TY - JOUR
T1 - Risk-adapted targeted intraoperative radiotherapy versus whole-breast radiotherapy for breast cancer
T2 - 5-year results for local control and overall survival from the TARGIT-A randomised trial
AU - Vaidya, Jayant S.
AU - Wenz, Frederik
AU - Bulsara, Max
AU - Tobias, Jeffrey S.
AU - Joseph, David J.
AU - Keshtgar, Mohammed
AU - Flyger, Henrik L.
AU - Massarut, Samuele
AU - Alvarado, Michael
AU - Saunders, Christobel
AU - Eiermann, Wolfgang
AU - Metaxas, Marinos
AU - Sperk, Elena
AU - Sütterlin, Marc
AU - Brown, Douglas
AU - Esserman, Laura
AU - Roncadin, Mario
AU - Thompson, Alastair
AU - Dewar, John A.
AU - Holtveg, Helle M R
AU - Pigorsch, Steffi
AU - Falzon, Mary
AU - Harris, Eleanor
AU - Matthews, April
AU - Brew-Graves, Chris
AU - Potyka, Ingrid
AU - Corica, Tammy
AU - Williams, Norman R.
AU - Baum, Michael
PY - 2014
Y1 - 2014
N2 - Background: The TARGIT-A trial compared risk-adapted radiotherapy using single-dose targeted intraoperative radiotherapy (TARGIT) versus fractionated external beam radiotherapy (EBRT) for breast cancer. We report 5-year results for local recurrence and the first analysis of overall survival. Methods TARGIT-A was a randomised, non-inferiority trial. Women aged 45 years and older with invasive ductal carcinoma were enrolled and randomly assigned in a 1:1 ratio to receive TARGIT or whole-breast EBRT, with blocks stratified by centre and by timing of delivery of targeted intraoperative radiotherapy: randomisation occurred either before lumpectomy (prepathology stratum, TARGIT concurrent with lumpectomy) or after lumpectomy (postpathology stratum, TARGIT given subsequently by reopening the wound). Patients in the TARGIT group received supplemental EBRT (excluding a boost) if unforeseen adverse features were detected on final pathology, thus radiotherapy was risk-adapted. The primary outcome was absolute difference in local recurrence in the conserved breast, with a prespecified non-inferiority margin of 2.5% at 5 years; prespecified analyses included outcomes as per timing of randomisation in relation to lumpectomy. Secondary outcomes included complications and mortality. This study is registered with ClinicalTrials.gov, number NCT00983684. Findings: Patients were enrolled at 33 centres in 11 countries, between March 24, 2000, and June 25, 2012. 1721 patients were randomised to TARGIT and 1730 to EBRT. Supplemental EBRT after TARGIT was necessary in 15.2% [239 of 1571] of patients who received TARGIT (21.6% prepathology, 3.6% postpathology). 3451 patients had a median follow-up of 2 years and 5 months (IQR 12-52 months), 2020 of 4 years, and 1222 of 5 years. The 5-year risk for local recurrence in the conserved breast was 3.3% (95% CI 2.1-5.1) for TARGIT versus 1.3% (0.7-2.5) for EBRT (p=0.042). TARGIT concurrently with lumpectomy (prepathology, n=2298) had much the same results as EBRT: 2.1% (1.1-4.2) versus 1.1% (0.5-2.5; p=0.31). With delayed TARGIT (postpathology, n=1153) the between-group difference was larger than 2.5% (TARGIT 5.4% [3.0-9.7] vs EBRT 1.7% [0.6-4.9]; p=0.069). Overall, breast cancer mortality was much the same between groups (2.6% [1.5-4.3] for TARGIT vs 1.9% [1.1-3.2] for EBRT; p=0.56) but there were significantly fewer non-breast-cancer deaths with TARGIT (1.4% [0.8-2.5] vs 3.5% [2.3-5.2]; p=0.0086), attributable to fewer deaths from cardiovascular causes and other cancers. Overall mortality was 3.9% (2.7-5.8) for TARGIT versus 5.3% (3.9-7.3) for EBRT (p=0.099). Wound-related complications were much the same between groups but grade 3 or 4 skin complications were significantly reduced with TARGIT (four of 1720 vs 13 of 1731, p=0.029). Interpretation: TARGIT concurrent with lumpectomy within a risk-adapted approach should be considered as an option for eligible patients with breast cancer carefully selected as per the TARGIT-A trial protocol, as an alternative to postoperative EBRT.
AB - Background: The TARGIT-A trial compared risk-adapted radiotherapy using single-dose targeted intraoperative radiotherapy (TARGIT) versus fractionated external beam radiotherapy (EBRT) for breast cancer. We report 5-year results for local recurrence and the first analysis of overall survival. Methods TARGIT-A was a randomised, non-inferiority trial. Women aged 45 years and older with invasive ductal carcinoma were enrolled and randomly assigned in a 1:1 ratio to receive TARGIT or whole-breast EBRT, with blocks stratified by centre and by timing of delivery of targeted intraoperative radiotherapy: randomisation occurred either before lumpectomy (prepathology stratum, TARGIT concurrent with lumpectomy) or after lumpectomy (postpathology stratum, TARGIT given subsequently by reopening the wound). Patients in the TARGIT group received supplemental EBRT (excluding a boost) if unforeseen adverse features were detected on final pathology, thus radiotherapy was risk-adapted. The primary outcome was absolute difference in local recurrence in the conserved breast, with a prespecified non-inferiority margin of 2.5% at 5 years; prespecified analyses included outcomes as per timing of randomisation in relation to lumpectomy. Secondary outcomes included complications and mortality. This study is registered with ClinicalTrials.gov, number NCT00983684. Findings: Patients were enrolled at 33 centres in 11 countries, between March 24, 2000, and June 25, 2012. 1721 patients were randomised to TARGIT and 1730 to EBRT. Supplemental EBRT after TARGIT was necessary in 15.2% [239 of 1571] of patients who received TARGIT (21.6% prepathology, 3.6% postpathology). 3451 patients had a median follow-up of 2 years and 5 months (IQR 12-52 months), 2020 of 4 years, and 1222 of 5 years. The 5-year risk for local recurrence in the conserved breast was 3.3% (95% CI 2.1-5.1) for TARGIT versus 1.3% (0.7-2.5) for EBRT (p=0.042). TARGIT concurrently with lumpectomy (prepathology, n=2298) had much the same results as EBRT: 2.1% (1.1-4.2) versus 1.1% (0.5-2.5; p=0.31). With delayed TARGIT (postpathology, n=1153) the between-group difference was larger than 2.5% (TARGIT 5.4% [3.0-9.7] vs EBRT 1.7% [0.6-4.9]; p=0.069). Overall, breast cancer mortality was much the same between groups (2.6% [1.5-4.3] for TARGIT vs 1.9% [1.1-3.2] for EBRT; p=0.56) but there were significantly fewer non-breast-cancer deaths with TARGIT (1.4% [0.8-2.5] vs 3.5% [2.3-5.2]; p=0.0086), attributable to fewer deaths from cardiovascular causes and other cancers. Overall mortality was 3.9% (2.7-5.8) for TARGIT versus 5.3% (3.9-7.3) for EBRT (p=0.099). Wound-related complications were much the same between groups but grade 3 or 4 skin complications were significantly reduced with TARGIT (four of 1720 vs 13 of 1731, p=0.029). Interpretation: TARGIT concurrent with lumpectomy within a risk-adapted approach should be considered as an option for eligible patients with breast cancer carefully selected as per the TARGIT-A trial protocol, as an alternative to postoperative EBRT.
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U2 - 10.1016/S0140-6736(13)61950-9
DO - 10.1016/S0140-6736(13)61950-9
M3 - Article
C2 - 24224997
AN - SCOPUS:84893877736
VL - 383
SP - 603
EP - 613
JO - The Lancet
JF - The Lancet
SN - 0140-6736
IS - 9917
ER -