Long term survival and local control outcomes from single dose targeted intraoperative radiotherapy during lumpectomy (TARGIT-IORT) for early breast cancer: TARGIT-A randomised clinical trial
Authors: Vaidya Jayant S , Bulsara Max , Baum Michael , Wenz Frederik , Massarut Samuele , Pigorsch Steffi , Alvarado Michael , Douek Michael , Saunders Christobel , Flyger Henrik L , Eiermann Wolfgang , Brew-Graves Chris , Williams Norman R , Potyka Ingrid , Roberts Nicholas , Bernstein Marcelle , Brown Douglas , Sperk Elena , Laws Siobhan , Sütterlin Marc , Corica Tammy , Lundgren Steinar , Holmes Dennis , Vinante Lorenzo , Bozza Fernando , Pazos Montserrat , Le Blanc-Onfroy Magali , Gruber Günther , Polkowski Wojciech , Dedes Konstantin J , Niewald Marcus , Blohmer Jens , McCready David , Hoefer Richard , Kelemen Pond , Petralia Gloria , Falzon Mary , Joseph David J , Tobias Jeffrey S 
Published: August 2020

Objective

To determine whether risk adapted intraoperative radiotherapy, delivered as a single dose during lumpectomy, can effectively replace postoperative whole breast external beam radiotherapy for early breast cancer.

Design

Prospective, open label, randomised controlled clinical trial.

Setting

32 centres in 10 countries in the United Kingdom, Europe, Australia, the United States, and Canada.

Participants

2298 women aged 45 years and older with invasive ductal carcinoma up to 3.5 cm in size, cN0-N1, eligible for breast conservation and randomised before lumpectomy (1:1 ratio, blocks stratified by centre) to either risk adapted targeted intraoperative radiotherapy (TARGIT-IORT) or external beam radiotherapy (EBRT).

Interventions

Random allocation was to the EBRT arm, which consisted of a standard daily fractionated course (three to six weeks) of whole breast radiotherapy, or the TARGIT-IORT arm. TARGIT-IORT was given immediately after lumpectomy under the same anaesthetic and was the only radiotherapy for most patients (around 80%). TARGIT-IORT was supplemented by EBRT when postoperative histopathology found unsuspected higher risk factors (around 20% of patients).

Main outcome measures

Non-inferiority with a margin of 2.5% for the absolute difference between the five year local recurrence rates of the two arms, and long term survival outcomes.

Results

Between 24 March 2000 and 25 June 2012, 1140 patients were randomised to TARGIT-IORT and 1158 to EBRT. TARGIT-IORT was non-inferior to EBRT: the local recurrence risk at five year complete follow-up was 2.11% for TARGIT-IORT compared with 0.95% for EBRT (difference 1.16%, 90% confidence interval 0.32 to 1.99). In the first five years, 13 additional local recurrences were reported (24/1140 v 11/1158) but 14 fewer deaths (42/1140 v 56/1158) for TARGIT-IORT compared with EBRT. With long term follow-up (median 8.6 years, maximum 18.90 years, interquartile range 7.0-10.6) no statistically significant difference was found for local recurrence-free survival (hazard ratio 1.13, 95% confidence interval 0.91 to 1.41, P=0.28), mastectomy-free survival (0.96, 0.78 to 1.19, P=0.74), distant disease-free survival (0.88, 0.69 to 1.12, P=0.30), overall survival (0.82, 0.63 to 1.05, P=0.13), and breast cancer mortality (1.12, 0.78 to 1.60, P=0.54). Mortality from other causes was significantly lower (0.59, 0.40 to 0.86, P=0.005).

Conclusion

For patients with early breast cancer who met our trial selection criteria, risk adapted immediate single dose TARGIT-IORT during lumpectomy was an effective alternative to EBRT, with comparable long term efficacy for cancer control and lower non-breast cancer mortality. TARGIT-IORT should be discussed with eligible patients when breast conserving surgery is planned.

Trial registration

ISRCTN34086741, NCT00983684.