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Taher MY, Hassouna E, El Hadidi A, El-aassar O, Fathy Bakosh M, Said Shater M. Serum CYFRA 21-1 and CK19-2G2 as Predictive Biomarkers of Response to Transarterial Chemoembolization in Hepatitis C-related Hepatocellular Carcinoma Among Egyptians: A Prospective Study. J Clin Exp Hepatol 2025; 15:102405. [PMID: 39309220 PMCID: PMC11414665 DOI: 10.1016/j.jceh.2024.102405] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2024] [Accepted: 08/12/2024] [Indexed: 09/25/2024] Open
Abstract
Background and aim Cytokeratin 19 (CK19)-positive HCC is a subtype of hepatocellular carcinoma (HCC) with poor biological behavior and resistance to different treatments including transarterial chemoembolization (TACE). The current study aimed to investigate the predictive value of serum CK 19 fragment 21-1 (CYFRA 21-1) and serum CK 19 fragment 2G2 (CK 19-2G2) for TACE response in patients with hepatitis C virus (HCV)-related HCC. Methods This prospective study assessed the pretreatment serum CYFRA 21-1 and CK 19-2G2 levels in 64 patients with HCV-related naïve HCC who underwent TACE to predict 1-year overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). Additionally, 40 healthy individuals were included as controls. Pretreatment alpha-fetoprotein (AFP) was also measured for comparison. Results After exclusions, 60 patients completed TACE sessions, and the 1-year OS was 52%, and ORR post TACE was 71.8%. HCC patients with elevated levels of CYFRA 21-1, CK 19-2G2, or baseline AFP measuring ≥400 ng/ml have decreased 1-year OS and PFS after TACE. Serum CK19-2G2 was an independent predictor of 1-year OS using multivariate hazard regression analysis. Pretreatment normal serum CYFRA 21-1 levels (P = 0.047), serum AFP measuring <400 ng/ml (P = 0.016), and lower AST (P = 0.002) were independent predictors of ORR to TACE using multivariate logistic regression analysis. The predictive ability of pretreatment elevated serum CYFRA 21-1, AFP measuring ≥400 ng/ml, AFP + CYFRA 21-1, AFP + CK 19-2G2, or AFP + CYFRA 21-1+ CK19-2G2 to predict nonresponse (progressive disease) to TACE (area under the curve = 0.795, 0.690, 0.830, 0.725, and 0.850, respectively). Conclusions This study demonstrated that incorporating the measurement of serum CYFRA 21-1 or CK19-2G2 levels, along with AFP, during the initial diagnosis can aid in predicting poor 1-year OS, PFS, and ORR to TACE in patients with HCV-related HCC.
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Affiliation(s)
- Mohamed Y. Taher
- Hepatobiliary Unit, Internal Medicine Department, Faculty of Medicine, Alexandria University, Egypt
| | - Ehab Hassouna
- Hepatobiliary Unit, Internal Medicine Department, Faculty of Medicine, Alexandria University, Egypt
| | - Abeer El Hadidi
- Clinical and Chemical Pathology, Faculty of Medicine, Alexandria University, Egypt
| | - Omar El-aassar
- Diagnostic and Interventional Radiology, Faculty of Medicine, Alexandria University, Egypt
| | - Mohamed Fathy Bakosh
- Hepatobiliary Unit, Internal Medicine Department, Faculty of Medicine, Alexandria University, Egypt
| | - Mohamed Said Shater
- Hepatobiliary Unit, Internal Medicine Department, Faculty of Medicine, Alexandria University, Egypt
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Fite EL, Makary MS. Transarterial Chemoembolization Treatment Paradigms for Hepatocellular Carcinoma. Cancers (Basel) 2024; 16:2430. [PMID: 39001491 PMCID: PMC11240648 DOI: 10.3390/cancers16132430] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2024] [Revised: 06/27/2024] [Accepted: 06/27/2024] [Indexed: 07/16/2024] Open
Abstract
Hepatocellular carcinoma (HCC) accounts for 90% of liver cancer cases worldwide and is currently the most quickly increasing cause of cancer-related deaths in the United States. The 5-year survival rate for primary liver cancer is estimated to be below 20%, and HCC mortality is expected to increase by 41% by 2040. Currently, surgical resection is the first-line approach to definitive treatment of early-stage HCC. However, the majority of patients present with late-stage, unresectable disease due to the asymptomatic nature of early HCC. For patients who present with unresectable HCC, locoregional therapies such as transarterial chemoembolization (TACE) represent an alternative approach to HCC treatment. TACE is a minimally invasive, catheter-based technique that allows for targeted delivery of chemotherapy to tumor sites while occluding tumor-feeding blood vessels. In appropriately selected patients, outcomes for TACE therapy have been shown to be more favorable than supportive care or conservative management. The increasing incidence and mortality of HCC, in addition to the late-stage presentation of most HCC patients, demonstrates the need to expand the role of locoregional therapies in the treatment of HCC. TACE represents an appealing approach to HCC management, including disease control, palliation, and potentially curative-intent strategies. In this review, we will describe the current utility of TACE in the treatment of HCC, characterize the outcomes of patients treated with TACE across different HCC stages, and outline future applications of TACE in the treatment paradigm.
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Affiliation(s)
- Elliott L Fite
- College of Medicine, The Ohio State University, Columbus, OH 43210, USA
| | - Mina S Makary
- Department of Radiology, The Ohio State University Medical Center, Columbus, OH 43210, USA
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Bajestani N, Wu G, Hussein A, Makary MS. Examining the Efficacy and Safety of Combined Locoregional Therapy and Immunotherapy in Treating Hepatocellular Carcinoma. Biomedicines 2024; 12:1432. [PMID: 39062006 PMCID: PMC11274263 DOI: 10.3390/biomedicines12071432] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2024] [Revised: 06/14/2024] [Accepted: 06/21/2024] [Indexed: 07/28/2024] Open
Abstract
More than 800,000 people worldwide are diagnosed with HCC (hepatocellular carcinoma) each year, with approximately 700,000 deaths alone occurring in that same year. Treatment of HCC presents complex therapeutic challenges, particularly in intermediate and advanced stages. LRTs such as transarterial chemoembolization (TACE) and ablations have been the mainstay treatment for early to intermediate-stage HCC, and systemic therapies are used to treat intermediate-late-stage HCC. However, novel literature describing combining LRT with systemic therapies has shown promising results. This review explores recent advances in both liver-directed techniques for hepatocellular carcinoma, including bland transarterial embolization, chemoembolization, radioembolization, and ablative therapies in conjunction as well as with systemic therapies, with a focus on combination therapies, patient selection, procedural technique, periprocedural management, and outcomes. Our findings suggest that LRT combined with systemic therapies is a viable strategy for improving progression-free survival and time to progression for patients with intermediate-to-late-stage HCC. However, further investigation is required to refine treatment protocols and define patient cohorts that would benefit the most.
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Affiliation(s)
- Nojan Bajestani
- College of Medicine, The Ohio State University, Columbus, OH 43210, USA; (G.W.); (A.H.)
| | - Gavin Wu
- College of Medicine, The Ohio State University, Columbus, OH 43210, USA; (G.W.); (A.H.)
| | - Ahmed Hussein
- College of Medicine, The Ohio State University, Columbus, OH 43210, USA; (G.W.); (A.H.)
| | - Mina S. Makary
- Division of Vascular and Interventional Radiology, Department of Radiology, The Ohio State University Wexner Medical Center, 395 W 12th Avenue, Columbus, OH 43210, USA;
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Zhu HD, Li X, Sun JH, Zhu X, Liu ZY, Li HL, Lu J, Yan ZP, Shao GL, He XF, Chao M, Lu LG, Zhong BY, Li R, Zhang Q, Teng GJ. Transarterial Chemoembolization with Epirubicin-Loaded Microspheres for Hepatocellular Carcinoma: A Prospective, Single-Arm, Multicenter, Phase 2 Study (STOPPER Trial). Cardiovasc Intervent Radiol 2024; 47:325-336. [PMID: 38413420 PMCID: PMC10920424 DOI: 10.1007/s00270-024-03666-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/24/2023] [Accepted: 01/16/2024] [Indexed: 02/29/2024]
Abstract
PURPOSE While the role of drug-eluting beads transarterial chemoembolization (DEB-TACE) for hepatocellular carcinoma (HCC) is established, questions regarding appropriate bead size for use in patients remain. This trial evaluated the effectiveness and safety of DEB-TACE using small-size (≤ 100 μm) microspheres loaded with epirubicin. MATERIALS AND METHODS This prospective, single-arm, multicenter study enrolled patients diagnosed with HCC who underwent DEB-TACE using 40 (range, 30-50), 75 (range, 60-90), or 100 (range, 75-125) μm epirubicin-loaded microspheres (TANDEM microspheres, Varian Medical). Bead size was at the discretion of treating physicians and based on tumor size and/or vascular structure. The primary outcome measure was 6-month objective response rate (ORR). Secondary outcome measures were 30-day and 3-month ORR, time to tumor progression and extrahepatic spread, proportion of progression-free survival and overall survival (OS) at one year, and incidence of treatment-associated adverse events. RESULTS Data from 108 patients from ten centers was analyzed. Six-month ORR was 73.3 and 71.3% based on European association for the study of the liver (EASL) and modified response evaluation criteria in solid tumors (mRECIST) criteria, respectively. Thirty-day ORR was 79.6% for both EASL and mRECIST criteria with 3-month ORR being 80.0 and 81.0%, respectively, for each criteria. One-year PPF and OS rate were 60.3 and 94.3%. There was a total of 30 SAEs reported to be likely to definitely associated with microsphere (n = 9), epirubicin (n = 9), or procedure (n = 12) with none resulting in death. CONCLUSION DEB-TACE using epirubicin-loaded small-sized (≤ 100 μm) microspheres demonstrates promising local tumor control and acceptable safety in patients with HCC. TRIAL REGISTRATION Clinicaltrials.gov NCT03113955; registered April 14, 2017. Trial Registration Clinicaltrials.gov NCT03113955; registered April 14, 2017. LEVEL OF EVIDENCE 2, Prospective, Non-randomized, Single-arm, study.
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Affiliation(s)
- Hai-Dong Zhu
- Center of Interventional Radiology and Vascular Surgery, Department of Radiology, Nurturing Center of Jiangsu Province for State Laboratory of AI Imaging & Interventional Radiology (Southeast University), Basic Medicine Research and Innovation Center of Ministry of Education, Zhongda Hospital, Medical School, Southeast University, 87 Dingjiaqiao Road, Nanjing, 210009, China
| | - Xiao Li
- Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jun-Hui Sun
- Division of Hepatobiliary and Pancreatic Surgery, Hepatobiliary and Pancreatic Interventional Treatment Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Xu Zhu
- Interventional Therapy Department, Peking University Cancer Hospital and Institute, Beijing, China
| | - Zhao-Yu Liu
- Department of Radiology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Hai-Liang Li
- Department of Minimal-Invasive Intervention, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China
| | - Jian Lu
- Center of Interventional Radiology and Vascular Surgery, Department of Radiology, Nurturing Center of Jiangsu Province for State Laboratory of AI Imaging & Interventional Radiology (Southeast University), Basic Medicine Research and Innovation Center of Ministry of Education, Zhongda Hospital, Medical School, Southeast University, 87 Dingjiaqiao Road, Nanjing, 210009, China
| | - Zhi-Ping Yan
- Department of Interventional Radiology, Zhongshan Hospital, Fudan University Shanghai Institution of Medical Imaging, Fudan University, Shanghai, China
| | - Guo-Liang Shao
- Department of Intervention, The Cancer Hospital of the University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Institute of Basic Medicine and Cancer, Chinese Academy of Sciences, Hangzhou, China
| | - Xiao-Feng He
- Division of Vascular and Interventional Radiology, Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Min Chao
- Department of Radiology, Second Affiliated Hospital of School of Medicine, Zhejiang University, Hangzhou, China
| | - Li-Gong Lu
- Zhuhai Interventional Medical Center, Zhuhai Precision Medical Center, Zhuhai People's Hospital, Zhuhai Hospital Affiliated with Jinan University, Jinan University, Zhuhai, China
| | - Bin-Yan Zhong
- Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou, China
| | - Rui Li
- Center of Interventional Radiology and Vascular Surgery, Department of Radiology, Nurturing Center of Jiangsu Province for State Laboratory of AI Imaging & Interventional Radiology (Southeast University), Basic Medicine Research and Innovation Center of Ministry of Education, Zhongda Hospital, Medical School, Southeast University, 87 Dingjiaqiao Road, Nanjing, 210009, China
| | - Qi Zhang
- Center of Interventional Radiology and Vascular Surgery, Department of Radiology, Nurturing Center of Jiangsu Province for State Laboratory of AI Imaging & Interventional Radiology (Southeast University), Basic Medicine Research and Innovation Center of Ministry of Education, Zhongda Hospital, Medical School, Southeast University, 87 Dingjiaqiao Road, Nanjing, 210009, China
| | - Gao-Jun Teng
- Center of Interventional Radiology and Vascular Surgery, Department of Radiology, Nurturing Center of Jiangsu Province for State Laboratory of AI Imaging & Interventional Radiology (Southeast University), Basic Medicine Research and Innovation Center of Ministry of Education, Zhongda Hospital, Medical School, Southeast University, 87 Dingjiaqiao Road, Nanjing, 210009, China.
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Ren Y, Zhao C, Xiong Y, Liu Z, Wu G. Comparison of Callisphere Drug-Eluting Beads Transarterial Chemoembolization and Conventional Transarterial Chemoembolization for the treatment of Hepatocellular Carcinoma. Pak J Med Sci 2024; 40:303-307. [PMID: 38356820 PMCID: PMC10862419 DOI: 10.12669/pjms.40.3.8572] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2023] [Revised: 08/11/2023] [Accepted: 11/08/2023] [Indexed: 02/16/2024] Open
Abstract
Objective To compare the efficacy of CalliSphere drug-eluting beads (DEBs) and conventional (c) transarterial chemoembolization (TACE) in the treatment of hepatocellular carcinoma (HCC). Methods We retrospectively reviewed the clinical data of 125 patients with HCC who had received treatment in Affiliated Hospital of North Sichuan Medical College from January 2018 to February 2019. Sixty-one patients underwent DEB-TACE (observation group) and 64 patients underwent cTACE (control group). The clinical efficacies, overall survivals, and incidence of postoperative adverse reactions between the two groups were compared. Results The objective response rate in the observation group (85.25%) was higher than that in the control group (70.31%; P<0.05). The disease control in the observation group (96.72%) was higher than that in the control group (85.94%; P<0.05). The median survival time of the observation group (24.85 months) was significantly higher than that in the control group (18.18 months; P<0.05). The incidence of adverse reactions in the observation group (4.92%) was lower than that in the control group (17.19%, P<0.05). Conclusions In the treatment of HCC, Callisphere DEB-TACE has better efficacy and longer patient survival with fewer adverse reactions compared to cTACE.
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Affiliation(s)
- Yongjun Ren
- Yongjun Ren, Department of Hepatobiliary Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan Province 637000, P.R. China
| | - Caixia Zhao
- Caixia Zhao, Department of Oncology, Nanchong Central Hospital, Nanchong, Sichuan Province 637000, P.R. China
| | - Yongfu Xiong
- Yongfu Xiong, Department of Hepatobiliary Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan Province 637000, P.R. China
| | - Zhongbai Liu
- Zhongbai Liu, Department of Hepatobiliary Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan Province 637000, P.R. China
| | - Guo Wu
- Guo Wu, Department of Hepatobiliary Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan Province 637000, P.R. China
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Wang DD, Zhang JF, Zhang LH, Niu M, Jiang HJ, Jia FC, Feng ST. Clinical-radiomics predictors to identify the suitability of transarterial chemoembolization treatment in intermediate-stage hepatocellular carcinoma: A multicenter study. Hepatobiliary Pancreat Dis Int 2023; 22:594-604. [PMID: 36456428 DOI: 10.1016/j.hbpd.2022.11.005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2021] [Accepted: 11/09/2022] [Indexed: 11/23/2022]
Abstract
BACKGROUND Although transarterial chemoembolization (TACE) is the first-line therapy for intermediate-stage hepatocellular carcinoma (HCC), it is not suitable for all patients. This study aimed to determine how to select patients who are not suitable for TACE as the first treatment choice. METHODS A total of 243 intermediate-stage HCC patients treated with TACE at three centers were retrospectively enrolled, of which 171 were used for model training and 72 for testing. Radiomics features were screened using the Spearman correlation analysis and the least absolute shrinkage and selection operator (LASSO) algorithm. Subsequently, a radiomics model was established using extreme gradient boosting (XGBoost) with 5-fold cross-validation. The Shapley additive explanations (SHAP) method was used to visualize the radiomics model. A clinical model was constructed using univariate and multivariate logistic regression. The combined model comprising the radiomics signature and clinical factors was then established. This model's performance was evaluated by discrimination, calibration, and clinical application. Generalization ability was evaluated by the testing cohort. Finally, the model was used to analyze overall and progression-free survival of different groups. RESULTS A third of the patients (81/243) were unsuitable for TACE treatment. The combined model had a high degree of accuracy as it identified TACE-unsuitable cases, at a sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) of 0.759, 0.885, 0.906 [95% confidence interval (CI): 0.859-0.953] in the training cohort and 0.826, 0.776, and 0.894 (95% CI: 0.815-0.972) in the testing cohort, respectively. CONCLUSIONS The high degree of accuracy of our clinical-radiomics model makes it clinically useful in identifying intermediate-stage HCC patients who are unsuitable for TACE treatment.
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Affiliation(s)
- Dan-Dan Wang
- Department of Radiology, the Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China; Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
| | - Jin-Feng Zhang
- Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin 150081, China
| | - Lin-Han Zhang
- Department of PET/CT, the First Affiliated Hospital of Harbin Medical University, Harbin 150007, China
| | - Meng Niu
- Department of Interventional Therapy, the First Affiliated Hospital of China Medical University, Shenyang 110001, China
| | - Hui-Jie Jiang
- Department of Radiology, the Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China.
| | - Fu-Cang Jia
- Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China.
| | - Shi-Ting Feng
- Department of Radiology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China.
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Zhang W, Du N, Wang L, Yu J, Yang M, Zhang W, Qu X, Luo J, Yan Z. Effects of HepaSphere microsphere encapsule epirubicin with a new loading method transarterial chemoembolization: in vitro and in vivo experiments. Discov Oncol 2023; 14:209. [PMID: 37993734 PMCID: PMC10665283 DOI: 10.1007/s12672-023-00831-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2023] [Accepted: 11/14/2023] [Indexed: 11/24/2023] Open
Abstract
METHODS HS microspheres were loaded in a solution of hypertonic saline and contrast medium at different ratios. Morphology, size distribution, and drug loading capacity of the microsphere were evaluated. Rabbits with hepatic VX2 tumors underwent conventional TACE, drug-eluting beads TACE with HS microsphere loading epirubicin by recommended method (dTACE) or a new loading method (ndTACE). The plasma and tissue epirubicin concentration, tumor necrosis, and the microsphere distribution within the tumor were assessed. RESULTS It was found that the mean diameter of HS microspheres was effectively reduced to 102 ± 14 μm after loading with 10.0% NaCl and Ultravist (370 mg I /mL) at a ratio of 2: 8 ml. The loading capacity reached 78.7%. It was noted that the concentration of tumor epirubicin was significantly higher (p = 0.016) in the ndTACE group (11,989.8 ± 5776.6 ng/g) than the concentration in the dTACE (6516.5 ± 3682.3 ng/g) and in cTACE groups (1564.1 ± 696.1 ng/g, p < 0.001). Further, the tumor necrosis in group with the new loading method (ndTACE) was 92.4%. CONCLUSIONS The size of HS microsphere can be effectively reduced when it is loaded with a mixture of hypertonic saline and non-ionic contrast material. HS microsphere loaded with epirubicin using the new method (ndTACE) can increase the drug concentration in tumor and hence exert better improved antitumor effect.
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Affiliation(s)
- Wen Zhang
- Department of Interventional Radiology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China
- Shanghai Institute of Medical Imaging, Shanghai, 200041, China
- National Clinical Research Center for Interventional Medicine, Shanghai, 200032, China
| | - Nan Du
- Department of Interventional Radiology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China
- Shanghai Institute of Medical Imaging, Shanghai, 200041, China
- National Clinical Research Center for Interventional Medicine, Shanghai, 200032, China
| | - Liangwen Wang
- Department of Interventional Radiology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China
- Shanghai Institute of Medical Imaging, Shanghai, 200041, China
- National Clinical Research Center for Interventional Medicine, Shanghai, 200032, China
| | - Jiaze Yu
- Department of Interventional Radiology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China
- Shanghai Institute of Medical Imaging, Shanghai, 200041, China
- National Clinical Research Center for Interventional Medicine, Shanghai, 200032, China
| | - Minjie Yang
- Department of Interventional Radiology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China
- Shanghai Institute of Medical Imaging, Shanghai, 200041, China
- National Clinical Research Center for Interventional Medicine, Shanghai, 200032, China
| | - Wei Zhang
- Department of Interventional Radiology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China
- Shanghai Institute of Medical Imaging, Shanghai, 200041, China
- National Clinical Research Center for Interventional Medicine, Shanghai, 200032, China
| | - Xvdong Qu
- Department of Interventional Radiology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China
- Shanghai Institute of Medical Imaging, Shanghai, 200041, China
- National Clinical Research Center for Interventional Medicine, Shanghai, 200032, China
| | - Jianjun Luo
- Department of Interventional Radiology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China
- Shanghai Institute of Medical Imaging, Shanghai, 200041, China
- National Clinical Research Center for Interventional Medicine, Shanghai, 200032, China
| | - Zhiping Yan
- Department of Interventional Radiology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China.
- Shanghai Institute of Medical Imaging, Shanghai, 200041, China.
- National Clinical Research Center for Interventional Medicine, Shanghai, 200032, China.
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Huang D, Huang D. Relationship between M6A methylation regulator and prognosis in patients with hepatocellular carcinoma after transcatheter arterial chemoembolization. Heliyon 2022; 8:e10931. [PMID: 36262291 PMCID: PMC9573888 DOI: 10.1016/j.heliyon.2022.e10931] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2022] [Revised: 08/02/2022] [Accepted: 09/29/2022] [Indexed: 11/05/2022] Open
Abstract
Background Patients with mid-stage HCC (hepatocellular carcinoma) may benefit from transcatheter arterial chemoembolization (TACE). However, patient efficacy varies widely, and the detailed assessment index is unknown. The most general methylation alteration in mRNA (Messenger RNA), N6-methyladenosine (m6A), is controlled by the m6A regulator, which is associated with the emergence of tumors. To include the molecular causes of cancer, competition with ceRNA (endogenous RNA) networks is crucial. However, the exact processes they contribute to TACE HCC remain uncertain. The purpose of this study was tantamount to investigating the possible function of ceRNA networks and m6A regulators in patients with TACE HCC. Methods Genes Associated with m6A were discovered using the TACE GEO (Gene Expression Omnibus) dataset. An additional estimate of M6A-associated DEGs (differentially expressed genes) was used to create a predictive response model, which is required. LncRNA-miRNA and miRNA-mRNA interactions were then predicted, the regulatory ceRNA network was set up using Cytoscape software, and target genes were identified using GEPIA online analysis. The connection between immunological checkpoints, immune cell marker genes, and target genes for immune cells was also examined. Results The detection of 4 m6A-associated DEGs, the development and evaluation of 2 Machine learning models, and the development of risk models that accurately predicted the response rate of specific patients. Additionally, we obtained two miRNAs (micro RNAs)and six lncRNAs (Long non-coding RNAs), forming an 8-pair ceRNA network, and the target gene LRPPRC deletion of one copy number and gene expression was highly correlated with the amount of Tregs immune cells. LRPPRC was related positively with NRP1, IRF5, and ITGAM and negatively with CCR7 and CD8B among immune cell marker genes. We also discovered that LRPPRC correlates positively with immune checkpoint CD274 cells. Conclusion The response of HCC patients to TACE therapy may be predicted using a model based on four gene expression data. We also developed a ceRNA network for TACE HCC related to m6A, which offered suggestions for more research into its molecular processes and possible prognostic indicators.
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Affiliation(s)
- Deliang Huang
- Department of Interventional Medicine, Yellow River Central Hospital, Zhengzhou, Henan Province, China
| | - Dejing Huang
- Department of Thoracic Surgery, The Second Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China,Corresponding author.
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Afif AM, Laroco OD, Lau SMD, Teo SM, Rahman ASA, Too CW, Venkatanarasimha N, Gogna A. Usefulness of ultrasound fusion technology for hepatocellular carcinoma localisation, pre- and post-thermal ablation. ULTRASOUND (LEEDS, ENGLAND) 2022; 30:194-200. [PMID: 35936962 PMCID: PMC9354184 DOI: 10.1177/1742271x211049525] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/22/2021] [Accepted: 09/02/2021] [Indexed: 06/15/2023]
Abstract
INTRODUCTION Percutaneous thermal ablation of inconspicuous lesions can be challenging. Fusion ultrasound (FUS) allows the use of previously performed diagnostic imaging like computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography (PET-CT) to localise hepatocellular carcinoma (HCC) for treatment. This paper illustrates FUS case studies of pre-, intra- and post-ablation imaging of inconspicuous HCC, supplemented by use of contrast-enhanced ultrasound (CEUS). METHOD Four prospective cases during September 2014 to October 2018, with HCC amenable to ablation, which were poorly identified on ultrasound, underwent FUS. FUS pre-screening was scheduled within three months of the previous CT or MRI, and between one to four weeks prior to the scheduled ablation date. Post-ablation imaging with FUS was performed between four to six weeks to coincide with their routine follow-up CT or MRI. FINDINGS There were potential benefits observed in the cases with combined techniques of FUS and CEUS for limiting circumstances such as heat sink effect, multiple lesions targeting, inconspicuous lesion detection and pre-ablation technical feasibility assessment. DISCUSSION The combined use of FUS and CEUS improves tumour visibility, increases operator imaging confidence and reduces heat sink effect during percutaneous thermal ablation. CONCLUSION FUS imaging is helpful in targeting poor conspicuity lesions that cannot be detected on grey-scale ultrasound. It facilitates in ensuring optimal treatment of hepatic lesions for improvement of patient prognosis and follow-up imaging.
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Affiliation(s)
- A Mohamed Afif
- A Mohamed Afif, Block 2, Level 1, Department of Diagnostic Radiology, Singapore General Hospital, Outram Road, Singapore 169608.
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Zane KE, Nagib PB, Jalil S, Mumtaz K, Makary MS. Emerging curative-intent minimally-invasive therapies for hepatocellular carcinoma. World J Hepatol 2022; 14:885-895. [PMID: 35721283 PMCID: PMC9157708 DOI: 10.4254/wjh.v14.i5.885] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2021] [Revised: 02/20/2022] [Accepted: 04/25/2022] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common cause of liver malignancy and the fourth leading cause of cancer deaths universally. Cure can be achieved for early stage HCC, which is defined as 3 or fewer lesions less than or equal to 3 cm in the setting of Child-Pugh A or B and an ECOG of 0. Patients outside of these criteria who can be down-staged with loco-regional therapies to resection or liver transplantation (LT) also achieve curative outcomes. Traditionally, surgical resection, LT, and ablation are considered curative therapies for early HCC. However, results from recently conducted LEGACY study and DOSISPHERE trial demonstrate that transarterial radio-embolization has curative outcomes for early HCC, leading to its recent incorporation into the Barcelona clinic liver criteria guidelines for early HCC. This review is based on current evidence for curative-intent loco-regional therapies including radioembolization for early-stage HCC.
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Affiliation(s)
- Kylie E Zane
- College of Medicine, The Ohio State University, Columbus, OH 43210, United States
| | - Paul B Nagib
- College of Medicine, The Ohio State University, Columbus, OH 43210, United States
| | - Sajid Jalil
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
| | - Khalid Mumtaz
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
| | - Mina S Makary
- Division of Vascular and Interventional Radiology, Department of Radiology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States.
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A 10-Gene Signature Identified by Machine Learning for Predicting the Response to Transarterial Chemoembolization in Patients with Hepatocellular Carcinoma. JOURNAL OF ONCOLOGY 2022; 2022:3822773. [PMID: 35111225 PMCID: PMC8803430 DOI: 10.1155/2022/3822773] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/08/2021] [Revised: 12/28/2021] [Accepted: 12/29/2021] [Indexed: 12/15/2022]
Abstract
Background Transarterial chemoembolization (TACE) is recommended for intermediate-stage HCC patients. Owing to substantial variation in its efficacy, indicators of patient responses to TACE need to be determined. Methods A Gene Expression Omnibus (GEO) dataset consisting of patients of different TACE-response status was retrieved. Differentially expressed genes (DEGs) were calculated and variable gene ontology analyses were conducted. Potential drugs and response to immunotherapy were predicted using multiple bioinformatic algorithms. We built and compared 5 machine-learning models with finite genes to predict patients' response to TACE. The model was also externally validated to discern different survival outcomes after TACE. Tumor-infiltrating lymphocytes (TILs) and tumor stemness index were evaluated to explore potential mechanism of our model. Results The gene set variation analysis revealed enhanced pathways related to G2/M checkpoint, E2F, mTORC1, and myc in TACE nonresponders. TACE responders had better immunotherapy response too. 373 DEGs were detected and the upregulated DEGs in nonresponders were enriched in IL-17 signal pathway. 5 machine-learning models were constructed and evaluated, and a linear support vector machine (SVM)-based model with 10 genes was selected (AQP1, FABP4, HERC6, LOX, PEG10, S100A8, SPARCL1, TIAM1, TSPAN8, and TYRO3). The model achieved an AUC and accuracy of 0.944 and 0.844, respectively, in the development cohort. In the external validation cohort comprised of patients receiving adjuvant TACE and postrecurrence TACE treatment, the predicted response group significantly outlived the predicted nonresponse counterparts. TACE nonresponders tend to have more macrophage M0 cells and lower resting mast cells in the tumor tissue and the stemness index is also higher than responders. Those characteristics were successfully captured by our model. Conclusion The model based on expression data of 10 genes could potentially predict HCC patients' response and prognosis after TACE treatment. The discriminating power was TACE-specific.
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Ouyang T, Liu J, Shi C, Zhu L, Guo X. Drug-Eluting Bead Transarterial Chemoembolization versus Conventional Transarterial Chemoembolization Both Combined Apatinib for Hepatocellular Carcinoma: A Retrospective, Propensity-Score Matched Study. J Hepatocell Carcinoma 2021; 8:1459-1471. [PMID: 34858890 PMCID: PMC8632616 DOI: 10.2147/jhc.s338309] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2021] [Accepted: 11/05/2021] [Indexed: 12/28/2022] Open
Abstract
Purpose This study aims to compare the efficacy of drug-eluting bead transarterial chemoembolization (DEB-TACE) versus conventional TACE (cTACE), both combined with apatinib, and to establish predictive nomograms to support individualized survival prediction in hepatocellular carcinoma (HCC) patients. Patients and Methods This retrospective study assessed HCC patients from June 2015 to December 2019. Patients were classified as DEB-TACE plus apatinib (D-apatinib) and cTACE plus apatinib (c-apatinib). The endpoints were overall survival (OS) and progression-free survival (PFS). The nomograms were constructed, and the C-index, receiver operating characteristic (ROC) curve, and calibration curves were used to validate the nomograms. Propensity score matching (PSM) analysis was applied to reduce patient selection bias. Results A total of 174 patients were included. After PSM analysis, 58 pairs of patients were selected. Before PSM analysis, the median OS and PFS were 21.0 and 8.0 months in the D-apatinib group, respectively, which were better than the 18.0 and 5.0 months observed in the c-apatinib group (P < 0.05). The complete response (CR) rate and objective response rate (ORR) of the D-apatinib group were higher than those of the c-apatinib group. The C-index values of the nomograms in the D-apatinib group and the c-apatinib group were 0.826 and 0.802, and the area under the curve (AUC) values in the ROC curve were 0.934 and 0.892. After PSM analysis, the survival of patients treated with D-apatinib was better than that of patients treated with c-apatinib (P < 0.05). The C-index values were 0.854 and 0.794 in the D-apatinib group and the c-apatinib group, respectively, and the AUC values were 0.960 and 0.890. The incidence of adverse events was higher in the c-apatinib group. Conclusion DEB-TACE in combination with apatinib showed better treatment effectiveness for unresectable HCC. The nomograms can identify HCC patients who may benefit most from the treatment.
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Affiliation(s)
- Tao Ouyang
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China
| | - Junxia Liu
- Cancer Medical Center, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, People's Republic of China
| | - Chengyang Shi
- Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China
| | - Lisheng Zhu
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China
| | - Xiaopeng Guo
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China
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Frenette CT. Highlights in Hepatocellular Carcinoma From the 2021 European Society for Medical Oncology Congress: Commentary. Gastroenterol Hepatol (N Y) 2021; 17:20-23. [PMID: 35611268 PMCID: PMC9122049] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
Affiliation(s)
- Catherine T Frenette
- Director, Liver and Hepatocellular Cancer Program Scripps MD Anderson Cancer Center La Jolla, California
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Transarterial Chemoembolization of Hepatocellular Carcinoma with Oncozene Microspheres: An Initial, Short-Term Clinical Experience-A Retrospective, Matched, Comparison Study. Life (Basel) 2021; 11:life11070600. [PMID: 34201468 PMCID: PMC8305898 DOI: 10.3390/life11070600] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2021] [Revised: 05/24/2021] [Accepted: 06/15/2021] [Indexed: 11/16/2022] Open
Abstract
Background: The purpose of this study is to describe a single institution's experience using Oncozene (OZ) microspheres for transarterial chemoembolization (OZ-TACE) of hepatocellular carcinoma (HCC), and to compare tolerability, safety, short-term radiographic tumor response, progression-free survival (PFS), and overall survival (OS) of these procedures to TACE (LC-TACE) performed with LC beads (LC). Methods: A retrospective, matched cohort study of patients undergoing DEB-TACE (drug-eluting bead transarterial chemoembolization) with OZ or LC was performed. The cohort comprised 23 patients undergoing 29 TACE with 75 or 100 μm OZ and 24 patients undergoing 29 TACE with 100-300 μm LC. Outcome measures were changes in liver function tests, complications, treatment tolerability, short-term radiographic tumor response according to modified RECIST criteria for HCC, PFS, and 1-year OS. The Mann-Whitney U test, Fisher exact test, and log rank test were used to compare the groups. Results: The BCLC or Child-Pugh scores were similar between the OZ and LC group. However, the two groups differed with respect to the etiology of background cirrhosis (p = 0.02). All other initial demographic and tumor characteristics were similar between the two groups. OZ-TACE used less doxorubicin per treatment compared to LC-TACE (median 50 vs. 75 mg; p = 0.0005). Rates of pain, nausea, and postembolization syndrome were similar, irrespective of the embolic agent used. OZ-TACE resulted in an overall complication rate comparable to LC-TACE (20.7% vs. 10.3%; p = 0.47). LC-TACE resulted in a higher percent increase in total bilirubin on post-procedure day 1 (median 18.8 vs. 0%; p = 0.05), but this difference resolved at 1 month. Both OZ-TACE and LC-TACE resulted in similar complete (31% vs. 24%) and objective (66% vs. 79%) target lesion response rates on 1-month post-TACE imaging. Both OZ-TACE and LC-TACE had similar median progression-free survival (283 vs. 209 days; p = 0.14) and 1-year overall survival rates (85% vs. 76%; p = 0.30). Conclusion: With a significantly reduced dose of doxorubicin, TACE performed with Oncozene microspheres in a heterogeneous patient population is well-tolerated, safe, and produces a similar radiological response and survival rate when compared to LC Bead TACE.
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