+ All Categories
Home > Documents > Internal mammary node irradiaon in early node … mammary node irradiaon in early node-posive ......

Internal mammary node irradiaon in early node … mammary node irradiaon in early node-posive ......

Date post: 29-Jun-2018
Category:
Upload: buinhu
View: 267 times
Download: 0 times
Share this document with a friend
28
Internal mammary node irradia.on in early node-posi.ve breast cancer Lise B J Thorsen, MD, PhD Department of Oncology, Aarhus University Hospital May 17th 2017
Transcript
Page 1: Internal mammary node irradiaon in early node … mammary node irradiaon in early node-posive ... breast cancer are offered internal mammary node irradiaon as part ... , Radiother

Internalmammarynodeirradia.onin

earlynode-posi.vebreastcancer

LiseBJThorsen,MD,PhDDepartmentofOncology,AarhusUniversityHospital

May17th2017

Page 2: Internal mammary node irradiaon in early node … mammary node irradiaon in early node-posive ... breast cancer are offered internal mammary node irradiaon as part ... , Radiother

Breastcancer

•  Womenofthewesternworld•  Life-Hmerisk>10%•  2012:500,000newcasesinEurope

•  Origininbreast•  Spreadtoregionalnodes•  Spreadtodistantsites

Page 3: Internal mammary node irradiaon in early node … mammary node irradiaon in early node-posive ... breast cancer are offered internal mammary node irradiaon as part ... , Radiother

Breastcancertreatment

•  Loco-regional–  Surgery

•  Mastectomy•  Breastconservingsurgery/lumpectomy

•  N+:Axillarynoderemoval–  Radiotherapy

•  Systemictreatment–  Chemotherapy–  Endocrinetreatment–  Targetedtreatment

Page 4: Internal mammary node irradiaon in early node … mammary node irradiaon in early node-posive ... breast cancer are offered internal mammary node irradiaon as part ... , Radiother

Internalmammarynodes

•  IMNmetastases–  MoreoXenw.large/medialtumor/

axillaryN+disease•  IMNmetastases:apoorprognosHcsign•  10-yearsurvival

•  IMNN0&AxN0:76%•  IMNN+&AxN+:25%

•  1960’s:Surgicalrandomizedcontrolledtrials:nobeneficialeffectofIMNdissecHon

•  RetrospecHveanalysesofinternalmammarynodeirradiaHon:noconclusiveresults

Page 5: Internal mammary node irradiaon in early node … mammary node irradiaon in early node-posive ... breast cancer are offered internal mammary node irradiaon as part ... , Radiother

DBCG

•  DanishBreastCancerGroup(DBCG)iniHated1976

•  NaHonalguidelinesondiagnosis&treatmentofbreastcancer

•  NaHonalDBCGregistrysince1977– Aim:AllDanishpaHentswithprimaryinvasivebreastcancer

–  InformaHon:Demography,disease,treatment,follow-up

•  NaHonalclinicaltrials

Page 6: Internal mammary node irradiaon in early node … mammary node irradiaon in early node-posive ... breast cancer are offered internal mammary node irradiaon as part ... , Radiother

DBCG1980’s

Internalmammarynode(IMN)RTforallN+breastcancer

paHents

1987

2000Anthracyclines

?Rightside+IMNRTLeXsideNoIMN-RT

2003

NoevidenceforeffectofIMN-RT

LeXsideheartdosehigh

Cuzick,etal.CancerTreatRep,1987

2003

Overallsurvival

Page 7: Internal mammary node irradiaon in early node … mammary node irradiaon in early node-posive ... breast cancer are offered internal mammary node irradiaon as part ... , Radiother

DBCG

Rightside+IMNRT

↑Breastcancerdeath

↓Heartdeath

Le@sideNoIMN-RT

NaHon-wideprospecHvepopulaHonbased

cohortstudy

Page 8: Internal mammary node irradiaon in early node … mammary node irradiaon in early node-posive ... breast cancer are offered internal mammary node irradiaon as part ... , Radiother

Hypotheses

InpaHentswithearlynodeposiHvebreastcancer,IMN-RT•  Improvesoverallsurvival•  Reducesbreastcancermortality•  Reducestheriskofdistantrecurrence

Page 9: Internal mammary node irradiaon in early node … mammary node irradiaon in early node-posive ... breast cancer are offered internal mammary node irradiaon as part ... , Radiother

StudypopulaHon

•  Inclusion:– TreatedwithstandardRT[2003–2007]– UnilateralearlyBC– OneormoremacrometastaHcaxillarylymphnodes

– StageII-III– Nopriormalignancies– Age<70years

Page 10: Internal mammary node irradiaon in early node … mammary node irradiaon in early node-posive ... breast cancer are offered internal mammary node irradiaon as part ... , Radiother

Materialsandmethods

Data-sources•  DBCGregistry•  TheDanishCivilRegistraHonsystem(CPR)•  Registryoncausesofdeath(COD)•  Hospitalrecords•  Treatment-planningsystems•  InformaHonfromgeneralpracHHoners

Page 11: Internal mammary node irradiaon in early node … mammary node irradiaon in early node-posive ... breast cancer are offered internal mammary node irradiaon as part ... , Radiother

DBCG-IMN:Design

Right-sidedbreastcancer(n=1492)

LeX-sidedbreastcancer(n=1597)

Inclusioncriterianotmet(n=55)

Eligible(n=3089)

Assessedforeligibility(n=3377)•  Registry:Early-stageN+breastcancer

ValidaHonofregistrydata(n=3322)•  Consistencyonhistopathology+adjuvanttreatment•  MissingdataacquiredfrompaHentfiles Inclusioncriteria

notmet(n=233)

Ineligible nNoornon-standardRT 134RecurrencebeforeRT 34Micrometastases 33Stage4diseaseatdiagnosis 38Inoperable 24Priormalignancy 21Bilateralcancer 4Total 288

Page 12: Internal mammary node irradiaon in early node … mammary node irradiaon in early node-posive ... breast cancer are offered internal mammary node irradiaon as part ... , Radiother

PaHentandtumorcharacterisHcsIMNRT(n=1492) NoIMNRT(n=1597)

Medianage(range) 56(22-70) 57(27-70)

Pre-menopausal 612(41%) 649(41%)

EstrogenreceptorposiHve(%) 1207(81%) 1279(80%)

InvasiveductalcarcinomaInvasivelobularcarcinomaOther

1311(88%)135(9%)46(3%)

1356(85%)164(10%)77(5%)

GradeIGradeIIGradeIII

353(24%)715(48%)416(28%)

384(24%)747(47%)462(29%)

pT1pT2pT3

625(42%)773(52%)92(6%)

653(41%)836(52%)106(4%)

pN1pN2pN3

868(58%)401(27%)223(15%)

950(60%)417(26%)230(14%)

LateralMedial/central

907(61%)582(39%)

950(60%)644(40%)

Page 13: Internal mammary node irradiaon in early node … mammary node irradiaon in early node-posive ... breast cancer are offered internal mammary node irradiaon as part ... , Radiother

DBCG-IMN:Treatment

IMNRT(n=1492) NoIMNRT(n=1597)

Radiotherapy:48Gy/24FIMN-RT(%)AxillarylevelII-III-IV(%)AxillarylevelI-II-III-IV(%)BoostaXerBCS(%)

1437(97%)1219(82%)273(18%)192(13%)

161(10%)1301(82%)296(18%)192(12%)

TypeofsurgeryMastectomy+AC(%)Breastconserving+AC(%)

962(65%)530(35%)

1054(66%)543(34%)

SystemictreatmentEndocrinetherapy(%)Chemotherapy(%)Endocrine+chemotherapy(%)

702(47%)276(18%)514(35%)

745(47%)310(19%)542(34%)

Page 14: Internal mammary node irradiaon in early node … mammary node irradiaon in early node-posive ... breast cancer are offered internal mammary node irradiaon as part ... , Radiother

DBCG-IMN:Follow-up

•  Follow-upevery6monthsfor5years,thenonceayearunHl10years•  Dateandsiteofrecurrence•  Contralateralbreastcancer•  Othermalignantdisease•  Deathandcauseofdeath

Page 15: Internal mammary node irradiaon in early node … mammary node irradiaon in early node-posive ... breast cancer are offered internal mammary node irradiaon as part ... , Radiother

Results

PaLernofrecurrenceMedianFU=8.0years

IMNRT(n=1492)

NoIMNRT(n=1597)

Localrecurrence

29(1.9%) 21(1.3%)

Regionallymphnoderecurrence

10(0.7%) 15(0.9%)

Contralateralbreastcancer

39(2.6%) 36(2.3%)

Page 16: Internal mammary node irradiaon in early node … mammary node irradiaon in early node-posive ... breast cancer are offered internal mammary node irradiaon as part ... , Radiother

010

2030

40

Cumulativeincide

nce(%)

Distantrecurrence

1586 1401 1229 1075 500NoIMNRT1485 1322 1193 1043 521IMNRT

Atrisk

0 1 2 3 4 5 6 7 8

Yearssinceradiotherapy

Distantrecurrence

29.7%27.4%AdjustedHR:0.89(0.78;1.01)P=0.07

Difference:2.3%

Events AllIMNRT 417 1492NoIMNRT 478 1597

No.AtriskIMNRTNoIMNRT

Page 17: Internal mammary node irradiaon in early node … mammary node irradiaon in early node-posive ... breast cancer are offered internal mammary node irradiaon as part ... , Radiother

Breastcancermortality

CauseofdeathMedianFU=8yrs

IMNRT(n=1492)

NoIMNRT(n=1597)

Breastcancer 329 400Cardiovascular 9 9Othermalignancy 26 39Other 21 32Unknown 0 3

Page 18: Internal mammary node irradiaon in early node … mammary node irradiaon in early node-posive ... breast cancer are offered internal mammary node irradiaon as part ... , Radiother

010

2030

40

Cumulativeincide

nce(%

)

Breastcancerd

eath

1586 1507 1352 1246 790NoIMNRT1485 1406 1299 1203 782IMNRT

Atrisk

0 1 2 3 4 5 6 7 8

Yearssinceradiotherapy

Breastcancermortality

23.4%20.9%AdjustedHR:0.85(0.73;0.98)P=0.03

Difference:2.5%

Events AllIMNRT 329 1492NoIMNRT 400 1597

No.AtriskIMNRTNoIMNRT

Page 19: Internal mammary node irradiaon in early node … mammary node irradiaon in early node-posive ... breast cancer are offered internal mammary node irradiaon as part ... , Radiother

025

5075

100

Alive(%

)

1586 1507 1352 1246 790NoIMNRT1485 1406 1299 1203 782IMNRT

Atrisk

0 1 2 3 4 5 6 7 8

Yearssinceradiotherapy

75.9%72.2%AdjustedHR:0.82(0.72;0.94)P=0.005

Primaryendpoint:OverallSurvival

Difference:3.7%

Events AllIMNRT 385 1492NoIMNRT 483 1597

No.AtriskIMNRTNoIMNRT

Page 20: Internal mammary node irradiaon in early node … mammary node irradiaon in early node-posive ... breast cancer are offered internal mammary node irradiaon as part ... , Radiother

Thorsenetal.JClinOncolfeb2016

Page 21: Internal mammary node irradiaon in early node … mammary node irradiaon in early node-posive ... breast cancer are offered internal mammary node irradiaon as part ... , Radiother

AssociaHon:ü-Causality?

•  IncreasingriskofIMNmetastaseswith:– IncreasingnumberofposiHveaxillarylymphnodes

– Medial/centraltumorlocaHon

Page 22: Internal mammary node irradiaon in early node … mammary node irradiaon in early node-posive ... breast cancer are offered internal mammary node irradiaon as part ... , Radiother

SubgroupanalysisEndpoint:Overallsurvival

Thorsenetal.JClinOncolfeb2016

Page 23: Internal mammary node irradiaon in early node … mammary node irradiaon in early node-posive ... breast cancer are offered internal mammary node irradiaon as part ... , Radiother

Hypotheses

InpaHentswithearlynodeposiHvebreastcancer,IMN-RT

•  Improvesoverallsurvival

•  Reducesbreastcancermortality

•  Reducestheriskofdistantrecurrence

PP(P)

Page 24: Internal mammary node irradiaon in early node … mammary node irradiaon in early node-posive ... breast cancer are offered internal mammary node irradiaon as part ... , Radiother

Consequence

New2014radiotherapyguidelines:•  AllDanishpaHentswithnode-posiHveearlybreastcancerareofferedinternalmammarynodeirradiaHonaspartofadjuvantradiotherapy

•  Treatmentisprovidedusingorgan-sparingradiotherapytechniques

Page 25: Internal mammary node irradiaon in early node … mammary node irradiaon in early node-posive ... breast cancer are offered internal mammary node irradiaon as part ... , Radiother

Resultsincontext

Whelanetal.:MA.20,2000-2007•  1832pts.ThemajoritystageI-IIbreastcancer,randomisedtowhole

breastirradiaHon(WBI)versusWBI+regionalRT.MFU9.5years•  Improveddiseasefreesurvivalanddistantdiseasefreesurvival•  BreastcancerspecificsurvivalandOSnotsignificantPoortmansetal.:EORTC22922-10925,1996-2004•  4004pts.withstageI-IIIbreastcancer.Medial/centraltumorand/or

N+diseaserandomisedtomedialsupraclavicular(MS)andIMN-RT.MFU10.9years

•  Improveddiseasefreesurvival,distantdiseasefreesurvivalandbreastcancerspecificsurvivalwithMS+IMN-RT

•  Overallsurvivalborderlinesignificant

Page 26: Internal mammary node irradiaon in early node … mammary node irradiaon in early node-posive ... breast cancer are offered internal mammary node irradiaon as part ... , Radiother

FutureperspecHvesInfavorofIMN-RT:•  Consistenteffectacross

studies:Improvessurvival•  NewRT-techniques:Low

dosestoorgansatrisk:âriskoftoxicity

•  Developmentsintreatmentofcardiovasculardisease:AmelioraHonoftoxicity?

AgainstIMN-RT:•  Efficientsystemictherapy:

•  ârecurrencerates•  âabsolutegainsw.RT

•  EarlydetecHon:ChangingbiologyàLessaggressivedisease?

•  Riskofcardiacdamageandsecondcancer*

*GrantzauT,RadiotherOncol.2015Jan;114(1):56-65

Page 27: Internal mammary node irradiaon in early node … mammary node irradiaon in early node-posive ... breast cancer are offered internal mammary node irradiaon as part ... , Radiother

FutureperspecHves

•  WhoneedsIMN-RT?–  IdenHficaHonofsub-groupswithlargereffectofIMN-RT

– DetecHonofIMN-metastases(SenHnelnode?PET?)

•  WhodoesnotneedIMN-RT?– GeneHcprofilesmaypredictlackofbenefitfromradiotherapyinbreastcancer*

•  Methodsforweighingbenefitsagainstharm–  Personalizingtreatment

*TrammTetal:ClinCancerRes.2014Oct15;20(20):5272-80

Page 28: Internal mammary node irradiaon in early node … mammary node irradiaon in early node-posive ... breast cancer are offered internal mammary node irradiaon as part ... , Radiother

Acknowledgements

Thisworkwassupportedby:•  TheDanishCancerSociety•  CIRRO–theLundbeckFoundaHonCenterforIntervenHonalResearchinRadiaHonOncology

•  TheBreastFriendsCancerCampaign•  MaxandIngerWørznersMemorialFoundaHon


Recommended