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Yao Y, Nong X, Liang JC, Zhang YM, Zhang ZM. Real-world effectiveness and safety of TACE combined with lenvatinib plus immune checkpoint inhibitors in patients with BCLC-B stage hepatocellular carcinoma. J Gastrointest Oncol 2025; 16:176-190. [PMID: 40115929 PMCID: PMC11921401 DOI: 10.21037/jgo-2025-33] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2025] [Accepted: 02/16/2025] [Indexed: 03/23/2025] Open
Abstract
Background More effective treatment strategies need to be established for patients with Barcelona Clinic Liver Cancer (BCLC)-B stage hepatocellular carcinoma (HCC). The combination of transarterial chemoembolization (TACE) with lenvatinib and immune checkpoint inhibitors (ICIs) has been shown to have potential in the treatment of unresectable HCC. However, the real-world data on the use of this combined therapy in patients with BCLC-B stage HCC are limited. Therefore, this study aimed to validate the efficacy and safety of the combination of TACE with lenvatinib plus ICIs in the treatment of patients with BCLC-B stage HCC in a real-world setting. Methods A total of 121 patients who were newly diagnosed with BCLC-B stage HCC were enrolled in this study. Of these patients, 52 received treatment with TACE combined with lenvatinib plus ICIs (the combination group), and 69 received TACE alone (the monotherapy group). Propensity score matching (PSM) was used to reduce potential biases. The primary endpoint of the study was overall survival (OS), while the secondary endpoints were progression-free survival (PFS), the objective response rate (ORR), and the disease control rate (DCR). Adverse events (AEs) were also recorded and evaluated. Results The OS of the combination group was longer than that of the monotherapy group (median OS: 30.9 vs. 13.0 months, P<0.001), as was the PFS (median PFS: 12.3 vs. 8.3 months, P=0.19). The ORR of the combination group was higher than that of the monotherapy group (61.5% vs. 33.3%, P=0.002), as was the DCR (92.3% vs. 76.8%, P=0.02). After PSM, the OS of the combination group was longer than that of the monotherapy group (median OS: not reached vs. 9.8 months, P<0.001), as was the PFS (median PFS: 13.4 vs. 7.6 months, P=0.28). The ORR of the combination group was higher than that of the monotherapy group (59.0% vs. 30.8%, P=0.01), as was the DCR (89.7% vs. 74.4%, P=0.08). In the multivariate Cox regression analysis, combination therapy was associated with a better OS (hazard ratio =0.36, 95% confidence interval: 0.20-0.64, P<0.001). In terms of the AEs, 8 of 52 patients (15.4%) in the combination group, and 4 of 69 patients (5.8%) in the monotherapy group experienced grade 3 or 4 AEs (P=0.08), but no grade 5 AEs were observed. Conclusions The combination of TACE with lenvatinib plus ICIs showed excellent efficacy in the treatment of patients with BCLC-B stage HCC, and the safety profile was acceptable.
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Affiliation(s)
- Yu Yao
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Xiang Nong
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Jing-Chang Liang
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Yu-Mei Zhang
- Department of Medical Oncology, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Zhi-Ming Zhang
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, China
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Shih HW, Lai Y, Hung HC, Lee JC, Wang YC, Wu TH, Lee CF, Wu TJ, Chou HS, Chan KM, Lee WC, Cheng CH. Liver Resection Criteria for Patients with Hepatocellular Carcinoma and Multiple Tumors Based on Total Tumor Volume. Dig Dis Sci 2024; 69:3069-3078. [PMID: 38824258 PMCID: PMC11341635 DOI: 10.1007/s10620-024-08500-y] [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: 01/26/2024] [Accepted: 05/11/2024] [Indexed: 06/03/2024]
Abstract
BACKGROUND In many Asian hepatocellular carcinoma (HCC) guidelines, resection is an option for multiple HCCs. It is difficult to compare small but multiple tumors vs. fewer large tumors in terms of the traditional tumor burden definition. We aimed to evaluate the role of liver resection for multiple HCCs and determine factors associated with survival benefits. METHODS We reviewed 160 patients with multiple HCCs who underwent liver resection between July 2003 and December 2018. The risk factors for tumor recurrence were assessed using Cox proportional hazards modeling, and survival was analyzed using the Kaplan-Meier method. RESULTS In all 160 patients, 133 (83.1%) exceeded the Milan criteria. Total tumor volume (TTV) > 275 cm3 and serum alpha-fetoprotein (AFP) level > 20 ng/mL were associated with disease-free survival. Patients beyond the Milan criteria were grouped into three risk categories: no risk (TTV ≤ 275 cm3 and AFP ≤ 20 ng/mL, n = 39), one risk (either TTV > 275 cm3 or AFP > 20 ng/mL, n = 76), and two risks (TTV > 275 cm3 and AFP > 20 ng/mL, n = 18). No-risk group had comparable disease-free survival (p = 0.269) and overall survival (p = 0.215) to patients who met the Milan criteria. CONCLUSION Patients with TTV ≤ 275 cm3 and AFP ≤ 20 ng/mL can have good outcomes even exceed the Milan criteria.
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Affiliation(s)
- Hao-Wen Shih
- Department of General Surgery, Chang-Gung Memorial Hospital, Chang-Gung University College of Medicine, Taoyuan, Taiwan
| | - Yin Lai
- Division of Liver and Transplantation Surgery, Department of General Surgery, Chang-Gung Memorial Hospital, Chang-Gung University College of Medicine, Taoyuan, Taiwan
| | - Hao-Chien Hung
- Division of Liver and Transplantation Surgery, Department of General Surgery, Chang-Gung Memorial Hospital, Chang-Gung University College of Medicine, Taoyuan, Taiwan
| | - Jin-Chiao Lee
- Division of Liver and Transplantation Surgery, Department of General Surgery, Chang-Gung Memorial Hospital, Chang-Gung University College of Medicine, Taoyuan, Taiwan
| | - Yu-Chao Wang
- Division of Liver and Transplantation Surgery, Department of General Surgery, Chang-Gung Memorial Hospital, Chang-Gung University College of Medicine, Taoyuan, Taiwan
| | - Tsung-Han Wu
- Division of Liver and Transplantation Surgery, Department of General Surgery, Chang-Gung Memorial Hospital, Chang-Gung University College of Medicine, Taoyuan, Taiwan
| | - Chen-Fang Lee
- Division of Liver and Transplantation Surgery, Department of General Surgery, Chang-Gung Memorial Hospital, Chang-Gung University College of Medicine, Taoyuan, Taiwan
| | - Ting-Jung Wu
- Division of Liver and Transplantation Surgery, Department of General Surgery, Chang-Gung Memorial Hospital, Chang-Gung University College of Medicine, Taoyuan, Taiwan
| | - Hong-Shiue Chou
- Division of Liver and Transplantation Surgery, Department of General Surgery, Chang-Gung Memorial Hospital, Chang-Gung University College of Medicine, Taoyuan, Taiwan
| | - Kun-Ming Chan
- Division of Liver and Transplantation Surgery, Department of General Surgery, Chang-Gung Memorial Hospital, Chang-Gung University College of Medicine, Taoyuan, Taiwan
| | - Wei-Chen Lee
- Division of Liver and Transplantation Surgery, Department of General Surgery, Chang-Gung Memorial Hospital, Chang-Gung University College of Medicine, Taoyuan, Taiwan
| | - Chih-Hsien Cheng
- Division of Liver and Transplantation Surgery, Department of General Surgery, Chang-Gung Memorial Hospital, Chang-Gung University College of Medicine, Taoyuan, Taiwan.
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Stefanini B, Ielasi L, Pallotta DP, Penazza S, Marseglia M, Piscaglia F. Intermediate-stage hepatocellular carcinoma: refining substaging or shifting paradigm? JOURNAL OF LIVER CANCER 2024; 24:23-32. [PMID: 38468499 PMCID: PMC10990660 DOI: 10.17998/jlc.2024.02.21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/30/2024] [Revised: 02/20/2024] [Accepted: 02/21/2024] [Indexed: 03/13/2024]
Abstract
This review explores the evolution of cancer staging, focusing on intermediate hepatocellular carcinoma (HCC), and the challenges faced by physicians. The Barcelona Clinic Liver Cancer (BCLC) staging system, introduced in 1999, was designed to address the limitations associated with providing accurate prognostic information for HCC and allocating specific treatments, to avoid overtreatment. However, criticism has emerged, particularly regarding the intermediate stage of HCC (BCLC-B) and its heterogeneous patient population. To overcome this limitation, various subclassification systems, such as the Bolondi and Kinki criteria, have been proposed. These systems are aimed at refining categorizations within the intermediate stage and have demonstrated varying degrees of success in predicting outcomes through external validation. This study discusses the shift in treatment paradigms, emphasizing the need for a more personalized approach rather than strictly adhering to cancer stages, without dismissing the relevance of staging systems. It assesses the available treatment options for intermediate-stage HCC, highlighting the importance of considering surgical and nonsurgical options alongside transarterial chemoembolization for optimal outcomes. In conclusion, the text advocates for a paradigm shift in staging systems prioritizing treatment suitability over cancer stage. This reflects the evolving landscape of HCC management, where a multidisciplinary approach is crucial for tailoring treatments to individual patients, ultimately aiming to improve overall survival.
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Affiliation(s)
- Bernardo Stefanini
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Luca Ielasi
- Department of Internal Medicine, Ospedale degli Infermi, Faenza, Italy
| | - Dante Pio Pallotta
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Sofia Penazza
- Divison of Hepatobiliary and Immunoallergic Diseases, Department of Internal Medicine, IRCCS Azienda Ospedaliero, Universitaria di Bologna, Bologna, Italy
| | - Mariarosaria Marseglia
- Divison of Hepatobiliary and Immunoallergic Diseases, Department of Internal Medicine, IRCCS Azienda Ospedaliero, Universitaria di Bologna, Bologna, Italy
| | - Fabio Piscaglia
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
- Divison of Hepatobiliary and Immunoallergic Diseases, Department of Internal Medicine, IRCCS Azienda Ospedaliero, Universitaria di Bologna, Bologna, Italy
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Yang H, Lu L, Guo W, Gong B, Wang X, Chen Y, Chen X. A Longitudinal Study of AFP Trajectories and Clinical Outcomes in Intermediate-Stage Hepatocellular Carcinoma After Hepatectomy. J Hepatocell Carcinoma 2024; 11:219-228. [PMID: 38293613 PMCID: PMC10825584 DOI: 10.2147/jhc.s432011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2023] [Accepted: 12/07/2023] [Indexed: 02/01/2024] Open
Abstract
Background Previous studies have shown that the alpha-fetoprotein (AFP) response has been a key tumour marker in hepatocellular carcinoma (HCC), but its definition remains controversial. Recently, a new study has explored and defined the AFP serological response and used it to explain the subclass of intermediate-stage hepatocellular carcinoma (IM-HCC) with "sharp-falling" AFP change after transarterial chemoembolization (TACE). It may be a new and simple tool for assessing the prognosis of patients. This study aims to explore a simplified AFP trajectory and its impact on overall survival (OS) and disease-free survival (DFS) for IM-HCC after hepatectomy. Patients and Methods Between January 2007 and May 2012, data from the Sun Yat-sen University Cancer Center was examined in this longitudinal, retrospective cohort study. A generalized additive model was applied to distinguish potential AFP dynamic trajectories. The Kaplan-Meier method was applied to analyze OS and DFS, and multivariate Cox models were used to calculate adjusted hazard ratios (aHRs) and 95% CIs for overall survival. Results 144 patients who had IM-HCC with at least three AFP repeat measurements were included in the study. Three similar trajectories are displayed using the generalized additive model: low-stable (35.4%; n = 51), high-rising (36.1%; n = 52), and sharp-falling (28.5%; n = 41). Compared with the low-stable class, the aHRs for death were 2.84 (1.50, 5.41) and 0.59 (0.25, 1.40) for the high-rising and sharp-falling classes, adjusted by age and log AFP. Simplified AFP trajectory had higher relative importance than sex, intrahepatic tumor number, Child-Pugh class, and baseline AFP. Conclusion The simplified AFP trajectory is a promising biomarker for IM-HCC patients undergoing hepatectomy. In the future, it should be verified by a larger population containing various stages of HCC.
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Affiliation(s)
- Hongyi Yang
- Department of Oncology, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, People’s Republic of China
| | - Linbin Lu
- Department of Oncology, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, People’s Republic of China
| | - Wanting Guo
- Department of Oncology, The 900th Hospital of Joint Logistic Support Force, People’s Liberation Army (PLA), Fuzong Clinical College of Fujian Medical University, Fuzhou, People’s Republic of China
| | - Baocuo Gong
- Department of Oncology, The 900th Hospital of Joint Logistic Support Force, People’s Liberation Army (PLA), Fuzong Clinical College of Fujian Medical University, Fuzhou, People’s Republic of China
| | - Xuewen Wang
- Department of Oncology, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, People’s Republic of China
| | - Yaying Chen
- Department of Oncology, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, People’s Republic of China
| | - Xiong Chen
- Department of Oncology, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, People’s Republic of China
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Han JE, Cho HJ, Cheong JY, Lim SG, Yang MJ, Noh CK, Lee GH, Kim SS. Impact of guideline adherence on the prognosis of Barcelona clinic liver cancer stage B hepatocellular carcinoma. World J Gastroenterol 2023; 29:6122-6137. [PMID: 38186683 PMCID: PMC10768406 DOI: 10.3748/wjg.v29.i47.6122] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2023] [Revised: 10/23/2023] [Accepted: 12/01/2023] [Indexed: 12/19/2023] Open
Abstract
BACKGROUND Patients with Barcelona clinic liver cancer (BCLC) stage B hepatocellular carcinoma (HCC) are considerably heterogeneous in terms of tumor burden, liver function, and performance status. To improve the poor survival outcomes of these patients, treatment approaches other than transarterial chemoembolization (TACE), which is recommended by HCC guidelines, have been adopted in real-world clinical practice. We hypothesize that this non-adherence to treatment guidelines, particularly with respect to the use of liver resection, improves survival in patients with stage B HCC. AIM To assess guideline adherence in South Korean patients with stage B HCC and study its impact on survival. METHODS A retrospective analysis was conducted using data from 2008 to 2016 obtained from the Korea Central Cancer Registry. Patients with stage B HCC were categorized into three treatment groups, guideline-adherent, upward, and downward, based on HCC guidelines recommended by the Asian Pacific Association for the Study of the Liver (APASL), the European Association for the Study of the Liver (EASL), and the American Association for the Study of Liver Diseases (AASLD). The primary outcome was HCC-related deaths; tumor recurrence served as the secondary outcome. Survival among the groups was compared using the Kaplan-Meier method and the log-rank test. Predictors of survival outcomes were identified using multivariable Cox regression analysis. RESULTS In South Korea, over the study period from 2008 to 2016, a notable trend was observed in adherence to HCC guidelines. Adherence to the EASL guidelines started relatively high, ranging from 77% to 80% between 2008 and 2012, but it gradually declined to 58.8% to 71.6% from 2013 to 2016. Adherence to the AASLD guidelines began at 71.7% to 75.9% from 2008 to 2010, and then it fluctuated between 49.2% and 73.8% from 2011 to 2016. In contrast, adherence to the APASL guidelines remained consistently high, staying within the range of 90.14% to 94.5% throughout the entire study period. Upward treatment, for example with liver resection, liver transplantation, or radiofrequency ablation, significantly improved the survival of patients with BCLC stage B HCC compared to that of patients treated in adherence to the guidelines (for patients analyzed according to the 2000 EASL guidelines, the 5-year survival rates were 63.4% vs 27.2%, P < 0.001), although results varied depending on the guidelines. Progression-free survival rates were also significantly improved upon the use of upward treatments in certain groups. Patients receiving upward treatments were typically < 70 years old, had platelet counts > 105/μL, and serum albumin levels ≥ 3.5 g/dL. CONCLUSION Adherence to guidelines significantly influences survival in South Korean stage B HCC patients. Curative treatments outperform TACE, but liver resection should be selected with caution due to disease heterogeneity.
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Affiliation(s)
- Ji Eun Han
- Department of Gastroenterology, Ajou University School of Medicine, Suwon 16499, Gyeonggi-do, South Korea
| | - Hyo Jung Cho
- Department of Gastroenterology, Ajou University School of Medicine, Suwon 16499, Gyeonggi-do, South Korea
| | - Jae Youn Cheong
- Department of Gastroenterology, Ajou University School of Medicine, Suwon 16499, Gyeonggi-do, South Korea
| | - Sun Gyo Lim
- Department of Gastroenterology, Ajou University School of Medicine, Suwon 16499, Gyeonggi-do, South Korea
| | - Min Jae Yang
- Department of Gastroenterology, Ajou University School of Medicine, Suwon 16499, Gyeonggi-do, South Korea
| | - Choong-Kyun Noh
- Department of Gastroenterology, Ajou University School of Medicine, Suwon 16499, Gyeonggi-do, South Korea
| | - Gil Ho Lee
- Department of Gastroenterology, Ajou University School of Medicine, Suwon 16499, Gyeonggi-do, South Korea
| | - Soon Sun Kim
- Department of Gastroenterology, Ajou University School of Medicine, Suwon 16499, Gyeonggi-do, South Korea
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Oshita K, Kobayashi T, Namba Y, Fukuhara S, Matsubara K, Takei D, Nakano R, Okamoto W, Sakai H, Tanimine N, Nakahara T, Kuroda S, Tahara H, Ohira M, Kawaoka T, Ide K, Imamura M, Aikata H, Ohdan H. Efficacy and safety of lenvatinib-transcatheter arterial chemoembolisation sequential therapy followed by surgical resection for intermediate-stage hepatocellular carcinoma beyond Up-to-7 criteria: a study protocol for a multicentre, single-arm, prospective study. BMJ Open 2023; 13:e073797. [PMID: 37798025 PMCID: PMC10565137 DOI: 10.1136/bmjopen-2023-073797] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2023] [Accepted: 09/04/2023] [Indexed: 10/07/2023] Open
Abstract
INTRODUCTION The feasibility and efficacy of surgical resection following systemic therapy for intermediate-stage hepatocellular carcinoma (HCC) beyond the Up-to-7 criteria is unclear. The combination of lenvatinib (LEN) and transcatheter arterial chemoembolisation (TACE), termed LEN-TACE sequential therapy, has shown a high response rate and survival benefit in patients with intermediate-stage HCC. This trial aims to evaluate the efficacy and safety of LEN-TACE sequential therapy and the feasibility of surgical resection for intermediate-stage HCC beyond the Up-to-7 criteria. METHODS AND ANALYSIS This is a multicentre, single-arm, prospective clinical trial. Thirty patients with intermediate-stage HCC beyond the Up-to-7 criteria will be enrolled. Patients eligible for this study will undergo LEN-TACE sequential therapy in which LEN is administered for 4 weeks, followed by TACE, and then further LEN for another 4 weeks. Patients will be assessed for efficacy of LEN-TACE sequential therapy and resectability, and surgical resection will be performed if the HCC is considered radically resectable. The primary outcome of this study is the resection rate after LEN-TACE sequential therapy. The secondary outcomes are the objective response rate of LEN-TACE sequential therapy, safety, curative resection rate, overall survival and recurrence-free survival. ETHICS AND DISSEMINATION This trial was approved by the Institutional Review Board of Hiroshima University, Japan (approval no. CRB210003), and has been registered with the Japan Registry of Clinical Trials (jRCTs061220007). The results of this study will be submitted for publication in a peer-reviewed journal and shared with the scientific community at international conferences. TRIAL REGISTRATION NUMBER jRCTs061220007 (https://jrct.niph.go.jp/latest-detail/jRCTs061220007).
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Affiliation(s)
- Ko Oshita
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Tsuyoshi Kobayashi
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Yosuke Namba
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Sotaro Fukuhara
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Keiso Matsubara
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Daisuke Takei
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Ryosuke Nakano
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Wataru Okamoto
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
- Research Center for Hepatology and Gastroenterology, Hiroshima University, Hiroshima, Japan
- Cancer Treatment Center, Hiroshima University, Hiroshima, Japan
| | - Hiroshi Sakai
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Naoki Tanimine
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Takashi Nakahara
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
- Research Center for Hepatology and Gastroenterology, Hiroshima University, Hiroshima, Japan
| | - Shintaro Kuroda
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Hiroyuki Tahara
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Masahiro Ohira
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Tomokazu Kawaoka
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
- Research Center for Hepatology and Gastroenterology, Hiroshima University, Hiroshima, Japan
| | - Kentaro Ide
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Michio Imamura
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
- Research Center for Hepatology and Gastroenterology, Hiroshima University, Hiroshima, Japan
| | - Hiroshi Aikata
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
- Research Center for Hepatology and Gastroenterology, Hiroshima University, Hiroshima, Japan
| | - Hideki Ohdan
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
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Bogdanovic A, Djokic Kovac J, Zdujic P, Djindjic U, Dugalic V. Liver resection versus transarterial chemoembolisation for the treatment of intermediate hepatocellular carcinoma: a systematic review and meta-analysis. Int J Surg 2023; 109:1439-1446. [PMID: 37222718 PMCID: PMC10389385 DOI: 10.1097/js9.0000000000000344] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2022] [Accepted: 03/09/2023] [Indexed: 05/25/2023]
Abstract
BACKGROUND Transarterial chemoembolisation (TACE) is the primary treatment for intermediate-stage hepatocellular carcinoma (HCC), according to the updated Barcelona Clinic Liver Cancer (BCLC) staging system. Although growing evidence favours liver resection (LR) over TACE for intermediate-stage HCC, the best treatment option remains controversial. This meta-analysis aimed to compare the overall survival (OS) after LR versus TACE for intermediate-stage HCC. METHODS A comprehensive literature review of PubMed, Embase, Cochrane Library, and Web of Science was performed. Studies that compared the efficacy of LR and TACE in patients with intermediate (BCLC stage B) HCC were selected. According to the recent updated BCLC classification, intermediate stage of HCC was defined as follows: (a) four or more HCC nodules of any size, or (b) two or three nodules, but if at least one tumour is larger than 3 cm. The main outcome was OS, expressed as the hazard ratio. RESULTS Nine eligible studies of 3355 patients were included in the review. The OS of patients who underwent LR was significantly longer than that of patients who underwent TACE (hazard ratio=0.52; 95% CI: 0.39-0.69; I2=79%). Prolonged survival following LR was confirmed after sensitivity analysis of five studies using propensity score matching (HR=0.45; 95% CI: 0.34-0.59; I2=55%). CONCLUSION Patients with intermediate-stage HCC who underwent LR had a longer OS that those who underwent TACE. The role of LR in patients with BCLC stage B should be clarified in future randomised controlled trials.
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Affiliation(s)
- Aleksandar Bogdanovic
- Clinic for Digestive Surgery
- School of Medicine, University of Belgrade, Belgrade, Serbia
| | - Jelena Djokic Kovac
- Center for Radiology and Magnetic Resonance Imaging, University Clinical Center of Serbia
- School of Medicine, University of Belgrade, Belgrade, Serbia
| | | | | | - Vladimir Dugalic
- Clinic for Digestive Surgery
- School of Medicine, University of Belgrade, Belgrade, Serbia
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Wong JK, Lim HJ, Tam VC, Burak KW, Dawson LA, Chaudhury P, Abraham RJ, Meyers BM, Sapisochin G, Valenti D, Samimi S, Ramjeesingh R, Mujoomdar A, Martins I, Dixon E, Segedi M, Liu DM. Clinical consensus statement: Establishing the roles of locoregional and systemic therapies for the treatment of intermediate-stage hepatocellular carcinoma in Canada. Cancer Treat Rev 2023; 115:102526. [PMID: 36924644 DOI: 10.1016/j.ctrv.2023.102526] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2022] [Revised: 02/12/2023] [Accepted: 02/14/2023] [Indexed: 03/06/2023]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) a leading cause of cancer mortality worldwide and approximately one-third of patients present with intermediate-stage disease. The treatment landscape of intermediate-stage HCC is rapidly evolving due to developments in local, locoregional and systemic therapies. Treatment recommendations focused on this heterogenous disease stage and that take into account the Canadian reality are lacking. To address this gap, a pan-Canadian group of experts in hepatology, transplant, surgery, radiation therapy, nuclear medicine, interventional radiology, and medical oncology came together to develop consensus recommendations on management of intermediate-stage HCC relevant to the Canadian context. METHODS A modified Delphi framework was used to develop consensus statements with strengths of recommendation and supporting levels of evidence graded using the AHA/ACC classification system. Tentative consensus statements were drafted based on a systematic search and expert input in a series of iterative feedback cycles and were then circulated via online survey to assess the level of agreement. RESULTS & CONCLUSION The pre-defined ratification threshold of 80 % agreement was reached for all statements in the areas of multidisciplinary treatment (n = 4), intra-arterial therapy (n = 14), biologics (n = 5), radiation therapy (n = 3), surgical resection and transplantation (n = 7), and percutaneous ablative therapy (n = 4). These generally reflected an expansion in treatment options due to developments in previously established or emergent techniques, introduction of new and more active therapies and increased therapeutic flexibility. These developments have allowed for greater treatment tailoring and personalization as well as a paradigm shift toward strategies with curative intent in a wider range of disease settings.
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Affiliation(s)
- Jason K Wong
- University of Calgary, 2500 University Dr NW, Calgary, AB T2N 1N4, Canada.
| | - Howard J Lim
- BC Cancer Agency, 600 West 10th Avenue, Vancouver, BC V5Z 4E6, Canada.
| | - Vincent C Tam
- Tom Baker Cancer Centre, University of Calgary, 1331 29 St NW, Calgary, AB T2N 4N2, Canada.
| | - Kelly W Burak
- University of Calgary, 2500 University Dr NW, Calgary, AB T2N 1N4, Canada.
| | - Laura A Dawson
- Princess Margaret Cancer Centre, University of Toronto, 610 University Ave, Toronto, ON M5G 2C1, Canada.
| | | | - Robert J Abraham
- Department of Diagnostic Radiology, Dalhousie University, 6299 South St, Halifax, NS B3H 4R2, Canada.
| | - Brandon M Meyers
- Juravinski Cancer Centre, 699 Concession St, Hamilton, ON L8V 5C2, Canada.
| | | | - David Valenti
- McGill University, 845 Rue Sherbrooke O, Montréal, QC H3A 0G4, Canada.
| | - Setareh Samimi
- Hopital Sacre-Coeur de Montreal, University of Montreal, 5400 Boul Gouin O, Montréal, QC H4J 1C5, Canada.
| | - Ravi Ramjeesingh
- Department of Medicine, Dalhousie University, 6299 South St, Halifax, NS B3H 4R2, Canada.
| | - Amol Mujoomdar
- Western University, 1151 Richmond Street, London, ON N6A 5B9, Canada.
| | - Ilidio Martins
- Kaleidoscope Strategic, Inc. 1 King Street W, Suite 4800 - 117, Toronto, ON M5H 1A1, Canada.
| | - Elijah Dixon
- University of Calgary, 2500 University Dr NW, Calgary, AB T2N 1N4, Canada.
| | - Maja Segedi
- Department of Surgery, Vancouver General Hospital, Jim Pattison Pavilion, 899 W 12th Ave, Vancouver, BC V5Z 1M9, Canada.
| | - David M Liu
- School of Biomedical Engineering, University of British Columbia, 2329 West Mall Vancouver, BC V6T 1Z4, Canada.
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Lin Z, Ji X, Tian N, Gan Y, Ke L. Mapping Intellectual Structure for the Long Non-Coding RNA in Hepatocellular Carcinoma Development Research. Front Genet 2022; 12:771810. [PMID: 35047004 PMCID: PMC8762053 DOI: 10.3389/fgene.2021.771810] [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: 09/09/2021] [Accepted: 11/22/2021] [Indexed: 01/09/2023] Open
Abstract
Background: Emerging research suggests that long non-coding RNAs (lncRNAs) play an important role in a variety of developmental or physiological processes of hepatocellular carcinoma (HCC). Various differentially expressed lncRNAs have been identified in HCC. Thus, a deeper analysis of recent research concerning lncRNA and HCC development could provide scientists with a valuable reference for future studies. Methods: Related publications were retrieved from the Web of Science Core Collection database. CiteSpace version 5.6.R4 was employed to conduct bibliometric analysis. Several network maps were constructed to evaluate the collaborations between different countries, institutions, authors, journals, and keywords. Results: A total of 2,667 records were initially found from the year of 2010–2020. The annual related publications output had increased dramatically during these years. Although China was the most prolific country in terms of research publication, the United States played a leading role in collaborative network. The Nanjing Medical University was the most productive institute in the field of lncRNAs in HCC development. Gang Chen was the most prolific researcher, while Yang F was the most frequently co-cited author. Oncotarget, Cell, and Oncogene were the most highly co-cited journals. The most recent burst keywords were interaction, database, and pathway. Conclusion: This study provides a comprehensive overview for the field of lncRNAs in HCC development based on bibliometric and visualized methods. The results would provide a reference for scholars focusing on this field.
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Affiliation(s)
- Zhifeng Lin
- Key Laboratory for Major Obstetric Diseases of Guangdong Province, Department of Medical Record, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Xiaohui Ji
- Department of Obstetrics and Gynaecology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Nana Tian
- Department of Medical Record, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Yu Gan
- Department of Medical Record, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Li Ke
- Key Laboratory for Major Obstetric Diseases of Guangdong Province, Department of Medical Record, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
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