Proton Therapy Congress 2016

Hope, hype, misinformation and clinical evidence

Prof Michael Brada, University of Liverpool, UK

The title of my talk was “Hope, Hype, Misinformation and Clinical Evidence” and I was essentially talking about the information that exists about the value of protons as an alternative to photon radiotherapy. I have provided analysis of the published literature in terms of the evidence based on systematic reviews and how this is perceived by the public and how it is being publicised outside by the media which unfortunately is not always represented in the way… doesn’t always represent the true facts of the situation.

Proton therapy is a potential advance in radiotherapy and certainly the evidence based on the physical dose distribution of radiation is in favour of it being perhaps a safer way of giving treatment, with fewer side effects.  I certainly buy into this as a potential new treatment which would be of value to people with cancer. Now any new treatment with the complexity of the technology that’s involved in proton therapy, will be associated with uncertainties and it’s important not to be swayed by a single parameter as a marker of benefit because in complex situations there’ll be a number of factors that will influence the clinical outcome. So I am very keen, based on my academic clinical experience, very keen to see that proton therapy is put through the same rigorous set of tests as any other treatment, be it modern conventional radiotherapy or drugs, and that it has to demonstrate for it to be applicable, clear benefit. The analysis of the literature so far unfortunately doesn’t show a benefit yet; it doesn’t mean that it won’t come but it’s not there yet. Therefore, to promote it on the basis of really no data that’s better to the general public as being a revolutionary new treatment that will, as the public perceives it, will cure cancer that has previously not been cured. It’s not the way I would like to see the development of normal treatments because my concern is that whatever is offered to the public should be of clear benefit with no risks, no additional risks and I think the jury is out on that yet. Now I certainly believe that in the UK, the approach is correct in having two centres that are funded by the Health Service, where part of the remit will be to clearly identify the correct indications and provide objective data which will then allow us to say what are the real indications where it can be used and indications where perhaps the benefit is not there. And obviously as with any new technologies there are risks and I think any introduction of the technology, the public needs to be aware that there are risks that are not known. It doesn’t mean that it shouldn’t be tested, but it should be acknowledged that’s it’s tested under those conditions.

Is the current data strong enough?

There is a lot of data, I have personally been involved in systematic reviews, of quite a high standard systematic reviews, and all the systematic reviews so far do not show any benefit over best conventional treatment and admittedly the data is limited but I would have expected if you think of new data as being a kind of quasi phase II study I would have expected that some of the phase II studies of selected patients would show objective benefit in some of the parameters they’d like to test.  So I have some concern about this, but I don’t think that should stop the development and testing. Whether you should with this information actually to sell it to the public as potential better treatment, I don’t think this is the appropriate way forward.

How have people responded to your stance on proton therapy?

Certainly the clinicians in the audience feel that this is the correct approach and I don’t think I’ve been told that that is incorrect. I am being labelled as being negative and of course as far as the people with interest in the technology, a vested interest in the technology, I don’t think they like my message very much.

The SHIVA trial raised similar discussions about personalised therapy…

The whole concept of personalised medicine is, I guess it’s like everything in medicine, there are fashions and it’s a fashion. There are some indicators that it has some benefit, in small indications, as a way of solving a cancer problem. There will be some doubters out there who will say it’ll be only a small proportion of patients and there may be, there are likely to be, other solutions that we haven’t seen yet. The concern always is if you have one particular fashion you may actually stop research into maybe slightly more esoteric ways of treating cancer.  So, for example, the personalised medicine concept, which I have nothing against, it’s a very reasonable concept and, as I said, it’s applicable in a number of situations, didn’t foresee the concept of immune checkpoint inhibitors and it’s a paradigm shift and where do they sit together? So I have an open mind. But radiotherapy, in the end proton radiotherapy is the same as photon in some ways, it’s the mechanism of DNA damage and the mechanism of inhibiting cell proliferation is very similar. I don’t think there are great differences. There is likely to be, if it’s of benefit which I hope it is and maybe, it’s likely to be a smell incremental benefit rather than a quantum leap, you know it’s not a paradigm shift as you see with a completely new set of drugs.

Any final thoughts?

I personally would be in favour of a system of regulation of technology which requires the same rigour as the evaluation of new drugs. Then we would have the true answer both in terms of effectiveness and in terms of cost effectiveness. There should be certain hurdles that technology has to pass the same way as drugs have to pass. At the moment it seems like a discussion between people who like to look at academic data and people who believe in technology and we seem to be driven by the belief rather than data. I feel it’s an advance in radiotherapy and it should be tested and I very much hope that that will be the future.