DrLiao心脑血管药理、食管癌放疗

NormalTissueToxicityinThoracicIrradiation,ZhongxingLiao,MDTheUniversityofTexasM.D.AndersonCancerCenter,The5thShanghaiInternationalConferenceonRadiationOncology,Shanghai,ChinaNovember18-21,2006,COMBINEDMODALITYTHERAPY,Concurrentchemo-radiationimprovesbothlocal-regionaltumorcontrolandsurvivalofNSCLCpatientsbutattheexpenseofincreasedtoxicity,Outcomeof265NSCLCtreatedwithconcurrentChemoradiation,2-yearOS41%5-yearOS19%,Wangetal.,IJROBP,2006,TheOnsetTimeforMaximalEsophagitisScore,Wei,Xiong,IJROBP,2006,Grade1-4:93.0%,Grade=3:20.5%,Chemo-Radiotherapy-ImprovementStrategies:,Technologyimprovements(IMRT,IGRT,Proton)Moreeffectivechemotherapeuticagentsorconjugates(orradioenhancers)MultimodalitytherapyChemotherapy+Radiotherapy+MolecularTargetingChemotherapy+Radiotherapy+ImmunotherapyChemotherapy+Radiotherapy+Protectors,ThoracicirradiationEsophagealcancerNSCLCSCLCMesotheliomaMajordoselimitingtoxicities:PulmonarytoxicitiesEsophagealtoxicitiesCardiactoxicities,ThoracicRadiationTherapy,TreatmentRelatedToxicity,Gradedependsonscoringsystem(SWOG,RTOG,CTC)Patientfactors:smoking,intrinsicsensitivitytointervention,co-morbidity,lungfunctionTumorfactors:GTV,locationTreatmentfactors:Chemotherapy:agents,schedule,intensityRadiation:dose,volume,fractionation,modality,TRPandscoringsystemsSWOG/CTC,TRPandscoringsystems-RTOG,HJRadiatOncolbiolphys2001,51:650-659,ClinicalFactorsandSymptomaticTRP,CourtesyofDr.ThomasGuerrero,MD,PhD,Intrinsicsensitivity,CourtesyofDr.ThomasGuerrero,MD,PhD,Patients:higherincidenceofRPforlowerlobetumorsYESGraham1995,Yorke2002Seppenwoolde2004,Bradley2005NOYu2003,Lungregions,tumorlocation,Responseofmouse/ratlungtopartialvolumebase=moresensitivethanapexLiao1995,TravisandTucker1997Kahn1998,2002,Moiseenko2000Vujaskovic,inpress,Tumorlocationandheartdose,Marksetal.MeanheartdosehigherforlowerlobetumorsNoassociationbetweenmeanheartdoseandRT-associateddyspneaBUT:nohigherincidenceofTRPforlowerlobetumorsinthisdataset(Yu2003)Heartdosemaystillbeimportant,Lungfunctionlossandheartdoseinratsafterprotonirradiation,PeterVanLuijkCancerResearch2005;65(15):6509-6511,ConcurrentChemotherapyandTRP,TypeofchemotherapyIntensityofchemotherapyDifferentcombinationsofchemotherapy,Concurrentchemotherapy,CRTaloneSeppenwooldeetal.2003,ConChTandCRTLiao2005TaxanesCisplatin/carboplatinEtoposide,Concurrentchemotherapy,Seppenwooldeetal.2003,inregardtoTsujinoetal.2003,Cisplatin/carboplatinplustaxane,RPgrade2,Freedomfromgrade2TRPasafunctionoftime,Wangetal.,inpress,Freedomfromgrade2TRPasafunctionoftime,Wangetal.,inpress,Dose-volumeparameters,PointestimatesinDVHspace:Volumeabovethresholddose:V13,V20,V30V5Minimumdoseto“hottest”%volume:D15,D25,D45Overallparameters(wholeDVH)Meanlungdose(MLD)Effectivevolume(Veff),MLDandTRP,CorrelationoflungmeandoseandV5postoperativepneumonia/ARDS,Wangetal.,IJROBP,2005,V5andTRP,Wangetal.,IJROBP,2006,CorrelationofDosimetricfactors,Wangetal.,IJROBP,2006,Dosevolumeparametersarehighlycorrelated,Seppenwooldeetal.2003,Liao,2005,ReducingToxicity,Radiationtechnology3DCRTvsIMRTPhotonvsprotonUnderstandingthebiologyofToxicityCytokineCytoprotectionMoleculartargetofTRTanddevelopmentoftargetedtherapy,3DIMRT,IntensityModulatedRadiationforLungCancer,IMRTReducedTRPforNSCLCtreatedwithconcurrentchemoradiation,IMRTReducedTRPforNSCLCtreatedwithconcurrentchemoradiation,DVHofpatientswithgrade3TRP,DVHconsiderationinthoracicRadiotherapy,DoseconstraintforlungV2035%MeanLungdose=3:20.5%,AcuteEsophagitis,Weietal,IJROBP,2006,ReducingToxicity,Radiationtechnology3DCRTvsIMRTPhotonvsprotonUnderstandingthebiologyofToxicityCytokineCytoprotectionMoleculartargetofTRTanddevelopmentoftargetedtherapy(KGF,etc),Chemo-Radiotherapy-ImprovementStrategies:,Technologyimprovements(IMRT,IGRT,Proton)Moreeffectivechemotherapeuticagentsorconjugates(orradioenhancers)Multimod