Intensity modulated radiation therapy (IMRT) offers innovative techniques for planning and delivering cancer treatment to a wide variety of solid tumors. The hallmark of this approach is its ability to conform radiation beams or beamlets of varying intensities that maximize treatment dose to malignancies while sparing critical structures and normal tissues close to the target.
For example, prostate cancer treated with highly targeted 3D conformal planning results in a much higher dose administered safely that increases cure rates without escalating toxicity to adjacent anatomic structures. In some diseases, this may be purely a quality of life issue, but in others where dose escalation is paramount, normal tissue can be spared while the tumor receives maximum dosages of radiation.
Since IMRT was first introduced in 1992, the adoption rate has skyrocketed and additional, more sophisticated techniques have been developed as a result of improved medical imaging and advances in the planning and treatment systems.
Arno Mundt, MD, associate professor of radiation and cellular oncology at the University of Chicago Hospitals, has conducted a series of surveys to study adoption rates of IMRT.
In 2002, with an objective of assessing the level of IMRT use in the United States, his group surveyed 333 randomly selected radiation oncologists. Thirty-two percent of these clinicians were using IMRT, with academic physicians more likely to use these techniques than their private practice counterparts. In a follow-up study completed last year, the rate of IMRT use rose to 73.2 percent, including 62 percent of identified non-users from the first survey.
In addition to those studies, Mundt's group asked chief residents about whether or not they had learned about using IMRT in their training program, to provide a barometer of future practice. Seventy-one percent of the respondents reported receiving formal IMRT didactic education and 87 percent of them had received "hands-on" training.
As adoption rates of the basics of IMRT have become more widespread, Mundt finds that many people are using advanced techniques such as dose painting.
"In our latest survey, 50 to 60 percent of respondents said they had dose-painted at least once in their practice…" says Mundt. "This tells you that they are using IMRT in more sophisticated ways than just conforming the dose."
Advances in medical imaging have propelled treatment progress. Mundt, who uses a Varian system, describes additional information provided by MRI and PET scans to guide dose-painting activities.
PET can reveal metabolically active areas within the tumor that may require additional dose levels, he explains. "Nuclear medicine scans also can look at things like oxygen levels. Low oxygen levels can impair the efficacy of radiation, so if you find hypoxic or low oxygen levels of the tumor, that might be an area where you would want to provide an extra boost to overcome that situation." This is experimental work being conducted at MD Anderson Cancer Center, according to Mundt.
Advances in technology make the difference
Daniel Galmarini, DABR, director of physics at 21st Century Oncology, a wholly-owned subsidiary of Radiation Therapy Services, of Fort. Myers, Fla., explains that they use a number of different systems in their more than 50 treatment centers.
The Planning Target Volume (PTV) includes the tumor in addition to areas where microscopic disease could be present plus the critical structures that surround the tumor.
"One of the problems we had was with the speed of delivery," says Galmarini as he describes some of their patients who required 45 minutes for each of their daily treatments. "With the new algorithms that optimize the workings of the MLCs [multi-leaf collimators], we could expedite delivery." Future enhancements should provide respiratory-gated treatment for lung and upper abdominal tumors.
With current treatment activities, such as for prostate cancer, great care must be taken to insure that the tumor is in the precise position reflected in the plan. Several linear accelerators include kilovoltage auxiliary beams that provide diagnostic quality images at the point of treatment.
"You have a head that delivers radiation with a megavoltage portal vision system, and placed 90 degrees to that, there is a kilovoltage tube with a detector panel on the opposite side," explains Galmarini. Different manufacturers offer a variety of configurations to produce images that verify placement of the tumor and surrounding structures prior to delivery of radiation to the target.
Mitchell Machtay, MD, vice chairman of radiation oncology for the Kimmel Cancer Center at Jefferson University Hospital in Philadelphia is using the Elekta Synergy linac to treat head and neck cancers including some brain tumors as well as tumors at the base of the skull.
The primary feature that makes IMRT different is its ability to bend the dose into a concave dose distribution, Machtay explains. "With regular conformal radiotherapy or for that matter conventional stereotactic radiosurgery, you get a dose distribution that is roughly spherical. When you add IMRT into the mix, you can create dose distribution shapes that bend around critical structures and have a concave shape."
This capability is especially beneficial with tumors that are shaped like horseshoes such as one that wraps around the spinal cord.
In describing their system, Machtay relates the benefits kilovolt cone beam CT imaging capability which they will deploy soon. "We will be able to do CT scans with every treatment to verify that the tumor is in the same position and has not swollen or changed shape," he says.
Edward Gilbert, MD, radiation oncologist and medical director of the Lance Armstrong Shaped Beam Radiosurgery Program at Richardson Regional Cancer Center - UT Southwestern Medical Center in Texas is using the Novalis linac from BrainLAB with its mini MLCs that are only 3mm in size, which enables shaping small treatment fields with increased precision. He describes another benefit of the Novalis system as its ability to come at the target from many different angles. ExacTrac is designed to integrate treatment planning information with daily digital radiographs obtained at the time of treatment that use bony landmarks for verification purposes.
"Tumors don't recur in the shape of a circle, and in fact they may be very unusual shapes," says Gilbert. In this scenario, not only does the target have to be conformed with a more challenging shape, but the critical structures that may have been radiated with the original treatment must be avoided even more carefully.
Berna Roig, MD, radiation oncologist at Alta Bates Comprehensive Cancer Center in Berkley, Calif., is using the Varian Linac 2100EX with multileaf collimators for treating patients with prostate cancer, head and neck cancers, pediatric cranial/spinal tumors and for palliation in certain patients with metastatic disease. They use implanted fiducial markers that can be visualized on portal images to verify position of the prostate, and use immobilization for all of their other treatment functions.
Besides the obvious improvements in dose escalation, she notes that sometimes quality of life issues assume critical importance. In treating head and neck cancers, being able to spare salivary glands and preserve salivary function is very important.
Erik Assarsson, MD, an attending physician in the department of radiation oncology at Bryn Mawr Hospital in Bryn Mawr, Pa., has been using a Varian Clinac 21EX linear accelerator and an ADAC treatment planning system for the past 31/2 years to treat more than 300 prostate cancer patients with IMRT. The practice also uses IMRT to treat certain cancers of the pelvis, pancreas, lung, breast, head and neck region and brain.
Referring urologists have become very receptive and supportive of radiation therapy since the implementation of IMRT. Improved cancer control rates are being realized with a significant reduction in side effects.
"Through an eight-week course of IMRT we typically will see a modest increase in bladder and bowel frequency that occasionally will require medication use…[and] we find that within a few weeks of completing therapy their urinary and bowel patterns return to normal," Assarsson says. At this point, the department is using ultrasound guidance to verify target localization, and they plan to implement image-guided radiation therapy (IGRT) in the near future.
Larry Kestin, MD, program director in the department of radiation oncology for William Beaumont Hospital in Royal Oak, Mich., is using the Elekta Synergy linac to provide treatment for a variety of solid tumors. Besides the usual treatment that creates a complex dose distribution with a significant gradient between the maximum and minimum dose parameters, they also use IMRT for breast cancer.
"For breast cancer, IMRT is used to create a homogeneous distribution throughout the breast," explains Kestin. "By using IMRT, we reduce the toxicity of the treatment and we do a better job of covering the breast and the target of the lumpectomy cavity." They routinely treat close to 90 percent of their breast cancer patients with this approach.
They anticipate installation of the latest Elekta Synergy S system used for stereotactic radiosurgery by the end of 2006. "The Synergy S has mini or micro MLCs so it can shape radiation beams useful for finer delineation of smaller fields," he says.
Jeffrey Herman, MD, medical director of Unity Radiation Therapy Center in Fridley, Minn., describes their general radiation oncology practice where they use the Elekta Precise Linac to perform IMRT primarily for prostate, but also for head and neck (including brain) tumors and occasional pancreatic tumors.
He notes that their IT department has worked diligently to insure smooth flow between diagnostic imaging modalities and the therapy planning system through to the linac. With imaging equipment from a number of different vendors, they could have had difficulties that their IT department reduced to a minimum.
Herman raises an important concern as digital images become the norm because images can more easily be reversed, or the scale distorted. As they become more automated in functionality, they have taken great care to be cautious about potential disastrous problems produced by inattention to these circumstances.
A cautionary tale
One of the other surveys conducted by Arno Mundt and his colleagues was to review information on the internet, knowing that patients often turn to that resource to make decisions about treatment. Of the top 50 sites "hit" on the major search engines, they found that there was false or misleading information on 42 percent of those websites. This situation was equally common on academic and commercial sites, and was only balanced with the pros and cons of IMRT on 24 percent of the sites.
They were surprised that the more balanced representations were found on commercial insurance sites.
Given the fact that many patients come for treatment with pre-conceived notions about IMRT, it behooves physicians to make sure the information their patients obtain is correct. Additionally, if physicians decide to provide information on the internet, they must make sure that their website presents accurate explanations of IMRT.
IMRT has gained wide acceptance among many radiation therapy practices. It has proven to be an outstanding tool both in providing maximum dose to the tumor target, but also in reducing side effects when nearby normal tissue and critical structures receive lower levels of radiation. As systems continue to gain sophistication, the types of clinical applications will no doubt increase.