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ManagementofunresectablestageⅢnon-smallcelllungcancer:theroleofcombinedchemoradiationManagementofunresectablesta1introduction
Untilthelate1980s,thoracicradiationtherapy(TRT)remainedthestandardcareforlocallyadvancedNSCLC.introductionUntilthelate12Radiationalone?Sequentialchemoradiation?Radiationalone?Sequentialch3CALGB8433RT60GyPV2cycles＋RT60GyNo.7779MST9.713.81-yearsurvival40552yearsurvival13263yearsurvival11235yearsurvival719Pvalue0.0066DillmanRO,NEJM323:940-945,1990DillmanRO,JNCI88:1210-1215,1996CALGB8433RT60GyPV2cycles＋RT60G4RTOG8808RT60GyCT+RTH-RT69.6GyNo152152154MST11.413.2121-yearsurvival4759522-yearsurvival2132243-yearsurvival1117145-yearsurvival6119Pvalue
0.04SauseW,JNCI1995;87:198-205SauseW,CHEST2000;117:358-364RTOG8808RT60GyCT+RTH-RT69.6GyN5OSOS6<60ysurvival<60ysurvival7FRANCERT65GyCT+RT65GyP值No177176MST10120.081-yearsurvival41502-yearsurvival14213-yearsurvival511Metastasisrate3826<0.0011-yearLCR1715ThierryLeChevaliar,JNCI1991;83:417-423CT:VCPC,vindesine,cyclophosphamide,cisplatin,lomustineFRANCERT65GyCT+RT65GyP值No177178Concurrentchemoradiation?Radiationalone?Concurrentchemoradiation?Radi9EORTCRT55PDD(W)+RTPDD(D)+RTNo3113113111-ysurvival4644542-ysurvival1319263-ysurvival21316Pvalue0.0091-yLCR193031Pvalue0.003Schaake-KoningC,NEJM1992;326:524-530EORTCRT55PDD(W)+RTPDD(D)+RTNo310IntensifiedregimenH-RTH-RT/CTH-RT/CTNo615256methods64.8Gy64.8/CE64.8/CEMST818133-ysurvival6.62316JeremicB,JCO1995;13:452-458LeeJS,JCO1994;14:1055-1064CT:weekly,100mg/m2CBPD1,D2;100mg/m2VP-16D1-3CT:200mg/m2CBPD1,D2;100mg/m2VP-16D1-5,thefirst,third,andfifthweeks
IntensifiedregimenH-RTH-RT/CT11MetaAnalysisResults(52trials,9387pts)
2-yearsurvival4%。
Hazard
ratio:0.87。NSCLCCG,BMJ1995;311:899-909MetaAnalysisResults(52trial12Concurrentchemoradiation?Sequentialchemoradiation?Concurrentchemoradiation?Sequ13concurrentsequentialPvalueNo156158methods56Gy/MVP2CMVP2C+56MST16.513.30.042-ysurvival34.627.43-ysurvival22.314.74-ysurvival16.910.15-ysurvival15.88.9ResponseR84660.0002FuruseK,JCO1999;17:2692-2699JapanconcurrentsequentialPvalueNo114RTOG9410sequentialconcurrentconcurrent+HFNo(total)611RT606069.6methodsPV2CPV2CPEMST14.61715.6A-Toxicity304862L-Toxicity141516CurranWJ,PASCO2000;19:484aRTOG9410sequentialconcurrentco15ACR427(phaseⅡ)seqCon(ind/con)Con(con/adi)No(total)276RT636363CTPC2PC2+CONCON+PC2MST12.51116.1Esophogitis(≥3）42028ChoyH,PASCO2002;abstract:1160ACR427(phaseⅡ)seqCon(ind/con)16GLOT9501SEQCONNo(total)212RT66Gy66CTNP3CindCE+CE2Cadi3/4neutropenia
87.8753/4oesophagitis026.1MST13.915.61-ysurvival56562-ysurvival2335PierreF,PASCO2001;abstract:1246GLOT9501SEQCONNo(total)212RT6617MSTOSE-toxicity
S
C
SCSCfuruse13.3
16.5
916(5)423RTOG14.617.1
1221(4)
425GLOT13.915.6
2435(2)317Czech13.220.6
1542(2)428BROCAT14.019.0
--026ACR42713.817.4
3133(2)328MSTOSE-toxicityS18CALGB9431G/PP/PN/PNo.625855RR7467731-ySur6862653-ySur281923MST18.314.817.7DFSMethods:2cyclesinductionfollowedby2cyclesandconcurrentTRT,66GyVokesEE,JCO2002;20:4191-4198CALGB9431G/PP/PN/PNo.625855RR719CALGB9431CALGB943120SWOG9019Patients:
50pts.IIIB
Treatment:PE2cycles/RTPE2cyclesAlbainKS,JCO2002;20:3454-3460SWOG9019Patients:50pts.IIIB21SWOG9019MST:15months1y-sur:58%2y-sur:33%3y-sur:17%5y-sur:15%SWOG9019MST:15months1y-sur:522SWOG9504Patients:
83pts.IIIB
Treatment:PE2cycles/RTDocetaxel3cycles(75mg/m2forthefirstand100mg/m2forthelasttwocycles).GandaraDR,JCO2003;21:2004-2010SWOG9504Patients:83pts.IIIB23SWOG95041y-sur:76%MST:26months2y-sur:54%3y-sur:37%SWOG95041y-sur:76%MST:26mont24SWOG9019/9504studyNoSurvivaltime2y-Survival3y-survivalmedian95%CImedian95%CImedian95%CI9019501510-223421-47177-279504832618-355443-653722-52GandaraDR,JCO2003;21:2004-2010SWOG9019/9504studyNoSurvivalt25HossierOncologyGroupInductioncisplatin/etoposideTRTDocetaxelObservationHossierOncologyGroupInductio26CALGB9801InductionPCNoInductionPCconcurrentcarboplatin/paclitaxelTRTCALGB9801InductionPCNoInduct27SWOG0023PE/TRTConsolidationdocetaxelOralGefitinibplaceboSWOG0023PE/TRTConsolidationdo28ManagementofunresectablestageⅢnon-smallcelllungcancer:theroleofcombinedchemoradiationManagementofunresectablesta29introduction
Untilthelate1980s,thoracicradiationtherapy(TRT)remainedthestandardcareforlocallyadvancedNSCLC.introductionUntilthelate130Radiationalone?Sequentialchemoradiation?Radiationalone?Sequentialch31CALGB8433RT60GyPV2cycles＋RT60GyNo.7779MST9.713.81-yearsurvival40552yearsurvival13263yearsurvival11235yearsurvival719Pvalue0.0066DillmanRO,NEJM323:940-945,1990DillmanRO,JNCI88:1210-1215,1996CALGB8433RT60GyPV2cycles＋RT60G32RTOG8808RT60GyCT+RTH-RT69.6GyNo152152154MST11.413.2121-yearsurvival4759522-yearsurvival2132243-yearsurvival1117145-yearsurvival6119Pvalue
0.04SauseW,JNCI1995;87:198-205SauseW,CHEST2000;117:358-364RTOG8808RT60GyCT+RTH-RT69.6GyN33OSOS34<60ysurvival<60ysurvival35FRANCERT65GyCT+RT65GyP值No177176MST10120.081-yearsurvival41502-yearsurvival14213-yearsurvival511Metastasisrate3826<0.0011-yearLCR1715ThierryLeChevaliar,JNCI1991;83:417-423CT:VCPC,vindesine,cyclophosphamide,cisplatin,lomustineFRANCERT65GyCT+RT65GyP值No1771736Concurrentchemoradiation?Radiationalone?Concurrentchemoradiation?Radi37EORTCRT55PDD(W)+RTPDD(D)+RTNo3113113111-ysurvival4644542-ysurvival1319263-ysurvival21316Pvalue0.0091-yLCR193031Pvalue0.003Schaake-KoningC,NEJM1992;326:524-530EORTCRT55PDD(W)+RTPDD(D)+RTNo338IntensifiedregimenH-RTH-RT/CTH-RT/CTNo615256methods64.8Gy64.8/CE64.8/CEMST818133-ysurvival6.62316JeremicB,JCO1995;13:452-458LeeJS,JCO1994;14:1055-1064CT:weekly,100mg/m2CBPD1,D2;100mg/m2VP-16D1-3CT:200mg/m2CBPD1,D2;100mg/m2VP-16D1-5,thefirst,third,andfifthweeks
IntensifiedregimenH-RTH-RT/CT39MetaAnalysisResults(52trials,9387pts)
2-yearsurvival4%。
Hazard
ratio:0.87。NSCLCCG,BMJ1995;311:899-909MetaAnalysisResults(52trial40Concurrentchemoradiation?Sequentialchemoradiation?Concurrentchemoradiation?Sequ41concurrentsequentialPvalueNo156158methods56Gy/MVP2CMVP2C+56MST16.513.30.042-ysurvival34.627.43-ysurvival22.314.74-ysurvival16.910.15-ysurvival15.88.9ResponseR84660.0002FuruseK,JCO1999;17:2692-2699JapanconcurrentsequentialPvalueNo142RTOG9410sequentialconcurrentconcurrent+HFNo(total)611RT606069.6methodsPV2CPV2CPEMST14.61715.6A-Toxicity304862L-Toxicity141516CurranWJ,PASCO2000;19:484aRTOG9410sequentialconcurrentco43ACR427(phaseⅡ)seqCon(ind/con)Con(con/adi)No(total)276RT636363CTPC2PC2+CONCON+PC2MST12.51116.1Esophogitis(≥3）42028ChoyH,PASCO2002;abstract:1160ACR427(phaseⅡ)seqCon(ind/con)44GLOT9501SEQCONNo(total)212RT66Gy66CTNP3CindCE+CE2Cadi3/4neutropenia
87.8753/4oesophagitis026.1MST13.915.61-ysurvival56562-ysurvival2335PierreF,PASCO2001;abstract:1246GLOT9501SEQCONNo(total)212RT6645MSTOSE-toxicity
S
C
SCSCfuruse13.3
16.5
916(5)423RTOG14.617.1
1221(4)
425GLOT13.915.6
2435(2)317Czech13.220.6
1542(2)428BROCAT14.019.0
--026ACR42713.817.4
3133(2)328MSTOSE-toxicityS46CALGB9431G/PP/PN/PNo.625855RR7467731-ySur6862653-ySur281923MST18.314.817.7DFSMethods:2cyclesinductionfollowedby2cyclesandconcurrentTRT,66GyVokesEE,JCO2002;20:4191-4198CALGB9431G/PP/PN/PNo.625855RR747CALGB9431CALGB943148SWOG9019Patients:
50pts.IIIB
Treatment:PE2cycles/RTPE2cyclesAlbainKS,JCO2002
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