Thank you. I’ll be presenting the results of NSABP B-39 RTOG-0413 on behalf of the NRG oncology group. I don’t have a disclosure slide but I don’t have any relevant financial disclosures. Just as a little bit of a background, standard breast conserving therapy consists of lumpectomy plus about 5-7 weeks of whole breast irradiation, that was the standard for the past fifty years or so. In an effort to improve the quality of life of our patients we studied whether or not we could reduce the overall treatment time significantly in these patients down to a week or less by doing a technique referred to as partial breast irradiation, meaning limiting the radiation only to the lumpectomy cavity region and accelerating the treatment down to five days or less.

That’s how this protocol was developed, we randomised, I don’t have the number here, but 4,216 women to either whole breast irradiation, the standard of care at that time – 5-6 weeks of radiation therapy, or partial breast irradiation using one of three techniques that were in use at that time and still are in use today, meaning either 3D conformal external beam radiation therapy completed in five days, or interstitial brachytherapy, again completed in five days, or a device-based brachytherapy.  This was a diverse group of patients, as you’ll see in a moment, but we stratified these patients based upon their disease stage, their menopausal status, their hormone receptor status and their intention to receive chemotherapy. The endpoints of the study, of course the primary endpoint was to determine whether or not partial breast irradiation controlled the tumour in the breast, in other words the ipsilateral breast tumour recurrence rate was the same as whole breast irradiation. But the secondary endpoints were also distant disease free interval, recurrence free interval which I’ll define in a moment and overall survival.

Getting directly into the results of the study, this was an equivalence test for protocol defined margin for us to declare that partial breast irradiation and whole breast irradiation were equivalent regarding the ipsilateral breast tumour recurrence risk. The 90% confidence interval for the observed hazard ratio had to lie entirely between 0.667 and 1.5; I’ll show you that diagram in a moment. So we observed 161 recurrences, ipsilateral breast tumour recurrences, as first events. There were 90 in the partial breast irradiation arm and 71 in the whole breast irradiation arm. The hazard ratio was 1.22 and the confidence interval was 0.94 to 1.58. Partial breast irradiation did not meet the criteria for equivalence to whole breast irradiation based upon the upper limit of the hazard ratio confidence interval. We wanted it to lie between 0.667 and 1.5. However, the absolute difference in the ten year cumulative incidence of IBTR between partial and whole breast irradiation was 0.7%.

This slide just shows for you, diagrams for you, the upper limit of the confidence interval – we wanted it to be 1.5 and it was 1.58. This is the ten year cumulative incidence of ipsilateral breast tumour recurrence between partial breast irradiation patients and whole breast irradiation. The absolute difference was 0.7%. As a secondary endpoint we also looked at the recurrence free interval which was defined as the time from randomisation to the development of the first event, either a local, regional or distant recurrence regardless of any intervening contralateral or second breast cancer. At ten years the recurrence free interval for whole breast irradiation patients was 93.4% and for partial breast irradiation was 91.8%, a difference of 1.6% but this was statistically significant. We did not see any statistically significant differences, however, in distant disease free interval, in overall survival and in disease free survival.

So basically the intent to treat and as treated analysis could not refute the hypothesis that PBI is inferior and could not declare that whole breast irradiation and partial breast irradiation were equivalent in controlling local in breast tumour recurrence. However, as I pointed out, the absolute difference between the techniques at ten years was 0.7%. The risk of a relapse free interval was statistically significantly higher, again, for partial breast compared to whole breast but again this absolute difference at ten years was also small, 1.6%.

Interestingly the breast cancer event rates at a median follow-up of 10.2 years in this population were overall very good and quite low. The IBTR rate was about 4-5%; the distant metastasis rate was around 3% and the overall breast cancer death rate was about 2%. As I mentioned earlier, the distant disease free interval, overall survival and disease free survival were not statistically significant between the two arms of the study. I didn’t show the data but grade 3-5 toxicities were low, as well as the rate of second cancers and were not different between the two arms. We are performing additional analyses currently to evaluate the secondary endpoints, of course, of quality of life and cosmesis. Because the differences relative to both ipsilateral breast tumour recurrence and relapse free interval were very small, PBI may be an acceptable alternative to whole breast irradiation for a proportion of women who are undergoing breast conserving surgery. Thank you.