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
(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.