Trials and tribulations in charged particle radiotherapy.

A number of aspects of radiotherapy using protons and ions such as carbon and neon are discussed, focusing less on the oft-enumerated advantages or potential advantages of these particles as on those aspects which are, or may be, problematic. First, for protons and so-called heavy ions separately, the potential advantages and disadvantages of the particles, on physical and radiobiological grounds, are reviewed and some outstanding problems, both technical and scientific, are enumerated. Then, mention is made of the danger that financial pressures can lead to suboptimal medical care of patients. Finally, the issue of clinical trials, and especially randomized clinical trials, is addressed. On the one hand, very few randomized trials have been reported. On the other hand, there is a widespread desire to see trials of charged particle therapy undertaken. The ethical considerations are briefly reviewed and it is concluded that they pose strong limitations on the types of trials which can be undertaken. Nevertheless, some clinical trials would certainly be appropriate and desirable and a number are suggested, under the categories of retrospective non-randomized clinical trials, prospective non-randomized clinical trials, and prospective-randomized clinical trials.