Abstract S4-2: Targeted intraoperative radiotherapy for early breast cancer: TARGIT-A trial- updated analysis of local recurrence and first analysis of survival

Abstract

Background TARGIT-A, an international phase 3 randomised trial (Lancet 2010;376:91–102) compared outcomes in patients undergoing breast conserving surgery followed by either whole breast external beam radiotherapy (EBRT) over several weeks, or a risk-adaptive approach using single dose targeted intra-operative radiotherapy (TARGIT). Risk-adaptive approach meant that if the final pathology report demonstrated unpredicted pre-specified adverse features, then EBRT was to be added to TARGIT. Method 3451 women aged 45 years or older with invasive ductal carcinoma were enrolled from 33 centres in 10 countries between 2000 and 2012. Randomisation to TARGIT or EBRT arm was done either before lumpectomy (pre-pathology) or after lumpectomy (postpathology). If allocated to TARGIT, patients in the pre-pathology group received it immediately after surgical excision under the same anaesthesia; patients in the post-pathology group received it as a subsequent procedure. We pre-specified that analysis would be performed overall as the primary analysis and for these groups separately as a secondary analysis. The primary outcome was ipsilateral within breast recurrence (IBR) with an absolute non-inferiority margin of 2.5% at 5 years and secondary outcome was survival. We performed exploratory analyses for loco-regional recurrence, ‘all recurrence’ (ipsilateral or contralateral breast, axilla or distant), distant recurrence, and causes of death. Results 1721 patients were randomly allocated to receive TARGIT and 1730 to EBRT. 1010 patients have a minimum 4 years follow up and 611 patients have minimum 5 years follow up. Primary events have increased from 13 to 34 since 2010. For the primary outcome of ipsilateral breast recurrence, the absolute difference at 5-years was 2.0%, which was higher with TARGIT and reached the conventional levels of statistical significance (p = 0.042), but was within the pre-specified non-inferiority margin; in prepathology the absolute difference in 5-year IBR was 1%; in postpathology it was 3.7%. For the secondary outcome, there was a non-significant trend for improved overall survival with TARGIT (HR = 0.70(0.46–1.07)) due to fewer non-breast cancer deaths (17 vs. 35, HR 0.47 (0.26–0.84)). Cardiovascular deaths were 1 vs. 10 and deaths from cancers other than breast were 7 vs.16. Conclusion The risk-adapted approach using single dose TARGIT has a slightly higher local recurrence rate than EBRT for the primary endpoint of IBR, but was within the preset non-inferiority boundary, with the prepathology apparently performing better than the postpathology stratum. In addition there was a trend for improved overall survival in the TARGIT arm due to fewer non-breast cancer deaths. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr S4-2.

The Emerging Role of Intraoperative Radiation Therapy [IORT] in Breast Cancer

“…They concluded: "The overall recurrence rate of the TARGIT-A trial have remained stable with a longer followup and it is therefore statistically implausible that one particular arm has a signifi cantly higher local recurrence." The latest TARGIT-A updates, presented at the 2012 SABCS [ 50 ] and published in Lancet [ 51 ], showed that the earlier optimism expressed in the 2010 Lancet publication and the 2011 SABCS poster was likely unfounded. An additional 1,219 patients were added to TARGIT-A since the 2010 Lancet publication, for a study total of 3,442 patients.…”

“…28.12b ) which was presented at the SABCS but not shown in the Lancet publication. The nearly statistically breast recurrences (ipsilateral, regional, contralateral, and distant) [ 50 ]; ( c ) pre-pathology only TARGIT-A ipsilateral recurrences [ 51 ] signifi cant difference in overall breast recurrences in the two groups ( p = 0.053) is a reason for concern, especially since the breast cancer deaths are already, even at 29 months median follow-up, higher with TARGIT (20 deaths, 2.6 %) than with EBRT (16 deaths, 1.9 %),…”

Czy napromienianie części piersi powinno się stać standardowym elementem oszczędzającego leczenia chorych na wczesnego raka piersi? Głos na nie

“…Kolejnym badaniem z randomizacją było badanie TAR-GIT A, którego wyniki zostały opublikowane w 2010 r. [36] i uaktualnione na Konferencji w San Antonio w 2012 roku [37]. W grupie 3 451 chorych przydzielanych do losowo napromieniania 1 frakcją 20 Gy promieniami rtg o energii 50 kV lub do ramienia kontrolnego napromienianiem standardowym na całą pierś, po czasie obserwacji 2 lat i 5 miesięcy w ramieniu badanym stwierdzono 3,3% wznów w piersi w porównaniu z 1,3% w ramieniu kontrolnym (p = 0,04).…”

“…W grupie 3 451 chorych przydzielanych do losowo napromieniania 1 frakcją 20 Gy promieniami rtg o energii 50 kV lub do ramienia kontrolnego napromienianiem standardowym na całą pierś, po czasie obserwacji 2 lat i 5 miesięcy w ramieniu badanym stwierdzono 3,3% wznów w piersi w porównaniu z 1,3% w ramieniu kontrolnym (p = 0,04). Zaobserwowano też statystycznie większą liczbę wznów lokoregionalnych i przerzutów odległych w ramieniu z APBI (p = 0,02) [37].…”

Intraoperative Radiation Therapy in Breast Cancer: Not Ready for Prime Time

“…While initial data with short follow-up (median follow-up \2 years) and limited events (n = 11) was promising, a recent update found that IORT, even with WBI supplementation in one-fifth of the IORT cohort, was associated with inferior local control at 5 years (3.3 vs. 1.3 %, p = 0.04). 7,8 A second randomized trial from Milan randomized 1,186 patients to IORT or WBI. This trial used IORT delivered with electrons (21 Gy delivered to the 90 % isodose line).…”