ASTRO 2015

ASTRO 2015 highlights: UK perspective

Dr Ajay Aggarwal – London School of Hygiene and Tropical Medicine, London, UK

I found the presentations of a very high standard. It’s incredibly interesting coming from the UK, coming to America and a predominantly US audience, as such, as to how their cultural differences and how they approach cancer care, especially radiation oncology. One of the things that underlines that is something like hypofractionation which is radiotherapy that you have potentially two equivalent treatments in terms of outcomes but hypofractionation you give the same dose over a shorter period of time using fewer fractions of treatment. It’s something that we’ve engaged with in the UK for three, four, five decades, partly because of our system of funding and also because the early research suggests that the outcomes are equivalent and so you have a more efficient service. In the US this was not a model that was predominantly used and, partly because of the reimbursement mechanism, you’re funded on the basis of each fraction of treatment that you provide so the incentive to actually reduce the number of fractions might not be there. But interestingly, hearing the comments that have been in the different presentations, the way they’ve engaged with hypofractionation but they’ve seen the growth in technologies and the precision of radiotherapy as being the precursor to offering hypofractionated treatment. So you’ve got this technological evolution and the uptake of that technology now defining what areas you treat, how you treat it. That’s very different culturally from what I’ve seen in London.

Could you comment on the safety and tolerability of hypofractionation that has been used in the UK?

It’s interesting, so the UK have done some excellent trials in this area, so the CHIP study has been recently published or will be very shortly. That was looking at three different strategies so you had the 7½ week strategy versus the 4-5 week strategy of different doses. But there are some centres that are treating to that hypofractionated regime and actually the outputs that I’ve seen from that is that the rates of toxicity are very similar. You might have slightly worse grade 1 toxicity acutely but that quickly subsides. But actually in terms of grade 3 toxicities which we’re concerned about in terms of incontinence and erectile dysfunction, that’s actually comparable. I think the evidence is overwhelming that we should be moving towards that and actually there was a Dutch study which I saw presented today which had ten years of data looking at exactly that. They found, again, comparable outputs in terms of toxicity.

Were there any other presentations you thought were interesting?

There was a really interesting presentation about looking at the interface of targeted agents, which are so big in the medical oncology field. If you go to ASCO most of the trials are looking at targeted agents of the cellular pathway, many different levels. Actually for something like radiotherapy which has got such a strong scientific radiobiological basis you would think that the two would completely coexist. There was a very interesting overview that was produced that showed that of the 5,000 current trials that are being undertaken within oncology, only 45 or 50 are involving a combination of radiotherapy and targeted agents. I think that’s slightly worrying in a way because actually we should be engaging with the science and I think this has been mentioned a lot in the read journal publications that we’re trying to improve the therapeutic ratio, we’re trying to reduce toxicity to normal tissues and improve that tumour cell kill and, actually, fundamentally by understanding the biology of the way radiotherapy works we can gain from that. But at a deeper level it would be very interesting to know who’s funding a lot of the research – is it national institutes, is it federal, is it charity funded or is there actually an obvious interface between industry and pharma. I think that’s very important but actually that’s an area that has to grow because at the moment, from my own opinion we have become very technology focussed and we’re dealing with ever decreasing outcomes or benefits. And this is such a novice area as such, not in the sense of the research has been going on for a number of years but it has got so much potential that we really need to be looking at that. That was essentially what the presentation was saying.

When you say targeted agents, do you mean immunotherapy?

I’m talking about targeted agents, things like the TKI inhibitors, EGFR inhibitors and various pathway analogues that can be used. Actually it’s a real eye-opener that actually there’s only one type of targeted agent that’s shown to be effective and that’s cetuximab. Given the number of drugs that are being produced, the number of areas, I was very heartened that there is good work happening in the US in that area. But much more needs to be done.

What about using ipilimumab and other immunotherapies?

Definite potential. I hadn’t engaged with the literature enough to probably give you a formal comment but anything looking at those lines of the way that a tumour cell reacts to radiation, the way it repairs, affecting that process of metastasis to different areas, anything that can modulate that can only be a beneficial thing. Interestingly, when they were talking about stereotactic radiotherapy and hypofractionating, they said one of the things that occurred compared to if you give conventional doses is that you get a sort of recrudescence of T-cells and that actually you might prevent metastatic disease later by the fact that you’re giving that treatment and these T-cells are coming. So you’re almost conferring immunity as a result of it. So there’s a lot more that we need to understand.