October 12, 2009

Ultrasound IGRT — Looking to Improve Prostate and Breast Cancer Treatments
By Beth W. Orenstein
For The Record
Vol. 21 No. 19 P. 24

Marc Posner, MD, a radiation oncologist at Lake Forest Hospital in Chicago, was surprised by how much 3D ultrasound improved the accuracy of radiation delivery to his prostate cancer patients.

“Quite frankly, I was not expecting much out of the treatment side of the system,” he says of the Resonant Medical Clarity system, which uses 3D ultrasound to provide image-guided radiation therapy (IGRT). “I was not expecting an improvement in the accuracy but rather a verification of what I had already been doing. That is not what happened. What happened was, as I started treating these men and looking at the way their prostates were moving on a day-to-day basis, I discovered that they were not moving in the direction I had expected them to be moving.”

Subsequently, Posner questioned whether the $300,000 Clarity system was providing accurate information. “You always look at the new thing first,” he says.

Resonant Medical, based in Montreal, Quebec, Canada, sent engineers to Lake Forest to make sure the system was accurate and the radiation oncology staff were using it properly. “Sure enough, they verified that what we were seeing was real,” Posner says. “That changed the way I give my treatments because now I’m actually seeing where the prostate is rather than relying on measurements that have not proven to be as accurate as I would have hoped.”

 Posner adds that the men he treated before he had the Clarity system are doing extremely well. “It just means that moving forward with this new technology, my future patients will get even better treatment,” he says.

The Clarity ultrasound system for the prostate has been available since early 2005. Resonant has developed a similar product for the breast, which has been available commercially for about one year. Like the prostate gland, the cavity created after a woman has a breast tumor removed can change shape and location in the days and weeks after surgery. The lumpectomy cavity is the most likely site of cancer recurrence. The radiation treatment usually involves five weeks of radiation of the whole breast and an additional 1 1⁄2 weeks focused on the lumpectomy cavity.

Statistical Averages
Radiation treatments for prostate cancer are largely planned based on statistical averages. Traditionally, physicians develop a treatment plan for the prostate tumor based on an initial CT and then on the results of decades-old prostate motion studies to determine how the gland is likely to shift.

“What those studies did way back when is they took a series of men and did a CT scan on them every day and then treated them with radiation and then calculated how far the prostate moved from center on a day-to-day basis and came up with averages,” Posner says. “You figure you study enough patients and you come up with an average, which is all that is. Some men will fall outside the average, but you have to assume that most men on most days will be within the average, so they’re getting most of the dose. Also, we’re giving a whole lot of dose of radiation, so you figure that it is sufficient for treatment.”

For breast cancer patients, physicians typically use the lumpectomy scar on the surface of the breast as a proxy to localize the tumor cavity. However, several studies have shown that when the location of the tumor cavity is based solely on the lumpectomy scar, more than one half of the time, radiation treatments miss at least part of the cavity.

Joseph Imperato, MD, FACR, medical director of radiation oncology at Lake Forest, remembers back in the “olden days” when he would “stand there and palpate the area around the lumpectomy scar and try to determine, based on mammograms, what I felt.” When a CT scan became standard, “We realized we were pretty far off sometimes, but at least we could see from the CT scan approximately where the surgical cavity is going to be located.”

However, Imperato says, the lumpectomy cavity is not always in the center of the abnormality seen on the CT scan. “It may be deeper or more to the side, depending on how tissue was disrupted as part of the surgery,” he says. “Since I’ve been using the Clarity breast system, I’ve often found that the cavity appears larger on the CT than it actually is.”

Physicians have been reluctant to image the prostate or breast with x-rays or CT more often during treatment because, while it may help them to visualize the tumor or cavity and deliver radiation more precisely, it could result in unnecessary doses of radiation to healthy tissue. Besides, x-ray is not the ideal modality for distinguishing soft tissue.

Fusing Ultrasound and CT
While working on his doctorate in medical physics at Canada’s McGill University, Tony Falco, PhD, FCCPM, CEO and founder of Resonant Medical, thought he could find a better way to image the prostate, breast, and other soft tissues. Though his first try failed, when Falco switched his focus to sonographic technology, he was successful. “McGill allowed me to develop and run the first clinical trials on the first prototype of the Clarity product,” a fusion of ultrasound and CT at the planning stage followed by ultrasound on each daily treatment, he says. “When it worked on those first patients, it was an ‘a-ha’ moment. I realized, ‘This can really change the way physicians plan and treat breast and prostate cancer patients.’”

With the Clarity system, radiation therapists image the tumor cavity at the time of treatment planning and then daily with each consecutive radiation treatment to get a regular, real-time, visual image and location of the tumor cavity. At the planning stage, the patient is scanned first with CT followed by a Clarity sonogram of the same area.

“We determine the coordinate system of the CT scanner by looking at the data that is acquired,” Falco says. “How we do that is proprietary, sort of a trade secret. We have our own coordinate system from our 3D ultrasound, which we know because it’s our product. We know exactly where each pixel in the 3D ultrasound is relative to the coordinate system of our product. Then we automatically match the two coordinate systems from the CT and the ultrasound. Once you match the data, the data should lie on top of one another, without any user intervention, which saves time and avoids human errors. The anatomy should line up perfectly. We have a quick validation step that the physician goes through to make sure all the anatomy is lined up the way it should be and, in 99% of the cases, it is.”

The fused CT and Clarity 3D ultrasound data prove more useful than CT data alone to locate the tumor and surrounding healthy anatomy for planning, Falco says.

On each treatment day, radiation therapists acquire ultrasound data for comparison with data taken at the reference planning stage. Changes in the tumor’s location or size are reported to the radiation oncologist.

“We tell the physicians that the anatomy has changed to this degree or that degree from the reference plan, and we apply daily corrections to ensure that the right dose is delivered to the tumor,” Falco says. “Sometimes, the anatomy changes are so large during the course of treatment that then it is up to the physician to make the decision whether to re-plan the patient’s treatment. It’s a more sophisticated fusion of imaging technologies that allows us to track changes over time and to correct for these changes to deliver the best treatment every day.”

Old Idea, New Use
Posner says the idea of using sonograms to locate prostate tumors isn’t new. “But up until Clarity, they were used exclusively in the treatment room and not in the setup room and, as a result, they weren’t particularly accurate because they didn’t have anything to refer back to,” Posner says. “With no reference point, there was no improvement in accuracy. But since the Clarity ultrasound is digitally fused onto the initial planning CT, there is now an absolute frame of reference for us to go by when comparing day-to-day setups. This is the first time that’s been done, and that’s why the system works so well and other systems don’t.”

 The Clarity system is an add-on and can be used with any linear accelerator. “We’re vendor neutral at both the planning stage, with any CT scanner or any MRI scanner for that matter, and with any linear accelerator at the time of treatment delivery,” Falco says. “So whether it’s Varian, Siemens, Elekta, Accuray, or TomoTherapy, our product works.” Resonant has a close partnership with an original equipment manufacturer provider for its ultrasound equipment.

 The newest breed of linear accelerators use cone-beam CT to help radiation oncologists guide treatments. Falco says ultrasound can do a better job of imaging soft tissue than CT. Linear accelerators equipped with cone-beam technology “are still not able to distinguish in many areas the soft tissue of the cancerous organ with respect to the healthy soft tissue surrounding that organ,” Falco says. “That’s something the Clarity is adept at.”

Cone-Beam Competition
Even if they have linear accelerators equipped with cone-beam detectors, according to Falco, some centers are placing fiducial marker seeds in the prostate to track their movement because cone beam alone can’t see the prostate. “One of the benefits of our product is that it is noninvasive. You don’t have to place any surrogates in the anatomy in order to track it. We track the actual anatomy you’re treating,” he notes.

Also, Falco says, the additional radiation from the cone-beam CT scans is an issue. “To image the prostate, they keep the beam very wide, so you’re adding dose that we don’t have. We don’t have the ionizing dose that x-rays do that may increase the chances of more cancers in the future,” he explains.

Vendors typically sell the linear accelerator and the cone-beam CT technology as a package, so buyers don’t realize they’re paying $500,000 to $700,000 for the attachment, Falco says. “The cost of our system is about half that, and you get better planning information through fusion that is not possible with cone beam,” he says.

Posner says some facilities that are buying new linear accelerators with some form of image guidance built in may not want to spend the money for the additional piece of equipment. “Economically, a lot of centers are going to have a hard time just on the surface justifying the purchase,” he says. “We got ours because we knew we were not going to be able to replace our linear accelerators for quite some time, and we wanted image guidance. We needed to get an external system, so it made sense to us.”

Clinical Data Needed
Studies are underway to look at the accuracy of ultrasound-based IGRT vs. cone-beam–guided IGRT. “Once that data is available, if it demonstrates definitively that the ultrasound-based IGRT is more accurate, it will be easier for centers that care about accuracy to justify the expense because it’s better than what’s built into the machine,” Posner says. “That’s the kind of study we really need to see to get this particular piece of equipment rolling into more centers.”

In 2004, the FDA cleared Clarity for guidance in the planning and treatment of prostate and breast cancers and other soft tissue anatomies such as gynecological cancers. A study in the February issue of the International Journal of Radiation Oncology*Biology*Physics found that in 20 cases of women with early-stage breast cancer who were enrolled after breast-conserving surgery, radiation oncologists were able to use ultrasound images from Clarity to locate the target with improved consistency when compared with traditional CT images.

Imperato says he hasn’t been using the Clarity system for breast cancer long enough to have statistical data. “The nature of breast cancer is that most recurrences don’t recur until after two years,” he says. “So we’re not going to be able to determine whether we’re getting better results for a while, but in terms of ease of setup and confidence and in terms of volume, I know we’re better.

“Also, it has allowed me to limit the amount of normal breast tissue that we need to treat, especially in the final week and a half when we get to the boost volumes, and the significance of that is that the cosmetic results are significantly greater,” he adds.

 The Clarity system also has an advantage on a practical level, according to Falco. “It takes much longer to acquire a 3D x-ray image with the cone-beam technology than it does with ours. Cone-beam CT can quite drastically impact throughput. Faster guidance technology means less stress for the patient and staff. In Canada and Europe, where there are backlogs of patients being treated, speed can be important,” he says.

Posner says he will always use the Clarity system when planning treatment for his prostate cancer patients because it allows him to do so without a urethrogram, where dye is injected into the urethra and a metal clamp is used to hold it in place. “Statistically speaking, based on other anatomic studies, I knew where the dye ended was 12 mm, plus or minus 3 mm, from the end of the prostate on the average man,” he says.

Patients appreciate not having to undergo a urethrogram, Posner says. Also, they no longer need enemas “because the positioning of the prostate at the time of the setup simulation is not as critical as it used to be,” he says.

Partial Breast Irradiation
Imperato says a treatment trend in breast cancer is to perform partial breast irradiation rather than treating the whole breast. “If that really does catch on and does prove to be a good alternative, you’re going to need this type of unit because this is what is going to let you know exactly where the cavity is,” he says. “If you’re going to do partial breast radiation, you’re going to have far more confidence as far as you’re encompassing the critical tumor volume and, at the same time, you’re not unnecessarily irradiating more of the breast than necessary. I think going forward, if partial breast irradiation does catch on and prove to be a viable alternative, the Clarity system is going to be a critical component of that.”

Imperato says Clarity provides more confidence that the treatment is accurately reaching its target and spares healthy surrounding tissues, which in the case of the breast, can be the lung and the heart.

Currently, more than 50 centers in the United States, Canada, and Europe have Clarity systems, Falco says. The system is also used to treat some head and neck cancers and other organs such as the liver and the bladder.

— Beth W. Orenstein is a freelance medical writer based in Northampton, Pa.