RecentAdvancesInBrachytherapy:UnconventionalApplicationsofBrachytherapy
59th AnnualNationalConferenceoftheAAPMAugust2,2017
BenjaminP.Fahimian,PhD,DABR*ClinicalAssistantProfessor,AssociateDirector,TherapeuticMedicalPhysicsResidency,BrachytherapyPhysicsLead,[email protected]*FinancialDisclosures:None
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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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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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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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StereotacticAblativeRadiotherapy(SABR/SBRT)
Advantages• Highlocalcontrolrate• Non-invasive• Accessanywhereinlung• DoseconformalityChallenges• Motionmanagement• Potential forgeometricalmiss• Substantial volumeoflungcanreceive lowerdoses• Airwayandlungcollapse, radiationpneumonitis, lungfibrosis,orvertebral
fracture
SABR
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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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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Image-GuidedPercutaneousTechniques
• Numberofsitesincludingliver,renal,lung,lymphnodes• Surveyofinterstitialimage-guidedHDRofinnerorgans(Bretschneider,etal.,2016)
Bretschneider,etal.,JournalofContemporaryBrachytherapy(2016/volume8/number3)
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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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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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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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Robotics-AssistedIntraoperativeApproaches
CurrentRespiratoryMedicineReviews,2011,Vol.7,No.5
• Laparoscopic robotassistedseedimplantation
• Coupledwithelectromagneticnavigationtogobeyondvideoassistedmethods
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OpticalBronchoscopyandEndoluminal Approaches
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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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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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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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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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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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Grid-basedBoltzmannTransportEquationSolver
43
43
TG
AcurosTG
DDD −
=Δ
IncollaborationwithDr.MarianAxente
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Dosimetric ComparisonofHDRAblationvs.SABRSABR EM-GuidedHDR
• Dosimetric charactristics ofHDRablationvs.SABR– Increasedheterogeneity inthePTV,andsteepergradients inthenormaltissue– IncreasedV100%/V50%ratios– IncreasedDmax/DPrescription ratios
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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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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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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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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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DemonstrationofCoringTechnology
Video(CourtesyofCovidien)
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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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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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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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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.