惡性嗜鉻細胞瘤的治療

TherapyofMalignantPheochromocytoma

惡性嗜鉻細胞瘤的治療LiteratureReport12/22/20221Introduction

ruleof10sforpheochromocytoma(PCC)

10%bilateral10%extra-adrenal10%extra-abdomen10%malignant10%familial10%children10%normalbloodpressure12/22/20222IntroductionThemostfrequentsiteofmetastasesistheskeletonAdditionalsitesareliver,retroperitoneumwithlymphnodes,CNS,pleura,andkidney12/22/20223Malignantvs.BenignCurrently,thereisnoeffectivecureformalignantpheochromocytoma.Therearealsonoreliablehistopathologicalmethodsfordistinguishingbenignfrommalignanttumors.Malignancyrequiresevidenceofmetastasesatnon-chromaffinsitesdistantfromthatoftheprimarytumor.12/22/20224Metastaticdiseaseinpheochromocytomamaybepresentatthetimeofinitialdiagnosisormayonlybecameevidentaftersurgicalremovaloftheprimarytumor,usuallywithin5years,butsometimes16ormoreyearslater.12/22/20225Duetotherarityofthetumor,clinicalstudiesaboutpheochromocytomasufferfromafragmentednatureandusuallyinvolvetoosmallanumberofcasestoreachconclusiveresults.12/22/20226Becausethereiscurrentlynoeffectivecureformalignantpheochromocytoma,mosttreatmentarepalliative,butinsomecasesmayreducetumorburdenandprolongsurvival.Withouttreatment,the5-yearsurvivalisgenerallylessthan50%.Thecourse,however,canbehighlyvariablewithoccasionalpatientslivingmorethan20yearsafterdiagnosis.12/22/20227Oncemalignancyisdiagnosed,therapyisgenerallydirectedatcontrollingbloodpressure,butmayalsoincludetumordebulking.12/22/20228AlternativeofCurrentTherapySurgeryRadiopharmaceuticalsCombinedChemotherapyArterialEmbolization12/22/20229AlternativeofCurrentTherapySurgeryRadiopharmaceuticalsCombinedChemotherapyArterialEmbolization12/22/202210PrimarysurgicalresectionisthetreatmentofchoicewheneverpossibleLimiteddisease:curativeintentionExtendeddisease:stilltobeconsideredinthefirstplacefordebulkingandaspalliativetreatment(Mundschenketal.1998)12/22/202211ProblemWhensignsofregionalinvolvementordistantdiseaseareabsent,thereiscurrentlynoreliablepreoperativediagnostictestthatcandifferentiatebetweenmalignantandbenignpheochromocytomasShouldpheochromocytomasizeinfluencesurgicalapproach?12/22/202212Acomparisonof90malignantand60benignpheochromocytomas

(WenT.Shenetal.2004)ComparisonoftumorsizeforbenignpheochromocytomasandmalignantpheochromocytomaswithlocaldiseaseonlySizedoesnotreliablypredictmalignancyinpheochromocytomaswithlocaldiseaseonly12/22/20221312/22/202214MalignantPCCspresentingwithonlylocaldiseasecannotbediscriminatedfrombenignPCCsbysizealone.WhenPCCsdonothaveevidenceofinvasionordistantmetastasesandthesurgeonacquiresanappropriatelevelofexperience,themajorityofthesetumorscanbesafelyresectedlaparoscopically.12/22/202215Laparoscopicadrenalectomyforpheochromocytomashouldbeconvertedtoopenadrenalectomyfordifficultdissection,invasion,adhesions,orsurgeoninexperience12/22/202216SurgicalapproachTransabdominalapproachisnecessaryminimallyinvasiveproceduresretroperitonealapproachesshouldbeabandonedtodefinitelypreservethetumorcapsuleandperformtotallymphadecectomy(Orchardetal.1993)12/22/202217SecondaryTumorsNoexperiencewithadjuvantpreandpostoperativeradiationexistsGenerallyaremultipleRadicalsurgicalresectionisoftenimpossibleOthertreatmentmodalitieshavetobeconsidered12/22/202218AlternativeofCurrentTherapySurgeryRadiopharmaceuticalsCombinedChemotherapyArterialEmbolization12/22/20221912/22/202220131I-MIBGisthetreatmentofchoiceforallunresectable,MIBGpositivetumors58casesofmalignantPCCtreatedby131I-MIBG—therapeuticresultsandadverseevents(ZHURuisenetal.1999)12/22/202221Patientswereclassifiedinto3groupsaccordingtotheirtumorsize<8cm3(11cases),8～20cm3(21cases),>20cm3(26cases)Ingroup1,themeanabsorptiondosepergramoftumorwasabove1000cGy.Aftertreatment,tumorsdisappearedorshrinkedinallpatients12/22/202222Ingroup2,theabsorptiondosewassimilartothatofgroup1,butthemeanabsorptiondosepergramwas717.6cGy,andtumormassregressionwas36%;76%reducedurinarycatecholamineIngroup3,theabsorptiondosepergramtumortissuewas277cGy,and30%tumorenlargement,20%died;theremaining50%symptomaticimprovementwithoutanychangeintumorsize12/22/202223131I-MIBGisofcertaintherapeuticeffectivenessofsymptomaticimprovementCompletetumormassdisappearancehasonlybeenfoundinsmalltumorsTreatmentwith131I-MIBGshouldbeinstitutedimmediatelyaftersurgicalresectiontoeradicatetheresidualtumorcellsandtopreventrecurrencesBonemarrowsuppressionistemporaryandnotdosagerelated12/22/202224In1997,Lohetal.publishedareviewoftheworldwideexperienceinvolving116patientstreatedwith131I-MIBGformalignantpheochromocytoma.Overall,therewasasymptomaticresponsein76%,ahormonalresponsein45%,andtumorregressionin30%.Theactivityof131I-MIBGpersingledosewas96–300mCi,andthemeancumulativeactivitywas490±350mCi.OnlyfiveCRsto131I-MIBGwerereported.12/22/202225LimitationsNotallpatientswithmultiplemetastasesofmalignantpheochromocytomashavesufficientuptakeofMIBGtoallowMIBGtherapyMIBGnegativelesionscoexistwithMIBGpostivelesions,requiringcombinedtreatment12/22/202226Asasingleagent,131I-MIBGhaslimitedefficacyintreatingmalignantpheochromocytoma.Itsuseincombinationwithothercytotoxicagents,asiscurrentlybeingstudiedinpatientswithneuroblastoma,mayresultinadditionalbenefit(Sissonetal.1999)12/22/202227AlternativeofCurrentTherapySurgeryRadiopharmaceuticalsCombinedChemotherapyArterialEmbolization12/22/202228Onlysparsedataonchemotherapeuticregimensareavailable,mostoftheminreportsoffewcasesThemostwell-establishedregimenisCVD(Averbuchetal.1988)CTX750mg/m2d1,VCR1.4mg/m2d1,Dacarbazine600mg/m2d1,2Cycle21days12/22/202229TheCVDregimenwasbasedonthetreatmentforadvancedneuroblastoma.Thisregimenhasbeenreportedtoproducegoodresponsesinmalignantpheochromocytoma,butthemediandurationofremissionis21monthsCompletelong-termdiseaseremissionswithchemotherapyhavenotbeenreported.12/22/202230AlternativeofCurrentTherapySurgery