GIST肝转移介入治疗课件

单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,GIST,肝转移的介入治疗,GIST 肝转移的介入治疗,1,胃肠间质瘤（,GIST,）概述,胃肠间质瘤（GIST）概述,2,GIST,：与平滑肌肿瘤相似的形态,平滑肌瘤,平滑肌肉瘤,低度恶性,GIST,高度恶性,GIST,Courtesy of Dr.C.Corless.,GIST：与平滑肌肿瘤相似的形态平滑肌瘤平滑肌肉瘤低度恶性,3,GIST,名称的发展,1962,年，,Stout“,胃的奇异型平滑肌瘤”,1983,年，,Mazur and Clark“,胃肠间质瘤”,1998,年,，确定了,c-kit,为,GIST,的定义性特征,GIST名称的发展1962年，Stout“胃的奇异型平滑肌,4,GIST,的细胞起源,GIST,与,Cajal,间质干细胞,(ICC),具有一些相同特性,电镜下同时具有神经性和肌性细胞的特征,约,95%,的病例表达,KIT(CD117),家族性,GIST,患者的胃肠道中,ICC,细胞增生,GIST,和,ICC,可能共同起源于与肠神经丛相关的间叶干细胞,Sircar et al.,Am J Surg Pathol.,1999;23:377.,Wang et al.,Arch Pathol Lab Med.,2000;124:1471.,GIST的细胞起源GIST 与Cajal间质干细胞(ICC),5,GIST,的流行病学特征,胃肠道,(GI),最常见的肉瘤,间叶源（结缔组织）性肿瘤,占所有胃肠道肿瘤的,1-2%,高发年龄为,50-60,岁,男、女发病率相当，但有些报道提示男性发病率略高，儿童少见,GIST,的年发病率为,10-20/100,万,14.5/,百万（瑞典）,11/,百万（冰岛）,4500-6000,例新发,/,年（美国）,GOLD registry,（全球）？,GIST的流行病学特征胃肠道(GI)最常见的肉瘤,6,胃肠间质瘤（,GIST,）病理,胃肠间质瘤（GIST）病理,7,GIST,的形态学特征,梭形细胞型,(60%-80%),上皮样细胞型,(10%-30%,）,混合细胞型,(,少见,),GIST的形态学特征,8,形态学特征（图示）,上皮样细胞型,梭形细胞型,形态学特征（图示）上皮样细胞型梭形细胞型,9,GIST,的免疫组化分析,CD117(KIT),：,95%(100%).,CD34,：,60%-70%.,确定诊断,SMA,：,30%-40%.,平滑肌瘤,Desmin,：,1%-2%.,平滑肌瘤,S-100,：,5%.,神经源性肿瘤,鉴别诊断,GIST的免疫组化分析CD117(KIT)：确定诊断SMA：,10,GIST,的临床分期,尚无统一分期标准,早期,TGM,分期（软组织肉瘤分期）,Crosby(2001,年）分期,NCCN,：局限期、广泛期,GIST的临床分期尚无统一分期标准,11,常见转移部位,肝脏,:54 to 65%,腹膜,:20 to 21%,淋巴结,:2 to 6%,骨,:6%,肺,:2%,abdomen-pelvic,常见转移部位 肝脏:54 to 65%abd,12,GIST,传统治疗,手术,对于可完整切除的,GIST,患者仍是首选治疗,肿瘤完整切除术后,5,年生存率,:35,65%,中位复发时间：,7ms,2yr,；,由于极少出现区域淋巴结转移，故不推荐,区域淋巴结清扫,腹腔镜手术需在有经验的中心进行,放疗、化疗,:,有效率,7%,GIST传统治疗手术 对于可完整切除的GIST患者仍,13,复发或转移性,GIST,的靶向治疗,复发或转移性GIST的靶向治疗,14,甲磺酸伊马替尼（,Glivec,、,STI571,）,小分子,选择性酪氨酸激酶抑制剂,Bcr-Abl,、,PDGFR,和,KIT,甲磺酸伊马替尼（Glivec、STI571）小分子,15,伊马替尼在 晚期,GIST,治疗中的应用,2000.3.,首例患者使用（芬兰）,2000.7.phase trial(B2222),2001.8.phase trials(S0033,EORTC),2002.2.FDA,、,CPMP,2002.3.China,伊马替尼在 晚期GIST治疗中的应用2000.3.首例,16,Imatinib,治疗晚期,GIST,小结,Imatinib 400mg Qd,标准一线治疗,肿瘤控制率在,80%,左右,TTP,在,2.0-2.5,年,Imatinib 400mg Qd,失败后加量仍旧可以获益,基因突变可以预测,Imatinib,疗效，,exon-11,疗效最佳,Imatinib治疗晚期GIST小结Imatinib 400,17,Imatinib,耐药,GIST,的二线治疗,Imatinib耐药GIST的二线治疗,18,GIST,耐药机制,Imatinib,治疗开始后,6,月,内未能达到疾病稳定,发生率,10%-26%,与无,KIT/PDGFRA,突变或含,PDGFRA D842V,突变有关,起初治疗有效或疾病稳定,之后发生的疾病进展,中位进展时间,20,24,个月,与,KIT/PDGFRA,继发突变、,基因扩增、新的酪氨酸,激酶活化等因素有关,原发耐药,继发耐药,1.Trent JC,et al.Curr Opin Oncol 2006,18:386-95,2.,Hohenberger P,et al.,2006 ASCO Part I 2006,24(18S):9500.,3.Agaram NP,et al.Clin Cancer Res 2007,13(1),170-181,GIST耐药机制Imatinib治疗开始后6月起初治疗有效或,19,新生血管形成,苹果酸舒尼替尼（,sunitinib,）,外膜细胞,血管内皮细胞,肿瘤细胞,抗增殖效应,抑制肿瘤生长，周细胞增殖，内皮细胞增殖,新生血管形成,20,Novel statistical analysis of long-term survival to account for crossover in a phase III trial of sunitinib(SU)vs.placebo(PL)in advanced GIST after imatinib(IM)failure,G.D.Demetri,X.Huang,C.R.Garrett,P.Schffski,M.E.Blackstein,M.H.Shah,J.Verweij,V.Tassell,C.M.Baum,P.G.Casali,J Clin Oncol 26:2008(May 20 suppl;abstr 10524),，,2008 ASCO Annual Meeting,Ann Oncol 19:2008(suppl 8;abstr 865O),2008 ESMO Congress,舒尼替尼治疗晚期耐药,GIST,重要研究,Novel statistical analysi,21,-,22,-,共识,TACE,肝动脉化疗栓塞作为标准治疗失败后,选择之一,-22-共识 TACE肝动脉化疗栓塞作为标准治疗失败,22,World J Gastroenterol.,2012 Nov 14;18(42):6134-40.,Transcatheter arterial chemoembolization for gastrointestinal stromal tumors with liver metastases,The median PFS in TACE group was longer than in control group(30.0 wk,95%CI:20.1-39.9 vs 12.9 wk,95%CI:11.9-13.9)(P=0.0001).,The median overall survival in TACE group was also longer than in control group(68.5 wk,95%CI:57.4-79.6 vs 25.7 wk,95%CI:23.2-28.2)(P=0.0001).,TACE treatment signicantly reduced the risk of death(hazard ratio:0.109).,World J Gastroenterol.2012 No,23,Chin J Cancer Res.,2014 Feb;26(1):124-31.,A comparative study between Embosphere()and conventional transcatheter arterial chemoembolization for treatment of unresectable liver metastasis fromGIST.,The PFS was significantly better in the Embosphere()-group than in the cTACE group(56.6 and 42.1 weeks,respectively;P=0.003).,The median OS in the Embo-TAE group was longer than that in the cTACE group(74.0 weeks,95%CI:68.2-79.8 vs.61.7 weeks,95%CI:56.2-67.2 weeks)(unadjusted P=0.045).,The use of Embo-TAE significantly reduced the risk of death in patients withGISTwith liver metastases according to the Cox proportional hazards regression model hazard ratio(HR):0.149;95%CI:0.064-0.475.,Chin J Cancer Res.2014 Feb;26,24,GIST肝转移介入治疗课件,25,GIST肝转移介入治疗课件,26,GIST肝转移介入治疗课件,27,GIST肝转移介入治疗课件,28,GIST肝转移介入治疗课件,29,GIST肝转移介入治疗课件,30,GIST肝转移介入治疗课件,31,GIST肝转移介入治疗课件,32,GIST肝转移介入治疗课件,33,GIST肝转移介入治疗课件,34,GIST肝转移介入治疗课件,35,GIST肝转移介入治疗课件,36,GIST肝转移介入治疗课件,37,GIST肝转移介入治疗课件,38,GIST肝转移介入治疗课件,39,