Risk-adapted targeted intraoperative radiotherapy versus whole-breast radiotherapy for breast cancer:5-year results for local control and overall survival from the TARGIT-A randomised trial
Vaidya, Jayant S; Wenz, Frederik; Bulsara, Max; Tobias, Jeffrey S; Joseph, David J; Keshtgar, Mohammed; Flyger, Henrik L; Massarut, Samuele; Alvarado, Michael; Saunders, Christobel; Eiermann, Wolfgang; Metaxas, Marinos; Sperk, Elena; Sütterlin, Marc; Brown, Douglas; Esserman, Laura; Roncadin, Mario; Thompson, Alastair; Dewar, John A; Holtveg, Helle M R; Pigorsch, Steffi; Falzon, Mary; Harris, Eleanor; Matthews, April; Brew-Graves, Chris; Potyka, Ingrid; Corica, Tammy; Williams, Norman R; Baum, Michael
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 withClinicalTrials.gov, numberNCT00983684. 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]vsEBRT 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 TARGITvs1·9% [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]vs3·5% [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 1720vs13 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.
Vaidya, Jayant S, & Wenz, Frederik, & Bulsara, Max, & Tobias, Jeffrey S, & Joseph, David J, & Keshtgar, Mohammed, & Flyger, Henrik L, & Massarut, Samuele, & Alvarado, Michael, & Saunders, Christobel, & Eiermann, Wolfgang, & Metaxas, Marinos, & Sperk, Elena, & Sütterlin, Marc, & Brown, Douglas, & Esserman, Laura, & Roncadin, Mario, & Thompson, Alastair, & Dewar, John A, & Holtveg, Helle M R, & Pigorsch, Steffi, & Falzon, Mary, & Harris, Eleanor, & Matthews, April, & Brew-Graves, Chris, & Potyka, Ingrid, & Corica, Tammy, & Williams, Norman R, & Baum, Michael. (February 2014). Risk-adapted targeted intraoperative radiotherapy versus whole-breast radiotherapy for breast cancer:5-year results for local control and overall survival from the TARGIT-A randomised trial. The Lancet, (383:9917), p.603-613. Retrieved from http://hdl.handle.net/10342/8277
Vaidya, Jayant S, and Wenz, Frederik, and Bulsara, Max, and Tobias, Jeffrey S, and Joseph, David J, and Keshtgar, Mohammed, and Flyger, Henrik L, and Massarut, Samuele, and Alvarado, Michael, and Saunders, Christobel, and Eiermann, Wolfgang, and Metaxas, Marinos, and Sperk, Elena, and Sütterlin, Marc, and Brown, Douglas, and Esserman, Laura, and Roncadin, Mario, and Thompson, Alastair, and Dewar, John A, and Holtveg, Helle M R, and Pigorsch, Steffi, and Falzon, Mary, and Harris, Eleanor, and Matthews, April, and Brew-Graves, Chris, and Potyka, Ingrid, and Corica, Tammy, and Williams, Norman R, and Baum, Michael. "Risk-adapted targeted intraoperative radiotherapy versus whole-breast radiotherapy for breast cancer:5-year results for local control and overall survival from the TARGIT-A randomised trial". The Lancet. 383:9917. (603-613.), February 2014. October 31, 2020. http://hdl.handle.net/10342/8277.
Vaidya, Jayant S and Wenz, Frederik and Bulsara, Max and Tobias, Jeffrey S and Joseph, David J and Keshtgar, Mohammed and Flyger, Henrik L and Massarut, Samuele and Alvarado, Michael and Saunders, Christobel and Eiermann, Wolfgang and Metaxas, Marinos and Sperk, Elena and Sütterlin, Marc and Brown, Douglas and Esserman, Laura and Roncadin, Mario and Thompson, Alastair and Dewar, John A and Holtveg, Helle M R and Pigorsch, Steffi and Falzon, Mary and Harris, Eleanor and Matthews, April and Brew-Graves, Chris and Potyka, Ingrid and Corica, Tammy and Williams, Norman R and Baum, Michael, "Risk-adapted targeted intraoperative radiotherapy versus whole-breast radiotherapy for breast cancer:5-year results for local control and overall survival from the TARGIT-A randomised trial," The Lancet 383, no. 9917 (February 2014), http://hdl.handle.net/10342/8277 (accessed October 31, 2020).
Vaidya, Jayant S, Wenz, Frederik, Bulsara, Max, Tobias, Jeffrey S, Joseph, David J, Keshtgar, Mohammed, Flyger, Henrik L, Massarut, Samuele, Alvarado, Michael, Saunders, Christobel, Eiermann, Wolfgang, Metaxas, Marinos, Sperk, Elena, Sütterlin, Marc, Brown, Douglas, Esserman, Laura, Roncadin, Mario, Thompson, Alastair, Dewar, John A, Holtveg, Helle M R, Pigorsch, Steffi, Falzon, Mary, Harris, Eleanor, Matthews, April, Brew-Graves, Chris, Potyka, Ingrid, Corica, Tammy, Williams, Norman R, Baum, Michael. Risk-adapted targeted intraoperative radiotherapy versus whole-breast radiotherapy for breast cancer:5-year results for local control and overall survival from the TARGIT-A randomised trial. The Lancet. February 2014; 383(9917) 603-613. http://hdl.handle.net/10342/8277. Accessed October 31, 2020.