PET-CT在淋巴瘤中的应用

PET/CT在淋巴瘤中的应用,复旦大学附属肿瘤医院肿瘤内科郭晔,指南更新,JCO2007;25:579-586,JCO2014;32:3048-3058,新的淋巴瘤分期,JCO2014;32:3059-3067,内容,背景介绍PET/CT用于淋巴瘤的分期评估PET/CT用于淋巴瘤治疗后评估PET/CT用于淋巴瘤治疗中期评估,背景知识,PET：正电子发射型计算机断层显象，是以人体解剖结构为基础，利用正电子核素标记药物的示踪作用，显示人体内物质代谢，细胞增殖，血流灌注及脏器功能状态。缺点是不能准确测量肿瘤大小CT：显示人体解剖结构及形态学改变，有较强的空间分辨率PET/CT：PET和CT图像同机融合，一次成象获得全身PET和CT的图象，将功能影象与解剖形态学优化组合，两者结合取长补短,18FDG在肿瘤细胞中的摄取,FDG在常见淋巴瘤中的摄取,进行FDG-PET的要求,JuweidME,etal.JClinOncol2007;25:571-578.,PET图像的解读标准(视觉判断法),JuweidME,etal.JClinOncol2007;25:571-578.,5分类法(Deauville标准),BarringtonS,etal.JClinOncol2014;32:3048,举例：治疗前,治疗后：1分,Exampleofscore1:completemetabolicresponsewithnouptakeinnormal-sizelymphnodesatsiteofinitialdiseaseinleftneck(arrow).,举例：治疗前,治疗后：2分,Exampleofscore2:residualuptakeofintensitymediastinalbloodpoolbutliverinresidualmediastinalmass(arrow).Maximumstandardizeduptakevalue(SUVmax)inmasswas4.5;SUVmaxinliverwas3.2.,举例：治疗前,治疗后：5分,Exampleofscore5:residualuptakeinmediastinumwithintensitymarkedlyhigherthannormalliver.Maximumstandardizeduptakevalue(SUVmax)inmasswas13.0;SUVmaxinliverwas2.3.,新的指南推荐级别,Expertsinnuclearmedicineandradiologyappliedtolymphomaundertookaliteraturereviewandsharedknowledgeaboutresearchinprogress.Recommendationswereformulatedasfollows:Basedonestablishedcurrentknowledge(type1)Toidentifyemergingapplications(type2)Tohighlightkeyareasrequiringfurtherresearch(type3),BarringtonS,etal.JClinOncol2014;32:3048,肿瘤缓解术语,CTCR：completeresponseCRu：completeresponseunconfirmedPR：partialresponseSD：stablediseasePD：progressivedisease,PET/CTCMR：completemetabolicresponsePMR：partialmetabolicresponseNMR：nometabolicresponsePMR：progressivemetabolicdisease,ChesonBD,etal.JClinOncol1999;17:1244.,ChesonBD,etal.JClinOncol2014;32:3059,InterpretationofPET-CTscans,StagingofFDG-avidlymphomasisrecommendedusingvisualassessment,withPET-CTimagesscaledtofixedSUVdisplayandcolortable;focaluptakeinHLandaggressiveNHLissensitiveforbonemarrowinvolvementandmayobviateneedforbiopsy;MRIismodalityofchoiceforsuspectedCNSlymphoma(type1)Five-pointscaleisrecommendedforreportingPET-CT;resultsshouldbeinterpretedincontextofanticipatedprognosis,clinicalfindings,andothermarkersofresponse;scores1and2representCMR;score3alsoprobablyrepresentsCMRinpatientsreceivingstandardtreatment(type1)Score4or5withreduceduptakefrombaselinelikelyrepresentspartialmetabolicresponse,butatendoftreatmentrepresentsresidualmetabolicdisease;increaseinFDGuptaketoscore5,score5withnodecreaseinuptake,andnewFDG-avidfociconsistentwithlymphomarepresenttreatmentfailureand/orprogression(type2),BarringtonS,etal.JClinOncol2014;32:3048,PET结果假阳性产生的原因,化疗/放疗后的坏死/炎症反应化疗间隔：至少3周（最佳6-8周）放疗间隔：8-12周造血因子的骨髓刺激增生的胸腺组织某些摄取FDG的良性疾病免疫细胞的影响不规范的操作和图像的解读,内容,背景介绍PET/CT用于淋巴瘤的分期评估PET/CT用于淋巴瘤治疗后评估PET/CT用于淋巴瘤治疗中期评估,传统CT分期评估的缺点,仅根据病变/淋巴结的形态和大小决定临床意义对于结外病变的判断能力不足评估能力受扫描区域或部位的限制需要增强扫描，无法用于碘过敏的患者,PET与CT用于分期评估的比较,PET分期评估的结果,RoleofPET-CTforstaging,PET-CTshouldbeusedforstaginginclinicalpracticeandclinicaltrialsbutisnotroutinelyrecommendedinlymphomaswithlowFDGavidity;PET-CTmaybeusedtoselectbestsitetobiopsy(type1)Contrast-enhancedCTwhenusedatstagingorrestagingshouldideallyoccurduringsinglevisitcombinedwithPET-CT,ifnotalreadyperformed;baselinefindingswilldeterminewhethercontrast-enhancedPET-CTorlower-doseunenhancedPET-CTwillsufficeforadditionalimagingexaminations(type2)Bulkremainsanimportantprognosticfactorinsomelymphomas;volumetricmeasurementoftumorbulkandtotaltumorburden,includingmethodscombiningmetabolicactivityandanatomicalsizeorvolume,shouldbeexploredaspotentialprognosticators(type3),BarringtonS,etal.JClinOncol2014;32:3048,内容,背景介绍PET/CT用于淋巴瘤的分期评估PET/CT用于淋巴瘤治疗后评估PET/CT用于淋巴瘤治疗中期评估,基于CT的IWG标准,1999年IWG制定了淋巴瘤疗效评价和预后评估指南IWG指南统一了原本各异的疗效评估标准该指南得到了临床医生和监管机构的广泛认可，并用于大量新药的审批程序,ChesonBD,etal.JClinOncol1999;17:1244.,疗效评估标准,1999年，IWG国际工作小组发布了NHL疗效评估标准,ChesonBD,etal.JClinOncol1999;17:1244.,IWG标准的缺点,无法区分肿瘤残留抑或纤维化CRu的解读容易发生歧义没有针对骨髓以外结外病变的评价,PET疗效评估的阳性和阴性预测值,基于PET的IHP标准,ChesonBD,etal.JClinOncol2007;25:579,2007年IHP制定了新的淋巴瘤疗效评价标准IHP标准是对于IWG标准的改进和补充IHP标准适用于以治愈为目的的淋巴瘤类型，特别是DLBCL和HL,IHP标准的淋巴瘤类型推荐,ChesonBD,etal.JClinOncol2007;25:579,临床试验中的疗效定义,ChesonBD,etal.JClinOncol2007;25:579,新的PET疗效定义,CMR:completemetabolicresponseScore1,2,or3withorwithoutaresidualmasson5PSPMR:partialmetabolicresponseScore4or5withreduceduptakecomparedwithbaselineandresidualmass(es)ofanysizeAtinterim,thesefindingssuggestrespondingdiseaseAtendoftreatment,thesefindingsindicateresidualdiseaseNMR:nometabolicresponseScore4or5withnosignificantchangeinFDGuptakefrombaselineatinterimorendoftreatmentPMR:progressivemetabolicdiseaseScore4or5withanincreaseinintensityofuptakefrombaselineand/orNewFDG-avidfociconsistentwithlymphomaatinterimorend-of-treatmentassessment,ChesonBD,etal.JClinOncol2014;32:3059,RoleofPETatendoftreatment,PET-CTisstandardofcareforremissionassessmentinFDG-avidlymphoma;inpresenceofresidualmetabolicallyactivetissue,wheresalvagetreatmentisbeingconsidered,biopsyisrecommended(type1)InvestigationofsignificanceofPET-negativeresidualmassesshouldbecollectedprospectivelyinclinicaltrials;residualmasssizeandlocationshouldberecordedonend-of-treatmentPET-CTreportswherepossible(type3)EmergingdatasupportuseofPET-CTafterrituximab-containingchemotherapyinhightumorburdenFL;studiesarewarrantedtoconfirmthisfindinginpatientsreceivingmaintenancetherapy(type2)AssessmentwithPET-CTcouldbeusedtoguidedecisionsbeforehigh-dosechemotherapyandASCT,butadditionalstudiesarewarranted(type3),BarringtonS,etal.JClinOncol2014;32:3048,内容,背景介绍PET/CT用于淋巴瘤的分期评估PET/CT用于淋巴瘤治疗后评估PET/CT用于淋巴瘤治疗中期评估,背景,淋巴瘤包括DLBCL是一个异质性很大的疾病现有的预后因素有助于判断总体预后，但往往难以据此作出个体化的治疗方案选择如何早期筛选出难治性或容易复发的患者，有助于尽早实施解救方案，如化疗、移植或新的靶向药物等，从而改善预后如何早期筛选出预后良好的患者，有助于调整治疗强度，从而减少远期毒性或第二原发肿瘤,重要的预后因素-治疗敏感性,治疗的敏感性即肿瘤缓解情况往往与预后具有相关性治疗后的缓解状态有助于早期调整治疗方案对于肿瘤缓解状态的判断，PET/CT优于普通增强CTPET/CT可以判断肿瘤内部的代谢情况，从而有助于早期明确治疗的敏感性,PET图像的解读方法,视觉判断法(IHP标准)5分类法(Deauville标准)半定量法(SUVmax),视觉判断法,103例DLBCL接受CHOP利妥昔单抗的治疗2-4个周期后行CT和PET评价疗效,DupuisJ,etal.AnnOncol2009;20(3):503-507.,系统性综述,TerasawaT,etal.JClinOncol2009;27(11):1906-1914,视觉判断法存在的重要问题,过低的结果判断一致率,一致率：68%,一致率：71%,HorningSJ,etal.Blood2010;115(4):775-777,过高的假阳性率,(假阳性：87%),MSKCC研究,MoskowitzCH,etal.JClinOncol2010;28(11):1896-1903,扫描时间的重要性,HttmannA,etal.JClinOncol2010;28(27):e488-e489,5分类法(Deauville标准),MeignanM,etal.LeukLymphoma2010;51(12):21712180,采用纵隔血池和肝脏作为参照的比较,IttiE,etal.JNuclMed2010;51(12):1857-1862,半定量法(SUVmax),优点：SUVmax的变化反映了肿瘤的动态代谢半定量标准有助于个体化判断疗效与视觉判断法/五分类法相比减少了假阳性的几率解读的一致性和重复性较高缺点：需要强制性的基线PET检查对于PET操作标准化的要求