BMJ (Clinical research ed.)
Aged; Breast Neoplasms; Carcinoma, Ductal, Breast; Combined Modality Therapy; Female; Humans; Intraoperative Care; Mastectomy, Segmental; Middle Aged; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Prospective Studies; Radiotherapy Dosage; Survival Rate
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
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.
Women & Children
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 R; 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; and Tobias, Jeffrey S, "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." (2020). Articles, Abstracts, and Reports. 3660.