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1、Primary Clinical Study of CT-guided Iodine-125 Seed Implantation Therapy in Patients with Advanced Pancreatic Cancer上海交通大学医学院附属瑞金医院卢湾分院上海交通大学医学院附属瑞金医院卢湾分院 王忠敏王忠敏Brachytherapyu1898年居里夫人发现镭年居里夫人发现镭u1905年即进行了第年即进行了第1例镭针插管治疗例镭针插管治疗u1930年年Paterson及及Parker建立了曼切斯特建立了曼切斯特（Manchester）系统）系统u1935年小居里夫妇发现了人工放射性
2、同位素年小居里夫妇发现了人工放射性同位素u80年代中期，现代近距离治疗迅速发展年代中期，现代近距离治疗迅速发展生物学优势（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Implant radioactive seeds into tumorsEmit continueous low energy raysInjury of tissues and cellsCell death and mutation leading to cancerInteract with biomacromolecule Animal Animal experimen
3、texperimentClinical Clinical researchresearchHuman pancreatic cancer Sw1990 cellBABL/c was inoculated into the dorsal side of right lower extremity inguinal region of nude micePassaged for 3 tims subcutaneously, initiate the experiments after tumor formation was stablizedExperimental design Subcutan
4、eous pancreatic cancer xenograft in nude miceSeed implantation groupSeed implantation groupC Controlontrol group groupExperimental methodChange of xenograft volume in nude miceComparison of tumor inhibition rateObvious liquefaction necrosis can be seen in the centeral area of Experimental group tumo
5、r, there are sparse cells aroud the necrosis area (100)HE stainingThere is no or little necrosis area in center of control group tumor, there are multiple tumor cells (100)Experimental group positive TK1 staining cells are exiguous（200）Control group positive TK1 staining cells are abundent （200）HE s
6、taining碘碘-125放射粒子组织间植入治疗属放射治疗，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裸鼠移植瘤组织植入碘-125粒子后，实验组心、粒子后，实验组心、 肺、肝、肾、脾脏外观大致正常，病理检查未肺、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见明显放射性炎症表现 Preliminary resultZM. Wang MD, Shanghai Ruijin HospitalIntroductionPancreaticcancerisadevastatingdiseaseandtheprogn
7、osisremainspoorFewpatientsareeligibleforcurativesurgicalresectionAlternativetherapeuticoptionsareindemandTraditionaltherapyvs.Externalirradiationtherapyvs.percutaneousseedimplantationZM. Wang MD, Shanghai Ruijin HospitalExternalirradiationtherapywasregardedasinsensitivetopancreaticcancerandassociate
8、dwithmoresystemicsideeffectsRadioactiveiodine-125seedimplantationhasminimalsurgicaltraumaandfewcomplicationsThemostcommonlyusedisotopeisiodine-125125IplacementwasroutinelyusedatourinstitutionforrecurrenttumorsatvarioussitesTheaimofthisstudywastotestitsfeasibilityforpancreaticlesionsCurrent Controver
9、sies 11th IO 2010, May 23Methods and materialsPatientpopulationoDecember2004toAugust2007,31consecutivepatientswereincludedinthisprospective,nonrandomizedstudyoPatientswerediagnosedbyCTorMRIwithhistologicalconfirmationofthediagnosisbyFNAoAllpatientsenrolleddisplayedcontraindicationstosurgeryorhadreje
10、ctedsurgicaltreatmentduetopersonalreasonsZM. Wang MD, Shanghai Ruijin HospitalMethods and materialsThetotalvolumeofeachtumorwascalculatedwiththetreatmentplanningsystem(TPS)beforeimplantationTheexpectednumberofimplantedseedwascalculatedaccordingtothemodifiedlevelformulaPatientswerekeptinourradiooncol
11、ogy/interventionalwardwithanusualstayof4fulldaysMethods and materialsClinicalbenefitresponsewasderivedfrommeasurementofpain,functionalimpairmentandweightlossPatientswereexaminedbyCTaftertheoperationResponseratewasdefinedasthesumofCRandPRLocaltumorcontrolwasdefinedastheabsenceoftumorprogression(SD+PR
12、+CR)Methods and materials10patientsreceivedconcurrentchemotherapywitharterialinfusionofgemcitabinand5-fluorouracil(5-Fu)ChemotherapywasinitiatedoneweekafterandrepeateduptofourcyclesFollow-upvisitsat1month,3month,andevery3monthsforclinicalexamination,bloodsampling,andCTexaminationZM. Wang MD, Shangha
13、i Ruijin Hospital适应症适应症实体瘤（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禁忌证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Iodine-125 Therapy in Advanced Pancreatic CancerResultsChangeofKarnofskyphysicalscore%(cases)Karnofsky score 1009080706050Pre-op0（0/31）3.2（1/31
14、）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)Results Change of pain score % (cases)Iodine-125 Therapy in Advanced Pancreatic CancerNo Pain (%)Mild Pain (%)Moderate Pain (%)Severe Pain (%)Pre-op6.5（2/31）22.5(7/31)32.3(10/31)38.7(12/31)Post-op
15、38.7(12/31)32.3(10/31)16.1(5/31)12.9(4/31)ResultsOverallrespondingrate(CR+PR)=61.3%Localtumorcontrolratewas90.3%Mediansurvivaltimeforthewholegroupwas10.31monthsMediansurvivaltimeforpureseedsimplantation(21cases)was7monthsmediansurvivaltimefordrug-seedscombinedwas11monthPre-implantCTscan(Caseone)ZM.
16、Wang MD, Shanghai Ruijin HospitalPost-implantCTscanZM. Wang MD, Shanghai Ruijin HospitalPre-implantCTscan(CaseTwo)术后术后CTCT扫描扫描术中穿刺碘粒子植入术中穿刺碘粒子植入Post-implantCTscanPost-implantCTscan病例病例2 2 男性男性 7676岁岁 胰腺癌胰腺癌（胰体尾部）胰体尾部）Pre-implantCTscan(CaseThree)术后术后CTCT扫描扫描Post-implantCTscanPre-implantCTscan(CaseFou
17、r)Post-implantCTscan 术后术后CTCT二维重建二维重建Post-implantCTscanComplicationsNoseriouscomplicationsencountered2seedsofradioactive125Ifoundtomigratetoliverin2patientsLeukopeniaandrenalfunctionimpairmentwerefoundin4patientsofdrug-seedscombinationgroupIodine-125 Therapy in advanced Pancreatic CancerDiscussionPe
18、rcutaneousimage-guidedseedimplantationhasattractedincreasingattentionExtensiveexperienceswiththistechniquehadbeencollectedtargetingliverandlungmalignanciesThemostcommonlyusedisotopeis125I,and125IplacementhasbecomearoutinetreatmentforrecurrenttumorsatvarioussitesinourinstitutionZM. Wang MD, Shanghai
19、Ruijin HospitalTechnicalpointsduringtheprocedurePatientsfastedfor24hoursEnsuresteadybreathmovementduringtheprocedurePancreaticsecretionwasinhibitedTransgressstomachissaferthanintestine,avoidingcolonespeciallywhenusinglarge-boreneedlesForpatientswithjaundice,doPTCDfirstImmediateCTscanpostimplantation
20、wasdonetoverifythedistributionoftheseedsZM. Wang MD, Shanghai Ruijin HospitalDrug-seedscombinedtherapyThereisdatasuggeststhatlocalcontrolratescanbeenhancedbytheadditionofchemotherapyInourstudythemediansurvivaltimebetweenthetwogroupsreachedstatasticallysignificantandencouragedfurtherevaluationZM. Wan
21、g MD, Shanghai Ruijin HospitalConclusionsThisstudysuggestedthatCT-guidedbrachytherapyusing125Iseedsimplantationappearedtobesafe,effective,lesscomplicatedandcouldproduceadequatepainrelieffortreatingunresectablepancreaticcancerIodine-125 Therapy in Advanced Pancreatic Cancer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
22、，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展展 望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Thanks for your attention
