of Guangxi Medical University, Nanning, China
| | - Lang-Lin Fan
- Grade 2016, Basic medical college of Guangxi Medical University, Nanning, China
| | - Bhavesh K Ahir
- Section of Hematology and Oncology, Department of Medicine, University of Illinois at Chicago, Chicago, IL, USA
| | - Wan-Guang Zhang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jian-Hong Zhong
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China
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Chan MY, She WH, Dai WC, Tsang SHY, Chok KSH, Chan ACY, Fung J, Lo CM, Cheung TT. Prognostic value of preoperative alpha-fetoprotein (AFP) level in patients receiving curative hepatectomy- an analysis of 1,182 patients in Hong Kong. Transl Gastroenterol Hepatol 2019; 4:52. [PMID: 31463411 PMCID: PMC6691082 DOI: 10.21037/tgh.2019.06.07] [Citation(s) in RCA: 38] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2018] [Accepted: 06/23/2019] [Indexed: 01/27/2023] Open
Abstract
BACKGROUND The value of alpha-fetoprotein (AFP) as a prognostic indicator in patients with hepatocellular carcinoma (HCC) has been proposed in recent studies, but the evidence so far is still contradictory. This analysis aims to evaluate the prognostic value of preoperative AFP level in patients undergoing curative resection. METHODS This retrospective study reviewed the prospectively collected data of all patients who underwent initial liver resection for HCC at Queen Mary Hospital during the period from March 1999 to March 2013. Patients with palliative resection, positive margin after pathological examination or distant metastasis were excluded from the study. Survival of patients with AFP level of <20, 20-400 and >400 ng/mL were compared with Kaplan-Meier analysis. Subgroup analysis was performed according to tumour stage (7th edition UICC staging) and tumour size. The optimal cutoff value was determined by area under receiver operating characteristic curve. RESULTS A total of 1,182 patients were included. Best overall (OS) and disease free survival (DFS) was observed in patients with AFP level <20 ng/mL. Progressively worse outcomes were seen for patients with increasing level of AFP. The median OS were 132.9, 77.2 and 38.4 months for patients with AFP <20, 20-400 and >400 ng/mL respectively (P<0.001). The median DFS for these three groups were 55.6, 25 and 8.4 months respectively (P<0.001). There was significant difference in both OS and DFS among all 3 groups. With subgroup analysis according to tumour stage (stage I and II versus stage III and IV) and tumour size (5 cm or less versus larger than 5 cm), such difference was still observed and remained statistically significant. Optimal cutoff value by discriminant analysis was 12,918.3 ng/mL for OS and 9,733.3 ng/mL for DFS. CONCLUSIONS This study demonstrates that AFP is a significant prognostic indicator in HCC. Despite tumour stage and size, high level of AFP is associated with poorer OS and DFS. Whether the level of AFP should be included in current staging systems, or treatment protocols, is yet to be determined.
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Affiliation(s)
- Miu Yee Chan
- Department of Surgery, The University of Hong Kong, Hong Kong, China
| | - Wong Hoi She
- Department of Surgery, The University of Hong Kong, Hong Kong, China
| | - Wing Chiu Dai
- Department of Surgery, The University of Hong Kong, Hong Kong, China
| | | | | | | | - Jame Fung
- Department of Medicine, The University of Hong Kong, Hong Kong, China
| | - Chung Mau Lo
- Department of Surgery, The University of Hong Kong, Hong Kong, China
| | - Tan To Cheung
- Department of Surgery, The University of Hong Kong, Hong Kong, China
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Chen ZH, Zhang XP, Zhou TF, Wang K, Wang H, Chai ZT, Shi J, Guo WX, Cheng SQ. Adjuvant transarterial chemoembolization improves survival outcomes in hepatocellular carcinoma with microvascular invasion: A systematic review and meta-analysis. Eur J Surg Oncol 2019; 45:2188-2196. [PMID: 31256949 DOI: 10.1016/j.ejso.2019.06.031] [Citation(s) in RCA: 55] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2019] [Revised: 04/28/2019] [Accepted: 06/24/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The benefits of adjuvant transarterial chemoembolization (TACE) in hepatocellular carcinoma (HCC) patients with microvascular invasion (MVI) remain controversial. We compared the efficacy and safety of adjuvant TACE and hepatic resection (HR) alone for HCC patients with MVI. METHODS The PubMed, EMBASE, Cochrane Library, VIP, Wan Fang, and Sino Med databases were systematically searched to compare adjuvant TACE and HR alone for the treatment of HCC with MVI from inception to January 1, 2019. The study outcomes, including overall survival (OS) and disease-free survival (DFS), were extracted independently by two authors. RESULTS 12 trials involving 2190 patients were evaluated. A meta-analysis of 11 studies suggested that the 1-, 3-, and 5-year overall survival (OS) rates (OR = 0.33, P < 0.001; OR = 0.49, P < 0.001; and OR = 0.59, P < 0.01; respectively), favored adjuvant TACE over HR alone. 11 studies were included in the meta-analysis of DFS, and adjuvant TACE showed better 1-, 3-, and 5-DFS (OR = 0.45, P < 0.001; OR = 0.50, P < 0.001; and OR = 0.58, P < 0.001; respectively) compared to HR alone. Subgroup analysis demonstrated that adjuvant TACE could benefit HCC patients with MVI with tumor diameter >5 cm or multinodular tumors. CONCLUSION Adjuvant TACE may improve OS and DFS for HCC patients with MVI compared to HR alone and should be recommended for selected HCC patients with MVI. However, these results need to be validated through further high-quality clinical studies. LAY SUMMARY The benefits of adjuvant TACE in HCC patients with microvascular invasion remain controversial. Twelve studies involving 2190 patients were include in our meta-analysis. Adjuvant TACE may improve OS and DFS for HCC patients with MVI compared to HR alone and should be recommended for selected HCC patients with MVI.
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Affiliation(s)
- Zhen-Hua Chen
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Xiu-Ping Zhang
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | | | - Kang Wang
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Hang Wang
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Zong-Tao Chai
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Jie Shi
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Wei-Xing Guo
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Shu-Qun Cheng
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
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Segmental Distribution of Hepatocellular Carcinoma Correlates with Microvascular Invasion in Liver Explants Undergoing Transplantation. J Cancer Epidemiol 2019; 2019:8534372. [PMID: 31186641 PMCID: PMC6521314 DOI: 10.1155/2019/8534372] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2019] [Revised: 03/12/2019] [Accepted: 04/15/2019] [Indexed: 12/13/2022] Open
Abstract
Introduction Microvascular invasion (MVI) in hepatocellular carcinoma (HCC) patients is a poor prognostic factor after liver transplantation and/or resection. Any correlation between MVI and segmental location of HCC has yet to be studied. Our aim is to evaluate the segmental location of HCC and any correlation with the presence of MVI, portal vein thrombosis (PVT) in explanted livers, and the recurrence of HCC after transplantation. Another objective of the study is to assess the treatment history (ablation or transarterial chemoembolization (TACE)) and size of the tumor with respect to the risk of MVI. Methods A single center, retrospective chart review, including 98 HCC patients, aged 18 years and older who had liver transplantation in our institute between 2012 and 2017. We reviewed the radiological images of the HCC tumors, the pathological findings of the explanted livers, and the follow-up imaging after transplantation. Results 98 patients with the diagnosis of HCC underwent liver transplantation between 2012 and 2017. The mean age of the cohort was 63 ± 8.2. Males represented 75% and Caucasian race represented 75% of the cohort. The most common etiology of cirrhosis was chronic hepatitis C virus infection followed by alcohol abuse and nonalcoholic steatohepatitis (NASH) with percentages of 50%, 23%, and 10%, respectively. Microvascular invasion was found in 16% of the patients while PVT and the recurrence of HCC were found in 17% and 6 % of the cohort, respectively. MVI was found in 10 single HCC and 6 multifocal HCC. Right lobe HCC had more MVI when compared to the left and multilobar HCC, with percentages of 11%, 2%, and 3%, respectively. Localization of HCC in segment 8 was associated with the highest percentage of MVI when compared to all other segments. The risk of MVI in segment 8 HCC was 3.5 times higher than the risk from the other segments (p=0.002) while no vascular invasion was found in segments 1, 3, and 5. The risk of vascular invasion in untreated HCC is 3 times the risk in treated HCC (P=0.03). Conclusion Our data indicate that the risk of microvascular invasion is highest in tumors localized to segment 8. The size and number of HCC tumors were not associated with an increased risk of microvascular invasion.
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Lazuardi F, Valencia J, Zheng S. Adjuvant transcatheter arterial chemoembolization after radical resection of hepatocellular carcinoma patients with tumor size less than 5 cm: a retrospective study. Scand J Gastroenterol 2019; 54:617-622. [PMID: 31079496 DOI: 10.1080/00365521.2019.1607896] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Objective: Our aim is to retrospectively compare the disease-free survival (DFS) of adjuvant TACE after surgical resection on patients with tumor less than 5 cm. Methods: A total of 307 patients with HCC underwent hepatic resection between January 2014 to December 2016 were enrolled in this study. Among these, 172 patients underwent surgical treatment only (group A) and 135 patients received surgical resection followed by adjuvant TACE (group B). Propensity score matching (PSM) analysis is used to minimize baseline differences between two groups. DFS was compared between the two groups and Cox proportional hazard model was used to predict the factor for recurrence. Results: Before PSM, the 1, 2, 3 year DFS rate of group A and B were 90.1%, 83.3%, 75.3% versus 85.2%, 73.9%, 68.1%, respectively (p = .286). After PSM, the 1, 2, 3 year DFS rate of group A and group B were 90.3%, 80.8%, 71.9% versus 89.2%, 77.8%, 71.3%, respectively (p = .791). In subgroup analysis where patients presented with microvascular invasion (MiVI), before PSM the 1, 2, 3 year DFS rate were 77.8%, 77.8%, 77.8% and 70%, 70%, 47.3%, for group A and B, respectively (p = .491). After PSM the 1, 2, 3 year DFS rate for group A and B were 71.4%, 71.4%, 71.4% and 100%, 100%, 50%, respectively (p = .440). Cox proportional hazard model identified tumor size ≥3 cm as factor related to recurrence. Conclusions: Adjuvant TACE does not improve the DFS of HCC patients with tumor size less than 5 cm.
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Affiliation(s)
- Freliska Lazuardi
- a Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery , First Affiliated Hospital, Zhejiang University School of Medicine , Hangzhou , China
| | - Jacqueline Valencia
- a Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery , First Affiliated Hospital, Zhejiang University School of Medicine , Hangzhou , China
| | - Shusen Zheng
- a Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery , First Affiliated Hospital, Zhejiang University School of Medicine , Hangzhou , China
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Qi YP, Zhong JH, Liang ZY, Zhang J, Chen B, Chen CZ, Li LQ, Xiang BD. Adjuvant transarterial chemoembolization for patients with hepatocellular carcinoma involving microvascular invasion. Am J Surg 2019; 217:739-744. [PMID: 30103903 DOI: 10.1016/j.amjsurg.2018.07.054] [Citation(s) in RCA: 52] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2018] [Revised: 07/06/2018] [Accepted: 07/12/2018] [Indexed: 01/27/2023]
Abstract
BACKGROUND Microvascular invasion (MVI) has recently been reported to be an independent prognostic factor in patients with hepatocellular carcinoma (HCC). This study compared the outcomes of adjuvant transarterial chemoembolization (A-TACE) after hepatic resection (HR) in patients with HCC involving MVI. METHODS This prospective study involved 200 consecutive patients with MVI-HCC who underwent HR alone (n = 109) or HR with A-TACE (n = 91).The Kaplan-Meier method was used to compare disease-free survival (DFS) and overall survival (OS). RESULTS The two groups showed similar DFS at 1, 2, and 3 years (P = 0.077). The A-TACE group showed significantly higher OS than the HR-only group (P = 0.030). Subgroup analysis showed that A-TACE was associated with significantly higher DFS and OS among patients with a tumor diameter >5 cm or with multinodular tumors. CONCLUSIONS A-TACE may improve postoperative outcomes for MVI-HCC patients, especially those with tumor diameter >5 cm or multinodular tumors.
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Affiliation(s)
- Ya-Peng Qi
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, 530021, China; Key Laboratory for High-Incidence Tumor Prevention and Treatment, Ministry of Education, China
| | - Jian-Hong Zhong
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, 530021, China; Key Laboratory for High-Incidence Tumor Prevention and Treatment, Ministry of Education, China; Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Nanning, 530021, China
| | - Zhi-Yin Liang
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, 530021, China; Key Laboratory for High-Incidence Tumor Prevention and Treatment, Ministry of Education, China
| | - Jie Zhang
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, 530021, China; Key Laboratory for High-Incidence Tumor Prevention and Treatment, Ministry of Education, China
| | - Bin Chen
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, 530021, China; Key Laboratory for High-Incidence Tumor Prevention and Treatment, Ministry of Education, China
| | - Chang-Zhi Chen
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, 530021, China; Key Laboratory for High-Incidence Tumor Prevention and Treatment, Ministry of Education, China
| | - Le-Qun Li
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, 530021, China; Key Laboratory for High-Incidence Tumor Prevention and Treatment, Ministry of Education, China; Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Nanning, 530021, China.
| | - Bang-De Xiang
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, 530021, China; Key Laboratory for High-Incidence Tumor Prevention and Treatment, Ministry of Education, China; Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Nanning, 530021, China.
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Wang L, Chen B, Li Z, Yao X, Liu M, Rong W, Wu F, Lin S, Liu Y, Zheng Y, Li Y, Wang W, Wu J. Optimal postoperative adjuvant treatment strategy for HBV-related hepatocellular carcinoma with microvascular invasion: a propensity score analysis. Onco Targets Ther 2019; 12:1237-1247. [PMID: 30863091 PMCID: PMC6388954 DOI: 10.2147/ott.s179247] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Background Microvascular invasion (MVI) is the most important risk factor associated with early postoperative recurrence in patients with hepatocellular carcinoma (HCC). However, the efficacy of postoperative adjuvant treatment for preventing recurrence in HCC patients with MVI has not been assessed. This study investigated the efficacy of postoperative adjuvant radiotherapy (RT) and transcatheter arterial chemoembolization (TACE) in HCC patients with MVI. Materials and methods From July 2008 to December 2016, 117 hepatitis B virus (HBV)-related HCC patients with MVI were retrospectively divided into two groups based on postoperative adjuvant treatments. Propensity score matching (PSM) was performed to adjust for significant differences in baseline characteristics. Relapse-free survival (RFS) and overall survival (OS) of the two groups were analyzed before and after PSM. Results Of all patients, the RT group had significantly smaller tumor size and milder MVI classification. PSM analysis created 46 pairs of patients. After matching, the two groups of patients were similar in baseline characteristics. Multivariate analysis indicated that tumor size, MVI classification, and postoperative treatment strategies were independently associated with RFS; tumor size and MVI classification were independently associated with OS. Similar multivariate analysis results were demonstrated after matching propensity score. Survival analysis revealed that the estimated median RFS and OS of patients with RT and TACE were 25.74±8.12 vs 9.18±1.67 months (P=0.003) and 60.69±7.36 vs 36.53±5.34 months (P=0.262), respectively. The RT group had significantly longer RFS than the TACE group. Conclusion Postoperative adjuvant RT offers better RFS for HCC patients with MVI than TACE.
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Affiliation(s)
- Liming Wang
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China,
| | - Bo Chen
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zhuo Li
- Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xuesong Yao
- 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, Beijing, China
| | - Mei Liu
- Laboratory of Cell and Molecular Biology & State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Weiqi Rong
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China,
| | - Fan Wu
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China,
| | - Shengtao Lin
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China,
| | - Yunhe Liu
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China,
| | - Yiling Zheng
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China,
| | - Yexiong Li
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Weihu Wang
- Department of Radiation Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital & Institute, Beijing, China,
| | - Jianxiong Wu
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China,
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Liu S, Li H, Guo L, Zhang B, Zhou B, Zhang W, Zhou J, Fan J, Ye Q. Tumor Size Affects Efficacy of Adjuvant Transarterial Chemoembolization in Patients with Hepatocellular Carcinoma and Microvascular Invasion. Oncologist 2018; 24:513-520. [PMID: 30552155 DOI: 10.1634/theoncologist.2018-0305] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2018] [Accepted: 10/16/2018] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Patients with hepatocellular carcinoma (HCC) and microvascular invasion (mVI) have shown dismal postoperative prognosis; however, whether adjuvant transarterial chemoembolization (TACE) can improve their outcomes remains unclear. MATERIALS AND METHODS We retrospectively identified 549 eligible patients to form the crude cohort and adopted propensity score matching method to assemble another cohort of 444 patients with similar baseline characteristics. We assessed the effects of adjuvant TACE by stratified analyses and multivariate Cox analyses in two cohorts. RESULTS There was significant interaction between tumor size and adjuvant TACE with respect to overall survival (OS; p = .006 for interaction). In the matched cohort, patients who received adjuvant TACE showed higher rates of 5-year OS (72.4% vs. 50.9%, p = .005) and 5-year recurrence-free survival (50.5% vs. 36.4%, p = .003) in the tumor ≤5 cm subgroup, but not in the tumor >5 cm subgroup (32.3% vs. 24.9%, p = .350 and 18.8% vs. 19.7%, p = .180). The independent protective role of adjuvant TACE on OS was observed in patients with tumor ≤5 cm (adjusted odds ratio [OR] = 0.59, 95% confidence interval [CI] 0.36-0.97) but not in patients with tumor >5 cm (adjusted OR = 1.17, 95% CI 0.84-1.62). The effects of adjuvant TACE did not change materially while the analysis was performed in the crude cohort. CONCLUSION For patients with HCC and mVI, adjuvant TACE was associated with improved outcomes, but not for those with tumor >5 cm, according to the current protocol. IMPLICATIONS FOR PRACTICE The outcomes of patients with hepatocellular carcinoma and microvascular invasion who received adjuvant transarterial chemoembolization were inconsistent in this study. According to the current protocol, adjuvant transarterial chemoembolization was associated with improved prognosis in patients with microvascular invasion, except for those with tumor >5 cm. Multivariate Cox models confirmed adjuvant transarterial chemoembolization was an independent protective factor in the tumor ≤5 cm subgroup but not in the tumor >5 cm subgroup.
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Affiliation(s)
- Shuang Liu
- Department of Liver Surgery, Liver Cancer Institute and Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Fudan University, Shanghai, People's Republic of China
| | - Hui Li
- Department of Liver Surgery, Liver Cancer Institute and Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Fudan University, Shanghai, People's Republic of China
| | - Lei Guo
- Department of Liver Surgery, Liver Cancer Institute and Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Fudan University, Shanghai, People's Republic of China
| | - Bo Zhang
- Department of Liver Surgery, Liver Cancer Institute and Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Fudan University, Shanghai, People's Republic of China
| | - Binghai Zhou
- Department of Liver Surgery, Liver Cancer Institute and Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Fudan University, Shanghai, People's Republic of China
| | - Wentao Zhang
- Department of Liver Surgery, Liver Cancer Institute and Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Fudan University, Shanghai, People's Republic of China
| | - Jian Zhou
- Department of Liver Surgery, Liver Cancer Institute and Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Fudan University, Shanghai, People's Republic of China
| | - Jia Fan
- Department of Liver Surgery, Liver Cancer Institute and Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Fudan University, Shanghai, People's Republic of China
| | - Qinghai Ye
- Department of Liver Surgery, Liver Cancer Institute and Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Fudan University, Shanghai, People's Republic of China
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Chong CCN, Cheung ST, Cheung YS, Chan AWH, Chan SL, Yu SCH, Lai PBS. Novel biomarkers GEP/ABCB5 regulate response to adjuvant transarterial chemoembolization after curative hepatectomy for hepatocellular carcinoma. Hepatobiliary Pancreat Dis Int 2018; 17:524-530. [PMID: 30413348 DOI: 10.1016/j.hbpd.2018.10.003] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/01/2018] [Accepted: 10/12/2018] [Indexed: 02/05/2023]
Abstract
BACKGROUND Transarterial chemoembolization (TACE) is the most commonly used adjuvant therapy for hepatocellular carcinoma (HCC) after curative resection. Responses to TACE are variable due to tumor and patient heterogeneity. We had previously demonstrated that expression of Granulin-epithelin precursor (GEP) and ATP-dependent binding cassette (ABC)B5 in liver cancer stem cells was associated with chemoresistance. The present study aimed to evaluate the association between GEP/ABCB5 expression and response to adjuvant TACE after curative resection for HCC. METHODS Patients received adjuvant TACE after curative resection for HCC and patients received curative resection alone were identified from a prospectively collected database. Clinical samples were retrieved for biomarker analysis. Patients were categorized into 3 risk groups according to their GEP/ABCB5 status for survival analysis: low (GEP-/ABCB5-), intermediate (either GEP+/ABCB5- or GEP-/ABCB5+) and high (GEP+/ABCB5+). Early recurrence (recurrence within 2 years after resection) and disease-free survival were analyzed. RESULTS Clinical samples from 44 patients who had followed-up for more than 2 years were retrieved for further biomarker analysis. Among them, 18 received adjuvant TACE and 26 received surgery alone. Patients with adjuvant TACE in the intermediate risk group was associated with significantly better overall survival and 2-year disease-free survival than those who had surgery alone (P = 0.036 and P = 0.011, respectively). Adjuvant TACE did not offer any significant differences in the early recurrence rate, 2-year disease-free survival and overall survival for patients in low and high risk groups. CONCLUSIONS Adjuvant TACE can only provide survival benefits for patients in the intermediate risk group (either GEP+/ABCB5- or GEP-/ABCB5+). A larger clinical study is warranted to confirm its role in patient selection for adjuvant TACE.
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Affiliation(s)
- Charing Ching-Ning Chong
- Department of Surgery, Prince of Wales Hospital, The Chinese University of Hong Kong, 4/F Clinical Science Building, 30-32 Ngan Shing Street, Shatin, Hong Kong, China
| | - Siu Tim Cheung
- Department of Surgery, Prince of Wales Hospital, The Chinese University of Hong Kong, 4/F Clinical Science Building, 30-32 Ngan Shing Street, Shatin, Hong Kong, China
| | - Yue-Sun Cheung
- Department of Surgery, Prince of Wales Hospital, The Chinese University of Hong Kong, 4/F Clinical Science Building, 30-32 Ngan Shing Street, Shatin, Hong Kong, China
| | - Anthony Wing-Hung Chan
- Department of Anatomical and Cellular Pathology, State Key Laboratory in Oncology in South China, Prince of Wales Hospital, The Chinese University of Hong Kong, 30-32 Ngan Shing Street, Shatin, Hong Kong, China
| | - Stephen Lam Chan
- Department of Clinical Oncology, Prince of Wales Hospital, The Chinese University of Hong Kong, 30-32 Ngan Shing Street, Shatin, Hong Kong, China
| | - Simon Chun-Ho Yu
- Department of Imaging and Interventional Radiology, Prince of Wales Hospital, The Chinese University of Hong Kong, 30-32 Ngan Shing Street, Shatin, Hong Kong, China
| | - Paul Bo-San Lai
- Department of Surgery, Prince of Wales Hospital, The Chinese University of Hong Kong, 4/F Clinical Science Building, 30-32 Ngan Shing Street, Shatin, Hong Kong, China.
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Chen S, Gao Y, Li Z, Jia J, Fang M, Wang M, Feng H, Chen Q, Guan W, Wang Z, Gao C. A Nomogram Predicting Extrahepatic Metastases for Patients with Adjuvant Transarterial Chemoembolization after Hepatectomy. J Cancer 2018; 9:4223-4233. [PMID: 30519323 PMCID: PMC6277617 DOI: 10.7150/jca.25886] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2018] [Accepted: 08/15/2018] [Indexed: 01/27/2023] Open
Abstract
Background: Prognosis remains poor for hepatocellular carcinoma (HCC) patients with extrahepatic metastases (EHMs). This study aimed to develop a nomogram to predict EHMs in HCC patients who underwent adjuvant transarterial chemoembolization (TACE) following hepatectomy. Methods: Data of 578 HCC patients who underwent TACE after hepatectomy at the Eastern Hepatobiliary Surgery Hospital was retrospectively reviewed. Cox regression analyses was used to select variables to construct the nomogram. Predictive accuracy and discriminative ability of the model were performed using concordance index (C-index), calibration curve and the area under time-dependent receiver operating characteristic (ROC) curve. Results: Postoperative EHMs were detected in 89 and 31 patients in the training cohort (n = 453) and validation cohort (n = 125), respectively. Multivariate analysis showed that tumor size (HR, 1.099; 95% CI, 1.049-1.152), coarse beam type of tumor histopathological structure (HR, 2.382; 95% CI, 1.030-5.512), presence of satellite nodules (HR, 1.936; 95% CI, 1.156-3.244) and alpha-fetoprotein (AFP) (HR, 1.399; 95% CI, 1.098-1.783) were independent risk factors for EHMs (all p < 0.05). The nomogram incorporated these factors achieved good agreement between prediction and actual observation with a concordance index (C-index) of 0.73 (95% CI, 0.68 to 0.78) and 0.71 (95% CI, 0.63 to 0.79) in the training cohort and validation cohort, respectively. In addition, patients who had a nomogram score > 17 were considered to have higher risk for EHMs compared with those scored ≤ 12. Furthermore, the time-dependent area under the ROC curve indicated comparative stability and adequate discriminative ability of the model. Conclusions: This novel nomogram can identify those with high risk of EHMs after adjuvant TACE following hepatectomy. The validation cohort showed a good performance, suggesting it could benefit surgeons on decision-making.
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Affiliation(s)
- Shipeng Chen
- Department of Laboratory Medicine, Third Affiliated Hospital of Second Military Medical University, Shanghai, China.,Clinical Medical College, Fujian Medical University, Fuzhou, China
| | - Yuzhen Gao
- Department of Molecular Diagnosis, Clinical Medical College, Yangzhou University, Yangzhou, China
| | - Zheng Li
- Department of Hepatic Surgery, Third Affiliated Hospital of Second Military Medical University, Shanghai, China
| | - Jian'an Jia
- Department of Laboratory Medicine, Third Affiliated Hospital of Second Military Medical University, Shanghai, China
| | - Meng Fang
- Department of Laboratory Medicine, Third Affiliated Hospital of Second Military Medical University, Shanghai, China
| | - Mengmeng Wang
- Department of Laboratory Medicine, Third Affiliated Hospital of Second Military Medical University, Shanghai, China
| | - Huijuan Feng
- Department of Laboratory Medicine, Third Affiliated Hospital of Second Military Medical University, Shanghai, China
| | - Qinjunjie Chen
- Department of Hepatic Surgery, Third Affiliated Hospital of Second Military Medical University, Shanghai, China
| | - Wenqian Guan
- Department of Laboratory Medicine, Third Affiliated Hospital of Second Military Medical University, Shanghai, China.,Clinical Medical College, Fujian Medical University, Fuzhou, China
| | - Ziyi Wang
- Shanghai Institute of Technology, Shanghai, China
| | - Chunfang Gao
- Department of Laboratory Medicine, Third Affiliated Hospital of Second Military Medical University, Shanghai, China
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Adjuvant transcatheter arterial chemoembolization after curative resection for hepatocellular carcinoma patients with solitary tumor and microvascular invasion: a randomized clinical trial of efficacy and safety. Cancer Commun (Lond) 2018; 38:61. [PMID: 30305149 PMCID: PMC6235393 DOI: 10.1186/s40880-018-0331-y] [Citation(s) in RCA: 98] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2018] [Accepted: 09/28/2018] [Indexed: 02/06/2023] Open
Abstract
Background The optimal strategy for adjuvant therapy after curative resection for hepatocellular carcinoma (HCC) patients with solitary tumor and microvascular invasion (MVI) is controversial. This trial evaluated the efficacy and safety of adjuvant transcatheter arterial chemoembolization (TACE) after hepatectomy versus hepatectomy alone in HCC patients with a solitary tumor ≥ 5 cm and MVI. Methods In this randomized, open-labeled, phase III trial, HCC patients with a solitary tumor ≥ 5 cm and MVI were randomly assigned (1:1) to receive either 1–2 cycles of adjuvant TACE after hepatectomy (Hepatectomy-TACE) or hepatectomy alone (Hepatectomy Alone). The primary endpoint was disease-free survival (DFS); the secondary endpoints included overall survival (OS) and adverse events. Results Between June 1, 2009, and December 31, 2012, 250 patients were enrolled and randomly assigned to the Hepatectomy-TACE group (n = 125) or the Hepatectomy Alone group (n = 125). Clinicopathological characteristics were balanced between the two groups. The median follow-up time from randomization was 37.5 months [interquartile range 18.3–48.2 months]. The median DFS was significantly longer in the Hepatectomy-TACE group than in the Hepatectomy Alone group [17.45 months (95% confidence interval [CI] 11.99–29.14) vs. 9.27 months (95% CI 6.05–13.70), hazard ratio [HR] = 0.70 (95% CI 0.52–0.95), P = 0.020], respectively. The median OS was also significantly longer in the Hepatectomy-TACE group than in the Hepatectomy Alone group [44.29 months (95% CI 25.99–62.58) vs. 22.37 months (95% CI 10.84–33.91), HR = 0.68 (95% CI 0.48–0.97), P = 0.029]. Treatment-related adverse events were more frequently observed in the Hepatectomy-TACE group, although these were generally mild and manageable. The most common grade 3 or 4 adverse events in both groups were neutropenia and liver dysfunction. Conclusion Hepatectomy followed by adjuvant TACE is an appropriate option after radical resection in HCC patients with solitary tumor ≥ 5 cm and MVI, with acceptable toxicity.
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Wang JC, Xia AL, Xu Y, Lu XJ. Comprehensive treatments for hepatocellular carcinoma with portal vein tumor thrombosis. J Cell Physiol 2018; 234:1062-1070. [PMID: 30256409 DOI: 10.1002/jcp.27324] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2017] [Accepted: 08/03/2018] [Indexed: 12/31/2022]
Abstract
Portal vein tumor thrombosis (PVTT) is one of the most common complications in hepatocellular carcinoma (HCC). HCC with PVTT usually indicates poor prognosis, which has a number of characteristics including a rapidly progressive disease course, worse liver function, complications connected with portal hypertension, and poorer tolerance to treatment. The exact mechanisms of PVTT remain unknown, even though some concerned signal transduction or molecular pathways have been identified. In western countries, sorafenib is the only recommended therapeutic strategy regardless of PVTT types. However, multiple treatment options including transhepatic arterial chemoembolization, hepatectomy, radiotherapy, and sorafenib available in the clinic. In this review, we enumerate and discuss therapeutics against patients with HCC having PVTT available in the clinic and put forward directions for future research.
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Affiliation(s)
- Jin-Cheng Wang
- Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - An-Liang Xia
- Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Yong Xu
- Department of Nephrology, Huai'an Second People' Hospital and The Affiliated Huai'an Hospital of Xuzhou Medical University, Huai'an, Jiangsu, China
| | - Xiao-Jie Lu
- Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
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Zhang YF, Shang H, Zeng XL, Ji H, Li YM, Lu HW. Postoperative adjuvant chemo (embolization) therapy for hepatocellular carcinoma with portal vein tumor thrombosis. Onco Targets Ther 2018; 11:5407-5417. [PMID: 30214246 PMCID: PMC6128276 DOI: 10.2147/ott.s171612] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Abstract
Background The present meta-analysis was aimed to evaluate the effects of postoperative adjuvant chemotherapy/transarterial chemoembolization (TACE) on the survival/disease-free survival (DFS) rate in hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT). Methods The relevant trials were collected using a database search of MEDLINE, Embase, Cochrane Library, Web of Science, ScienceDirect, the China Journal Full-text Database, and the National Institute of Health Clinical Trials Database. The 1-, 3-, and 5-year survival/DFS rates were considered to be the primary end points. A sensitivity analysis was conducted by reanalyzing the data using different statistical approaches. Results Eight studies met the inclusion criteria. When compared with surgery alone, the pooled OR showed that the postoperative adjuvant therapy significantly increased the 1-, 3-, and 5-year survival rates for HCC patients with PVTT (the pooled OR and 95% CI of the 1-, 3-, and 5-year survival rates, respectively, were as follows: 2.72, 1.98-3.74; 1.62, 1.13-2.33; 1.99, 1.20-3.29). In addition, when compared with surgery alone, subgroup analysis showed that the postoperative chemotherapy improved the 1-, 3-, and 5-year survival rates of HCC patients with PVTT. Conclusion Compared with surgery alone, postoperative adjuvant chemotherapy can improve the 1-, 3- and 5-year survival rates of HCC patients with PVTT. However, postoperative TACE can only increase the 1-year survival rate. However, due to the limitations of this meta-analysis, additional relevant trials are required to confirm these findings.
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Affiliation(s)
- Ya-Fei Zhang
- Department of General Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China,
| | - Hao Shang
- Department of General Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China,
| | - Xian-Ling Zeng
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Hong Ji
- Department of General Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China,
| | - Yi-Ming Li
- Department of General Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China,
| | - Hong-Wei Lu
- Department of General Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China,
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Zhong C, Zhang YF, Huang JH, Xiong CM, Wang ZY, Chen QL, Guo RP. Comparison of hepatic resection and transarterial chemoembolization for UICC stage T3 hepatocellular carcinoma: a propensity score matching study. BMC Cancer 2018; 18:643. [PMID: 29879928 PMCID: PMC5992633 DOI: 10.1186/s12885-018-4557-5] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2017] [Accepted: 05/28/2018] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND The optimal therapeutic strategy in UICC stage T3 hepatocellular carcinoma (HCC) patients that maximizes both safety and long-term outcome has not yet been determined. Our aim was to compare clinical outcomes following hepatic resection (HR) versus transarterial chemoembolization (TACE) for stage T3 HCC. METHODS From 2005 to 2013, 1179 patients with T3 HCC who underwent HR or TACE were divided into two groups, HR group (n = 280) or TACE group (n = 899). The clinical outcomes were compared before and after propensity score matching. RESULTS The propensity model matched 244 patients in each group for further analyses. After matching, medium overall survival (OS), 1, 3, and 5-year OS rates in TACE group were 11.8 (95%CI, 9.9-13.7) months, 49.6, 16.5, and 8.4%, respectively; which in HR group were 17.8 (95% CI, 14.8-20.8) months, 63.1, 33.3, and 26.4%, respectively; (log rank = 19.908, P < 0.01). Patients in HR group were more likely to develop pleural effusion, compared with those in TACE group (0.4% vs. 5.3%, P = 0.01). However, no significant differences in other adverse events (AEs) were found between two groups. Similar results were also demonstrated prior to the matched analysis. Multivariate analysis indicated that prothrombin time (PT), tumor size, tumor numbers, UICC staging status, and initial treatment were independent prognostic factors. CONCLUSIONS Our study revealed that TACE was an option for UICC T3 HCC patients. However, HR seemed to be safe and yield a survival benefit compared with TACE, especially for patients with a good underlying liver function.
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Affiliation(s)
- Chong Zhong
- Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, 16 Airport Road, Guangzhou, 510405 China
- Department of Hepatobiliary Surgery, the First Affiliated Hospital of Guangzhou University of Chinese Medicine, 16 Airport Road, Guangzhou, 510405 China
| | - Yong-Fa Zhang
- Department of Liver Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032 China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032 China
- Department of Hepatobiliary Oncology, Cancer Center of Sun Yat-sen University, Guangzhou, 510060 China
| | - Jun-Hai Huang
- Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, 16 Airport Road, Guangzhou, 510405 China
- Department of Hepatobiliary Surgery, the First Affiliated Hospital of Guangzhou University of Chinese Medicine, 16 Airport Road, Guangzhou, 510405 China
| | - Cheng-Ming Xiong
- The First Clinical Medical School of Guangzhou University of Chinese Medicine, Guangzhou, 510405 China
| | - Zi-Yu Wang
- The First Clinical Medical School of Guangzhou University of Chinese Medicine, Guangzhou, 510405 China
| | - Qing-Lian Chen
- The First Clinical Medical School of Guangzhou University of Chinese Medicine, Guangzhou, 510405 China
| | - Rong-Ping Guo
- Department of Hepatobiliary Oncology, Cancer Center of Sun Yat-sen University, Guangzhou, 510060 China
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Liu S, Guo L, Li H, Zhang B, Sun J, Zhou C, Zhou J, Fan J, Ye Q. Postoperative Adjuvant Trans-Arterial Chemoembolization for Patients with Hepatocellular Carcinoma and Portal Vein Tumor Thrombus. Ann Surg Oncol 2018; 25:2098-2104. [DOI: 10.1245/s10434-018-6438-1] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2017] [Indexed: 12/23/2022]
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Wang Z, Ren Z, Chen Y, Hu J, Yang G, Yu L, Yang X, Huang A, Zhang X, Zhou S, Sun H, Wang Y, Ge N, Xu X, Tang Z, Lau W, Fan J, Wang J, Zhou J. Adjuvant Transarterial Chemoembolization for HBV-Related Hepatocellular Carcinoma After Resection: A Randomized Controlled Study. Clin Cancer Res 2018; 24:2074-2081. [PMID: 29420221 DOI: 10.1158/1078-0432.ccr-17-2899] [Citation(s) in RCA: 201] [Impact Index Per Article: 28.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2017] [Revised: 12/14/2017] [Accepted: 01/30/2018] [Indexed: 02/06/2023]
Abstract
Purpose: The survival of patients with hepatocellular carcinoma (HCC) recurrence after curative resection is usually poor. We sought to evaluate the safety and efficacy of adjuvant transarterial chemoembolization (TACE) in HBV-related HCC patients with an intermediate (a single tumor larger than 5 cm without microvascular invasion) or high risk (a single tumor with microvascular invasion, or two or three tumors) of recurrence.Experimental Design: In this randomized phase 3 trial, 280 eligible patients were assigned to adjuvant TACE (n = 140) or no adjuvant treatment (control; n = 140) groups. The primary endpoint was recurrence-free survival (RFS); secondary endpoints included overall survival (OS) and safety. Multivariable Cox-proportional hazards model was used to determine the independent impact of TACE on patients' outcomes.Results: Patients who received adjuvant TACE had a significantly longer RFS than those in the control group [56.0% vs. 42.1%, P = 0.01; HR, 0.68; 95% confidence interval (CI), 0.49-0.93]. Patients in the adjuvant TACE group had 7.8% higher 3-year OS rate than the control group (85.2% vs. 77.4%; P = 0.04; HR, 0.59; 95% CI, 0.36-0.97). The impact of adjuvant TACE on RFS and OS remained significant after controlling for other known prognostic factors (HR, 0.67; P = 0.01 for RFS; and HR, 0.59; P = 0.04 for OS). There was no grade 3 or 4 toxicity after adjuvant TACE.Conclusions: For patients with HBV-related HCC who had an intermediate or high risk of recurrence after curative hepatectomy, our study showed adjuvant TACE significantly reduced tumor recurrence, improved RFS and OS, and the procedure was well tolerated. Clin Cancer Res; 24(9); 2074-81. ©2018 AACR.
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Affiliation(s)
- Zheng Wang
- Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, Shanghai, China
| | - Zhenggang Ren
- Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, Shanghai, China
| | - Yi Chen
- Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, Shanghai, China
| | - Jie Hu
- Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, Shanghai, China
| | - Guohuan Yang
- Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, Shanghai, China
| | - Lei Yu
- Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, Shanghai, China
| | - Xinrong Yang
- Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, Shanghai, China
| | - Ao Huang
- Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, Shanghai, China
| | - Xin Zhang
- Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, Shanghai, China
| | - Shaolai Zhou
- Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, Shanghai, China
| | - Huichuan Sun
- Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, Shanghai, China
| | - Yanhong Wang
- Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, Shanghai, China
| | - Ningling Ge
- Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, Shanghai, China
| | - Xiaoyu Xu
- Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, Shanghai, China
| | - Zhaoyou Tang
- Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, Shanghai, China
| | - Wanyee Lau
- Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, Shanghai, China
- Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, HKSAR, China
| | - Jia Fan
- Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, Shanghai, China
- Institute of Biomedical Sciences, Fudan University, Shanghai, China
- State Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai, China
| | - Jiping Wang
- Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, Shanghai, China.
- Division of Surgical Oncology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Jian Zhou
- Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, Shanghai, China.
- Institute of Biomedical Sciences, Fudan University, Shanghai, China
- State Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai, China
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