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SanAntonioBreastCancerSymposium

-RadiationTherapyUpdates-

TracySherertz,MDUCSFRadiationOncology

RadiotherapyAbstracts

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Impactofradiotherapyoncomplicationsandpatient-reportedsatisfactionwithbreastreconstruction:Findingsfromthe

prospectivemulticenterMROCstudy

*OralPresentation*

Jagsi R,Momoh AO,QiJ,HamillJB,Billig J,KimHM,Pusic AL,WilkinsEGUniversityofMichigan,AnnArbor,MI;MemorialSloanKetteringCancer

Center,NewYork,NY

ImpactofRTonReconstructionOutcomes

• Prospective,multicentercohortstudy(MastectomyReconstructionOutcomesConsortium,MROC,fundedbyNCI)

• 11institutions,2012-15• Responsesfrom553radiatedand1461non-radiatedpts whoreceived

differentapproachestoreconstruction

• Primaryvariablesofinterestwere– developmentofanybreastcomplications(e.g.hematoma,woundinfection)

byoneyearpost-reconstruction– satisfactionmeasuredwiththevalidatedBREAST-Qinstrument.

Jagsi etalSABCS2016

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ImpactofRTonReconstructionOutcomes

• Mixed-effectsregressionmodelsassessedimpactofreconstructiontypeandRTontheoutcomesofinterest

• Covariateadjustmentincluded:• reconstructiontiming• age• extentofdisease• bilateralvs unilateraltreatment• chemotherapyreceipt• nodalmanagement• BMI• smoking

Jagsi etalSABCS2016

• diabetes• race• ethnicity• education• employment• income• maritalstatus• hospitalsite

• Medianage:49

• Bilateralmastectomyreceivedby45.6%ofradiatedand53.3%ofnon-radiatedpts (p=0.002)

• Autologousreconstructionmorecommonlyreceivedbyradiatedpts (38.3%vs25.1%,p<0.001)

• Immediatereconstructionwaslesscommoninradiatedpts (82.6%vs 95.6%,p<0.001)

• Byoneyear,atleastonecomplicationoccurredin– 28.8%ofradiatedpts (30.8%ofimplantpts and25.5%ofautologouspts)– 22.3%ofnon-radiatedpts (20.4%ofimplantpts and28.1%ofautologouspts)

• At2yrs,acomplicationhadoccurredin34.1%of331radiatedpts vs 22.5%of946non-radiatedpts

ImpactofRTonReconstructionOutcomes:Results

Jagsi etalSABCS2016

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• Onmultivariableanalysis,predictorsofcomplicationsat1year:– immediatereconstruction– bilateraltreatment– higherBMI

• RTeffectdifferedbyreconstructiontype– RTwasassociatedwith2.1(95%CI=1.45,3.10)timeshigheroddsof

complicationinimplantpts– Nodifferenceinautologouspts (OR=1.3,95%CI=0.76,2.09)

ImpactofRTonReconstructionOutcomes:Results

Jagsi etalSABCS2016

• RTeffectonpatientoutcomesalsodifferedbyreconstructiontypes

• Inimplant pts,adjustedmeanBREAST-Qsatisfactionwithbreastscoresweresignificantlylowerinradiatedpts thaninnon-radiatedpts (51.5vs.58.0at1year,p<.001;48.9vs.59.8at2years,p<.001)

• Whilesatisfactioninautologous pts didnotdifferbyradiation(61.3inradiatedvs.63.5innon-radiatedat1year;62.8vs.65.8at2years)

ImpactofRTonReconstructionOutcomes:Results

Jagsi etalSABCS2016

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• Conclusions:– Inthelargestprospectivemulticenterstudyofoutcomesofbreastreconstructionto

date,autologousreconstructionappearstoyieldsuperiorpatient-reportedoutcomesandlowerriskofcomplicationsthanimplant-basedapproachesamongpatientsreceivingPMRT

• Validatescommonperceptionthatpatientsatisfactionisimprovedwithautologousvs implant-basedreconstruction

ImpactofRTonReconstructionOutcomes

Jagsi etalSABCS2016

AretherepatientswithT1-T2,node-negativebreastcancerwhoareathighriskforlocoregional recurrence?

Mamtani A,Patil S,Stempel M,MorrowMBreastService,MemorialSloanKetteringCancerCenter,NewYork,NY

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T1-T2N0patientsathighriskforlocoregional recurrence?

• Indicationsforpost-mastectomyradiotherapy(PMRT)inT1-T2,nodenegative(N0)breastcancerpts with“high-risk”featuresarecontroversialbasedonlackofconsensusastowhatconstitutes“high-risk”,andvariableresultsofsmallretrospectivestudies

• EORTC22922andMA20trialsreportedimproved10-yeardisease-freesurvivalwithnodalirradiationincludedhigh-riskN0patientsbutthesepatientswerenotanalyzedseparatelyanddidnotreceivemodernsystemictherapy

• Question:Whatisthelong-termlocoregional controlinT1-T2N0patientswithhigh-riskfeaturesundergoingmastectomyinthecontemporaryera?

Mamtani etalSABCS2016

T1-T2N0patientsathighriskforlocoregional recurrence?

• Methods:Retrospectivelyreviewedpts withT1-T2N0breastcancerwith≥1high-riskfeaturetreatedwithmastectomyfrom2006-2011– High-riskfeaturesweredefinedas

• age<40years• multifocal/multicentric disease• lymphovascular invasion(LVI)• medialorcentraltumorlocation

• PrimaryoutcomeofinterestwasLRR

Mamtani etalSABCS2016

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T1-T2N0patientsathighriskforlocoregional recurrence?

• 672pts– 187(28%)had1riskfactor:

• 21(3%)wereage<40years• 132(20%)weremultifocal/multicentric• 34(5%)hadLVI

– 449(67%)patientshad≥2high-riskfeatures

Mamtani etalSABCS2016

-PMRTwasreceivedby15(2%)pts(excluded)

T1-T2N0patientsathighriskforlocoregional recurrence?

• SLNbx alonein98%pts• Median4LNsretrieved(range1-15).• Adjuvantsystemictherapyreceivedby86%pts• Medianf/u5.6years

– LRRratewas4.7%(n=31)– Majority(55%)ofeventsinvolvingthechestwall– IncreasingtumorsizewasassociatedwithLRR(HR1.70,95%CI1.26–2.29,p=0.006)– Age,histology,grade,subtype,LVI,multifocality/multicentricity,andtumorlocation

werenot(allp>0.05)

Mamtani etalSABCS2016

-AlthoughLRRincreasedfrom3.8% to9.4%with1vs.≥4high-riskfeatures,acomparisonof1vs.2vs.3vs.≥4riskfactorswasnotsignificantbyKaplan-Meierestimation(p=0.54).

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T1-T2N0patientsathighriskforlocoregional recurrence?

• Conclusions:– AlowLRRrateof4.7%wasseeninthislargeunselectedcohortofT1-T2N0

cancerswith"high-risk"featurestreatedbymastectomyandsystemictherapywithoutPMRT

– Whileincreasingtumorsizewaspredictive,otherfeaturesdidnotconferahigherriskofLRReitherindependentlyortogether,anddonotbythemselvesmandatetheuseofPMRTinthispopulation.

Mamtani etalSABCS2016

Hypofractionated nodalradiotherapy(RT)didnotincreasearmmorbiditycomparedtoconventionalfractionatednodalRT

LeongN,TruongP,Tankel K,KwanW,WeirL,Olivotto ISaskatchewanCancerAgencyAllanBlairCancerCentre,Regina,SK,Canada;BCCancerAgencyVancouverIslandCentre,Victoria,BC,Canada;AlbertaHealthServicesTomBakerCancerCentre,

Calgary,AB,Canada;BCCancerAgencyFraserValleyCentre,Surrey,BC,Canada;BCCancerAgencyVancouverCentre,Vancouver,BC,Canada;AlbertaHealthServices

CrossCancerInstitute,Edmonton,AB,Canada

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Hypofractionated RNI

• Regionalnodalirradiationcancontributetoadversearmsymptomsandlymphedema

• Hypofractionation (HF),definedas>2Gy/fraction,improvesconveniencebutwhetheritincreasesarmmorbidityisunclear

• Canadianstudyevaluatespatient-reportedarmsymptomsinwomentreatedwithHFcomparedtoconventionalfractionation(CF)RT(definedas≤2Gy/fraction)

LeongetalSABCS2016

Hypofractionated RNI

• Pts whoreceived3DCTnodalRTforpT1-3pN0-2M0breastcancerfrom2007-2009inBritishColumbiaand2008– 2010inAlberta,Canada

• Patientsmailedanexplanationletterandanexternallyvalidated,Self-reportedArmSymptomScale(SASS)survey

• TheSASSincluded8questionsaboutarmsymptoms,withresponsesona5-pointLikert scaleregardingarm/handproblems(numbness,pain,stiffness,immobilityandswelling),and5questionsrelatedtoactivitiesofdailyliving(ADL)

• Clinicopathologic characteristicsandSASSscoreswerecomparedbetweenHFvs.CFnodalRTcohorts

LeongetalSABCS2016

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Hypofractionated RNI

• 708pts (non-metastatic,non-recurrent)• 406(57%)patientsreceivedHFRT- 40Gy/15fx and45Gy/20fx• 302(43%)receivedCFRT- 45Gy/25fx,48-50Gy/25fx,and50.4Gy/28fx• Boostdeliveredin22%ofsubjectsinbothgroups• MediantimeintervalsinceRTcompletion:5.67years• Meanageatdiagnosis:59.0inHFvs 53.8yearsinCF cohorts(p<0.001)• Mean#positive(n=3)andexcised(n=12)LNssimilarbetweencohorts(p=0.44)• PrimarytumorsizewasmarginallylargerintheCFgroup(2.8vs.2.7cm,p=0.03)• 42.9%ofpatientsweretreatedwithpartialmastectomywithnosignificant

differenceinfractionation(p=0.54)• Overall,602(75.3%)patientsreceivedchemotherapy• AtrendtowardincreaseduseofCFafterchemotherapywasobserved(78.8%vs.

72.7%,p=0.07)

LeongetalSABCS2016

Hypofractionated RNI

• Results:– CFgrouphadahigherprevalenceofself-reportedsymptoms,includingshoulder

stiffness(p=0.04),troublemovingthearm(p=0.02),andabilitytoreachoverhead(p<0.01)

– Nodifferenceinself-reportedarmswellingbetweenthetwogroups(p=0.57)

• Conclusions:– Hypofractionated nodalRTwasnotassociatedwithanincreaseinpatient-reportedarm

symptomsordisabilitycomparedtoconventionalfractionatednodalRT.– SubjectstreatedwithCFRTreportedmoredisabilityincertainaspectsofarmand

shoulderfunction– Thesedatasupporttheuseofshorterfractionationwhentheregionallymphnodesare

partofthetherapeutictarget

LeongetalSABCS2016

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Theuseofhypofractionated radiotherapyforthetreatmentofwomenwithearlybreastcancerintheBrazilianpublichealthsystemmayincreaseaccesstotreatment:Costeffectiveness

andbudgetimpactanalyses

AndradeTRdM,Nazário ACP,FonsecaMCMFederalUniversityofSãoPaulo,SãoPaulo,Brazil

Costeffectivenessofhypofractionated RTinBrazil

• OBJECTIVES:– Toevaluatethecosteffectivenessandeconomicimpactofincreasingtheuseofhypofractionated RTforthe

treatmentofwomenolderthan50years,withearlybreastcancer(stagesIandII)withintheBrazilianNationalHealthSystem(SUS)

• METHODS:– Authorsbuilta‘cost-effectiveness’MarkovmodelinExcelwhichquantifiesthecostandtheamountof

photonbeamslinearacceleratortimeusedforthetreatmentofpatientsusinghypofractionated(2.67Gy/fraction)orconventional(2Gy/fraction) over5yr period

• Effectivenessmeasuredas#hourssavedusinghypofractionated vs conventionalRT– CostsconsideredincludedRTplanning,physicsQA,andtheuseoflinearaccelerator

• Authorsdeterminedthe#ofwomen>50yo withStage1-2breastCAtreatedwithadjuvantRTin2013and2014,andthenprojectedthesepopulationsto2016to2020.

• Authorsconsideredayearlyincreaseof20%intheadoptionofhypofractionated RTfortheyears2016to2019(201620%;201740%;201860%;201980%and202090%)

• Thetreatmentfractiontimewassetas15minutes

AndradeetalSABCS2016

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Costeffectivenessofhypofractionated RTinBrazil

• RESULTS:– Useofhypofractionated RTat5yearswasabletodecreasethenumberofhoursof

treatment(-21,835hours)andthetotalcostoftreatment(-$11,790,229.64)

• Annualincrementalimpactwouldbeof-$243,202.65,-$490,294.13,-$741,085.61,-$995,388.73and-$1,127,712.81providing3,378,6.810,10,294,13,826and15,664freehoursofthelinearacceleratorfortheyears2016,2017,2018,2019and2020,respectively

• The“linac-free”hoursmayallow613,1,380,2,306,3,392and4,010additionalpatientstohaveaccesstobreastCAtreatmentduring2016to2020respectively.

AndradeetalSABCS2016

Costeffectivenessofhypofractionated RTinBrazil

• CONCLUSIONS:– Consideringtheconditionsproposedinthismodel,increasinguseof

hypofractionation totreatwomenolderthan50yearsisexpectedtoincreasethesystemefficiency,savemoneyandimproveaccesstotreatmentformorepatients

Manyhealthcaresystemsinterestedintheseanalysestoencouragepolicychange

AndradeetalSABCS2016

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OngoingRadiotherapyTrials

NRGoncology/NSABPB-51/RTOG1304:AphaseIIIsuperiorityclinicaltrialdesignedtodetermineifchestwallandregionalnodalradiotherapy(CWRNRT)post

mastectomy(Mx)ortheadditionofRNRTtobreastRTpostbreast-conservingsurgery(BCS)willreduceinvasivecancereventsinpatients(pts)withpositiveaxillary(Ax)nodesandconverttoypN0afterneoadjuvant chemotherapy(NC)

Mamounas EP,Bandos H,WhiteJR,JulianTB,KhanAJ,Shaitelman SF,TorresMA,Vicini FA,Ganz PA,McCloskeySA,PaikS,GuptaN,LiXA,DiCostanzoDJ,Curran,Jr WJ,Wolmark NNRGOncology/NSABP(NSABPLegacyTrialsAreNowPartoftheNRGOncologyPortfolio),Pittsburgh,PA;UFHealth

CancerCenteratOrlandoHealth,Orlando,FL;UniversityofPittsburgh,Pittsburgh,PA;NRGOncology/RTOG,Philadelphia,PA;OhioStateUniversity,Columbus,OH;AlleghenyHealthNetworkCancerInstitute,Pittsburgh,PA;RutgersCancerInstituteofNewJersey,NewBrunswick,NJ;UniversityofTexasMDAndersonCancerCenter,Houston,TX;Winship CancerInstituteEmoryUniversity,Atlanta,GA;St.JosephMercyOakland,Pontiac,MI;

UniversityofCaliforniaatLosAngeles,LosAngeles,CA;SeveranceBiomedicalSci Inst andYonsei Univ CollegeofMedicine,Seoul,Korea;MedicalCollegeofWisconsin,Milwaukee,WI;TheOhioStateUniversityWexner MedicalCenter,Columbus,OH

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• DecisionsontheuseofRNIaregenerallybasedonthepathologicalnodalstatusatthetimeofsurgicalstaging

• Neoadjuvant chemohasbeenshowntodown-sizelargeprimarytumorsanddown-stageinvolvedaxillarynodes

NSABP51

• Severalrandomizedandnon-randomizedstudieshaveshownthatachievingapathCRinthebreastandLNsleadstoimprovedlocalregionalcontrol

[datafromNSABP18and27]

• PhaseIIIrandomizedpost-neoadjuvant chemotherapytrialevaluatesifCWRNRTpostMx orwholebreastirradiation(WBI)withRNRTafterBCSsignificantlyreducestheinvasivebreastcancerrecurrence-freeinterval(IBC-RFI)rateinptspresentingwithpositiveAxnodesthatarepathologicallynegativeafterNC.– SecondaryaimsareOS,LRRFI,DRFI,andsecondprimarycancer,aswellas

comparingRTeffectoncosmesis inreconstructedMx pts.

• CorrelativesciencestudiesexamineRTeffectbytumorsubtype,molecularoutcomepredictorsforresidualdiseasepts,andpredictorsforthedegreeofreductioninloco-regionalrecurrence.

NSABP51

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NSABP51

• 1636pts tobeenrolledover5yrs withdefinitiveanalysisat7.5yr

• Accrualasof6/13/16is356

Arandomizedtrialof15fractionvs 25fractionpencilbeamscanningprotonradiotherapyaftermastectomyinpatients

requiringregionalnodalirradiation

MutterRW,ParkSS,Hieken TJ,VargasCE,Mei-YinPC,KathrynRJ,HectorVR,KimberlyCS,ElizabethYS,DanielVWMayoClinic,Rochester,MN

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Hypofractionated ProtonPMRT

• Background:– Pencilbeamscanningprotontherapyisattractiveduetopotentialtoreducethedosetotheheartandlungscomparedwithtraditionalphotontechniqueswhileimprovingconformality andlimitingskindosecomparedwithpassivelyscannedprotontherapy

– Theoptimaldoseandfractionationforpencil-beamscanningprotontherapyremainsunknown

Hypofractionated ProtonPMRT

• TrialDesign:– multi-centeropenlabelphaseIIrandomizedcontrolledtrialto

determinethesafetyof15fractionvs 25fractionpencilbeamscanningprotonradiotherapyaftermastectomyinpatientsrequiringRNI

– Patients≥18yearswithprimary,non-inflammatoryinvasivebreastcancerwhohaveundergonemastectomywithorwithoutimmediatereconstructionandchestwallandregionalnodalirradiationplanned

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Hypofractionated ProtonPMRT

• Aims:– Determinewhetherthe24monthcomplicationrate(definedasgrade3or

greaterlateadverseevents,andunplannedsurgicalinterventioninpatientswhoundergomastectomywithreconstruction)of15fractionchestwallandregionalnodepencilbeamscanningprotonradiotherapyisacceptablerelativetoa25fractionregimen

• Statisticalmethods:Thestudyisdesignedasanon-inferiority/superioritydesign

• Accrual:ThestudyopenedinJune2016.Fiveofaplannedeighty-twopatientshavebeenaccruedtodate

Thankyou!