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IN AUGUST 2014, the British public were gripped by the story of Ashya King, a 5-year-old boy who had a form of brain cancer called medulloblastoma. He was removed from hospital by his parents without the consent or knowledge of his doctors.

An international hunt was sparked when it was realised they had taken Ashya abroad in the hope of getting him high-energy proton beam therapy (PBT), a type of radiotherapy unavailable in the UK.

Like so many parents of children with brain cancer, Brett and Naghmeh King were worried about the side effects of X-ray-based radiotherapy and how this could affect his future development. Scouring the web for alternatives, they decided that PBT would put Ashya at lower risk. So they set off for a PBT centre in Prague, only to be jailed in Spain for over 24 hours while en route.

A few days later, a UK court ruled that Ashya could receive treatment at the Proton Therapy Centre in Prague, which was eventually paid for by the UK鈥檚 National 91色情片 Service. Fast forward two years and Ashya is now well enough to attend school. Meanwhile, two PBT centres are scheduled to open in the UK in 2018.

Although more expensive than conventional radiotherapy, the push for protons is based on the idea that they cause less collateral damage. Protons can be programmed to deliver their energy in a powerful punch at well-defined points within a tumour. In contrast, X-rays pass through tumours and irradiate nearby healthy tissues.

Yet the data in support of proton therapy, especially for medulloblastoma, is contentious 鈥� hence the NHS鈥檚 reluctance to send Ashya abroad for treatment, something it has done for only a small number of people since 2008. So what is the evidence to support protons over X-rays? And if it鈥檚 so scant, why the global proton drive?

Medical arms race

Proton therapy has been used on a small scale for decades. But recently there has been a surge in interest, stoked by the media and technical advances that mean a 拢100-million particle accelerator the size of a football field is no longer the only option. Today鈥檚 machines can cost as little as 拢15 million.

It is estimated that worldwide there are 43 high-energy proton beam centres. By 2018 that number will rise to 66, including the two NHS centres being built at the Christie hospital in Manchester and University College Hospital in London. Both were approved in 2011 at a combined cost of 拢250 million. According to a senior NHS adviser, the government decided to go ahead with the centres on the basis of the physics of how X-rays and protons behave rather than any convincing clinical data.

In the US, where there are upwards of 20 centres, critics have described the situation as , with big hospitals each wanting their own shiny piece of kit.

The controversy arises because there is little undisputed data to support the idea that the more expensive protons are significantly better than conventional radiotherapy in terms of overall patient survival. In fact, for 10 years or more, several studies have attempted without much success to formulate a cost-benefit analysis of protons for a range of cancers.

But it hasn鈥檛 been possible to set up randomised clinical trials capable of comparing protons with X-rays, especially for rare childhood cancers. In part, this is because parents 鈥� often informed by media coverage 鈥� can be reluctant for their child to 鈥渕iss out鈥� on what they see as a superior treatment, says Richard Grundy at the University of Nottingham, UK. Much of the evidence is therefore based on weaker data provided by other types of study.

In 2012, for instance, a review of PBT for central nervous system tumours, gastrointestinal malignancies, lung, head and neck, prostate and paediatric tumours produced mixed results with no clear benefit over conventional radiotherapy, except perhaps for tumours in children鈥檚 nervous systems (Radiotherapy & Oncology, ). And a review this year found that for 11 of 15 childhood cancers there was little evidence to suggest protons were any better than X-rays (International Journal of Radiation Oncology, Biology, Physics, ).

But now a study has provided the first evidence that PBT might indeed be worth it for children with medulloblastoma. It wasn鈥檛 a randomised trial but it followed children who had one of the two treatments for around seven years, and has been described as the most detailed study of its kind on this type of cancer.

鈥淪urvival rates are similar but proton proponents say there are fewer side effects than with X-rays鈥�

As expected, both were much the same in terms of overall survival rates, and there was some evidence that PBT, like X-rays, still resulted in side effects such as hearing loss and a reduction in cognitive function. However, other effects that can develop from X-rays, such as cardiac, pulmonary and gastrointestinal problems, were absent (The Lancet Oncology, ).

This finding has been seized on by the pro-proton community, notably Karol Sikora, ex-head of the World 91色情片 Organization鈥檚 cancer programme who is now chief medical director of Proton Partners International, a private initiative spearheading the building of PBT centres. Sikora believes this paper will change the landscape in favour of PBT for medulloblastoma, and is lobbying for the NHS to change its stance on whether they send children with the cancer abroad for PBT while the UK centres are being built.

However, not everyone is convinced of the long-term benefits. The conclusion that PBT won鈥檛 result in certain kinds of long-term damage is premature as it could take 20 years to see the effects, a group of oncologists, including Grundy, responded last month (The Lancet Oncology, ). 鈥淚deally, a randomised clinical trial between conventional and proton beam radiotherapy would be done, but it has not, and it is now neither realistic nor appropriate for such a trial to take place,鈥� they added.

鈥淐ompany lobbying, fanned by patient anxiety, is putting pressure on health services to meet demand鈥�

Despite these concerns, lobbying from proton beam companies, fanned by patient anxiety, is putting pressure on health services around the world to meet demand for proton therapy.

鈥淲e won鈥檛 know if there are any real benefits of protons in terms of long-term side effects for 20 or 30 years, but it would have been unacceptable to wait until then before building the [new NHS] machines, especially over an emotive issue as paediatric cancer,鈥� says Nicky Thorp of the Clatterbridge Cancer Centre near Liverpool, who sits on an NHS committee advising on PBT.

As well as the two NHS hospitals, three other companies are building five private centres in the UK 鈥� three in London and one each in Newcastle and Cardiff.

There鈥檚 no sign of the proton rush abating elsewhere either. The Belgian company IBA, the world鈥檚 biggest manufacturer of proton machines, reported sales of 鈧�270 million in 2015, a 23 per cent annual increase. It now boasts 41 customers worldwide.

The upshot is more choice for doctors and those wishing to undergo PBT. But as is always the case with tightly balanced healthcare budgets, if PBT isn鈥檛 what it is cracked up to be, patients who would have benefited from a different allocation of money will have missed out. The trouble is, those unidentified patients are always going to be less evocative than a boy with a brain tumour.

This article appeared in print under the headline 鈥淭he rush for protons鈥�