Staging of HcC.docx

Staging of HcC.docx

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StagingofHcC

10.1148/rg.25si055507October2005RadioGraphics,25,S3-S23

StagingandCurrentTreatmentofHepatocellularCarcinoma

HollinsP.Clark,MD,W.ForrestCarson,MD,PeterV.Kavanagh,MD,CotyP.H.Ho,MD,PerryShen,MDandRonaldJ.Zagoria,MD

1FromtheDepartmentsofRadiology（H.P.C.,W.F.C.,P.V.K.,R.J.Z.）,InternalMedicine（C.P.H.H.）,andSurgery（P.S.）,WakeForestUniversitySchoolofMedicine,MeadsHall,2ndFloor,MedicalCenterBlvd,Winston-Salem,NC27157-1088.Presentedasaneducationexhibitatthe2004RSNAAnnualMeeting.ReceivedFebruary8,2005;revisionrequestedMarch29andreceivedMay24;acceptedMay31.ThearticlediscussesaninvestigationalorunlabeleduseofacommercialdeviceorpharmaceuticalthathasnotbeenapprovedforsuchpurposebytheFDA.TheraSphere®（MDSNordion,Ottawa,Ontario,Canada）hasreceivedhumanitariandeviceexemptionapprovalfromtheU.S.FDAfortreatmentofunresectablehepatocellularcarcinomaandcanbeusedonlyinaninvestigationalcapacity.SIR-Spheres®（SirtexMedical,LakeForest,Ill）hasreceivedpremarketapprovalfromtheFDAforuseincombinationwithhepaticarterialfluorouraciltherapytotreatcolorectalmetastasistotheliver;itsusefortreatmentofprimaryhepaticneoplasticdiseaseisanoff-labelapplication.Likewise,intraarterialadministrationofcisplatin,doxorubicin,andmitomycinCfortreatmentofhepatocellularcarcinomaconstitutesoff-labeluseofthesepharmacologicproducts.Allauthorshavenofinancialrelationshipstodisclose.AddresscorrespondencetoH.P.C.（e-mail:

hclark@wfubmc.edu）.

Abstract

Early-stagehepatocellularcarcinoma（HCC）istypicallyclinicallysilent,andHCCisoftenadvancedatfirstmanifestation.Withouttreatment,the5-yearsurvivalrateislessthan5%.Theselectedtreatmentdependsonthepresenceofcomorbidity;tumorsize,location,andmorphology;andthepresenceofmetastaticdisease.Completesurgicalresectionfollowedbyhepatictransplantationoffersthebestlong-termsurvival,butfewpatientsareeligibleforthistherapy.Allothertherapiesarepalliative.RadiofrequencyablationisthepreferredmethodformanagingunresectablesmallHCCsthatarefewinnumber.Morewidespreaddiseaseistreatedwithpercutaneoustherapiessuchaschemoembolizationandselectiveinternalradiationtherapy.SystemicadministrationofbiologicandchemotherapeuticagentsisminimallysuccessfulinslowingthegrowthofHCCandtypicallyisusedtocontrolsymptomsinpatientswithoverwhelmingdisease.Amultidisciplinaryapproachthatincludessurgery,systemictherapy,andradiationtherapyandthatisbasedonthecooperationofradiationoncologists,interventionalanddiagnosticradiologists,hepatologists,andpathologistsmayofferthebestchanceofacureoratleastalongerandmorenormallife.Toparticipateeffectivelyinthiseffort,radiologistsmustbefamiliarwithstagingandtreatmentoptionsforHCCandwiththefactorsthataffectthechoiceofmanagementmethod.

©RSNA,2005

LEARNINGOBJECTIVESFORTEST1

Afterreadingthisarticleandtakingthetest,thereaderwillbeableto:

∙Identifytheanatomicandclinicalparametersthatinfluencethetreatmentoptionsandprognosisforpatientswithhepatocellularcarcinoma.

∙Discusstheevolvingroleofimage-guidedtherapiesinthetreatmentofhepatocellularcarcinoma.

∙Describethelimitationsoftraditionalsurgicalandmedicalmanagementofhepatocellularcarcinoma.

Introduction

Hepatocellularcarcinoma（HCC）isthecauseof250,000deathsworldwideeachyear.EarlyHCCistypicallyclinicallysilent,andthediseaseisoftenwelladvancedatthefirstmanifestation.Withouttreatment,thereisa5-yearsurvivalrateoflessthan5%

（1）.AccordingtotheWorldHealthOrganization,bytheyear2010,HCCwillhavesurpassedlungcancerastheforemostcauseofcancermortality

（2）.IntheUnitedStatesalone,theincidenceofhistologicallyprovedHCCincreasedfrom1.4of100,000peopleinthe1976–1980populationto2.4of100,000peopleinthe1991–1995population（3）.HCCpredominantlyaffectstheelderly,andinvestigatorsinarecentstudyofMedicarepatientsfoundthattheage-adjustedincidenceofHCCamongindividuals65yearsandolderhadincreasedfrom14.2per100,000in1993to18.1per100,000in1999（4）.Theincreasingincidenceinthisagegroupmayberelatedtothewidespreadtransmissionofviralhepatitis,specificallyoftypesBandC,duringthelate1960sand1970s,whenillicituseofintravenousnarcotics,needlesharing,unsafesexualactivity,andtransfusionofunsafebloodandbloodproductswerecommonpractices（3）.

AdiagnosisofHCCimpliesapoorprognosis.Currently,long-termsurvivalisbestachievedthroughsurgicalmanagement.However,onlyabout20%ofpatientsaresurgicalcandidatesatinitialmanifestationofHCC（5）.Overallsurvivalforpatientswithunresectablediseaseisbasedontumorstageandsize,liverfunction,andsymptoms.Llovetetal（6）,inastudyof102patientswithunresectableHCC,determinedthatsurvivalwas54%at1year,40%at2years,and28%at3years.ManytreatmentoptionshavebeendevelopedtoimprovethequalityanddurationoflifeforpatientswithunresectableHCC.Presently,intheUnitedStates,commonlyusedpalliativetherapiesincludesystemictherapies,radiofrequency（RF）ablation,transarterialchemoembolization（TACE）,andselectiveinternalradiationtherapy.

Inthisarticle,wereviewthetriageofpatientswithHCCamongthevarioustreatmentoptions（Fig1）andanalyzethecapacityofeachtreatmenttoprolongandtoimprovethequalityoflife.However,thisreviewisonlyabroadoutline.Individualcasemanagementandtreatmenteffectivenessareinfluencedbymanyintangibleandunpredictablefactors.

Figure1.FlowchartshowsthealgorithmusedforselectingtheappropriatetreatmentforHCCwhentheprincipalalternativesaresurgicalresection（thepreferredtreatmentmethod）,transplantation,RFablation,TACE,selectiveinternalradiationtherapy（SIRT）,systemictherapy,andsupportivecare.TreatmentforunresectableHCCisselectedonthebasisofclinicalandimagingfindings.

StagingofHCC

Cancerstagingisanever-evolvingprocessthatisimportantforbothpatientmanagementandresearchadvancement.Atpresent,multiplestagingsystemsforHCCarerecognized.Severalstagingsystemsincorporatevariousclinicalandradiologicparametersintointegratedscoringschemes（Okuda,BarcelonaClinicLiverCancer,andCanceroftheLiverItalianProgram[CLIP]）.Thesemedicalstagingsystemsaremostapplicabletopatientswithadvanceddiseasewhoarenotconsideredcandidatesforsurgery.Systemsofstagingthatarebasedontheresultsofpathologicanalysis（eg,AmericanJointCommitteeonCancer[AJCC]/UnionInternationaleContreleCancer[UICC]andLiverCancerStudyGroupofJapanclassificationsystems）incorporateanatomicandhistologicfindingsattumorresection（7）.GiventheheterogeneityofpatientswithHCCandthesmallpercentagewhoaresurgicalcandidates,boththeclinicalandthehistopathologicsystemsofstagingareneeded.Ina2002consensusstatement,theAmericanHepato-Pancreato-BiliaryAssociationandtheAJCCadvocatedtheuseoftheCLIPclassificationsystemformedicalstagingbecausethatsystemhasbeenwellvalidated,isapplicabletomostpatients,andincludeseasilycollecteddata（8,9）.Forpatientswithresectabledisease,theAJCC/UICCstagingsystemismostuseful,becauseittoohasbeenvalidated,itisbasedonthestandardsystemoftumor,node,andmetastasisclassification,anditcanbeappliedafterresectionortransplantation（9,10）.AttheFirstInternationalSymposiumonImage-guidedTherapyforCancer,inMay2005,Jean-NicolasVauthey,MD,chiefoftheLiverServiceintheDepartmentofSurgicalOncologyattheUniversityofTexasM.D.AndersonCancerCenter,Houston,Tex,presentedastrongargumentforacceptanceoftheAJCC/UICCsystembecauseofitscapacitytohelpmoreaccuratelypredicttheprognosisandtodirectpostoperativeadjuvanttherapy（7）.However,theUnitedNetworkofOrganSharingalsorecognizesthemodifiedtumor,node,andmetastasisclassificationsystemdevelopedbytheAmericanLiverTumorStudyGroupforassessmentofHCCinpatientsconsideredforlivertransplantation（Tables1–3）（11,12）.

Table1.CLIPScoringSystem

Note.—Adapted,withpermission,fromreference7;dataarederivedfromreference8.

Table2.AJCC/UICCClassificationSystem

∙Note.—Adapted,withpermission,fromreference7;dataarederivedfromreference10

Table3.AmericanLiverTumorStudyGroupModifiedTNMClassificationandStagingSystem

Note.—Adapted,withpermission,fromreferences11and12.

SurgicalTreatment

CompletesurgicalresectionandhepatictransplantationofferthebestchanceofacureforHCC.However,surgeryisoftenprecludedbyextensivediseaseorpoorhepaticfunctionalreserve（Figs2,3）.Furthermore,patientselectionandoutcomeareinevitablyinfluencedbytheskillandexperienceofthesurgeon.Evenwithsurgicalresection,theoverall5-yearsurvivalisapproximately30%（13）.

Figure2a.UnresectableHCCina48-year-oldman.（a）Contrast-enhancedportalphaseCTimageshowsHCCthatinvolvesliversegmentV（blackarrow）andthegallbladder（whitearrow）.

Figure2b.UnresectableHCCina48-year-oldman.（b）Contrast-enhancedportalphaseCTimageobtainedatalowerlevelthanashowsenlargedportallymphnodes（arrowhead）,whichprovedtobemetastaticdiseaseathistopathologicanalysisafterfine-needleaspirationperformedwithendoscopicUSguidance.

Figure2c.UnresectableHCCin