NEW ORLEANSBrachytherapy as the sole method of radiation treatment for patients undergoing breast-conserving therapy provides excellent local control, a cosmetic outcome comparable to external beam radiation therapy, and a low complication rate, according to several speakers at the American Society of Breast Disease meeting.
Robert R. Kuske, MD, and John S. Bolton, MD, described a study done at their institution, Ochsner Medical Foundation, that validated the use of this form of therapy in patients with segmental mastectomy for early-stage breast cancer.
At a median follow-up of 6½ years, the method appears comparable in every way to external beam radiotherapy, they reported. Dr. Kuske is chairman of radiation oncology and Dr. Bolton is staff surgeon at Ochsner.
Dr. Bolton said the advantage of brachytherapy is that it facilitates breast-conserving surgery. While three fourths of his patients are eligible for breast-conserving surgery, it is vastly underutilized because of the inconvenience and duration of the radiotherapy schedule, he said.
Brachytherapy markedly shortens the treatment time from 6 weeks to less than 1 week, without sacrificing any benefits in terms of preventing local recurrences, he said.
The Ochsner study was a prospective phase I/II study of 50 patients with carcinoma in situ, T1, T2, and N0-1 breast cancer who underwent segmental mastectomy. Tumors were less than 4 cm (mean, 1.4 cm) and patients had fewer than four positive axillary nodes. Among the 50 patients, there were 5 in situ tumors and 45 invasive (T1, T2) tumors; 7 tumors had an extensive intraductal component. Margins were negative (no ink on tumor) in all patients.
Treatment consisted of brachytherapy to a generous field around the segmental mastectomy site. Irradiation was either by a continuous low-dose-rate implant delivering 4,500 cGy over 4 days or a fractionated high-dose-rate implant of 3,200 cGy over 4 days in eight fractions.
Twenty-three implants were placed with the cavity open at the time of initial excision or at re-excision, and 28 were placed with the wound closed, mostly at axillary dissection. The median number of catheters was 15 (see drawing ). Tamoxifen(Drug information on tamoxifen) (Nolvadex) and/or chemotherapy was begun 2 to 6 weeks after catheter removal.
100% Local Control
No patient has developed a local recurrence at a median of 6½ years follow-up. Four patients developed regional nodal recurrence, and four developed distant metastatic disease. No significant cosmetic differences have been noted between patients and a matched control group having external beam radiotherapy.
Two patients developed grade 3 radiation therapy complications, consisting of fat necrosis within the radiation field requiring surgical debridement. One of these patients had a co-existing mixed connective tissue disorder, and the second had a high-dose-rate implant with suboptimal dosimetry delivering excessive central radiation, Dr. Bolton said.
Five patients had marked skin erythema over the target volume, and 20 had moderate to marked transient erythema at the skin entry/exit sites. Two had localized areas of moist desquamation. Twenty-four patients had one or more grade 2-3 late toxicities, especially fat necrosis and telangiectasia.
The 6½-year results of this single-institution pilot trial demonstrate tumor control within the vicinity of the tumor excision site (the most common site of local failure after brachytherapy) that compares favorably to published results with external beam radiotherapy, Dr. Kuske said. Remote relapses typically occur after 5 years, so longer follow-up will be needed.
He conceded that not all studies have produced such good results. However, those studies used small implants, achieved less surgical clearance, and had poor quality control, Dr. Kuske said. Risk of recurrence can be further reduced by intensifying treatment to the tissue at greatest risk for subclinical disease and by properly selecting patients, he noted.
The reproducibility of the Ochsner trial is being tested through RTOG 95-17, which opened in 1997. This phase II multi-institutional study will address quality control, toxicity, cosmesis, and tumor control. More than 80 patients have been accrued to this national study.
Frank Vicini, MD, clinical associate professor of radiation oncology, William Beaumont Hospital, Royal Oak, Michigan, also reported on his experience with brachytherapy as the sole radiation treatment after lumpectomy in 120 patients.
Dr. Vicini initiates the implant either during re-excision/axillary dissection or with a closed cavity. The closed cavity technique applies virtual 3D imagery to create a skin surface grid to guide catheter placement. In all procedures, he uses a template to give fixed positions at catheter entry points. This improves the quality of the implant by standardizing the delivered doses of radiation. The 120 patients received 5,000 cGy over 96 hours (the low-dose rate) or 3,200 cGy in 8 fractions over 4 days (high-dose rate).
Dr. Vicini said that his patient population was a highly selected group. All had small tumors (median, 11 mm); more than 2 mm negative margins; and well or moderately differentiated tumors. Most patients were postmenopausal, ER positive, and node negative. Half received adjuvant tamoxifen, and only 10% received systemic chemotherapy.
After a mean follow-up of 48 months for the low-dose-rate patients and 23 months for the high-dose-rate patients, there have been no local, regional, or distant failures. The cosmetic results are good to excellent in more than 85% of patients, Dr. Vicini reported.
These results appear quite excellent, but skeptics might suggest they are due to patient selection bias or short follow-up, he said. To examine these issues, his study compared the 120 brachytherapy patients to 120 well-matched controls from his external beam radiotherapy database.
The comparison at 5-year follow-up found no significant difference in rates of local, regional, or distant failure. There were no such failures in the brachytherapy group vs three local failures and five distant failures in the external beam radiotherapy group.