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Long-Term
Results of Hypofractionated Radiation Therapy for Breast Cancer
Timothy J. Whelan, B.M., B.Ch.,
Jean-Philipp NEJM 2010;362:513
Background The optimal
fractionation schedule for whole-breast irradiation after
breast-conserving surgery is unknown.
In women with breast cancer who
undergo breast-conserving surgery, whole-breast
irradiation reduces the risk of local recurrence and can
prevent the need for mastectomy.
An update of a meta-analysis conducted by the
Early Breast Cancer Trialists' Collaborative Group showed
that breast irradiation after breast-conserving surgery
reduces mortality from breast cancer. However, up to 30%
of women in North America who undergo breast-conserving
surgery do not undergo breast irradiation, in part because of
the inconvenience of the therapy and its cost.Randomization
was performed centrally through the Ontario Clinical
Oncology Group coordinating center in Hamilton, Ontario. Patients
were stratified according to age (<50 years or
 50
years), tumor size ( 2
cm or >2 cm), systematic adjuvant therapy (tamoxifen, any
chemotherapy, or no therapy), and center. A computer-generated
randomization schedule assigned patients to
standard whole-breast
irradiation at
a dose of 50 Gy given in 25 fractions over a
period of 35
days (the control group) or accelerated, hypofractionated
whole-breast
irradiation at a dose of 42.5 Gy given in 16 fractions
over a period
of 22 days (the hypofractionated-radiation group).
Radiation was delivered by means of two opposed tangential fields,
with treatment provided daily from Monday through Friday. No
attempt was made to treat the axilla or the supraclavicular
or internal mammary nodes, and boost irradiation of the tumor
bed was not used.
In the original trials that
evaluated whole-breast irradiation after
breast-conserving surgery, 50.0 Gy of radiation was commonly
given in 25 fractions over a period of 5 weeks in daily
fractions of 2.0 Gy. Radiobiologic models suggest that a
larger daily dose (hypofractionation) given over a
shorter time (accelerated therapy) might be just as
effective this regimen may also be more convenient for
patients and less resource-intensive than the standard
schedule. Low rates of local recurrence and limited
radiation-induced morbidity have been reported with such
approaches. Schedules used in these studies ranged from
40.0 to 44.0 Gy given in 15 to 16 fractions over a 3-week
period, with daily fractions of 2.5 to 2.7 Gy.
In 2002, we reported the
5-year results of a
randomized trial in which whole-breast irradiation at a
dose of 50.0 Gy given in 25 fractions over a period of 35
days was compared with accelerated, hypofractionated
whole-breast irradiation, at a dose of 42.5 Gy given in
16 fractions over a period of 22 days, after breast-conserving
surgery in women with axillary lymph node–negative breast
cancer. Local
recurrence rates were 3% and cosmetic outcomes,
which reflect radiation-related morbidity, were similar in both
groups. Toxic effects of radiation, in particular toxicity
related to large doses per fraction, can increase over
time this raised concerns that inhibited the universal
adoption of the hypofractionated approach.In this
article, we describe the results of our trial at a median
follow-up of 12 years.
Women with
invasive breast cancer who had undergone
breast-conserving surgery and in whom resection margins
were clear and axillary lymph nodes were negative were
randomly assigned. Results The risk of
local recurrence at 10 years
was 6.7% among the 612 women assigned to standard
irradiation as compared with 6.2% among the 622 women
assigned to the hypofractionated regimen (absolute
difference, 0.5 percentage points). At 10 years, 71.3% of women
in the control group as compared with 69.8% of the women in
the hypofractionated-radiation group had a good or excellent
cosmetic outcome (absolute difference, 1.5 percentage points).
Conclusions Ten years
after treatment, accelerated, hypofractionated
whole-breast irradiation was not inferior to standard radiation
treatment in women who had undergone breast-conserving surgery
for invasive breast cancer with clear surgical margins and
negative axillary nodes
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