Proton therapy: good news and big challenges.

Chuvilo et al.,’ in this issue, present their experience with proton beam radiation therapy at the ITEP synchrotron in Moscow, U.S.S.R. This is one of three high-energy proton accelerators being used in part for radiotherapy in the U.S.S.R. The others are the 1000 MeV synchrocyclotron in Gatchina near Leningrad and the 680 MeV synchrocyclotron in Dubna. The report here is a welcome addition to the regrettably small literature in English about proton therapy in the U.S.S.R. Some additional descriptions can be found in the Proceedings of the First International Seminar on the Uses of Proton Beams in Radiation Therapy held in Moscow in 1977.3 Proton therapy is, indeed, a truly international affair. In addition to the contributions from the U.S.S.R., there have been important programs in Uppsala, Sweden, in Chiba, Japan, and in Berkeley (if we accept helium ions, with their low LET, as honorary protons), and Harvard in the U.S.A. This work has been extensively reviewed by Raju4 and recently updated.’ The first observation which the present account from the U.S.S.R. stimulates is that the work reported is technologically sophisticated. The accelerator itself, the beam transport systems, the patient support assemblies, and the dosimetric techniques are all complex systems. This, indeed, is a feature of all the heavy charged particle radiation therapy programs. When visiting these facilities, one cannot help but be impressed by the breadth and depth of technical expertise that goes into them. We should not, however, be surprised by it. In part it is the scale of the equipment which makes this impact. In fact, a very comparable level of sophistication goes into modern linear accelerators used in conventional X-ray and electron beam radiotherapy. We tend to forget the complexity of the equipment which is usually hidden by those streamlined fiberglass covers. The clinical impression of Chuvilo et al.’ is very positive. Their experience has led them to conclude that “the advantages of proton irradiation of such lesions [as small structures and formations including pituitary, ocular, orbital and other cranial targets] are now wholly proved”. In fact, investigators at all the heavy charged particle facilities have acquired a comparably positive impression from their own experience. Such favorable impressions are clearly encouraging to those who would study the value of improved dose distributions. On the other hand, no prospective randomized clinical trials are reported in this paper, nor have such trials been concluded at other proton therapy facilities. Indeed, there are few in progress. One cannot avoid asking why. Three considerations may contribute. First, all the work to date has been undertaken at accelerators primarily dedicated to physics research, and the facilities, and most importantly, time available to the medical effort have been quite severely limited, particularly in the early work. As a result, conventional fractionation was often not feasible and development of a clinical operation of the size which could support randomized trials has been slow. A second factor may be that the predicted benefits of charged particle dose distributions tend to be highly patient-specific. The extent to which critical normal structures can be excluded from the treatment volume depends on the shape of the individual target volumes, and this can vary much between patients with disease nominally at the same site. Third, for some sites, such as choroidal melanomas and tumors abutting CNS structures, the advantage of the proton treatment may be judged sufficiently great as to preclude a randomized trial. This having been said, there is a cleai need for randomized clinical trials to establish the extent of the benefits perceived by practitioners of proton therapy from results of the nonrandomized trials which have been conducted so far. It is also clear that, with the limited number of proton beam facilities available for treatment both now and in the foreseeable future, international cooperation is essential if adequate numbers of patients are to be evaluated in prospective randomized clinical trials. Such cooperation is, of course, not without its difficulties. One area of concern is that the control arm of such studies be subject to the same level of supervision and be executed with the same level of attention as the proton arm. Finally, it is probably fair to say that the clinical evaluation of protons for radiation therapy is essentially