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Proton Therapy Comes into Its Ownby Dawn ChalaireIt may come as a surprise to many to learn that patients were first treated with protons more than 50 years ago at the University of California’s Cyclotron Laboratory in Berkeley. Beginning in the early 1960s, the Harvard Cyclotron Laboratory in Cambridge, Massachusetts, in collaboration with Massachusetts General Hospital and the Massachusetts Eye and Ear Infirmary in Boston, provided continual proton therapy until it was replaced with a modern facility at Massachusetts General Hospital in 2002. So far, about 36,000 patients worldwide have been treated with proton therapy. Yet, in the United States, the field has only recently begun to come into its own, with a number of new facilities dedicated to proton therapy scheduled to open in the next few years. According to Alfred R. Smith, Ph.D., a professor in the Department of Radiation Physics at The University of Texas M. D. Anderson Cancer Center, the surge in new proton therapy centers in the United States can be attributed to three factors: (1) positive results of clinical studies of proton therapy were published; (2) proton facilities applied for and were granted procedure codes from the American Medical Association, and Medicare and insurance providers set reimbursement rates, which enabled proton therapy providers to be paid; and (3) once it became evident that such centers would be able to charge for their services, more vendors became interested in designing and building proton therapy facilities. The economic feasibility of proton therapy centers coincided with the development of more precise imaging and proton treatment delivery methods. Although the precision of proton beam therapy has been known for decades, applications were limited to a few anatomic sites because of energy and treatment delivery limitations and the difficulty in precisely defining the tumor volume to be treated. Beginning in the late 1970s, improved imaging modalities and improved means of contrast enhancement greatly increased the precision with which tumors could be visualized. These improvements, combined with a better understanding of tumor biology and the power of sophisticated computers for treatment planning, helped to justify the cost and effort required to build clinical proton therapy facilities. A new $125 million Proton Therapy Center under construction at M. D. Anderson (see Building from the Ground Up) will join 20 proton therapy facilities worldwide (four in the United States) that are treating patients. A hospital-based center is under construction at the University of Florida at Jacksonville, and at least five other centers are in the initial planning stages. “So it’s a very exciting period for proton therapy. Those of us who have spent most of our lives in particle therapy are of course very happy about this,” said Dr. Smith. The advantages of protons The main advantage of protons over photons has to do with the way their energy is released. Much of the total dose of a photon is deposited before it gets to a tumor, and a photon beam continues to deposit energy after passing through the tumor. Protons, on the other hand, deposit a much lower dose before arriving at the tumor and can be stopped immediately after exiting the tumor. This results in a much lower dose to normal surrounding tissues while allowing for the delivery of a higher treatment dose to the tumor with fewer side effects. Higher doses delivered to the tumor will result in higher rates of local control and disease-free survival in many tumor sites. “It is our strong belief that most tumors that are treated with x-rays can receive a more localized dose distribution with protons,” Dr. Smith said. “In those cases where local control is quite good with photons, you can decrease late effects using protons.”
Improving proton therapy In standard proton therapy, a proton beam entering the treatment delivery nozzle is scattered into a broad, uniform beam and shaped to conform to the tumor. The process of scattering the protons generates neutrons, which could cause late effects, including new tumors years after treatment. These effects are comparable to those caused by radiation therapy using photons, which can be cause for concern. Using computerized treatment planning methods, a team of researchers led by Radhe Mohan, Ph.D., professor and chair of the Department of Radiation Physics, is applying intensity-modulated delivery techniques to proton therapy. This method of treatment delivery will use a pencil-beam scanning nozzle that was designed especially for the M. D. Anderson facility. With intensity-modulated proton therapy, or IMPT, a single, narrow proton beam about a centimeter in diameter is swept across the tumor from multiple directions, depositing the radiation dose, mostly near the end of the beam’s range. The energy of the proton beam can be changed at any time to penetrate the tumor at varying depths. The technique is also known as pencil-beam scanning, but Dr. Mohan describes the process as using a paintbrush to apply proton energy to the tumor. “Using magnets, we make it sweep across the tumor,” he said, “but as it is sweeping, we can also change its energy. In a way, we have a brush that we’re painting the tumor with. We can deposit some dose here, then come from another direction and paint it from a different direction.” The software needed to plan IMPT treatments for individual patients is being developed by Dr. Mohan and his colleagues. The treatment planning process involves simulating the treatment on a computer, making adjustments, and calculating the optimum dose. “Treatment planning is a very large part of the whole thing,” Dr. Mohan said. “You have the treatment delivery component, which is what the machine will do, but then you have to tell the machine what to do.” In addition, Drs. Mohan and Smith and their teams are developing techniques for respiratory-correlated, image-guided proton therapy, in which movement caused by breathing is incorporated into the treatment planning model. Defining proton therapy’s potential All patients treated in M. D. Anderson’s new Proton Therapy Center will be entered into protocols. In general, these studies will help clinicians understand how to use proton therapy optimally and quantify the improvements in clinical outcomes that can be achieved with proton therapy. A specific question that the researchers will try to answer is whether proton therapy can be delivered in fewer fractions at higher doses per fraction. Completing treatments during a shorter period of time by delivering fewer fractions would allow for minimal tumor growth, be less expensive, and enable the center to treat more patients. However, clinical studies are needed to determine how much treatments can be shortened without sacrificing efficacy or safety. Because, on average, protons deliver half the dose to normal tissues that photons deliver, it may be possible to give a more intense regimen of chemotherapy in conjunction with proton therapy, with fewer side effects than can be expected with chemotherapy combined with photon therapy. Another question about proton therapy that researchers hope to answer has to do with the biological effect of protons. Owing in part to the ability of protons to kill tumor cells in the absence of oxygen, proton therapy produces an elevated biological response in tumor cells. In general, this effect is believed to be about 10% greater than that of photon therapy, but the response appears to vary depending on the type of tumor, the dose, and other factors. “I think there can be a number of studies done to more clearly define the tissue-, organ-, and tumor-specific biological response. Once we do that, it will enable us to give even better treatment. Instead of using a generalized factor for all tissues and all tumors, we will be able to optimize the treatment even more,” Dr. Smith said. For more information on this topic or for questions about M. D. Anderson’s treatments, programs, or services, call askMDAnderson at (877) MDA-6789. Other articles in OncoLog, July/August 2004 issue:
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