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Buckstein M. Ablative Radiation for Oligoprogression: Another Promising but Unproven Role for Radiation in Hepatocellular Carcinoma. Int J Radiat Oncol Biol Phys 2025; 122:339-340. [PMID: 40382166 DOI: 10.1016/j.ijrobp.2025.01.029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2025] [Accepted: 01/25/2025] [Indexed: 05/20/2025]
Affiliation(s)
- Michael Buckstein
- Department of Radiation Oncology, Icahn School of Medicine at Mount Sinai, New York, New York.
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Peng Y, Liu H, Miao M, Cheng X, Chen S, Yan K, Mu J, Cheng H, Liu G. Micro-Nano Convergence-Driven Radiotheranostic Revolution in Hepatocellular Carcinoma. ACS APPLIED MATERIALS & INTERFACES 2025; 17:29047-29081. [PMID: 40347149 DOI: 10.1021/acsami.5c05525] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/12/2025]
Abstract
Radiotherapy, as an important means of treating hepatocellular carcinoma (HCC), has shown unique therapeutic advantages, especially in patients who are unable to undergo surgery or transplantation. It mainly includes external radiotherapy, transarterial radioembolization and intratumoral radioactive particle implantation. However, under the influence of factors such as the hypoxic characteristics of the liver tumor microenvironment and the radioresistance of tumor cells, the effect of radiotherapy may be unstable and may cause side effects, affecting the quality of life of patients. In recent years, with the development of nanotechnology, drug delivery systems based on micro-nanomaterials have provided new solutions for improving the effect of radiotherapy for HCC. Despite this, the application of micro-nano drug delivery systems in the treatment of HCC still faces some challenges, mainly including the in vivo safety and in vivo metabolism of micro-nano materials. This article reviews the latest progress of micro-nano materials in the treatment of HCC, especially their application in radiosensitization and their clinical translation potential. This article systematically analyzes the role of micro-nanomaterials in external or internal radiotherapy sensitization and radioimmunotherapy and explores the advantages of micro-nanomaterials in improving the treatment effect of HCC.
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Affiliation(s)
- Yisheng Peng
- State Key Laboratory of Vaccine for Infectious Diseases, Xiang An Biomedicine Laboratory, National Innovation Platform for Industry-Education Integration in Vaccine Research, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen 361102, China
| | - Hui Liu
- State Key Laboratory of Vaccine for Infectious Diseases, Xiang An Biomedicine Laboratory, National Innovation Platform for Industry-Education Integration in Vaccine Research, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen 361102, China
| | - Mengmeng Miao
- State Key Laboratory of Vaccine for Infectious Diseases, Xiang An Biomedicine Laboratory, National Innovation Platform for Industry-Education Integration in Vaccine Research, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen 361102, China
| | - Xu Cheng
- State Key Laboratory of Vaccine for Infectious Diseases, Xiang An Biomedicine Laboratory, National Innovation Platform for Industry-Education Integration in Vaccine Research, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen 361102, China
| | - Shangqing Chen
- State Key Laboratory of Vaccine for Infectious Diseases, Xiang An Biomedicine Laboratory, National Innovation Platform for Industry-Education Integration in Vaccine Research, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen 361102, China
| | - Kaifei Yan
- State Key Laboratory of Vaccine for Infectious Diseases, Xiang An Biomedicine Laboratory, National Innovation Platform for Industry-Education Integration in Vaccine Research, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen 361102, China
| | - Jing Mu
- Institute of Precision Medicine, Peking University Shenzhen Hospital, Shenzhen 518036, China
| | - Hongwei Cheng
- State Key Laboratory of Vaccine for Infectious Diseases, Xiang An Biomedicine Laboratory, National Innovation Platform for Industry-Education Integration in Vaccine Research, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen 361102, China
- Zhuhai UM Science & Technology Research Institute, University of Macau, Macau SAR 999078, China
| | - Gang Liu
- State Key Laboratory of Vaccine for Infectious Diseases, Xiang An Biomedicine Laboratory, National Innovation Platform for Industry-Education Integration in Vaccine Research, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen 361102, China
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Chung SW, Kim JS, Choi WM, Choi J, Lee D, Shim JH, Lim YS, Lee HC, Kim KM. Synergistic Effects of Transarterial Chemoembolization and Lenvatinib on HIF-1α Ubiquitination and Prognosis Improvement in Hepatocellular Carcinoma. Clin Cancer Res 2025; 31:2046-2055. [PMID: 39992640 DOI: 10.1158/1078-0432.ccr-24-1228] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2024] [Revised: 12/09/2024] [Accepted: 02/20/2025] [Indexed: 02/26/2025]
Abstract
PURPOSE A recent trial has shown that adding transarterial chemoembolization (TACE) to lenvatinib therapy results in enhanced therapeutic efficacy in hepatocellular carcinoma (HCC). We aimed to assess the effectiveness of the lenvatinib and TACE combination in a real-world clinical context for managing HCC and to elucidate the molecular pathways involved. EXPERIMENTAL DESIGN This retrospective analysis included 199 patients diagnosed with HCC and having intrahepatic lesions between 2018 and 2021. The cohort was divided into those who received lenvatinib plus TACE (n = 62, combination group) and those who received lenvatinib monotherapy (n = 137, monotherapy group). To further explore the underlying mechanisms, Huh-7 cells were exposed to lenvatinib or a vehicle for 48 hours under normoxic or hypoxic conditions. RESULTS Propensity score-matched analysis revealed a significant improvement in both overall survival (adjusted HR, 0.38; 95% confidence interval, 0.24-0.59; P < 0.001) and progression-free survival (adjusted HR, 0.41; 95% confidence interval, 0.26-0.64; P < 0.001) in the combination group compared with the monotherapy group. In laboratory experiments, under hypoxic conditions, lenvatinib notably attenuated hypoxia-inducible factor-1α (HIF-1α) protein levels in Huh-7 cells without altering its mRNA levels. Intriguingly, lenvatinib facilitated the mouse double minute 2 homolog-mediated ubiquitination and subsequent degradation of HIF-1α. Additionally, cell viability assays confirmed a significant decrease in Huh-7 cell survival following lenvatinib treatment under hypoxic conditions. CONCLUSIONS The combination of lenvatinib and TACE significantly improved survival in patients with HCC. The mechanistic foundation seems to be the lenvatinib-triggered degradation of HIF-1α via the mouse double minute 2 homolog-dependent ubiquitination pathway, highlighting a potential therapeutic target in HCC treatment.
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Affiliation(s)
- Sung Won Chung
- Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Jin Sun Kim
- Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Won-Mook Choi
- Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Jonggi Choi
- Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Danbi Lee
- Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Ju Hyun Shim
- Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Young-Suk Lim
- Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Han Chu Lee
- Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Kang Mo Kim
- Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
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Le XY, Feng JB, Yu XL, Li SL, Zhang X, Li J, Li CM. A network meta-analysis of different interventional treatment strategies for unresectable hepatocellular carcinoma. BMC Gastroenterol 2025; 25:360. [PMID: 40355829 PMCID: PMC12067877 DOI: 10.1186/s12876-025-03980-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2025] [Accepted: 05/07/2025] [Indexed: 05/15/2025] Open
Abstract
BACKGROUND The optimal clinical management of unresectable hepatocellular carcinoma (uHCC) is challenging for clinicians. Bayesian network meta-analysis was conducted to compare the efficacy and safety of different interventional strategies for uHCC. METHODS A systematic search was conducted in PubMed, Embase, the Cochrane Library, Web of Science, and CNKI databases. Bayesian network meta-analysis was applied to evaluate the disease control rate (DCR), 1-year survival rate and 2-year survival rate, as well as the incidence of serious adverse events associated with seven interventional strategies. Odds ratios (ORs) were estimated using pairwise and network meta-analysis with random effects. Treatment rankings utilized surface under the cumulative ranking curve (SUCRA), whereas heterogeneity was examined via I-square and meta-regression. RESULTS A total of 40 randomized controlled studies were included. Compared with transarterial chemoembolization (TACE) alone, all of the combination treatments, including TACE with radiofrequency ablation (RFA), microwave ablation (MWA), high-intensity focused ultrasound (HIFU), percutaneous ethanol injection (PEI), and radiotherapy (RT), significantly improved the DCR. TACE combined with RFA was observed to be superior to hepatic arterial infusion chemotherapy (HAIC) (OR: 1.91; 95% CI: 1.03-3.81) and TACE (OR: 3.85; 95% CI: 2.66-5.69), with the highest probability (SUCRA 0.836). TACE combined with HIFU ranks highest 1-year survival (SUCRA 0.919) and 2-year survival (SUCRA 0.925) rates, and also exhibited a better 1-year survival rate than HAIC (OR: 2.99; 95% CI: 1.09-9.03). Compared with TACE alone, HAIC exhibited a greater DCR (OR: 2.02; 95% CI: 1.15-3.40) and a potential advantage in 2-year survival (OR: 1.95; 95% CI: 1.02-3.78). No significant differences in serious adverse events were observed across treatments. CONCLUSIONS Compared with TACE alone, combined treatments for uHCC patients demonstrates better efficacy and survival. Moreover, compared with TACE and HAIC, TACE combined with RFA provides better efficacy, whereas TACE combined with HIFU offers the highest 1-year survival rate. HAIC alone outperforms TACE in DCR and 2-year survival rate.
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Affiliation(s)
- Xing-Yan Le
- Medical Imaging Department, Chongqing Emergency Medical Center, Chongqing University Central Hospital, School of Medicine, Chongqing University, No. 1 Jiankang Road, Chongqing, 400014, China
| | - Jun-Bang Feng
- Medical Imaging Department, Chongqing Emergency Medical Center, Chongqing University Central Hospital, School of Medicine, Chongqing University, No. 1 Jiankang Road, Chongqing, 400014, China
| | - Xiao-Li Yu
- Medical Imaging Department, Chongqing Emergency Medical Center, Chongqing University Central Hospital, School of Medicine, Chongqing University, No. 1 Jiankang Road, Chongqing, 400014, China
| | - Sui-Li Li
- Medical Imaging Department, Chongqing Emergency Medical Center, Chongqing University Central Hospital, School of Medicine, Chongqing University, No. 1 Jiankang Road, Chongqing, 400014, China
| | - Xiaocai Zhang
- Medical Imaging Department, The 956th Hospital of the Chinese People's Liberation Army, Xizang, China
| | - Jiaqing Li
- Department of Information, Chongqing Emergency Medical Center, Chongqing University Central Hospital, School of Medicine, Chongqing University, Chongqing, China
| | - Chuan-Ming Li
- Medical Imaging Department, Chongqing Emergency Medical Center, Chongqing University Central Hospital, School of Medicine, Chongqing University, No. 1 Jiankang Road, Chongqing, 400014, China.
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Yu J, Li Y, Yang Y, Guo H, Chen Y, Yi P. PD-1 inhibitors improve the efficacy of tyrosine kinase inhibitors combined with transcatheter arterial chemoembolization in advanced hepatocellular carcinoma: a meta-analysis and trial sequential analysis. Scand J Gastroenterol 2025; 60:472-484. [PMID: 40152031 DOI: 10.1080/00365521.2025.2479193] [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: 11/20/2024] [Revised: 02/21/2025] [Accepted: 03/09/2025] [Indexed: 03/29/2025]
Abstract
BACKGROUND This meta-analysis and trial sequential analysis (TSA) aimed to evaluate the efficacy and safety of triple therapy with tyrosine kinase inhibitors (TKIs) combined with transcatheter arterial chemoembolization (TACE) plus programmed death 1 (PD-1) inhibitors (T-T-P) and dual therapy with TKIs combined with TACE (T-T) for the treatment of advanced unresectable hepatocellular carcinoma (uHCC). METHODS Literature related to the efficacy of TKIs combined with TACE plus PD-1 inhibitors in uHCC was searched using the Embase, PubMed, and Cocrane libraries. TSA was used to reduce false positive results due to random error. RESULTS Seventeen articles were included in this meta-analysis, including 2,561 patients. In the T-T-P group, OS [HR 0.45, 95% confidence interval (CI) 0.39-0.52; p = 0.000], PFS [HR 0.43, 95% CI 0.38 - 0.48; p = 0.000], were significantly prolonged compared to those in the T-T group; ORR (RR 1.59 [95% CI 1.39-1.81]; p = 0.000) and DCR (RR 1.26 [95% CI 1.15-1.37]; p = 0.000) were significantly higher. TSA analysis showed early results without further testing. Prognostic factor analysis demonstrated that portal vein tumor thrombus (PVTT) and extrahepatic metastasis were common independent risk factors for OS and PFS. Regarding grade 3/4 adverse events results showed no statistically significant differences in any of them. CONCLUSIONS Compared with T-T treatment group, the T-T-P treatment group exhibited a notable improvement in OS and PFS, particularly in cases of PVTT and extrahepatic metastasis. Furthermore, it can markedly enhance the ORR and DCR in patients with uHCC.
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Affiliation(s)
- Jiahui Yu
- Department of hepato-biliary-pancrease II, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, P. R. China
| | - Yong Li
- Department of hepato-biliary-pancrease II, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, P. R. China
| | - Yuting Yang
- Department of Educational Technology, Institute of Education, China West Normal University, Nanchong, Sichuan, P. R. China
| | - Hao Guo
- Department of hepato-biliary-pancrease II, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, P. R. China
| | - Yimiao Chen
- Department of hepato-biliary-pancrease II, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, P. R. China
| | - Pengsheng Yi
- Department of hepato-biliary-pancrease II, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, P. R. China
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Wang J, Liao C, Luo J, Li M, Gu L, Li X, Chen L. NEIL3 Deficiency Enhances HCC Cell Sensitivity to Oxaliplatin by Inhibiting the Fanconi Anaemia Pathway. Cell Biol Int 2025. [PMID: 40263742 DOI: 10.1002/cbin.70023] [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: 01/03/2025] [Revised: 03/13/2025] [Accepted: 04/03/2025] [Indexed: 04/24/2025]
Abstract
Despite some achievements in oxaliplatin-based chemotherapy for the treatment of advanced hepatocellular carcinoma (HCC), the abnormal activation of DNA damage repair pathways in HCC cells remains a major problem, limiting the efficacy of oxaliplatin-based chemotherapy. In a previous study, we found that endonuclease VIII-like protein 3 (NEIL3) is expressed in a high proportion of patients with HCC and associated with an unfavourable prognosis. However, the role of NEIL3 in chemoresistance is still unclear. The aim of this study was to evaluate whether and how NEIL3 regulates oxaliplatin anti-tumour efficacy. Gene expression after oxaliplatin treatment in HCC cell lines was assessed by real-time quantitative PCR, western blot analysis and bioinformatics analysis. The effect of NEIL3 on regulating oxaliplatin efficacy was assessed using cell counting kit-8 assays, colony formation assays, flow cytometry and an in vivo nude mice study. Mechanistic insights into the sensitivity to oxaliplatin mediated by the inhibition of NEIL3 were obtained through immunofluorescence and RNA sequencing analyses. Our findings demonstrated that NEIL3 expression was markedly downregulated after oxaliplatin administration. NEIL3 knockdown impaired cell viability and colony formation and increased apoptosis in HCC cells exposed to oxaliplatin. In addition, NEIL3 inhibition reduced tumour progression and enhanced oxaliplatin efficacy in xenograft nude mice models. Furthermore, knocking down NEIL3 significantly increased the oxaliplatin-mediated inhibition of the Fanconi anaemia pathway. Our results revealed that NEIL3 may be a promising therapeutic target for improving oxaliplatin efficacy in the treatment of HCC.
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Affiliation(s)
- Jialiang Wang
- Guangdong Provincial Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Chunhong Liao
- Guangdong Provincial Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Jing Luo
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Mingna Li
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Lin Gu
- Guangdong Provincial Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Xiaoyan Li
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Lubiao Chen
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
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Lee SM, Choi JH, Yoon JH, Kim YJ, Yu SJ, Lee JH, Kang HC, Chie EK, Kim KS. Efficacy and safety of image-guided hypofractionated radiotherapy for hepatocellular carcinoma with portal vein tumor thrombosis: a retrospective, multicenter study. BMC Cancer 2025; 25:736. [PMID: 40254568 PMCID: PMC12010600 DOI: 10.1186/s12885-025-13739-3] [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: 08/21/2023] [Accepted: 02/14/2025] [Indexed: 04/22/2025] Open
Abstract
BACKGROUND External beam radiation therapy (RT) has shown promising effects for hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT) in recent studies. However, there is still a lack of consensus on the optimal RT scheme for PVTT treatment. We evaluated the efficacy and safety of image-guided 10-fraction hypofractionated RT in these patients. METHODS Between January 2016 and March 2022, a total of 95 HCC patients with PVTT received 10-fraction hypofractionated image-guided radiation therapy (IGRT) at two institutes, and 69 patients were analyzed. Follow-up imaging was performed at three-month intervals after the completion of RT. The extent of PVTT was described according to the Liver Cancer Study Group of Japan classification: Vp1 = segmental portal vein branch, Vp2 = right/left anterior/posterior portal vein, Vp3 = right/left portal vein, and Vp4 = main portal vein. Response evaluation was performed using Response Evaluation Criteria in Solid Tumors, version 1.1. Freedom from local progression (FFLP), progression-free survival (PFS), and overall survival (OS) were calculated from the start date of RT. RESULTS The median prescribed dose of 50 Gy (range: 40-50 Gy; biologically effective dose [BED]: 56-75Gy10) was delivered in 10 fractions. In this cohort, 4.3% of patients had Vp1, 20.3% had Vp2, 37.7% had Vp3, and 37.7% had Vp4. Median Planning target volume was 105.3 cc (interquartile range [IQR], 74.1-179.4 cc). Fifty-two (75.4%) patients received 50 Gy. With a median follow-up of 10.2 months (IQR, 6-21 months), the median OS was 20.3 months, and 1-year FFLP, PFS, and OS rates were 88.7%, 26.9%, and 62.2%, respectively. At 3 months follow-up, 13.0% had a complete response, 36.2% had a partial response, 46.4% had a stable disease and 4.4% had a progressive disease. In the multivariate analysis, alpha-fetoprotein level ≥ 600 IU/ml (hazard ratio [HR] 2.06, p = 0.03), Child-Pugh Class B or C (HR 2.30, p = 0.02), and stage IVA or IVB (4.05, p = 0.02) were significantly related to OS. During the follow-up period, there were 2 (2.9%) cases of grade ≥ 3 toxicity: grade 3 liver enzyme elevation (n = 1), and acute cholangitis (n = 1). CONCLUSIONS Hypofractionated RT demonstrated promising local PVTT control and OS rates with acceptable toxicity. These data suggest that 10-fraction image-guided hypofractionated RT (BED: 56-75 Gy10) is a feasible treatment option for PVTT in HCC patients.
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Affiliation(s)
- Sang Min Lee
- Department of Radiation Oncology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Jin Hwa Choi
- Department of Radiation Oncology, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Republic of Korea
| | - Jung-Hwan Yoon
- Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul National University, Seoul, Republic of Korea
| | - Yoon Jun Kim
- Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul National University, Seoul, Republic of Korea
| | - Su Jong Yu
- Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul National University, Seoul, Republic of Korea
| | - Jeong-Hoon Lee
- Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul National University, Seoul, Republic of Korea
| | - Hyun-Cheol Kang
- Department of Radiation Oncology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.
| | - Eui Kyu Chie
- Department of Radiation Oncology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.
| | - Kyung Su Kim
- Department of Radiation Oncology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.
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Dudzinski SO, Newman NB, McIntyre J, Engineer R, Sanford NN, Wo JY, Seong J, Guha C, Chang DT, Hong TS, Dawson LA, Koay EJ, Ludmir EB. Emerging evidence-based role for external-beam radiation therapy in hepatocellular carcinoma. Lancet Gastroenterol Hepatol 2025; 10:387-398. [PMID: 39993402 DOI: 10.1016/s2468-1253(24)00267-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2024] [Revised: 07/30/2024] [Accepted: 08/02/2024] [Indexed: 02/26/2025]
Abstract
The primary curative therapies for hepatocellular carcinoma are resection or liver transplantation. For patients requiring downstaging or who are unresectable at presentation, the landscape of local treatment options has vastly changed over the past decades. This change is partly due to the paucity of high-level evidence to guide the selection of liver-directed therapies, where physician preference and treatment patterns have historically resulted in relegating external-beam radiation therapy (EBRT) to a secondary option in the treatment of hepatocellular carcinoma in cases where arterially directed therapies or thermal ablations were not possible. However, technology advancements have substantially improved the ability to treat liver malignancies with high doses of radiation therapy and to minimise doses to uninvolved hepatic parenchyma and other nearby organs. These advancements have enabled safe treatment of hepatocellular carcinoma with EBRT, with low risk of toxicity. Recent randomised trials support the role of EBRT in the treatment of hepatocellular carcinoma from early to advanced stages. These trials identified that EBRT improved several key patient-centred outcomes, including overall survival when using stereotactic body radiotherapy and sorafenib compared with sorafenib alone in unresectable hepatocellular carcinoma, recurrence-free survival with the use of adjuvant EBRT in select patients after hepatocellular carcinoma resection, and quality of life for patients with painful hepatocellular carcinoma masses treated with palliative EBRT. With emerging high-quality evidence, hepatocellular carcinoma therapeutic guidelines should include the growing role of EBRT in improving the quality and quantity of life for patients with liver cancer.
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Affiliation(s)
- Stephanie O Dudzinski
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Neil B Newman
- Department of Radiation Oncology, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
| | | | - Reena Engineer
- Department of Radiation Oncology, Tata Memorial Hospital, Tata Memorial Centre, Maharashtra, India
| | - Nina N Sanford
- Department of Radiation Oncology, The University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Jennifer Y Wo
- Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Jinsil Seong
- Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea
| | - Chandan Guha
- Department of Radiation Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, New York City, NY, USA
| | - Daniel T Chang
- Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA
| | - Theodore S Hong
- Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Laura A Dawson
- Radiation Medicine Program, Princess Margaret Cancer Centre, Department of Radiation Oncology, University of Toronto, ON, Canada
| | - Eugene J Koay
- Department of Gastrointestinal Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Ethan B Ludmir
- Department of Gastrointestinal Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
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9
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Yariv O, Newman NB, Yarchoan M, Rabiee A, Wood BJ, Salem R, Hernandez JM, Bang CK, Yanagihara TK, Escorcia FE. Advances in radiation therapy for HCC: Integration with liver-directed treatments. Hepatol Commun 2025; 9:e0653. [PMID: 40163776 PMCID: PMC11927661 DOI: 10.1097/hc9.0000000000000653] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/23/2024] [Accepted: 12/03/2024] [Indexed: 04/02/2025] Open
Abstract
HCC is the fourth leading cause of cancer-related mortality with increasing incidence worldwide. Historically, treatment for early disease includes liver transplantation, surgical resection, and/or other local therapies, such as thermal ablation. As a result of technical advances and high-quality prospective data, the use of definitive external beam radiotherapy with ablative doses has emerged. Intermediate-stage disease has been generally addressed with arterially directed therapies (eg, chemoembolization or radioembolization) and external beam radiotherapy, while advanced stages have been addressed by systemic therapy or best supportive care. The role of each local/locoregional therapy has rapidly evolved in the context of novel pharmacotherapies, including immunotherapies and antiangiogenic agents. The combinations, indications, and timing of treatments vary widely among specialties and geographies. Here, we aim to synthesize the best quality evidence available regarding the efficacy and safety of different liver-directed modalities, with a focus on recent prospective clinical data of external beam radiotherapy within the context of other available liver-directed therapies across Barcelona Liver Classification (BCLC) stages.
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Affiliation(s)
- Orly Yariv
- Radiation Oncology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland, USA
| | - Neil B. Newman
- Department of Radiation Oncology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA
| | - Mark Yarchoan
- Department of Medical Oncology, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland, USA
| | - Atoosa Rabiee
- Division of Gastroenterology and Hepatology, Washington DC Veterans Affairs Medical Center, Washington, District of Columbia, USA
| | - Bradford J. Wood
- Interventional Radiology, Center for Interventional Oncology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland, USA
- Liver Cancer Program, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland, USA
| | - Riad Salem
- Department of Radiology, Northwestern Feinberg School of Medicine, Chicago, Illinois, USA
| | - Jonathan M. Hernandez
- Liver Cancer Program, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland, USA
- Surgical Oncology Program, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland, USA
| | - Christine K. Bang
- Radiation Oncology Clinical Care Center, Baltimore Veterans Affairs Medical Center, Baltimore, Maryland, USA
| | - Ted K. Yanagihara
- Department of Radiation Oncology, University of North Carolina School of Medicine, Lineberger Comprehensive Cancer Center, Chapel Hill, North Carolina, USA
| | - Freddy E. Escorcia
- Radiation Oncology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland, USA
- Liver Cancer Program, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland, USA
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10
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Yu J, Yu J, Chen Y, Yang Y, Yi P. PD-1 inhibitors improve the efficacy of transcatheter arterial chemoembolization combined with apatinib in advanced hepatocellular carcinoma: a meta-analysis and trial sequential analysis. BMC Cancer 2025; 25:564. [PMID: 40155828 PMCID: PMC11951536 DOI: 10.1186/s12885-025-13932-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2025] [Accepted: 03/12/2025] [Indexed: 04/01/2025] Open
Abstract
BACKGROUND The efficacy of adding programmed death-1 (PD-1) inhibitors to transcatheter arterial chemoembolization (TACE) combined with apatinib for advanced hepatocellular carcinoma (HCC) remains controversial. This study aimed to evaluate the efficacy of incorporating PD-1 inhibitors into TACE combined with apatinib. METHODS Relevant literature on TACE combined with apatinib plus PD-1 inhibitors for advanced HCC was searched in PubMed, Cochrane Library, Embase, and Web of Science databases. Trial sequential analysis (TSA) was conducted to minimize randomization errors and assess whether the meta-analysis provided conclusive evidence. RESULTS Six studies involving 1,452 patients were included. Compared with the TACE combined with apatinib treatment group (T-A), TACE combined with apatinib plus PD-1 inhibitors (T-A-P) significantly prolonged overall survival (OS) (Hazard Ratio [HR] 2.22, 95% Confidence Interval [CI] 1.93-2.56; p < 0.001) and progression-free survival (PFS) (HR 2.36, 95% CI 2.01-2.77; p < 0.001), while also improving the objective response rate (ORR) (risk ratios [RR] 1.60, 95% CI 1.20-2.14; p < 0.001) and disease control rate (DCR) (RR 1.06, 95% CI 1.00-1.12; p < 0.001). TSA results indicated that additional studies were required to confirm the significance of DCR. Prognostic analysis identified treatment regimen and extrahepatic metastasis as common independent risk factors for OS and PFS. The incidence of adverse events in the T-A-P treatment group was comparable to that in the T-A treatment group. CONCLUSION Adding PD-1 inhibitors to TACE combined with apatinib significantly prolonged OS and PFS, particularly in patients without extrahepatic metastases. It also improved ORR and DCR in patients with HCC.
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Affiliation(s)
- Jiahui Yu
- Department of Hepato-Biliary-Pancrease II, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, 637000, People's Republic of China
| | - Jinxin Yu
- North Sichuan Medical College, Nanchong, Sichuan, 637000, People's Republic of China
| | - Yimiao Chen
- Department of Hepato-Biliary-Pancrease II, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, 637000, People's Republic of China
| | - Yuting Yang
- Department of Educational Technology, Institute of Education, China West Normal University, Nanchong, Sichuan, 637000, People's Republic of China
- Nanchong Gaoping District Wangcheng Primary School, Nanchong, People's Republic of China
| | - Pengsheng Yi
- Department of Hepato-Biliary-Pancrease II, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, 637000, People's Republic of China.
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11
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Choi JW, Kim GM, Hyun D, Jang MJ, Kim HC. Radioembolization as a Spearhead Treatment of Hepatocellular Carcinoma with Localized Portal Vein Tumor Thrombosis (RESOLVE): Protocol for an Open-label, Multi-center, Single-arm Trial. Cardiovasc Intervent Radiol 2025; 48:398-404. [PMID: 39948248 DOI: 10.1007/s00270-024-03935-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2024] [Accepted: 11/27/2024] [Indexed: 03/08/2025]
Abstract
PURPOSE To evaluate the efficacy, safety, and clinical course following ablative radioembolization with glass microspheres for hepatocellular carcinoma (HCC) with localized portal vein tumor thrombosis (PVTT) in patients with well-preserved liver function. MATERIALS AND METHODS This is a prospective, open-label, multi-center, single-arm, phase II trial. Key inclusion criteria are unilobar HCC, PVTT confined to the ipsilateral lobe (Vp1-3), no extrahepatic spread, Child-Pugh class A, and a performance status of ≤ 1. Main exclusion criteria are hepatic venous tumor thrombus, bile duct invasion, and massive arterioportal shunting. Depending on the extent of the tumor and PVTT, patients will undergo radiation segmentectomy, modified radiation lobectomy, or ablative lobar treatment, while adhering to dose limits for the non-tumorous liver and lung. The primary outcome measure is overall survival, with the overall survival rate at two years provided as the summary measurement. STATISTICS This study will enroll 30 patients to explore the efficacy and safety of ablative radioembolization for HCC with localized PVTT. Efficacy will be evaluated by intention-to-treat and per-protocol populations. Safety will be assessed for all patients who received radioembolization at any dose. EXPECTED GAIN OF KNOWLEDGE This study aims to address the potential of ablative radioembolization as a definitive or effective downstaging treatment for HCC with localized PVTT, where locoregional treatments may be more beneficial than systemic treatments. The results will help establish treatment outcomes that can serve as a standard for future comparative studies and contribute to the standardization of radioembolization approaches for HCC with localized PVTT. TRIAL REGISTRATION ClinicalTrials.gov ( https://classic. CLINICALTRIALS gov/ct2/show/NCT06166576 ). Identifier: NCT06166576.
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Affiliation(s)
- Jin Woo Choi
- Department of Radiology, Seoul National University Hospital, Seoul National University College of Medicine, #101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.
| | - Gyoung Min Kim
- Department of Radiology, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Dongho Hyun
- Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Myoung-Jin Jang
- Medical Research Collaborating Center, Seoul National University Hospital, Seoul, Republic of Korea
| | - Hyo-Cheol Kim
- Department of Radiology, Seoul National University Hospital, Seoul National University College of Medicine, #101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea
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12
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Shin H, Yu SJ. A concise review of updated global guidelines for the management of hepatocellular carcinoma: 2017-2024. JOURNAL OF LIVER CANCER 2025; 25:19-30. [PMID: 39925090 PMCID: PMC12010826 DOI: 10.17998/jlc.2025.02.03] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/25/2024] [Revised: 01/30/2025] [Accepted: 02/03/2025] [Indexed: 02/11/2025]
Abstract
Many guidelines for hepatocellular carcinoma (HCC) have been published and are regularly updated worldwide. HCC management involves a broad range of treatment options and requires multidisciplinary care, resulting in significant heterogeneity in management practices across international communities. To support standardized care for HCC, we systematically appraised 13 globally recognized guidelines and expert consensus statements, including five from Asia, four from Europe, and four from the United States. These guidelines share similarities but reveal notable discrepancies in surveillance strategies, treatment allocation, and other recommendations. Geographic differences in tumor biology (e.g., prevalence of viral hepatitis, alcohol-related liver disease, or metabolic dysfunction-associated steatotic liver disease) and disparities in available medical resources (e.g., organ availability, healthcare infrastructure, and treatment accessibility) complicate the creation of universally applicable guidelines. Previously, significant gaps existed between Asian and Western guidelines, particularly regarding treatment strategies. However, these differences have diminished over the years. Presently, variations are often more attributable to publication dates than to regional differences. Nonetheless, Asia-Pacific experts continue to diverge from the Barcelona Clinic Liver Cancer system, particularly with respect to surgical resection and locoregional therapies, which are viewed as overly conservative in Western guidelines. Advancements in systemic therapies have prompted ongoing updates to these guidelines. Given that each set of guidelines reflects distinct regional characteristics, strengths, and limitations, fostering collaboration and mutual complementarity is essential for addressing discrepancies and advancing global HCC care.
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Affiliation(s)
- Hyunjae Shin
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
- Liver Research Institute, Seoul National University, Seoul, Korea
| | - Su Jong Yu
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
- Liver Research Institute, Seoul National University, Seoul, Korea
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13
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Yan M, Li Z, Claasen MPAW, Santiago AT, Rajendran L, Munoz-Schuffenegger P, Lee C, Magyar CTJ, McGilvray I, Shwaartz C, Reichman T, Moulton CA, Cleary S, O'Kane G, Vogel A, Grant R, Kim TK, Naidoo CSY, Hosni A, Mesci A, Dawson LA, Sapisochin G. Outcomes of Stereotactic Body Radiotherapy Compared with Surgical Resection in Patients with Hepatocellular Carcinoma and Macrovascular Invasion: A Propensity Score-Matched Analysis. Ann Surg Oncol 2025; 32:1771-1783. [PMID: 39692983 DOI: 10.1245/s10434-024-16456-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2024] [Accepted: 10/20/2024] [Indexed: 12/19/2024]
Abstract
INTRODUCTION Patients with advanced hepatocellular carcinoma (HCC) and macrovascular invasion (MVI) are recommended to receive systemic therapy according to guidelines. Stereotactic body radiotherapy (SBRT) and surgery are increasingly used in this patient population. This study compares outcomes from these local treatments. METHODS Patients diagnosed with HCC with MVI and treated with surgery or SBRT between 1999 and 2022 were included. Propensity score matching minimized bias from confounders. Overall survival (OS) was analyzed using the Kaplan-Meier method,. and local, regional, and distant recurrences were assessed via competing risk methods. Univariable and multivariable analyses adjusted by the Lasso method evaluated OS predictors. RESULTS Among 175 patients, 38 underwent surgery and 137 received SBRT. The median age was 61 years, tumor volume was 158.6 cc, and α-fetoprotein level was 197 IU/mL. Most surgical patients had major resection (74%) via an open approach (97%). The median biologically effective dose (BED) for SBRT was 53.7 Gy. After matching, 35 patients per group had a median OS of 16 months. Local failure was higher in the SBRT group (20%) than in the surgery group (12%) at 1 year (p = 0.028). Distant failure was more frequent in surgery (54%) compared with SBRT (17%) [p = 0.003]. Excluding SBRT patients receiving adjuvant systemic therapy did not change the results. In-hospital mortality was 9% post-surgery and 14% experienced post-SBRT liver impairment. CONCLUSION Both surgery and SBRT offer good long-term OS and control. Surgery provides better local control, while SBRT had lower distant relapse. While SBRT has acceptable toxicity, surgery carries a significant mortality risk.
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Affiliation(s)
- Michael Yan
- Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
| | - Zhihao Li
- HBP and Multi-Organ Transplant Program, Division of General Surgery, University Health Network, University of Toronto, Toronto, ON, Canada
| | - Marco P A W Claasen
- HBP and Multi-Organ Transplant Program, Division of General Surgery, University Health Network, University of Toronto, Toronto, ON, Canada
- Department of Surgery, Division of HPB and Transplant Surgery, Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Anna T Santiago
- Department of Biostatistics, University Health Network, Toronto, ON, Canada
| | - Luckshi Rajendran
- HBP and Multi-Organ Transplant Program, Division of General Surgery, University Health Network, University of Toronto, Toronto, ON, Canada
| | - Pablo Munoz-Schuffenegger
- Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
- Radiation Oncology Unit, Department of Hematology - Oncology, Pontificia Universidad Catolica de Chile, Santiago, Chile
| | - Cameron Lee
- Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
| | - Christian T J Magyar
- HBP and Multi-Organ Transplant Program, Division of General Surgery, University Health Network, University of Toronto, Toronto, ON, Canada
- Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Ian McGilvray
- HBP and Multi-Organ Transplant Program, Division of General Surgery, University Health Network, University of Toronto, Toronto, ON, Canada
| | - Chaya Shwaartz
- HBP and Multi-Organ Transplant Program, Division of General Surgery, University Health Network, University of Toronto, Toronto, ON, Canada
| | - Trevor Reichman
- HBP and Multi-Organ Transplant Program, Division of General Surgery, University Health Network, University of Toronto, Toronto, ON, Canada
| | - Carol-Anne Moulton
- HBP and Multi-Organ Transplant Program, Division of General Surgery, University Health Network, University of Toronto, Toronto, ON, Canada
| | - Sean Cleary
- HBP and Multi-Organ Transplant Program, Division of General Surgery, University Health Network, University of Toronto, Toronto, ON, Canada
| | - Grainne O'Kane
- Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
- Department of Medical Oncology, Trinity St James's Cancer Institute, Dublin, Republic of Ireland
| | - Arndt Vogel
- Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Robert Grant
- Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
| | - Tae Kyoung Kim
- Department of Medical Imaging, University of Toronto, Toronto, ON, Canada
| | | | - Ali Hosni
- Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
| | - Aruz Mesci
- Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
| | - Laura A Dawson
- Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
| | - Gonzalo Sapisochin
- HBP and Multi-Organ Transplant Program, Division of General Surgery, University Health Network, University of Toronto, Toronto, ON, Canada.
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14
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Bitzer M, Groß S, Albert J, Blödt S, Boda-Heggemann J, Borucki K, Brunner T, Caspari R, Dombrowski F, Evert M, Follmann M, Freudenberger P, Gani C, Gebert J, Geier A, Gkika E, Götz M, Helmberger T, Hoffmann RT, Huppert P, Krug D, La Fougère C, Lang H, Langer T, Lenz P, Lüdde T, Mahnken A, Nadalin S, Nguyen HHP, Nothacker M, Ockenga J, Oldhafer K, Ott J, Paprottka P, Pereira P, Persigehl T, Plentz R, Pohl J, Recken H, Reimer P, Riemer J, Ringe K, Roeb E, Rüssel J, Schellhaas B, Schirmacher P, Schlitt HJ, Schmid I, Schütte K, Schuler A, Seehofer D, Sinn M, Stengel A, Steubesand N, Stoll C, Tannapfel A, Taubert A, Trojan J, van Thiel I, Utzig M, Vogel A, Vogl T, Wacker F, Waidmann O, Wedemeyer H, Wege H, Wenzel G, Wildner D, Wörns MA, Galle P, Malek N. [Not Available]. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2025; 63:e159-e260. [PMID: 40064172 DOI: 10.1055/a-2460-6298] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/04/2025]
Affiliation(s)
- Michael Bitzer
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| | - Sabrina Groß
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| | - Jörg Albert
- Katharinenhospital, Klinik für Allgemeine Innere Medizin, Gastroenterologie, Hepatologie, Infektiologie und Pneumologie, Stuttgart
| | - Susanne Blödt
- Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e. V. (AWMF), Berlin
| | | | - Katrin Borucki
- Otto-von-Guericke-Universität Magdeburg, Medizinische Fakultät, Institut für Klinische Chemie und Pathobiochemie
| | - Thomas Brunner
- Universitätsklinik für Strahlentherapie-Radioonkologie, Medizinische Universität Graz
| | - Reiner Caspari
- Klinik Niederrhein Erkrankungen des Stoffwechsels der Verdauungsorgane und Tumorerkrankungen, Bad Neuenahr-Ahrweiler
| | | | | | - Markus Follmann
- Office des Leitlinienprogrammes Onkologie, Deutsche Krebsgesellschaft e.V., Berlin
| | | | - Cihan Gani
- Klinik für Radioonkologie, Universitätsklinikum Tübingen
| | - Jamila Gebert
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| | - Andreas Geier
- Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg
| | - Eleni Gkika
- Klinik für Strahlenheilkunde, Department für Radiologische Diagnostik und Therapie, Universitätsklinikum Freiburg
| | - Martin Götz
- Medizinische Klinik IV - Gastroenterologie/Onkologie, Klinikverbund Südwest, Böblingen
| | - Thomas Helmberger
- Institut für Radiologie, Neuroradiologie und minimal invasive Therapie, München Klinik Bogenhausen
| | - Ralf-Thorsten Hoffmann
- Institut und Poliklinik für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Dresden
| | - Peter Huppert
- Radiologisches Zentrum, Max Grundig Klinik, Bühlerhöhe
| | - David Krug
- Strahlentherapie Campus Kiel, Universitätsklinikum Schleswig-Holstein
| | - Christian La Fougère
- Nuklearmedizin und Klinische Molekulare Bildgebung, Eberhard-Karls Universität, Tübingen
| | - Hauke Lang
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Johannes Gutenberg-Universität, Mainz
| | - Thomas Langer
- Office des Leitlinienprogrammes Onkologie, Deutsche Krebsgesellschaft e.V., Berlin
| | - Philipp Lenz
- Zentrale Einrichtung Palliativmedizin, Universitätsklinikum Münster
| | - Tom Lüdde
- Medizinische Klinik für Gastroenterologie, Hepatologie und Infektiologie, Universitätsklinikum Düsseldorf
| | - Andreas Mahnken
- Klinik für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Marburg
| | - Silvio Nadalin
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Eberhard-Karls Universität, Tübingen
| | | | - Monika Nothacker
- Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e. V. (AWMF), Berlin
| | - Johann Ockenga
- Medizinische Klinik II, Gesundheit Nord, Klinikverbund Bremen
| | - Karl Oldhafer
- Klinik für Leber-, Gallenwegs- und Pankreaschirurgie, Asklepios Klinik Barmbek
| | - Julia Ott
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| | - Philipp Paprottka
- Sektion für Interventionelle Radiologie, Klinikum rechts der Isar, Technische Universität München
| | - Philippe Pereira
- Zentrum für Radiologie, Minimal-invasive Therapien und Nuklearmedizin, SLK-Klinken Heilbronn
| | - Thorsten Persigehl
- Institut für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Köln
| | - Ruben Plentz
- Digestive Diseases and Nutrition, Gastroenterology, University of Kentucky
| | - Jürgen Pohl
- Abteilung für Gastroenterologie, Asklepios Klinik Altona
| | | | - Peter Reimer
- Institut für Diagnostische und Interventionelle Radiologie, Städtisches Klinikum Karlsruhe
| | | | - Kristina Ringe
- Institut für Diagnostische und Interventionelle Radiologie, Medizinische Hochschule Hannover
| | - Elke Roeb
- Medizinische Klinik II Pneumologie, Nephrologie und Gastroenterologie, Universitätsklinikum Gießen
| | - Jörn Rüssel
- Medizinische Klinik IV Hämatologie und Onkologie, Universitätsklinikum Halle (Saale)
| | - Barbara Schellhaas
- Medizinische Klinik I Gastroenterologie, Pneumologie und Endokrinologie, Friedrich-Alexander-Universität, Erlangen
| | - Peter Schirmacher
- Allgemeine Pathologie und pathologische Anatomie, Universitätsklinikum Heidelberg
| | | | - Irene Schmid
- Kinderklinik und Kinderpoliklinik im Dr. von Haunerschen Kinderspital, LMU München
| | - Kerstin Schütte
- Klinik für Innere Medizin und Gastroenterologie, Niels-Stensen-Kliniken, Marienhospital Osnabrück
| | - Andreas Schuler
- Medizinische Klinik, Gastroenterologie, Alb-Fils-Kliniken, Geislingen an der Steige
| | - Daniel Seehofer
- Klinik und Poliklinik für Viszeral-, Transplantations-, Thorax- und Gefäßchirurgie, Universitätsklinikum Leipzig
| | - Marianne Sinn
- II. Medizinische Klinik und Poliklinik (Onkologie, Hämatologie, Knochenmarktransplantation mit Abteilung für Pneumologie), Universitätsklinikum Hamburg-Eppendorf
| | - Andreas Stengel
- Innere Medizin VI - Psychosomatische Medizin und Psychotherapie, Eberhard-Karls Universität, Tübingen
| | | | | | | | - Anne Taubert
- Klinische Sozialarbeit, Universitätsklinikum Heidelberg
| | - Jörg Trojan
- Medizinische Klinik 1: Gastroenterologie und Hepatologie, Pneumologie und Allergologie, Endokrinologie und Diabetologie sowie Ernährungsmedizin, Goethe-Universität, Frankfurt
| | | | - Martin Utzig
- Abteilung Zertifizierung, Deutsche Krebsgesellschaft e.V., Berlin
| | - Arndt Vogel
- Institute of Medical Science, University of Toronto
| | - Thomas Vogl
- Institut für Diagnostische und Interventionelle Radiologie, Goethe-Universität, Frankfurt
| | - Frank Wacker
- Institut für Diagnostische und Interventionelle Radiologie, Medizinische Hochschule Hannover
| | | | - Heiner Wedemeyer
- Klinik für Gastroenterologie, Hepatologie, Infektiologie und Endokrinologie, Medizinische Hochschule Hannover
| | - Henning Wege
- Klinik für Allgemeine Innere Medizin, Onkologie/Hämatologie, Gastroenterologie und Infektiologie, Klinikum Esslingen
| | - Gregor Wenzel
- Office des Leitlinienprogrammes Onkologie, Deutsche Krebsgesellschaft e.V., Berlin
| | - Dane Wildner
- Innere Medizin, Krankenhäuser Nürnberger Land GmbH, Standort Lauf
| | - Marcus-Alexander Wörns
- Klinik für Gastroenterologie, Hämatologie und internistische Onkologie und Endokrinologie, Klinikum Dortmund
| | - Peter Galle
- 1. Medizinische Klinik und Poliklinik, Gastroenterologie, Hepatologie, Nephrologie, Rheumatologie, Infektiologie, Johannes Gutenberg-Universität, Mainz
| | - Nisar Malek
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
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15
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Zhai Y, Wang L, Zhao H, Wu F, Xin L, Ye F, Sun W, Song Y, Niu L, Zeng H, Wang J, Tang Y, Song Y, Liu Y, Fang H, Lu N, Jing H, Qi S, Zhang W, Wang S, Li YX, Wu J, Chen B. Phase II study with sorafenib plus radiotherapy for advanced HCC with portal and/or hepatic vein tumor thrombosis. JHEP Rep 2025; 7:101287. [PMID: 39980754 PMCID: PMC11840495 DOI: 10.1016/j.jhepr.2024.101287] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2024] [Revised: 11/01/2024] [Accepted: 11/20/2024] [Indexed: 02/22/2025] Open
Abstract
BACKGROUND & AIMS Portal and hepatic vein tumor thrombosis is associated with inferior outcomes in patients with hepatocellular carcinoma (HCC), and systemic treatment alone is often insufficient. This phase II trial evaluated the efficacy and safety of combining sorafenib with radiotherapy in advanced HCC with thrombosis. METHODS Registered at ClinicalTrials.gov (NCT03535259), this phase II single-arm prospective trial targeted patients with HCC with portal or hepatic vein tumor thrombosis, liver minus gross tumor volume >700 ml, and Eastern Cooperative Oncology Group Performance Status scores of 0 or 1. Participants underwent 40-66 Gy radiotherapy for the hepatic primary tumor and vein tumor thrombosis, with concurrent oral sorafenib (400 mg twice daily) until disease progression or unacceptable adverse events. The primary endpoint was median overall survival (mOS) and the secondary endpoints included overall response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and Modified Response Evaluation Criteria in Solid Tumors (mRECIST), median progression-free survival (mPFS), time to tumor progression (TTP), tumor thrombosis control, and grade ≥3 adverse events. RESULTS Between May 2018 and January 2020, 86 patients were enrolled with a median radiotherapy dose of 54 Gy (40-65 Gy). At a median follow-up of 17.2 months, mOS, mPFS, and TTP stood at 16.5, 6.1, and 6.8 months, respectively. ORR reached 47.7% and 52.3% per RECIST and mRECIST, respectively. For the tumor thrombosis, 2-year control rates per mRECIST were 93.1%. No grade 5 adverse events were noted, whereas thrombocytopenia (22.1%) and leukopenia (14.0%) were the main grade 3 adverse events. CONCLUSIONS Concurrent sorafenib and radiotherapy is an effective and well-tolerated treatment for patients with HCC with portal or hepatic vein tumor thrombosis. IMPACT AND IMPLICATIONS Treatment options for patients with hepatocellular carcinoma (HCC) and vascular tumor thrombus are limited. The efficacy and safety of concurrent sorafenib and radiation for HCC with portal or hepatic vein tumor thrombosis has not been elucidated. This phase II trial shows that concurrent sorafenib and radiotherapy is effective and well-tolerated in the treatment of advanced HCC with portal vein or hepatic vein tumor thrombosis. CLINICAL TRIALS REGISTRATION This study is registered at ClinicalTrials.gov (NCT03535259).
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Affiliation(s)
- Yirui Zhai
- 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
| | - 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
| | - Hong Zhao
- 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
| | - Lingxia Xin
- 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
| | - Feng Ye
- Department of Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Wei Sun
- 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
| | - Yan Song
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Lijuan Niu
- Department of Ultrasound, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Huiying Zeng
- 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
| | - Jingbo Wang
- 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
| | - Yuan Tang
- 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
| | - Yongwen Song
- 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
| | - Yueping Liu
- 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
| | - Hui Fang
- 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
| | - Ningning Lu
- 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
| | - Hao Jing
- 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
| | - Shunan Qi
- 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
| | - Wenwen Zhang
- 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
| | - Shulian Wang
- 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
| | - Ye-Xiong 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
| | - 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
| | - 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
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Arendt N, Kopsida M, Khaled J, Sjöblom M, Heindryckx F. Gastrointestinal side effects in hepatocellular carcinoma patients receiving transarterial chemoembolization: a meta-analysis of 81 studies and 9495 patients. Ther Adv Med Oncol 2025; 17:17588359251316663. [PMID: 39926261 PMCID: PMC11806495 DOI: 10.1177/17588359251316663] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2024] [Accepted: 01/14/2025] [Indexed: 02/11/2025] Open
Abstract
Background Transarterial chemoembolization (TACE) is a widely used treatment for hepatocellular carcinoma (HCC), combining targeted chemotherapy and embolization. While effective, TACE can be associated with significant gastrointestinal (GI) side effects, impacting a patient's quality of life. Objectives Quantify the prevalence of key GI complications (diarrhea, nausea, GI toxicity, abdominal pain) following TACE. Design Systematic review was performed following Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines, focusing on studies that reported side effects of TACE. Studies not involving cTACE or drug-eluting bead TACE (DEB-TACE), non-HCC studies, meta-analyses or systematic reviews, and inaccessible publications were excluded. Data sources and methods A PubMed search for clinical and randomized trials was conducted. Extracted data included study identifiers, demographics, TACE details, and GI side effect prevalences. The Mixed Methods Appraisal Tool assessed study quality and bias. Results The analysis included data from 81 studies with 121 individual study arms and 9495 patients. Diarrhea was reported in 38 studies, with a mean prevalence of 23.46% (2.5; 95% confidence interval (CI): 18.39-28.544) and a weighted prevalence of 23.5%. Nausea was most frequently reported, mentioned in 67 studies, with a mean prevalence of 34.66% (2.4; 95% CI: 29.89-39.44) and a weighted prevalence of 32.5%. Abdominal pain was reported in 59 studies, with the highest mean prevalence of 48.07% (2.9; 95% CI: 42.20-53.93) and a weighted prevalence of 46.1%. GI toxicity was reported in 32 studies, with a mean prevalence of 8.85% (1.4; 95% CI: 5.99-11.70) and a weighted prevalence of 9.9%. DEB-TACE generally led to slightly higher rates of nausea, diarrhea, abdominal pain, and GI toxicity compared to conventional TACE. The type of chemotherapy agent influenced prevalence of GI-side effects, with high prevalences observed for agents such as zinostatin and cisplatin. Conclusion This meta-analysis synthesizes current evidence on managing GI side effects in TACE. Standardizing reporting and developing effective management strategies are crucial to improving patient outcomes.
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Affiliation(s)
- Nathalie Arendt
- Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden
| | - Maria Kopsida
- Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden
| | - Jaafar Khaled
- Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden
| | - Markus Sjöblom
- Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden
| | - Femke Heindryckx
- Department of Medical Cell Biology, Uppsala University, Husargatan 3, Uppsala 75431, Sweden
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17
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Kuehnle RA, Tchelebi LT, Ludmir EB, Escorcia FE, Shrestha S, Sanford N, Court CM, Ryckman JM, Arora SP, Lehrer EJ, Gelfond J, Jethwa KR, Newman NB. Meta-analysis of randomized controlled trials of external-beam radiation versus transarterial chemoembolization for hepatocellular carcinoma. Cancer 2025; 131:e35720. [PMID: 39887736 DOI: 10.1002/cncr.35720] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2024] [Revised: 12/05/2024] [Accepted: 12/06/2024] [Indexed: 02/01/2025]
Abstract
BACKGROUND External-beam radiation (EBRT) is a noninvasive therapeutic alternative to transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC). The objective of this study was to conduct a systematic review and meta-analysis of prospective randomized clinical trials to assess the clinical efficacy of EBRT versus TACE for HCC as either a definitive monotherapy or as a bridge to transplantation/surgery. METHODS A systematic review and meta-analysis were performed to include prospective randomized trials comparing EBRT versus TACE. Data was analyzed with random and fixed-effects models. The inconsistency index (I2) was chosen to assess heterogeneity. Three publications were included with a total of 142 patients. Outcomes included local control (LC), overall survival (OS), progression-free survival (PFS), and occurrences of grade ≥3 toxicity. Comparisons are reported as hazard ratios (HRs) or risk ratios (RRs) with 95% confidence intervals (CIs). RESULTS There were three randomized trials that met inclusion criteria. The EBRT was delivered in three to 15 fractions with a total dose between 30 and 75 gray(Gy). EBRT was associated with significantly improved LC (HR, 0.16; 95% CI, 0.08-0.34; I2 = 0%) and PFS (HR, 0.37; 95% CI, 0.23-0.60; I2, 0%) compared with TACE. There was no significant difference between EBRT and TACE in OS (RR, 0.79; 95% CI, 0.51-1.22; I2 = 0%) or grade ≥3 toxicity (RR, 0.86; 95% CI, 0.31-2.37; I2 = 57%). None of the analyses had statistically significant heterogeneity. CONCLUSIONS Compared with TACE, EBRT yields superior LC and PFS without providing a survival benefit in early and intermediate stage HCC. Additional larger prospective randomized controlled trials should be conducted to further investigate differences in clinical outcomes amongst patients with more advanced disease.
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Affiliation(s)
- Ryan A Kuehnle
- Long School of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA
| | | | - Ethan B Ludmir
- Division of Radiation Oncology, Department of Gastrointestinal Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Freddy E Escorcia
- Radiation Oncology Branch, Molecular Imaging Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA
| | - Sabi Shrestha
- Department of Radiation Oncology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA
| | - Nina Sanford
- Department of Radiation Oncology, Southwestern Medical Center, University of Texas, Dallas, Texas, USA
| | - Colin M Court
- Division of Surgical Oncology, Department of Surgery, Mays Cancer Center, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA
| | - Jeff M Ryckman
- Department of Radiation Oncology, West Virginia University School of Medicine, Camden Clark Medical Center, Parkersburg, West Virginia, USA
| | - Sukeshi P Arora
- Division of Hematology/Oncology, Department of Medicine, Mays Cancer Center, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA
| | - Eric J Lehrer
- Department of Radiation Oncology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
| | - Jonathan Gelfond
- Department of Population Health Sciences, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA
| | - Krishan R Jethwa
- Department of Radiation Oncology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
| | - Neil B Newman
- Department of Radiation Oncology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA
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18
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Liu Q, Zhang R, Shen W. Advancements in locoregional therapy for advanced hepatocellular carcinoma: Emerging perspectives on combined treatment strategies. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2025; 51:109502. [PMID: 39615292 DOI: 10.1016/j.ejso.2024.109502] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2024] [Revised: 11/17/2024] [Accepted: 11/23/2024] [Indexed: 01/03/2025]
Abstract
Hepatocellular carcinoma (HCC) persists as a leading cause of cancer-related mortality, often diagnosed at advanced stages with limited treatment options. Locoregional therapies (LRTs) are crucial in HCC management, playing significant roles in neoadjuvant and palliative treatments, among others. However, the unique disease background of HCC necessitates multidisciplinary and integrated treatment strategies. The therapeutic landscape for advanced HCC has been significantly broadened by the advent of combined therapies, presenting multiple approaches aimed at improving long-term survival, which remains a critical challenge. This review offers a comprehensive overview of major LRTs for HCC, highlighting recent technological advancements and exploring the challenges and limitations in their application, and presents the latest developments in combination therapies, including combinations between different LRTs and their integration with systemic treatments. Additionally, we outline future directions for the development of integrated treatment modalities for advanced HCC.
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Affiliation(s)
- Qi Liu
- Department of Oncology, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150001, People's Republic of China; The Second Clinical Medical College of Harbin Medical University, Harbin, 150081, People's Republic of China
| | - Renjie Zhang
- Department of Oncology, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150001, People's Republic of China; The Second Clinical Medical College of Harbin Medical University, Harbin, 150081, People's Republic of China
| | - Weixi Shen
- Department of Oncology, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150001, People's Republic of China.
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19
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Chen Y, Hu Y, Shen J, Du S, Yan J, Zhou L, Wang Z, Lu H, Xiao L, Yang P, Zhu W, Wang J, Yang G, Luo J, Liu R, Zeng Z. External Beam Radiation therapy After Transarterial Chemoembolization Versus Transarterial Chemoembolization Alone for Treatment of Inoperable Hepatocellular Carcinoma: A Randomized Phase 3 Trial. Int J Radiat Oncol Biol Phys 2025; 121:414-422. [PMID: 39299550 DOI: 10.1016/j.ijrobp.2024.09.021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2024] [Revised: 09/05/2024] [Accepted: 09/09/2024] [Indexed: 09/22/2024]
Abstract
PURPOSE To compare the outcomes of transarterial chemoembolization (TACE) alone with those of TACE combined with external beam radiation therapy (EBRT) in patients with hepatocellular carcinoma (HCC) in a multicenter randomized study. METHODS AND MATERIALS From 2017 to 2022, 74 HCC patients with tumors confined to the liver without vascular invasion were treated with either TACE only (TACE group, 39 patients) or TACE combined with EBRT (TACE + EBRT group, 35 patients). The primary outcome measured was overall survival (OS). Secondary outcomes included progression-free survival (PFS), local tumor control, and the assessment of treatment-related toxicity. RESULTS Due to slow accrual, the trial was closed prematurely after enrolling 74 patients. All patients received 2 cycles of TACE before randomization. The TACE and TACE + EBRT groups showed comparable patient and tumor characteristics. The TACE group underwent a median of 3 TACE cycles, and the TACE + EBRT group received 2 cycles of TACE, and a median of 5500 cGy in 15 fractions. For the TACE group, the median local control (LC) duration was 13.1 months, whereas for the TACE + EBRT group, the median LC was not achieved (P < .001). The PFS was recorded at 11.6 months in the TACE group compared with 15.4 months in the TACE + EBRT group (P = .072). The median OS reached 36.8 months for the TACE group and extended to 47.1 months for the TACE + EBRT group (P = .654). The incidence of toxicity was comparable between both groups. CONCLUSIONS Although the number of patients enrolled in this clinical trial did not meet expectations. TACE combined with EBRT was shown to be more effective than TACE alone in improving LC without increasing toxicity, whereas PFS and OS were slightly improved. TACE + EBRT can be used as a standard treatment option for patients with inoperable but confined intrahepatic HCC.
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Affiliation(s)
- YiXing Chen
- Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yong Hu
- Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Jie Shen
- Comprehensive Cancer Centre, Department of Oncology, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - ShiSuo Du
- Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Jing Yan
- Comprehensive Cancer Centre, Department of Oncology, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - LeYuan Zhou
- Department of Radiation Oncology, the Fourth Affiliated Hospital of Soochow University, Suzhou, China
| | - Zhe Wang
- Departement of Medical Oncology, Affiliated Zhongshan Hospital of Dalian University, Dalian, China
| | - HaiJie Lu
- Department of Radiation Oncology, Affiliated Zhongshan Hospital of Xiamen University, Xiamen, China
| | - Lei Xiao
- Cancer Center, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China
| | - Ping Yang
- Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - WenChao Zhu
- Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Jun Wang
- Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - GuoWei Yang
- Department of Interventional Radiology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - JianFeng Luo
- Department of Biostatistics, School of Public Health, Fudan University, Shanghai, China
| | - Rong Liu
- Department of Interventional Radiology, Zhongshan Hospital, Fudan University, Shanghai, China.
| | - ZhaoChong Zeng
- Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai, China.
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20
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Dawson LA, Winter KA, Knox JJ, Zhu AX, Krishnan S, Guha C, Kachnic LA, Gillin MT, Hong TS, Craig TD, Williams TM, Hosni A, Chen E, Noonan AM, Koay EJ, Sinha R, Lock MI, Ohri N, Dorth JA, Delouya G, Swaminath A, Moughan J, Crane CH. Stereotactic Body Radiotherapy vs Sorafenib Alone in Hepatocellular Carcinoma: The NRG Oncology/RTOG 1112 Phase 3 Randomized Clinical Trial. JAMA Oncol 2025; 11:136-144. [PMID: 39699905 PMCID: PMC11843352 DOI: 10.1001/jamaoncol.2024.5403] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2024] [Accepted: 09/12/2024] [Indexed: 12/20/2024]
Abstract
Importance Most patients with locally advanced hepatocellular carcinoma (HCC) recur within the liver following systemic therapy. Objective To determine whether stereotactic body radiation therapy (SBRT) improves outcomes in patients with locally advanced HCC compared with sorafenib alone. Design, Setting, and Participants This multicenter phase 3 randomized clinical trial randomized patients with HCC 1:1 to sorafenib or SBRT followed by sorafenib, stratified by performance status, liver function, degree of metastases, and macrovascular invasion. Eligible patients had HCC unsuitable for or refractory to standard local-regional therapies and were candidates for first-line systemic therapy. Data were collected from April 2013 to March 2021, and data were analyzed from July 2022 to August 2023. Intervention Personalized SBRT, 27.5 to 50 Gy in 5 fractions. Main Outcomes and Measures The primary end point was overall survival (OS). Secondary end points were progression-free survival (PFS), adverse events, and quality of life. Results Of 193 patients randomized, 177 were eligible. Accrual was stopped early due to a change in standard-of-care systemic therapy. Of 177 included patients, 150 (84.7%) were male, and the median (IQR) age was 66 (60-72) years. Macrovascular invasion was seen in 131 (74.0%). As of July 1, 2022, the median OS was 12.3 months (90% CI, 10.6-14.3) with sorafenib vs 15.8 months (90% CI, 11.4-19.2) following SBRT and sorafenib (hazard ratio [HR], 0.77; 90% CI, 0.59-1.01; 1-sided P = .06). Adjusting for stratification factors, OS was improved with SBRT (HR, 0.72; 95% CI, 0.52-0.99; 2-sided P = .04). Median PFS was improved from 5.5 months (95% CI, 3.4-6.3) with sorafenib to 9.2 months (95% CI, 7.5-11.9) with SBRT and sorafenib (HR, 0.55; 95% CI, 0.40-0.75; 2-sided P < .001). Treatment-related grade 3 or higher adverse events were seen in 37 of 88 (42%) and 39 of 83 (47%) of patients treated with sorafenib vs SBRT and sorafenib, respectively (P = .52). There were 2 treatment-related deaths in the sorafenib group (death not otherwise specified and liver failure) and 1 in the SBRT and sorafenib group (lung infection). At 6 months, improved quality of life was seen in 2 of 20 (10%) and 6 of 17 (35%) of patients treated with sorafenib and SBRT and sorafenib, respectively. Conclusions and Relevance In this phase 3 randomized clinical trial, among patients with locally advanced HCC, SBRT was associated with a clinically important but not statistically significant improved overall survival compared with sorafenib alone. Trial Registration ClinicalTrials.gov Identifier: NCT01730937.
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Affiliation(s)
- Laura A. Dawson
- University Health Network–Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada
| | - Kathryn A. Winter
- NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvania
- American College of Radiology, Philadelphia, Pennsylvania
| | - Jennifer J. Knox
- University Health Network–Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada
| | - Andrew X. Zhu
- Massachusetts General Hospital Cancer Center, Boston
| | | | | | - Lisa A. Kachnic
- NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center, New York, New York
| | | | | | - Timothy D. Craig
- University Health Network–Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada
| | | | - Ali Hosni
- University Health Network–Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada
| | - Eric Chen
- University Health Network–Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada
| | - Anne M. Noonan
- Ohio State University Comprehensive Cancer Center, Columbus
| | | | - Rishi Sinha
- Tom Baker Cancer Centre, Calgary, Alberta, Canada
| | | | - Nitin Ohri
- Montefiore Medical Center, Bronx, New York
| | | | - Guila Delouya
- CHUM-Centre Hospitalier de l’Universite de Montreal, Montreal, Quebec, Canada
| | - Anand Swaminath
- Juravinski Cancer Centre at Hamilton Health Sciences, Hamilton, Ontario, Canada
| | - Jennifer Moughan
- NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvania
- American College of Radiology, Philadelphia, Pennsylvania
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21
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Groß S, Bitzer M, Albert J, Blödt S, Boda-Heggemann J, Borucki K, Brunner T, Caspari R, Dombrowski F, Evert M, Follmann M, Freudenberger P, Gani C, Gebert J, Geier A, Gkika E, Götz M, Helmberger T, Hoffmann RT, Huppert P, Krug D, Fougère CL, Lang H, Langer T, Lenz P, Lüdde T, Mahnken A, Nadalin S, Nguyen HHP, Nothacker M, Ockenga J, Oldhafer K, Ott J, Paprottka P, Pereira P, Persigehl T, Plentz R, Pohl J, Recken H, Reimer P, Riemer J, Ringe K, Roeb E, Rüssel J, Schellhaas B, Schirmacher P, Schlitt HJ, Schmid I, Schütte K, Schuler A, Seehofer D, Sinn M, Stengel A, Steubesand N, Stoll C, Tannapfel A, Taubert A, Trojan J, van Thiel I, Utzig M, Vogel A, Vogl T, Wacker F, Waidmann O, Wedemeyer H, Wege H, Wenzel G, Wildner D, Wörns MA, Galle P, Malek N. [Not Available]. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2025; 63:e82-e158. [PMID: 39919781 DOI: 10.1055/a-2460-6347] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/09/2025]
Affiliation(s)
- Sabrina Groß
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| | - Michael Bitzer
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| | - Jörg Albert
- Katharinenhospital, Klinik für Allgemeine Innere Medizin, Gastroenterologie, Hepatologie, Infektiologie und Pneumologie, Stuttgart
| | - Susanne Blödt
- Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e. V. (AWMF), Berlin
| | | | - Katrin Borucki
- Otto-von-Guericke-Universität Magdeburg, Medizinische Fakultät, Institut für Klinische Chemie und Pathobiochemie
| | - Thomas Brunner
- Universitätsklinik für Strahlentherapie-Radioonkologie, Medizinische Universität Graz
| | - Reiner Caspari
- Klinik Niederrhein Erkrankungen des Stoffwechsels der Verdauungsorgane und Tumorerkrankungen, Bad Neuenahr-Ahrweiler
| | | | | | - Markus Follmann
- Office des Leitlinienprogrammes Onkologie, Deutsche Krebsgesellschaft e.V., Berlin
| | | | - Cihan Gani
- Klinik für Radioonkologie, Universitätsklinikum Tübingen
| | - Jamila Gebert
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| | - Andreas Geier
- Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg
| | - Eleni Gkika
- Klinik für Strahlenheilkunde, Department für Radiologische Diagnostik und Therapie, Universitätsklinikum Freiburg
| | - Martin Götz
- Medizinische Klinik IV - Gastroenterologie/Onkologie, Klinikverbund Südwest, Böblingen
| | - Thomas Helmberger
- Institut für Radiologie, Neuroradiologie und minimal invasive Therapie, München Klinik Bogenhausen
| | - Ralf-Thorsten Hoffmann
- Institut und Poliklinik für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Dresden
| | - Peter Huppert
- Radiologisches Zentrum, Max Grundig Klinik, Bühlerhöhe
| | - David Krug
- Strahlentherapie Campus Kiel, Universitätsklinikum Schleswig-Holstein
| | - Christian La Fougère
- Nuklearmedizin und Klinische Molekulare Bildgebung, Eberhard-Karls Universität, Tübingen
| | - Hauke Lang
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Johannes Gutenberg-Universität, Mainz
| | - Thomas Langer
- Office des Leitlinienprogrammes Onkologie, Deutsche Krebsgesellschaft e.V., Berlin
| | - Philipp Lenz
- Zentrale Einrichtung Palliativmedizin, Universitätsklinikum Münster
| | - Tom Lüdde
- Medizinische Klinik für Gastroenterologie, Hepatologie und Infektiologie, Universitätsklinikum Düsseldorf
| | - Andreas Mahnken
- Klinik für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Marburg
| | - Silvio Nadalin
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Eberhard-Karls Universität, Tübingen
| | | | - Monika Nothacker
- Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e. V. (AWMF), Berlin
| | - Johann Ockenga
- Medizinische Klinik II, Gesundheit Nord, Klinikverbund Bremen
| | - Karl Oldhafer
- Klinik für Leber-, Gallenwegs- und Pankreaschirurgie, Asklepios Klinik Barmbek
| | - Julia Ott
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| | - Philipp Paprottka
- Sektion für Interventionelle Radiologie, Klinikum rechts der Isar, Technische Universität München
| | - Philippe Pereira
- Zentrum für Radiologie, Minimal-invasive Therapien und Nuklearmedizin, SLK-Klinken Heilbronn
| | - Thorsten Persigehl
- Institut für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Köln
| | - Ruben Plentz
- Digestive Diseases and Nutrition, Gastroenterology, University of Kentucky
| | - Jürgen Pohl
- Abteilung für Gastroenterologie, Asklepios Klinik Altona
| | | | - Peter Reimer
- Institut für Diagnostische und Interventionelle Radiologie, Städtisches Klinikum Karlsruhe
| | | | - Kristina Ringe
- Institut für Diagnostische und Interventionelle Radiologie, Medizinische Hochschule Hannover
| | - Elke Roeb
- Medizinische Klinik II Pneumologie, Nephrologie und Gastroenterologie, Universitätsklinikum Gießen
| | - Jörn Rüssel
- Medizinische Klinik IV Hämatologie und Onkologie, Universitätsklinikum Halle (Saale)
| | - Barbara Schellhaas
- Medizinische Klinik I Gastroenterologie, Pneumologie und Endokrinologie, Friedrich-Alexander-Universität, Erlangen
| | - Peter Schirmacher
- Allgemeine Pathologie und pathologische Anatomie, Universitätsklinikum Heidelberg
| | | | - Irene Schmid
- Kinderklinik und Kinderpoliklinik im Dr. von Haunerschen Kinderspital, LMU München
| | - Kerstin Schütte
- Klinik für Innere Medizin und Gastroenterologie, Niels-Stensen-Kliniken, Marienhospital Osnabrück
| | - Andreas Schuler
- Medizinische Klinik, Gastroenterologie, Alb-Fils-Kliniken, Geislingen an der Steige
| | - Daniel Seehofer
- Klinik und Poliklinik für Viszeral-, Transplantations-, Thorax- und Gefäßchirurgie, Universitätsklinikum Leipzig
| | - Marianne Sinn
- II. Medizinische Klinik und Poliklinik (Onkologie, Hämatologie, Knochenmarktransplantation mit Abteilung für Pneumologie), Universitätsklinikum Hamburg-Eppendorf
| | - Andreas Stengel
- Innere Medizin VI - Psychosomatische Medizin und Psychotherapie, Eberhard-Karls Universität, Tübingen
| | | | | | | | - Anne Taubert
- Klinische Sozialarbeit, Universitätsklinikum Heidelberg
| | - Jörg Trojan
- Medizinische Klinik 1: Gastroenterologie und Hepatologie, Pneumologie und Allergologie, Endokrinologie und Diabetologie sowie Ernährungsmedizin, Goethe-Universität, Frankfurt
| | | | - Martin Utzig
- Abteilung Zertifizierung, Deutsche Krebsgesellschaft e.V., Berlin
| | - Arndt Vogel
- Institute of Medical Science, University of Toronto
| | - Thomas Vogl
- Institut für Diagnostische und Interventionelle Radiologie, Goethe-Universität, Frankfurt
| | - Frank Wacker
- Institut für Diagnostische und Interventionelle Radiologie, Medizinische Hochschule Hannover
| | | | - Heiner Wedemeyer
- Klinik für Gastroenterologie, Hepatologie, Infektiologie und Endokrinologie, Medizinische Hochschule Hannover
| | - Henning Wege
- Klinik für Allgemeine Innere Medizin, Onkologie/Hämatologie, Gastroenterologie und Infektiologie, Klinikum Esslingen
| | - Gregor Wenzel
- Office des Leitlinienprogrammes Onkologie, Deutsche Krebsgesellschaft e.V., Berlin
| | - Dane Wildner
- Innere Medizin, Krankenhäuser Nürnberger Land GmbH, Standort Lauf
| | - Marcus-Alexander Wörns
- Klinik für Gastroenterologie, Hämatologie und internistische Onkologie und Endokrinologie, Klinikum Dortmund
| | - Peter Galle
- 1. Medizinische Klinik und Poliklinik, Gastroenterologie, Hepatologie, Nephrologie, Rheumatologie, Infektiologie, Johannes Gutenberg-Universität, Mainz
| | - Nisar Malek
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
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22
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Vutien P, Kim NJ, Nguyen MH. The Diagnosis and Staging of Hepatocellular Carcinoma: A Review of Current Practices. Clin Liver Dis 2025; 29:33-48. [PMID: 39608956 DOI: 10.1016/j.cld.2024.08.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2024]
Abstract
Promoting the early detection and diagnosis of hepatocellular carcinoma (HCC) is a critical strategy to improve patient outcomes as this can lead to greater access to curative treatments. This review highlights the diagnostic tests for HCC, including the use of the Liver Imaging Reporting and Data System systems and histopathology. Staging is essential for informing prognosis and guiding treatment decisions; this review also covers a widely used and well-validated staging system called the Barcelona-Clinic Liver Cancer (BCLC) algorithm. The BCLC incorporates tumor status, liver function, and patient performance to stage patients with newly diagnosed HCC.
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Affiliation(s)
- Philip Vutien
- Division of Gastroenterology and Hepatology, University of Washington Medical Center, 1536 North 115th Street, Suite 105, Box 358811, Seattle, WA 98133, USA.
| | - Nicole J Kim
- Division of Gastroenterology and Hepatology, University of Washington Medical Center, 1536 North 115th Street, Suite 105, Box 358811, Seattle, WA 98133, USA
| | - Mindie H Nguyen
- Division of Gastroenterology and Hepatology, University of Washington Medical Center, 325 9th Avenue, Box 359773, Seattle, WA 98104, USA; Stanford University Medical Center, 780 Welch Road, Suite CJ250K, Palo Alto, CA 94304, USA
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23
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Sangro B, Argemi J, Ronot M, Paradis V, Meyer T, Mazzaferro V, Jepsen P, Golfieri R, Galle P, Dawson L, Reig M. EASL Clinical Practice Guidelines on the management of hepatocellular carcinoma. J Hepatol 2025; 82:315-374. [PMID: 39690085 DOI: 10.1016/j.jhep.2024.08.028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2024] [Accepted: 08/29/2024] [Indexed: 12/19/2024]
Abstract
Liver cancer is the third leading cause of cancer-related deaths worldwide, with hepatocellular carcinoma (HCC) accounting for approximately 90% of primary liver cancers. Advances in diagnostic and therapeutic tools, along with improved understanding of their application, are transforming patient treatment. Integrating these innovations into clinical practice presents challenges and necessitates guidance. These clinical practice guidelines offer updated advice for managing patients with HCC and provide a comprehensive review of pertinent data. Key updates from the 2018 EASL guidelines include personalised surveillance based on individual risk assessment and the use of new tools, standardisation of liver imaging procedures and diagnostic criteria, use of minimally invasive surgery in complex cases together with updates on the integrated role of liver transplantation, transitions between surgical, locoregional, and systemic therapies, the role of radiation therapies, and the use of combination immunotherapies at various stages of disease. Above all, there is an absolute need for a multiparametric assessment of individual risks and benefits, considering the patient's perspective, by a multidisciplinary team encompassing various specialties.
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24
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Hwang SY, Danpanichkul P, Agopian V, Mehta N, Parikh ND, Abou-Alfa GK, Singal AG, Yang JD. Hepatocellular carcinoma: updates on epidemiology, surveillance, diagnosis and treatment. Clin Mol Hepatol 2025; 31:S228-S254. [PMID: 39722614 PMCID: PMC11925437 DOI: 10.3350/cmh.2024.0824] [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: 09/22/2024] [Revised: 11/08/2024] [Accepted: 12/20/2024] [Indexed: 12/28/2024] Open
Abstract
Hepatocellular carcinoma (HCC) is a major global burden, ranking as the third leading cause of cancer-related mortality. HCC due to chronic hepatitis B virus (HBV) or C virus (HCV) infection has decreased due to universal vaccination for HBV and effective antiviral therapy for both HBV and HCV, but HCC related to metabolic dysfunction-associated steatotic liver disease and alcohol-associated liver disease is increasing. Biannual liver ultrasonography and serum α-fetoprotein are the primary surveillance tools for early HCC detection among high-risk patients (e.g., cirrhosis, chronic HBV). Alternative surveillance tools such as blood-based biomarker panels and abbreviated magnetic resonance imaging (MRI) are being investigated. Multiphasic computed tomography or MRI is the standard for HCC diagnosis, but histological confirmation should be considered, especially when inconclusive findings are seen on cross-sectional imaging. Staging and treatment decisions are complex and should be made in multidisciplinary settings, incorporating multiple factors including tumor burden, degree of liver dysfunction, patient performance status, available expertise, and patient preferences. Early-stage HCC is best treated with curative options such as resection, ablation, or transplantation. For intermediate-stage disease, locoregional therapies are primarily recommended although systemic therapies may be preferred for patients with large intrahepatic tumor burden. In advanced-stage disease, immune checkpoint inhibitor-based therapy is the preferred treatment regimen. In this review article, we discuss the recent global epidemiology, risk factors, and HCC care continuum encompassing surveillance, diagnosis, staging, and treatments.
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Affiliation(s)
- Soo Young Hwang
- Department of Internal Medicine, University of Maryland Medical Center, Midtown Campus, Baltimore, Maryland, USA
| | - Pojsakorn Danpanichkul
- Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, Texas, USA
| | - Vatche Agopian
- Dumont-UCLA Transplant and Liver Cancer Centers, Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, California, USA
| | - Neil Mehta
- Division of Gastroenterology, Department of Medicine, University of California, San Francisco, California, USA
| | - Neehar D. Parikh
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan, USA
| | - Ghassan K. Abou-Alfa
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, USA
- Department of Medicine, Weill Medical College at Cornell University, New York, USA
- Trinity College Dublin, Dublin, Ireland
| | - Amit G. Singal
- Division of Digestive and Liver Diseases, UT Southwestern Medical Center, Dallas, Texas, USA
| | - Ju Dong Yang
- Karsh Division of Gastroenterology and Hepatology, Comprehensive Transplant Center, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA
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25
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Li X, Cao K, Fu Z, Chen X, Zhong J, Liu L, Ding N, Zhang X, Qu Z, Zhu L, Zhai J. Clinical Outcomes of Hepatic Arterial Infusion Chemotherapy Plus Lenvatinib and Tislelizumab for Treating Hepatocellular Carcinoma and Type IV Portal Vein Tumor Thrombus. J Hepatocell Carcinoma 2025; 12:169-182. [PMID: 39881676 PMCID: PMC11776929 DOI: 10.2147/jhc.s488734] [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: 09/24/2024] [Accepted: 01/14/2025] [Indexed: 01/31/2025] Open
Abstract
Purpose To assess the activity and toxicity of hepatic arterial infusion chemotherapy (HAIC)+tislelizumab+lenvatinib (HAIC+tisle+len) in hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) type IV (Vp4 hCC) in a real-world context. Methods Fifty-five patients, with Vp4 hCC receiving HAIC+tisle+len therapy from April 2021 to December 2022, were analyzed retrospectively. Data on patient characteristics, adverse events (AEs), treatment, and survival were collected. Outcomes were disease control rate (DCR), overall response rate (ORR), overall survival (OS), progression-free survival (PFS), and treatment-related AEs (TRAEs). Results As of December 20, 2023, the median follow-up was 17.5 months (95% confidence interval [CI]: 14.7-22.5). The ORR was 52.7% (3 complete response [CR], 26 partial response [PR]) as per RECIST v1.1 and 65.5% (12 CR, 24 PR) as per mRECIST. The DCR was 94.5% using both RECIST v1.1 and mRECIST. The median PFS and the median OS were 8.0 months (95% CI: 6.2-12.3) and 16.7 months (95% CI: 12.0-not reached), respectively. Additionally, PFS was independently predicted only by the best tumor response. In patients with the best tumor response (PR or CR), the median PFS was 11.7 months (95% CI: 8.02-not reached) by mRECIST and 15.4 months (95% CI: 7.39-not reached) by RECIST v1.1. Hypertension (14.5%), decreased albumin levels (10.9%) and anorexia (9.1%) were the most frequently observed grade 3-4 TRAEs. Conclusion HAIC+tisle+len regimen demonstrated a promising efficacy and favorable safety for patients with HCC and Vp4, providing valuable real-world evidence to complement the trial data for Vp4 hCC.
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Affiliation(s)
- Xiaowei Li
- Department II of Interventional Radiology, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, 200438, People’s Republic of China
| | - Kunkun Cao
- Department II of Interventional Radiology, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, 200438, People’s Republic of China
| | - Zhigang Fu
- Department II of Interventional Radiology, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, 200438, People’s Republic of China
| | - Xiaoxia Chen
- Department II of Interventional Radiology, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, 200438, People’s Republic of China
| | - Jiaming Zhong
- Department II of Interventional Radiology, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, 200438, People’s Republic of China
| | - Li Liu
- Department II of Interventional Radiology, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, 200438, People’s Republic of China
| | - Ning Ding
- Department II of Interventional Radiology, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, 200438, People’s Republic of China
| | - Xiaoli Zhang
- Department II of Interventional Radiology, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, 200438, People’s Republic of China
| | - Zengqiang Qu
- Department II of Interventional Radiology, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, 200438, People’s Republic of China
| | - Lijun Zhu
- Department II of Interventional Radiology, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, 200438, People’s Republic of China
| | - Jian Zhai
- Department II of Interventional Radiology, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, 200438, People’s Republic of China
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26
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Tang H, Zhang W, Cao J, Cao Y, Bi X, Zhao H, Zhang Z, Liu Z, Wan T, Lang R, Sun W, Du S, Yang Y, Lu Y, Zeng D, Wu J, Duan B, Lin D, Li F, Meng Q, Zhou J, Xing B, Tian X, Zhu J, Gao J, Hao C, Wang Z, Duan F, Wang Z, Wang M, Liang B, Chen Y, Xu Y, Li K, Li C, Hu M, Wang Z, Cai S, Ji W, Xia N, Zheng W, Wang H, Li G, Zhu Z, Huang Z, Zhang W, Tao K, Liang J, Zhang K, Dai C, Li J, Qiu Q, Guo Y, Wu L, Ding W, Zhu Z, Gu W, Cao J, Wang Z, Tian L, Ding H, Li G, Zeng Y, Wang K, Yang N, Jin H, Chen Y, Yang Y, Xiu D, Yan M, Wang X, Han Q, Jiao S, Tan G, Wang J, Liu L, Song J, Liao J, Zhao H, Li P, Song T, Wang Z, Yuan J, Hu B, Yuan Y, Zhang M, Sun S, Zhang J, Wang W, Wen T, Yang J, Du X, Peng T, Xia F, Liu Z, Niu W, Liang P, Xu J, Zhao X, Zhu M, et alTang H, Zhang W, Cao J, Cao Y, Bi X, Zhao H, Zhang Z, Liu Z, Wan T, Lang R, Sun W, Du S, Yang Y, Lu Y, Zeng D, Wu J, Duan B, Lin D, Li F, Meng Q, Zhou J, Xing B, Tian X, Zhu J, Gao J, Hao C, Wang Z, Duan F, Wang Z, Wang M, Liang B, Chen Y, Xu Y, Li K, Li C, Hu M, Wang Z, Cai S, Ji W, Xia N, Zheng W, Wang H, Li G, Zhu Z, Huang Z, Zhang W, Tao K, Liang J, Zhang K, Dai C, Li J, Qiu Q, Guo Y, Wu L, Ding W, Zhu Z, Gu W, Cao J, Wang Z, Tian L, Ding H, Li G, Zeng Y, Wang K, Yang N, Jin H, Chen Y, Yang Y, Xiu D, Yan M, Wang X, Han Q, Jiao S, Tan G, Wang J, Liu L, Song J, Liao J, Zhao H, Li P, Song T, Wang Z, Yuan J, Hu B, Yuan Y, Zhang M, Sun S, Zhang J, Wang W, Wen T, Yang J, Du X, Peng T, Xia F, Liu Z, Niu W, Liang P, Xu J, Zhao X, Zhu M, Wang H, Kuang M, Shen S, Cui X, Zhou J, Liu R, Sun H, Fan J, Chen X, Zhou J, Cai J, Lu S. Chinese expert consensus on sequential surgery following conversion therapy based on combination of immune checkpoint inhibitors and antiangiogenic targeted drugs for advanced hepatocellular carcinoma (2024 edition). Biosci Trends 2025; 18:505-524. [PMID: 39721704 DOI: 10.5582/bst.2024.01394] [Show More Authors] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2024]
Abstract
Up to half of hepatocellular carcinoma (HCC) cases are diagnosed at an advanced stage, for which effective treatment options are lacking, resulting in a poor prognosis. Over the past few years, the combination of immune checkpoint inhibitors and anti-angiogenic targeted therapy has proven highly efficacious in treating advanced HCC, significantly extending patients' survival and providing a potential for sequential curative surgery. After sequential curative hepatectomy or liver transplantation following conversion therapy, patients can receive long-term survival benefits. In order to improve the long-term survival rate of the overall population with liver cancer and achieve the goal of a 15% increase in the overall 5-year survival rate outlined in the Healthy China 2030 blueprint, the Professional Committee for Prevention and Control of Hepatobiliary and Pancreatic Diseases of Chinese Preventive Medicine Association, Chinese Society of Liver Cancer, and the Liver Study Group of Surgery Committee of Beijing Medical Association organized in-depth discussions among relevant domestic experts in the field. These discussions focused on the latest progress since the release of the Chinese expert consensus on conversion therapy of immune checkpoint inhibitors combined antiangiogenic targeted drugs for advanced hepatocellular carcinoma (2021 Edition) and resulted in a new consensus on the modifications and supplements to related key points. This consensus aims to further guide clinical practice, standardize medical care, and promote the development of the discipline.
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Affiliation(s)
- Haowen Tang
- Faculty of Hepato-Pancreato-Biliary Surgery, the First Medical Center of the Chinese PLA General Hospital, Institute of Hepatobiliary Surgery of the Chinese PLA, Beijing, China
| | - Wenwen Zhang
- Faculty of Hepato-Pancreato-Biliary Surgery, the First Medical Center of the Chinese PLA General Hospital, Institute of Hepatobiliary Surgery of the Chinese PLA, Beijing, China
| | - Junning Cao
- Organ Transplantation Center, the Affiliated Hospital of Qingdao University, Shandong, China
| | - Yinbiao Cao
- Faculty of Hepato-Pancreato-Biliary Surgery, the First Medical Center of the Chinese PLA General Hospital, Institute of Hepatobiliary Surgery of the Chinese PLA, Beijing, China
| | - Xinyu Bi
- 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
| | - Haitao Zhao
- Department of Liver Surgery, Peking Union Medical College (PUMC) Hospital, PUMC & Chinese Academy of Medical Sciences, Beijing, China
| | - Ze Zhang
- Faculty of Hepato-Pancreato-Biliary Surgery, the First Medical Center of the Chinese PLA General Hospital, Institute of Hepatobiliary Surgery of the Chinese PLA, Beijing, China
| | - Zhe Liu
- Faculty of Hepato-Pancreato-Biliary Surgery, the First Medical Center of the Chinese PLA General Hospital, Institute of Hepatobiliary Surgery of the Chinese PLA, Beijing, China
| | - Tao Wan
- Faculty of Hepato-Pancreato-Biliary Surgery, the Eighth Medical Center of the Chinese PLA General Hospital, Beijing, China
| | - Ren Lang
- Department of Hepatobiliary Surgery, Beijing ChaoYang Hospital, Capital Medical University, Beijing, China
| | - Wenbing Sun
- Department of Hepatobiliary Surgery, Beijing ChaoYang Hospital, Capital Medical University, Beijing, China
| | - Shunda Du
- Department of Liver Surgery, Peking Union Medical College (PUMC) Hospital, PUMC & Chinese Academy of Medical Sciences, Beijing, China
| | - Yongping Yang
- Senior Department of Hepatology, the Fifth Medical Center of the Chinese PLA General Hospital, Beijing, China
| | - Yinying Lu
- Comprehensive Liver Cancer Center, the Fifth Medical Center of the Chinese PLA General Hospital, Beijing, China
| | - Daobing Zeng
- Department of General Surgery Center, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Jushan Wu
- Department of General Surgery Center, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Binwei Duan
- Department of General Surgery Center, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Dongdong Lin
- Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Fei Li
- Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Qinghua Meng
- Department of Medical Oncology, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Jun Zhou
- Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China
| | - Baocai Xing
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Hepatopancreatobiliary Surgery Department I, Peking University Cancer Hospital & Institute, Beijing, China
| | - Xiaodong Tian
- Department of General Surgery, Peking University First Hospital, Beijing, China
| | - Jiye Zhu
- Department of Hepatobiliary Surgery, Peking University People's Hospital, Beijing, China
| | - Jie Gao
- Department of Hepatobiliary Surgery, Peking University People's Hospital, Beijing, China
| | - Chunyi Hao
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Sarcoma Center, Peking University Cancer Hospital & Institute, Beijing, China
| | - Zhiqiang Wang
- Department of Hepatobiliary and Pancreatic Surgery, Qinghai Red Cross Hospital, Qinghai, China
| | - Feng Duan
- Department of Interventional Radiology, the First Medical Center of the Chinese PLA General Hospital, Beijing, China
| | - Zhijun Wang
- Department of Interventional Radiology, the First Medical Center of the Chinese PLA General Hospital, Beijing, China
| | - Maoqiang Wang
- Department of Interventional Radiology, the First Medical Center of the Chinese PLA General Hospital, Beijing, China
| | - Bin Liang
- Faculty of Hepato-Pancreato-Biliary Surgery, the First Medical Center of the Chinese PLA General Hospital, Institute of Hepatobiliary Surgery of the Chinese PLA, Beijing, China
| | - Yongwei Chen
- Faculty of Hepato-Pancreato-Biliary Surgery, the First Medical Center of the Chinese PLA General Hospital, Institute of Hepatobiliary Surgery of the Chinese PLA, Beijing, China
| | - Yinzhe Xu
- Faculty of Hepato-Pancreato-Biliary Surgery, the First Medical Center of the Chinese PLA General Hospital, Institute of Hepatobiliary Surgery of the Chinese PLA, Beijing, China
| | - Kai Li
- Faculty of Hepato-Pancreato-Biliary Surgery, the First Medical Center of the Chinese PLA General Hospital, Institute of Hepatobiliary Surgery of the Chinese PLA, Beijing, China
| | - Chengang Li
- Faculty of Hepato-Pancreato-Biliary Surgery, the First Medical Center of the Chinese PLA General Hospital, Institute of Hepatobiliary Surgery of the Chinese PLA, Beijing, China
| | - Minggen Hu
- Faculty of Hepato-Pancreato-Biliary Surgery, the First Medical Center of the Chinese PLA General Hospital, Institute of Hepatobiliary Surgery of the Chinese PLA, Beijing, China
| | - Zhaohai Wang
- Faculty of Hepato-Pancreato-Biliary Surgery, the First Medical Center of the Chinese PLA General Hospital, Institute of Hepatobiliary Surgery of the Chinese PLA, Beijing, China
| | - Shouwang Cai
- Faculty of Hepato-Pancreato-Biliary Surgery, the First Medical Center of the Chinese PLA General Hospital, Institute of Hepatobiliary Surgery of the Chinese PLA, Beijing, China
| | - Wenbin Ji
- Faculty of Hepato-Pancreato-Biliary Surgery, the First Medical Center of the Chinese PLA General Hospital, Institute of Hepatobiliary Surgery of the Chinese PLA, Beijing, China
| | - Nianxin Xia
- Faculty of Hepato-Pancreato-Biliary Surgery, the Sixth Medical Center of the Chinese PLA General Hospital, Beijing, China
| | - Wenheng Zheng
- Department of Interventional Therapy, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Liaoning, China
| | - Hongguang 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
| | - Gong Li
- Department of Radiation Oncology, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing, China
| | - Ziman Zhu
- Faculty of Hepato-Pancreato-Biliary Surgery, the Fourth Medical Center of the Chinese PLA General Hospital, Beijing, China
| | - Zhiyong Huang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei, China
| | - Wanguang Zhang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei, China
| | - Kaishan Tao
- Department of Hepatobiliary Surgery, Xijing Hosptial, the Fourth Military Medical University, Shanxi, China
| | - Jun Liang
- Department of Medical Oncology, Peking University International Hospital, Beijing, China
| | - Keming Zhang
- Department of Hepatobiliary Surgery, Peking University International Hospital, Beijing, China
| | - Chaoliu Dai
- Department of General Surgery, Shengjing Hospital of China Medical University, Liaoning, China
| | - Jiangtao Li
- Department of Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang, China
| | - Qiu Qiu
- Department of Gastroenterology, People's Hospital of Chongqing Hechuan, Chongqing, China
| | - Yuan Guo
- Organ Transplantation Center, the Affiliated Hospital of Qingdao University, Shandong, China
| | - Liqun Wu
- Organ Transplantation Center, the Affiliated Hospital of Qingdao University, Shandong, China
| | - Weibao Ding
- Department of Hepatobiliary Surgery, Weifang People's Hospital, Shandong, China
| | - Zhenyu Zhu
- Hepatobiliary Surgery Center, the Fifth Medical Center of the Chinese PLA General Hospital, Beijing, China
| | - Wanqing Gu
- Chinese Journal of Hepatobiliary Surgery, Beijing, China
| | - Jingyu Cao
- Department of Hepatobiliary and Pancreatic Surgery, the Affiliated Hospital of Qingdao University, Shandong China
| | - Zusen Wang
- Department of Hepatobiliary and Pancreatic Surgery, the Affiliated Hospital of Qingdao University, Shandong China
| | - Lantian Tian
- Department of Hepatobiliary and Pancreatic Surgery, the Affiliated Hospital of Qingdao University, Shandong China
| | - Huiguo Ding
- Department of Hepatology and Gastroenterology, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Guangming Li
- Department of Liver Transplantation Center, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Yongyi Zeng
- Department of Hepatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fujian, China
| | - Kui Wang
- Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, China
| | - Ning Yang
- Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, China
| | - Haosheng Jin
- Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangdong, China
| | - Yajin Chen
- Department of Hepatobiliopancreatic Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangdong, China
| | - Yinmo Yang
- Department of Hepatobiliary and Pancreatic Surgery, Peking University First Hospital, Beijing, China
| | - Dianrong Xiu
- Department of General Surgery, Peking University Third Hospital, Beijing, China
| | - Maolin Yan
- Department of Hepatobiliary and Pancreatic Surgery, Fujian Provincial Hospital, Fujian, China
| | - Xiaodong Wang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Interventional Therapy, Peking UniversityCancer Hospital & Institute, Beijing, China
| | - Quanli Han
- Department of Medical Oncology, the First Medical Center of the Chinese PLA General Hospital, Beijing, China
| | - Shunchang Jiao
- Department of Medical Oncology, the First Medical Center of the Chinese PLA General Hospital, Beijing, China
| | - Guang Tan
- Department of General Surgery, the First Affiliated Hospital of Dalian Medical University, Liaoning, China
| | - Jizhou Wang
- Department of Hepatobiliary Surgery and Organ Transplantation Center, The First Affiliated Hospital of USTC, Division of Life Science andMedicine, University of Science and Technology of China, Anhui, China
| | - Lianxin Liu
- Department of Hepatobiliary Surgery and Organ Transplantation Center, The First Affiliated Hospital of USTC, Division of Life Science andMedicine, University of Science and Technology of China, Anhui, China
| | - Jinghai Song
- Department of General Surgery, Beijing Hospital, National Center of Gerontology; Institute of Geriatric Medicine, Chinese Academy of MedicalSciences, Beijing, China
| | - Jiajie Liao
- Zhongshan Hospital, Fudan University, Shanghai, China
| | - Hong Zhao
- 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
| | - Peng Li
- The Department of Hepatobiliary Surgery, the Second Affiliated Hospital of Hainan Medical University, Hainan, China
| | - Tianqiang Song
- Department of Hepatobiliary Cancer, Liver Cancer Center, Tianjin Medical University Cancer Institute & Hospital, National Clinical ResearchCenter for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin Key Laboratory ofDigestive Cancer, Tianjin, China
| | - Zhanbo Wang
- Department of Pathology, the First Medical Center of the Chinese PLA General Hospital, Beijing, China
| | - Jing Yuan
- Department of Pathology, the First Medical Center of the Chinese PLA General Hospital, Beijing, China
| | - Bingyang Hu
- Department of General Surgery, Beijing Shijingshan Hospital, Beijing, China
| | - Yufeng Yuan
- Department of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Hubei, China
| | - Meng Zhang
- Department of Hepatobiliary Surgery, the Fourth Hospital of Hebei Medical University, Hebei, China
| | - Shuyang Sun
- Department of Gastroenterology, Beijing Chest Hospital, Capital Medical University, Beijing, China
| | - Jialin Zhang
- Department of Radiology, the First Hospital of China Medical University, Liaoning, China
| | - Wentao Wang
- Department of Liver Surgery, West China Hospital, Sichuan University, Sichuan, China
| | - Tianfu Wen
- Department of Liver Surgery, West China Hospital, Sichuan University, Sichuan, China
| | - Jiayin Yang
- Department of Liver Surgery, West China Hospital, Sichuan University, Sichuan, China
| | - Xilin Du
- Department of General Surgery, Tangdu Hospital, the Fourth Military Medical University, Shanxi, China
| | - Tao Peng
- Department of Hepatobiliary Surgery, the First Affiliated Hospital of Guangxi Medical University, Guangxi, China
| | - Feng Xia
- Institute of Hepatobiliary Surgery, Southwest Hospital, Army Medical University, Chongqing, China
| | - Zuojin Liu
- Department of Hepatobiliary Surgery, the Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Weibo Niu
- Department of Hepatobiliary Surgery, Qilu Hospital of Shandong University, Shandong, China
| | - Ping Liang
- Department of Interventional Ultrasound, the Fifth Medical Center of the Chinese PLA General Hospital, Beijing, China
| | - Jianming Xu
- Department of Gastrointestinal Oncology, the Fifth Medical Center of the Chinese PLA General Hospital, Beijing, China
| | - Xiao Zhao
- Department of Immunology and National Center for Biomedicine Analysis, the Fifth Medical Center of the Chinese PLA General Hospital, Beijing,China
| | - Min Zhu
- Department of Transplant Surgery, Qilu Hospital of Shandong University, Shandong, China
| | - Huaizhi Wang
- Institute of Hepatopancreatobiliary Surgery, Chongqing General Hospital, Chongqing University, Chongqing, China
| | - Ming Kuang
- Center of Hepato Pancreato Biliary Surgery, the First Affiliated Hospital, Sun Yat-sen University, Guangdong, China
| | - Shunli Shen
- Center of Hepato Pancreato Biliary Surgery, the First Affiliated Hospital, Sun Yat-sen University, Guangdong, China
| | - Xing Cui
- Department of Oncology and Hematology, the Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Shandong,China
| | - Jinxue Zhou
- Department of Hepatobiliary and Pancreatic Surgery, the Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Henan,China
| | - Rong Liu
- Faculty of Hepato-Pancreato-Biliary Surgery, the First Medical Center of the Chinese PLA General Hospital, Institute of Hepatobiliary Surgery of the Chinese PLA, Beijing, China
| | - Huichuan Sun
- Department of Liver Surgery and Transplantation, Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry ofEducation, Shanghai Key Laboratory of Organ Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Zhongshan Hospital,Fudan University, Shanghai, China
| | - Jia Fan
- Department of Liver Surgery and Transplantation, Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry ofEducation, Shanghai Key Laboratory of Organ Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Zhongshan Hospital,Fudan University, Shanghai, China
| | - Xiaoping Chen
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei, China
| | - Jian Zhou
- Department of Liver Surgery and Transplantation, Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry ofEducation, Shanghai Key Laboratory of Organ Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Zhongshan Hospital,Fudan University, Shanghai, China
| | - Jianqiang Cai
- 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
| | - Shichun Lu
- Faculty of Hepato-Pancreato-Biliary Surgery, the First Medical Center of the Chinese PLA General Hospital, Institute of Hepatobiliary Surgery of the Chinese PLA, Beijing, China
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Hosui A, Hayata N, Kurahashi T, Namiki A, Okamoto A, Aochi K, Ashida M, Tanimoto T, Murai H, Ohnishi K, Hirao M, Yamada T, Hiramatsu N. Efficacy of Adding Locoregional Therapy in ATZ/BEV-Treated Patients with Stable HCC. Cancers (Basel) 2025; 17:185. [PMID: 39857967 PMCID: PMC11763424 DOI: 10.3390/cancers17020185] [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: 12/09/2024] [Revised: 12/29/2024] [Accepted: 01/06/2025] [Indexed: 01/27/2025] Open
Abstract
Background/Objectives: Combination therapy with atezolizumab and bevacizumab (ATZ/BEV) is extremely effective and yields a high response rate in patients with hepatocellular carcinoma (HCC). In this study, the efficacy of adding locoregional therapy to ATZ/BEV in patients with stable disease (SD) HCC was investigated. Methods: One hundred five HCC patients who were treated with ATZ/BEV or lenvatinib (LEN) as first-line chemotherapy for unresectable HCC were evaluated on the basis of the modified RECIST criteria. SD patients whose initial antitumor effect was achieved received locoregional therapy, and the overall survival (OS) rate was assessed. Results: This study included 58 ATZ/BEV-treated participants and 47 LEN-treated participants. Twenty-eight SD patients (ATZ/BEV) and 20 SD patients (LEN) were identified. OS was significantly greater in ATZ/BEV-treated patients who also received locoregional therapy than in those who did not receive this additional therapy (p = 0.0343), whereas there was no difference between LEN-treated patients who also received locoregional therapy and those who did not. The locoregional therapy consisted of transcatheter arterial chemoembolization (TACE) and/or radiofrequency ablation (RFA). When assessing the add-on effect of TACE and/or RFA in the SD patients treated with ATZ/BEV, five patients were found to achieve CR. Conclusions: The addition of locoregional therapy, such as TACE/RFA, was found to affect SD patients. When a response is limited during ATZ/BEV therapy, it is important to consider the therapeutic option of adding locoregional therapy, as this additional treatment may contribute to improved prognosis via immune modulation.
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Affiliation(s)
- Atsushi Hosui
- Department of Gastroenterology and Hepatology, Osaka Rosai Hospital, 1179-3 Nagasonecho, Kita Ward, Sakai 591-8025, Osaka, Japan; (N.H.); (T.K.); (A.N.); (A.O.); (K.A.); (M.A.); (T.T.); (H.M.); (K.O.); (M.H.); (T.Y.); (N.H.)
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Hernandez L, Parent L, Molinier V, Suc B, Izar F, Moyal E, Peron JM, Otal P, Lusque A, Modesto A. Stereotactic body radiation therapy in primary liver tumor: Local control, outcomes and toxicities. Clin Transl Radiat Oncol 2025; 50:100892. [PMID: 39651455 PMCID: PMC11625365 DOI: 10.1016/j.ctro.2024.100892] [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: 05/25/2024] [Revised: 09/01/2024] [Accepted: 11/17/2024] [Indexed: 12/11/2024] Open
Abstract
Objective Stereotactic body radiation therapy (SBRT) is a therapeutic option in the guidelines for liver primaries after standard strategies like surgery or thermoablation have failed. To assess its efficacy and safety, we reviewed all patients treated by SBRT for a hepatocellular carcinoma (HCC) over a six-year period. Methods and materials The study included all patients treated by SBRT for HCC between April 2015 and November 2021 in the University Cancer Institute at Toulouse-Oncopole. All patients were inoperable and not eligible for thermoablation, or after a failure. All tumor sizes were included and cirrhosis up to Child-Pugh B was accepted. Local control (LC), overall survival (OS) and progression-free survival (PFS) were estimated by the Kaplan-Meier method. Treatment response was assessed using mRECIST criteria. Toxicity was graded using CTCAE (v4.0). Results One hundred and nine patients with 118 lesions were treated. Half underwent prior standard treatment. Median dose was 50 Grays in five fractions for most patients. Chronic liver disease represented 90.8 % of cases with a median age of 69 years. Median tumor size was 4.0 cm. Median follow-up was 22.2 months [95 %CI: 15.1-30.4]. LC, OS and PFS at two years were 82.4 % [95 %CI: 71.3; 89.5], 73.2 % [95 %CI: 61.5; 81.8] and 35.8 % [95 %CI: 25.1; 46.7], respectively. Acute toxicities occurred in 20.2 % of patients, including 10.1 % grade 3-4 and 1.8 % grade 5. Late toxicities occurred in 5.5 % of patients including 4.6 % grade 3-4. Grade ≥ 3 toxicity was related to digestive perforation or liver failure. Conclusion SBRT provides good LC with an acceptable safety profile. It can be used in several settings such as salvage therapy or in combination with validated treatment. Prospective randomized trials are needed to validate SBRT as a standard alternative.
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Affiliation(s)
- Ludovic Hernandez
- Department of Radiotherapy, University Cancer Institute of Toulouse-Oncopole, 31100 Toulouse, France
| | - Laure Parent
- Department of Radiotherapy, University Cancer Institute of Toulouse-Oncopole, 31100 Toulouse, France
| | - Victoire Molinier
- Department of Radiotherapy, University Cancer Institute of Toulouse-Oncopole, 31100 Toulouse, France
| | - Bertrand Suc
- Department of Digestive Surgery and Liver Transplantation, Rangueil University Hospital, 31059 Toulouse, France
| | - Françoise Izar
- Department of Radiotherapy, University Cancer Institute of Toulouse-Oncopole, 31100 Toulouse, France
| | - Elisabeth Moyal
- Department of Radiotherapy, University Cancer Institute of Toulouse-Oncopole, 31100 Toulouse, France
| | - Jean-Marie Peron
- Department of Hepatogastroenterology, Rangueil University Hospital, 31059 Toulouse, France
| | - Philippe Otal
- Department of Radiology, Rangueil University Hospital, 31059 Toulouse, France
| | - Amélie Lusque
- Biostatistics Unit, University Cancer Institute of Toulouse-Oncopole, 31100 Toulouse, France
| | - Anouchka Modesto
- Department of Radiotherapy, University Cancer Institute of Toulouse-Oncopole, 31100 Toulouse, France
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Wu C, Chen Q, Wang H, Guan Y, Mian Z, Huang C, Ruan C, Song Q, Jiang H, Pan J, Li X. A review of deep learning approaches for multimodal image segmentation of liver cancer. J Appl Clin Med Phys 2024; 25:e14540. [PMID: 39374312 PMCID: PMC11633801 DOI: 10.1002/acm2.14540] [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: 03/27/2024] [Revised: 05/30/2024] [Accepted: 08/13/2024] [Indexed: 10/09/2024] Open
Abstract
This review examines the recent developments in deep learning (DL) techniques applied to multimodal fusion image segmentation for liver cancer. Hepatocellular carcinoma is a highly dangerous malignant tumor that requires accurate image segmentation for effective treatment and disease monitoring. Multimodal image fusion has the potential to offer more comprehensive information and more precise segmentation, and DL techniques have achieved remarkable progress in this domain. This paper starts with an introduction to liver cancer, then explains the preprocessing and fusion methods for multimodal images, then explores the application of DL methods in this area. Various DL architectures such as convolutional neural networks (CNN) and U-Net are discussed and their benefits in multimodal image fusion segmentation. Furthermore, various evaluation metrics and datasets currently used to measure the performance of segmentation models are reviewed. While reviewing the progress, the challenges of current research, such as data imbalance, model generalization, and model interpretability, are emphasized and future research directions are suggested. The application of DL in multimodal image segmentation for liver cancer is transforming the field of medical imaging and is expected to further enhance the accuracy and efficiency of clinical decision making. This review provides useful insights and guidance for medical practitioners.
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Affiliation(s)
- Chaopeng Wu
- Department of Radiation OncologyRenmin HospitalWuhan UniversityWuhanHubeiChina
| | - Qiyao Chen
- Department of Radiation OncologyRenmin HospitalWuhan UniversityWuhanHubeiChina
| | - Haoyu Wang
- Department of Radiation OncologyRenmin HospitalWuhan UniversityWuhanHubeiChina
| | - Yu Guan
- Department of Radiation OncologyRenmin HospitalWuhan UniversityWuhanHubeiChina
| | - Zhangyang Mian
- Department of Radiation OncologyRenmin HospitalWuhan UniversityWuhanHubeiChina
| | - Cong Huang
- Department of Radiation OncologyRenmin HospitalWuhan UniversityWuhanHubeiChina
| | - Changli Ruan
- Department of Radiation OncologyRenmin HospitalWuhan UniversityWuhanHubeiChina
| | - Qibin Song
- Department of Radiation OncologyRenmin HospitalWuhan UniversityWuhanHubeiChina
| | - Hao Jiang
- School of Electronic InformationWuhan UniversityWuhanHubeiChina
| | - Jinghui Pan
- Department of Radiation OncologyRenmin HospitalWuhan UniversityWuhanHubeiChina
- School of Electronic InformationWuhan UniversityWuhanHubeiChina
| | - Xiangpan Li
- Department of Radiation OncologyRenmin HospitalWuhan UniversityWuhanHubeiChina
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Zhang X, Deng X, Tan J, Liu H, Zhang H, Li C, Li Q, Zhou J, Xiao Z, Li J. Idarubicin-loaded degradable hydrogel for TACE therapy enhances anti-tumor immunity in hepatocellular carcinoma. Mater Today Bio 2024; 29:101343. [PMID: 39687797 PMCID: PMC11647502 DOI: 10.1016/j.mtbio.2024.101343] [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: 08/23/2024] [Revised: 10/22/2024] [Accepted: 11/14/2024] [Indexed: 12/18/2024] Open
Abstract
Hepatocellular carcinoma (HCC) is a common and deadly cancer, often diagnosed at advanced stages, limiting surgical options. Transcatheter arterial chemoembolization (TACE) is a primary treatment for inoperable and involves the use of drug-eluting microspheres to slowly release chemotherapy drugs. However, patient responses to TACE vary, with some experiencing tumor progression and recurrence. Traditional TACE uses agents like oil-based drug emulsions and polyvinyl alcohol particles, which can permanently block blood vessels and increase tumor hypoxia. Additionally, TACE can suppress the immune system by reducing immune cell numbers and function, contributing to poor treatment outcomes. New approaches, like TACE using degradable starch microspheres and hydrogel-based materials, offer the potential to create different tumor environments that could improve both safety and efficacy. In our research, we developed a composite hydrogel (IF@Gel) made of Poloxamer-407 gel and Fe3O4 nanoparticles, loaded with idarubicin, to use as an embolic material for TACE in a rat model of orthotopic HCC. We observed promising therapeutic effects and investigated the impact on the tumor immune microenvironment, focusing on the role of immunogenic cell death (ICD). The composite hydrogel demonstrated excellent potential as an embolic material for TACE, and IF@Gel-based TACE demonstrated significant efficacy in rat HCC. Furthermore, our findings highlight the potential synergistic effects of ICD with anti-PD-L1 therapy, providing new insights into HCC treatment strategies. This study aims to provide improved treatment options for HCC and to deepen our understanding of the mechanisms of TACE and tumor environment regulation.
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Affiliation(s)
- Xiaokai Zhang
- Department of Hepatobiliopancreatic Surgery, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou 450003, China
- Department of Interventional Oncology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China
| | - Xiujiao Deng
- The Guangzhou Key Laboratory of Molecular and Functional Imaging for Clinical Translation, Department of Radiology and Nuclear Medicine, The First Affiliated Hospital of Jinan University, Guangzhou 510632, China
- Department of Pharmacy, The First Affiliated Hospital of Jinan University, Guangzhou, 510632, China
| | - Jizhou Tan
- Department of Stomatology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China
| | - Haikuan Liu
- Department of Interventional Oncology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China
| | - Hong Zhang
- Department of Interventional Radiology and Vascular Surgery, The Sixth Affiliated Hospital of Jinan University, Dongguan 523067, China
| | - Chengzhi Li
- The Guangzhou Key Laboratory of Molecular and Functional Imaging for Clinical Translation, Department of Radiology and Nuclear Medicine, The First Affiliated Hospital of Jinan University, Guangzhou 510632, China
| | - Qingjun Li
- Department of Hepatobiliopancreatic Surgery, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou 450003, China
| | - Jinxue Zhou
- Department of Hepatobiliopancreatic Surgery, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou 450003, China
| | - Zeyu Xiao
- The Guangzhou Key Laboratory of Molecular and Functional Imaging for Clinical Translation, Department of Radiology and Nuclear Medicine, The First Affiliated Hospital of Jinan University, Guangzhou 510632, China
| | - Jiaping Li
- Department of Interventional Oncology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China
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Patel KR, Menon H, Patel RR, Huang EP, Verma V, Escorcia FE. Locoregional Therapies for Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis. JAMA Netw Open 2024; 7:e2447995. [PMID: 39602117 DOI: 10.1001/jamanetworkopen.2024.47995] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/29/2024] Open
Abstract
Importance Several locoregional therapies (LRTs) for nonmetastatic hepatocellular carcinoma (HCC) are available; however, a global comparison of the relative efficacy of each is needed. Objective To conduct a systematic review and direct, pairwise meta-analytic comparison of all identified randomized clinical trials evaluating the treatment of nonmetastatic HCC. Data Sources A comprehensive search of PubMed and the proceedings of the American Society of Clinical Oncology and American Society for Radiation Oncology annual meetings from January 1, 2010, to November 1, 2023, was performed. Study Selection Randomized clinical trials using a form of LRT (surgery with or without adjuvant therapy, radiofrequency ablation [RFA], microwave ablation [MWA], radiotherapy [RT], hepatic arterial infusion chemotherapy [HAIC], transarterial bland embolization [TAE], transarterial chemoembolization [TACE], or transarterial radioembolization [TARE]). Data Extraction and Synthesis Study eligibility and data extraction were each reviewed by 2 authors independently. Random-effects meta-analyses were used to compare treatment categories. Main Outcomes and Measures Progression-free survival (PFS) was the primary outcome; overall survival (OS) was the secondary outcome. Results Forty randomized clinical trials reporting on comparative outcomes of 11 576 total patients with localized HCC treated with LRT were included. The median follow-up was 30.0 (IQR, 18.5-40.8) months. Direct pooled comparisons between treatment classes suggested improved outcomes for surgery combined with adjuvant therapy over surgery alone (PFS: hazard ratio [HR], 0.62 [95% CI, 0.51-0.75]; P < .001; OS: HR, 0.61 [95% CI, 0.48-0.78]; P < .001), surgery over RFA (PFS: HR, 0.74 [95% CI, 0.63-0.87]; P < .001; OS: HR, 0.71 [95% CI, 0.54-0.95]; P = .02), RT over TACE (PFS: HR, 0.35 [95% CI, 0.21-0.60]; P < .001; OS: HR, 0.35 [95% CI, 0.13-0.97]; P = .04), and HAIC over TACE (PFS: HR, 0.57 [95% CI, 0.45-0.72]; P < .001; OS: HR, 0.58 [95% CI, 0.45-0.75]; P < .001). No substantial heterogeneity was noted for any pairwise comparison with the exception of RT-based regimens compared with tyrosine kinase inhibitor therapy. Conclusions and Relevance The findings of this systematic review and direct, pairwise meta-analysis suggest that all LRTs are not equivalent for the treatment of localized HCC. The efficacy of LRTs appears hierarchical, with surgery-based management outcomes associated with the best treatment outcomes and embolization-based treatment options associated with the worst treatment outcomes.
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Affiliation(s)
- Krishnan R Patel
- Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
| | - Hari Menon
- Department of Human Oncology, University of Wisconsin, Madison
| | - Roshal R Patel
- Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York
| | - Erich P Huang
- Biometric Research Program, National Cancer Institute, Bethesda, Maryland
| | - Vivek Verma
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston
| | - Freddy E Escorcia
- Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
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Liao Z, Zhang H, Liu F, Wang W, Liu Y, Su C, Zhu H, Chen X, Zhang B, Zhang Z. m 6A-Dependent ITIH1 Regulated by TGF-β Acts as a Target for Hepatocellular Carcinoma Progression. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2024; 11:e2401013. [PMID: 39234824 PMCID: PMC11558142 DOI: 10.1002/advs.202401013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/27/2024] [Revised: 07/29/2024] [Indexed: 09/06/2024]
Abstract
Both the transforming growth factor beta (TGF-β) signaling pathway and N6-methyladenosine (m6A) modification for mRNA play an important role in hepatocellular carcinoma (HCC) progression. However, the relationship between TGF-β and m6A in hepatocellular carcinoma (HCC) remains unclear. Here, it is found that TGF-β can promote the liquid phase separation of METTL3, which further leads to the reduction of mRNA stability of ITIH1. As a secreted protein, ITIH1 can act as a ligand of integrin α5β1 to antagonize fibronectin, induce the inhibition of focal adhesion kinase signaling pathway, and inhibit the progression of HCC. In the preclinical model (mouse model, patient-derived organoid, patient-derived xenografts), purified recombinant ITIH1 (r-ITIH1) protein can be targeted for HCC. More importantly, r-ITIH1 can play a synergistic role in targeting HCC with TGF-β inhibitor. The downstream ITIH1 regulatory mechanism of TGF-β and m6A modification is revealed, and ITIH1 can be translational as a potential target for HCC.
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Affiliation(s)
- Zhibin Liao
- Hepatic Surgery CenterTongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei430030China
- Hubei Key Laboratory of Hepato‐Pancreato‐Biliary DiseasesWuhanHubei430030China
| | - Hongwei Zhang
- Hepatic Surgery CenterTongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei430030China
- Hubei Key Laboratory of Hepato‐Pancreato‐Biliary DiseasesWuhanHubei430030China
| | - Furong Liu
- Hepatic Surgery CenterTongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei430030China
- Hubei Key Laboratory of Hepato‐Pancreato‐Biliary DiseasesWuhanHubei430030China
| | - Weijian Wang
- Hepatic Surgery CenterTongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei430030China
- Hubei Key Laboratory of Hepato‐Pancreato‐Biliary DiseasesWuhanHubei430030China
| | - Yachong Liu
- Hepatic Surgery CenterTongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei430030China
- Hubei Key Laboratory of Hepato‐Pancreato‐Biliary DiseasesWuhanHubei430030China
| | - Chen Su
- Hepatic Surgery CenterTongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei430030China
- Hubei Key Laboratory of Hepato‐Pancreato‐Biliary DiseasesWuhanHubei430030China
| | - He Zhu
- Hepatic Surgery CenterTongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei430030China
- Hubei Key Laboratory of Hepato‐Pancreato‐Biliary DiseasesWuhanHubei430030China
| | - Xiaoping Chen
- Hepatic Surgery CenterTongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei430030China
- Hubei Key Laboratory of Hepato‐Pancreato‐Biliary DiseasesWuhanHubei430030China
- Key Laboratory of Organ TransplantationMinistry of Education and Ministry of HealthWuhanHubei430030China
| | - Bixiang Zhang
- Hepatic Surgery CenterTongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei430030China
- Hubei Key Laboratory of Hepato‐Pancreato‐Biliary DiseasesWuhanHubei430030China
- Key Laboratory of Organ TransplantationMinistry of Education and Ministry of HealthWuhanHubei430030China
| | - Zhanguo Zhang
- Hepatic Surgery CenterTongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei430030China
- Hubei Key Laboratory of Hepato‐Pancreato‐Biliary DiseasesWuhanHubei430030China
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Tong W, Zhong J, Yang Q, Lin H, Chen B, Lu T, Chen J, Luo N. Single-cell and bulk transcriptomic datasets enable the development of prognostic models based on dynamic changes in the tumor immune microenvironment in patients with hepatocellular carcinoma and portal vein tumor thrombus. Front Immunol 2024; 15:1414121. [PMID: 39530087 PMCID: PMC11550977 DOI: 10.3389/fimmu.2024.1414121] [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: 04/08/2024] [Accepted: 10/08/2024] [Indexed: 11/16/2024] Open
Abstract
Background Hepatocellular carcinoma (HCC) patients exhibiting portal vein tumor thrombosis (PVTT) face a high risk of rapid malignant progression and poor outcomes, with this issue being compounded by a lack of effective treatment options. The integration of bulk RNA-sequencing (RNA-seq) and single-cell RNA-seq (scRNA-seq) datasets focused on samples from HCC patients with PVTT has the potential to yield unprecedented insight into the dynamic changes in the tumor microenvironment (TME) and associated immunological characteristics in these patients, providing an invaluable tool for the reliable prediction of disease progression and treatment responses. Methods scRNA-seq data from both primary tumor (PT) and PVTT cells were downloaded from the Gene Expression Omnibus (GEO) database, while the International Cancer Genome Consortium (ICGC) and Cancer Genome Atlas (TCGA) databases were used to access bulk RNA-seq datasets. scRNA-seq, clustering, GSVA enrichment, mutational profiling, and predictive immunotherapeutic treatment analyses were conducted using these data with the goal of systematically assessing the heterogeneity of PT and PVTT cells and establishing a model capable of predicting immunotherapeutic and prognostic outcomes in patients with HCC. Results These analyses revealed that PVTT cells exhibited patterns of tumor proliferation, stromal activation, and low levels of immune cell infiltration, presenting with immune desert and immune rejection-like phenotypes. PT cells, in contrast, were found to exhibit a pattern of immunoinflammatory activity. Core PVTT-associated genes were clustered into three patterns consistent with the tumor immune rejection and immune desert phenotypes. An established clustering model was capable of predicting tumor inflammatory stage, subtype, TME stromal activity, and patient outcomes. PVTT signature genes were further used to establish a risk model, with the risk scores derived from this model providing a tool to evaluate patient clinicopathological features including clinical stage, tumor differentiation, histological subtype, microsatellite instability status, and tumor mutational burden. These risk scores were also able to serve as an independent predictor of patient survival outcomes, responses to adjuvant chemotherapy, and responses to immunotherapy. In vitro experiments were used to partially validate the biological prediction results. Conclusion These results offer new insight into the biological and immunological landscape of PVTT in HCC patients, By utilizing individual patient risk scores, providing an opportunity to guide more effective immunotherapeutic interventional efforts.
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Affiliation(s)
- Wangxia Tong
- Department of Hepatology, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, Guangxi, China
| | - Jieyue Zhong
- Department of Hepatology, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, Guangxi, China
| | - Qiuyan Yang
- Department of Hepatology, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, Guangxi, China
| | - Han Lin
- Department of Hepatology, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, Guangxi, China
| | - Bolun Chen
- Department of Hepatology, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, Guangxi, China
| | - Tao Lu
- Department of Hepatobiliary Surgery, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, Guangxi, China
| | - Jibing Chen
- Center for Translational Medicine of Integrated Traditional Chinese and Western Medicine, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, Guangxi, China
| | - Ning Luo
- Department of Neurology, RuiKang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, Guangxi, China
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Yang Y, Sun J, Cai J, Chen M, Dai C, Wen T, Xia J, Ying M, Zhang Z, Zhang X, Fang C, Shen F, An P, Cai Q, Cao J, Zeng Z, Chen G, Chen J, Chen P, Chen Y, Shan Y, Dang S, Guo WX, He J, Hu H, Huang B, Jia W, Jiang K, Jin Y, Jin Y, Jin Y, Li G, Liang Y, Liu E, Liu H, Peng W, Peng Z, Peng Z, Qian Y, Ren W, Shi J, Song Y, Tao M, Tie J, Wan X, Wang B, Wang J, Wang K, Wang K, Wang X, Wei W, Wu FX, Xiang B, Xie L, Xu J, Yan ML, Ye Y, Yue J, Zhang X, Zhang Y, Zhang A, Zhao H, Zhao W, Zheng X, Zhou H, Zhou H, Zhou J, Zhou X, Cheng SQ, Li Q, on behalf of Chinese Association of Liver Cancer and Chinese Medical Doctor Association. Chinese Expert Consensus on the Whole-Course Management of Hepatocellular Carcinoma (2023 Edition). Liver Cancer 2024:1-23. [DOI: 10.1159/000541622] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/11/2025] Open
Abstract
Background: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in China. Most HCC patients have the complications of chronic liver disease and need overall consideration and whole-course management, including diagnosis, treatment, and follow-up. To develop a reasonable, long-term, and complete management plan, multiple factors need to be considered, including the patient’s general condition, basic liver diseases, tumor stage, tumor biological characteristics, treatment requirements, and economic cost. Summary: To better guide the whole-course management of HCC patients, the Chinese Association of Liver Cancer and the Chinese Medical Doctor Association has gathered multidisciplinary experts and scholars in relevant fields to formulate the “Chinese Expert Consensus on The Whole-Course Management of Hepatocellular Carcinoma (2023).” Key Messages: This expert consensus, based on the current clinical evidence and experience, proposes surgical and nonsurgical HCC management pathways and involves 18 recommendations, including perioperative treatment, systematic treatment combined with local treatment, conversion treatment, special population management, symptomatic support treatment, and follow-up management.
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Plant N, Mylonas A, Sengupta C, Nguyen DT, Silvester S, Pryor D, Greer P, Lee YYD, Ramachandran P, Seshadri V, Trada Y, Khor R, Wang T, Hardcastle N, Keall P. Radio-opaque contrast agents for liver cancer targeting with KIM during radiation therapy (ROCK-RT): an observational feasibility study. Radiat Oncol 2024; 19:139. [PMID: 39380004 PMCID: PMC11462695 DOI: 10.1186/s13014-024-02524-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2024] [Accepted: 09/17/2024] [Indexed: 10/10/2024] Open
Abstract
BACKGROUND This observational study aims to establish the feasibility of using x-ray images of radio-opaque chemoembolisation deposits in patients as a method for real-time image-guided radiation therapy of hepatocellular carcinoma. METHODS This study will recruit 50 hepatocellular carcinoma patients who have had or will have stereotactic ablative radiation therapy and have had transarterial chemoembolisation with a radio-opaque agent. X-ray and computed tomography images of the patients will be analysed retrospectively. Additionally, a deep learning method for real-time motion tracking will be developed. We hypothesise that: (i) deep learning software can be developed that will successfully track the contrast agent mass on two thirds of cone beam computed tomography (CBCT) projection and intra-treatment images (ii), the mean and standard deviation (mm) difference in the location of the mass between ground truth and deep learning detection are ≤ 2 mm and ≤ 3 mm respectively and (iii) statistical modelling of study data will predict tracking success in 85% of trial participants. DISCUSSION Developing a real-time tracking method will enable increased targeting accuracy, without the need for additional invasive procedures to implant fiducial markers. TRIAL REGISTRATION Registered to ClinicalTrials.gov (NCT05169177) 12th October 2021.
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Affiliation(s)
- Natalie Plant
- Image X Institute, University of Sydney, Suite 201, Biomedical Building (C81), 1 Central Ave, Eveleigh, NSW, 2015, Australia
| | - Adam Mylonas
- Image X Institute, University of Sydney, Suite 201, Biomedical Building (C81), 1 Central Ave, Eveleigh, NSW, 2015, Australia
| | - Chandrima Sengupta
- Image X Institute, University of Sydney, Suite 201, Biomedical Building (C81), 1 Central Ave, Eveleigh, NSW, 2015, Australia
| | - Doan Trang Nguyen
- Image X Institute, University of Sydney, Suite 201, Biomedical Building (C81), 1 Central Ave, Eveleigh, NSW, 2015, Australia
| | - Shona Silvester
- Image X Institute, University of Sydney, Suite 201, Biomedical Building (C81), 1 Central Ave, Eveleigh, NSW, 2015, Australia
| | - David Pryor
- Department of Radiation Oncology, Princess Alexandra Hospital, Brisbane, QLD, Australia
| | - Peter Greer
- Department of Radiation Oncology, Calvary Mater Newcastle, Newcastle, NSW, Australia
| | | | | | | | - Yuvnik Trada
- Department of Radiation Oncology, Calvary Mater Newcastle, Newcastle, NSW, Australia
| | - Richard Khor
- Olivia Newton-John Cancer Wellness & Research Centre, Austin Health, Melbourne, VIC, Australia
| | - Tim Wang
- Department of Radiation Oncology, Crown Princess Mary Cancer Centre, Sydney, NSW, Australia
| | | | - Paul Keall
- Image X Institute, University of Sydney, Suite 201, Biomedical Building (C81), 1 Central Ave, Eveleigh, NSW, 2015, Australia.
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Zhu M, Liu Z, Chen S, Luo Z, Tu J, Qiao L, Wu J, Fan W, Peng Z. Sintilimab plus bevacizumab combined with radiotherapy as first-line treatment for hepatocellular carcinoma with portal vein tumor thrombus: A multicenter, single-arm, phase 2 study. Hepatology 2024; 80:807-815. [PMID: 38358542 DOI: 10.1097/hep.0000000000000776] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2023] [Accepted: 01/11/2024] [Indexed: 02/16/2024]
Abstract
BACKGROUND AND AIMS Systemic treatments are listed as first-line therapies for HCC with portal vein tumor thrombus (PVTT), resulting in modest efficacy. We aimed to evaluate the efficacy and safety of sintilimab plus bevacizumab combined with radiotherapy in HCC with PVTT and to identify prognostic biomarkers. APPROACH AND RESULTS This open-label, multicenter, single-arm, phase 2 clinical trial was conducted at 3 tertiary hospitals in China. A total of 46 patients with HCC with PVTT were enrolled. All the patients received the first cycle of i.v. sintilimab (200 mg, day 1) plus bevacizumab (15 mg/kg, day 1) within 3 days after enrollment. Radiotherapy (30-50 Gy/10 fractions) was administered after 2 cycles of Sin-Bev. Sin-Bev was disrupted during radiotherapy and resumed 2 weeks after radiotherapy and continued every 3 weeks thereafter until disease progression, unacceptable toxicity, or withdrawal of consent. The primary end point was objective response rate. Patients obtained an objective response rate of 58.7% and a disease control rate of 100%. After a median follow-up time of 26.0 months (95% CI: 24.0-26.0), the median OS was 24.0 months (95% CI: 19.0 to not applicable) and the median progression-free survival was 13.8 months (95% CI: 12.0-21.0), respectively. No unexpected adverse events or treatment-related deaths occurred. Mutations of PCTMD1 were predictive of shorter OS and progression-free survival. CONCLUSIONS Sintilimab plus bevacizumab combined with radiotherapy provides favorable treatment response and survival outcomes along with an acceptable safety profile in the first-line setting for patients with HCC with PVTT (ClinicalTrials.gov Identifier: NCT05010434).
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Affiliation(s)
- Meiyan Zhu
- Department of Radiation Oncology, Cancer Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Zelong Liu
- Department of Radiation Oncology, Cancer Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Shuling Chen
- Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Zhenhua Luo
- Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Jianfei Tu
- Department of Radiology, Affiliated Lishui Hospital of Zhejiang University, Lishui, China
| | - Liangliang Qiao
- Department of Interventional Oncology, Jinshazhou Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Jian Wu
- Center of Hepato-Pancreato-Biliary Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Wenzhe Fan
- Department of Interventional Oncology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Zhenwei Peng
- Department of Radiation Oncology, Cancer Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
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Liu Y, Pan R, Ouyang Y, Gu W, Xiao T, Yang H, Tang L, Wang H, Xiang B, Chen P. Pyroptosis in health and disease: mechanisms, regulation and clinical perspective. Signal Transduct Target Ther 2024; 9:245. [PMID: 39300122 DOI: 10.1038/s41392-024-01958-2] [Citation(s) in RCA: 35] [Impact Index Per Article: 35.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2024] [Revised: 08/14/2024] [Accepted: 08/26/2024] [Indexed: 09/22/2024] Open
Abstract
Pyroptosis is a type of programmed cell death characterized by cell swelling and osmotic lysis, resulting in cytomembrane rupture and release of immunostimulatory components, which play a role in several pathological processes. Significant cellular responses to various stimuli involve the formation of inflammasomes, maturation of inflammatory caspases, and caspase-mediated cleavage of gasdermin. The function of pyroptosis in disease is complex but not a simple angelic or demonic role. While inflammatory diseases such as sepsis are associated with uncontrollable pyroptosis, the potent immune response induced by pyroptosis can be exploited as a therapeutic target for anti-tumor therapy. Thus, a comprehensive review of the role of pyroptosis in disease is crucial for further research and clinical translation from bench to bedside. In this review, we summarize the recent advancements in understanding the role of pyroptosis in disease, covering the related development history, molecular mechanisms including canonical, non-canonical, caspase 3/8, and granzyme-mediated pathways, and its regulatory function in health and multiple diseases. Moreover, this review also provides updates on promising therapeutic strategies by applying novel small molecule inhibitors and traditional medicines to regulate pyroptosis. The present dilemmas and future directions in the landscape of pyroptosis are also discussed from a clinical perspective, providing clues for scientists to develop novel drugs targeting pyroptosis.
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Affiliation(s)
- Yifan Liu
- The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University/Hunan Cancer Hospital, Changsha, 410013, China
- Department of Oncology, Xiangya Hospital, Central South University, 87th Xiangya road, Changsha, 410008, Hunan province, China
| | - Renjie Pan
- The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University/Hunan Cancer Hospital, Changsha, 410013, China
| | - Yuzhen Ouyang
- The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University/Hunan Cancer Hospital, Changsha, 410013, China
- Department of Neurology, Xiangya Hospital, Central South University, 87th Xiangya road, Changsha, 410008, Hunan province, China
| | - Wangning Gu
- The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University/Hunan Cancer Hospital, Changsha, 410013, China
| | - Tengfei Xiao
- The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University/Hunan Cancer Hospital, Changsha, 410013, China
| | - Hongmin Yang
- The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University/Hunan Cancer Hospital, Changsha, 410013, China
| | - Ling Tang
- The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University/Hunan Cancer Hospital, Changsha, 410013, China
| | - Hui Wang
- The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University/Hunan Cancer Hospital, Changsha, 410013, China.
| | - Bo Xiang
- The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University/Hunan Cancer Hospital, Changsha, 410013, China.
| | - Pan Chen
- The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University/Hunan Cancer Hospital, Changsha, 410013, China.
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Zhou MT, Zhang P, Mao Q, Wei XQ, Yang L, Zhang XM. Current research status of transarterial therapies for hepatocellular carcinoma. World J Gastrointest Oncol 2024; 16:3752-3760. [PMID: 39350995 PMCID: PMC11438772 DOI: 10.4251/wjgo.v16.i9.3752] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2024] [Revised: 05/22/2024] [Accepted: 05/30/2024] [Indexed: 09/09/2024] Open
Abstract
With continuous advancements in interventional radiology, considerable progress has been made in transarterial therapies for hepatocellular carcinoma (HCC) in recent years, and an increasing number of research papers on transarterial therapies for HCC have been published. In this editorial, we comment on the article by Ma et al published in the recent issue of the World Journal of Gastro intestinal Oncology: "Efficacy and predictive factors of transarterial chemoembolization combined with lenvatinib plus programmed cell death protein-1 inhibition for unresectable HCC". We focus specifically on the current research status and future directions of transarterial therapies. In the future, more studies are needed to determine the optimal transarterial local treatment for HCC. With the emergence of checkpoint immunotherapy modalities, it is expected that the results of trials of transarterial local therapy combined with systemic therapy will bring new hope to HCC patients.
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Affiliation(s)
- Mao-Ting Zhou
- Department of Radiology, Interventional Medical Center, Science and Technology Innovation Center, The Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, Sichuan Province, China
| | - Peng Zhang
- Department of Radiology, Interventional Medical Center, Science and Technology Innovation Center, The Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, Sichuan Province, China
| | - Qi Mao
- Department of Radiology, Interventional Medical Center, Science and Technology Innovation Center, The Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, Sichuan Province, China
| | - Xiao-Qin Wei
- School of Medical Imaging, North Sichuan Medical College, Nanchong 637000, Sichuan Province, China
| | - Lin Yang
- Department of Radiology, Interventional Medical Center, Science and Technology Innovation Center, The Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, Sichuan Province, China
| | - Xiao-Ming Zhang
- Department of Radiology, Interventional Medical Center, Science and Technology Innovation Center, The Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, Sichuan Province, China
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Li R, Wang X, Li H, Wang M, Wang J, Wang W, Zhou Q. Hepatic Arterial Infusion Chemotherapy Combined Lenvatinib and PD-1 Inhibitor Showed Improved Survival for Infiltrative Hepatocellular Carcinoma: A Multicenter Cohort Study. J Hepatocell Carcinoma 2024; 11:1727-1740. [PMID: 39281003 PMCID: PMC11397264 DOI: 10.2147/jhc.s477872] [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: 05/12/2024] [Accepted: 09/03/2024] [Indexed: 09/18/2024] Open
Abstract
Purpose Lenvatinib and programmed cell death protein-1 (PD-1) inhibitor on infiltrative hepatocellular carcinoma (HCC) have obtained demonstrated efficacy and still need improvement. Hepatic arterial infusion chemotherapy (HAIC) has shown promising results for advanced HCC. This study aimed to compare the efficacy of HAIC combined Lenvatinib and PD-1 inhibitor versus Lenvatinib combined PD-1 inhibitor for infiltrative HCC. Patients and Methods A total of 232 patients were enrolled. There were 114 patients received Lenvatinib combined PD-1 inhibitor (Len+PD-1 group) and 118 patients received HAIC combined Lenvatinib and PD-1 inhibitor (HAIC+Len+PD-1 group). Overall survival (OS), progression-free survival (PFS) and safety of patients were compared between the two groups by propensity score-matching (PSM). Results The 6-, 12-, and 24-month OS rates were 93.8%, 65.1% and 13.4% in Len+PD-1 group, and 100%, 77.3% and 32.1% in HAIC+Len+PD-1 group, respectively. The 3-, 6-, and 12-month PFS rates were 86.4%, 45.7% and 14.1% in Len+PD-1 group, and 95.1%, 59.3% and 25.9% in HAIC+Len+PD-1 group, respectively. The HAIC+Len+PD-1 group had obviously better survival than the Len+PD-1 group both in OS (P=0.002) and PFS (P=0.004). Subgroup analysis revealed that OS in patients with metastasis was improved with HAIC+Len+PD-1 treatment. Patients with alpha-fetoprotein (AFP) response after treatment showed better survival than the non-response. In addition, HAIC+Len+PD-1 group showed manageable adverse events (AEs). Conclusion Patient with infiltrative HCC, HAIC+Len+PD-1 treatment had longer OS and PFS than Len+PD-1 treatment. Early AFP response was an effective indicator of better survival and tumor response to therapy.
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Affiliation(s)
- Ruixia Li
- Department of Thyroid Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong Province, People's Republic of China
| | - Xiaohui Wang
- Department of Hepatobiliary Surgery, Hunan Provincial People's Hospital, Changsha, Hunan Province, People's Republic of China
| | - Hui Li
- Department of Minimally Invasive Interventional Radiology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong Province, People's Republic of China
| | - Murong Wang
- Department of Minimally Invasive Interventional Radiology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong Province, People's Republic of China
| | - Juncheng Wang
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong Province, People's Republic of China
| | - Wei Wang
- Department of General surgery, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning Province, People's Republic of China
| | - Qunfang Zhou
- Department of Interventional Radiology, 5th Medical Center of Chinese PLA General Hospital, Beijing, People's Republic of China
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Zhu G, Luo L, He Y, Xiao Y, Cai Z, Tong W, Deng W, Xie J, Zhong Y, Hu Z, Shan R. AURKB targets DHX9 to promote hepatocellular carcinoma progression via PI3K/AKT/mTOR pathway. Mol Carcinog 2024; 63:1814-1826. [PMID: 38874176 DOI: 10.1002/mc.23775] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2023] [Revised: 05/10/2024] [Accepted: 06/03/2024] [Indexed: 06/15/2024]
Abstract
Aurora kinase B (AURKB) is known to play a carcinogenic role in a variety of cancers, but its underlying mechanism in liver cancer is unknown. This study aimed to investigate the role of AURKB in hepatocellular carcinoma (HCC) and its underlying molecular mechanism. Bioinformatics analysis revealed that AURKB was significantly overexpressed in HCC tissues and cell lines, and its high expression was associated with a poorer prognosis in HCC patients. Furthermore, downregulation of AURKB inhibited HCC cell proliferation, migration, and invasion, induced apoptosis, and caused cell cycle arrest. Moreover, AURKB downregulation also inhibited lung metastasis of HCC. AURKB interacted with DExH-Box helicase 9 (DHX9) and targeted its expression in HCC cells. Rescue experiments further demonstrated that AURKB targeting DHX9 promoted HCC progression through the PI3K/AKT/mTOR pathway. Our results suggest that AURKB is significantly highly expressed in HCC and correlates with patient prognosis. Targeting DHX9 with AURKB promotes HCC progression via the PI3K/AKT/mTOR pathway.
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Affiliation(s)
- Guoqing Zhu
- Department of General Surgery, The First Hospital of Nanchang, The Third Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China
- Department of General Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China
| | - Laihui Luo
- Department of General Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China
| | - Yongzhu He
- Department of General Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China
- Department of General Surgery, Division of Hepatobiliary and Pancreas Surgery, Shenzhen People's Hospital, The Second Clinical Medical College, Jinan University, Shenzhen, Guangdong Province, China
- The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen, Guangdong Province, China
| | - Yongqiang Xiao
- Department of General Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China
| | - Ziwei Cai
- Department of General Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China
| | - Weilai Tong
- Department of Orthopedics, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China
| | - Wei Deng
- Department of General Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China
| | - Jin Xie
- Department of General Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China
| | - Yanxin Zhong
- Department of Orthopedics, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China
| | - Zhigao Hu
- Department of General Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China
| | - Renfeng Shan
- Department of General Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China
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Bae SH, Jang WI, Mortensen HR, Weber B, Kim MS, Høyer M. Recent update of proton beam therapy for hepatocellular carcinoma: a systematic review and meta-analysis. JOURNAL OF LIVER CANCER 2024; 24:286-302. [PMID: 38961722 PMCID: PMC11449586 DOI: 10.17998/jlc.2024.06.26] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/16/2024] [Accepted: 06/26/2024] [Indexed: 07/05/2024]
Abstract
BACKGROUNDS/AIMS Although access to proton beam therapy (PBT) is limited worldwide, its use for the treatment of hepatocellular carcinoma (HCC) is gradually increasing with the expansion of new facilities. Therefore, we conducted a systematic review and metaanalysis to investigate the updated evidence of PBT for HCC. METHODS The MEDLINE, EMBASE, Cochrane Library, and Web of Science databases were systematically searched for studies that enrolled patients with liver-confined HCC that were treated with PBT for a cure up to February 2024. RESULTS A total of 1,858 HCC patients receiving PBT from 22 studies between 2004 and 2023 were selected for this meta-analysis. The median proportion of Child-Pugh class A was 86% (range, 41-100), and the median tumor size was 3.6 cm (range, 1.2-9.0). The median total dose ranged from 55 GyE to 76 GyE (median, 69). The pooled rates of 3- and 5-year local progression-free survival after PBT were 88% (95% confidence interval [CI], 85-91) and 86% (95% CI, 82-90), respectively. The pooled 3- and 5-year overall rates were 60% (95% CI, 54-66) and 46% (95% CI, 38-54), respectively. The pooled rates of grade 3 hepatic toxicity, classic radiationinduced liver disease (RILD), and non-classic RILD were 1%, 2%, and 1%, respectively. CONCLUSIONS The current study supports PBT for HCC and demonstrates favorable long-term survival and low hepatic toxicities compared with other published studies on other radiotherapy modalities. However, further studies are needed to identify the subgroups that will benefit from PBT.
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Affiliation(s)
- Sun Hyun Bae
- Department of Radiation Oncology, Soonchunhyang University Hospital Bucheon, Soonchunhyang University College of Medicine, Bucheon, Korea
| | - Won Il Jang
- Department of Radiation Oncology, Korea Institute of Radiological & Medical Sciences, Seoul, Korea
| | | | - Britta Weber
- Danish Center for Particle Therapy, Aarhus University Hospital, Aarhus, Denmark
| | - Mi Sook Kim
- Department of Radiation Oncology, Korea Institute of Radiological & Medical Sciences, Seoul, Korea
| | - Morten Høyer
- Danish Center for Particle Therapy, Aarhus University Hospital, Aarhus, Denmark
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Gerum S, Grambozov B, Roeder F. Stereotactic body radiation therapy (SBRT) in patients with hepatocellular cancer-a narrative review and expert opinion. J Gastrointest Oncol 2024; 15:1880-1892. [PMID: 39279965 PMCID: PMC11399857 DOI: 10.21037/jgo-23-771] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2023] [Accepted: 12/26/2023] [Indexed: 09/18/2024] Open
Abstract
Background and Objective Stereotactic body radiation therapy (SBRT) is a highly conformal technique of external beam radiotherapy precisely delivering high total (ablative) doses in a small number of fractions to clearly defined target volumes. Its development enabled efficient and safe radiation treatments in patients with localized hepatocellular cancer (HCC) unsuitable for other local treatment options. Moreover, it can be easily combined with several other therapy approaches. Thus, the aim of this narrative review is to outline the current role of SBRT in the multifocal treatment of HCC patients. Methods We searched PubMed for articles dealing with SBRT alone, in combination with other local or systemic treatments or in comparison to other local treatments in patients with HCC. This included original articles, reviews and conceptional articles dealing with the technique of SBRT. All articles were analysed for suitability by two independent reviewers. Key Content and Findings This review summarizes the currently available evidence for SBRT as a definitive treatment for HCC as well as its role within combination approaches including bridging to transplantation. SBRT is an effective and safe definitive treatment option in patients with localized HCC unsuitable for surgery and/or other local therapies based on retrospective and prospective series. Its combination with other local treatments yields superior results compared to single modality treatment based on non-randomized data. A growing number of prospective trials confirmed at least similar if not superior rates of local control with low toxicities compared to well established other local treatments even in non-selected patients. Conclusions SBRT is a promising tool in the treatment of HCC. It can be used either as definitive treatment, within combination approaches or as a bridging tool. Several phase III trials comparing SBRT with other local options are ongoing, which will further clarify its encouraging role.
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Affiliation(s)
- Sabine Gerum
- Department of Radiotherapy and Radiation Oncology, Paracelsus Medical University (PMU), Salzburg, Austria
| | - Brane Grambozov
- Department of Radiotherapy and Radiation Oncology, Paracelsus Medical University (PMU), Salzburg, Austria
| | - Falk Roeder
- Department of Radiotherapy and Radiation Oncology, Paracelsus Medical University (PMU), Salzburg, Austria
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Raghav A, Jeong GB. Phase I-IV Drug Trials on Hepatocellular Carcinoma in Asian Populations: A Systematic Review of Ten Years of Studies. Int J Mol Sci 2024; 25:9286. [PMID: 39273237 PMCID: PMC11395253 DOI: 10.3390/ijms25179286] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2024] [Revised: 08/02/2024] [Accepted: 08/07/2024] [Indexed: 09/15/2024] Open
Abstract
Despite advances in the treatment of hepatocellular carcinoma (HCC) over the last few decades, treatment opportunities for patients with HCC remain limited. HCC is the most common form of liver cancer, accounting for approximately 90% of all cases worldwide. Moreover, apart from the current pharmacological interventions, hepatic resection and liver transplantation are the mainstay curative approaches for patients with HCC. This systematic review included phase I, II, III, and IV clinical trials (CTs) and randomized controlled trials (RCTs) on current treatments for patients with HCC in Asian populations (2013-2023). A total of 427 articles were screened, and 184 non-duplicate publications were identified. After screening the titles and abstracts, 96 publications were excluded, and another 28 were excluded after full-text screening. The remaining 60 eligible RCTs/CTs were finally included. A total of 60 clinical trials fulfilled our inclusion criteria with 36 drugs used as monotherapy or combination therapy for HCC. Most studies used sorafenib alone or in combination with any of the treatment regimens. Lenvatinib or atezolizumab with bevacizumab was used for HCC after initial sorafenib treatment. Eighteen studies compared the efficacy of sorafenib with that of other drugs, including lenvatinib, cabozantinib, tepotinib, tigatuzumab, linifanib, erlotinib, resminostat, brivanib, tislelizumab, selumetinib, and refametinib. This study provides comprehensive insights into effective treatment interventions for HCC in Asian populations. The overall assessment indicates that sorafenib, used alone or in combination with atezolizumab and bevacizumab, has been the first treatment choice in the past decade to achieve better outcomes in patients with HCC in Asian populations.
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Affiliation(s)
- Alok Raghav
- Department of Anatomy and Cell Biology, College of Medicine, Gachon University, 155 Getbeol-ro, Yeonsu-gu, Incheon 21999, Republic of Korea
| | - Goo Bo Jeong
- Department of Anatomy and Cell Biology, College of Medicine, Gachon University, 155 Getbeol-ro, Yeonsu-gu, Incheon 21999, Republic of Korea
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Hogen R, Barry T, Subramanian V. Expanding Indications for Liver Transplantation in the Treatment of Hepatocellular Carcinoma. Curr Oncol 2024; 31:4753-4761. [PMID: 39195338 PMCID: PMC11353861 DOI: 10.3390/curroncol31080355] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2024] [Revised: 08/12/2024] [Accepted: 08/18/2024] [Indexed: 08/29/2024] Open
Abstract
Improvements in downstaging therapies have expanded the indications for liver transplantation (LT) for hepatocellular carcinoma (HCC). Patients with more advanced disease are now considered candidates due to advancements in radiation therapy, combination therapies, and immunotherapy. Combination stereotactic body radiation therapy (SBRT) and trans-arterial chemoembolization (TACE) has been shown to be superior to the historic treatment, sorafenib, in patients with macrovascular invasion. These patients are now candidates for LT with stable disease after LRT. Patients with ruptured HCC and prolonged stability have also been shown to have acceptable outcomes. The role of neoadjuvant immunotherapy needs to be further defined and has the potential to further improve tumor control prior to transplant.
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Affiliation(s)
- Rachel Hogen
- Transplant Institute, Tampa General Hospital, Tampa, FL 33606, USA; (T.B.); (V.S.)
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Yu J, Yan D, Wei S, Yang L, Yi P. Efficacy and safety of TACE combined with tyrosine kinase inhibitors and camrelizumab for unresectable hepatocellular carcinoma: A systematic review and meta‑analysis. Oncol Lett 2024; 28:401. [PMID: 38979553 PMCID: PMC11228926 DOI: 10.3892/ol.2024.14534] [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: 02/21/2024] [Accepted: 05/10/2024] [Indexed: 07/10/2024] Open
Abstract
Transcatheter arterial chemoembolization (TACE) combined with tyrosine kinase inhibitors (TKIs) and camrelizumab (collectively: T-T-C) is a novel treatment strategy for unresectable hepatocellular carcinoma (HCC). The present systematic review and meta-analysis aimed to evaluate the efficacy and safety of T-T-C compared with TACE combined with TKIs only (T-T) in the treatment of patients with unresectable HCC. A systematic literature search was conducted on T-T and T-T-C using PubMed, Embase and the Cochrane Library. Data regarding the clinical outcome, including overall survival (OS), progression-free survival (PFS), tumor response and adverse events (AEs), were independently extracted and analyzed by two researchers using standardized protocols. In total, 7 cohort studies, including 1,798 patients (T-T-C, 838; T-T, 960), were included in the meta-analysis. The results of the present study demonstrated that the T-T-C group had significantly prolonged OS [hazard ratio (HR), 0.38; 95% confidence interval (CI), 0.29-0.50; I2=61.5%; P=0.016)] and PFS (HR, 0.37; 95% CI, 0.30-0.46; I2=44.5%; P=0.109), and showed significantly higher objective response rates [risk ratio (RR), 0.82; 95% CI, 0.69-0.96; I2=25.1%; P=0.237)] and slightly higher disease control rates without a significant difference (RR, 0.96; 95% CI, 0.89-1.03; I2=0.0%; P=0.969). In addition, grade 3/4 AEs were more common in the T-T group, including hypertension (RR, 1.15; 95% CI, 0.85-1.56), vomiting or nausea (RR, 0.88; 95% CI, 0.44-1.76) and pain (RR, 0.74; 95% CI, 0.45-1.21); however, these results were not statistically significant. In conclusion, compared with T-T combination therapy, T-T-C demonstrated a notable advantage in terms of OS, PFS, ORR and DCR in patients with unresectable HCC. For manageable AEs, although the results were not statistically significant, the incidence of AEs in the T-T group was higher than that in the T-T-C group in terms of event probability.
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Affiliation(s)
- Jiahui Yu
- Department of Hepato-Biliary-Pancreas II, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637000, P.R. China
| | - Duan Yan
- Department of Hepato-Biliary-Pancreas II, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637000, P.R. China
| | - Song Wei
- Department of Hepato-Biliary-Pancreas II, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637000, P.R. China
| | - Linfeng Yang
- Department of Hepato-Biliary-Pancreas II, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637000, P.R. China
| | - Pengsheng Yi
- Department of Hepato-Biliary-Pancreas II, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637000, P.R. China
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Ramaswamy A, Shukla A, Engineer R, Sundaram S, Srinivas S, Kulkarni S, Patkar S, Baijal S, Kale A, Kapoor A, Mukund A, Choudhari A, Rauthan A, Mathew AS, Panchal R, Bhattacharya K, Patil P, Shetty N, Gala K, Kumar L, Thiruchunapalli D, Kalra N, Sahoo TP, Krishna MV, Lavingia V, Mohanka R, Talwar V, Ostwal V, Bhargava P, Poddar J, Singal A, Goel M. Evaluation and Management of Unresectable Hepatocellular Carcinoma: Multidisciplinary Indian Consensus Statements from a Delphi Panel. South Asian J Cancer 2024. [DOI: 10.1055/s-0044-1788569] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/10/2025] Open
Abstract
Background India, like many parts of Asia, likely faces a high burden of hepatocellular carcinoma (HCC), though large-scale data on etiology, presentation, and outcomes are lacking. There appears to be a predominance of unresectable, advanced-stage HCC at presentation in India with variable level of expertise in India to manage these scenarios. This publication summarizes the latest evidence with cognizance of the unique challenges faced in India by treating clinicians.
Methods A multidisciplinary panel of medical oncologists, gastroenterologists, hepatologists, interventional radiologists, and hepatobiliary surgical oncologists held a meeting in June 2022 and reviewed the evidence available for management of HCC. The meeting concentrated on the recognition and management of HCC not amenable to surgical approaches in the Indian context. A literature review of these aspects of management was conducted and consensus statements with level of evidence and grades of recommendation were prepared by individual specialists in each field. Statements were evaluated by the modified Delphi method.
Key Content and Findings The panel comprising 22 experts formulated 40 consensus statements with regard to defining unresectable HCC, optimization of underlying conditions prior to management, rationale use of various liver-directed therapies (LDTs) in unresectable HCC, and systemic therapeutic options in this group of patients.
Conclusion Our consensus statements offer practical, yet evidence-based management guidelines for treating unresectable HCC in the Indian context. There is an emphasis on the crucial need for combining available approaches for LDT, even if less well studied though possibly effective, with standard systemic therapy.
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Affiliation(s)
- Anant Ramaswamy
- Department of Medical Oncology, Tata Memorial Centre, Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, India
| | - Akash Shukla
- Department of Gastroenterology, Seth Gordhandas Sunderdas Medical College (GSMC) & King Edward Memorial (KEM) Hospital, Mumbai, Maharashtra, India
- Department of Hepatology, Sir H.N. Reliance Foundation Hospital, Mumbai, Maharashtra, India
| | - Reena Engineer
- Department of Radiation Oncology, Tata Memorial Hospital, Mumbai, Maharashtra, India
| | - Sridhar Sundaram
- Department of Digestive Diseases and Clinical Nutrition, Tata Memorial Hospital, Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, India
| | - Sujay Srinivas
- Department of Medical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, India
| | - Suyash Kulkarni
- Department of Radiodiagnosis, Tata Memorial Hospital, Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, India
| | - Shraddha Patkar
- Department of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, India
| | - Sanjay Baijal
- Department of Diagnostic and Interventional Radiology, Medanta Hospital, Gurugram, Haryana, India
| | - Aditya Kale
- Department of Digestive Diseases and Clinical Nutrition, Tata Memorial Hospital, Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, India
| | - Akhil Kapoor
- Department of Medical Oncology, Tata Memorial Hospital (TMH), Homi Bhabha Cancer Hospital (HBCH) and Mahamana Pt Madan Mohan Malaviya Cancer Centre (MPMMCC), Varanasi, Uttar Pradesh, India
| | - Amar Mukund
- Department of Interventional Radiology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Amit Choudhari
- Department of Radio-diagnosis, Tata Memorial Hospital, Mumbai, Maharashtra, India
| | - Amit Rauthan
- Department of Medical Oncology, Manipal Hospital, Bangalore, Karnataka, India
| | - Ashwathy Susan Mathew
- Department of Radiation Oncology, Apollo Proton Cancer Centre, Chennai, Tamil Nadu, India
| | - Rushi Panchal
- Department of Radiation Oncology, MS Patel Cancer Centre, Shree Krishna Hospital, Bhaikaka University, Karamsad-Anand, Gujarat, India
| | - Kausik Bhattacharya
- Department of Radiation Oncology, AIG Hospitals. Hyderabad, Telangana, India
| | - Prachi Patil
- Department of Digestive Diseases and Clinical Nutrition, Tata Memorial Hospital, Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, India
| | - Nitin Shetty
- Department of Radiodiagnosis, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Mumbai, Maharashtra, India
| | - Kunal Gala
- Department of Radio-diagnosis, Tata Memorial Hospital, Mumbai, Maharashtra, India
| | - Lijesh Kumar
- Department of Endovascular and Interventional Radiology, Lisie Hospital, Kochi, Kerala, India
| | - Deepashree Thiruchunapalli
- Department of Interventional Radiology, Dr. Rela Institute and Medical Centre, Chennai, Tamil Nadu, India
| | - Naveen Kalra
- Department of Radio-diagnosis, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
| | - Tarini Prasad Sahoo
- Department of Medical Oncology, Silverline Hospital, Bhopal, Madhya Pradesh, India
| | - M Vamshi Krishna
- Department of Medical Oncology and Hematology, Institute of Oncology, AIG Hospital, Hyderabad, Telangana, India
| | - Viraj Lavingia
- Department of Medical Oncology, HCG Cancer Centre, Ahmedabad, Gujarat, India
| | - Ravi Mohanka
- Department of Liver Transplant and HPB Surgery, Sir H.N. Reliance Hospital, Mumbai, Maharashtra, India
| | - Vineet Talwar
- Department of Medical Oncology Rajiv Gandhi Cancer Institute, Delhi, India
| | - Vikas Ostwal
- Department of Medical Oncology, Tata Memorial Centre, Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, India
| | - Prabhat Bhargava
- Department of Medical Oncology, Tata Memorial Centre, Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, India
| | - Jyoti Poddar
- Radiation Oncologist, Therapy Area Medical Expert (Hepatocellular Carcinoma) Roche (India) Pvt Limited
| | - Amit Singal
- Department of Medicine, UT Southwestern Medical Center, Dallas, Texas, United States
| | - Mahesh Goel
- Department of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, India
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Shiba S, Shiraishi S, Tokuuye K, Shirata R, Omura M. Proton-beam Therapy for Locally Advanced Hepatocellular Carcinoma With Inferior Vena Cava Tumor Thrombus: Case Report. In Vivo 2024; 38:2080-2084. [PMID: 38936928 PMCID: PMC11215571 DOI: 10.21873/invivo.13667] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2024] [Revised: 04/25/2024] [Accepted: 04/26/2024] [Indexed: 06/29/2024]
Abstract
BACKGROUND/AIM We report on a case of locally advanced hepatocellular carcinoma (HCC) accompanied by an inferior vena cava tumor thrombus (IVCTT), treated successfully with proton-beam therapy (PBT). CASE REPORT A 63-year-old male presented with a primary, single HCC with IVCTT, without metastasis to the intrahepatic region, lymph nodes, or distant organs. The clinical staging was identified as T4N0M0 Stage IIIB. The patient's liver function was classified as Child-Pugh class A (score: 6), with a modified albumin-bilirubin (mALBI) grade of 2a. The patient had liver cirrhosis due to non-alcoholic steatohepatitis. Magnetic resonance imaging revealed a nodular tumor measuring 13.2×8.9×9.8 cm across segments 1, 6, 7, and 8, along with IVCTT. The patient received PBT, with a total dose of 72.6 Gy (relative biological effectiveness) delivered in 22 fractions. Throughout the PBT treatment, the patient experienced no acute toxicities and completed the therapy as planned. Twelve months following PBT, the patient was alive without evidence of local recurrence, lymph node involvement, or distant organ metastasis. The only late toxicity observed was a mild worsening of the mALBI grade. CONCLUSION We observed a favorable local response with manageable toxicities in a patient with locally advanced HCC and IVCTT treated with PBT. While this is a single case report, our findings suggest that PBT could be considered a viable treatment option for HCC with IVCTT.
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Affiliation(s)
- Shintaro Shiba
- Department of Radiation Oncology, Shonan Kamakura General Hospital, Kamakura, Japan;
- Department of Radiation Oncology, Gunma University Graduate School of Medicine, Maebashi, Japan
| | - Sachika Shiraishi
- Department of Radiation Oncology, Shonan Kamakura General Hospital, Kamakura, Japan
| | - Koichi Tokuuye
- Department of Radiation Oncology, Shonan Kamakura General Hospital, Kamakura, Japan
| | - Ryosuke Shirata
- Department of Medical Physics, Shonan Kamakura General Hospital, Kamakura, Japan
| | - Motoko Omura
- Department of Radiation Oncology, Shonan Kamakura General Hospital, Kamakura, Japan
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Sun B, Chen L, Lei Y, Zhang L, Sun T, Liu Y, Zheng C. Sorafenib plus transcatheter arterial chemoembolization with or without camrelizumab for the treatment of intermediate and advanced hepatocellular carcinoma. Br J Radiol 2024; 97:1320-1327. [PMID: 38711192 PMCID: PMC11186562 DOI: 10.1093/bjr/tqae087] [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: 08/14/2023] [Revised: 04/22/2024] [Accepted: 04/28/2024] [Indexed: 05/08/2024] Open
Abstract
OBJECTIVES To compare the efficacy and safety of transcatheter arterial chemoembolization (TACE) combined with sorafenib and camrelizumab or with sorafenib alone in patients with intermediate or advanced hepatocellular carcinoma (HCC). METHODS We retrospectively analysed 78 patients with intermediate or advanced HCC who were treated at our centres between January 2018 and December 2021. Twenty-six of them received sorafenib and camrelizumab plus TACE (the TACE + Sor + C group), while 52 received TACE and sorafenib (the TACE + Sor group). Overall survival (OS), progression-free survival (PFS), and adverse events (AEs) were evaluated. Univariate and multivariate analyses were used to determine the factors affecting survival. RESULTS The median OS (22 vs 10 months, P < .001) and median PFS (11 vs 6 months, P = .008) of the TACE + Sor + C group were significantly higher than those of the TACE + Sor group. Multivariate analysis showed that compared with TACE + Sor + C, TACE + Sor increased the risk of all-cause mortality and tumour progression. For grade I and II AEs, the incidence of skin capillary hyperplasia and hypothyroidism in the TACE + Sor + C group was significantly higher than that in the TACE + Sor group. For serious AEs (grade III or IV), there was no significant difference in any adverse reaction between the 2 groups (P > .05). CONCLUSION Patients with intermediate or advanced HCC appeared to benefit more in terms of survival from TACE + Sor + C than from TACE + Sor, and the AEs were tolerable. ADVANCES IN KNOWLEDGE (1) Subgroup analysis demonstrated that TACE + sorafenib + camrelizumab could benefit HCC patients regardless of whether they had portal vein tumour thrombosis, Barcelona Clinic Liver Cancer B or C, or CHILD A or B; (2) We reported the immunotherapy-related AEs occurred with a significantly higher incidence in triple treatment, but all the AEs are tolerable.
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Affiliation(s)
- Bo Sun
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, China
- Department of Interventional Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Lei Chen
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, China
- Department of Interventional Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Yu Lei
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, China
- Department of Interventional Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Lijie Zhang
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, China
- Department of Interventional Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
- Department of Interventional Radiology, The Fifth Medical Center of Chinese, PLA General Hospital, Beijing 100039, China
| | - Tao Sun
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, China
- Department of Interventional Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Yiming Liu
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, China
- Department of Interventional Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Chuansheng Zheng
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, China
- Department of Interventional Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
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Wang H, Bo W, Feng X, Zhang J, Li G, Chen Y. Strategies and Recent Advances on Improving Efficient Antitumor of Lenvatinib Based on Nanoparticle Delivery System. Int J Nanomedicine 2024; 19:5581-5603. [PMID: 38882543 PMCID: PMC11177867 DOI: 10.2147/ijn.s460844] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2024] [Accepted: 05/28/2024] [Indexed: 06/18/2024] Open
Abstract
Lenvatinib (LVN) is a potentially effective multiple-targeted receptor tyrosine kinase inhibitor approved for treating hepatocellular carcinoma, metastatic renal cell carcinoma and thyroid cancer. Nonetheless, poor pharmacokinetic properties including poor water solubility and rapid metabolic, complex tumor microenvironment, and drug resistance have impeded its satisfactory therapeutic efficacy. This article comprehensively reviews the uses of nanotechnology in LVN to improve antitumor effects. With the characteristic of high modifiability and loading capacity of the nano-drug delivery system, an active targeting approach, controllable drug release, and biomimetic strategies have been devised to deliver LVN to target tumors in sequence, compensating for the lack of passive targeting. The existing applications and advances of LVN in improving therapeutic efficacy include improving longer-term efficiency, achieving higher efficiency, combination therapy, tracking and diagnosing application and reducing toxicity. Therefore, using multiple strategies combined with photothermal, photodynamic, and immunoregulatory therapies potentially overcomes multi-drug resistance, regulates unfavorable tumor microenvironment, and yields higher synergistic antitumor effects. In brief, the nano-LVN delivery system has brought light to the war against cancer while at the same time improving the antitumor effect. More intelligent and multifunctional nanoparticles should be investigated and further converted into clinical applications in the future.
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Affiliation(s)
- Haiqing Wang
- Department of Hepatopancreatobiliary Surgery, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital and Institute, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, People’s Republic of China
| | - Wentao Bo
- Department of Hepatopancreatobiliary Surgery, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital and Institute, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, People’s Republic of China
| | - Xielin Feng
- Department of Hepatopancreatobiliary Surgery, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital and Institute, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, People’s Republic of China
| | - Jinliang Zhang
- Department of Hepatopancreatobiliary Surgery, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital and Institute, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, People’s Republic of China
| | - Ge Li
- Department of Emergency, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital and Institute, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, People’s Republic of China
| | - Yan Chen
- Department of Pharmacy, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital and Institute, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, People’s Republic of China
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Wu Q, Wang Y, Wei Y, Yang Z, Chen K, Li J, Li L, Su T, Liang S. Development and validation of a nomogram for radiation-induced hepatic toxicity after intensity modulated radiotherapy for hepatocellular carcinoma: a retrospective study. Jpn J Clin Oncol 2024; 54:699-707. [PMID: 38376811 PMCID: PMC11144290 DOI: 10.1093/jjco/hyae024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2023] [Accepted: 01/30/2024] [Indexed: 02/21/2024] Open
Abstract
OBJECTIVE This study aimed to construct a nomogram to predict radiation-induced hepatic toxicity in patients with hepatocellular carcinoma treated with intensity-modulated radiotherapy. METHODS This study reviewed the clinical characteristics and dose-volume parameters of 196 patients with hepatocellular carcinoma. Radiation-induced hepatic toxicity was defined as progression of the Child-Pugh score caused by intensity-modulated radiotherapy. Factors relevant to radiation-induced hepatic toxicity were selected using receiver operating characteristic and univariate logistic analysis. A risk assessment model was developed, and its discrimination was validated. RESULTS Eighty-eight (44.90%) and 28 (14.29%) patients had radiation-induced hepatic toxicity ≥ 1 (Child-Pugh ≥ 1) and radiation-induced hepatic toxicity ≥ 2 (Child-Pugh ≥ 2). Pre-treatment Child-Pugh, body mass index and dose-volume parameters were correlated with radiation-induced hepatic toxicity ≥ 1 using univariate logistic analysis. V15 had the best predictive effectiveness among the dose-volume parameters in both the training (area under the curve: 0.763, 95% confidence interval: 0.683-0.842, P < 0.001) and validation cohorts (area under the curve: 0.759, 95% confidence interval: 0.635-0.883, P < 0.001). The area under the curve values of the model that was constructed by pre-treatment Child-Pugh, body mass index and V15 for radiation-induced hepatic toxicity ≥1 were 0.799 (95% confidence interval: 0.719-0.878, P < 0.001) and 0.775 (95% confidence interval: 0.657-0.894, P < 0.001) in the training and validation cohorts, respectively. Patients with a body mass index ≤ 20.425, Barcelona clinic liver cancer = C, Hepatitis B Virus-positive, Eastern Cooperative Oncology Group = 1-2 and hepatic fibrosis require lower V15 dose limits. CONCLUSIONS Risk assessment model constructed from Pre-treatment Child-Pugh, V15 and body mass index can guide individualized patient selection of toxicity minimization strategies.
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Affiliation(s)
- Qiaoyuan Wu
- Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Yudan Wang
- Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Yuxin Wei
- Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Zhengqiang Yang
- Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Kai Chen
- Department of Biostatistics and Data Science, The University of Texas Health Science Center at Houston, Houston, TX, USA, and Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Jianxu Li
- Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Liqing Li
- Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Tingshi Su
- Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Shixiong Liang
- Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, China
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