BB&T Contributing Writer
PHOENIX — Cupcakes were served at this year’s annual meeting of the American Society of Breast Surgeons (Columbia, Maryland). The reason: to celebrate the “5th-year birthday” of the first commercially widespread accelerated partial breast irradiation (APBI) product — the MammoSite Balloon — manufactured by Cytyc (Marlborough, Massachusetts).
Prior to introduction of the MammoSite, irradiating only the tumor bed of the lumpectomy cavity instead of the entire breast was considered “experimental”; now APBI is considered standard-of-care following lumpectomy and there are several new and exciting ways to do it, many of them featured and discussed at the conference.
While post-lumpectomy radiation had initially required irradiation of the entire breast with an external beam for 30 days, several companies have developed an approach that targets the tumor site from inside the breast and reduces the 30-day program to five-seven days, with research investigating even less.
For eligible women, breast brachytherapy, a form of APBI, typically involves two treatments per day for only five days, targeting the portion of the breast at highest risk of recurrence.
Early data using a variety of methods and forms of energy were presented on novel approaches at reducing the length of time to deliver a lethal dose of energy to potential cancer cells remaining in the lumpectomy cavity.
According to the American Cancer Society (Atlanta, Georgia), there were 276,000 new cases of breast cancer diagnosed in the U.S. in 2006. Of these, only about 50% of those who would qualify for a lumpectomy elected to have a lumpectomy plus radiation.
Those having a mastectomy instead of a lumpectomy typically fell into one of three groups: 1) Those who have large tumors, many tumors or diffuse cancer and are not candidates; 2) those who fear recurrence (in spite of the fact that large bodies of studies have proven lumpectomy plus radiation has a lower recurrence rate than mastectomy alone); and 3) those who refuse or are unable to attend the required radiation therapy that lasts from five to 30 days following the lumpectomy.
Those who do not have access to a facility that provides APBI, often elect mastectomy in order to avoid the inconvenience and cost of staying far away from their home for a period of time.
Shortening post-op time
In order to be able to provide more patients with the option of lumpectomy, technologies have been developed to shorten the time it takes to deliver the post-op radiation or increase the number of available sites who can offer the therapy. The first commercially viable product was the Mammosite balloon which is inserted into the lumpectomy space after surgery and has isotopes placed into it twice a day for only five to seven days. Data has demonstrated equal or superior recurrence rates when compared to whole breast irradiation.
In an attempt to make the course of therapy even shorter, Michelle Wallace, MD, William Beaumont Hospital (Royal Oak, Michigan) presented her research on using a two-day dose schedule for the Mammosite balloon. She found that “preliminary results indicate that acute and chronic toxicities are of similar rates as those treated on the five-day dose schedule. Patient accrual and follow-up of current patients will continue.”
Being able to reduce the therapy from five to two days should attract more patients, but not all lumpectomy patients are candidates for brachytherapy balloons.
If the tumor bed is close to the skin or the chest wall, or if the patient has small breasts, the balloon delivers radiation too close to surrounding healthy tissues. Several novel methods have been developed to expand the number of patients who could be eligible for brachytherapy (see Table 6).
Another way to examine why only about half of the potential patients eligible for lumpectomy with radiation are actually receiving this patient-friendly regimen is to look at the accessibility of this new technology.
There are 2,100 radiation oncology facilities in the U.S., with only one-third of them having access to radioisotopes. And of those almost 700 sites, only 400-500 of them treat breast cancer. So a key goal for expanding the use of APBI is to provide all 2100 radiation oncology centers with at least one method for APBI.
Eliminating the bunker
Although each new technology has its own distinct advantage, one issue that may accelerate adoption is whether a leaded room, or bunker, is required. The non-radioisotope technologies such as those from Intraop Medical (Sunnyvale, California) or Xoft (Fremont, California) would not require a leaded room for delivery, eliminating expense, construction of a bunker, and opening up new avenues for placement. To that same end, research is being performed to determine if other non-radiation therapies will kill all cancer cells as effectively as radiation.
In a poster presentation at the conference, Kambiz Dowlatshahi, MD, of Rush University Medical Center (Chicago), hypothesized that “a 1 cm shell of breast tissue surrounding the site of primary carcinoma may be effectively treated with a hot balloon inserted into the lumpectomy site intraoperatively.” Using goat mammary glands as models, he found that “preliminary microscopic observations indicate tissue necrosis with increasing time.”
Previous research performed by Suzanne Klimberg, MD, of the University of Arkansas for Medical Sciences (Little Rock), has demonstrated that RF energy can be used to kill a 4 mm zone surrounding the lumpectomy cavity — again, without the use of a radioisotope.
These technologies that eliminate the requirement for lead-shielded rooms may provide for more available treatment centers and better accessibility for patients, though data to determine that the recurrence rate is equivalent to that of radiation therapy needs to be ascertained.
Dose-shaping and cages
Second-generation devices for APBI have recently entered the market, offering options for women who desire breast-conserving surgery.
BioLucent’s SAVI applicator is a single-entry, multi-catheter design that looks like a cage once it is deployed and allows the radioactive strands to be placed in a customized fashion, avoiding any potential hot spots and contouring the dose of radiation away from healthy tissue, such as the skin surface or chest wall. This ability is called dose-shaping and is utilized by several of the newer technologies as an advantage over the first generation devices where homogenous radiation may get too close to healthy tissue, causing a “hot spot.”
Dose-shaping may allow more women to have APBI because it is easier to steer the dose away from a close chest wall or skin in those women who might not have been a candidate for balloon brachytherapy.
Similarly, North American Scientific (Chatsworth, California) has developed a multi-stranded cage-type device that can keep toxic doses of radiation away from healthy tissue. Their design is a cage-within-a-cage so that the outer struts maintain a distance between the cavity and the inner strands that delivers the energy.
In addition to their high dose brachytherapy, they also offer a similar low dose system that allows insertion of the cage at the beginning of treatment and then extraction at the end of the five days without the twice-daily visits for high dose radiation. Although much more patient friendly, there is no data on low dose radiation of the breast and long term studies will be required for adoption. SenoRx (Los Altos, California) is planning on introducing a multi-lumen brachytherapy balloon that can deliver any type of energy source later this year following FDA approval.
Xoft uses a miniature X-ray source inside a balloon, and because it is not radiation, it has the potential to be placed in more locations and, hopefully, will offer more patients access to breast-conserving surgery and possibly avoid mastectomy.
The Mobetron from Intraop is a mobile electron linear accelerator designed to deliver electron radiation intra-operatively to the tumor prior to excision, theoretically killing all cancer cells before the tumor is removed, eliminating the chance of leaving any cancer cells behind in the cavity. Since it uses X-rays instead of a radioisotope, it does not require a bunker, and if the long-term studies prove out the theory, no follow-up radiation would be required — only the high-dose during surgery.
Similarly, the Intrabeam from Carl Zeiss (Jena, Germany) could be a one-time-only radiation done immediately post-op if clinical data supports its efficacy.
Most importantly, all these new technologies allow for more women to be able to have breast conserving cancer surgery without compromising their risk for future recurrence.