Follow up: Firstly, the follow up is not short. The TARGIT-A trial has a substantial number of patients (n=1222) with a median follow up of 5 years. The whole trial (n=3451) includes the data from all these longer-term patients as well as the data of recently recruited patients – which may give an appearance that the follow up is short. Secondly, there was no significant loss to follow up. 93·7% [3234 of 3451] of patients were seen within the year before the datalock or had at least 5 years of follow up.
Most importantly, the results remain stable with longer follow up periods, even after restricting the analysis to the earliest patients (median follow up 5 years). Furthermore, the difference between the two treatments at 5 years is not expected to be different from that seen at 8 or 10 years, as seen in other similar trials (ELIOT and START-B). It has been repeatedly shown that the hazard of relapse of breast cancer peaks during the 2nd /3rd year – which is already well covered in the TARGIT-A trial follow up.
Effectiveness: We found that TARGIT concurrent with lumpectomy is effective in reducing local recurrence. Absence of radiotherapy increases local recurrence (7% at 5 years in CALGB trial). TARGIT given as a second procedure (postpathology) was not effective – this provided us with an internal control. The patients in the postpathology stratum (n=1153) were highly selected for favorable pathological entry criteria yet they showed a difference of 3·7% (5·4% vs 1·7%) in local recurrence, much the same as for patients in studies with a non-irradiated experimental group. In the larger (n=2298) prepathology stratum the difference was a non-significant 1·0%, suggesting that TARGIT is effective in reducing local recurrence when given concurrently with lumpectomy.
Reduced non-breast-cancer mortality: Importantly, there are significantly fewer non-breast-cancer deaths with TARGIT. The author appears to have missed this significant finding. Mortality from causes other than breast cancer - such as cardiovascular causes and other cancers was significantly reduced with TARGIT leading to a trend in lower overall mortality.
In brief, when TARGIT is given with lumpectomy, breast cancer outcomes (local recurrence or death) are not statistically different from whole breast radiotherapy; mortality from causes other than breast cancer is significantly lower - 1.3% with TARGIT and 4.4% with whole breast radiotherapy.
Hence the interpretation is valid: “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.
We recognize that an opposition to the policy of limiting radiotherapy to the tumor bed rather than the whole breast in selected cases is not very different from the resistance to the change from mastectomy to lumpectomy 30 years ago. We hope that there will be enough clinicians with open minds who will embrace this approach of targeted intraoperative radiotherapy in the same way that breast conserving surgery for selected cases was adopted within a few years of the results of randomized trials were published.
Jayant S Vaidya, Frederik Wenz, Max Bulsara, Jeffrey S Tobias, David Joseph and Michael Baum