局部晚期非小细胞肺癌的治疗课件

非小细胞肺癌背景绝大多数局部晚期,特别是纵隔淋巴结受累的患者在只进行局部治疗后将在数月后出现远处转移手术治疗N2的III期非小细胞肺癌其5年生存率为7-16%N2不仅仅是局部问题,它其实是全身性疾病的一个标志术前化疗的有效率为30%-70%,根据所用化疗及患者临床分期,临床根治手术率约为2/31980s因为经常出现远处转移,1980年以后进行了相关的术前与术后再加上化疗的研究研究背景2004年在美国有170,000例新发肺小细胞肺癌，1/5患者为N2或者IIIa期患者。最近研究显示经过术前化疗后降低了临床分期，并随后进行手术的患者起五年生存率可达40%-50%。CT诊断纵隔淋巴结大小与淋巴结转移的关系

*FromTheAmericanSocietyofClinicalOncology.淋巴结大小cm病理证实转移%<1131–2252–367PaulA.Bunn,Jr,MD;JamesMaultetal.Chest.2000;117:119S-122S.

诱导化疗疗效评价（临床评价VS组织病理学评价）

Abbreviations:c,clinical;p,pathologic;*TherewerenoCR’sinCALGB8935.

cPRandSDwerereportedinaggregate.InductionregimenClinicalresponse(%)Pathologicresponse(%)cCR+cPRSDpCRpPRChemotherapyCALGB89350*88

0*22Martinietal73231910ChemoradiotherapyFaberetal65232026SWOG880559291557MalcolmM.DeCampetal.ClinicalCancerResearchVol.11,5033s-5037s,July1,2005手术切除后复发部位

Adenocarcinoma/LargeCellSquamousCellRegional1724Distant7971Regionalanddistant45PaulA.Bunn,Jr,MD;JamesMaultetal.Chest.2000;117:119S-122S.

ImportantmultimodalitytrialsinN2NSCLCAbbreviations:MDACC,M.D.AndersonCancerCenter;CALGB,CancerandLeukemiaGroupB;INT,Intergroup;CTX,chemotherapy;RT,radiotherapy;S,surgeryYearAuthor/affiliationDesignnStrategyOverallsurvival1994Roth/MDACCPhaseIII60CTX-S-CTX/RTvsS-RT43%,3y;36%,5yversus19%,3y;15%,5y1994Rosell/BarcelonaPhaseIII60CTX-S-RTvsS-RT20%,3y;17%,5yversus5%,3y;0%,y1995Sugarbaker/CALGBPhaseII74CTX-S-RT23%,3y1995Albain/SWOGPhaseII75CTX/RT-S26%,3y2003INT0139PhaseIII392Chemo/RTvsChemo/RT-S33%,3yversus38%,3yMalcolmM.DeCampetal.ClinicalCancerResearchVol.11,5033s-5037s,July1,2005IIIA期非小细胞肺癌N=60手术组（N=30）化疗组（N=30）MMC6mg/m2ivd1IFO3g/m2ivd1DDP50mg/m2ivd13周期手术化疗/手术手术P值DFS205P<0.001OS268P<0.001EndpointsDFSOSRadiotherapyNEnglJMed1994;330:153–8.ResectableIIIANSCLCN=60CTXVp16

3cycles

CDDPN=28SurgerySurgeryN=32EndPointsDFSOSChemo3cycles

PDSurgeryCHEMO-SURSURPvalueRR35%MS(m)6411<.0082Y60%25%3Y56%15%JackA.Rothetal.JNCIJournaloftheNationalCancerInstitute199486(9):673-680

ResectablestageI(exceptT1N0),II,andIIIAmitomycin6mg/m2,d1ifosfamide1.5g/m2,d132cisplatin30mg/m2,d13surgerysurgerychemo2pT3orN2RadiotherapyDFSOSJournalofClinicalOncology,Vol20,Issue1(January),2002:247-253InductionMIC-SurgeryvsSurgery

DepierreTrialinLocallyAdvancedNSCLCMIC+SurgerySurgeryEntered179176ResponseRate65%N/ASurgery94%99%MedianDFS26.7mos12.9mosMedianSurvival37mos26mos1YearSurvival77.1%73.3%2YearSurvival59.2%52.3%3YearSurvival51.6%41.2%4YearSurvival43.9%35.3%MIC=Mitomycin/Ifosfamide/Cisplatin DepierreJCO2003PhaseIIIstudyofconcurrentchemotherapyandradiotherapy(CT/RT)vsCT/RTfollowedbysurgicalresectionforstageIIIA(pN2)non-smallcelllungcancer(NSCLC):OutcomesupdateofNorthAmericanIntergroup0139(RTOG9309)K.S.Albain,R.S.Swann,V.R.Ruschetal.

Albainetal.

JournalofClinicalOncology,2005ASCOAnnualMeetingProceedings.Vol23,No.16S,

Albainetal.

JournalofClinicalOncology,2005ASCOAnnualMeetingProceedings.Vol23,No.16S,

Pneumonectomy“Matched”SurgeryRTMedianOverallSurvival19mo29mo3-yrsurvival36%45%5-yrsurvival22%24%#Dead3842Lobectomy“Matched”SurgeryRTMedianOverallSurvival34mo22mo5-yrsurvival36%18%#Dead5774MediastinalLymphNodeClearanceAfterDocetaxel-CisplatinNeoadjuvantChemotherapyIsPrognosticofSurvivalinPatientsWithStageIIIApN2Non–Small-CellLungCancer:AMulticenterPhaseIITrialDanielC.Betticher,Shu-FangHsuSchmitz,MartinTötschetalJournalofClinicalOncology,Vol21,No9(May1),2003:pp1752-1759Prognosticfactorsaffectinglong-termoutcomesinpatientswithresectedstageIIIApN2non-small-celllungcancer:5-year

BritishJournalofCancer(2006)94,1099–1106

N=90NSCLCIIIA(pN2)N=75docetaxel85mg/m2d1cisplatin40or50mg/m2d1、2resectionOSEFSPrognosticfactorsaffectinglong-termoutcomesinpatientswithresectedstageIIIApN2non-small-celllungcancer:5-yearfollow-upofaphaseIIstudy

BritishJournalofCancer(2006)94,1099–1106

Clinicalcontroltrials19942004Eighttrialswereincludedinmetaanalysis1965patientswereincludedintheanalysis(1001casesintheneoadjuvantgroupand964inthesurgerygroup)statisticalsignificantdifferenceinsurvivalbetweenthetwogroups.Theoddsratio(OR)was0.68with95%CI0.56to0.83,p=0.0002).Nostatisticalsignificantdifferenceinsurvivalinthehigherqualitytrials(reviewscores>8).TheORwas0.80with95%CI0.58to1.09,p=0.15).statisticalsignificantdifferenceinsurvivalinthelowerqualitytrials(reviewscores<8).TheORwas0.62with95%CI0.48to0.62,p=0.0002).ItisnotcertainthatneoadjuvantchemotherapyimprovedsurvivalinpatientswithresectablestageI–IIIANSCLC.ItisneededmoreRCTtoanswerthisquestionJournalofClinicalOncology,2005ASCOAnnualMeetingProceedings.

Vol23,No16S(June1Supplement),2005:7265Neo-adjuvantchemotherapyinresectable

stageIIInon-smallcelllungcancer:

-Meta-AnalysisT.Berghmansetal.LungCancer(2005)49Surgeryfornon-smallcelllungcancer:systematicreviewandmeta-analysisofrandomisedcontrolledtrialsGWright,RLManser,GByrnesGWright,RLManser,GByrnesThorax2006;61:597-603分析了8个临床研究对于I–IIIA非小细胞肺癌与只进行纵隔淋巴结取样相比纵隔淋巴结清扫可以显著延长患者的4年生存率(hazardratioestimatedat0.78(95%CI0.65to0.93)。对于I–IIIA非小细胞肺癌完整的纵隔淋巴结清扫较淋巴结取样可以延长患者的生存时间GWright,RLManser,GByrnesThorax2006;61:597-603PrognosticStratificationofStageIIIA-N2Non–Small-CellLungCancerAfterInductionChemotherapy:

AModelBasedontheCombinationofMorphometric-PathologicResponseinMediastinalNodesandPrimaryTumorResponseonSerial18-Fluoro-2-Deoxy-GlucosePositronEmissionTomography

ChristopheDooms,etal.JClinOncol,2008,26:p1128-1134.Fig2.Fig3.PrognosticStratificationofStageIIIA-N2Non–Small-CellLungCa