局部晚期非小细胞肺癌综合治疗

王长利天津医科大学附属肿瘤医院天津市肺癌诊治中心局部晚期非小细胞肺癌综合治疗2肺癌的5年生存率

1963 9.0% 2007 15.0%注意5年生存率:

乳腺癌:88.5% 结直肠癌:64.1%非小细胞肺癌CancerFacts/Figures2007肺癌的治疗不确定切除切缘镜下阴性，但出现下列情况之一者：

1）淋巴结清扫未达要求

2）切除的最高纵隔淋巴结阳性

3）支气管切缘为原位癌

4）胸腔冲洗液细胞学阳性Maggietal.IntSurg,1990p=0.0000p=0.0000左全肺切除系统性淋巴结清扫：

2-12组检测多项肿瘤标志物预测预后指导临床1年生存率82.3%3年生存率56.7%5年生存率45%IIIAN2期患者为312例1年生存率71.9％3年生存率36.7％5年生存率25.6％局部晚期非小细胞肺癌（IIIAN2）综合治疗SubsetsofStageIIIA(N2)SubsetDescriptionIIIA1术前和术中未发现而术后病理确诊有N2淋巴结转移IIIA2术中冰冻发现N2淋巴结转移IIIA3术前分期检查(纵隔镜,其它淋巴结活检方法及PET-CT)N2淋巴结有单组或多组转移，但转移的淋巴结无固定IIIA4N2呈大块状（短轴>2cm）或多组固定的转移淋巴结RuckdeschelJCetal.Seminoncol.1997:24:429-439TreatmentofNSCLC-StageIIIA1-2Management:StageIIIA(1-2)NSCLCGoldstrawPetal.JThoracCardiovascSurg,1994全肺切除vs肺叶切除2000~2003年312例IIIAN2期病人手术方式例数1年生存率3年生存率5年生存率P值肺叶切除24175.6%39%28.6%全肺切除7159.9%28.8%14.7%0.029放疗(AdjuvantRadiotherapy)化疗(AdjuvantChemotherapy)联合化放疗(AdjuvantCombinationChemoradiotherapy)ChoiNetal.IntJRadiatOncolBiolPhys1980;6:31-35GreenNetal.Radiology1975;116:405-407KirschMetal.AnnThoracSurg1982;33:459-463Randomizedcontrolledtrialsof

surgeryplusadjuvantradiotherapyvssurgeryaloneSourceYearPatientsNoXRTDose,GyStageSurvivalLocalRecurrenceSurgery+XRT/SurgeryPaterson196220245AnyNSBagma19717346AnyNSVanHoutte198022460I,IINS4.8/20.7(p=0.002)Weisenberger198521050II,IIIANS1/19(p=0.02)Stephens199630840II,IIIANS18/29(p=0.003)Debevec19967430IIIANSDautzenberg199972860II,IIIAWorseforXRTNS=no

significant

difference;XRT=radiotherapy.LaryA.Robinsonetal.CHEST.2007,132:243-265OkawaraG,etal.LungCancer2004;44:1-11RandomizedControlledTrialsofSurgeryPlusAdjuvantCisplatin-BasedChemotherapyvsSurgeryAlone(WithorWithoutAdjuvantRadiotherapy)*SourceYearPatientsNoStageDisease-FreeSurvival5yearSurvivalSurgery+Chemo/Surgery,%Ohta1993181IIINS35/41(p=0.86)(CAP)Figlin1994188II-IIINSNS(CAP)SGACLC1995333I–III(I,61%)NS68.7/58.1(p=0.35)(CDDP/A/UFT)ALPI20031209I–IIIA(IIIA,29%)NS(p=0.13)NS(MVP)BigLungTrial

2003381I–IIIA(IIIA,34%)54%(p=0.98)NSCV,MIC,MVPorNP3cyclesIALT20041867I–IIIA(IIIA,39%)39.4%/34.3%(p<0.003)44.5/40.4(p<0.03)CDDP+Et,VnorVbANITA2006840I-IIIA(IIIA39%)42vs26(p=0.013)NP4cyclesLaryA.Robinsonetal.CHEST.2007,132:243-265DouilllardJYetal.LancetOncol2006,7:719-27NS=no

significant

difference;Chemo=chemotherapy.CDDP=cisplatin;Et=etoposide;Vn=vinorelbine;Vb=vinblastine;CAP=cyclophosphamide-doxorubicin-cisplatin;A=doxorubicin;UFT=uracil-tegafur;MVP=mitomycinC,Vindesine,cisplatin;HottaKetal.JClinOncol2004,22:3860BerghmansT,etal.LungCancer2005;49:13–23Pignonetal.JClinOncol2006,24:18sM.S.Tsaoetal.

2008ASCO会议遗憾的是JBR.10实验并不包括III期的患者2000~2003年312例IIIAN2期病人术后化疗例数1年生存率3年生存率5年生存率P值是18674.1%39.4%29.9%否12668.7%32.7%21.1%0.047SourceYearPatientsNoStageDisease-FreeSurvivalLong-termSurvival:Surgery-XRT/ChemovsSurgery-XRT,%Ladetal1988164II-IIIChemofavoredP=0.00454/68(p=0.1);1yr

Sawamura198852II-IIINSNSPistersetal199472IIINS44/31(p=0.42);2yrDautzenberg1995267I–IIINS12/13(p=0.68);10yr

Kelleretal2000488II–IIIANS30mo/38mo(p=0.56median)RandomizedControlledTrialsofSurgeryPlusAdjuvantChemoradiotherapyvsSurgeryPlusAdjuvantRadiotherapyLaryA.Robinsonetal.CHEST.2007,132:243-265NS=no

significant

difference;XRT=radiotherapy；Chemo=chemotherapyPerryMc,etal.ClinLungCancer2007,8:268-72TreatmentofNSCLC-StageIIIA3RandomizedControlledTrialsofPreoperativeNeoadjuvantTherapyandSurgeryvsSurgeryAloneinStageIIIANSCLCSourceYearPatientsNoMedianSurvival,Neoadjuvant/None,MonthSurvivalRateNeoadjuvant/None,%Pass19922729/16(p=0.095)42(3yr)/12(3yr)Rosell1994/19996022/10(p<0.005)29(2yr),17(5yr)/5(2yr),0(5yr)Roth1994/19986021/14(p=0.048)46(3yr),36(5yr)/19(3yr),15(5yr)

Wagner19945712/1227%at4yrforbotharms

Elias19975723/19(p=0.64)NR/NRDePierre2002167NR

28(5yr,chemo)/20(5yr,estimated);p=NSNagai20036217/1610(5yr,chemo)/22(5yr,estimated);p=0.5274

LaryA.Robinsonetal.CHEST.2007,132:243-265NS=no

significant

difference;NR=notreported.新辅助治疗近况-Meta分析2005年Berghmas等挑选了6个随机对照试验,对1990～2003年的590例患者的资料进行Meta分析，但新辅助化疗对III期NSCLC却没有统计学优势HR0.65（）.2006年Burdett,收集了1990～2005年的7个随机对照试验（IA-IIIA）,包括988例患者结合系统回顾和Meta分析,得出结论新辅助化疗提高了生存率,且5年生存优势提高了6%。HR0.82（，p=0.02）.BerghmansTetal.LungCancer2005,49:13BurdettSetal.JThoracicOncology2006,1:611新辅助治疗近况GilliganD,etal.Lancet2007,369:1929-37BerghmansTetal.LungCancer2005,49:13UyKL,etal.JThoracCardiovascSurg2007,134:188-93RandomizedControlledTrialsofPreoperativeNeoadjuvantTherapyandSurgeryvsChemotherapy/RadiotherapyAlone(NoSurgery)inStageIIIANSCLC

SourceYearPatientsNoMedianSurvival,Surgery/Nosurgery,MonthSurvivalRateSurgery/Nosurgery,%Johnstone20027619.4(surgery)vs17.4(p=NS)70(surgery)vs66at1yr(p=NS)Taylor200410731(surgery)vs27(p=NS)33(surgery)vs30at5yr(p=NS)vanMeerbeeck200533316.4(surgery)vs17.5(p=NS)16(surgery)vs13at5yr(p=NS)Albain200539612.8(surgery)vs10.5(progression-free)(p=0.017)27.2(surgery)vs20.3at5yr(p=0.10)NS=no

significant

difference;NR=notreported.LaryA.Robinsonetal.CHEST.2007,132:243-265新辅助治疗试验结果显示两组生存率并无显著差异Tayloretal.IntJRadiatOncolBiolPhys2004;58:204-212Albainetal.JClinOncol2005;23(suppl):7014Buenoetal.AnnThoracSurg2000;70:1826-1831Albainetal.JClinOncol1995;1880-1892Takedasetal.EurJCardiothoracSurg.2006Jul;30(1)2000~2003年312例IIIAN2期病人新辅助化疗例数1年生存率3年生存率5年生存率P值是10573.1%38.4%28.3%否20769.7%31.3%23.1%0.315术后放疗例数1年生存率3年生存率5年生存率P值是8476.6%44.7%35.9%否22869.2%33.7%21.7%0.024我们的研究显示单组转移者5年生存率较高(32.1%)，明显优于多站转移者(16.1%)淋巴结转移组数例数1年生存率3年生存率5年生存率P值1组17876.0%42.0%32.1%＞1组13465.7%29.5%16.1%0.007TreatmentofNSCLC-StageIIIA4StageIIIA4(UnresectableBulkyN2Disease)RandomizedControlledTrialsofSequentialorConcurrentChemoradiotherapyvsRadiotherapyAloneforUnresectableStageIIINSCLC

SourceYearPatientsNoTimingCT/RTStudyResult2-yearSurvivalCT+RT/RT,%Morton1991183SequentialNeg21/16Trovo1992173ConcurrentNeg13/13Schaake-Koning1992308ConcurrentPos26/13Wolf199485Sequential+ConcurrentPos24/12Chevalier1994353SequentialPos21/14Dillman1996155SequentialPos26/13

Jeremic1996131ConcurrentPos52/38Cullen1999446SequentialNeg20/16(p=0.14)Sause2000490SequentialPos32/21(p=0.04)NS=no