2012 EDUCATIONAL BOOK - American Society of Clinical Oncology

POSTMASTECTOMY RADIATION AND PARTIAL BREAST IRRADIATION
trial indirectly validates the findings of the three modern
PMXRT trials.
It is likely that other factors can aid in predicting LRR
risk after mastectomy. For example, researchers have
shown that the 21-gene recurrence score assay (Oncotype
DX; Genomic Health, Inc., Redwood City, CA), commonly
used to determine the risk of distant recurrence, may also be
predictive of the risk of locoregional recurrence. 9 Other
factors reported to be associated with increased locoregional
failure include tumor size, positive margins, extracapsular
extension, lymphovascular invasion, response to neoadjuvant
chemotherapy, age, ER/PR status, p53 overexpression,
and breast cancer subtypes. 5,8,9 While we await evaluation
of putative biologic, genetic and clinical factors predictive of
LRR such that we can judge a patient’s need for PMXRT, it
is perhaps prudent to at least seriously consider PMXRT for
women with one to three positive axillary LNs.
PBI
In-breast failures after breast-conserving therapy (defined
here as lumpectomy and WBI) occur in the vicinity of the
original primary tumor approximately 70 to 90% of the time.
This phenomenon gave birth to the concept of PBI. Benefits
of this proposed new treatment paradigm include shorter
overall treatment course, increased efficacy via the larger
biologically effective doses that are possible with PBI, and
decreased toxicity because less tissue is exposed to radiation.
PBI can be divided into two general techniques: brachytherapy
based (radiation close to the target) and teletherapy
based (external beam). Brachytherapy-based PBI normally
occurs postoperatively and may be delivered by interstitial
(needles) or intracavitary (mammosite, contura, etc.) techniques.
Teletherapy-based PBI can be delivered either intraoperatively
or postoperatively. Of the three largest
randomized controlled trials comparing various PBI techniques
versus standard WBI, only one has been published;
another is closed to accrual but the results have not been
KEY POINTS
● Three modern postmastectomy radiation therapy
(PMXRT) trials reported improved overall survival
with adjuvant radiation in patients with one to three
positive lymph nodes.
● Meta-analyses support the conclusion of these modern
PMXRT trials.
● A new trial from the National Cancer Institute of
Canada (NCIC), which reported a survival benefit in
women receiving treatment with whole-breast irradiation
(WBI) and regional nodal irradiation when
compared with WBI alone, indirectly supports
PMXRT.
● Partial breast irradiation (PBI) has been shown to be
comparable with WBI in a single large randomized
controlled trial using intraoperative PBI.
● Although smaller trials and retrospective studies
support PBI, it may be best to await the results of
other large randomized controlled trials evaluating
various PBI techniques.
presented, and a third remains open to accrual. The largest
trial published to date is the TARGIT trial in which more
than 2,000 women were randomly assigned to receive WBI
or intraoperative radiation therapy (IORT). Patients received
20 Gy (photons) to the surface of the lumpectomy
bed. 10 Patients enrolled were generally low risk: More than
80% were 50 years of age or older, node negative, ERpositive,
and HER2-negative. Interestingly, as a result of
various high-risk features, approximately 14% of the patients
randomly assigned to receive PBI also received WBI.
Estimates of ipsilateral breast tumor recurrence rates at 4
years were 1.2% and 1.0% for PBI and WBI, respectively.
Although the results are promising, skepticism has prevented
wide acceptance. There are concerns that the
follow-up period is too short, the prescribed dose is too low,
and delivery of IORT is logistically too difficult. Nonetheless,
the TARGIT trial supports the concept of PBI.
The second large randomized controlled trial of PBI is
from Milan. Similar to the TARGIT trial, PBI consists of 20
Gy (electrons) delivered to the lumpectomy bed intraoperatively.
The accrual goal of approximately 1,306 women was
reached some time ago. So far, one of the investigators has
stated that the there is no difference in survival between the
two arms at 10 years. 11 We eagerly await the results of this
important study.
The largest trial is that of NSABP B-39/Radiation Therapy
Oncology Group (RTOG) 0413. 12 This trial is unique not
only for its accrual goal of 4,300 women but also because
three separate PBI techniques are permitted. Women randomly
assigned to receive PBI may be offered, depending on
the hosting institution, interstitial or intracavitary brachytherapy
or postoperative teletherapy. Interestingly, with
more than 4,100 patients enrolled thus far (and on target to
complete accrual in 2012), more than 70% of the patients
receiving treatment with PBI received it via the postoperative
teletherapy technique. The trial completed accrual of
low-risk patients, and now remains open to accrue patients
with a higher risk of recurrence (e.g., ER-negative, LNpositive,
or age younger than 50 years).
Another potential benefit of PBI is that it could be combined
with systemic therapy, thereby not only shortening
the course of radiation but shortening the the overall
treatment course. For example in a small feasibility study,
patients received treatment with PBI (2.7 Gy twice daily
for 15 days) and concurrent dose-dense doxorubicin and
cyclophosphamide. 13 The authors reported that systemic
toxicity was minimal, radiation dermatitis was far less than
that seen in standard WBI without concurrent chemotherapy,
and cosmetic outcome was good to excellent in more
than 90% of the patients. This small pilot study deserves
validation in larger trials but may hint to a new era of
combined-modality therapy in the management of breast
cancer.
Given the general public interest in PBI, and the fact that
smaller randomized controlled trials and retrospective
studies support its use, the American Society for Therapeutic
Radiology and Oncology (ASTRO) published guidelines
defining patient characteristics most appropriate for this
new treatment option. Many practitioners have accepted
these guidelines and use them in daily practice. However, a
recent presentation of a study comparing brachytherapybased
PBI versus WBI may have placed a pall over the
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