High-Dose Brachytherapy Gaining Converts in War on Early Stage Breast Cancer

High-dose breast brachytherapy is but a blip on the century-old timeline of brachytherapy milestones in modern medicine. Yet in just the five years since its introduction in the U.S., it is showing significant promise not only as a viable alternative to mastectomy, but may one day rival whole breast external irradiation in the fight against early stage breast cancer.
While a decade will pass before results of a massive clinical study prove or disprove it as an effective alternative to external radiation, high-dose brachytherapy today is increasingly being employed as a monotherapy for breast radiation, and in limited cases, as a boost for whole breast irradiation following surgical lumpectomy.
High-dose brachytherapy, it seems, is a technology tailor made for the outpatient setting: It accomplishes what whole breast radiation does in almost one-tenth of the time, making it quite appealing to patients who want to get on with their lives. And thanks to remarkable innovations in just the past five years, procedures have become standardized, more affordable and safer to perform. Reimbursement also is making it increasingly attractive to physicians.
Defining a New Trend
Breast brachytherapy, also called accelerated partial breast irradiation, is based on the proven premise that the greatest chance of early stage cancer recurrence occurs just a few centimeters from the tissue surrounding a tumor. “The greatest risk of recurrence is within 1 cm of the walls of the tumor bed,” Ellen Sheets, M.D., chief medical officer for Alpharetta, GA-based Cytyc Corp., told Outpatient Care Technology. Researchers say approximately 80 percent of breast cancer recurrences after lumpectomy occur near the original tumor site.
Instead of exposing healthy breast tissue, the chest wall and vital organs to a blast of radiation from an external source, brachytherapy brings the radiation inside the cavity left from a lumpectomy. The most prevalent form of radiation is in the form of tiny “seeds” made of titanium or other material and encapsulating a naturally occurring isotope such as iridium 192. In fact, one company, Fremont, CA-based XOFT Inc., recently received FDA clearance for a seed alternative, a device best described as a tiny X-ray tube.
High-dose breast brachytherapy typically entails 10 treatments (also called “fractions”) over a period of five days. During each treatment, performed twice a day, the seeds are placed into the lumpectomy cavity by special wires inserted through tiny catheters, left for a small, predetermined amount of time, and then removed. The number of seeds, the dosage and placement of each seed are determined by special treatment planning software.
In the first few years after its introduction, high-dose brachytherapy was most commonly administered through a technique called “interstitial high-dose rate multicatheter brachytherapy,” in which up to 30 catheters were inserted into the breast and left there during the five-day treatment regimen. One of the most significant innovations in this technique came in the form of the “Kuske Breast Template,” a perforated grid used to ensure the exact placement of seeds within the lesion bed. The device was co-developed in 1998 by Dr. Robert Kuske and Columbia, MD-based Nucletron Corp. Because of the multiple entry points interstitial brachytherapy is able to conform dosages to specific targets inside the lesion bed. However, the procedure, while proven to be effective, was complex, and many women complained of the discomfort from having to wear the catheters.
In 2002, Proxima Therapeutics pioneered a new technique called “intracavitary balloon catheter brachytherapy” (trademarked as “MammoSite”), in which a deflated balloon was inserted into the lesion bed and inflated with saline. Instead of multiple catheters at various locations through the breast tissue, only one catheter was needed. Today, balloon brachytherapy is the most widely practiced form of high-dose breast brachytherapy, chiefly because it is simpler to perform and as effective as its predecessor.
Gearing Up
Breast brachytherapy systems typically require an electromechanical remote-controlled loading device called an “afterloader,” which stores and administers the radioactive seeds through a series of channels. Treatment facilities must install the afterloaders in specially designed, heavily shielded “bunkers.” Other equipment may include: control consoles, computer hard drives, flat-panel monitors, software (most suppliers include customized Windows-based applications for treatment planning, training and billing and reimbursement) and various bundled or unbundled products such as catheters, special needles and templates. Treatment times will increase slightly as the seeds age, and depending how often they are used, will need to be replaced (typically every three to four months).
Thomas Pollatz, product manager for Nucletron, noted that systems may enable such techniques as image guided brachytherapy; image fusion using physiologic and anatomic imaging; auto catheter recognition for interstitial applications; various optimization techniques to optimize needle/catheter placement; the ability to perform intracavitary or interstitial techniques with or without templates; DICOM connectivity; and the ability to perform 2-D- or 3-D-based planning.
Recent Innovations
Here’s a look at recent innovations from the key players:
• Nucletron Corp.: Pollatz said key company innovations have included: turnkey body-site-specific solutions such as the first commercially available CT/MR compatible Kuske Breast Template; its Oncosmart catheter system (also called “Comfort Catheters); enhanced contouring and margining tools through Oncentra Anatomy Modeling (PC-based) and PLATO BPS Insight (a Unix-based software) for both interstitial and balloon breast brachytherapy; and introduction of new software to facilitate National Cancer Institute-sponsored clinical trials. Nucletron also introduced the first commercially available true real-time image guidance treatment planning system.
• Cytyc Corp.: With its March 2005 acquisition of Proxima and its MammoSite radiation therapy system, Cytyc entered the breast brachytherapy market in a major way. “With MammoSite, the dose is delivered in a standardized fashion,” Sheets said. “There’s no guesswork.” Thanks to approved Medicare reimbursement in 2004, MammoSite has been used to treat more than 8,000 women to date, making it the most widely used form of accelerated partial breast irradiation, market researcher Medtech stated in its 2005 report.
• XOFT Inc.: The company’s most significant innovation is likely its newest: the Axxent Electronic Brachytherapy System, which delivers low-energy X-rays to the lesion bed by way of a disposable miniature (2.2 mm) X-ray tube at the tip of a disposable source wire. The energy is delivered by a portable X-ray afterloader and is comparable in dosage strength to iridium 192. Its biggest advantage is its most obvious, said Marga Ortigas-Wedekind, director of Marketing. The system eliminates the need to handle and store radioactive material, something which the company hopes will open a huge market for the therapy in the outpatient arena. “This is where we think the market is headed,” Ortigas-Wedekind told Outpatient Care Technology. “We hope to capture the market not served by isotope therapy,” she added, noting that of the 21,000 U.S. radiation oncology centers, only about 600 have the capability of using iridium isotopes because shielding is expensive, and the regulations for handling radioactive material are very restrictive and costly. XOFT plans a human use trial later this year.
• Varian BrachyTherapy: According to Dave Hall, marketing manager, the Palo Alto, CA-based company recently developed its own advanced breast template system. Many of the company’s recent innovations have focused on image-guided therapy techniques and conformal dose radiotherapy. Its Varian SmartSeed System includes customized transportable VariSource 200 or GammaMedplus HDR series afterloaders and BrachyVision 3-D treatment planning software. Varian BrachyTherapy afterloaders and treatment planning systems are used in more than 600 clinics worldwide.
• North American Scientific: According to David Stiles, vice president of Sales and Marketing, the Chatsworth, CA-based company has developed a multichannel catheter system with a tiny 12-arm device that expands inside the cavity to deploy seeds. The lengths of each arm can be adjusted to conform to the wall of the lesion bed. Stiles said the company will unveil the device, which will be capable of low-dose temporary brachytherapy and high-dose brachytherapy, at the American Society of Therapeutic Radiology and Oncology (ASTRO) meeting in November. “This new product will offer the best features of afterloader and interstitial HDR with better conformality to the lesion site,” Stiles said. “It will also offer a new option of temporary seeding, which will not require a HDR machine, leaded vaults or the patient to return 10 times in five days for treatment.”
Surge in Popularity
“High-dose brachytherapy is not yet the gold standard in breast cancer therapy, but companies are trying to find a niche,” said Ortigas-Wedekind. And many signs are pointing to a very big niche in a market that is expected to be $578 million by 2008, according to market researcher Bio-Tech Systems.
High-dose brachytherapy has many advantages over whole breast radiation, including fewer side effects, decreased hospitalization, reduced risk of postoperative infections and faster transition to chemotherapy.
“Accelerated partial breast radiation offers the principal benefit of treatment time,” said Hall. “The benefit is to working women who may wish to reduce the duration their radiation treatment, to patients who live far from a radiation oncology center and may not be able to make the daily trips, or be away from home for an extended period, and to those elderly patients for whom multiple trips to even a local radiation oncology center may prove onerous.”
“Why is high-dose breast brachytherapy becoming hot? The results are starting to come in,” added Stiles. Indeed, a series of high-profile clinical studies in recent years, including one by the National Cancer Institute, have helped give greater credence to the technique.
And organizations such as the American Brachytherapy Society (ABS) are beginning to rally behind high-dose breast brachytherapy. “This accelerated treatment approach is presently only offered in select locations,” the group noted on its Web site. “However, the ABS anticipates that this will change over the next few years and become a more widely offered treatment option based on the treatment results, the enthusiasm seen from treated patients, and the interest shown by physicians treating breast cancer.”
That said, the downsides of the technology could be significant. “For radioisotopic brachytherapy, there are regulatory issues regarding radioactive licensure, as well as shielding requirements,” Pollatz said. In addition to networking infrastructure and integration issues, some outpatient facilities are experiencing difficulties in training and retaining qualified staff to perform brachytherapy procedures, treatment planning and quality assurance. The cost of maintaining a system (sources, service contracts, treatment planning contracts) may be prohibitive for low-volume users, he added.
Current guidelines from the American Society for Breast Surgeons and the American Brachytherapy Society state that high-dose brachytherapy should be used in patients older than 45 with discreet disease locations of 2 cm or less and no positive nodes or metastasis. “Even given the guidelines, that pool of candidates for brachytherapy is still rather hefty in size, and in fact, more than half of the women with breast cancer right now would be candidates for brachytherapy,” Ortigas-Wedekind said. Still, she added, only 10 percent of them are actually getting the treatment.
The American Brachytherapy Society found that many women with early stage breast cancer either choose mastectomy or actually refuse external radiation following a lumpectomy for reasons that include long treatment times and inconvenience. “We know from the data that many women who are eligible for breast conserving treatment are still not getting it, and further that many who do get lumpectomies are not getting the follow up course of radiation,” added Hall. “The hope is that by lowering the barrier to radiation treatment, we can see improvement in both the numbers of breast conservation treatments and better compliance with a follow-up course of radiation.”