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Singal AG, Salem R, Pinato DJ, Pillai A. Advances in Locoregional and Systemic Treatments for Hepatocellular Carcinoma. Gastroenterology 2025:S0016-5085(25)00660-2. [PMID: 40320088 DOI: 10.1053/j.gastro.2025.03.047] [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: 01/05/2025] [Revised: 03/20/2025] [Accepted: 03/26/2025] [Indexed: 05/29/2025]
Abstract
Significant advances have occurred in the locoregional and systemic therapy landscape for hepatocellular carcinoma (HCC), with the most notable being the introduction of immune checkpoint inhibitor (ICI) combinations. ICI combinations have significantly improved the overall survival of patients with unresectable HCC, affording median survival over 2 years and long-term survival exceeding 5 years in a subset of patients. Accordingly, there has been increased interest in the earlier application of systemic therapies, including (neo)adjuvant therapy in the perioperative setting or in combination with intra-arterial therapies. However, recent data failed to demonstrate improved recurrence-free survival with use of adjuvant ICI therapy. Conversely, 2 trials showed improved progression-free survival when ICI therapies were combined with transarterial chemoembolization, although data regarding the impact on overall survival are still immature. These improved outcomes raise several new questions, including which patients with liver-localized HCC should receive systemic therapy, how should this be sequenced or combined with other available therapies, and how to manage those patients with marked responses, including consideration of liver transplantation. These questions are often determined on a case-by-case basis and best made in a multidisciplinary manner considering several factors, including tumor burden, degree of liver dysfunction, performance status, and patient's long-term goals of care.
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Affiliation(s)
- Amit G Singal
- Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas (UT) Southwestern Medical Center, Dallas Texas.
| | - Riad Salem
- Department of Radiology, Northwestern University, Chicago, Illinois
| | - David J Pinato
- Department of Surgery & Cancer, Imperial College London, London, United Kingdom; Department of Translational Medicine (DIMET), University of Piemonte Orientale, Novara, Italy
| | - Anjana Pillai
- Department of Internal Medicine, University of Chicago, Chicago, Illinois
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Owen J, Negussie AH, Burks SR, Delgado J, Mikhail AS, Rivera J, Pritchard WF, Karanian JW, Stride E, Frank JA, Wood BJ. Microbubbles bound to drug-eluting beads enable ultrasound imaging and enhanced delivery of therapeutics. Sci Rep 2024; 14:20929. [PMID: 39251665 PMCID: PMC11383944 DOI: 10.1038/s41598-024-71831-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2024] [Accepted: 08/30/2024] [Indexed: 09/11/2024] Open
Abstract
Transarterial chemoembolization (TACE) is an image-guided minimally invasive treatment for liver cancer which involves delivery of chemotherapy and embolic material into tumor-supplying arteries to block blood flow to a liver tumor and to deliver chemotherapy directly to the tumor. However, the released drug diffuses only less than a millimeter away from the beads. To enhance the efficacy of TACE, the development of microbubbles electrostatically bound to the surface of drug-eluting beads loaded with different amounts of doxorubicin (0-37.5 mg of Dox/mL of beads) is reported. Up to 400 microbubbles were bound to Dox-loaded beads (70-150 microns). This facilitated ultrasound imaging of the beads and increased the release rate of Dox upon exposure to high intensity focused ultrasound (HIFU). Furthermore, ultrasound exposure (1 MPa peak negative pressure) increased the distance at which Dox could be detected from beads embedded in a tissue-mimicking phantom, compared with a no ultrasound control.
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Affiliation(s)
- Joshua Owen
- Center for Interventional Oncology, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD, USA
| | - Ayele H Negussie
- Center for Interventional Oncology, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD, USA
| | - Scott R Burks
- Frank Laboratory, Radiology and Imaging Sciences, Clinical Center, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD, USA
| | - Jose Delgado
- Center for Interventional Oncology, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD, USA
| | - Andrew S Mikhail
- Center for Interventional Oncology, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD, USA
| | - Jocelyne Rivera
- Center for Interventional Oncology, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD, USA
- Institute of Biomedical Engineering, Department of Engineering Science, University of Oxford, Oxford, UK
| | - William F Pritchard
- Center for Interventional Oncology, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD, USA
| | - John W Karanian
- Center for Interventional Oncology, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD, USA
| | - Eleanor Stride
- Institute of Biomedical Engineering, Department of Engineering Science, University of Oxford, Oxford, UK
| | - Joseph A Frank
- Frank Laboratory, Radiology and Imaging Sciences, Clinical Center, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD, USA
| | - Bradford J Wood
- Center for Interventional Oncology, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD, USA.
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Jin B, Gu Y, Xi S, Liu X, Wu X, Wang X, Li G. Efficacy of CalliSpheres ® drug-loaded microspheres combined with doxorubicin in hepatocellular carcinoma. Scand J Gastroenterol 2024; 59:1087-1092. [PMID: 39154241 DOI: 10.1080/00365521.2024.2390025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2024] [Revised: 07/30/2024] [Accepted: 08/02/2024] [Indexed: 08/19/2024]
Abstract
OBJECTIVE This study compared the efficacy and safety of the transarterial chemoembolization with CalliSpheres® drug-eluting beads loading with doxorubicin (DEB-TACE) versus conventional lipiodol (cTACE) in patients with unresectable hepatocellular carcinoma (HCC). METHODS A randomized controlled trial (RCT) was conducted with 144 patients, who were randomly assigned to receive either DEB-TACE with doxorubicin-loaded CalliSpheres® microspheres or cTACE with doxorubicin-lipiodol emulsion. Patients were followed up for 12 months, with assessments at 3 and 12 months posttreatment. The primary endpoint was the clinical response rate (CR), and the secondary endpoints were the overall survival (OS), the progression-free survival (PFS), and the safety profile of the two treatments. RESULTS The results showed that DEB-TACE was superior to cTACE in terms of CR (50.0% vs 30.6% at 3 months, p = 0.03; 43.1% vs 25.0% at 12 months, p = 0.04), OS (18.2 months vs 14.6 months, p < 0.05), and PFS (7.4 months vs 4.8 months, p < 0.05), and that the safety profile of the two treatments was similar (p > 0.05 for all comparisons). However, the efficacy of DEB-TACE and cTACE varied according to the tumor morphology. DEB-TACE showed better CR rates in patients with nodular tumors, while no significant difference in CR between the two groups in patients with infiltrative tumors. CONCLUSION DEB-TACE showed superior efficacy to cTACE in terms of CR, OS, and PFS, particularly in patients with nodular tumors, while maintaining a similar safety profile. These findings suggest that tumor morphology could inform treatment decisions for TACE in HCC patients.
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Affiliation(s)
- Boxun Jin
- Department of Intensive Care Unit, Beijing You An Hospital Affiliated to the Capital Medical University, Beijing, China
| | - Yanmei Gu
- Department of Intensive Care Unit, Beijing You An Hospital Affiliated to the Capital Medical University, Beijing, China
| | - Shuangmei Xi
- Department of Intensive Care Unit, Beijing You An Hospital Affiliated to the Capital Medical University, Beijing, China
| | - Xin Liu
- Department of Intensive Care Unit, Beijing You An Hospital Affiliated to the Capital Medical University, Beijing, China
| | - Xiulian Wu
- Department of Intensive Care Unit, Beijing You An Hospital Affiliated to the Capital Medical University, Beijing, China
| | - Xin Wang
- Department of Intensive Care Unit, Beijing You An Hospital Affiliated to the Capital Medical University, Beijing, China
| | - Guangming Li
- Department of Intensive Care Unit, Beijing You An Hospital Affiliated to the Capital Medical University, Beijing, China
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Wang ZY, Xie CF, Feng KL, Xiong CM, Huang JH, Chen QL, Zhong C, Zhou ZW. Drug-eluting beads versus conventional transarterial chemoembolization for the treatment of unresectable hepatocellular carcinoma: A meta-analysis. Medicine (Baltimore) 2023; 102:e34527. [PMID: 37653749 PMCID: PMC10470720 DOI: 10.1097/md.0000000000034527] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2020] [Accepted: 06/19/2023] [Indexed: 09/02/2023] Open
Abstract
BACKGROUND Transarterial chemoembolization (TACE) consists of conventional TACE (cTACE) and drug-eluting beads TACE (DEB-TACE). The benefits of the 2 treatments remain controversial. We conduct this meta-analysis to assess the efficacy and safety of the 2 methods for the patients with unresectable hepatocellular carcinoma. METHODS In order to get a sound conclusion, we did thorough search all relevant studies with clear and stringent keyword criteria on the main databases. Objective tumor response rate, overall survival (OS) rate and adverse events were calculated and analyzed by RevMan 5.3 software. The random-effects or fixed-effects model was applied to pool the estimates according to Cochran Q test and I2 statistics. RESULTS Twenty-four studies involving 2987 patients were eligible. DEB-TACE significantly improved objective tumor response rate (OR) (risk ratio [RR] = 1.27, 95% confidence interval [CI] [1.08, 1.48]; P = .003). While as for 1-year, 2-year, 3-year, 5-year OS rates, there were no evidences to indicate that DEB-TACE was significantly better than cTACE (RR = 1.05, 95% CI [0.99, 1.11]; P = .08), (RR = 1.02, 95% CI [0.93, 1.11]; P = .68), (RR = 0.92, 95% CI [0.77, 1.10]; P = .37), (RR = 0.92, 95% CI [0.47, 1.80]; P = .81), respectively. Adverse events rate (AE) was also similar in both groups (RR = 1.11, 95% CI [0.99,1.26]; P = .08). CONCLUSION This meta-analysis demonstrates that DEB-TACE is not superior than cTACE regarding to OS and AE. However, DEB-TACE still be considered to provide a better objective tumor response rate for patients with unresectable hepatocellular carcinoma.
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Affiliation(s)
- Zi-Yu Wang
- Department of Hepatobiliary Surgery, the First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
- Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou, China
- The First Clinical Medical School of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Chun-Feng Xie
- Department of Hepatobiliary Surgery, the First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
- Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou, China
- The First Clinical Medical School of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Kun-Liang Feng
- Department of Hepatobiliary Surgery, the First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
- Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou, China
- The First Clinical Medical School of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Cheng-Ming Xiong
- Department of Hepatobiliary Surgery, the First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
- Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Jun-Hai Huang
- Department of Hepatobiliary Surgery, the First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
- Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Qing-Lian Chen
- Department of Hepatobiliary Surgery, the First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
- Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Chong Zhong
- Department of Hepatobiliary Surgery, the First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
- Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Zhai-Wen Zhou
- Department of Radiology, the First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
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Chen J, Lai L, Zhou C, Luo J, Wang H, Li M, Huang M. Safety, efficacy, and survival of drug-eluting beads-transarterial chemoembolization vs. conventional-transarterial chemoembolization in advanced HCC patients with main portal vein tumor thrombus. Cancer Imaging 2023; 23:70. [PMID: 37481660 PMCID: PMC10362718 DOI: 10.1186/s40644-023-00581-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2022] [Accepted: 06/01/2023] [Indexed: 07/24/2023] Open
Abstract
OBJECTIVES To compare the efficacy, overall survival (OS) and safety of drug-eluting beads-TACE (DEB-TACE) and C-TACE as initial treatment in advanced hepatocellular carcinoma (HCC) patients with main portal vein tumor thrombus (mPVTT). METHODS The medical records of consecutive advanced HCC patients with mPVTT who underwent initial DEB-TACE or C-TACE from September 2015 to October 2021 were retrospectively evaluated. Treatment crossover was allowed in this retrospective research. The adverse events, disease control rate (DCR), time to tumor progression (TTP) and OS of patients who underwent DEB-TACE were compared with those of patients who underwent C-TACE. RESULTS Eighty-three patients were included: 42 patients in DEB-TACE group and 41 patients in C-TACE group. DEB-TACE could be safely performed in HCC patients with mPVTT, and they gained a better DCR than those submitted to the C-TACE (76.2% vs. 53.7%, P = 0.031), which might have resulted in longer TTP (median TTP: 9.0 months vs. 3.0 months, P < 0.001). Furthermore, DEB-TACE showed significant OS benefits compared with C-TACE (median OS: 12.0 months vs. 5.0 months, P < 0.001). DEB-TACE, absence of arterioportal shunts (APS), leisons with capsular non-infiltration were found to be independent prognostic factors for better OS. Furthermore, subgroup analysis proved that patients with good DCR gained longer OS in DEB-TACE group. CONCLUSIONS DEB-TACE could be safely performed and improve the DCR of HCC patients with mPVTT, which resulting in longer TTP and OS, compared with C-TACE.
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Affiliation(s)
- Junwei Chen
- Department of Interventional Radiology, the Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630, China
| | - Lisha Lai
- Department of Radiology, School of Medicine, Guangzhou First People's Hospital, South China University of Technology, Guangzhou, 510180, China
| | - Churen Zhou
- Department of Interventional Radiology, the Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630, China
| | - Junyang Luo
- Department of Interventional Radiology, the Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630, China
| | - Haofan Wang
- Department of Interventional Radiology, the Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630, China
| | - Mingan Li
- Department of Interventional Radiology, the Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630, China.
| | - Mingsheng Huang
- Department of Interventional Radiology, the Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630, China.
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Wu SJ, Ruan DD, Wu QY, Tang Y, Zhang JH, Cai SL, Zhou YF, Luo JW, Fang ZT. Safety and Efficacy of Drug-Eluting Bead Transarterial Chemoembolization Combined with Lenvatinib and Anti-PD-1 Antibodies for Unresectable Hepatocellular Carcinoma: A Retrospective Analysis. J Hepatocell Carcinoma 2023; 10:807-820. [PMID: 37292114 PMCID: PMC10244613 DOI: 10.2147/jhc.s408819] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2023] [Accepted: 05/20/2023] [Indexed: 06/10/2023] Open
Abstract
Background Drug-eluting bead transarterial chemoembolization (DEB-TACE) has good efficacy in the treatment of unresectable hepatocellular carcinoma (uHCC), with a relatively high objective response rate (ORR) compared to conventional transarterial chemoembolization (cTACE). This study aimed to evaluate the safety and medium-term clinical efficacy of DEB-TACE combined with lenvatinib (LEN) plus PD-1 inhibitors as a triple therapy for the treatment of uHCC. Methods Data of patients with uHCC who received triple therapy of DEB-TACE combined with LEN plus PD-1 inhibitors from January 2019 to June 2021 were analyzed retrospectively. The study endpoints were ORR, progression-free survival (PFS), and treatment-related adverse events based on the modified Response Evaluation Criteria in Solid Tumors (mRECIST). Results Thirty-five patients were included in this study, with a median follow-up period of 15 months. The median cycle of DEB-TACE was 1, while that of all forms of TACE procedures per patient was 2. The median administration time of LEN was 7 months, and the median number of PD-1 inhibitor treatment was 4 cycles. The ORR based on mRECIST was 82.9%, disease control rate was 91.4%, and the median time to response was 7 weeks. Among these, the ORR of Barcelona Clinic Liver Cancer (BCLC) stage A reached 100%, while that of BCLC stages B and C reached 84.6% and 78.9%, respectively. The median PFS was 9 months; the mOS was not reached. Fourteen patients (40%) successfully underwent downstaging conversion and surgical resection, 32 patients (91.4%) experienced treatment-related adverse events, and no grade 5-related adverse reactions occurred. Conclusion DEB-TACE combined with LEN and PD-1 inhibitors has a high ORR and surgical conversion rate in the treatment of uHCC tumors, and the toxicity and side effects were tolerable.
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Affiliation(s)
- Shao-Jie Wu
- Fujian Provincial Hospital, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, People’s Republic of China
- Department of Interventional Radiology, Fujian Provincial Hospital, Fuzhou, People’s Republic of China
| | - Dan-Dan Ruan
- Fujian Provincial Hospital, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, People’s Republic of China
| | - Qiu-Yan Wu
- Fujian Provincial Hospital, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, People’s Republic of China
| | - Yi Tang
- Fujian Provincial Hospital, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, People’s Republic of China
- Department of Interventional Radiology, Fujian Provincial Hospital, Fuzhou, People’s Republic of China
| | - Jian-Hui Zhang
- Fujian Provincial Hospital, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, People’s Republic of China
| | - Sen-Lin Cai
- Fujian Provincial Hospital, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, People’s Republic of China
- Department of Interventional Radiology, Fujian Provincial Hospital, Fuzhou, People’s Republic of China
| | - Yan-Feng Zhou
- Fujian Provincial Hospital, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, People’s Republic of China
- Department of Interventional Radiology, Fujian Provincial Hospital, Fuzhou, People’s Republic of China
| | - Jie-Wei Luo
- Fujian Provincial Hospital, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, People’s Republic of China
- Department of Traditional Chinese Medicine, Fujian provincial hospital, Fuzhou, People’s Republic of China
| | - Zhu-Ting Fang
- Fujian Provincial Hospital, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, People’s Republic of China
- Department of Interventional Radiology, Fujian Provincial Hospital, Fuzhou, People’s Republic of China
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Burrel M, Bermúdez P. Drug-Eluting Embolic TACE (DEB-TACE). TRANSARTERIAL CHEMOEMBOLIZATION (TACE) 2023:57-64. [DOI: 10.1007/978-3-031-36261-3_7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/07/2025]
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Elnekave E, Ben Ami E, Shamai S, Peretz I, Tamir S, Bruckheimer E, Stemmer A, Erinjeri J, Abu Quider A, Seidensticker M, Wildgruber M, Ricke J, Anazodo A, Fung KF, Zer A, Ash S. Selective Intra-Arterial Doxorubicin Eluting Microsphere Embolization for Desmoid Fibromatosis: A Combined Prospective and Retrospective Study. Cancers (Basel) 2022; 14:cancers14205045. [PMID: 36291829 PMCID: PMC9599870 DOI: 10.3390/cancers14205045] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2022] [Revised: 10/03/2022] [Accepted: 10/08/2022] [Indexed: 11/16/2022] Open
Abstract
Simple Summary Desmoid fibromatoses (DFs) are locally aggressive tumors composed of monoclonal fibroblasts within an abundant extracellular matrix. Systemic treatment with doxorubicin is effective, but associated with significant toxicity. We investigated arterial doxorubicin eluting embolization (DEE), an approach that delivers high doxorubicin concentrations to the tumor with limited systemic drug exposure, in 24 patients (median age, 24 years; interquartile range, 16–34). Most patients (71%) had one or more than one prior DFs treatment (surgery, systemic therapy, or both). Patients underwent a median of two (range, 1–4) DEE treatments, with a median of 49 mg (range, 8–75) doxorubicin per treatment. Efficacy outcomes were available for 23 patients. With a median follow-up of 8 months (interquartile range, 3–13), median tumor volumes decreased by 59% (interquartile range, 40–71%). Of 23 patients, 9 (39%), 12 (52%), and 2 (9%) had a partial response, stable disease, and progressive disease, respectively. The procedure was safe and well tolerated. Abstract Desmoid fibromatoses (DFs) are locally aggressive tumors composed of monoclonal fibroblasts within an abundant extracellular matrix. Systemic doxorubicin treatment is effective, but toxic. We investigated arterial doxorubicin eluting embolization (DEE), an approach characterized by high drug concentrations in the tumor alongside limited systemic drug exposure. The primary and secondary endpoints were radiological response using MRI and RECIST 1.1, respectively. The study included 24 patients (median age, 24; interquartile range, 16–34 years). Data were collected prospectively for 9 patients and retrospectively for 15 patients. The most frequent tumor locations were chest/abdomen wall and neck/shoulder/axilla (29% each). Of 24 patients, 7 (24%) were treatment naïve, and 17 (71%) had received one or two prior treatments. Patients underwent a median of two treatments (range, 1–4), with a median of 49 mg (range, 8–75) doxorubicin/treatment. Efficacy outcomes were available for 23 patients. With a median follow-up of 8 months (interquartile range, 3–13), median tumor volumes decreased by 59% (interquartile range, 40–71%) and T2 signal intensity decreased by 36% (interquartile range, 19–55%). Of 23 patients, 9 (39%), 12 (52%), and 2 (9%) had a partial response, stable disease, and progressive disease, respectively. DEE was safe and well tolerated, with one reported grade 3–4 adverse event (cord injury). In conclusion, DEE was safe and achieved rapid clinical/volumetric responses in DFs.
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Affiliation(s)
- Eldad Elnekave
- Unit of Interventional Radiology, Shaare Tzedek Medical Center, Jerusalem 9103102, Israel
- Department of Diagnostic Radiology, Rabin Medical Center, Petah Tikva 4941492, Israel
- Correspondence: ; Tel.: +972-54-9762744
| | - Eytan Ben Ami
- Sarcoma and Bone Oncology Unit, Oncology Division, Chaim Sheba Medical Center, Ramat Gan 52621, Israel
| | - Sivan Shamai
- Sarcoma and Bone Oncology Unit, Oncology Division, Tel Aviv Sourasky Medical Center, Tel Aviv 6423906, Israel
| | - Idit Peretz
- Davidoff Cancer Institute, Rabin Medical Center, Petah Tikva 4941492, Israel
| | - Shlomit Tamir
- Department of Diagnostic Radiology, Rabin Medical Center, Petah Tikva 4941492, Israel
| | - Elchanan Bruckheimer
- Section of Pediatric Cardiology, Schneider Children’s Medical Center, Petah Tikva 4941492, Israel
| | - Amos Stemmer
- Oncology Division, Chaim Sheba Medical Center, Ramat Gan 52621, Israel
| | - Joseph Erinjeri
- Interventional Radiology Service, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
| | - Abed Abu Quider
- Department of Pediatric Hematology Oncology, Saban Pediatric Medical Center, Soroka University Medical Center, Beer Sheva 84101, Israel
| | - Max Seidensticker
- Department of Radiology, University Hospital, Ludwig Maximilian University, 80539 Munich, Germany
| | - Moritz Wildgruber
- Department of Radiology, University Hospital, Ludwig Maximilian University, 80539 Munich, Germany
| | - Jens Ricke
- Department of Radiology, University Hospital, Ludwig Maximilian University, 80539 Munich, Germany
| | - Antoinette Anazodo
- Kids Cancer Centre, Sydney Children’s Hospital, Randwick, Sydney, NSW 2031, Australia
| | - Kin Fen Fung
- Department of Radiology, Hong Kong Children’s Hospital, Hong Kong 999077, China
| | - Alona Zer
- Department of Oncology, Rambam Medical Center, Haifa 3109601, Israel
| | - Shifra Ash
- Department of Pediatric Hematology-Oncology, Rambam Medical Center, Haifa 3109601, Israel
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Samuel N, Weisse C, Berent AC, Rogatko CP, Wittenburg L, Lamb K. Pharmacokinetic study comparing doxorubicin concentrations after chemoembolization or intravenous administration in dogs with naturally occurring nonresectable hepatic carcinoma. J Vet Intern Med 2022; 36:1792-1799. [PMID: 35971921 PMCID: PMC9511073 DOI: 10.1111/jvim.16520] [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: 02/02/2022] [Accepted: 08/02/2022] [Indexed: 11/28/2022] Open
Abstract
Background Chemoembolization is a viable treatment option for patients with nonresectable hepatic carcinoma (HC) and may allow delivery of chemotherapeutic drugs with decreased systemic toxicity. Hypothesis/Objective Compare the serum concentrations of doxorubicin after chemoembolization or IV administration in the same patient. We hypothesized that locoregional delivery may result in increased tumor chemotherapeutic drug concentrations, reflected by decreased measurable serum drug concentrations. Adverse hematological events were hypothesized to be decreased after locoregional delivery. Animals Seventeen client‐owned dogs with incompletely resectable HC. Methods Prospective, single‐arm clinical trial. Drug‐eluting bead transarterial chemoembolization was performed to varying levels of blood flow stasis (NO STASIS, STASIS). Intravenous doxorubicin (IVC) subsequently was administered in selected patients. Systemic exposure was quantified by area under the serum doxorubicin concentration time curve (AUC), maximum serum doxorubicin concentration (Cmax), and time doxorubicin was last above the limit of quantitation (Tlast). Nadir test results after treatments were used to evaluate adverse hematological events. Results Thirteen NO STASIS treatments, 15 STASIS treatments, and 9 IVC treatments were performed. Maximum serum doxorubicin concentration, AUC, and Tlast were significantly lower when comparing NO STASIS or STASIS to IVC treatments. Of the patients with nadir results available, no adverse hematological events were observed after NO STASIS or STASIS treatments. Two patients developed adverse hematological events after IVC treatment. Conclusions/Clinical Relevance Drug‐eluting bead transarterial chemoembolization offers a viable treatment option for patients with incompletely resectable HC with the potential for increased local tumor doxorubicin concentrations, decreased systemic chemotherapeutic exposure, and fewer adverse hematological events.
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Affiliation(s)
- Nina Samuel
- The Schwarzman Animal Medical Center, New York City, New York, USA.,University of California Davis Veterinary Medical Teaching Hospital, Davis, California, USA
| | - Chick Weisse
- The Schwarzman Animal Medical Center, New York City, New York, USA
| | - Allyson C Berent
- The Schwarzman Animal Medical Center, New York City, New York, USA
| | - Cléo P Rogatko
- The Schwarzman Animal Medical Center, New York City, New York, USA.,Veterinary Surgical Centers, Vienna, Virginia, USA
| | - Luke Wittenburg
- University of California Davis Veterinary Medical Teaching Hospital, Davis, California, USA
| | - Kenneth Lamb
- Lamb Statistical Consulting LLC, West Saint Paul, Minnesota, USA
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Su TH, Hsu SJ, Kao JH. Paradigm shift in the treatment options of hepatocellular carcinoma. Liver Int 2022; 42:2067-2079. [PMID: 34515412 DOI: 10.1111/liv.15052] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2021] [Revised: 08/31/2021] [Accepted: 09/03/2021] [Indexed: 01/27/2023]
Abstract
Hepatocellular carcinoma (HCC) is prevalent worldwide with suboptimal therapeutic outcomes. The advancement of therapeutic options and the development of new systemic therapies expand the armamentarium to tackle HCC. Treatment options should be provided based on the hierarchy of efficacy in a multidisciplinary perspective, instead of the traditional stage-guided scheme. In advanced HCC, lenvatinib has a comparable efficacy as sorafenib for the first-line therapy of HCC; while regorafenib, cabozantinib, and ramucirumab have been approved as second-line therapy after the failure of sorafenib. Immune checkpoint inhibitor therapy prolongs response rate and survival and enables long-term cure. Atezolizumab plus bevacizumab is superior to sorafenib as the first-line therapy for advanced HCC. Several emerging regimens by the combination of various systemic therapies are currently under clinical trials. Systemic therapy may be used in the neoadjuvant, adjuvant or even as initial therapy for intermediate-stage HCC. The paradigm shift of HCC treatment will improve patient outcomes.
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Affiliation(s)
- Tung-Hung Su
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Shih-Jer Hsu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan.,Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital Yun-Lin Branch, Yunlin, Taiwan
| | - Jia-Horng Kao
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan.,Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.,Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan
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11
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Mikhail AS, Pritchard WF, Negussie AH, Inkiyad G, Long DJ, Mauda-Havakuk M, Wakim PG, van der Sterren W, Levy EB, Lewis AL, Karanian JW, Wood BJ. Cone-Beam Computed Tomography-Based Spatial Prediction of Drug Dose After Transarterial Chemoembolization Using Radiopaque Drug-Eluting Beads in Woodchuck Hepatocellular Carcinoma. Invest Radiol 2022; 57:495-501. [PMID: 35239613 PMCID: PMC11493181 DOI: 10.1097/rli.0000000000000864] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
OBJECTIVES The aims of this study were to develop a model to estimate drug dose delivered to tumors after transarterial chemoembolization (TACE) with radiopaque drug-eluting beads (DEBs) based on DEB density on cone-beam computed tomography (CT) and to evaluate drug penetration into tissue in a woodchuck hepatoma model. MATERIALS AND METHODS Transarterial chemoembolization was performed in woodchucks with hepatocellular carcinoma (N = 5) using DEBs (70-150 μm, LC Bead LUMI) loaded with doxorubicin. Livers were resected 45 minutes after embolization, immediately frozen, and cut using liver-specific, 3D-printed sectioning molds. Doxorubicin levels in tumor specimens were measured by high-performance liquid chromatography and correlated with DEB iodine content that was measured using prototype cone-beam CT-based embolization treatment planning software. Doxorubicin penetration into tissue surrounding DEBs was assessed by fluorescence microscopy of tumor sections. Fluorescence intensity was converted into doxorubicin concentration using calibration standards. Intensity-thresholded color heatmaps were generated representing extravascular drug penetration. RESULTS Consistent segmentation of DEBs on cone-beam CT was achieved using a semiautomated intensity thresholding method. A positive linear correlation (0.96) was found between DEB iodine content measured on cone-beam CT and the amount of doxorubicin measured in tumor specimens. Prediction of doxorubicin levels in tumor sections that were not included in model development was accurate, with a root-mean-square error of 0.08 mg of doxorubicin. Tumor penetration of eluted doxorubicin resulted in concentration gradients where drug content decreased with increasing distance from blood vessels containing DEBs. Drug penetration was greater for blood vessels containing DEB clusters compared with single DEB, with higher doxorubicin concentrations extending further away from the vessels. CONCLUSIONS Estimation of drug dose delivered during transarterial chemoembolization in a woodchuck hepatocellular carcinoma model was possible using DEB radiopacity on cone-beam CT as a surrogate marker. Doxorubicin penetration was greatest adjacent to vessels containing DEB clusters compared with single DEB. Intraprocedural estimation of the spatial distribution of drug dose within the tumor could enable real-time adjustments to DEB delivery, to maximize treatment coverage or identify regions of tumor at risk for undertreatment.
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Affiliation(s)
- Andrew S Mikhail
- From the Center for Interventional Oncology, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD
| | - William F Pritchard
- From the Center for Interventional Oncology, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD
| | - Ayele H Negussie
- From the Center for Interventional Oncology, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD
| | - Gazi Inkiyad
- Biomedical Engineering Summer Internship Program, Center for Interventional Oncology, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD
| | - Dilara J Long
- From the Center for Interventional Oncology, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD
| | | | - Paul G Wakim
- Biostatistics and Clinical Epidemiology Service, Clinical Center, National Institutes of Health, Bethesda, MD
| | | | - Elliot B Levy
- From the Center for Interventional Oncology, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD
| | - Andrew L Lewis
- Owen Mumford Ltd, Woodstock, Oxfordshire, United Kingdom
| | - John W Karanian
- From the Center for Interventional Oncology, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD
| | - Bradford J Wood
- From the Center for Interventional Oncology, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD
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12
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Systematic Review and Pharmacokinetic Meta-analysis of Doxorubicin Exposure in Transcatheter Arterial Chemoembolization and Doxorubicin-Eluted Beads Chemoembolization for Treatment of Unresectable Hepatocellular Carcinoma. Eur J Drug Metab Pharmacokinet 2022; 47:449-466. [PMID: 35543895 DOI: 10.1007/s13318-022-00762-z] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/14/2022] [Indexed: 11/03/2022]
Abstract
BACKGROUND Almost 15 years after the introduction of transarterial chemoembolization (TACE) with drug-eluting beads (DEB-TACE) for hepatocellular carcinoma (HCC) therapy, the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) for doxorubicin have still not been systematically reviewed or meta-analyzed. OBJECTIVE To conduct a systematic review and meta-analysis of available data and establish a reference range for Cmax and AUC of doxorubicin DEB-TACE and TACE, as well as explore the potential influence of microspheres' size and type on these parameters. METHODS PubMed, EMBASE, and Web of Science were searched from August 1992 through December 2021. Studies measuring exposure parameters among HCC patients treated with doxorubicin DEB-TACE without restriction on language were included. Two independent reviewers extracted and unified data sets for pooled estimate analysis. The quality of the evidence was assessed via the Grading of Recommendations Assessment, Development and Evaluation framework. The ClinPK Statement checklist and Newcastle-Ottawa Scale (NOS) were used to determine the quality of studies. RESULTS Out of 666 studies, 246 full-text were reviewed, and 8 studies entered the meta-analysis (120 patients). Cmax and AUC of doxorubicin were 7.52-fold (95% CI 7.65 to 7.42-fold; P < 0.0001) and 1.91-fold (95% CI 1.95 to 1.88-fold; P = 0.0001) lower with DEB-TACE compared to TACE. Significant reduction in pooled standardized mean difference (SMD) of Cmax and AUC was observed with DEB-TACE versus TACE in direct comparison analysis (- 2.93; 95% CI - 3.60 to - 2.26, P < 0.00001, and - 1.73 95% CI - 2.55 to - 0.91, P < 0.0001, respectively). Moreover, in DEB-TACE stratification analysis, small microspheres revealed higher Cmax, AUC and tumor response rate as well as lower complication rate. LIMITATION The heterogeneity could not be completely addressed through sensitivity and stratification analysis. CONCLUSION This meta-analysis provides exposure parameters of doxorubicin and justifies the advantage of DEB-TACE over TACE in terms of safety for patients with unresectable HCC. This study showed a marked association between the size of microsphere and exposure parameters of doxorubicin supporting the preference for small microspheres in DEB-TACE. The moderate and low quality of evidence is assigned to the Cmax and AUC, respectively.
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13
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Deng J, Wen F. Transarterial Chemoembolization Combined With Tyrosine Kinase Inhibitors for Intermediate-Stage Hepatocellular Carcinoma, What Else Can We Do? Front Oncol 2022; 12:824799. [PMID: 35425716 PMCID: PMC9001928 DOI: 10.3389/fonc.2022.824799] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2021] [Accepted: 03/01/2022] [Indexed: 12/12/2022] Open
Abstract
Transarterial chemoembolization (TACE) has been considered the standard treatment for intermediate-stage hepatocellular carcinoma (HCC). However, intermediate‐stage HCC is highly heterogeneous with a broad population with varying tumour burdens, liver function. This suggests that TACE monotherapy treatment might not be suitable for all patients with intermediate‐stage HCC. The administration of tyrosine kinase inhibitors (TKIs) has become an important treatment option for improving the prognosis of patients with advanced HCC. Over the years, several trials have been conducted to explore the effects of TACE combined with TKIs for intermediate-stage HCC. However, the clinical efficacy is still controversial, and its potential clinical utility needs to be confirmed. This review will focus on the recent progress of TACE combined TKIs for intermediate-stage HCC.
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Affiliation(s)
- Jun Deng
- Department of Radiology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Feng Wen
- Department of Radiology, Shengjing Hospital of China Medical University, Shenyang, China
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14
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Malagari K, Denys A, Burrel M, Reig M, Brunet M, Duran R, Kiakidis T, Moschouris H, Sanduzzi-Zamparell M, Bruix J. POLYETHYLENE-GLYCOL DRUG-ELUTING EMBOLIC MICROSPHERES LOADED WITH DOXORUBICIN FOR THE TREATMENT OF HEPATOCELLULAR CARCINOMA: FEASIBILITY, SAFETY AND PHARMACOKINETIC STUDY. J Vasc Interv Radiol 2022; 33:752-761. [PMID: 35351630 DOI: 10.1016/j.jvir.2021.11.019] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2021] [Revised: 11/01/2021] [Accepted: 11/24/2021] [Indexed: 11/30/2022] Open
Abstract
PURPOSE Polyethylene-glycol drug-eluting microspheres (PEG-DEM) can be loaded to elute doxorubicin. This study evaluated the pharmacokinetic profile and safety of PEG-DEMs in the treatment of patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS This prospective, multicentre, dose escalation study enrolled 25 patients (68% men) with early or intermediate stage HCC and performance status of 0. Patients in cohort I were assigned to receive target doxorubicin doses of 75, 100, or 150 mg. Analyses were performed based on the specific dose of doxorubicin that patients received, since some patients received less than the assigned dose. Patients in cohort II received the maximum safe tested dose. Adverse events (AEs) were classified according to Common Terminology Criteria for Adverse Events v.4.03. Tumor response was evaluated every 3 months according to European Association for the Study of the Liver criteria and modified Response Evaluation Criteria in Solid Tumors. RESULTS The maximum tested safe dose of doxorubicin was 150 mg. For the groups that received ≤75, 75-100, and 101-150 mg, the Cmax were 286.7±220.1, 157.1±94.6 and 245.4±142.8 ng/mL, respectively; AUC0-24h were 421.7±221.2, 288.1±100.9 and 608.3±319.3 (ng x hours)/mL respectively, with almost complete clearance at 24 hours. There were no deaths within 30 days. The best objective response rate was 81% and the disease control rate was 91%. Median overall survival was 27.2 (95% CI, 17.5-n.e) months; median progression free survival was 9.8 (95% CI, 5.5-n.e.) months. CONCLUSION PEG-DEMs demonstrated a favorable safety profile with low systemic concentration of doxorubicin, and promising efficacy.
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Affiliation(s)
- Katerina Malagari
- National and Kapodistrian University of Athens, Medical School, Evgenidion Hospital, Greece
| | - Alban Denys
- Department of Diagnostic and Interventional Radiology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
| | - Martha Burrel
- BCLC group. Liver Unit, Hospital Clínic-IDIBAPS, CIBEREHD, University of Barcelona, Spain
| | - Maria Reig
- BCLC group. Liver Unit, Hospital Clínic-IDIBAPS, CIBEREHD, University of Barcelona, Spain
| | - Mercé Brunet
- BCLC group. Liver Unit, Hospital Clínic-IDIBAPS, CIBEREHD, University of Barcelona, Spain; Laboratory of Pharmacology & Toxicology, Hospital Clínic of Barcelona, Spain
| | - Rafael Duran
- Department of Diagnostic and Interventional Radiology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
| | - Theodoros Kiakidis
- National and Kapodistrian University of Athens, Medical School, Evgenidion Hospital, Greece
| | - Hippokratis Moschouris
- National and Kapodistrian University of Athens, Medical School, Evgenidion Hospital, Greece
| | | | - Jordi Bruix
- BCLC group. Liver Unit, Hospital Clínic-IDIBAPS, CIBEREHD, University of Barcelona, Spain
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15
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Mikhail AS, Mauda-Havakuk M, Negussie AH, Hong N, Hawken NM, Carlson CJ, Owen JW, Franco-Mahecha O, Wakim PG, Lewis AL, Pritchard WF, Karanian JW, Wood BJ. Evaluation of immune-modulating drugs for use in drug-eluting microsphere transarterial embolization. Int J Pharm 2022; 616:121466. [PMID: 35065205 PMCID: PMC9139086 DOI: 10.1016/j.ijpharm.2022.121466] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2020] [Revised: 01/06/2022] [Accepted: 01/07/2022] [Indexed: 12/30/2022]
Abstract
Cancer immunotherapy has yet to reach its full potential due in part to limited response rates and side effects inherent to systemic delivery of immune-modulating drugs. Local administration of immunotherapy using drug-eluting embolic (DEE) microspheres as drug delivery vehicles for direct infusion into tumor-feeding arteries might increase and prolong tumor drug concentrations and reduce systemic drug exposure, potentially improving the risk-to-benefit ratio of these agents. The purpose of this study was to evaluate the ability of four immune modulators affecting two different immune pathways to potentiate replication of immune cells from a woodchuck model of hepatocellular carcinoma. DSR 6434, a Toll-like receptor agonist, and BMS-202, a PD-L1 checkpoint inhibitor, induced immune cell replication and were successfully loaded into radiopaque DEE microspheres in high concentrations. Release of DSR 6434 from the DEE microspheres was rapid (t99% = 0.4 h) upon submersion in a physiologic saline solution while BMS-202 demonstrated a more sustained release profile (t99% = 17.9 h). These findings demonstrate the feasibility of controlled delivery of immune-modulating drugs via a local DEE microsphere delivery paradigm.
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Affiliation(s)
- Andrew S Mikhail
- Center for Interventional Oncology, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD, USA.
| | - Michal Mauda-Havakuk
- Center for Interventional Oncology, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD, USA
| | - Ayele H Negussie
- Center for Interventional Oncology, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD, USA
| | - Natalie Hong
- Center for Interventional Oncology, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD, USA
| | - Natalie M Hawken
- Center for Interventional Oncology, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD, USA
| | - Camella J Carlson
- Center for Interventional Oncology, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD, USA
| | - Joshua W Owen
- Center for Interventional Oncology, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD, USA
| | - Olga Franco-Mahecha
- Center for Interventional Oncology, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD, USA
| | - Paul G Wakim
- Biostatistics and Clinical Epidemiology Service, Clinical Center, National Institutes of Health, Bethesda, MD, USA
| | - Andrew L Lewis
- Biocompatibles UK Ltd (a BTG International Group Company), Lakeview, Riverside Way, Watchmoor Park, Camberley, Surrey, UK
| | - William F Pritchard
- Center for Interventional Oncology, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD, USA
| | - John W Karanian
- Center for Interventional Oncology, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD, USA
| | - Bradford J Wood
- Center for Interventional Oncology, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD, USA
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16
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Huang W, Gong J, Wang Q, Wang Z, Liu Q, Liu J, Gu J, Ding X, Wu Z. Evaluation of D-TACE combined with endovascular brachytherapy for HCC with MPVTT. Front Oncol 2022; 12:973357. [PMID: 36059634 PMCID: PMC9434401 DOI: 10.3389/fonc.2022.973357] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2022] [Accepted: 07/18/2022] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) patients with main portal vein tumor thrombus (MPVTT) may be able to have TACE through stent implantation into the portal vein with thrombosis to recover portal blood flow. PURPOSE The goal of this study was to compare clinical results of conventional transcatheter arterial chemoembolization (C-TACE) and doxorubicin-eluting bead transcatheter arterial chemoembolization (D-TACE) combined with endovascular brachytherapy in HCC patients with MPVTT. METHODS This study was a retrospective controlled study with follow-up dates spanning from Mar 2015 to Feb 2020. Patients with both HCC and MPVTT were divided into two groups. Portal vein stents with iodine-125 seed strands were implanted first; then, C-TACE or D-TACE was administered to all patients. Objective response rates were assessed. RESULTS A total of 26 patients were enrolled, with 13 in each group. During follow-up, the portal stent patency times were 112.3 ± 98.2 days in the C-TACE group and 101.7 ± 90.4 days in the D-TACE group. The time to disease progression was 42 days in the C-TACE group and 120 days in the D-TACE group (p=0.03). The overall survival time from the first intervention procedure was 216 days in the C-TACE group and 239 days in the D-TACE group (p=0.047). The D-TACE group was superior to the C-TACE group in terms of progression-free survival (PFS) and overall survival (OS) times. CONCLUSION Endovascular implantation of brachytherapy combined with TACE is safe and effective in HCC patients with MPVTT. This combination therapy may be helpful for survival benefits to patients with stage BCLC-C HCC.
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Affiliation(s)
- Wei Huang
- Department of Interventional Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Ju Gong
- Department of Interventional Radiology, Ruijin Hospital Luwan Branch, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Qingbing Wang
- Department of Interventional Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Ziyin Wang
- Department of Interventional Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Qin Liu
- Department of Interventional Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jingjing Liu
- Department of Interventional Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Junwei Gu
- Department of Interventional Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xiaoyi Ding
- Department of Interventional Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- *Correspondence: Zhiyuan Wu, ; Xiaoyi Ding,
| | - Zhiyuan Wu
- Department of Interventional Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Department of Interventional Radiology, Ruijin Hospital Luwan Branch, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- *Correspondence: Zhiyuan Wu, ; Xiaoyi Ding,
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Renzulli M, Peta G, Vasuri F, Marasco G, Caretti D, Bartalena L, Spinelli D, Giampalma E, D'Errico A, Golfieri R. Standardization of conventional chemoembolization for hepatocellular carcinoma. Ann Hepatol 2021; 22:100278. [PMID: 33129978 DOI: 10.1016/j.aohep.2020.10.006] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2020] [Accepted: 10/19/2020] [Indexed: 02/04/2023]
Abstract
INTRODUCTION AND OBJECTIVES Conventional transarterial chemoembolization (cTACE) has several limitations due to the lack of standardization. The aim of this study was to evaluate the chemical and physical characteristics and behaviors over time of emulsions for cTACE and to assess intra- and inter-operator variabilities in the preparation processes. MATERIALS AND METHODS This in vitro study involved evaluation of emulsions for cTACE prepared using two methods: water-in-oil (WiO) and chemotherapeutic-in-oil (CiO). Three emulsions were prepared with each method and obtained after 20, 50, and 100 pumping exchanges. A drop from each final mixture was analyzed via light microscopy (time 1) and after 5, 10, 15, and 20min since the end of preparation. After 20min, all preparations were re-mixed and new drops were re-evaluated. The intra- and inter-operator variabilities were analyzed. RESULTS The mean droplet diameter decreased non-significantly when the number of pumping exchanges increased and increased significantly over time for both WiO and CiO. The droplets returned to their initial diameters after re-mixing. There were no significant differences in the intra- and inter-operator variabilities (P>0.01). CONCLUSIONS Any interventional radiologist, regardless of their experience, may prepare these emulsions. These data may represent a set of instructions to standardize cTACE.
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Affiliation(s)
- Matteo Renzulli
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, Bologna, Italy.
| | - Giuliano Peta
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, Bologna, Italy
| | - Francesco Vasuri
- Pathology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, Bologna, Italy
| | - Giovanni Marasco
- Gastroenterology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, Bologna, Italy
| | - Daniele Caretti
- "Toso Montanari" Industrial Chemistry Department, University of Bologna, Bologna, Italy
| | - Laura Bartalena
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, Bologna, Italy
| | - Daniele Spinelli
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, Bologna, Italy
| | | | - Antonietta D'Errico
- Pathology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, Bologna, Italy
| | - Rita Golfieri
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, Bologna, Italy
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18
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Liver MRI and clinical findings to predict response after drug eluting bead transarterial chemoembolization in hepatocellular carcinoma. Sci Rep 2021; 11:24076. [PMID: 34911966 PMCID: PMC8674226 DOI: 10.1038/s41598-021-01839-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2021] [Accepted: 11/01/2021] [Indexed: 12/24/2022] Open
Abstract
To identify the gadoxetic acid (GA)-enhanced magnetic resonance imaging (MRI) and laboratory findings that enable prediction of treatment response and disease-free survival (DFS) after the first session of drug eluting bead transarterial chemoembolization (DEB-TACE) in patients with hepatocellular carcinoma (HCC). A total of 55 patients who underwent GA-enhanced MRI and DEB-TACE from January 2014 to December 2018 were included. All MRI features were reviewed by two radiologists. Treatment response was evaluated according to the modified Response Evaluation Criteria in Solid Tumors. Univariate and multivariate logistic regression analyses were used to determine predictive factors of treatment response and DFS, respectively. A total of 27 patients (49.1%) achieved complete response (CR) after one session of treatment. There were no significant differences between the two groups in terms of clinical and laboratory characteristics. Heterogeneous signal intensity in the hepatobiliary phase (HBP) was the only independent predictor of non-CR (odds ratio, 4.807; p = 0.048). Recurrent HCC was detected in 19 patients (70.4%) after CR. In the multivariate analysis, elevated serum alpha-fetoprotein (AFP) level (≥ 30 ng/mL) was the only significant parameter associated with DFS (hazard ratio, 2.916; p = 0.040). This preliminary study demonstrated that heterogeneous signal intensity in the HBP and high serum AFP were useful predictive factors for poor treatment response and short DFS after DEB-TACE, respectively.
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19
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Long Term Survival Analysis in a Cohort of 125 Patients with Hepatocellular Carcinoma Treated with Transarterial Chemoembolization Using Small Drug Eluting Beads. Cardiovasc Intervent Radiol 2021; 45:54-61. [PMID: 34820694 DOI: 10.1007/s00270-021-02991-2] [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: 04/09/2021] [Accepted: 10/11/2021] [Indexed: 02/07/2023]
Abstract
PURPOSE Different types of drug-eluting beads have been proposed for hepatocellular carcinoma (HCC) treatment, but long-term results are not well known. We report safety, efficacy and long-term overall survival of HCC patients not amenable of curative therapies treated with transcatheter arterial chemoembolization (TACE) using drug-eluting beads sized 70-150 micron. MATERIALS AND METHODS This single-center retrospective study included 125 patients with Barcelona Clinic Liver Cancer stage A (80), B (45) and compensated cirrhosis. TACE was executed injecting drug-elutings microparticles loaded with 75 mg of Doxorubicine and was repeated in patients with partial response or stable disease after one month. Adverse events, response according to modified Response Evaluation Criteria in Solid Tumors and overall survival were assessed. RESULTS Chemoembolization with 70-150 micron beads revealed an objective response rate of 88% according to mRECIST criteria and complete response was 60%. After a median follow-up of 53.3 months, overall survival was 36.6 months. Data were censored at the date of liver transplantation in 35 patients. 33 on 125 patients (26,4%) experienced at least one adverse event. We recorded a total of 102 adverse events and 18 were of a high grade (G3-G4). 30 day mortality was 0%. CONCLUSION Chemoembolization with very small particles (70-150 µm) is an effective and safe treatment in unresectable HCC both as a primary therapy or as bridge to transplantation.
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20
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Makary MS, Ramsell S, Miller E, Beal EW, Dowell JD. Hepatocellular carcinoma locoregional therapies: Outcomes and future horizons. World J Gastroenterol 2021; 27:7462-7479. [PMID: 34887643 PMCID: PMC8613749 DOI: 10.3748/wjg.v27.i43.7462] [Citation(s) in RCA: 40] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2021] [Revised: 07/09/2021] [Accepted: 10/27/2021] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common primary cancer of the liver and has an overall five-year survival rate of less than twenty percent. For patients with unresectable disease, evolving liver-directed locoregional therapies provide efficacious treatment across the spectrum of disease stages and via a variety of catheter-directed and percutaneous techniques. Goals of locoregional therapies in HCC may include curative intent in early-stage disease, bridging or downstaging to surgical resection or transplantation for early or intermediate-stage disease, and local disease control and palliation in advanced-stage disease. This review explores the outcomes of chemoembolization, bland embolization, radioembolization, and percutaneous ablative therapies. Attention is also given to prognostic factors related to each of the respective techniques, as well as future directions of locoregional therapies for HCC.
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Affiliation(s)
- Mina S Makary
- Department of Radiology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
| | - Stuart Ramsell
- Department of Radiology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
| | - Eric Miller
- Department of Radiation Oncology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
| | - Eliza W Beal
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
| | - Joshua D Dowell
- Department of Radiology, Northwest Radiology, St. Vincent Health, Indianapolis, IN 46260, United States
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21
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Lee M, Chung JW, Lee KH, Won JY, Chun HJ, Lee HC, Kim JH, Lee IJ, Hur S, Kim HC, Kim YJ, Kim GM, Joo SM, Oh JS. Prospective Multi-Center Korean Registry of Transcatheter Arterial Chemoembolization with Drug-Eluting Embolics for Nodular Hepatocellular Carcinoma: A Two-Year Outcome Analysis. Korean J Radiol 2021; 22:1658-1670. [PMID: 34132079 PMCID: PMC8484153 DOI: 10.3348/kjr.2020.1117] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2019] [Revised: 01/11/2021] [Accepted: 02/22/2021] [Indexed: 11/25/2022] Open
Abstract
OBJECTIVE To assess the two-year treatment outcomes of chemoembolization with drug-eluting embolics (DEE) for nodular hepatocellular carcinoma (HCC). MATERIALS AND METHODS This study was a prospective, multicenter, registry-based, single-arm trial conducted at five university hospitals in Korea. Patients were recruited between May 2011 and April 2013, with a target population of 200. A DC Bead loaded with doxorubicin was used as the DEE agent. Patients were followed up for two years. Per-patient and per-lesion tumor response analysis, per-patient overall survival (OS) and progression-free survival (PFS) analysis, and per-lesion tumor control analysis were performed. RESULTS The final study population included 152 patients, with 207 target lesions for the per-lesion analysis. At one-month, six-month, one-year, and two-year per-patient assessments, complete response (CR) rates were 40.1%, 43.0%, 33.3%, and 19.6%, respectively. The objective response (OR) rates were 91.4%, 55.4%, 35.1%, and 19.6%, respectively. The cumulative two-year OS rate was 79.7%. The cumulative two-year PFS rate was 22.4% and the median survival was 9.3 months. In multivariable analysis, the Child-Pugh score (p = 0.019) was an independent predictor of OS, and tumor multiplicity (p < 0.001), tumor size (p = 0.020), and Child-Pugh score (p = 0.006) were independent predictors of PFS. In per-lesion analysis, one-month, six-month, one-year and two-year CR rates were 57.5%, 58.5%, 45.2%, and 33.3%, respectively, and the OR rates were 84.1%, 65.2%, 46.6%, and 33.3%, respectively. The cumulative two-year per-lesion tumor control rate was 36.2%, and the median time was 14.1 months. The Child-Pugh score (p < 0.001) was the only independent predictor of tumor control. Serious adverse events were reported in 11 patients (7.2%). CONCLUSION DEE chemoembolization for nodular HCCs in the Korean population showed acceptable survival, tumor response, and safety profiles after a two-year follow-up. Good liver function (Child-Pugh score A5) was a key predictor of per-patient OS, PFS, and per-lesion tumor control.
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Affiliation(s)
- Myungsu Lee
- Department of Radiology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Jin Wook Chung
- Department of Radiology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
- Institute of Radiation Medicine, Seoul National University Medical Research Center, Seoul, Korea.
| | - Kwang-Hun Lee
- Department of Radiology, Gangnam Severance Hospital, Research Institute of Radiological Science, Yonsei University College of Medicine, Seoul, Korea
| | - Jong Yun Won
- Department of Radiology, Severance Hospital, Research Institute of Radiological Science, Yonsei University College of Medicine, Seoul, Korea
| | - Ho Jong Chun
- Department of Radiology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Han Chu Lee
- Department of Gastroenterology, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jin Hyoung Kim
- Department of Radiology and Research Institute of Radiology, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - In Joon Lee
- Department of Radiology, National Cancer Center, Goyang, Korea
| | - Saebeom Hur
- Department of Radiology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Hyo-Cheol Kim
- Department of Radiology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Yoon Jun Kim
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Gyoung Min Kim
- Department of Radiology, Severance Hospital, Research Institute of Radiological Science, Yonsei University College of Medicine, Seoul, Korea
| | - Seung-Moon Joo
- Department of Radiology, Gangnam Severance Hospital, Research Institute of Radiological Science, Yonsei University College of Medicine, Seoul, Korea
| | - Jung Suk Oh
- Department of Radiology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
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Lin JN, Su JH, Fu TY, Shih SL. Transarterial chemoembolization as a part of multi-modality treatment with drug-eluting beads for locally advanced breast cancer: A case report. Radiol Case Rep 2021; 16:3383-3388. [PMID: 34504630 PMCID: PMC8411206 DOI: 10.1016/j.radcr.2021.08.007] [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: 07/14/2021] [Revised: 08/03/2021] [Accepted: 08/03/2021] [Indexed: 11/28/2022] Open
Abstract
Locally advanced breast cancer (LABC) is generally treated with combined-modality therapy including systemic chemotherapy, surgery, radiotherapy, and targeted therapy due to its nature of rapid onset of metastatic disease and poor prognosis. In this case report, we present a 61-year-old female who suffered from a huge protruding breast mass (16.2cm) with superficial ulcerative wound noted for three months. LABC was diagnosed via core needle biopsy and PET-CT examination. Initially, she received combined systemic chemotherapy, hormone therapy and radiation therapy; however, severe necrosis caused rupture in part of the breast mass and extensive wound discharge resulting in difficulty in wound care and prolonged disease course. Trans-arterial chemoembolization with drug-eluting beads (DEB-TACE) was applied as a part of combined-modality therapy for shortening the time before surgery. HepaSphere (as one of the DEB) loaded with high dose of epirubicin (total 80mg) was infused intra-arterially due to the nature of slow-releasing effect and longer duration of ischemic effect. Shortly after DEB-TACE following in about 40 days, surgery was smoothly performed. Post-operative adjuvant target therapy and adjuvant chemotherapy with taxane were administered. There was no evidence of local recurrence or distal metastases after 9 months of follow-up. It is suggested that performing DEB-TACE prior to surgery becomes a part of multimodality treatment of LABC to achieve better local control, better wound care and shortened treatment course.
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Affiliation(s)
- Jau-Nan Lin
- Department of Radiology, Yuan's General Hospital, Taiwan
| | - Jung-Hui Su
- Department of Nurse Practitioner, Yuan's General Hospital, Taiwan
| | - Ting-Ying Fu
- Department of Pathology, Yuan's General Hospital, Taiwan
| | - Shen-Liang Shih
- Division of Breast Surgery, department of Surgery, Kaohsiung Medical University Chung-Ho Memorial Hospital, Taiwan
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23
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Kim TH, Kim NH, Kim JD, Kim YN, Kim YJ, Kim EJ, Yoo KD, Ryu CH, Song HH, Kim H. Transarterial chemoembolization using drug-eluting bead compared with radiofrequency ablation for treatment of single small hepatocellular carcinoma: a pilot non-randomized trial. JOURNAL OF LIVER CANCER 2021; 21:146-154. [PMID: 37383084 PMCID: PMC10035690 DOI: 10.17998/jlc.2021.05.20] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/26/2021] [Revised: 05/20/2021] [Accepted: 05/27/2021] [Indexed: 06/30/2023]
Abstract
Background/Aims Surgical resection, transplantation, and radiofrequency ablation (RFA) are generally accepted as amenable treatments for small hepatocellular carcinoma (HCC). Recently drug-eluting beads (DEB) which had several treatment advantages were introduced for transarterial chemoembolization (TACE). The aim of this study was to evaluate feasibility and safety of DEB-TACE compared with RFA for the treatment of single small HCC. Methods In this pilot non-randomized trial, we assessed retrospective data of 40 patients who underwent DEB-TACE (n=21) or RFA (n=19) for single small (≤3 centimeter in greatest dimension) HCC. The primary outcomes were tumor response and time to recurrence. The secondary outcome was treatment-related complications. Results Complete response rate to DEB-TACE and RFA after first follow-up assessment was 90.5% and 94.7%, respectively (P=1.000). During mean follow-up of 87.6 months (95% confidence interval, 74.4-102), 7 patients experienced local recurrence. The 6- and 12-month cumulative local recurrence rate was 5.0% and 21.8% in DEB-TACE vs. 11.1% and 17.0% in RFA group (P=0.877). A total 14 distant intrahepatic recurrences were developed and 12- and 24-month cumulative distant intrahepatic recurrence rate was 20.6% and 42.7% in DEB-TACE vs. 17.2% and 36.3% in RFA group (P=0.844). Two patients experienced gangrenous cholecystitis after DEB-TACE requiring cholecystectomy as treatment-related adverse event. Conclusions Tumor response and recurrence rate after single session of DEB-TACE or RFA were similar. DEB-TACE could be applied selectively in patients with a single small HCC if the other therapeutic modality is unfeasible.
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Affiliation(s)
- Tae Hoon Kim
- Department of Internal Medicine, Cheju Halla General Hospital, Jeju, Korea
| | - Na Hye Kim
- Yonsei University College of Medicine, Seoul, Korea
| | - Jin Dong Kim
- Department of Internal Medicine, Cheju Halla General Hospital, Jeju, Korea
| | - Young Nam Kim
- Department of Internal Medicine, Cheju Halla General Hospital, Jeju, Korea
| | - Yu Jin Kim
- Department of Internal Medicine, Cheju Halla General Hospital, Jeju, Korea
| | - Eun Jung Kim
- Department of Internal Medicine, Cheju Halla General Hospital, Jeju, Korea
| | - Ki Deok Yoo
- Department of Internal Medicine, Cheju Halla General Hospital, Jeju, Korea
| | - Choong Heon Ryu
- Department of Internal Medicine, Cheju Halla General Hospital, Jeju, Korea
| | - Ha Hun Song
- Department of Radiology, Cheju Halla General Hospital, Jeju, Korea
| | - Hyun Kim
- Department of Radiology, Cheju Halla General Hospital, Jeju, Korea
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Liu L, Liang X, Xu X, Zhang X, Wen J, Chen K, Su X, Teng Z, Lu G, Xu J. Magnetic mesoporous embolic microspheres in transcatheter arterial chemoembolization for liver cancer. Acta Biomater 2021; 130:374-384. [PMID: 34082098 DOI: 10.1016/j.actbio.2021.05.031] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2020] [Revised: 05/15/2021] [Accepted: 05/20/2021] [Indexed: 02/07/2023]
Abstract
Transcatheter arterial chemoembolization (TACE) is the main treatment for liver cancer. Although many embolic agents have been exploited in TACE, embolic agents combining embolization, drug loading, and imaging properties have not yet been constructed. Herein, we report a new magnetic mesoporous embolic microsphere that can simultaneously be loaded with doxorubicin (Dox), block vessels, and be observed by magnetic resonance imaging (MRI). The microspheres were prepared by decorating magnetic polystyrene/Fe3O4 particles with mesoporous organosilica microparticles (denoted as PS/Fe3O4@MONs). The PS/Fe3O4@MONs were uniformly spherical and large (50 µm), with a high specific surface area, uniform mesopores, and a Dox loading capacity of 460.8 µg mg-1. Dox-loaded PS/Fe3O4@MONs (PS/Fe3O4@MON@Dox) effectively inhibited liver cancer cell growth. A VX2 rabbit liver tumor model was constructed to study the efficacy of TACE with PS/Fe3O4@MON@Dox. In vivo, PS/Fe3O4@MON@Dox could be smoothly delivered through an arterial catheter to achieve chemoembolization. Moreover, PS/Fe3O4@MON@Dox and residual tumor parenchyma could be distinguished on MRI, which is of great significance for evaluating the efficacy of TACE. Histopathology showed that PS/Fe3O4@MON@Dox could be deposited in the tumor vessels, completely blocking the blood supply. Overall, PS/Fe3O4@MON@Dox showed good drug loading, embolization and imaging performance as well as potential for use in TACE. STATEMENT OF SIGNIFICANCE: Transcatheter arterial chemoembolization (TACE) is the main treatment for liver cancer. Although many embolic agents have been exploited in TACE, embolic agents combining embolization, drug-loading, and imaging properties have not yet been constructed. In this work, we prepared magnetic mesoporous microspheres as a new embolic agent that can simultaneously load doxorubicin (Dox), block blood vessels and enable magnetic resonance imaging. Overall, this new embolic microsphere-mediated TACE strategy for liver cancer showed good therapeutic effects, and the PS/Fe3O4@MON@Dox embolic microspheres provide a new avenue for improving the efficacy of TACE for liver cancer and postoperative evaluation.
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25
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Samant H, Amiri HS, Zibari GB. Addressing the worldwide hepatocellular carcinoma: epidemiology, prevention and management. J Gastrointest Oncol 2021; 12:S361-S373. [PMID: 34422400 PMCID: PMC8343080 DOI: 10.21037/jgo.2020.02.08] [Citation(s) in RCA: 84] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2019] [Accepted: 01/22/2020] [Indexed: 12/24/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is the sixth most common cancer in the world with rising incidence. Globally, there has been substantial variation in prevalence of risk factors for HCC over years, like control of viral hepatitis in developing countries but growing epidemic of fatty liver disease in developed world. Changing epidemiology of HCC is related to trends in these risk factors. HCC remains asymptomatic until it is very advanced which makes early detection by surveillance important in reducing HCC related mortality. Management of HCC. depends on stage of the tumor and severity of underlying liver disease. At present, resection and transplant are still the best curative options for small HCC, but recent advances in locoregional therapy and molecular targeted systemic therapy has changed the management for HCC at intermediate and advanced stages. This review is overview of global epidemiology, prevention, surveillance and emerging therapies for hepatocellular carcinoma.
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Affiliation(s)
- Hrishikesh Samant
- Division of Gastroenterology and Hepatology, LSU Health Science Center, Shreveport, LA, USA
| | - Hosein Shokouh Amiri
- John C McDonald Transplant Center, Willis Knighton Health System, Shreveport, LA, USA
| | - Gazi B. Zibari
- John C McDonald Transplant Center, Willis Knighton Health System, Shreveport, LA, USA
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26
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Benson AB, D'Angelica MI, Abbott DE, Anaya DA, Anders R, Are C, Bachini M, Borad M, Brown D, Burgoyne A, Chahal P, Chang DT, Cloyd J, Covey AM, Glazer ES, Goyal L, Hawkins WG, Iyer R, Jacob R, Kelley RK, Kim R, Levine M, Palta M, Park JO, Raman S, Reddy S, Sahai V, Schefter T, Singh G, Stein S, Vauthey JN, Venook AP, Yopp A, McMillian NR, Hochstetler C, Darlow SD. Hepatobiliary Cancers, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw 2021; 19:541-565. [PMID: 34030131 DOI: 10.6004/jnccn.2021.0022] [Citation(s) in RCA: 539] [Impact Index Per Article: 134.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
The NCCN Guidelines for Hepatobiliary Cancers focus on the screening, diagnosis, staging, treatment, and management of hepatocellular carcinoma (HCC), gallbladder cancer, and cancer of the bile ducts (intrahepatic and extrahepatic cholangiocarcinoma). Due to the multiple modalities that can be used to treat the disease and the complications that can arise from comorbid liver dysfunction, a multidisciplinary evaluation is essential for determining an optimal treatment strategy. A multidisciplinary team should include hepatologists, diagnostic radiologists, interventional radiologists, surgeons, medical oncologists, and pathologists with hepatobiliary cancer expertise. In addition to surgery, transplant, and intra-arterial therapies, there have been great advances in the systemic treatment of HCC. Until recently, sorafenib was the only systemic therapy option for patients with advanced HCC. In 2020, the combination of atezolizumab and bevacizumab became the first regimen to show superior survival to sorafenib, gaining it FDA approval as a new frontline standard regimen for unresectable or metastatic HCC. This article discusses the NCCN Guidelines recommendations for HCC.
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Affiliation(s)
- Al B Benson
- 1Robert H. Lurie Comprehensive Cancer Center of Northwestern University
| | | | | | | | - Robert Anders
- 5The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
| | | | | | | | | | | | - Prabhleen Chahal
- 11Case Comprehensive Cancer Center, University Hospitals Seidman Cancer Center and Cleveland Clinic Taussig Cancer Institute
| | | | - Jordan Cloyd
- 13The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute
| | | | - Evan S Glazer
- 14St. Jude Children's Research HospitalThe University of Tennessee Health Science Center
| | | | - William G Hawkins
- 16Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine
| | | | | | - R Kate Kelley
- 19UCSF Helen Diller Family Comprehensive Cancer Center
| | - Robin Kim
- 20Huntsman Cancer Institute at the University of Utah
| | - Matthew Levine
- 21Abramson Cancer Center at the University of Pennsylvania
| | | | - James O Park
- 23Fred Hutchinson Cancer Research CenterSeattle Cancer Care Alliance
| | | | | | | | | | | | | | | | - Alan P Venook
- 19UCSF Helen Diller Family Comprehensive Cancer Center
| | - Adam Yopp
- 31UT Southwestern Simmons Comprehensive Cancer Center; and
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27
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Chen S, Yu W, Zhang K, Liu W, Chen C. Comparison of the efficacy and safety of conventional transarterial chemoembolization with and without drug-eluting beads embolization for the treatment of unresectable large hepatocellular carcinoma. Hepatol Res 2021; 51:482-489. [PMID: 33462925 DOI: 10.1111/hepr.13620] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2020] [Revised: 12/09/2020] [Accepted: 12/26/2020] [Indexed: 12/22/2022]
Abstract
AIM Hepatocellular carcinoma (HCC) has a poor prognosis. Moreover, large HCCs have been commonly observed. We aimed to evaluate the efficacy and safety of drug-eluting beads transarterial chemoembolization (DEB-TACE) combined with conventional TACE (cTACE) for the treatment of patients with unresectable large HCCs (main tumor ≥5 cm in diameter) compared with cTACE alone. METHODS A retrospective matched cohort study was performed on consecutive patients with unresectable large HCCs who underwent TACE as the initial treatment at the Fujian Medical University Cancer Hospital from May 2017 and March 2019. Fifty-five patients who underwent DEB-TACE combined with cTACE were compared with a case-matched control group of 110 patients who received cTACE alone. We compared the tumor response at 1 and 3 months after TACE, time to progression (TTP), and adverse events between the groups. RESULTS The objective response rate was higher for the DEB-TACE combined with cTACE group than for the cTACE alone group at 1 (39 of 55 [70.9%] vs. 57 of 110 [51.8%], p = 0.019) and 3 months (27 of 43 [62.8%] vs. 31 of 71 [43.7%], p = 0.048) post-treatment. The DEB-TACE combined with cTACE group also had a significantly longer median TTP than that of the cTACE group (7.2 vs. 5.3 months, p = 0.039). Compared with the cTACE group, occurrences of abdominal pain, nausea/vomiting, and constipation were significantly more frequent in the DEB-TACE combined with cTACE group (p < 0.05). CONCLUSION Compared with cTACE alone, DEB-TACE combined with cTACE significantly increased the objective response rate at 1 and 3 months after the treatment of unresectable large HCCs, and had a longer TTP, without any significant increase in the number of severe complications.
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Affiliation(s)
- Shiguang Chen
- Department of Interventional Oncology, Fujian Medical University Cancer Hospital, Fuzhou, China
| | - Wenchang Yu
- Department of Interventional Oncology, Fujian Medical University Cancer Hospital, Fuzhou, China
| | - Kongzhi Zhang
- Department of Interventional Oncology, Fujian Medical University Cancer Hospital, Fuzhou, China
| | - Weifu Liu
- Department of Interventional Oncology, Fujian Medical University Cancer Hospital, Fuzhou, China
| | - Chuanben Chen
- Department of Radiotherapy Oncology, Fujian Medical University Cancer Hospital, Fuzhou, China
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28
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Shao G, Zou Y, Lucatelli P, Tsilimigras DI, Shimise S, Kawaguchi T. Chinese expert consensus on technical recommendations for the standard operation of drug-eluting beads for transvascular embolization. ANNALS OF TRANSLATIONAL MEDICINE 2021; 9:714. [PMID: 33987412 PMCID: PMC8106009 DOI: 10.21037/atm-21-1678] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
Liver cancer is among the 10 most common tumors globally. In China, liver cancer ranks 4th for prevalence and 3rd for mortality among all malignant tumors. With respect to the treatment of primary liver cancer, there are a number of therapies currently available, including surgical resection, liver transplantation, ablation, transarterial chemoembolization (TACE), systemic chemotherapy, radiation therapy, targeted drug therapy and immunotherapy. Clinical practice and research have shown that, compared with conventional TACE (cTACE), drug-eluting bead TACE (DEB-TACE) can achieve a higher response rate and longer survival time in patients with primary liver cancer. Compared with that of cTACE, DEB-TACE has more favorable basic conditions for achieving uniformity, which could facilitate the standardization of operation techniques. China is the country with the highest incidence of primary liver cancer, accounting for more than 50% of the global patients, and its etiology and epidemiology in Chinese patients differ from those in Europeans and Americans. Therefore, experts in China have drafted these technical recommendations for the standard operation of drug-eluting beads for the treatment of liver cancer on the basis of accumulated abundant clinical experience and evidence-based medical data.
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Affiliation(s)
- Guoliang Shao
- Department of Intervention, Cancer Hospital of University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, China
| | - Yinghua Zou
- Department of Interventional Radiology and Vascular Surgery, Peking University First Hospital, Beijing, China
| | - Pierleone Lucatelli
- Vascular and Interventional Radiology Unit, Sapienza University of Rome, Rome, Italy
| | - Diamantis I Tsilimigras
- Department of Surgery, Division of Surgical Oncology, The Ohio State University, Wexner Medical Center, Columbus, OH, USA
| | - Shigeo Shimise
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
| | - Takumi Kawaguchi
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
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Mikhail AS, Negussie AH, Mauda-Havakuk M, Owen JW, Pritchard WF, Lewis AL, Wood BJ. Drug-eluting embolic microspheres: State-of-the-art and emerging clinical applications. Expert Opin Drug Deliv 2021; 18:383-398. [PMID: 33480306 PMCID: PMC11247414 DOI: 10.1080/17425247.2021.1835858] [Citation(s) in RCA: 36] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2020] [Accepted: 10/07/2020] [Indexed: 12/13/2022]
Abstract
INTRODUCTION Drug-eluting embolic (DEE) microspheres, or drug-eluting beads (DEB), delivered by transarterial chemoembolization (TACE) serve as a therapeutic embolic to stop blood flow to tumors and a drug delivery vehicle. New combinations of drugs and DEE microspheres may exploit the potential synergy between mechanisms of drug activity and local tissue responses generated by TACE to enhance the efficacy of this mainstay therapy. AREAS COVERED This review provides an overview of key drug delivery concepts related to DEE microspheres with a focus on recent technological developments and promising emerging clinical applications as well as speculation into the future. EXPERT OPINION TACE has been performed for nearly four decades by injecting chemotherapy drugs into the arterial supply of tumors while simultaneously cutting off their blood supply, trying to starve and kill cancer cells, with varying degrees of success. The practice has evolved over the decades but has yet to fulfill the promise of truly personalized therapies envisioned through rational selection of drugs and real-time multi-parametric image guidance to target tumor clonality or heterogeneity. Recent technologic and pharmacologic developments have opened the door for potentially groundbreaking advances in how TACE with DEE microspheres is performed with the goal of achieving advancements that benefit patients.
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Affiliation(s)
- Andrew S Mikhail
- Center for Interventional Oncology, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD, USA
| | - Ayele H Negussie
- Center for Interventional Oncology, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD, USA
| | - Michal Mauda-Havakuk
- Center for Interventional Oncology, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD, USA
| | - Joshua W Owen
- Center for Interventional Oncology, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD, USA
| | - William F Pritchard
- Center for Interventional Oncology, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD, USA
| | - Andrew L Lewis
- Interventional Medicine Innovation Group, Biocompatibles UK, Ltd. (Now Boston Scientific Corp.), Camberley, UK
| | - Bradford J Wood
- Center for Interventional Oncology, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD, USA
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Ono Y, Osuga K, Nagai K, Hongyo H, Kimura Y, Tanaka K, Higashihara H, Tomiyama N. Local Efficacy and Safety of Transarterial Chemoembolization for Hepatocellular Carcinoma: Epirubicin-Loaded DC Beads vs. Epirubicin-Lipiodol Emulsion with Gelatin Sponge (cTACE). INTERVENTIONAL RADIOLOGY 2021; 6:14-20. [PMID: 35910524 PMCID: PMC9327354 DOI: 10.22575/interventionalradiology.2020-0025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/29/2020] [Accepted: 12/18/2020] [Indexed: 11/29/2022]
Abstract
Purpose: To compare the efficacy and safety between epirubicin-loaded DC Beads (DCB-TACE) and conventional TACE (cTACE) used in transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC). Materials and Methods: This retrospective study enrolled 64 patients (mean age, 73.3 years; 44 men, 20 women) who underwent initial DCB-TACE between 2014 and 2015, and 66 patients (mean age, 71.3 years; 38 men, 28 women) who underwent initial cTACE between 2011 and 2013 as historical controls. Treatment effects on the target lesions at 3 months after TACE, the period until re-treatment of the target lesion, and adverse events after TACE were compared between the groups. Univariate and multivariate analyses were also performed to estimate the factors influencing the treatment effects. Results: Based on the Response Evaluation Criteria in Cancer of the Liver version 2015, treatment response of the target lesions equivalent to a complete response and termed as TE4, was 51.0% (53/104) in the DCB-TACE group and 74.4% (64/86) in the cTACE group (p<0.001). Multivariate analysis revealed that the TACE procedure, Child-Pugh score, serum aspartate aminotransferase (AST) level, alpha fetoprotein level, and tumor size were independent significant predictors of TE4. The frequencies of elevated serum AST and alanine transaminase levels after TACE were significantly lower in patients in the DCB-TACE group (p<0.001 each). No significant difference in biliary/liver damage was evident between the groups. Conclusion: The local efficacy of cTACE was higher than that of DCB-TACE. Adverse events were milder after DCB-TACE than after cTACE.
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Affiliation(s)
- Yusuke Ono
- Department of Diagnosis and Interventional Radiology, Osaka University Graduate School of Medicine
| | - Keigo Osuga
- Department of Diagnosis and Interventional Radiology, Osaka University Graduate School of Medicine
- Department of Diagnostic Radiology, Osaka Medical College
| | - Keisuke Nagai
- Department of Diagnosis and Interventional Radiology, Osaka University Graduate School of Medicine
| | - Hidenari Hongyo
- Department of Diagnosis and Interventional Radiology, Osaka University Graduate School of Medicine
| | - Yasushi Kimura
- Department of Diagnosis and Interventional Radiology, Osaka University Graduate School of Medicine
| | - Kaisyu Tanaka
- Department of Diagnosis and Interventional Radiology, Osaka University Graduate School of Medicine
| | - Hiroki Higashihara
- Department of Diagnosis and Interventional Radiology, Osaka University Graduate School of Medicine
| | - Noriyuki Tomiyama
- Department of Diagnosis and Interventional Radiology, Osaka University Graduate School of Medicine
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Pérez-López A, Martín-Sabroso C, Torres-Suárez AI, Aparicio-Blanco J. Timeline of Translational Formulation Technologies for Cancer Therapy: Successes, Failures, and Lessons Learned Therefrom. Pharmaceutics 2020; 12:E1028. [PMID: 33126622 PMCID: PMC7692572 DOI: 10.3390/pharmaceutics12111028] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2020] [Revised: 10/21/2020] [Accepted: 10/26/2020] [Indexed: 02/07/2023] Open
Abstract
Over the past few decades, the field of cancer therapy has seen a significant change in the way in which formulations are designed and developed, resulting in more efficient products that allow us to ultimately achieve improved drug bioavailability, efficacy, and safety. However, although many formulations have entered the market, many others have fallen by the wayside leaving the scientific community with several lessons to learn. The successes (and failures) achieved with formulations that have been approved in Europe and/or by the FDA for the three major types of cancer therapy (peptide-based therapy, chemotherapy, and radiotherapy) are reviewed herein, covering the period from the approval of the first prolonged-release system for hormonal therapy to the appearance of the first biodegradable microspheres intended for chemoembolization in 2020. In addition, those products that have entered phase III clinical trials that have been active over the last five years are summarized in order to outline future research trends and possibilities that lie ahead to develop clinically translatable formulations for cancer treatment.
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Affiliation(s)
- Alexandre Pérez-López
- Department of Pharmaceutics and Food Technology, Faculty of Pharmacy, Complutense University of Madrid, 28040 Madrid, Spain; (A.P.-L.); (C.M.-S.); (J.A.-B.)
| | - Cristina Martín-Sabroso
- Department of Pharmaceutics and Food Technology, Faculty of Pharmacy, Complutense University of Madrid, 28040 Madrid, Spain; (A.P.-L.); (C.M.-S.); (J.A.-B.)
- Institute of Industrial Pharmacy, Complutense University of Madrid, 28040 Madrid, Spain
| | - Ana Isabel Torres-Suárez
- Department of Pharmaceutics and Food Technology, Faculty of Pharmacy, Complutense University of Madrid, 28040 Madrid, Spain; (A.P.-L.); (C.M.-S.); (J.A.-B.)
- Institute of Industrial Pharmacy, Complutense University of Madrid, 28040 Madrid, Spain
| | - Juan Aparicio-Blanco
- Department of Pharmaceutics and Food Technology, Faculty of Pharmacy, Complutense University of Madrid, 28040 Madrid, Spain; (A.P.-L.); (C.M.-S.); (J.A.-B.)
- Institute of Industrial Pharmacy, Complutense University of Madrid, 28040 Madrid, Spain
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Transarterial chemoembolization for hepatocellular carcinoma: quality of life, tumour response, safety and survival comparing two types of drug-eluting beads. Abdom Radiol (NY) 2020; 45:3326-3336. [PMID: 31781900 DOI: 10.1007/s00261-019-02349-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
PURPOSE To compare two different types of drug-eluting microspheres with regard to impact on HRQoL after first TACE, tumour response, peri-procedural complications, adverse events and 1-year survival in patients suffering from unresectable hepatocellular carcinoma (HCC). METHODS HRQoL was prospectively assessed with validated questionnaires (EORTC QLQ-C30 and -HCC18) before and 2 weeks after treatment with their first drug-eluting beads (DEB-)TACE with either acrylamido-polyvinylalcohol-AMPS hydrogel microspheres (groupDCB; 20 patients) or polyvinyl alcohol-co-acrylic acid microspheres (groupHS; 16 patients). Baseline characteristics, peri-procedural complications, treatment-related adverse events and 1-year survival were compared between both types of microspheres. Treatment response and objective response rates (ORR) were analysed using established tumour response criteria. Subgroup analysis for pooled groups with small (groupSMALL; 21 patients) versus large particles (groupLARGE; 15 patients) was performed. RESULTS At baseline, there were no significant differences between the treated microsphere groups. No significant differences were found in absolute HRQoL changes after first DEB-TACE between the different types of microspheres. Response rates and survival were comparable between the investigated microsphere groups. For groupSMALL, we found a significant difference in post-interventional deterioration of physical function (- 19.4%) compared to groupLARGE (- 8%; p = 0.025). Tumour response and ORR according to mRECIST were significantly higher in groupSMALL (p = 0.008; p = 0.009). CONCLUSION DEB-TACE is generally well tolerated and effective, with comparable changes in HRQoL for both types of drug-eluting microspheres. Tumour response is better with small microspheres. A relevant deterioration of physical function underlines that an aggressive TACE using small beads should be well deliberated.
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Karina A, Benzina A, Tazhibayeva S, Fan H, Koole LH. Polymer microparticles with a cavity designed for transarterial chemo-embolization with crystalline drug formulations. J Biomed Mater Res B Appl Biomater 2020; 109:401-409. [PMID: 32860336 DOI: 10.1002/jbm.b.34708] [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: 02/09/2020] [Revised: 07/29/2020] [Accepted: 08/04/2020] [Indexed: 11/05/2022]
Abstract
Transarterial chemo-embolization with drug-eluting embolic beads (DEB-TACE) is still evolving. Recent developments include the introduction of radiopaque (X-ray imageable) drug-eluting particles. Here, we report on conceptually different radiopaque polymeric drug-eluting embolic particles, which are (i), cross-linked poly(methacrylates); (ii), radiopaque; (iii), microporous. Furthermore, the particles are not perfectly spherical: they have a large indentation in the sense that they are either a spherical/cup-shaped or ellipsoid/mouth-shaped. The micropores and the large indentation can confer useful features upon the particles, since they can be filled with a crystalline lipophilic chemotherapeutic drug. It is important, in this respect that (i), many potent chemotherapeutics are lipophilic and crystalline; (ii), available drug-eluting beads (DEBs) have the limitation that they can only be used in combination with water-soluble chemotherapeutic agents. Cup- and mouth-shaped particles were obtained in a Cu(0) catalyzed free-radical polymerization reaction. The microparticles could be charged with crystalline drug, in such a manner that the crystals reside in both the micropores and the large cavity, and in quantities that would be required for effective local chemotherapy. The antifungal drug voriconazole, lipophilic, and crystalline, was used to demonstrate this. We believe that the ability of the microporous/cavitated DEBs to carry lipophilic chemotherapeutic drugs is especially important. DEB-TACE is likely to become a cornerstone method of interventional oncology in the years ahead, and the new embolic particles described herein hold the promise of becoming scope widening for the technique.
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Affiliation(s)
- Aigerim Karina
- Department of Chemical and Materials Engineering, School of Engineering and Digital Sciences, Nazarbayev University, Nur-Sultan, Kazakhstan
| | - Abderazak Benzina
- Department of Chemical and Materials Engineering, School of Engineering and Digital Sciences, Nazarbayev University, Nur-Sultan, Kazakhstan
| | - Samal Tazhibayeva
- Department of Biology, School of Science and Humanities, Nazarbayev University, Nur-Sultan, Kazakhstan
| | - Haiyan Fan
- Department of Chemistry, School of Science and Humanities, Nazarbayev University, Nur-Sultan, Kazakhstan
| | - Levinus H Koole
- Department of Chemical and Materials Engineering, School of Engineering and Digital Sciences, Nazarbayev University, Nur-Sultan, Kazakhstan
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Ou HY, Cheng YF, Chuang YH, Hsu HW, Chen CL, Lazo MZ, Weng CC, Yu CY, Tsang LLC, Huang TL, Tong YS. Quantification of Functional MR Predicts Early Response in Post-doxorubicin Drug-Eluting Beads Chemoembolization for Hepatocellular Carcinoma. Dig Dis Sci 2020; 65:2433-2441. [PMID: 31732907 DOI: 10.1007/s10620-019-05951-6] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2019] [Accepted: 11/07/2019] [Indexed: 12/14/2022]
Abstract
BACKGROUND The purpose of this study was to assess the value of functional MRI (fMRI) of post-doxorubicin drug-eluting beads transcatheter arterial chemoembolization (DEB-TACE) for hepatocellular carcinoma (HCC) as an early imaging biomarker of response to therapy. METHODS This prospective analysis included 21 consecutive patients undergoing fMRI before and after DEB-TACE at a single medical center from January 2013 to December 2014. Functional MRI, including relative changes in apparent diffusion coefficient (ADC) and choline levels measured at hydrogen-1 magnetic resonance spectroscopy (MRS) of treated lesions, was recorded at baseline before DEB-TACE, and at 1, 2, and 4 weeks after DEB-TACE therapy. Assessment of tumor response was based on dynamic contrast-enhanced computer tomography imaging response according to modified response evaluation criteria in solid tumors. RESULTS At post-therapy, 76% (n = 16) of patients demonstrated objective tumor response, 10% (n = 2) had stable disease, and 3 (14%) had progressive disease. Stable disease and progressive disease were designated as non-response. At week 2, the mean change in ADC value of responsive tumors was 0.35 ± 0.24 mm2/s, which was greater than that of non-response tumors (mean 0.01 ± 0.13 × 10-3 mm2/s) (P = 0.006). Significant differences were found in mean choline/water ratio between responsive (7.8 ± 4.9 × 10-3) and non-responsive (17.2 ± 4.9 × 10-3) tumors (P = 0.005). Composite scores of choline/water ratio and relative change of ADC showed significantly better diagnostic accuracy in non-responsive tumors than responsive tumors (area under the curve = 1.0; P < 0.001). CONCLUSIONS Combined DWI and MRS may be used as an early imaging biomarker of therapy response in HCC patients after chemoembolization therapy.
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Affiliation(s)
- Hsin-You Ou
- Liver Transplantation Program and Departments of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 123 Ta-Pei Road, Niao-Sung, Kaohsiung, 83305, Taiwan.
| | - Yu-Fan Cheng
- Liver Transplantation Program and Departments of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 123 Ta-Pei Road, Niao-Sung, Kaohsiung, 83305, Taiwan
| | - Yi-Hsuan Chuang
- Liver Transplantation Program and Departments of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 123 Ta-Pei Road, Niao-Sung, Kaohsiung, 83305, Taiwan
| | - Hsien-Wen Hsu
- Liver Transplantation Program and Departments of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 123 Ta-Pei Road, Niao-Sung, Kaohsiung, 83305, Taiwan
| | - Chao-Long Chen
- Liver Transplantation Program and Departments of Surgery, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 123 Ta-Pei Road, Niao-Sung, Kaohsiung, 83305, Taiwan
| | - Marirose Zingapan Lazo
- Liver Transplantation Program and Departments of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 123 Ta-Pei Road, Niao-Sung, Kaohsiung, 83305, Taiwan
| | - Ching-Chun Weng
- Liver Transplantation Program and Departments of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 123 Ta-Pei Road, Niao-Sung, Kaohsiung, 83305, Taiwan
| | - Chun-Yen Yu
- Liver Transplantation Program and Departments of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 123 Ta-Pei Road, Niao-Sung, Kaohsiung, 83305, Taiwan
| | - Leo Leung-Chit Tsang
- Liver Transplantation Program and Departments of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 123 Ta-Pei Road, Niao-Sung, Kaohsiung, 83305, Taiwan
| | - Tung-Liang Huang
- Liver Transplantation Program and Departments of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 123 Ta-Pei Road, Niao-Sung, Kaohsiung, 83305, Taiwan
| | - Yu-Shun Tong
- Liver Transplantation Program and Departments of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 123 Ta-Pei Road, Niao-Sung, Kaohsiung, 83305, Taiwan
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Abstract
Hepatocellular carcinoma (HCC) is one of the most common types of malignant tumor. Although radical surgery and liver transplantation are possible cures for the disease, most patients are beyond the optimum stage for radical treatment at the time of diagnosis. Transarterial chemoembolization (TACE) is the first choice of treatment for advanced HCC. Owing to the widespread use of conventional TACE (cTACE), the problems with this treatment cannot be ignored. Drug-eluting beads (DEBs), a new type of embolization material, appear to overcome the problems of cTACE, and they have other advantages such as synchronous controlled continuous drug release after chemotherapy and embolization and low blood concentrations after treatment. This review summarizes the recent advances in the use of DEB-TACE to treat HCC.
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Affiliation(s)
- Guangxu Wei
- Interventional Department, Changhai Hospital, Naval Medical University, No. 168, ChangHai Road, Shanghai, 200433, China
| | - Jijin Yang
- Interventional Department, Changhai Hospital, Naval Medical University, No. 168, ChangHai Road, Shanghai, 200433, China
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The development of early ascites is associated with shorter overall survival in patients with hepatocellular carcinoma treated with drug-eluting embolic chemoembolization. BMC Gastroenterol 2020; 20:166. [PMID: 32487071 PMCID: PMC7268728 DOI: 10.1186/s12876-020-01307-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2019] [Accepted: 05/18/2020] [Indexed: 02/07/2023] Open
Abstract
Background A single-centre cohort study was performed to identify the independent factors associated with the overall survival (OS) of hepatocellular carcinoma (HCC) patients treated with transarterial chemoembolization with drug-eluting beads (DEB-TACE). Methods A total of 216 HCC patients who underwent DEB-TACE from October 2008 to October 2015 at a tertiary hospital were consecutively recruited. The analysis of prognostic factors associated with overall survival after DEB-TACE, stressing the role of post-TACE events, was performed. Results The objective response (OR) rate (Modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria) to the first DEB-TACE (DEB-TACE-1) was 70.3%; the median OS from DEB-TACE-1 was 27 months (95% confidence interval (CI), 24–30). In the multivariate analysis, tumor size, AFP < 100 ng/mL and serum alkaline phosphatase were independent factors for survival following DEB-TACE-1. The most important clinical event associated with poor survival was the development of early ascites after DEB-TACE-1 (median OS, 17 months), which was closely related to the history of ascites, albumin and hemoglobin but not to tumour load or to response to therapy. Conclusions Early ascites post-DEB-TACE is associated with the survival of patients despite adequate liver function and the use of a supra-selective technical approach. History of ascites, albumin and hemoglobin are major determinants of the development of early ascites post-DEB-TACE.
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Han X, Chen Q, Sun Y, Han L, Sha X. Morphology, Loadability, and Releasing Profiles of CalliSpheres Microspheres in Delivering Oxaliplatin: An In Vitro Study. Technol Cancer Res Treat 2020; 18:1533033819877989. [PMID: 31630671 PMCID: PMC6801889 DOI: 10.1177/1533033819877989] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023] Open
Abstract
Objectives: This study aimed to explore the morphology, loadability, and releasing profiles of
CalliSpheres microspheres in delivering oxaliplatin. Methods: Varied amount (20, 40, 60, and 80 mg oxaliplatin) and concentration (1.25, 2.5, 5.0
mg/mL oxaliplatin) of oxaliplatin were mixed with CalliSpheres microspheres with 3 sizes
(50-150 μm, 100-300 μm, and 300-500 μm) to measure the loadability. Of all, 20 mg
oxaliplatin-loaded CalliSpheres microspheres with 3 sizes was prepared to measure the
releasing profiles, meanwhile, fetal bovine serum was added to determine the effect of
serum on oxaliplatin releasing. The morphology and size distribution of CalliSpheres
microspheres with 3 sizes before and after 20 mg oxaliplatin loading were detected. Results: Oxaliplatin amount was negatively correlated with loading efficiency with highest
loadability in 20 mg oxaliplatin group (maximum 40% in 50-100 µm CalliSpheres
microspheres, 52% in 100-300 µm CalliSpheres microspheres, and 52% in 300-500 µm
CalliSpheres microspheres), while oxaliplatin concentration was positively associated
with loading efficiency. Similar drug-releasing profiles were observed among
oxaliplatin-loaded CalliSpheres microspheres with 3 sizes, and a rapid drug release was
discovered in CalliSpheres microspheres with 3 sizes as well. We also found that fetal
bovine serum did not affect the drug-releasing profiles of oxaliplatin-loaded
CalliSpheres microspheres. In addition, CalliSpheres microspheres was modified a little
to ellipse shape and less smooth after oxaliplatin loading, and it was enlarged to some
extent. Conclusion: This study discloses drug loadability, releasing profiles, and morphology change of
CalliSpheres microspheres for delivering oxaliplatin, which provides potential evidences
for application of oxaliplatin-loaded drug-eluting beads in clinical practice.
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Affiliation(s)
- Xiaoli Han
- Center for Medical Research and Innovation, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Key Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, China
| | - Qinyue Chen
- Center for Medical Research and Innovation, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Key Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, China
| | - Yali Sun
- Center for Medical Research and Innovation, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Key Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, China
| | - Limei Han
- Center for Medical Research and Innovation, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Key Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, China
| | - Xianyi Sha
- Center for Medical Research and Innovation, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Key Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, China
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Liang B, Xiang H, Ma C, Xiong B, Ma Y, Zhao C, Yao Y, Zhang Z, Chen C, Li H, Long Q, Zhou J, Luo C, Qiu H, Hu H, Zhao H, Zhou G, Zheng C. Comparison of chemoembolization with CalliSpheres ® microspheres and conventional chemoembolization in the treatment of hepatocellular carcinoma: a multicenter retrospective study. Cancer Manag Res 2020; 12:941-956. [PMID: 32104076 PMCID: PMC7020935 DOI: 10.2147/cmar.s187203] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2018] [Accepted: 06/27/2019] [Indexed: 12/13/2022] Open
Abstract
Purpose This study aimed to compare the efficacy and safety between transarterial chemoembolization (TACE) with CalliSpheres® microspheres (CSM-TACE) and conventional TACE (cTACE) in patients with hepatocellular carcinoma (HCC). Patients and Methods Three hundred and thirty-five HCC patients receiving CSM-TACE or cTACE were consecutively enrolled in this multi-center, retrospective cohort study, and then divided into CSM-TACE group and cTACE group accordingly. Complete response (CR), objective response (ORR) and disease control response (DCR) was assessed according to mRECIST criteria at 1 month (M1), 3 months(M3) and 6 months(M6) after treatment. Progression-free survival (PFS) and overall survival (OS) were assessed. Liver function indexes and adverse events (AEs) were also evaluated. Results CR at M3 (P=0.020) and ORR at M1 (P<0.001), M3 (P<0.001) and M6 (P=0.017) after treatment were significantly higher in the CSM-TACE compared with cTACE group. DCRs, PFS (25.3 months vs 24.2 months, P=0.503) and OS (27.8 months vs 25.3 months, P=0.203) were similar between the two groups. CSM-TACE was independently correlated with higher ORR at M1 (P=0.002) and longer OS (P=0.023). Abnormal alkaline phosphatase (ALP) (P=0.049) was independently associated with lower ORR at M3, and history of alcohol intake (P=0.019) and largest nodule size ≥7 cm (P=0.015) independently correlated with lower ORR at M6 (P=0.015). Largest nodule size ≥7 cm (P=0.029) and abnormal albumin (ALB) (P=0.046) were independently associated with shorter PFS. Child-Pugh stage B/C (P=0.023), abnormal ALB (P=0.001), ALP (P=0.008) and alpha-fetoprotein (AFP) (P=0.005) were independently associated with shorter OS. Most liver function indexes and AEs were similar between the two groups (P>0.05), except that ALP (P=0.005), total bilirubin (P=0.031), pain during procedure (P=0.034) and occurrence of fever post(treatment (P=0.017) were significantly elevated in the CSM-TACE compared with cTACE group. Conclusion CSM-TACE presents with a better treatment response and similar survival profile compared with cTACE in HCC patients.
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Affiliation(s)
- Bin Liang
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China
| | - Hua Xiang
- Department of Interventional Radiology, Hunan Provincial People's Hospital, Changsha, People's Republic of China
| | - Cong Ma
- Department of Radiology, The Second Xiangya Hospital of Central South University, Changsha, People's Republic of China
| | - Bin Xiong
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China
| | - Yilong Ma
- Department of Interventional Radiology, Cancer Hospital Affiliated to Guangxi Medical University, Nanning, People's Republic of China
| | - Chang Zhao
- Department of Interventional Radiology, Cancer Hospital Affiliated to Guangxi Medical University, Nanning, People's Republic of China
| | - Yuanhui Yao
- Department of Interventional Radiology, Hunan Provincial People's Hospital, Changsha, People's Republic of China
| | - Zishu Zhang
- Department of Radiology, The Second Xiangya Hospital of Central South University, Changsha, People's Republic of China
| | - Changyong Chen
- Department of Radiology, Xiangya Hospital General South University, Changsha, People's Republic of China
| | - Haiping Li
- Department of Radiology, Xiangya Hospital General South University, Changsha, People's Republic of China
| | - Qingyun Long
- Department of Interventional Radiology, Zhongnan Hospital of Wuhan University, Wuhan, People's Republic of China
| | - Jun Zhou
- Department of Interventional Radiology, Zhongnan Hospital of Wuhan University, Wuhan, People's Republic of China
| | - Chao Luo
- Department of Radiology, Wuhan General Hospital of Guangzhou Military Region, Wuhan, People's Republic of China
| | - Huaiming Qiu
- Department of Radiology, Wuhan General Hospital of Guangzhou Military Region, Wuhan, People's Republic of China
| | - Hongyao Hu
- Department of Interventional Radiology, Renmin Hospital of Wuhan University, Hubei General Hospital, Wuhan, People's Republic of China
| | - Hui Zhao
- Department of Interventional Radiology, Renmin Hospital of Wuhan University, Hubei General Hospital, Wuhan, People's Republic of China
| | - Guofeng Zhou
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China
| | - Chuansheng Zheng
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China
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Peng Z, Cao G, Hou Q, Li L, Ying S, Sun J, Zhou G, Zhou J, Zhang X, Ji W, Yu Z, Li T, Zhu D, Hu W, Ji J, Du H, Shi C, Guo X, Fang J, Han J, Gu W, Xie X, Sun Z, Xu H, Wu X, Hu T, Huang J, Hu H, Zheng J, Luo J, Chen Y, Yu W, Shao G. The Comprehensive Analysis of Efficacy and Safety of CalliSpheres ® Drug-Eluting Beads Transarterial Chemoembolization in 367 Liver Cancer Patients: A Multiple-Center, Cohort Study. Oncol Res 2019; 28:249-271. [PMID: 31856933 PMCID: PMC7851534 DOI: 10.3727/096504019x15766663541105] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
This study aimed to investigate the efficacy, safety, and prognostic factors of drug-eluting beads transarterial chemoembolization (DEB-TACE) in treating Chinese patients with liver cancer. A total of 367 liver cancer patients from 24 medical centers were consecutively enrolled in this multiple-center, prospective cohort study, including 275 hepatocellular carcinoma (HCC) cases, 37 intrahepatic cholangiocarcinoma (ICC) cases, and 55 secondary liver cancer cases. All the patients received CalliSpheres® DEB-TACE treatment. Treatment response, overall survival (OS), change of liver function, and adverse events (AEs) were assessed. DEB-TACE treatment achieved 19.9% complete response (CR) and 79.6% objective response rate (ORR), with mean OS of 384 days [95% confidence interval (CI): 375–393 days]. CR and ORR were both higher in HCC patients compared with primary ICC patients and secondary liver cancer patients, while no difference was discovered in OS. Portal vein invasion was an independent risk factor for CR, while portal vein invasion, previous conventional TACE (cTACE) treatment, and abnormal blood creatinine (BCr) were independent risk factors for ORR. In addition, largest nodule size ≥5.0 cm, abnormal albumin (ALB), and abnormal total bilirubin (TBIL) independently correlated with unfavorable OS. Most liver function indexes were recovered to baseline levels at 1–3 months after DEB-TACE. Common AEs were pain, fever, vomiting, and nausea; most of them were at mild grade. CalliSpheres® DEB-TACE is efficient and well tolerated in Chinese liver cancer patients. Portal vein invasion, previous cTACE treatment, largest nodule size, abnormal BCr, ALB, and TBIL correlate with worse prognosis independently.
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Affiliation(s)
- Zhiyi Peng
- Department of Radiology, The First Affiliated Hospital, College of Medicine, Zhejiang UniversityHangzhouChina
| | - Guohong Cao
- Department of Radiology, Shulan (Hangzhou) Hospital, Zhejiang University International HospitalHangzhouChina
| | - Qinming Hou
- Department of Radiology, Xixi Hospital of Hangzhou, Hangzhou 6th People's HospitalHangzhouChina
| | - Ling Li
- Department of Liver Oncology, Ningbo No. 2 HospitalNingboChina
| | - Shihong Ying
- Department of Radiology, The First Affiliated Hospital, College of Medicine, Zhejiang UniversityHangzhouChina
| | - Junhui Sun
- Hepatobiliary and Pancreatic Interventional Treatment Center, Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang UniversityHangzhouChina
| | - Guanhui Zhou
- Hepatobiliary and Pancreatic Interventional Treatment Center, Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang UniversityHangzhouChina
| | - Jian Zhou
- Department of Radiology, Hangzhou Cancer HospitalHangzhouChina
| | - Xin Zhang
- Department of Radiology, The First Affiliated Hospital, College of Medicine, Zhejiang UniversityHangzhouChina
| | - Wenbin Ji
- Department of Radiology, Taizhou Hospital of Zhejiang ProvinceLinhaiChina
| | - Zhihai Yu
- Department of Vascular and Interventional Radiology, The Affiliated Hospital of Medical College of Ningbo UniversityNingboChina
| | - Tiefeng Li
- Department of Radiology, Beilun District People's Hospital of NingboNingboChina
| | - Dedong Zhu
- Department of Liver Oncology, Ningbo No. 2 HospitalNingboChina
| | - Wenhao Hu
- Department of Intervention, The First Affiliated Hospital of Wenzhou Medical UniversityWenzhouChina
| | - Jiansong Ji
- Department of Radiology, Lishui Central Hospital, Lishui Hospital of Zhejiang University, The Fifth Affiliated Hospital of Wenzhou Medical UniversityLishuiChina
| | - Haijun Du
- Department of Intervention, Dongyang People's HospitalDongyangChina
| | - Changsheng Shi
- Department of Intervention, The Third Affiliated Hospital of Wenzhou Medical UniversityRuianChina
| | - Xiaohua Guo
- Department of Intervention, Jinhua Central HospitalJinhuaChina
| | - Jian Fang
- Department of Hepatobiliary Surgery, Quzhou People's HospitalQuzhouChina
| | - Jun Han
- Department of Intervention, Jiaxing First HospitalJiaxingChina
| | - Wenjiang Gu
- Department of Intervention, Jiaxing Second HospitalJiaxingChina
| | - Xiaoxi Xie
- Interventional Center, Xinchang People's HospitalShaoxingChina
| | - Zhichao Sun
- Department of Radiology, The First Affiliated Hospital of Zhejiang Chinese Medical UniversityHangzhouChina
| | - Huanhai Xu
- Division of Digestive Endoscopy, Yueqing City People's HospitalYueqingChina
| | - Xia Wu
- Department of Radiology, Sir Run Run Shaw Hospital, Zhejiang University College of MedicineHangzhouChina
| | - Tingyang Hu
- Department of Intervention, Zhejiang Provincial People's HospitalHangzhouChina
| | - Jing Huang
- Department of Hepatobiliary Surgery, Ningbo Medical Center, Lihuili Eastern HospitalNingboChina
| | - Hongjie Hu
- Department of Radiology, Sir Run Run Shaw Hospital, Zhejiang University College of MedicineHangzhouChina
| | - Jiaping Zheng
- Department of Intervention, Zhejiang Cancer HospitalHangzhouChina
| | - Jun Luo
- Department of Intervention, Zhejiang Cancer HospitalHangzhouChina
| | - Yutang Chen
- Department of Intervention, Zhejiang Cancer HospitalHangzhouChina
| | - Wenqiang Yu
- Department of Intervention, Zhejiang Provincial People's HospitalHangzhouChina
| | - Guoliang Shao
- Department of Intervention, Zhejiang Cancer HospitalHangzhouChina
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Liver Cancer: Current and Future Trends Using Biomaterials. Cancers (Basel) 2019; 11:cancers11122026. [PMID: 31888198 PMCID: PMC6966667 DOI: 10.3390/cancers11122026] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2019] [Revised: 12/11/2019] [Accepted: 12/13/2019] [Indexed: 02/07/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common type of cancer diagnosed and the second leading cause of death worldwide. Despite advancement in current treatments for HCC, the prognosis for this cancer is still unfavorable. This comprehensive review article focuses on all the current technology that applies biomaterials to treat and study liver cancer, thus showing the versatility of biomaterials to be used as smart tools in this complex pathologic scenario. Specifically, after introducing the liver anatomy and pathology by focusing on the available treatments for HCC, this review summarizes the current biomaterial-based approaches for systemic delivery and implantable tools for locally administrating bioactive factors and provides a comprehensive discussion of the specific therapies and targeting agents to efficiently deliver those factors. This review also highlights the novel application of biomaterials to study HCC, which includes hydrogels and scaffolds to tissue engineer 3D in vitro models representative of the tumor environment. Such models will serve to better understand the tumor biology and investigate new therapies for HCC. Special focus is given to innovative approaches, e.g., combined delivery therapies, and to alternative approaches-e.g., cell capture-as promising future trends in the application of biomaterials to treat HCC.
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Wang Z, Niu H, Li Z, Zhang J, Sha L, Zeng Q, Liu X, Huang J. Superselective arterial embolization with drug-loaded microspheres for the treatment of unresectable breast cancer. Gland Surg 2019; 8:740-747. [PMID: 32042682 DOI: 10.21037/gs.2019.12.06] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Background To investigate the short-term efficacy and safety of drug-eluting bead transcatheter arterial chemoembolization (DEB-TACE) using CalliSpheres® microspheres in the treatment of unresectable locally advanced breast cancer (LABC). Methods DEB-TACE using CSM was performed in 15 patients with LABC after failure of medical treatment. The efficacy was evaluated based on the modified Response Evaluation Criteria in Solid Tumors (mRECIST). The postoperative adverse reactions and complications were analyzed. The changes of white blood cell (WBC) count, creatine kinase isoenzyme-MB (CK-MB), B-type natriuretic peptide (BNP), and carbohydrate antigen15-3 (CA15-3) before and after treatment were compared by using Wilcoxon signed-rank test. Results The surgeries were successful in all patients. The subjects were followed up for 2-60 months (median: 10 months). According to the mRECIST, no patient achieved complete remission (CR) 1, 3, and 5 months after surgery, and partial response (PR) was achieved in 9, 11, and 11 cases; also, there were 6, 4, and 2 stable disease (SD) cases, and 0, 0, and 2 progressive disease (PD) cases. The postoperative WBC count, CK-MB level, and BNP level were not significantly different from those before surgery, whereas the CA15-3 level significantly decreased. The main postoperative adverse reactions were pain, fever, and gastrointestinal reactions. No severe adverse reactions were observed. Conclusions DEB-TACE with CalliSpheres® microspheres is a safe and feasible treatment for LABC. However, more multi-center studies with larger sample sizes are still warranted.
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Affiliation(s)
| | - Huimin Niu
- Hainan Cancer Hospital, Haikou 570000, China
| | - Zhiyong Li
- Hainan Cancer Hospital, Haikou 570000, China
| | - Jie Zhang
- Hainan Cancer Hospital, Haikou 570000, China
| | - Longjin Sha
- Hainan Cancer Hospital, Haikou 570000, China
| | - Qian Zeng
- Hainan Cancer Hospital, Haikou 570000, China
| | - Xia Liu
- Hainan Cancer Hospital, Haikou 570000, China
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Cao WZ, Zhou ZQ, Jiang S, Li H, Niu W, Gao P, Li GJ, Chen F. Efficacy and safety of drug-eluting beads for transarterial chemoembolization in patients with advanced hepatocellular carcinoma. Exp Ther Med 2019; 18:4625-4630. [PMID: 31798699 DOI: 10.3892/etm.2019.8163] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2019] [Accepted: 09/26/2019] [Indexed: 12/15/2022] Open
Abstract
Hepatocellular carcinoma (HCC) has more recently become a leading cause of cancer-associated mortality worldwide. Particularly at an advanced stage, the prognosis is generally poor due to lack of effective treatments. Transarterial chemoembolization (TACE) is now a recognized therapy for advanced HCC, serving to deprive tumors of feeder arteries through induced ischemic necrosis. However, there is also a potential for undesired circulatory toxicity owing to drug reflux from tumor artery to surrounding healthy tissues. Although effective chemotherapeutic drug concentrations are thus lowered, the side effects of systemic chemotherapy are aggravated. The mid-2000 emergence of drug-eluting beads (DEB) loaded with anti-neoplastic drugs has proven particularly advantageous, enabling localized treatment and directed delivery of chemotherapeutics. DEB-TACE (dTACE) augments local infusion of anti-neoplastic agents to prolong agent/tumor contact, expanding upon conventional TACE. At present, data on DEB use in China are limited, particularly in terms of proprietary microspheres (CalliSpheres; Hengrui Medicine Co.). To explore the efficacy and safety of CalliSpheres, A total of 90 patients receiving this means of dTACE for advanced HCC were assessed in the present study. Clinical efficacy was evaluated based on tumor response and overall survival rates using the National Cancer Institute Common Terminology Criteria for Adverse Events to assess tolerability. The satisfactory tumor response and acceptable tolerability demonstrated in the follow-up confirm the promising utility of CalliSpheres in treating patients with advanced HCC.
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Affiliation(s)
- Wen-Zhen Cao
- Intensive Care Unit, Shandong Provincial Qianfoshan Hospital, The First Affiliated Hospital of Shandong First Medical University, Jinan, Shandong 250014, P.R. China
| | - Zhu-Qian Zhou
- Department of Interventional Radiology, Shandong Provincial Qianfoshan Hospital, The First Affiliated Hospital of Shandong First Medical University, Jinan, Shandong 250014, P.R. China
| | - Song Jiang
- Department of Interventional Radiology, Shandong Provincial Qianfoshan Hospital, The First Affiliated Hospital of Shandong First Medical University, Jinan, Shandong 250014, P.R. China
| | - Hao Li
- Department of Interventional Radiology, Shandong Provincial Qianfoshan Hospital, The First Affiliated Hospital of Shandong First Medical University, Jinan, Shandong 250014, P.R. China
| | - Wei Niu
- Department of Interventional Radiology, Shandong Provincial Qianfoshan Hospital, The First Affiliated Hospital of Shandong First Medical University, Jinan, Shandong 250014, P.R. China
| | - Peng Gao
- Medical Research Center, Shandong Provincial Qianfoshan Hospital, The First Affiliated Hospital of Shandong First Medical University, Jinan, Shandong 250014, P.R. China
| | - Gui-Jie Li
- Department of Interventional Radiology, Shandong Provincial Qianfoshan Hospital, The First Affiliated Hospital of Shandong First Medical University, Jinan, Shandong 250014, P.R. China
| | - Feng Chen
- Department of Interventional Radiology, Shandong Provincial Qianfoshan Hospital, The First Affiliated Hospital of Shandong First Medical University, Jinan, Shandong 250014, P.R. China
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Beaton L, Tregidgo HFJ, Znati SA, Forsyth S, Clarkson MJ, Bandula S, Chouhan M, Lowe HL, Zaw Thin M, Hague J, Sharma D, Pollok JM, Davidson BR, Raja J, Munneke G, Stuckey DJ, Bascal ZA, Wilde PE, Cooper S, Ryan S, Czuczman P, Boucher E, Hartley JA, Lewis AL, Jansen M, Meyer T, Sharma RA. VEROnA Protocol: A Pilot, Open-Label, Single-Arm, Phase 0, Window-of-Opportunity Study of Vandetanib-Eluting Radiopaque Embolic Beads (BTG-002814) in Patients With Resectable Liver Malignancies. JMIR Res Protoc 2019; 8:e13696. [PMID: 31579027 PMCID: PMC6777276 DOI: 10.2196/13696] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2019] [Revised: 07/08/2019] [Accepted: 07/16/2019] [Indexed: 12/31/2022] Open
Abstract
BACKGROUND Transarterial chemoembolization (TACE) is the current standard of care for patients with intermediate-stage hepatocellular carcinoma (HCC) and is also a treatment option for patients with liver metastases from colorectal cancer. However, TACE is not a curative treatment, and tumor progression occurs in more than half of the patients treated. Despite advances and technical refinements of TACE, including the introduction of drug-eluting beads-TACE, the clinical efficacy of TACE has not been optimized, and improved arterial therapies are required. OBJECTIVE The primary objectives of the VEROnA study are to evaluate the safety and tolerability of vandetanib-eluting radiopaque embolic beads (BTG-002814) in patients with resectable liver malignancies and to determine concentrations of vandetanib and the N-desmethyl metabolite in plasma and resected liver following treatment with BTG-002814. METHODS The VEROnA study is a first-in-human, open-label, single-arm, phase 0, window-of-opportunity study of BTG-002814 (containing 100 mg vandetanib) delivered transarterially, 7 to 21 days before surgery in patients with resectable liver malignancies. Eligible patients have a diagnosis of colorectal liver metastases, or HCC (Childs Pugh A), diagnosed histologically or radiologically, and are candidates for liver surgery. All patients are followed up for 28 days following surgery. Secondary objectives of this study are to evaluate the anatomical distribution of BTG-002814 on noncontrast-enhanced imaging, to evaluate histopathological features in the surgical specimen, and to assess changes in blood flow on dynamic contrast-enhanced magnetic resonance imaging following treatment with BTG-002814. Exploratory objectives of this study are to study blood biomarkers with the potential to identify patients likely to respond to treatment and to correlate the distribution of BTG-002814 on imaging with pathology by 3-dimensional modeling. RESULTS Enrollment for the study was completed in February 2019. Results of a planned interim analysis were reviewed by a safety committee after the first 3 patients completed follow-up. The recommendation of the committee was to continue the study without any changes to the dose or trial design, as there were no significant unexpected toxicities related to BTG-002814. CONCLUSIONS The VEROnA study is studying the feasibility of administering BTG-002814 to optimize the use of this novel technology as liver-directed therapy for patients with primary and secondary liver cancer. TRIAL REGISTRATION ClinicalTrial.gov NCT03291379; https://clinicaltrials.gov/ct2/show/NCT03291379. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID) DERR1-10.2196/13696.
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Affiliation(s)
- Laura Beaton
- University College London Cancer Institute, University College London, London, United Kingdom
| | - Henry F J Tregidgo
- Department of Medical Physics and Biomedical Engineering, University College London, London, United Kingdom
| | - Sami A Znati
- University College London Cancer Institute, University College London, London, United Kingdom
| | - Sharon Forsyth
- Cancer Research UK University College London Cancer Trials Centre, London, United Kingdom
| | - Matthew J Clarkson
- Department of Medical Physics and Biomedical Engineering, University College London, London, United Kingdom
| | - Steven Bandula
- University College London Centre for Medical Imaging, University College London, London, United Kingdom
| | - Manil Chouhan
- University College London Centre for Medical Imaging, University College London, London, United Kingdom
| | - Helen L Lowe
- University College London Experimental Cancer Medicine Centre Good Clinical Laboratory Practice Facility, University College London, London, United Kingdom
| | - May Zaw Thin
- Centre for Advanced Biomedical Imaging, University College London, London, United Kingdom
| | - Julian Hague
- University College London Hospitals NHS Foundation Trust, London, United Kingdom
| | - Dinesh Sharma
- Division of Transplantation and Immunology, Royal Free Hospital NHS Foundation Trust, London, United Kingdom
| | - Joerg-Matthias Pollok
- Division of Surgery and Interventional Science, University College London, London, United Kingdom
- Hepatopancreatobiliary Surgery and Liver Transplantation, Royal Free Hospital NHS Foundation Trust, London, United Kingdom
| | - Brian R Davidson
- Division of Surgery and Interventional Science, University College London, London, United Kingdom
- Hepatopancreatobiliary Surgery and Liver Transplantation, Royal Free Hospital NHS Foundation Trust, London, United Kingdom
| | - Jowad Raja
- University College London Hospitals NHS Foundation Trust, London, United Kingdom
| | - Graham Munneke
- University College London Hospitals NHS Foundation Trust, London, United Kingdom
| | - Daniel J Stuckey
- Centre for Advanced Biomedical Imaging, University College London, London, United Kingdom
| | | | | | | | | | | | | | - John A Hartley
- University College London Cancer Institute, University College London, London, United Kingdom
| | | | - Marnix Jansen
- University College London Cancer Institute, University College London, London, United Kingdom
| | - Tim Meyer
- University College London Cancer Institute, University College London, London, United Kingdom
- Department of Oncology, Royal Free Hospital NHS Foundation Trust, London, United Kingdom
| | - Ricky A Sharma
- National Institute for Health Research University College London Hospitals Biomedical Centre, University College London Cancer Institute, London, United Kingdom
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Change in Perfusion Angiography During Transcatheter Arterial Chemoembolization for Hepatocellular Carcinoma Predicts Short-Term Outcomes. AJR Am J Roentgenol 2019; 213:746-754. [DOI: 10.2214/ajr.18.20499] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
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Inchingolo R, Posa A, Mariappan M, Spiliopoulos S. Locoregional treatments for hepatocellular carcinoma: Current evidence and future directions. World J Gastroenterol 2019; 25:4614-4628. [PMID: 31528090 PMCID: PMC6718039 DOI: 10.3748/wjg.v25.i32.4614] [Citation(s) in RCA: 57] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2019] [Revised: 07/12/2019] [Accepted: 07/19/2019] [Indexed: 02/06/2023] Open
Abstract
Liver cancers are the second most frequent cause of global cancer-related mortality of which 90% are attributable to hepatocellular carcinoma (HCC). Despite the advent of screening programmes for patients with known risk factors, a substantial number of patients are ineligible for curative surgery at presentation with limited outcomes achievable with systemic chemotherapy/external radiotherapy. This has led to the advent of numerous minimally invasive options including but not limited to trans-arterial chemoembolization, radiofrequency/microwave ablation and more recently selective internal radiation therapy many of which are often the first-line treatment for select stages of HCC or serve as a conduit to liver transplant. The authors aim to provide a comprehensive overview of these various image guided minimally invasive therapies with a brief focus on the technical aspects accompanied by a critical analysis of the literature to assess the most up-to-date evidence from comparative systematic reviews and meta-analyses finishing with an assessment of novel combination regimens and future directions of travel.
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Affiliation(s)
- Riccardo Inchingolo
- Division of Interventional Radiology, Department of Radiology, Madonna delle Grazie Hospital, Matera 75100, Italy
- Department of Radiology, King´s College Hospital, London SE5 9RS, United Kingdom
| | - Alessandro Posa
- Department of Radiology, IRCSS Fatebenefratelli Hospital, Roma 00186, Italy
| | - Martin Mariappan
- Interventional Radiology Department, Aberdeen Royal Infirmary Hospital, Aberdeen AB25 2ZN, United Kingdom
| | - Stavros Spiliopoulos
- 2nd Radiology Department, School of Medicine; National and Kapodistrian University of Athens, Chaidari Athens 12461, Greece
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Hu J, Albadawi H, Oklu R, Chong BW, Deipolyi AR, Sheth RA, Khademhosseini A. Advances in Biomaterials and Technologies for Vascular Embolization. ADVANCED MATERIALS (DEERFIELD BEACH, FLA.) 2019; 31:e1901071. [PMID: 31168915 PMCID: PMC7014563 DOI: 10.1002/adma.201901071] [Citation(s) in RCA: 143] [Impact Index Per Article: 23.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/15/2019] [Revised: 03/24/2019] [Indexed: 05/03/2023]
Abstract
Minimally invasive transcatheter embolization is a common nonsurgical procedure in interventional radiology used for the deliberate occlusion of blood vessels for the treatment of diseased or injured vasculature. A wide variety of embolic agents including metallic coils, calibrated microspheres, and liquids are available for clinical practice. Additionally, advances in biomaterials, such as shape-memory foams, biodegradable polymers, and in situ gelling solutions have led to the development of novel preclinical embolic agents. The aim here is to provide a comprehensive overview of current and emerging technologies in endovascular embolization with respect to devices, materials, mechanisms, and design guidelines. Limitations and challenges in embolic materials are also discussed to promote advancement in the field.
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Affiliation(s)
- Jingjie Hu
- Division of Vascular & Interventional Radiology, Minimally Invasive Therapeutics Laboratory, Mayo Clinic, 13400 East Shea Blvd., Scottsdale, Arizona 85259, USA
| | - Hassan Albadawi
- Division of Vascular & Interventional Radiology, Minimally Invasive Therapeutics Laboratory, Mayo Clinic, 13400 East Shea Blvd., Scottsdale, Arizona 85259, USA
| | - Rahmi Oklu
- Division of Vascular & Interventional Radiology, Minimally Invasive Therapeutics Laboratory, Mayo Clinic, 13400 East Shea Blvd., Scottsdale, Arizona 85259, USA
| | - Brian W Chong
- Departments of Radiology and Neurological Surgery, Mayo Clinic, 13400 East Shea Blvd., Scottsdale, Arizona 85259, USA
| | - Amy R. Deipolyi
- Department of Interventional Radiology, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical Center, 1275 York Avenue, New York, New York 10065, USA
| | - Rahul A. Sheth
- Department of Interventional Radiology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77054, USA
| | - Ali Khademhosseini
- Department of Bioengineering, Department of Radiological Sciences, Department of Chemical and Biomolecular Engineering, Center for Minimally Invasive Therapeutics, California Nanosystems Institute, University of California, 410 Westwood Plaza, Los Angeles, California 90095, USA
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Caine M, Chung T, Kilpatrick H, Bascal Z, Willis S, Tang Y, de Baere T, Dreher M, Lewis A. Evaluation of novel formulations for transarterial chemoembolization: combining elements of Lipiodol emulsions with Drug-eluting Beads. Am J Cancer Res 2019; 9:5626-5641. [PMID: 31534507 PMCID: PMC6735388 DOI: 10.7150/thno.34778] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2019] [Accepted: 06/19/2019] [Indexed: 02/06/2023] Open
Abstract
There are currently two methods widely used in clinical practice to perform transarterial chemoembolization (TACE). One is based on mixing an aqueous drug with an iodized oil (Lipiodol) and creating an emulsion that is delivered intraarterially, followed by embolization with a particulate agent. The other is based on a one-step TACE using Drug-eluting Beads (DEBs) loaded with drug. It is not recommended to mix Lipiodol with DEBs due to incompatibility. For the first time, novel DEB: Lipiodol: doxorubicin (Dox) emulsions are identified using lyophilized polyvinyl alcohol (PVA) hydrogels (non-iodinated or iodinated) DEBs. Methods: 15 DEB emulsions (50mg Dox) were assessed for stability and deliverability in vitro and in vivo in a swine model. Dox release from selected formulations was measured in vitro using a vascular flow model and in vivo in a VX2 rabbit tumor model. Results: Both DEB formats were shown to be able to form emulsions, however only Iodinated DEBs consistently met defined handling criteria. Those based on the non-iodinated DEB achieved >99%+ Dox loading in <5 minutes but were generally less stable. Those prepared using iodinated DEBs, which are more hydrophobic, were able to form stable Pickering-like emulsions (separation time ≥ 20 minutes) and demonstrated handling, administration and imaging observations more akin to Lipiodol™ TACE emulsions in both embolization models. Controlled Dox release and hence beneficial in vivo pharmacokinetics associated with DEB-TACE were maintained. Conclusions: This study demonstrates that it is possible to formulate novel DEB emulsions suitable for TACE that combine positive elements of both Lipiodol™ based and DEB-TACE procedures.
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Cho S, Min NG, Park W, Kim SH, Kim DH. Janus Microcarriers for Magnetic Field-controlled Combination Chemotherapy of Hepatocellular Carcinoma †. ADVANCED FUNCTIONAL MATERIALS 2019; 29:1901384. [PMID: 38957778 PMCID: PMC11219019 DOI: 10.1002/adfm.201901384] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/15/2019] [Indexed: 07/04/2024]
Abstract
Combination chemotherapy administering multiple chemo-agents is widely exploited for the treatment of various cancers in the clinic. Specially for hepatocellular carcinoma (HCC), one of the most common malignancies, a co-administration of combinational cytostatic multi-kinase inhibitors and cytotoxic chemo-agents has been suggested as a potential curative approach. Here, Janus microcarriers were developed for the controlled local combination chemotherapy of HCC. The Janus microcarriers are composed of polycaprolactone (PCL) compartment and magnetic nanoparticles-loaded poly(lactide-co-glycolic acid) (PLGA) compartment which contain hydrophobic regorafenib and hydrophilic doxorubicin, respectively. Exploiting the magnetic anisotropy, rotational motion of the Janus microcarriers is controlled with magnetic field, which enables the active co-release of dual chemo-agents. Furthermore, Janus microcarriers exhibit magnetic resonance (MR) contrast effect, supporting the successful transcatheter intra-arterial delivery of the combination chemo-agents loaded the microcarriers to the targeted tumor. This Janus microcarriers potentially serve as a general combinational chemo-therapeutic platform for the co-delivery of various combinations of multi-chemo-agents.
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Affiliation(s)
- Soojeong Cho
- Department of Radiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA
| | - Nam Gi Min
- Department of Chemical and Biomolecular Engineering, KAIST, Daejeon, South Korea
| | - Wooram Park
- Department of Radiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA
| | - Shin-Hyun Kim
- Department of Chemical and Biomolecular Engineering, KAIST, Daejeon, South Korea
| | - Dong-Hyun Kim
- Robert H. Lurie Comprehensive Cancer Center, Chicago, Illinois 60611, USA
- Department of Radiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA
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Fidelman N, Johanson C, Kohi MP, Kolli KP, Kohlbrenner RM, Lehrman ED, Taylor AG, Kelley RK, Yao FY, Roberts JP, Kerlan RK. Prospective Phase II trial of drug-eluting bead chemoembolization for liver transplant candidates with hepatocellular carcinoma and marginal hepatic reserve. J Hepatocell Carcinoma 2019; 6:93-103. [PMID: 31355158 PMCID: PMC6588798 DOI: 10.2147/jhc.s206979] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2019] [Accepted: 05/07/2019] [Indexed: 12/27/2022] Open
Abstract
Purpose: To determine whether chemoembolization using drug-eluting beads (DEB-TACE) is safe and effective for liver transplantation candidates with liver-limited hepatocellular carcinoma (HCC) without vascular invasion and baseline hepatic dysfunction. Materials and methods: Seventeen adult liver transplantation candidates (median age 66 years, range 58–73 years; 13 men) with HCC were treated with DEB-TACE as a part of Stage 1 of a prospective single-institution Phase II trial. All patients had marginal hepatic reserve based on at least one of the following criteria: ascites (n=14), bilirubin between 3 and 6 mg/dL (n=5), AST 5–10 times upper normal limit (n=1), INR between 1.6 and 2.5 (n=4), portal vein thrombosis (n=2), and/or portosystemic shunt (n=2). Primary study objectives were safety and best observed radiographic response. Results: Thirty-seven DEB-TACE procedures were performed. Objective response rate and disease control rate were 63% and 88%, respectively. HCC progression was observed in 12 patients. Median time to progression was 5.6 months (range 0.9–13.6 months). Within 1 month following DEB-TACE, 13 patients (76%) developed grade 3 or 4 AE attributable to the procedure. Four patients (all within Milan Criteria) were transplanted (2.7–6.9 months after DEB-TACE), and 12 patients died (1.8–32 months after DEB-TACE). All deaths were due to liver failure that was either unrelated to HCC (n=5), in the setting of metastatic HCC (n=5), or in the setting of locally advanced HCC (n=2). Mortality rate at 1 month was 0%. Conclusions: DEB-TACE achieves tumor responses but carries a high risk of hepatotoxicity for liver transplant candidates with HCC and marginal hepatic reserve.
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Affiliation(s)
| | | | | | | | | | | | | | - R Kate Kelley
- Department of Medicine - Division of Gastrointestinal Oncology
| | | | - John P Roberts
- Department of Surgery - Division of Transplant Surgery, University of California San Francisco, San Francisco, CA, USA
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Abstract
With the increasing incidence of hepatocellular carcinoma (HCC) and its high mortality rates, effective treatment options are of urgent need, preferably in a multidisciplinary setting. In the management of those patients, interventional radiologists play a key role. In this article, we reviewed the current literature for regional, intraarterial treatment strategies of advanced-stage HCC including conventional transarterial chemoembolization, transarterial embolization, transarterial embolization with drug-eluting beads, and selective internal radiation therapy.
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Affiliation(s)
- Thomas J Vogl
- Institute for Diagnostic and Interventional Radiology, University Hospital Frankfurt, Theodor-Stern-Kai 7, 60590, Frankfurt am Main, Germany.
| | - Tatjana Gruber-Rouh
- Institute for Diagnostic and Interventional Radiology, University Hospital Frankfurt, Theodor-Stern-Kai 7, 60590, Frankfurt am Main, Germany
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