非小细胞肺癌放射治疗进展-王绿化PPT课件

.,1,肺癌的放射治疗进展,中国医学科学院协和医科大学肿瘤医院王绿化,.,2,影像技术和计算机技术的进步为精确放射治疗的实现提供可能,.,3,.,4,.,5,屏气技术举例:ElektaABC,.,6,四维CT影像技术,呼气,吸气,螺旋开始,时相,由吸转呼,呼气末,由呼转吸,由吸转呼,呼气,吸气,螺旋开始,呼吸曲线,床位,.,7,影像引导放射治疗技术IGRT,40对叶片MLC,KV级X射线球管,KV级探测器阵列,MV级探测器阵列,.,8,在线校正影像匹配,.,9,一、放射治疗在肺癌治疗中的地位二、早期NSCL的放射治疗三、局部晚期NSCL的放疗/化疗综合治疗四、3DCRT提高NSCLC的生存率五、术后放射治疗,.,10,一、放射治疗在肺癌治疗中的地位,应用循证医学的方法评价放射治疗在肺癌治疗中的地位。,.,11,.,12,RT在SCLC治疗中的地位,53.6%3.3%SCLC病例在其疾病的不同时期需要接受放射治疗45.4%4.3%为首程治疗（intheinitialtreatment）.8.2%1.5%为复发和进展病例的治疗（laterforrecurrenceorprogression）,.,13,RT在NSCLC治疗中的地位,64.3%4.7%ofNSCLCcasesrequireRT.45.9%4.3%intheirinitialtreatment.18.3%1.8%laterinthecouseoftheillness,.,14,二、早期非小细胞肺癌的放射治疗,放射治疗能够使早期NSCLC获得治愈,.,15,JapaneseStudiesI期NSCLC大剂量分割SRT获得满意的局部控制率,InstituteDose/fx/OTTLC/Follow-upUematsu50-60/5-10/5d94%(47/50)36MKyoto48Gy/4fr/12d96%(49/51)20MArimoto60Gy/8fr/11d92%(22/24)24MOnimaru60Gy/8fr/11d:88%(50/57)18MNagataY,KyotoUniv,IASLC,2004,.,16,SummaryofJapaneseStudies,Totalcases：281Age:39-92(median76)yearsPulmonarydisease:Positive:172,Negative:109Histology:Sqamous:122Adeno:131,Others:28Stage:IA:178,IB:103Tumordiameter:7-58(median23)mmMedicalOperability:Inoperable:177,Operable:104OnishiH,ASCO2004,.,17,LocalControlandComplication,Follow-upperiod2-128(median30)monthsLocalresponseCR26.9%PR59.1%NC14.0%Pneumonitis(NCI-CTC)Grade0:33.7%Grade1:59.9%Grade2:4.0%Grade3:1.2%Grage4:1.2%Esophagitis(Grade3)1.2%Pleuraleffusion(transient)1.6%Ribfracture1.2%Bonemarrowsuppression0.0%OnishiH,ASCO2004,.,18,LocalFailureRates,Totalcases38/281(13.5%)BED100Gy17/211(8.1%)StageIA17/177(9.6%)BED100Gy9/136(6.6%)StageIB21/102(20.6%)BED100Gy8/73(11.0%)Adenocarcinoma17/122(14.0%)Squamouscellca.18/131(13.7%)OnishiH,ASCO2004,.,19,Mountain*,JCOG*,JNCCH*,StageIAStageIB,67%57%,80%63%,74%53%,STI*,90%,84%,*Surgery,*StereotacticIrradiation,Comparisonof5-YrOverallSurvivalBetweenSurgery17:2692-2699,RTOG9410:III期NSCLC同步放化疗vs序贯放化疗,序贯:PV-RT(60Gy,2GyQD)day50同步:PV/RT(60Gy,2GyQD)day1同步/HFRT:PE/HFRT(69.2Gy,1.2GyBID)day1PV:顺铂/长春花碱PE:顺铂/oral足叶乙甙RT:放疗;QD:每日一次;HFRT:超分隔放疗,Curran:ASCO,2000;updatedIASLC2000;ASTRO2001,2003,RANDOMIZE,二.同时化放疗vs序贯化放疗(2)SEQCON-QDCON-BID中位生存期：14.61715.6（月）4年生存率：12%21%17%p=0.046G3急性和晚期非血液系统毒性：30%，48%，62%和14%，15%，16%。CurranWetal.Pro.AmSocClinOncol.J.Clin.Oncol.2003;(abstract2499),结论：同步放化疗优于序贯放化疗，但是，急性毒性反应增加,同步放化疗,？诱导化疗,?巩固化疗,同步放化疗,诱导化疗,InductionChemotherapyFollowedbyChemoradiotherapyWithChemoradio-therapyAloneforRegionallyAdvancedUnresectableStageIIINonSmall-CellLung:CancerandLeukemiaGroupBCALGB39801,JClinOncol.2007May1;25(13):1698-704.Epub2007Apr,CALGB39801studydesign,July1998andwasclosedinMay2002,Totally366patientsregistered,Survivalintenttotreat,Survivalofeligiblepatientswithaweightlossof5%,Discussion,增加毒性inductionchemotherapyincreasesneutropeniaandoverallmaximaltoxicity没有生存优势Nosurvivalbenefitoverconcurrenttherapyalone同期放化疗是标准的治疗模式ConcomitantchemoradiotherapyiscurrentstandardtherapyforunresectablestageIIIBNSCLC,SimultaneousChemoradiotherapyComparedWithRadiotherapyAloneAfterInductionChemotherapyinInoperableStageIIIAorIIIBNonSmall-CellLungCancer:,StudyCTRT99/97bytheBronchialCarcinomaTherapyGroupRudolfM.Huber,MichaelFlentje,MichaelSchmidt,BarbaraPllinger,HelgaGosse,JochenWillner,andKurtUlm,paclitaxel200mg/m2carboplatinAUC=6every3weeksX2cycles,paclitaxel60mg/m2weekly,Radiotherapyalone,Survivalafterinductionchemotherapyforpatientswithcompleteorpartialresponse,同步放化疗,巩固化疗,SWOG9504:同步放化疗后应用泰索帝巩固化疗治疗IIIb期NSCLC,顺铂/VP-16XXRT泰索帝XXX,顺铂50mg/m2d1,8,29,36VP-1650mg/m2d1-5,29-33RT:61Gy:45Gy(1.8Gy/fx),16Gy缩野(2Gy/fx)泰索帝:75mg/m2cycle1-100mg/m2cycle2-3,SWOG9504:总生存,%,%,%,%,%,%,0,4,8,入组时间（月）,NEvents中位生存834526月,2年生存率:54%3年生存率:37%,SWOG9504和SWOG9019比较,*95%CI,SWAG0023,ConcurrentChemo/RadioDDP+Vp16/RT,ConsolidationChemoDocetaxel,MaintenanceGEFITINIBorPLACEBO,同步放化疗,巩固化疗,ResultsofASCO2007,HOGLUN01-24PhaseIIIStudyDesign,Hannaetal.ASCO2007:Abstract7512.,ChemoRTCisplatin50mg/m2IVd1,8,29,36Etoposide50mg/m2IVd1-5ConsolidationDdoesnotfurtherimprovesurvival,isassociatedwithsignificanttoxicityincludinganincreasedrateofhospitalizationandprematuredeath,AndshouldnolongerbeusedforptswithunresectablestageIIINSCLC,Conclusions,.,61,术前同时化放疗的临床研究,.,62,可手术（Operable）A(N2)放/化疗vs放化疗+手术RTOG93-09INT：0139,.,63,CT/RT/S145/202CT/RT155/194,Logrankp=0.24危险比=0.87(0.70,1.10),存活率%,0,25,50,75,100,从随机分组开始后的月数,0,12,24,36,48,60,死亡/总数,INT0139试验:总生存,中位FU81个月,Albainetal.ASCO2005.Abstract7014.,.,64,随机分组后的月数,MS3yrOS5yrOS,19月36%22%,CT/RT/S,CT/RT,存活率%,0,25,50,75,100,0,12,24,36,48,60,/,/,/,/,/,/,/,/,/,/,29月45%24%,死亡/总计,CT/RT/S,38/51,CT/RT,42/51,Logrankp=NS,INT0139试验:肺切除亚组和相应化疗/放疗亚组的总生存的比较,Albainetal.ASCO2005.Abstract7014.,.,65,INT0139试验:肺叶切除亚组和相应化疗/放疗亚组的总生存的比较,Albainetal.ASCO2005.Abstract7014.,.,66,.,67,EORTC08941A：UnresectablepN2,不能手术的ApN2病例通过诱导化疗后成为可手术病例是选择手术还是选择放疗？,.,68,.,69,.,70,.,71,.,72,四、NSCLC术后放射治疗,NewdatasupportsPORTinN2cases,.,73,1998PORT,死亡风险增加21%2年OS下降755%-48%pN0pN1有害pN2降低局部复发对OS无明确结论,PORTMeta-analysisLancet,1998.352:257-63UpdateofPORTLungCancer,2005.47:81-3,.,74,NewData1回顾分析PORT,SEER1988年2001年、期NSCLC7465例根治性术后PORT3508例（47%）,SEERJClinOncol,2006.24:2998-3006,.,75,PORT在N2中的作用,PORT既能够提高OS也能够提高DSS,N0,N1,N2,.,76,NewData2ResultsfromANITA:PhaseIIIAdjuvantVinorelbineandCisplatinversusObservationinCompletelyResectedNon-Small-CellLungCancerPatients,RRosell,MDeLena,FCarpagnano,RRamlau,JLGonzalez-Larriba,TGrodzki,ALeGroumelec,DAubert,JGasmi,JYDouillardonbehalfoftheAdjuvantNavelbineInternationalTrialAssociation,.,77,PORTinN1Patients,RTisbetterthanOBS.ForpatientwhocannottolerateCT,RTwouldberecommended.,PORTinN2Patients,0.00,0.25,0.50,0.75,1.00,DURATIONOFSURVIVAL(MONTHS),0,20,40,60,80,100,120,CT&RTisthebest,RTisbetterthanOBS,.,79,NewData3fromCancerHospital&InstituteofCAMS,2003.01.01-2005.12.30根治性切除NSCLCT1-3,N2具备完整治疗信息一般临床资料术中所见及术后病理治疗模式及参数随访资料,.,80,材料与方法排除标准,T4N2者pN3病例及N分期不明者手术后3个月内死亡的患者手术后3个月内肿瘤进展者单纯探查术或纵隔镜活检术,.,81,材料与方法,生存率,DFS,治疗模式与生存率,非肿瘤死亡,有无术后放疗组的非肿瘤死亡率并无差异（p=0.493）,S+C+RS+CS+RS,5yOS47.0%34.0%21.3%16.6%,5yOS38.2%31.9%33.7%23.1%,MST（M）47.423.822.712.7,MST（M）48.333.138.321.6,ANITA的结果,医科院肿瘤医院的结果,完全切除的AN2NCSLC推荐术后化疗+放疗,.,87,PORTcanbesafelyusedwith3DCRT,Graph1.&Table4.ROCcurse:TheareaundercurveinreceiveroperatingcharacteristiccurvesbasedontherelationshipbetweenincidenceofRPandthevalueofVipsi-dosewas0.757(P=0.020).,Graph1.&Table4.ROCcurse:TheareaundercurveinreceiveroperatingcharacteristiccurvesbasedontherelationshipbetweenincidenceofRPandthevalueofVipsi-dosewas0.757(P=0.020).,Graph1.&Table4.ROCcurse:TheareaundercurveinreceiveroperatingcharacteristiccurvesbasedontherelationshipbetweenincidenceofRPandthevalueofVipsi-dosewas0.757(P=0.020).,Graph1.&Table4.ROCcurse:TheareaundercurveinreceiveroperatingcharacteristiccurvesbasedontherelationshipbetweenincidenceofRPandthevalueofVipsi-dosewas0.757(P=0.020).,JiWeietal:ASTROmeeting2008Boston,Conclusion：ItwassafeforpatientswithNSCLCtoreceivepostoperative3DCRT，ifirradiationdosetolungtissuewaswelldefined.,.,88,3DCRT能够提高NSCLC的治疗疗效,.,89,Int.J.RadiationOncologyBiol.Phys.,Vol.66,No.1,pp.108116,2006,3Dvs2DinMEDICALLYINOPERABLESTAGEINONSMALL-CELLLUNGCANCER,(a)Overallsu