TRENDS IN RESEARCH AND TRIAL UPDATES FOR BREAST CANCER DETECTION AND TREATMENT IMPLICATIONS FOR SURGEONS

Role of Accelerated Partial-Breast Radiation Therapy on Prognosis and Quality of Life in Breast Cancer

The use of accelerated partial-breast irradiation (PBI), delivery of high-dose/fraction radiation to the lumpectomy cavity plus appropriate margins, is one method that may allow for greater utility of breast-conserving therapy (BCT) as well as shorter treatment duration and reduced toxicity in appropriately selected patients with early-stage breast cancer, said Frank A. Vicini, MD, William Beaumont Hospital, Royal Oak, Michigan, in a symposium moderated by Program Chairs Anthony Lucci, Jr., MD, and V. Suzanne Klimberg, MD. According to Dr. Vicini, the scientific rationale for the use of PBI after lumpectomy includes the potential for reducing the risk of recurrence in the tumor bed, where 80% to 90% of recurrences occur (Table 1).

Low-Dose and High-Dose Brachytherapy
In the early 1990s, Dr. Vicini’s group began a study of post-BCT PBI treatment, using low-dose rate and high-dose rate brachytherapy methods. Patients included those who had undergone BCT for infiltrating ductal carcinoma < 3 cm, had final margins of >2 mm, were sentinel node
biopsy negative, and had no residual mammographic calcifications. Brachytherapy catheters were placed around the lumpectomy cavity at the time of lumpectomy. Within 8 weeks, small radioactive sources were placed into the catheters, with patients receiving 5000 cGy over 96 hours on an inpatient basis. The high-dose brachytherapy protocol, initiated 2 years later, involved a similar technique, but entailed 3200 cGy (400 cGy x 8 in 4 days) administered on an outpatient basis. Dr. Vicini’s group also participated in the Radiation Therapy Oncology Group (RTOG) trial (Kuske et al), for which accrual was completed in May 2000.

As of December 2001, Vicini and colleagues had treated 197 women with the PBI brachytherapy method, with 120 receiving the low-dose regimen. After a median follow-up of over 4 years (5.2 yrs low dose; 2.5 yrs high dose), the results show no recurrences in the tumor bed region, a low rate of recurrence outside the tumor bed (comparable to that observed with or without postsurgical radiation therapy), and high overall survival rates. In addition, according to Harvard criteria, cosmetic results have been excellent or good in 90% (low dose) to 99% (high dose) of patients. Finally, according to RTOG/European Organisation for Research and Treatment of Cancer criteria, toxicity has been minimal, with almost no fat necrosis (1%) or telangiectasis (6%) in the high-dose group.

In addition, Vicini and colleagues compared the outcome of each patient treated by PBI brachytherapy with that of a patient treated by conventional external-beam radiation therapy. Patients were matched for age, disease criteria, and prognostic factors. “It appears that outcomes for those receiving PBI brachytherapy are comparable to those undergoing conventional external-beam radiation therapy,” Dr. Vicini said. According to Dr. Vicini, several other U.S. and international researchers have reported similar findings using PBI high-dose brachytherapy
regimens.

Other Accelerated Partial-Breast Irradiation Methods
In addition to the use of brachytherapy regimens, several new PBI techniques are showing promise. One such technique, use of a MammoSite balloon catheter, involves placement of an inflatable balloon in the lumpectomy cavity at the time of surgery. The balloon is connected to a standard remote afterloading unit, a small radiation source is delivered to the center of the balloon, delivering a tumoricidal dose approximately 1 cm from the balloon surface. Vicini’s group participated in one study in which 43 patients undergoing BCT received 3400 cGy (340 cGy x 10) over 5 days. U.S. Food and Drug Administration approval is currently being awaited for this method.

Also under study are PBI external-beam radiation therapy regimens. Initial data of PBI using intraoperative single-fraction external-beam radiation techniques (Veronesi et al; Vaidya et al) have been promising, and phase III trials are underway. In addition, use of 3D conformal external-beam radiation techniques appears to allow a tight conformal dose targeted to the lumpectomy cavity. Preliminary data by Formenti et al and William Beaumont Hospital researchers have been encouraging, and phase II studies are being initiated.

In closing, Dr. Vicini noted that these and other promising PBI methods are under further study, and may offer the potential for increased utilization of BCT, reduced toxicity, and improved cosmetic results for select women undergoing surgery for early-stage breast cancer.