COMMENTARY

Expert Insight: The Future of Proton Therapy in the UK

Karol Sikora, PhD, FRCR, FRCP, FFPM

Disclosures

August 14, 2018

I'm Professor Karol Sikora. I'm the Chief Medical Officer of Proton Partners International and I'd like to talk to you about proton therapy for cancer.

Obviously I'm slightly conflicted in that I was the founder of Proton Partners and I believe they do have a very significant role in the delivery of modern radiotherapy.

Protons are particles, positively charged particles. The first proton therapy machine was actually in Loma Linda in California in 1954 and since then, after a period of real quietness about protons from academic centres around the world, they've suddenly burst to the forefront because commercial suppliers of machines are out there.

Proton machines are about 15 times more expensive than conventional radiotherapy. The advantage of protons is because they're particles, they stop at a defined point in the body. We control where they stop by the energy we speed them up to in the cyclotron. That allows the delivery of radiotherapy to a  defined tumour, sparing any tissue beyond the cancer. And that's the difference, [with] conventional radiotherapy there's an exit dose, it goes right through and up the other side. So any critical tissue, and depending on the part of the body that's being irradiated, there are different critical tissues, can be avoided. And that's why protons have an advantage.

Growing Number of Proton Centres

Now the problem is because they're expensive one has to make sure one is giving them to the right patient to get maximum value, and that's where the controversy begins. Different countries have adopted different stances towards proton therapy.

America, the United States, has some 34 operational centres and another 18 at the stages of planning and development. Europe has far fewer. The UK at the moment, until April this year, was the only country that didn't have a functional proton service. Now it does, from Proton Partners, and again from the NHS building two centres, one in the Christie Hospital, Manchester, and one at UCLH, University College Hospital in London.

So what sorts of treatments can be delivered better with protons? It's not really the tumour type. It's more the configuration, the anatomy of the cancer and the surrounding normal tissue. But there are certain hints, brain tumours, spinal cord tumours, children's tumours, sarcomas, tumours in the abdomen and pelvis are all categorised by how beneficial protons would be there. They're the sort of tumours that are likely to have the biggest proton use. In breast cancer for example, left breast tumours where the left internal mammary chain is being irradiated to try and reduce the risk of lymph node recurrence is another category, and there the aim is to spare the heart and the lung underneath the breast, which is sort of inevitably radiated, even with the best of conventional radiotherapy.

Lack of Trial Data

So how is it going forward? Obviously, why are there no clinical trials? Why can't we just get some trial data? And that reflects what's happened in radiotherapy. The drivers for advances in radiotherapy, better imaging and better computation of those images to make sure the dose is going to the tumour and not the normal tissue. And so if you see a better plan, is it ethical to randomise it to the poorer plan? And that's been the problem with radiotherapy trials since the beginning. So we moved from cobalt machines to linear accelerators. We moved from Kaplan planning to CT planning. We moved to various types of intensity-modulated radiotherapy - IMRT - no clinical trials were involved. There were a few, but they were very minimal. And the move of technical progression in radiotherapy is all based on the surrogate endpoint of a better dose distribution, as judged by the radiotherapist anatomically. And that's where we've got to with proton therapy.

Different Strategies

Different countries in Europe are adopting different strategies. 

In Sweden, for example, all 70 clinical oncologists, radiotherapists, have been trained in proton therapy, to work in a single centre, Uppsala to the north of Stockholm, where they're going to go once a year for a month to service the patients there and they'll refer the patients. 

In Holland, four centres have been created for a country a quarter of the size of us. So it would mean 16 centres in the UK, and the doctors there are taking referrals, and the doctors, the consultants, are being trained in proton therapy.

Questions Remain

Proton therapy still has questions about it. First of all, does it really reduce toxicity? And there are some uncertainties in proton treatment that you don't have with conventional. The uncertainties lie in what's called the Bragg peak. As the protons go into tissue, they slow down when they get to the critical depth, depending on their energy, and then release all our energy in what's called the Bragg peak invented by William Bragg in 1902. And the problem with that is in the Bragg peak, they change the way in which they damage DNA. The linear energy of transfer as it's called, the LET, increases as they die down, as they slow down, and that could have profound biological effects especially if normal tissue that was critical was trapped in that zone where the protons are slowing down. And you could get surprising effects, necrosis in the brain, you could get critical tissue damage in the abdomen, bowel damage, and so on, if the Bragg peak happens to be in a critical tissue.

The other uncertainty of protons is the dose range, how far the protons really go. Now all these problems require a combination of better imaging so you know where everything is in the body, and better planning algorithms to show you where the dose distribution is going. And that's the future, the future of protons is understanding the physics better, and then the radiobiology.

Looking Forward

So how's it going to look in 5 years' time? There'll probably be about nine centres, two NHS and seven from the private sector hopefully working together treating a range of patients mainly children, young adults with brain tumours, and a range of other solid tumour indications. 

It's vital that it is a partnership, that we collect the data. It's unlikely that randomised studies will really contribute to this for the reasons I've explained. And so those that pay for healthcare, be they governments such as the NHS, or private insurers, need to know they're getting value for money. And it's so important they collect all the data on outcomes, not just outcomes survival, which we're used to in oncology, but the softer data of late toxicity, which is difficult to collect because it's variable on the patient's personality, how much they complain about toxic symptoms 10 years on. We also need to do better health economic analyses to see do, by using protons, you actually save on the financial implications of long-term complications that may need surgery, for example, fistulas in the bowel, strictures in the urethra, and so on.

So I think protons are going to be very exciting. Things like immunotherapy, chemotherapy, are there, and maybe they need to be looked at in combination with proton therapy. But I see it just very much as an extension of normal radiotherapy. 

My view is that we need about 10% of radical radiotherapy using protons, which is about 16 machines for the country. When the National Radiotherapy Advisory Group met in 2007,  it made the calculation it would only be 1%. I think that's out of kilter with the rest of Europe that are planning 10 to 15%. So I think we're going to see a lot of excitement in the proton space over the next 5 years. And it's great really to be part of it. I'd love to hear your views. It's Karol Sikora here. I am slightly conflicted as a founder of Proton Partners International, which is a commercial organisation bringing proton therapy to the UK and other countries, but I'd love to hear your views.

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