BOSTON--Advances in three fields--imaging, medical physics, and computer technology--have led to the development of a radiation therapy modality that may represent a significant breakthrough in cancer treatment.
"Intensity modulated radiation therapy (IMRT) is the most sophisticated form of computer-delivered radiation therapy currently available," said David E. Wazer, MD, director of the Radiation Oncology Center of the New England Medical Center, which has pioneered the technique.
Mark J. Engler, PhD, physicist-in-chief at the Radiation Oncology Center, said that the technique is not just an improvement on state-of-the-art radiation therapy technology, but rather offers a complete change in the way in which radiation therapy is administered. Dr. Engler headed one of the first physics teams responsible for making IMRT a reality.
IMRT is a three-dimensional conformal radiation treatment that uses a powerful computer model to plan therapy and a multileaf intensity-modulated collimator to deliver highly focused radiation doses with minimal damage to surrounding tissue (see images ).
In an interview with Oncology News International, Dr. Engler said that, in effect, all radiation therapy is conformal. "Obviously, from the time the first physicians aimed an x-ray tube at a cancer, they wanted the dose to conform to the target." But unlike conventional 3D-conformal radiation therapy (3D-CRT), IMRT treatment decisions are based on complex mathematical models, resulting in a level of precision previously unattainable, Dr. Engler said.
A Brief History of IMRT
When Mark Carol, MD, first envisioned dose optimization using a computer-controlled intensity-modulating multileaf collimator, the year was 1975, and computer technology could not meet the needs of the idea.
In 1989, London physicist Steve Webb, PhD, published a paper applying complex mathematical principles to radiation oncology, and, in 1992, Dr. Carol began working on a prototype IMRT system, based on Dr. Webb's article.
He named the system Peacock, from the fan of peacock feathers that symbolize the multifaceted beam patterns utilized in IMRT.
In 1996, Dr. Mark Engler and his colleague Jen-San Tsai, PhD, defined the international safety standards for IMRT in two papers presented at ASTRO. The FDA gave final clearance to the Peacock hardware in 1994 and the planning software in 1995. It is made by NOMOS Corp. (Sewickley, Penn), founded by Dr. Carol.
The Planning Phase
For treatment planning with IMRT, a series of 40 to 80 CT images are obtained and sent to the planning computer where radiation oncology personnel delineate targets and sensitive surrounding normal tissues. The clinician then determines the optimal dosage for the tumor site and the maximum tolerated dosages for the surrounding normal organs and tissues. This allows for a radiation prescription that expresses the relative importance of sparing different normal tissues.
"In a prostate cancer patient, for example, the physician can tell the computer the maximum tolerated dose for the rectum, the bladder, the heads of the femurs, and so forth," Dr. Engler said. "In a brain tumor patient, the system forces the physician to quantify the relative importance of, say, the auditory nerve versus the optic nerve."
Once all the data are entered, the IMRT software simulates the radiation physics for the desired doses, using mathematical models to search for the plan that best satisfies the physician's multifaceted prescription. The plan typically includes "an astronomical number of beam patterns, providing dynamic, optimized, intensity-modulated 3D radiation therapy," Dr. Engler said.
The data for the optimal plan are then transferred to a disk, which is inserted into the MIMic collimator controller on the accelerator for delivery of the treatment plan. (The MIMic--multileaf intensity-modulated collimator--is part of the Peacock IMRT system, manufactured by NOMOS Corporation.)
As the MIMic rotates around the patient, it constantly measures the beam angle and adjusts the small vanes that shape the beam. Thus, the field shape and intensity of the beam are continuously varied so as to mold the radiation beam to the target and modulate the intensity of the radiation across the target.
In contrast, with conventional 3D-CRT, Dr. Engler said "you're aiming at a silhouette of the target, and you're treating normal tissues in front of and behind that silhouette in a somewhat arbitrary fashion. IMRT technology is aimed at minimizing the dose to these tissues in front of and behind the target in a very systematic manner with intensity modulatation."
The conformity of the dose distribution to the target using IMRT is shown in the images , in which a set of colored lines represents the actual radiation dose that was delivered with IMRT.
Typically, the prescription dose (shown by the innermost overlapping red-yellow lines around the tumor) is about 85% of the maximum dose, falling off to 55% of maximum at the outermost blue-black line. "The whole point of this system is that it creates a very sharp fall off of dose right around the target," Dr. Engler said.
While IMRT is currently being used primarily on head and neck tumors, in the near future, refinements in immobilization and imaging techniques should allow its use to treat cancers in almost any location, including the breast and lung.
"We are already seeing dramatic outcomes in patients with head and neck tumors," Dr. Wazer said. "One patient with a brain tumor wrapped around the optical nerve would have been blinded as a result of the tumor. Using IMRT, we were able to dramatically reduce the size of the tumor and preserve the person's eyesight without damaging the optical nerve with radiation."
Dr. Wazer has submitted the results of preliminary clinical trials using IMRT for presentation at the annual ASTRO meeting this fall. Nine other American sites are involved in IMRT clinical trials, but the Radiation Oncology Center has treated about one quarter of the more than 360 IMRT patients in the United States.
Dr. Engler noted that many of the initial brain cancer patients were treated under investigational device exemptions and protocols with criteria that resulted in "extremely sick patients who did not have other options." Nonetheless, he said, one of the preliminary observations is that with IMRT most of these patients have not needed repeat surgery for aggressive brain tumors.
He said that prostate cancers are now being treated using IMRT, and "the system is allowing us to cut down the dos-ages to the rectum and bladder by about 50%." Several years of follow-up will be necessary to determine if the technique does indeed produce fewer complications.
National research groups, including RTOG, have drafted dose escalation protocols to be used with IMRT in prostate cancer patients, he added.