The most crucial element-and biggest challenge-of radiation therapy cancer treatments is dosage. Specifically, research and development has reflected a continual effort to escalate dosage to tumors while decreasing exposure to surrounding healthy structures.

Thus far, the greatest breakthrough is intensity modulated radiation therapy (IMRT). An advance over 3-D conformal radiation therapy (3-DCRT), IMRT is the most precise method yet to increase dose with fewer side effects. It doubles the rate of tumor control while significantly enhancing patients’ quality of life during and after treatment. Radiation to targeted organs can be increased up to 40% higher than traditional methods. At the same time, exposure to surrounding tissues is reduced by 70%. Recently, researchers and clinicians have managed to raise dose levels from the 76-78 Gy range to the 80-86 Gy range.

Put to Good Use

Robotics are involved in an inventive image-guided radiation therapy (IGRT) device developed by Varian Medical Systems (Palo Alto, Calif) called the On-Board Imager, which can track and reveal tumor motion during treatment. A digital imaging system that produces high-resolution images, the On-Board Imager is mounted on the treatment machine via robotically controlled arms that operate along three axes of motion. These can be positioned to provide the best view of the tumor.

In addition, in the area of IMRT, Varian offers what it calls high-resolution IMRT in its SmartBeam product. According to the company, it minimizes “hot spots,” improves target dose homogeneity, provides detailed dose painting to the target, and sculpts the dose around critical structures more effectively. SmartBeam enables physicians to choose the resolution they need according to each clinical situation, without increasing treatment times. It supports all types of IMRT delivery: segmental, dynamic, combined dynamic and segmental in the same field, and conformal arc.

Also in the arena of new IMRT products, Philips Medical Systems (Bothell, Wash) offers the Pinnacle3 RTP system with its advanced P3IMRT software. The software has two new subsystems for biological optimization and direct machine parameter optimization. Reveals Keith Tipton of Philips, “We are the only vendor that supports radiobiological optimization in our IMRT module.”

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“It’s the next step in the evolution that has, so far, taken us from X-ray-based radiation to CT-based radiation,” comments Srinath Sundararaman, MD, medical director of radiation oncology for the Memorial Healthcare System Comprehensive Cancer Program (Hollywood, Fla). At this facility, oncologists use IMRT mostly to treat patients with tumors in the prostate, breast, and head and neck. “IMRT has brought us close to the most dynamic form of treatment, with respect to moving with the body or changing how we look at the tumor. It allows us a measure beyond 3-DCRT.”

Only about 2 years ago, IMRT was considered far too complex to be viable outside of the largest hospitals and research centers. Since then, however, clinical application has spread to smaller facilities. According to a recent study conducted by the market research firm IMV Ltd’s Medical Information Division (Des Plaines, Ill), 38% of all US radiation oncology facilities perform IMRT today, compared with 4% in 1998. Keith Tipton, general manager of planning radiation oncology systems for Philips Medical Systems (Madison, Wis), indicates that the pace of IMRT adoption in the United States quickened-most notably in smaller community hospitals-after newer systems became more automated and easy to use. “We certainly believe this trend will continue,” he adds.

Still, IMRT remains complex and requires a collaboration of medical physicists, physicians, and dosimetrists. Also, it requires a great deal of education that goes well beyond merely learning how to operate equipment.

Pioneers and Innovators

Perhaps IMRT’s most complex element is treatment planning, which involves a major paradigm shift in radiation delivery. Essentially, inverse planning requires that a clinician work backward when designing a patient treatment. The approach involves a steep learning curve. Tipton explains that vendors, with their newer IMRT systems, have been trying to make this concept easier to perform.

IMRT was pioneered by NOMOS Corp (Cranberry Township, Pa), a company that was recently acquired by North American Scientific (Chatsworth, Calif), which then formed the NOMOS Radiation Oncology Division. Its Peacock system, which was FDA cleared in 1994 and first used in 1995, was the first treatment planning and delivery system created exclusively for IMRT. Now one of the most widely used systems, Peacock’s innovative design helped plan and deliver a highly conformal dosage to tumors, regardless of size.

NOMOS’ latest IMRT products all feature Active Rx, a fully automated and interactive set of tools that provides high-speed optimization and dose calculation. Dose delivery can be manipulated directly, and it reduces the inverse planning cycle from hours to minutes. “Active Rx lets the user define and manipulate the dose on a computer screen,” says Rick Chevallier, product manager of planning systems for the NOMOS Radiation Oncology Division. “It generates a plan and provides a distribution. Then you can mold the distribution onscreen. This makes the planning process faster.”

A facility that pioneered the use of IMRT with NOMOS’ technology is Fox Chase Cancer Center (Philadelphia). Always at the vanguard of cancer research, Fox Chase helped develop and pioneer the use of 3-DCRT for prostate cancer. When the center’s oncologists found that IMRT allows for even more precise radiation delivery, they started using it on all prostate cancer patients during the entire course of treatment. “Many facilities that have adopted IMRT only use it during the final 2 weeks of treatment,” says Eric M. Horwitz, MD, director of Fox Chase’s radiation oncology training program. “All of our prostate patients [are treated with] IMRT only.”

After pointing the way with the prostate, Fox Chase began using IMRT for other cancer sites. It’s one of the few facilities that offers IMRT for breast cancer treatment. The main purpose, Horwitz says, is to minimize side effects. Traditional radiation treatments can result in exposure to the lung, coronary arteries, and heart. Other side effects include skin irritation, swelling, redness, or hardening of the breast. IMRT significantly reduces these complications and shortens radiation treatment time from 7 to 5 weeks.

“As people become more comfortable with IMRT, they are cautiously moving into other areas,” indicates Kenneth J. Russell, MD, medical director of radiation oncology for the Seattle Cancer Care Alliance.

One of those areas is the head and neck, where IMRT has proven especially useful in controlling cancer while reducing side effects. A recent study1 revealed that when used alone or combined with surgery, IMRT significantly increases the chance of survival for patients with head and neck cancer.

Russell adds that interest has increased in IMRT for partial breast irradiation as well as for tumors of muscle and bone and gynecologic neoplasms.

3-DCRT for IMRT: An Easy Swap?

IMRT’s effectiveness raises the question of whether it will entirely replace other forms of radiation treatment. Opinions differ. Memorial Healthcare’s Sundararaman thinks it’s a matter of volume at risk. He points to cancerous lymph glands located in the pelvic region as an example. In such a situation, he thinks 3-DCRT would be more useful than IMRT. “That’s a very large field,” he says, “too large, in fact, for IMRT. So I don’t believe there will ever be a time where we are not using 3-DCRT or large-volume treatment.”

But Seattle Cancer Care’s Russell thinks that IMRT could make it possible to narrow the focus of treatment even in such large areas. “Historically, treating people for cancer-containing lymph glands in the pelvis meant treating the entire pelvis. We didn’t have the computer processing power or delivery systems to treat the lymph themselves,” he explains. “Now, we can create maps of these glands, and we have computers that can figure out how many different angles and beams it will take to crossfire just those chains of glands. We can start thinking whether we need to treat the entire pelvis to get at those glands or whether IMRT will allow us to focus on just the glands and spare the organs and tissues that reside nearby.”

On the other hand, for certain situations, IMRT might simply be technological overkill. “Is it going to be used everywhere as an alternative?” Russell asks. “In some cases, it probably wouldn’t be necessary. Technologically, it’s too much for simple circumstances, because IMRT involves an awful lot of quality assurance and quality control.”

Another likely scenario is that treatments like 3-DCRT will continue to be useful, just less frequently. “Any advancement in quality assurance and the amount of time it takes to deliver that treatment, the more I think it will be adopted for other body regions and the more it will replace things like 3-DCRT,” says NOMOS’ Chevallier. “I don’t think 3-DCRT will ever completely go away, but I think we’ll see a shift toward more IMRT.”

Another question about the future of IMRT, particularly as it relates to different cancer sites, is whether it will be useful in treating lung cancer.

“Right now, that is something best left to the university hospitals, because you need to use respiratory gating,” Sundararaman says. “A lung tumor will move 2 or 3 cm or even an inch while the patient is breathing. So if you try to get too precise, you might miss the tumor.”

Russell agrees, adding, “Gating is one of the challenges with lung cancer, or any tumor where there is a lot of organ motion.”

A Guided Hand

The subject of motion and its problems inevitably leads into another area of radiation therapy that has witnessed a good deal of recent research and innovation: image-guided radiation therapy (IGRT). Because it is designed to improve the precision and effectiveness of cancer treatments by enabling more accurate tracking of and adjustment for tumor positions, IGRT addresses problems associated with movement-patient breathing or organ displacement.

Previously, physicians addressed problems with patient positioning and motion by treating a margin of healthy tissue around the tumor. Now, IGRT helps doctors minimize the margin. “Image guidance allows you to align the target on a daily basis,” says Joseph W. Habovick, product manager of image-guided therapy for the NOMOS Radiation Oncology Division. “Improvements will enable physicians to further shrink the margins, which will allow for dose escalation.”

Actually, IGRT does not refer to one specific procedure. Different modalities can be used to achieve the image guidance. Along with ultrasound, these include electronic portal imaging and tomotherapy.

A radiation therapy area that NOMOS helped pioneer, IGRT provides fast ultrasound localization, particularly with ultrasound image guidance and its B-mode acquisition and targeting (BAT) system. Combining ultrasound with a 3-D tracking system and a touch-screen-based treatment room interface, BAT noninvasively pinpoints tumor targets rapidly and accurately.

BAT applications were most commonly used in prostate cancer treatment, but recent upgrades have made them useful in locating soft-tissue targets anywhere in the body. These upgrades include original articulated arm technology and an optical camera targeting solution. The added functionality these bring to the system provides the ability to track objects or an apparatus connected to the treatment table or to the patient. NOMOS’ latest system version, BAT SXi, features ImageSync software, a real-time imaging/positioning technology that provides a continuous stream of ultrasound images that can localize cancer targets before treatment.

New Options With Brachytherapy

Brachytherapy has been most commonly used to treat prostate cancer. Increasingly, it is being used in fresh ways to treat different cancer sites. A new technique called high dose rate (HDR) brachytherapy enables more even precise treatments for many types of cancer.

Sundararaman and colleagues have started using a computer-controlled, remote HDR brachytherapy machine. Besides the improved precision, the major advantage this provides over low dose rate treatment is that it can be delivered in just a few minutes. “It has made treatment very easy for people who are working or for older patients, who can’t tolerate long admission,” Sundararaman says.

He adds that it can be used for cervix, vaginal, endometrial, breast, prostate, uterine, and lung cancers. He explains how it works in a vaginal application, where the goal is to treat the upper section: “On the first visit, an applicator is placed into the bladder, so we can get a dose to the bladder, and a catheter is placed in the rectum, so we can see that on X-ray and give dose to the rectum. A plastic cylinder is inserted into the vagina, and a holding device keeps it in place. Dummy seeds are placed inside the cylinder, mimicking the radiation sources or source positions that will take place inside.”

X-rays are then taken and imported into a computer, which looks at the bladder, rectum, and vagina. Users can then determine exactly where the dose needs to go and place it accordingly. “The beauty of it is that you have a single source of high radiation, and we can have it sit in a dwell position for 5 or 10 seconds,” Sundararaman says. “By adjusting the dwell time and position, you can shape a 3-D volume, or cloud, of radiation to cover your target.”

Another new brachytherapy tool is the GliaSite Radiation Therapy System (RTS), developed by Proxima Therapeutics Inc (Alpharetta, Ga). The system treats newly diagnosed, metastatic, and malignant brain tumors by delivering radiation directly at the site from within the cavity created by the surgical removal of the tumor. A directed dose reduces exposure to healthy tissue.

The system is especially important for patients with recurrent brain tumors who can’t undergo external beam radiation for fear of further damaging healthy brain tissue. “The GliaSite is very simple but effective. Almost any neurosurgeon trained to take out a brain tumor could use it,” says Mark Rosenblum, MD, who has used the system at Henry Ford Hospital (Detroit).

It involves an uninflated balloon catheter placed in the tumor site after resection. Following patient recovery, saline and Iotrex (a liquid radiation source specifically developed to treat malignant tumors) are injected into the catheter, filling the balloon. Iotrex targets the edges of the cavity, where cancer might remain. The mixture stays in the catheter for 3-7 days, until the right amount of radiation is delivered. Finally, the mixture is withdrawn and the catheter removed. The system’s efficacy was demonstrated in a clinical study, sponsored by the National Cancer Institute in 2001, involving patients with recurrent brain tumors.2 On average, patients treated with GliaSite had a survival rate of 387 days, with a 52% survival rate after one year.

Rosenblum says the main advantage is that there is less tumor volume to irradiate, because tumors have been removed. “I believe it will impact local control and longevity better than other types of brachytherapy,” he adds.

Proxima also has developed a brachytherapy system for breast cancer called the MammoSite RTS, an application that provides more postsurgical treatment options for women with early stage breast cancer. Because of its invasiveness, conventional brachytherapy is rarely used for breast conservation therapy. But the MammoSite procedure, with its single catheter approach, is far less complex and invasive. It involves a site-specific, prescribed dose of radiation given over 5 days. The radiation is directed to the tissue surrounding the original tumor, which minimizes exposure to the rest of the breast and the skin, ribs, lungs, and heart.

Wrapping Up

New methods of radiation delivery-whether accomplished externally with techniques like IMRT or internally via brachytherapy-have been shown to be viable and effective, and are expected to have an enormous impact on outcomes and quality of life.

In particular, IMRT is regarded as the most significant radiation therapy advance for cancer. The consensus is that the procedure is here to stay. “Scientifically and intellectually, everyone knows IMRT makes more sense,” says Tipton of Philips.

Seattle Cancer Care’s Russell agrees, adding, “In medicine, things come and go, but IMRT won’t. Now that we have the computational power and the machinery to deliver the treatment, there really isn’t any reason to go back.”

Dan Harvey is a contributing writer for Medical Imaging.

References

  1. Chao KS, Ozyigit G, Blanco AI, Thorstad WL, Deasy JO, Haughey BH, et al. Intensity-modulated radiation therapy for oropharyngeal carcinoma: impact of tumor volume. Int J Radiat Oncol Biol Phys. 2004 May 1;59(1):43-50.
  2. Tatter S, Shaw E, Rosenblum M, Karvelis K, Kleinberg L, Weingart J, et al. An inflatable balloon catheter and liquid 125I radiation source (GliaSite Radiation Therapy System) for treatment of recurrent malignant glioma: multicenter safety and feasibility trial. J Neurosurg. 2003;99(2):297-303.