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Harnessing the Power of Protonsby Dianne C. Witter
Protons accelerate to nearly light speed as they whip through a vacuum chamber, guided by powerful magnets. Near the end of the journey, the beam delivery system shapes the proton beam so that it delivers its radiation precisely to the dimensions of the patient’s tumor. These subatomic particles then slow down and stop in their target, depositing their energy within the malignant tissue and leaving adjoining tissues unharmed. The patient feels nothing, and yet in 20 minutes, a positron emission tomography scan will allow the physician to begin to see the cancer cells die. The appeal of proton therapy, it turns out, is not in the type of radiation it delivers, but in its precise delivery. Consider the size of the “C” at the beginning of this sentence. That is the size of the specificity with which proton beams can be directed at a target. When you’re talking about a malignant tumor nestled among critical nerves and sensitive human tissues, that pinpoint aim takes on enormous significance. “Proton beams can be conformed to the exact dimensions of a tumor and delivered directly to it without damaging the surrounding organs or tissues,” explained James Cox, M.D., head of the Division of Radiation Oncology and medical director of the Proton Therapy Center at The University of Texas M. D. Anderson Cancer Center. Because the radiation doesn’t stray to healthy tissues, patients experience fewer side effects and are less likely to have long-term complications. The radiation from protons has the same effect on tumor tissue as the X-rays traditionally used in radiation therapy, but with a more advanced delivery system, explained Dr. Cox. “While X-ray beams go all the way through the body, affecting any tissues in their path, proton beams have a very low entrance dose and no exit dose—the protons stop when they reach the defined target and release the radiation,” he said. While delivering radiation with a proton beam is an advanced technology available at only a few hospital-based proton therapy centers in the country, Dr. Cox notes that proton therapy has actually been in use for some time. “People often assume proton therapy is experimental,” said Dr. Cox. “They want to know, ‘Is it safe?’ and ‘Is it effective?’ They’re usually surprised to learn that proton therapy has been in use for medical purposes for over 50 years and that it has been approved by the U.S. Food and Drug Administration for cancer treatment since 1988.” More recently, advances in imaging technology have significantly expanded the potential applications for proton therapy. Cancer treatment has long been a hazardous balancing act of determining how to deliver enough toxic chemicals or radiation to effectively kill a tumor without causing substantial harm, or even death, to the patient. Like molecularly targeted therapies, proton therapy represents an important leap forward in our ability to kill the cancer while sparing the patient.
Dr. Cox cautions that proton therapy is more appropriate for some tumor types than others, and careful selection of candidates is essential to the treatment’s success. In some cancers, the broader penetration of X-rays is preferable—in breast cancer, for instance, it’s advantageous for the radiation to go all the way through the breast to kill any stray cancer cells, he noted. Proton therapy also is not needed if tumors are especially sensitive to radiation or if high doses of radiation are not required. Conventional radiation therapy remains a proven and important cancer treatment and will often be the treatment of choice, especially given the limited availability of proton therapy around the country. Proton therapy is optimal for certain localized solid tumors with well-defined borders, including those of the prostate, eye, lung, brain, head, and neck (see box at right). Prime candidates for proton therapy are patients who need a higher dose of radiation than would be safe with X-rays or whose malignancy is next to critical structures. The question of exactly which patients will ultimately benefit most from proton therapy is still being addressed in clinical trials at the Proton Therapy Center, which currently has 6 clinical trials under way and another 25 or so in the works. The trials capture data about effectiveness and toxicity and look at ways to increase the effectiveness of proton therapy, such as by giving it in combination with other treatments. Dr. Cox described a quality-of-life study under way in prostate cancer patients who undergo proton therapy. “It’s too early to know if the proton therapy will improve survival, but the acute effects typically seen with X-rays have been amazingly absent,” he said. “Maintaining functions like bladder control and erectile capability after treatment can have a major effect on a man’s quality of life.” Dr. Cox believes proton therapy has particular promise in lung cancer. In an analysis of patients treated for non–small cell lung cancer, published in the July 2006 issue of the International Journal of Radiation Oncology, Biology, Physics, Dr. Cox and colleagues found that, even with dose escalation, proton treatment significantly reduced radiation to healthy lung tissue, the esophagus, the spinal cord, and the heart, as compared to standard-dose X-ray beams. Based on these findings, the group hypothesized that proton therapy with dose escalation could result in longer survival without increased toxicity. Studies are currently under way in the Proton Therapy Center to look at this and other questions. “One of the key areas of proton therapy research right now is combining chemotherapy or other agents with proton therapy for a synergistic effect,” Dr. Cox said. “It’s a huge, relatively unexplored area with a lot of potential. We’re looking at this in clinical trials right now—the decrease in toxicity from giving radiation with proton beams allows us to give higher doses of both radiation and chemotherapy than is typically possible with chemoradiation. “So far—the studies are still under way—we’ve delivered proton radiation at doses 15% higher than is possible with X-ray/chemotherapy combinations; and the acute side effects, particularly esophageal effects, have been much lower or non-existent,” Dr. Cox noted. “This is an exciting area because, potentially, remissions and survival rates will increase as well. “This, for me, is the real promise of proton therapy.”
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 2007 issue:
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