Please wait a minute...
J Zhejiang Univ (Med Sci)  2017, Vol. 46 Issue (1): 44-51    DOI: 10.3785/j.issn.1008-9292.2017.02.07
    
Clinical investigation on transarterial chemoembolization with indigenous drug-eluting beads in treatment of unresectable hepatocellular carcinoma
CHEN Gang1,2(),ZHANG Ding2,YING Yacao2,WANG Zhifeng2,TAO Wei2,ZHU Hao2,ZHANG Jingfeng1,*(),PENG Zhiyi1,*()
(1) Department of Radiology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
(2) Department of Radiology, Traditional Chinese Medicine Hospital of Ningbo, Ningbo 315010, China
Download: HTML   HTML( 7 )   PDF(1197KB)
Export: BibTeX | EndNote (RIS)      

Abstract  Objective

To evaluate the efficacy and safety of drug-eluding beads transarterial chemoembolization (DEB-TACE) in treatment of unrecectable hepatocellular carcinoma (HCC).

Methods

The clinical data of 42 consecutive HCC patients undergoing TACE were retrospectively analyzed, including 20 cases received conventional TACE (cTACE group) and 22 cases received TACE with epirubicine-loaded microspheres (CalliSpheres?) (DEB-TACE group). MRI scans were performed 1 week before and 1, 3 and 6 months after initial therapy. The response to treatment, disease recurrence, complications and adverse effects were documented and compared between two groups.

Results

There were no significant differences in 1-month, 3-month and 6-month objective response rate (CR+PR) and disease control rate (CR+PR+SD), disease recurrence, complications and adverse effects of interventional therapy between cTACE group and DEB-TACE group. Additionally, there were no significant differences about locoregional biliary injuries, intrahepatic biloma, and newly detected intra-or extrahepatic HCC on MRI between cTACE group and DEB-TACE group.

Conclusion

There were no statistically significant differences between cTACE group and DEB-TACE group with regard to the short-term response, disease recurrence, complications and side effects. Hepatic-locoregional complications may be more frequent in DEB-TACE group than those in cTACE group.



Key wordsCarcinoma, hepatocellular/drug therapy      Liver neoplasms/drug therapy      Drug-eluting stents      Chemoembolization, therapeutic      Hepatic artery      Microspheres      Treatment outcome      Case-control studies     
Received: 20 December 2016      Published: 06 July 2017
CLC:  R735.7  
Corresponding Authors: ZHANG Jingfeng,PENG Zhiyi     E-mail: chengang09@126.com;jingfengzhang73@163.com;pengzhiyi2010@163.com
About author: ZHANG Jingfeng. E-mail: jingfengzhang73@163.com|PENG Zhiyi. E-mail: pengzhiyi2010@163.com
Cite this article:

CHEN Gang,ZHANG Ding,YING Yacao,WANG Zhifeng,TAO Wei,ZHU Hao,ZHANG Jingfeng,PENG Zhiyi. Clinical investigation on transarterial chemoembolization with indigenous drug-eluting beads in treatment of unresectable hepatocellular carcinoma. J Zhejiang Univ (Med Sci), 2017, 46(1): 44-51.

URL:

http://www.zjujournals.com/med/10.3785/j.issn.1008-9292.2017.02.07     OR     http://www.zjujournals.com/med/Y2017/V46/I1/44


国产载药微球经动脉化疗栓塞治疗不可切除原发性肝癌的临床研究

目的

比较国产CalliSpheres?载药微球经动脉化疗栓塞(DEB-TACE)与常规经动脉化疗栓塞(cTACE)治疗不可切除原发性肝癌的近期临床疗效和安全性。

方法

42例不可切除原发性肝癌患者接受经导管动脉化疗栓塞(TACE)中使用CalliSpheres? DEB-TACE或cTACE治疗,在介入前1周及介入后1个月、3个月、6个月行MRI检查,对患者的随访影像资料和临床资料等进行汇总和分析,采用国际通用的改良实体瘤评价标准进行评价,比较两种方法在患者肿瘤反应、复发情况、并发症及不良反应发生率的差异。

结果

DEB-TACE组与cTACE组在介入治疗后1个月、3个月、6个月疾病缓解率、疾病控制率、治疗后并发症发生及肿瘤复发情况差异均无统计学意义(均P>0.05),且DEB-TACE组局部胆道损伤和胆汁瘤发生率以及瘤体外新发病灶发生率差异均无统计学意义(均P>0.05)。

结论

DEB-TACE与cTACE治疗用于不可切除原发性肝癌患者在肿瘤反应、治疗后并发症及肿瘤复发方面等结果相似。DEB-TACE治疗较cTACE治疗可能更易发生肝脏局部的并发症。


关键词: 癌, 肝细胞/药物疗法,  肝肿瘤/药物疗法,  药物洗脱支架,  化学栓塞, 治疗性,  肝动脉,  微球体,  治疗结果,  病例对照研究 
[n(%)]
相关指标 cTACE组 DEB-TACE组 合计
性别?男性 17(85.0) 19(86.4) 36(85.7)
???女性 3(15.0) 3(13.6) 6(14.3)
肿瘤负荷
?单叶 8(40.0) 12(54.5) 20(47.6)
?双叶 12(60.0) 10(45.5) 22(52.4)
?多发结节 (≥4个病灶) 9(45.0) 13(59.1) 22(52.4)
Okuda分期?Ⅰ 10(50.0) 12(54.5) 22(52.4)
????? Ⅱ 10(50.0) 10(45.5) 20(47.6)
Child-Pugh分级?A 17(85.0) 15(68.2) 32(76.2)
??????? B 3(15.0) 7(31.8) 10(23.8)
巴塞罗那肝癌分期?A 2(10.0) 5(22.7) 7(16.7)
?????????B 12(60.0) 9(40.9) 21(50.0)
?????????C 6(30.0) 8(36.4) 14(33.3)
门脉癌栓或转移?有 5(25.0) 7(31.8) 12(28.6)
????????无 15(75.0) 15(68.2) 30(71.4)
Tab 1 Analysis of clinical characteristics of cTACE and DEB-TACE groups
[n(%)]
组别 随访时间 n CR PR SD PD CR+PR CR+PR+SD
cTACE组 1个月 16 2(12.5) 7(43.8) 4(25.0) 3(18.8) 9(56.3) 13(81.2)
3个月 16 0(0.0) 7(43.8) 5(31.3) 4(25.0) 7(43.8) 12(75.0)
6个月 16 0(0.0) 4(25.0) 6(37.5) 6(37.5) 4(25.0) 10(62.5)
DEB-TACE组 1个月 17 3(17.6) 9(52.9) 4(23.5) 1(5.9) 12(70.6) 16(94.1)
3个月 17 3(17.6) 7(41.2) 3(17.6) 4(23.5) 10(58.8) 13(76.5)
6个月 17 2(11.8) 2(11.8) 6(35.3) 7(41.2) 4(23.5) 10(58.8)
Tab 2 Tumor response after cTACE and DEB-TACE
[n(%)]
组别 随访时间 n 局部复发 新发病灶或肝外转移
cTACE组 3个月 16 2(12.5) 2(12.5)
6个月 16 4(25.0) 5(31.2)
DEB-TACE组 3个月 17 0(0.0) 4(23.5)
6个月 17 2(11.8) 7(41.2)
Tab 3 Tumor recurrence after cTACE and DEB-TACE
[n(%) 或 ($\overline x$±s)]
组别 n 不良反应及并发症
体温大于38° 腹痛 使用止痛药 使用吗啡 恶心 呕吐 乏力 局部胆道损伤
cTACE组209(45.0)11(55.0)3(15.0)0(0.0)5(25.0)4(20.0)7(35.0)0(0.0)
DEB-TACE组228(36.4)8(36.4)5(22.7)1(4.5)3(13.6)3(13.6)3(13.6)2(9.1)
P0.5690.2260.8081.0000.5870.8900.2070.489
组别n肝功能指标
白蛋白
(g/L)
ALT
(U/L)
AST
(U/L)
总胆红素
(μmol/L)
胆碱酯酶
(U/L)
凝血酶原
时间 (s)
甲胎蛋白
(ng/mL)
cTACE组2037.2±3.7130.0±51.1167.0±118.722.0±3.55171.2±1181.112.0±0.796.6(42.2~7277.6)
DEB-TACE组2236.6±7.491.1±76.5104.5±89.324.5±13.94914.1±2031.513.0±2.066.1(15.1~4894.9)
P0.7490.1020.2480.5450.8230.3390.507
Tab 4 Complications and side effects of interventional therapy after cTACE and DEB-TACE
Fig 1 MR image of biliary cast
Fig 2 MR image of intrahepatic biloma and bile duct dilatation
[1]   PARKIN D M, BRAY F, FERLAY J et al. Global cancer statistics, 2002. CA Cancer J Clin. 2005, 55(2): 74-108 doi: 10.3322/canjclin.55.2.74
doi: 10.3322/canjclin.55.2.74
[2]   CUCCHETTI A, TREVISANI F, CESCON M et al. Cost-effectiveness of semi-annual surveillance for hepatocellular carcinoma in cirrhotic patients of the Italian Liver Cancer population. J Hepatol. 2012, 56(5): 1089-1096 doi: 10.1016/j.jhep.2011.11.022
doi: 10.1016/j.jhep.2011.11.022 pmid: 22245900
[3]   BRUIX J, SHERMAN M . Management of hepatocellular carcinoma. Hepatology. 2005, 42(5): 1208-1236 doi: 10.1002/hep.v42:5
[4]   European Association for the Study of the Liver, European Organisation for Research and Treatment of Cancer . EASL-EORTC clinical practice guidelines:management of hepatocellular carcinoma. J Hepatol. 2012, 56(4): 908-943 doi: 10.1016/j.jhep.2011.12.001
doi: 10.1016/j.jhep.2011.12.001 pmid: 22424438
[5]   MARELLI L, STIGLIANO R, TRIANTOS C et al. Transarterial therapy for hepatocellular carcinoma:which technique is more effective? a systematic review of cohort and randomized studies. Cardiovasc Intervent Radiol. 2007, 30(1): 6-25 doi: 10.1007/s00270-006-0062-3
[6]   VARELA M, REAL M I, BURREL M et al. Chemoembolization of hepatocellular carcinoma with drug eluting beads:efficacy and doxorubicin pharmacokinetics. J Hepatol. 2007, 46(3): 474-481 doi: 10.1016/j.jhep.2006.10.020
doi: 10.1016/j.jhep.2006.10.020
[7]   POON R T, TSO W K, PANG R W et al. A phase Ⅰ/Ⅱ trial of chemoembolization for hepatocellular carcinoma using a novel intra-arterial drug-eluting bead. Clin Gastroenterol Hepatol. 2007, 5(9): 1100-1108 doi: 10.1016/j.cgh.2007.04.021
doi: 10.1016/j.cgh.2007.04.021 pmid: 17627902
[8]   LENCIONI R, PETRUZZI P, CROCETTI L . Chemoembolization of hepatocellular carcinoma. Semin Intervent Radiol. 2013, 30(1): 3-11 doi: 10.1055/s-00000068
[9]   DHANASEKARAN R, KOOBY D A, STALEY C A et al. Comparison of conventional transarterial chemoembolization (TACE) and chemoembolization with doxorubicin drug eluting beads (DEB) for unresectable hepatocelluar carcinoma (HCC). J Surg Oncol. 2010, 101(6): 476-480
[10]   VOGL T J, LAMMER J, LENCIONI R et al. Liver, gastrointestinal, and cardiac toxicity in intermediate hepatocellular carcinoma treated with PRECISION TACE with drug-eluting beads:results from the PRECISION V randomized trial. AJR Am J Roentgenol. 2011, 197(4): W562-W570 doi: 10.2214/AJR.10.4379
doi: 10.2214/AJR.10.4379 pmid: 21940527
[11]   FORNER A, REIG M E, DE LOPE C R et al. Current strategy for staging and treatment:the BCLC update and future prospects. Semin Liver Dis. 2010, 30(1): 61-74 doi: 10.1055/s-0030-1247133
doi: 10.1055/s-0030-1247133 pmid: 20175034
[12]   LEWIS A L, TAYLOR R R, HALL B et al. Pharmacokinetic and safety study of doxorubicin-eluting beads in a porcine model of hepatic arterial embolization. J Vasc Interv Radiol. 2006, 17(8): 1335-1343 doi: 10.1097/01.RVI.0000228416.21560.7F
doi: 10.1097/01.RVI.0000228416.21560.7F pmid: 16923981
[13]   HONG K, KHWAJA A, LIAPI E et al. New intra-arterial drug delivery system for the treatment of liver cancer:preclinical assessment in a rabbit model of liver cancer. Clin Cancer Res. 2006, 12(8): 2563-2567 doi: 10.1158/1078-0432.CCR-05-2225
doi: 10.1158/1078-0432.CCR-05-2225 pmid: 16638866
[14]   Varela M, Real M I, Burrel M et al. Chemoembolization of hepatocellular carcinoma with drug eluting beads:efficacy and doxorubicin pharmacokinetics. J Hepatol. 2007, 46(3): 474-481 doi: 10.1016/j.jhep.2006.10.020
doi: 10.1016/j.jhep.2006.10.020
[15]   MALAGARI K, ALEXOPOULOU E, CHATZIMICHAIL K et al. Transcatheter chemoembolization in the treatment of HCC in patients not eligible for curative treatments:midterm results of doxorubicin-loaded DC bead. Abdom Imaging. 2008, 33(5): 512-519 doi: 10.1007/s00261-007-9334-x
doi: 10.1007/s00261-007-9334-x pmid: 17938995
[16]   SONG M J, PARK C H, KIM J D et al. Drug-eluting bead loaded with doxorubicin versus conventional Lipiodol-based transarterial chemoembolization in the treatment of hepatocellular carcinoma:a case-control study of Asian patients. Eur J Gastroenterol Hepatol. 2011, 23(6): 521-527 doi: 10.1097/MEG.0b013e328346d505
doi: 10.1097/MEG.0b013e328346d505 pmid: 21537127
[17]   LAMMER J, MALAGARI K, VOGL T et al. Prospective randomized study of doxorubicin-eluting-bead embolization in the treatment of hepatocellular carcinoma:results of the PRECISION V study. Cardiovasc Intervent Radiol. 2010, 33(1): 41-52 doi: 10.1007/s00270-009-9711-7
doi: 10.1007/s00270-009-9711-7 pmid: 2816794
[18]   GOLFIERI R, GIAMPALMA E, RENZULLI M et al. Randomised controlled trial of doxorubicin-eluting beads vs conventional chemoembolisation for hepatocellular carcinoma. Br J Cancer. 2014, 111(2): 255-264 doi: 10.1038/bjc.2014.199
doi: 10.1038/bjc.2014.199 pmid: 24937669
[19]   FACCIORUSSO A, MARIANI L, SPOSITO C et al. Drug-eluting beads versus conventional chemoembolization for the treatment of unresectable hepatocellular carcinoma. J Gastroenterol Hepatol. 2016, 31(3): 645-653 doi: 10.1111/jgh.2016.31.issue-3
doi: 10.1016/j.dld.2016.02.005 pmid: 26965785
[20]   BAUR J, RITTER C O, GERMER C T et al. Transarterial chemoembolization with drug-eluting beads versus conventional transarterial chemoembolization in locally advanced hepatocellular carcinoma. Hepat Med. 2016, 8: 69-74
[21]   SCARTOZZI M, BARONI G S, FALOPPI L et al. Trans-arterial chemo-embolization (TACE), with either lipiodol (traditional TACE) or drug-eluting microspheres (precision TACE, pTACE) in the treatment of hepatocellular carcinoma:efficacy and safety results from a large mono-institutional analysis. J Exp Clin Cancer Res. 2010, 29: 164 doi: 10.1186/1756-9966-29-164
[22]   VOGL T J, LAMMER J, LENCIONI R et al. Liver, gastrointestinal, and cardiac toxicity in intermediate hepatocellular carcinoma treated with PRECISION TACE with drug-eluting beads:results from the PRECISION V randomized trial. AJR Am J Roentgenol. 2011, 197(4): W562-W570 doi: 10.2214/AJR.10.4379
doi: 10.2214/AJR.10.4379 pmid: 21940527
[23]   GOLFIERI R, GIAMPALMA E, RENZULLI M et al. Randomised controlled trial of doxorubicin-eluting beads vs conventional chemoembolisation for hepatocellular carcinoma. Br J Cancer. 2014, 111(2): 255-264 doi: 10.1038/bjc.2014.199
doi: 10.1038/bjc.2014.199 pmid: 24937669
[24]   WALDRAM R, WILLIAMS R, CALNE R Y . Bile composition and bile cast formation after transplantation of the liver in man. Transplantation. 1975, 19(5): 382-387 doi: 10.1097/00007890-197505000-00004
doi: 10.1097/00007890-197505000-00004 pmid: 168674
[25]   BRANDSAETER B, SCHRUMPF E, CLAUSEN O P et al. Recurrent sclerosing cholangitis or ischemic bile duct lesions-a diagnostic challenge?. Liver Transpl. 2004, 10(8): 1073-1074 doi: 10.1002/lt.20192
doi: 10.1002/lt.20192
[26]   PFAU P R, KOCHMAN M L, LEWIS J D et al. Endoscopic management of postoperative biliary complications in orthotopic liver transplantation. Gastrointest Endosc. 2000, 52(1): 55-63 doi: 10.1067/mge.2000.106687
doi: 10.1067/mge.2000.106687 pmid: 10882963
[27]   CLERMONTS S H, VAN DAM R M . Obstructive putty-like cast of the biliary tree. Hepatobiliary Surg Nutr. 2014, 3(1): 47-49
[28]   BENNINGER J, GROBHOLZ R, OEZTUERK Y et al. Sclerosing cholangitis following severe trauma:description of a remarkable disease entity with emphasis on possible pathophysiologic mechanisms. World J Gastroenterol. 2005, 11(27): 4199-4205 doi: 10.3748/wjg.v11.i27.4199
doi: 10.1055/s-2005-858505 pmid: 16015689
[29]   GELBMANN C M, RUMMELE P, WIMMER M et al. Ischemic-like cholangiopathy with secondary sclerosing cholangitis in critically ill patients. Am J Gastroenterol. 2007, 102(6): 1221-1229 doi: 10.1111/ajg.2007.102.issue-6
doi: 10.1111/j.1572-0241.2007.01118.x pmid: 17531010
[30]   MONIER A, GUIU B, DURAN R et al. Liver and biliary damages following transarterial chemoembolization of hepatocellular carcinoma:comparison between drug-eluting beads and lipiodol emulsion. Eur Radiol. 2017, 27(4): 1431-1439 doi: 10.1007/s00330-016-4488-y
doi: 10.1007/s00330-016-4488-y pmid: 27436016
[1] DING Yuan, SUN Zhongquan, ZHANG Wenyan, ZHANG Xiangying, JIANG Yuancong, YAN Sheng, WANG Weilin. Application of enhanced recovery program in laparoscopic distal pancreatectomy[J]. J Zhejiang Univ (Med Sci), 2017, 46(6): 625-629.
[2] ZHU Ziyi, LI Zhijun, HE Zhengfu, WANG Yunzhen. Endoscopic trans-fistula drainage for gastroesophageal anastomotic fistula with para-fistula abscess after esophagectomy[J]. J Zhejiang Univ (Med Sci), 2017, 46(6): 637-642.
[3] LU Wei, LIN Mengna, ZHAO Shifang, WANG Huiming, HE Fuming. Application of modified lateral window for maxillary sinus floor augmentation[J]. J Zhejiang Univ (Med Sci), 2017, 46(6): 630-636.
[4] ZHANG Siying, CHEN Feng. Research progress of CT/MRI parametric response map in precision evaluation of therapeutic response of cancer patients[J]. J Zhejiang Univ (Med Sci), 2017, 46(5): 468-472.
[5] PAN Jingying, HE Mengye, KE Wei, HU Menglin, WANG Meifang, SHEN Peng. Advances on correlation of PET-CT findings with breast cancer molecular subtypes, treatment response and prognosis[J]. J Zhejiang Univ (Med Sci), 2017, 46(5): 473-480.
[6] ZOU Lixia, LU Meiping, GUO Li, TENG Liping, XU Yiping, ZHENG Qi. Efficacy and safety of humanized interleukin-6 receptor antibody in treatment of systemic juvenile idiopathic arthritis[J]. J Zhejiang Univ (Med Sci), 2017, 46(4): 421-426.
[7] ZHANG Meixia, ZHOU Ying, ZHANG Ruiting, ZHANG Sheng, LOU Min. Maximal infarct volume to benefit from intravenous thrombolysis and its relation with onset to treatment time[J]. J Zhejiang Univ (Med Sci), 2017, 46(4): 384-389.
[8] ZHANG Xiaoqun, WANG Qiwen, WANG Xin, XU Xiaolei, ZHU Jianhua. Comparison of limus-eluting stent with paclitaxel-eluting stent for patients with coronary small vessel disease:a systematic review and meta-analysis[J]. J Zhejiang Univ (Med Sci), 2017, 46(3): 305-314.
[9] CHEN Yiming, ZHANG Wen, LU sha, MEI Jin, WANG Hao, WANG Shan, GU Linyuan, ZHANG Lidan, CHU Xuelian. Maternal serum alpha fetoprotein and free β-hCG of second trimester for screening of fetal gastroschisis and omphalocele[J]. J Zhejiang Univ (Med Sci), 2017, 46(3): 268-273.
[10] WENG Luxi, SONG Xiaojia, LI Juan, LIU Pengruofeng, LIN Jun. Midpalatal cortex osteotomy assisted rapid maxillary expansion for correction of maxillary transverse deficiency in young adults[J]. J Zhejiang Univ (Med Sci), 2017, 46(2): 198-205.
[11] WENG Luxi,SONG Xiaojia,LI Juan,LIU Pengruofeng,LIN Jun. Midpalatal cortex osteotomy assisted rapid maxillary expansion for correction of maxillary transverse deficiency in young adults[J]. J Zhejiang Univ (Med Sci), 2017, 46(2): 198-205.
[12] LI Wenbo, DING Gaoheng, LIU Jun, SHI Jie, ZHANG Chao, GAO Qiuming. Operative versus non-operative treatment for three- or four-part proximal humeral fractures in elderly patients: a meta-analysis of randomized controlled trials[J]. J Zhejiang Univ (Med Sci), 2016, 45(6): 641-647.
[13] XIA Guangfa, ZHU Juanying, YUAN Jun, CAO Bo, TANG Jie, CHEN Yiding. Efficacy of adjuvant endocrine therapy in breast cancer patients with a positive-to-negative switch of hormone receptor status after neoadjuvant chemotherapy[J]. J Zhejiang Univ (Med Sci), 2016, 45(6): 614-619.
[14] FANG Minbo, CHEN Qixing, WU Shuijing, FANG Xiangming. Association of single nucleotide polymorphism in exon of transient receptor potential melastatin 2 gene with sepsis[J]. J Zhejiang Univ (Med Sci), 2016, 45(4): 410-415.
[15] HE Bin, CHAI Yanlan, WANG Tao, ZHOU Zhenxing, LIU Zi. Progress on clinical application of bevacizumab for the treatment of refractory cervical cancer[J]. J Zhejiang Univ (Med Sci), 2016, 45(4): 395-402.