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Editorial |
The commentary in this issue [1], along with several other recent publications [2–8], draws our attention to important developments that should be of particular interest to readers of the BJR. Physicists, engineers, radiobiologists and clinicians should be aware that in Europe, the Far East and in the USA there has recently been considerable activity in the field of particle therapy. For worse, or perhaps for better, there has been little progress in the UK. The outstanding exception being the meticulous work on proton therapy for ocular tumours carried out using the cyclotron at Clatterbridge, near Liverpool [9, 10]. There are two ways of looking at the British inertia when it comes to particle therapy: one is the perspective of Professor Jones, that it is reprehensible sloth which puts us in danger of being left behind scientifically and which denies a significant number of patients with cancer the treatment they need and deserve; the other view is that the recent renaissance of particle therapy is based on hope, rather than evidence, and that, as a nation, we do ourselves no great disservice by failing enthusiastically to adopt unproven therapeutic technologies. Should we be prudent, or should we be (relatively) early adopters?
Perhaps some of the explanation for our apparent reluctance to rush out and embrace particle therapy lies with our recent history. We were, after all, enthusiastic early adopters of neutron therapy and spent the best part of 25 years finding out that, in the long run, we might have been better putting our efforts elsewhere. The lessons learnt were: that an apparently compelling biological rationale does not always translate into improved clinical results; and that even "randomized controlled" trials may be no bulwark against misplaced enthusiasm. These things reverberate. It is not just about the wasted money, or even the futile intellectual effort. It is about the false hopes that we raised in the public; we ended up expending patients' goodwill and altruism on proving a negative. There was also an opportunity cost to all of this: because we were doing things we need have not done, we could not do the things we should have done.
This journal published the inquest into the MRC trials of neutron therapy for Head & Neck cancer [11], and in 1987 the BIR awarded the Röntgen Prize to Professor William Duncan and team for their meticulous clinical studies demonstrating that fast neutron therapy offered no significant advantage over conventional therapy with photons. It is entirely appropriate, therefore, that the BJR should take the lead in encouraging an open debate concerning particle therapy in the 21st century. We cannot assume that, because particle therapy ought to be better than conventional therapy, it necessarily will be better. Nor can we assume that our melancholy experience with neutrons will not be repeated. For proton therapy, at least, we only have to consider potential physical advantages; with a relative biological effectiveness (RBE) of 1.1 we are unlikely to encounter unpleasant biological surprises. The position of ion therapy is, however, more complex: we have to consider both the physical advantages associated with the Bragg peak as well as the potential biological advantages associated with high linear energy transfer. If particle therapy does have a role in cancer management, then that role needs to be carefully defined, on the basis of evidence, not opinion.
The peer-reviewed literature contains little evidence upon which we might base decisions concerning the efficacy and cost-effectiveness of particle therapy. Most of the information is hidden in meeting reports and discussion documents. For the moment at least, the benefits from particle therapy appear to be limited to certain uncommon tumours: ocular tumours; tumours of the base of skull; chordomas. Good evidence for cost-effectiveness is non-existent: such studies as have been performed have been methodologically unsound and poorly reported. The onus is now firmly on the advocates of particle therapy to expose their results to peer review rather than simply presenting them to meetings of like-minded people.
As Professor Jones points out, the main benefit from particle therapy may be for patients with rare tumours. If this is the case, then randomized controlled trials will be neither feasible nor appropriate. We need to think of other methods to construct an evidence-base for particle therapy. The main criticism of the literature on particle therapy at present is that it represents little more than a series of anecdotal reports on the results of treating patients who may, or may not, be representative of patients with a given type of tumour. It is interesting to find that although over 8000 patients have been referred for particle therapy in Italy, it would seem that only 54 have been treated [1]. I would argue strongly that, as soon as possible, we need to construct a central database including information on all patients treated with particle therapy. In the first instance, a Europe-wide initiative would be sufficient. The database would function prospectively as a particle therapy register and should, for each patient, include demographic data as well as information on tumour type, stage and grade, treatment details and outcome. The register could then be linked to cancer registries and we would therefore be able to bring a sense of perspective to the potential role of particle therapy as well as sensibly plan future developments. The idea of centres springing up simply because some EU development funds are available, or there happens to be a basic physics research facility, or because a private health care company thinks there might be a market to exploit, is unappealing. Particle therapy for cancer is an unproven intervention and its development needs to be part of a co-ordinated scientific research programme. Professor Jones's commentary is an extremely useful reminder of where we might be investing – but it is not just about where: it is also about why, how and when.
Conflict of interest and acknowledgments
The author worked at both the Hammersmith Hospital, London and the Western General Hospital, Edinburgh at the time of the clinical trials of fast neutron therapy. He would like to thank the following colleagues for helpful discussions: Mark Lodge; Dirk De Ruysscher, Tom Jefferson, Madelon Pijls-Johannesma, Lisa Stirk and Nancy Owens. The opinions expressed above are entirely his own.
References
This article has been cited by other articles:
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  R E Taylor Particle matters? Br. J. Radiol., October 1, 2006; 79(946): 850 - 851. [Full Text] [PDF]
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