碘 125放射粒子组织间植入治疗恶性肿瘤课件

PrimaryClinicalStudyofCT-guidedIodine-125SeedImplantationTherapyinPatientswithAdvancedPancreaticCancer上海交通大学医学院附属瑞金医院卢湾分院

王忠敏碘125放射粒子组织间植入治疗恶性肿瘤课件1Brachytherapy1898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Brachytherapy1898年居里夫人发现镭2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

生物学优势（外放疗相比）肿瘤局部治疗的持续时间长3ImplantradioactiveseedsintotumorsEmitcontinueouslowenergyγraysInjuryoftissuesandcellsCelldeathandmutationleadingtocancerInteractwithbiomacromoleculeImplantradioactiveseedsinto4AnimalexperimentClinicalresearchAnimalexperimentClinicalre5HumanpancreaticcancerSw1990cellBABL/cwasinoculatedintothedorsalsideofrightlowerextremityinguinalregionofnudemicePassagedfor3timssubcutaneously,initiatetheexperimentsaftertumorformationwasstablizedExperimentaldesignExperimentaldesign6

SubcutaneouspancreaticcancerxenograftinnudemiceSeedimplantationgroupControlgroupExperimentalmethodSubcutaneouspancreaticcance7ChangeofxenograftvolumeinnudemiceChangeofxenograftvolumein8ComparisonoftumorinhibitionrateComparisonoftumorinhibition9碘125放射粒子组织间植入治疗恶性肿瘤课件10ObviousliquefactionnecrosiscanbeseeninthecenteralareaofExperimentalgrouptumor,therearesparsecellsaroudthenecrosisarea(×100)HE

stainingThereisnoorlittlenecrosisareaincenterofcontrolgrouptumor,therearemultipletumorcells(×100)Obviousliquefactionnecrosis11ExperimentalgrouppositiveTK1stainingcellsareexiguous（×200）ControlgrouppositiveTK1stainingcellsareabundent（×200）HE

staining

ExperimentalgrouppositiveTK12碘125放射粒子组织间植入治疗恶性肿瘤课件13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

PreliminaryresultPreliminaryresult14ZM.WangMD,ShanghaiRuijinHospitalIntroductionPancreaticcancerisadevastatingdiseaseandtheprognosisremainspoorFewpatientsareeligibleforcurativesurgicalresectionAlternativetherapeuticoptionsareindemand

ZM.WangMD,ShanghaiRuijin15Traditionaltherapyvs.Externalirradiationtherapy

vs.percutaneousseedimplantationZM.WangMD,ShanghaiRuijinHospitalTraditionaltherapyvs.Extern16ExternalirradiationtherapywasregardedasinsensitivetopancreaticcancerandassociatedwithmoresystemicsideeffectsRadioactiveiodine-125seedimplantationhasminimalsurgicaltraumaandfewcomplications

Themostcommonlyusedisotopeisiodine-125125IplacementwasroutinelyusedatourinstitutionforrecurrenttumorsatvarioussitesTheaimofthisstudywastotestitsfeasibilityforpancreaticlesions

CurrentControversiesExternalirradiationtherapyw17

11thIO2010,May

23Methodsandmaterials

PatientpopulationDecember2004toAugust2007,31consecutivepatientswereincludedinthisprospective,nonrandomizedstudy

PatientswerediagnosedbyCTorMRIwithhistologicalconfirmationofthediagnosisbyFNAAllpatientsenrolleddisplayedcontraindicationstosurgeryorhadrejectedsurgicaltreatmentduetopersonalreasons

11thIO2010,May23Methods18ZM.WangMD,ShanghaiRuijinHospitalMethodsandmaterials

Thetotalvolumeofeachtumorwascalculatedwiththetreatmentplanningsystem(TPS)beforeimplantationTheexpectednumberofimplantedseedwascalculatedaccordingtothemodifiedlevelformulaPatientswerekeptinourradiooncology/interventionalwardwithanusualstayof4fulldays

ZM.WangMD,ShanghaiRuijin19Methodsandmaterials

Clinicalbenefitresponsewasderivedfrommeasurementofpain,functionalimpairmentandweightlossPatientswereexaminedbyCTaftertheoperationResponseratewasdefinedasthesumofCRandPR

Localtumorcontrolwasdefinedastheabsenceoftumorprogression(SD+PR+CR)

MethodsandmaterialsClinical20Methodsandmaterials

10patientsreceivedconcurrentchemotherapywitharterialinfusionofgemcitabinand5-fluorouracil(5-Fu)ChemotherapywasinitiatedoneweekafterandrepeateduptofourcyclesFollow-upvisitsat1month,3month,andevery3monthsforclinicalexamination,bloodsampling,andCTexaminationZM.WangMD,ShanghaiRuijinHospitalMethodsandmaterials10patie21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适应症22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禁忌证放射性治疗不宜(如血液病等)及有麻醉禁忌等23Iodine-125TherapyinAdvancedPancreaticCancerResultsChangeofKarnofskyphysicalscore%(cases)Iodine-125TherapyinAdvanced24ResultsChangeofpainscore%(cases)Iodine-125TherapyinAdvancedPancreaticCancerResultsChangeofpainscore%25ResultsOverallrespondingrate(CR+PR)=61.3%Localtumorcontrolratewas90.3%Mediansurvivaltimeforthewholegroupwas10.31monthsMediansurvivaltimeforpureseedsimplantation(21cases)was7monthsmediansurvivaltimefordrug-seedscombinedwas11monthResultsOverallrespondingrate26Pre-implantCTscan(Caseone)

ZM.WangMD,ShanghaiRuijinHospitalPre-implantCTscan(Caseone)27Post-implantCTscan

ZM.WangMD,ShanghaiRuijinHospitalPost-implantCTscanZM.Wang28Pre-implantCTscan(CaseTwo)

Pre-implantCTscan(CaseTwo)29术后CT扫描术中穿刺碘粒子植入Post-implantCTscan术后CT扫描术中穿刺碘粒子植入Post-implantCT30Post-implantCTscanPost-implantCTscan31病例2男性76岁

胰腺癌（胰体尾部）Pre-implantCTscan(CaseThree)

病例2男性76岁胰腺癌（胰体尾部）P32术后CT扫描Post-implantCTscan术后CT扫描Post-implantCTscan33Pre-implantCTscan(CaseFour)

Pre-implantCTscan(CaseFour34Post-implantCTscan

术后CT二维重建Post-implantCTscan术后CT二维重建35Post-implantCTscanPost-implantCTscan36ComplicationsNoseriouscomplicationsencountered2seedsofradioactive125Ifoundtomigratetoliverin2patientsLeukopeniaandrenalfunctionimpairmentwerefoundin4patientsofdrug-seedscombinationgroupIodine-125TherapyinadvancedPancreaticCancerComplicationsNoseriouscompli37DiscussionPercutaneousimage-guidedseedimplantationhasattractedincreasingattentionExtensiveexperienceswiththistechniquehadbeencollectedtargetingliverandlungmalignanciesThemostcommonlyusedisotopeis125I,and125Iplacementhasbecomearoutinetreatmentforrecurrenttumorsatvarioussitesinourinstitution

ZM.WangMD,ShanghaiRuijinHospitalDiscussionPercutaneousimage-g38TechnicalpointsduringtheprocedurePatientsfastedfor24hoursEnsuresteadybreathmovementduringtheprocedurePancreaticsecretionwasinhibitedTransgressstomachissaferthanintestine,avoidingcolonespeciallywhenusinglarge-boreneedlesForpatientswithjaundice,doPTCDfirstImmediateCTscanpostimplantationwasdonetoverifythedistributionoftheseeds

ZM.WangMD,ShanghaiRuijinHospitalTechnicalpointsduringthepr39Drug-seedscombinedtherapyThereisdatasuggeststhatlocalcontrolratescanbeenhancedbytheadditionofchemotherapyInourstudythemediansurvivaltimebetweenthetwogroupsreachedstatasticallysignificantandencouragedfurtherevaluation

ZM.WangMD,ShanghaiRuijinHospitalDrug-seedscombinedtherapyThe40ConclusionsThisstudysuggestedthatCT-guidedbrachytherapyusing125Iseedsimplantationappearedtobesafe,effective,lesscomplicatedandcouldproduceadequatepainrelieffortreatingunresectablepancreaticcancer

Iodine-125TherapyinAdvancedPancreaticCancerConclusionsThisstudysuggeste41国内临床尚有许多问题需要解决

临床应用适应症选择标准不一，造成不同医院应用放射性粒子植入治疗技术后疗效评价缺乏标准，尤其在放射性粒子治疗肿瘤的过程中，现在面临的缺乏行业管理标准和操作技术规范如不同增殖速率的肿瘤如何选择不同放射性核素,以获得最大的杀伤效应

粒子种植治疗仍是局部治疗手段，是外科和外放疗的补充和延伸，单纯放射性粒子植入治疗并不能解决所有肿瘤治疗问题，如何合理、科学地与外科、外放疗和化疗结合，最大限度发挥粒子植入治疗的优势

国内临床尚有许多问题需要解决临床应用适应症选择标准不一，造42展望

由于放射性粒子植入治疗恶性肿瘤创伤小，靶区剂量分布较均匀和对周围正常组织损伤较小等特点，在临床应用展现了广阔的前景同样放射性粒子植入技术治疗肿瘤需要多学科联合，特别需要准确的治疗计划、娴熟的治疗技术和严谨的术后质量评估展望由于放射性粒子植入治疗恶性肿瘤创伤小，靶区剂量43ThanksforyourattentionThanksforyourattention44PrimaryClinicalStudyofCT-guidedIodine-125SeedImplantationTherapyinPatientswithAdvancedPancreaticCancer上海交通大学医学院附属瑞金医院卢湾分院

王忠敏碘125放射粒子组织间植入治疗恶性肿瘤课件45Brachytherapy1898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Brachytherapy1898年居里夫人发现镭46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

生物学优势（外放疗相比）肿瘤局部治疗的持续时间长47ImplantradioactiveseedsintotumorsEmitcontinueouslowenergyγraysInjuryoftissuesandcellsCelldeathandmutationleadingtocancerInteractwithbiomacromoleculeImplantradioactiveseedsinto48AnimalexperimentClinicalresearchAnimalexperimentClinicalre49HumanpancreaticcancerSw1990cellBABL/cwasinoculatedintothedorsalsideofrightlowerextremityinguinalregionofnudemicePassagedfor3timssubcutaneously,initiatetheexperimentsaftertumorformationwasstablizedExperimentaldesignExperimentaldesign50

SubcutaneouspancreaticcancerxenograftinnudemiceSeedimplantationgroupControlgroupExperimentalmethodSubcutaneouspancreaticcance51ChangeofxenograftvolumeinnudemiceChangeofxenograftvolumein52ComparisonoftumorinhibitionrateComparisonoftumorinhibition53碘125放射粒子组织间植入治疗恶性肿瘤课件54ObviousliquefactionnecrosiscanbeseeninthecenteralareaofExperimentalgrouptumor,therearesparsecellsaroudthenecrosisarea(×100)HE

stainingThereisnoorlittlenecrosisareaincenterofcontrolgrouptumor,therearemultipletumorcells(×100)Obviousliquefactionnecrosis55ExperimentalgrouppositiveTK1stainingcellsareexiguous（×200）ControlgrouppositiveTK1stainingcellsareabundent（×200）HE

staining

ExperimentalgrouppositiveTK56碘125放射粒子组织间植入治疗恶性肿瘤课件57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

PreliminaryresultPreliminaryresult58ZM.WangMD,ShanghaiRuijinHospitalIntroductionPancreaticcancerisadevastatingdiseaseandtheprognosisremainspoorFewpatientsareeligibleforcurativesurgicalresectionAlternativetherapeuticoptionsareindemand

ZM.WangMD,ShanghaiRuijin59Traditionaltherapyvs.Externalirradiationtherapy

vs.percutaneousseedimplantationZM.WangMD,ShanghaiRuijinHospitalTraditionaltherapyvs.Extern60ExternalirradiationtherapywasregardedasinsensitivetopancreaticcancerandassociatedwithmoresystemicsideeffectsRadioactiveiodine-125seedimplantationhasminimalsurgicaltraumaandfewcomplications

Themostcommonlyusedisotopeisiodine-125125IplacementwasroutinelyusedatourinstitutionforrecurrenttumorsatvarioussitesTheaimofthisstudywastotestitsfeasibilityforpancreaticlesions

CurrentControversiesExternalirradiationtherapyw61

11thIO2010,May

23Methodsandmaterials

PatientpopulationDecember2004toAugust2007,31consecutivepatientswereincludedinthisprospective,nonrandomizedstudy

PatientswerediagnosedbyCTorMRIwithhistologicalconfirmationofthediagnosisbyFNAAllpatientsenrolleddisplayedcontraindicationstosurgeryorhadrejectedsurgicaltreatmentduetopersonalreasons

11thIO2010,May23Methods62ZM.WangMD,ShanghaiRuijinHospitalMethodsandmaterials

Thetotalvolumeofeachtumorwascalculatedwiththetreatmentplanningsystem(TPS)beforeimplantationTheexpectednumberofimplantedseedwascalculatedaccordingtothemodifiedlevelformulaPatientswerekeptinourradiooncology/interventionalwardwithanusualstayof4fulldays

ZM.WangMD,ShanghaiRuijin63Methodsandmaterials

Clinicalbenefitresponsewasderivedfrommeasurementofpain,functionalimpairmentandweightlossPatientswereexaminedbyCTaftertheoperationResponseratewasdefinedasthesumofCRandPR

Localtumorcontrolwasdefinedastheabsenceoftumorprogression(SD+PR+CR)

MethodsandmaterialsClinical64Methodsandmaterials

10patientsreceivedconcurrentchemotherapywitharterialinfusionofgemcitabinand5-fluorouracil(5-Fu)ChemotherapywasinitiatedoneweekafterandrepeateduptofourcyclesFollow-upvisitsat1month,3month,andevery3monthsforclinicalexamination,bloodsampling,andCTexaminationZM.WangMD,ShanghaiRuijinHospitalMethodsandmaterials10patie65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适应症66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禁忌证放射性治疗不宜(如血液病等)及有麻醉禁忌等67Iodine-125TherapyinAdvancedPancreaticCancerResultsChangeofKarnofskyphysicalscore%(cases)Iodine-125TherapyinAdvanced68ResultsChangeofpainscore%(cases)Iodine-125TherapyinAdvancedPancreaticCancerResultsChangeofpainscore%69ResultsOverallrespondingrate(CR+PR)=61.3%Localtumorcontrolratewas90.3%Mediansurvivaltimeforthewholegroupwas10.31monthsMediansurvivaltimeforpureseedsimplantation(21cases)was7monthsmediansurvivaltimefordrug-seedscombinedwas11monthResultsOverallrespondingrate70Pre-implantCTscan(Caseone)

ZM.WangMD,ShanghaiRuijinHospitalPre-implantCTscan(Caseone)71Post-implantCTscan

ZM.WangMD,ShanghaiRuijinHospitalPost-implantCTscanZM.Wang72Pre-implantCTscan(CaseTwo)

Pre-implantCTscan(CaseTwo)73术后CT扫描术中穿刺碘粒子植入Post-implantCTscan术后CT扫描术中穿刺碘粒子植入Post-implantCT74Post-implantCTscanPost-implantCTscan75病例2男性76岁

胰腺癌（胰体尾部）Pre-implantCTscan(CaseThree)

病例2男性76岁胰腺癌（胰体尾部）P76术后CT扫描Post-implantCTscan术后CT扫描Post-implantCTscan77Pre-implantCTscan(CaseFour)

Pre-implantCTscan(CaseFour78Post-implantCTscan

术后CT二维重建Post-implantCTscan术后CT二维重建79Post-implantCTscanPost-implantCTscan80ComplicationsNoseriouscomplicationsencountered2seedsofradioactive125Ifoundtomigratetoliverin2patientsLeukopeniaandrenalfunctionimpairmentwerefoundin4patientsofdrug-seedscombinationgroupIodine-125TherapyinadvancedPancreaticCancerComplicationsNoseriouscompli81DiscussionPercutaneousimage-guidedseedimplantationhasattractedincreasingattentionExtensiveexperienceswiththistechniquehadbeencollectedtargetingliverandlungmalignanciesThemostcommonlyusedisotopeis125I,and125Iplacementhasbecomearoutinetreatmentforrecurrenttumorsatvarioussitesinour