Partial Breast
Irradiation
Carol Marquez, M.D.
Associate Professor,
Department of Radiation Medicine
Oregon Health and Sciences
University
Goals of discussion
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Discuss the changing epidemiology of breast
cancer
Present the data supporting breast
preservation therapy (BPT)
Discuss the rationale for partial breast
irradiation (PBI)
Show the techniques and difficulties with PBI
Breast Cancer Statistics
The good news: Mortality declined by 2% per
year from 1990 to 2001, with the greatest
declines in women younger than 50 years.
Estimated deaths in 2007 = 40,910.
The bad news: An estimated 180,510 new
cases will be diagnosed in 2007. The incidence
has continued to gradually increase since 1990.
Recent decline in ER + breast cancer incidence
may be secondary to 40% decline in use of
hormone replacement therapy between 20002003.
SEER Age-Adjusted Incidence Rate Comparison
For Breast Cancer
SEER 9 Registries for 1975-2004
Stage at presentation is declining
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The increase in incidence from 1980-87 was largely
due to increased use of screening mammography.
During that time, the incidence rates of tumors <2
cm more than doubled while the rates of tumors >3
cm decreased by 27%.
The incidence rates of DCIS has increased more
than sevenfold from 1980-2001.
Breast cancer is still a disease of
older women
Current age Risk of breast cancer in
next 10 years
20
0.05%
Or 1 in:
30
0.44%
229
40
1.46%
68
50
2.73%
37
60
3.82%
26
70
4.14%
24
Lifetime
13.22%
8
1,985
Who is eligible for breast
preservation therapy?
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Classically the size cutoff was 4 cm but recent consensus
conference stated that any size is eligible as long as clear
margins are obtained with an acceptable cosmetic result;
NCCN states that tumors > 5 cm are a “relative”
contraindication to BPT.
If multicentric tumors can be excised in a single specimen
with clear margins (including in situ disease) and the
imaging shows no other suspicious lesions, the patient is
still a candidate.
No absolute age cutoff; NCCN 2008 guidelines states that
women < 35 years have a relative contraindication.
Prior chest XRT and pregnancy are absolute
contraindications while active connective tissue disease,
especially lupus and scleroderma are relative
contraindications.
Where are we in 2008?
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Majority (~ 85%) of women who present with breast
cancer are eligible for breast preservation therapy (BPT).
Survey by American College of Surgeons of 16,643 pts
treated in 1994 shows that 43% of St I/II pts treated with
BPT.
Only 86% of women treated with preserving surgery
received XRT.
Women don’t receive their XRT after preserving surgery
because of age, distance, payer, race and type of
hospital (academic vs community).
Who doesn’t need XRT?
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Four randomized trials comparing
lumpectomy to lumpectomy + XRT.
All trials showed an improvement in local
control with addition of XRT.
All trials showed no difference in overall
survival between two arms.
Trials had varied in terms of surgery and
tumor size allowed.
Features of four trials
Trial
N
F/U
(yrs)
Tumor
size
Margins
(cm)
Chemo
NSABP-06
1256
20
< 4 cm
0
+
Uppsala
381
5
< 2 cm
2
-
Ontario
837
5
< 4 cm
0.5-1
-
Milan
394
<4
< 2.5 cm
NA
+
Results of four trials
IBTR
IBTR
no XRT + XRT
NSABP-06 39.2
14.3
Survival
no XRT
46
Survival
+ XRT
47
Uppsala
18
2
90
91
Ontario
29
7
85
87
Milan
9
<1
NA
NA
IBTR= In breast tumor recurrence
What can you conclude from
these trials?
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Margins and tumor size do matter even in the face
of radiation; a 2cm tumor treated with good surgical
margins has approximately a 20% recurrence rate
without XRT not 40%.
Longer f/u is necessary to evaluate the recurrences
after XRT.
Radiation does work and does not have a
deleterious impact on overall survival.
NSABP B-06: Landmark study
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1851 women included
in analysis
Mean follow up is 20
years
First results published
in 1985
Most recent update
published in 2002
IBTR after 20 years
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Risk of recurrence
without XRT is 40%.
Risk of recurrence with
XRT is 14%.
Most of the early
recurrences are near
the original primary
tumor.
Disease-free Survival (Panel A), Distant-Disease-free Survival (Panel B), and Overall Survival
(Panel C) among 589 Women Treated with Total Mastectomy, 634 Treated with Lumpectomy
Alone, and 628 Treated with Lumpectomy plus Irradiation
Fisher, B. et al. N Engl J Med 2002;347:1233-1241
What else did we learn from
NSABP-06?
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Addition of chemotherapy does not eliminate the
need for XRT but does improve the local control in
those receiving XRT; chemo + no XRT, IBTR = 44%
vs. chemo + XRT, IBTR= 9% (no chemo + XRT,
IBTR= 14%).
Recurrences after XRT may occur later than if no
XRT is given; no XRT, 73% of recurrences occurred
in the 1st 5 yrs while with XRT, 40% of recurrences
occurred in the 1st 5 yrs.
What else can be done instead of
whole breast irradiation?
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Hormonal therapy
Selection of patients
Minimizing treatment volume
What about hormonal therapy?
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NSABP-21 enrolled pts with ER/PR + tumors, < 1cm
in size with – margins, and node negative.
Randomized pts to XRT, tamoxifen, or XRT +
tamoxifen.
Found that XRT was still warranted in this select
group; at 8 yrs, IBTR with Tam = 16%, with XRT=
9%, with XRT + Tam = 3%.
Recent articles on avoiding
XRT in older women
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Two recent (2004) articles examined the use of
Tamoxifen only after surgery in select older women
to avoid radiation.
The overall survival was equal in both arms. The
local recurrence was low without radiation,
especially in those over 70 with ER+ tumors.
Those receiving XRT had a lower rate of recurrence
(4-7% vs. 0-1%). They also reported more breast
pain.
Why partial breast irradiation
(PBI)?
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Rationale is that by having a therapy that can be
completed in a short period of time (e.g. 1 week)
more patients can be eligible for BPT.
Majority of recurrences seen in those pts not
receiving XRT occur at or near tumor bed so rest of
breast may not need treatment.
Treating less of the breast may produce fewer side
effects, specifically pain and fatigue.
How is PBI performed?
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Several methods now available including
brachytherapy, 3D conformal, IORT, protons.
Initial experience was with interstitial
brachytherapy, either HDR or LDR.
Target volume is the tumor cavity plus 1 cm.
Treatment is given in twice daily treatments
of 3.4 Gy per treatment.
Single Institution results with PBI
Institution
N
F/U
(mos)
IBTR Cosmesis
Ochsner (HDR)
26
20
1
75
Ontario (HDR)
39
20
2.6
NA
Ochsner (LDR)
26
20
1
78
Beaumont (LDR)
120
82
1
91
Beaumont (XRT)
22
20
0
100
Techniques for PBI
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Interstitial brachytherapy with HDR or LDR
Intracavitary brachytherapy with Mammosite
Intraoperative electron beam therapy
3D conformal radiation therapy
Proton beam
Interstitial brachytherapy
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Catheters are placed
intraoperatively or later;
usually 2 planes
Typical doses with HDR
= 30-36 Gy and LDR =
45-60 Gy
Treatment delivered
over one week.
Difficulties with interstitial
brachytherapy
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Very user dependent, especially on number
of cases performed.
Certain toxicities increase over time
(telangiectasias and fat necrosis) while others
stabilize (breast pain, breast edema).
Cosmetic results appear to improve over
time.
Features of Hungarian Trial
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Randomized women to whole breast (50 Gy, no
boost) vs. PBI; n=258 women with median f/u of 66
months.
For PBI, 69% delivered with HDR interstitial, 5.2 Gy
x 7 bid over 4 days. For the others, electron beam
used, 50 Gy in 2 Gy fractions.
No lobular carcinoma included; 96% had margins >
2 mm, 95% were < 2 cm, and 94% were node
negative.
In the PBI arm, 63% were grade 1 while in whole
breast, 50% were grade 1.
Results of Hungarian Trial
WBI (%)
PBI (%)
IBTR- marginal
1.5
2.3
IBTR-elsewhere
1.5
2.3
Excellent-good
cosmesis
65% photons;
52% cobalt
Fair-poor cosmesis
24% photons;
48% cobalt
Grade 2-4 Fat
necrosis
9%
81% HDR;
70% EB
19% HDR;
30% EB
10% HDR;
8% EB
MammoSite brachytherapy
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Balloon is placed into
surgical cavity.
Balloon available in
spherical and elliptical
shapes.
Balloon sizes are 4-5
cm.
Ten fractions given in 5
days, 34 Gy.
Difficulties with Mammosite
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Balloon must conform to
cavity shape without air
gaps. Device explanted in ~
10-15% of pts.
Ideal is to have 7 mm b/w
balloon and skin to
decrease risk of erythema.
Very dependent on surgical
placement.
“Long” term results with
Mammosite
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Three year results from the American Society
of Breast Surgeons registry trial showed a
IBTR 2 year actuarial rate of 1.04% with
good to excellent cosmetic results were seen
in 93% of patients (n=67).
William Beaumont experience showed 2.9%
3 year actuarial rate of IBTR with good to
excellent cosmetic results in 88% of patients
at 36 months.
Toxicities of Mammosite
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Seroma formation: Risk is increased with
open technique for placement. In Beaumont
series, found 60% risk with open cavity vs.
30% in closed cavity; overall rate of 45%,
with 10% symptomatic.
Fat necrosis: Risk may be slightly lower than
with HDR and no difference with placement
technique.
3D Conformal PBI
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Surgical clips (6) are placed at the time of
lumpectomy.
The clips define the excision cavity which is
expanded by 15 mm to get the CTV and 10
mm are added to establish the PTV.
Ten fractions over 5 days giving 38.5 Gy, with
6 hours between treatments.
The good and bad of 3D
conformal PBI
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Performed on a standard
linear accelerator; less
invasive.
Requires more time for
target delineation and
planning; typically plans
use 3-5 non-coplanar
beams.
Greater concern for dose
to heart, lung, and
contralateral breast in
developing treatment
plan.
More issues with
breathing motion and
setup uncertainties.
Limited results with 3D
Conformal
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Recent update from William Beaumont
Hospital presented interim analysis with
median followup of 2 years for 91 patients.
No IBTRs were observed but 2 patients
developed distant mets (1 patient was node
positive).
Good to excellent cosmesis was seen in 95%
of patients, with treatment related toxicities
stabilizing by 3 years post treatment.
Proton beam for PBI
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Early experience from MGH
in 20 women showed
acceptable cosmetic results
with increase skin toxicity
as compared to photons.
Dose modified to 32 CGE
given the increased RBE of
protons; 8 fractions
delivered over 4 days.
Intraoperative Radiation
Therapy (IORT) for PBI
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TARGIT trial is comparing whole breast
irradiation to IORT delivering a single dose of
20 Gy. Primary accrual is in Europe.
Using the Intrabeam Photon Radiosurgery
System, 50 kV x-rays.
Trial has enrolled 900 patients with target of
2200 patients.
Problems with IORT with
Intrabeam
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Margin status: with
delivery of treatment at
the time of lumpectomy,
may have persistent
positive margins found.
Depth of penetration:
limited coverage with
dose distribution.
Patient must have
complete excision.
Who is eligible for PBI?
(Off study)
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Tumors < 3 cm
Negative margins (> 2mm)
Node negative
Invasive ductal carcinoma or DCIS
Older women (>45 yrs)
Revised Consensus Statement for Accelerated Partial
Breast Irradiation, 12/8/05
Randomized trial of whole breast vs. partial
breast (NSABP B-39/ RTOG 0413)
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Will accrue 3000 patients to 2 arms: Whole breast
irradiation (standard) vs. Partial breast irradiation.
Three techniques are allowed: Mammosite,
interstitial brachytherapy, and 3D conformal.
Patients must have tumor < 3 cm, < 3 positive nodes
and tumor may be DCIS or invasive ductal
carcinoma.
Patients will be stratified on basis of stage,
menopausal status, hormone receptor status, and
intent to receive chemotherapy.
Endpoints of the study are local control and
cosmesis.
Anticipated problems with NSABP
B-39
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While most of the single institution experience is
with brachytherapy, most of the patients are treated
with 3D conformal.
The study did not allow for planning with IMRT.
The cosmetic follow up will be short and may need
to wait at least 5 years before we have adequate
information.
Just to make it confusing….
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Update from the Canadian accelerated whole breast
trial: Randomized women with negative margins and
nodes to 42.5 Gy in 16 fractions or 50 Gy in 25
fractions. Patients with breast separation > 25 cm
excluded.
1234 women have been followed for median of 69
months. No difference in local recurrence, overall
survival or cosmetic outcome.
10 year local recurrence =6%
10 year good/excellent cosmesis = 70%. Cosmetic
results declined between 3-10 years.
Where will be in 2012?
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We should have results of
B-39 re: local failure and
complications of
techniques.
We will continue to refine
selection criteria for patients
that do not need XRT or
who can be treated with
PBI.
More patients will be treated
with advanced planning,
e.g. IMRT.