Goitein, Lomax, and Pedroni reply: We deeply regret having failed to acknowledge the roles of the Harvard Cyclotron Laboratory and the Massachusetts Eye and Ear Infirmary in developing the proton treatment of ocular tumors. We know better than most how central and vital those roles were to that highly successful program. By April 2002, when the HCL stopped operations, it and the Paul Scherrer Institute were neck and neck in the number of eye tumors treated: HCL had 3466 and PSI had 3538.
Bernard Gottschalk, Andreas Koehler, and Richard Wilson take the view that proton therapy has not yet achieved the efficiencies and the reliability to justify the claim that it is a routine clinical option—and that we “glossed over” the problems that remain. In just what state proton therapy now finds itself is a matter of judgment. At Loma Linda University Medical Center, 7176 patients had been treated with protons as of April 2002, and LLUMC now treats more than 1000 patients per year. The new Massachusetts General Hospital facility treated 228 patients in its first full year of operation. Given that only one of MGH’s two gantries was in operation, that figure does not compare badly with the current throughput at LLUMC with its three gantries and 10 years’ experience.
In addition to LLUMC and MGH, two hospital-based proton centers are operating in Japan; worldwide, several clinical facilities are under construction and others are in mature planning stages. So our opinion that the “move to the clinic” has taken place seems quite reasonable.
Regarding maintenance, although LLUMC appears to have a large support team, HCL achieved a superb three-decade record of availability with about a half dozen maintenance staff members. Nevertheless, Gottschalk and colleagues rightly point out that many unsolved problems remain and that new facilities must carefully assess their staffing needs. Commercial vendors must address these problems and make proton facilities more efficient to operate and, hence, less expensive.
Expense seems most important to Schulz and Kagan. Nevertheless, their comments appear to be less a criticism of proton therapy than an argument against the need for improvements in cancer radiotherapy in general. However, we know no radiation oncologists who think that current radiotherapy achieves an ideal local control rate with negligible morbidity; we know many who yearn to do better in both areas. We expect that the assertion that radiotherapy has reached a plateau will prove, like similar past predictions, to be unfounded. We agree that it is important to know whether protons offer better radiotherapy than do conventional x-ray and electron beams and, if so, whether their benefit is worth their additional cost. To address cost-effectiveness, one must know both sides of the equation.
Recently, the cost ratio between high-technology proton and x-ray treatments has been evaluated, 1 with the conclusions that the cost ratio (taking into account the equipment costs) is now about 2.4 and, with readily achieved improvements and additional, more speculative ones, can probably be reduced to about 1.7. Those numbers are greater than unity, but perhaps not as much greater as Schulz and Kagan imply. The cost ratios between many forms of chemotherapy and conventional x-ray therapy, for example, can be considerably larger—but nevertheless, in practice, are accepted.
The other side of the equation is effectiveness. There are two approaches to assessing effectiveness: theoretical arguments based on the physical properties of protons and arguments based on clinical results. Our article concentrated on the former; we could not give more than a superficial overview of the latter. However, the physics arguments are very strong. Protons indisputably can deliver a smaller dose to tissues outside the target volume. There are many reasons to think that this would be beneficial and few to indicate it might be deleterious. Clinically, ocular melanomas and skullbase chordomas and chondrosarcomas in several series with many patients and with long follow-ups—together with paranasal sinus tumors in unpublished data—have been shown to be more effectively treated with protons than with other techniques. That the successes so far are in uncommon tumors has less to do with their rarity than with their accessibility to the restricted-penetration beams, the only beams that have so far received a mature clinical evaluation. Schulz and Kagan seem to imply that they could support “the establishment of a few national referral centers.” So, the issue becomes “how many” rather than “whether.”
Our judgment is that a clinical and worthwhile benefit has been shown for some tumors, and experience reinforces the expectation that we will see similar improvements in many other cancers as more clinical facilities gain experience with protons.