局部晚期非小細(xì)胞肺癌綜合治療

王長(zhǎng)利天津醫(yī)科大學(xué)附屬腫瘤醫(yī)院天津市肺癌診治中心局部晚期非小細(xì)胞肺癌綜合治療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% 結(jié)直腸癌:64.1%非小細(xì)胞肺癌CancerFacts/Figures2007肺癌的治療不確定切除切緣鏡下陰性，但出現(xiàn)下列情況之一者：

1）淋巴結(jié)清掃未達(dá)要求

2）切除的最高縱隔淋巴結(jié)陽性

3）支氣管切緣為原位癌

4）胸腔沖洗液細(xì)胞學(xué)陽性Maggietal.IntSurg,1990p=0.0000p=0.0000左全肺切除系統(tǒng)性淋巴結(jié)清掃：

2-12組檢測(cè)多項(xiàng)腫瘤標(biāo)志物預(yù)測(cè)預(yù)后指導(dǎo)臨床1年生存率82.3%3年生存率56.7%5年生存率45%IIIAN2期患者為312例1年生存率71.9％3年生存率36.7％5年生存率25.6％局部晚期非小細(xì)胞肺癌（IIIAN2）綜合治療SubsetsofStageIIIA(N2)SubsetDescriptionIIIA1術(shù)前和術(shù)中未發(fā)現(xiàn)而術(shù)后病理確診有N2淋巴結(jié)轉(zhuǎn)移IIIA2術(shù)中冰凍發(fā)現(xiàn)N2淋巴結(jié)轉(zhuǎn)移IIIA3術(shù)前分期檢查(縱隔鏡,其它淋巴結(jié)活檢方法及PET-CT)N2淋巴結(jié)有單組或多組轉(zhuǎn)移，但轉(zhuǎn)移的淋巴結(jié)無固定IIIA4N2呈大塊狀（短軸>2cm）或多組固定的轉(zhuǎn)移淋巴結(jié)RuckdeschelJCetal.Seminoncol.1997:24:429-439TreatmentofNSCLC-StageIIIA1-2Management:StageIIIA(1-2)NSCLCGoldstrawPetal.JThoracCardiovascSurg,1994全肺切除vs肺葉切除2000~2003年312例IIIAN2期病人手術(shù)方式例數(shù)1年生存率3年生存率5年生存率P值肺葉切除24175.6%39%28.6%全肺切除7159.9%28.8%14.7%0.029放療(AdjuvantRadiotherapy)化療(AdjuvantChemotherapy)聯(lián)合化放療(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會(huì)議遺憾的是JBR.10實(shí)驗(yàn)并不包括III期的患者2000~2003年312例IIIAN2期病人術(shù)后化療例數(shù)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.新輔助治療近況-Meta分析2005年Berghmas等挑選了6個(gè)隨機(jī)對(duì)照試驗(yàn),對(duì)1990～2003年的590例患者的資料進(jìn)行Meta分析，但新輔助化療對(duì)III期NSCLC卻沒有統(tǒng)計(jì)學(xué)優(yōu)勢(shì)HR0.65（）.2006年Burdett,收集了1990～2005年的7個(gè)隨機(jī)對(duì)照試驗(yàn)（IA-IIIA）,包括988例患者結(jié)合系統(tǒng)回顧和Meta分析,得出結(jié)論新輔助化療提高了生存率,且5年生存優(yōu)勢(shì)提高了6%。HR0.82（，p=0.02）.BerghmansTetal.LungCancer2005,49:13BurdettSetal.JThoracicOncology2006,1:611新輔助治療近況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新輔助治療試驗(yàn)結(jié)果顯示兩組生存率并無顯著差異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期病人新輔助化療例數(shù)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術(shù)后放療例數(shù)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我們的研究顯示單組轉(zhuǎn)移者5年生存率較高(32.1%)，明顯優(yōu)于多站轉(zhuǎn)移者(16.1%)淋巴結(jié)轉(zhuǎn)移組數(shù)例數(shù)1年生存率3年生存率5年生存率P值1組17876.0%42.0%32.1%＞1組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