TY - JOUR
T1 - Effect of Delayed Targeted Intraoperative Radiotherapy vs Whole-Breast Radiotherapy on Local Recurrence and Survival
T2 - Long-term Results from the TARGIT-A Randomized Clinical Trial in Early Breast Cancer
AU - Vaidya, Jayant S.
AU - Bulsara, Max
AU - Saunders, Christobel
AU - Flyger, Henrik
AU - Tobias, Jeffrey S.
AU - Corica, Tammy
AU - Massarut, Samuele
AU - Wenz, Frederik
AU - Pigorsch, Steffi
AU - Alvarado, Michael
AU - Douek, Michael
AU - Eiermann, Wolfgang
AU - Brew-Graves, Chris
AU - Williams, Norman
AU - Potyka, Ingrid
AU - Roberts, Nicholas
AU - Bernstein, Marcelle
AU - Brown, Douglas
AU - Sperk, Elena
AU - Laws, Siobhan
AU - Sütterlin, Marc
AU - Lundgren, Steinar
AU - Holmes, Dennis
AU - Vinante, Lorenzo
AU - Bozza, Fernando
AU - Pazos, Montserrat
AU - Le Blanc-Onfroy, Magali
AU - Gruber, Günther
AU - Polkowski, Wojciech
AU - Dedes, Konstantin J.
AU - Niewald, Marcus
AU - Blohmer, Jens
AU - McCready, David
AU - Hoefer, Richard
AU - Kelemen, Pond
AU - Petralia, Gloria
AU - Falzon, Mary
AU - Baum, Michael
AU - Joseph, David
N1 - Funding Information:
received a research grant from Photoelectron Corp (1996-1999) and from Carl Zeiss for supporting data management at the University of Dundee (2004-2008) and has subsequently received honoraria. Drs Vaidya, Tobias, Williams, Potyka, Ms Brew-Graves, and Mr Roberts receive funding from Health Technology Assessment Programme, National Institute for Health Research (NIHR), Department of Health for some activities related to the TARGIT trials. Dr Baum was on the scientific advisory board of Carl Zeiss and was paid monthly consultancy fees briefly before 2010. Dr Wenz has received a research grant from Carl Zeiss for supporting radiobiological research. Carl Zeiss sponsors some of the travel and accommodation for meetings of the international steering committee and data monitoring committee and when necessary for conferences where a presentation about targeted intraoperative radiotherapy is being made for all authors apart from Dr Eiermann who declares that he has no conflicts of interest. No other conflicts are reported.
Funding Information:
Funding/Support: The study was sponsored by
Funding Information:
University College London Hospitals (UCLH)/UCL Comprehensive Biomedical Research Centre. Funding was provided by UCLH Charities, NIHR Health Technology Assessment Programme, Ninewells Cancer Campaign, National Health and Medical Research Council, and German Federal Ministry of Education and Research (FKZ 01ZP0508). The infrastructure of the trial operations office in London, United Kingdom, was supported by core funding from Cancer Research Campaign (now Cancer Research UK) when the trial was initiated.
Publisher Copyright:
© 2020 American Medical Association. All rights reserved.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/7
Y1 - 2020/7
N2 - 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 [7] years) were randomized to delayed TARGIT-IORT and 572 patients (mean [SD] age, 63 [8] 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.
AB - 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 [7] years) were randomized to delayed TARGIT-IORT and 572 patients (mean [SD] age, 63 [8] 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.
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U2 - 10.1001/jamaoncol.2020.0249
DO - 10.1001/jamaoncol.2020.0249
M3 - Article
VL - 6
JO - JAMA oncology
JF - JAMA oncology
SN - 2374-2437
IS - 7
M1 - e200249
ER -