The session today was predominantly focussed on radiotherapy treatment and there were a number of presentations on partial breast radiotherapy on the AMAROS trial and a couple of other things. But my particular session was on the work that we’ve done in Oxford at EBCTCG on the role of regional radiation therapy. This is radiation therapy not focussed on the breast or the post-mastectomy chest wall but the question that we were addressing within EBCTCG was the role of regional radiation, that’s radiotherapy delivered to the internal mammary chain, to the supraclavicular region and the axilla or a combination of those target regions.
We conducted a meta-analysis in EBCTCG of around fourteen trials. They span over a very long time frame, the earliest trial in fact began in 1961. Because of the improvements in radiotherapy techniques we divided these trials up into two main groups, essentially based on radiotherapy quality but they also break down just as simply into the older trials and the more new trials, those that are more relevant to contemporary practice and how we might want to manage patients today.
There are a number of findings. Overall treatment was beneficial and it was beneficial at reducing recurrence at any site, in fact, not just local recurrence and also improving mortality from breast cancer. When you break the trials down into the older group and the newer group in fact we found that in the older trials there was actually some harm, that there was an increased risk of mortality from causes other than breast cancer. That’s likely to be because of cardiac irradiation and the induction of cardiac disease and deaths from cardiac disease and also probably because of the higher incidence of lung cancer.
The treatment given in the older trials was not beneficial in terms of reducing breast cancer mortality, however in the newer trials, starting in around 1989 and including very well-known trials like the MA.20 trial based in Canada and the EORTC trial based in Europe, if you include all of those trials that’s many more patients, that’s around 11,000 women in those trials and the picture was very different. The first thing is that this treatment appeared safe. There was no increase in non-breast cancer mortality, no increase in deaths related to causes other than breast cancer. There were significant improvements in both recurrence of breast cancer and also in mortality from breast cancer.
One of the other important findings is how that benefit is distributed amongst patient groups. It was very clear from our work that the patients who benefit the most from regional radiation are those at higher risk because they had extensive axillary nodal involvement, the involvement of four or more axillary lymph glands, where the benefit was large and statistically significant but, importantly, clinically very meaningful.
So that was the summary of our work. This is a controversial area, regional radiation, it’s been controversial for at least twenty years. I’m a senior consultant and we’ve always had uncertainty about the role of this therapy. But with the publication of the recent large trials of the ones I’ve mentioned and now the work that we’ve done in EBCTCG on a meta-analysis of all these trials things are becoming very much clearer.
We can be very definite about those benefits. What’s always more difficult is to understand how we manage this information and use it to treat patients today and to make treatment recommendations. That’s always a problem because although these are newer trials they still started 15-20 years ago and things have changed. Contemporary practice involves a lot more neoadjuvant chemotherapy; there were no patients who had neoadjuvant chemotherapy in our work. So there’s still an important role for taking these results and using the information but having to interpret it in the context of what we do with patients and what we advise with patients today. That’s probably the main challenge at the moment.
We wouldn’t have been able to have done this work within Oxford, within EBCTCG, without the cooperation and the enthusiastic cooperation of all the triallists. That involves a great deal of trust and common working and understanding; we move forward together on this. The more recent larger studies and trials comprise the majority of the important component of this work and, as I’ve already mentioned, the MA.20 trial, my colleague and friend, the Principal Investigator, was Tim Whelan, in the EORTC trial it was Philip Poortmans. We have a Danish cohort study and Jens Overgaard was responsible for that. Then finally the French IM study based in Lyon and Christophe Hennequin was the Chief Investigator for that. And there are others as well and all of these people and the statistical and analytical teams within the trial offices we should congratulate and thank them for their support in this important work. Probably most importantly of all is the roughly 13,500 women who at a time of great personal difficulty and a recent diagnosis of breast cancer considered and accepted to be involved in a randomised trial. That is not an easy thing to accept or to go forward with so they certainly deserve significant thanks.