Targeted intraoperative radiotherapy was noninferior to external-beam radiotherapy in preventing local recurrence among all patients and among patients receiving targeted intraoperative radiotherapy concurrently with lumpectomy but not among those receiving the treatment postpathology.
Five-year breast cancer mortality did not differ between groups, but targeted intraoperative radiotherapy was associated with reduced non–breast cancer mortality.
In a randomized noninferiority trial (TARGIT-A) reported in The Lancet, Jayant S. Vaidya, PhD, and Michael Baum, MD, of University College London, and colleagues compared risk-adapted radiotherapy using single-dose targeted intraoperative radiotherapy vs fractionated external-beam radiotherapy in women with breast cancer. Targeted intraoperative radiotherapy met the noninferiority margin for 5-year local recurrence among all patients and when given concurrently with lumpectomy but not when delayed until after lumpectomy (postpathology). Breast cancer mortality did not differ significantly between the two groups, but targeted intraoperative radiotherapy was associated with reduced non–breast cancer mortality.
In this open-label, randomized trial, 3,451 women aged ≥ 45 years with invasive ductal carcinoma were randomly assigned to receive single-dose targeted intraoperative radiotherapy (n = 1,721) or whole-breast external-beam radiotherapy according to standard schedules over several weeks (n = 1,730) at 33 centers in 11 countries between March 2000 and June 2012. Patients were stratified by center and by timing of targeted intraoperative radiotherapy; randomization occurred either before lumpectomy (prepathology stratum, targeted intraoperative radiotherapy given concurrent with lumpectomy, total n = 2,298) or after lumpectomy (postpathology stratum, targeted intraoperative given subsequently by reopening the wound, total n = 1,153).
In the risk-adapted strategy, patients in the targeted intraoperative radiotherapy group were to receive supplemental external-beam radiotherapy (excluding a boost) if deemed necessary based on final pathology; overall, 15.2% of the targeted intraoperative radiotherapy group received external-beam radiotherapy, including 21.6% in the prepathology stratum and 3.6% in the postpathology stratum. The primary outcome was the absolute difference in local recurrence in the conserved breast, with a prespecified noninferiority margin of 2.5% at 5 years. The current report consisted of 5-year results for local recurrence and the first analysis of overall survival.
Overall, median follow-up was 2 years and 5 months in 3,451 patients, 4 years in 2,020, and 5 years in 1,222. The 5-year risk for local recurrence in the conserved breast was 3.3% in the TARGIT group vs 1.3% in the external-beam radiotherapy group (P = .042) among all patients, 2.1% vs 1.1% (P = .31) among patents in the prepathology stratum, and 5.4% vs 1.7% (difference > 2.5%; P = .069) in the postpathology stratum.
Post hoc exploratory analyses showed no significant differences in 5-year rates of regional recurrence (1.1% vs 0.9%), distant recurrence (3.9% vs 3.2%), any other recurrence (4.9% vs 4.4%), or all recurrence (8.2% vs 5.7%). The difference in all recurrence was smaller in the prepathology stratum (6.9% vs 5.8%) than in the postpathology stratum (10.4% vs 5.4%). The difference in locoregional recurrence (4.2% vs 2.0%) was also smaller in the prepathology stratum (3.1% vs 2.0%) than in the postpathology stratum (6.2% vs 2.0%).
Overall mortality was 3.9% in the targeted intraoperative radiotherapy group vs 5.3% in the external-beam radiotherapy group (P = .099), with no significant difference in breast cancer mortality (2.6% vs 1.9%) but a significant advantage for TARGIT in non–breast cancer mortality (1.4% vs 3.5%, P = .0086) reflecting fewer deaths from cardiovascular causes and other cancers.
There were no significant differences between groups in wound-related complications, but external-beam radiotherapy was associated with a significantly greater frequency of grade 3 or 4 radiotherapy-related skin complications (0.8% vs 0.2%, P=.029).
The study was supported by 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.
For more information on intraoperative radiotherapy for early breast cancer, listen to a recent podcast discussion by Dr. Vaidya and Umberto Veronesi, MD, on the TARGIT and ELIOT trials.