乳腺癌放射治疗进展 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,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,*,乳腺癌放射治疗进展,中国医学科学院肿瘤医院,余子豪,早 期 乳 腺 癌 的放 射 治 疗,保乳手术与根治术的美容差异,作者,时间,例数,期,期总数,肿瘤最大径,(cm),5,年复发率（,%,）,5,年生存率（,%,）,美容效果,满意 一般 差,王成峰、,余子豪等,1984,1995,25,43,68,3,6.1,78.8,60.6,33.3,6.06,张斌,1985,1996,17,19,36,4.4,6,100,91,于金明等,1987,1990,29,34,65,4.6,94.4,92.3,崔晓利、李瑞英，等,1990,1998,79,30,110,6.25,98.9,93.8,李文如等,1995,1998,52,3,0,100,金冶宁等,14,19,36,0,100,国内早期乳腺癌保乳治疗研究概况,乳腺癌保乳手术和放疗综合治疗的进展,适应证扩大,1,、,导管内原位癌,2,、,侵润性小叶癌,3,、,腋窝淋巴结转移,4,个,4,、,原发肿瘤,4cm,术前化疗,术前放疗,乳腺导管内原位癌,发病率有上升趋势：,1982,年,3.3%,1995,年,17.35%,乳腺导管内原位癌,临床特点：,多中心性：,32%,（,0-47%,）,潜隐性浸润癌,21%,（,0-18%,）,广泛切除术后残留,DCIS,达,9/22,（,41%,）,广泛切除术后复发率,25%,其中,50%,为浸润癌,乳腺导管内原位癌,治疗模式的改变：,1982-1995,乳腺单纯切除术由,100%,降至,22.5%,肿块切除术加放疗或单纯肿块切除术,由,0%,升至,77.5%,。,导管内原位癌保守治疗结果,（,Fox Chase Cancer Center:Fowble),19831992 : 110,例,病变情况：,钙 化,72%,肿块,+,钙化,27%,肿 块,中位值,导管内原位癌保守治疗结果,（,Fox Chase Cancer Center:Fowble),放疗：,全乳,50Gy,，原发灶加量,10Gy,随访：,年（,0.5-12),结果：,乳腺复发：,3/110,生存率：,5,年,96%,10,年,94%,侵润性小叶癌保守手术治疗,1970-1986,：,1536,例,侵润性导管癌,1089,侵润性小叶癌,93,混合型,59,侵润性小叶癌保守手术治疗,项目,5,年（,%,）,10,年（,%,）,局部复发,10,8,10,13,15,13,远地,/,区域复发,16,13,14,20,22,23,NED,生存期,67,75,68,55,56,42,对侧乳癌,4,2,7,6,4,13,腋窝淋巴结转移,4,个的保守治疗,（,Lingos JCRT),项目,1-3,（,+,）,4-9,（,+,）,10,（,+,）,10,年乳腺复发率,10%,8%,9%,区域淋巴结复发率,0.5%,2%,0%,1976-1986:,T,1,、,T,2,1047,例,LN 4-9,（,+,）,86,例,LN 10,（,+,）,24,例,ALN+4,个的保乳手术和放疗,Metha et al. Yale Univ. School of Medicine,病例数,: 1040,例,LN+4 : 51,例,10,年内乳腺复发,5,例,淋巴结转移,2,例,5,年 生 存 率,86%,10,年生存率,58%,术前放疗和保守治疗的研究,（,Sain-Gaudens et al,）,1981-1993,：,311,例,乳腺肿瘤,:,3.57cm,，中位数,4cm,治疗,:,术前放疗周,+,肿块扩大切除术,腋窝解剖,辅助性化疗或内分泌治疗,术前放疗和保守治疗的研究,（,Sain-Gaudens et al,）,疗效：,中位随访期,106,月（,10-188,月）,9,年乳腺保留率,84%5%,9,年乳腺复发率,22%5%,9,年 生 存 率,69%6%,综合治疗,术前化疗和放疗,1982-1990 147,例,治疗方法：,化疗,4,周期（,ADR+VCR+CTX+5-Fu),RT 45 Gy,第,5,周期化疗,局部治疗,第,6,周期化疗,辅助性化疗,结 果,治疗方式,人数,复发率,改良根治术,52(NC),6%,保守手术,47(PR),23%,单独放疗,48(CR),20%,10,年生存率 ：,66%,10,年局部区域复发率：,(Touboul et al,1997),保乳手术和放疗的绝对禁忌症,（,Morrow,1999),1,、,不同象限内两个或两个以上肿瘤,或弥散性显微钙化,2,、,乳腺区作过放疗者,3,、,肿瘤切缘持续阳性,4,、,妊娠期妇女,保乳手术和放疗的相对禁忌症,（,Morrow,1999),1,、,有胶原性脉管病史,2,、,肿瘤与乳房比例失调,3,、,大乳房与下垂型乳房,下列情况不应成为拒绝的理由,（,Morrow,1999),临床或病理证实腋窝淋巴结有转移,乳晕区肿瘤应按具体情况而定,有全身转移高危因素者,二、治疗技术更精炼,（一）腋窝淋巴结解剖的问题,腋窝淋巴结解剖的目的,治疗,判断预后,腋窝淋巴结解剖的后遗症：,上臂水肿、肩关节活动障碍、,感觉麻木、臂从神经损伤等,前 哨 淋 巴 结,（,Sentinel lymph node),区域淋巴引流中,最先接受肿瘤淋巴引流,最早发生转移的淋巴结,腋 窝 前 哨 淋 巴 结 检 测,前哨站淋巴结解剖（,SLD,）,方法：活性染料或放射性同位素,结果：检出率,95%,对淋巴结阳性预测率：,100%,淋巴结假阴性率,4%,Radio-Colloid Method Sentinel Node Biopsy,(incision size),放射胶体定位法（切口大小如下）,Blue Dye Method,Sentinel Node Biopsy,(incision size),蓝色染料淋巴定位法（切口大小如下）,前哨站淋巴结解剖（,SLD,）,优点：,腋窝放疗与腋窝解剖的疗效相同，,放疗的并发症少,可免作腋窝淋巴结解剖,可用分子生物学或免疫组化方法,检测阴性淋巴结中的微小转移灶,抗细胞角蛋白单克隆抗体,AE1/AE3,检测腋窝淋巴结阴,(ANN),乳腺癌患者淋巴结中微小转移灶及其临床意义,研究生吴进冬,导 师余子豪教授,微小转移灶检测的临床意义,CK,阴性,CK,阳性,例数,36,9,复发,4,5,5,年复发率,5.6%,44.4%,5,年生存率,94.4%,66.7%,10,年复发率,12.8%,55.6%,10,年生存率,90.2%,44.4%,生存曲线,好,差,Reference,No. of,patients,Mean,Follow-Up,(months),Overall Survival (%),Dissection Radiation None,Langlands et al,1980,275,72,62,50,ND,Fisher et al,1985,1079,126,58,59,54,Hayword&,Caleffi,1987,258,120,71,53,ND,Cabanes et al,1992,658,54,97,ND,93,White et al,1996,474,64,95,ND,64,Cerrote et al,1997,413,120,81,61,ND,ND,52,ND,Haffty et al,1997,955,96,75,ND,67,Overall Survival in Clinically Node-Negative BreastCancer Patients as a Function of Axillary Treatment,Reference,Follow-up(months),No. of,Patients,Axillary,Failure (%),Baeza et al,1988,62,171,1,Cabanes et al,1992,54,332,2,Delouche et al,1987,60,281,1,Fisher et al,1985,126,352,3,Leung et al,1986,120,446,0,Osborne et al,1984,120,211,1,Peirquin et al,1986,60,1040,0,Recht et al,1991,73,335,1,Wazer et al,1994,54,73,1,Axillary Failure Rates in Clinically Node-NegativeBreast Cancer Patients Treated With Adequate AxillaryRadiotherapy Without Axillary Dissection,前哨站淋巴结解剖（,SLD,）,腋窝前哨淋巴结检出结果,检出率：,96.7%,（,29/30,）,腋窝淋巴结清扫,30,例，,9,例有转移,前哨淋巴结检测，,8,例有转移,阳性符合率：,88.9%,（,8/9,）,假阴性率：,11%,（,1/9,）,早期乳腺癌保乳治疗腋窝放疗疗效,中国医学科学院肿瘤医院,1984-1995,组别,病例数,5,年局部复发率,5,年生存率,乳腺肿块切除,+,腋窝放疗,33,6.1%,78.8%,乳腺肿块切除,+,腋窝清扫术,35,5.7%,80.0%,放射治疗的发展,内乳淋巴结照射的争论,放射敏感性预测,时间,-,剂量因子的研究,适形放疗的研究,内乳淋巴结照射的争议,内乳淋巴结临床复发率低：,0-7%,内乳淋巴结（,+,）：,10%,内乳淋巴结,(,),：,6%,治疗内乳淋巴结的疗效不确切,照射内乳淋巴结的副作用,降低对化疗的耐受性,心肌梗死或心血管疾病死亡率高,Original Paper,The Dissection of Internal Nodes does not Improve the Survival of Breast Cancer Patients.,30-Year Results of a Randomised Trial,U.Veronesi,1,2,3,L .Mariani,3,P.Valajussa,33,1,European Institute of Oncology, Via Ripamond 435,2041;,2,Stastistic and Biometric Institute, Universita degli Studi di Milano; and,3,Istiuto Nazionale Tumori, Milano, Italy,Table 2. First events and cause of deaths,Neoplastic events,(type of recurrence),Local,44,46,90,Distant,130,131,261,Local+Distant,18,24,42,Contralateral,4,2,6,Cause of deaths,Breast Cancer,194,201,395,Another tumor,5,14,19,Not tumor,52,53,105,Unknown,13,26,39,Total,264,294,558,Extended n,Halsted n,Total n,INTERNAL MAMMARY NODAL IRRADIATION IN CONSERVATIVELY MANAGED BREAST CANCER PATIENTS:IS THERE A BENEFIT?,Edward Ibedian,M.D. and Bruce G.Haffty,M.D.,Department of Therapeutic Radiology,Yale University School of Medicine,New Haven, CT,Table 3.Clinical outcomes of node-positive patients,Total,IM-yes,IM-no,P,-value,Clinical status,P,0.001,A.WD,42,27,(5%),15,(4%),A.NED,693,345,(64%),348,(85%),D.WD,123,96,(18%),27,(7%),D.NED,88,67,(13%),21,(5%),A = alive; WD = with disease,NED = no evidence of disease; D = dead.,Table 3.Clinical outcomes of node-positive patients,Total,IM-yes,IM-no,P,-value,Site of recurrence,P,0.001,None,724,366,(68%),358,(87%),Breast only,82,65,(12%),17,(4%),Nodes only,12,9,(2%),3,(0.7%),Distant only,119,86,(16%),33,(8%),Breast & Nodes,1,1,(0.2%),0,(0%),Breast & Distant,5,5,(1%),0,(0%),Breast & Distant,5,5,(1%),0,(0%),接上表,内象限或中央区病变内乳淋巴结照射的研究,Fowble,等,2000,照射内乳区,不照射内乳区,P,乳腺内复发,3,(8),3,(7),0.60,区域淋巴结,1,(1),1,(,1),0.11,5,年和,（,10,年）,复发率（,%,）,5,年和,（,10,年）,生存率（,%,）,照射内乳区,不照射内乳区,P,肿瘤特异生存率,全组,91,(83),91,(87),0.81,N,0,92,(90),91,(87),0.44,N,1,83,(62),85,(78),0.38,总生存率,全组,90,(82),89,(81),0.60,N,0,88,(88),89,(80),0.19,N,1,83,(62),84,(77),0.43,内乳淋巴结转移术后放疗的随机研究,(YAMASHITA,等，,1997,年,),项目,根治性切除,+CMF 6,XRT 42Gy,+CMF 6,CMF 6,5,年,DFS,57%,53%,51%,DM,15/50,15/50,11/50,LRF,6/50,0/50,8/50,1985,年,9,月,1993,年,9,月：,150,例,病理证实,Urban,& Marjani,项 目,术后放疗,不做放疗,183,45,局部区域复发,17%,16%,5,年生存率,55%,16%,5,年无病生存率,41%,49%,IMN(+) 148,例,(Am J.Roentgenol Radiam Ther Nucl Med 1971,3:130),乳癌术后放疗内乳淋巴结照射的研究,中国医学科学院肿瘤医院王淑莲 余子豪,项 目,内乳淋巴结复发率,照射,不照射,内象限和中央区,病变腋窝（,-,）,0/85,0/63,内象限和中央区,病变腋窝（,+,）,0/78,1/23,内乳淋巴结复发率,内乳淋巴结治疗对策,不治疗,改进照射技术,只照射同侧,1-3,肋间,胰岛素生长因子受体,(IGF),与乳腺癌放射敏感性,(Turner et al,1996),IBTR,对照组,P,例数,25,25,IGF-1R +,72%,20%,0.001,阳性范围,40%,56%,4%,0.001,H-Score 100%,56%,4%,0.001,胰岛素样生长因子,1,受体（,IGF-1R,）与乳腺癌术后放疗后复发的相关性研究,研究生 吴君心,导 师 余子豪教授,复发组和对照组与,IGF-1R,过度表达的关系,复发组,对照组,IGF,1R,低表达,6,（,24%,）,39,（,78%,）,IGF,1R,过度表达,19,（,76%,）,11,（,22%,）,（,P,）,表,3.,复发组和对照组与,IGF-1R,不同表达的关系,IGF-1R,表达,复发组,对照组,P,值,(-),2,(8%),19,(38%),P,0.01,(+),4,(16%),20,(40%),P,0.05,(2+),8,(32%),5,(10%),P,0.05,(3+),11,(44%),6,(12%),P,0.01,(P,0.01),IGR,1R,高表达患者保乳手术后乳腺内复发率高。,对,IGF,1,高表达者增加局部照射剂量，减少复发率,乳腺癌保守手术治疗后加速超分割放疗,（,Schhombery,等,1997,）,病例数：,37,年 龄 ：,3380,乳腺及区域淋巴结：,次，每天二次,总量,48Gy,原 发 灶 加 量：,次，每天二次,总量,结果：,3,级急性皮肤反应,1,3,级 急 性 水 肿,1,适形调强放疗的优点,乳腺内剂量分布更均匀,肺、心脏及大血管剂量更少,乳腺及正常组织的后期放疗反应更轻,乳腺癌的调强适形放疗,切线楔形板,调强,降低幅度,冠状,A,（左乳）,36Gy,27Gy,25%,对侧乳腺,1.2Gy,0.7Gy,42%,肺高量区体积,10%,7%,30%,周围组织高量区体积,48%,33%,31%,靶区内均匀度改进,乳腺上下部,8%,内 外 侧,4%,