Effect of Delayed Targeted Intraoperative Radiotherapy vs Whole-Breast Radiotherapy on Local Recurrence and Survival: Long-term Results From the TARGIT-A Randomized Clinical Trial in Early Breast Cancer.
Importance: Conventional adjuvant radiotherapy for breast cancer given daily for several weeks is onerous and expensive. Some patients may be obliged to choose a mastectomy instead, and some may forgo radiotherapy altogether. We proposed a clinical trial to test whether radiotherapy could be safely limited to the tumor bed.
Objective: To determine whether delayed second-procedure targeted intraoperative radiotherapy (TARGIT-IORT) is noninferior to whole-breast external beam radiotherapy (EBRT) in terms of local control.
Design, Setting, and Participants: In this prospective, randomized (1:1 ratio) noninferiority trial, 1153 patients aged 45 years or older with invasive ductal breast carcinoma smaller than 3.5 cm treated with breast conservation were enrolled from 28 centers in 9 countries. Data were locked in on July 3, 2019.
Interventions: The TARGIT-A trial was started in March 2000; patients were randomized after needle biopsy to receive TARGIT-IORT immediately after lumpectomy under the same anesthetic vs EBRT and results have been shown to be noninferior. A parallel study, described in this article, was initiated in 2004; patients who had their cancer excised were randomly allocated using separate randomization tables to receive EBRT or delayed TARGIT-IORT given as a second procedure by reopening the lumpectomy wound.
Main Outcomes and Measures: A noninferiority margin for local recurrence rate of 2.5% at 5 years, and long-term survival outcomes.
Results: Overall, 581 women (mean [SD] age, 63  years) were randomized to delayed TARGIT-IORT and 572 patients (mean [SD] age, 63  years) were randomized to EBRT. Sixty patients (5%) had tumors larger than 2 cm, or had positive nodes and only 32 (2.7%) were younger than 50 years. Delayed TARGIT-IORT was not noninferior to EBRT. The local recurrence rates at 5-year complete follow-up were: delayed TARGIT-IORT vs EBRT (23/581 [3.96%] vs 6/572 [1.05%], respectively; difference, 2.91%; upper 90% CI, 4.4%). With long-term follow-up (median [IQR], 9.0 [7.5-10.5] years), there was no statistically significant difference in local recurrence-free survival (HR, 0.75; 95% CI, 0.57-1.003; P = .052), mastectomy-free survival (HR, 0.88; 95% CI, 0.65-1.18; P = .38), distant disease-free survival (HR, 1.00; 95% CI, 0.72-1.39; P = .98), or overall survival (HR, 0.96; 95% CI, 0.68-1.35; P = .80).
Conclusions and Relevance: These long-term data show that despite an increase in the number of local recurrences with delayed TARGIT-IORT, there was no statistically significant decrease in mastectomy-free survival, distant disease-free survival, or overall survival.
Trial Registration: ISRCTN34086741, ClinicalTrials.gov Identifier: NCT00983684.
Women & Children
Vaidya, Jayant S; Bulsara, Max; Saunders, Christobel; Flyger, Henrik; Tobias, Jeffrey S; Corica, Tammy; Massarut, Samuele; Wenz, Frederik; Pigorsch, Steffi; Alvarado, Michael; Douek, Michael; Eiermann, Wolfgang; Brew-Graves, Chris; Williams, Norman; Potyka, Ingrid; Roberts, Nicholas; Bernstein, Marcelle; Brown, Douglas; Sperk, Elena; Laws, Siobhan; Sütterlin, Marc; 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; Baum, Michael; and Joseph, David, "Effect of Delayed Targeted Intraoperative Radiotherapy vs Whole-Breast Radiotherapy on Local Recurrence and Survival: Long-term Results From the TARGIT-A Randomized Clinical Trial in Early Breast Cancer." (2020). Articles, Abstracts, and Reports. 3108.