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1
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DePietro DM, Li X, Shamimi-Noori SM. Chemoembolization Beyond Hepatocellular Carcinoma: What Tumors Can We Treat and When? Semin Intervent Radiol 2024; 41:27-47. [PMID: 38495263 PMCID: PMC10940046 DOI: 10.1055/s-0043-1777716] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/19/2024]
Abstract
Liver metastases are the most common malignancy found in the liver and are 20 to 40 times more common than primary hepatic tumors, including hepatocellular carcinoma. Patients with liver metastases often present with advanced disease and are not eligible for curative-intent surgery or ablative techniques. The unique hepatic arterial blood supply of liver metastases allows interventional radiologists to target these tumors with transarterial therapies. Transarterial chemoembolization (TACE) has been studied in the treatment of liver metastases originating from a variety of primary malignancies and has demonstrated benefits in terms of hepatic progression-free survival, overall survival, and symptomatic relief, among other benefits. Depending on the primary tumor from which they originate, liver metastases may have different indications for TACE, may utilize different TACE regimens and techniques, and may result in different post-procedural outcomes. This review offers an overview of TACE techniques and specific considerations in the treatment of liver metastases, provides an in-depth review of TACE in the treatment of liver metastases originating from colorectal cancer, neuroendocrine tumor, and uveal melanoma, which represent some of the many tumors beyond hepatocellular carcinoma that can be treated by TACE, and summarizes data regarding when one should consider TACE in their treatment algorithms.
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Affiliation(s)
- Daniel M. DePietro
- Division of Interventional Radiology, Department of Radiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
| | - Xin Li
- Department of Radiology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania
| | - Susan M. Shamimi-Noori
- Division of Interventional Radiology, Department of Radiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
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2
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Winuprasith T, Koirala P, McClements DJ, Khomein P. Emulsion Technology in Nuclear Medicine: Targeted Radionuclide Therapies, Radiosensitizers, and Imaging Agents. Int J Nanomedicine 2023; 18:4449-4470. [PMID: 37555189 PMCID: PMC10406121 DOI: 10.2147/ijn.s416737] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2023] [Accepted: 07/19/2023] [Indexed: 08/10/2023] Open
Abstract
Radiopharmaceuticals serve as a major part of nuclear medicine contributing to both diagnosis and treatment of several diseases, especially cancers. Currently, most radiopharmaceuticals are based on small molecules with targeting ability. However, some concerns over their stability or non-specific interactions leading to off-target localization are among the major challenges that need to be overcome. Emulsion technology has great potential for the fabrication of carrier systems for radiopharmaceuticals. It can be used to create particles with different compositions, structures, sizes, and surface characteristics from a wide range of generally recognized as safe (GRAS) materials, which allows their functionality to be tuned for specific applications. In particular, it is possible to carry out surface modifications to introduce targeting and stealth properties, as well as to control the particle dimensions to manipulate diffusion and penetration properties. Moreover, emulsion preparation methods are usually simple, economic, robust, and scalable, which makes them suitable for medical applications. In this review, we highlight the potential of emulsion technology in nuclear medicine for developing targeted radionuclide therapies, for use as radiosensitizers, and for application in radiotracer delivery in gamma imaging techniques.
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Affiliation(s)
| | - Pankaj Koirala
- Institute of Nutrition, Mahidol University, Nakhon Pathom, 73170, Thailand
| | - David J McClements
- Department of Food Science, University of Massachusetts Amherst, Amherst, MA, 01003, USA
| | - Piyachai Khomein
- Division of Nuclear Medicine, Department of Radiology, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand
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3
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Chang PY, Lee RC, Liang PC, Liu YS, Chuang VP, Wu DK, Cheng YF, Huang JI, Tseng HS, Hung CF, Wu RH, Chern MC, Cheng HM, Wu CH, Cheng SM, Chiang CL, Liang HL. Multidisciplinary Taiwan consensus for the use of conventional TACE in hepatocellular carcinoma treatment. Front Oncol 2023; 13:1186674. [PMID: 37427137 PMCID: PMC10328116 DOI: 10.3389/fonc.2023.1186674] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2023] [Accepted: 06/05/2023] [Indexed: 07/11/2023] Open
Abstract
Developed in early 1980s, transarterial chemoembolization (TACE) with Lipiodol was adopted globally after large-scale randomized control trials and meta-analyses proving its effectiveness were completed. Also known as "conventional TACE" (cTACE), TACE is currently the first-line treatment for patients with unresectable intermediate stage hepatocellular carcinoma (HCC) and delivers both ischemic and cytotoxic effects to targeted tumors. Although new technology and clinical studies have contributed to a more comprehensive understanding of when and how to apply this widely-adopted therapeutic modality, some of these new findings and techniques have yet to be incorporated into a guideline appropriate for Taiwan. In addition, differences in the underlying liver pathologies and treatment practices for transcatheter embolization between Taiwan and other Asian or Western populations have not been adequately addressed, with significant variations in the cTACE protocols adopted in different parts of the world. These mainly revolve around the amount and type of chemotherapeutic agents used, the type of embolic materials, reliance on Lipiodol, and the degree of selectiveness in catheter positioning. Subsequently, interpreting and comparing results obtained from different centers in a systematic fashion remain difficult, even for experienced practitioners. To address these concerns, we convened a panel of experts specializing in different aspects of HCC treatment to devise modernized recommendations that reflect recent clinical experiences, as well as cTACE protocols which are tailored for use in Taiwan. The conclusions of this expert panel are described herein.
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Affiliation(s)
- Pi-Yi Chang
- Department of Radiology, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Rheun-Chuan Lee
- Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Po-Chin Liang
- Department of Radiology, National Taiwan University Hospital Hsin-Chu Branch, Hsinchu, Taiwan
| | - Yi-Sheng Liu
- Department of Medical Imagine, National Cheng Kung University Hospital, Tainan, Taiwan
| | - Vicent P. Chuang
- Department of Radiology, Koo Foundation Sun Yat-Sen Cancer Center, Taipei, Taiwan
| | - Ding-Kwo Wu
- Department of Radiology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Yu-Fan Cheng
- Department of Radiology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Jen-I. Huang
- Department of Radiology, Tungs’ Taichung Metroharbor Hospital, Taichung, Taiwan
| | - Hsiuo-Shan Tseng
- Department of Radiology, Cheng Hsin General Hospital, Taipei, Taiwan
| | - Chien-Fu Hung
- Department of Radiology, Chang−Gung Memorial Hospital, Taoyuan, Taiwan
| | - Reng-Hong Wu
- Department of Radiology, Chi Mei Medical Center, Tainan, Taiwan
| | - Ming-Chih Chern
- Department of Radiology, Koo Foundation Sun Yat-Sen Cancer Center, Taipei, Taiwan
| | - Hua-Ming Cheng
- Department of Radiology, Chi Mei Medical Center, Tainan, Taiwan
| | - Chih-Horng Wu
- Department of Radiology, National Taiwan University Hospital Hsin-Chu Branch, Hsinchu, Taiwan
| | - She-Meng Cheng
- Department of Radiology, MacKay Memorial Hospital, Taipei, Taiwan
| | - Chia-Ling Chiang
- Department of Radiology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| | - Huei-Lung Liang
- Department of Radiology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
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Saghafian Larijani R, Shabani Ravari N, Goodarzi N, Akhlaghpour S, Saghafian Larijani S, Rouini MR, Dinarvand R. Current status of transarterial chemoembolization (TACE) agents in hepatocellular carcinoma treatment. J Drug Deliv Sci Technol 2022. [DOI: 10.1016/j.jddst.2022.103905] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
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de Baere T, Ronot M, Chung JW, Golfieri R, Kloeckner R, Park JW, Gebauer B, Kibriya N, Ananthakrishnan G, Miyayama S. Initiative on Superselective Conventional Transarterial Chemoembolization Results (INSPIRE). Cardiovasc Intervent Radiol 2022; 45:1430-1440. [PMID: 35978174 PMCID: PMC9499883 DOI: 10.1007/s00270-022-03233-9] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2022] [Accepted: 07/18/2022] [Indexed: 12/05/2022]
Abstract
Several publications show that superselective conventional TransArterial ChemoEmbolization (cTACE), meaning cTACE performed selectively with a microcatheter positioned as close as possible to the tumor, improves outcomes, maximizing the anti-tumoral effect and minimizing the collateral damages of the surrounding liver parenchyma. Recent recommendations coming from the European Association for the Study of the Liver (EASL) and European Society of Medical Oncology (ESMO) highlighted that TACE must be used in Hepatocellular Carcinoma (HCC) "selectively targetable" and "accessible to supraselective catheterization." The goal of the manuscript is to better define such population and to standardize superselective cTACE (ss-cTACE) technique. An expert panel with extensive clinical-procedural experience in TACE, have come together in a virtual meeting to generate recommendations and express their consensus. Experts recommend that anytime cTACE is proposed, it should be ss-cTACE, preferably with a 1.5-2.0 Fr microcatheter. Ideally, ss-cTACE should be proposed to patients with less than five lesions and a maximum number of two segments involved, with largest tumor smaller than 5 cm. Angio Cone-Beam Computed Tomography (CBCT) should be used to detect enhancing tumors, tumor feeders and guide tumor targeting. Whole tumor volume should be covered to obtain the best response. Adding peritumoral margins is encouraged but not mandatory. The treatment should involve a water-in-oil emulsion, whose quality is assessable with the "drop test." Additional particulate embolization should be systematically performed, as per definition of cTACE procedure. Non-contrast CBCT or Multi-Detector Computed Tomography (MDCT) combined with angiography has been considered the gold standard for imaging during TACE, and should be used to assess tumor coverage during the procedure. Experts convene that superselectivity decreases incidence of adverse effects and improves tolerance. Experts recommend contrast-enhanced Computed Tomography (CT) as initial imaging on first follow-up after ss-cTACE, and Magnetic Resonance Imaging (MRI) if remaining tumor viability cannot be confidently assessed on CT. If no response is obtained after two ss-cTACE sessions within six months, patient must be considered unsuitable for TACE and proposed for alternative therapy. Patients are best served by multidisciplinary decision-making, and Interventional Radiologists should take an active role in patient selection, treatment allocation, and post-procedural care.
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Affiliation(s)
- Thierry de Baere
- Institut Gustave Roussy, Service Radiodiagnostic et Imagerie Médicale, 39, rue Camille Desmoulins, 94800, Villejuif, France.
| | - Maxime Ronot
- Department of Medical Imaging, Beaujon University Hospital, Clichy, France
| | - Jin Wook Chung
- Department of Radiology, Seoul National University College of Medicine, Seoul, South Korea
| | - Rita Golfieri
- Unità Operativa Radiologia Universitaria (Pad 1, 2), Dipartimento delle Radiologie, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Policlinico S. Orsola-Malpighi, Bologna, Italy
| | - Roman Kloeckner
- Radiology Department, Mainz University: Johannes Gutenberg Universitat Mainz, Mainz, Germany
| | - Joong-Won Park
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center (NCC), Goyang-si, South Korea
| | - Bernhard Gebauer
- Department of Diagnostic Radiology, Charité Universitätsmedizin Berlin, Campus Virchow-Klinikum: Charite, Berlin, Germany
| | - Nabil Kibriya
- Department of Radiology, Kings College Hospital, NHS Foundation Trust, London, UK
| | | | - Shiro Miyayama
- Department of Diagnostic Radiology, Fukui-Ken Saiseikai Hospital, Fukui, Japan
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Pascale F, Pelage JP, Wassef M, Ghegediban SH, Saint-Maurice JP, De Baere T, Denys A, Duran R, Deschamps F, Pellerin O, Maeda N, Laurent A, Namur J. Rabbit VX2 Liver Tumor Model: A Review of Clinical, Biology, Histology, and Tumor Microenvironment Characteristics. Front Oncol 2022; 12:871829. [PMID: 35619923 PMCID: PMC9128410 DOI: 10.3389/fonc.2022.871829] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2022] [Accepted: 04/05/2022] [Indexed: 11/17/2022] Open
Abstract
The rabbit VX2 is a large animal model of cancer used for decades by interventional radiologists to demonstrate the efficacy of various locoregional treatments against liver tumors. What do we know about this tumor in the new era of targeted therapy and immune-oncology? The present paper describes the current knowledge on the clinics, biology, histopathology, and tumor microenvironment of VX2 based on a literature review of 741 publications in the liver and in other organs. It reveals the resemblance with human cancer (anatomy, vascularity, angiogenic profile, drug sensitivity, immune microenvironment), the differences (etiology, growth rate, histology), and the questions still poorly explored (serum and tissue biomarkers, genomic alterations, immune checkpoint inhibitors efficacy).
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Affiliation(s)
- Florentina Pascale
- Research and Development Department, Archimmed Société à responsabilité limtée Limited liability Company (SARL), Jouy-en-Josas, France
| | - Jean-Pierre Pelage
- Université de Caen Normandie (UNICEAN), Centre d'Energie atomique (CEA), Centre National de la Recherche Scientifique, Imagerie et Stratégies Thérapeutiques pour les Cancers et Tissus Cérébraux CERVOxy (ISTCT-CERVOxy) Normandie University, Caen, France.,Department of Interventional and Diagnostic Imaging, University Hospital of Caen, Avenue de la Côte de Nacre, Caen, France
| | - Michel Wassef
- Service d'Anatomie et Cytologie Pathologiques, Hôpital Lariboisière, Assistance Publique Hopitaux de Paris (APHP); Unité de Formation et de Recherche (URF) de Médecine Paris Nord, Université de Paris, Paris, France
| | - Saïda H Ghegediban
- Research and Development Department, Archimmed Société à responsabilité limtée Limited liability Company (SARL), Jouy-en-Josas, France
| | - Jean-Pierre Saint-Maurice
- Department of Neuroradiology, Hôpital Lariboisière, Assistance Publique Hopitaux de Paris (APHP); Unité de Formation et de Recherche (URF) de Médecine Paris Nord, Université de Paris, Paris, France
| | - Thierry De Baere
- Department of Interventional Radiology, Gustave Roussy Cancer Center, Villejuif, France.,Unité de Formation et de Recherche (URF) Médecine Le Kremlin-Bicêtre, Université Paris-Saclay, Le Kremlin-Bicêtre, France
| | - Alban Denys
- Department of Radiology and Interventional Radiology, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland
| | - Rafael Duran
- Department of Radiology and Interventional Radiology, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland
| | - Frédéric Deschamps
- Department of Interventional Radiology, Gustave Roussy Cancer Center, Villejuif, France.,Unité de Formation et de Recherche (URF) Médecine Le Kremlin-Bicêtre, Université Paris-Saclay, Le Kremlin-Bicêtre, France
| | - Olivier Pellerin
- Department of Interventional Radiology, Hôpital Européen Georges Pompidou, Assistance Publique Hopitaux de Paris (APHP) Université de Paris, Paris, France
| | - Noboru Maeda
- Department of Diagnostic and Interventional Radiology, Osaka International Cancer Institute, Osaka, Japan
| | - Alexandre Laurent
- Department of Neuroradiology, Hôpital Lariboisière, Assistance Publique Hopitaux de Paris (APHP); Unité de Formation et de Recherche (URF) de Médecine Paris Nord, Université de Paris, Paris, France
| | - Julien Namur
- Research and Development Department, Archimmed Société à responsabilité limtée Limited liability Company (SARL), Jouy-en-Josas, France
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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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Zhu J, Chu C, Li D, Zhang Y, Cheng Y, Lin H, Wang X, Liu J, Pang X, Cheng J, Liu G. Superior Fluorescent Nanoemulsion Illuminates Hepatocellular Carcinoma for Surgical Navigation. Front Bioeng Biotechnol 2022; 10:890668. [PMID: 35547157 PMCID: PMC9081524 DOI: 10.3389/fbioe.2022.890668] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2022] [Accepted: 04/08/2022] [Indexed: 01/16/2023] Open
Abstract
Hepatocellular carcinoma (HCC), the fifth most common cancer worldwide, poses a severe threat to public health. Intraoperative fluorescence imaging provides a golden opportunity for surgeons to visualize tumor-involved margins, thereby implementing precise HCC resection with minimal damage to normal tissues. Here, a novel-acting contrast agent, which facilely bridges indocyanine green (ICG) and lipiodol using self-emulsifying nanotechnology, was developed for optical surgical navigation. Compared to clinically available ICG probe, our prepared nanoemulsion showed obviously red-shifted optical absorption and enhanced fluorescence intensity. Further benefiting from the shielding effect of lipiodol, the fluorescence stability and anti-photobleaching ability of nanoemulsion were highly improved, indicating a great capacity for long-lasting in vivo intraoperative imaging. Under the fluorescence guidance of nanoemulsion, the tumor tissues were clearly delineated with a signal-to-noise ratio above 5-fold, and then underwent a complete surgical resection from orthotopic HCC-bearing mice. Such superior fluorescence performances, ultrahigh tumor-to-liver contrast, as well as great bio-safety, warrants the great translational potential of nanoemulsion in precise HCC imaging and intraoperative navigation.
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Affiliation(s)
- Jing Zhu
- Department of Magnetic Resonance Imaging, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, China
| | - Chengchao Chu
- Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, China
| | - Dongsheng Li
- Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, China
| | - Yang Zhang
- Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, China
| | - Yi Cheng
- Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, China
| | - Huirong Lin
- Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, China
| | - Xiaoyong Wang
- Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, China
| | - Junxian Liu
- Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, China
| | - Xin Pang
- Department of Magnetic Resonance Imaging, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, China
| | - Jingliang Cheng
- Department of Magnetic Resonance Imaging, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Gang Liu
- Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, China
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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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10
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Higashihara H, Ono Y, Tanaka K, Tomotake K, Tomiyama N. Recent technical advances in conventional transarterial chemoembolization for hepatocellular carcinoma in Japan. INTERNATIONAL JOURNAL OF GASTROINTESTINAL INTERVENTION 2021. [DOI: 10.18528/ijgii210042] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Affiliation(s)
- Hiroki Higashihara
- Department of Diagnostic and Interventional Radiology, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Yusuke Ono
- Department of Diagnostic and Interventional Radiology, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Kaisyu Tanaka
- Department of Diagnostic and Interventional Radiology, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Kosuke Tomotake
- Department of Diagnostic and Interventional Radiology, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Noriyuki Tomiyama
- Department of Diagnostic and Interventional Radiology, Osaka University Graduate School of Medicine, Osaka, Japan
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11
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Lucatelli P, Burrel M, Guiu B, de Rubeis G, van Delden O, Helmberger T. CIRSE Standards of Practice on Hepatic Transarterial Chemoembolisation. Cardiovasc Intervent Radiol 2021; 44:1851-1867. [PMID: 34694454 DOI: 10.1007/s00270-021-02968-1] [Citation(s) in RCA: 52] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2021] [Accepted: 09/04/2021] [Indexed: 12/15/2022]
Abstract
This CIRSE Standards of Practice document is aimed at interventional radiologists and provides best practices for performing transarterial chemoembolisation. It has been developed by an expert writing group under the guidance of the CIRSE Standards of Practice Committee. It will encompass all technical details reflecting European practice of different TACE procedures (Lp-TACE, DEM-TACE, DSM-TACE, b-TACE) as well as revising the existing literature on the various clinical indications (HCC, mCRC, ICC, NET). Finally, new frontiers of development will also be discussed.
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Affiliation(s)
- Pierleone Lucatelli
- Vascular and Interventional Radiology Unit, Department of Radiological Oncological and Anatomo-Pathological Sciences, Sapienza University of Rome, Rome, Italy.
| | - Marta Burrel
- Radiology Department, Hospital Clínic of Barcelona, Barcelona, Spain
| | - Boris Guiu
- Department of Radiology, Montpellier School of Medicine, St-Eloi University Hospital, Montpellier, France
| | - Gianluca de Rubeis
- Vascular and Interventional Radiology Unit, Department of Radiological Oncological and Anatomo-Pathological Sciences, Sapienza University of Rome, Rome, Italy
- Department of Diagnostic Radiology, Azienda Ospedaliera San Camillo Forlanini, Rome, Italy
| | - Otto van Delden
- Department of Interventional Radiology, Amsterdam University Medical Centers, Amsterdam, The Netherlands
| | - Thomas Helmberger
- Institute for Diagnostic and Interventional Radiology and Neuroradiology, Bogenhausen Hospital, Munich, Germany
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12
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Melancon MP, Yevich S, Avritscher R, Swigost A, Lu L, Tian L, Damasco JA, Dixon K, Cortes AC, Munoz NM, Liang D, Liu D, Tam AL. A novel irinotecan-lipiodol nanoemulsion for intravascular administration: pharmacokinetics and biodistribution in the normal and tumor bearing rat liver. Drug Deliv 2021; 28:240-251. [PMID: 33501859 PMCID: PMC8725905 DOI: 10.1080/10717544.2020.1869863] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Colorectal cancer is one of the most common cancers in the United States and treatment options are limited for patients who develop liver metastases. Several chemotherapeutic regimens have been used for transvascular liver-directed therapy in the treatment of colorectal liver metastases without clear evidence of superiority of one therapy over another. We describe the development of a novel nanoemulsion through combining irinotecan (IRI), a first line systemic agent used for the treatment of colon cancer, with lipiodol, an oily contrast medium derived from poppy seed oil, and evaluated its pharmacokinetic and biodistribution profile as a function of portal venous chemoembolization (PVCE) versus transarterial chemoembolization (TACE) delivery. The Tessari technique was used to create a stable emulsion (20 mg IRI mixed with 2 mL lipiodol) with resultant particle size ranging from 28.9 nm to 56.4 nm. Pharmacokinetic profile established through venous sampling in Buffalo rats demonstrate that the area under the curve (AUC0−∞) of IRI was significantly less after PVCE with IRI-lipiodol as compared to IRI alone (131 vs. 316 µg*min/mL, p-value = .023), suggesting significantly higher amounts of IRI retention in the liver with the IRI-lipiodol nanoemulsion via first-pass extraction. Subseqent biodistribution studies in tumor-bearing WAG/Rjj rats revealed more IRI present in the tumor following TACE versus PVCE (29.19 ± 12.33 µg/g versus 3.42 ± 1.62; p-value = .0033) or IV (29.19 ± 12.33 µg/g versus 1.05 ± 0.47; p-value = .0035). The IRI-lipiodol nanoemulsion demonstrated an acceptable hepatotoxicity profile in all routes of administration. In conclusion, the IRI-lipiodol nanoemulsion via TACE showed promise and warrants further investigation as an option for the treatment of metastatic colorectal cancer.
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Affiliation(s)
- Marites P Melancon
- Department of Interventional Radiology, Division of Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.,The University of Texas MD Anderson Cancer Center UT Health Graduate School of Biomedical Sciences, Houston, TX, USA
| | - Steven Yevich
- Department of Interventional Radiology, Division of Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Rony Avritscher
- Department of Interventional Radiology, Division of Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Adam Swigost
- Department of Interventional Radiology, Division of Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.,Medstar Georgetown University Hospital, Washington Hospital Center, Washington, DC, USA
| | - Linfeng Lu
- Department of Interventional Radiology, Division of Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.,Baylor College of Medicine, Houston, TX, USA
| | - Li Tian
- Department of Interventional Radiology, Division of Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Jossana A Damasco
- Department of Interventional Radiology, Division of Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Katherine Dixon
- Department of Interventional Radiology, Division of Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Andrea C Cortes
- Department of Interventional Radiology, Division of Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Nina M Munoz
- Department of Interventional Radiology, Division of Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Dong Liang
- College of Pharmacy and Health Sciences, Texas Southern University, Houston, TX, USA
| | - David Liu
- The University of British Columbia, Vancouver, Canada
| | - Alda L Tam
- Department of Interventional Radiology, Division of Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
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13
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Boas FE, Kemeny NE, Sofocleous CT, Yeh R, Thompson VR, Hsu M, Moskowitz CS, Ziv E, Yarmohammadi H, Bendet A, Solomon SB. Bronchial or Pulmonary Artery Chemoembolization for Unresectable and Unablatable Lung Metastases: A Phase I Clinical Trial. Radiology 2021; 301:474-484. [PMID: 34463550 DOI: 10.1148/radiol.2021210213] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
Background Lung chemoembolization is an emerging treatment option for lung tumors, but the optimal embolic, drug, and technique are unknown. Purpose To determine the technical success rate and safety of bronchial or pulmonary artery chemoembolization of lung metastases using ethiodized oil, mitomycin, and microspheres. Materials and Methods Patients with unresectable and unablatable lung, endobronchial, or mediastinal metastases, who failed systemic chemotherapy, were enrolled in this prospective, single-center, single-arm, phase I clinical trial (December 2019-September 2020). Pulmonary and bronchial angiography was performed to determine the blood supply to the lung metastases. Based on the angiographic findings, bronchial or pulmonary artery chemoembolization was performed using an ethiodized oil and mitomycin emulsion, followed by microspheres. The primary objectives were technical success rate and safety, according to the National Cancer Institute Common Terminology Criteria for Adverse Events. CIs of proportions were estimated with the equal-tailed Jeffreys prior interval, and correlations were evaluated with the Spearman test. Results Ten participants (median age, 60 years; interquartile range, 52-70 years; six women) were evaluated. Nine of the 10 participants (90%) had lung metastases supplied by the bronchial artery, and one of the 10 participants (10%) had lung metastases supplied by the pulmonary artery. The technical success rate of intratumoral drug delivery was 10 of 10 (100%) (95% CI: 78, 100). There were no severe adverse events (95% CI: 0, 22). The response rate of treated tumors was one of 10 (10%) according to the Response Evaluation Criteria in Solid Tumors and four of 10 (40%) according to the PET Response Criteria in Solid Tumors. Ethiodized oil retention at 4-6 weeks was correlated with reduced tumor size (ρ = -0.83, P = .003) and metabolic activity (ρ = -0.71, P = .03). Pharmacokinetics showed that 45% of the mitomycin dose underwent burst release in 2 minutes, and 55% of the dose was retained intratumorally with a half-life of more than 5 hours. The initial tumor-to-plasma ratio of mitomycin concentration was 380. Conclusion Lung chemoembolization was technically successful for the treatment of lung, mediastinal, and endobronchial metastases, with no severe adverse events. Clinical trial registration no. NCT04200417 © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Georgiades et al in this issue.
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Affiliation(s)
- F Edward Boas
- From the Department of Radiology, City of Hope Cancer Center, 1500 E Duarte Rd, Duarte, CA 91010 (F.E.B.); Interventional Radiology Service, Department of Radiology (F.E.B., C.T.S., E.Z., H.Y., A.B., S.B.S.), Department of Medicine (N.E.K.), Molecular Imaging and Therapy Service (R.Y.), and Department of Epidemiology and Biostatistics (M.H., C.S.M.), Memorial Sloan-Kettering Cancer Center, New York, NY; and Antitumor Assessment Core Facility, Sloan Kettering Institute, New York, NY (V.R.T.)
| | - Nancy E Kemeny
- From the Department of Radiology, City of Hope Cancer Center, 1500 E Duarte Rd, Duarte, CA 91010 (F.E.B.); Interventional Radiology Service, Department of Radiology (F.E.B., C.T.S., E.Z., H.Y., A.B., S.B.S.), Department of Medicine (N.E.K.), Molecular Imaging and Therapy Service (R.Y.), and Department of Epidemiology and Biostatistics (M.H., C.S.M.), Memorial Sloan-Kettering Cancer Center, New York, NY; and Antitumor Assessment Core Facility, Sloan Kettering Institute, New York, NY (V.R.T.)
| | - Constantinos T Sofocleous
- From the Department of Radiology, City of Hope Cancer Center, 1500 E Duarte Rd, Duarte, CA 91010 (F.E.B.); Interventional Radiology Service, Department of Radiology (F.E.B., C.T.S., E.Z., H.Y., A.B., S.B.S.), Department of Medicine (N.E.K.), Molecular Imaging and Therapy Service (R.Y.), and Department of Epidemiology and Biostatistics (M.H., C.S.M.), Memorial Sloan-Kettering Cancer Center, New York, NY; and Antitumor Assessment Core Facility, Sloan Kettering Institute, New York, NY (V.R.T.)
| | - Randy Yeh
- From the Department of Radiology, City of Hope Cancer Center, 1500 E Duarte Rd, Duarte, CA 91010 (F.E.B.); Interventional Radiology Service, Department of Radiology (F.E.B., C.T.S., E.Z., H.Y., A.B., S.B.S.), Department of Medicine (N.E.K.), Molecular Imaging and Therapy Service (R.Y.), and Department of Epidemiology and Biostatistics (M.H., C.S.M.), Memorial Sloan-Kettering Cancer Center, New York, NY; and Antitumor Assessment Core Facility, Sloan Kettering Institute, New York, NY (V.R.T.)
| | - Vanessa R Thompson
- From the Department of Radiology, City of Hope Cancer Center, 1500 E Duarte Rd, Duarte, CA 91010 (F.E.B.); Interventional Radiology Service, Department of Radiology (F.E.B., C.T.S., E.Z., H.Y., A.B., S.B.S.), Department of Medicine (N.E.K.), Molecular Imaging and Therapy Service (R.Y.), and Department of Epidemiology and Biostatistics (M.H., C.S.M.), Memorial Sloan-Kettering Cancer Center, New York, NY; and Antitumor Assessment Core Facility, Sloan Kettering Institute, New York, NY (V.R.T.)
| | - Meier Hsu
- From the Department of Radiology, City of Hope Cancer Center, 1500 E Duarte Rd, Duarte, CA 91010 (F.E.B.); Interventional Radiology Service, Department of Radiology (F.E.B., C.T.S., E.Z., H.Y., A.B., S.B.S.), Department of Medicine (N.E.K.), Molecular Imaging and Therapy Service (R.Y.), and Department of Epidemiology and Biostatistics (M.H., C.S.M.), Memorial Sloan-Kettering Cancer Center, New York, NY; and Antitumor Assessment Core Facility, Sloan Kettering Institute, New York, NY (V.R.T.)
| | - Chaya S Moskowitz
- From the Department of Radiology, City of Hope Cancer Center, 1500 E Duarte Rd, Duarte, CA 91010 (F.E.B.); Interventional Radiology Service, Department of Radiology (F.E.B., C.T.S., E.Z., H.Y., A.B., S.B.S.), Department of Medicine (N.E.K.), Molecular Imaging and Therapy Service (R.Y.), and Department of Epidemiology and Biostatistics (M.H., C.S.M.), Memorial Sloan-Kettering Cancer Center, New York, NY; and Antitumor Assessment Core Facility, Sloan Kettering Institute, New York, NY (V.R.T.)
| | - Etay Ziv
- From the Department of Radiology, City of Hope Cancer Center, 1500 E Duarte Rd, Duarte, CA 91010 (F.E.B.); Interventional Radiology Service, Department of Radiology (F.E.B., C.T.S., E.Z., H.Y., A.B., S.B.S.), Department of Medicine (N.E.K.), Molecular Imaging and Therapy Service (R.Y.), and Department of Epidemiology and Biostatistics (M.H., C.S.M.), Memorial Sloan-Kettering Cancer Center, New York, NY; and Antitumor Assessment Core Facility, Sloan Kettering Institute, New York, NY (V.R.T.)
| | - Hooman Yarmohammadi
- From the Department of Radiology, City of Hope Cancer Center, 1500 E Duarte Rd, Duarte, CA 91010 (F.E.B.); Interventional Radiology Service, Department of Radiology (F.E.B., C.T.S., E.Z., H.Y., A.B., S.B.S.), Department of Medicine (N.E.K.), Molecular Imaging and Therapy Service (R.Y.), and Department of Epidemiology and Biostatistics (M.H., C.S.M.), Memorial Sloan-Kettering Cancer Center, New York, NY; and Antitumor Assessment Core Facility, Sloan Kettering Institute, New York, NY (V.R.T.)
| | - Achiude Bendet
- From the Department of Radiology, City of Hope Cancer Center, 1500 E Duarte Rd, Duarte, CA 91010 (F.E.B.); Interventional Radiology Service, Department of Radiology (F.E.B., C.T.S., E.Z., H.Y., A.B., S.B.S.), Department of Medicine (N.E.K.), Molecular Imaging and Therapy Service (R.Y.), and Department of Epidemiology and Biostatistics (M.H., C.S.M.), Memorial Sloan-Kettering Cancer Center, New York, NY; and Antitumor Assessment Core Facility, Sloan Kettering Institute, New York, NY (V.R.T.)
| | - Stephen B Solomon
- From the Department of Radiology, City of Hope Cancer Center, 1500 E Duarte Rd, Duarte, CA 91010 (F.E.B.); Interventional Radiology Service, Department of Radiology (F.E.B., C.T.S., E.Z., H.Y., A.B., S.B.S.), Department of Medicine (N.E.K.), Molecular Imaging and Therapy Service (R.Y.), and Department of Epidemiology and Biostatistics (M.H., C.S.M.), Memorial Sloan-Kettering Cancer Center, New York, NY; and Antitumor Assessment Core Facility, Sloan Kettering Institute, New York, NY (V.R.T.)
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14
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Automated feature quantification of Lipiodol as imaging biomarker to predict therapeutic efficacy of conventional transarterial chemoembolization of liver cancer. Sci Rep 2020; 10:18026. [PMID: 33093524 PMCID: PMC7582153 DOI: 10.1038/s41598-020-75120-7] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2020] [Accepted: 10/09/2020] [Indexed: 02/08/2023] Open
Abstract
Conventional transarterial chemoembolization (cTACE) is a guideline-approved image-guided therapy option for liver cancer using the radiopaque drug-carrier and micro-embolic agent Lipiodol, which has been previously established as an imaging biomarker for tumor response. To establish automated quantitative and pattern-based image analysis techniques of Lipiodol deposition on 24 h post-cTACE CT as biomarker for treatment response. The density of Lipiodol deposits in 65 liver lesions was automatically quantified using Hounsfield Unit thresholds. Lipiodol deposition within the tumor was automatically assessed for patterns including homogeneity, sparsity, rim, and peripheral deposition. Lipiodol deposition was correlated with enhancing tumor volume (ETV) on baseline and follow-up MRI. ETV on baseline MRI strongly correlated with Lipiodol deposition on 24 h CT (p < 0.0001), with 8.22% ± 14.59 more Lipiodol in viable than necrotic tumor areas. On follow-up, tumor regions with Lipiodol showed higher rates of ETV reduction than areas without Lipiodol (p = 0.0475) and increasing densities of Lipiodol enhanced this effect. Also, homogeneous (p = 0.0006), non-sparse (p < 0.0001), rim deposition within sparse tumors (p = 0.045), and peripheral deposition (p < 0.0001) of Lipiodol showed improved response. This technical innovation study showed that an automated threshold-based volumetric feature characterization of Lipiodol deposits is feasible and enables practical use of Lipiodol as imaging biomarker for therapeutic efficacy after cTACE.
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15
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Yamada R, Bassaco B, Bracewell S, Volin S, Collins H, Hannegan C, Guimarares M. Combined conventional transarterial chemoembolization with Mitomycin and percutaneous ablation for unresectable hepatocellular carcinoma. J Gastrointest Oncol 2020; 11:298-303. [PMID: 32399271 DOI: 10.21037/jgo.2019.01.07] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Background Conventional transarterial chemoembolization (cTACE) has been the standard treatment for intermediate stage hepatocellular carcinoma (HCC). For early stage HCC, percutaneous ablation is a curative option. There is growing evidence to support combined therapy to improve tumor response and overall survival (OS) in patients with unresectable HCC. The goal of this study is to retrospectively review a single institution patient population who underwent the combined approach to determine its efficacy and safety, and possible predictive factors for OS and tumor response. Methods Retrospective analysis identified all patients that underwent c-TACE with Mitomycin followed by percutaneous ablation from 2011 to 2016 at our institution. Efficacy was assessed by OS, time to progression (TTP), and tumor response according to mRECIST criteria. Initial imaging was obtained 1 month after each treatment and after complete response was achieved, every 3 months for 2 years. Percentage of Lipiodol uptake was determined at 30-day follow-up with contrasted abdominal CT. Safety was assessed using Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Multiple linear regressions were conducted to predict OS and number of progression-free survival days based on potential predictive factors. Results A total of 50 patients were identified. At 1-month follow-up, objective response (CR + PR) was achieved in 44 patients (88%). The median OS was 26.6 months and median TTP was 9.7 months (n=50). There was no statistically significant difference in median OS between patients with different lesion size (P=0.95), BCLC stage (P=0.84) or Lipiodol uptake (P=0.36). Higher albumin/bilirubin ratio was significantly correlated with improved OS (P=0.024). Conclusions Combined c-TACE and PTA is a safe and effective approach for patients with unresectable HCC. Elevated albumin/bilirubin ratio was a predictor for improved OS.
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Affiliation(s)
- Ricardo Yamada
- Division of Vascular & Interventional Radiology, Department of Radiology, Medical University of South Carolina, Charleston, SC, USA
| | - Beatriz Bassaco
- Division of Vascular & Interventional Radiology, Department of Radiology, Medical University of South Carolina, Charleston, SC, USA
| | - Stephen Bracewell
- Division of Vascular & Interventional Radiology, Department of Radiology, Medical University of South Carolina, Charleston, SC, USA
| | - Samuel Volin
- Division of Vascular & Interventional Radiology, Department of Radiology, Medical University of South Carolina, Charleston, SC, USA
| | - Heather Collins
- Division of Vascular & Interventional Radiology, Department of Radiology, Medical University of South Carolina, Charleston, SC, USA
| | - Christopher Hannegan
- Division of Vascular & Interventional Radiology, Department of Radiology, Medical University of South Carolina, Charleston, SC, USA
| | - Marcelo Guimarares
- Division of Vascular & Interventional Radiology, Department of Radiology, Medical University of South Carolina, Charleston, SC, USA
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16
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Lord J, Britton H, Spain SG, Lewis AL. Advancements in the development on new liquid embolic agents for use in therapeutic embolisation. J Mater Chem B 2020; 8:8207-8218. [DOI: 10.1039/d0tb01576h] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
This review covers the current state-of-the-art in the development of liquid embolics for therapeutic embolisation.
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Affiliation(s)
- Jasmine Lord
- Department of Chemistry
- University of Sheffield
- Sheffield
- UK
| | - Hugh Britton
- Biocompatibles UK Ltd (a BTG International group company)
- Lakeview
- Camberley
- UK
| | | | - Andrew L. Lewis
- Biocompatibles UK Ltd (a BTG International group company)
- Lakeview
- Camberley
- UK
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17
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Savic LJ, Schobert IT, Peters D, Walsh JJ, Laage-Gaupp FM, Hamm CA, Tritz N, Doemel LA, Lin M, Sinusas A, Schlachter T, Duncan JS, Hyder F, Coman D, Chapiro J. Molecular Imaging of Extracellular Tumor pH to Reveal Effects of Locoregional Therapy on Liver Cancer Microenvironment. Clin Cancer Res 2019; 26:428-438. [PMID: 31582517 DOI: 10.1158/1078-0432.ccr-19-1702] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2019] [Revised: 07/24/2019] [Accepted: 09/30/2019] [Indexed: 02/06/2023]
Abstract
PURPOSE To establish magnetic resonance (MR)-based molecular imaging paradigms for the noninvasive monitoring of extracellular pH (pHe) as a functional surrogate biomarker for metabolic changes induced by locoregional therapy of liver cancer. EXPERIMENTAL DESIGN Thirty-two VX2 tumor-bearing New Zealand white rabbits underwent longitudinal imaging on clinical 3T-MRI and CT scanners before and up to 2 weeks after complete conventional transarterial chemoembolization (cTACE) using ethiodized oil (lipiodol) and doxorubicin. MR-spectroscopic imaging (MRSI) was employed for pHe mapping. Multiparametric MRI and CT were performed to quantify tumor enhancement, diffusion, and lipiodol coverage of the tumor posttherapy. In addition, incomplete cTACE with reduced chemoembolic doses was applied to mimic undertreatment and exploit pHe mapping to detect viable tumor residuals. Imaging findings were correlated with histopathologic markers indicative of metabolic state (HIF-1α, GLUT-1, and LAMP-2) and viability (proliferating cell nuclear antigen and terminal deoxynucleotidyl-transferase dUTP nick-end labeling). RESULTS Untreated VX2 tumors demonstrated a significantly lower pHe (6.80 ± 0.09) than liver parenchyma (7.19 ± 0.03, P < 0.001). Upregulation of HIF-1α, GLUT-1, and LAMP-2 confirmed a hyperglycolytic tumor phenotype and acidosis. A gradual tumor pHe increase toward normalization similar to parenchyma was revealed within 2 weeks after complete cTACE, which correlated with decreasing detectability of metabolic markers. In contrast, pHe mapping after incomplete cTACE indicated both acidic viable residuals and increased tumor pHe of treated regions. Multimodal imaging revealed durable tumor devascularization immediately after complete cTACE, gradually increasing necrosis, and sustained lipiodol coverage of the tumor. CONCLUSIONS MRSI-based pHe mapping can serve as a longitudinal monitoring tool for viable tumors. As most liver tumors are hyperglycolytic creating microenvironmental acidosis, therapy-induced normalization of tumor pHe may be used as a functional biomarker for positive therapeutic outcome.
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Affiliation(s)
- Lynn Jeanette Savic
- Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, Connecticut.,Institute of Radiology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität, and Berlin Institute of Health, Berlin, Germany
| | - Isabel Theresa Schobert
- Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, Connecticut.,Institute of Radiology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität, and Berlin Institute of Health, Berlin, Germany
| | - Dana Peters
- Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, Connecticut
| | - John J Walsh
- Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, Connecticut
| | - Fabian Max Laage-Gaupp
- Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, Connecticut
| | - Charlie Alexander Hamm
- Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, Connecticut.,Institute of Radiology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität, and Berlin Institute of Health, Berlin, Germany
| | - Nina Tritz
- Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, Connecticut
| | - Luzie A Doemel
- Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, Connecticut.,Institute of Radiology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität, and Berlin Institute of Health, Berlin, Germany
| | - MingDe Lin
- Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, Connecticut.,Visage Imaging, Inc., San Diego, California
| | - Albert Sinusas
- Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, Connecticut.,Department of Internal Medicine (Cardiology), Yale School of Medicine, New Haven, Connecticut
| | - Todd Schlachter
- Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, Connecticut
| | - James S Duncan
- Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, Connecticut.,Department of Biomedical Engineering, Yale School of Engineering and Applied Science, New Haven, Connecticut
| | - Fahmeed Hyder
- Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, Connecticut
| | - Daniel Coman
- Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, Connecticut
| | - Julius Chapiro
- Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, Connecticut.
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18
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Drug Release Property of Lipiodol Emulsion Formed by Glass Membrane Emulsification Device for Transarterial Chemoembolization. Cardiovasc Intervent Radiol 2019; 43:135-139. [DOI: 10.1007/s00270-019-02311-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2019] [Accepted: 08/13/2019] [Indexed: 02/07/2023]
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19
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Pistre P, Guiu B, Gehin S, Boulin M. Intra-arterial idarubicin_lipiodol without embolization can provide prolonged complete response in hepatocellular carcinoma: A case report. J Oncol Pharm Pract 2019; 26:507-510. [PMID: 31315548 DOI: 10.1177/1078155219861422] [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: 01/13/2023]
Abstract
Hepatocellular carcinoma is the fourth leading cause of cancer death. For unresectable intermediate-stage hepatocellular carcinoma, the standard treatment is transarterial chemoembolization. To date, the overall survival at three years remains low, and there is currently no consensus about the best anticancer agent and optimal treatment regimen. We report the case of a hepatocellular carcinoma patient with a vascular contraindication to embolization who achieved a complete response after four intra-arterial infusions of idarubicin emulsified with lipiodol. The patient maintained his response over a three-year period without any hepatocellular carcinoma treatment, demonstrating the major role of the anticancer agent in the efficacy of transarterial therapies for intermediate-stage hepatocellular carcinoma.
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Affiliation(s)
- Pauline Pistre
- Department of Pharmacy, CHU Francois Mitterrand, Dijon, France
| | - Boris Guiu
- Department of Diagnostic and Interventional Radiology, CHU Saint Eloi, Montpellier, France
| | - Sophie Gehin
- Department of Radiology, CHU Francois Mitterrand, Dijon, France
| | - Mathieu Boulin
- Department of Pharmacy, University Hospital and EPICAD LNC UMR1231, University of Burgundy & Franche Comte, Dijon, France
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20
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van Breugel JMM, Geschwind JF, Mirpour S, Savic LJ, Zhang X, Duran R, Lin M, Miszczuk M, Liapi E, Chapiro J. Theranostic application of lipiodol for transarterial chemoembolization in a VX2 rabbit liver tumor model. Theranostics 2019; 9:3674-3686. [PMID: 31281506 PMCID: PMC6587357 DOI: 10.7150/thno.32943] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2019] [Accepted: 03/25/2019] [Indexed: 02/07/2023] Open
Abstract
UNLABELLED The goal of this study was to investigate the role of Lipiodol as a tumor-specific imaging biomarker to determine therapeutic efficacy of cTACE and investigate its inter-dependency with tumor perfusion using radiological-pathological correlation in an animal model of liver cancer. METHODS A total of N=36 rabbits were implanted in the left lobe of the liver with VX2 tumors, treated with cTACE using doxorubicin suspended in Lipiodol, and randomly sacrificed at 24 h, 7 days, or 20 days post-TACE. Unenhanced and contrast-enhanced CT scans including a perfusion protocol were obtained before cTACE and immediately before sacrifice. Tumor vascularity and Lipiodol deposition within tumors and hepatic tissue (non-target deposits) were quantified using 3D quantitative assessment tools and measurements of arterial flow, portal flow, and perfusion index (PI). After sacrifice histologic staining, including hematoxylin and eosin (H&E), CD31, and Oil Red O (ORO) were performed on tumor and liver samples to evaluate necrosis, microvascular density (MVD), and Lipiodol retention over time. Transmission electron microscopy (TEM) was performed to assess Lipiodol deposition and clearance over time. RESULTS All cTACE procedures were carried out successfully except for one, which was excluded from further analysis. Twenty-four hours post-TACE, tumor PI (p=0.04) was significantly decreased, which was maintained at 7 days (p=0.003), but not at 20 days (p=0.4). A strong correlation (R2 = 0.894) was found between the volume of enhancing tumor tissue at baseline and Lipiodol-positive tumor volume post-TACE. Both ORO and TEM showed deposition of Lipiodol across all imaging time points within the VX2 tumors. However, gradual and ultimately near-complete Lipiodol washout was observed over time in the non-tumoral liver. MVD decreased between 24 h and 7 days post-TACE, and then increased 20 days post-TACE (both p<0.01). CONCLUSIONS Our data provide radiology-pathology evidence for the function of Lipiodol as a theranostic, tumor-specific drug delivery agent because it is both imageable and tumor-seeking, whereby it is preferentially taken up and retained by tumor cells. Those tumor-specific functions also enable Lipiodol to act as an imaging biomarker for the therapeutic efficacy of cTACE. Together with volumetric quantification of tumor vascularization on CT, Lipiodol could be used as a predictor of a patient's response to cTACE and contribute to the therapeutic management of patients with liver cancer.
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Affiliation(s)
- Johanna Maria Mijntje van Breugel
- Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, Connecticut, USA
- Department of Radiology, University Medical Center Utrecht, Utrecht, The Netherlands
- Medical faculty, Utrecht University, Utrecht, The Netherlands
| | | | - Sahar Mirpour
- Russell H. Morgan Department of Radiology and Radiological Science, Division of Vascular and Interventional Radiology, The Johns Hopkins Hospital, Baltimore, Maryland
| | - Lynn Jeanette Savic
- Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, Connecticut, USA
| | - Xuchen Zhang
- Department of Pathology, Yale School of Medicine, New Haven, Connecticut, USA
| | - Rafael Duran
- Department of Diagnostic and Interventional Radiology, Lausanne University Hospital, Lausanne, Switzerland
| | - MingDe Lin
- Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, Connecticut, USA
| | - Milena Miszczuk
- Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, Connecticut, USA
| | - Eleni Liapi
- Russell H. Morgan Department of Radiology and Radiological Science, Division of Vascular and Interventional Radiology, The Johns Hopkins Hospital, Baltimore, Maryland
| | - Julius Chapiro
- Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, Connecticut, USA
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Miyayama S. Ultraselective conventional transarterial chemoembolization: When and how? Clin Mol Hepatol 2019; 25:344-353. [PMID: 31022779 PMCID: PMC6933118 DOI: 10.3350/cmh.2019.0016] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2019] [Accepted: 02/07/2019] [Indexed: 12/12/2022] Open
Abstract
Ultraselective conventional transarterial chemoembolization (cTACE), defined as cTACE at the most distal portion of the subsubsegmental hepatic artery, is mainly performed for hepatocellular carcinoma (HCC) ≤5 cm. Distal advancement of a microcatheter enables injection of a larger volume of iodized oil into the portal vein in the limited area under non-physiological hemodynamics. As a result, the reversed portal flow into the tumor through the drainage route of the tumor that occurs when the hepatic artery is embolized is temporarily blocked. By adding gelatin sponge slurry embolization, both the hepatic artery and portal vein are embolized and not only complete necrosis of can be achieved. Ultraselective cTACE can cure small HCCs including less hypervascular tumor portions and replace surgical resection and radiofrequency ablation in selected patients.
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Affiliation(s)
- Shiro Miyayama
- Department of Diagnostic Radiology, Fukui-ken Saiseikai Hospital, Fukui, Japan
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22
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Yamada R, Bassaco B, Bracewell S, Gillen K, Kocher M, Collins H, Anderson MB, Guimaraes M. Long-term follow-up after conventional transarterial chemoembolization (c-TACE) with mitomycin for hepatocellular carcinoma (HCC). J Gastrointest Oncol 2019; 10:348-353. [PMID: 31032104 DOI: 10.21037/jgo.2019.01.01] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Background Conventional transarterial chemoembolization (c-TACE) is a common treatment for unresectable hepatocellular carcinoma (HCC). It is associated with increased overall survival (OS) when compared to conservative management. The purpose of this study is to analyze all c-TACE with mitomycin in patients with HCC at a single institution to determine safety, efficacy, and prognostic factors in a long-term follow-up. Methods Retrospective analysis of patients with HCC treated only with c-TACE with Mitomycin between 2007 and 2012. Efficacy was determined by OS at 1, 3, and 5 years, censored by date of death or last known follow-up. Treatment response was assessed according to mRECIST criteria and the degree of lipiodol uptake by the lesions was assessed by CT at 1-month follow-up. Prognostic factors were analyzed by multiple linear regression analysis, significance levels set at 0.05. Results A total of 60 patients were identified. OS rate at 1, 3 and 5 years was 72.1%, 47.8% and 39.3%, respectively. Median OS was 15 months. Tumor response by mRECIST criteria was complete; objective response, defined as combination of complete response (CR) and partial response (PR) patients, was 76%. When stratified by tumor response, risk of death in patients with progressive disease in 5 years was significantly higher compared to patients with objective response [hazard ratio (HR): 2.531, 95% confidence interval (CI): 1.110-5.778, P=0.0273]. Lipiodol uptake analysis was available in 51 patients; there was no statistically significant difference in OS in patients with higher lipiodol uptake compared to less uptake (<50% versus >50% uptake; HR: 0.713, 95% CI: 0.316-1.611, P=0.4161]. Conclusions c-TACE with mitomycin was effective and safe in this long-term follow-up study. Risk of death was significantly higher in patients without objective tumor response.
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Affiliation(s)
- Ricardo Yamada
- Division of Vascular & Interventional Radiology, Department of Radiology, Medical University of South Carolina, Charleston, SC, USA
| | - Beatriz Bassaco
- Division of Vascular & Interventional Radiology, Department of Radiology, Medical University of South Carolina, Charleston, SC, USA
| | - Stephen Bracewell
- Division of Vascular & Interventional Radiology, Department of Radiology, Medical University of South Carolina, Charleston, SC, USA
| | - Kirkpatrick Gillen
- Division of Vascular & Interventional Radiology, Department of Radiology, Medical University of South Carolina, Charleston, SC, USA
| | - Madison Kocher
- Division of Vascular & Interventional Radiology, Department of Radiology, Medical University of South Carolina, Charleston, SC, USA
| | - Heather Collins
- Division of Vascular & Interventional Radiology, Department of Radiology, Medical University of South Carolina, Charleston, SC, USA
| | - Michael Bret Anderson
- Division of Vascular & Interventional Radiology, Department of Radiology, Medical University of South Carolina, Charleston, SC, USA
| | - Marcelo Guimaraes
- Division of Vascular & Interventional Radiology, Department of Radiology, Medical University of South Carolina, Charleston, SC, USA
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He MK, Zou RH, Wei W, Shen JX, Zhao M, Zhang YF, Lin XJ, Zhang YJ, Guo RP, Shi M. Comparison of Stable and Unstable Ethiodized Oil Emulsions for Transarterial Chemoembolization of Hepatocellular Carcinoma: Results of a Single-Center Double-Blind Prospective Randomized Controlled Trial. J Vasc Interv Radiol 2018; 29:1068-1077.e2. [PMID: 30042075 DOI: 10.1016/j.jvir.2018.03.027] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2017] [Revised: 03/21/2018] [Accepted: 03/23/2018] [Indexed: 01/13/2023] Open
Abstract
PURPOSE To compare the stability of stable and unstable water-in-oil emulsions and the efficacy and safety of these emulsions in a single-center, prospective double-blind trial of transarterial chemoembolization for hepatocellular carcinoma (HCC). MATERIALS AND METHODS A total of 812 patients with inoperable HCC were randomized (stable emulsion, n = 402; unstable emulsion, n = 410). The 2 emulsions were prepared by using the same protocol except that different solvents were used for chemotherapy agents, including epirubicin, lobaplatin, and mitomycin C. The solvent in the stable emulsion arm was contrast medium and distilled water, and the solvent in the unstable emulsion arm was distilled water. The primary endpoint was overall survival (OS), and secondary endpoints were time to progression (TTP), tumor response, adverse events (AEs), and plasma epirubicin concentrations. RESULTS In vitro, stable emulsions did not occur until 1 day, and unstable emulsions, with a lower peak plasma concentration (P = .001) in vivo, exhibited rapid separation of the oil and aqueous phases after 10 minutes. Median OS times in the stable and unstable emulsion arms were 17.7 and 19.2 months, respectively (P = .81). No differences were found in TTP, tumor response, and AEs except for myelosuppression (anemia, 3.5% vs 7.6%; thrombocytopenia, 11.5% vs 17.7%), which was significantly more severe and frequent in the unstable emulsion arm (P = .013). CONCLUSIONS Chemoembolization is equally effective with the use of stable and unstable emulsions, but the use of a stable emulsion has the advantage of less myelosuppression and a favorable pharmacokinetic profile.
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Affiliation(s)
- Min-Ke He
- Department of Hepatobiliary Oncology, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangzhou 510060, P.R. China
| | - Ru-Hai Zou
- Department of Ultrasonography, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangzhou 510060, P.R. China
| | - Wei Wei
- Department of Hepatobiliary Oncology, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangzhou 510060, P.R. China
| | - Jing-Xian Shen
- Department of Radiology, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangzhou 510060, P.R. China
| | - Ming Zhao
- Minimally Invasive Interventional Division, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangzhou 510060, P.R. China
| | - Yong-Fa Zhang
- Department of Liver Surgery, Fudan University Shanghai Cancer Center, Shanghai, P.R. China
| | - Xiao-Jun Lin
- Department of Hepatobiliary Oncology, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangzhou 510060, P.R. China
| | - Yao-Jun Zhang
- Department of Hepatobiliary Oncology, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangzhou 510060, P.R. China
| | - Rong-Ping Guo
- Department of Hepatobiliary Oncology, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangzhou 510060, P.R. China
| | - Ming Shi
- Department of Hepatobiliary Oncology, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangzhou 510060, P.R. China.
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Delicque J, Guiu B, Boulin M, Schwanz H, Piron L, Cassinotto C. Liver chemoembolization of hepatocellular carcinoma using TANDEM ® microspheres. Future Oncol 2018; 14:2761-2772. [PMID: 29953255 DOI: 10.2217/fon-2018-0237] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
Transarterial chemoembolization (TACE) combines intra-arterial delivery of a chemotherapeutic agent with selective embolization to obtain a synergistic effect. TACE is recognized as the standard treatment of hepatocellular carcinoma patients at an intermediate stage. If conventional TACE, defined as the injection of an emulsion of a drug with ethiodized oil, still has a role to play, the development of drug-eluting beads has allowed many improvements and optimization of the technique. TANDEM® microspheres are second-generation drug-loadable microspheres. This device raised a special interest due to its tightly calibrated spherical microspheres, with small sizes down to 40 μm available. In this review, we describe the technical characteristics of these microspheres, analyze the scientific literature and hypothesize on the future perspectives.
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Affiliation(s)
- Julien Delicque
- Department of Radiology, St-Eloi University Hospital, 34980 Montpellier, France
| | - Boris Guiu
- Department of Radiology, St-Eloi University Hospital, 34980 Montpellier, France.,INSERM U1194, Montpellier Cancer Research Institute, 34298 Montpellier, France
| | - Mathieu Boulin
- Department of Pharmacy, University Hospital of Dijon, 21000 Dijon, France
| | | | - Lauranne Piron
- Department of Radiology, St-Eloi University Hospital, 34980 Montpellier, France
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Guiu B, Jouve JL, Schmitt A, Minello A, Bonnetain F, Cassinotto C, Piron L, Cercueil JP, Loffroy R, Latournerie M, Wendremaire M, Lepage C, Boulin M. Intra-arterial idarubicin_lipiodol without embolisation in hepatocellular carcinoma: The LIDA-B phase I trial. J Hepatol 2018; 68:1163-1171. [PMID: 29427728 DOI: 10.1016/j.jhep.2018.01.022] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2017] [Revised: 01/04/2018] [Accepted: 01/20/2018] [Indexed: 01/02/2023]
Abstract
BACKGROUND & AIMS Idarubicin shows high cytotoxicity against hepatocellular carcinoma (HCC) cells, a high hepatic extraction ratio, and high lipophilicity leading to stable emulsions with lipiodol. A dose-escalation phase I trial of idarubicin_lipiodol (without embolisation) was conducted in patients with cirrhotic HCC to estimate the maximum-tolerated dose (MTD) and to assess the safety, efficacy, and pharmacokinetics of the drug, and the health-related quality of life achieved by patients. METHODS Patients underwent two sessions of treatment with a transarterial idarubicin_lipiodol emulsion without embolisation. The idarubicin dose was escalated according to a modified continuous reassessment method. The MTD was defined as the dose closest to that causing dose-limiting toxicity (DLT) in 20% of patients. RESULTS A group of 15 patients were enrolled, including one patient at 10 mg, four patients at 15 mg, seven patients at 20 mg, and three patients at 25 mg. Only two patients experienced DLT: oedematous ascitic decompensation and abdominal pain at 20 and 25 mg, respectively. The calculated MTD of idarubicin was 20 mg. The most frequent grade ≥3 adverse events were biological. One month after the second session, the objective response rate was 29% (complete response, 0%; partial response, 29%) based on modified Response Evaluation Criteria In Solid Tumours. The median time to progression was 5.4 months [95% confidence limit (CI) 3.0-14.6 months] and median overall survival was 20.6 months (95% CI 5.7-28.7 months). Pharmacokinetic analysis of idarubicin showed that the mean Cmax of idarubicin after intra-arterial injection of the idarubicin-lipiodol emulsion is approximately half the Cmax after intravenous administration. Health-related quality of life results confirmed the good safety results associated with use of the drug. CONCLUSIONS The MTD of idarubicin was 20 mg after two chemolipiodolisation sessions. Encouraging safety results, and patient responses and survival were observed. A phase II trial has been scheduled. LAY SUMMARY There is a need for transarterial regimens that improve the responses and survival of patients with unresectable HCC. In this phase I trial, we showed that two sessions of treatment with a transarterial idarubicin_lipiodol emulsion without embolisation was well tolerated and gave promising efficacy in terms of tumour control and patient survival.
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Affiliation(s)
- Boris Guiu
- Department of Interventional Radiology, INSERM U1194, St-Eloi University Hospital, Montpellier School of Medicine, 80 Avenue Augustin Fliche, 34295 Montpellier, France.
| | - Jean-Louis Jouve
- Department of Hepatogastroenterology, Dijon University Hospital and EPICAD LNC-UMR1231, Burgundy & Franche Comté University, BP 87900, 21079 Dijon, France
| | - Antonin Schmitt
- Department of Pharmacy, Georges-François Leclerc Anticancer Centre and LNC-UMR1231, Burgundy & Franche Comté University, BP 87900, 21079 Dijon, France
| | - Anne Minello
- Department of Hepatogastroenterology, Dijon University Hospital and EPICAD LNC-UMR1231, Burgundy & Franche Comté University, BP 87900, 21079 Dijon, France
| | - Franck Bonnetain
- Methodology and Quality of Life in Oncology Unit (EA 3181) and Quality of Life and Cancer Clinical Research Platform, University Hospital Besançon, 2 Place Saint Jacques, 25000 Besançon, France
| | - Christophe Cassinotto
- Department of Interventional Radiology, INSERM U1194, St-Eloi University Hospital, Montpellier School of Medicine, 80 Avenue Augustin Fliche, 34295 Montpellier, France
| | - Lauranne Piron
- Department of Interventional Radiology, INSERM U1194, St-Eloi University Hospital, Montpellier School of Medicine, 80 Avenue Augustin Fliche, 34295 Montpellier, France
| | - Jean-Pierre Cercueil
- Department of Interventional Radiology, University Hospital, 14 rue Gaffarel, 21000 Dijon, France
| | - Romaric Loffroy
- Department of Interventional Radiology, University Hospital, 14 rue Gaffarel, 21000 Dijon, France
| | - Marianne Latournerie
- Department of Hepatogastroenterology, Dijon University Hospital and EPICAD LNC-UMR1231, Burgundy & Franche Comté University, BP 87900, 21079 Dijon, France
| | - Maëva Wendremaire
- Department of Pharmacology-Toxicology, University Hospital, 2 rue Angélique Ducoudray, 21000 Dijon, France
| | - Côme Lepage
- Department of Hepatogastroenterology, Dijon University Hospital and EPICAD LNC-UMR1231, Burgundy & Franche Comté University, BP 87900, 21079 Dijon, France
| | - Mathieu Boulin
- Department of Pharmacy, Dijon University Hospital and EPICAD LNC-UMR1231, Burgundy & Franche Comté University, BP 87900, 21079 Dijon, France
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Deschamps F, Harris KR, Moine L, Li W, Tselikas L, Isoardo T, Lewandowski RJ, Paci A, Huang N, de Baere T, Salem R, Larson AC. Pickering-Emulsion for Liver Trans-Arterial Chemo-Embolization with Oxaliplatin. Cardiovasc Intervent Radiol 2018; 41:781-788. [PMID: 29468287 DOI: 10.1007/s00270-018-1899-y] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2017] [Accepted: 02/07/2018] [Indexed: 12/17/2022]
Abstract
PURPOSE Biodegradable polylactic-co-glycolic acid (PLGA) nanoparticles can adsorb at the water/oil interface to stabilize the emulsion (forming Pickering-emulsion). The purpose of this study was to compare the release profiles of oxaliplatin from Pickering-emulsion and Lipiodol-emulsion. MATERIALS/METHODS Pickering-emulsions and Lipiodol-emulsions were both formulated with oxaliplatin (5 mg/mL) and Lipiodol (water/oil ratio: 1/3). For Pickering-emulsion only, PLGA nanoparticles (15 mg/mL) were dissolved into oxaliplatin before formulation. In vitro release of oxaliplatin from both emulsions was evaluated. Then, oxaliplatin was selectively injected into left hepatic arteries of 18 rabbits bearing VX2 liver tumors using either 0.5 mL Pickering-emulsion (n = 10) or 0.5 mL Lipiodol-emulsion (n = 8). In each group, half of the rabbits were killed at 1 h and half at 24 h. Mass spectrometry was used to quantify drug pharmacokinetics in blood and resulting tissue (tumors, right, and left livers) oxaliplatin concentrations. RESULTS Pickering-emulsion demonstrated a slow oxaliplatin release compared to Lipiodol-emulsion (1.5 ± 0.2 vs. 12.0 ± 6% at 1 h and 15.8 ± 3.0 vs. 85.3 ± 3.3% at 24 h) during in vitro comparison studies. For animal model studies, the plasmatic peak (Cmax) and the area under the curve (AUC) were significantly lower with Pickering-emulsion compared to Lipiodol-emulsion (Cmax = 0.49 ± 0.14 vs. 1.08 ± 0.41 ng/mL, p = 0.01 and AUC = 19.8 ± 5.9 vs. 31.8 ± 14.9, p = 0.03). This resulted in significantly lower oxaliplatin concentrations in tissues at 1 h with Pickering-emulsion but higher ratio between tumor and left liver at 24 h (43.4 vs. 14.5, p = 0.04). CONCLUSION Slow release of oxaliplatin from Pickering-emulsion results in a significant decrease in systemic drug exposure and higher ratio between tumor and left liver oxaliplatin concentration at 24 h.
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Affiliation(s)
- Frederic Deschamps
- Département de radiologie Interventionnelle, Gustave Roussy, Université Paris-Saclay, 114 rue Edouard Vaillant, 94805, Villejuif, France. .,CNRS, UMR 8203, Université Paris-Saclay, Villejuif, France.
| | | | - Laurence Moine
- Institut Galien, CNRS, UMR 8612, Faculté de Pharmacie, Université Paris-Saclay, Châtenay-Malabry, France
| | - Weiguo Li
- Department of Radiology, Northwestern University, Chicago, USA
| | - Lambros Tselikas
- Département de radiologie Interventionnelle, Gustave Roussy, Université Paris-Saclay, 114 rue Edouard Vaillant, 94805, Villejuif, France
| | - Thomas Isoardo
- Institut Galien, CNRS, UMR 8612, Faculté de Pharmacie, Université Paris-Saclay, Châtenay-Malabry, France
| | | | - Angelo Paci
- CNRS, UMR 8203, Université Paris-Saclay, Villejuif, France
| | - Nicolas Huang
- Institut Galien, CNRS, UMR 8612, Faculté de Pharmacie, Université Paris-Saclay, Châtenay-Malabry, France
| | - Thierry de Baere
- Département de radiologie Interventionnelle, Gustave Roussy, Université Paris-Saclay, 114 rue Edouard Vaillant, 94805, Villejuif, France
| | - Riad Salem
- Department of Radiology, Northwestern University, Chicago, USA
| | - Andrew C Larson
- Department of Radiology, Northwestern University, Chicago, USA
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Mechanism of Action, Pharmacokinetics, Efficacy, and Safety of Transarterial Therapies Using Ethiodized Oil: Preclinical Review in Liver Cancer Models. J Vasc Interv Radiol 2017; 29:413-424. [PMID: 29289495 DOI: 10.1016/j.jvir.2017.09.025] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2017] [Revised: 09/20/2017] [Accepted: 09/27/2017] [Indexed: 02/06/2023] Open
Abstract
PURPOSE To systematically review mechanism of action, pharmacokinetics (PKs), efficacy, and safety of ethiodized oil-based locoregional therapy (LRT) for liver cancer in preclinical models. MATERIALS AND METHODS A MEDLINE search was performed from 1988 to 2016. Search terms included hepatocellular carcinoma (HCC), HCC, liver-cell carcinoma, liver, hepatic, hepatocarcinoma, transarterial or chemoembolization, TACE, animal, Lipiodol, Ethiodol, iodized oil, and/or poppy-seed oil. Inclusion criteria were: publication in a peer-reviewed journal, an accepted animal model, and PK/safety/efficacy data reported. Exclusion criteria were: inadequate PK, safety, or efficacy data; anticancer drug name/dose not available; and article not in English. Outcomes included intratumoral anticancer drug uptake, PKs, tolerance, tumor response, and survival. RESULTS Of 102 identified articles, 49 (49%) met the inclusion criteria. Seventeen, 35, and 2 articles used rat, rabbit, and pig models. Mechanism of action was investigated in 11 articles. Eleven articles reported drug uptake, PK, and tolerance data, showing 0.5%-9.5% of injected chemotherapy dose in tumor. Tumor-to-liver drug distribution ratios were 2-157. Toxicology data across 6 articles showed transient liver laboratory level elevations 1 day after LRT. There was no noteworthy liver or extrahepatic histologic damage. Nine articles reported tumor response, with 0%-30% viable tumor and -10% to -38% tumor growth at 7 days after LRT. Two articles reported survival, showing significantly longer survival after LRT vs untreated controls (56/60 d vs 33/28 d). Several articles described ethiodized oil mixed with radiopharmaceutical (n = 7), antiangiogenic (n = 6), gene (n = 6), nanoembolic (n = 5), immune (n = 2), or other novel (n = 1) agents. CONCLUSIONS Animal studies show preferential tumor uptake of anticancer agent, good hepatic/systemic tolerance, high tumor response, and enhanced survival after ethiodized oil-based LRT.
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Deschamps F, Moine L, Isoardo T, Tselikas L, Paci A, Mir LM, Huang N, Fattal E, de Baère T. Parameters for Stable Water-in-Oil Lipiodol Emulsion for Liver Trans-Arterial Chemo-Eembolization. Cardiovasc Intervent Radiol 2017; 40:1927-1932. [DOI: 10.1007/s00270-017-1763-5] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2017] [Accepted: 07/27/2017] [Indexed: 11/25/2022]
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Deschamps F, Farouil G, Gonzalez W, Robic C, Paci A, Mir LM, Tselikas L, de Baère T. Stabilization Improves Theranostic Properties of Lipiodol®-Based Emulsion During Liver Trans-arterial Chemo-embolization in a VX2 Rabbit Model. Cardiovasc Intervent Radiol 2017; 40:907-913. [DOI: 10.1007/s00270-017-1616-2] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2016] [Accepted: 03/02/2017] [Indexed: 01/08/2023]
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Treatment of Liver Tumors with Lipiodol TACE: Technical Recommendations from Experts Opinion. Cardiovasc Intervent Radiol 2015; 39:334-43. [PMID: 26390875 DOI: 10.1007/s00270-015-1208-y] [Citation(s) in RCA: 199] [Impact Index Per Article: 19.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2015] [Accepted: 08/25/2015] [Indexed: 12/12/2022]
Abstract
Transarterial chemoembolization with Lipiodol (Lipiodol TACE), also called conventional TACE, was developed in the early 1980s and widely adopted worldwide after randomized control trials and meta-analysis demonstrated superiority of Lipiodol TACE to best supportive care. Presently, there is no level one evidence that other TACE techniques are superior to Lipiodol TACE for intermediate stage hepatocellular carcinoma (HCC), which includes patients with preserved liver function and nonsurgical large or multinodular HCC without distant metastases. In addition, TACE is part of the treatment for progressive or symptomatic liver metastases from gastroenteropancreatic neuroendocrine tumors. When injected into the hepatic artery, Lipiodol has the unique property of selective uptake and retention in hyperarterialyzed liver tumors. Lipiodol/drug emulsion followed by particle embolization has been demonstrated to improve the pharmacokinetic of the drug and tumor response. Radio opacity of Lipiodol helps to monitor treatment delivery, with retention of Lipiodol serving as an imaging biomarker for tumor response. For 30 years, Lipiodol TACE has been inconsistently referenced in many publications with various levels of details for the method of preparation and administration, with reported progressive outcomes following improvements in the technique and the devices used to deliver the treatment and better patient selection. Consequently, there is no consensus on the standard method of TACE regarding the use of anticancer agents, embolic material, technical details, and the treatment schedule. In order to develop an internationally validated technical recommendation to standardize the Lipiodol TACE procedure, a worldwide panel of experts participated in a consensus meeting held on May 10, 2014 .
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She HL, Burgmans MC, Coenraadm M, Saraqueta AF. In Vivo Proof of Superselective Transarterial Chemoembolization with 40-μm Drug-Eluting Beads in a Patient with Hepatocellular Carcinoma. Cardiovasc Intervent Radiol 2015; 39:137-40. [DOI: 10.1007/s00270-015-1154-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2015] [Accepted: 04/19/2015] [Indexed: 11/28/2022]
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Wáng YXJ, De Baere T, Idée JM, Ballet S. Transcatheter embolization therapy in liver cancer: an update of clinical evidences. Chin J Cancer Res 2015; 27:96-121. [PMID: 25937772 PMCID: PMC4409973 DOI: 10.3978/j.issn.1000-9604.2015.03.03] [Citation(s) in RCA: 59] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2015] [Accepted: 02/05/2015] [Indexed: 12/20/2022] Open
Abstract
Transarterial chemoembolization (TACE) is a form of intra-arterial catheter-based chemotherapy that selectively delivers high doses of cytotoxic drug to the tumor bed combining with the effect of ischemic necrosis induced by arterial embolization. Chemoembolization and radioembolization are at the core of the treatment of liver hepatocellular carcinoma (HCC) patients who cannot receive potentially curative therapies such as transplantation, resection or percutaneous ablation. TACE for liver cancer has been proven to be useful in local tumor control, to prevent tumor progression, prolong patients' life and control patient symptoms. Recent evidence showed in patients with single-nodule HCC of 3 cm or smaller without vascular invasion, the 5-year overall survival (OS) with TACE was similar to that with hepatic resection and radiofrequency ablation. Although being used for decades, Lipiodol(®) (Lipiodol(®) Ultra Fluid(®), Guerbet, France) remains important as a tumor-seeking and radio-opaque drug delivery vector in interventional oncology. There have been efforts to improve the delivery of chemotherapeutic agents to tumors. Drug-eluting bead (DEB) is a relatively novel drug delivery embolization system which allows for fixed dosing and the ability to release the anticancer agents in a sustained manner. Three DEBs are available, i.e., Tandem(®) (CeloNova Biosciences Inc., USA), DC-Beads(®) (BTG, UK) and HepaSphere(®) (BioSphere Medical, Inc., USA). Transarterial radioembolization (TARE) technique has been developed, and proven to be efficient and safe in advanced liver cancers and those with vascular complications. Two types of radioembolization microspheres are available i.e., SIR-Spheres(®) (Sirtex Medical Limited, Australia) and TheraSphere(®) (BTG, UK). This review describes the basic procedure of TACE, properties and efficacy of some chemoembolization systems and radioembolization agents which are commercially available and/or currently under clinical evaluation. The key clinical trials of transcatheter arterial therapy for liver cancer are summarized.
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Liu YS, Ou MC, Tsai YS, Lin XZ, Wang CK, Tsai HM, Chuang MT. Transarterial chemoembolization using gelatin sponges or microspheres plus lipiodol-doxorubicin versus doxorubicin-loaded beads for the treatment of hepatocellular carcinoma. Korean J Radiol 2015; 16:125-32. [PMID: 25598680 PMCID: PMC4296259 DOI: 10.3348/kjr.2015.16.1.125] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2014] [Accepted: 09/25/2014] [Indexed: 02/07/2023] Open
Abstract
Objective To retrospectively compare treatment of hepatocellular carcinoma (HCC) with transarterial chemoembolization (TACE) using gelatin sponges or microspheres plus lipiodol-doxorubicin vs. doxorubicin-loaded drug-eluting beads (DEB). Materials and Methods A total of 158 patients with HCC received TACE from November 2010 to November 2011 were enrolled in this study, including 64 (40.5%) received TACE with lipiodol-doxorubicin and gelatin sponges (group A), 41 (25.9%) received TACE with lipiodol-doxorubicin and microspheres (group B), and 53 (33.5%) received TACE with doxorubicin-loaded DEB (group C). Tumor response and adverse events (AEs) were evaluated. Results No significant difference was found at baseline among the three groups. The doxorubicin dosage in group C was significantly (p < 0.001) higher compared to the dose used in groups A or B (median, 50 mg vs. 31 mg or 25 mg). Significantly (p < 0.001) more patients in group C achieved complete response compared to those in groups A or B (32.1% vs. 6.3% or 2.4%). Significantly (p < 0.001) less patients in group C had progressive disease compared to those in groups A or B (34.0% vs. 57.8% or 68.3%). Minor AEs were more common in groups A and B compared to group C, with rates of 54.7%, 34.1%, and 5.7%, respectively. Conclusion In patients with HCC, TACE with DEB offers better safety and efficacy profiles compared to either TACE with gelatin sponges or TACE with microspheres.
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Affiliation(s)
- Yi-Sheng Liu
- Department of Diagnostic Radiology, National Cheng-Kung University Hospital, Tainan 704, Taiwan, R.O.C. ; Liver Cancer Collaborative Oncology Group, National Cheng-Kung University Hospital, Tainan 704, Taiwan, R.O.C
| | - Ming-Ching Ou
- Department of Diagnostic Radiology, National Cheng-Kung University Hospital, Tainan 704, Taiwan, R.O.C
| | - Yi-Shan Tsai
- Department of Diagnostic Radiology, National Cheng-Kung University Hospital, Tainan 704, Taiwan, R.O.C
| | - Xi-Zhang Lin
- Liver Cancer Collaborative Oncology Group, National Cheng-Kung University Hospital, Tainan 704, Taiwan, R.O.C. ; Department of Internal Medicine, National Cheng-Kung University Hospital, Tainan 704, Taiwan, R.O.C
| | - Chien-Kuo Wang
- Department of Diagnostic Radiology, National Cheng-Kung University Hospital, Tainan 704, Taiwan, R.O.C
| | - Hong-Ming Tsai
- Department of Diagnostic Radiology, National Cheng-Kung University Hospital, Tainan 704, Taiwan, R.O.C. ; Liver Cancer Collaborative Oncology Group, National Cheng-Kung University Hospital, Tainan 704, Taiwan, R.O.C
| | - Ming-Tsung Chuang
- Department of Diagnostic Radiology, National Cheng-Kung University Hospital, Tainan 704, Taiwan, R.O.C
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Comparison of drug release and pharmacokinetics after transarterial chemoembolization using diverse lipiodol emulsions and drug-eluting beads. PLoS One 2014; 9:e115898. [PMID: 25551760 PMCID: PMC4281073 DOI: 10.1371/journal.pone.0115898] [Citation(s) in RCA: 51] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2014] [Accepted: 12/02/2014] [Indexed: 01/26/2023] Open
Abstract
In many studies for chemoembolization of hepatocellular carcinoma, the Lipiodol emulsion preparation protocols, especially the mixing steps, were unclear or even unrevealed at all. However, doxorubicin (DOX) release may depend on the composition and volume ratio (Lipiodol to DOX solution) of a Lipiodol emulsion. Therefore, we conducted a preclinical study to compare in-vitro drug release and in-vivo pharmacokinetics of DOX from diverse Lipiodol emulsions and drug-eluting beads (DEBs) and to compare the tumor response in a rabbit VX2 carcinoma model. DOX release profiles of four types of Lipiodol emulsions with different media (normal saline or Pamiray as an iodinated contrast medium), volume ratio (Lipiodol to DOX solution), and DEBs were investigated in-vitro. For the in-vivo study, 15 rabbits bearing VX2 carcinoma in the liver were treated with 4∶1 volume ratio Lipiodol emulsion (group A), 1∶1 volume ratio Lipiodol emulsion (group B), and DEBs (group C) chemoembolization. Blood and tissue sampling was conducted to evaluate DOX concentration in plasma and tissues, histological changes, and liver toxicity. The most stable emulsion was formed with Pamiray (including DOX) at a 4∶1 volume ratio. The AUC value of group A was significantly lower than that of group B (p = 0.003) but comparable to that of group C (p = 0.071). The Cmax value of group A was significantly different compared with those of group B (p = 0.004) and C (p = 0.015). The tissue drug concentration in group A was comparable to that in group C (p = 0.251). No viable tumor was detected in rabbits of group A and B. In group C, viable tumor less than 10% was seen in two of the five rabbits. There were no significant differences in liver enzyme levels after the procedure. In conclusion, DOX release and pharmacokinetics of presented emulsion systems depend substantially on their composition. Therefore, Lipiodol emulsion type should be considered when interpreting data and designing new studies dealing with chemoembolization.
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Imai N, Ishigami M, Ishizu Y, Kuzuya T, Honda T, Hayashi K, Hirooka Y, Goto H. Transarterial chemoembolization for hepatocellular carcinoma: A review of techniques. World J Hepatol 2014; 6:844-850. [PMID: 25544871 PMCID: PMC4269903 DOI: 10.4254/wjh.v6.i12.844] [Citation(s) in RCA: 49] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2014] [Revised: 10/07/2014] [Accepted: 10/29/2014] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the most common malignant diseases worldwide. While curative therapies, including resection, liver transplantation, and percutaneous ablation (percutaneous ethanol injection and radiofrequency ablation), are applicable for only a portion of the HCC population, transcatheter arterial chemoembolization (TACE) has been recognized as an effective palliative treatment option for patients with advanced HCC. TACE is also used even for single HCCs in which it is difficult to perform surgical resection or locoregional treatment due to systemic co-morbidities or anatomical problems. TACE has become widely adopted in the treatment of HCC. By using computed tomography-angiography, TACE is capable of performing diagnosis and treatment at the same time. Furthermore, TACE plays an important role in the multidisciplinary treatment for HCC when combined with other treatment. In this review, we first discuss the history of TACE, and then review the previous findings about techniques of achieving a locoregional treatment effect (liver infarction treatment, e.g., ultra-selective TACE, balloon-occluded TACE), and the use of TACE as a drug delivery system for anti-cancer agents (palliative, e.g., platinum complex agents, drug-eluting beads) for multiple lesions.
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Joskin J, de Baere T, Auperin A, Tselikas L, Guiu B, Farouil G, Boige V, Malka D, Leboulleux S, Ducreux M, Baudin E, Deschamps F. Predisposing Factors of Liver Necrosis after Transcatheter Arterial Chemoembolization in Liver Metastases from Neuroendocrine Tumor. Cardiovasc Intervent Radiol 2014; 38:372-80. [DOI: 10.1007/s00270-014-0914-1] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2013] [Accepted: 04/09/2014] [Indexed: 01/11/2023]
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Idée JM, Guiu B. Use of Lipiodol as a drug-delivery system for transcatheter arterial chemoembolization of hepatocellular carcinoma: a review. Crit Rev Oncol Hematol 2013; 88:530-49. [PMID: 23921081 DOI: 10.1016/j.critrevonc.2013.07.003] [Citation(s) in RCA: 153] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2013] [Revised: 06/05/2013] [Accepted: 07/09/2013] [Indexed: 12/12/2022] Open
Abstract
Hepatocellular carcinoma (HCC) remains a major public health problem. Transarterial chemoembolization (TACE) is recognized as the standard of care for patients with unresectable, asymptomatic, noninvasive and multinodular HCC. This procedure is based on percutaneous administration of a cytotoxic drug emulsified with Lipiodol followed by embolization of the tumour-feeding arteries. The standard procedure involves Lipiodol, an oily contrast medium which consists of a mixture of long-chain di-iodinated ethyl esters of poppy seed fatty acids. The aim of this review is to discuss the physical properties, tumour uptake behaviour and drug delivery effects of Lipiodol, the parameters influencing tumour uptake and future prospects. Lipiodol has a unique place in TACE as it combines three specific characteristics: drug delivery, transient and plastic embolization and radiopacity properties. Substantial heterogeneity in the physicochemical characteristics of Lipiodol/cytotoxic agent emulsions might reduce the efficacy of this procedure and justifies the current interest in Lipiodol for drug delivery.
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Affiliation(s)
- Jean-Marc Idée
- Guerbet, Research and Innovation Division, BP 57400, 95943 Roissy-Charles de Gaulle cedex, France.
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Antitumor effect of miriplatin-lipiodol suspension/emulsion using a VX2 liver tumor model. Jpn J Radiol 2013; 31:662-7. [DOI: 10.1007/s11604-013-0231-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2012] [Accepted: 06/20/2013] [Indexed: 01/28/2023]
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Irie T, Kuramochi M, Takahashi N. Dense accumulation of lipiodol emulsion in hepatocellular carcinoma nodule during selective balloon-occluded transarterial chemoembolization: measurement of balloon-occluded arterial stump pressure. Cardiovasc Intervent Radiol 2012; 36:706-13. [PMID: 22996589 DOI: 10.1007/s00270-012-0476-z] [Citation(s) in RCA: 97] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2012] [Accepted: 08/27/2012] [Indexed: 01/01/2023]
Abstract
PURPOSE To reveal the mechanism of dense accumulation of lipiodol emulsion (LE) in hepatocellular carcinoma (HCC) during selective balloon-occluded transarterial chemoembolization (B-TACE). METHODS Balloon-occluded arterial stump pressure (BOASP) at the embolization portion was measured during selective B-TACE for 43 nodules in 42 patients. Fluoroscopy and digital subtraction angiography were prospectively observed during selective B-TACE to note whether dense LE accumulation in HCC occurred. The LE concentration ratio of HCC to embolized liver parenchyma (LECHL ratio) was also calculated for each treatment on the basis of the computed tomographic scan obtained immediately after selective B-TACE. The relationships between degree of LE accumulation and the BOASP, as well as the LECHL ratio, were analyzed. RESULTS Arterial flow beyond the catheter tip was maintained even after balloon inflation. In 39 of 43 treatments, LE inflow into the nontumorous liver parenchyma ceased immediately after LE droplets were filled in arteries of the nontumorous liver parenchyma while LE inflow into the HCC nodule continued (group 1). More dense LE accumulation in HCC nodule was obtained in these 39 treatments. In four treatments, LE inflow both into the nontumorous liver parenchyma and into the HCC nodule continued, and no dense LE accumulation in HCC nodule was observed (group 2). In these four treatments, thick anastomotic vessels with collateral artery were noted. The BOASP in group 1 was (mean ± SD) 33.8 ± 12.8 mmHg (range 13-64 mmHg) and that in group 2 was 92.3 ± 7.4 mmHg (range 83-100 mmHg). There was a statistically significant difference in BOASP between groups (p = 0.00004, Welch's t test). The LECHL ratio in group 1 was 18.3 ± 13.9 (range 2.9-54.2) and that in group 2 was 2.6 ± 1.1 (range 1.7-4.2). There was a statistically significant difference in the LECHL ratio between the groups (p = 0.000034, Welch's t test). CONCLUSION Selective B-TACE induced dense LE accumulation in HCC nodules in 39 (91 %) of 43 treatments in which BOASP was 64 mmHg or less.
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Affiliation(s)
- Toshiyuki Irie
- Department of Radiology, Hitachi General Hospital, Jyonann 2-1-1, Hitachi, Ibaraki 317-0077, Japan.
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Pascale F, Ghegediban SH, Bonneau M, Bedouet L, Namur J, Verret V, Schwartz-Cornil I, Wassef M, Laurent A. Modified Model of VX2 Tumor Overexpressing Vascular Endothelial Growth Factor. J Vasc Interv Radiol 2012; 23:809-817.e2. [DOI: 10.1016/j.jvir.2012.02.003] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2011] [Revised: 02/02/2012] [Accepted: 02/06/2012] [Indexed: 10/28/2022] Open
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Mine T, Murata S, Ueda T, Onozawa S, Onda M, Naito Z, Kumita S. Comparative study of cisplatin-iodized oil suspension and emulsion for transcatheter arterial chemoembolization of rabbit VX2 liver tumors. Hepatol Res 2012; 42:473-81. [PMID: 22176437 DOI: 10.1111/j.1872-034x.2011.00942.x] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
AIM To evaluate the antitumor effects and hepatotoxicity of transcatheter arterial chemoembolization (TACE) with cisplatin-iodized oil suspension and emulsion in a rabbit tumor model. METHODS Transcatheter arterial chemoembolization was performed on 12 rabbits with hepatic VX2 tumors using a cisplatin suspension (1 mg/kg cisplatin and 0.1 mL/kg iodized oil, n = 6) or emulsion (1 mg/kg cisplatin, 0.1 mL/kg of iodized oil, and 0.1 mL/kg saline solution, n = 6). Time series changes in plasma platinum concentration were compared over 24 h. All rabbits were killed at 7 days after TACE, and the growth ratio and residual viable proportion of tumors were calculated on the basis of ultrasonographic and histopathological findings. Hepatotoxicity was also evaluated. Differences between the two groups were statistically assessed with the Mann-Whitney U-test. The animal care committee of our institute approved this study. RESULTS Plasma platinum concentrations were significantly higher in the suspension group than in the emulsion group at 0.5-24 h after TACE (P < 0.05). Growth ratios (-24.6 ± 9.98% vs. 21.4 ± 8.87%, respectively; P = 0.004) and residual viable proportions of tumors (25.8 ± 5.02% vs. 51.1 ± 11.4%, respectively; P = 0.009) were significantly lower in the suspension group than in the emulsion group. Hepatotoxicity was transient in all rabbits. CONCLUSION Cisplatin-iodized oil suspensions facilitated the slow release of cisplatin at the tumor border. A suspension is preferable to an emulsion for drug delivery and the antitumor effect during the treatment of VX2 liver tumors with TACE.
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Affiliation(s)
- Takahiko Mine
- Departments of Radiology Integrative Pathology, Nippon Medical School, Bunkyo-ku, Tokyo, Japan
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Becker S, Lepareur N, Cadeillan V, Ardisson V, Bayat S, Noiret N, Garin E. Optimization of hepatocarcinoma uptake with radiolabeled lipiodol: development of new lipiodol formulations with increased viscosity. Cancer Biother Radiopharm 2012; 27:149-155. [PMID: 22149684 DOI: 10.1089/cbr.2011.1072] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
The aim of this study was to develop new Lipiodol formulations with increased viscosities to augment Lipiodol embolic effect and optimize efficiency of radiolabeled Lipiodol in hepatocarcinoma treatments. New Lipiodol formulations consist of Lipiodol mixtures with different stearic acid concentrations (0.8%, 1.3%, and 1.8%). These formulations were fully characterized in vitro (viscosity, rheologic profiles) and labeled with 99mTc. Their viscosities at 20°C are 54, 60, and 67cP respectively, versus 45cP for Lipiodol ultra-fluide. Second, their biodistribution profiles were studied in vivo, at 24 and 72 hours, in hepatoma-bearing rats, and compared to control group (99mTc-Lipiodol). Biodistribution at 24 hours show a Gaussian tumor uptake profile with a maximum obtained with 1.3% stearic acid, and a tumor uptake superior to control group (+67%) (p<0.05). At 72 hours, optimal tumor uptake is reached with the 0.8% formulation, with 89% increase compared with control group (p<0.05). Moreover, we show a tendency to the decrease of pulmonary uptake for the new formulations at 24 hours and 72 hours. These results suggest a correlation between viscosity and Lipiodol tumor uptake. The new 0.8% stearic acid/Lipiodol formulation appears to be the optimized formulation for Lipiodol treatments of hepatocarcinoma, since it leads to a significant increase of tumor uptake at 72 hours and possibly to a decrease of undesirable pulmonary effects.
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Affiliation(s)
- Stéphanie Becker
- Centre Eugène Marquis, Nuclear Medicine Department, Rennes, France.
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Comparison of local control effects of superselective transcatheter arterial chemoembolization using epirubicin plus mitomycin C and miriplatin for hepatocellular carcinoma. Jpn J Radiol 2012; 30:263-70. [PMID: 22223074 DOI: 10.1007/s11604-011-0043-6] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2011] [Accepted: 12/05/2011] [Indexed: 01/11/2023]
Abstract
PURPOSE To compare local control effects of superselective transcatheter arterial chemoembolization (TACE) using epirubicin (EPI) plus mitomycin C (M) and miriplatin (MPT) for hepatocellular carcinoma (HCC). MATERIALS AND METHODS One-hundred and twenty-nine HCCs treated with superselective TACE were divided into three groups according to the type of anticancer drug; EPI-M-TACE (n = 51), MPT-TACE (n = 21), and MPT-I-TACE (MPT emulsion) (n = 57). Local recurrence, patterns of recurrence (intratumoral recurrence; IR), and follow-up angiograms were evaluated. RESULTS Mean tumor diameter and follow-up period for the EPI-M-TACE, MPT-TACE, and MPT-I-TACE groups were 16.9 mm and 15.5 months, 20.7 mm and 12.0 months, and 18.8 mm and 9.6 months, respectively. Local recurrence for the EPI-M-TACE, MPT-TACE, and MPT-I-TACE groups at 5, 10, and 15 months was 6.1, 47.6, and 40.1%, 23.5, 67.3, and 63.9%, and 26.2, 75.4, and 72.9%, respectively. IR for the EPI-M-TACE, MPT-TACE, and MPT-I-TACE groups was 23.1, 71.4, and 71.0%, respectively. Local recurrence and IR in the EPI-M-TACE group were significantly less than those in the MPT-TACE and MPT-I-TACE groups. Follow-up angiograms revealed less arterial damage in the MPT-TACE and MPT-I-TACE groups. CONCLUSION Superselective TACE using MPT resulted in very frequent local recurrence, in particular IR, despite less arterial damage.
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Becker S, Ardisson V, Lepareur N, Sergent O, Bayat S, Noiret N, Gaboriau F, Clément B, Boucher E, Raoul JL, Garin E. Increased Lipiodol uptake in hepatocellular carcinoma possibly due to increased membrane fluidity by dexamethasone and tamoxifen. Nucl Med Biol 2010; 37:777-784. [PMID: 20870152 DOI: 10.1016/j.nucmedbio.2010.03.013] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2010] [Revised: 03/16/2010] [Accepted: 03/31/2010] [Indexed: 12/01/2022]
Abstract
INTRODUCTION Lipiodol is used as a vector for chemoembolization or internal radiotherapy in unresectable hepatocellular carcinomas (HCCs). The aim of this study is to improve the tumoral uptake of Lipiodol by modulating membrane fluidizing agents to optimize the effectiveness of Lipiodol vectorized therapy. METHODS The effect of dexamethasone and tamoxifen on membrane fluidity was studied in vitro by electron paramagnetic resonance applied to rat hepatocarcinoma cell line N1S1. The tumoral uptake of Lipiodol was studied in vivo on rats with HCC, which had been previously treated by dexamethasone and/or tamoxifen, after intra-arterial administration of (99m)Tc-SSS-Lipiodol. RESULTS The two molecules studied here exhibit a fluidizing effect in vitro which appears dependent on time and dose, with a maximum fluidity obtained after 1 hr at concentrations of 20 μM for dexamethasone and 200 nM for tamoxifen. In vivo, while the use of dexamethasone or tamoxifen alone tends to lead to increased tumoral uptake of Lipiodol, this effect does not reach levels of significance. On the other hand, there is a significant increase in the tumoral uptake of (99m)Tc-SSS-Lipiodol in rats pretreated by both dexamethasone and tamoxifen, with a tumoral uptake (expressed in % of injected activity per g of tumor) of 13.57 ± 3.65% after treatment, as against 9.45 ± 4.44% without treatment (P<.05). CONCLUSIONS Dexamethasone and tamoxifen fluidify the N1S1 cells membrane, leading to an increase in the tumoral uptake of Lipiodol. These drugs could be combined with chemo-Lipiodol-embolization or radiolabeled Lipiodol, with a view to improving the effectiveness of HCCs therapy.
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Affiliation(s)
- Stéphanie Becker
- Department of Nuclear Medicine, Centre E. Marquis, F-35042 Rennes, France.
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Shin SW. The current practice of transarterial chemoembolization for the treatment of hepatocellular carcinoma. Korean J Radiol 2009; 10:425-34. [PMID: 19721826 PMCID: PMC2731859 DOI: 10.3348/kjr.2009.10.5.425] [Citation(s) in RCA: 127] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2009] [Accepted: 04/03/2009] [Indexed: 12/27/2022] Open
Abstract
Despite remarkable advancement in the surveillance and treatment of hepatocellular carcinoma (HCC) and the availability of novel curative options, a great proportion of HCC patients are still not eligible for curative treatment due to an advanced tumor stage or poor hepatic functional reserve. Therefore, there is a continuing need for effective palliative treatments. Although practiced widely, it has only recently been demonstrated that the use of transarterial chemoembolization (TACE) provides a survival benefit based on randomized controlled studies. Hence, TACE has become standard treatment in selected patients. TACE combines the effect of targeted chemotherapy with the effect of ischemic necrosis induced by arterial embolization. Most of the TACE procedures have been based on iodized oil utilizing the microembolic and drug-carrying characteristic of iodized oil. Recently, there have been efforts to improve the delivery of chemotherapeutic agents to a tumor. In this review, the basic principles, technical issues and complications of TACE are reviewed and recent advancement in TACE technique and clinical applicability are briefed.
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Affiliation(s)
- Sung Wook Shin
- Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
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Abstract
Last years, calibrated microspheres have proven their superiority in targeting embolization over non spherical particles in many applications. For the very near future they represent the best tool for controlling drug delivery in chemoembolization, under the two conditions that they would be image detectable and that the "dosimetry" would be tailored to pathological process.
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Affiliation(s)
- A Laurent
- Assistance Publique, Hôpitaux de Paris, Hôpital Lariboisière, Department of Interventional Neuroradiology, Paris, France.
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48
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Tzeng WS, Wu RH, Chang SC, Chou CK, Lin CY, Chen JJ, Yang SC, Lin CH. Ionic Versus Nonionic Contrast Media Solvents Used with an Epirubicin-based Agent for Transarterial Chemoembolization of Hepatocellular Carcinoma. J Vasc Interv Radiol 2008; 19:342-50. [DOI: 10.1016/j.jvir.2007.10.021] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2007] [Revised: 10/12/2007] [Accepted: 10/13/2007] [Indexed: 01/28/2023] Open
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49
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Garin E, Bourguet P. Intra-arterial Therapy of Liver Tumours. Clin Nucl Med 2008. [DOI: 10.1007/978-3-540-28026-2_27] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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50
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Abstract
Interventional radiologists are often called on to help with quality of life issues in end-stage cancer patients. Many times, the discomfort can be directly associated to the tumor mass itself, but in other instances, tumors can cause secondary obstruction of normal structures that can lead to patient distress. As with most palliative care patients, their medical conditions are not conducive to major surgery; therefore minimally invasive techniques are ideal for the treatment of these conditions. The following discussion addresses the various nonvascular interventions available to these patients, including the indications and limitations of these procedures.
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Affiliation(s)
- Kent T Sato
- Department of Radiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
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