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Image-Guided Radiation Therapy: A New Paradigm Emerges in Cancer Treatment
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(From left) Radiation oncologists Kenneth Rosenzweig; Beryl McCormick, Acting Chair of the Department of Radiation Oncology; and Michael Zelefsky, Chief of the Brachytherapy Service, work to deliver radiation more effectively to treat patients with cancer. |
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Twenty years ago, radiation oncologists had to build in an approximately two-centimeter margin of healthy tissue around a tumor to make certain that radiation treatments would be delivered to the tumor at therapeutic levels. The movement of internal organs between treatments and the patient's relative positioning at the time of each treatment were among the factors that required the delivery of radiation to some healthy tissue to ensure that the tumor itself received a full dose of radiation. This margin often increased the toxicity associated with radiotherapy and limited the amount of radiation that could be safely delivered to a patient. About ten years ago, with the advent of machines on which the angle and intensity of radiation beams could be adjusted to aim at tumors with greater accuracy, physicians were able to reduce the margin to roughly a centimeter.
Today, using a technology known as image-guided radiation therapy (IGRT), a tumor can be imaged just before the delivery of radiotherapy or even during a treatment, enabling radiation oncologists to verify its exact location, thereby reducing the margin of healthy tissue exposed to radiation to five millimeters and, in certain cases, to as little as one or two millimeters. If a tumor has shifted even slightly since a patient's last visit, the radiation beams can be adjusted so that they hit it precisely. This degree of accuracy is allowing Memorial Sloan-Kettering radiation oncologists to change the way they treat certain types of cancers.
"It has always been the goal of this field to be as precise as possible, and IGRT is a tool that's better than anything we've ever had," said Beryl McCormick, Acting Chair of Memorial Sloan-Kettering's Department of Radiation Oncology. "We're really seeing exactly what we're going to treat."
At Memorial Sloan-Kettering, radiation oncologists are now delivering radiation more effectively to tumors in areas prone to movement, such as the lung and the prostate gland. They are also able to more safely deliver higher doses of radiation to control or kill tumors located close to the spine and other radiation-sensitive organs and tissues.
Before IGRT, the radiation oncology team -- consisting of the radiation oncologist, a medical physicist, and a radiation therapist -- marked the location of a tumor to be treated with tiny drops of permanent ink applied to a patient's skin or with small metallic markers implanted in the patient's body during the planning, or simulation, stage that precedes radiotherapy. The treatment area beyond the tumor was expanded to compensate for movement and possible changes in the tumor's shape, size, or position between treatments. For example, eating or drinking prior to a treatment can make a difference in the position of a tumor, as can breathing during treatment. (Permanent ink is still used in the treatment of certain cancers; and, in IGRT of the prostate, metallic markers are still embedded in the gland to help target radiation accurately during treatment delivery.)
Now, however, several of Memorial Sloan-Kettering's linear accelerators -- the machines that deliver the radiation -- are equipped with sophisticated imaging technology that allows physicians to verify a tumor's position on the day of treatment while the patient is on the treatment table. After obtaining two- or three-dimensional scans, the radiation oncology team uses specialized computer software to compare these treatment-day images to CT scans or other images captured during the simulation phase and to adjust the radiation beams if necessary. According to Dr. McCormick, Memorial Sloan-Kettering will continue to equip its linear accelerators with advanced imaging technology as older machines are replaced.
Memorial Sloan-Kettering radiation oncologists began employing image-guided techniques in 1999, even before commercially manufactured equipment was available. According to radiation oncologist Yoshiya Yamada, who took a leading role in the work, radiation oncology team members devised their own technology by calibrating a portable x-ray machine and lining it up with the laser beams inside a linear accelerator. "The x-ray pictures enabled us to see in much greater detail the location of the tumor," Dr. Yamada recalled. "The idea was that by getting better quality images, we would be able to more accurately target tumors."
Currently, IGRT is also in use at Memorial Sloan-Kettering's regional facility in Basking Ridge, New Jersey, and the technology is expected to be introduced at Memorial Sloan-Kettering Cancer Center Commack on Long Island in 2008.
At Memorial Sloan-Kettering Cancer Center Basking Ridge, IGRT is currently used to treat lung cancer patients with single tumors who are not candidates for surgery -- for example, patients with emphysema who cannot tolerate losing part of their lungs -- and prostate cancer patients who are candidates for external-beam radiotherapy. Memorial Sloan-Kettering Cancer Center Basking Ridge also uses IGRT for patients in whom cancer has recurred and for whom radiation was not an option in the past because of the potential for injury to healthy tissue.
"Our objective is to continue to adopt the same treatment approaches in use at Memorial Sloan-Kettering's Manhattan campus and bring them to patients in New Jersey," said Sang Sim, Chief of Radiation Oncology at Basking Ridge. Dr. Sim added that Memorial Sloan-Kettering Cancer Center Basking Ridge will soon begin using IGRT to treat brain tumors as well as tumors that have spread (metastasized) to the spine.
Treating tumors that have metastasized to the spine from other organs is one of the most challenging problems in clinical oncology -- and one of the most promising areas for the use of IGRT. "Image-guided radiation therapy is the greatest advance in the treatment of spinal tumors in the past ten years," observed Memorial Sloan-Kettering neurosurgeon Mark H. Bilsky. Spinal tumors can inflict debilitating pain and may also cause nerve damage and paralysis. Although surgery can offer relief of symptoms, it is not without significant risk and is often only a temporary solution. Traditional radiotherapy also has serious drawbacks because physicians are unable to deliver a radiation dose strong enough to destroy the cancer while at the same time sparing the spinal cord.
The emergence of advanced technologies -- including intensity-modulated radiation therapy (IMRT), which gives radiation oncologists the added ability to vary the doses and angles of radiation beams -- has helped to deliver ever-more-targeted radiation therapy. Incorporating image guidance and IMRT, physicians now have the ability to administer a single dose of radiation high enough to destroy cancer, yet so accurate that healthy spinal tissue remains undamaged.
Memorial Sloan-Kettering researchers recently studied 93 patients, each of whom was treated between 2003 and 2006 with a single high dose of radiation using image-guided IMRT for metastatic spinal tumors. To date, the tumors have not recurred in 90 percent of the patients. According to Dr. Yamada, the study's lead investigator, the recurrence rate would have been between 40 and 85 percent in the long term had conventional radiation therapy been used. "We're gaining control over tumors that we never imagined possible before the use of this technology," concluded Dr. Bilsky.
“Our dream is that we'll be able to have a paradigm shift in treating cancer -- including metastatic disease -- such that it will become much more of a chronic illness rather than a deadly one.” |
Memorial Sloan-Kettering radiation oncologist Kenneth Rosenzweig, who focuses on lung cancer, notes that the survival rate for patients who undergo surgery for early-stage lung tumors is 70 to 80 percent, while, historically, for patients with early-stage lung tumors treated with conventional radiation the survival rate has been between 30 and 40 percent. With the use of high-dose image-guided IMRT, the survival rate is approaching the percentages associated with surgery, Dr. Rosenzweig said. "Over the next five to ten years, we may actually see a shift in the standard of care for certain patients with early-stage lung cancer," he elaborated, "in which radiation might replace or be on an equal footing with surgery as a primary treatment option."
Before IGRT, radiation oncologists typically delivered a series of low-dose treatments administered over a period of weeks to give healthy cells time to recover. However, such treatment plans also gave cancer cells the chance to repair themselves. Today, even when Memorial Sloan-Kettering physicians do not use image-guided IMRT to deliver single high doses of radiation, the technology has enabled them to replace the traditional regimen of daily low-dose treatments that spanned six to ten weeks with several larger doses given over a shorter time period.
Among the dozens of patients whom Dr. Rosenzweig has treated using just a few high-dose IGRT treatments was an elderly woman with a small lung tumor. Four image-guided treatments over the course of nine days made it possible for the woman, a Long Island resident, to avoid both the risks of surgery and a taxing commute to Manhattan for the six to eight weeks that would have been necessary in the past. Fifteen months after treatment, she is symptom free with no signs of cancer.
Michael J. Zelefsky, Chief of Memorial Sloan-Kettering Cancer Center's Brachytherapy Service, is currently leading a clinical trial to determine the most-effective and safe dose levels for image-guided IMRT to treat cancer that has spread to soft tissue, lymph nodes, or bone. Dr. Zelefsky, a specialist in the treatment of prostate cancer, has also employed single high-dose radiotherapy to treat tumors that were difficult, if not impossible, to treat in the past. For example, radiation can be risky in treating cancer that has spread to pelvic lymph nodes because of their proximity to the bowels, which have a limited tolerance for radiation. "IGRT provides an opportunity to target the tumors with exquisite accuracy," said Dr. Zelefsky, "while at the same time sparing the bowels and other normal tissues from high doses of radiation."
The promise of IGRT high-dose treatment is embodied in one of Dr. Zelefsky's patients, a 68-year-old man with prostate cancer that had metastasized to his pelvic lymph nodes. The patient opted for a single image-guided radiation dose to his lymph nodes rather than suffer the side effects associated with hormonal therapy, one of the protocols for the treatment of metastatic prostate cancer. "Approaching the one-year mark, this gentleman remains disease-free and sexually active with a high quality of life," Dr. Zelefsky reported.
Yet not every patient is a candidate for IGRT. "In breast cancer, for instance, we need to treat a broad area," explained Dr. McCormick, "and because the target tumor doesn't move much, IGRT isn't appropriate. It's important that patients understand that their physicians will make the decision as to whether or not IGRT is right for them."
Added Dr. Yamada, "Ultimately, our dream is that we'll be able to have a paradigm shift in treating cancer -- including metastatic disease -- such that it will become much more of a chronic illness rather than a deadly one."
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