by Roberto Orecchia, Umberto Veronesi, Patrick Maisonneuve,
Viviana Enrica Galimberti, Roberta Lazzari, Paolo Veronesi, Barbara Alicja
Jereczek-Fossa, Federica Cattani, Claudia Sangalli, Alberto Luini, Pietro
Caldarella, Marco Venturino, Daniele Sances, Stefano Zurrida, Giuseppe Viale,
Maria Cristina Leonardi, Mattia Intra
The Lancet Oncology : VOLUME 22,
ISSUE 5, P597-608, MAY 01, 2021
Background
In the randomised, phase 3 equivalence trial on electron
intraoperative radiotherapy (ELIOT), accelerated partial breast irradiation (APBI)
with the use of intraoperative radiotherapy was associated with a higher rate
of ipsilateral breast tumour recurrence (IBTR) than whole-breast irradiation
(WBI) in patients with early-stage breast cancer. Here, we aimed to examine the
planned long-term recurrence and survival outcomes from the ELIOT trial.
Methods
This single-centre, randomised, phase 3 equivalence trial
was done at the European Institute of Oncology (Milan, Italy). Eligible women,
aged 48–75 years with a clinical diagnosis of a unicentric breast carcinoma
with an ultrasound diameter not exceeding 25 mm, clinically negative axillary
lymph nodes, and who were suitable for breast-conserving surgery, were randomly
assigned (1:1) via a web-based system, with a random permuted block design
(block size of 16) and stratified by clinical tumour size, to receive
post-operative WBI with conventional fractionation (50 Gy given as 25 fractions
of 2 Gy, plus a 10 Gy boost), or 21 Gy intraoperative radiotherapy with
electrons (ELIOT) in a single dose to the tumour bed during surgery. The trial
was open label and no-one was masked to treatment group assignment. The primary
endpoint was the occurrence of IBTR. The trial was designed assuming a 5-year
IBTR rate of 3% in the WBI group and equivalence of the two groups, if the
5-year IBTR rate in the ELIOT group did not exceed a 2·5 times excess,
corresponding to 7·5%. Overall survival was the secondary endpoint. The main
analysis was done by intention to treat. The cumulative incidence of IBTR
events and overall survival were assessed at 5, 10, and 15 years of follow-up.
This trial is registered with ClinicalTrials.gov, NCT01849133.
Findings
Between Nov 20, 2000, and Dec 27, 2007, 1305 women were enrolled
and randomly assigned: 654 to the WBI group and 651 to the ELIOT group. After a
median follow-up of 12·4 years (IQR 9·7–14·7), 86 (7%) patients developed IBTR,
with 70 (11%) cases in the ELIOT group and 16 (2%) in the WBI group,
corresponding to an absolute excess of 54 IBTRs in the ELIOT group (HR 4·62,
95% CI 2·68–7·95, p<0·0001). In the ELIOT group, the 5-year IBTR rate was
4·2% (95% CI 2·8–5·9), the 10-year rate was 8·1% (6·1–10·3), and the 15-year
rate was 12·6% (9·8–15·9). In the WBI group, the 5-year IBTR rate was 0·5% (95%
CI 0·1–1·3), the 10-year rate was 1·1% (0·5–2·2), and the 15-year rate was 2·4%
(1·4–4·0). At final follow-up on March 11, 2019, 193 (15%) women had died from
any cause, with no difference between the two groups (98 deaths in the ELIOT
group vs 95 in the WBI group; HR 1·03, 95% CI 0·77–1·36, p=0·85). In
the ELIOT group, the overall survival rate was 96·8% (95% CI 95·1–97·9) at 5
years, 90·7% (88·2–92·7) at 10 years, and 83·4% (79·7–86·4) at 15 years; and in
the WBI group, the overall survival rate was 96·8% (95·1–97·9) at 5 years,
92·7% (90·4–94·4) at 10 years, and 82·4% (78·5–85·6) at 15 years. We did not
collect long-term data on adverse events.
Interpretation
The long-term results of this trial confirmed the higher
rate of IBTR in the ELIOT group than in the WBI group, without any differences
in overall survival. ELIOT should be offered to selected patients at low-risk
of IBTR.
