放疗在结直肠肿瘤课件

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,*,*,放疗在结直肠肿瘤,综合治疗中的应用,2009,年,美,国,癌,症,病,种,死,亡,比,例,ONS=Other nervous system.Source: American Cancer Society, 2009.,26%,Lung & bronchus,15%,Breast,9%,Colon & rectum,6%,Pancreas,5%,Ovary,4%,Non-Hodgkin lymphoma,3%,Leukemia,3%,Uterine corpus,2% Liver & intrahepatic,bile duct,2%,Brain/ONS,25% All other sites,Men,292,540,Women,269,800,Lung & bronchus,30%,Prostate,9%,Colon & rectum,9%,Pancreas,6%,Leukemia,4%,Liver & intrahepatic,4%,bile duct,Esophagus,4%,Urinary bladder,3%,Non-Hodgkin lymphoma 3%,Kidney & renal pelvis,3%,All other sites 25%,全球大肠癌发病状况,(1),?,中国结直肠癌发病率仅次于肺、胃、肝癌位于第四位,?,死亡率仅次于肺、肝、胃癌位于第四位,?,每年,10,万以上患者死于结直肠癌，且死亡人数正逐年增加,?,规范治疗、提高生存率是重中之重,1,4.,5,1,5.,1,1,7.,2,8.,3,8.,6,9.,9,0,5,1,0,1,5,2,0,2,0,0,0,2,0,0,2,2,0,0,5,发病,死亡,万,（,人,数,）,杨玲等,.,中国卫生统计，,2005,；,22,（,4,）：,218-231,中国发病状况,资,料来源：,Jemal.,CA Cancer J Clin,.,2008;58:71.,局部侵犯,远处转,移,区域侵犯,不同分期相,应,的,5,年生存率,S,u,r,v,i,v,a,l,(,%,),90%,68%,10%,0,10,20,30,40,50,60,70,80,90,100,68%,90%,区域侵犯,远处转,移,19%,39%,36%,诊,断分期,局部侵犯,全球大肠癌发病状况,(2),TNM stage,5y survival,T1-2N0M0,90%,A,T3N0M0,60%-85%,B,T4N0M0,A,T1-2N1M0,25%-65%,B,T3-4N1M0,C,Any TN2M0,any T any NM1,5%-7%,直肠癌术后,5,年生存率,全球大肠癌发病状况,(3),5y relative OS of CRC,2001-2007, 66.0%,1996-2000, 63.6%;,1993-1995, 60.1%;,1990-1992, 61.4%;,1987-1989, 59.8%;,1984-1986, 57.9%;,1981-1983, 54.3%;,1978-1980, 51.4%;,1975-1977, 50%;,the improvement of 5-years OS is attributable to:,（,1,）,dagnosis at early stage;,（,2,）,MDT,（,3,）,optimal surgery(TME);,（,4,）,more agents available;,（,5,）,chemoradiation,in rectal cancer,全球大肠癌发病状况,(4),Main causes of failure,：,（,1,）,Local recurrence after radical surgery,：,T1-2N0M0:10%;,T3N0M0,、,T1N1M0:15%35%;,T3-4N1-2M0:45%65%,（,2,）,metastases,全球大肠癌发病状况,(5),直肠癌的辅助治疗,?,术后放疗,?,术前放疗,?,术前放化疗,?,术后放化疗,?,TME,需要辅助治疗？,What is the standard adjuvant therapy for resectable colorectal cancer,？,Question 1,：,which is better postoperative RT or,surgery alone for rectal cancer?,(,术后放疗,vs,单纯手术）,？,术后放疗,vs,单纯手术,Lancet, 358:1291-1304, 2001,7,项术后放疗,RCT,荟萃分析,:,局部复发率,Question 2,：,which is better preoperative RT or,surgery alone for rectal cancer?,(,术前放疗,vs,单纯手术）,？,单纯术前放疗的疗效,研究组年代,治疗组,病例数,总量,/,单次量（,Gy,）,手术间隔,(,天）,5y,局部复发率（,%,）,p,5y OS,（,%,）,p,美国,VASOG,(1975),RT+S,20/2,14,29,0.05,43.4,0.042,S,40,31.6,美国,VASOG,(1986),RT+S,180,31.5/1.75,立即,10,0.9,S,272,20/2,7,52.9,40.0,英国,MRC,(1996),RT+S,139,40/2,45,40,0.04,31,0.10,S,140,52,28,欧洲,EORTC,(1988),RT+S,224,34.5/2.3,11,15,0.003,51.6,0.69,S,226,30,49,斯德哥尔摩,(1990),RT+S,424,25/5,7,不详,0.01,36,NS,S,425,36,斯德哥尔摩,(1996),RT+S,272,25/5,7,10,0.05,不详,不详,S,285,21,Goldberg,(1994),RT+S,228,15/5,2,17,0.05,39,NS,S,239,24,40,Marsh(1994),RT+S,143,20/5,7,12.8,0.0001,30.1,0.21,S,141,36.5,30.5,瑞典（,1997,）,RT+S,573,25/5,7,11,0.001,58,0.004,S,574,27,48,荷兰（,2001,）,RT+TME,924,25/5,10,2.4,0.001,82(2y),0.84,TME,937,8.2,81.8(2y),分层分析显示，对,DukersB,C,局控率尤,为有效，对,DukersA,无效,可切除直肠癌术前放疗价值何在？,1,、,Preoperative radiotherapy for resectable rectal cancer: A meta-analysis.,Camma C,Giunta M, Fiorica F,et al JAMA,2000, 284:1008-1015,.,14,个可切除直肠癌的术前放疗随机对照研究，,n =,6426,，,DukersB,C,（,1,）术前放疗显著降低局部复发率（,OR=0.49,；,95%CI,，,0.38-0.62,，,p0.001,）,（,2,）显著降低总死亡率（,OR=0.71,；,95%CI,，,0.61-0.82,，,p30Gy,时，能显著降低局部复发率（,45.9% vs 52.9%,，,p2.5cm,，手术切缘据肿瘤,2cm,与,3cm,，术前放疗后，可通过肿瘤退缩，降,期，提高保肛率。,3,、,2,个随机临床研究：,lyonR90-01,、,lyonR90-02,Influence of the interval between preoperative radiation therapy,and surgery on downstaging and on the rate of sphincter-sparing,surgery for rectal cancer.,The lyon,R90-01,randomized trail. J Clin Oncol,1999,17:2396.,入组标准：,T,2-3,N,0-3,M,0,，距肛门,5.7cm(1-11cm),，,DT39 Gy/13f,2w,6-8w,p,例数（,n,）,99,102,总反应率,(%),53.1,71.7,0.007,病理降期（,%,）,10.3,26,0.005,保肛率（,%,）,68,79,0.27,肿瘤距肛缘,5cm,（,%,）,23,41,NS,3,年,OS,（,%,）,78,73,NS,局控率（,%,）,78.8,80.4,NS,观察手术间隔的影响：,6cm,，否则，即使术前,放疗，也很难保肛；,2,、术前放疗后，手术间隔时间,4-6w,即,可，太近，手术并发症多；太长，,放射区域纤维化。,Improved sphincter preservation in low rectal cancer with,high-dose preoperative radiotherapy,The lyon,R90-02,randomized trail. J Clin Oncol,2004,22:2404-2409,.,入组标准：,T,2-3,N,x,M,0,，距肛门,6cm,，肿瘤侵犯周径,30Gy,可提高保肛率，延长,OS,；,?,注意照射技术与照射范围，以降低放疗相关并发症；,?,放疗后手术切除的最佳间隔时间为,4-6w,；,?,期术前放疗无获益，术前有效分期很重要。,?,术前分期为,T3-4,，,N+,，,12cm,以下直肠,癌需进行新辅助放化疗,?,新辅助放化疗多采用常规分割照射，,DT 50Gy/25f,?,放化疗后,4-6,周手术治疗,?,术后需继续巩固放,/,化疗,直肠癌术前放化疗的指征,?,有利点,?,不利点,?,早期（,T1-2N0M0),过度治疗,?,降低分期，提高切除率,?,减少术中肿瘤种植,?,低位直肠癌增加保肛机会，提高生活质量,?,术前小肠位于腹膜返折线上，未粘连固定，,小肠不良反应发生率低,?,肿瘤细胞氧合好，对射线敏感,直肠癌术前精确分期很重要,Question 3,：,which is better preoperative CRTor preoperative RT?,术前放化疗,vs,术前放疗？,FFCD9203,EORTC 22921,RT46Gy,RT46Gy,+5FU/LV,RT45Gy,RT45Gy+5FU/LV,Pathological,complete response,3.6%,11.4 %,5.3 %,13.7 %,5-y local,recurrence,16.5 %,8.1 %,17 %,8 %,5-y disease free,survival,55.5%,59.4 %,54.4 %,56.1 %,5-y overall,survival,67.9 %,67.4 %,64.8 %,65.8 %,p0.001;,P0.01,Result,；术前,CRT,优于,SCRT,1,、,pCR,：,15% vs 1%,；,2,、,downing T stage,;,3,、,sphincter sparing,：,58% vs 61%,，,p=0.57,欧洲各国主张：,SCRT+S,北美各国主张：,CRT+S,Poland,Question 4,：,which is the optimal setting:preoperative or,postoperative chemoradio?,术前放化疗,vs,术后放化疗？,直肠癌根治术后单纯放疗随机分组研究,盆腔复发率,No survival benefit in all trials!,Study,Gy/F,单纯手术,手术,+,放疗,P,值,复发数,/,总数,%,复发数,/,总数,%,Odense,50/25,57/250,23,46/244,19,NS,MRC3,40/20,79/235,34,48/234,21,0.01,GITSG,40-48/23-26,27/106,25,15/96,16,NS,NSABP,46.5/26,45/184,24,30/184,16,0.06,EORTC,46/23,30/88,34,25/84,30,NS,Rotterdam,50/25,28/84,33,21/88,24,NS,/,直肠癌根治,术后同步放化疗,的随机分组研究,术后,CRT vs,术后,RT,术后,CRT vs,术后,CT,术后,CRT vs S,随机分组,局部复发率,5yDFS,5y OS,(%),p,(%),p,(%),p,GTSG-7175,(1985,年,),post-CRT,70,0.009,58,0.005,S,46,45,Mayn/NCCTG,794751 (1991,年,),post-CRT (n=104),13.5,0.036,59,0.002,58,0.025,post-RT (n=100),25,37,48,Norway,(1997,年,),post-CRT (n=66),12,0.01,64,0.05,64,0.01,S (n=70),30,46,50,NSABP R02,(2000,年,),post-CRT (n=346),8,0.02,66,0.89,post-CT (n=348),13,66,美国,NCI,已经明确规定，,/,直肠癌根治术后的临床研究，,必须以同步放化疗为对照，以免损伤患者利益，类证据。,先化疗，术后,3,月才开始放,疗，延迟同步放化疗的时,间，降低了放疗疗效,1991,年开始，,术后同步放,化疗成为标,准辅助治疗,术后,CRT,的放疗时间对疗效的影响,韩国的一项随机对照研究,n=308,分组：早放组,术后立即,CRT,CT*6,；,晚放组,术后,CT*2,CRT,CT*4,早放组,晚放组,p,局部复发率,(%),17,27,0.047,4y DFS(%),81,70,0.043,4y OS(%),84,82,0.387,German trail,（,CAO/ARO-094),NSABP R-03,p,Pre-op+CRT,(50Gy),Post-op+CRT,(55Gy),Pre-op+CRT,(50Gy),Post-op+CRT,(50Gy),Pathological,complete response,8%,0 %,16.5 %,0 %,0.001,5-y local,recurrence,6 %,13 %,10.7 %,10.7 %,0.011,5-y disease free,survival,68 %,65 %,64.7 %,53.4 %,5-y overall,survival,76 %,74 %,74.5 %,65.5 %,sphincter sparing,39%,19%,0.004,Acute grade,/,toxicity,27%,40%,41%,49%,0.01,术前,CRT,能显著性降低,LR,、,/,毒副反应发生率、提高,p-CR,保肛率，,但不提高生存率,NCCN,指南推荐,/,直肠癌的标准治疗模式：,术前,CRT/,术后,CRT,