Thank you very much, thank you. It’s a big opportunity for me today being here. So I have now several conflict of interest statements to declare.
As we well know recent developments in radiation oncology for breast cancer show a faster move towards a de-escalation strategy for breast cancer in early breast cancer including accelerated and not partial breast irradiation. What we have learned from major phase III trials in the last years where we presented the RAPID trial and the NSABP B-39/RTOG 0413 trial just published last week in The Lancet that if the disease control is closely related to the adequate selection of patients for partial breast irradiation the safety profile and the cosmetic outcome is more strongly associated to the technique concerned, technical choices, so the approach, the dose, the number of fractions per day and then the total dose.
The accelerated partial breast irradiation trial for our NSABP IMRT trial is a phase III trial, single centred, that enrolled between 2003 and 2013 520 patients that received breast conserving surgery, PT less than 25mm, final surgical margins more than 5mm in patients aged more than 40 years old that were randomised one to one to receive accelerated partial breast irradiation using an IMRT technique, 30Gy in five fractions, non-consecutive schedule every other day, as compared to conventionally fractionated whole breast irradiation, 50Gy in 25 fractions and a tumour bed boost of 10Gy in five fractions. The primary endpoint of the study was the ipsilateral breast tumour recurrence and the five year results were presented here in San Antonio in 2014.
At the time of this analysis the median follow-up of both arms are more than ten years and every patient in every single arm received a follow-up of at least seven years. This is something about target delineations and quality assurance of our technique, it’s a very easy technique. We need at least four mandatory surgical clips to identify the target and the CTB was obtained by an isotropic 1cm expansion. The BTV is obtained by another isotropic 1cm expansion limiting 3mm by the skin and up to 4mm towards the lung. These are the organs at risk that we contour very simple contralateral, homolateral lung, homolateral breast, contralateral breast and heart using these constraints.
Coming to the results, to know the patient characteristics that will be presented this afternoon, most of the patients were aged more than 50, more than 90%, T1 tumour, negative nodal status, ER positive and margins more than 5mm.
This is the primary endpoint. At a median follow-up of ten years the ten year cumulative incidence was 3.9 in the APBI arm as compared to 2.6 in the whole breast irradiation arm. Very low rate of events – nine events at the ten year in the APBI arm as compared to six events. The hazard ratio is 1.57, p-value of 0.39.
Just to show you the other local control outcomes. There is no difference, just nine events as compared to seven events in the local regional recurrence rate, so 3.9% as compared to 3%. Concerning contralateral breast cancer, to note we observed just two events in the APBI arm as compared to eight events in the WBI arm. It’s a less than 1% rate at ten years, cumulative incidence at ten years, for the APBI arm as compared to 3.5% in the whole BI arm, again not significant.
Concerning survival outcomes, we had just seven events in each arm concerning distant metastases so the rate in each arm was 3.1%, not significant. As you can observe in the slides, there’s a complete overlap also concerning breast cancer specific survival and overall survival where we observed for the breast cancer specific survival at least 97.5% in each arm, a hazard ratio of 0.87, not significant, and the overall survival they basically completely overlap.
Coming to the analysis of the adverse events, this is our results in terms of acute toxicity as assessed by the RTOG and the OTC acute toxicity scale. As you can observe, we have very good results in both arms but significantly in favour of the APBI arm even if you consider any grade of toxicity incidence, any single grade, and grades equal or greater than 2. Late events, again, we observed very nice results but in general terms always significantly in favour of the APBI arm. If you consider any grade, if you consider any single grade, no grade greater than 3, all grades equal or more than 2.
Finally, cosmesis, this is a crucial point since other trials have some concerns in terms of schedule adopted. We observed very nice results in each arm. We used the Harvard breast cosmesis scale so it’s a cosmesis scale that evaluates just the effect of radiation therapy on cosmesis. So very excellent good results but, again, this is the physician rated cosmesis outcome again in favour of the APBI arm. Concerning the patient rated, that’s a difference, a clear difference, since patients are more self-critical but again we have more than 90% of good or excellent results but again in favour of the APBI arm. Please note our 15% rate of favourable results in the whole breast irradiation arm.
So coming briefly to a conclusion, our ten year cumulative ipsilateral breast tumour recurrence incidence rate in these early breast cancer patients treated with an external accelerated partial breast approach using an intensity modulated radiotherapy, this is five once daily fractions in a schedule every other day, 30Gy in five fractions, is low and basically not significantly different from patients treated with conventionally fractionated whole breast irradiation.
We also observed comparable results in terms of local regional relapse, distant metastases, breast cancer specific and overall survival rates. Acute and late adverse events and cosmetic outcomes as assessed by patients and physicians were also in favour of the APBI arm. So basically this is just another piece of the puzzle but we could consider that APBI might be a standard alternative to the WBI arm in very low risk early breast cancer patients. Thank you.