Controversies in Radiation Therapy for Breast Cancer? Prof. Yazid Belkacemi.
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Transcript of Controversies in Radiation Therapy for Breast Cancer? Prof. Yazid Belkacemi.
Controversies in Radiation Therapy for Breast Cancer?
Prof. Yazid Belkacemi
Patients’ selection for APBI out of trial?
Patients’ selection for IORT?
Hypofractionation RT new standard in BC?
Controversies in Radiation Therapy for Breast Cancer?
Is there a subgroup of patients who may benefit equally from APBI or WBI?
Standard RT in Breast Cancer
Tumor bed
TechniquesIntra opIntra opproceduresprocedures
Intra or post op Intra or post op implantation implantation
Post op irradiationPost op irradiation
CASE 1CASE 1Ms. D. Ms. D. 54y of age 54y of ageMenopausal status confirmed since 50 y Menopausal status confirmed since 50 y No significant co morbidityNo significant co morbidityRegular mammograms since 10 years : no Regular mammograms since 10 years : no
abnormalitiesabnormalitiesSelf discovery of a 1 cm mass in the Upper Self discovery of a 1 cm mass in the Upper
Outer Quadrant of the right breastOuter Quadrant of the right breastMammogram and US: ACR5Mammogram and US: ACR5Biopsy: ductal ADK grade I, HR+Biopsy: ductal ADK grade I, HR+
CASE 1CASE 1Lumpectomy + SLNBLumpectomy + SLNBPathology report: Pathology report:
Ductal invasive carcinoma, size: 15 mmDuctal invasive carcinoma, size: 15 mmDCIS component 10%DCIS component 10%Grade I Grade I Minimal margins size 2mmMinimal margins size 2mmER+ PR-, HER2-, Ki67 5%ER+ PR-, HER2-, Ki67 5%No LVINo LVI2SN - 2SN -
Would you recommend APBI out of clinical trial ?
YES
NO
54 ypT1 11mmMargins 2mmER+ HER2-SN-
If this patient was 70yWould you recommend APBI out of
clinical trial ?
YES
NO
70 ypT1 11mmMargins 2mmER+ HER-SN-
APBI consensus statement from the ASTROAPBI consensus statement from the ASTRO― Based on 645 original research articlesBased on 645 original research articles― 4 published randomized clinical trials4 published randomized clinical trials― 38 published prospective single arm studies38 published prospective single arm studies
““Suitable” groupSuitable” group““Cautionary” groupCautionary” group““Unsuitable” groupUnsuitable” group
Sélection des patientesSélection des patientes
Smith BD et al. IJROBP, 2009
APBI consensus statement from the ASTROAPBI consensus statement from the ASTROASTRO consensus statement guidelines regarding patient selection for
accelerated partial breast irradiation off clinical trial
Smith BD et al. IJROBP, 2009
GEC - ESTROGEC - ESTRO
DIFFERENCESDIFFERENCES
3 bras
SHARE
2 bras2 bras2 bras2 bras2 bras
2800
> 50 et Ménop< 20
pN0 pN0(i+)I, II, III< 2mm
RTC 3D
40Gy/10f
Hypo 40Gy/3W 42.5Gy/3w50Gy/25+16 NON
3 bras
If this patient was 70yWould you recommend INTRAOP out
of clinical trial ?YES
NO
70 ypT1 11mmMargins 2mmER+ HER2-SN-
Novac-7Novac-7 4-12 MeV 4-12 MeV 20 Gy 20 Gy in 3-5 minin 3-5 min 650 kgs650 kgs(Hithesys)(Hithesys)
MobetronMobetron 4-12 MeV 4-12 MeV 20 Gy 20 Gy in 3-5 minin 3-5 min 1275 kgs1275 kgs(SRCLinac)(SRCLinac)
Intrabeam X-Ray 50kV Intrabeam X-Ray 50kV 5 Gy @ 1cm 5 Gy @ 1cm in 25-30 minin 25-30 min 1.8 kg1.8 kg 20 Gy @ surface20 Gy @ surface
0
20
40
60
80
100
120
0 20 40 60Depth (mm)
Rel
ativ
e d
ose
(%
)
INTRAOP techniquesINTRAOP techniques
DoseDose
Uniform spherical radiation fieldUniform spherical radiation field Steep dose gradientSteep dose gradient High dose rateHigh dose rate
Design Design (n = 2232, 9 countries – 28 (n = 2232, 9 countries – 28 centres)centres)
Randomisation 1.1 (pre ou per operative)Randomisation 1.1 (pre ou per operative) Patients criteriaPatients criteria Age 63 y , pT ≤ 3cm: 86 %, grade I/II: 84 %, N-: 83 %, HR+: Age 63 y , pT ≤ 3cm: 86 %, grade I/II: 84 %, N-: 83 %, HR+:
90%90%
TreatmentTreatmentTargit Arm : 86% received the planned RTTargit Arm : 86% received the planned RTWBI in 14%WBI in 14%
FUPFUP > 4 y n = 420> 4 y n = 420
Lancet 2010, 376, 91-102
The Lancet 2010
ToxicityToxicity IntrabeamIntrabeam WBIWBI SeromaSeroma 2.1%2.1% 0.8%0.8% Grade 3-4Grade 3-4 0.5%0.5% 2.1%2.1%Local Control at 4yLocal Control at 4y LR rate LR rate 1.20 %1.20 % 0.95%0.95% (p=0.41)(p=0.41)ConclusionConclusion
There is non inferiority with INTRABEAM compared to WRIThere is non inferiority with INTRABEAM compared to WRI
Lancet 2010, 376, 91-102
San Antonio 2012San Antonio 2012 UpdateUpdate
Whole populationWhole population n=3451 n=3451 INTRABEAM armINTRABEAM arm n=1721n=1721EBRT armEBRT arm n=1730n=1730Minimal FUP of 4yMinimal FUP of 4y n=1010 n=1010 Minimal FUP of 5yMinimal FUP of 5y n=610n=610
Since 2010 : local recurrence events increased from 13 Since 2010 : local recurrence events increased from 13 to 34to 34
Local recurrence probability at 5 y is in favour of EBRTLocal recurrence probability at 5 y is in favour of EBRTInferiority of INTRABEAMInferiority of INTRABEAM
INTRABEAM 23 (3.3%) vs EBRT 11 (1.3%), INTRABEAM 23 (3.3%) vs EBRT 11 (1.3%), p=0.042p=0.042
Vaidya J.S Vaidya J.S et al., et al., SABCS 2012, S4-2SABCS 2012, S4-2
ConclusionConclusion
No difference if PgR+
Suitable group for INTRABEAM
(> 60 y, HR+, tumor < 2 cm, SN-)
Vaidya J.S et al., SABCS 2012, S4-2
Is there anymore discussion for Hypofractionation RT in BC ?
CASE 2CASE 2 Ms A-R. Ms A-R. 50y of age50y of age Peri menopausal status Peri menopausal status No significant morbidityNo significant morbidity Large size breast (100 D)Large size breast (100 D) Lumpectomy + SNBLumpectomy + SNB
Ductal invasive carcinoma pT1 18 mm; margins: 3mm Ductal invasive carcinoma pT1 18 mm; margins: 3mm Grade III (3,2,3), No LVI, Ki 67: 25%Grade III (3,2,3), No LVI, Ki 67: 25% ER+ 40% PR+ 20% HER2- ER+ 40% PR+ 20% HER2- 2 SN : 1 micromets. 2 SN : 1 micromets. No secondary ALND No secondary ALND
Adjuvant CTAdjuvant CT 4FEC 100 and 2TXT. Neurotoxicity G34FEC 100 and 2TXT. Neurotoxicity G3
Radiotherapy modalityRadiotherapy modality
Would you recommend:
1. Hypofractionated schedule in 3 weeks
2. Standard in 6.5 weeks
50y peri menopausalpT1 18mmSN micrometastsis/2No secondary ALND
Radiotherapy modalityRadiotherapy modalityWould you recommend nodal irradiation ?
YES
NO
50y peri menopausalpT1 18mmSN micrometastsis/2No secondary ALND
HypofractionationCanadian trial
50Gy in 25 fractions - 5 wvs
42.5Gy in 16 fractions - 3 wStratification : age (50); T (< 2cm); adjuvant TRT & centre
0,1
0,08
0,06
0,04
0,02
0
6,2 %
Years since randomization0 2 4 6 8 10 12
6,7 %
Recu
rren
ce (%
)
1 3 5 7 9 11
612
622
578
592
550
548
499
500
470
447
410
406
218
214
597
609
592
569
553
524
485
472
449
430
317
330
SWBI
AHWBI
FUP : 144 m
Cancer Care Ontario Regional Cancer Centres; Princess Margaret Hospital; Montreal General Hospital
Whelan et al. NEJM 2010
Hypofractionation
Stratification by tumor size < 2cm
No boost, no nodal RT
No N+ patients included
No large breast
Small proportion of pts with CT
Better cosmetic results
Impact of age and T size
Canadian trialComments: the results could be extrapolated to all pts?
Whelan et al. NEJM 2010
50y peri menopausalpT1 18mmSN micrometastsis/2No secondary ALND
START TRIALS
TrialTrial PopulationPopulation FUPFUP(y)(y) TreatmentTreatment
Local Local recurrencerecurrence
(%)(%)
Start BStart B(n= 2215)(n= 2215)
T1-T2T1-T2N-N-R0R0
6640 Gy/15fr/40 Gy/15fr/
(2.67 Gy/fr) 19j(2.67 Gy/fr) 19j 22
50 Gy/25fr/35j50 Gy/25fr/35j 3.33.3
Start AStart A(n=2236)(n=2236)
T1-3T1-3N0-1N0-1M0M0BCS or total BCS or total mastectomymastectomy
5.15.1
41.6 Gy/13 Fr41.6 Gy/13 Fr(3.2 Gy/fr)(3.2 Gy/fr) 3.23.2
39 Gy/13 fr39 Gy/13 fr (3 Gy/fr)(3 Gy/fr) 4.64.6
50 Gy/25 fr/35j50 Gy/25 fr/35j 3.23.2
START TRIALS
Meta-analysis of START pilot & START A&BSubgroup analyses of LR relapse (n=5861)
better
.4
Hazard Ratio (95% CI)
Fraction sizes > 2.0 Gy Fraction size 2.0 Gybetter
AgeAge
Primary surgery
Axillary nodes (pN)
Tumour gradeTumour grade
Boost RT
Adjuvant CTAdjuvant CT
.6 .8 1 1.2 1.4 1.6 1.8 2
< 50 yrs< 50 yrs> 50 yrsBreast conservingMastectomy
NegativePositive
1233NoYes
NoYesYes
138944725348513
43181421
12132398127227493071
43461480
0.84 (0.62, 1.15)1.07 (0.83, 1.38)0.97 (0.80, 1.19)0.91 (0.46, 1.81)
1.10 (0.86, 1.40)0.80 (0.57, 1.11)
0.96 (0.51, 1.82)1.07 (0.72, 1.59)0.86 (0.59, 1.25)0.99 (0.74, 1.32)0.99 (0.76, 1.29)
1.09 (0.86, 1.38)0.81 (0.57, 1.14)
No of patients
Hazard ratio (95% CI)
Haviland JS et al., SABCS 2012, S4-1
50y peri menopausalpT1 18mm GIIISN microM/2, No ALNDCT+
Haviland JS et al., SABCS 2012, S4-1
Patients50y peri menopausalpT1 18mm GIIISN microM/2, No ALNDCT+
ThaThank you!nk you!