Current Status of Accelerated
Partial Breast Irradiation
Julia White MD Professor, Radiation Oncology
I have no disclosures relative to
the presented material
Agenda
• ABPI Timeline
• APBI by Method
• Clinical Trials
• Consensus Guideline
• Summary
Accelerated Partial Breast
Irradiation (APBI): Definition
Delivery of larger doses/fraction of radiation therapy (RT) to the lumpectomy cavity (plus 1-2 cm margin) after breast conserving surgery using brachytherapy or external beam irradiation techniques
Complete RT in < 5-8 days after lumpectomy instead of 6-7 weeks
17 years of APBI: What have we learned?
1997 -2000 RTOG 9517 Multi catheter APBI Phase II/ feasibility
2000-2001 Mammosite APBI Phase II/ feasibility
2002 MammoSite FDA Approval
2002-2004 ASBS Registry MammoSite APBI
2003-2004 RTOG 0319 3DCRT APBI Phase II/ feasibility
2004 NASBP B39/ RTOG 0413 Phase III opens
2006 OCOG 3DCRT RAPID Phase III opens
2009 ASTRO Consensus Guidelines
2011 OCOG 3DCRT RAPID Phase III closes
2013 NSABP B39/ RTOG 0413 Phase III closes
Lumpectomy
Breast
Advantages: Irregularly shaped
cavities, skin and chestwall sparing
RTOG 95-17 phase I/II Multi-catheter APBI
- 100 patients accrued between 1997- 2000
› 10 institutions: HDR 66, LDR 33
› 34 Gy in 10 fractions, BID 5-8 days
› Median Tsz. 1.3 cm, N-1 19%, ER/PR+ 77%
– Overall satisfaction with treatment at 5 yrs: 75%
– 94.6% would choose multicatheter APBI again
Target volume: 1.5 cm breast
tissue around the cavity
#
5 year 10 year
Median follow-up: 12.1 yrs Event (%)
# at
risk (%)
# at
risk
ISOLATED in-breast recurrence 4 3.1 84 4.2 68
In field 3 2.1 85 3.1 69
Out of field 1 1.0 85 1.0 69
In-breast & Regional recurrence 2 1.0 84 2.1 68
ALL In-breast recurrences 6 4.1 86 6.2 69
ISOLATED Regional recurrence 3 3.1 84 3.1 68
ALL Regional recurrences 5 4.1 87 5.2 71
Contralateral Breast Cancer 5 3.1 88 4.2 70
RTOG 95-17: A phase I/II trial to
evaluate multi-catheter interstitial PBI
MultiCatheter PBI (HDR/ LDR): Summary
Institution
Pt.
No.
Median
age
F/U
mo.
T size
(cm)
median
N+
%
ER +
%
Tam
%
LR
%
Exc/ good
Cosmesis
%
Oschner 163 63 65 - 15 65 - 3 -
Beaumont 199 65 65 1.1 12 - 57 1.2 99
Tufts-NEMC 32 63 84 1.3 9 79 61 9 93
*VCU 44 62 42 1.2 18 - 66 0 80
Nat. In. Onc. Budapest 45 56 81 1.2 2 82 16 6.7 97
Guys Cs 137 49 58 75 2.5 46 - - 18 81
* U. WI -low -high
183 90
63 47
48 49
1.1 1.4
0 18
100 83
57 50
2.2 4.4
95
*MCW 74 68 40 1.2 1.5 88 76 1.3 82
Ger-Austrian Multicenter 274 60.5 63 1.2 0 100 91.2 2.9 90
RTOG-9517 99 62 144 1.3 19 75 - 4 -
Median
age
60.7
T size
(cm)
median
1.35
N+
13%
ER +
84%
LR
4.8%
Exc/
good
Cosmesis
89%
DOSE
50%
80%
100%
120%
140%
200%
APBI: Single Entry Brachytherapy Devices
Dose : 34 Gy, 10 fractions 3.4 Gy BID, over 5-8 days
Minimal balloon surface-skin distance –
- ideally 7 mm,
- if 5-7 mm then confirm skin dose <145%
1st Generation: Mammosite® balloon Target volume: 1 cm breast tissue
around the balloon
Advantages: Simplified approach,
improved technology access
Initial MammoSite® Multi-institutional
Phase II Study-Manufacturer
Overview: 43 patients enrolled 5/2000- 10/2001
34 Gy, 10 fractions BID @ 1 cm, 5-8 days
Results: Median follow-up 65.2 months (n=36)
- Median Age 69 years
- All T1 N0, 79% > 10 mm in size
Grade 1-2: 77%, G3 14%
- No local recurrences
- Telangiectasias 39.5%, Retraction 20.9%
- 80% good/ excellent cosmesis
- Cosmesis worse- skin spacing < 7 mm
Keisch et al, IJROBP 2: 2003, Benitez, et al. Amer. J. Surg, 2007
ASBS APBI Registry
• 2002 – 2004: 1440 patients , 97 facilities
• 95% 34Gy/10 fractions BID, 89% > 7mm skin spacing
• > 20 Publications
• Median F/U: 58 months
Invasive: (n=1249)
• median age: 66
• median T-size: 10 mm
• 97% N-0
• ER/PR: 87%
• In-breast failure: 3.9%
DCIS: (n=194)
• median age: 62.1
• median TIS size: 8 mm
• In-breast failure: 3.4%
Vicini, IJROBP 79: 2011, Shah, IJROBP
2012
APBI Single Entry Brachytherapy:
Next Generation
Contura SenoRx SAVI Ciana medical
Advantages:
• dosimetric coverage
• sparing of skin and
chestwall
Trends in the use of implantable
APBI in the U.S.
FDA approval
of MammoSite
0.4% in 2000 versus 6.8% in 2007 p < 0.001 SEER Database
Abbott, et al, Cancer 2011
Select Single Entry Brachy APBI: Summary
Institution Pt.
No.
Median
age (yr)
F/U
mo.
T size (cm)
median
N+
%
ER +
%
Local
relapse
%
Exc/ good
Cosmesis
%
Initial
Manufacturer
Multi- Institution
43 69 65 1.0 0 - 0 81
*Rush Univ. 112 64 - 88% Tis/T1 7 - 0 80
*Tufts/ VCU 28 62 19 1.1 0 100 0 86
St. Vincent
Hospital 32 62 11 97% T-1 9 94 - 86
*Kaiser-
Permanente 51 64 16 1.2 16 86 0 95
*MUSC 111 61 46 - 8 - 5 -
*Pooled multi-
institution 483 - 24 - - - 1.2 91
*ASBS Registry 1440 65.9 54 1.0 3 51 3.8 93
Median
age
64
T size
(cm)
median
1.1
N+
5%
ER +
88%
LR
1%
Exc/
good
Cosmesis
87%
sagittal
coronal Advantage: Linear accelerator delivery
RTOG 0319 Phase I/II 3DCRT APBI
– 58 patients accrued 2003-2004
– Feasibility of external beam method for APBI
– 38 Gy in 10 Fraction, BID 5-8 days
– Overall satisfaction at 3 years 86%
– 100% would choose 3DCRT APBI again
RTOG 0319
Results at 8 year median follow-up
n
5-year
estimate
7-year
estimate
Ipsilateral Breast Failure* 4 5.8% 7.7%
Contralateral Breast
Failure 0 0% 0%
Ipsilateral Nodal
Failure** 3 5.8% 5.8%
Distant Failure 4 7.7% 7.7%
* All IBFs were in T1N0, postmenopausal patients
**All INFs were in T1N0, ER+, postmenopausal patients
Rabinovitch, ASTRO 2013
3-DCRT APBI: Summary
Institution Pt.
No.
Median
age
F/U
mo.
T size
(cm)
median
N+
%
ER +
%
Local
relapse
%
% Exc./
Good
Cosmesis
Beaumont 96 62 36 - 1 - 1 90
NYU 100 67.5 60 0.9 0 100 1 94
MGH 98 60 71 0.9 0 89 5 97
British
Columbia 127 62.6 37 - 0 82 1 82
Esperanza 105 67 60 1.4 0 96 0 100
RTOG 0319 58 61 40 1.0 8 - 6 -
Median
age
64
T size
(cm)
median
1.0
N+
1.8%
ER +
90%
LR
2.2%
Exc/
good
Cosmesis
90%
NSABP B-39/RTOG 0413 Trial Phase III
Stage 0, I-II breast cancer treated by lumpectomy
Randomization
WBI • 50-50.4 Gy (1.8-2.0 Gy)
Fractions to the whole breast
followed by boost to 60 -66.6 Gy
APBI • 34 Gy in 3.4 Gy fxs bid
Mammosite® , Contura, SAVI or
Multicatheter brachytherapy
OR
• 38.5 Gy in 3.85 Gy fxs bid
3D-CRT
Targeted accrual = 4300
NSABP B39 / RTOG 0413 • March 21, 2005 – Opened for accrual
- 3000 targeted accrual
• January 1, 2007 – Accrual closed to “low-risk”
population and targeted accrual increased
• April 11, 2013 Closed for accrual– 4,216 accrued (Among patients with follow-up, mean follow-up time is
60.5 months.)
APBI - # of patients randomized: 2107
Methods: – 70.5 % (n=1474) 3-DCRT,
– 24.3% (n=512) MammoSite/other
– 5.2 % (n=109) MultiCatheter
NSABP B39 / RTOG 0413: Population
Variable: %
Age < 50 y
50-69
> 70
38.4
47.7
13.9
Race/ Ethnicity
White
Black
Hispanic
89.8
7.1
4.1
Disease Stage
DCIS
Invasive N-0
Invasive N-1
24.3
65.4
10.1
Hormonal Status
ER or PR +
ER and Pr-
81.3
18.7
Phase III Trials Comparing APBI to WBI
Closed! Accrual
PBI
Method Eligibility
NSABP B-39/
RTOG 0413
2013 4214
3-DCRT
MST
MCT
> 18 yo, Stage 0-II, < 3cm,
N-0 – N-1 (< 3 LN+)
GEC-ESTRO
2009 1300 MCT
> 40 yo, Stage 0-II, < 3 cm,
N-0 – Nmi,
Negative margins (2 mm)
RAPID
OCOG
2012 2135 3-DCRT
> 40 yo, Stage 0-II, < 3 cm,
N-0, excludes inf. lobular
(7649)
Suitable Cautionary Unsuitable
Patient Factors Age > 60 years 50-59 < 50
BRCA 1-2 no no Yes
Path Features T-size < 2 cm 2.1-3.0 cm > 3.0 cm
T stage T-1 T-0 – T-2 T 3- T4
Margins Negative ( 2 mm) Close (< 2 mm) Positive
LVSI No Limited, focal Extensive
ER Pos. Neg. -
Multicentric Unicentric Unicentric Present
Multifocal Clinically unifocal Clinically unifocal Clinically multifocal
Histo IDC ILC -
DCIS, EIC No, No Yes, Yes (< 3 cm) > 3 cm
Nodes N stage pN0 (i+ , -) - pN1, N2-3
Nodal Surgery yes yes no
ASTRO Consensus Statement for
Treatment with APBI Outside a Clinical Trial
Smith, IJROBP,4:2009
5 year Mastectomy Rate
Brachytherapy APBI versus WBI
SEER-Medicare
• 92,735 cases
• Age > 67
• 2003-2008
3.95%
2.19%
Smith, et al. JAMA, 307:2012
5 year Mastectomy Rate
by ASTRO Consensus Guideline
SEER-Medicare
n Lump APBI EBRT p
ALL 35,9457 4.2 3.0 1.4 < 0.001/0.001
Suitable 9,966 3.7 1.6 0.8 < 0.001/0.002
Cautionary 5,509 6.7 5.4 2.2 < 0.001/0.006
Unsuitable 10,119 5.0 3.6 1.6 < 0.001/0.02
Smith G, et al., IJROBP, 2:2014
No Difference in Mastectomy Rate
in “Older Suitable” SEER-Medicare
n = 7,450
Age > 70
Distribution by ASTRO
Consensus Statement Grouping
SEER: 4,172 Breast Cancer Cases
treated with Brachytherapy Husain, Brachytherapy, 2011
Outcomes after APBI
“Cautionary”
• University of Wisconsin
• 2001-2006
• Median f/u: 60 mo.s
• 322 MCT APBI
– 79 Suitable
– 136 Cautionary
– 107 Unsuitable
• Reason Cautionary
– 63% age 50-59
– 23.5% DCIS
– 12.5 % EIC
– 9.6% 2 cm- 3cm T-size
– 8.1% ER neg.
– 7.4% ILC
– 7.4 % < 2 mm margin
– 27.9% multiple factors
McHaffie, et al, IJROBP 2011
Stage I-II: IBTR by “Cautionary”
Determinant
Age: 0%
Histopath: 12.7%
p=0.018
McHaffie, et al, IJROBP 2011
MGH: 3DCRT APBI Using 32 Gy/ 8 BID
5-Year Results of a Prospective Study
• 2000-2005
• N= 98
• Stage I
• Er/Pr +: 89%
• Median F/U: 71 mo.
Pashtan, IJROBP, 2012
ASBS MammoSite® Registry
• 1225 invasive
breast cancer
• Median f/u:
60 mo.
• 5 yr LR: 3.6%
Beitsch, Ann Surg Onc 2012
Relationship of
Breast Cancer
Recurrence and
Mortality by
absolute reduction
in 10 -year risk of
Any 1st Recurrence
Bre
ast
Can
cer
Mo
rtali
ty
-
Absolu
te r
eduction (
%)
in 1
5-y
ear
risk (9
5%
CI)
Any First Recurrence Absolute reduction (%) in 10-year risk Lancet 378: 1707-16, 2011
< 10% absolute reduction
in any recurrence risk by 10
years
RCT in Hormone Responsive pN0 Breast
Cancer Evaluating RT Benefit in Addition to
Anti Endocrine Therapy Post-lumpectomy
Clinical Trial n
F/U yrs
Age > 50 y
(%)
T sz < 2 cm (%)
ER/PR+ (%)
Tam/AI (%)
Grade 1-2 (%)
In-breast
recurrence (%)
RT No RT PMH 769 5.6 100 83 80.5 100 68.3 0.6 7.7
ABCSG 8a 869 4.48 99 90 100 100 95 0.4 5.1
CALGB
9343 626 12.6 100 98 97 100 - 2 8
Low risk features: Older age, pN0, small size, ER/PR+,
G1-2, anti endocrine therapy
Recurrence rate indicates UNLIKELY survival
benefit from breast radiotherapy
OCOG RAPID Early Reporting
of Cosmetic Results
WBI
ABPI-
3DCRT
Difference
APBI-WBI
(95% CI) p value
Baseline
n=1995 17% 19% 2% (-2-5%) 0.35
3 years
n=850 19% 32% 135 (7-19%) < 0.0001
Adverse Cosmetic Outcome ( Fair –Poor)
Nurse Assessment at Baseline and 3 years
Olivotto et al, JCO 2013
APBI so far has demonstrated acceptable local control in
mostly low risk cases: Stage 1, ER+, > 60 yo breast
cancer patients
Need to complete randomized trials to define broader
applicability and durability of outcome in comparison to
standard WBI
Rigorous attention to technical delivery and Q/A is
crucial
Summary: APBI
Thank you