放射粒子组织间植入治疗恶性肿瘤

放射粒子组织间植入治疗恶性肿瘤第1页/共45页Brachytherapy1898年居里夫人发现镭1905年即进行了第1例镭针插管治疗1930年Paterson及Parker建立了曼切斯特（Manchester）系统1935年小居里夫妇发现了人工放射性同位素80年代中期，现代近距离治疗迅速发展第2页/共45页生物学优势（外放疗相比）肿瘤局部治疗的持续时间长放射治疗的剂量较低对周围正常组织的损伤小对肿瘤细胞的杀伤力强

第3页/共45页ImplantradioactiveseedsintotumorsEmitcontinueouslowenergyγraysInjuryoftissuesandcellsCelldeathandmutationleadingtocancerInteractwithbiomacromolecule第4页/共45页AnimalexperimentClinicalresearch第5页/共45页HumanpancreaticcancerSw1990cellBABL/cwasinoculatedintothedorsalsideofrightlowerextremityinguinalregionofnudemicePassagedfor3timssubcutaneously,initiatetheexperimentsaftertumorformationwasstablizedExperimentaldesign第6页/共45页

SubcutaneouspancreaticcancerxenograftinnudemiceSeedimplantationgroupControlgroupExperimentalmethod第7页/共45页Changeofxenograftvolumeinnudemice第8页/共45页Comparisonoftumorinhibitionrate第9页/共45页第10页/共45页ObviousliquefactionnecrosiscanbeseeninthecenteralareaofExperimentalgrouptumor,therearesparsecellsaroudthenecrosisarea(×100)HE

stainingThereisnoorlittlenecrosisareaincenterofcontrolgrouptumor,therearemultipletumorcells(×100)第11页/共45页ExperimentalgrouppositiveTK1stainingcellsareexiguous（×200）ControlgrouppositiveTK1stainingcellsareabundent（×200）HE

staining

第12页/共45页第13页/共45页碘-125放射粒子组织间植入治疗属放射治疗，对周围正常器官组织无明显放射损伤裸鼠移植瘤组织植入碘-125粒子后，实验组心、肺、肝、肾、脾脏外观大致正常，病理检查未见明显放射性炎症表现

Preliminaryresult第14页/共45页ZM.WangMD,ShanghaiRuijinHospitalIntroductionPancreaticcancerisadevastatingdiseaseandtheprognosisremainspoorFewpatientsareeligibleforcurativesurgicalresectionAlternativetherapeuticoptionsareindemand第15页/共45页Traditionaltherapyvs.Externalirradiationtherapy

vs.percutaneousseedimplantationZM.WangMD,ShanghaiRuijinHospital第16页/共45页ExternalirradiationtherapywasregardedasinsensitivetopancreaticcancerandassociatedwithmoresystemicsideeffectsRadioactiveiodine-125seedimplantationhasminimalsurgicaltraumaandfewcomplications

Themostcommonlyusedisotopeisiodine-125125IplacementwasroutinelyusedatourinstitutionforrecurrenttumorsatvarioussitesTheaimofthisstudywastotestitsfeasibilityforpancreaticlesions

CurrentControversies第17页/共45页

11thIO2010,May

23Methodsandmaterials

PatientpopulationDecember2004toAugust2007,31consecutivepatientswereincludedinthisprospective,nonrandomizedstudy

PatientswerediagnosedbyCTorMRIwithhistologicalconfirmationofthediagnosisbyFNAAllpatientsenrolleddisplayedcontraindicationstosurgeryorhadrejectedsurgicaltreatmentduetopersonalreasons

第18页/共45页ZM.WangMD,ShanghaiRuijinHospitalMethodsandmaterials

Thetotalvolumeofeachtumorwascalculatedwiththetreatmentplanningsystem(TPS)beforeimplantationTheexpectednumberofimplantedseedwascalculatedaccordingtothemodifiedlevelformulaPatientswerekeptinourradiooncology/interventionalwardwithanusualstayof4fulldays第19页/共45页Methodsandmaterials

Clinicalbenefitresponsewasderivedfrommeasurementofpain,functionalimpairmentandweightlossPatientswereexaminedbyCTaftertheoperationResponseratewasdefinedasthesumofCRandPRLocaltumorcontrolwasdefinedastheabsenceoftumorprogression(SD+PR+CR)第20页/共45页Methodsandmaterials

10patientsreceivedconcurrentchemotherapywitharterialinfusionofgemcitabinand5-fluorouracil(5-Fu)ChemotherapywasinitiatedoneweekafterandrepeateduptofourcyclesFollow-upvisitsat1month,3month,andevery3monthsforclinicalexamination,bloodsampling,andCTexaminationZM.WangMD,ShanghaiRuijinHospital第21页/共45页适应症实体瘤（如前列腺癌）的根治性治疗实体瘤术后残余组织的预防性治疗转移性肿瘤病灶或术后孤立性肿瘤转移灶而失去手术价值者无法手术的原发肿瘤的姑息性治疗第22页/共45页禁忌证

放射性治疗不宜(如血液病等)及有麻醉禁忌等病灶范围广泛恶液质、全身衰竭肿瘤部位有活动性出血、坏死或溃疡严重糖尿病第23页/共45页Iodine-125TherapyinAdvancedPancreaticCancerResultsChangeofKarnofskyphysicalscore%(cases)Karnofskyscore

1009080706050Pre-op0（0/31）3.2（1/31）9.7(3/31)

41.9(13/31)

35.5(11/31)

9.7（3/31）Post-op0（0/31）48.4(15/31)

16.1(5/31)

9.7(3/31)

19.4(6/31)

6.4(2/31)

第24页/共45页ResultsChangeofpainscore%(cases)Iodine-125TherapyinAdvancedPancreaticCancerNoPain(%)MildPain(%)ModeratePain(%)SeverePain(%)Pre-op6.5（2/31）22.5(7/31)

32.3(10/31)

38.7(12/31)

Post-op38.7(12/31)

32.3(10/31)

16.1(5/31)

12.9(4/31)

第25页/共45页ResultsOverallrespondingrate(CR+PR)=61.3%Localtumorcontrolratewas90.3%Mediansurvivaltimeforthewholegroupwas10.31monthsMediansurvivaltimeforpureseedsimplantation(21cases)was7monthsmediansurvivaltimefordrug-seedscombinedwas11month第26页/共45页Pre-implantCTscan(Caseone)

ZM.WangMD,ShanghaiRuijinHospital第27页/共45页Post-implantCTscan

ZM.WangMD,ShanghaiRuijinHospital第28页/共45页Pre-implantCTscan(CaseTwo)

第29页/共45页术后CT扫描术中穿刺碘粒子植入Post-implantCTscan第30页/共45页Post-implantCTscan第31页/共45页病例2男性76岁

胰腺癌（胰体尾部）Pre-implantCTscan(CaseThree)

第32页/共45页术后CT扫描Post-implantCTscan第33页/共45页Pre-implantCTscan(CaseFour)

第34页/共45页Post-implantCTscan

术后CT二维重建第35页/共45页Post-implantCTscan第36页/共45页ComplicationsNoseriouscomplicationsencountered2seedsofradioactive125Ifoundtomigratetoliverin2patientsLeukopeniaandrenalfunctionimpairmentwerefoundin4patientsofdrug-seedscombinationgroupIodine-125TherapyinadvancedPancreaticCancer第37页/共45页DiscussionPercutaneousimage-guidedseedimplantationhasattractedincreasingattentionExtensiveexperienceswiththistechniquehadbeencollectedtargetingliverandlungmalignanciesThemostcommonlyusedisotopeis125I,and125IplacementhasbecomearoutinetreatmentforrecurrenttumorsatvarioussitesinourinstitutionZM.WangMD,ShanghaiRuijinHospital第38页/共45页TechnicalpointsduringtheprocedurePatientsfastedfor24hoursEnsuresteadybreathmovementduringtheprocedurePancreaticsecretionwasinhibitedTransgressstomachissaferthanintestine,avoidingcolonespeciallywhenusinglarge-boreneedlesForpatientswithjaundice,doPTCDfirstImmediateCTscanpostimplantationwasdonetoverifythedistributionoftheseedsZM.WangMD,ShanghaiRuijinHospital第39页/共45页Drug-seedscombinedtherapyThereisdatasuggeststhatlocalcontrolratescanbeenhancedbytheadditionofchemotherapyInourstudythemediansurvivaltimebetweenthetwogroupsreachedstatasticallysignificantandencouragedfurtherevaluationZ