放射粒子組織間植入治療惡性腫瘤

放射粒子組織間植入治療惡性腫瘤第1頁/共45頁Brachytherapy1898年居里夫人發(fā)現(xiàn)鐳1905年即進(jìn)行了第1例鐳針插管治療1930年P(guān)aterson及Parker建立了曼切斯特（Manchester）系統(tǒng)1935年小居里夫婦發(fā)現(xiàn)了人工放射性同位素80年代中期，現(xiàn)代近距離治療迅速發(fā)展第2頁/共45頁生物學(xué)優(yōu)勢(shì)（外放療相比）腫瘤局部治療的持續(xù)時(shí)間長(zhǎng)放射治療的劑量較低對(duì)周圍正常組織的損傷小對(duì)腫瘤細(xì)胞的殺傷力強(qiáng)

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

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

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

staining

第12頁/共45頁第13頁/共45頁碘-125放射粒子組織間植入治療屬放射治療，對(duì)周圍正常器官組織無明顯放射損傷裸鼠移植瘤組織植入碘-125粒子后，實(shí)驗(yàn)組心、肺、肝、腎、脾臟外觀大致正常，病理檢查未見明顯放射性炎癥表現(xiàn)

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

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

Themostcommonlyusedisotopeisiodine-125125IplacementwasroutinelyusedatourinstitutionforrecurrenttumorsatvarioussitesTheaimofthisstudywastotestitsfeasibilityforpancreaticlesions

CurrentControversies第17頁/共45頁

11thIO2010,May

23Methodsandmaterials

PatientpopulationDecember2004toAugust2007,31consecutivepatientswereincludedinthisprospective,nonrandomizedstudy

PatientswerediagnosedbyCTorMRIwithhistologicalconfirmationofthediagnosisbyFNAAllpatientsenrolleddisplayedcontraindicationstosurgeryorhadrejectedsurgicaltreatmentduetopersonalreasons

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

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

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

10patientsreceivedconcurrentchemotherapywitharterialinfusionofgemcitabinand5-fluorouracil(5-Fu)ChemotherapywasinitiatedoneweekafterandrepeateduptofourcyclesFollow-upvisitsat1month,3month,andevery3monthsforclinicalexamination,bloodsampling,andCTexaminationZM.WangMD,ShanghaiRuijinHospital第21頁/共45頁適應(yīng)癥實(shí)體瘤（如前列腺癌）的根治性治療實(shí)體瘤術(shù)后殘余組織的預(yù)防性治療轉(zhuǎn)移性腫瘤病灶或術(shù)后孤立性腫瘤轉(zhuǎn)移灶而失去手術(shù)價(jià)值者無法手術(shù)的原發(fā)腫瘤的姑息性治療第22頁/共45頁禁忌證

放射性治療不宜(如血液病等)及有麻醉禁忌等病灶范圍廣泛惡液質(zhì)、全身衰竭腫瘤部位有活動(dòng)性出血、壞死或潰瘍嚴(yán)重糖尿病第23頁/共45頁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頁/共45頁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頁/共45頁ResultsOverallrespondingrate(CR+PR)=61.3%Localtumorcontrolratewas90.3%Mediansurvivaltimeforthewholegroupwas10.31monthsMediansurvivaltimeforpureseedsimplantation(21cases)was7monthsmediansurvivaltimefordrug-seedscombinedwas11month第26頁/共45頁P(yáng)re-implantCTscan(Caseone)

ZM.WangMD,ShanghaiRuijinHospital第27頁/共45頁P(yáng)ost-implantCTscan

ZM.WangMD,ShanghaiRuijinHospital第28頁/共45頁P(yáng)re-implantCTscan(CaseTwo)

第29頁/共45頁術(shù)后CT掃描術(shù)中穿刺碘粒子植入Post-implantCTscan第30頁/共45頁P(yáng)ost-implantCTscan第31頁/共45頁病例2男性76歲

胰腺癌（胰體尾部）Pre-implantCTscan(CaseThree)

第32頁/共45頁術(shù)后CT掃描Post-implantCTscan第33頁/共45頁P(yáng)re-implantCTscan(CaseFour)

第34頁/共45頁P(yáng)ost-implantCTscan

術(shù)后CT二維重建第35頁/共45頁P(yáng)ost-implantCTscan第36頁/共45頁ComplicationsNoseriouscomplicationsencountered2seedsofradioactive125Ifoundtomigratetoliverin2patientsLeukopeniaandrenalfunctionimpairmentwerefoundin4patientsofdrug-seedscombinationgroupIodine-125TherapyinadvancedPancreaticCancer第37頁/共45頁DiscussionPercutaneousimage-guidedseedimplantationhasattractedincreasingattentionExtensiveexperienceswiththistechniquehadbeencollectedtargetingliverandlungmalignanciesThemostcommonlyusedisotopeis125I,and125IplacementhasbecomearoutinetreatmentforrecurrenttumorsatvarioussitesinourinstitutionZM.WangMD,ShanghaiRuijinHospital第38頁/共45頁TechnicalpointsduringtheprocedurePatientsfastedfor24hoursEnsuresteadybreathmovementduringtheprocedurePancreaticsecretionwasinhibitedTransgressstomachissaferthanintestine,avoidingcolonespeciallywhenusinglarge-boreneedlesForpatientswithjaundice,doPTCDfirstImmediateCTscanpostimplantationwasdonetoverifythedistributionoftheseedsZM.WangMD,ShanghaiRuijinHospital第39頁/共45頁Drug-seedscombinedtherapyThereisdatasuggeststhatlocalcontrolratescanbeenhancedbytheadditionofchemotherapyInourstudythemediansurvivaltimebetweenthetwogroupsreachedstatasticallysignificantandencouragedfurtherevaluationZ