Transcript Postmastectomy Radiation therapy (PMRT): Who needs it in 2008? Carol Marquez, M.D. Associate Professor, Department of Radiation Medicine Oregon Health and Sciences University.

Postmastectomy Radiation
therapy (PMRT): Who
needs it in 2008?
Carol Marquez, M.D.
Associate Professor,
Department of Radiation Medicine
Oregon Health and Sciences University
Goals of discussion
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Present evolution of thought and use
of PMRT from the 1970’s to 1997.
Discuss result of recent randomized
trials.
Present recent retrospective analyses
to determine patients at greatest risk
of recurrence.
Discuss techniques for PMRT.
What we did prior to the
1970’s
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Many patients received PMRT after their surgery,
RM or MRM.
NSABP B-02 randomized pts after RM to receive
regional radiation. No difference in overall survival
but decrease in regional recurrence.
Initiated in 1971, NSABP B-04 randomized pts after
RM, TM, or TM + XRT if clinically node neg and if
node + to RM or TM +XRT.
Ten year results showed no difference in disease
free or overall survival among the groups. Radiation
arms did show decrease in local recurrences.
What happened in the
80’s?
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By the mid-80’s, the safety of regional nodal
irradiation was questioned with an excess of cardiac
mortality seen in patients followed for 10 years.
Meta-analysis of 7 randomized trials of PMRT
initiated before 1975 showed an increase in
cardiac-related deaths in those receiving RT that
was almost balanced by a reduction in the deaths
due to breast cancer.
The excess cardiac mortality was largely due to the
increase in cardiac dose from radiation to the
internal mammary nodes.
Paradigm shift to
Alternate hypothesis
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Breast cancer is
both a local and
systemic problem at
presentation.
More extensive
local treatment will
not improve
survival.
Supported the trials
examining less
extensive surgery.
Who did we treat in the
1990’s?
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Because of the concern of late toxicity, the
indications for PMRT were greatly limited to include
only those patients with more advanced disease:
T3/4, more than 4 positive nodes.
The rationale for choosing these patients is that
their risk for local recurrence was at least 30%
which radiation could reduce by at least half. The
goal of treatment was only to reduce local and
regional recurrence and not to improve overall
survival.
The treatment volume typically included the chest
wall, supraclavicular nodes, and axillary nodes and
much less often, the internal mammary nodes.
What did we learn in
1997?
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Two articles published in the NEJM 10/97 showed
improvement in survival with PMRT in
premenopausal women, all of whom also received
chemotherapy (CMF).
Patients enrolled in these trials included were
(generally) node + with the majority having only 13 positive nodes and the majority having tumors <
5 cm in size.
Fields treated included chest wall and all regional
nodes (including internal mammary).
Similar results seen in postmenopausal stage II/III
women treated with tamoxifen and XRT,
improvement in DFS and overall survival.
Overall survival results
Figure 1A.
Overall survival in the Danish Breast Cancer Cooperative Group Trial. (5)
Figure 1B.
Overall survival in the British Columbia Trial. (6)
British Columbia
Randomized trial: 20 year
results
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1. Breast Cancer Specific
Survival
2. Overall Survival
Where did we go in 2000?
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Many people began recommending
treatment for any node positive patient
following mastectomy.
Intergroup study attempted to address role
of postmastectomy XRT in women with 1-3
positive nodes but closed in June 2003
secondary to lack of accrual.
Many discussions regarding the value of
treating clinically uninvolved nodes and how
that may impact overall survival.
What is the downside of
PMRT?
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Greater risk for lymphedema of breast and
arm
Increased amount of lung that is fibrosed by
radiation, primarily from treatment of either
the supraclavicular nodes or internal
mammary nodes.
May expose contralateral breast to radiation.
Decrease in the quality of the cosmetic
outcome following reconstruction, especially
with implants.
Who needs PMRT in
2008?
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All women with > 3 positive nodes.
All women with any positive node and
a tumor larger than 5 cm.
? Women with positive margins
? Women with T3N0
? Women with 1-3 positive nodes and
T1/T2.
When positive margins
are the only risk factor
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Hard to demonstrate the value of PMRT in
patients where positive margins is the only
risk factor for local recurrence; retrospective
reviews have found LRF rates of <15%
without XRT.
Retrospective multivariate analysis of large
group in Canada found a LRF rate of >20%
in those pts with positive margins who also
had T2 tumor, <51 years old, grade 3, or
LVSI.
Canadian retrospective
review of + margins
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Included T1-2, N0
patients with +
margins; n=98.
Admitted bias inherent
in retrospective review.
Found longer time to
local relapse in those
receiving XRT (3 vs. 4
years).
T3N0, Do they really need
it?
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Retrospective review of 5 NSABP studies
found that in pts treated with or without
systemic therapy and without PMRT, those
with T3N0 had a LRF rate of 7% at 10 years
(not significantly decreased by systemic
therapy).
Similar review from combined data base of
MGH, Yale, and MDACC showed a similar
LRF rate of 7% (at 5 years) but showed that
presence of LVSI significantly increased risk
of LRF.
Review of 5 NSABP Trials:
T3N0 do not need PMRT
JCO 24: 3927-32, 2006
The common group: 1-3
positive nodes
Randomized data: Canadian
Trial, Just the 1-3 + node
group
Still see benefit in this
group both in
breast cancer
specific and overall
survival.
Magnitude of benefit
is slightly less than
in the 4 or more
node + group.
Retrospective reviews
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Review of 5 NSABP trials found a 19% LRF
in pts <50 yrs with T2 tumor with 1-3
positive nodes; those >50 with 1-3 nodes
had LRF rates of 3-12%.
Analysis of large Canadian database
examining pts with T1/2 tumors and 1-3
nodes showed <45 years, ER-, medial tumor
location, and >25% of nodes positive
associated with increased risk of LRF.
Review of NSABP trials: T13, N+ treated with chemo
Concluded that the routine use of PMRT in this group is not
warranted. JCO 22: 4247-4254, 2004
Canadian retrospective
review of 1-3+ nodes: Risk
classification
IJROBP 61:1337-1347, 2005
Who needs PMRT in
2007?
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All women with > 3 positive nodes.
All women with any positive node and a
tumor larger than 5 cm.
? Women with positive margins: Only with
other risk factors like size, age, or grade.
? Women with T3N0: Probably not,
especially in older women.
? Women with 1-3 positive nodes and
T1/T2: Definitely worth a discussion in
young women (<50).
Why has our thinking
changed?
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Systemic therapy has improved; with
this, improvements in local control
may be more meaningful.
The “paradigm” for breast cancer is
again shifting to somewhere between
Halsted and Fisher.
Impact of local control on
systemic recurrence
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Long term follow of
Canadian trial shows
that there is a
decrease in systemic
recurrence in those
patients receiving XRT.
“Alternate hypothesis”
may need to be
modified where the
impact of local control
is emphasized.
Techniques for PMRT
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Toxicity of PMRT increases with inclusion of
internal mammary nodes.
Comparison of various methods (standard
tangents, reverse hockey stick,
photon/electron mix, and partial wide
tangents) for CW and IMN coverage showed
no single best technique.
Partial wide tangents gave the best balance
between target coverage and normal tissue
sparing. (IJROBP 52:1220-30, 2002)
Importance of 3D
treatment planning
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3D planning is critical
in the sparing of
normal tissues.
Use of IMRT
techniques are
increasing; problems
remain motion and
dose to contralateral
breast and lung.
Toxicity of PMRT
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Lung: With addition of
nodal fields, V20Gy can
increase to 30%.
Arm: Incidence of
lymphedema may
increase to 20-30%
with axillary field; risk
increases with
increased BMI.
Heart: Some dose to
the heart but clinical
impact is small.
Use of PMRT with
reconstruction
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Any pt irradiated with implant reconstruction
will not look as good as a pt who does not
receive XRT.
Autologous reconstruction appear to
“tolerate” XRT better, with better cosmesis.
Less long term data on cosmetic results with
newer methods of reconstruction, eg. DIEP
flap.
PMRT with implant
reconstruction
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MSKCC recently published their algorithm
for PMRT with implant reconstruction. They
recommend placement of permanent
implant after expansion during
chemotherapy and before start of XRT.
Report that interval between end of chemo
and start of XRT did not deleteriously impact
outcomes.
Dosimetry studies around metallic ports of
expander have shown no significant impact
on dose or complications.