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Zhang W, Fu H, Liu ZR, Xu L, Che X, Ning YT, Zhan ZY, Zhou GC. Transarterial chemoembolization combined with lenvatinib vs transarterial chemoembolization combined with sorafenib for unresectable hepatocellular carcinoma: A systematic review and meta-analysis. World J Gastrointest Oncol 2025; 17:105887. [DOI: 10.4251/wjgo.v17.i6.105887] [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: 02/09/2025] [Revised: 03/25/2025] [Accepted: 04/23/2025] [Indexed: 06/13/2025] Open
Abstract
BACKGROUND Lenvatinib and sorafenib are tyrosine kinase inhibitors that are effective in the treatment of unresectable hepatocellular carcinoma (uHCC). The efficacy of which of them is better suited to combine transarterial chemoembolization (TACE) for the treatment of uHCC is ripe.
AIM To compare the effectiveness of TACE combined with lenvatinib (TACE-lenvatinib) and TACE combined with sorafenib (TACE-sorafenib) in the treatment of uHCC, this study was carried out.
METHODS Publicly available studies comparing the efficacy of TACE-lenvatinib and TACE-sorafenib in the treatment of uHCC were collected from PubMed, Embase and Cochrane Library, with a cut-off date of December 2024. Stata SE 15 software was used for statistical analysis.
RESULTS A total of six studies involving 547 patients were included, 248 in the TACE-lenvatinib group and 299 in the TACE-sorafenib group. Meta-analysis results showed that TACE-lenvatinib was more effective than TACE-sorafenib in complete response [relative risk (RR) = 1.81, 95% confidence interval (CI): 1.11-2.96, P = 0.02], partial response (RR = 1.38, 95%CI: 1.12-1.70, P = 0.002), objective response rate (RR = 1.47, 95%CI: 1.24-1.74, P < 0.0001) and disease control rate (RR = 1.22, 95%CI: 1.00-1.49, P = 0.05). TACE-lenvatinib was significantly lower than TACE-sorafenib in progressive disease rate (RR = 0.54, 95%CI: 0.39-0.74, P = 0.002). No significant difference was found in stable disease rate (RR = 0.89, 95%CI: 0.60-1.33, P = 0.58) between the two groups. TACE-lenvatinib was significantly more effective than TACE-sorafenib in overall survival (hazard ratio = 2.00, 95%CI: 1.59-2.50, P < 0.05) and progression free survival (hazard ratio = 2.04, 95%CI: 1.49-2.86, P < 0.05). As regards adverse events, TACE-lenvatinib was better in reducing the incidence of hypertension than TACE-sorafenib, while no significant difference was found in overall adverse events, abdominal pain, fever, fatigue, nausea and vomiting, decreased appetite, liver dysfunction, hand-foot skin reaction, diarrhea, thrombocytopenia, and rash between the two groups.
CONCLUSION In patients with uHCC, TACE-lenvatinib induced a better tumor response rate and survival outcome than TACE-sorafenib, while TACE-lenvatinib resulted in a higher incidence of hypertension than TACE-sorafenib. However, these conclusions are derived from currently available medical evidence, and further confirmation by more rigorously designed randomized controlled studies is still needed.
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Affiliation(s)
- Wei Zhang
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen 518116, Guangdong Province, China
| | - Hua Fu
- Department of Hepatobiliary Surgery, People’s Hospital of Xiangxi Autonomous Prefecture, Jishou 416000, Hunan Province, China
| | - Zi-Rong Liu
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen 518116, Guangdong Province, China
| | - Lin Xu
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen 518116, Guangdong Province, China
| | - Xu Che
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen 518116, Guangdong Province, China
| | - Yan-Ting Ning
- Department of Nursing, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen 518116, Guangdong Province, China
| | - Zheng-Yin Zhan
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen 518116, Guangdong Province, China
| | - Guo-Chao Zhou
- Department of Hepatobiliary Surgery, People’s Hospital of Xiangxi Autonomous Prefecture, Jishou 416000, Hunan Province, China
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Kudo M. Systemic Therapy Combined with Locoregional Therapy in Intermediate-stage Hepatocellular Carcinoma. INTERVENTIONAL RADIOLOGY (HIGASHIMATSUYAMA-SHI (JAPAN) 2025; 10:e20230035. [PMID: 40384918 PMCID: PMC12078074 DOI: 10.22575/interventionalradiology.2023-0035] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/22/2023] [Accepted: 02/24/2024] [Indexed: 05/20/2025]
Abstract
Recent advances in systemic therapy for hepatocellular carcinoma are remarkable. The treatment goal for advanced hepatocellular carcinoma is to prolong survival, while for intermediate-stage hepatocellular carcinoma, it is to achieve a cancer-free and drug-free status. Patients unsuitable for transarterial chemoembolization may benefit from prior systemic therapy with lenvatinib or atezolizumab plus bevacizumab. The TACTICS-L trial, a prospective phase II trial, demonstrated favorable progression-free and overall survival by lenvatinib-transarterial chemoembolization sequential therapy. The REPLACEMENT trial, a multicenter, prospective, single-arm phase II trial, confirmed combination immunotherapy efficacy with atezolizumab plus bevacizumabin a population exceeding up-to-seven criteria. In a proof-of-concept study, atezolizumab plus bevacizumab plus curative therapy showed a 35% complete response rate and 23% drug-free status in intermediate-stage hepatocellular carcinoma patients with a tumor burden exceeding up-to-seven criteria.
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Affiliation(s)
- Masatoshi Kudo
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Japan
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Rinka K, Kioka K, Amano Y, Nakai T, Kawasaki Y, Kawada N. Three effective cases of transcatheter arterial embolization after atezolizumab and bevacizumab treatment for hepatocellular carcinoma: a case report. J Med Case Rep 2025; 19:38. [PMID: 39871286 PMCID: PMC11770955 DOI: 10.1186/s13256-025-05040-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2023] [Accepted: 01/06/2025] [Indexed: 01/29/2025] Open
Abstract
BACKGROUND The Barcelona Clinic Liver Cancer staging system classifies hepatocellular carcinoma on the basis of tumor characteristics, liver function, and Eastern Cooperative Oncology Group performance status. Hepatocellular carcinoma is divided into five stages, and the treatment options for intermediate-stage hepatocellular carcinoma have evolved in recent years. Transcatheter arterial chemoembolization remains the standard treatment for intermediate-stage (stage B) hepatocellular carcinoma. However, the concepts of transcatheter-arterial-chemoembolization-unsuitable and transcatheter-arterial-chemoembolization-refractory tumors have emerged. The authors herein describe three Japanese patients with hepatocellular carcinoma who were treated with atezolizumab and bevacizumab followed by transcatheter arterial embolization or transcatheter arterial chemoembolization. Cases 1 and 2 were transcatheter-arterial-chemoembolization-unsuitable, and Case 3 was transcatheter-arterial-chemoembolization-refractory. All patients achieved a complete response, assessed according to the modified Response Evaluation Criteria in Solid Tumors guidelines. CASE PRESENTATION The first patient was a 65-year-old Japanese man with a primary 11 cm hepatocellular carcinoma. He started treatment with atezolizumab and bevacizumab but developed grade 3 liver injury after two courses, leading to the discontinuation of these drugs and subsequent bland transcatheter arterial embolization. The second patient was an 82-year-old Japanese woman with multiple primary hepatocellular carcinomas. After one course of atezolizumab and bevacizumab, the treatment was interrupted because of grade 3 proteinuria. Bland transcatheter arterial embolization was performed after completing one course of atezolizumab and bevacizumab and one course of atezolizumab alone. The third patient was an 83-year-old Japanese man with recurrent multiple hepatocellular carcinomas. Despite 12 courses of atezolizumab and bevacizumab, the tumor in segment 4 of the liver increased in size and showed arterial-phase enhancement. Transcatheter arterial chemoembolization was performed to treat this tumor. All three patients achieved a complete response based on the modified Response Evaluation Criteria in Solid Tumors guidelines. CONCLUSION Atezolizumab and bevacizumab followed by transcatheter arterial embolization may be an effective treatment strategy for patients with intermediate-stage hepatocellular carcinoma that is transcatheter-arterial-chemoembolization-refractory or transcatheter-arterial-chemoembolization-unsuitable.
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MESH Headings
- Humans
- Carcinoma, Hepatocellular/therapy
- Carcinoma, Hepatocellular/pathology
- Carcinoma, Hepatocellular/diagnostic imaging
- Liver Neoplasms/therapy
- Liver Neoplasms/pathology
- Liver Neoplasms/diagnostic imaging
- Bevacizumab/therapeutic use
- Bevacizumab/administration & dosage
- Antibodies, Monoclonal, Humanized/therapeutic use
- Antibodies, Monoclonal, Humanized/administration & dosage
- Male
- Aged
- Chemoembolization, Therapeutic/methods
- Female
- Treatment Outcome
- Embolization, Therapeutic/methods
- Antineoplastic Agents, Immunological/therapeutic use
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Affiliation(s)
- Koji Rinka
- Department of Hepatology, Osaka City General Hospital, 2-13-22 Miyakojima-Hondori Miyakojima-Ku, Osaka, 534-0021, Japan.
| | - Kiyohide Kioka
- Department of Hepatology, Osaka City General Hospital, 2-13-22 Miyakojima-Hondori Miyakojima-Ku, Osaka, 534-0021, Japan
| | - Yuga Amano
- Department of Hepatology, Osaka City General Hospital, 2-13-22 Miyakojima-Hondori Miyakojima-Ku, Osaka, 534-0021, Japan
| | - Takashi Nakai
- Department of Hepatology, Osaka City General Hospital, 2-13-22 Miyakojima-Hondori Miyakojima-Ku, Osaka, 534-0021, Japan
| | - Yasuko Kawasaki
- Department of Hepatology, Osaka City General Hospital, 2-13-22 Miyakojima-Hondori Miyakojima-Ku, Osaka, 534-0021, Japan
| | - Norifumi Kawada
- Department of Hepatology, Osaka Metropolitan University Graduate School of Medicine, 1-5-7, Asahimachi, Abeno-Ku, Osaka, 545-8585, Japan
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Sun Q, Wu Z, Yin X, Li F, Liu R. Association between transarterial chemoembolization refractoriness and prognosis in Chinese patients with hepatocellular carcinoma: a large retrospective cohort study. Front Oncol 2025; 14:1483949. [PMID: 39902133 PMCID: PMC11788167 DOI: 10.3389/fonc.2024.1483949] [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: 08/20/2024] [Accepted: 12/27/2024] [Indexed: 02/05/2025] Open
Abstract
Background Hepatocellular carcinoma (HCC) is commonly treated with transarterial chemoembolization (TACE) in intermediate stages. Existing international definitions of TACE refractoriness may not fully suit Chinese patients. The Chinese College of Interventionalists (CCI) proposed a tailored definition, but its impact on HCC prognosis is still limited. Methods This study included 844 patients with Barcelona Clinic Liver Cancer (BCLC) stage B HCC from a multicenter dataset. Propensity score matching (PSM) was used to minimize baseline differences between the TACE-Refractoriness (n = 54) and TACE-Non-Refractoriness (n = 108) groups. Kaplan-Meier survival analysis and multivariate Cox regression models were performed to evaluate the association between TACE-Refractoriness and OS. Subgroup analyses were conducted across key clinical and tumor-related characteristics. Results Kaplan-Meier survival analysis indicated that patients classified as TACE-Refractory exhibited significantly shorter OS compared to those categorized as TACE-Non-Refractory in both the original and matched cohorts (P < 0.001). Furthermore, multivariate analysis identified TACE refractoriness as a significant predictor of poorer OS, yielding an adjusted hazard ratio (HR) of 5.96 (95% CI: 3.39-10.5, P < 0.001). Subgroup analysis further demonstrated the robustness of these findings across subgroups, except in female patients (HR = 3.0, 95% CI: 0.72-12.52; P=0.131). Conclusions CCI-defined TACE refractoriness is associated with reduced OS in patients with BCLC stage B HCC undergoing TACE.
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Affiliation(s)
- Qinxue Sun
- Department of Interventional Radiology, Ningbo Medical Center LiHuiLi Hospital (The Affiliated LiHuiLi Hospital of Ningbo University), Ningbo, Zhejiang, China
| | - Ziliang Wu
- Department of Interventional Radiology, Ningbo Medical Center LiHuiLi Hospital (The Affiliated LiHuiLi Hospital of Ningbo University), Ningbo, Zhejiang, China
| | - Xi Yin
- Department of Radiology, Mental Health Institute of Inner Mongolia Autonomous Region (The Third Hospital of Inner Mongolia Autonomous Region, Brain Hospital of Inner Mongolia Autonomous Region), Hohhot, Inner Mongolia, China
| | - Feng Li
- Department of Interventional Radiology, Ningbo Medical Center LiHuiLi Hospital (The Affiliated LiHuiLi Hospital of Ningbo University), Ningbo, Zhejiang, China
| | - Ri Liu
- Department of Interventional Radiology, Ningbo Medical Center LiHuiLi Hospital (The Affiliated LiHuiLi Hospital of Ningbo University), Ningbo, Zhejiang, China
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Han F, Wang XH, Xu CZ. Clinical benefits of transarterial chemoembolization combined with tyrosine kinase and immune checkpoint inhibitors for unresectable hepatocellular carcinoma. World J Gastrointest Oncol 2024; 16:3308-3320. [PMID: 39072161 PMCID: PMC11271784 DOI: 10.4251/wjgo.v16.i7.3308] [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: 04/24/2024] [Revised: 05/17/2024] [Accepted: 05/20/2024] [Indexed: 07/12/2024] Open
Abstract
BACKGROUND Combination therapy has emerged as the focus of research for unresectable hepatocellular carcinoma (HCC). In recent years, several studies have explored the clinical efficacy and safety of the combination therapies of transarterial chemoembolization (TACE) with tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs). AIM To conduct an updated meta-analysis verifying the clinical benefits and adverse effects of the triple combination therapy for unresectable HCC. METHODS All eligible cohort, non-randomized controlled, and randomized controlled trial studies from the PubMed, Web of Science, Embase, Cochrane Library, and MedLine databases up to March 20, 2024 were screened for the present meta-analysis. The study endpoints included complete response (CR), objective response rate (ORR), disease control rate (DCR), overall survival (OS), progression-free survival (PFS), and adverse events (AEs). Stata 16/18 software was used for this meta-analysis, and a P value of <0.05 was considered statistically significant. RESULTS A total of 29 studies with 1754 patients were included. Among the patients who received the TACE therapy with TKIs and ICIs, the tumor response results revealed a pooled CR, ORR, and DCR of 14% [95%CI (0.11-0.18)], 61% [95%CI (0.55-0.66)], and 85% [95%CI (0.83-0.87)], respectively. In terms of the survival outcomes, the pooled median PFS and OS were 10.25 months [95%CI (9.31-11.18)] and 20.47 months [95%CI (18.98-21.97)], respectively. The pooled prevalence of all-grade AEs during the triple treatment was 90% [95%CI (0.84-0.94)] and that of grade ≥ 3 AEs was 32% [95%CI (0.24-0.42)]. CONCLUSION The combination therapy of TACE, TKIs, and ICIs exhibits great clinical benefits for unresectable HCC in terms of tumor responses and survival outcomes without increasing the risk of severe AEs.
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Affiliation(s)
- Feng Han
- Department of Gastroenterology, The First Hospital of Jiaxing, The Affiliated Hospital of Jiaxing University, Jiaxing 314001, Zhejiang Province, China
| | - Xiao-Han Wang
- Department of Gastroenterology, The First Hospital of Jiaxing, The Affiliated Hospital of Jiaxing University, Jiaxing 314001, Zhejiang Province, China
| | - Chen-Zhou Xu
- Department of Gastroenterology, The First Hospital of Jiaxing, The Affiliated Hospital of Jiaxing University, Jiaxing 314001, Zhejiang Province, China
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Yang C, Yang HC, Luo YG, Li FT, Cong TH, Li YJ, Ye F, Li X. Predicting Survival Using Whole-Liver MRI Radiomics in Patients with Hepatocellular Carcinoma After TACE Refractoriness. Cardiovasc Intervent Radiol 2024; 47:964-977. [PMID: 38750156 DOI: 10.1007/s00270-024-03730-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2023] [Accepted: 04/07/2024] [Indexed: 07/12/2024]
Abstract
PURPOSE To develop a model based on whole-liver radiomics features of pre-treatment enhanced MRI for predicting the prognosis of hepatocellular carcinoma (HCC) patients undergoing continued transarterial chemoembolization (TACE) after TACE-resistance. MATERIALS AND METHODS Data from 111 TACE-resistant HCC patients between January 2014 and March 2018 were retrospectively collected. At a ratio of 7:3, patients were randomly assigned to developing and validation cohorts. The whole-liver were manually segmented, and the radiomics signature was extracted. The tumor and liver radiomics score (TLrad-score) was calculated. Models were trained by machine learning algorithms and their predictive efficacies were compared. RESULTS Tumor stage, tumor burden, body mass index, alpha-fetoprotein, and vascular invasion were revealed as independent risk factors for survival. The model trained by Random Forest algorithms based on tumor burden, whole-liver radiomics signature, and clinical features had the highest predictive efficacy, with c-index values of 0.85 and 0.80 and areas under the ROC curve of 0.96 and 0.83 in the developing cohort and validation cohort, respectively. In the high-rad-score group (TLrad-score > - 0.34), the median overall survival (mOS) was significantly shorter than in the low-rad-score group (17 m vs. 37 m, p < 0.001). A shorter mOS was observed in patients with high tumor burden compared to those with low tumor burden (14 m vs. 29 m, p = 0.007). CONCLUSION The combined radiomics model from whole-liver signatures may effectively predict survival for HCC patients continuing TACE after TACE refractoriness. The TLrad-score and tumor burden are potential prognostic markers for TACE therapy following TACE-resistance.
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Affiliation(s)
- Chao Yang
- Department of Radiology, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, China
| | - Hong-Cai Yang
- Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17 Panjiayuan Nanli, Chaoyang District, Beijing, 100021, China
| | - Yin-Gen Luo
- Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17 Panjiayuan Nanli, Chaoyang District, Beijing, 100021, China
| | - Fu-Tian Li
- Huiying Medical Technology (Beijing) Co., Ltd, Beijing, 100192, China
| | - Tian-Hao Cong
- Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17 Panjiayuan Nanli, Chaoyang District, Beijing, 100021, China
| | - Yu-Jie Li
- Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17 Panjiayuan Nanli, Chaoyang District, Beijing, 100021, China
| | - Feng Ye
- Department of Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
| | - Xiao Li
- Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17 Panjiayuan Nanli, Chaoyang District, Beijing, 100021, China.
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Chen YX, Zhang JX, Zhou CG, Liu J, Liu S, Shi HB, Zu QQ, Cheng Y. Efficacy and Safety of TACE Combined with a Tyrosine Kinase Inhibitor for the Treatment of TACE-Refractory Hepatocellular Carcinoma: A Retrospective Comparative Study. J Gastrointest Cancer 2024; 55:924-931. [PMID: 38470522 DOI: 10.1007/s12029-024-01036-4] [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] [Accepted: 03/02/2024] [Indexed: 03/14/2024]
Abstract
PURPOSE Combining angiogenesis inhibitors may enhance therapeutic efficacy synergistically after TACE refractoriness. The purpose of this study was to compare the outcomes of transarterial chemoembolization (TACE) plus a tyrosine kinase inhibitor (TACE-TKI) with TKI only for patients with TACE-refractory hepatocellular carcinoma (HCC). METHODS From January 2019 to March 2022, 101 HCC patients confirmed with TACE-refractory were retrospectively reviewed in the study. Progression-free survival (PFS), overall survival (OS), tumor response, and adverse events (AEs) were evaluated between groups. RESULTS Fifty-two patients undergoing TACE-TKI, while 32 patients receiving TKI alone were included. The objective response rate (ORR) was higher in the TACE-TKI group compared with the TKI group (55.8% vs. 25.0%, P = 0.006). The median PFS in the TACE-TKI group was significantly longer than that in the TKI group (7.6 months vs. 4.9 months, P = 0.018). The median OS was non reach to statistical longer than that in the TKI alone group (19.5 months vs. 17.7 months, P = 0.055). Subgroup analysis showed that TACE-TKI treatment resulted in a significantly longer median PFS and OS for Barcelona Clinic Liver Cancer (BCLC) stage B patients (PFS 11.8 months vs. 5.1 months, P = 0.017; OS 30.3 months vs. 19.4 months, P = 0.022). CONCLUSION For patients with TACE-refractory HCC, TACE-TKI appeared to be superior to TKI monotherapy with regard to tumor control and PFS. Furthermore, for the BCLC stage B subgroup, TACE-TKI therapy was superior to TKI monotherapy in both OS and PFS.
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Affiliation(s)
- Yu-Xing Chen
- Department of Interventional Radiology, The First Affiliated Hospital With Nanjing Medical University, No. 300, Guangzhou Rd, Nanjing, 210029, China
| | - Jin-Xing Zhang
- Department of Interventional Radiology, The First Affiliated Hospital With Nanjing Medical University, No. 300, Guangzhou Rd, Nanjing, 210029, China
| | - Chun-Gao Zhou
- Department of Interventional Radiology, The First Affiliated Hospital With Nanjing Medical University, No. 300, Guangzhou Rd, Nanjing, 210029, China
| | - Jin Liu
- Department of Clinical Medicine Research Institution, The First Affiliated Hospital With Nanjing Medical University, Nanjing, 210029, China
| | - Sheng Liu
- Department of Interventional Radiology, The First Affiliated Hospital With Nanjing Medical University, No. 300, Guangzhou Rd, Nanjing, 210029, China
| | - Hai-Bin Shi
- Department of Interventional Radiology, The First Affiliated Hospital With Nanjing Medical University, No. 300, Guangzhou Rd, Nanjing, 210029, China
| | - Qing-Quan Zu
- Department of Interventional Radiology, The First Affiliated Hospital With Nanjing Medical University, No. 300, Guangzhou Rd, Nanjing, 210029, China.
| | - Yuan Cheng
- Department of Medical Oncology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210002, China.
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Diao L, Wang C, You R, Leng B, Yu Z, Xu Q, Cheng Y, Yin G. Hepatic arterial infusion chemotherapy combined with lenvatinib and PD-1 inhibitors versus lenvatinib and PD-1 inhibitors for HCC refractory to TACE. J Gastroenterol Hepatol 2024; 39:746-753. [PMID: 38240156 DOI: 10.1111/jgh.16463] [Citation(s) in RCA: 9] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2023] [Revised: 11/21/2023] [Accepted: 12/08/2023] [Indexed: 04/04/2024]
Abstract
BACKGROUND AND AIM The study aims to investigate the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) combined with lenvatinib and immune checkpoint inhibitors (ICIs) versus lenvatinib and ICIs for hepatocellular carcinoma (HCC) with transarterial chemoembolization (TACE) refractoriness. METHODS Patients with intermediate or advanced TACE-refractory HCC who received lenvatinib and ICIs with or without HAIC between 2020 and 2022 were retrospectively reviewed. The tumor response, overall survival (OS), progression-free survival (PFS), and treatment-related adverse events (TRAEs) were evaluated and compared between the two groups. Factors affecting OS and PFS were identified with univariate and multivariate Cox regression analyses. RESULTS A total of 121 patients were enrolled, with 58 patients assigned to the HAIC-Len-ICI group and 63 patients assigned to the Len-ICI group. A higher objective response rate and disease control rate were found in the HAIC-Len-ICI group than in the Len-ICI group (48.30% vs 23.80%, P = 0.005; 87.90% vs 69.80%, P = 0.02, respectively). The median OS was 24.0 months in the HAIC-Len-ICI group and 13.0 months in the Len-ICI group (P = 0.001). The median PFS was 13.0 months in the HAIC-Len-ICI group and 7.2 months in the Len-ICI group (P < 0.001). Multivariable analyses suggested that the presence of cirrhosis, Child-Pugh B stage, and HAIC-Len-ICI therapy option were prognostic factors for OS and PFS. The incidences of any grade and grade 3/4 TRAEs were both comparable between the two groups. CONCLUSIONS HAIC combined with lenvatinib and ICIs yielded better OS, PFS, ORR, and DCR than lenvatinib-ICI therapy in patients with HCC refractory to TACE, with manageable adverse events.
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Affiliation(s)
- Lingfeng Diao
- Department of Interventional Oncology, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China
| | - Chendong Wang
- Department of Interventional Oncology, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China
| | - Ran You
- Department of Interventional Oncology, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China
| | - Bin Leng
- Department of Interventional Oncology, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China
| | - Zeyu Yu
- Department of Interventional Oncology, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China
| | - Qingyu Xu
- Department of Interventional Oncology, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China
| | - Yuan Cheng
- Department of Oncology, Bayi Hospital Affiliated to Nanjing University of Chinese Medicine, Nanjing, China
| | - Guowen Yin
- Department of Interventional Oncology, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China
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Li J, Liu Y, Zheng R, Qu C, Li J. Molecular mechanisms of TACE refractoriness: Directions for improvement of the TACE procedure. Life Sci 2024; 342:122540. [PMID: 38428568 DOI: 10.1016/j.lfs.2024.122540] [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: 12/08/2023] [Revised: 02/24/2024] [Accepted: 02/25/2024] [Indexed: 03/03/2024]
Abstract
Transcatheter arterial chemoembolisation (TACE) is the standard of care for intermediate-stage hepatocellular carcinoma and selected patients with advanced hepatocellular carcinoma. However, TACE does not achieve a satisfactory objective response rate, and the concept of TACE refractoriness has been proposed to identify patients who do not fully benefit from TACE. Moreover, repeated TACE is necessary to obtain an optimal and sustained anti-tumour response, which may damage the patient's liver function. Therefore, studies have recently been performed to improve the effectiveness of TACE. In this review, we summarise the detailed molecular mechanisms associated with TACE responsiveness and relapse after this treatment to provide more effective targets for adjuvant therapy while helping to improve TACE regimens.
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Affiliation(s)
- Jiahao Li
- Department of Interventional Therapy, The First Hospital of Jilin University, Changchun, Jilin Province, People's Republic of China; The Public Laboratory Platform of the First Hospital of Jilin University, Changchun, Jilin Province, People's Republic of China
| | - Yingnan Liu
- Department of Radiology, The First Hospital of Jilin University, Changchun, Jilin Province, People's Republic of China
| | - Ruipeng Zheng
- Department of Interventional Therapy, The First Hospital of Jilin University, Changchun, Jilin Province, People's Republic of China
| | - Chao Qu
- Department of Interventional Therapy, The First Hospital of Jilin University, Changchun, Jilin Province, People's Republic of China; The Public Laboratory Platform of the First Hospital of Jilin University, Changchun, Jilin Province, People's Republic of China
| | - Jiarui Li
- Department of Interventional Therapy, The First Hospital of Jilin University, Changchun, Jilin Province, People's Republic of China.
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10
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Yuan G, Li W, Zang M, Li R, Li Q, Hu X, Zhang Q, Huang W, Ruan J, Pang H, Chen J. Transarterial chemoembolization with/without immune checkpoint inhibitors plus tyrosine kinase inhibitors for unresectable hepatocellular carcinoma: a single center, propensity score matching real-world study. Discov Oncol 2024; 15:68. [PMID: 38460053 PMCID: PMC10924872 DOI: 10.1007/s12672-024-00917-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/24/2023] [Accepted: 02/28/2024] [Indexed: 03/11/2024] Open
Abstract
OBJECTIVES To explore the efficacy and safety of Transarterial chemoembolization (TACE) in combination with immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs) in patients with unresectable hepatocellular carcinoma (uHCC). METHODS 456 patients with HCC receiving either TACE in combination with ICIs and TKIs (combination group, n = 139) or TACE monotherapy (monotherapy group, n = 317) were included from Apr 2016 to Dec 2021 in this retrospective study. We employed propensity score matching (PSM), performed 1:2 optimal pair matching, to balance potential bias. RESULTS The mean follow-up time is 24.7 months (95% CI 22.6-26.8) for matched patients as of March 2022. After matching, the combination group achieved longer OS and PFS (median OS:21.9 vs. 16.3 months, P = 0.022; median PFS: 8.3 vs. 5.1 months, P < 0.0001) than TACE monotherapy group. The combination group had better objective response rate (ORR) and disease control rate (DCR) (ORR: 52.5% vs. 32.8%, P < 0.001; DCR: 82.7% vs. 59.6%, P < 0.001). Subgroup analysis showed that patients who received "TKIs + ICIs" after the first TACE procedure (after TACE group) achieved longer OS than those before the first TACE procedure (before TACE group) (26.8 vs. 19.2 months, P = 0.011). Adverse events were consistent with previous studies of TACE-related trials. CONCLUSIONS TACE plus TKIs and ICIs appeared to deliver longer PFS and OS in HCC patients than TACE monotherapy. "TKIs + ICIs" co-treatment within 3 months after the first TACE procedure might be a better medication strategy.
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Affiliation(s)
- Guosheng Yuan
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, People's Republic of China
| | - Wenli Li
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, People's Republic of China
| | - Mengya Zang
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, People's Republic of China
| | - Rong Li
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, People's Republic of China
| | - Qi Li
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, People's Republic of China
| | - Xiaoyun Hu
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, People's Republic of China
| | - Qi Zhang
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, People's Republic of China
| | - Wei Huang
- Department of Oncology, Shunde Hospital, Southern Medical University, Shunde, Guangdong, 528300, People's Republic of China
| | - Jian Ruan
- Department of Medical Oncology, School of Medicine, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, 310003, People's Republic of China
| | - Huajin Pang
- Division of Vascular and Interventional Radiology, Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, People's Republic of China.
| | - Jinzhang Chen
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, People's Republic of China.
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11
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Ren Y, Liu Y, Song S, Zheng C. Efficacy and Safety of TACE Combined with Regorafenib versus TACE Combined with Camrelizumab in Hepatocellular Carcinoma With Untreatable Progression After TACE Combined with Sorafenib Therapy: A Case Control Study. Cancer Control 2024; 31:10732748241275004. [PMID: 39163892 PMCID: PMC11339741 DOI: 10.1177/10732748241275004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2024] [Revised: 07/03/2024] [Accepted: 07/30/2024] [Indexed: 08/22/2024] Open
Abstract
PURPOSE To evaluate the efficacy and safety of transarterial chemoembolization (TACE) combined with regorafenib (hereafter, TACE-regorafenib) or camrelizumab (hereafter, TACE-camrelizumab) for treating hepatocellular carcinoma (HCC) with untreatable progression after TACE and sorafenib therapy. METHODS The medical records of patients with HCC who received TACE-regorafenib or TACE-camrelizumab between September 2018 and December 2023 were retrospectively evaluated. Therapeutic response, overall survival (OS), progression-free survival (PFS), and adverse events (AEs) were compared between the two groups. RESULTS A total of 76 patients were enrolled in this study, with 41 and 35 patients in the TACE-regorafenib and TACE-camrelizumab groups, respectively. The objective response rates in the TACE-regorafenib and TACE-camrelizumab groups were 9.8% and 8.6%, respectively, with no statistically significant difference between the two groups (P = 0.859). Similarly, there was no statistically significant difference in disease control rates between the two groups (61.0% vs 68.6%, P = 0.838). The median OS was 11 months in the TACE-regorafenib group and 10 months in the TACE-camrelizumab group, with no significant difference between the two groups (P = 0.348). The TACE-regorafenib group had a median PFS of 7 months, which was significantly longer than that of the TACE-camrelizumab group (4 months, P = 0.004). There was no significant difference in the incidence of AEs between the two groups (P = 0.544). CONCLUSIONS TACE-regorafenib was safe, well-tolerated, and showed promising efficacy in patients with sorafenib-refractory advanced HCC, whereas TACE-camrelizumab demonstrated similar survival benefits.
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MESH Headings
- Humans
- Carcinoma, Hepatocellular/therapy
- Carcinoma, Hepatocellular/drug therapy
- Carcinoma, Hepatocellular/pathology
- Carcinoma, Hepatocellular/mortality
- Liver Neoplasms/therapy
- Liver Neoplasms/drug therapy
- Liver Neoplasms/pathology
- Liver Neoplasms/mortality
- Chemoembolization, Therapeutic/methods
- Chemoembolization, Therapeutic/adverse effects
- Sorafenib/therapeutic use
- Sorafenib/administration & dosage
- Male
- Female
- Middle Aged
- Phenylurea Compounds/therapeutic use
- Phenylurea Compounds/adverse effects
- Phenylurea Compounds/administration & dosage
- Pyridines/therapeutic use
- Pyridines/administration & dosage
- Pyridines/adverse effects
- Antibodies, Monoclonal, Humanized/therapeutic use
- Antibodies, Monoclonal, Humanized/administration & dosage
- Retrospective Studies
- Case-Control Studies
- Aged
- Combined Modality Therapy
- Disease Progression
- Treatment Outcome
- Adult
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Affiliation(s)
- Yanqiao Ren
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yiming Liu
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Songlin Song
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Chuansheng Zheng
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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12
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Kudo M. Current Therapeutic Strategies for Hepatocellular Carcinoma in Japan. Liver Cancer 2023; 12:497-509. [PMID: 38098744 PMCID: PMC10721236 DOI: 10.1159/000534304] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2023] [Accepted: 09/25/2023] [Indexed: 12/17/2023] Open
Affiliation(s)
- Masatoshi Kudo
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan
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13
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Omar A, Kaseb A, Elbaz T, El-Kassas M, El Fouly A, Hanno AF, El Dorry A, Hosni A, Helmy A, Saad AS, Alolayan A, Eysa BE, Hamada E, Azim H, Khattab H, Elghazaly H, Tawfik H, Ayoub H, Khaled H, Saadeldin I, Waked I, Barakat EMF, El Meteini M, Hamed Shaaban M, EzzElarab M, Fathy M, Shaker M, Sobhi M, Shaker MK, ElGharib M, Abdullah M, Mokhtar M, Elshazli M, Heikal OMK, Hetta O, ElWakil RM, Abdel Wahab S, Eid SS, Rostom Y, On behalf of the Egyptian Liver Cancer Committee Study Group. Egyptian Society of Liver Cancer Recommendation Guidelines for the Management of Hepatocellular Carcinoma. J Hepatocell Carcinoma 2023; 10:1547-1571. [PMID: 37744303 PMCID: PMC10516190 DOI: 10.2147/jhc.s404424] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2023] [Accepted: 09/01/2023] [Indexed: 09/26/2023] Open
Abstract
Globally, hepatocellular carcinoma (HCC) is the fourth most common cause of death from cancer. The prevalence of this pathology, which has been on the rise in the last 30 years, has been predicted to continue increasing. HCC is the most common cause of cancer-related morbidity and mortality in Egypt and is also the most common cancer in males. Chronic liver diseases, including chronic hepatitis C, which is a primary health concern in Egypt, are considered major risk factors for HCC. However, HCC surveillance is recommended for patients with chronic hepatitis B virus (HBV) and liver cirrhosis; those above 40 with HBV but without cirrhosis; individuals with hepatitis D co-infection or a family history of HCC; and Nonalcoholic fatty liver disease (NAFLD) patients exhibiting significant fibrosis or cirrhosis. Several international guidelines aid physicians in the management of HCC. However, the availability and cost of diagnostic modalities and treatment options vary from one country to another. Therefore, the current guidelines aim to standardize the management of HCC in Egypt. The recommendations presented in this report represent the current management strategy at HCC treatment centers in Egypt. Recommendations were developed by an expert panel consisting of hepatologists, oncologists, gastroenterologists, surgeons, pathologists, and radiologists working under the umbrella of the Egyptian Society of Liver Cancer. The recommendations, which are based on the currently available local diagnostic aids and treatments in the country, include recommendations for future prospects.
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Affiliation(s)
- Ashraf Omar
- Department of Gastroenterology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Ahmed Kaseb
- Department of Gastrointestinal Medical Oncology, the University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Tamer Elbaz
- Department of Gastroenterology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Mohamed El-Kassas
- Department of Endemic Medicine, Faculty of Medicine, Helwan University, Cairo, Egypt
| | - Amr El Fouly
- Department of Endemic Medicine, Faculty of Medicine, Helwan University, Cairo, Egypt
| | - Abdel Fatah Hanno
- Department of Gastroenterology, Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | - Ahmed El Dorry
- Department of Interventional Radiology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Ahmed Hosni
- Department of Interventional Radiology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Amr Helmy
- Department of Surgery, National Liver Institute Menoufia University, Menoufia, Egypt
| | - Amr S Saad
- Department of Oncology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Ashwaq Alolayan
- Department of Oncology, National Guard Hospital, Riyadh, Saudi Arabia
| | - Basem Elsayed Eysa
- Department of Gastroenterology, National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt
| | - Emad Hamada
- Department of Oncology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Hamdy Azim
- Department of Oncology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Hany Khattab
- Department of Pathology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Hesham Elghazaly
- Department of Oncology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Hesham Tawfik
- Department of Oncology, Faculty of Medicine, Tanta University, TantaEgypt
| | - Hisham Ayoub
- Department of Gastroenterology, Military Medical Academy, Cairo, Egypt
| | - Hussein Khaled
- Department of Oncology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Ibtessam Saadeldin
- Department of Oncology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Imam Waked
- Department of Gastroenterology, Menoufia Liver Institute, Menoufia, Egypt
| | - Eman M F Barakat
- Department of Gastroenterology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Mahmoud El Meteini
- Department of Surgery, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Mohamed Hamed Shaaban
- Department of Interventional Radiology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Mohamed EzzElarab
- Department of Gastroenterology, National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt
| | - Mohamed Fathy
- Department of Surgery, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Mohamed Shaker
- Department of Interventional Radiology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Mohamed Sobhi
- Department of Interventional Radiology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Mohamed Kamal Shaker
- Department of Gastroenterology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Mohamed ElGharib
- Department of Interventional Radiology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Mohammed Abdullah
- Department of Oncology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Mohesn Mokhtar
- Department of Oncology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Mostafa Elshazli
- Department of Surgery, Faculty of Medicine, Cairo University, Cairo, Egypt
| | | | - Osama Hetta
- Department of Interventional Radiology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Reda Mahmoud ElWakil
- Department of Gastroenterology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Sameh Abdel Wahab
- Department of Interventional Radiology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Samir Shehata Eid
- Department of Oncology, Faculty of Medicine, Assiut University, Assiut, Egypt
| | - Yousri Rostom
- Department of Oncology, Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | - On behalf of the Egyptian Liver Cancer Committee Study Group
- Department of Gastroenterology, Faculty of Medicine, Cairo University, Cairo, Egypt
- Department of Gastrointestinal Medical Oncology, the University of Texas MD Anderson Cancer Center, Houston, TX, USA
- Department of Endemic Medicine, Faculty of Medicine, Helwan University, Cairo, Egypt
- Department of Gastroenterology, Faculty of Medicine, Alexandria University, Alexandria, Egypt
- Department of Interventional Radiology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
- Department of Interventional Radiology, Faculty of Medicine, Cairo University, Cairo, Egypt
- Department of Surgery, National Liver Institute Menoufia University, Menoufia, Egypt
- Department of Oncology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
- Department of Oncology, National Guard Hospital, Riyadh, Saudi Arabia
- Department of Gastroenterology, National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt
- Department of Oncology, Faculty of Medicine, Cairo University, Cairo, Egypt
- Department of Pathology, Faculty of Medicine, Cairo University, Cairo, Egypt
- Department of Oncology, Faculty of Medicine, Tanta University, TantaEgypt
- Department of Gastroenterology, Military Medical Academy, Cairo, Egypt
- Department of Gastroenterology, Menoufia Liver Institute, Menoufia, Egypt
- Department of Gastroenterology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
- Department of Surgery, Faculty of Medicine, Ain Shams University, Cairo, Egypt
- Department of Surgery, Faculty of Medicine, Cairo University, Cairo, Egypt
- Department of Oncology, Faculty of Medicine, Assiut University, Assiut, Egypt
- Department of Oncology, Faculty of Medicine, Alexandria University, Alexandria, Egypt
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14
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Singal AG, Kudo M, Bruix J. Breakthroughs in Hepatocellular Carcinoma Therapies. Clin Gastroenterol Hepatol 2023; 21:2135-2149. [PMID: 36813012 PMCID: PMC10293061 DOI: 10.1016/j.cgh.2023.01.039] [Citation(s) in RCA: 72] [Impact Index Per Article: 36.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2022] [Revised: 12/22/2022] [Accepted: 01/23/2023] [Indexed: 02/24/2023]
Abstract
Several breakthroughs in hepatocellular carcinoma (HCC) therapy across tumor stages provide hope to improve its dismal prognosis. Although surgical and local ablative therapies have few significant changes in technique, an improved understanding of tumor biology has facilitated increase numbers of patients who are now eligible to undergo curative-intent procedures. Most notably, acceptable post-transplant outcomes can be achieved in well selected patients whose tumors are downstaged into Milan Criteria. Adjuvant therapy in patients at high risk of recurrence also significantly improves recurrence-free survival after resection or ablation. For patients with liver-localized disease who are not eligible for curative-intent procedures, transarterial chemoembolization (TACE) was historically the treatment modality of choice, regardless of tumor burden; however, there is now increased recognition of patients who are "TACE unsuitable" and may be better treated with systemic therapy. The greatest evolution in HCC treatment options has occurred with systemic therapy, where several new agents are now available in the first- and second-line setting, including immune checkpoint inhibitor combinations. Objective responses are observed in approximately 30% of patients and median survival is approaching 2 years. The availability of immune checkpoint inhibitors has renewed interest in combination therapies for earlier tumor stages, with several phase III trials ongoing. Considering increasing complexities of HCC care, requiring decisions between therapies delivered by different providers, multidisciplinary care is critical and is associated with improved clinical outcomes. In this review, we detail major breakthroughs in HCC therapy, how these breakthroughs can be applied in clinical practice, and remaining areas in need of further research.
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Affiliation(s)
- Amit G Singal
- Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, Texas.
| | - Masatoshi Kudo
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka Japan.
| | - Jordi Bruix
- Barcelona Clinic Liver Cancer Group, Liver Unit, August Pi i Sunyer Biomedical Research Institute, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Hospital Clinic, University of Barcelona, Barcelona, Spain.
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15
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Chang PY, Lee RC, Liang PC, Liu YS, Chuang VP, Wu DK, Cheng YF, Huang JI, Tseng HS, Hung CF, Wu RH, Chern MC, Cheng HM, Wu CH, Cheng SM, Chiang CL, Liang HL. Multidisciplinary Taiwan consensus for the use of conventional TACE in hepatocellular carcinoma treatment. Front Oncol 2023; 13:1186674. [PMID: 37427137 PMCID: PMC10328116 DOI: 10.3389/fonc.2023.1186674] [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: 03/15/2023] [Accepted: 06/05/2023] [Indexed: 07/11/2023] Open
Abstract
Developed in early 1980s, transarterial chemoembolization (TACE) with Lipiodol was adopted globally after large-scale randomized control trials and meta-analyses proving its effectiveness were completed. Also known as "conventional TACE" (cTACE), TACE is currently the first-line treatment for patients with unresectable intermediate stage hepatocellular carcinoma (HCC) and delivers both ischemic and cytotoxic effects to targeted tumors. Although new technology and clinical studies have contributed to a more comprehensive understanding of when and how to apply this widely-adopted therapeutic modality, some of these new findings and techniques have yet to be incorporated into a guideline appropriate for Taiwan. In addition, differences in the underlying liver pathologies and treatment practices for transcatheter embolization between Taiwan and other Asian or Western populations have not been adequately addressed, with significant variations in the cTACE protocols adopted in different parts of the world. These mainly revolve around the amount and type of chemotherapeutic agents used, the type of embolic materials, reliance on Lipiodol, and the degree of selectiveness in catheter positioning. Subsequently, interpreting and comparing results obtained from different centers in a systematic fashion remain difficult, even for experienced practitioners. To address these concerns, we convened a panel of experts specializing in different aspects of HCC treatment to devise modernized recommendations that reflect recent clinical experiences, as well as cTACE protocols which are tailored for use in Taiwan. The conclusions of this expert panel are described herein.
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Affiliation(s)
- Pi-Yi Chang
- Department of Radiology, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Rheun-Chuan Lee
- Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Po-Chin Liang
- Department of Radiology, National Taiwan University Hospital Hsin-Chu Branch, Hsinchu, Taiwan
| | - Yi-Sheng Liu
- Department of Medical Imagine, National Cheng Kung University Hospital, Tainan, Taiwan
| | - Vicent P. Chuang
- Department of Radiology, Koo Foundation Sun Yat-Sen Cancer Center, Taipei, Taiwan
| | - Ding-Kwo Wu
- Department of Radiology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Yu-Fan Cheng
- Department of Radiology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Jen-I. Huang
- Department of Radiology, Tungs’ Taichung Metroharbor Hospital, Taichung, Taiwan
| | - Hsiuo-Shan Tseng
- Department of Radiology, Cheng Hsin General Hospital, Taipei, Taiwan
| | - Chien-Fu Hung
- Department of Radiology, Chang−Gung Memorial Hospital, Taoyuan, Taiwan
| | - Reng-Hong Wu
- Department of Radiology, Chi Mei Medical Center, Tainan, Taiwan
| | - Ming-Chih Chern
- Department of Radiology, Koo Foundation Sun Yat-Sen Cancer Center, Taipei, Taiwan
| | - Hua-Ming Cheng
- Department of Radiology, Chi Mei Medical Center, Tainan, Taiwan
| | - Chih-Horng Wu
- Department of Radiology, National Taiwan University Hospital Hsin-Chu Branch, Hsinchu, Taiwan
| | - She-Meng Cheng
- Department of Radiology, MacKay Memorial Hospital, Taipei, Taiwan
| | - Chia-Ling Chiang
- Department of Radiology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| | - Huei-Lung Liang
- Department of Radiology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
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16
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Zhong BY, Jin ZC, Chen JJ, Zhu HD, Zhu XL. Role of Transarterial Chemoembolization in the Treatment of Hepatocellular Carcinoma. J Clin Transl Hepatol 2023; 11:480-489. [PMID: 36643046 PMCID: PMC9817054 DOI: 10.14218/jcth.2022.00293] [Citation(s) in RCA: 35] [Impact Index Per Article: 17.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2022] [Revised: 08/17/2022] [Accepted: 08/22/2022] [Indexed: 01/18/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. According to the Barcelona Clinic Liver Cancer (BCLC) staging system, transarterial chemoembolization (TACE) is the first-line recommendation for intermediate-stage HCC. In real-world clinical practice, TACE also plays an important role in early- and advanced-stage HCC. This review article by the experts from Chinese Liver Cancer Clinical Study Alliance (CHANCE) summarizes the available clinical evidence pertaining to the current application of TACE in patients with early-, intermediate-, and advanced-stage HCC. In addition, combination of TACE with other treatment modalities, especially immunotherapy, is reviewed.
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Affiliation(s)
- Bin-Yan Zhong
- Department of Interventional Radiology, the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Zhi-Cheng Jin
- Center of Interventional Radiology & Vascular Surgery, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, Jiangsu, China
| | - Jian-Jian Chen
- Center of Interventional Radiology & Vascular Surgery, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, Jiangsu, China
| | - Hai-Dong Zhu
- Center of Interventional Radiology & Vascular Surgery, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, Jiangsu, China
- Correspondence to: Xiao-Li Zhu, Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, No. 188, Shizi Street, Suzhou, Jiangsu 215006, China; ORCID: https://orcid.org/0000-0002-5504-9528. Tel/Fax: +86-512-67780375, E-mail: ; Hai-Dong Zhu, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, 87 DingjiaqiaoRoad, Nanjing, Jiangsu 210009, China. ORCID: https://orcid.org/0000-0003-1798-7641. Tel/Fax: +86-25-83792121, E-mail:
| | - Xiao-Li Zhu
- Department of Interventional Radiology, the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
- Correspondence to: Xiao-Li Zhu, Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, No. 188, Shizi Street, Suzhou, Jiangsu 215006, China; ORCID: https://orcid.org/0000-0002-5504-9528. Tel/Fax: +86-512-67780375, E-mail: ; Hai-Dong Zhu, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, 87 DingjiaqiaoRoad, Nanjing, Jiangsu 210009, China. ORCID: https://orcid.org/0000-0003-1798-7641. Tel/Fax: +86-25-83792121, E-mail:
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17
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Wong JK, Lim HJ, Tam VC, Burak KW, Dawson LA, Chaudhury P, Abraham RJ, Meyers BM, Sapisochin G, Valenti D, Samimi S, Ramjeesingh R, Mujoomdar A, Martins I, Dixon E, Segedi M, Liu DM. Clinical consensus statement: Establishing the roles of locoregional and systemic therapies for the treatment of intermediate-stage hepatocellular carcinoma in Canada. Cancer Treat Rev 2023; 115:102526. [PMID: 36924644 DOI: 10.1016/j.ctrv.2023.102526] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2022] [Revised: 02/12/2023] [Accepted: 02/14/2023] [Indexed: 03/06/2023]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) a leading cause of cancer mortality worldwide and approximately one-third of patients present with intermediate-stage disease. The treatment landscape of intermediate-stage HCC is rapidly evolving due to developments in local, locoregional and systemic therapies. Treatment recommendations focused on this heterogenous disease stage and that take into account the Canadian reality are lacking. To address this gap, a pan-Canadian group of experts in hepatology, transplant, surgery, radiation therapy, nuclear medicine, interventional radiology, and medical oncology came together to develop consensus recommendations on management of intermediate-stage HCC relevant to the Canadian context. METHODS A modified Delphi framework was used to develop consensus statements with strengths of recommendation and supporting levels of evidence graded using the AHA/ACC classification system. Tentative consensus statements were drafted based on a systematic search and expert input in a series of iterative feedback cycles and were then circulated via online survey to assess the level of agreement. RESULTS & CONCLUSION The pre-defined ratification threshold of 80 % agreement was reached for all statements in the areas of multidisciplinary treatment (n = 4), intra-arterial therapy (n = 14), biologics (n = 5), radiation therapy (n = 3), surgical resection and transplantation (n = 7), and percutaneous ablative therapy (n = 4). These generally reflected an expansion in treatment options due to developments in previously established or emergent techniques, introduction of new and more active therapies and increased therapeutic flexibility. These developments have allowed for greater treatment tailoring and personalization as well as a paradigm shift toward strategies with curative intent in a wider range of disease settings.
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Affiliation(s)
- Jason K Wong
- University of Calgary, 2500 University Dr NW, Calgary, AB T2N 1N4, Canada.
| | - Howard J Lim
- BC Cancer Agency, 600 West 10th Avenue, Vancouver, BC V5Z 4E6, Canada.
| | - Vincent C Tam
- Tom Baker Cancer Centre, University of Calgary, 1331 29 St NW, Calgary, AB T2N 4N2, Canada.
| | - Kelly W Burak
- University of Calgary, 2500 University Dr NW, Calgary, AB T2N 1N4, Canada.
| | - Laura A Dawson
- Princess Margaret Cancer Centre, University of Toronto, 610 University Ave, Toronto, ON M5G 2C1, Canada.
| | | | - Robert J Abraham
- Department of Diagnostic Radiology, Dalhousie University, 6299 South St, Halifax, NS B3H 4R2, Canada.
| | - Brandon M Meyers
- Juravinski Cancer Centre, 699 Concession St, Hamilton, ON L8V 5C2, Canada.
| | | | - David Valenti
- McGill University, 845 Rue Sherbrooke O, Montréal, QC H3A 0G4, Canada.
| | - Setareh Samimi
- Hopital Sacre-Coeur de Montreal, University of Montreal, 5400 Boul Gouin O, Montréal, QC H4J 1C5, Canada.
| | - Ravi Ramjeesingh
- Department of Medicine, Dalhousie University, 6299 South St, Halifax, NS B3H 4R2, Canada.
| | - Amol Mujoomdar
- Western University, 1151 Richmond Street, London, ON N6A 5B9, Canada.
| | - Ilidio Martins
- Kaleidoscope Strategic, Inc. 1 King Street W, Suite 4800 - 117, Toronto, ON M5H 1A1, Canada.
| | - Elijah Dixon
- University of Calgary, 2500 University Dr NW, Calgary, AB T2N 1N4, Canada.
| | - Maja Segedi
- Department of Surgery, Vancouver General Hospital, Jim Pattison Pavilion, 899 W 12th Ave, Vancouver, BC V5Z 1M9, Canada.
| | - David M Liu
- School of Biomedical Engineering, University of British Columbia, 2329 West Mall Vancouver, BC V6T 1Z4, Canada.
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18
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Zhang L, Zhang X, Li Q, Makamure J, Liu Z, Zhao D, Li X, Shi H, Zheng C, Liu F, Liang B. Transarterial chemoembolization failure in patients with hepatocellular carcinoma: Incidence, manifestation and risk factors. Clin Res Hepatol Gastroenterol 2023; 47:102071. [PMID: 36539181 DOI: 10.1016/j.clinre.2022.102071] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2022] [Revised: 11/16/2022] [Accepted: 12/16/2022] [Indexed: 12/23/2022]
Abstract
BACKGROUND To identify the incidence, manifestation and risk factors of transarterial chemoembolization (TACE) failure defined as untreatable progression (UP) in patients with hepatocellular carcinoma (HCC) on short-term observation. METHODS Patients from two hospitals with HCC treated with TACE were considered. According to the definition of UP, TACE failure was considered to be present in at least one of the following situations: situation I, failure to achieve objective response in the targeted tumor after at least two initial TACE treatments; situation II, failure to achieve objective response in local tumor progression or new intrahepatic tumor after another TACE session; situation III, presence of major progression; and situation IV, presence of impaired liver function or performance status that contraindicates TACE treatment. Patients were assessed for TACE failure on follow-up visits after two or three TACE sessions. Risk factors for TACE failure were evaluated with logistic regression analysis. RESULTS A total of 206 patients were included. TACE failure occurred in 42 (42/206, 20.4%) patients, of whom 21, 1, 4, 0 and 16 patients manifested as situation I, II, III, IV alone, and combination of situation I with the others, respectively. Multivariate analysis showed that tumor without complete capsule (P < .001) and non-smooth margin (P = .004) were independent predictors of the presence of TACE failure. CONCLUSIONS TACE failure was uncommon in patients with HCC, which manifested predominantly as failure of treatment response of the initial intrahepatic tumor. Non-smooth tumor margin and tumors without complete capsule were associated with the presence of TACE failure.
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Affiliation(s)
- Lijie Zhang
- Department of Radiology, Hubei Key Laboratory of Molecular Imaging, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Road, Wuhan 430022, China; Department of Interventional Radiology, The Fifth Medical Center of Chinese, PLA General Hospital, Beijing 100039, PR China
| | - Xin Zhang
- Department of Radiology, Hubei Key Laboratory of Molecular Imaging, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Road, Wuhan 430022, China
| | - Qing Li
- Department of Radiology, Hubei Key Laboratory of Molecular Imaging, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Road, Wuhan 430022, China
| | - Joyman Makamure
- Department of Radiology, Hubei Key Laboratory of Molecular Imaging, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Road, Wuhan 430022, China
| | - Ziyi Liu
- Department of Radiology, Hubei Key Laboratory of Molecular Imaging, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Road, Wuhan 430022, China
| | - Dan Zhao
- Department of Radiology, Hubei Key Laboratory of Molecular Imaging, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Road, Wuhan 430022, China
| | - Xin Li
- Department of Radiology, Hubei Key Laboratory of Molecular Imaging, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Road, Wuhan 430022, China
| | - Heshui Shi
- Department of Radiology, Hubei Key Laboratory of Molecular Imaging, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Road, Wuhan 430022, China
| | - Chuansheng Zheng
- Department of Radiology, Hubei Key Laboratory of Molecular Imaging, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Road, Wuhan 430022, China
| | - Fengyong Liu
- Department of Interventional Radiology, The Fifth Medical Center of Chinese, PLA General Hospital, Beijing 100039, PR China.
| | - Bin Liang
- Department of Radiology, Hubei Key Laboratory of Molecular Imaging, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Road, Wuhan 430022, China.
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19
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Xu Q, Wang C, Yin G. Immune-related gene signature to predict TACE refractoriness in patients with hepatocellular carcinoma based on artificial neural network. Front Genet 2023; 13:993509. [PMID: 36685822 PMCID: PMC9846524 DOI: 10.3389/fgene.2022.993509] [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: 07/13/2022] [Accepted: 12/19/2022] [Indexed: 01/06/2023] Open
Abstract
Background: Transarterial chemoembolization (TACE) is the standard treatment option for intermediate-stage hepatocellular carcinoma (HCC), while response varies among patients. This study aimed to identify novel immune-related genes (IRGs) and establish a prediction model for TACE refractoriness in HCC patients based on machine learning methods. Methods: Gene expression data were downloaded from GSE104580 dataset of Gene Expression Omnibus (GEO) database, differential analysis was first performed to screen differentially expressed genes (DEGs). The least absolute shrinkage and selection operator (LASSO) regression analysis was performed to further select significant DEGs. Weighted gene co-expression network analysis (WGCNA) was utilized to build a gene co-expression network and filter the hub genes. Final signature genes were determined by the intersection of LASSO analysis results, WGCNA results and IRGs list. Based on the above results, the artificial neural network (ANN) model was constructed in the training cohort and verified in the validation cohort. Receiver operating characteristics (ROC) analysis was used to assess the prediction accuracy. Correlation of signature genes with tumor microenvironment scores, immune cells and immune checkpoint molecules were further analyzed. The tumor immune dysfunction and exclusion (TIDE) score was used to evaluate the response to immunotherapy. Results: One hundred and forty-seven samples were included in this study, which was randomly divided into the training cohort (n = 103) and validation cohort (n = 44). In total, 224 genes were identified as DEGs. Further LASSO regression analysis screened out 25 genes from all DEGs. Through the intersection of LASSO results, WGCNA results and IRGs list, S100A9, TREM1, COLEC12, and IFIT1 were integrated to construct the ANN model. The areas under the curves (AUCs) of the model were .887 in training cohort and .765 in validation cohort. The four IRGs also correlated with tumor microenvironment scores, infiltrated immune cells and immune checkpoint genes in various degrees. Patients with TACE-Response, lower expression of COLEC12, S100A9, TREM1 and higher expression of IFIT1 had better response to immunotherapy. Conclusion: This study constructed and validated an IRG signature to predict the refractoriness to TACE in patients with HCC, which may have the potential to provide insights into the TACE refractoriness in HCC and become the immunotherapeutic targets for HCC patients with TACE refractoriness.
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20
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Lin LW, Ke K, Yan LY, Chen R, Huang JY. Efficacy and safety of hepatic artery infusion chemotherapy combined with tyrosine kinase inhibitors plus programmed death-1 inhibitors for hepatocellular carcinoma refractory to transarterial chemoembolization. Front Oncol 2023; 13:1178428. [PMID: 37207144 PMCID: PMC10189040 DOI: 10.3389/fonc.2023.1178428] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2023] [Accepted: 04/18/2023] [Indexed: 05/21/2023] Open
Abstract
Background The subsequent therapy for hepatocellular carcinoma (HCC) patients with refractory to transarterial chemoembolization (TACE) is still controversial. This study was performed to evaluate the efficacy and safety of combination therapy comprising hepatic artery infusion chemotherapy (HAIC), lenvatinib, and programmed death-1 inhibitors relative to HAIC combined with lenvatinib. Methods In this single-center retrospective study, we analyzed data from HCC patients with refractory to TACE from June 2017 to July 2022. Primary study outcomes were overall survival (OS) and progression-free survival (PFS), while the secondary outcomes were the objective response rate (ORR), disease control rate (DCR), and treatment-related adverse events. Results We enrolled 149 patients finally, including 75 patients who received HAIC combined with lenvatinib plus PD-1 inhibitors therapy (HAIC+L+P group) and 74 patients who received HAIC combined with lenvatinib therapy (HAIC+L group). The median OS in the HAIC+L+P group (16.0; 95% CI: 13.6~18.3 months) was significantly higher compared to the HAIC+L group (9.0; 95% CI: 6.5~11.4 months) (p = 0.002), while the median PFS in the HAIC+L+P group (11.0; 95% CI: 8.6~13.3 months) was significantly higher compared to the HAIC+L group (6.0; 95% CI: 5.0~6.9 months) (p < 0.001). Significant between-group differences in DCR (p = 0.027) were found. Additionally, 48 pairs of patients were matched after propensity matching analysis. The survival prognosis between two groups before propensity matching is similar to that after propensity matching. Moreover, the percentage of patients with hypertension in the HAIC+L+P group was significantly higher compared to the HAIC+L group (28.00% vs. 13.51%; p = 0.029). Conclusions A combination therapy of HAIC, lenvatinib, and programmed death-1 inhibitors significantly improved oncologic response and prolonged survival duration, showing a better survival prognosis for HCC patients with refractory toTACE.
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21
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Huang Y, Zhang L, He M, Lai Z, Bu X, Wen D, Li Q, Xu L, Wei W, Zhang Y, Zhou Z, Chen M, Guo R, Shi M, Kan A. Hepatic Arterial Infusion of Oxaliplatin, Fluorouracil, and Leucovorin Versus Sorafenib for Hepatocellular Carcinoma Refractory to Transarterial Chemoembolization: Retrospective Subgroup Analysis of 2 Prospective Trials. Technol Cancer Res Treat 2022; 21:15330338221117389. [PMID: 36529949 PMCID: PMC9772936 DOI: 10.1177/15330338221117389] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
Purpose:Sorafenib is recommended for patients with hepatocellular carcinoma refractory to transarterial chemoembolization but with unsatisfactory overall survival and tumor response rate. Previously published studies showed hepatic arterial infusion chemotherapy of oxaliplatin, fluorouracil, and leucovorin was an effective and safe treatment. The aims of this study were to compare the clinical efficacy and safety of oxaliplatin, fluorouracil, and leucovorin-based hepatic arterial infusion chemotherapy with sorafenib in patients with hepatocellular carcinoma refractory to transarterial chemoembolization. Methods: This was a retrospective subgroup analysis of 2 prospective clinical trials, including 114 patients with hepatocellular carcinoma who were confirmed to be transarterial chemoembolization refractoriness. Of these, 55 patients received hepatic arterial infusion chemotherapy of fluorouracil, and leucovorin (FOLFOX-HAIC group, oxaliplatin 85 or 130 mg/m2, leucovorin 400 mg/m2, fluorouracil bolus 400 mg/m2, and 2400 mg/m2 for 23 or 46 h, every 3 weeks), and 59 patients were treated with sorafenib (sorafenib group, 400 mg sorafenib twice daily). Overall survival, progression-free survival, objective response rate, and treatment-related adverse events were compared between the 2 groups. Results: The FOLFOX-HAIC group showed a longer overall survival (17.1 months [95% confidence interval 13.4-20.8] vs 9.1 months [95% confidence interval 7.5-10.6]; hazard ratio 0.35 [95% confidence interval 0.23-0.53]; P < .001), a higher objective response rate (RECIST: 18 [32.7%] vs 1 [1.7%], P < .001), and a longer progression-free survival (7.6 months [95% confidence interval 5.6-9.6] vs 3.9 months [95% confidence interval 2.3-5.4]; hazard ratio 0.49 [95% confidence interval 0.33-0.72]; P < .001) than the sorafenib group. The safety results suggested that both oxaliplatin, fluorouracil, and leucovorin-based hepatic arterial infusion chemotherapy and sorafenib had acceptable treatment-related toxic effects. No significant difference was observed in the overall occurrence of any grade, grade 3/4, or serious adverse events between the 2 groups. Conclusions: Oxaliplatin, fluorouracil, and leucovorin-based hepatic arterial infusion chemotherapy might be a better choice than sorafenib for patients with hepatocellular carcinoma refractory to transarterial chemoembolization.
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Affiliation(s)
- YeXing Huang
- Department of Hepatobiliary Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - LiHong Zhang
- Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - MinKe He
- Department of Hepatobiliary Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - ZhiCheng Lai
- Department of Hepatobiliary Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - XiaoYun Bu
- Department of Hepatobiliary Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - DongSheng Wen
- Department of Hepatobiliary Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - QiJiong Li
- Department of Hepatobiliary Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Li Xu
- Department of Hepatobiliary Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Wei Wei
- Department of Hepatobiliary Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - YaoJun Zhang
- Department of Hepatobiliary Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - ZhongGuo Zhou
- Department of Hepatobiliary Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - MinShan Chen
- Department of Hepatobiliary Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - RongPing Guo
- Department of Hepatobiliary Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Ming Shi
- Department of Hepatobiliary Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Anna Kan
- Department of Hepatobiliary Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China,Anna Kan, Department of Hepatobiliary Oncology, Cancer Center, Sun Yat-sen University, Guangzhou, 510060, P.R. China.
Ming Shi, Department of Hepatobiliary Oncology, Cancer Center, Sun Yat-sen University, Guangzhou, 510060, P.R. China.
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22
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Comito T, Loi M, Franzese C, Clerici E, Franceschini D, Badalamenti M, Teriaca MA, Rimassa L, Pedicini V, Poretti D, Solbiati LA, Torzilli G, Ceriani R, Lleo A, Aghemo A, Santoro A, Scorsetti M. Stereotactic Radiotherapy after Incomplete Transarterial (Chemo-) Embolization (TAE\TACE) versus Exclusive TAE or TACE for Treatment of Inoperable HCC: A Phase III Trial (NCT02323360). Curr Oncol 2022; 29:8802-8813. [PMID: 36421345 PMCID: PMC9689962 DOI: 10.3390/curroncol29110692] [Citation(s) in RCA: 32] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Revised: 11/09/2022] [Accepted: 11/14/2022] [Indexed: 11/18/2022] Open
Abstract
Background: Hepatocellular carcinoma (HCC) is the most frequent liver malignancy and a leading cause of cancer death in the world. In unresectable HCC patients, transcatheter arterial (chemo-) embolization (TAE/TACE) has shown a disease response in 15-55% of cases. Though multiple TAE/TACE courses can be administered in principle, Stereotactic Body Radiotherapy (SBRT) has emerged as an alternative option in the case of local relapse following multiple TAE/TACE courses. Methods: This is a single-center, prospective, randomized, controlled, parallel-group superiority trial of SBRT versus standard TAE/TACE for the curative treatment of the intermediate stage of HCC after an incomplete response following TAE/TACE (NCT02323360). The primary endpoint is 1-year local control (LC): 18 events were needed to assess a 45% difference (HR: 0.18) in favor of SBRT. The secondary endpoints are 1-year Progression-Free Survival (PFS), Distant Recurrence-Free Survival (DRFS), Overall Survival (OS) and the incidence of acute and late complications. Results: At the time of the final analysis, 40 patients were enrolled, 19 (49%) in the TAE/TACE arm and 21 (51%) in the SBRT arm. The trial was prematurely closed due to slow accrual. The 1- and 2-year LC rates were 57% and 36%. The use of SBRT resulted in superior LC as compared to TAE/TACE rechallenge (median not reached versus 8 months, p = 0.0002). PFS was 29% and 16% at 1 and 2 years, respectively. OS was 86% and 62% at 1 year and 2 years, respectively. In the TAE arm, PFS was 13% and 6% at 1 and 2 years, respectively. In the SBRT arm, at 1 and 2 years, PFS was 37% and 21%, respectively. OS at 1 and 2 years was 75% and 64% in the SBRT arm and 95% and 57% in the TACE arm, respectively. No grade >3 toxicity was recorded. Conclusions: SBRT is an effective treatment option in patients affected by inoperable HCC experiencing an incomplete response following ≥1 cycle of TAE/TAC.
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Affiliation(s)
- Tiziana Comito
- Radiotherapy and Radiosurgery Department, IRCCS Humanitas Research Hospital, Rozzano, 20089 Milan, Italy
| | - Mauro Loi
- Radiation Oncology Unit, Azienda Ospedaliero Universitaria Careggi, 50134 Florence, Italy
| | - Ciro Franzese
- Radiotherapy and Radiosurgery Department, IRCCS Humanitas Research Hospital, Rozzano, 20089 Milan, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, 20072 Milan, Italy
| | - Elena Clerici
- Radiotherapy and Radiosurgery Department, IRCCS Humanitas Research Hospital, Rozzano, 20089 Milan, Italy
| | - Davide Franceschini
- Radiotherapy and Radiosurgery Department, IRCCS Humanitas Research Hospital, Rozzano, 20089 Milan, Italy
| | - Marco Badalamenti
- Radiotherapy and Radiosurgery Department, IRCCS Humanitas Research Hospital, Rozzano, 20089 Milan, Italy
| | - Maria Ausilia Teriaca
- Radiotherapy and Radiosurgery Department, IRCCS Humanitas Research Hospital, Rozzano, 20089 Milan, Italy
| | - Lorenza Rimassa
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, 20072 Milan, Italy
- Medical Oncology and Hematology Unit, IRCCS Humanitas Research Hospital, Rozzano, 20089 Milan, Italy
| | - Vittorio Pedicini
- Department of Radiology, IRCCS Humanitas Research Hospital, Rozzano, 20089 Milan, Italy
| | - Dario Poretti
- Department of Radiology, IRCCS Humanitas Research Hospital, Rozzano, 20089 Milan, Italy
| | - Luigi Alessandro Solbiati
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, 20072 Milan, Italy
- Department of Radiology, IRCCS Humanitas Research Hospital, Rozzano, 20089 Milan, Italy
| | - Guido Torzilli
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, 20072 Milan, Italy
- Division of Hepatobiliary and General Surgery, IRCCS Humanitas Research Hospital, Rozzano, 20089 Milan, Italy
| | - Roberto Ceriani
- Department of Hepatology, IRCCS Humanitas Research Hospital, Rozzano, 20089 Milan, Italy
| | - Ana Lleo
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, 20072 Milan, Italy
- Department of Hepatology, IRCCS Humanitas Research Hospital, Rozzano, 20089 Milan, Italy
| | - Alessio Aghemo
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, 20072 Milan, Italy
- Department of Hepatology, IRCCS Humanitas Research Hospital, Rozzano, 20089 Milan, Italy
| | - Armando Santoro
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, 20072 Milan, Italy
- Medical Oncology and Hematology Unit, IRCCS Humanitas Research Hospital, Rozzano, 20089 Milan, Italy
| | - Marta Scorsetti
- Radiotherapy and Radiosurgery Department, IRCCS Humanitas Research Hospital, Rozzano, 20089 Milan, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, 20072 Milan, Italy
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23
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Ren Y, Liu Z, Makamure J, Kan X, Song S, Liu Y, Qian K, Zheng C, Liang B. Addition of Camrelizumab to Transarterial Chemoembolization in Hepatocellular Carcinoma With Untreatable Progression. Technol Cancer Res Treat 2022; 21:15330338221131385. [PMID: 36259117 PMCID: PMC9583233 DOI: 10.1177/15330338221131385] [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] [Indexed: 11/05/2022] Open
Abstract
Purpose: The present retrospective study aimed to evaluate the efficacy and safety of camrelizumab addition to transarterial chemoembolization (TACE) in the treatment of hepatocellular carcinoma (HCC) with TACE-related untreatable progression (UP). Methods: Patients with HCC who received addition of camrelizumab due to UP after initial TACE treatment were enrolled at our institution between May 2019 and January 2021. Patients were assessed for tumor response, progression-free survival (PFS), and adverse events (AEs). Risk factors for PFS were evaluated with logistic regression analysis. Results: A total of 41 patients were included. The objective response rates (ORR) and disease control rates (DCR) were 24.4% and 61.0% at 2 to 3 months, and 12.2% and 58.5% at 6 months, respectively. The median PFS of the patients were 6 months (95% confidence interval [CI]: 3.8 months, 8.2 months). Of the 41 patients, 23 received camrelizumab combined with TACE (hereafter, camrelizumab-TACE) on whom 52 combined TACE procedures were performed, with a median of 2 procedures (range: 1-6) per patient. The remaining 18 patients received camrelizumab alone due to TACE contraindications. Multivariable analysis indicated that camrelizumab-TACE was an independent prognostic factor for PFS. Subgroup analysis showed a median PFS of 8 months in the camrelizumab-TACE group and 3 months in the camrelizumab monotherapy group (P < .001). No treatment-related mortalities occurred. Seventeen patients (41.5%) developed at least 1 type of AE after treatment with camrelizumab, with reactive cutaneous capillary endothelial proliferation (RCCEP) (n = 14, 34.1%) being the most common AE. Conclusion: Addition of camrelizumab to TACE offered an effective and safe treatment for HCC with UP.
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Affiliation(s)
- Yanqiao Ren
- Department of Radiology, Union Hospital, Tongji Medical College,
Huazhong University of Science and Technology, Wuhan, China,Hubei Provinve Key Laboratory of Molecular Imaging, Wuhan,
China
| | - Ziyi Liu
- Department of Radiology, Union Hospital, Tongji Medical College,
Huazhong University of Science and Technology, Wuhan, China,Hubei Provinve Key Laboratory of Molecular Imaging, Wuhan,
China
| | - Joyman Makamure
- Department of Radiology, Union Hospital, Tongji Medical College,
Huazhong University of Science and Technology, Wuhan, China,Hubei Provinve Key Laboratory of Molecular Imaging, Wuhan,
China
| | - Xuefeng Kan
- Department of Radiology, Union Hospital, Tongji Medical College,
Huazhong University of Science and Technology, Wuhan, China,Hubei Provinve Key Laboratory of Molecular Imaging, Wuhan,
China
| | - Songlin Song
- Department of Radiology, Union Hospital, Tongji Medical College,
Huazhong University of Science and Technology, Wuhan, China,Hubei Provinve Key Laboratory of Molecular Imaging, Wuhan,
China
| | - Yiming Liu
- Department of Radiology, Union Hospital, Tongji Medical College,
Huazhong University of Science and Technology, Wuhan, China,Hubei Provinve Key Laboratory of Molecular Imaging, Wuhan,
China
| | - Kun Qian
- Department of Radiology, Union Hospital, Tongji Medical College,
Huazhong University of Science and Technology, Wuhan, China,Hubei Provinve Key Laboratory of Molecular Imaging, Wuhan,
China
| | - Chuansheng Zheng
- Department of Radiology, Union Hospital, Tongji Medical College,
Huazhong University of Science and Technology, Wuhan, China,Hubei Provinve Key Laboratory of Molecular Imaging, Wuhan,
China,Chuansheng Zheng, Department of Radiology,
Union Hospital, Tongji Medical College, Huazhong University of Science and
Technology, Wuhan 430022, China.
| | - Bin Liang
- Department of Radiology, Union Hospital, Tongji Medical College,
Huazhong University of Science and Technology, Wuhan, China,Hubei Provinve Key Laboratory of Molecular Imaging, Wuhan,
China,Bin Liang, Department of Radiology, Union
Hospital, Tongji Medical College, Huazhong University of Science and Technology,
Wuhan 430022, China.
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Kuhn RV, Ignacio GMG, Jamias JD, Teh CS. Predictors of Refractoriness and Survival following Transarterial Chemoembolization for Hepatocellular Carcinoma: Outcomes from a Southeast Asian Cohort. JOURNAL OF CLINICAL INTERVENTIONAL RADIOLOGY ISVIR 2022. [DOI: 10.1055/s-0042-1756647] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/14/2022] Open
Abstract
Abstract
Aim Patients with hepatocellular carcinoma (HCC) become refractory to repeated sessions of transarterial chemoembolization (TACE). The aim of this study was to identify predictors associated with overall survival and refractoriness following repetitive TACE of HCC among patients in Southeast Asia.
Materials and Methods The clinical and laboratory characteristics and radiologic response of 39 patients treated with conventional TACE (range 2 to 5) with mitomycin from January 2012 to June 2018 were retrospectively analyzed. Patients were mostly male with a median age of 59 years and belonged to the BCLC B stage with a median tumor size of 7.5 cm.
Results The median overall survival was 23.2 months and the overall mortality at 5 years was 36%. Multivariate Cox regression analysis revealed that Child–Pugh (CP) score (hazard ratio [HR] = 3.47, p = 0.044), AST (HR = 7.6, p = 0.021), tumor size (HR = 5.47, p = 0.033), progressive disease on Choi criteria (HR = 5.47, confidence interval [CI] 1.15–25.99, p = 0.033), neutrophil-lymphocyte ratio (HR = 1.25, p = 0.049), and nodular enhancement on follow-up computed tomography (CT; HR = 1.98, p = 0.034) were independent risk factors for poor survival. ALT (p = 0.005), enhancement (p = 0.003), CP score (p = 0.010), and progressive disease on Choi criteria (p = 0.022) were predictive of TACE refractoriness/failure.
Conclusion Elevated liver enzymes, CP score, and progressive disease on Choi criteria accurately predict TACE refractoriness and failure, allowing early identification of patients who might benefit from other therapies.
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Affiliation(s)
- Rudolf V. Kuhn
- Department of Medical Imaging and Therapeutic Radiology, National Kidney and Transplant Institute, East Avenue, Quezon City, Philippines
| | - Glenn Marc G. Ignacio
- Department of Medical Imaging and Therapeutic Radiology, National Kidney and Transplant Institute, East Avenue, Quezon City, Philippines
| | - Jade D. Jamias
- Division of Internal Medicine, National Kidney and Transplant Institute, East Avenue, Quezon City, Philippines
| | - Catherine S.C. Teh
- Department of Surgery, National Kidney and Transplant Institute, East Avenue, Quezon City, Philippines
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25
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Yang C, Luo YG, Yang HC, Yao ZH, Li X. Effects of Early TACE Refractoriness on Survival in Patients with Hepatocellular Carcinoma: A Real-World Study. J Hepatocell Carcinoma 2022; 9:621-631. [PMID: 35903756 PMCID: PMC9317376 DOI: 10.2147/jhc.s373112] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2022] [Accepted: 07/13/2022] [Indexed: 11/30/2022] Open
Abstract
Purpose To investigate the effect of early transarterial chemoembolization (TACE) refractoriness on hepatocellular carcinoma (HCC) patient survival and to explore whether viable lesions > 50% after two consecutive TACE treatments negatively affect the prognosis of HCC patients. Patients and Methods From January 2014 to August 2017, 323 HCC patients who received TACE as the initial treatment were analyzed. TACE refractoriness was diagnosed according to the Japan Society of Hepatology 2021 version. Propensity score matching (PSM) was used to create a 1:1 matched group (nonrefractoriness vs refractoriness). To determine survival outcomes and prognostic factors, the Kaplan-Meier method and Cox proportional hazards model were used. Results In total, 51.1% of patients developed early TACE refractoriness (n = 165). After PSM, 120 patients from each group were matched and analyzed. The median overall survival (OS) time of the early TACE refractoriness group was significantly shorter than that of the nonrefractory group [21 months (95% CI: 15.7–26.3) vs 34 months (95% CI: 27.5–40.5), p = 0.002]. Thirty-eight patients with viable lesions >50% after two consecutive TACE procedures were identified and matched with patients of non-refractoriness. No significant difference in median OS was observed [35 months (95% CI: 21.6–48.5) vs 31 months (95% CI: 25.4–36.6), p = 0.611]. Multivariate analysis revealed that the BCLC stage, tumor size, tumor capsule, tumor distribution, α-fetoprotein level (AFP), and early TACE refractoriness were independent risk factors for prognosis in HCC patients. Conclusion Early TACE refractoriness may shorten the OS of HCC patients. However, viable lesions >50% after two consecutive TACE treatments did not impair the survival of patients. It may be inappropriate to consider these patients as having developed TACE refractoriness.
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Affiliation(s)
- Chao 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, People's Republic of China
| | - Yin-Gen Luo
- Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China
| | - Hong-Cai Yang
- Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China
| | - Zhi-Hang Yao
- Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China
| | - Xiao Li
- Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China
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26
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Zhang M, Lai W, Zhang J, Hu B, Huang L, Chu C. Efficacy Investigation of TACE Combined with Lenvatinib and Sintilimab in Intermediate-Stage Hepatocellular Carcinoma. DISEASE MARKERS 2022; 2022:6957580. [PMID: 35845129 PMCID: PMC9279099 DOI: 10.1155/2022/6957580] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/26/2022] [Accepted: 06/22/2022] [Indexed: 12/24/2022]
Abstract
Objective To evaluate the effectiveness of transarterial chemoembolization (TACE) combined with lenvatinib and sintilimab in treating patients with midstage hepatocellular carcinoma (HCC). Methods Sixty-two patients with midstage HCC were enrolled in this study. All of them were firstly treated in our hospital between September 1, 2019, and March 1, 2020. According to different treatment regimens, they were divided into the control group (31 cases, TACE group) and the observation group (31 cases, TACE combined with lenvatinib and sintilimab group). Each patient was followed up for at least 30 months to compare the short-term clinical efficacy and survival rate between the two groups. Results The objective response rate (ORR) and disease control rate (DCR) of the observation group at 3 months were 77.4% and 93.5%, respectively, which were higher than those of the control group (P < 0.05). The 2-year cumulative overall survival rate of the observation group was 64.5%, which was significantly higher than that of the control group (P < 0.05). The survival curve of the disease-free survival rate in the observation group was higher than that in the control group, and the difference was statistically significant (X 2 = 4.313, P < 0.05). Conclusion TACE combined with lenvatinib and sintilimab in the treatment of Barcelona Clinic Liver Cancer (BCLC) stage B hepatocellular carcinoma can effectively control the tumor progression and prolong the survival time of patients. Those preliminary findings need validation in larger studies, with a prospective design and longer follow-up.
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Affiliation(s)
- Menglong Zhang
- Ganzhou People's Hospital, No. 16, MeiGuan Road, Zhanggong District, Ganzhou, 341000 Jiangxi, China
| | - Weiguo Lai
- Ganzhou People's Hospital, No. 16, MeiGuan Road, Zhanggong District, Ganzhou, 341000 Jiangxi, China
| | - Jian Zhang
- Ganzhou People's Hospital, No. 16, MeiGuan Road, Zhanggong District, Ganzhou, 341000 Jiangxi, China
| | - Bijuan Hu
- Ganzhou People's Hospital, No. 16, MeiGuan Road, Zhanggong District, Ganzhou, 341000 Jiangxi, China
| | - Liyin Huang
- Ganzhou People's Hospital, No. 16, MeiGuan Road, Zhanggong District, Ganzhou, 341000 Jiangxi, China
| | - Cunkun Chu
- Library, Shandong First Medical University & Shandong Academy of Medical Sciences, Tai'an, 271000 Shandong Province, China
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27
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Kudo M. New treatment paradigm with systemic therapy in intermediate-stage hepatocellular carcinoma. Int J Clin Oncol 2022; 27:1110-1119. [PMID: 35527313 PMCID: PMC9209396 DOI: 10.1007/s10147-022-02166-0] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Accepted: 03/24/2022] [Indexed: 12/11/2022]
Abstract
Since the approval of sorafenib for the treatment of unresectable hepatocellular carcinoma in 2007 (in 2009 in Japan), five more regimens have been approved: lenvatinib, and atezolizumab plus bevacizumab for first-line treatment, and regorafenib, cabozantinib, and ramucirumab for second-line treatment, which are currently available for clinical use. The positive results of durvalumab, a programmed cell death ligand 1 antibody, plus tremelimumab, an anti-cytotoxic T-lymphocyte-associated protein 4 antibody, were also presented at the 2022 American Society Clinical Oncology Gastrointestinal Cancers Symposium as superior to sorafenib in prolonging the overall survival; this combination is expected to be approved by the end of 2022. These systemic therapies are changing the treatment paradigm not only for advanced hepatocellular carcinoma but also for intermediate-stage hepatocellular carcinoma. This review focuses on the role of systemic therapy in intermediate-stage hepatocellular carcinoma.
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Affiliation(s)
- Masatoshi Kudo
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Kindai University, 377-2, Ohno-Higashi, Osaka-Sayama, Osaka, 589-8511, Japan.
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28
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Zhang S, Zhong BY, Zhang L, Wang WS, Ni CF. Transarterial chemoembolization failure/refractoriness: A scientific concept or pseudo-proposition. World J Gastrointest Surg 2022; 14:528-537. [PMID: 35979416 PMCID: PMC9258238 DOI: 10.4240/wjgs.v14.i6.528] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2021] [Revised: 02/08/2022] [Accepted: 06/03/2022] [Indexed: 02/06/2023] Open
Abstract
Multi-session transarterial chemoembolization (TACE) is usually needed for the treatment of intermediate-stage hepatocellular carcinoma (HCC), but it may not always have a positive influence on prognosis due to high heterogeneity of HCC. To avoid ineffective repeated TACE, the concept of TACE failure/refractoriness has been proposed by several organizations and is being addressed using tyrosine kinase inhibitors. The concept of TACE failure/refractoriness is controversial due to ambiguous definitions and low evidence-based data. To date, only a few studies have examined the rationality concerning the definition of TACE failure/refractoriness, although the concept has been introduced and applied in many TACE-related clinical trials. This review focuses on some of the issues related to different versions of TACE failure/refractoriness, the rationality of related definitions, and the feasibility of continuing TACE after so-called failure/refractoriness based on published evidence. A suggestion to re-define TAEC failure/refractoriness is also put forward.
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Affiliation(s)
- Shen Zhang
- Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China
| | - Bin-Yan Zhong
- Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China
| | - Lei Zhang
- Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China
| | - Wan-Sheng Wang
- Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China
| | - Cai-Fang Ni
- Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China
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He Q, Yang J, Jin Y. Development and Validation of TACE Refractoriness-Related Diagnostic and Prognostic Scores and Characterization of Tumor Microenvironment Infiltration in Hepatocellular Carcinoma. Front Immunol 2022; 13:869993. [PMID: 35493518 PMCID: PMC9043752 DOI: 10.3389/fimmu.2022.869993] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2022] [Accepted: 03/21/2022] [Indexed: 01/11/2023] Open
Abstract
Background Transcatheter arterial chemoembolization LIHC, Liver hepatocellular carcinoma; (TACE) is a valid therapeutic method for hepatocellular carcinoma (HCC). However, many patients respond poorly to TACE, thus leading to an adverse outcome. Therefore, finding new biomarkers for forecasting TACE refractoriness occurrence and prognosis becomes one of the current research priorities in the field of HCC treatment. Materials and Methods Based on microarray datasets and a high-throughput sequencing dataset, the TACE refractoriness–related genes (TRGs) were identified by differential expression analysis. LASSO and Cox regression were applied to construct TACE refractoriness diagnostic score (TRD score) and prognostic score (TRP score) and validated their accuracy in external datasets. Functional correlation of TRP score was analyzed by gene set variation analysis and Gene Ontology. CIBERSORT and IMMUNCELL AI algorithms were performed to understand the correlation between the two scores and immune activity. We further carried out the efficacy analysis of immunotherapy and targeted drugs in the different TRP score groups. Furthermore, a nomogram was built by integrating various independent prognostic factors and validated its effectiveness in different datasets. Results We identified 487 TRGs combined with GSE104580 and TCGA datasets. Then four novel TRGs (TTK, EPO, SLC7A11, and PON1) were screened out to construct TRD score and TRP score models, and both two scores had good predictive ability in external datasets. Tumors with high TRP score show an immunosuppressive phenotype with more infiltrations of regulatory T cells and macrophages. Immunotherapy and chemotherapy response evaluation revealed patients with a high TRP score demonstrated well reactions to immune checkpoint inhibitors (ICIs) and sorafenib. TRP score, TNM stage, and cancer type were brought into the combined nomogram with optimum prediction. Conclusions Our research provided dependable and simplified methods for patients with HCC to assess tumors’ susceptibility to TACE refractoriness and prognosis and guide patients’ clinical therapy choices.
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Affiliation(s)
- Qifan He
- Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Jian Yang
- Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Yonghai Jin
- Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, Suzhou, China
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Cao F, Yang Y, Si T, Luo J, Zeng H, Zhang Z, Feng D, Chen Y, Zheng J. The Efficacy of TACE Combined With Lenvatinib Plus Sintilimab in Unresectable Hepatocellular Carcinoma: A Multicenter Retrospective Study. Front Oncol 2022; 11:783480. [PMID: 34988019 PMCID: PMC8721033 DOI: 10.3389/fonc.2021.783480] [Citation(s) in RCA: 63] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2021] [Accepted: 11/15/2021] [Indexed: 12/24/2022] Open
Abstract
Objective To assess the efficacy and safety of transarterial Chemoembolization (TACE) combined with lenvatinib plus sintilimab in unresectable hepatocellular carcinoma (HCC). Patients and Methods The data of patients with unresectable HCC administered a combination therapy with TACE and lenvatinib plus sintilimab were retrospectively assessed. Patients received lenvatinib orally once daily 2 weeks before TACE, followed by sintilimab administration at 200 mg intravenously on day 1 of a 21-day therapeutic cycle after TACE. The primary endpoints were objective response rate (ORR) and duration of response (DOR) by the modified RECIST criteria. Results Median duration of follow-up was 12.5 months (95%CI 9.1 to 14.8 months). ORR was 46.7% (28/60). Median DOR in confirmed responders was 10.0 months (95%CI 9.0-11.0 months). Median progression-free survival (PFS) was 13.3 months (95%CI 11.9-14.7 months). Median overall survival (OS) was 23.6 months (95%CI 22.2-25.0 months). Conclusions TACE combined with lenvatinib plus sintilimab is a promising therapeutic regimen in unresectable hepatocellular carcinoma.
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Affiliation(s)
- Fei Cao
- Department of Interventional Radiology, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, China
| | - Yi Yang
- 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.,Key Laboratory of Gene Editing Screening and Research and Development (R&D) of Digestive System Tumor Drugs, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Tongguo Si
- Department of Interventional Therapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, China
| | - Jun Luo
- Department of Interventional Radiology, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, China
| | - Hui Zeng
- Department of Interventional Radiology, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, China
| | - Zhewei Zhang
- Department of Interventional Radiology, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, China
| | - Duiping Feng
- Department of Interventional Radiology, First Hospital of Shanxi Medical University, Taiyuan, China
| | - Yi Chen
- Department of Interventional Radiology, First Hospital of Shanxi Medical University, Taiyuan, China
| | - Jiaping Zheng
- Department of Interventional Radiology, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, China
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Zhang S, Wang WS, Zhong BY, Ni CF. Subsequent Treatment after Transarterial Chemoembolization Failure/Refractoriness: A Review Based on Published Evidence. J Clin Transl Hepatol 2022; 10:740-747. [PMID: 36062280 PMCID: PMC9396332 DOI: 10.14218/jcth.2021.00336] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2021] [Revised: 10/29/2021] [Accepted: 11/27/2021] [Indexed: 12/04/2022] Open
Abstract
Transarterial chemoembolization (TACE) is widely applied for the treatment of hepatocellular carcinoma. Repeat TACE is often required in clinical practice because a satisfactory tumor response may not be achieved with a single session. However, repeated TACE procedures can impair liver function and increase treatment-related adverse events, all of which prompted the introduction of the concept of “TACE failure/refractoriness”. Mainly based on evidence from two retrospective studies conducted in Japan, sorafenib is recommended as the first choice for subsequent treatment after TACE failure/refractoriness. Several studies have investigated the outcomes of other subsequent treatments, including locoregional, other molecular targeted, anti-programmed death-1/anti-programed death ligand-1 therapies, and combination therapies after TACE failure/refractoriness. In this review, we summarize the up-to-date information about the outcomes of several subsequent treatment modalities after TACE failure/refractoriness.
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Affiliation(s)
| | | | - Bin-Yan Zhong
- Correspondence to: Cai-Fang Ni and Bin-Yan Zhong, Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, No. 188, Shizi Street, Suzhou, Jiangsu 215006, China. Tel/Fax: +86-512-67780375, E-mail: , (CFN) or Tel/Fax: +86-512-67972173, E-mail: (BYZ)
| | - Cai-Fang Ni
- Correspondence to: Cai-Fang Ni and Bin-Yan Zhong, Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, No. 188, Shizi Street, Suzhou, Jiangsu 215006, China. Tel/Fax: +86-512-67780375, E-mail: , (CFN) or Tel/Fax: +86-512-67972173, E-mail: (BYZ)
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Byun J, Kim SY, Kim JH, Kim MJ, Yoo C, Shim JH, Lee SS. Prediction of transarterial chemoembolization refractoriness in patients with hepatocellular carcinoma using imaging features of gadoxetic acid-enhanced magnetic resonance imaging. Acta Radiol 2021; 62:1548-1558. [PMID: 33197329 DOI: 10.1177/0284185120971844] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
BACKGROUND Repeated transarterial chemoembolization (TACE) can be associated with loss of its efficacy and subsequent tumor progression. PURPOSE To identify features of gadoxetic acid-enhanced magnetic resonance imaging (MRI) associated with TACE refractoriness and to develop a prediction model for estimating the risk of TACE refractoriness. MATERIAL AND METHODS Among 1025 patients with intermediate-stage hepatocellular carcinoma (HCC) who underwent TACE as a first-line treatment during 2010-2017, 427 patients who underwent preoperative gadoxetic acid-enhanced MRI were analyzed. According to the date of initial TACE, patients were divided into the development cohort (n = 211) and the test cohort (n = 216). TACE refractoriness was determined according to the Japan Society of Hepatology guidelines. Univariable and multivariable analyses were performed to investigate the association between clinical/MRI features and TACE refractoriness. The performance of the prediction model was internally and externally assessed using the C-index of discrimination and a Hosmer-Lemeshow goodness-of-fit test for calibration. RESULTS By analyzing 427 patients, we constructed a prediction model with the following independent features associated with TACE refractoriness: maximum tumor size; tumor number; peritumoral hypointensity on hepatobiliary phase (HBP); and the presence of non-hypervascular hypointense nodule on HBP. This system enabled the prediction of TACE refractoriness in the development cohort (C-index, 0.796) and the test cohort (C-index, 0.738) with good discrimination and calibration abilities. CONCLUSION The prediction model based on gadoxetic acid-enhanced MRI features in addition to the known predictors including tumor size and number can be used to estimate the risk of TACE refractoriness in patients with intermediate-stage HCC.
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Affiliation(s)
- Jieun Byun
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
- Department of Radiology, Hallym University College of Medicine, Kangnam Sacred Heart Hospital, Seoul, Republic of Korea
| | - So Yeon Kim
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
- Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Jin Hyoung Kim
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
- Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Min Ju Kim
- Department of Clinical Epidemiology and Biostatistics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Changhoon Yoo
- Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Ju Hyun Shim
- Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Seung Soo Lee
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
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Kang H, Lee HW. Current role of systemic therapy in transarterial chemotherapy refractory hepatocellular carcinoma patients. INTERNATIONAL JOURNAL OF GASTROINTESTINAL INTERVENTION 2021. [DOI: 10.18528/ijgii210046] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Affiliation(s)
- Hansung Kang
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Hye Won Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
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Zhong BY, Wang WS, Zhang S, Zhu HD, Zhang L, Shen J, Zhu XL, Teng GJ, Ni CF. Re-evaluating Transarterial Chemoembolization Failure/Refractoriness: A Survey by Chinese College of Interventionalists. J Clin Transl Hepatol 2021; 9:521-527. [PMID: 34447681 PMCID: PMC8369015 DOI: 10.14218/jcth.2021.00049] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2021] [Revised: 03/02/2021] [Accepted: 03/08/2021] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND AND AIMS The recognition of transarterial chemoembolization (TACE) failure/refractoriness among Chinese clinicians remains unclear. Using an online survey conducted by the Chinese College of Interventionalists (CCI), the aim of this study was to explore the recognition of TACE failure/refractoriness and review TACE application for hepatocellular carcinoma (HCC) treatment in clinical practice. METHODS From 27 August 2020 to 30 August 2020 during the CCI 2020 annual meeting, a survey with 34 questions was sent by email to 264 CCI clinicians in China with more than 10 years of experience using TACE for HCC treatment. RESULTS A total of 257 clinicians participated and responded to the survey. Most participants agreed that the concept of "TACE failure/refractoriness" has scientific and clinical significance (n=191, 74.3%). Nearly half of these participants chose TACE-based combination treatment as subsequent therapy after so-called TACE failure/refractoriness (n=88, 46.1%). None of the existing TACE failure/refractoriness definitions were widely accepted by the participants; thus, it is necessary to re-define this concept for the treatment of HCC in China (n=235, 91.4%). Most participants agreed that continuing TACE should be performed for patients with preserved liver function, presenting portal vein tumor thrombosis (n=242, 94.2%) or extrahepatic spread (n=253, 98.4%), after the previous TACE treatment to control intrahepatic lesion(s). CONCLUSIONS There is an obvious difference in the recognition of TACE failure/refractoriness among Chinese clinicians based on existing definitions. Further work should be carried out to re-define TACE failure/refractoriness.
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Affiliation(s)
- Bin-Yan Zhong
- Department of Interventional Radiology, the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Wan-Sheng Wang
- Department of Interventional Radiology, the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Shen Zhang
- Department of Interventional Radiology, the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Hai-Dong Zhu
- Center of Interventional Radiology & Vascular Surgery, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, Jiangsu, China
| | - Lei Zhang
- Department of Interventional Radiology, the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Jian Shen
- Department of Interventional Radiology, the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Xiao-Li Zhu
- Department of Interventional Radiology, the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Gao-Jun Teng
- Center of Interventional Radiology & Vascular Surgery, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, Jiangsu, China
- Correspondence to: Cai-Fang Ni, Department of Interventional Radiology, First Affiliated Hospital of Soochow University, 188 Shizi St, Suzhou, Jiangsu 215006, China. ORCID: https://orcid.org/0000-0002-5953-781X. Tel/Fax: +86-512-6797-2173, E-mail: ; Gao-Jun Teng, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, 87 DingjiaqiaoRoad, Nanjing Jiangsu 210009, China. ORCID: https://orcid.org/0000-0003-1145-0798. Tel/Fax: +86-25-8379-2103, E-mail:
| | - Cai-Fang Ni
- Department of Interventional Radiology, the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
- Correspondence to: Cai-Fang Ni, Department of Interventional Radiology, First Affiliated Hospital of Soochow University, 188 Shizi St, Suzhou, Jiangsu 215006, China. ORCID: https://orcid.org/0000-0002-5953-781X. Tel/Fax: +86-512-6797-2173, E-mail: ; Gao-Jun Teng, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, 87 DingjiaqiaoRoad, Nanjing Jiangsu 210009, China. ORCID: https://orcid.org/0000-0003-1145-0798. Tel/Fax: +86-25-8379-2103, E-mail:
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Jeong J, Park JG, Seo KI, Ahn JH, Park JC, Yun BC, Lee SU, Lee JW, Yun JH. Microvascular invasion may be the determining factor in selecting TACE as the initial treatment in patients with hepatocellular carcinoma. Medicine (Baltimore) 2021; 100:e26584. [PMID: 34232206 PMCID: PMC8270609 DOI: 10.1097/md.0000000000026584] [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: 08/12/2020] [Revised: 05/06/2021] [Accepted: 06/20/2021] [Indexed: 11/26/2022] Open
Abstract
ABSTRACT The aim of this study was to investigate factors affecting tumor necrosis with transcatheter arterial chemoembolization (TACE). Factors associated with early hepatocellular carcinoma recurrence after curative hepatectomy were also evaluated.Data of 51 patients who underwent surgery after a single session of TACE at a single university hospital were retrospectively analyzed. Factors that might affect tumor necrosis were determined by evaluating the TACE approach and by analyzing computed tomography and TACE findings, pathologic reports, and laboratory findings.In univariate analysis, microvascular invasion (MVI), radiological capsule appearance on the computed tomography, chronic hepatitis B, diabetes mellitus and serum albumin, MVI were significantly associated with tumor necrosis by TACE (P < .02). In multivariate analysis, MVI was the only statistically significant factor in TACE-induced tumor necrosis (P = .001). In univariate and multivariate analysis, MVI was the strongest factor for recurrence-free survival rate within 2 years (P = .008, P = .002).MVI could be a crucial factor in determining TACE as an initial treatment for hepatocellular carcinoma. MVI is also a strong indicator of recurrence within 2 years after curative hepatic resection.
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Affiliation(s)
- Joonho Jeong
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Ulsan University Hospital, Ulsan University College of Medicine, Ulsan
| | | | - Kwang Ill Seo
- Division of Hepatology, Department of Internal Medicine
| | - Ji Hyun Ahn
- Department of Pathology, Kosin University College of Medicine, Busan, Korea
| | | | | | - Sang Uk Lee
- Division of Hepatology, Department of Internal Medicine
| | - Jin Wook Lee
- Division of Hepatology, Department of Internal Medicine
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36
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Soliman MH, Ragheb MA, Elzayat EM, Mohamed MS, El-Ekiaby N, Abdelaziz AI, Abdel-Wahab AHA. MicroRNA-372-3p Predicts Response of TACE Patients Treated with Doxorubicin and Enhances Chemosensitivity in Hepatocellular Carcinoma. Anticancer Agents Med Chem 2021; 21:246-253. [PMID: 32416702 DOI: 10.2174/1871520620666200516145830] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2019] [Revised: 02/21/2020] [Accepted: 03/05/2020] [Indexed: 11/22/2022]
Abstract
BACKGROUND Identification of factors to detect and improve chemotherapy.response in cancer is the main concern. microRNA-372-3p (miR-372-3p) has been demonstrated to play a crucial role in cellular proliferation, apoptosis and metastasis of various cancers including Hepatocellular Carcinoma (HCC). However, its contribution towards Doxorubicin (Dox) chemosensitivity in HCC has never been studied. OBJECTIVE This study aims to investigate the potential role of miR-372-3p in enhancing Dox effects on HCC cell line (HepG2). Additionally, the correlation between miR-372-3p and HCC patients who received Transarterial Chemoembolization (TACE) with Dox treatment has been analyzed. METHODS Different cell processes were elucidated by cell viability, colony formation, apoptosis and wound healing assays after miR-372-3p transfection in HepG2 cells Furthermore, the miR-372-3p level has been estimated in the blood of primary HCC patients treated with TACE/Dox by quantitative real-time PCR assay. Receiver Operating Curve (ROC) analysis for serum miR-372-3p was constructed for its prognostic significance. Finally, the protein level of Mcl-1, the anti-apoptotic player, has been evaluated using western blot. RESULTS We found a significantly higher level of miR-372-3p in the blood of the responder group of HCC patients who received TACE with Dox than of non-responders. Ectopic expression of miR-372-3p reduced cell proliferation, migration and significantly induced apoptosis in HepG2 cells which was coupled with a decrease of anti-apoptotic protein Mcl-1. CONCLUSION Our study demonstrated that miR-372-3p acts as a tumor suppressor in HCC and can act as a predictor biomarker for drug response. Furthermore, the data referred for the first time its potential role in drug sensitivity that might be a therapeutic target for HCC.
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Affiliation(s)
- Marwa H Soliman
- Department of Chemistry (Biochemistry Division), Faculty of Science, Cairo University, Giza, Egypt
| | - Mohamed A Ragheb
- Department of Chemistry (Biochemistry Division), Faculty of Science, Cairo University, Giza, Egypt
| | - Emad M Elzayat
- Department of Zoology, Faculty of Science, Cairo University, Giza, Egypt
| | - Mervat S Mohamed
- Department of Chemistry (Biochemistry Division), Faculty of Science, Cairo University, Giza, Egypt
| | - Nada El-Ekiaby
- School of Medicine, New Giza University (NGU), Cairo, Egypt
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Kudo M, Kawamura Y, Hasegawa K, Tateishi R, Kariyama K, Shiina S, Toyoda H, Imai Y, Hiraoka A, Ikeda M, Izumi N, Moriguchi M, Ogasawara S, Minami Y, Ueshima K, Murakami T, Miyayama S, Nakashima O, Yano H, Sakamoto M, Hatano E, Shimada M, Kokudo N, Mochida S, Takehara T. Management of Hepatocellular Carcinoma in Japan: JSH Consensus Statements and Recommendations 2021 Update. Liver Cancer 2021; 10:181-223. [PMID: 34239808 PMCID: PMC8237791 DOI: 10.1159/000514174] [Citation(s) in RCA: 434] [Impact Index Per Article: 108.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2020] [Accepted: 12/23/2020] [Indexed: 02/06/2023] Open
Abstract
The Clinical Practice Manual for Hepatocellular Carcinoma was published based on evidence confirmed by the Evidence-based Clinical Practice Guidelines for Hepatocellular Carcinoma along with consensus opinion among a Japan Society of Hepatology (JSH) expert panel on hepatocellular carcinoma (HCC). Since the JSH Clinical Practice Guidelines are based on original articles with extremely high levels of evidence, expert opinions on HCC management in clinical practice or consensus on newly developed treatments are not included. However, the practice manual incorporates the literature based on clinical data, expert opinion, and real-world clinical practice currently conducted in Japan to facilitate its use by clinicians. Alongside each revision of the JSH Guidelines, we issued an update to the manual, with the first edition of the manual published in 2007, the second edition in 2010, the third edition in 2015, and the fourth edition in 2020, which includes the 2017 edition of the JSH Guideline. This article is an excerpt from the fourth edition of the HCC Clinical Practice Manual focusing on pathology, diagnosis, and treatment of HCC. It is designed as a practical manual different from the latest version of the JSH Clinical Practice Guidelines. This practice manual was written by an expert panel from the JSH, with emphasis on the consensus statements and recommendations for the management of HCC proposed by the JSH expert panel. In this article, we included newly developed clinical practices that are relatively common among Japanese experts in this field, although all of their statements are not associated with a high level of evidence, but these practices are likely to be incorporated into guidelines in the future. To write this article, coauthors from different institutions drafted the content and then critically reviewed each other's work. The revised content was then critically reviewed by the Board of Directors and the Planning and Public Relations Committee of JSH before publication to confirm the consensus statements and recommendations. The consensus statements and recommendations presented in this report represent measures actually being conducted at the highest-level HCC treatment centers in Japan. We hope this article provides insight into the actual situation of HCC practice in Japan, thereby affecting the global practice pattern in the management of HCC.
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Affiliation(s)
- Masatoshi Kudo
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan,*Masatoshi Kudo,
| | | | - Kiyoshi Hasegawa
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Ryosuke Tateishi
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Kazuya Kariyama
- Department of Gastroenterology, Okayama City Hospital, Okayama, Japan
| | - Shuichiro Shiina
- Department of Gastroenterology, Juntendo University, Tokyo, Japan
| | - Hidenori Toyoda
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Gifu, Japan
| | - Yasuharu Imai
- Department of Gastroenterology, Ikeda Municipal Hospital, Osaka, Japan
| | - Atsushi Hiraoka
- Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan
| | - Masafumi Ikeda
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Kashiwa, Japan
| | - Namiki Izumi
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Michihisa Moriguchi
- Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Sadahisa Ogasawara
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Yasunori Minami
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan
| | - Kazuomi Ueshima
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan
| | - Takamichi Murakami
- Department of Radiology, Kobe University Graduate School of Medicine, Hyogo, Japan
| | - Shiro Miyayama
- Department of Diagnostic Radiology, Fukui-ken Saiseikai Hospital, Fukui, Japan
| | - Osamu Nakashima
- Department of Clinical Laboratory Medicine, Kurume University Hospital, Kurume, Japan
| | - Hirohisa Yano
- Department of Pathology, Kurume University School of Medicine, Kurume, Japan
| | - Michiie Sakamoto
- Department of Pathology, Keio University School of Medicine, Tokyo, Japan
| | - Etsuro Hatano
- Department of Gastroenterological Surgery, Hyogo College of Medicine, Nishinomiya, Japan
| | - Mitsuo Shimada
- Department of Surgery, Tokushima University, Tokushima, Japan
| | - Norihiro Kokudo
- Department of Surgery, National Center for Global Health and Medicine, Tokyo, Japan
| | - Satoshi Mochida
- Department of Gastroenterology and Hepatology, Saitama Medical University, Saitama, Japan
| | - Tetsuo Takehara
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Osaka, Japan
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Müller L, Stoehr F, Mähringer-Kunz A, Hahn F, Weinmann A, Kloeckner R. Current Strategies to Identify Patients That Will Benefit from TACE Treatment and Future Directions a Practical Step-by-Step Guide. J Hepatocell Carcinoma 2021; 8:403-419. [PMID: 34012930 PMCID: PMC8128497 DOI: 10.2147/jhc.s285735] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2021] [Accepted: 04/21/2021] [Indexed: 12/11/2022] Open
Abstract
Treatment of hepatocellular carcinoma (HCC) depends on the stage of disease. In the Western Hemisphere, the Barcelona Clinic Liver Cancer classification (BCLC) is the preferred staging system. Approximately one-third of patients initially present with intermediate-stage disease. For these patients, transarterial chemoembolization (TACE) is the treatment of choice. However, the intermediate-stage comprises a heterogeneous subgroup of patients with considerable differences in tumor burden and liver function. In addition, differences in individual factors that are not captured by the BCLC framework, such as the tumor growth pattern, degree of hypervascularity, and vascular supply, complicate further evaluation of these patients. Due to these differences, not all patients benefit equally from TACE. Several tools and scoring systems have been devised to provide decision-making support. All of these have shown promising initial results but failed external evaluation and have not been translated to the clinic. Nevertheless, criteria for objectifying treatment decisions in daily clinical practice are needed in all stages of disease. Therefore, this review provides a concise practical step-by-step guide on current strategies for patient selection and decision-making, with a focus on TACE, to critically evaluate the existing decision-support tools and provide a summary of the latest updates in the field.
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Affiliation(s)
- Lukas Müller
- Department of Diagnostic and Interventional Radiology, University Medical Centre of the Johannes Gutenberg-University Mainz, Mainz, Germany
| | - Fabian Stoehr
- Department of Diagnostic and Interventional Radiology, University Medical Centre of the Johannes Gutenberg-University Mainz, Mainz, Germany
| | - Aline Mähringer-Kunz
- Department of Diagnostic and Interventional Radiology, University Medical Centre of the Johannes Gutenberg-University Mainz, Mainz, Germany
| | - Felix Hahn
- Department of Diagnostic and Interventional Radiology, University Medical Centre of the Johannes Gutenberg-University Mainz, Mainz, Germany
| | - Arndt Weinmann
- Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
| | - Roman Kloeckner
- Department of Diagnostic and Interventional Radiology, University Medical Centre of the Johannes Gutenberg-University Mainz, Mainz, Germany
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Yang HK, Kim JH, Lee HJ, Moon H, Ryu H, Han JK. Early response evaluation of doxorubicin-nanoparticle-microbubble therapy in orthotopic hepatocellular carcinoma rat model using contrast-enhanced ultrasound and intravoxel incoherent motion-diffusion MRI. ULTRASONOGRAPHY (SEOUL, KOREA) 2021; 41:150-163. [PMID: 34304481 PMCID: PMC8696148 DOI: 10.14366/usg.21036] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/17/2021] [Accepted: 05/10/2021] [Indexed: 11/11/2022]
Abstract
Purpose This study aimed to apply doxorubicin-loaded nanoparticle microbubble (Dox-NP-MB) therapy in an orthotopic rat model of hepatocellular carcinoma (HCC) and investigate the utility of contrast-enhanced ultrasound (CEUS) and intravoxel incoherent motion diffusion-weighted magnetic resonance imaging (IVIM-DWI) for response evaluation. Methods Twenty-eight N1S1 HCC model rats were treated with either Dox-NP-MB (group [G] 1, n=8), doxorubicin (Dox) alone (G2, n=7), nanoparticle microbubbles alone (G3, n=7), or saline (G4, control, n=6) on days 0 and 7, and were sacrificed on day 11. IVIM-DWI and CEUS were performed before each treatment and before euthanasia. Efficacy was estimated by the percentage of tumor volume growth inhibition compared with control. Toxicity was assessed by body weight changes and blood tests. Post-treatment changes in IVIM-DWI and CEUS parameters were analyzed. Results Tumor volume growth was inhibited by 48.4% and 90.2% in G1 and G2 compared to G4, respectively. Compared to G2, G1 had a significantly lower degree of body weight change (median, 91.0% [interquartile range, 88.5%-97.0%] vs. 88.0% [82.5%-88.8%], P<0.05) and leukopenia (1.75×103 cells/μL [1.53-2.77] vs. 1.20×103 cells/μL [0.89-1.51], P<0.05). After the first treatment, an increase in peak enhancement, wash-in rate, and wash-in perfusion index on CEUS was observed in G3 and G4 but suppressed in G1 and G2; the apparent diffusion coefficients, true diffusion coefficients, and perfusion fractions significantly increased in G1 and G2 compared to baseline (P<0.05). Conclusion Dox-NP-MB showed reduced Dox toxicity. Early changes in some CEUS and IVIM-DWI parameters correlated with the therapeutic response.
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Affiliation(s)
- Hyun Kyung Yang
- Department of Radiology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.,Department of Radiology, Seoul National University Hospital, Seoul National University, Seoul, Korea
| | - Jung Hoon Kim
- Department of Radiology, Seoul National University Hospital, Seoul National University, Seoul, Korea.,Department of Radiology, Seoul National University College of Medicine, Seoul, Korea
| | - Hak Jong Lee
- Department of Radiology, Seoul National University College of Medicine, Seoul, Korea.,Department of Radiology, Seoul National University Bundang Hospital, Seoul National University, Seongnam, Korea
| | | | - Hwaseong Ryu
- Department of Radiology, Pusan National University Yangsan Hospital, Yangsan, Korea
| | - Joon Koo Han
- Department of Radiology, Seoul National University Hospital, Seoul National University, Seoul, Korea.,Department of Radiology, Seoul National University College of Medicine, Seoul, Korea
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Villani R, Cavallone F, Sangineto M, Fioravanti G, Romano AD, Serviddio G. Management of intermediate-stage hepatocellular carcinoma in the elderly with transcatheter arterial chemoembolization failure: Retreatment or switching to systemic therapy? Int J Clin Pract 2021; 75:e13733. [PMID: 32981175 DOI: 10.1111/ijcp.13733] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2020] [Accepted: 09/18/2020] [Indexed: 12/25/2022] Open
Abstract
BACKGROUND Transcatheter Arterial chemoembolization (TACE) is the first-line option for the intermediate-stage hepatocellular carcinoma. Guidelines do not define the number of TACE sessions to be repeated before stopping treatment and switching to sorafenib. METHODS We retrospectively analysed 76 patients aged ≥65 years who were treated by multiple TACE sessions (re-TACE group; N = 36 patients) or one TACE session followed by sorafenib (TACE/Sorafenib group; N = 40 patients). The primary outcome was the overall survival (Kaplan-Meier analysis and log-rank test). RESULTS Median overall survival was 320 days (range: 70-420 days) in re-TACE subgroup and 285 days (range: 50-368 days) in TACE/Sorafenib subgroup without significant differences between the two groups (log-rank test P = .72; HR = 0.87; 95% IC 0.41-1.87). The survival rate at one year was 43.6% and 32% in the re-TACE and in the TACE/sorafenib groups (P = .12), respectively. Subgroup analysis by gender, number of nodules at baseline and etiology of liver cirrhosis was performed but no differences were found. No statistical difference was observed in the frequency of side effects, but sorafenib was associated with severe diarrhoea in most patients requiring dose reduction. CONCLUSION In our study including HCC patients aged ≥65 years, no differences in survival rate and side effects were found between patients Retreated with further TACE sessions and patients with treatment stage migration to sorafenib after first TACE failure. We included in our analysis a small study population; therefore, larger prospective studies are needed to confirm these findings.
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Affiliation(s)
- Rosanna Villani
- C.U.R.E. (University Centre for Liver Disease Research and Treatment), Liver Unit, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy
| | - Francesco Cavallone
- C.U.R.E. (University Centre for Liver Disease Research and Treatment), Liver Unit, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy
| | - Moris Sangineto
- C.U.R.E. (University Centre for Liver Disease Research and Treatment), Liver Unit, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy
| | - Gilda Fioravanti
- C.U.R.E. (University Centre for Liver Disease Research and Treatment), Liver Unit, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy
| | - Antonino Davide Romano
- C.U.R.E. (University Centre for Liver Disease Research and Treatment), Liver Unit, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy
| | - Gaetano Serviddio
- C.U.R.E. (University Centre for Liver Disease Research and Treatment), Liver Unit, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy
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Kaibori M, Matsushima H, Ishizaki M, Kosaka H, Matsui K, Kariya S, Yoshii K, Sekimoto M. The Impact of Sorafenib in Combination with Transarterial Chemoembolization on the Outcomes of Intermediate-Stage Hepatocellular Carcinoma. Asian Pac J Cancer Prev 2021; 22:1217-1224. [PMID: 33906315 PMCID: PMC8325117 DOI: 10.31557/apjcp.2021.22.4.1217] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2021] [Indexed: 01/10/2023] Open
Abstract
Background: We investigated the treatment outcomes and hepatic reserve of transarterial chemoembolization (TACE)-refractory patients with recurrent advanced hepatocellular carcinoma (HCC) treated with TACE plus sorafenib. Methods: Forty-one patients with intermediate-stage HCC defined as being TACE refractory on imaging were treated with sorafenib and TACE between 2009 and 2012 and comprised the combination treatment group. Twenty-nine patients who received repeated TACE after becoming refractory to TACE between 2005 and 2008 comprised the TACE continuation group. Results: Although the interval between successive rounds of TACE was significantly shorter before the patients developed TACE refractoriness, it was significantly longer after the development of TACE refractoriness, in the combination treatment group compared with the TACE continuation group. The appearance of extrahepatic spread and/or vascular invasion differed significantly between the two groups. The median overall survival was significantly longer in the combination treatment group than in the TACE continuation group (20.5 vs. 15.4 months, respectively; hazard ratio = 2.04; 95% confidence interval = 1.20–3.48). The 3-year overall survival rate was 33.4% in the combination treatment group and 3.5% in the TACE continuation group. Downstaging of the Child–Pugh class was significantly less frequent in the combination treatment group than in the TACE continuation group. In COX proportional hazards analyses, sorafenib plus TACE resulted in a better prognosis compared with repeated TACE. Conclusions: Treatment with sorafenib plus TACE in TACE-refractory patients with intermediate-stage HCC resulted in longer intervals between TACE rounds, better maintenance of hepatic reserve, and significantly longer OS compared with repeated TACE.
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Affiliation(s)
- Masaki Kaibori
- Department of Surgery, Kansai Medical University, Hirakata, Osaka, Japan
| | | | - Morihiko Ishizaki
- Department of Surgery, Kansai Medical University, Hirakata, Osaka, Japan
| | - Hisashi Kosaka
- Department of Surgery, Kansai Medical University, Hirakata, Osaka, Japan
| | - Kousuke Matsui
- Department of Surgery, Kansai Medical University, Hirakata, Osaka, Japan
| | - Shuji Kariya
- Department of Radiology, Kansai Medical University, Hirakata, Osaka, Japan
| | - Kengo Yoshii
- Department of Mathematics and Statistics in Medical Sciences, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Mitsugu Sekimoto
- Department of Surgery, Kansai Medical University, Hirakata, Osaka, Japan
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Chen L, Yu CX, Zhong BY, Zhu HD, Jin ZC, Zhu GY, Zhang Q, Ni CF, Teng GJ. Development of TACE Refractoriness Scores in Hepatocellular Carcinoma. Front Mol Biosci 2021; 8:615133. [PMID: 33981722 PMCID: PMC8109267 DOI: 10.3389/fmolb.2021.615133] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2020] [Accepted: 01/27/2021] [Indexed: 12/11/2022] Open
Abstract
Purpose: To identify the independent risk factors for transarterial embolization (TACE) refractoriness and to develop a novel TACE refractoriness score and nomogram for predicting TACE refractoriness in patients with hepatocellular carcinoma (HCC). Methods: Between March 2006 and March 2016, HCC patients who underwent TACE monotherapy as initial treatment at two hospitals formed the study cohort and validation cohort. The criteria of TACE refractoriness followed the Japan Society of Hepatology 2014 version of TACE refractoriness. In the study cohort, the independent risk factors for TACE refractoriness were identified, and TACE refractoriness score and nomogram were then developed. The accuracy of the systems was validated externally in the validation cohort. Results: In total, 113 patients from hospital A formed the study cohort and 122 patients from hospital B formed the validation cohort. In the study cohort, 82.3% of the patients (n = 93) developed TACE refractoriness with a median overall survival (OS) of 540 days (95% CI, 400.8–679.1), and the remaining 20 patients in the TACE-non-refractory group had a median OS of 1,257 days (95% CI, 338.8–2,175.2) (p = 0.019). The median time for developing TACE refractoriness was 207 days (95% CI, 134.8–279.2), and a median number of two TACE procedures were performed after refractoriness developed. The independent risk factors for TACE refractoriness were the number of tumors and bilobular invasion of HCC. TACE refractoriness scores <3.5 indicated a lower incidence of TACE refractoriness, whereas scores >3.5 points indicated a higher incidence (p < 0.001). In the validation cohort, 77.9% of the patients (n = 95) developed TACE refractoriness with a median OS of 568 days (95% CI, 416.3–719.7), and a median OS of 1,324 days was observed in the TACE-non-refractory group (n = 27; 95% CI, 183.5–2,464.5). Conclusions: TACE refractoriness impairs the OS of HCC patients. The number of tumors and bilobular invasion status were independent risk factors for TACE refractoriness. The TACE refractoriness score can be an effective tool and easy approach to predict the risk of TACE refractoriness status.
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Affiliation(s)
- Li Chen
- Center of Interventional Radiology and Vascular Surgery, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China
| | - Chen-Xi Yu
- Center of Interventional Radiology and Vascular Surgery, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China
| | - Bin-Yan Zhong
- Department of Interventional Radiology, the First Affiliated Hospital of Soochow University, Suzhou, China
| | - Hai-Dong Zhu
- Center of Interventional Radiology and Vascular Surgery, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China
| | - Zhi-Cheng Jin
- Center of Interventional Radiology and Vascular Surgery, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China
| | - Guang-Yu Zhu
- Center of Interventional Radiology and Vascular Surgery, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China
| | - Qi Zhang
- Center of Interventional Radiology and Vascular Surgery, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China
| | - Cai-Fang Ni
- Department of Interventional Radiology, the First Affiliated Hospital of Soochow University, Suzhou, China
| | - Gao-Jun Teng
- Center of Interventional Radiology and Vascular Surgery, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China
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43
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Pollock RF, Brennan VK, Shergill S, Colaone F. A systematic literature review and network meta-analysis of first-line treatments for unresectable hepatocellular carcinoma based on data from randomized controlled trials. Expert Rev Anticancer Ther 2021; 21:341-349. [PMID: 33131346 DOI: 10.1080/14737140.2021.1842204] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer. First-line treatment options for unresectable HCC include sorafenib, lenvatinib, selective internal radiation therapy (SIRT), and transarterial chemoembolization (TACE). The present study reviewed randomized controlled trials (RCTs) of first-line therapies for unresectable HCC in TACE-ineligible patients. RESEARCH DESIGN AND METHODS A systematic literature review (SLR) was conducted to identify RCTs of first-line treatments for TACE-ineligible patients with unresectable HCC. Data on overall survival (OS) and progression-free survival were extracted and a contrast-based Bayesian network meta-analysis (NMA) was conducted using Markov Chain Monte Carlo techniques. RESULTS The SLR identified three RCTs: two comparing Y-90 resin microspheres with sorafenib, and one comparing sorafenib with lenvatinib. No RCTs were identified comparing other SIRT technologies with any other approved first-line HCC therapies. The NMA showed no significant OS differences between Y-90 resin microspheres and sorafenib (hazard ratio [HR] 0.92, 95% credible interval [CrI]: 0.79-1.08) or lenvatinib (HR: 0.88, 95% CrI: 0.63-1.22). CONCLUSIONS An SLR and NMA showed no significant differences between sorafenib, lenvatinib, and Y-90 resin microspheres in treating unresectable HCC. RCT evidence was not available for any other SIRT technologies and an evaluation of their relative efficacy was therefore not possible.
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Affiliation(s)
- Richard F Pollock
- Health Economics and Outcomes Research, Covalence Research Ltd, London, UK
| | - Victoria K Brennan
- Health Economics, Pricing, Reimbursement and Market Access, Sirtex Medical United Kingdom Ltd, London, UK
| | - Suki Shergill
- Health Economics, Pricing, Reimbursement and Market Access, Sirtex Medical United Kingdom Ltd, London, UK
| | - Fabien Colaone
- Health Economics, Pricing, Reimbursement and Market Access, Sirtex Medical United Kingdom Ltd, London, UK
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Fawzy MS, Toraih EA. MicroRNA signatures as predictive biomarkers in transarterial chemoembolization‐treated hepatocellular carcinoma. PRECISION MEDICAL SCIENCES 2021. [DOI: 10.1002/prm2.12031] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Affiliation(s)
- Manal S. Fawzy
- Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine Suez Canal University Ismailia Egypt
- Biochemistry Department, Faculty of Medicine Northern Border University Arar KSA
| | - Eman A. Toraih
- Department of Surgery Tulane University, School of Medicine New Orleans Louisiana USA
- Genetics Unit, Department of Histology and Cell Biology, Faculty of Medicine Suez Canal University Ismailia Egypt
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45
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Effect and Molecular Mechanisms of Jiedu Recipe on Hypoxia-Induced Angiogenesis after Transcatheter Arterial Chemoembolization in Hepatocellular Carcinoma. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2021; 2021:6529376. [PMID: 33505496 PMCID: PMC7815394 DOI: 10.1155/2021/6529376] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/05/2020] [Revised: 07/23/2020] [Accepted: 12/30/2020] [Indexed: 12/25/2022]
Abstract
Transcatheter arterial chemoembolization (TACE) is one of the effective treatment methods for hepatocellular carcinoma (HCC) in middle and late phases. However, TACE-induced hypoxia may promote the angiogenesis and section of some cytokines, such as IL-8, and, thereby, lead to tumor metastasis. Therefore, we investigated the effect of Jiedu Recipe (JR), which has been demonstrated as an effective Traditional Chinese Medicine (TCM) recipe on HCC, on TACE-induced cytokines upregulation and hypoxia-induced angiogenesis. A total of 88 hepatocellular carcinoma (HCC) patients treated with TACE were enrolled and divided into a JR group or control group. TACE induced significant increases of neutrophil lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), IL-1β, IL-2R, IL-6, and IL-8. JR treatment significantly inhibited the elevation of IL-8 compared with control. In vitro, JR significantly inhibited the hypoxia-induced overexpression of IL-8, HIF-1α, and VEGF mRNA in Huh 7 cells. ELISA assay demonstrated the effect of JR on IL-8 expression. Both hypoxia and IL-8 may promote angiogenesis which was suppressed by JR. Western blot showed that IL-8 upregulated the expression of phosphorylation of AKT, ERK, NF-κB, and VEGFR, which were inhibited by JR. On the other hand, effects of IL-8 on the increase of p-AKT and p-ERK were also blocked by LY294002 and U0126, respectively. In conclusion, our results indicated that JR may inhibit hypoxia-induced angiogenesis through suppressing IL-8/HIF-1α/PI3K and MAPK/ERK pathways after TACE in HCC patients.
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46
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Kloeckner R, Galle PR, Bruix J. Local and Regional Therapies for Hepatocellular Carcinoma. Hepatology 2021; 73 Suppl 1:137-149. [PMID: 32557715 DOI: 10.1002/hep.31424] [Citation(s) in RCA: 91] [Impact Index Per Article: 22.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2020] [Revised: 05/21/2020] [Accepted: 05/26/2020] [Indexed: 12/11/2022]
Affiliation(s)
- Roman Kloeckner
- Department of Diagnostic and Interventional Radiology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany
| | - Peter Robert Galle
- Department of Internal Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany
| | - Jordi Bruix
- Barcelona Clinic Liver Cancer Group, Liver Unit, Hospital Clínic, IDIBAPS, University of Barcelona, CIBEREHD Barcelona, Barcelona, Spain
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47
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Adhoute X, Anty R, Bourlière M. Transarterial chemoembolization (TACE) plus sorafenib: a real winning combination? ANNALS OF TRANSLATIONAL MEDICINE 2020; 8:1616. [PMID: 33437815 PMCID: PMC7791214 DOI: 10.21037/atm-20-4268] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Affiliation(s)
- Xavier Adhoute
- Department of Gastroenterology and Hepatology, Hôpital Saint-Joseph, Marseille, France
| | - Rodolphe Anty
- Department of Gastroenterology and Hepatology, Hôpital Universitaire de l'Archet, Nice, France
| | - Marc Bourlière
- Department of Gastroenterology and Hepatology, Hôpital Saint-Joseph, Marseille, France
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48
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Chang Y, Jeong SW, Young Jang J, Jae Kim Y. Recent Updates of Transarterial Chemoembolilzation in Hepatocellular Carcinoma. Int J Mol Sci 2020; 21:E8165. [PMID: 33142892 PMCID: PMC7662786 DOI: 10.3390/ijms21218165] [Citation(s) in RCA: 189] [Impact Index Per Article: 37.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2020] [Revised: 10/28/2020] [Accepted: 10/28/2020] [Indexed: 12/24/2022] Open
Abstract
Transarterial chemoembolization (TACE) is a standard treatment for intermediate-stage hepatocellular carcinoma (HCC). In this review, we summarize recent updates on the use of TACE for HCC. TACE can be performed using two techniques; conventional TACE (cTACE) and drug-eluting beads using TACE (DEB-TACE). The anti-tumor effect of the two has been reported to be similar; however, DEB-TACE carries a higher risk of hepatic artery and biliary injuries and a relatively lower risk of post-procedural pain than cTACE. TACE can be used for early stage HCC if other curative treatments are not feasible or as a neoadjuvant treatment before liver transplantation. TACE can also be considered for selected patients with limited portal vein thrombosis and preserved liver function. When deciding to repeat TACE, the ART (Assessment for Retreatment with TACE) score and ABCR (AFP, BCLC, Child-Pugh, and Response) score can guide the decision process, and TACE refractoriness needs to be considered. Studies on the combination therapy of TACE with other treatment modalities, such as local ablation, radiation therapy, or systemic therapy, have been actively conducted and are still ongoing. Recently, new prognostic models, including analysis of the neutrophil-lymphocyte ratio, radiomics, and deep learning, have been developed to help predict survival after TACE.
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Affiliation(s)
- Young Chang
- Department of Internal Medicine, Digestive Disease Center, Institute for Digestive Research, Soonchunhyang University College of Medicine, Seoul 04401, Korea; (Y.C.); (J.Y.J.)
| | - Soung Won Jeong
- Department of Internal Medicine, Digestive Disease Center, Institute for Digestive Research, Soonchunhyang University College of Medicine, Seoul 04401, Korea; (Y.C.); (J.Y.J.)
| | - Jae Young Jang
- Department of Internal Medicine, Digestive Disease Center, Institute for Digestive Research, Soonchunhyang University College of Medicine, Seoul 04401, Korea; (Y.C.); (J.Y.J.)
| | - Yong Jae Kim
- Department of Radiology, Soonchunhyang University College of Medicine, Seoul 04401, Korea;
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Chen S, Shi M, Shen L, Qi H, Wan W, Cao F, Xie L, Wu Y, Chen G, Mo J, Zhu G, Ye D, Zhang Y, Feng Z, Xu L, Fan W. Microwave ablation versus sorafenib for intermediate-Stage Hepatocellular carcinoma with transcatheter arterial chemoembolization refractoriness: a propensity score matching analysis. Int J Hyperthermia 2020; 37:384-391. [PMID: 32323585 DOI: 10.1080/02656736.2020.1752400] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023] Open
Abstract
Purpose: To compared the benefits of sorafenib with microwave ablation (MWA) in intermediate-stage hepatocellular carcinoma (HCC) patients with tumor size ≤7 cm and tumor number ≤5 after Transcatheter Arterial Chemoembolization (TACE) failure.Methods: A retrospective, single-center study was conducted using a one-to-one propensity score matching (PSM) analysis and involved 52 intermediate-stage HCC patients with absence of evidence of intrahepatic vascular invasion and extrahepatic metastasis after TACE failure and underwent treatment with MWA or sorafenib between 2007 and 2019. The overall survival (OS) and progression-free survival (PFS) were evaluated by the Kaplan-Meier method. The factors with OS and PFS were determined by Cox regression.Results: Of the 52 patients included in our study, 30 (57.7%) underwent MWA and 22 (42.3%) received sorafenib. After PSM, 22 pairs were enrolled into different groups for further analysis. Patients in the MWA-group had a significantly longer median PFS than patients in the sorafenib-group on both before (median, 9.3 vs. 2.8 months, p = .001) and after PSM (median, 9.0 vs. 2.8 months, p = .006). They also had a significantly longer median OS than patients in the sorafenib-group on before (median, 48.8 vs. 16.6 months, p = .001) and after PSM (median, Not reached vs. 16.6 months, p = .001). Besides, Cox regression analysis showed that the treatment and age were the independent prognostic factors of OS and PFS (p＜0.05).Conclusions: MWA was superior to sorafenib in improving survival for intermediate-stage hepatocellular carcinoma (HCC) patients with tumor size ≤7 cm and tumor number ≤5 after TACE failure.Key PointsCompared with sorafenib, microwave ablation may be a more reasonable alternative treatment for intermediate-stage hepatocellular carcinoma (HCC) patients with tumor size ≤7 cm and tumor number ≤5 after TACE refractoriness.The treatment (MWA vs sorafenib) and the age of patients were the independent prognostic factors of OS and PFS.
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Affiliation(s)
- Shuanggang Chen
- Department of Minimally Invasive Interventional Therapy, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China.,People's Republic of China State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University, Guangzhou, People's Republic of China
| | - Mengting Shi
- People's Republic of China State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University, Guangzhou, People's Republic of China.,Zhong Shan Medical School, Sun Yat-sen University, Guangzhou, People's Republic of China
| | - Lujun Shen
- Department of Minimally Invasive Interventional Therapy, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China.,People's Republic of China State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University, Guangzhou, People's Republic of China
| | - Han Qi
- Department of Minimally Invasive Interventional Therapy, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China.,People's Republic of China State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University, Guangzhou, People's Republic of China
| | - Weiqi Wan
- People's Republic of China State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University, Guangzhou, People's Republic of China.,Zhong Shan Medical School, Sun Yat-sen University, Guangzhou, People's Republic of China
| | - Fei Cao
- Department of Minimally Invasive Interventional Therapy, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China.,People's Republic of China State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University, Guangzhou, People's Republic of China
| | - Lin Xie
- Department of Minimally Invasive Interventional Therapy, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China.,People's Republic of China State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University, Guangzhou, People's Republic of China
| | - Ying Wu
- Department of Minimally Invasive Interventional Therapy, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China.,People's Republic of China State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University, Guangzhou, People's Republic of China
| | - Guanjian Chen
- People's Republic of China State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University, Guangzhou, People's Republic of China.,Zhong Shan Medical School, Sun Yat-sen University, Guangzhou, People's Republic of China
| | - Jinqing Mo
- People's Republic of China State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University, Guangzhou, People's Republic of China.,Zhong Shan Medical School, Sun Yat-sen University, Guangzhou, People's Republic of China
| | - Guolian Zhu
- People's Republic of China State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University, Guangzhou, People's Republic of China.,Department of Oncology, Chenghai District People's Hospital, Shantou, People's Republic of China
| | - Dongdong Ye
- People's Republic of China State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University, Guangzhou, People's Republic of China.,Zhong Shan Medical School, Sun Yat-sen University, Guangzhou, People's Republic of China
| | - Yinqi Zhang
- People's Republic of China State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University, Guangzhou, People's Republic of China.,Zhong Shan Medical School, Sun Yat-sen University, Guangzhou, People's Republic of China
| | - Ziqing Feng
- People's Republic of China State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University, Guangzhou, People's Republic of China.,Zhong Shan Medical School, Sun Yat-sen University, Guangzhou, People's Republic of China
| | - Li Xu
- People's Republic of China State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University, Guangzhou, People's Republic of China.,Department of Hepatobiliary Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China
| | - Weijun Fan
- Department of Minimally Invasive Interventional Therapy, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China.,People's Republic of China State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University, Guangzhou, People's Republic of China
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50
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Becker LS, Maschke SK, Dewald CLA, Meine TC, Winther HBM, Kirstein MM, Kloeckner R, Meyer BC, Wacker F, Hinrichs JB. Two-dimensional parametric parenchymal blood flow in transarterial chemoembolisation for hepatocellular carcinoma: perfusion change quantification and tumour response prediction at 3 months post-intervention. Clin Radiol 2020; 76:160.e27-160.e33. [PMID: 33028487 DOI: 10.1016/j.crad.2020.09.012] [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: 05/14/2020] [Accepted: 09/09/2020] [Indexed: 11/19/2022]
Abstract
AIM To evaluate the feasibility and potential value of two-dimensional (2D) parametric parenchymal blood flow (2D-PPBF) for the assessment of perfusion changes during transarterial chemoembolisation with drug-eluting beads (DEB-TACE) and to analyse correlations of 2D-PPBF parameters and tumour response. MATERIALS AND METHODS Thirty-two patients (six women, 26 men, mean age: 67±8.9 years) with unresectable hepatocellular carcinoma (HCC) who underwent their first DEB-TACE were included in this study. To quantify perfusion changes using 2D-PPBF, the acquired digital subtraction angiography (DSA) series were post-processed. Ratios were calculated between the reference region of interest (ROI) and the wash-in rate (WIR), the arrival to peak (AP) and the area under the curve (AUC) of the generated time-density curves. Comparisons between pre- and post-embolisation data were made using the Wilcoxon signed-rank test. Tumour response was assessed at 3 months using the modified Response Evaluation Criteria in Solid Tumours (mRECIST) and correlated to changes of 2D-PPBF parameters. RESULTS All 2D-PPBF parameters derived from the ROI-based time-attenuation curves were significantly different pre-versus post-DEB-TACE. Although the AUC, the WIR and target lesion size measured in accordance with mRECIST decreased (p≤0.0001) significantly, AP values showed a significant increase (p = 0.0033). Tumour response after DEB-TACE correlated with changes in the AUC (p = 0.01, r = -0.45). CONCLUSION 2D-PPBF offers an objective approach to analyse perfusion changes of embolised tumour tissue following DEB-TACE and can therefore be used to predict tumour response.
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Affiliation(s)
- L S Becker
- Department of Diagnostic and Interventional Radiology, Hannover Medical School, Hannover, Germany
| | - S K Maschke
- Department of Diagnostic and Interventional Radiology, Hannover Medical School, Hannover, Germany
| | - C L A Dewald
- Department of Diagnostic and Interventional Radiology, Hannover Medical School, Hannover, Germany
| | - T C Meine
- Department of Diagnostic and Interventional Radiology, Hannover Medical School, Hannover, Germany
| | - H B M Winther
- Department of Diagnostic and Interventional Radiology, Hannover Medical School, Hannover, Germany
| | - M M Kirstein
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
| | - R Kloeckner
- Department of Diagnostic and Interventional Radiology, Johannes Gutenberg-University Medical Centre, Mainz, Germany
| | - B C Meyer
- Department of Diagnostic and Interventional Radiology, Hannover Medical School, Hannover, Germany
| | - F Wacker
- Department of Diagnostic and Interventional Radiology, Hannover Medical School, Hannover, Germany
| | - J B Hinrichs
- Department of Diagnostic and Interventional Radiology, Hannover Medical School, Hannover, Germany.
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