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EORTCAMAROStrial临床试验课件doc
EORTC_AMAROS_trial临床试验课件
Radiotherapyorsurgeryoftheaxi1Iaafterapositivesentinelnodeinbreastcancerpatients:
finalanalysisoftheEORTCAMAROStrial
BytheEORTCBreastCancerGroupandRadiationOncologyGroup
IncollaborationwiththeDutchBOOGGroupNameofpresenterandALMANACTrialists'GroupFunctionofpresenterEmielJ.T.Rutgers
TheNetherlandsCancerInstitute,Amsterdam
Clinicaltrialinformation:
NCT00014612BackgroundSentinelnodeSNbiopsyhasreplacedtheaxillarylymphnodedissectionALNDifcNOIfaxillarySN+AxSN+andindicationforaxillary
treatment,ALNDisstandardofcareALNDisassociatedwith
highratesofsideeffectsAxillaryradiotherapyAxRTprovides
good
regionalcontrolwithIimitedsideeffectsincNODeutschetal,IJROBP2008
Hoebersetal,Cancer2000
Fisheretal,NEJM2002
Louis-Sylvestreetal,JCO2004IIypothesis
AxillaryradiotherapyprovideslocalcontrolandsurvivalcomparabletoALNDwithfewersideeffectsinwomenwithapositiveaxillarySNEligibilityCriteriaInclusion
Exc1usionInvasivebreastcancerMulticentricdisease
0.5-5cmNeoadjuvantClinicallyNO
systemictreatmentBCTormastectomyPreviousaxillaryAnyagetreatmentInformedconsentPriormalignancyTrialdesign
AxSN+
AxSN+
ALND
ALND
cTl-2
SNB
R
R
NO
NO
AxRT
AxRT
AxSN-
AxSN-
Stratification:
institution
AdjuvantsystemictherapybychoiceObjectives
Primary:
Todemonstratenon-inferiorityinaxi1laryrecurrencerateSecondary:
1.TocompareoverallsurvivalOSanddisease-freesurvivalDFS
2.TocompareIymphedema,shouIderfunctionand
QualityofLifeQoLEndpointsandstatisticaldesign
Primary:
5-yearsaxillaryrecurrencefreerateNoninferiorityhypothesisdesign:
assumption:
ALND98%;AxRT96%one-sidedlog-rank;alpha0.05;power80%52eventsneeded
Secondary:
Efficacy:
OSandDFSSafety:
shoulderfunction,1ymphedema,QoLAxRTTiming:
Start12weeksafterSNBExtent:
levelI+II+III+medialSCDose&schedule:
25x2GyorequivalentQualitycontrol:
dummyrun
Hurkmansetal,RadiotherOncol2003ALNDTiming:
12weeksafterSNBExtent:
LevelI+IImandatory
LeveIIIIoptionalAdditionalAxRT:
N4positivenodesRESULTS
Accrualofstudy10981
Theoretical
4,500
Study
4,000
Expectedtoday:
4766
Observedtoday:
4813
3,500
Expectedly:
298
3,000
Observedly:
205
Expected2y:
894
2,500
Observed2y:
560
2,000
ExpectedQ4+Q5:
262
ObservedQ4+Q5:
159
1,500
ExpectedQ8+Q9:
298
ObservedQ8+Q9:
205
1,000
500
0
23/09/0222/09/0422/09/0621/09/0821/09/1020/09/12
Timeyearsfromstart
2001-2010:
4806patientsenrolled4766required
NumberofpatientsAllincludedpatients
n4806
SNBnotidentifiedSNBother
SNBnegativeAxSNBpositive
N1322.7%N1202.5%
N313165.1%N142529.7%
Intent-to-treatiII
ALNDAxRT
samp1e
N744N681
lOnoteligible8
Excluded
Excluded
85ITConlybeforeamendment67
N146
N146
51Non-compliance71
ALNDPerProtocolPP
AxRT
N598sample
N535EfficacyanalysesOSandDFS:
1.perprotocolPP
2.byintent-to-treatITTBothPPandITTanalysesgavesimilarresults
Intent~to~treatanalysisreportedTreatmentcompliance
ALNDAxRT
744pts681pts
Randomizedtreatment63184.8%
59086.6%
Bothtreatments
415.5%
10.1%
Cross-over
466.2%6810.0%
Noaxillarytreatment
243.2%
223.2%Baselineclinical
ALNDAxRT
744pts681pts
MedianageQ1-Q3
5648-645548-63
Menopausalstage
38.1%42.5%
pre-menopausal
post-menopausal
57.7%54.5%
MediantumorsizeQ1-Q3
17mm13-2218mm13-23
Grade24.1%22.6%
1
47.8%45.7%
2
25.8%29.4%
3
59.2%
Pre-operativeultrasoundaxilla61.5%Baselinetreatment
ALNDAxRT
744pts681pts
Breastsurgery
81.9%
BCS81.8%
17.1%
Mastectomy17.8%
Systemictreatment
61.3%
chemotherapy60.9%
hormonaltherapy77.1%
78.6%
immunotherapy6.4%
6.0%nosystemictreatment9.4%
9.0%
RTbreast/chestwa1184.8%87.7%SNresults
ALNDAxRT
744pts681pts
MediannumberofSN
21-321-3
removedQ1-Q3
SizeofmetastasesinSN
inacroinetastases59.4%61.5%
micrometastases28.9%28.6%
ITC11.7%9.8%
Straveretal,AnnSurgOncol2010ALNDresults
ALND
744pts
MediannumberofallnodesremovedQ1-Q31512-20
NumberofadditionalpositivenodesbesidesSN
067.1%
25.0%
1-3
7.8%
N4Axillaryrecurrencerate5-yearsaxiIIaryrecurrencerate:
ALND0.43%4/744events0.54%
AxRT1.19%7/681events1.03%
hypothesis2%
Consequence:
plannedcomparisonisunderpoweredAxi1laryrecurrencerateSN-
5-yearsaxillaryrecurrencerate:
0.72%25/3131events0.80%Disease-freesurvival
HR:
1.17;95%CI:
0.93-1.51
P0.180verallsurvival
Breastcancer
specificdeaths:
ALND:
537.1%
AxRT:
547.9%
HR:
1.17;95%CI:
0.85-1.62
P0.34Resultssideeffects
50-70%formcomplianceatalltimepointsLymphedemaofthearm
Measured:
1,3and5yearsaftertreatment
Items:
ClinicalobservationTreatmentforedema:
-sleevegarment
-lymphdrainagetherapy
一compressiontherapyLymphedema:
clinicalobservation
and/ortreatment
40.0%
%
29.8%
21.7%
16.7%
13.6%
P0.0001P0.0001P0.0001
Yearsafterrandomization
24Lymphedema:
cIinicalobservation
27.8%
%
23.2%
22.5%
15.1%
13.8%
10.8%
P0.0001P0.0027P0.0001
YearsafterrandomizationLymphedema:
treatment
31.5%
%
16.8%
16.1%
9.7%
6.6%
P0.0001P0.0001P0.0001
YearsafterrandomizationShoulderfunction
Measured:
1,3and5yearsaftertreatment
180°
Items:
90°
1.Ante/retroversion
20°-40°
2.Ab/adductionShoulderfunction
Results:
Nosignificantdifferencesinall4excursions
TrendtowardsimpairedmovementafterAxRTinfirstyearon1y
Relativemovement:
Excursiontreatedarm
Excursionuntreatedarm
Multivariate
ANOVA:
p0.29
YearsafterrandomizationQualityofLife
Measured:
1,2,3and5yearsaftertreatment
Questionnaire:
1.EORTC-QLQ-C3Ocorequestionnaireversion3
2.QLQ-BR23breastcancermoduIe
Results:
Nosignificantdifferences
Selectedscales:
armsymptoms,pain&bodyimageQualityofLife
Results:
Trendtowardsmoredifficulties
tomovethearmafterART
ALND
AxRT
Trendtowardsmoreswelling
afterALND
ALNDAxRTDiscussionTheaxillaryrecurrenceratewasfarbe1ow
hypothesized,hence,thetrialwasunderpoweredAxRT:
level
I+II+III+SCImbalanceinAxSN+patientsperarm
-independentcommittee:
noexplanationIndicationforaxillarytreatment?
Conclusion
BothALNDandAxRTprovideexceIlentandcomparablelocoregionalcontrolinAxSN+patients
SignificantlylesslymphedemaafterAxRTAxRTcanbeconsideredstandardAcknowledgement
Weareverygratefu1toal1the
patientswhoparticipatedinthistrialAcknowledgement
Researchfellows:
MilaDonker,MariekeStraver,PhilipMeijnen
Principalinvestigators:
CornellsvandeVelde,RobertManseI,
GeertJanvanTienhoven
EORTCheadquarters:
NicoleDuez,LeenSlaets,Jan
Bogaerts,CarloMessina,CorneelCoens,theIDMCEORTC
BreastCancerGroup
EORTCRadiationOncologyGroup
DutchBOOGGroup
A1AIANACTrialists,GroupParticipatinginstitutes
Arnhem,ZIIRijnstate,theNetherlandsDenHaag,BronovoZII,theNetherlands
Hardewijk,StJansdalZH,theNetherlandsGroningen,UMCG,theNetherlands
Hardenberg,R?
pcke-ZweersZH,theNetherlands
Amsterdam,NKI-AVL,theNetherlands
DenHaag,HagaZH,theNetherlands
Firenze,UnivHospCareggi,Italy
Cardiff,UnivHospWales,UnitedKingdom
Drachten,ZHNijSmelIinghe,theNetherlands
Manchester,ManchesterUnivHosp,United
Utrecht,Diakonessenhuis,theNetherlands
Kingdom
Leiden,LUMC,theNetherlands
Amsterdam,AMC,theNetherlandsTorino,SanGiovanni
BattistaHosp,Italy
DenHaag,MCHWesteinde,theNetherlandsApe!
doom,GeIreZH,theNetherlands
Ljubljana,UnivHosp,SloveniaEindhoven,CatharinaZH,theNetherlands
Lille,CentreOscarLambret,FranceAmstelveen,Amstelland
ZH,theNetherIands
Delft,RdeGraafGII,theNetherlands
Geneva,HospCantonal,Swiss
Haarlem,KennemerGH,theNetherlands
Nijmegen,UMCStRadbout,theNetherlands
Istanbul,MarmaraUnivHosp,Turkey
Grenoble,CHUGGrenoble,France
Haifa,RambamMedCenter,Israe1
Gdansk,MedicalUniv,Poland
Roermond,LaurentiusZH,theNetherlandsParis,InstCurie,FranceThankyouFormcompIiance
%validformsreceived
1year2years3years5years
lymphedema65.3-61.968.6
Shoulderfunction59.6-56.764.0
QualityofLife64.949.662.566.OSNBConduct:
-UseofradiocolloidmandatoryDefinitionof“positiveaxilIarySN”AxSN+:
-Atleast1positivesentinelnodeinaxilla
-Positive:
Macrometastases/micrometastases/ITC^Qualitycontrol:
-LearningphasewithN30SNBrequired
*ITCon1yexcludedfromAxSN+groupsinceApri12008Distantmetastasisfreesurvival
HR:
1.27;95%CI:
0.96-1.68
P0.0980
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