膠質瘤治療隨訪與影像評估

膠質瘤治療隨訪與影像評估浙江大學醫(yī)學院附屬第二醫(yī)院

幽閉恐懼癥Thedeterminationoftreatmentresponseandclinicaldecisionmakingisbasedontheaccuracyofradiographicassessment.

腫瘤解剖像曲面重建及MRVBOLD功能激活區(qū)和白質束追蹤術前2016-04-2118:48:08術后2016-04-2818:52:00手術結束時間2016年04月26日18時50分2016-04-2118:48:082016-04-2818:52:002009-06-13男，32歲，2007-12-28手術，術后恢復順利。術后行規(guī)范放化療。1,1,3,6月…復查2013-04-062014-11-29出血及強化2015-06-022015-06-022015-06-1009:26:452015-06-1018:20:13病理（右額葉）高級別膠質瘤,傾向膠質母細胞瘤,WHOIV級。免疫組化結果：GFAP+，MGMT+，MMP-9+++，PTEN-，IDH1-，EGFR-，VEGF+，Ki-6710%，P53+。2015-06-26放療定位2015-09-072015-

12-072016-05-03女，59y，因“記憶力減退1月”2012.11入院。2014.06.19Copyright?RadiologicalSocietyofNorthAmerica,2007Figure:FlowchartillustratesorderofmethodsusedtodiagnoseanddifferentiateintraaxialmassesAl-Okaili,R.N.,MelhemE.etal.Radiology2007;243:539-550LawMetal.AJNR200324:1989-1998ABCDEFUSCSchoolofMedicineRadiology&NeurosurgeryStandardofcare

ThecurrentSOCforpatientswithnewlydiagnosedGBismaximumsafesurgicalresectionfollowedbyconcurrentTMZ(75mg/m2/dayfor6weeks)andRT(60Gyin30fractions)andthen6maintenancecyclesofpost-RTadjuvantTMZ(150–200mg/m2/dayforconsecutive5daystherapyevery28days,standard5/28TMZ[sdTMZ])accordingtotheresultsofthepivotaltrialbytheEORTC/NationalCancerInstituteofCanada(NCIC)ClinicalTrialsGroup,inwhichbothPFSandOSwereimprovedwithcombinationtherapy(RT+TMZ)relativetoRTonly.Theevaluationoftreatmentinhigh-gradegliomascurrentlyrelieseitheronthedurationofpatientsurvivalor,morecommonlyinpatientswithrecurrentdisease,theradiographicresponserateorprogression-freesurvivalNeuroimagingNeuroimagingplaysacrucialroleindiagnosingandassessingthelocation,extent,andbiologicactivityofthetumorbefore,during,andaftertreatment.Itsroleinlow-gradetumorsliesinthemonitoringofpossiblerecurrentdiseaseoranaplastictransformationintohigh-gradetumors.Inhighgradetumors,neuroimagingismuchneededfordifferentiatingrecurrenttumorfromtreatment-inducedchangessuchasradiationnecrosis.Radiologicassessmentof

tumorresponsecriteriaMacdonaldCriteria(1990)ResponseEvaluationCriteriainSolidTumors(RECIST,2000)ResponseAssessmentinNeuro-Oncology(RANO,2010)MacdonaldCriteriahadanumberofimportantlimitations:thedifficultyofmeasuringirregularlyshapedtumors,interobservervariability,thelackofassessmentofthenonenhancingcomponentofthetumor,lackofguidancefortheassessmentofmultifocaltumors,thedifficultyinmeasuringenhancinglesionsinthewallofcysticorsurgicalcavitiesbecausethecyst/cavityitselfmaybeincludedinthetumormeasurementDetectionofEnhancingTumorVolumeDespiteResectionCavityCollapse.A)T1-weightedpost-contrastaxialimageshowingaresectioncavitywithrimenhancement.RECISTmeasurementwouldbeAandMacdonaldmeasurementwouldbe“A*B”.B)T1-weightedpost-contrastaxialimageshowingthesamepatient3monthspostoperativelywhohadcollapseofhisresectioncavity.RECISTmeasurementwouldbe“a”andMacdonaldmeasurementwouldbe“a*b”,bothofwhichwouldbesmallerthanthemeasurementsfromtheinitialscanabove,butthischangewouldbedescribingonlytheresectioncavityconfigurationandnottheunderlyingtumorburden.DetectionofEnhancementthatisObscuredbyBloodProducts.A)UncontrastedT1-weightedaxialimageshowingresectioncavitybloodproducts(brightonT1).B)T1-weightedpost-contrastaxialimageshowingthedifficultyindeterminingresidualenhancingtumor.C)Ourvolumetricanalysisisabletodetecttheobscuredenhancingtumortissue(showningreen).D)T1-weightedpost-contrastaxialimageat2.5monthslaterafterthebloodhasresolvedverifyingtheunderlyingenhancingtumorvolume.神經(jīng)腫瘤療效評估（RANO）標準“在放療完成的12周內(nèi)，新出現(xiàn)的強化灶，只有當其主體不在放療區(qū)域，或者病理學證實為腫瘤進展時，才可以認定為進展”Progressivedisease<12weeksaftercompletionofchemoradiotherapyProgressioncanonlybedefinedusingdiagnosticimagingifthereisnewenhancementoutsideoftheradiationfield(beyondthehigh-doseregionor80%isodoseline)orifthereisunequivocalevidenceofviabletumoronhistopathologicsampling(eg,solidtumorareasie,70%tumorcellnucleiinareas,highorprogressiveincreaseinMIB-1proliferationindexcomparedwithpriorbiopsy,orevidenceforhistologicprogressionorincreasedanaplasiaintumor).Note:Giventhedifficultyofdifferentiatingtrueprogressionfrompseudoprogression,clinicaldeclinealone,intheabsenceofradiographicorhistologicconfirmationofprogression,willnotbesufficientfordefinitionofprogressivediseaseinthefirst12weeksaftercompletionofconcurrentchemoradiotherapy.Progressivedisease12weeksafterchemoradiotherapycompletionNewcontrast-enhancinglesionoutsideofradiationfieldondecreasing,stable,orincreasingdosesofcorticosteroids.Increaseby25%inthesumoftheproductsofperpendiculardiametersbetweenthefirstpostradiotherapyscan,orasubsequentscanwithsmallertumorsize,andthescanat12weeksorlateronstableorincreasingdosesofcorticosteroids.Clinicaldeteriorationnotattributabletoconcurrentmedicationorcomorbidconditionsissufficienttodeclareprogressiononcurrenttreatmentbutnotforentryontoaclinicaltrialforrecurrence.Forpatientsreceivingantiangiogenictherapy,significantincreaseinT2/FLAIRnonenhancinglesionmayalsobeconsideredprogressivedisease.TheincreasedT2/FLAIRmusthaveoccurredwiththepatientonstableorincreasingdosesofcorticosteroidscomparedwithbaselinescanorbestresponseafterinitiationoftherapyandnotbearesultofcomorbidevents(eg,effectsofradiationtherapy,demyelination,ischemicinjury,infection,seizures,postoperativechanges,orothertreatmenteffects).Pseudoprogression/pseudoresponsePseudoprogressionofgliomasisatreatment-relatedreactionofthetumorwithanincreaseinenhancementand/oredemaonMRI,suggestiveoftumorprogression,butwithoutincreasedtumoractivity.Typically,theabsenceoftruetumorprogressionisshownbyastabilizationordecreaseinsizeofthelesionduringfurtherfollow-upandwithoutnewtreatment.Pseudoprogressionoccursfrequentlyaftercombinedchemo-irradiationwithtemozolomide,thecurrentstandardofcareforglioblastomas.Pseudoresponse,isthedecreaseincontrast-enhancementand/oredemaofbraintumorsonMRIwithoutatrueantitumoreffect.Itoccursaftertreatmentwithagentsthatinducearapidnormalizationofabnormallypermeablebloodvesselsorregionalcerebralbloodflow.Thesetwoopposingphenomenaemphasizethatenhancementbyitselfisnotameasureoftumoractivity,butonlyreflectsadisturbedBBB.A54-year-oldpatientwithrecurrentglioblastomashowingnonenhancingprogressionafterbevacizumabtherapy.Axialcontrast-enhanced,T1-weightedimagesshow(A)scanatrecurrenceshowingmultifocalrightfrontalglioblastoma;(B)decreasedenhancementafter7monthsoftherapythatqualifiesbyMacdonaldCriteriaaspartialresponse;(C)axialfluidattenuatedinversionrecoveryimageatbaselineand(D)after7monthsoftherapyshowingnonenhancingtumorprogressingthroughcorpuscallosumtotheleftfrontallobe.Pseudoprogression

afterchemoradiotherapyPreOPPostOPAfterradiotherapyandTMZRe-operation2daysafterstereotacticbiopsy4weeksaftertherapyAfteradditional4weeksTMZAfter8cyclesTMZNote:Giventhedifficultyofdifferentiatingtrueprogressionfrompseudoprogression,clinicaldeclinealone,intheabsenceofradiographicorhistologicconfirmationofprogression,willnotbesufficientfordefinitionofprogressivediseaseinthefirst12weeksaftercompletionofconcurrentchemoradiotherapy.彌散和DSC灌注成像的差別彌散假設真性進展細胞結構增加-ADC下降假性進展細胞結構減少-ADC上升DSC灌注假設真性進展血管分布增加-CBV增加假性進展血管分布減少-CBV下降AdvancedImagingTechniquesforEvaluationofTreatmentResponseDifferentiatingpseudoprogressionfromtumorprogressionPerfusionDSC:WithanrCBVthresholdof0.71,pseudoprogressioncanbedifferentiatedfromprogres-sive/recurrenttumorwithasensitivityof91.7%andaspecificityof100%inthissmallseries.DCE:AKtranscutoffvaluehigherthan0.19showed100%sensitivityand83%specificityfordetectingprogressive/recurrentgliomas.SignificantlyhigherMSIVP(maximumslopeofenhancementininitialvascularphase)andiAUC(initialareaunderthesignalintensity–timecurve,at60and120s)wereobservedintheprogressive/recurrenttumorgroup,withMSIVPbeingthebettersinglepredictorwithhighsensitivity(95%)andspecificity(78%).ASL:ASLislimitedbylowersignalintensity-to-noiseratioandlongeracquisitiontimecomparedtoDCE-MRIandDSC-MRI,themajoradvantageofASLtechniqueisitsapplicationinpatientswithinsufficientrenalexcretoryfunctionandtheabilitytorepeatASLacquisitionsduringasinglestudy.

Anewenhancinglesionappearedaroundtheresectioncavity1monthfollowingcompletionofchemoradiation,withoutevidenceofelevatedrCBVonDSC-MRI.Thelesioncontinuedtogrowduringthenext2monthsbuteventuallydecreasedinsize,consistentwithpseudoprogression.

Newenhancingareainapatientwithglioblastomafollowingchemoradiationtreatment,withpathologicallyconfirmedtumorprogression.TheuncorrectedCBVmapshowedanapparentlylowerbloodvolumerelativetonormalbrain.Presenceofsignificantleakageisseenwithintheenhancinglesionasindicatedbysignalintensitycurveandleakagemap.Followingleakagecorrection,elevatedcerebralbloodvolumeintheenhancingregionisconfirmed.Anewenhancinglesionappearedadjacenttotheresectioncavity3?monthsfollowingcompletionofchemoradiation(A),withoutevidenceofelevatedkTrans(B)onDCE-MRI.Thelesionremainedunchangedinsizeforthesubsequent4?months,consistentwithpseudoprogression.Anewenhancinglesionappearedalongmedialmarginofrighttemporalresectioncavity2?monthsfollowingcompletionofchemoradiation(A),withoutevidenceofneitherelevatedCBFonASLperfusion(B),norelevatedrCBV(C)onDSC-MRI.Thelesionwasconfirmedaspseudoprogressiononsubsequentimaging.MagneticresonancediffusionimagingADChasbeenshowntoinverselycorrelatewithtumorcelldensityOneimportantcauseofneworincreasedenhancementfollowingchemoradiationisduetopostsurgicalinfarction

AnincreaseintumorADCvaluesfollowingtherapycomparedtopre-treatmentADChasbeenshowntobepredictiveoffavorableresponse

Histogram-basedmethodshavebeendevelopedtocharacterizerelativemixturesofADCvaluesandtestedaspredictorsofpatientoutcome

Enlargingleftparieto-occipitallobeenhancement4?monthsfollowingchemoradiationtherapy(A).TheenhancingregiondemonstratedlowADC

(B)

onDWI,mildlyelevatedrCBV

(C)

onDSC-MRI.FDG-PET

(D)

ofthesamelesionhadlessconspicuouslesiontobackgrounduptakecomparedtoFLT-PET

(E)

andFET-PET

(F).Subsequentresectionconfirmedprogressive/recurrentglioblastoma.GenerationofADChistograms.(a)TotalenhancingtumorvolumewassegmentedonaxialpostcontrastT1-weightedimagesina52-year-oldwomanwithrecurrentGBMandtransferredto(b)thecorrespondingADCmapimageforgenerationofADChistogram(c,d).(c)Asingledistributionfittingcurveprovidedapoorfitofthedata,whichcouldbesubstantiallyimprovedbyusing(d)atwo-componentnormalmixturemodel.Radiology.

2009Jul;252(1):182-9.doi:10.1148/radiol.2521081534.Recurrentglioblastomamultiforme:ADChistogramanalysispredictsresponsetobevacizumabtreatment.PopeWB1,

KimHJ,

HuoJ,

AlgerJ,

BrownMS,

GjertsonD,

SaiV,

YoungJR,

TekchandaniL,

CloughesyT,MischelPS,

LaiA,

NghiemphuP,

RahmanuddinS,

GoldinJ.(a,e)ADC1000mapsand(b,f)ADC3000mapswithcorresponding(c,g)histogramsand(d,h)cumulativehistogramsforrepresentative(a–d)low-gradegliomaina67-year-oldwomanand(e–h)high-gradegliomaina48-year-oldman.ADCsofthehigh-gradegliomaweredispersedoverawiderrangethanwerethoseofthelow-gradeglioma,indicatingtheheterogeneousspectrumofcellularitywithintheentiretumorvolume.ADCsdecreasedwhenbvaluewasincreasedfrom1000to3000sec/mm2.Gliomas:Histogramanalysisofapparentdiffusioncoefficientmapswithstandard-orhigh-b-valuediffusion-weightedMRimaging--correlationwithtumorgrade.KangY,ChoiSH,KimYJ,KimKG,SohnCH,KimJH,YunTJ,ChangKHRadiology.2011Dec;261(3):882-90.MagneticresonancespectroscopyArecentmeta-analysisreportedthatthediagnosticperformanceindifferentiatinggliomaprogressionfromradiationnecrosisusingcholinetoNAAratiohassensitivityandspecificityof0.88and0.86,respectivelyBiochemicalchangesduringpost-treatmentnecrosisappeartohavetemporalvariability,includingdecreasedNAAconcentrationsovertimeandatransientincreaseincholinefollowingradiationtherapy,suggestingthatalongitudinalevaluationusingMRSmayprovidegreaterspecificity.Roleofmagneticresonancespectroscopyforthedifferentiationofrecurrentgliomafromradiationnecrosis:asystematicreviewandmeta-analysis.ZhangH,MaL,WangQ,ZhengX,WuC,XuBNEurJRadiol.2014Dec;83(12):2181-9.ComparisonofPerfusion,Diffusion,andMRSpectroscopybetweenLow-GradeEnhancingPilocyticAstrocytomasandHigh-GradeAstrocytomas.AJNRAmJNeuroradiol35:1495–502Aug2014LowerrelativecerebralbloodvolumeandhigherADCvaluesfavoradiagnosisofpilocyticastrocytoma,whilehigherlipid-lactateintumor/creatineintumorratiosplusnecrosisfavoradiagnosisofhigh-gradeastrocytomas.AntiangiogenictherapyandpseudoresponseThroughnormalizationofleakytumorbloodvessels,theseagentscancausereductioninenhancementwithin1–2?daysafteradministration,witharadiographicresponsein25–60%ofpatients；thisrapidradiographicresponserepresentsadirectactiononbloodvesselpermeabilityratherthanatrueanti-tumoreffectBevacizumab：arecombinanthumanizedmonoclonalantibodytoVEGF-ACediranib：

apan-VEGFreceptortyrosinekinaseinhibitortoVEGFreceptorTheRANOcriteriaaddressthisissuebyrequiringaradiographicresponsetopersistformorethan4?weeksinordertobeconsideredatrueresponse

PseudoresponsesAfterTreatmentWithAntiangiogenicTherapiesAxialT1-weightedcontrastenhancedMRIofleftfrontalrecurrentglioblastomaa)beforeandb)onedayaftertherapywithcediranib(pan-VEGFRinhibitor)showingsignificantreductionincontrastenhancement.Thereductionincontrastenhancementwithin1dayoftherapyismorelikelytobecausedbyreducedvascularpermeabilitytocontrastthantoatrueantitumoreffect.DetectingtumorinantiangiogenictherapyT1subtractionmapT2mappingDiffusionMRIinantiangiogenictherapy：MRIbiomarkersidentifythedifferentialresponseofglioblastomamultiformetoanti-angiogenictherapy.JalaliS,ChungC,FoltzW,BurrellK,SinghS,HillR,ZadehGNeuroOncol.2014Jun;16(6):868-79.High

b-valueMRdiffusionimagingMRperfusionimagingCET1-weightedMRimage

(T1wMRI)

ina44-year-oldfemalepatientwithrecurrentGBMdemonstratesanapparentreductionincontrastenhancementafterbevacizumabtherapy.

A,

Nonenhanced

(Pre-Contrast)T1-weightedMRimage.

B,

CE

(Post-Contrast)

T1-weightedMRimage.

C,

Subtractionmap.

D,

CET1-weightedsubtraction

(CE-ΔT1w)

mapshowsdemarcationofanareaofresidualtumoridentifiedasapositiveincreaseinMRsignalintensityafteradministrationofcontrastagent.

Post-Pre

=differencebetweenafterbevacizumabtherapyandbeforebevacizumabtherapy.CET1-weightedsubtractionmapswerecreatedbyfirstperforminglinearregistrationbetweennonenhancedandCET1-weightedimagesbyusinga12–degree-of-freedomtransformationandacorrelationcoefficientcostfunctioninFSL(FLIRT;FMRIBSoftwareLibrary,Oxford,England）Radiology.

2014Apr;271(1):200-10.doi:10.1148/radiol.13131305.Epub2013Nov27.Recurrentglioblastomatreatedwithbevacizumab:contrast-enhancedT1-weightedsubtractionmapsimprovetumordelineationandaidpredictionofsurvivalinamulticenterclinicaltrial.EllingsonBM1,

KimHJ,

WoodworthDC,

PopeWB,

CloughesyJN,

HarrisRJ,

LaiA,

NghiemphuPL,CloughesyTF.T1subtractionmapTraditionalNon-VolumetricMeasurementsdonotAdequatelyDescribeResidualEnhancementinSurgicalResectionCavities.A)Thisschematicresectioncavityhasresidualrimenhancementingray.RECISTcriteriameasurement‘A’or‘a(chǎn)’or‘b’orMacdonaldcriteriameasurement‘A*B’or‘a(chǎn)*b’wouldnotadequatelydescriberesidualtumorvolumeandadditionaltumorgrowtharoundtherimorcollapseoftheresectioncavitymaybeover-orunder-interpreted.B)Differencesinaxialsliceacquisitionalsoimpactmeasurementsmadebytraditionalcriteriamorethanvolumentricmeasurements.Onescancouldobtainaxialslice‘c’withenhancingtumormeasurement‘x’butasubsequentscaninthesamepatientcouldobtainaxialslice‘d’,causinganincorrectassessmentoftumorresponse.PLoSOne.

2011Jan26;6(1):e16031.doi:10.1371/journal.pone.0016031.AnovelmethodforvolumetricMRIresponseassessmentofenhancingbraintumors.KanalyCW1,

DingD,

MehtaAI,

WallerAF,

CrockerI,

DesjardinsA,

ReardonDA,

FriedmanAH,

BignerDD,

SampsonJH.AutomatedAssessmentofEnhancingTumorVolume.A)T1-weightedpost-contrastaxialimagesareautomaticallyfusedwiththepre-contrastsequences.B)Thetumorregionofinterest(bluearea)andnearbynormalbrain(purplearea)areoutlinedroughlybyhand.C)Theenhancingnasalmucosaregionisautomaticallydetectedwithabuilt-inanatomicatlas(redarea)andservesasathresholdforenhancement.D)Tissuethatispresentonthepost-contrastimagesbutnotthepre-contrastthatisabovetheenhancementthresholdappearsinyellow.Thisincludesenhancingtissuesuchasvasculature,tumor,andsuperficialstructures.Enhancingtumorvolumeisdefinedasthegreenareawithinthemanually-definedbluetumorregionofinterest.EffectofInter-observerDifferencesinDefinitionofTumorVolume.A)AxialT1-weightedpost-contrastimageshowingalimiteduser-definedtumorregionofinterest.B)Thesameaxialimagenowshowingalargeuser-definedtumorregionofinterestthatencompassesthemeningealenhancement.C)Whileincludingthemeningesincreasestheenhancingvolume,similartrendsinchangesofvolumeovertimeareseen.EffectofDifferentEnhancementThresholds.A)AxialT1-weightedpost-contrastimageaftervolumetricanalysishasbeenperformedwhichshowsingreenthedetectedenhancingtumorvolumeusinga25%thresholdlevel.B)Detectedenhancingtumorvolumeusinga40%thresholdlevel.C)Whileincreasingthethresholddecreasesthecalculatedtumorvolume,thevolumesacrossdifferentthresholdlevelsarehighlycorrelated.T2mapping

DifferentialquantitativeT2maps.MoreapparentchangesonthedifferentialT2map(bottomrow)intheleftfrontallobe(arrows)comparedtoT2-weightedimages(toprow).ThesechangesarehardlyvisibleonconventionalT2-weightedimages(arrows).QuantificationofedemareductionusingdifferentialquantitativeT2(DQT2)relaxometrymappinginrecurrentglioblastomatreatedwithbevacizumab.EllingsonBM,CloughesyTF,LaiA,NghiemphuPL,LalezariS,ZawT,MotevalibashinaeiniK,MischelPS,PopeWBJNeurooncol.2012Jan;106(1):111-9.Predictinggliomarecurrence

-DTIpatterns(a)adiffusepatternofabnormalitywherepexceededqinalldirectionsandwasassociatedwithdiffuseincreaseintumoursize;(b)alocalisedpatternofabnormalitywherethetumourrecurredinoneparticulardirection;(c)apatternofminimalabnormalityseeninsomepatientswithorwithoutevidenceofrecurrence.Predictingpatternsofgliomarecurrenceusingdiffusiontensorimaging.EurRadiol(2007)17:1675–168420