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Chen YF, Lin ZY, Chen LT, Zhang Y, Du ZQ. Cystic artery embolism after transarterial chemoembolization for hepatocellular carcinoma: A case report and review of the literature. World J Gastrointest Oncol 2025; 17:99129. [PMID: 40092942 PMCID: PMC11866240 DOI: 10.4251/wjgo.v17.i3.99129] [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: 07/14/2024] [Revised: 11/22/2024] [Accepted: 12/19/2024] [Indexed: 02/14/2025] Open
Abstract
BACKGROUND Acute cholecystitis due to unintended cystic artery embolism is an uncommon and mostly self-limiting complication after transarterial chemoembolization procedure for treatment of hepatocellular carcinoma. Usually, conservative management is sufficient for complete recovery of patients who develop this complication. If conservative treatment is ineffective, urgent surgical intervention may be required to prevent the progression of complications. CASE SUMMARY This article reports a rare and serious case of acute cholecystitis complicated by gallbladder necrosis and biliary peritonitis, which was initially treated conservatively but eventually necessitated emergency laparotomy. The patient initially presented with equivocal symptoms of fever and upper abdominal pain and distention, which worsened at the two weeks mark along with emergence of signs of peritonitis. This was managed by emergency laparotomy and cholecystostomy, allowing rapid symptom relief. The patient ultimately discharged and succumbed to advanced liver cancer 11 months after diagnosis. CONCLUSION After cholecystostomy, the patient showed symptom relief and was discharged, surviving 11 months post-stage IIIB liver cancer diagnosis.
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Affiliation(s)
- Yi-Fan Chen
- Department of Hepatobiliary Surgery, Shaanxi Provincial People’s Hospital, Xi’an 710068, Shaanxi Province, China
- Department of Gastroenterology, Peking University Third Hospital, Beijing 100191, China
| | - Zhen-Yi Lin
- Department of Hepatobiliary Surgery, Shaanxi Provincial People’s Hospital, Xi’an 710068, Shaanxi Province, China
- Medical Student, 10 Medical Dr, Singapore 117597, Singapore
| | - Lin-Tao Chen
- Department of Hepatobiliary Surgery, Shaanxi Provincial People’s Hospital, Xi’an 710068, Shaanxi Province, China
- Xizang Minzu University, Xianyang 712082, Shaanxi Province, China
| | - Yu Zhang
- Department of Hepatobiliary Surgery, Shaanxi Provincial People’s Hospital, Xi’an 710068, Shaanxi Province, China
| | - Zhao-Qing Du
- Department of Hepatobiliary Surgery, Shaanxi Provincial People’s Hospital, Xi’an 710068, Shaanxi Province, China
- National Engineering Research Center for Miniaturized Detection Systems, College of Life Science, Northwest University of Xi'an, Xi'an 710069, Shaanxi Province, China
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Khilwani H, Stettner S, Sonnabend K, Chen Y, Jain S, Gaba RC. Treatment of Hepatocellular Carcinoma with Combined Transarterial Chemoembolization and Systemic Therapy. Semin Intervent Radiol 2024; 41:309-316. [PMID: 39165657 PMCID: PMC11333115 DOI: 10.1055/s-0044-1787835] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/22/2024]
Affiliation(s)
- Harsh Khilwani
- University of Illinois College of Medicine, Chicago, Illinois
| | - Sarah Stettner
- University of Illinois College of Medicine, Chicago, Illinois
| | - Kyle Sonnabend
- Division of Hematology and Oncology, Department of Medicine, University of Illinois at Chicago, Chicago, Illinois
| | - Yolande Chen
- University of Illinois College of Medicine, Chicago, Illinois
- Division of Hematology and Oncology, Department of Medicine, University of Illinois at Chicago, Chicago, Illinois
| | - Shikha Jain
- University of Illinois College of Medicine, Chicago, Illinois
- Division of Hematology and Oncology, Department of Medicine, University of Illinois at Chicago, Chicago, Illinois
| | - Ron C. Gaba
- University of Illinois College of Medicine, Chicago, Illinois
- Division of Interventional Radiology, Department of Radiology, University of Illinois at Chicago, Chicago, Illinois
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Guo C, Zhang J, Huang X, Chen Y, Sheng J, Huang X, Sun J, Xiao W, Sun K, Gao S, Que R, Shen Y, Zhang M, Wu J, Bai X, Liang T. Preoperative sintilimab plus transarterial chemoembolization for hepatocellular carcinoma exceeding the Milan criteria: A phase II trial. Hepatol Commun 2023; 7:e0054. [PMID: 36757445 PMCID: PMC9916103 DOI: 10.1097/hc9.0000000000000054] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2022] [Accepted: 12/01/2022] [Indexed: 02/10/2023] Open
Abstract
BACKGROUND AND AIMS Many patients with HCC of Barcelona Clinic Liver Cancer (BCLC) stage A exceeding the Milan criteria, or of BCLC stage B, can undergo resection after successful preoperative therapy, but an optimal approach has not been identified. We investigated preoperative drug-eluting bead transarterial chemoembolization (DEB-TACE) plus sintilimab, in this setting. APPROACH AND RESULTS In this prospective, phase II study (NCT04174781), adults with HCC of BCLC stage A exceeding the Milan criteria, or BCLC stage B, and ineligible for surgical resection, received sintilimab 200 mg and DEB-TACE. The primary endpoint was progression-free survival by modified RECIST. Secondary endpoints included objective response rate, pathologic response rate, and safety. At the data cutoff (July 2022), among 60 patients, the objective response rate was 62% (37/60) and 51 patients had undergone surgery. After a median follow-up of 26.0 months (range, 3.4-31.8), the median progression-free survival was 30.5 months (95% CI: 16.1-not reached). Among patients undergoing surgery, median progression-free survival was not reached and the 12-month progression-free survival rate was 76% (95% CI: 67-91). A pathologic complete response was achieved in 14% (7/51) of these patients. All patients experienced at least one adverse event, but these were generally manageable. Exploratory analyses showed an association between cytokeratin, V-domain Ig-containing Suppressor of T-cell Activation, CD68, CD169, and cluster 13 fibroblasts and recurrence after surgery. CONCLUSIONS Sintilimab plus DEB-TACE before surgery showed good efficacy and safety in patients with HCC of BCLC stage A exceeding the Milan criteria or BCLC stage B.
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Affiliation(s)
- Chengxiang Guo
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou, China
- Zhejiang Provincial Clinical Research Center for the Study of Hepatobiliary and Pancreatic Diseases, Hangzhou, China
- Cancer Center, Zhejiang University, Hangzhou, China
| | - Junlei Zhang
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou, China
- Zhejiang Provincial Clinical Research Center for the Study of Hepatobiliary and Pancreatic Diseases, Hangzhou, China
- Cancer Center, Zhejiang University, Hangzhou, China
| | - Xin Huang
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou, China
- Zhejiang Provincial Clinical Research Center for the Study of Hepatobiliary and Pancreatic Diseases, Hangzhou, China
- Cancer Center, Zhejiang University, Hangzhou, China
| | - Yiwen Chen
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou, China
- Zhejiang Provincial Clinical Research Center for the Study of Hepatobiliary and Pancreatic Diseases, Hangzhou, China
- Cancer Center, Zhejiang University, Hangzhou, China
| | - Jianpeng Sheng
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou, China
- Zhejiang Provincial Clinical Research Center for the Study of Hepatobiliary and Pancreatic Diseases, Hangzhou, China
- Cancer Center, Zhejiang University, Hangzhou, China
| | - Xing Huang
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou, China
- Zhejiang Provincial Clinical Research Center for the Study of Hepatobiliary and Pancreatic Diseases, Hangzhou, China
- Cancer Center, Zhejiang University, Hangzhou, China
| | - Junhui Sun
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Wenbo Xiao
- Department of Radiology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Ke Sun
- Department of Pathology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Shunliang Gao
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Risheng Que
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Yan Shen
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Min Zhang
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Jian Wu
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Xueli Bai
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou, China
- Zhejiang Provincial Clinical Research Center for the Study of Hepatobiliary and Pancreatic Diseases, Hangzhou, China
- Cancer Center, Zhejiang University, Hangzhou, China
| | - Tingbo Liang
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou, China
- Zhejiang Provincial Clinical Research Center for the Study of Hepatobiliary and Pancreatic Diseases, Hangzhou, China
- Cancer Center, Zhejiang University, Hangzhou, China
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Wang XH, Duan WB, Liang W, Li H, Xie XY, Li SQ, Chen MS, Liang P, Mao XH, Zhou QF. Efficacy of radiofrequency ablation following transarterial chemoembolisation combined with sorafenib for intermediate stage recurrent hepatocellular carcinoma: a retrospective, multicentre, cohort study. EClinicalMedicine 2023; 56:101816. [PMID: 36703645 PMCID: PMC9871741 DOI: 10.1016/j.eclinm.2022.101816] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/15/2022] [Revised: 12/14/2022] [Accepted: 12/19/2022] [Indexed: 01/21/2023] Open
Abstract
BACKGROUND The evidence of radiofrequency ablation (RFA) following transarterial chemoembolisation (TACE) combined with sorafenib for intermediate-stage recurrent hepatocellular carcinoma (RHCC) is limited. Patient responses to this treatment vary because of the heterogeneous nature of RHCC, making it important to identify patients who are most likely to benefit from this combination therapy. The aim of this study was to evaluate the efficacy of RFA following TACE and sorafenib for the intermediate-stage RHCC. METHODS This retrospective, multicentre, cohort study included 363 patients with intermediate-stage RHCC underwent TACE combined with sorafenib (TACE-sorafenib group) or RFA following TACE and sorafenib (TACE-sorafenib + RFA group) between January 01, 2009 to December 31, 2015 from four institutions in China. Overall survival (OS), progression-free survival (PFS) and efficacy of patients were compared between the two groups by propensity score-matching (PSM). FINDINGS The 1-, 3-, and 5-year OS rates were 97.7%, 83.7%, 54.7% in TACE-sorafenib + RFA group, and 93.3%, 57.0%, 32.7% in TACE-sorafenib group. The 1-, 2-, and 3-year PFS rates were 85.3%, 58.0%, 26.9% in TACE-sorafenib + RFA group, and 55.3%, 30.7%, 15.3% in TACE-sorafenib group. Compared with the TACE-sorafenib group, the TACE-sorafenib + RFA group had significantly longer OS (HR, 0.54; 95%CI, 0.40-0.73; P < 0.001) and PFS (HR, 0.52; 95% CI, 0.41-0.66; P < 0.001). Subgroup analysis was conducted to precisely screen out the beneficial population from RFA treatment. INTERPRETATION Our findings suggest that addition of RFA following TACE and sorafenib combination was superior to TACE combined with sorafenib for intermediate-stage RHCC, resulting in longer OS and PFS. Patients who had good response to TACE and achieved downstaging successfully could not benefit from the RFA therapy. FUNDING This research was funded by National Natural Science Foundation of China (No. 81627803), Chen Xiao-Ping Science and Technology Development Fund (CXPJJH1200009-06).
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Affiliation(s)
- Xiao-Hui Wang
- Department of Hepatobiliary Surgery, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University) Changsha, Hunan province, 410005, China
| | - Wen-Bin Duan
- Department of Hepatobiliary Surgery, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University) Changsha, Hunan province, 410005, China
| | - Wei Liang
- Department of Minimally Invasive Interventional Radiology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510260, China
| | - Hui Li
- Department of Minimally Invasive Interventional Radiology, Sun Yat-sen University Cancer Centre, Guangzhou, Guangdong, 510060, China
| | - Xiao-Yan Xie
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510060, China
| | - Shao-Qiang Li
- Department of Liver Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, 510060, China
| | - Min-Shan Chen
- Department of Liver Surgery, Sun Yat-sen University Cancer Centre, Guangzhou, Guangdong, 510060, China
| | - Ping Liang
- Department of Interventional Ultrasound, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853, China
- Corresponding author.
| | - Xian-Hai Mao
- Department of Hepatobiliary Surgery, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University) Changsha, Hunan province, 410005, China
- Corresponding author.
| | - Qun-Fang Zhou
- Department of Interventional Ultrasound, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853, China
- Corresponding author.
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Zhang C, Dai YH, Lian SF, Liu L, Zhao T, Wen JY. Efficacy of transcatheter arterial chemoembolization using pirarubicin-loaded microspheres combined with lobaplatin for primary liver cancer. World J Clin Cases 2022; 10:9650-9656. [PMID: 36186198 PMCID: PMC9516916 DOI: 10.12998/wjcc.v10.i27.9650] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2022] [Revised: 07/19/2022] [Accepted: 08/17/2022] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Drug-eluting beads show good safety and promising efficacy when used as part of a transarterial chemoembolization regimen for primary liver cancer. However, data on the clinical efficacy and safety of pirarubicin-loaded beads combined with lobaplatin are lacking in China.
AIM To evaluate the efficacy and safety of transcatheter arterial chemoembolization using pirarubicin-loaded beads combined with lobaplatin for primary liver cancer.
METHODS Between January 2019 and March 2020, 60 patients with primary liver cancer were selected at Hebei North University Affiliated First Hospital. According to different treatment methods, the participants were categorized into two groups with 30 patients treated with pirarubicin-loaded microspheres combined with lobaplatin included in an observation group and 30 patients treated with pirarubicin emulsion with lipiodol combined with lobaplatin were included in a control group. The progression-free survival, overall survival, clinical response rate, disease control rate, liver and kidney function and adverse reactions were compared between the two groups.
RESULTS The progression-free survival was 14 mo in the observation group, which was significantly higher than 9 mo of the control group (P < 0.05). The 6-mo, 12-mo and 18-mo survival rates were 93.33% (28/30), 66.67% (20/30) and 23.33% (7/30), respectively in the observation group, which were significantly higher than 83.33% (25/30), 50.00% (15/30) and 13.33% (4/30), respectively, of the control group (all P < 0.05). The clinical efficacy rate and disease control rate were 73.33% and 93.33%, respectively, in the observation group, which were significantly higher than those of the control group (53.55% and 80.00%, respectively, all P < 0.05). There was no significant difference in alpha-fetoprotein between the two groups before the treatment (P > 0.05). After the treatment, alpha-fetoprotein was 289.06 ± 76.21 ng/mL in the observation group and 365.01 ± 73.11 ng/mL in the control group, which were low in both groups compared with those before the treatment (all P < 0.05). The incidence of nausea and vomiting was significantly lower in the observation group than in the control group (P < 0.05). There was no significant difference for the adverse reactions of pain and fever between the two groups (P < 0.05).
CONCLUSION The combination of pirarubicin-loaded beads and lobaplatin can improve treatment efficacy resulting in mild liver function damage and postoperative complications in patients with primary liver cancer. It can be used in clinical practice.
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Affiliation(s)
- Chao Zhang
- Department of Interventional Therapy, Hebei North University Affiliated First Hospital, Zhangjiakou 075000, Hebei Province, China
| | - Yu-Hui Dai
- Department of Interventional Therapy, Hebei North University Affiliated First Hospital, Zhangjiakou 075000, Hebei Province, China
| | - Shu-Feng Lian
- Zhangjiakou Qiaoxi District Maternal and Child Health Care Hospital, Zhangjiakou 075000, Hebei Province, China
| | - Liang Liu
- Department of Interventional Therapy, Hebei North University Affiliated First Hospital, Zhangjiakou 075000, Hebei Province, China
| | - Ting Zhao
- Department of Interventional Therapy, Hebei North University Affiliated First Hospital, Zhangjiakou 075000, Hebei Province, China
| | - Jun-Ye Wen
- Department of Hepatobiliary Surgery, Hebei People’s Hospital, Shijiazhuang 050055, Hebei Province, China
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Wang W, Li F, Gan P, Li B, Li S. Callispheres drug-eluting bead transhepatic artery chemoembolization with oral delivery of sorafenib for the treatment of unresectable liver cancer. Front Surg 2022; 9:981116. [PMID: 36117819 PMCID: PMC9478363 DOI: 10.3389/fsurg.2022.981116] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2022] [Accepted: 08/12/2022] [Indexed: 11/13/2022] Open
Abstract
Objective Liver cancer is a significant contributor to global burden of cancer. Transcatheter arterial chemoembolization (TACE) is the standard of care for patients with unresectable liver cancer, and CalliSpheres, as novel drug-eluting bead (DEB) microspheres, have been found to be associated with a high tumor response rate. However, the outcomes after DEB-TACE treatment are not always satisfactory with tumor recurrence. Herein, we attempt to compare the clinical efficacy and safety of DEB-TACE with sorafenib and conventional TACE in treating advanced liver cancer. Methods The study retrospectively reviewed clinical records of 96 patients with liver cancer, among which there were 48 cases receiving DEB-TACE with sorafenib and 48 cases receiving conventional TACE. The physical properties of Callispheres were evaluated in HepG2 cells and a B6/J mouse model. Results DEB-TACE with Callispheres were demonstrated to effectively maintain stability and prolong the half-life of epirubicin. Compared with the patients receiving conventional TACE, those receiving DEB-TACE with sorafenib exhibited better patient outcomes with increased survival rate, reduced tumor volume, and declined levels of tumor markers. Additionally, DEB-TACE with Callispheres could effectively protect liver function, as well as reduce the toxic effects of loaded epirubicin, and its combination with sorafenib would not increase the incidence of adverse reactions. Conclusion DEB-TACE using CalliSpheres combined with sorafenib could prevent the progression of liver cancer and bring a better prognosis.
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Affiliation(s)
- Wenhui Wang
- Department of Interventional Medicine, The First Hospital of Lanzhou University, Lanzhou, China
- Correspondence: Wenhui Wang
| | - Fenqiang Li
- Department of Interventional Medicine, The First Hospital of Lanzhou University, Lanzhou, China
| | - Peiying Gan
- Department of Neurosurgery, The First Hospital of Lanzhou University, Lanzhou, China
| | - Baohua Li
- Department of Interventional Medicine, The First Hospital of Lanzhou University, Lanzhou, China
| | - Shuangxi Li
- Department of Interventional Medicine, The First Hospital of Lanzhou University, Lanzhou, China
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Cao G, Liu Y, Li L, Zhao X, Liu R, Liu J, Liu J, Cao H. A Comparison of Adverse Events Among Radiofrequency Ablation, Conventional Transarterial Chemoembolization (TACE) and Drug-Eluting Bead TACE in Treating Hepatocellular Carcinoma Patients. Cancer Manag Res 2021; 13:5373-5382. [PMID: 34262345 PMCID: PMC8275035 DOI: 10.2147/cmar.s308097] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2021] [Accepted: 06/11/2021] [Indexed: 01/10/2023] Open
Abstract
Background There has been very limited investigation regarding the comparison of adverse events (AEs) among radiofrequency ablation (RFA), conventional transarterial chemoembolization (cTACE), and drug-eluting bead TACE (DEB-TACE) in treating HCC patients; therefore, the present study aimed to resolve this issue. Methods Two-hundred and forty-six HCC patients (with a total of 267 procedures [treatment times]) treated with RFA (73 patients with 79 procedures), cTACE (86 patients with 94 procedures), or DEB-TACE (87 patients with 94 procedures) were included. Demographic and clinical data were collected. The information on AEs was also retrieved and analyzed. Results Total AEs incidence was notably different among the RFA group, cTACE group, and DEB-TACE group and was the highest in cTACE group (86.2%), then in DEB-TACE group (76.6%), and the lowest in RFA group (63.3%). Regarding specific AEs incidence, the incidences of fever, fatigue, and nausea were distinctive among the three groups, while no distinctiveness was found in incidence of other AEs. Furthermore, multivariate logistic regression revealed that cTACE (versus RFA) was independently correlated with increased risk of total AEs, fatigue, and nausea/vomiting; however, the interventional therapies were not independently correlated with the risk of pain, fever or constipation. Other independent predictive factors for total AEs risk were male gender, bronchial asthma, and disease duration. Conclusion cTACE resulted in the highest AEs incidence compared with RFA and DEB-TACE in treating HCC patients.
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Affiliation(s)
- Guangshao Cao
- Department of Intervention, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, People's Hospital of Henan University, Zhengzhou, Henan, People's Republic of China
| | - Yuyan Liu
- Department of Intervention, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, People's Hospital of Henan University, Zhengzhou, Henan, People's Republic of China
| | - Lupeng Li
- Department of Intervention, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, People's Hospital of Henan University, Zhengzhou, Henan, People's Republic of China
| | - Xiaoyang Zhao
- Department of Intervention, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, People's Hospital of Henan University, Zhengzhou, Henan, People's Republic of China
| | - Ruiqing Liu
- Department of Intervention, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, People's Hospital of Henan University, Zhengzhou, Henan, People's Republic of China
| | - Jian Liu
- Department of Intervention, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, People's Hospital of Henan University, Zhengzhou, Henan, People's Republic of China
| | - Jianwen Liu
- Department of Intervention, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, People's Hospital of Henan University, Zhengzhou, Henan, People's Republic of China
| | - Huicun Cao
- Department of Intervention, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, People's Hospital of Henan University, Zhengzhou, Henan, People's Republic of China
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Chen C, Qiu H, Yao Y, Zhang Z, Ma C, Ma Y, Zhao C, Xiang H, Zhao H, Zheng C, Xiong B, Li H, Long Q, Zhou J, Luo C, Hu H. Comprehensive predictive factors for CalliSpheres® microspheres (CSM) drug-eluting bead-transarterial chemoembolization and conventional transarterial chemoembolization on treatment response and survival in hepatocellular carcinoma patients. Clin Res Hepatol Gastroenterol 2021; 45:101460. [PMID: 32593695 DOI: 10.1016/j.clinre.2020.05.008] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2020] [Revised: 05/12/2020] [Accepted: 05/26/2020] [Indexed: 02/04/2023]
Abstract
BACKGROUND Transarterial chemoembolization (TACE) is widely applied in hepatocellular carcinoma (HCC) patients who are not suitable for surgical treatment. We aimed to investigate the treatment outcomes and comprehensive prognostic factors of CalliSpheres® microspheres (CSM) drug-eluting bead TACE (DEB-TACE) treatment and conventional TACE (cTACE) treatment in HCC patients. METHODS Three hundred and thirty-five HCC patients received DEB-TACE or cTACE treatment were consecutively enrolled in multi-center, retrospective cohort study. Treatment response was conducted at M1, M3 or M6 after treatment. Progression free survival (PFS) and overall survival (OS) were recorded. Thirty-seven baseline factors including demographic characteristics, clinical features, biochemical indexes and previous treatment histories were selected. RESULTS In total patients, history of drink and largest nodule size≥7cm independently predicted worse ORR, DEB-TACE predicted better OS, while largest nodule size≥7cm, increased Child-Pugh stage, ALB abnormal, ALP abnormal or AFP abnormal predicted worse survival. For DEB-TACE group, previous cTACE and ANC abnormal independently predicted worse ORR, and hepatic vein invasion, increased Child-Pugh stage or AFP abnormal independently predicted poor survival. For cTACE group, largest nodule size≥7cm independently predicted poor ORR, and multifocal disease as well as ALB abnormal predicted poor OS. CONCLUSIONS History of drink, largest nodule size≥7cm, DEB-TACE, increased Child-Pugh stage, abnormal ALB, ALP or AFP are potential prognostic factors in total patients, previous cTACE and ANC abnormal, hepatic vein invasion, increased Child-Pugh stage or AFP abnormal are potential prognostic factors in DEB-TA group, and largest nodule size≥7cm, multifocal disease and ALB abnormal are potential prognostic factors in cTACE group.
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Affiliation(s)
- Changyong Chen
- Department of Radiology, Xiangya Hospital Central South University, Changsha, China
| | - Huaiming Qiu
- Department of Radiology, Wuhan General Hospita of Guangzhou Military, 627 Wuluo Road, Wuhan 430070, China.
| | - Yuanhui Yao
- Department of Intervention, Hunan Provincial People's Hospital, Changsha, China
| | - Zishu Zhang
- Department of Radiology, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Cong Ma
- Department of Radiology, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Yilong Ma
- Department of Interventional Therapy, Guangxi Medical University Affiliated Tumor Hospital, Nanning, China
| | - Chang Zhao
- Department of Interventional Therapy, Guangxi Medical University Affiliated Tumor Hospital, Nanning, China
| | - Hua Xiang
- Department of Intervention, Hunan Provincial People's Hospital, Changsha, China
| | - Hui Zhao
- Department of Interventional Radiology,Department of Radiology, Renmin Hospital of Wuhan University, Jiefang Road 238, Wuhan 430060, China
| | - Chuansheng Zheng
- Department of Interventional Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Bin Xiong
- Department of Interventional Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Haiping Li
- Department of Radiology, Xiangya Hospital Central South University, Changsha, China
| | - Qingyun Long
- Department of Radiology, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Jun Zhou
- Department of Radiology, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Chao Luo
- Department of Radiology, Wuhan General Hospita of Guangzhou Military, 627 Wuluo Road, Wuhan 430070, China
| | - Hongyao Hu
- Department of Interventional Radiology,Department of Radiology, Renmin Hospital of Wuhan University, Jiefang Road 238, Wuhan 430060, China.
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9
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Chen A, Li S, Yao Z, Hu J, Cao J, Topatana W, Juengpanich S, Yu H, Shen J, Chen M. Adjuvant transarterial chemoembolization to sorafenib in unresectable hepatocellular carcinoma: A meta-analysis. J Gastroenterol Hepatol 2021; 36:302-310. [PMID: 32652685 DOI: 10.1111/jgh.15180] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2020] [Revised: 06/11/2020] [Accepted: 07/04/2020] [Indexed: 12/26/2022]
Abstract
BACKGROUND AND AIM An increasing number of transarterial chemoembolization (TACE) plus sorafenib combination therapy has been applied for unresectable hepatocellular carcinoma (HCC). However, it remains controversial whether combination therapy is superior to sorafenib monotherapy. Therefore, we aimed to perform a meta-analysis to evaluate the efficacy and safety of the combination therapy of TACE plus sorafenib for unresectable HCC. METHODS This meta-analysis was based on the relative outcomes from a specific search of online databases between January 2008 and November 2019, and subgroup analyses were conducted to identify potential predictive factors. RESULTS A total of 3868 patients (TACE plus sorafenib vs sorafenib, 1181 vs 2687) were identified from nine studies, including one randomized controlled trial and eight retrospective cohort studies. The pooled results revealed that TACE plus sorafenib combination therapy significantly improves overall survival with the combined hazard ratio 0.74 (95% confidence interval [CI] = 0.66-0.84, P < 0.001), time to progression (hazard ratio = 0.73, 95%CI = 0.65-0.82, P < 0.001), and objective response rate (odds ratio = 2.19, 95% CI = 1.31-3.66, P = 0.003). Subgroup analysis indicated that patients who developed macrovascular invasion achieve significantly great overall survival (P for interaction = 0.001) with combination therapy, in contrast to nonmacrovascular invasion patients. In addition, no significant differences in adverse events were observed. CONCLUSION This meta-analysis demonstrated that TACE plus sorafenib combination therapy is superior to sorafenib monotherapy and should be recommended as an optimal treatment choice for unresectable HCC.
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Affiliation(s)
- Anxin Chen
- Nanshan School, Guangzhou Medical University, Guangzhou, China
| | - Shijie Li
- Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University, Hangzhou, China
| | - Zhiyuan Yao
- Nanshan School, Guangzhou Medical University, Guangzhou, China
| | - Jiahao Hu
- Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University, Hangzhou, China
| | - Jiasheng Cao
- Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University, Hangzhou, China
| | - Win Topatana
- Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University, Hangzhou, China
| | - Sarun Juengpanich
- Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University, Hangzhou, China
| | - Hong Yu
- Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University, Hangzhou, China
| | - Jiliang Shen
- Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University, Hangzhou, China
| | - Mingyu Chen
- Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University, Hangzhou, China.,Engineering Research Center of Cognitive Healthcare of Zhejiang Province, Hangzhou, China
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10
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Chang Y, Lee YB, Cho EJ, Lee JH, Yu SJ, Kim YJ, Yoon JH. CKD-5, a novel pan-histone deacetylase inhibitor, synergistically enhances the efficacy of sorafenib for hepatocellular carcinoma. BMC Cancer 2020; 20:1001. [PMID: 33059615 PMCID: PMC7559883 DOI: 10.1186/s12885-020-07471-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2019] [Accepted: 09/29/2020] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND Histone deacetylase inhibitors (HDACIs) have distinctive epigenetic targets involved in hepatocarcinogenesis and chemoresistance. A recent phase I/II study reported the possibility of HDACI as a chemosensitizer in sorafenib-resistant patients. In this study, we evaluated whether CKD-5, a novel pan-HDACI, can potentiate the efficacy of sorafenib. METHODS The anticancer effect of CKD-5 with and without sorafenib was evaluated in vitro using an MTS assay with human HCC cells (SNU-3058 and SNU-761) under both normoxic and hypoxic conditions. Microarray analysis was performed to investigate the mechanism of cell death, which was also evaluated by small interfering RNA (siRNA) transfection and subsequent immunoblot assays. In vivo experiments were conducted using two different murine HCC models. C3H mice implanted with MH134 cells and C57BL/6 mice implanted with RIL-175 cells were treated with weekly CKD-5 with and without sorafenib for 2 weeks. RESULTS CKD-5 treatment significantly suppressed human HCC cell growth in both normoxic and hypoxic conditions. Microarray analysis and real-time PCR showed that CKD-5 treatment significantly increased peripherin expression in HCC cells and that downregulation of peripherin by siRNA decreased CKD-5-induced apoptosis. The combination of CKD-5 and sorafenib decreased cell viability more effectively than sorafenib or CKD-5 monotherapy in human and murine HCC cells. The effectiveness of the combination therapy was consistently demonstrated in the animal models. Histological and biochemical analyses demonstrated good tolerance of CKD-5 plus sorafenib in vivo. CONCLUSION CKD-5 may enhance sorafenib efficacy through epigenetic regulation. The combination of CKD-5 and sorafenib might be a novel therapeutic option for the treatment of HCC.
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Affiliation(s)
- Young Chang
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.,Institute for Digestive Research, Digestive Disease Center, Department of Internal Medicine, Soonchunhyang University College of Medicine, Seoul, Korea
| | - Yun Bin Lee
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea
| | - Eun Ju Cho
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea
| | - Jeong-Hoon Lee
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea
| | - Su Jong Yu
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea
| | - Yoon Jun Kim
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea
| | - Jung-Hwan Yoon
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.
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11
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Chen L, Sun T, Chen S, Ren Y, Yang F, Zheng C. The efficacy of surgery in advanced hepatocellular carcinoma: a cohort study. World J Surg Oncol 2020; 18:119. [PMID: 32487104 PMCID: PMC7268283 DOI: 10.1186/s12957-020-01887-8] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2020] [Accepted: 05/18/2020] [Indexed: 02/07/2023] Open
Abstract
Background It is still controversial whether hepatocellular carcinoma (HCC) patients with lymph node invasion should receive surgery treatment. This study aimed to evaluate the efficacy of surgery (liver resection and local tumor destruction treatments) in HCC patients with regional lymph node metastasis. Methods The study utilized data from the Surveillance, Epidemiology, and End Results-18 (SEER-18) cancer registry. Patients for whom the treatment type was not clear or those with distant metastasis or without regional lymph nodule invasion were excluded. For survival analysis, patients with the survival months coded as 0 and 999 were excluded. All 1434 patients were included in the analysis. Among them, 168 patients were treated surgically and the other 1266 received non-surgery therapy. Propensity score matching (PSM) model was used to reduce selection bias. Results Before PSM, the median overall survival (mOS) and median cancer-specific survival (mCSS) of patients treated surgically were longer than that of receiving non-surgery treatment (mOS 20 months, 95% CI 15.3–24.7 vs. 7 months, 95% CI 6.4–7.6, P < 0.001; mCSS 21 months, 95% CI 115.5–26.5 vs. 6 months, 95% CI 5.3–6.7, P < 0.001). Subgroup analysis found no significant differences in mOS and mCSS between liver resection and non-liver resection surgery cohorts (P = 0.886 and P = 0.813, respectively). Similar results were obtained in the PSM analysis. The mOS and mCSS in the surgery group were longer than those in the non-surgery group (mOS 20 months vs. 7 months, P < 0.001; mCSS 20 months vs. 6 months, P < 0.001). The multivariate analysis documented that surgery was an independent predictor for OS and CSS before and after PSM. Conclusions HCC patients with invasion of regional lymph nodules may get more survival benefit from surgery than other types of treatment.
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Affiliation(s)
- Lei Chen
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.,Hubei Province Key Laboratory of Molecular Imaging, Wuhan, 430022, China.,Department of Interventional Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Tao Sun
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.,Hubei Province Key Laboratory of Molecular Imaging, Wuhan, 430022, China.,Department of Interventional Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Shi Chen
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.,Hubei Province Key Laboratory of Molecular Imaging, Wuhan, 430022, China
| | - Yanqiao Ren
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.,Hubei Province Key Laboratory of Molecular Imaging, Wuhan, 430022, China.,Department of Interventional Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Fan Yang
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. .,Hubei Province Key Laboratory of Molecular Imaging, Wuhan, 430022, China.
| | - Chuansheng Zheng
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. .,Hubei Province Key Laboratory of Molecular Imaging, Wuhan, 430022, China. .,Department of Interventional Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
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12
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Liu J, Xu J, Zhang W, Chen J, Zhou X, Li Z, Han X. Safety and Efficacy of Drug-Eluting Bead Transarterial Chemoembolization Combined with Apatinib in Patients with Advanced Hepatocellular Carcinoma. Acad Radiol 2020; 27:704-709. [PMID: 31375353 DOI: 10.1016/j.acra.2019.07.003] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2019] [Revised: 07/04/2019] [Accepted: 07/08/2019] [Indexed: 02/08/2023]
Abstract
RATIONALE AND OBJECTIVE The goal of this study was to determine the clinical efficacy and safety of drug-eluting bead (DEB) transarterial chemoembolization (TACE) in combination with apatinib administration in patients with advanced hepatocellular carcinoma (HCC). MATERIALS AND METHODS From December 2015 to May 2017, a total of 32 patients with advanced HCC treated with DEB-TACE combined with apatinib were consecutively enrolled in this study. The treatment response and laboratory outcomes were assessed at the first- and third month after DEB-TACE therapy. Overall survival, progression-free survival, and adverse events were also analyzed and assessed. RESULTS The objective response rate and disease control rate were 62.5% and 96.9% at the first month after treatment, respectively. At the third month after the first therapy, a slightly higher objective response rate (68.8%) and lower disease control rate (90.6%) were achieved. There were no differences in the levels of aspartate aminotransferase, alanine aminotransferase, serum albumin, or total bilirubin at M1 or M3 compared to M0 (all p> 0.05) The median progression-free survival was 9.5 months (95% confidence interval, 8.1-10.9 months), and the median overall survival was 22.0 months (95% confidence interval, 20.2-23.9 months). Among the 32 patients, 2 had hypertension and 1 had grade 3 diarrhea; the rest of the patients had mild to moderate adverse reactions that were acceptable, and no serious adverse reactions occurred. CONCLUSION DEB-TACE combined with apatinib is a safe and promising treatment approach for patients with advanced HCC.
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13
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Kok VC, Chen YC, Chen YY, Su YC, Ku MC, Kuo JT, Yoshida GJ. Sorafenib with Transarterial Chemoembolization Achieves Improved Survival vs. Sorafenib Alone in Advanced Hepatocellular Carcinoma: A Nationwide Population-Based Cohort Study. Cancers (Basel) 2019; 11:cancers11070985. [PMID: 31311148 PMCID: PMC6679028 DOI: 10.3390/cancers11070985] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2019] [Revised: 07/06/2019] [Accepted: 07/12/2019] [Indexed: 02/07/2023] Open
Abstract
We hypothesized that sorafenib plus transarterial chemoembolization (TACE) would confer survival benefits over sorafenib alone for advanced hepatocellular carcinoma (aHCC). We investigated this while using the population-based All-Cancer Dataset to assemble a cohort (n = 3674; median age, 60; 83% men) of patients receiving sorafenib for aHCC (Child-Pugh A) with macro-vascular invasion or nodal/distant metastases. The patients were classified into the sorafenib-TACE group (n = 426) or the propensity score-matched sorafenib-alone group (n = 1686). All of the participants were followed up until death or the end of the study. Time-dependent Cox model and the Mantel-Byar test were used for survival analysis. During the median follow-ups of 221 and 133 days for the sorafenib-TACE and sorafenib-alone groups, 164 (39%) and 916 (54%) deaths occurred, respectively; the corresponding median overall survivals (OS) were 381 and 204 days, respectively (hazard ratio, HR: 0.74; 95% confidence interval, CI, 0.63-0.88; p = 0.021). The one-year and six-month OS were 53.5% and 80.3% in the sorafenib-TACE group and 32.4% and 54.4% in the sorafenib-alone group, respectively. The major complications were comparable between the two groups. The addition of TACE to sorafenib improves survival, with a 26% reduction in mortality. These findings provide strong real-world evidence that supports this combination strategy for eligible Child-Pugh A aHCC patients.
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Affiliation(s)
- Victor C Kok
- Division of Medical Oncology, Department of Internal Medicine, Kuang Tien General Hospital, Taichung 43303, Taiwan.
- Disease Informatics Research Group, Department of Bioinformatics and Medical Engineering, Asia University Taiwan, Taichung 41354, Taiwan.
- Student, Cancer Biology and Therapeutics: High-Impact Cancer Research Postgraduate Certificate Program, Harvard Medical School, Boston, MA 02115, USA.
| | - Yu-Ching Chen
- Disease Informatics Research Group, Department of Bioinformatics and Medical Engineering, Asia University Taiwan, Taichung 41354, Taiwan
| | - Yang-Yuan Chen
- Department of Gastroenterology, Changhua Christian Medical Foundation Changhua Christian Hospital, Changhua 50006, Taiwan
| | - Yu-Chieh Su
- Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
- Division of Hematology and Oncology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan
| | - Ming-Chang Ku
- Interventional Radiology Unit, Department of Radiology, Kuang Tien General Hospital, Taichung 43303, Taiwan
| | - Jung-Tsung Kuo
- Artificial Intelligence Center for Medical Diagnosis, China Medical University Hospital, Taichung 40447, Taiwan
| | - Go J Yoshida
- Department of Pathology and Oncology, Juntendo University School of Medicine, Tokyo 113-8421, Japan
- Faculty of Medical Science, Graduate School Juntendo University, Tokyo 113-8421, Japan
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14
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Peng Z, Chen S, Xiao H, Wang Y, Li J, Mei J, Chen Z, Zhou Q, Feng S, Chen M, Qian G, Peng S, Kuang M. Microvascular Invasion as a Predictor of Response to Treatment with Sorafenib and Transarterial Chemoembolization for Recurrent Intermediate-Stage Hepatocellular Carcinoma. Radiology 2019; 292:237-247. [PMID: 31135299 DOI: 10.1148/radiol.2019181818] [Citation(s) in RCA: 51] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Background The evidence of combining sorafenib with transarterial chemoembolization (TACE) for intermediate-stage recurrent hepatocellular carcinoma (HCC) is limited. Patient responses to this treatment varied because of the heterogeneous nature of intermediate-stage recurrent HCC, making it important to identify patients who are most likely to benefit from this combination therapy. Purpose To compare sorafenib administered in combination with TACE versus TACE alone in the treatment of recurrent intermediate-stage HCC after initial hepatectomy and to determine the relationship of microvascular invasion (MVI) to survival. Materials and Methods In this retrospective multicenter study, 3652 consecutive patients were found to have intrahepatic recurrences after initial hepatectomy of primary HCC from January 2010 to December 2016. Of these, 260 patients with intermediate-stage recurrent HCC underwent combination treatment with sorafenib and TACE or TACE alone. Overall survival (OS) and progression-free survival (PFS) were compared between these two treatments according to MVI status by using log-rank tests. Results A total of 128 patients were administered combination therapy (mean age, 55 years ± 7.6 [standard deviation]; 107 men) and 132 patients were administered TACE alone (mean age, 56 years ± 8.3; 110 men). The 5-year OS and PFS were higher in the combination group than in the TACE group (OS: 38.9% vs 20.5%, respectively, P = .01; PFS, 37.5% vs 18.7%, respectively, P = .003). For patients with MVI-positive lesions, the median OS and PFS after combination treatment (n = 55) were longer than those after TACE alone (n = 72; OS: 17.2 months vs 12.1 months, respectively, P = .02; PFS: 17.0 months vs 11.0 months, respectively, P = .02). Multivariable analysis showed that tumor number, MVI status, and treatment allocation were significant predictors of OS and PFS, whereas tumor size was a prognostic factor for PFS. Conclusion Patients with recurrent intermediate-stage hepatocellular carcinoma and lesions positive for microvascular invasion (MVI) had longer survival times by using a combined treatment of sorafenib with transarterial chemoembolization (TACE) compared with TACE alone; patients with MVI-negative lesions did not show survival benefit from combined therapy. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Malloy in this issue.
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Affiliation(s)
- Zhenwei Peng
- From the Clinical Trials Unit (Z.P., J.M., Q.Z., S.P.), Department of Oncology (Z.P.), Division of Interventional Ultrasound (S.C., M.K.), Departments of Gastroenterology (H.X., S.P.), Interventional Oncology (Y.W., J.L.), Liver Surgery (Z.C., M.K.), and Radiology (S.F.), The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, China; Department of Hepatobiliary Surgery, Cancer Centre of Sun Yat-sen University, Guangzhou, China (M.C.); and Department of Minimal Invasion Therapy, The Affiliated Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Guangzhou, China (G.Q.)
| | - Shuling Chen
- From the Clinical Trials Unit (Z.P., J.M., Q.Z., S.P.), Department of Oncology (Z.P.), Division of Interventional Ultrasound (S.C., M.K.), Departments of Gastroenterology (H.X., S.P.), Interventional Oncology (Y.W., J.L.), Liver Surgery (Z.C., M.K.), and Radiology (S.F.), The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, China; Department of Hepatobiliary Surgery, Cancer Centre of Sun Yat-sen University, Guangzhou, China (M.C.); and Department of Minimal Invasion Therapy, The Affiliated Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Guangzhou, China (G.Q.)
| | - Han Xiao
- From the Clinical Trials Unit (Z.P., J.M., Q.Z., S.P.), Department of Oncology (Z.P.), Division of Interventional Ultrasound (S.C., M.K.), Departments of Gastroenterology (H.X., S.P.), Interventional Oncology (Y.W., J.L.), Liver Surgery (Z.C., M.K.), and Radiology (S.F.), The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, China; Department of Hepatobiliary Surgery, Cancer Centre of Sun Yat-sen University, Guangzhou, China (M.C.); and Department of Minimal Invasion Therapy, The Affiliated Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Guangzhou, China (G.Q.)
| | - Yu Wang
- From the Clinical Trials Unit (Z.P., J.M., Q.Z., S.P.), Department of Oncology (Z.P.), Division of Interventional Ultrasound (S.C., M.K.), Departments of Gastroenterology (H.X., S.P.), Interventional Oncology (Y.W., J.L.), Liver Surgery (Z.C., M.K.), and Radiology (S.F.), The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, China; Department of Hepatobiliary Surgery, Cancer Centre of Sun Yat-sen University, Guangzhou, China (M.C.); and Department of Minimal Invasion Therapy, The Affiliated Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Guangzhou, China (G.Q.)
| | - Jiaping Li
- From the Clinical Trials Unit (Z.P., J.M., Q.Z., S.P.), Department of Oncology (Z.P.), Division of Interventional Ultrasound (S.C., M.K.), Departments of Gastroenterology (H.X., S.P.), Interventional Oncology (Y.W., J.L.), Liver Surgery (Z.C., M.K.), and Radiology (S.F.), The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, China; Department of Hepatobiliary Surgery, Cancer Centre of Sun Yat-sen University, Guangzhou, China (M.C.); and Department of Minimal Invasion Therapy, The Affiliated Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Guangzhou, China (G.Q.)
| | - Jie Mei
- From the Clinical Trials Unit (Z.P., J.M., Q.Z., S.P.), Department of Oncology (Z.P.), Division of Interventional Ultrasound (S.C., M.K.), Departments of Gastroenterology (H.X., S.P.), Interventional Oncology (Y.W., J.L.), Liver Surgery (Z.C., M.K.), and Radiology (S.F.), The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, China; Department of Hepatobiliary Surgery, Cancer Centre of Sun Yat-sen University, Guangzhou, China (M.C.); and Department of Minimal Invasion Therapy, The Affiliated Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Guangzhou, China (G.Q.)
| | - Zebin Chen
- From the Clinical Trials Unit (Z.P., J.M., Q.Z., S.P.), Department of Oncology (Z.P.), Division of Interventional Ultrasound (S.C., M.K.), Departments of Gastroenterology (H.X., S.P.), Interventional Oncology (Y.W., J.L.), Liver Surgery (Z.C., M.K.), and Radiology (S.F.), The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, China; Department of Hepatobiliary Surgery, Cancer Centre of Sun Yat-sen University, Guangzhou, China (M.C.); and Department of Minimal Invasion Therapy, The Affiliated Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Guangzhou, China (G.Q.)
| | - Qian Zhou
- From the Clinical Trials Unit (Z.P., J.M., Q.Z., S.P.), Department of Oncology (Z.P.), Division of Interventional Ultrasound (S.C., M.K.), Departments of Gastroenterology (H.X., S.P.), Interventional Oncology (Y.W., J.L.), Liver Surgery (Z.C., M.K.), and Radiology (S.F.), The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, China; Department of Hepatobiliary Surgery, Cancer Centre of Sun Yat-sen University, Guangzhou, China (M.C.); and Department of Minimal Invasion Therapy, The Affiliated Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Guangzhou, China (G.Q.)
| | - Shiting Feng
- From the Clinical Trials Unit (Z.P., J.M., Q.Z., S.P.), Department of Oncology (Z.P.), Division of Interventional Ultrasound (S.C., M.K.), Departments of Gastroenterology (H.X., S.P.), Interventional Oncology (Y.W., J.L.), Liver Surgery (Z.C., M.K.), and Radiology (S.F.), The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, China; Department of Hepatobiliary Surgery, Cancer Centre of Sun Yat-sen University, Guangzhou, China (M.C.); and Department of Minimal Invasion Therapy, The Affiliated Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Guangzhou, China (G.Q.)
| | - Minshan Chen
- From the Clinical Trials Unit (Z.P., J.M., Q.Z., S.P.), Department of Oncology (Z.P.), Division of Interventional Ultrasound (S.C., M.K.), Departments of Gastroenterology (H.X., S.P.), Interventional Oncology (Y.W., J.L.), Liver Surgery (Z.C., M.K.), and Radiology (S.F.), The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, China; Department of Hepatobiliary Surgery, Cancer Centre of Sun Yat-sen University, Guangzhou, China (M.C.); and Department of Minimal Invasion Therapy, The Affiliated Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Guangzhou, China (G.Q.)
| | - Guojun Qian
- From the Clinical Trials Unit (Z.P., J.M., Q.Z., S.P.), Department of Oncology (Z.P.), Division of Interventional Ultrasound (S.C., M.K.), Departments of Gastroenterology (H.X., S.P.), Interventional Oncology (Y.W., J.L.), Liver Surgery (Z.C., M.K.), and Radiology (S.F.), The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, China; Department of Hepatobiliary Surgery, Cancer Centre of Sun Yat-sen University, Guangzhou, China (M.C.); and Department of Minimal Invasion Therapy, The Affiliated Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Guangzhou, China (G.Q.)
| | - Sui Peng
- From the Clinical Trials Unit (Z.P., J.M., Q.Z., S.P.), Department of Oncology (Z.P.), Division of Interventional Ultrasound (S.C., M.K.), Departments of Gastroenterology (H.X., S.P.), Interventional Oncology (Y.W., J.L.), Liver Surgery (Z.C., M.K.), and Radiology (S.F.), The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, China; Department of Hepatobiliary Surgery, Cancer Centre of Sun Yat-sen University, Guangzhou, China (M.C.); and Department of Minimal Invasion Therapy, The Affiliated Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Guangzhou, China (G.Q.)
| | - Ming Kuang
- From the Clinical Trials Unit (Z.P., J.M., Q.Z., S.P.), Department of Oncology (Z.P.), Division of Interventional Ultrasound (S.C., M.K.), Departments of Gastroenterology (H.X., S.P.), Interventional Oncology (Y.W., J.L.), Liver Surgery (Z.C., M.K.), and Radiology (S.F.), The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, China; Department of Hepatobiliary Surgery, Cancer Centre of Sun Yat-sen University, Guangzhou, China (M.C.); and Department of Minimal Invasion Therapy, The Affiliated Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Guangzhou, China (G.Q.)
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15
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Li L, Zhao W, Wang M, Hu J, Wang E, Zhao Y, Liu L. Transarterial chemoembolization plus sorafenib for the management of unresectable hepatocellular carcinoma: a systematic review and meta-analysis. BMC Gastroenterol 2018; 18:138. [PMID: 30180810 PMCID: PMC6124009 DOI: 10.1186/s12876-018-0849-0] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/09/2017] [Accepted: 07/23/2018] [Indexed: 12/22/2022] Open
Abstract
Background Transarterial chemoembolization (TACE) is the recommended treatment for hepatocellular carcinoma (HCC) patients at Barcelona Clinic Liver Cancer (BCLC) B-stage, whereas sorafenib is an orally administered small molecule target drug for BCLC C-stage. This updated systemic review and meta-analysis focuses on identifying the efficacy of the combination of TACE with sorafenib, which remains controversial despite years of exploration. Methods PubMed, EMBASE, Scopus and the Cochrane Library were systematically reviewed to search for studies published from January 1990 to May 2017. Studies focusing on the efficacy of combination therapy for unresectable HCC were eligible. The hazard ratio (HR) with 95% confidence intervals (95% CIs) for time to progression (TTP), overall survival (OS), disease control rate (DCR) and aetiology were collected. The data were then analysed through fixed/random effects meta-analysis models with STATA 13.0. The incidence and severity of treatment-related adverse events (AEs) were also evaluated. Results Twenty-seven studies were included. Thirteen non-comparative studies reported median OS (ranging from 18.5 to 20.4 months), median TTP (ranging from 7 to 13.9 months) and DCR (ranging from 18.4 to 95%). Fourteen comparative studies provided median OS (ranging from 7.0 to 29.7 months) and median TTP (ranging from 2.6 to 10.2 months). Five comparative studies provided DCR (ranging from 32 to 97.2%). Forest plots showed that combination therapy significantly improved TTP (HR = 0.66, 95% CI 0.50–0.81, P = 0.002) rather than OS (HR = 0.63, 95% CI 0.55–0.71, P = 0.058), compared to TACE alone. DCR increased significantly in the combination therapy group (OR = 2.93, 95% CI 1.59–5.41, P = 0.005). Additional forest plots were drawn and no significant differences were observed with regard to survival outcome among various aetiologies. Forest plots for separate analysis of regions showed the HR for TTP was 0.62 (95% CI 0.45–0.79, P = 0.002) in the Asian countries group, and 0.82 (95% CI 0.59–1.05, P = 0.504)) in western countries. The HR for OS was 0.61 (95% CI 0.48–0.75, P = 0.050) in the Asian countries group and was 0.88 (95% CI 0.56–1.20, P = 0.845) in western countries. These data may indicate positive TTP outcome in Asian patients but not in European patients while no positive findings regarding OS were observed in either region. The most common AEs included fatigue, hand-foot skin reaction, diarrhoea and hypertension. Conclusions Combination therapy may benefit unresectable HCC patients in terms of prolonged TTP and DCR. More well-designed studies are needed to investigate its superiority for OS. Electronic supplementary material The online version of this article (10.1186/s12876-018-0849-0) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Lin Li
- Department of Gastroenterology, Tangdu Hospital, Military Medical University of PLA Airforce (Fourth Military Medical University), 1 Xinsi Road, Xi'an, 710038, China
| | - Wenzhuo Zhao
- Department of Gastroenterology, Tangdu Hospital, Military Medical University of PLA Airforce (Fourth Military Medical University), 1 Xinsi Road, Xi'an, 710038, China
| | - Mengmeng Wang
- Department of Drug and Equipment, Aeromedicine Identification and Training Centre of Air Force, Lintong District, Xi'an, China
| | - Jie Hu
- Department of Liver Disease and Digestive Interventional Radiology, Xijing Hospital of Digestive Diseases, Military Medical University of PLA Airforce (Fourth Military Medical University), Xi'an, China
| | - Enxin Wang
- Department of Liver Disease and Digestive Interventional Radiology, Xijing Hospital of Digestive Diseases, Military Medical University of PLA Airforce (Fourth Military Medical University), Xi'an, China
| | - Yan Zhao
- Department of Gastroenterology, First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta Road, Xi'an, 710061, China.
| | - Lei Liu
- Department of Gastroenterology, Tangdu Hospital, Military Medical University of PLA Airforce (Fourth Military Medical University), 1 Xinsi Road, Xi'an, 710038, China. .,Cell Engineering Research Center and Department of Cell Biology, State Key Laboratory of Cancer Biology, Military Medical University of PLA Airforce), Xi'an, China.
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16
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Sato Y, Nishiofuku H, Yasumoto T, Nakatsuka A, Matsuo K, Kodama Y, Okubo H, Abo D, Takaki H, Inaba Y, Yamakado K. Multicenter Phase II Clinical Trial of Sorafenib Combined with Transarterial Chemoembolization for Advanced Stage Hepatocellular Carcinomas (Barcelona Clinic Liver Cancer Stage C): STAB Study. J Vasc Interv Radiol 2018; 29:1061-1067. [PMID: 29934260 DOI: 10.1016/j.jvir.2018.03.020] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2017] [Revised: 02/10/2018] [Accepted: 03/19/2018] [Indexed: 12/25/2022] Open
Abstract
PURPOSE To evaluate safety and efficacy of combining sorafenib with transarterial chemoembolization in patients with advanced stage hepatocellular carcinomas (HCCs). MATERIALS AND METHODS Systemic chemotherapy-naïve patients with a Child-Pugh class A liver profile and advanced stage HCCs were enrolled. Sorafenib therapy (daily dose 800 mg) was initiated within 4 weeks after initial conventional transarterial chemoembolization with an allowance of subsequent on-demand conventional chemoembolization. The primary endpoint was rate of protocol treatment completion, which was defined as sorafenib administration for at least 2 months. Secondary endpoints included objective response rate, disease control rate, overall survival, progression-free survival, and incidence of adverse events. Thirty-one patients (24 men, 7 women; median age, 75 years; vascular invasion, n = 19; extrahepatic metastases, n = 18; both, n = 6) who met the inclusion criteria were enrolled. RESULTS Protocol treatment was completed in 28 patients (90.3%, 28/31) with median protocol treatment duration of 7.0 months (range, 0.5-30 months) and median of 2 (range, 1-4) transarterial chemoembolization sessions. Objective response rate was 77.4% with median overall and progression-free survival of 17.3 months (95% confidence interval, 11.9-22.6 months) and 5.4 months (95% confidence interval, 4.6-6.2 months), respectively. The most common grade 3 or 4 adverse events were self-limiting elevation of aspartate aminotransferase (54.8%, 17/31) and alanine aminotransferase (45.2%, 14/31). CONCLUSIONS This combination therapy is feasible and promising in patients with advanced stage HCCs.
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Affiliation(s)
- Yozo Sato
- Department of Diagnostic and Interventional Radiology, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya 464-8681, Japan.
| | | | - Taku Yasumoto
- Department of Radiology, Toyonaka Municipal Hospital, Toyonaka, Japan
| | | | | | - Yoshihisa Kodama
- Department of Radiology, Teine Keijinkai Hospital, Sapporo, Japan
| | - Hironao Okubo
- Department of Gastroenterology, Juntendo University Nerima Hospital, Tokyo, Japan
| | - Daisuke Abo
- Department of Radiology, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | - Haruyuki Takaki
- Department of Radiology, Hyogo College of Medicine, Nishinomiya, Japan
| | - Yoshitaka Inaba
- Department of Diagnostic and Interventional Radiology, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya 464-8681, Japan
| | - Koichiro Yamakado
- Department of Radiology, Hyogo College of Medicine, Nishinomiya, Japan
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17
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Chen J, Lu S, Zhang Y, Xu L, Chen J, Wang J, Chen M, Zhang R, Zhou Z. Sorafenib Monotherapy Versus Sorafenib Combined with Regional Therapies for Hepatocellular Carcinoma Patients with Pulmonary Oligometastases: A Propensity Score-matched Analysis. J Cancer 2018; 9:1745-1753. [PMID: 29805700 PMCID: PMC5968762 DOI: 10.7150/jca.24568] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2017] [Accepted: 03/15/2018] [Indexed: 12/11/2022] Open
Abstract
Background: Sorafenib has been recommended as the standard therapy for advanced HCC with extrahepatic metastasis. The purpose of this retrospective study was to investigate the difference in overall survival (OS) between treatments with sorafenib combined with regional therapies versus sorafenib monotherapy in hepatocellular carcinoma (HCC) patients with pulmonary oligometastases. Methods: The study retrospectively enrolled 95 consecutive patients who underwent sorafenib therapy. A combined group (CG) of 40 patients received regional therapy in addition to sorafenib, and a monotherapy group (MG) of 55 patients received only sorafenib. OS was the primary endpoint, and time to progression (TTP) was the secondary endpoint. Subgroup analysis was further performed to evaluate the differences between the two groups. A propensity score-matched analysis was performed to overcome the bias. Results: Median OS was significantly longer in the CG than in the MG (18.37 vs. 7.13 months; P = 0.002). Multivariate analysis identified three baseline characteristics that were prognostic indicators of OS: macrovascular invasion, regional therapy, and alpha-fetoprotein. Median TTP was significantly longer in the CG than in the MG (2.93 vs. 2.23 months; P = 0.004). Further multivariate analysis showed alpha-fetoprotein, total bilirubin, and regional therapy as prognostic indicators of TTP. After propensity score matching, 34 paired patients constituted each group. Patients in the adjusted CG showed a longer OS and TTP than those in the adjusted MG (OS: 18.37 vs. 7.37 months, P = 0.015; TTP: 3.12 vs. 2.265 months, P = 0.009). Multivariate analysis showed that combining regional therapies was still a prognostic indicator of OS (P = 0.01) and TTP (P = 0.001). Conclusions: Sorafenib combined with regional therapies may be associated with prolonged OS and TTP in HCC patients with pulmonary oligometastases compared with sorafenib monotherapy.
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Affiliation(s)
- Jinbin Chen
- Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, P. R. China.,Department of Hepatobiliary Oncology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P. R. China
| | - Shixun Lu
- Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, P. R. China.,Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P. R. China
| | - Yaojun Zhang
- Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, P. R. China.,Department of Hepatobiliary Oncology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P. R. China
| | - Li Xu
- Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, P. R. China.,Department of Hepatobiliary Oncology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P. R. China
| | - Jiancong Chen
- Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, P. R. China.,Department of Hepatobiliary Oncology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P. R. China
| | - Juncheng Wang
- Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, P. R. China.,Department of Hepatobiliary Oncology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P. R. China
| | - Minshan Chen
- Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, P. R. China.,Department of Hepatobiliary Oncology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P. R. China
| | - Rongxin Zhang
- Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, P. R. China.,Department of Colorectal Cancer, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P. R. China
| | - Zhongguo Zhou
- Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, P. R. China.,Department of Hepatobiliary Oncology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P. R. China
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18
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Kaplan DE, Mehta R, D'Addeo K, Gade TP, Taddei TH. Transarterial Chemoembolization within First 3 Months of Sorafenib Initiation Improves Overall Survival in Hepatocellular Carcinoma: A Retrospective, Multi-Institutional Study with Propensity Matching. J Vasc Interv Radiol 2018; 29:540-549.e4. [PMID: 29477619 DOI: 10.1016/j.jvir.2017.11.033] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2017] [Revised: 11/14/2017] [Accepted: 11/14/2017] [Indexed: 02/07/2023] Open
Abstract
PURPOSE The impact of transarterial chemoembolization after initiation of sorafenib (SOR) has not been prospectively compared with SOR alone in unresectable hepatocellular carcinoma (HCC). The objective of this study was to assess whether SOR + transarterial chemoembolization provides benefit over SOR alone in this setting. MATERIALS AND METHODS A retrospective cohort study with propensity matching using data from patients prescribed SOR for HCC at Veterans Health Administration hospitals from 2007 to 2015. The primary outcome was overall survival from the time of SOR prescription and stratified by receipt of transarterial chemoembolization within 90 days of SOR initiation. RESULTS A total of 4,896 patients received SOR for HCC, of whom 232 (4.7%) underwent transarterial chemoembolization within 90 days. Patients receiving transarterial chemoembolization + SOR were highly selected, being younger and with less significant hepatic dysfunction, earlier Barcelona Clinic Liver Cancer stage (P < .0001), and fewer tumors with lower rates of macrovascular invasion (MVI) and metastases (all P < .0001) than SOR-alone patients. In unadjusted analysis, SOR + transarterial chemoembolization was associated with reduced mortality (hazard ratio [HR] 0.61, 95% confidence interval [CI] 0.53-0.71; P < .0001). After propensity matching, SOR + transarterial chemoembolization continued to show significant associations with reduced mortality with HR 0.75 (95% CI 0.62-0.92; P = .0005). Subgroup analysis suggests that the addition of transarterial chemoembolization to SOR improves outcomes in most patients, particularly those with Model for End-Stage Liver Disease score <15, platelets >50,000/μL, and >3 tumors with or without macrovascular invasion, without local invasion or metastases. CONCLUSIONS Patients with unresectable HCC started on systemic therapy with SOR appear to benefit from adjuvant transarterial chemoembolization. Optimal application of multimodal therapy in this setting should be prospectively investigated.
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Affiliation(s)
- David E Kaplan
- Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania; Corporal Michael J. Crescenz VA Medical Center, 3900 Woodland Avenue, Bldg 21, Room A422, Philadelphia, PA 19014.
| | - Rajni Mehta
- Yale University School of Medicine, New Haven, Connecticut; VA Connecticut Healthcare System, West Haven, Connecticut
| | - Kathryn D'Addeo
- Yale University School of Medicine, New Haven, Connecticut; VA Connecticut Healthcare System, West Haven, Connecticut
| | - Terence P Gade
- Corporal Michael J. Crescenz VA Medical Center, 3900 Woodland Avenue, Bldg 21, Room A422, Philadelphia, PA 19014; Department of Radiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania
| | - Tamar H Taddei
- Yale University School of Medicine, New Haven, Connecticut; VA Connecticut Healthcare System, West Haven, Connecticut
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19
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Meng XC, Chen BH, Huang JJ, Huang WS, Cai MY, Zhou JW, Guo YJ, Zhu KS. Early prediction of survival in hepatocellular carcinoma patients treated with transarterial chemoembolization plus sorafenib. World J Gastroenterol 2018; 24:484-493. [PMID: 29398869 PMCID: PMC5787783 DOI: 10.3748/wjg.v24.i4.484] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2017] [Revised: 12/10/2017] [Accepted: 12/20/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To identify clinical biomarkers that could early predict improved survival in patients with advanced-stage hepatocellular carcinoma (HCC) treated with transarterial chemoembolization combined with sorafenib (TACE-S).
METHODS We retrospectively evaluated the medical records of consecutive patients with advanced-stage HCC who underwent TACE-S from January 2012 to December 2015. At the first follow-up 4-6 wk after TACE-S (median, 38 d; range, 33-45 d), patients exhibiting the modified Response Evaluation Criteria in Solid Tumors (mRECIST)-evaluated complete response, partial response, and stable disease were categorized as early disease control. At this time point, multiple variables were analyzed to identify the related factors affecting survival.
RESULTS Ninety-five patients were included in this study, and 60 of these patients achieved early disease control, with an overall disease control rate (DCR) of 63.2%. Patients who got sorafenib at the first TACE (no previous TACE) and patients without portal vein tumor thrombus (PVTT) had a higher DCR than those who underwent previous TACE before TACE-S (72.4% vs 48.6%, P = 0.019) and those with PVTT (75.5% vs 50.0%, P = 0.010). Early disease control after TACE-S, no previous TACE, and no PVTT were the independent prognostic factors for survival in the uni- and multivariate analyses.
CONCLUSION The first follow-up 4-6 wk after TACE-S can be used as the earliest time point to assess the response to TACE-S, and patients with mRECIST-evaluated early disease control, no previous TACE, and no PVTT had better survival.
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Affiliation(s)
- Xiao-Chun Meng
- Department of Radiology, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, Guangdong Province, China
| | - Bing-Hui Chen
- Department of Radiology, the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000, Guangdong Province, China
| | - Jing-Jun Huang
- Kang-shun Zhu, Department of Minimally Invasive Interventional Radiology, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, Guangdong Province, China
| | - Wen-Sou Huang
- Kang-shun Zhu, Department of Minimally Invasive Interventional Radiology, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, Guangdong Province, China
| | - Ming-Yue Cai
- Kang-shun Zhu, Department of Minimally Invasive Interventional Radiology, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, Guangdong Province, China
| | - Jing-Wen Zhou
- Kang-shun Zhu, Department of Minimally Invasive Interventional Radiology, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, Guangdong Province, China
| | - Yong-Jian Guo
- Kang-shun Zhu, Department of Minimally Invasive Interventional Radiology, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, Guangdong Province, China
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20
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Shah C, Mramba LK, Bishnoi R, Bejjanki H, Chhatrala HS, Chandana SR. Survival differences among patients with hepatocellular carcinoma based on the stage of disease and therapy received: pre and post sorafenib era. J Gastrointest Oncol 2017; 8:789-798. [PMID: 29184682 DOI: 10.21037/jgo.2017.06.16] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
Abstract
Background The incidence of hepatocellular carcinoma (HCC) is increasing. Development of newer therapeutic modalities has changed the paradigm of HCC treatment in recent years. So, the aim of our study is to analyze the impact of these treatment modalities into the survival of HCC patients, based on the stage of HCC in real life practice. Methods We analyzed the data from the SEER database: Incidence - SEER 18 Regs Research Data + Hurricane Katrina Impacted Louisiana Cases, Nov 2015 Sub (1973-2013 varying). Relative survival rates (RSRs) and hazard ratios (HRs) were measured for patients diagnosed with HCC between 2001 and 2013. Rates were compared between pre sorafenib [2001-2007] and post sorafenib [2008-2013] eras. Results A total of 50,088 patients (21,435 in pre sorafenib era and 28,653 in the post-sorafenib era) were included with HCC from SEER database. The median relative survival for the entire population was 14 months with 5-year RSR of 21.20%; 11 months for those diagnosed in 2001-2007 with 5-year RSR 19.30% and 17 months for those diagnosed in 2008-2013 with 5-year RSR 22.40% (P<0.01). This survival improvement was largely limited to HCC patients with single nodule (5-year RSR; 35.1% vs. 37.00% for pre and post sorafenib era respectively; P value <0.01) and multiple nodules without vascular invasion (5-year RSR; 19.90% vs. 22.60% for pre and post sorafenib era respectively; P value <0.01). RSR remained extremely poor with no significant improvement for advanced stage HCC who had vascular invasion (P=0.37) or distant metastasis (P=0.10), respectively for pre and post sorafenib era in each category. Survival improved since 2008, for HCC patients who received either no surgical intervention (P<0.01) or received tumor-directed therapy (P<0.01), however, it remained significantly poor compared to the patients who received lobectomy or hepatectomy and transplant. Approximately 70% of patients from our study population did not receive any HCC directed surgical intervention and among this, more than 40% of patients were with single nodule in the liver. Conclusions Survival in patients with HCC has improved since 2008, which is limited to early stage HCC. Survival of advanced stage HCC patients is extremely poor and has not shown any significant improvement since the approval of sorafenib, emphasizing the need for better therapeutic options. Not receiving any surgical intervention is associated with significantly poor prognosis. Large numbers of early stage HCC patients were not able to receive surgical interventions. This can impose a significant financial burden, as these patients would progress on to the advanced stage, where treatment options are very limited and not as cost-effective. This emphasizes the need for further research to identify various barriers and the possible need for healthcare policy changes.
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Affiliation(s)
- Chintan Shah
- Division of Hospital Medicine, Department of Medicine, University of Florida, Gainesville, FL, USA
| | - Lazarus K Mramba
- Department of Medicine, University of Florida, Gainesville, FL, USA
| | - Rohit Bishnoi
- Division of Hospital Medicine, Department of Medicine, University of Florida, Gainesville, FL, USA
| | - Harini Bejjanki
- Division of Hospital Medicine, Department of Medicine, University of Florida, Gainesville, FL, USA
| | | | - Sreenivasa R Chandana
- Department of Medicine, Western Michigan University School of Medicine, Kalamazoo, MI, USA.,Divisionof Hematology and Medical Oncology, Cancer and Hematology Centers of West Michigan, Grand Rapids, MI, USA
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21
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Sacco R, Tapete G, Simonetti N, Sellitri R, Natali V, Melissari S, Cabibbo G, Biscaglia L, Bresci G, Giacomelli L. Transarterial chemoembolization for the treatment of hepatocellular carcinoma: a review. J Hepatocell Carcinoma 2017; 4:105-110. [PMID: 28795053 PMCID: PMC5538681 DOI: 10.2147/jhc.s103661] [Citation(s) in RCA: 53] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
According to the current European Association for the Study of Liver guidelines, transarterial chemoembolization (TACE) is the recommended first-line therapy for patients with intermediate-stage (Barcelona Clinic Liver Cancer-B class) hepatocellular carcinoma (HCC). The efficacy of this therapy is supported by robust evidence; however, there is still a lack of standardization in treatment methodology, and TACE protocols are widely variable. Moreover, TACE can be associated with a number of contraindications. Despite these limitations, research on TACE is still ongoing with the aim of optimizing the use of this methodology in the current management of HCC. In particular, TACE represents a control in comparative studies, and it is currently being investigated in combination schemes, for example, with sorafenib. In this review, we briefly describe the current scenario and the clinical innovations regarding TACE for the treatment of HCC.
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Affiliation(s)
- Rodolfo Sacco
- Department of Gastroenterology, Pisa University Hospital, Pisa
| | - Gherardo Tapete
- Department of Gastroenterology, Pisa University Hospital, Pisa
| | | | | | - Veronica Natali
- Department of Gastroenterology, Pisa University Hospital, Pisa
| | - Sara Melissari
- Department of Gastroenterology, Pisa University Hospital, Pisa
| | | | - Lilia Biscaglia
- Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome
| | | | - Luca Giacomelli
- Department of Surgical Sciences and Integrated Diagnostics, University of Genoa, Genoa, Italy
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22
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Gaba RC, Lokken RP, Hickey RM, Lipnik AJ, Lewandowski RJ, Salem R, Brown DB, Walker TG, Silberzweig JE, Baerlocher MO, Echenique AM, Midia M, Mitchell JW, Padia SA, Ganguli S, Ward TJ, Weinstein JL, Nikolic B, Dariushnia SR. Quality Improvement Guidelines for Transarterial Chemoembolization and Embolization of Hepatic Malignancy. J Vasc Interv Radiol 2017; 28:1210-1223.e3. [PMID: 28669744 DOI: 10.1016/j.jvir.2017.04.025] [Citation(s) in RCA: 86] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2017] [Accepted: 04/29/2017] [Indexed: 02/07/2023] Open
Affiliation(s)
- Ron C Gaba
- Division of Interventional Radiology, Department of Radiology, University of Illinois Hospital & Health Sciences System, 1740 West Taylor Street, MC 931, Chicago, IL 60612.
| | - R Peter Lokken
- Division of Interventional Radiology, Department of Radiology, University of Illinois Hospital & Health Sciences System, 1740 West Taylor Street, MC 931, Chicago, IL 60612
| | - Ryan M Hickey
- Section of Vascular and Interventional Radiology, Department of Radiology, Northwestern Memorial Hospital, Chicago, Illinois
| | - Andrew J Lipnik
- Division of Interventional Radiology, Department of Radiology, University of Illinois Hospital & Health Sciences System, 1740 West Taylor Street, MC 931, Chicago, IL 60612
| | - Robert J Lewandowski
- Section of Vascular and Interventional Radiology, Department of Radiology, Northwestern Memorial Hospital, Chicago, Illinois
| | - Riad Salem
- Section of Vascular and Interventional Radiology, Department of Radiology, Northwestern Memorial Hospital, Chicago, Illinois
| | - Daniel B Brown
- Department of Radiology, Vanderbilt University Medical Center, Nashville, Tennessee
| | - T Gregory Walker
- Division of Interventional Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
| | | | | | - Ana Maria Echenique
- Department of Interventional Radiology, University of Miami School of Medicine, Coral Gables, Florida
| | - Mehran Midia
- Interventional Radiology, McMaster University, Hamilton, Ontario, Canada
| | - Jason W Mitchell
- Interventional Radiology and Image Guided Medicine, Emory University School of Medicine, Atlanta, Georgia
| | - Siddharth A Padia
- Division of Interventional Radiology, Department of Radiology, David Geffen School of Medicine at University of California, Los Angeles, California
| | - Suvranu Ganguli
- Division of Interventional Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Center for Image Guided Cancer Therapy, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
| | - Thomas J Ward
- Vascular and Interventional Radiology, Florida Hospital, Orlando, Florida
| | - Jeffrey L Weinstein
- Vascular and Interventional Radiology, Department of Radiology, Beth Israel Deaconess Medical Center, Boston, Massachusetts
| | - Boris Nikolic
- Department of Radiology, Stratton Medical Center, Albany, New York
| | - Sean R Dariushnia
- Interventional Radiology and Image Guided Medicine, Emory University School of Medicine, Atlanta, Georgia
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23
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Boas FE, Ziv E, Yarmohammadi H, Brown KT, Erinjeri JP, Sofocleous CT, Harding JJ, Solomon SB. Adjuvant Medications That Improve Survival after Locoregional Therapy. J Vasc Interv Radiol 2017; 28:971-977.e4. [PMID: 28527884 DOI: 10.1016/j.jvir.2017.04.016] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2017] [Revised: 04/15/2017] [Accepted: 04/16/2017] [Indexed: 12/21/2022] Open
Abstract
PURPOSE To determine if outpatient medications taken at the time of liver tumor embolization or ablation affect survival. MATERIALS AND METHODS A retrospective review was done of 2,032 liver tumor embolization, radioembolization, and ablation procedures performed in 1,092 patients from June 2009 to April 2016. Pathology, hepatocellular carcinoma (HCC) stage (American Joint Committee on Cancer), neuroendocrine tumor (NET) grade, initial locoregional therapy, overall survival after initial locoregional therapy, Child-Pugh score, Eastern Cooperative Oncology Group performance status, Charlson Comorbidity Index, and outpatient medications taken at the time of locoregional therapy were analyzed for each patient. Kaplan-Meier survival curves were calculated for patients taking 29 medications or medication classes (including prescription and nonprescription medications) for reasons unrelated to their primary cancer diagnosis. Kaplan-Meier curves were compared using the log-rank test. RESULTS For patients with HCC initially treated with embolization (n = 304 patients), the following medications were associated with improved survival when taken at the time of embolization: beta-blockers (P = .0007), aspirin (P = .0008) and other nonsteroidal antiinflammatory drugs (P = .009), proton pump inhibitors (P = .004), and antivirals for hepatitis B or C (P = .01). For colorectal liver metastases initially treated with ablation (n = 172 patients), beta-blockers were associated with improved survival when taken at the time of ablation (P = .02). CONCLUSIONS Aspirin and beta-blockers are associated with significantly improved survival when taken at the time of embolization for HCC. Aspirin was not associated with survival differences after locoregional therapy for NET or colorectal liver metastases, suggesting an HCC-specific effect.
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Affiliation(s)
- F Edward Boas
- Interventional Radiology Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065.
| | - Etay Ziv
- Interventional Radiology Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065
| | - Hooman Yarmohammadi
- Interventional Radiology Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065
| | - Karen T Brown
- Interventional Radiology Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065
| | - Joseph P Erinjeri
- Interventional Radiology Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065
| | - Constantinos T Sofocleous
- Interventional Radiology Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065
| | - James J Harding
- Gastrointestinal Medical Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065; Department of Medicine, Weill Cornell Medical College, New York, New York
| | - Stephen B Solomon
- Interventional Radiology Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065
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24
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Taussig MD, Irene Koran ME, Mouli SK, Ahmad A, Geevarghese S, Baker JC, Lipnik AJ, Banovac F, Brown DB. Neutrophil to lymphocyte ratio predicts disease progression following intra-arterial therapy of hepatocellular carcinoma. HPB (Oxford) 2017; 19:458-464. [PMID: 28190710 DOI: 10.1016/j.hpb.2017.01.013] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2016] [Revised: 12/23/2016] [Accepted: 01/04/2017] [Indexed: 12/12/2022]
Abstract
BACKGROUND Prospectively predicting response to intra-arterial therapy for hepatocellular carcinoma (HCC) is challenging. Neutrophil/lymphocyte ratio (NLR) is a serum biomarker that is associated with survival for multiple malignancies. It was hypothesized that increased NLR would be associated with early disease progression after intra-arterial therapy of HCC. METHODS The outcomes of 86 treatment-naïve patients who had chemoembolization or radioembolization of HCC between July 2013-July 2014 were reviewed. Pre-treatment laboratory tests and imaging were used to measure NLR, Child-Pugh (CP) score, tumor number and tumor size. High/low NLR groups were defined as >3 and <3 respectively. Follow-up imaging at two months with assessed response using modified response criteria in solid tumors (mRECIST). RESULTS NLR >3 was seen in 25/86 patients (range 3.0-21.6). NLR >3 patients had a significantly higher baseline CP score. Comorbidities were otherwise similar between groups as was tumor number/size. Disease control was significantly worse (p = 0.014) with NLR >3. Logistic regression for tumor response revealed NLR >3 as the best predictor of early progression (p < 0.0001). DISCUSSION NLR may be a serologic biomarker of early progressive disease after intra-arterial therapy of HCC. Future research should focus on outcomes by treatment type or potentially combining arterial therapies with ablation and/or targeted biologic agents.
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Affiliation(s)
| | | | | | - Asma Ahmad
- Department of Radiology and Radiologic Sciences, USA
| | | | | | | | - Fil Banovac
- Department of Radiology and Radiologic Sciences, USA
| | - Daniel B Brown
- Department of Radiology and Radiologic Sciences, USA; Department of Biomedical Engineering, USA.
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25
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Zhao Y, Li H, Bai W, Liu J, Lv W, Sahu S, Guan S, Qin X, Wang W, Ren W, Mu W, Guo W, Gu S, Ma Y, Yin Z, Guo W, Wang W, Wang Y, Duran R, Fan D, Zhang Z, Han G. Early sorafenib-related adverse events predict therapy response of TACE plus sorafenib: A multicenter clinical study of 606 HCC patients. Int J Cancer 2017; 139:928-37. [PMID: 27038145 DOI: 10.1002/ijc.30124] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2015] [Revised: 02/04/2016] [Accepted: 03/22/2016] [Indexed: 12/18/2022]
Abstract
The purpose of our study was to test the hypothesis that sorafenib-related dermatologic adverse events (AEs) as an early biomarker can predict the long-term outcomes following the combination therapy of transarterial chemoembolization (TACE) plus sorafenib (TACE-S). The intermediate-stage hepatocellular carcinoma patients who received either TACE-S or TACE-alone treatment were consecutively included into analysis. In the TACE-S group, patients with ≥ grade 2 dermatologic AEs within the first month of sorafenib initiation were defined as responders; whereas those with < grade 2 were defined as nonresponders. In the TACE-S group, the median overall survival (OS) of the responders was significantly longer than that of nonresponders (28.9 months vs. 16.8 months, respectively; p = 0.004). Multivariate analysis demonstrated that nonresponders were significantly associated with an increased risk of death compared with responders (HR = 1.9; 95% confidence Interval-CI: 1.3-2.7; p = 0.001). The survival analysis showed that the median OS was 27.9 months (95% CI: 25.0-30.8) among responders treated with TACE-S vs.18.3 months (95% CI: 14.5-22.1) among those who received TACE-alone (p = 0.046). The median time to progression was 13.1 months (95% CI: 4.4-21.8) in the TACE-S group, a duration that was significantly longer than that in the TACE-alone group [5 months (95% CI: 6.4-13.3), p = 0.014]. This study demonstrated that sorafenib-related dermatologic AEs are clinical biomarkers to identify responders from all of the patients for TACE-S therapy. Sorafenib-related dermatologic AEs, clinical biomarkers, can predict the efficacy of TACE-S in future randomized controlled trials.
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Affiliation(s)
- Yan Zhao
- Department of Liver Disease and Digestive Interventional Radiology, Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Hailiang Li
- Department of Interventional Radiology, Henan Cancer Hospital, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China
| | - Wei Bai
- Department of Liver Disease and Digestive Interventional Radiology, Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Jueshi Liu
- Department of Interventional Radiology and Vascular Surgery, Hunan Provincial People's Hospital, Changsha, China
| | - Weifu Lv
- Department of Radiology, Anhui Provincial Hospital, Hefei, China
| | - Sonia Sahu
- Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston
| | - Sheng Guan
- Second Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Xiao Qin
- Department of Hepatobiliary Surgery & Vascular Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Wenhui Wang
- Department of Interventional Medicine, The First Affiliated Hospital of Lanzhou University, Lanzhou, China
| | - Weixin Ren
- Department of Interventional Radiology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
| | - Wei Mu
- Department of Radiology, The Southwest Hospital, Third Military Medical University, Chongqing, China
| | - Weidong Guo
- Cancer Treatment Center, Baogang Hospital of Inner Mongolia, Baotou, China
| | - Shanzhi Gu
- Department of Interventional Radiology, Hunan Cancer Hospital of Central South University, Changsha, China
| | - Yilong Ma
- Department of Interventional Therapy, Tumor Hospital of Guangxi Medical University, Nanning, China
| | - Zhanxin Yin
- Department of Liver Disease and Digestive Interventional Radiology, Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Wengang Guo
- Department of Liver Disease and Digestive Interventional Radiology, Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Wenjun Wang
- Department of Liver Disease and Digestive Interventional Radiology, Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Yongji Wang
- Department of Medical Statistics, Fourth Military Medical University, Xi'an, China
| | - Rafael Duran
- Department of Radiology, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland
| | - Daiming Fan
- Department of Liver Disease and Digestive Interventional Radiology, Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, China.,State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China
| | - Zhuoli Zhang
- Department of Radiology, Northwestern University, Chicago
| | - Guohong Han
- Department of Liver Disease and Digestive Interventional Radiology, Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, China
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26
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Abstract
Hepatocellular carcinoma (HCC) is the second most common cause of cancer-related deaths worldwide with rapidly growing incidence rates in the USA and Europe. Despite improving surveillance programs, most patients are diagnosed at intermediate to advanced stages and are no longer amenable to curative therapies, such as ablation, surgical resection and liver transplantation. For such patients, catheter-based image-guided embolotherapies such as transarterial chemoembolization (TACE) represent the standard of care and mainstay therapy, as recommended and endorsed by a variety of national guidelines and staging systems. The main benefit of these therapies is explained by the preferentially arterial blood supply of liver tumors, which allows to deliver the anticancer therapy directly to the tumor-feeding artery while sparing the healthy hepatic tissue mainly supplied by the portal vein. The tool box of an interventional oncologist contains several different variants of transarterial treatment modalities. Ever since the first TACE more than 30 years ago, these techniques have been progressively refined, both with respect to drug delivery materials and with respect to angiographic micro-catheter and image-guidance technology, thus substantially improving therapeutic outcomes of HCC. This review will summarize the fundamental principles, technical and clinical data on the application of different embolotherapies, such as bland transarterial embolization, Lipiodol-based conventional transarterial chemoembolization as well as TACE with drug-eluting beads (DEB-TACE). Clinical data on 90Yttrium radioembolization as an emerging alternative, mostly applied for niche indications such as HCC with portal vein invasion, will be discussed. Furthermore, we will summarize the principle of HCC staging, patient allocation and response assessment in the setting of HCC embolotherapy. In addition, we will evaluate the role of cone-beam computed tomography as a novel intra-procedural image-guidance technology. Finally, this review will touch on new technical developments such as radiopaque, imageable DEBs and the rationale and role of combined systemic and locoregional therapies, mostly in combination with Sorafenib.
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27
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Abdel-Rahman O. Role of liver-directed local tumor therapy in the management of hepatocellular carcinoma with extrahepatic metastases: a SEER database analysis. Expert Rev Gastroenterol Hepatol 2017; 11:183-189. [PMID: 27830958 DOI: 10.1080/17474124.2017.1259563] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND This study assessed the prognostic impact of the liver-directed local tumor therapy in the management of hepatocellular carcinoma (HCC) with extrahepatic metastases. METHODS Metastatic HCC patients diagnosed between 2004 and 2013 were identified from the SEER (Surveillance, Epidemiology, and End Results) database. Propensity-matched analysis was performed considering baseline characteristics (age, gender, race, histology, TNM stage, site of metastases, fibrosis score and alpha fetoprotein). RESULTS A total of 2529 patients were identified. The median age was 65 years, and 151 patients received liver-directed local treatment (either surgical treatment or local destructive treatment). Both before and after propensity score matching, cancer-specific and overall survival (p < 0.0001 for all) were better in the liver-directed local therapy group. When the overall survival was stratified by the type of local treatment (surgical resection versus destructive treatment), both types of treatment improved overall survival (p < 0.0001 for both). In multivariate analysis of the matched population, the only factor correlated with better survival receiving is local therapy (p < 0.0001). CONCLUSION This analysis suggests that liver-directed local treatment may play a role -in addition to systemic treatment- in the management of selected patients with metastatic HCC. Further prospective randomized controlled trials are needed to confirm or deny this hypothesis.
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Affiliation(s)
- Omar Abdel-Rahman
- a Clinical Oncology Department, Faculty of Medicine , Ain Shams University , Cairo , Egypt
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28
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Wang W, Bai W, Wang E, Zhao Y, Liu L, Yang M, Cai H, Xia D, Zhang L, Niu J, Yin Z, Zhang Z, Fan D, Xia J, Han G. mRECIST response combined with sorafenib-related adverse events is superior to either criterion alone in predicting survival in HCC patients treated with TACE plus sorafenib. Int J Cancer 2016; 140:390-399. [PMID: 27681592 DOI: 10.1002/ijc.30451] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2016] [Accepted: 09/15/2016] [Indexed: 12/11/2022]
Abstract
The mRECIST and dermatologic adverse events (AEs) can be used to assess the patient response to transarterial chemoembolization (TACE) and/or sorafenib for hepatocellular carcinoma (HCC). Here, we aimed to combine the two criteria to stratify the prognosis in patients with unresectable HCC receiving TACE plus sorafenib (TACE-S). In total, 176 consecutive HCC patients treated with TACE-S were enrolled. CT scans and laboratory tests were conducted pretreatment (at baseline, 5-7 days before the TACE-S) and post-treatment (at 1, 2 and 3 months). The radiological response was assessed according to mRECIST. Sorafenib-related AEs were recorded every 2 weeks after oral administration, and patients with dermatologic AEs of Grade 2 or more were defined as dermatologic responders. The earliest time at which mRECIST and dermatologic responses correlated with survival was 2 months after therapy. The mRECIST-dermatologic AE combination assessment stratified patients into three different prognoses; responders on both assessments exhibited the longest median overall survival (OS), followed by responders on one assessment and non-responders on both assessments (30.5, 17.4 and 8.3 months, respectively; p < 0.001). Achieving the highest C-index, the mRECIST-dermatologic AE combination showed better performance in predicting survival than either mRECIST or dermatologic AEs alone. Furthermore, the mRECIST-dermatologic AE combination remained a significant predictor of OS, even when the patients were stratified according to the BCLC stage, ECOG score or alpha-fetoprotein (AFP) value. This study showed that the combination of mRECIST response and dermatologic AEs is superior to either criterion used alone for predicting the survival of HCC patients treated with TACE-S.
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Affiliation(s)
- Wenjun Wang
- Department of Liver Disease and Digestive Interventional Radiology, Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Wei Bai
- Department of Liver Disease and Digestive Interventional Radiology, Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Enxin Wang
- Department of Liver Disease and Digestive Interventional Radiology, Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Yan Zhao
- Department of Liver Disease and Digestive Interventional Radiology, Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Lei Liu
- Department of Liver Disease and Digestive Interventional Radiology, Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Man Yang
- Department of Liver Disease and Digestive Interventional Radiology, Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Hongwei Cai
- Information Center, School of Stomatology, Fourth Military Medical University, Xi'an, China
| | - Dongdong Xia
- Department of Liver Disease and Digestive Interventional Radiology, Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Lei Zhang
- Department of Liver Disease and Digestive Interventional Radiology, Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Jing Niu
- Department of Liver Disease and Digestive Interventional Radiology, Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Zhanxin Yin
- Department of Liver Disease and Digestive Interventional Radiology, Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Zhuoli Zhang
- Department of Liver Disease and Digestive Interventional Radiology, Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, China.,Department of Radiology, Northwestern University, Chicago, IL
| | - Daiming Fan
- State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Jielai Xia
- Department of Medical Statistics, Fourth Military Medical University, Xi'an, China
| | - Guohong Han
- Department of Liver Disease and Digestive Interventional Radiology, Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, China
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29
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Poursaid A, Jensen MM, Nourbakhsh I, Weisenberger M, Hellgeth JW, Sampath S, Cappello J, Ghandehari H. Silk-Elastinlike Protein Polymer Liquid Chemoembolic for Localized Release of Doxorubicin and Sorafenib. Mol Pharm 2016; 13:2736-48. [DOI: 10.1021/acs.molpharmaceut.6b00325] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Affiliation(s)
- Azadeh Poursaid
- Department
of Bioengineering, University of Utah, Salt Lake City, Utah 84112, United States
- Utah
Center for Nanomedicine, Nano Institute of Utah, University of Utah, Salt Lake
City, Utah 84112, United States
| | - Mark Martin Jensen
- Department
of Bioengineering, University of Utah, Salt Lake City, Utah 84112, United States
- Utah
Center for Nanomedicine, Nano Institute of Utah, University of Utah, Salt Lake
City, Utah 84112, United States
| | - Ida Nourbakhsh
- Department
of Biology, University of Utah, Salt Lake City, Utah 84112, United States
| | - Mitchell Weisenberger
- Department
of Bioengineering, University of Utah, Salt Lake City, Utah 84112, United States
| | - John W. Hellgeth
- Merit Medical Systems, Inc., South Jordan, Utah 84095, United States
| | - Sujatha Sampath
- Department
of Bioengineering, University of Utah, Salt Lake City, Utah 84112, United States
- Utah
Center for Nanomedicine, Nano Institute of Utah, University of Utah, Salt Lake
City, Utah 84112, United States
| | - Joseph Cappello
- Department
of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake
City, Utah 84112, United States
| | - Hamidreza Ghandehari
- Department
of Bioengineering, University of Utah, Salt Lake City, Utah 84112, United States
- Utah
Center for Nanomedicine, Nano Institute of Utah, University of Utah, Salt Lake
City, Utah 84112, United States
- Department
of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake
City, Utah 84112, United States
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30
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Wang YY, Zhong JH, Qin HG, Li LQ. Comment on: Surgical resection versus transarterial chemoembolization for BCLC stage C hepatocellular carcinoma. J Surg Oncol 2016; 112:907-8. [PMID: 26768513 DOI: 10.1002/jso.24066] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2015] [Accepted: 09/29/2015] [Indexed: 02/03/2023]
Affiliation(s)
- Yan-Yan Wang
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China
| | - Jian-Hong Zhong
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China
| | - Hong-Gui Qin
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China
| | - Le-Qun Li
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China
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