功能影像学技术在头颈部肿瘤放疗计划制定、疗效评估和个体化治疗中应用课件

FunctionalImagingforRadiationTreatmentPlanning,ResponseAssessment,andAdaptiveTherapyinHeadandNeckCancerFunctionalImagingforRadiati1Role

of

routine

and

functional

Imaging(FI)Screening

and

diagnosis

of

neoplasmsPrecisestaging

of

malignancyResponse

assessment

of

cancer

treatmentMonitor

recurrencesRoleofroutineandfunctional2Benefit

of

FIMajor

modalities

of

FI:positronemissiontomography(PET)combinedwithCTormagneticresonance(MR)imagingfMRI:

DWI,

DCE-MRI,

BOLD,

spectroscopy

etc.Emerging

techniques:

PET-MRI,

DKI,

IVIM,

APT,

CEST

etc.Offercomplementaryinformationincluding

metabolism

of

FDG,proliferation,hypoxia,andcellmembranesynthesisby

PEThypoxia

and

permeability

by

DCE

MRI

and

IVIM,cellproliferationandapoptosis

by

DWI,

IVIM

and

DKI,andepidermalgrowthfactorreceptorstatus.BenefitofFIMajormodalities3About

this

articlePart

I:

Discussesthepracticalaspectsofintegratingfunctionalimagingintohead-and-neckradiationtherapyplanning.Part

II:

Reviewsthepotentialofmolecularimagingbiomarkersforresponseassessmentandtherapyadaptation.Authors

concluded

that

FI

allowedmoreindividualizedtreatmentplanninginpatientswithheadandneckSCCsintheemergingeraofpersonalizedmedicine.AboutthisarticlePartI:Disc4Part

I

RoleofFunctionalImaginginRadiationTherapyPlanningTherewasa20%decreaseinOS

amongpatientswhounderwentradiationtherapywithaprotocolthatdidnotcomplywithestablishedinstitutionalstandards.Reasons:

Inaccuraciesintumortargetdelineation

Inter-observervariabilityin

clinical

practice

based

on

CT

fortargetdelineationFunctionalMRIandPETtechniquesprovidedifferentandpotentiallycomplementaryinformationaboutthetumorextentandbiologicactivity.PartIRoleofFunctionalImag5PET-basedTumorTargetContouringTumoruptakeofPETradioactivetracerscanprovideexcellentcontrastresolutionbetweenneoplasticandnormaltissues.There

are

two

DOSE

CONTOURING

methods:

visualinterpretationandautomateddelineationmethods.PET-basedTumorTargetContour6Example

of

automateddelineationFigure2.SCCarisingfromtheepiglottis(T2N2bM0)ina67-year-oldman.AxialfusedFDGPET/CTimageshowstumorcontoursautomaticallygeneratedwithdiagnosticsoftware

byusingpercentagesofthemaximumSUV(20%,30%,40%,and50%)andafixedSUVcutoffof2.5.Automated

delineation

is

believe

to

be

more

objective

than

visual

delineation.

Because,

an

alterationoftheSUVscalecanchangetheapparenttumorvolumeandleadtoincreasedinter-observervariability.Exampleofautomateddelineati7Status

of

PET-contouring

at

presentAtpresent,thereisnoconsensusregardingtheoptimalcontouringmethod.ThemostpracticalapproachtodefiningthetumortargetistorelyonexpertvisualinterpretationsbynuclearmedicinephysiciansandradiologistsAnd

rely

onknowledgeofthelikelypatternsofdiseaseinfiltrationwithinstrictSUVscalelimits.

However,limitedspatialresolutionandpartialvolumeeffectsblurtheedgesofFDG-avidtumorsatPET.StatusofPET-contouringatpr8PET-basedRadiationTherapyPlanningtheFDGPET–definedgrosstumorvolume(GTV)wasfoundtobesmallerandmoreaccuratethantheCT-orMRimaging–definedGTVandclosertothetumorvolumeatpathologicanalysis.however,nosingleimagingmodalityallowedperfectlyaccuratethree-dimensionalestimationofthetumorvolume.Allmodalitiesfailedtodetectabout10%ofthetumorvolume,mainlybecauseofsuperficialtumorextension.PETwasfoundtoallowtheidentificationofpotentialdiseaseextensionbeyondtheCT-definedGTVin29%–64%ofcases.PET-basedRadiationTherapyPl9PET-basedRadiationTherapyPlanningDuprezetal(24)demonstratedthefeasibilityofapplyingdoseescalationtoanFDGPET–avidGTVwithdosepaintingbynumbersinsteadofwithGTVcontouring.TheuseofmultimodalityimagingraisesthequestionofwhethertheGTVshouldbedefinedonthebasisofimagingwithonlyoneorwithseveralmodalities？

Thelackofconcordancefoundbetweenvariousimagingmodalitiessuggeststhatthesafestapproachwhendefiningatargetistouseallimagingmodalitiesalongwithphysicalexamination.

Anatomicandfunctionalimagingmodalitiescould

providedifferentbutcomplementaryinformationduringcontouring

and

planning

for

cancer

RT

treatment.PET-basedRadiationTherapyPl10Contourlinesarecolorcodedtoshowtheimagingmodalityonwhichtheyarebased(green=CT,blue=MRimaging,orange=PET).Contourlinesarecolorcoded11AdaptiveRadiationTherapyPlanningThereisconsiderableinterestinpersonalizingtreatmentinanattempttooptimizethetherapeuticratioforindividualpatients.Oneavenueforachievingthisistoalterthedeliveryofradiationtherapyonthebasisofchangesinthetumorand/ornormalorgansduringacourseoftreatment.Mainly

current

radiationtherapyisplannedatasinglepretreatmenttime-pointtodelineatethetargetvolumeandanyorgansatrisk,withnoaccounttakenofanatomicchangesduringthecourseoffractionatedradiationtherapy.AdaptiveRadiationTherapyPla12AdaptiveRadiationTherapyPlanningGeetsetal

showedreductionsof51%intheclinicaltargetvolumeand48%intheplanningtargetvolumeafterapartialcourse(45-Gydose)ofradiationtherapy.InasubsequentstudyofpatientsreceivingCRT

therapyforlaryngopharyngealcancer,PET-basedandCT-basedprimarytumorGTVswerefoundtodecreaseatameanrateof3.2%and3.9%pertreatmentday,respectivelywhilenodalGTVsdecreasedatarateof2.2%pertreatmentday.Inaddition,positionalshiftswerenotedintheGTV.AdaptiveRadiationTherapyPla13AdaptiveRadiationTherapyPlanningIt

providesanopportunitytoimprovethetherapeuticratiobyminimizingtheoveralldosetoorgansatriskandescalatingthedosetoareasoftumortissue.18F-fluorothymidine(FLT)PET/CTisanoninvasivemethodformonitoringproliferationduringtreatment.Troostetalshowedthatdecreasesintumor-relatedFLTuptakeoccurredearlyaftertheadministrationofthefifthradiationdosefraction.Bycontrast,changesintheCT-definedGTVweredetectableonlyafter4weeksofradiationtherapy.Thesedatademonstratedthefeasibilityofescalatingtheradiationdoseadministeredtotumorsub-volumeswithhighproliferativeactivityinthe2ndweekoftreatment.AdaptiveRadiationTherapyPla14Figure6.Adaptivetherapyplanningina68-year-oldmanwithasupraglotticSCC(T2N2bM0)treatedwithchemoradiationtherapy.(a)AxialfusedPET/CTimageobtainedbeforethestartoftherapyshowsmarkedmetabolicactivity(SUVmax,22.2)inthetumor(arrowhead).(b)AxialfusedPET/CTimageobtainedafter11fractionsofradiationtherapyshowsareductionintumorsizeandmetabolicactivity(SUVmax,9.7).(c)AxialfusedPET/CTimage,obtainedafter21fractionsofradiationtherapy,showscontinuedreductionintumorsizeandmetabolicactivity(SUVmax,7.9).Figure6.Adaptivetherapypla15AdaptiveRadiationTherapyPlanningOther

limited

fMRI

data

alsosuggestthatchangesondiffusion-weightedordynamiccontrast-enhancedMRimagescouldbeusedtoguideadaptivedoseescalationstrategies.a

and

b

–beforec

and

d

–after

21

fractionshowthetumor(arrow)andnode(arrowhead)withreducedsignalintensityincandincreasedsignalintensityind,findingsindicativeofresponsetotreatment.AdaptiveRadiationTherapyPla16Mainly

issues

of

FI

to

guide

A-RT

planning1、

thechoiceofimagingmodality.2、imagingcharacteristicsmaynotbe

reproducibleatsuccessiveimagingevaluations.3、theoptimaltimingofimagingassessmentsduring

thecourseoftreatmentisunknown.4、theoptimalmethodfordefiningtumorcontours

isunclear.MainlyissuesofFItoguideA17PART

II

FunctionalImagingforDiseaseResponseAssessmentfunctionalimagingappearstobeapromisingadditiontoclinicalexaminationandanatomicimagingforassessingtheresponseofheadandneckSCCtumorstoradiationtherapy.Thisisparticularlytrueintheclinicalscenarioofresidualmasses,whereanatomicimagingtechniquesareinaccurate.TheuseofFDGPETisnowsupportedbyconsiderabledata.ArolealsomaybeestablishedforotherPET-andMRimaging–basedtechniques.I

selected

fMRI

as

my

favorite

lecture

today.

While

leave

PET

for

colleaguefrom

nuclear

medicine

department.PARTIIFunctionalImagingfor18FunctionalMRImagingTechniquesAdvancedMRimagingtechniquessuchasdynamiccontrast-enhancedimaging,diffusion-weightedimagingbloodoxygenationlevel–dependent(BOLD)imagingspectroscopyholdthepromiseofprovidingfunctionalinformationaboutdisease.Thesetechniquescanbeusedforplanning,monitoring,andassessingtheresultsofradiationtherapyinpatientswithheadandneckSCCs.FunctionalMRImagingTechniqu19DynamicContrast-enhancedImagingitisanoninvasivetechniquethathelpscharacterizethemicrovasculature,therebyprovidingmarkersspecifictoperfusion,permeabilityofbloodvessels,andthevolumeofextracellularspace.Abnormalmicrovesselsseenatdynamiccontrast-enhancedMRimagingthemselvesmaybeamarkerofhypoxiaTumorangiogenesisisassociatedwithchaoticvesselformationandincompetentarteriovenousshunts,whichleadtolesseffectiveperfusionandamorehypoxicenvironmentthanexistsinnormaltissues.DynamicContrast-enhancedImag20Previous

studies

of

DCE

MRINewboldetaldemonstratedastatisticallysignificantcorrelationbetweenvariousDCE-MRI

parameters,particularlyKtrans(whichrepresentsthepermeabilityofbloodvessels)andpimonidazolestaining(anexogenousmarkerforhypoxia).TheappearanceofheadandneckSCCsatdynamiccontrast-enhancedMRimagingalsohasbeenusedtosuccessfullypredicttreatmentresponsetochemoradiationtherapyinthetumors(85).PreviousstudiesofDCEMRINew21(a)AxialT1-weightedMRimageobtainedforplanningofchemoradiationtherapyina62-year-oldmanshowsaprimarySCCintheleftaspectofthetonguebase(T4N2bM0)(arrow)andanodalmetastasis(arrowhead).(b,c)Axialdynamiccontrast-enhancedMRimagesbefore

and

after

RTshowincreasedvascularpermeability(Ktrans)beforeradiationtherapyintheprimarytumor(arrowinb)andcervicalnode(arrowheadinb)decreasedpermeabilityafter11fractionateddosesofradiationtherapyinthetumor(arrowinc)andnode(arrowheadinc).Thesefindingsareindicativeoftherapeuticresponse.(a)AxialT1-weightedMRimage22Diffusion-weightedImagingDiffusion-weightedMRimagingisanoninvasiveimagingtechniquethatfacilitatestissuecharacterizationonthebasisofthemolecularmotionofwatermolecules.DiffusionisquantifiedbyusingtheADC,whichisinverselycorrelatedwithcellularityandisapotentialbiomarkerforapoptosis.TheincreaseddensityofcellswithinmalignantlymphnodesreducestheirADCatdiffusion-weightedMRimaging.Diffusion-weightedImagingDiff23StudieshaveshownthatDWIcanbeusefulfordifferentiatingsmallmalignantlymphnodesfromnonmalignantonesInonestudy,asensitivityof76%wasobtainedwiththeuseofADCatdiffusion-weightedimagingfordetectingsubcentimetriclymphnodemetastases,incomparisonwithasensitivityof7%obtainedwiththeuseofmorphologicfeaturesandsizedepictedatconventionalMRimagingInanotherstudy,in33patientswithheadandneckSCCs,changeinADCwasusedasamarkeroftumorresponsejust

1weekafterchemoradiationtherapy.StudieshaveshownthatDWIca24Dirixetal(31)evaluatedtheusefulnessofDWIforra