局部晚期非小細胞肺癌的治療課件

非小細胞肺癌背景絕大多數局部晚期,特別是縱隔淋巴結受累的患者在只進行局部治療后將在數月后出現(xiàn)遠處轉移手術治療N2的III期非小細胞肺癌其5年生存率為7-16%N2不僅僅是局部問題,它其實是全身性疾病的一個標志術前化療的有效率為30%-70%,根據所用化療及患者臨床分期,臨床根治手術率約為2/31980s因為經常出現(xiàn)遠處轉移,1980年以后進行了相關的術前與術后再加上化療的研究研究背景2004年在美國有170,000例新發(fā)肺小細胞肺癌，1/5患者為N2或者IIIa期患者。最近研究顯示經過術前化療后降低了臨床分期，并隨后進行手術的患者起五年生存率可達40%-50%。CT診斷縱隔淋巴結大小與淋巴結轉移的關系

*FromTheAmericanSocietyofClinicalOncology.淋巴結大小cm病理證實轉移%<1131–2252–367PaulA.Bunn,Jr,MD;JamesMaultetal.Chest.2000;117:119S-122S.

誘導化療療效評價（臨床評價VS組織病理學評價）

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

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

0*22Martinietal73231910ChemoradiotherapyFaberetal65232026SWOG880559291557MalcolmM.DeCampetal.ClinicalCancerResearchVol.11,5033s-5037s,July1,2005手術切除后復發(fā)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期非小細胞肺癌N=60手術組（N=30）化療組（N=30）MMC6mg/m2ivd1IFO3g/m2ivd1DDP50mg/m2ivd13周期手術化療/手術手術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,MartinT?tschetalJournalofClinicalOncology,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個臨床研究對于I–IIIA非小細胞肺癌與只進行縱隔淋巴結取樣相比縱隔淋巴結清掃可以顯著延長患者的4年生存率(hazardratioestimatedat0.78(95%CI0.65to0.93)。對于I–IIIA非小細胞肺癌完整的縱隔淋巴結清掃較淋巴結取樣可以延長患者的生存時間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