After breast-conserving surgery, 90% of local recurrences occur within the index quadrant
despite the presence of multicentric cancers elsewhere in the breast. Thus, restriction
of radiation therapy to the tumour bed during surgery might be adequate for selected
patients. We compared targeted intraoperative radiotherapy with the conventional policy
of whole breast external beam radiotherapy.
Having safely piloted the new technique of single-dose targeted intraoperative radiotherapy
with Intrabeam, we launched the TARGIT-A trial on March 24, 2000. In this prospective,
randomised, non-inferiority trial, women aged 45 years or older with invasive ductal
breast carcinoma undergoing breast-conserving surgery were enrolled from 28 centres
in nine countries. Patients were randomly assigned in a 1:1 ratio to receive targeted
intraoperative radiotherapy or whole breast external beam radiotherapy, with blocks
stratified by centre and by timing of delivery of targeted intraoperative radiotherapy.
Neither patients nor investigators or their teams were masked to treatment assignment.
Postoperative discovery of predefined factors (eg, lobular carcinoma) could trigger
addition of external beam radiotherapy to targeted intraoperative radiotherapy (in
an expected 15% of patients). The primary outcome was local recurrence in the conserved
breast. The predefined non-inferiority margin was an absolute difference of 2.5% in
the primary endpoint. All randomised patients were included in the intention-to-treat
analysis. This trial is registered with ClinicalTrials.gov, number NCT00983684.
1113 patients were randomly allocated to targeted intraoperative radiotherapy and
1119 were allocated to external beam radiotherapy. Of 996 patients who received the
allocated treatment in the targeted intraoperative radiotherapy group, 854 (86%) received
targeted intraoperative radiotherapy only and 142 (14%) received targeted intraoperative
radiotherapy plus external beam radiotherapy. 1025 (92%) patients in the external
beam radiotherapy group received the allocated treatment. At 4 years, there were six
local recurrences in the intraoperative radiotherapy group and five in the external
beam radiotherapy group. The Kaplan-Meier estimate of local recurrence in the conserved
breast at 4 years was 1.20% (95% CI 0.53-2.71) in the targeted intraoperative radiotherapy
and 0.95% (0.39-2.31) in the external beam radiotherapy group (difference between
groups 0.25%, -1.04 to 1.54; p=0.41). The frequency of any complications and major
toxicity was similar in the two groups (for major toxicity, targeted intraoperative
radiotherapy, 37 [3.3%] of 1113 vs external beam radiotherapy, 44 [3.9%] of 1119;
p=0.44). Radiotherapy toxicity (Radiation Therapy Oncology Group grade 3) was lower
in the targeted intraoperative radiotherapy group (six patients [0.5%]) than in the
external beam radiotherapy group (23 patients [2.1%]; p=0.002).
For selected patients with early breast cancer, a single dose of radiotherapy delivered
at the time of surgery by use of targeted intraoperative radiotherapy should be considered
as an alternative to external beam radiotherapy delivered over several weeks.
University College London Hospitals (UCLH)/UCL Comprehensive Biomedical Research Centre,
UCLH Charities, National Institute for Health Research Health Technology Assessment
programme, Ninewells Cancer Campaign, National Health and Medical Research Council,
and German Federal Ministry of Education and Research (BMBF).
Copyright 2010 Elsevier Ltd. All rights reserved.