6 / 36
Noninferiority of Partial-Breast and
Reduced-Dose Radiotherapy After Breast
Conservation Surgery for Patients With Early
Breast Cancer
The Lancet
Take-home message
•
This phase III noninferiority trial enrolled 2016 women who had undergone
breast-conserving surgery for grade 1–3 unifocal invasive ductal adenocarcinoma.
They were randomized 1:1:1 to receive 40 Gy whole-breast radiotherapy (control;
n = 674), 36 Gy whole-breast radiotherapy and 40 Gy restricted to the vicinity
of the original tumor (reduced-dose group; n = 673), or 40 Gy restricted to the
vicinity of the original tumor only (partial-breast group; n = 669) to evaluate the
balance of beneficial versus adverse effects among treatment groups. Compared
with the control group, estimated 5-year differences in local relapse were −0.73%
and −0.38% in the reduced-dose and partial-breast groups, respectively. Both the
reduced-dose group and the partial-breast group exhibited noninferiority. Similar
adverse events were reported among treatment groups, with significantly fewer
reports of change in breast appearance (partial-breast group) and breast harder
or firmer (partial-breast and reduced-dose groups).
•
These data demonstrate the noninferiority of reduced-dose and partial-breast
radiotherapy compared with standard radiotherapy, approaches that can be imple-
mented globally.
Abstract
BACKGROUND
Local cancer relapse risk
after breast conservation surgery fol-
lowed by radiotherapy has fallen sharply
in many countries, and is influenced by
patient age and clinicopathological fac-
tors. We hypothesise that partial-breast
radiotherapy restricted to the vicinity of the
original tumour in women at lower than
average risk of local relapse will improve
the balance of beneficial versus adverse effects
compared with whole-breast radiotherapy.
METHODS
IMPORT LOW is a multicentre, ran-
domised, controlled, phase 3, non-inferiority
trial done in 30 radiotherapy centres in the UK.
Women aged 50 years or older who had under-
gone breast-conserving surgery for unifocal
invasive ductal adenocarcinoma of grade 1-3,
with a tumour size of 3 cm or less (pT1-2), none
to three positive axillary nodes (pN0-1), and min-
imum microscopic margins of non-cancerous
COMMENT
By Noam VanderWalde
MD
I
n their impressive, phase III noninferi-
ority trial, Coles et al randomized very
early-stage breast cancer patients
to one of three different techniques for
adjuvant radiotherapy: 1) whole-breast
radiotherapy using a hypofractionated
technique (40 Gy in 15 fractions); 2)
reduced dose of 36 Gy to the whole breast
and an additional 40 Gy to the lumpec-
tomy cavity (reduced-dose group); 3) 40
Gy in 15 fractions to the lumpectomy cav-
ity (partial-breast group). All three groups
were treated with forward planning field-
in-field tangents, which is standard in
most radiotherapy clinics. With 5 years
of median follow-up, there were very few
local recurrences (1.1% in the whole-breast
group, 0.2% in the reduced-dose group,
and 0.5% in the partial-breast group), and
noninferiority for local recurrence was
demonstrated among the three groups.
Additionally, the results showed a statis-
tically significantly lower patient-reported
firmness of the breast in the reduced-
dose and partial-breast groups, but no
difference among the groups in any of
the other adverse events. Many of late
adverse events, including heart, lung, and
secondary cancers, occur so rarely that
differences cannot realistically be demon-
strated in a single study.
This study is the first in what will likely be
a number of studies to publish results
comparing partial-breast radiotherapy to
whole-breast radiotherapy (NSABP/RTOG,
RAPID, SHARE, IRMA, etc), and the com-
pilation of evidence will hopefully allow
clinicians to make evidence-based deci-
sions. What is unique about this study is
that, as opposed to other partial-breast
techniques that entail acceleration of tim-
ing and other techniques of delivering
radiotherapy (from one-dose intraoper-
ative radiotherapy [IORT] to accelerated
partial-breast irradiation [APBI] given over
1–2 weeks), this study only compared a
change in one variable (ie, the volume of
tissue being irradiated). The extremely
low recurrence rate in all three groups
and noninferiority demonstrate that it is
at least safe to reduce the volume of tis-
sue irradiated in this patient population
(specifically very low-risk patients with
unifocal non-lobular histology, >2 mm
margins, mostly hormone-positive (receiv-
ing endocrine therapy) and node-negative
(although the protocol allowed for N1 dis-
ease, very few patients were enrolled).
Although this study alone, with only 5
years of follow-up, may not convince
radiation oncologists to change their
current practice away from treating the
whole breast in this population, it does
offer supportive evidence that it is safe
to block the medial left breast (when
the tumor bed is not in that location) to
avoid the heart. Additionally, although not
directly addressed in this study, the low
recurrence rate may also lend evidence
to avoid boosting the lumpectomy cavity
(as is common practice in the US) in this
patient population.
Dr. VanderWalde is
Assistant Professor,
Department of Radiation
Oncology, University of
Tennessee West Cancer
Clinic.
EDITOR’S PICKS
6
PRACTICEUPDATE ONCOLOGY