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<h5 class="title" id="d629611e374">Background</h5>
<p id="P5">Whole-breast irradiation after breast-conserving surgery for patients with
early-stage
breast cancer decreases ipsilateral breast-tumour recurrence (IBTR), yielding comparable
results to mastectomy. It is unknown whether accelerated partial breast irradiation
(APBI) to only the tumour-bearing quadrant, which shortens treatment duration, is
equally effective. In our trial, we investigated whether APBI provides equivalent
local tumour control after lumpectomy compared with whole-breast irradiation.
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<h5 class="title" id="d629611e379">Methods</h5>
<p id="P6">We did this randomised, phase 3, equivalence trial (NSABP B-39/RTOG 0413)
in 154 clinical
centres in the USA, Canada, Ireland, and Israel. Adult women (>18 years) with early-stage
(0, I, or II; no evidence of distant metastases, but up to three axillary nodes could
be positive) breast cancer (tumour size ≤3 cm; including all histologies and multifocal
breast cancers), who had had lumpectomy with negative (ie, no detectable cancer cells)
surgical margins, were randomly assigned (1:1) using a biased-coin-based minimisation
algorithm to receive either whole-breast irradiation (whole-breast irradiation group)
or APBI (APBI group). Whole-breast irradiation was delivered in 25 daily fractions
of 50 Gy over 5 weeks, with or without a supplemental boost to the tumour bed, and
APBI was delivered as 34 Gy of brachytherapy or 38·5 Gy of external bream radiation
therapy in 10 fractions, over 5 treatment days within an 8-day period. Randomisation
was stratified by disease stage, menopausal status, hormone-receptor status, and intention
to receive chemotherapy. Patients, investigators, and statisticians could not be masked
to treatment allocation. The primary outcome of invasive and non-invasive IBTR as
a first recurrence was analysed in the intention-to-treat population, excluding those
patients who were lost to follow-up, with an equivalency test on the basis of a 50%
margin increase in the hazard ratio (90% CI for the observed HR between 0·667 and
1·5 for equivalence) and a Cox proportional hazard model. Survival was assessed by
intention to treat, and sensitivity analyses were done in the per-protocol population.
This trial is registered with
<a data-untrusted="" href="http://ClinicalTrials.gov" id="d629611e383" target="xrefwindow">ClinicalTrials.gov</a>,
<a data-untrusted="" href="https://clinicaltrials.gov/ct2/show/NCT00103181" id="d629611e386"
target="xrefwindow">NCT00103181</a>.
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<h5 class="title" id="d629611e390">Findings</h5>
<p id="P7">Between March 21, 2005, and April 16, 2013, 4216 women were enrolled. 2109
were assigned
to the whole-breast irradiation group and 2107 were assigned to the APBI group. 70
patients from the whole-breast irradiation group and 14 from the APBI group withdrew
consent or were lost to follow-up at this stage, so 2039 and 2093 patients respectively
were available for survival analysis. Further, three and four patients respectively
were lost to clinical follow-up (ie, survival status was assessed by phone but no
physical examination was done), leaving 2036 patients in the whole-breast irradiation
group and 2089 in the APBI group evaluable for the primary outcome. At a median follow-up
of 10·2 years (IQR 7·5–11·5), 90 (4%) of 2089 women eligible for the primary outcome
in the APBI group and 71 (3%) of 2036 women in the whole-breast irradiation group
had an IBTR (HR 1·22, 90% CI 0·94–1·58). The 10-year cumulative incidence of IBTR
was 4·6% (95% CI 3·7–5·7) in the APBI group versus 3·9% (3·1–5·0) in the whole-breast
irradiation group. 44 (2%) of 2039 patients in the whole-breast irradiation group
and 49 (2%) of 2093 patients in the APBI group died from recurring breast cancer.
There were no treatment-related deaths. Second cancers and treatment-related toxicities
were similar between the two groups. 2020 patients in the whole-breast irradiation
group and 2089 in APBI group had available data on adverse events. The highest toxicity
grade reported was: grade 1 in 845 (40%), grade 2 in 921 (44%), and grade 3 in 201
(10%) patients in the APBI group, compared with grade 1 in 626 (31%), grade 2 in 1193
(59%), and grade 3 in 143 (7%) in the whole-breast irradiation group.
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<h5 class="title" id="d629611e395">Interpretation</h5>
<p id="P8">APBI did not meet the criteria for equivalence to whole-breast irradiation
in controlling
IBTR for breast-conserving therapy. Our trial had broad eligibility criteria, leading
to a large, heterogeneous pool of patients and sufficient power to detect treatment
equivalence, but was not designed to test equivalence in patient subgroups or outcomes
from different APBI techniques. For patients with early-stage breast cancer, our findings
support whole-breast irradiation following lumpectomy; however, with an absolute difference
of less than 1% in the 10-year cumulative incidence of IBTR, APBI might be an acceptable
alternative for some women.
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