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Tonkaz M, Nas OF, Erkal Tonkaz D, Inecikli MF, Ongen G, Ozkaya G. Efficacy of transarterial chemoembolization treatment with 30-60-μm microspheres in patients with hepatocellular carcinoma. RADIOLOGIE (HEIDELBERG, GERMANY) 2024; 64:131-138. [PMID: 39112640 DOI: 10.1007/s00117-024-01351-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/21/2024] [Accepted: 06/27/2024] [Indexed: 11/28/2024]
Abstract
BACKGROUND Chemoembolization with small drug-eluting microspheres is widely used in the treatment of hepatocellular carcinoma (HCC). OBJECTIVES This study aimed to evaluate the efficacy and safety of transarterial chemoembolization with doxorubicin-eluting 30-60-µm microspheres (DEB-TACE) in patients with Barcelona Clinic Liver Cancer (BCLC) stage A and B HCC. MATERIALS AND METHODS In this single-center study, 88 patients with HCC (BCLC A/B: 15.9%/84.1%) who underwent 137 DEB-TACE sessions between January 2015 and December 2020 were retrospectively assessed. Response to treatment was assessed 4-8 weeks after each DEB-TACE procedure according to mRECIST (Modified Response Evaluation Criteria in Solid Tumors) criteria. Progression-free survival (PFS), time to progression (TTP), overall survival (OS), and adverse events were recorded. RESULTS In 88 patients (84.1% males; median age, 66.0 years; range, 22-83), the median follow-up was 17 months (range, 2-64). Eight patients (9.1%) had a complete response, 42 (47.8%) had partial regression, 10 (11.3%) had stable disease, and 28 (31.8%) had progressive disease. There was a statistically significant difference between serum alpha-fetoprotein (AFP) levels before and after DEB-TACE treatment (p < 0.001). The median OS was 17 months (95% confidence interval [CI], 10.3-23.7). Cox regression analyses found that preprocedural serum AFP level (400+ vs. < 400; p = 0.024), Child Pugh classification (B vs. A; p = 0.019), and number of DEB-TACE sessions (1 vs. > 1; p = 0.003) were independent risk factors affecting OS. The median PFS was 8 months (95% CI, 5.8-10.2) and TTP was 6 months (1-14 months). CONCLUSION Chemoembolization with 30-60-µm microspheres is an effective and safe treatment for HCC. The number of DEB-TACE sessions is also one of the factors affecting OS.
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Affiliation(s)
- Mehmet Tonkaz
- Department of Radiology, Gumushane State Hospital, Gumushane, Turkey.
| | - Omer Fatih Nas
- Department of Radiology, Bursa Uludag University School of Medicine, Bursa, Turkey
| | | | | | - Gokhan Ongen
- Department of Radiology, Bursa Uludag University School of Medicine, Bursa, Turkey
| | - Guven Ozkaya
- Department of Statistics, Bursa Uludag University School of Medicine, Bursa, Turkey
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Yang KL, Guo YP, Mao XY, Shen J, Zou JW, Li MM, Li Z. The Incidences and Related CT Features of Vascular Lake Phenomenon on Angiography Before Chemoembolization. Cardiovasc Intervent Radiol 2024; 47:225-233. [PMID: 38273130 DOI: 10.1007/s00270-023-03651-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2023] [Accepted: 12/11/2023] [Indexed: 01/27/2024]
Abstract
PURPOSE To elucidate incidence rates of vascular lake phenomenon (VLP) in hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), hepatic metastasis (HMT) on transarterial angiography before chemoembolization, and to identity CT features predictive for it. MATERIALS AND METHODS A comprehensive evaluation involved 665 subjects for incidence analysis, comprising 527 of HCC, 33 of ICC and 105 of HMT. VLP was characterized as intratumoral contrast material pool persisting late into venous phase. Incidences were cataloged on both super-selective and common hepatic artery angiography. For CT features analysis, a subset of 182 cases were analyzed. Enhancement ratio served as an index for comparative analysis of nodule enhancement degrees. RESULTS In HCC, incidence of VLP ascertained via super-selective angiography was 13.5%, whereas it as 7.8% on common hepatic artery angiography. Remarkably, no incidences of VLP were recorded in either ICC or HMT cases. On pre-interventional CT, the prevalence of pseudocapsule was statistically greater in VLP group than Non-VLP group (66.6% vs. 37.6%, P = 0.015). The Houndsfield units (HU) of tumors in plain scan (P = 0.007), arterial phase (P = 0.001), venous phase (P = 0.041), arterial phase enhancement ratio (P < 0.001) were statistically higher in VLP group compared to Non-VLP group. Arterial phase enhancement ratio (P = 0.025), presence of pseudocapsule (P = 0.001), HU of tumor in plain scan (P = 0.035) serve as independent risk factors for VLP manifestation. CONCLUSION VLP is a distinct angiography phenomenon uniquely associated with HCC. High arterial phase enhancement ratio, presence of pseudocapsule, high HU of tumor in plain scan are independent risk factors for VLP.
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Affiliation(s)
- Kai-Lun Yang
- Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, No.188 Shizi Street, Suzhou, 215006, Jiangsu, China
- Department of Radiology, Affiliated Lianyungang Hospital of Xuzhou Medical University, No.6 Zhenhuadong Road, Lianyungang, 222061, Jiangsu, China
| | - Ya-Pan Guo
- Department of Interventional Radiology, Suzhou Xiangcheng People's Hospital, No. 1060 Huayuan Road, Suzhou, 215131, China
| | - Xin-Yu Mao
- Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, No.188 Shizi Street, Suzhou, 215006, Jiangsu, China
| | - Jian Shen
- Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, No.188 Shizi Street, Suzhou, 215006, Jiangsu, China
| | - Jian-Wei Zou
- Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, No.188 Shizi Street, Suzhou, 215006, Jiangsu, China
| | - Ming-Ming Li
- Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, No.188 Shizi Street, Suzhou, 215006, Jiangsu, China
| | - Zhi Li
- Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, No.188 Shizi Street, Suzhou, 215006, Jiangsu, China.
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Narita A, Nakano Y, Okada H, Yamamoto T, Matsunaga N, Ikeda S, Izumi Y, Kitagawa A, Ota T, Suzuki K. In Vitro Characterization of Drug-Loaded Superabsorbent Polymer Microspheres: Absorption and Release Capacity of Contrast Material, Antibiotics and Analgesics. Cardiovasc Intervent Radiol 2023; 46:1632-1640. [PMID: 37759091 DOI: 10.1007/s00270-023-03559-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2023] [Accepted: 09/05/2023] [Indexed: 09/29/2023]
Abstract
PURPOSE To examine the characteristics of drug-loaded superabsorbent polymer microspheres (SAP-MS) such as drug absorption, drug release, diameter, and visibility. MATERIALS AND METHODS SAP-MS (HepaSphere150-200 µm; Merit Medical, South Jordan, UT, USA) were suspended in drug solutions: (a) cefazolin, (b) lidocaine, (c) iopamidol and cefazolin, (d) iopamidol and lidocaine, and (e) iopamidol, cefazolin, and lidocaine. The concentrations of drugs were measured, and the amount of each drug absorbed was calculated. Filtered drug-loaded SAP-MS were mixed with saline, and the drug release rates were calculated. The diameter changes of SAP-MS during absorption were observed. Radiography of drug-loaded SAP-MS was evaluated as radiopacity by contrast-to-noise ratio (CNR). RESULTS The drug concentration did not change during absorption. The release rates increased for 10 min and then came to an equilibrium. The mean amounts of drug absorbed at 180 min and mean release rates at 24 h were (a) cefazolin: 265.4 mg, 64.2%; (b) lidocaine: 19.6 mg, 75.6%; (c) iopamidol: 830.2 mg, 22.5%; cefazolin: 137.6 mg, 21.2%; (d) iopamidol: 1620.6 mg, 78.5%; lidocaine: 13.5 mg, 81.4%; and (e) iopamidol: 643.7 mg, 52.9%; cefazolin: 194.0 mg, 51.6%; lidocaine: 5.3 mg, 58.4%. The diameter of SAP-MS increased for approximately 15 min. Finally, the diameters of SAP-MS were (a) 3.9 times, (b) 5.0 times, (c) 2.2 times, (d) 5.5 times, and (e) 3.6 times larger than the original size. Drug-loaded SAP-MS containing iopamidol were visible under X-ray imaging, with CNRs of (c) 3.0, (d) 9.0, and (e) 4.5. CONCLUSION SAP-MS can absorb and release iopamidol, cefazolin, and lidocaine.
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Affiliation(s)
- Akiko Narita
- Department of Radiology, Aichi Medical University, 1-1 Yazako Karimata, Nagakute, Aichi, Japan.
| | - Yuta Nakano
- Department of Radiology, Aichi Medical University, 1-1 Yazako Karimata, Nagakute, Aichi, Japan
| | - Hiroaki Okada
- Department of Radiology, Aichi Medical University, 1-1 Yazako Karimata, Nagakute, Aichi, Japan
| | - Takahiro Yamamoto
- Department of Radiology, Aichi Medical University, 1-1 Yazako Karimata, Nagakute, Aichi, Japan
| | - Nozomu Matsunaga
- Department of Radiology, Aichi Medical University, 1-1 Yazako Karimata, Nagakute, Aichi, Japan
| | - Shuji Ikeda
- Department of Radiology, Aichi Medical University, 1-1 Yazako Karimata, Nagakute, Aichi, Japan
| | - Yuichiro Izumi
- Department of Radiology, Aichi Medical University, 1-1 Yazako Karimata, Nagakute, Aichi, Japan
| | - Akira Kitagawa
- Department of Radiology, Aichi Medical University, 1-1 Yazako Karimata, Nagakute, Aichi, Japan
| | - Toyohiro Ota
- Department of Radiology, Aichi Medical University, 1-1 Yazako Karimata, Nagakute, Aichi, Japan
| | - Kojiro Suzuki
- Department of Radiology, Aichi Medical University, 1-1 Yazako Karimata, Nagakute, Aichi, Japan
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Chen J, Lai L, Luo J, Wang H, Li M, Huang M. DEM-TACE as the initial treatment could improve the clinical efficacy of the hepatocellular carcinoma with portal vein tumor thrombus: a retrospective controlled study. BMC Cancer 2022; 22:1242. [PMID: 36451104 PMCID: PMC9714197 DOI: 10.1186/s12885-022-10361-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2022] [Accepted: 11/23/2022] [Indexed: 12/05/2022] Open
Abstract
BACKGROUND Conventional-transarterial chemoembolization (C-TACE) was proven to improve overall survival (OS) in hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT), drug-eluting microsphere-TACE (DEM-TACE) was supposed to provide more benefit than C-TACE in this respect. PURPOSE To compare the safety and efficacy between DEM-TACE and C-TACE as the initial treatment in HCC patients with PVTT and to identify prognostic factors of OS. METHODS The medical records of advanced HCC patients with PVTT who underwent DEM-TACE or C-TACE as the initial thearpy from September 2015 with mean follow-up time 14.9 ± 1.2 (95% CI 12.6-17.2) months were retrospectively evaluated. A total of 97 patients were included, 49 patients in the DEM-TACE group and 48 in the C-TACE group. Adverse events (AEs) related to TACE were compared. Tumor and PVTT radiologic response, time to tumor progression (TTP) and OS were calculated and compared in both groups. RESULTS Patients in DEM-TACE group had a better radiologic response (Tumr response: 89.8% vs. 75.0%; PVTT response: 85.7% vs. 70.8%; overall response: 79.6% vs. 58.3%, P = 0.024) and longer TTP (7.0 months vs. 4.0 months, P = 0.040) than patients in C-TACE group. A lower incidence of abdominal pain was found in the DEM-TACE group than in C-TACE group (21 vs. 31, P = 0.032), but there were no significant differences between DEM-TACE and C-TACE patients in any other AEs reported. When compared to C-TACE, DEM-TACE also showed significant OS benefits (12.0 months vs. 9.0 months, P = 0.027). DEM-TACE treatment, the absence of arterioportal shunt (APS), lower AFP value and better PVTT radiologic response were the independent prognostic factors for OS in univariate/multivariate analyses, which provided us with a guide for better patient selection. CONCLUSIONS Based on our retrospective study, DEM-TACE can be performed safely and might be superior to C-TACE as the initial treatment for HCC patients with PVTT. TRIAL REGISTRATION Retrospectively registered.
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Affiliation(s)
- Junwei Chen
- Department of Interventional Radiology, the Third Affiliated Hospital of Sun Yat-Sen University, Tianhe Road 600#, Tianhe District, Guangzhou, 510630, Guangdong, China
| | - Lisha Lai
- Department of Radiology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, 510030, China
| | - Junyang Luo
- Department of Interventional Radiology, the Third Affiliated Hospital of Sun Yat-Sen University, Tianhe Road 600#, Tianhe District, Guangzhou, 510630, Guangdong, China
| | - Haofan Wang
- Department of Interventional Radiology, the Third Affiliated Hospital of Sun Yat-Sen University, Tianhe Road 600#, Tianhe District, Guangzhou, 510630, Guangdong, China
| | - Mingan Li
- Department of Interventional Radiology, the Third Affiliated Hospital of Sun Yat-Sen University, Tianhe Road 600#, Tianhe District, Guangzhou, 510630, Guangdong, China
| | - Mingsheng Huang
- Department of Interventional Radiology, the Third Affiliated Hospital of Sun Yat-Sen University, Tianhe Road 600#, Tianhe District, Guangzhou, 510630, Guangdong, China.
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Hong H, Jianwei J, Qinhua W, Yunjuan Y, Chen G, Jiaqin L. Effects of Interventional Therapy on Liver Metastases-Measurement of Liver Volume by Abdominal Computed Tomography. JOURNAL OF MEDICAL IMAGING AND HEALTH INFORMATICS 2021. [DOI: 10.1166/jmihi.2021.3660] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
Purpose: To evaluate the effects of transhepatic arterial infusion (TAI) with transcatheter arterial embolization (TAE) on liver volume of patients with liver metastases, by liver volumetry using 256-slice CT (iCT 256, Philips Healthcare). Methods: A retrospective analysis
of 19 patients with liver metastases, who received combination treatment of TAI with TAE, were conducted. Residual liver volumes (LV) were measured before (LV0), after the first (LV1) and the second treatment (LV2) with iCT 256. Bland-Altman method was used
to evaluate the agreements of residual liver volume between two reviewers. Residual liver volume changes were compared by One-Way ANOVA. Results: For the first reviewer, LV0, LV1, LV2 were: 872.67±139.31, 960.63±143.91, 842.13±141.45
cc. LV1 > LV0, but the difference was not significant (P = 0.061). LV2 < LV0, the difference was statistically significant (P = 0.013). LV2 < LV0, and the difference was not statistically significant (P
= 0.509). For the second reviewer, LV0, LV1, LV2 were: 909.99±135.46, 996.36±180.10, 845.70±131.632 cc. LV1 > LV0, the difference was not statistically significant (P = 0.083). LV2 < LV1,
the difference was statistically significant (P = 0.003). LV2 < LV0, the difference was not statistically significant (P = 0.194). Conclusion: Combination treatment of TAI with TAE did not induce significant liver damage in patients with metastatic
liver cancer, and iCT256 volumetry provided a precise measurement of liver volume and may play a critical role in the development of interventional surgery.
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Affiliation(s)
- Huang Hong
- Department of Radiology, Affiliated Hospital of Jiang Nan University, Wuxi 214040, China
| | - Jiang Jianwei
- Department of Radiology, Affiliated Hospital of Jiang Nan University, Wuxi 214040, China
| | - Wu Qinhua
- Department of Radiology, Affiliated Hospital of Jiang Nan University, Wuxi 214040, China
| | - Yin Yunjuan
- Department of Radiology, Affiliated Hospital of Jiang Nan University, Wuxi 214040, China
| | - Gu Chen
- Department of Radiology, Affiliated Hospital of Jiang Nan University, Wuxi 214040, China
| | - Lu Jiaqin
- Department of Radiology, Affiliated Hospital of Jiang Nan University, Wuxi 214040, China
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Fukushima T, Morimoto M, Kobayashi S, Ueno M, Sano Y, Kawano K, Asama H, Nagashima S, Maeda S. Repeated transarterial chemoembolization with epirubicin-loaded superabsorbent polymer microspheres vs. conventional transarterial chemoembolization for hepatocellular carcinoma. Mol Clin Oncol 2021; 14:119. [PMID: 33903825 PMCID: PMC8060853 DOI: 10.3892/mco.2021.2281] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2020] [Accepted: 03/17/2021] [Indexed: 02/07/2023] Open
Abstract
The aim of the present study was to evaluate the long-term outcomes and the impact of repeated conventional transarterial chemoembolization (C-TACE) and transarterial chemoembolization with epirubicin-loaded superabsorbent polymer embolics (SAP-TACE) on liver function in TACE-naïve patients with unresectable hepatocellular carcinoma (HCC). Overall, 155 consecutive patients with HCC received either C-TACE or SAP-TACE. The first cohort (n=71), treated between 2011 and 2014, received C-TACE; the second cohort (n=84), treated between 2014 and 2016, received SAP-TACE. Overall survival and deterioration of liver function were compared between the two cohorts. The 1-, 2- and 3-year overall survival rates and median survival times were 74, 50, 35% and 26 months in the C-TACE cohort and 75, 60, 39% and 28 months in the SAP-TACE cohort, respectively. There were no significant differences between the two groups (P=0.289). Age <70 years, Child-Pugh class A, alpha-fetoprotein <400 ng/ml and des-gamma-carboxy prothrombin <1,000 mAU/ml were identified as favorable prognostic factors in multivariate analysis. In the subgroup of patients with a Child-Pugh score of 5, survival was 29 months for C-TACE vs. 55 months for SAP-TACE (P<0.05). In the C-TACE cohort, the median Child-Pugh score was 6 after 3 cycles and 7 after 5 cycles of TACE, and the score worsened significantly (before vs. 3 cycles, P<0.05; before vs. 5 cycles, P<0.05). In the SAP-TACE cohort, the median Child-Pugh score was 6 after 3 and 5 cycles of TACE, and the score did not worsen during the treatment cycles. There were no differences in overall survival between repeated C-TACE and SAP-TACE in TACE-naïve patients with HCC. However, liver function deterioration was more evident in patients treated with C-TACE than in those treated with SAP-TACE.
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Affiliation(s)
- Taito Fukushima
- Department of Hepatobiliary and Pancreatic Oncology, Kanagawa Cancer Center, Yokohama, Kanagawa 241-8515, Japan
| | - Manabu Morimoto
- Department of Hepatobiliary and Pancreatic Oncology, Kanagawa Cancer Center, Yokohama, Kanagawa 241-8515, Japan
| | - Satoshi Kobayashi
- Department of Hepatobiliary and Pancreatic Oncology, Kanagawa Cancer Center, Yokohama, Kanagawa 241-8515, Japan
| | - Makoto Ueno
- Department of Hepatobiliary and Pancreatic Oncology, Kanagawa Cancer Center, Yokohama, Kanagawa 241-8515, Japan
| | - Yusuke Sano
- Department of Hepatobiliary and Pancreatic Oncology, Kanagawa Cancer Center, Yokohama, Kanagawa 241-8515, Japan
| | - Kuniyuki Kawano
- Department of Hepatobiliary and Pancreatic Oncology, Kanagawa Cancer Center, Yokohama, Kanagawa 241-8515, Japan
| | - Hiroyuki Asama
- Department of Hepatobiliary and Pancreatic Oncology, Kanagawa Cancer Center, Yokohama, Kanagawa 241-8515, Japan
| | - Shuhei Nagashima
- Department of Hepatobiliary and Pancreatic Oncology, Kanagawa Cancer Center, Yokohama, Kanagawa 241-8515, Japan
| | - Shin Maeda
- Department of Gastroenterology, Yokohama City University Hospital, Yokohama, Kanagawa 236-0004, Japan
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Imaging Changes and Clinical Complications After Drug-Eluting Bead Versus Conventional Transarterial Chemoembolization for Unresectable Hepatocellular Carcinoma: Multicenter Study. AJR Am J Roentgenol 2020; 217:933-943. [PMID: 33245680 DOI: 10.2214/ajr.20.24708] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND. Drug-eluting bead transarterial chemoembolization (DEB-TACE) has emerged as an alternative to conventional TACE (cTACE) for treatment of hepatocellular carcinoma (HCC), although selection between the approaches remains controversial. OBJECTIVE. The purpose of this study was to compare DEB-TACE and cTACE in the treatment of patients with unresectable HCC in terms of hepatobiliary changes on imaging and clinical complications. METHODS. This retrospective study included 1002 patients (871 men, 131 women; mean age, 59 ± 12 years) from three centers who had previously untreated unresectable HCC and underwent DEB-TACE with epirubicin (780 procedures in 394 patients) or cTACE with ethiodized oil mixed with doxorubicin and oxaliplatin (1187 procedures in 608 patients) between May 2016 and November 2018. Among these patients 83.4% had hepatitis B-related liver disease, 57.6% had Barcelona Clinic Liver Cancer (BCLC) stage A or B HCC, and 42.4% had three or more nodules. Mean tumor size was 6.3 ± 4.2 cm. Hepatobiliary changes and tumor response were evaluated with CT or MRI 1 month after TACE. Clinical records were reviewed for adverse events. RESULTS. Bile duct dilatation (p < .001) and portal vein narrowing (p = .006) on imaging and liver failure (p = .03) and grade 3 abdominal pain (p < .001) in clinical follow-up occurred at higher frequency in the DEB-TACE group (15.5%, 4.6%, 2.3%, and 6.1%) than in the cTACE (7.4%, 1.6%, 0.7%, and 2.1%) group. Higher frequency of bile duct dilation in patients who underwent DEB-TACE was observed in subgroup analyses that included patients with BCLC stage A or B HCC (p = .001), with cirrhosis (p < .001), without cirrhosis (p = .04), and without main portal vein tumor thrombus (p = .002). Total bilirubin level 1 month after treatment was 1.5 ± 2.4 mg/dL (95% CI, 1.2-1.8 mg/dL) for DEB-TACE versus 1.3 ± 2.0 mg/dL (95% CI, 1.1-1.5 mg/dL) for cTACE (p = .02). The cTACE and DEB-TACE groups did not differ in other manifestations of postembolization syndrome or systemic toxicity (p > .05). Local tumor disease control rates did not differ between the cTACE and DEB-TACE groups (1 month, 96.7% vs 98.5%, p = .06; 3 months, 81.8% vs 82.4%, p = .87), but overall DCR was significantly higher in the cTACE than in the DEB-TACE group (1 month, 87.5% vs 80.0%, p = .001; 3 months, 78.5% vs 72.1%, p = .02). CONCLUSION. Compared with cTACE, DEB-TACE was associated with greater frequency of hepatobiliary injury and severe abdominal pain. CLINICAL IMPACT. Greater caution and closer follow-up are warranted for patients who undergo DEB-TACE for unresectable HCC than for those who undergo cTACE.
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Drug-Eluting Microsphere Versus Cisplatin-Based Transarterial Chemoembolization for the Treatment of Hepatocellular Carcinoma: Propensity Score-Matched Analysis. AJR Am J Roentgenol 2020; 215:745-752. [PMID: 32569514 DOI: 10.2214/ajr.19.21669] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVE. The purpose of this study was to compare the safety and efficacy of transarterial chemoembolization (TACE) with 30- to 60-μm drug-eluting microspheres with those of cisplatin-based TACE in the treatment of unresectable hepatocellular carcinoma (HCC). MATERIALS AND METHODS. This retrospective single-center study included 607 patients who underwent drug-eluting microsphere (30-60 μm, loaded with doxorubicin) TACE (n = 119) or cisplatin-based TACE (n = 488) as first-line treatment of unresectable HCC between April 2017 and April 2018. With a propensity model correcting for selection bias, patients were selected from each treatment group to compare the effectiveness of drug-eluting microsphere TACE with that of cisplatin TACE. RESULTS. In the entire study population, the rates of major complications (1.7% vs 1.8%, p > 0.999), objective tumor response (80.7% vs 79.7%, p = 0.899), and time to progression (p = 0.536) were not significantly different between the drug-eluting microsphere TACE and cisplatin TACE groups. However, the drug-eluting microsphere TACE group had significantly higher objective tumor regression rates in subgroups with Barcelona Clinic Liver Cancer (BCLC) stage C disease (p = 0.033) and a maximal tumor size larger than 5 cm (p = 0.011). After adjustment by propensity score matching, the rates of major complications, objective tumor response, and time to progression remained similar between the two groups. CONCLUSION. Both TACE with 30- to 60-μm drug-eluting microspheres and cisplatin TACE were safe and effective for treating unresectable HCC. In patients with BCLC stage C disease and patients with large (> 5 cm) HCCs, TACE with 30- to 60-μm drug-eluting micro-spheres may have a better chance of obtaining an objective tumor response than conventional TACE performed with the protocol used in this study.
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Occurrence of Vascular Lake Phenomenon Before Embolization for the Prediction of Lipiodol Uptake for Intermediate-Stage Hepatocellular Carcinoma Patients that Underwent cTACE. Cardiovasc Intervent Radiol 2020; 43:1460-1467. [PMID: 32500251 DOI: 10.1007/s00270-020-02501-w] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2019] [Accepted: 04/18/2020] [Indexed: 02/07/2023]
Abstract
PURPOSE To compare Lipiodol uptake and tumor response in intermediate-stage hepatocellular carcinoma (HCC) with and without pre-embolization vascular lake phenomenon (VLP) and to identify the incidence and predictive factors of this phenomenon, in patients treated by conventional transarterial chemoembolization (cTACE). MATERIALS AND METHODS This retrospective study included 151 consecutive patients with intermediate HCC totaling 232 nodules, who underwent cTACE from June 2015 to October 2018. Patients were divided into two groups according to the presence of VLP before embolization. Initial Lipiodol uptake was assessed using post-cTACE computed tomography (CT) within 1-1.5 months after cTACE. Enhanced CT or magnetic resonance imaging was performed at 6 months after the procedure to assess local recurrence and distant metastasis. RESULTS The VLP was demonstrated in 21.85% (33/151) patients and 16.81% (39/232) nodules on the super-selective angiography. On nodule-based analysis, significantly better Lipiodol uptake (p < 0.001) and higher ORR (60.61% vs. 26.49%, p < 0.001) and DCR (87.88% vs. 51.66%, p < 0.001) were observed in the VLP group compared to the non-VLP group. The multivariate logistic regression analysis showed that the presence of VLP (OR 6.431, 95% CI 2.495-16.579) might be a predictive factor for better Lipiodol uptake. Univariate and multivariate logistic regression analysis showed that poor differentiation of tumor (OR 6.397, 95% CI 2.804-19.635) remained predictive for the VLP. CONCLUSION The incidence of VLP before embolization is 21.19%. The presence of VLP is well correlated with tumor Lipiodol uptake after cTACE and may be a new predictive factor for evaluation of cTACE efficacy and prognosis of intermediate HCC.
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Hori A, Ohira R, Nakamura T, Kimura Y, Ueda S, Torii M, Kennoki N, Hori S. Transarterial chemoembolization for pulmonary or mediastinal metastases from hepatocellular carcinoma. Br J Radiol 2020; 93:20190407. [PMID: 32142364 PMCID: PMC10993213 DOI: 10.1259/bjr.20190407] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2019] [Revised: 12/11/2019] [Accepted: 03/02/2020] [Indexed: 12/18/2022] Open
Abstract
OBJECTIVE To evaluate the feasibility, efficacy and safety of transcatheter arterial chemoembolization (TACE) with HepaSphere for patients with pulmonary or mediastinal metastases from hepatocellular carcinoma (HCC). METHODS Between June 2009 and January 2018, 14 patients with pulmonary or mediastinal metastases from HCC were treated with TACE with a combination of 1-3 chemotherapeutic drugs followed by HepaSphere embolization. As first end point, local tumor response and adverse events were evaluated after the first session of TACE, with Response Evaluation Criteria In Solid Tumors v. 1.1 and Common Terminology Criteria for Adverse Events v. 4 criteria, respectively. Overall survival was evaluated as secondary end point. TACE was repeated on-demand. RESULTS TACE with HepaSphere was well tolerated with acceptable safety profile and no 30 day mortality. 1 month objective response and disease control rate were calculated to be 7.1 and 100%, respectively. Mean tumor size reduction rate was 15.6±9.5% at the first month. Two Grade 3 cytopenia events were seen (14.3 %), however none of the Grade 2 or more post-embolization syndrome was observed. The median overall survival time was 15.0 months and the 1 year, 3 year and 5 year survival rate were, 57.1%, 28.6%, 19.1%, respectively. CONCLUSION Early experience showed that the transarterial treatment with HepaSphere is safe and effective treatment for patients with pulmonary or mediastinal metastases from HCC. ADVANCES IN KNOWLEDGE Currently, the effects of molecular targeted drugs on HCC metastases are limited and side-effects are relatively frequent. In the present study, transarterial treatment might be a promising treatment for HCC metastasis.
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Affiliation(s)
- Atsushi Hori
- Department of Radiology, IGT Clinic, Image Guided
Therapy, Osaka,
Japan
| | - Ryosuke Ohira
- Department of Radiology, Kansai Rosai Hospital,
Osaka, Japan
| | | | - Yasushi Kimura
- Department of Diagnostic and Interventional Radiology, Osaka
University Graduate School of Medicine, Suita,
Osaka, Japan
| | - Shota Ueda
- Department of Radiology, IGT Clinic, Image Guided
Therapy, Osaka,
Japan
| | - Masahiro Torii
- Department of Radiology, IGT Clinic, Image Guided
Therapy, Osaka,
Japan
| | - Norifumi Kennoki
- Department of Radiology, IGT Clinic, Image Guided
Therapy, Osaka,
Japan
| | - Shinichi Hori
- Department of Radiology, IGT Clinic, Image Guided
Therapy, Osaka,
Japan
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11
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Malagari K, Moschouris H, Kiakidis T, Harward S, Kelekis A, Vrakas S, Koundouras D, Filipiadis D, Glantzounis G, Emmanouil E, Chatziioannou A, Vergadis V, Elefsiniotis I, Koskinas J, Dourakis S, Kelekis N. Five-Years Outcome Analysis of 142 Consecutive Hepatocellular Carcinoma Patients Treated with Doxorubicin Eluting Microspheres 30-60 μm: Results from a Single-Centre Prospective Phase II Trial. Cardiovasc Intervent Radiol 2019; 42:1551-1562. [PMID: 31321482 DOI: 10.1007/s00270-019-02260-3] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2019] [Accepted: 06/03/2019] [Indexed: 12/19/2022]
Abstract
PURPOSE To assess prospectively long-term results of doxorubicin-loaded HepaSphere 30-60 μm in consecutive patients with hepatocellular carcinoma (HCC) not amenable to curative treatments. PATIENTS AND METHODS Single-center study from June 2011 to December 2015 in 151 patients treated with 75 mg of doxorubicin per HepaSphere vial. Baseline: Barcelona Clinic Liver Cancer BCLC A/B was 49.3%/50.7%, and median diameter 6.1 cm (mean 6.7 ± 2.0). Liver function, local response (mRECIST), liver time to progression (LTTP), progression-free survival (PFS), overall survival (OS) and adverse events (AEs) were recorded. RESULTS Final analysis included 142 patients with median follow-up of 46.8 months (range 4-72) without grade 4/5 AEs, and 30-day mortality was 0%. Mean number of scheduled treatments was 2.6 (range 1-3) and on demand 3 (range 1-8). Complete response for single tumor ≤ 5 cm was 75.0% and 66.7% for Child A and Child B, while for > 5 cm was 28.6% and 11.8%, respectively. OS was 31.0 months (mean 33.3 ± 15.2; range 8-69), notably for BCLC A 41 months (mean 41.1 ± 15.3; range 13-69) and for BCLC B 26.0 (mean 26.0 ± 10.5; range 8-51). OS at 1, 3 and 5 years: 95.8%, 75.7% and 21.4% for BCLC A, and 94.4%, 36.1% and 2.7% for BCLC B. Median LTTP for BCLC A was 11 months (mean 11.9 ± 4.7; range 3-24) and 7.5 for BCLC B (mean 7.9 ± 2.9). Local response was significant for OS and LTTP (p < 0.0001), while size and lesion number affected LPFS and OS (p < 0.001). CONCLUSIONS HepaSphere 30-60 μm loaded with doxorubicin provides a safe and effective treatment option for patients with HCC.
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Affiliation(s)
- K Malagari
- 2nd Department of Radiology, Medical School, National and Kapodistrian University of Athens, 19 Monis Kyccou, 15669, Papagou, Athens, Greece. .,Attikon Hospital, Chaidari, Greece. .,Evgenidion Hospital, Athens, Greece.
| | - H Moschouris
- Radiology Department of Tzanion General Hospital, Athens, Greece
| | - Th Kiakidis
- 2nd Department of Radiology, Medical School, National and Kapodistrian University of Athens, 19 Monis Kyccou, 15669, Papagou, Athens, Greece.,Evgenidion Hospital, Athens, Greece
| | - S Harward
- University of Massachusets Medical School, Worcester, MA, USA
| | - A Kelekis
- 2nd Department of Radiology, Medical School, National and Kapodistrian University of Athens, 19 Monis Kyccou, 15669, Papagou, Athens, Greece.,Attikon Hospital, Chaidari, Greece.,Evgenidion Hospital, Athens, Greece
| | - S Vrakas
- Tzanion Hospital, Athens, Greece
| | - D Koundouras
- 2nd Clinic of Medicine and Hepatology Medical School, National and Kapodistrian University of Athens, Athens, Greece.,2nd Clinic of Internal Medicine University of Athens Hippokration Hospital, Athens, Greece
| | - D Filipiadis
- 2nd Department of Radiology, Medical School, National and Kapodistrian University of Athens, 19 Monis Kyccou, 15669, Papagou, Athens, Greece.,Attikon Hospital, Chaidari, Greece
| | - G Glantzounis
- Department of Surgery, University Hospital of Ioannina (UOI), Ioannina, Greece
| | - E Emmanouil
- 2nd Department of Radiology, Medical School, National and Kapodistrian University of Athens, 19 Monis Kyccou, 15669, Papagou, Athens, Greece.,Evgenidion Hospital, Athens, Greece
| | - A Chatziioannou
- Evgenidion Hospital, Athens, Greece.,1st Department of Radiology, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - V Vergadis
- Radiology Department of Laikon University Hospital, Athens, Greece
| | - I Elefsiniotis
- Department of Internal Medicine and Hepatology Unit, Agioi Anargyroi General and Oncology Hospital of Kifissia Hospital Timiou Stavrou and Noufaron, Kalyftaki, Athens, Greece
| | - J Koskinas
- 2nd Clinic of Medicine and Hepatology Medical School, National and Kapodistrian University of Athens, Athens, Greece.,2nd Clinic of Internal Medicine University of Athens Hippokration Hospital, Athens, Greece
| | - S Dourakis
- 2nd Clinic of Medicine and Hepatology Medical School, National and Kapodistrian University of Athens, Athens, Greece.,2nd Clinic of Internal Medicine University of Athens Hippokration Hospital, Athens, Greece
| | - N Kelekis
- 2nd Department of Radiology, Medical School, National and Kapodistrian University of Athens, 19 Monis Kyccou, 15669, Papagou, Athens, Greece.,Attikon Hospital, Chaidari, Greece.,Evgenidion Hospital, Athens, Greece
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12
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Chen YP, Zhang JL, Zou Y, Wu YL. Recent Advances on Polymeric Beads or Hydrogels as Embolization Agents for Improved Transcatheter Arterial Chemoembolization (TACE). Front Chem 2019; 7:408. [PMID: 31231636 PMCID: PMC6560223 DOI: 10.3389/fchem.2019.00408] [Citation(s) in RCA: 41] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2019] [Accepted: 05/20/2019] [Indexed: 12/17/2022] Open
Abstract
Transcatheter arterial chemoembolization (TACE), aiming to block the hepatic artery for inhibiting tumor blood supply, became a popular therapy for hepatocellular carcinoma (HCC) patients. Traditional TACE formulation of anticancer drug emulsion in ethiodized oil (i.e., Lipiodol®) and gelatin sponge (i.e., Gelfoam®) had drawbacks on patient tolerance and resulted in undesired systemic toxicity, which were both significantly improved by polymeric beads, microparticles, or hydrogels by taking advantage of the elegant design of biocompatible or biodegradable polymers, especially amphiphilic polymers or polymers with both hydrophilic and hydrophobic chains, which could self-assemble into proposed microspheres or hydrogels. In this review, we aimed to summarize recent advances on polymeric embolization beads or hydrogels as TACE agents, with emphasis on their material basis of polymer architectures, which are important but have not yet been comprehensively summarized.
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Affiliation(s)
- Yun-Ping Chen
- Department of Oncology, The 910 Hospital of PLA, Quanzhou, China
| | - Jiang-Ling Zhang
- Department of Oncology, The 910 Hospital of PLA, Quanzhou, China
| | - Yanhong Zou
- Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences, Xiamen University, Xiamen, China
| | - Yun-Long Wu
- Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences, Xiamen University, Xiamen, China
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13
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Ikeda K. Recent advances in medical management of hepatocellular carcinoma. Hepatol Res 2019; 49:14-32. [PMID: 30308081 DOI: 10.1111/hepr.13259] [Citation(s) in RCA: 51] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2018] [Revised: 09/20/2018] [Accepted: 10/02/2018] [Indexed: 12/18/2022]
Abstract
Transcatheter arterial therapies for hepatocellular carcinoma (HCC) have developed during the last decade. A fine powder formulation of cisplatin and the new platinum agent miriplatin became standard medicines in addition to anthracyclines in transcatheter arterial chemoembolization (TACE) in Japan. Recent prospective and retrospective studies supported the usefulness of platinum agents as a chemotherapeutic at the time of varied TACE therapy. Although balloon-occluded TACE is an effective therapy for localized HCC and drug-eluting microspheres seemed to show a higher response rate in certain HCCs, the definite advantages of those procedures still remain uncertain. Intermediate stage HCC, or Barcelona Clinic Liver Cancer stage B, is regarded as a heterogeneous category with a wide spectrum of tumors and patients, and several subclassifications of the stage have been proposed to show different prognoses; there are also different recommended therapies in each subgroup. Authors have subclassified patients based on combinations of tumor size, tumor number, and liver function, with or without performance status. Because of differences of available medical resources and techniques in treatment procedures between countries, the most ideal and useful subgrouping remains inconclusive at present. Recently, a few systemic chemotherapies proved to be effective for advanced stage HCC in phase III studies: lenvatinib as the first line of therapy, and regorafenib, cabozantinib, and ramucirumab as second-line therapy. Other molecular-targeted and immune-oncological medicines are expected to follow in the near future. Some studies have suggested an advantage of early introduction of molecular-targeted therapy for TACE-resistant HCC in the intermediate stage.
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Affiliation(s)
- Kenji Ikeda
- Department of Hepatology, Toranomon Hospital, Tokyo, Japan
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14
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Nouri YM, Kim JH, Yoon HK, Ko HK, Shin JH, Gwon DI. Update on Transarterial Chemoembolization with Drug-Eluting Microspheres for Hepatocellular Carcinoma. Korean J Radiol 2018; 20:34-49. [PMID: 30627020 PMCID: PMC6315076 DOI: 10.3348/kjr.2018.0088] [Citation(s) in RCA: 57] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2018] [Accepted: 07/24/2018] [Indexed: 01/27/2023] Open
Abstract
Conventional transcatheter arterial chemoembolization (c-TACE) is a widely used first-line palliative treatment for patients with unresectable hepatocellular carcinoma (HCC). Despite the effectiveness of c-TACE, to date, technique and procedure scheduling has not yet been standardized. Drug-eluting microspheres (DEMs) were therefore introduced to ensure more sustained and tumor-selective drug delivery for permanent embolization. These DEMs can load various drugs and release them in a sustained manner over a prolonged period. This approach ensures the delivery of high concentrations of chemotherapeutic agents to tumors, without increasing systemic concentrations, and promote tumor ischemia and necrosis. This review summarizes the recent advances in the use of DEM-TACE to treat HCC.
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Affiliation(s)
- Yasir M Nouri
- Department of Radiology and Research Institute of Radiology, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jin Hyoung Kim
- Department of Radiology and Research Institute of Radiology, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Hyun-Ki Yoon
- Department of Radiology and Research Institute of Radiology, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Heung-Kyu Ko
- Department of Radiology and Research Institute of Radiology, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Ji Hoon Shin
- Department of Radiology and Research Institute of Radiology, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Dong Il Gwon
- Department of Radiology and Research Institute of Radiology, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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15
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Chang PY, Huang CC, Hung CH, Yu CY, Wu DK, Hwang JI, Liang PC, Wu RH, Tsai WL, Lin YJ, Liu YS, Liang HL, Lee RC, Chen CH. Multidisciplinary Taiwan Consensus Recommendations for the Use of DEBDOX-TACE in Hepatocellular Carcinoma Treatment. Liver Cancer 2018; 7:312-322. [PMID: 30488021 PMCID: PMC6249590 DOI: 10.1159/000487608] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2017] [Accepted: 02/11/2018] [Indexed: 02/04/2023] Open
Abstract
Transarterial chemoembolization (TACE) is the first-line treatment in patients with unresectable hepatocellular carcinoma (HCC). In recent years, there has been increasing clinical evidence that drug-eluting beads provide a combined ischemic and cytotoxic effect that may be superior to conventional TACE, with low systemic toxicity. The therapeutic value of TACE performed using the embolic microsphere DC Bead loaded with doxorubicin (drug-eluting bead doxorubicin [DEBDOX]) has been shown by several randomized controlled trials. Since Lencioni et al. [Cardiovasc Intervent Radiol 2012; 35: 980-985] published the first widely accepted technical recommendations on HCC embolization with DEBDOX-TACE in 2012, new studies have contributed to a better understanding of when and how to apply this new therapeutic modality, and they have yet to be incorporated into an updated guideline. Additionally, differences in the underlying liver pathology and practice of transcatheter embolization between Asian and Western populations have not been adequately addressed, and there remain significant variations in the TACE protocols adopted in different parts of the world. These mainly revolve around the number and type of chemotherapeutic agents used, type of embolic material, reliance on Lipiodol, and selectivity of catheter positioning. As a result of these issues, it has been difficult to interpret and compare results obtained from different centers in a systematic fashion. To address these concerns, we convened a panel of experts specializing in different aspects of HCC treatment to craft an updated set of recommendations that better reflect recent clinical experiences and are tailored to the use of DEBDOX-TACE in Taiwan. The conclusions of this expert panel are described in the following article.
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Affiliation(s)
- Pi-Yi Chang
- Department of Radiology, Taichung Veterans General Hospital, Taichung City, Taiwan
| | - Chun-Chieh Huang
- Department of Radiology, Far Eastern Memorial Hospital, Taipei, Taiwan
| | - Chao-Hung Hung
- Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung City, Taiwan
| | - Chih-Yung Yu
- Department of Radiology, Tri-Service General Hospital, Taipei, Taiwan
| | - Ding-Kwo Wu
- Department of Radiology, Kaohsiung Medical University Chung-Ho Memorial Hospital, Kaohsiung City, Taiwan
| | - Jen-I Hwang
- Department of Radiology, Tungs' Taichung Metro Harbor Hospital, Taichung City, Taiwan
| | - Po-Chin Liang
- Department of Radiology, National Taiwan University Hospital, Taipei, Taiwan
| | - Reng-Hong Wu
- Department of Radiology, Chi Mei Hospital, Tainan City, Taiwan
| | - Wei-Lun Tsai
- Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung City, Taiwan
| | - Yih-Jyh Lin
- Department of Surgery, National Cheng Kung University Hospital, Tainan City, Taiwan
| | - Yi-Sheng Liu
- Department of Diagnostic Radiology, National Cheng Kung University Hospital, Tainan City, Taiwan
| | - Huei-Lung Liang
- Department of Radiology, Kaohsiung Veterans General Hospital, Kaohsiung City, Taiwan
| | - Rheun-Chuan Lee
- Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Chien-Hung Chen
- Department of Internal Medicine, National Taiwan University Hospital Yunlin Branch and National Taiwan University College of Medicine, Douliu City, Taiwan,*Chien-Hung Chen, MD, PhD, Department of Internal Medicine, National Taiwan University Hospital Yunlin Branch, and National Taiwan University College of Medicine, No. 579, Sec. 2, Yunlin Road, Douliu City, Yunlin County 640 (Taiwan), E-Mail
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16
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He SH, Xu W, Sun ZW, Liu WB, Liu YJ, Wei HF, Xiao JR. Selective Arterial Embolization for the Treatment of Sacral and Pelvic Giant Cell Tumor: A Systematic Review. Orthop Surg 2018. [PMID: 28644557 DOI: 10.1111/os.12336] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Abstract
Giant cell tumor of the bone (GCTB) is a locally aggressive tumor with a certain distant metastatic rate. For sacral GCT (SGCT) and pelvic GCT (PGCT), surgery has its limitations, especially for unresectable or recurrent tumors. Selective arterial embolization (SAE) is reported to be an option for treatment in several cases, but there are few systematic reviews on the effects of SAE on SGCT and/or PGCT. Medline and Embase databases were searched for eligible English articles. Inclusion and exclusion criteria were conducted before searching. All the clinical factors were measured by SPSS software, with P-values ≤0.05 considered statistically significant. A total of 9 articles were retrieved, including 44 patients receiving SAE ranging from 1 to 10 times. During the mean follow-up period of 85.8 months, the radiographic response rate was 81.8%, with a local control and overall survival rate of 75% and 81.8%, respectively. No bowel, bladder, or sexual dysfunction was observed. Three patients developed distant metastases and finally died. Patients with primary tumors tended to have better prognosis than those with recurrence (P = 0.039). The favorable outcomes of SAE suggest that it may be an alternative treatment for SGCT and PGCT patients for whom surgery is not appropriate.
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Affiliation(s)
- Shao-Hui He
- Department of Orthopaedic Oncology, Spinal Tumor Center, Changzheng Hospital, Second Military Medical University, Shanghai, China
| | - Wei Xu
- Department of Orthopaedic Oncology, Spinal Tumor Center, Changzheng Hospital, Second Military Medical University, Shanghai, China
| | - Zheng-Wang Sun
- Department of Orthopaedic Oncology, Spinal Tumor Center, Changzheng Hospital, Second Military Medical University, Shanghai, China
| | - Wei-Bo Liu
- Department of Orthopaedic Oncology, Spinal Tumor Center, Changzheng Hospital, Second Military Medical University, Shanghai, China.,Department of Spine Surgery, Central Hospital of Qingdao, Qingdao, China
| | - Yu-Jie Liu
- Department of Orthopaedic Oncology, Spinal Tumor Center, Changzheng Hospital, Second Military Medical University, Shanghai, China
| | - Hai-Feng Wei
- Department of Orthopaedic Oncology, Spinal Tumor Center, Changzheng Hospital, Second Military Medical University, Shanghai, China
| | - Jian-Ru Xiao
- Department of Orthopaedic Oncology, Spinal Tumor Center, Changzheng Hospital, Second Military Medical University, Shanghai, China
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17
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Cavalcante RN, Nasser F, Motta-Leal-Filho JM, Affonso BB, Galastri FL, De Fina B, Garcia RG, Wolosker N. Occurrence of Vascular Lake Phenomenon as a Predictor of Improved Tumor Response in HCC Patients That Underwent DEB-TACE. Cardiovasc Intervent Radiol 2017; 40:1044-1051. [PMID: 28500458 DOI: 10.1007/s00270-017-1678-1] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2017] [Accepted: 04/28/2017] [Indexed: 12/15/2022]
Abstract
PURPOSE To evaluate incidence and predictive factors for the vascular lake phenomenon (VLP), as well as to compare local and overall tumor response in patients with and without VLP induced during DEB-TACE for HCC. METHODS A total of 200 consecutive patients with 323 HCC nodules underwent first-session DEB-TACE from 2011 to 2014. Patients were divided in two groups, according to the presence of the VLP during DEB-TACE. Pre- and post-treatment imaging studies (CT or MRI) were performed. Primary endpoint was assessment of tumor response, evaluated by mRECIST. Comparison of response rates between the VLP group and the non-VLP group was performed. Secondary endpoints were the determination of incidence rate and predictive factors for the VLP. RESULTS The VLP was observed in 39/323 (12.1%) of the nodules treated. At multivariate logistic regression analysis, tumor size ≥3 cm in diameter (OR 13.95; 95% CI 3.60-54.05), presence of a pseudocapsule (OR 6.67; 95% CI 1.45-30.59) and alpha-fetoprotein levels (OR 1.004; 95% CI 1.000-1.007) remained predictive for the VLP occurrence. On a nodule-based analysis (p < 0.001), target lesion response analysis (p = 0.003) and overall response analysis (p = 0.004) the VLP group presented a higher objective response rate than the non-VLP group. CONCLUSION VLP is observed in 12% of the patients and happens more frequently in large and encapsulated tumors. It seems to be associated with better local and overall responses in HCC patients who underwent DEB-TACE.
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Affiliation(s)
- Rafael Noronha Cavalcante
- Department of Interventional Radiology, Hospital Israelita Albert Einstein, 627 Albert Einstein Street, São Paulo, 05652-900, Brazil.
| | - Felipe Nasser
- Department of Interventional Radiology, Hospital Israelita Albert Einstein, 627 Albert Einstein Street, São Paulo, 05652-900, Brazil
| | - Joaquim M Motta-Leal-Filho
- Department of Interventional Radiology, Hospital Israelita Albert Einstein, 627 Albert Einstein Street, São Paulo, 05652-900, Brazil
| | - Breno B Affonso
- Department of Interventional Radiology, Hospital Israelita Albert Einstein, 627 Albert Einstein Street, São Paulo, 05652-900, Brazil
| | - Francisco L Galastri
- Department of Interventional Radiology, Hospital Israelita Albert Einstein, 627 Albert Einstein Street, São Paulo, 05652-900, Brazil
| | - Bruna De Fina
- Department of Interventional Radiology, Hospital Israelita Albert Einstein, 627 Albert Einstein Street, São Paulo, 05652-900, Brazil
| | - Rodrigo G Garcia
- Department of Interventional Radiology, Hospital Israelita Albert Einstein, 627 Albert Einstein Street, São Paulo, 05652-900, Brazil
| | - Nelson Wolosker
- Department of Interventional Radiology, Hospital Israelita Albert Einstein, 627 Albert Einstein Street, São Paulo, 05652-900, Brazil
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18
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Asayama Y, Okamoto D, Ushijima Y, Nishie A, Ishigami K, Takayama Y, Fujita N, Honda H. Predictors of therapeutic effect of transarterial chemoembolisation using drug-eluting beads for hepatocellular carcinoma. Clin Radiol 2017; 72:780-785. [PMID: 28442142 DOI: 10.1016/j.crad.2017.03.023] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2017] [Revised: 01/31/2017] [Accepted: 03/27/2017] [Indexed: 01/29/2023]
Abstract
AIMS To identify predictors of a therapeutic effect after transarterial chemoembolisation using drug-eluting beads (DEB-TACE) for hepatocellular carcinoma (HCC). MATERIALS AND METHODS Between January 2015 and July 2015, tumour variables and angiographic data were collected for 25 patients (49 target lesions) after they had undergone the DEB-TACE procedure for HCC. The therapeutic effect was evaluated according to the Response Evaluation Criteria in Cancer of the Liver at follow-up dynamic computed tomography (CT) performed within 1-4 months after the procedure. A p<0.05 was considered significant. RESULTS On a target lesion basis, the objective response (TE3/4) rate was 63.3% (31 of 49). On univariate analysis, larger size (≥2 cm) was a predictor of an objective response (p=0.029). The tumour location of the medial (segment 4) or caudate (segment 1) lobe also indicated a poor therapeutic effect (TE1/2), but not at the level of significance (p=0.051). Multivariate analysis identified tumour size (odds ratio, 8.60; 95% confidence interval, 1.87-62.8) and tumour location (odds ratio, 12.2; 95% confidence interval, 2.12-129.8) as significant factors associated with a therapeutic effect. On a patient basis, 10 of 25 (40%) patients showed complete response/partial response. There were no significant differences between complete response/partial response and stable disease/progressive disease regarding age, gender, tumour markers, history of previous treatment, Child-Pugh class, T-stage, or Barcelona Clinic Liver Cancer Staging. CONCLUSION A short-term therapeutic effect was associated with tumour size and location on a target lesion basis.
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Affiliation(s)
- Y Asayama
- Department of Advanced Imaging and Interventional Radiology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
| | - D Okamoto
- Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
| | - Y Ushijima
- Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
| | - A Nishie
- Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
| | - K Ishigami
- Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
| | - Y Takayama
- Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
| | - N Fujita
- Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
| | - H Honda
- Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
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19
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Zurstrassen CE, Gireli LPDO, Tyng CJ, Bitencourt AGV, Guimarães MD, Barbosa PNV, Santos Cavalcante ACB, Matushita Junior JP, Amoedo MK, Coimbra FJ, Alves RCP, Chojniak R. Safety and efficacy of HepaSphere 50-100 μm in the treatment of hepatocellular carcinoma. MINIM INVASIV THER 2017. [PMID: 28635404 DOI: 10.1080/13645706.2017.1288142] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
AIM To evaluate the effects of HepaSphere 50-100 μm (Merit Medical) as a doxorubicin carrier and embolization agent for the treatment of hepatocellular carcinoma (HCC). MATERIAL AND METHODS A prospective analysis of 18 patients recruited from a national cancer center was conducted. This analysis evaluated the efficacy and safety of HepaSphere, as expressed by the treatment response rate (measured by the modified Response Evaluation Criteria in Solid Tumors, mRECIST) and by the prevalence of treatment-related adverse events, respectively. RESULTS The cohort was predominantly male, with a mean age of 69 years. The objective response rate (complete + partial response) was 53.3%. The variable most likely to be associated with objective response was Barcelona Clinic Liver Cancer (BCLC) staging. The most prevalent adverse events were nausea, vomiting and abdominal pain. CONCLUSION HepaSphere chemoembolization yielded a substantial objective response rate with an acceptable toxicity profile and should be considered an option for HCC treatment.
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Affiliation(s)
| | | | - Chiang Jeng Tyng
- a Interventional Radiology Department , A.C. Camargo Cancer Center , São Paulo , Brazil
| | | | | | | | | | | | | | - Felipe Jose Coimbra
- c Abdominal Surgery Department , A.C. Camargo Cancer Center , São Paulo , Brazil
| | | | - Rubens Chojniak
- b Imaging Department , A.C. Camargo Cancer Center , São Paulo , Brazil
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Morimoto M, Kobayashi S, Moriya S, Ueno M, Tezuka S, Irie K, Goda Y, Ohkawa S. Short-term efficacy of transarterial chemoembolization with epirubicin-loaded superabsorbent polymer microspheres for hepatocellular carcinoma: comparison with conventional transarterial chemoembolization. Abdom Radiol (NY) 2017; 42:612-619. [PMID: 27624498 DOI: 10.1007/s00261-016-0900-y] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
PURPOSE This study aimed to compare the short-term efficacy of transarterial chemoembolization (TACE) with epirubicin-loaded superabsorbent polymer embolics (SAP) and conventional TACE in TACE-naïve patients with unresectable hepatocellular carcinoma (HCC). METHODS Fifty consecutive patients (mean age, 72.8 years; hepatitis C, 46%; BCLC-A or B, 52% or 48%) treated with TACE with SAP during 2013-2015 and 55 consecutive patients (mean age, 71.8 years; hepatitis C, 40%; BCLC-A or B, 51% or 49%) treated with conventional TACE during 2011-2013 were evaluated. Safety evaluations were based on CTCAE ver. 4.0. Short-term efficacies, i.e., at 1 month after TACE, were assessed using the European Association for the Study of the Liver criteria. Overall survival rates were calculated using the Kaplan-Meier method. Short-term response markers were analyzed by univariate and multivariate analyses. RESULTS There was no significant difference in the incidence of any grade of adverse events. The objective response rates were 50% and 62% in patients treated with TACE with SAP and with conventional TACE, respectively (P = 0.358). The overall survival rates were not significantly different (P = 0.810); the 1-year survival rates and the median survival time of the patients treated with TACE with SAP and with conventional TACE were 76% and 74%, and 18 months and 21 months, respectively. Overall survival was related to the short-term response. An alpha-fetoprotein level <1,000 ng/mL was a significant short-term response marker on multivariate analysis. CONCLUSIONS For TACE-naïve patients, TACE with SAP and conventional TACE had comparable safety and short-term efficacies.
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Affiliation(s)
- Manabu Morimoto
- Hepatobiliary and Pancreatic Oncology, Kanagawa Cancer Center, 2-3-2 Nakao, Asahi-ku, Yokohama, 241-8515, Japan.
| | - Satoshi Kobayashi
- Hepatobiliary and Pancreatic Oncology, Kanagawa Cancer Center, 2-3-2 Nakao, Asahi-ku, Yokohama, 241-8515, Japan
| | - Satoshi Moriya
- Hepatobiliary and Pancreatic Oncology, Kanagawa Cancer Center, 2-3-2 Nakao, Asahi-ku, Yokohama, 241-8515, Japan
| | - Makoto Ueno
- Hepatobiliary and Pancreatic Oncology, Kanagawa Cancer Center, 2-3-2 Nakao, Asahi-ku, Yokohama, 241-8515, Japan
| | - Shun Tezuka
- Hepatobiliary and Pancreatic Oncology, Kanagawa Cancer Center, 2-3-2 Nakao, Asahi-ku, Yokohama, 241-8515, Japan
| | - Kuniyasu Irie
- Hepatobiliary and Pancreatic Oncology, Kanagawa Cancer Center, 2-3-2 Nakao, Asahi-ku, Yokohama, 241-8515, Japan
| | - Yoshihiro Goda
- Hepatobiliary and Pancreatic Oncology, Kanagawa Cancer Center, 2-3-2 Nakao, Asahi-ku, Yokohama, 241-8515, Japan
| | - Shinichi Ohkawa
- Hepatobiliary and Pancreatic Oncology, Kanagawa Cancer Center, 2-3-2 Nakao, Asahi-ku, Yokohama, 241-8515, Japan
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Savic LJ, Chapiro J, Geschwind JFH. Intra-arterial embolotherapy for intrahepatic cholangiocarcinoma: update and future prospects. Hepatobiliary Surg Nutr 2017; 6:7-21. [PMID: 28261591 DOI: 10.21037/hbsn.2016.11.02] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Intrahepatic cholangiocarcinoma (ICC) is a rare disease and carries a poor prognosis with surgery remaining the only curative treatment option. However, due to the late presentation of symptoms and close proximity of the tumors to central hepatic structures, only about 30% of patients are classified eligible to resection. As for palliative approaches, ICC constitutes a possible indication for loco-regional therapies (LRT). As such, intra-arterial therapies (IAT) are reported to be feasible, safe and effective in inducing tumor response in unresectable ICC. The paradigm of IAT is premised on the selective delivery of embolic, chemotherapeutic agents to the tumor via its feeding arteries, thus allowing dose escalation within the carcinoma and reduction of systemic toxicity. Conventional transcatheter arterial chemoembolization (cTACE) so far remains the most commonly used IAT modality. However, drug-eluting beads (DEB)-TACE was initiated with the idea of more selective targeting of the tumor owing to the combined embolizing as well as drug-eluting properties of the microspheres used in this setting. Moreover, radioembolization is performed by intra-arterial administration of very small spheres containing β-emitting yttrium-90 (Y90-RE) to the site of the tumor. Clinical evidence exists in support of survival benefits for IAT in the palliative treatment of ICC compared to surgery and systemic chemotherapy. As for combination regimens, cTACE, DEB-TACE and Y90-RE are reported to achieve conversion of patients to surgery in a sequential treatment planning and simultaneous IAT combinations may provide a therapeutic option for treatment escalation. Regarding the current status of literature, controlled randomized prospective trials to compare different IAT techniques and combination therapies as well as treatment recommendations for different IAT modalities are needed.
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Affiliation(s)
- Lynn Jeanette Savic
- Department of Radiology and Biomedical Imaging, Yale University School of Medicine, New Haven, USA; ; Department of Diagnostic and Interventional Radiology, Universitätsmedizin Charité, Berlin, Germany
| | - Julius Chapiro
- Department of Radiology and Biomedical Imaging, Yale University School of Medicine, New Haven, USA; ; Department of Diagnostic and Interventional Radiology, Universitätsmedizin Charité, Berlin, Germany
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22
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Lee S, Kim KM, Lee SJ, Lee KH, Lee DY, Kim MD, Kim DY, Kim SU, Won JY. Hepatic arterial damage after transarterial chemoembolization for the treatment of hepatocellular carcinoma: comparison of drug-eluting bead and conventional chemoembolization in a retrospective controlled study. Acta Radiol 2017; 58:131-139. [PMID: 27217418 DOI: 10.1177/0284185116648501] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Background Transarterial chemoembolization (TACE) of hepatocellular carcinoma (HCC) frequently causes feeding artery stenosis or occlusion that may interfere with repeated treatment. Purpose To investigate the incidence and predictors of hepatic arterial damage (HAD) after drug-eluting bead-TACE (DEB-TACE) in comparison with conventional TACE (Conv-TACE). Material and Methods We retrospectively analyzed 54 patients who underwent DEB-TACE for HCC as an initial treatment with follow-up angiography and 54 patients who underwent Conv-TACE using doxorubicin-lipiodol mixture and gelfoam particles for comparison. HAD was evaluated after a single session of TACE and graded as follows: grade I, no significant wall irregularity; grade II, overt stenosis; grade III, occlusion. Results The incidence of HAD was significantly higher in the DEB-TACE group than the Conv-TACE group when analyzed per branch (odds ratio [OR], 6.36; P < 0.001) and per patient (OR, 3.15; P = 0.005). For each HAD grade, the mean doxorubicin dose was greater in the DEB-TACE group than in the Conv-TACE group ( P < 0.001, P = 0.053, and P = 0.01 for grades I, II, and III, respectively). In multivariate analysis, risk factors of HAD included mean doxorubicin dose and selective embolization in the Conv-TACE group ( P = 0.03 and P < 0.001, respectively) and mean doxorubicin dose in the DEB-TACE group ( P = 0.004). Conclusion The incidence and grade of HAD were higher after DEB-TACE compared to Conv-TACE with doxorubicin dose as a possible risk factor. HAD was independent of overall survival in both groups.
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Affiliation(s)
- Seungsoo Lee
- 1 Department of Radiology, Research Institute of Radiological Science, Yonsei University, College of Medicine, Seoul, Republic of Korea
| | - Kyoung Min Kim
- 1 Department of Radiology, Research Institute of Radiological Science, Yonsei University, College of Medicine, Seoul, Republic of Korea
| | - Shin Jae Lee
- 1 Department of Radiology, Research Institute of Radiological Science, Yonsei University, College of Medicine, Seoul, Republic of Korea
| | - Kwang-Hun Lee
- 1 Department of Radiology, Research Institute of Radiological Science, Yonsei University, College of Medicine, Seoul, Republic of Korea
| | - Do Yun Lee
- 1 Department of Radiology, Research Institute of Radiological Science, Yonsei University, College of Medicine, Seoul, Republic of Korea
| | - Man Deuk Kim
- 1 Department of Radiology, Research Institute of Radiological Science, Yonsei University, College of Medicine, Seoul, Republic of Korea
| | - Do Young Kim
- 2 Department of Internal Medicine, Institute of Gastroenterology, Yonsei University, College of Medicine, Seoul, Korea
| | - Seung Up Kim
- 2 Department of Internal Medicine, Institute of Gastroenterology, Yonsei University, College of Medicine, Seoul, Korea
| | - Jong Yun Won
- 1 Department of Radiology, Research Institute of Radiological Science, Yonsei University, College of Medicine, Seoul, Republic of Korea
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Ogawa M, Takayasu K, Hirayama M, Miura T, Shiozawa K, Abe M, Matsumoto N, Nakagawara H, Ohshiro S, Yamamoto T, Tanaka N, Moriyama M, Mutou H, Yamamoto Y, Irie T. Efficacy of a microballoon catheter in transarterial chemoembolization of hepatocellular carcinoma using miriplatin, a lipophilic anticancer drug: Short-term results. Hepatol Res 2016; 46:E60-9. [PMID: 25974615 DOI: 10.1111/hepr.12527] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2014] [Revised: 04/14/2015] [Accepted: 04/18/2015] [Indexed: 12/14/2022]
Abstract
AIM The goal of the study was to evaluate the efficacy and safety of balloon-occluded transarterial chemoembolization (B-TACE) of hepatocellular carcinoma (HCC) using miriplatin (a lipophilic anticancer drug) and gelatin particles. METHODS B-TACE was performed for 62 HCC nodules in 33 patients who could not be treated by surgical resection or radiofrequency ablation. All 33 patients had a history of transarterial chemoembolization (TACE) treatment prior to B-TACE. As a historical comparison, we investigated 40 nodules in 28 patients treated by TACE using a conventional microcatheter (C-TACE), miriplatin and gelatin particles. The therapeutic effect per tumor was compared between the groups based on the Response Evaluation Criteria in Cancer Study Group of Japan (RECICL) and side-effects were compared based on the Common Terminology Criteria for Adverse Events (ver. 4.0). RESULTS The therapeutic efficacy after 4-12 weeks was evaluated in 59 nodules in the B-TACE group and in 37 nodules in the C-TACE group. Of these nodules, TE4 occurred in 29 (49.2%) in the B-TACE group and in 10 (27%) in the C-TACE group. Local efficacy was significantly higher in nodules treated by B-TACE than by C-TACE. The side-effects on hepatic function were similar in the two groups. CONCLUSION Our results suggest that B-TACE with miriplatin is a useful treatment for hepatocellular carcinoma.
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Affiliation(s)
| | | | | | - Takao Miura
- Department of Gastroenterology and Hepatology
| | | | | | | | | | - Shu Ohshiro
- Department of Gastroenterology and Hepatology
| | | | | | | | | | | | - Toshiyuki Irie
- Department of Radiology, Hitachi General Hospital, Hitachi, Japan
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Intra-arterial chemoembolization with hepasphere 50–100μm for patients with unresectable hepatocellular carcinoma: Initial experience in Egyptian Liver Hospital. THE EGYPTIAN JOURNAL OF RADIOLOGY AND NUCLEAR MEDICINE 2015. [DOI: 10.1016/j.ejrnm.2015.05.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
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Seki A, Hori S, Shimono C. Management of vascular lake phenomenon on angiography during chemoembolization with superabsorbent polymer microspheres. Jpn J Radiol 2015; 33:741-8. [PMID: 26493810 DOI: 10.1007/s11604-015-0486-2] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2015] [Accepted: 10/07/2015] [Indexed: 12/31/2022]
Abstract
PURPOSE Contrast material pooling on angiography within a tumor bed during embolization for hepatocellular carcinoma (HCC) presents as the vascular lake (VL) phenomenon. This retrospective study aimed to evaluate the frequency and management of VLs during chemoembolization with drug-eluting beads (DEBs) and the relationship between the VL and local response. MATERIALS AND METHODS A total of 123 HCC patients without vascular invasion or intrahepatic metastases who underwent chemoembolization with DEBs (50-100 µm superabsorbent polymer microspheres loaded with epirubicin) were enrolled. Gelatin sponge particles (GS) were injected for additional embolization in limited patients with steadily increasing size of VLs during DEB injection. Overall, 338 nodules were divided into three groups: lesions without a VL (non-VL; n = 250); lesions with a VL but without additional GS embolization [VL-GS (-), n = 58]; and lesions with both VL and additional GS embolization [VL-GS (+); n = 30]. The local responses were statistically compared by Fisher's exact test with the Bonferroni correction. RESULTS The frequency of VLs was 26.0% (88/338). The response rate in the non-VL group (54.0%) was significantly lower than those in the VL-GS (-) (91.4%; P < 0.0001) and VL-GS (+) (96.7%; P < 0.0001) groups. CONCLUSIONS VL is a common angiographic finding and might be associated with the local response.
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Affiliation(s)
- Akihiko Seki
- Department of Medical Oncology, Suita Tokushukai Hospital, 1-21 Senriokanishi, Suita, Osaka, 565-0814, Japan.
| | - Shinichi Hori
- Department of Radiology, Gate Tower Institute for Image Guided Therapy, 11F, Gate Tower Building, 1-Rinku Ohrai-Kita, Izumisano, Osaka, 598-0048, Japan
| | - Chigusa Shimono
- Department of Medical Oncology, Suita Tokushukai Hospital, 1-21 Senriokanishi, Suita, Osaka, 565-0814, Japan
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26
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Spindeldreier KC, Thiesen J, Krämer I. Loading, release and stability of epirubicin-loaded drug-eluting beads. J Oncol Pharm Pract 2015; 22:591-8. [DOI: 10.1177/1078155215594416] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Purpose The aim of this study was to determine the loading efficiency, physico-chemical stability and release of epirubicin-loaded DC Bead™ (Biocompatibles UK Ltd, a BTG International group company) (bead size 70–150 µm (=DC Bead M1™) and 100–300 µm) after loading with epirubicin solution (2 mg/ml) or reconstituted powder formulation (25 mg/ml) and controlled storage. Methods DC Bead™ were loaded with 76 mg epirubicin solution (Epimedac™, Medac GmbH) or 75 mg epirubicin powder formulation (Farmorubicin™, Pharmacia Pfizer GmbH) per 2 ml of beads. Drug loading efficiency and stability were determined by measuring the epirubicin concentration in the excess solution after predetermined intervals (maximum 24 h) and different agitation conditions. Syringes with loaded beads were stored protected from light at room temperature. At predetermined intervals the beads were transferred into 200 ml phosphate buffered solution (pH 7.2) as elution medium and stirred automatically for 2 h not followed or followed by addition of 200 ml of 20% sodium chloride (=NaCl) solution and stirred for another 2 h to analyse the drug release and integrity of the epirubicin-loaded beads. Elution experiments were performed and samples taken periodically over a four-week period (day 0, 7, 14 and 28). A reversed-phase high-performance liquid chromatography assay with ultraviolet detection was utilized to analyse the concentration and purity of epirubicin. Results The loading procedure for DC Bead™ with epirubicin drug solutions resulted in a loading percentage of 95–99% within 6 h dependent on the bead size, epirubicin concentration in the loading solution and loading conditions. Loading levels remained stable and no epirubicin degradation products were observed over the period of 28 days, while the loaded beads were stored light protected at room temperature. Release of epirubicin into 200 ml phosphate buffered solution elution medium and additionally followed by release into the admixture with 200 ml 20% NaCl solution amounted to 5% and about 20% of the loaded epirubicin, respectively. Integrity of loaded epirubicin was proven over 28 days. Conclusions Epirubicin can be loaded into DC Bead™ of different sizes using the epirubicin powder formulation (25 mg/ml) or epirubicin injection concentrate (2 mg/ml). Physico-chemical stability is maintained over a period of at least 28 days when stored light protected at room temperature. Elution of epirubicin is dependent on the volume and cation exchange capacity of the elution medium.
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Affiliation(s)
- Kirsten C Spindeldreier
- Department of Pharmacy, University Medical Center Mainz, Johannes Gutenberg-University, Mainz, Germany
| | - Judith Thiesen
- Department of Pharmacy, University Medical Center Mainz, Johannes Gutenberg-University, Mainz, Germany
| | - Irene Krämer
- Department of Pharmacy, University Medical Center Mainz, Johannes Gutenberg-University, Mainz, Germany
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Hiraki T, Koizumi J, Arai Y, Sakurai Y, Kumada H, Nambu Y, Hori S. Transcatheter arterial embolization of hypervascular tumors with HepaSphere: prospective multicenter open label clinical trial of microspheres in Japan. Jpn J Radiol 2015; 33:479-86. [DOI: 10.1007/s11604-015-0448-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2015] [Accepted: 06/16/2015] [Indexed: 10/23/2022]
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Malagari K, Pomoni A, Filippiadis D, Kelekis D. Chemoembolization of hepatocellular carcinoma with HepaSphere™. Hepat Oncol 2015; 2:147-157. [PMID: 30190994 PMCID: PMC6095161 DOI: 10.2217/hep.15.2] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Abstract
This review discusses the current data on Hepasphere™ in the treatment of hepatocellular carcinoma. HepaSphere is a drug-loadable microsphere that can be bound with doxorubicin, epirubicin, cisplatin or oxaliplatin. In vitro and in vivo studies confirm lower systemic exposure to the drug and fewer systemic doxorubicin-related side effects. Studies suggest that this technique is better tolerated than conventional lipiodol-based chemoembolization (c-TACE). In intermediate and early stage hepatocellular carcinoma - nonresponsive to curative treatments - complete response and partial response rates range from 22.2 to 48% and 43.7 to 51%, respectively. Studies with survival as an end-point are needed and head-to-head comparisons with other drug-eluting beads are necessary.
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Affiliation(s)
- Katerina Malagari
- Research & Imaging Unit, Evgenidion Hospital University of Athens, Medical School, Greece
- Department of Radiology, University of Athens, Medical School, Greece
| | - Anastasia Pomoni
- Research & Imaging Unit, Evgenidion Hospital University of Athens, Medical School, Greece
| | | | - Dimitrios Kelekis
- Research & Imaging Unit, Evgenidion Hospital University of Athens, Medical School, Greece
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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: 48] [Impact Index Per Article: 4.4] [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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Shiozawa K, Watanabe M, Ikehara T, Ogino Y, Umakoshi T, Matsukiyo Y, Kogame M, Matsui T, Kikuchi Y, Igarashi Y, Sumino Y. Delayed intratumoral hemorrhage after drug-eluting bead transarterial chemoembolization for hepatocellular carcinoma. Case Rep Oncol 2014; 7:739-45. [PMID: 25520649 PMCID: PMC4264514 DOI: 10.1159/000369005] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023] Open
Abstract
Transarterial chemoembolization (TACE) using a drug-eluting bead (DEB-TACE) for hepatocellular carcinoma (HCC) is a new treatment method. We report on a case of delayed intratumoral hemorrhage after DEB-TACE. An 81-year-old male with hepatitis C virus-related cirrhosis was diagnosed with a HCC of 35 mm in diameter in S5 detected by dynamic computed tomography (CT) and contrast-enhanced ultrasonography (CEUS). DEB-TACE with DC Bead (®) and epirubicin hydrochloride was performed because the patient declined to undergo surgical resection. The treatment was completed, and the course after DEB-TACE was favorable. However, right hypochondriac pain suddenly developed about 1 month after DEB-TACE. Unenhanced CT showed an increase of the tumor diameter and intratumoral high-intensity area, which was not enhanced in the arterial phase. CEUS performed at the time of right hypochondriac pain (5 weeks after DEB-TACE) showed nonenhancement of almost the entire tumor in the vascular phase. The cause of the symptom may have been DEB-TACE-associated intratumoral hemorrhage. Tumor hemorrhage has been reported after DEB-TACE with tumors >5 cm in diameter, and the tumor locations were subcapsular in all previous reports. There has been no case of a tumor with a diameter <5 cm distinct from the subcapsular, as was observed in our patient. Incomplete embolization might be the cause of the intratumoral hemorrhage experienced by this case presenting a few risks. To obtain the therapeutic effect of DEB-TACE while preventing the adverse events, it may be important to understand the characteristics of the beads and to apply the appropriate embolization to each individual case.
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Affiliation(s)
- Kazue Shiozawa
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Toho University Medical Center, Omori Hospital, Tokyo, Japan
| | - Manabu Watanabe
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Toho University Medical Center, Omori Hospital, Tokyo, Japan
| | - Takashi Ikehara
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Toho University Medical Center, Omori Hospital, Tokyo, Japan
| | - Yu Ogino
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Toho University Medical Center, Omori Hospital, Tokyo, Japan
| | - Tomoko Umakoshi
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Toho University Medical Center, Omori Hospital, Tokyo, Japan
| | - Yasushi Matsukiyo
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Toho University Medical Center, Omori Hospital, Tokyo, Japan
| | - Michio Kogame
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Toho University Medical Center, Omori Hospital, Tokyo, Japan
| | - Teppei Matsui
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Toho University Medical Center, Omori Hospital, Tokyo, Japan
| | - Yoshinori Kikuchi
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Toho University Medical Center, Omori Hospital, Tokyo, Japan
| | - Yoshinori Igarashi
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Toho University Medical Center, Omori Hospital, Tokyo, Japan
| | - Yasukiyo Sumino
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Toho University Medical Center, Omori Hospital, Tokyo, Japan
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Han S, Zhang X, Zou L, Lu C, Zhang J, Li J, Li M. Does drug-eluting bead transcatheter arterial chemoembolization improve the management of patients with hepatocellular carcinoma? A meta-analysis. PLoS One 2014; 9:e102686. [PMID: 25083860 PMCID: PMC4118844 DOI: 10.1371/journal.pone.0102686] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2013] [Accepted: 06/22/2014] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND Drug eluting beads (DEB) are relatively new embolic agents that allow sustained release of chemotherapeutic agents in a localized fashion to the tumor. This technique is associated with reduced systemic side effects relative to systemic chemotherapy and an increase in the dose of antineoplastic agent delivered to the lesion. The meta-analysis was undertaken to assess the effectiveness of DEB-transcatheter arterial chemoembolization (TACE) in the management of hepatocellular cancer. METHODS We searched the Web of Science, PubMed, EBSCO, EMBASE, the Wiley Library and Google Scholar for studies on DEB-TACE in the management of hepatocellular cancer from 1979 to April 2013. The risk of bias was assessed using RevMan 5 · 1. Random and fixed-effects meta-analytical models were used where indicated, and between-study heterogeneity was assessed. Disease control, complications and severe complications were recorded. RESULTS Five studies met the selection criteria, three RCTs and two case-control studies, published from 2010 to 2012, included 217 patients in the DEB-TACE group and 237 in the conventional-TACE group. There was no significance over disease control (OR 2.27, 95% CI 0.78-6.63) with moderate between-study heterogeneity (χ(2) = 6.83, degrees of freedom [df] = 3; p<0.08; I(2) = 56%). Complications in both groups were assessed and no significant difference was observed (χ(2) = 6.34, degrees of freedom [df] = 4; p<0.18; I(2)= 37%). Severe complications were also assessed and no significant difference was observed (χ(2) = 6.47, degrees of freedom [df] = 4; p<0.17; I(2)= 38%). No publication bias relating to the above outcomes was detected by funnel plot. DEB-TACE benefited disease control without an increase in complications and severe complications.
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Affiliation(s)
- Shilong Han
- Department of Interventional & Vascular Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China
| | - Xiaoping Zhang
- Department of Interventional & Vascular Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China
| | - Liling Zou
- Heart, Lung and Blood Vessel Center, Tongji University School of Medicine, Shanghai, China
| | - Chenhui Lu
- Department of Interventional & Vascular Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China
| | - Jun Zhang
- Heart, Lung and Blood Vessel Center, Tongji University School of Medicine, Shanghai, China
| | - Jue Li
- Heart, Lung and Blood Vessel Center, Tongji University School of Medicine, Shanghai, China
- * E-mail: (MQL); (JL)
| | - Maoquan Li
- Department of Interventional & Vascular Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China
- * E-mail: (MQL); (JL)
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INOUE T, MASAI N, OH RJ, SHIOMI H, HASHIDA N. Adaptive replanning intensity-modulated radiotherapy for choroidal metastasis of breast cancer using optical coherence tomography. JOURNAL OF RADIATION RESEARCH 2014; 55:502-508. [PMID: 24706996 PMCID: PMC4014173 DOI: 10.1093/jrr/rru023] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 06/21/2013] [Revised: 10/07/2013] [Accepted: 10/08/2013] [Indexed: 06/03/2023]
Abstract
Swept source optical coherence tomography (SS-OCT) is a convenient method for precise, early-stage detection of choroidal metastatic lesions, involving assessment of tumor response, and for regular follow-up studies. Using information obtained with SS-OCT, we performed intensity-modulated radiotherapy (IMRT) for a patient with choroidal metastasis from breast cancer with more accuracy than had been previously possible. We made replanning adaptive radiotherapy (ART) three times based on the rapid tumor shrinkage detected by weekly assessments with SS-OCT. Accordingly, the planning target volume (PTV) decreased from 1.6 cm(3) to 0.61 cm(3) (38%), with 0.95 cm(3) (59%) and 0.75 cm(3) (46%) as intermediate values during the treatment course. The D0.1 cm3 of the right optic nerve was also reduced from 1.70 Gy/fraction to 0.69 Gy/faction, with 1.41 Gy/fraction and 1.29 Gy/fraction as intermediate values. Adaptive replanning IMRT made it possible to perform locally curative treatment of the metastatic choroidal lesion with a higher dose for the PTV, and a lower dose for organs at risk (OARs).
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Affiliation(s)
- Toshihiko INOUE
- Miyakojima IGRT Clinic, 1-16-22 Miyakojima-ku, Osaka, 534-0021, Japan
| | - Norihisa MASAI
- Miyakojima IGRT Clinic, 1-16-22 Miyakojima-ku, Osaka, 534-0021, Japan
| | - Ryoong-Jin OH
- Miyakojima IGRT Clinic, 1-16-22 Miyakojima-ku, Osaka, 534-0021, Japan
| | - Hiroya SHIOMI
- Miyakojima IGRT Clinic, 1-16-22 Miyakojima-ku, Osaka, 534-0021, Japan
| | - Noriyasu HASHIDA
- Department of Ophthalmology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, 565-0871, Japan
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Dekervel J, van Malenstein H, Vandecaveye V, Nevens F, van Pelt J, Heye S, Laleman W, Van Steenbergen W, Vaninbroukx J, Verslype C, Maleux G. Transcatheter arterial chemoembolization with doxorubicin-eluting superabsorbent polymer microspheres in the treatment of hepatocellular carcinoma: midterm follow-up. J Vasc Interv Radiol 2013; 25:248-55.e1. [PMID: 24295569 DOI: 10.1016/j.jvir.2013.10.017] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2013] [Revised: 10/11/2013] [Accepted: 10/12/2013] [Indexed: 12/21/2022] Open
Abstract
PURPOSE To investigate prospectively the safety, tolerability, and efficacy of transarterial chemoembolization using superabsorbent polymer (SAP) microspheres loaded with doxorubicin for the treatment of hepatocellular carcinoma (HCC). MATERIALS AND METHODS During the years 2006-2011, 64 patients underwent 144 transarterial chemoembolization with SAP microspheres procedures. Most of the patients were staged as Barcelona Clinic Liver Cancer class B (65%). The most frequent underlying liver diseases were hepatitis C (35%) and alcoholic liver disease (28%) resulting in Child-Pugh A (73.4%) or Child-Pugh B (17%) liver cirrhosis. Tumor response was assessed using modified Response Evaluation Criteria in Solid Tumors with magnetic resonance (MR) imaging performed 4-6 weeks after each procedure. RESULTS Serious adverse events (n = 9) were ischemic or infectious in nature. Transarterial chemoembolization with SAP microspheres resulted in objective response rates of 67.5%, 44.5%, and 25% after first, second, and third sessions. There were 16 patients (25%) who underwent orthotopic liver transplantation after transarterial chemoembolization with SAP microspheres, of whom 2 experienced recurrent disease. During a median follow-up time of 14 months (range, 2-55 mo), 26 patients (40.5%) died. Median overall and transplant-free survivals were 20.5 months (95% confidence interval, 13.2-27.7) and 18 months (95% confidence interval, 14.2-21.8), respectively. CONCLUSIONS Transarterial chemoembolization with SAP microspheres has an excellent safety profile in cirrhotic patients, even in the presence of advanced liver disease (Child-Pugh B) or advanced stages of HCC. This treatment produced meaningful tumor response rates as assessed by MR imaging.
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Affiliation(s)
- Jeroen Dekervel
- Department of Hepatology, University Hospitals Leuven, Herestraat 49; Department of Clinical and Experimental Medicine, KU Leuven, 3000 Leuven, Belgium
| | - Hannah van Malenstein
- Department of Hepatology, University Hospitals Leuven, Herestraat 49; Department of Clinical and Experimental Medicine, KU Leuven, 3000 Leuven, Belgium
| | | | - Frederik Nevens
- Department of Hepatology, University Hospitals Leuven, Herestraat 49; Department of Clinical and Experimental Medicine, KU Leuven, 3000 Leuven, Belgium
| | - Jos van Pelt
- Department of Hepatology, University Hospitals Leuven, Herestraat 49; Department of Clinical and Experimental Medicine, KU Leuven, 3000 Leuven, Belgium
| | - Sam Heye
- Department of Radiology, University Hospitals Leuven, Herestraat 49
| | - Wim Laleman
- Department of Hepatology, University Hospitals Leuven, Herestraat 49; Department of Clinical and Experimental Medicine, KU Leuven, 3000 Leuven, Belgium
| | - Werner Van Steenbergen
- Department of Hepatology, University Hospitals Leuven, Herestraat 49; Department of Clinical and Experimental Medicine, KU Leuven, 3000 Leuven, Belgium
| | | | - Chris Verslype
- Department of Hepatology, University Hospitals Leuven, Herestraat 49; Department of Clinical and Experimental Medicine, KU Leuven, 3000 Leuven, Belgium
| | - Geert Maleux
- Department of Radiology, University Hospitals Leuven, Herestraat 49.
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Malagari K, Pomoni M, Moschouris H, Kelekis A, Charokopakis A, Bouma E, Spyridopoulos T, Chatziioannou A, Sotirchos V, Karampelas T, Tamvakopoulos C, Filippiadis D, Karagiannis E, Marinis A, Koskinas J, Kelekis DA. Chemoembolization of hepatocellular carcinoma with HepaSphere 30-60 μm. Safety and efficacy study. Cardiovasc Intervent Radiol 2013; 37:165-75. [PMID: 24263774 PMCID: PMC3895279 DOI: 10.1007/s00270-013-0777-x] [Citation(s) in RCA: 81] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2013] [Accepted: 09/01/2013] [Indexed: 02/07/2023]
Abstract
Background This study examined the safety, pharmacokinetics, and efficacy of transarterial chemoembolization of hepatocellular carcinoma (HCC) using a newly developed size of a superabsorbent polymer drug-eluting embolic material. Methods Forty-five patients with documented HCC (Child–Pugh score A/B: 55.5 %/44.5 %) were embolized with HepaSphere microspheres 30–60 μm with escalation of lesion, dose, and frequency of re-embolization. Local response was evaluated with modified response evaluation criteria in solid tumors (mRECIST). Plasma levels of doxorubicin were measured in 24 patients at baseline and at 5, 20, 40, 60, and 120 min, at 6, 24, and 48 h, and at 7 days, respectively, to determine doxorubicin in plasma (Cmax) and area under the curve (AUC). Measurements of three patients who underwent lipiodol-based conventional chemoembolization (c-TACE) were also performed. Results TACE with HepaSphere was well tolerated with an acceptable safety profile and no 30-day mortality. Response rates were calculated on intention-to-treat basis with complete response (CR) in 17.8 % reaching 22.2 % for the target lesion. Overall partial response (PR) was seen in 51.1 %, stable disease in 20 %, and progressive disease in 11.1 % of patients. Overall objective response (CR + PR), including patients treated at all dosages of doxorubicin, was seen in 68.9 % of cases. After a median follow-up of 15.6 months, 1-year survival is 100 %. Doxorubicin AUC was significantly lower in patients with HepaSphere 30–60 μm (35,195 ± 27,873 ng × min/ml) than in patients with conventional TACE (103,960 ± 16,652 ng × min/ml; p = 0.009). Cmax was also significantly lower with HepaSphere 30–60 μm (83.9 ± 32.1 ng/ml) compared with c-TACE (761.3 ± 58.8 ng/ml; p = 0.002). Conclusion HepaSphere 30–60 μm is an effective drug-eluting embolic material with a favourable pharmacokinetic profile.
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Chapiro J, Tacher V, Geschwind JF. Intraarterial therapies for primary liver cancer: state of the art. Expert Rev Anticancer Ther 2013; 13:1157-67. [PMID: 24099626 DOI: 10.1586/14737140.2013.845528] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Image-guided intraarterial therapies play an important role in the treatment of patients with hepatic malignancies. These therapies provide the dual benefit of reduced systemic toxicity and effective local tumor control. As a result, procedures such as transarterial chemoembolization have been included in the official treatment guidelines for hepatocellular carcinoma (HCC) and are fully accepted for the treatment of patients with intermediate stage disease. In this review, we will describe the scientific rationale for intraarterial therapies and discuss the available clinical evidence for primary liver cancer. Finally, we will touch on the current trends consisting of combining intraarterial approaches with systemically administered targeted agents.
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Affiliation(s)
- Julius Chapiro
- The Russell H. Morgan Department of Radiology and Radiological Sciences, Section of Vascular and Interventional Radiology, Johns Hopkins University School of Medicine, The Johns Hopkins Hospital, 1800 Orleans Street, Sheikh Zayed Tower, Suite 7203, Baltimore, MD 21287, USA
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Kasai K, Ushio A, Kasai Y, Sawara K, Miyamoto Y, Oikawa K, Takikawa Y, Suzuki K. Therapeutic efficacy of transarterial chemo-embolization with a fine-powder formulation of cisplatin for hepatocellular carcinoma. World J Gastroenterol 2013; 19:2242-2248. [PMID: 23599651 PMCID: PMC3627889 DOI: 10.3748/wjg.v19.i14.2242] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2012] [Revised: 01/05/2013] [Accepted: 01/19/2013] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate the efficacy of transarterial chemoembolization (TACE) using a suspension of a fine-powder formulation of cisplatin (DDPH) in lipiodol (LPD) in the treatment of hepatocellular carcinoma (HCC).
METHODS: The subjects were 262 HCC patients treated with TACE using a DDPH-LPD suspension. The DDPH-LPD suspension was prepared by mixing 50 mg of DDPH into 10 mL of LPD. TACE was repeated when treated lesions relapsed and/or new hepatic lesions were detected. These patients received additional TACE using the same agent. TACE was repeated until complete regression of the tumor was obtained. The primary efficacy endpoint of the current study was the objective early response rate. Secondary efficacy endpoints were progression-free survival (PFS) and overall survival.
RESULTS: The objective early response rate was 43.6%. Cumulative PFS rates were 56.7% at 6 mo, 23.1% at 12 mo, 13.4% at 18 mo, and 10.5% at 24 mo. The median PFS was 6.6 mo. Cumulative survival rates were 90.6% at 6 mo, 81.9% at 12 mo, 70.5% at 24 mo, and 58.8% at 36 mo. Median survival time was 46.6 mo. All adverse reactions were controllable by temporary suspension of treatment. No serious complications or treatment-related deaths were observed.
CONCLUSION: TACE using a suspension of DDPH in LPD may be a useful treatment for HCC.
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Park JW, Amarapurkar D, Chao Y, Chen PJ, Geschwind JFH, Goh KL, Han KH, Kudo M, Lee HC, Lee RC, Lesmana LA, Lim HY, Paik SW, Poon RT, Tan CK, Tanwandee T, Teng G, Cheng AL. Consensus recommendations and review by an International Expert Panel on Interventions in Hepatocellular Carcinoma (EPOIHCC). Liver Int 2013; 33:327-37. [PMID: 23331661 DOI: 10.1111/liv.12083] [Citation(s) in RCA: 67] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Hepatocellular carcinoma (HCC) presents with a high burden of disease in East Asian countries. Intermediate-stage HCC as defined by the Barcelona Clinic Liver Cancer (BCLC) staging system poses a clinical challenge as it includes a heterogeneous population of patients that can vary widely in terms of tumour burden, liver function and disease aetiology. Intermediate HCC patients often have unsatisfactory clinical outcomes with repeated transarterial chemoembolization (TACE, due to non-response of the target tumour or the development of further metastasis indicating progressive disease. In September 2011, an Expert Panel Opinion on Interventions in Hepatocellular Carcinoma (EPOIHCC) was convened in HK in an attempt to provide a consensus on the practice of TACE. To that end, current clinical practice throughout Asia was reviewed in detail including safety and efficacy data on TACE alone as well as in combination with targeted systemic therapies. This review summarises the evidence discussed at the meeting and provides expert recommendation regarding the available therapeutic options for unresectable intermediate stage HCC. A key consensus of the Expert Panel was that in order to improve patient outcomes and long-term survival, the possibility of using TACE in combination with targeted agents given systemically should be explored. While the currently available clinical data is promising, the expected completion of several pivotal phase II and III RCTs will provide further evidence in support of the rationale for combination therapy regimens.
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Affiliation(s)
- Joong-Won Park
- Centre for Liver Cancer, National Cancer Center Hospital, Seoul, Korea
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Cheng JW, Lv Y. New progress of non-surgical treatments for hepatocellular carcinoma. Med Oncol 2013; 30:381. [PMID: 23292867 DOI: 10.1007/s12032-012-0381-y] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2012] [Accepted: 12/11/2012] [Indexed: 02/07/2023]
Abstract
Many non-surgical treatments of hepatocellular carcinoma (HCC) have significantly improved in the last few decades and have shown survival benefits for selected patients with HCC. Today ablation can improve survival in individuals diagnosed in early HCC and even offer a curative treatment in selected candidates. Patients with intermediate-stage HCC benefit from transarterial chemoembolization (TACE). Drug-eluting bead transarterial chemoembolization (DEB-TACE) has shown a better combined ischemic and cytotoxic effect locally and less system toxicity when compared with conventional TACE. Those diagnosed at advanced stage benefit from sorafenib. In addition to TACE and sorafenib which could improve survival for selected patients, three-dimensional conformal radiotherapy treatment (3-DCRT), selection internal radiation therapy and systemic chemotherapy have also shown anti-tumor activity in the treatment of advanced HCC, but their survival benefit have not been proven. The limited effects of single therapy suggested that the combination would enhance the overall treatment effect. Other potential non-surgical therapies like gene therapy and immunotherapy are still in testing phases, except for some small-scale clinical trials which have been reported to show some beneficial effect. Here, we review the current non-surgical treatments in HCC and the new advances in this field.
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Affiliation(s)
- Ji-Wen Cheng
- Department of Hepatobiliary Surgery, First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, 76 Yanta West Road, Xi'an 710061, People's Republic of China.
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Vadot L, Boulin M, Malbranche C, Guiu B, Aho S, Musat A, Pernot C, Guignard MH, Hillon P, Fagnoni P. Result and cost of hepatic chemoembolisation with drug eluting beads in 21 patients. Diagn Interv Imaging 2012; 94:53-9. [PMID: 23146417 DOI: 10.1016/j.diii.2012.05.001] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
PURPOSE The aim of our study was to assess the results and cost of a treatment strategy involving transarterial chemoembolisation with drug eluting beads (DEB-TACE) in patients with unresectable non-metastatic hepatocellular carcinoma (HCC). PATIENTS AND METHODS This study included all patients treated with DEB-TACE in our hospital between January 2009 and December 2010. All patients received DEB-TACE on demand and were evaluated after each session. RESULTS Twenty-one patients received an average of 1.3 sessions. The median time to treatment discontinuation and median progression-free survival was 181 days and 295 days, respectively. Toxicity caused treatment discontinuation in three patients (14%). For the hospital, the average direct cost of treatment was €6,033 according to the analytical accounting system vs. €4,558 according to the official tariffs from the new French Diagnosis-Related Group prospective payment system (P=0.002). CONCLUSION In the treatment of HCC, on-demand DEB-TACE stabilises the disease in some patients but has not yet been thoroughly evaluated.
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Affiliation(s)
- L Vadot
- Pôle Pharmacie, CHU de Dijon, Bocage Central, 14, rue Gaffarel, 21000 Dijon, France.
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Lewis AL, Dreher MR. Locoregional drug delivery using image-guided intra-arterial drug eluting bead therapy. J Control Release 2012; 161:338-50. [PMID: 22285550 PMCID: PMC3351580 DOI: 10.1016/j.jconrel.2012.01.018] [Citation(s) in RCA: 81] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2011] [Revised: 01/13/2012] [Accepted: 01/15/2012] [Indexed: 12/30/2022]
Abstract
Lipiodol-based transarterial chemoembolization (TACE) has been performed for over 3 decades for the treatment of solid tumors and describes the infusion of chemotherapeutic agents followed by embolization with particles. TACE is an effective treatment for inoperable hepatic tumors, especially hypervascular tumors such as hepatocellular carcinoma. Recently, drug eluting beads (DEBs), in which a uniform embolic material is loaded with a drug and delivered in a single image-guided step, have been developed to reduce the variability in a TACE procedure. DEB-TACE results in localization of drug to targeted tumors while minimizing systemic exposure to chemotherapeutics. Once localized in the tissue, drug is eluted from the DEB in a controlled manner and penetrates hundreds of microns of tissue from the DEB surface. Necrosis is evident surrounding a DEB in tissue days to months after therapy; however, the contribution of drug and ischemia is currently unknown. Future advances in DEB technology may include image-ability, DEB size tailored to tumor anatomy and drug combinations.
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Affiliation(s)
- Andrew L Lewis
- Biocompatibles UK Ltd, Farnham Business Park, Weydon Lane, Farnham, Surrey, GU9 8QL, UK.
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Osuga K, Maeda N, Higashihara H, Hori S, Nakazawa T, Tanaka K, Nakamura M, Kishimoto K, Ono Y, Tomiyama N. Current status of embolic agents for liver tumor embolization. Int J Clin Oncol 2012; 17:306-15. [PMID: 22806426 DOI: 10.1007/s10147-012-0445-1] [Citation(s) in RCA: 54] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2012] [Indexed: 01/25/2023]
Abstract
Gelatin sponge and polyvinyl alcohol particles have been the most popular particulate embolic agents for transarterial chemoembolization (TACE) of liver tumors. Over the last decade, calibrated microspheres have been introduced and increasingly used in liver tumor embolization in Western countries. In addition, drug-eluting beads (DEB) have been introduced for sustained local drug release. Such long-awaited spherical embolic agents will be introduced in Japan in the near future. The advantages of these microspheres are that particles are uniform in size and shape, and easy to inject through a microcatheter. They can travel distally to vessels corresponding to the particle size; in other words, the occlusion level can be predicted according to the particle size chosen. Thus, new bland microspheres and DEB may bring a significant advancement to embolization for primary liver tumors as well as hepatic metastases from various cancers. However, at this point, the published data suggests that both conventional TACE and DEB-TACE are equally effective for treatment of unresectable hepatocellular carcinoma, when patients are carefully selected. Therefore, indication, patient selection, and embolization techniques will be essential in order to individually adapt newer embolic agents based on oncological, anatomical and technical considerations.
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Affiliation(s)
- Keigo Osuga
- Department of Diagnostic and Interventional Radiology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
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Kang JW, Kim JH, Ko GY, Gwon DI, Yoon HK, Sung KB. Transarterial chemoembolization for hepatocellular carcinoma after transjugular intrahepatic portosystemic shunt. Acta Radiol 2012; 53:545-50. [PMID: 22547388 DOI: 10.1258/ar.2012.110476] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND The decreased portal blood flow and the potential decrease in arterial nutrient hepatic blood flow after creation of a transjugular intrahepatic portosystemic shunt (TIPS) makes the treatment of hepatocellular carcinoma (HCC) challenging. PURPOSE To evaluate the safety and efficacy of transarterial chemoembolization (TACE) after TIPS in patients with HCC. MATERIAL AND METHODS From 1998 to 2009, 20 patients underwent selective (segmental or subsegmental) TACE for HCC after TIPS. Among 20 patients, seven patients had undergone one to three sessions of TACE for HCC before TIPS creation. TACE was performed using a mixture of iodized oil and cisplatin, and absorbable gelatin sponge particles. Tumor response, complications, and patient survival were evaluated after TACE. RESULTS After TACE, 14 of the 20 (70%) patients showed a tumor response, with only one (5%) experiencing a TACE-related major complication, spontaneous bacterial peritonitis. None of the patients who underwent TACE after TIPS died within 30 days. During the follow-up period (range 2.2-107 months; mean 32.6 months), 18 patients died and two remained alive. The median survival period after TACE was 23 months. Multivariate Cox regression analysis showed that tumor stage was the only independent prognostic factor for patient survival (P = 0.049). CONCLUSION Selective TACE may be safe and effective for the palliative treatment of HCC in patients with TIPS. Late tumor stage ( ≥III) was poor prognostic factor for determining the patient survival period after post-TIPS TACE.
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Affiliation(s)
- Ji-Won Kang
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Jin Hyoung Kim
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Gi-Young Ko
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Dong Il Gwon
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Hyun-Ki Yoon
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Kyu-Bo Sung
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
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Maeda N, Osuga K, Shimazu K, Morii E, Mikami K, Hori S, Nakazawa T, Higashihara H, Tomoda K, Nakamura H, Tomiyama N. In Vivo Evaluation of Cisplatin-loaded Superabsorbent Polymer Microspheres for Use in Chemoembolization of VX2 Liver Tumors. J Vasc Interv Radiol 2012; 23:397-404.e1. [DOI: 10.1016/j.jvir.2011.10.024] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2011] [Revised: 10/20/2011] [Accepted: 10/29/2011] [Indexed: 10/14/2022] Open
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Kudo M, Imanaka K, Chida N, Nakachi K, Tak WY, Takayama T, Yoon JH, Hori T, Kumada H, Hayashi N, Kaneko S, Tsubouchi H, Suh DJ, Furuse J, Okusaka T, Tanaka K, Matsui O, Wada M, Yamaguchi I, Ohya T, Meinhardt G, Okita K. Phase III study of sorafenib after transarterial chemoembolisation in Japanese and Korean patients with unresectable hepatocellular carcinoma. Eur J Cancer 2011; 47:2117-27. [PMID: 21664811 DOI: 10.1016/j.ejca.2011.05.007] [Citation(s) in RCA: 454] [Impact Index Per Article: 32.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2011] [Revised: 04/28/2011] [Accepted: 05/06/2011] [Indexed: 12/12/2022]
Abstract
BACKGROUND In Japan and South Korea, transarterial chemoembolisation (TACE) is an important locoregional treatment for patients with unresectable hepatocellular carcinoma (HCC). Sorafenib, a multikinase inhibitor, has been shown effective and safe in patients with advanced HCC. This phase III trial assessed the efficacy and safety of sorafenib in Japanese and Korean patients with unresectable HCC who responded to TACE. METHODS Patients (n=458) with unresectable HCC, Child-Pugh class A cirrhosis and ≥25% tumour necrosis/shrinkage 1-3 months after 1 or 2 TACE sessions were randomised 1:1 to sorafenib 400mg bid or placebo and treated until progression/recurrence or unacceptable toxicity. Primary end-point was time to progression/recurrence (TTP). Secondary end-point was overall survival (OS). FINDINGS Baseline characteristics in the two groups were similar; >50% of patients started sorafenib>9 weeks after TACE. Median TTP in the sorafenib and placebo groups was 5.4 and 3.7 months, respectively (hazard ratio (HR), 0.87; 95% confidence interval (CI), 0.70-1.09; P=0.252). HR (sorafenib/placebo) for OS was 1.06 (95% CI, 0.69-1.64; P=0.790). Median daily dose of sorafenib was 386 mg, with 73% of patients having dose reductions and 91% having dose interruptions. Median administration of sorafenib and placebo was 17.1 and 20.1 weeks, respectively. No unexpected adverse events were observed. INTERPRETATION This trial, conducted prior to the reporting of registrational phase III trials, found that sorafenib did not significantly prolong TTP in patients who responded to TACE. This may have been due to delays in starting sorafenib after TACE and/or low daily sorafenib doses.
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Affiliation(s)
- Masatoshi Kudo
- Department of Gastroenterology and Hepatology, Kinki University School of Medicine, Osaka-Sayama, Japan.
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Transcatheter treatment of hepatocellular carcinoma with Doxorubicin-loaded DC Bead (DEBDOX): technical recommendations. Cardiovasc Intervent Radiol 2011; 35:980-5. [PMID: 22009576 PMCID: PMC3447142 DOI: 10.1007/s00270-011-0287-7] [Citation(s) in RCA: 215] [Impact Index Per Article: 15.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2011] [Accepted: 09/27/2011] [Indexed: 12/16/2022]
Abstract
Tranarterial chemoembolization (TACE) has been established by a meta-analysis of randomized controlled trials as the standard of care for nonsurgical patients with large or multinodular noninvasive hepatocellular carcinoma (HCC) isolated to the liver and with preserved liver function. Although conventional TACE with administration of an anticancer-in-oil emulsion followed by embolic agents has been the most popular technique, the introduction of embolic drug-eluting beads has provided an alternative to lipiodol-based regimens. Experimental studies have shown that TACE with drug-eluting beads has a safe pharmacokinetic profile and results in effective tumor killing in animal models. Early clinical experiences have confirmed that drug-eluting beads provide a combined ischemic and cytotoxic effect locally with low systemic toxic exposure. Recently, the clinical value of a TACE protocol performed by using the embolic microsphere DC Bead loaded with doxorubicin (DEBDOX; drug-eluting bead doxorubicin) has been shown by randomized controlled trials. An important limitation of conventional TACE has been the inconsistency in the technique and the treatment schedules. This limitation has hampered the acceptance of TACE as a standard oncology treatment. Doxorubicin-loaded DC Bead provides levels of consistency and repeatability not available with conventional TACE and offers the opportunity to implement a standardized approach to HCC treatment. With this in mind, a panel of physicians took part in a consensus meeting held during the European Conference on Interventional Oncology in Florence, Italy, to develop a set of technical recommendations for the use of DEBDOX in HCC treatment. The conclusions of the expert panel are summarized.
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Liu DM, Kos S, Buczkowski A, Kee S, Munk PL, Klass D, Wasan E. Optimization of doxorubicin loading for superabsorbent polymer microspheres: in vitro analysis. Cardiovasc Intervent Radiol 2011; 35:391-8. [PMID: 21567274 DOI: 10.1007/s00270-011-0168-0] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2011] [Accepted: 04/07/2011] [Indexed: 01/01/2023]
Abstract
PURPOSE This study was designed to establish the ability of super-absorbent polymer microspheres (SAP) to actively uptake doxorubicin and to establish the proof of principle of SAP's ability to phase transfer doxorubicin onto the polymer matrix and to elute into buffer with a loading method that optimizes physical handling and elution characteristics. METHODS Phase I: 50-100 μm SAP subject to various prehydration methods (normal saline 10 cc, hypertonic saline 4 cc, iodinated contrast 10 cc) or left in their dry state, and combined with 50 mg of clinical grade lyophilized doxorubicin reconstituted with various methods (normal saline 10 cc and 25 cc, sterile water 4 cc, iodinated contrast 5 cc) were placed in buffer and assessed based on loading, handling, and elution utilizing high-performance liquid chromatography (HPLC). Phase II: top two performing methods were subject to loading of doxorubicin (50, 75, 100 mg) in a single bolus (group A) or as a serial loading method (group B) followed by measurement of loading vs. time and elution vs. time. RESULTS Phase I revealed the most effective loading mechanisms and easiest handling to be dry (group A) vs. normal saline prehydrated (group B) SAP with normal saline reconstituted doxorubicin (10 mg/mL) with loading efficiencies of 83.1% and 88.4%. Phase II results revealed unstable behavior of SAP with 100 mg of doxorubicin and similar loading/elution profiles of dry and prehydrated SAP, with superior handling characteristics of group B SAP at 50 and 75 mg. CONCLUSIONS SAP demonstrates the ability to load and bulk phase transfer doxorubicin at 50 and 75 mg with ease of handling and optimal efficiency through dry loading of SAP.
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Affiliation(s)
- David M Liu
- Department of Radiology, Vancouver General Hospital, University of British Columbia, 855 W 12th Ave., JP Pavillion G873, Vancouver, BC V5Z 1M9, Canada.
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Switching the loaded agent from epirubicin to cisplatin: salvage transcatheter arterial chemoembolization with drug-eluting microspheres for unresectable hepatocellular carcinoma. Cardiovasc Intervent Radiol 2011; 35:555-62. [PMID: 21562932 DOI: 10.1007/s00270-011-0176-0] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2011] [Accepted: 04/18/2011] [Indexed: 12/20/2022]
Abstract
PURPOSE There is no consensus on switching anticancer agents loaded onto drug carriers in transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC). This study aimed to evaluate the safety and clinical outcomes of TACE with cisplatin-loaded microspheres (CLM-TACE) in HCC patients refractory to TACE with epirubicin-loaded microspheres (ELM-TACE). METHODS Between February 2008 and June 2010, 85 patients with unresectable HCC refractory to ELM-TACE were enrolled to undergo CLM-TACE. The number of ELM-TACE sessions until judgment of resistance ranged from 1 to 4 (median, 2.1). CLM-TACE was performed using 50-100-μm superabsorbent polymer microspheres loaded with 1 mg cisplatin/1 mg microspheres together with hepatic arterial infusion of 25 mg cisplatin and 500 mg 5-fluorouracil per patient. Tumor responses were evaluated by computed tomography according to the European Association for the Study of the Liver criteria. RESULTS The median number of CLM-TACE treatment sessions was 1.8 (range, 1-5), and the mean total dose of cisplatin per session was 42.8 mg (range, 30.0-59.0). After 6 months, 3 (3.5%) patients achieved complete response, 31 (36.5%) had partial response, 15 (17.6%) had stable disease, and 36 (42.4%) had progressive disease. The median overall survival and time to treatment failure after initial CLM-TACE were 13.3 and 7.2 months, respectively. Overall, 9.4% of patients experienced grade 3/4 adverse events. CONCLUSION Switching the loaded agent from epirubicin to cisplatin is a safe, well-tolerated, and efficacious treatment strategy for salvage TACE with drug-eluting microspheres in HCC patients refractory to ELM-TACE.
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Seki A, Hori S. Transcatheter arterial chemoembolization with docetaxel-loaded microspheres controls heavily pretreated unresectable liver metastases from colorectal cancer: a case study. Int J Clin Oncol 2011; 16:613-6. [PMID: 21249412 DOI: 10.1007/s10147-010-0181-3] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2010] [Accepted: 12/23/2010] [Indexed: 01/12/2023]
Abstract
This is the first case report describing transcatheter arterial chemoembolization (TACE) with docetaxel-loaded microspheres which was successful in controlling liver metastases. We report on a 50-year-old woman with unresectable liver metastases from colorectal cancer. Since November 2007, the patient had received 12 courses of mFOLFOX6 (LV/5-FU/L-OHP) as the 1st line therapy, 18 courses of LV/5-FU as the 2nd line therapy, 16 courses of FOLFIRI (LV/5-FU/CPT-11) + bevacizumab as the 3rd line therapy, and 32 courses of cetuximab as the 4th line therapy. All treatments had been conducted after confirmation of the disease progression. The patient experienced hepatic dysfunction, upper abdominal pain and malaise due to the growth of metastatic liver tumors. Since December 2009, the patient received 3 courses of TACE with docetaxel-loaded microspheres in combination with hepatic arterial infusion of 20 mg cisplatin (CDDP) in a palliative setting for the treatment of liver metastases, which resulted in a reduction or necrosis of liver metastases and improvement in hepatic function and symptoms. TACE with docetaxel-loaded microspheres may be a palliative therapy for patients with colorectal cancer who are refractory to the current standard systemic chemotherapy and have predominant liver metastases.
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Affiliation(s)
- Akihiko Seki
- Department of Radiology, Gate Tower Institute for Image Guided Therapy, 11F, Gate Tower Building, 1-Rinku Ohrai-Kita, Izumisano, Osaka, 598-0048, Japan.
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