Miniature x-ray tube turns brachytherapy on and off

An electronic form of brachytherapy could propel radiotherapy beyond oncology clinics and into radiology departments and possibly even imaging centers.

The new technology, Axxent, was approved by the FDA last year. It uses miniature x-ray tubes in place of radioactive iridium seeds to treat early breast cancer in women whose tumors have been removed. Because the source of radiation can be turned on and off at will-and because the body absorbs virtually all of the radiation-treatments can be delivered in any clinical setting. A lead apron draped across the patient is all that's needed to ensure safety.

Much needs to be done, however, before Axxent can fan out across the U.S. Although cleared by the FDA, Axxent has not yet been used in humans. The product was judged by the FDA to be "substantially equivalent" to conventional brachytherapy. Clinical tests were not required as part of the review process.

If found safe and effective in clinical studies now under way, the technology could improve access to radiation therapy, according to Dr. Vivek Mehta, radiation oncologist and director of the Center of Advanced Targeted Radiation Therapy at the Swedish Cancer Institute in Seattle, one of two sites performing preliminary tests of the technology.

Axxent, with capital costs averaging one-tenth of those for either conventional brachytherapy or a linear accelerator, might be installed in communities where neither of these other options exist. The device might also be used to complement conventional approaches, as it promises a treatment regimen up to seven times shorter than competing technologies.

"This system might be especially useful to smaller centers that are reluctant to make a more sizable investment," Mehta said.

There is only one proven option for radiotherapy following a lumpectomy: whole breast radiotherapy using a linear accelerator, he said. Partial breast radiotherapy using brachytherapy or 3D conformal radiotherapy has not yet proved equal to this technology in terms of local control. Partial breast radiotherapy is the subject of a national randomized study, but results are not expected for seven to 10 years.

The key advantage of partial breast radiotherapy is its convenience. Techniques include interstitial brachytherapy using multiple catheters, balloon breast brachytherapy using a catheter-based technology, and 3D conformal radiotherapy using a linear accelerator.

Brachytherapy may employ low- or high-dose techniques. In each of these, the seeds or wires are inserted into the catheter/applicator, left in place for specific periods of time, and then removed.

Studies of U.S. patients indicate that many women considering lumpectomy opt out of breast-sparing surgery with radiation therapy due to time, distance, or difficulty accessing radiation therapy centers. Of the 2000 sites performing radiation therapy, only about 650 perform brachytherapy, and not all of these handle breast cancer.

"A lot of women in smaller communities do not have access to radiation therapy centers and, as a result, they opt for mastectomy," said Dr. Kambiz Dowlat, a professor of surgery at Rush University Medical Center in Chicago, the other site for preliminary testing of Axxent.

But Mehta is cool to the possibility of widespread adoption of the technology at women's health centers. He believes its best application would be in centers offering other alternatives.

"Ideally, I think that the system is most appropriate in centers that have a full arsenal of radiotherapy technologies available, so that the radiation oncologist can pick the best treatment for any given patient," Mehta said.

The possibility that Axxent might be of interest to imaging centers, however, has drawn the developer of this technology into talks about strategic alliances.

"If you listen to the vendors of mammography equipment talk about their vision, they are trying to parallel the needs of the imaging centers with therapy as these centers move from imaging to an increased focus on biopsy and ultimately treatment," said Michael Klein, CEO and president of Xoft in Fremont, CA.

The company will insist, however, that treatments be planned and administered under the direction of a radiation oncologist.

"While we are agnostic as to who actually pays the money to buy the equipment and where treatment occurs, we are militant about the need for the technology to stay within the realm of radiation oncology doing the treatment," he said.

The Swedish Cancer Institute will begin treating patients with the new device in April as part of a 40-patient study aimed at documenting safety and efficacy. By June, about a half dozen more sites, including Rush University Medical Center, are expected to be gathering clinical data about electronic brachytherapy.

Axxent delivers radiation mostly to the area at risk, while eliminating the cost and complex handling that accompanies the use of radioactive isotopes. The x-ray tube, about the size of a grain of rice, fires x-rays charged with up to 50,000 volts.

Even so, this source produces a weaker stream of x-rays than therapy utilizing a linear accelerator. This is not a problem, however, because the area being treated in this clinical situation is relatively small, Mehta said.

Treatment sessions will last about a half hour, including the cumulative five minutes during which the beam is on. These sessions will be performed twice a day over five days.

Electronic brachytherapy is not much different from a modified form of seed-based brachytherapy now being performed at some U.S. oncology centers. In this application, which uses the MammoSite Radiation Therapy System, a balloon is implanted in the cavity created by surgical excision of the tumor. As in the Axxent-based procedure, a radiation source is periodically placed in the balloon and removed, delivering high doses of radiation twice a day for five days. Instead of a miniature x-ray tube, however, MammoSite uses a radioactive seed. The technology, developed by Proxima Therapeutics, was cleared by the FDA in May 2002. The company was acquired about a year ago by Cytyc.

Dowlat, who was instrumental in testing MammoSite, notes that both the seed- and tube-based techniques shrink treatment time by up to six weeks when compared with conventional approaches. Electronic brachytherapy, however, offers two advantages over MammoSite. The first is eliminating the need for shielding. The second is vastly reducing capital expenditures.

"This is an important factor in this day and age of government and private sector complaining of expensive medical therapy," Dowlat said.

Xoft will market Axxent first for treatment of early breast cancer. Radiation therapy is an essential part of therapy following breast-sparing surgery, as it kills stray cancer cells, presumably reducing the rate of local recurrence and improving long-term survival. Axxent might also be applied to endometrial cancer. The company expects to submit an application this summer to the FDA for this application.

Xoft has contracted with Varian Medical to supply its Brachyvision treatment planning system, which Xoft will distribute as an adjunct to Axxent. Capital costs average $150,000 for Axxent and another $85,000 for the treatment planning system.

Customers should break even quickly, if the current reimbursement code for brachytherapy is applied. It allows $4500 for a disposable balloon and $7800 for 10 fractions of brachytherapy. Low-cost disposables used in electronic brachytherapy run about $5000 per treatment.

The company is pressing for a new reimbursement code, however. Klein cites as a model the changeover from conventional radiotherapy to intensity-modulated radiotherapy, which allowed highly precise 3D conformal therapy. This change in reimbursement code promotes adoption of the new technology.

Axxent has the potential to make isotope-based brachytherapy for breast cancer obsolete, Klein said. As a precedent, he points out the effect linear accelerators had on cobalt radiation therapy, once widely practiced in the U.S. but today all but nonexistent.

The device might even reduce demand for linear accelerators. The operators of this equipment, however, are not likely to balk at the introduction of Axxent. Many sites will welcome the opportunity to transfer some of their backlog of patients to electronic brachytherapy, Klein said.