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Page 1: Recent Advances In Brachytherapy: Unconventional ...amos3.aapm.org/abstracts/pdf/127-35266-418554... · Recent Advances In Brachytherapy: Unconventional Applications of Brachytherapy

RecentAdvancesInBrachytherapy:UnconventionalApplicationsofBrachytherapy

59th AnnualNationalConferenceoftheAAPMAugust2,2017

BenjaminP.Fahimian,PhD,DABR*ClinicalAssistantProfessor,AssociateDirector,TherapeuticMedicalPhysicsResidency,BrachytherapyPhysicsLead,[email protected]*FinancialDisclosures:None

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Fahimian,AAPM2017,Slide:3

Outline

• Wherearewe,andwherearewegoingwithclinicalapplicationsofbrachytherapy?• Roleofbrachytherapyasafocaltechniqueforablation

– SBRT/SABRandalternativetechniquesofablation• Reviewofunconventionalbrachytherapytechniques

– Image-guidedpercutaneoustechniques– Stereotacticimplantation

• MinimallyinvasiveimplantationviaElectromagneticGuidance• EMGuidedHDRforablativetreatmentoflunglesions

– Navigationandimplantation– Dosecalculation– Dosimetry relativetoSBRT/SABR

• Discussion– Limitations– Challenges– Futuredirections

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Fahimian,AAPM2017,Slide:4

ConventionalApplicationsofBrachytherapy

• Wherearewe,andwherearewegoingwithclinicalapplicationsofbrachytherapy?

ConventionalApplicationsofBrachytherapy

Gynecological Genitourinary Breast

Skin Ocular UnsealedSources

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“Unconventional”ApplicationsofBrachytherapy

• Lessconventional techniques

• Brachytherapy islimitedbyimplantationaccess• Newformsofminimallyinvasive implantationmaybethekeyforward

Head&Neck Intracranial Endobronchial Intraoperative

FocalTreatments• ImageGuidedInterstitialImplantation• Ablativedosing

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Fahimian,AAPM2017,Slide:6

ParadigmsforFocalandAblativeDelivery

ExternalBeam• SABR(SBRT)• RoboticRadiosurgery

Alternativetechniques• RadiofrequencyAblation• Cryoablation• HIFU• MicrowaveAblation• Electroporation

Nature Reviews Clinical Oncology 12, 175–186 (2015)

Cryoablation of Renal Tumors

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AlternativeTechniques

• Biologicalmechanismofactiondifferentforthermalablationandradiotherapy– DNAdamageviaionizingradiationvs.thermalablation(RFA,Microwave,Cryo)

Courtesy of Lee et al., Transl Lung Cancer Res 2013;2(5):340-353

Microwaveablationt=0 t=3months t=9months

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Fahimian,AAPM2017,Slide:8

StereotacticAblativeRadiotherapy(SABR/SBRT)

Advantages• Highlocalcontrolrate• Non-invasive• Accessanywhereinlung• DoseconformalityChallenges• Motionmanagement• Potential forgeometricalmiss• Substantial volumeoflungcanreceive lowerdoses• Airwayandlungcollapse, radiationpneumonitis, lungfibrosis,orvertebral

fracture

SABR

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Fahimian,AAPM2017,Slide:9 AAPM TG-76, 2006

Tumor trajectories of 23 patients, using tracking of implanted fiducials. Seppenwoolde, et al., 2002

RangeofTumorMotionforSBRTSites

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• Targetmotionisamajorcomplicatingfactor inSABR/SBRTdelivery– Notethatimplantedseedsmovewithtarget

• Targetsmustnotonlybelocalizedinspacebutalsointime

Videos of thoracic target motion. Courtesy of R. LiVideo

MotionManagementforExternalBeam

MotionManagementTechniques:

– Motion-encompassingirradiation

– Compression– Breath-hold– Gating– Dynamictracking

delivery

TechnicalComplexity

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Fahimian,AAPM2017,Slide:11

BrachytherapyasanAblativeAdjuncttoSBRT

Advantages• Deliverablativedoses tolocalizedvolume• Rapiddose fallofffornormal tissuesparing• Motionmanagement issues reduced• Enhanceddosimetry /higherablativedosesChallenges• Access– need forminimallyinvasive implantationtechniques• Dependence onqualityofimplant• Optimaldosingregimensneedfurther investigation

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Image-GuidedPercutaneousTechniques

• ProspectivePhaseIItrial(Ricke,etal.)• 30patientswith83singularlesions• Meantumordiameterwas2.5cm(0.6–11cm).

• 20Gy inasingleHDRfraction• Singleapplicatorexcept2caseswith2• Adverseeffects:nausea(n=3,6%),minor(n=6,12%)andonemajorpneumothorax(2%)

• 91%localcontrolat12months

StrahlentherOnkol2008·No.6

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Fahimian,AAPM2017,Slide:13

Image-GuidedPercutaneousTechniques

• Numberofsitesincludingliver,renal,lung,lymphnodes• Surveyofinterstitialimage-guidedHDRofinnerorgans(Bretschneider,etal.,2016)

Bretschneider,etal.,JournalofContemporaryBrachytherapy(2016/volume8/number3)

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Fahimian,AAPM2017,Slide:14

Image-GuidedPercutaneousTechniques

• Limitednumberofcatheters,1-3• Performedunderlocalanesthesia,conscioussedation• Generallywelltolerated,limitedcomplicationsrelatingtocatheterinsertion• CT,MRimagingwith3Dplanning

Renal LymphNodes Lung(NSCLC) Liver

Bretschneider,etal.,JournalofContemporaryBrachytherapy(2016/volume8/number3)

Ricke,etal.,SeminRadiat Oncol,2011,21:287-293

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Fahimian,AAPM2017,Slide:15

Image-GuidedPercutaneousTechniques

CTGuidedPlanning MRGuidedPlanning

ImagesCourtesyofBretschneider,etal.,JournalofContemporaryBrachytherapy(2016/volume8/number3)

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FramelessStereotacticImplantationofHeadandNeckLesions

Pappas et al., Med Phys. 2005 32:6,1796-1801 Bane, et al., Radiology 2000; 591-595

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Individualized3D-PrintedTemplatesforHeadandNeckBrachytherapy

• Huang,etal.:25HNpatientsimplantedwithI-125seeds• Entrancedeviationfor619needleswas1.18±0.81mm

Huang, et al., Journal of Radiation Research, Vol. 57, No. 6, 2016, pp. 662–667

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Fahimian,AAPM2017,Slide:18

EstablishedLungBrachytherapyTechniques

• Palliationofairwayconstriction,5-7.5Gy x3

• MinimallyinvasiveHDRviaopticalbronchoscopywithfluoroscopicverification

• Limited/noaccesstoperipherallesionsinlung

Endobronchial Intraoperative Focal- PercutaneousVicryl Mesh

Guidelines(1cmspacing)withseeds

• Emulatesclassicsplanarimplants

• RowsofI-125seedswith1cmspacing

• Limitedasanadjunctoptionforoperableportionofthepatientpopulation

ReviewReference:Skowronek,JournalofContemporaryBrachytherapy7:4(2015)

• Accesslimitedbytargetlocation

• Percutaneousimageguidedtransplantation

• Commonfractionationof20Gy x1

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Fahimian,AAPM2017,Slide:19

Robotics-AssistedIntraoperativeApproaches

CurrentRespiratoryMedicineReviews,2011,Vol.7,No.5

• Laparoscopic robotassistedseedimplantation

• Coupledwithelectromagneticnavigationtogobeyondvideoassistedmethods

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Fahimian,AAPM2017,Slide:20

OpticalBronchoscopyandEndoluminal Approaches

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Fahimian,AAPM2017,Slide:21

LimitationsofOpticalBronchoscopy

• Flexible opticalbronchoscopesrangeinsizeofouterdiameter2.8-6.9mm– Providesaccess toprimaryandportions

ofsecondarybronchus– Ingeneral limitedornoaccess totertiary

bronchusandbronchiole fortherapeuticscopes

• Navigationtotertiarybronchus,bronchiole,andperipheral lesionsrequiresuseofsmallerprobessuchaselectromagnetic transponders

Flexiblebronchoscope

Thinelectromagneticprobe

Peripherallesion

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Fahimian,AAPM2017,Slide:22

ElectromagneticNavigationBronchoscopy• SuperDimensionTM (Covidien) ENBsystem

routinelyutilized– Fiducial Placement– BiopsyofPeripheralLesions

• Requirestheco-registereduseof– ThoracicCTwithairwaysegmentation– Opticalbronchoscopy– InternalEMtransponderfornavigation

(locatableguide)

Schwarz, et al., CHEST 2006; 129:988–994)

Image: Courtesy of Covidien

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ElectromagneticNavigationBronchoscopy

• Clinical experience inthediagnostic realm– Recenttrialof56patients,Ozgul,etal., 2016

• Meanproceduretimewas20± 11.5min.• Meanregistrationerrorwas5.8± 1.5mm.• Meannavigationerrorwas1.2± 0.5mm• Well tolerated• Pneumothoraxoccurredinonly1patient(1.7%)

– Larger studyof151patientsbyWilson,etal.,2007• 3(1%)modbleeding,1(0.3%)hematoma

1(0.3%)pneumonia

Endosc Ultrasound.2016May-Jun;5(3):189–195; JBronchol.2007;14:227-232

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Fahimian,AAPM2017,Slide:24

ElectromagneticNavigationBronchoscopy

• Locatableguide:internaltransponderfornavigation

• Sensor1:1inchbelowthesternalnotchSensors2,3:alongthemid-axillarylineattheeighthrib

• Transmissionfrequencies:2.5,3.0,3.5kHZ

• Externalsensorsusedtoaccountforrespiratorymotion

BoardemitslowfrequencyEMenablingtrackingwithin~40x40x30cmbox

Extendedworkingchannelcontaininglocatableguide

ImageReference:S.Leongetal.,J.Thorac.Dis.,vol 4,pp173(2012)andCovidien

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Fahimian,AAPM2017,Slide:25

ElectromagneticNavigationBronchoscopy

Co-registrationoflocatable guide,CT,andopticalbronchoscope

Dr.DanielPinkham ExternalSensors

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ElectromagneticNavigationBronchoscopy

S.Leongetal.,J.Thorac.Dis.,vol 4,pp173(2012)

• 360degree(8way)steering

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Electromagnetic-GuidedHDRWorkflow

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Fahimian,AAPM2017,Slide:28

FirstProspectiveDemonstrationsEM-GuidedHDR

• Themajorityofpatients(75–80%)withnon-smallcell lungcancer(NSCLC)arediagnosedwithadvancedinoperabledisease resulting

• Peripheral targetspresentdifficultiesforpercutaneousimplantation

• Electromagnetic NavigationBronchoscopyofasingle6Fcatheter,implantedwith– CTbasedsegmentationoftheairway– Endobronchial Ultrasound– Fluoroscopicverification

• OneofthefirstdemonstrationsbyHarmsetal.in2006– 15Gy in3fractions(over5days)after50Gy external beam– CTbasedplanning– Catheterremaining inplace forthefractionatedtreatments

• CTverificationshowed<5mmvariationonsubsequentfractions

• Follow-uptrialoffeasibilityandsafetyin32patients– Clinical resultssuggestoptimaldosingneedsfurther

investigation

Harms,etal.Strahlenther Onkol 2006;182:108–11

Endobronchial US

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CanEM-GuidedHDRProvideanAlternativetoSABR?

RetrospectivestudyPatientsformerlytreatedwithSABR(n=10)

– Previouslytreatedto50GywithSABR– CT-visibleairwayadjacenttoGTV– GTVrangingfrom1.5ccto20cc

• Replanned usingsinglecatheterHDRtreatment• Planningconstraints

– 98%mindosetoGTV– Keep200%doselevelwithinoriginalSABRPTV

• PlannedwithEclipseBrachyVision (Acuros BV1.5.0)

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Fahimian,AAPM2017,Slide:30

Grid-basedBoltzmannTransportEquationSolver

43

43

TG

AcurosTG

DDD −

IncollaborationwithDr.MarianAxente

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Fahimian,AAPM2017,Slide:31

Dosimetric ComparisonofHDRAblationvs.SABRSABR EM-GuidedHDR

• Dosimetric charactristics ofHDRablationvs.SABR– Increasedheterogeneity inthePTV,andsteepergradients inthenormaltissue– IncreasedV100%/V50%ratios– IncreasedDmax/DPrescription ratios

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Fahimian,AAPM2017,Slide:32

ComparativeDosimetric AnalysisofHDRandSABR

OAR MedianOARDmaxReductionFactors

Heart 0.72

Aorta 0.39

SVC 0.45

Cord 0.29

• Fortargets<20cc,significant reductioninOARdoses

• Concurrentescalation ofdosetoGTVs(83%onaverage)receive>200%Rxdose

200%

Pinkham,etal.,Med.Phys.,42:6,2015,3595

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Fahimian,AAPM2017,Slide:33

LimitationinTargetSize

• Forsinglecatheter approaches,studysuggests dosimetric advantageforsmaller targets

• Optimalperformanceforforlung lesionslimited totumorsizes<20cc

• Potentialrolefortreatment ofmultiplemets andsalvagebrachytherapy

Pinkham,etal.,Med.Phys.,42:6,2015,3595

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Fahimian,AAPM2017,Slide:34

Discussion:LimitationsandChallenges

• Currentstudylimited tosingle catheterapproachesforlunglesions– Dose-shaping islimited– Planqualitydependent onimplantplacement andtargetsize

• Registration andplacement errorofcatheter– Catheterplacement should ideallybethroughcenterofmassandextend beyond

lesion

• Optimaldosingrequiresfurtherinvestigation– Construction ofablative doseregimens analogoustoSABRexperience

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Fahimian,AAPM2017,Slide:35

DevelopmentalAccess(Coring)Tool• Toolsareunderdevelopment toenable interstitial placement

throughcenterofmassandpassed thelesion• Workflowproposed

– Positionextendedworkingchannel (EWC)innearbyairway

– AdvanceEWCintoGTVusingmechanical action– Verifywithfluoro– Sendcompatible HDRcatheter intoEWC

Mechanicalaction:Advanceneedle intotissue,thencatheter,thenEWC

EWCCatheterNeedle

VerifywithFluoroPlanonCT

NeedleCatheter

EWC

Needle

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Fahimian,AAPM2017,Slide:36

DemonstrationofCoringTechnology

Video(CourtesyofCovidien)

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Fahimian,AAPM2017,Slide:37

PlacementAccuracyandRobustnessStudy

• Systemaccuracy:3mmforrigid simulatedlungmodel

• Depending onqualityofregistration, 5mmaccuracycanbeassumed

• Unlikeseeds,HDRislesssensitive topositioning– CT-basedplanningbasedinpost implant

image• Largervolumeofhealthylungparenchyma

willbeexposed tothehighestisodose levelsadjacenttotheHDRsource.

• Howeverevenwitha5mmerror isodoselevels(25%,50%,75%, and100%)comparedtoSABRdosimetric advantagesremain(i.e.VolHDR/VoLSABR<1)

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Fahimian,AAPM2017,Slide:38

OptimalDosingforHDRAblationofLungMets

• OptimaldosingforEM-GuidedHDRunknown,howeverdoseescalationforeseen• Percutaneousdata:

– ProspectivePhaseIItrial(Ricke,etal.),20Gy inasinglefractionfortumorsupto2.5cmindiameter

• EM-GuidedImplantation– Feasibilitytrials(Harms,etal.),15Gy in3fractionsinconjunctionwithexternalbeam

• ExperiencefromSABR,e.g.StanfordiSABR protocol(Loo,Diehn,etal.)

• BasedonexperiencefromSABRtrials,explorationofsizeandlocationdependentdoseescalationforHDRtechniqueswarranted

Peripheral Central<=10cc >10&<=30cc >30cc <=10cc >10&<=30cc >30cc

Rxdose(covering95%PTV)

25Gy in1fxn 50Gy in4fxns 54Gyin3fxns 40Gyin4fxns 50Gy in4fxns 60Gy in8fxns

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Fahimian,AAPM2017,Slide:39

Summary

• Returningtotheoriginalquestion:Wherearewe,andwherearewegoingwithclinicalapplicationsofbrachytherapy?– Ablativefocaltherapyimportantparadigmfortreatmentoftumors– Brachytherapyanidealcandidateforablativefocaltherapy– Advancednavigationforminimallyinvasiveimplantationiskeytomovingforward

• Opticalbronchoscopylimitedinaccesspassedsecondary/tertiarybronchi– Electromagneticnavigationenablesaccesspassedthelimitationsofopticalbronchoscopyto

peripherallungtumors– Feasibilityofimplantationdemonstrated

• InrelationtoSABR/SBRT, ablativebrachytherapyhasthepotentialenhanceddosimetryandreducedmotionmanagementcomplications– Dosimetric characteristicsincludessteeperfall-offofdoseandescalateddosestothetarget– Potentialroleasprimarytreatmentofsmalllesionsorinthesettingofsalvagetherapy– Numberofchallengesre

• Singlecatheterapproaches,doseshapingislimited,optimaltargetsize<20cc• Optimalablativedosingprimarysubjectoffutureclinicalinvestigation

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Fahimian,AAPM2017,Slide:40

Acknowledgements

Collaborators

• DanielPinkham,Ph.D.

• ArthurSung,M.D.• BillyLoo,M.D.,Ph.D.

• MichaelGensheimer,M.D.

• DavidSchultz,M.D.

• Maximilian Diehn,M.D.,Ph.D.• MarianAxente,Ph.D.

Covidien/Medtronic• ThomasCrowley

• JerryMcNamara

SpecialThanks

• AntonioDamato,Ph.D.

• MarkRivard,Ph.D.• William Song,Ph.D.


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