SAN FRANCISCO—Is the glass half full or half empty for the future of accelerated partial breast irradiation (APBI)?
A speaker asked that question during a poster discussion session on radiation oncology here at the Breast Cancer Symposium. During the discussion period, David E. Wazer, MD, Professor and Chief of Radiation Oncology at Tufts University School of Medicine and the Alpert Medical School of Brown University, pointed to some recent, less-than-favorable reports emerging about APBI as compared with whole breast irradiation (WBI). He said the question must now be asked whether accelerated partial breast irradiation off-study is acceptable as an alternative to whole breast irradiation.
One report he cited is a 2012 report based on Medicare data in which balloon catheter brachytherapy was associated with a risk of subsequent mastectomy about two percent higher than with whole breast irradiation, with no difference in survival (Smith et al: JAMA 2012;307:1827-1837). “I have a lot of issues with how that analysis was done, but nonetheless it has raised sufficient questions for a number of investigators in this field,” he said.
The first poster discussed, by Simona Flora Shaitelman, MD, Assistant Professor in the Department of Radiation Oncology at the University of Texas MD Anderson Cancer Center, and colleagues, asked whether a 2009 ASTRO consensus statement (Int J Radiat Oncol Biol Phys 2009; 74:987-1001) had an impact on utilization of radiation oncology therapy (Abstract 54). The consensus statement was based on four published randomized clinical trials, 38 prospective single-arm studies, and expert opinion.
The MD Anderson study was based on data from the American College of Surgeons' National Cancer Database from 2004 to 2010.
Shaitelman reported that use of breast brachytherapy for patients described as “suitable” in the consensus statement had increased but then stabilized around 2008, the year before the statement was published. But over that same period there was a decline in utilization of breast brachytherapy for patients classified as “cautionary” or “unsuitable” in the statement.
“This is reflective of a broader question of where we're at with APBI and brachytherapy,” Wazer commented. “I think we're at a crossroads with this modality, and we have to ask, is this the end of the beginning or the beginning of the end for APBI as a technology for the treatment of breast cancer?”
He acknowledged that the sophistication of brachytherapy applicator technology has improved greatly in the past few years, that prospective studies of APBI have been undertaken, and that there are guidelines for “off study” implementation.
He said the decline in the use of accelerated partial breast irradiation shown in the Shaitelman paper might be due to the toxicity concerns being reported, to alternatives that are evolving in short-course radiotherapy schedules, or to the rise of single-fraction intraoperative radiation therapy. And that is not to mention the alternative of hormonal therapy with no radiotherapy for low-risk patients, he said.
RAPID Interim Results
A study not mentioned by Wazer but relevant to the issue was noted in OT's September 25 issue (http://bit.ly/1dWx0zi?), an article about an interim report from the Randomized Trial of Accelerated Partial Breast Irradiation (RAPID) trial, which showed that cosmetic outcomes were significantly worse and low-grade late toxicities were slightly more prevalent among women who underwent APBI than among those treated with more traditional whole-breast irradiation (WBI).
Outcomes for WBI, APBI Similar at 10 Years
Also noted during the discussion was a study from researchers at Oakland University William Beaumont School of Medicine, a retrospective matched-pair analysis comparing locoregional recurrence, distant metastasis, and survival between patients undergoing whole breast irradiation vs. those undergoing APBI using interstitial catheter or balloon-based brachytherapy (Abstract 55). At a median follow-up of 10 years, there were no differences, the team reported.
First author Jessica Wobb, MD, a resident in radiation oncology, reported that 3,009 patients were treated with breast-conserving therapy at William Beaumont between 1980 and 2012, with 2,528 patients receiving WBI and 481 patients receiving APBI (interstitial or balloon-based brachytherapy).
A matched-pair analysis was performed with 548 patients (274 in each study arm), matching them according to age, T stage, and estrogen receptor status. Mean follow-up for both groups was approximately eight years.
At 10 years there was no difference in ipsilateral recurrence (4% in each study arm), regional recurrence (1% in each arm), distant metastases (3% for WBI vs. 6% for APBI), disease-free survival (93% vs. 91%, respectively), or contralateral breast failure (9% vs. 3%, respectively).
In addition, 10-year cause-specific survival was similar (94% vs. 93%, respectively) as was overall survival (82% vs. 75%).
And long-term cosmesis was good to excellent in 94 percent of patients with WBI and 95 percent with APBI.
“We've known for a long time that in breast-conserving surgery, when we do lumpectomy and whole breast irradiation and patients recur, they recur almost invariably at or near the initial tumor site,” Wazer said. “Elsewhere, failure is a rare event, and likely, in most cases, represents a new primary tumor. So we have been asking the question for more than two decades: Are there circumstances in which we can avoid whole breast irradiation?”
In the absence of randomized prospective trial data as a guide, decisions must be made base on the accumulation of institutional data, Wazer said. “And the institution that has contributed the most to our knowledge base is the group at William Beaumont Hospital.”
The study found no difference between the two modalities in locoregional recurrence, distant metastasis, and survival.
But Wazer pointed to limitations of the study: “In a matched pair analysis, we have to ask, how good is the match?” He said he thought the study's two groups in general were fairly well matched, although the WBI group had slightly larger tumors and slightly more node-positive patients.
“But perhaps the most unsettling aspect is that there was more hormonal therapy in the whole breast irradiation group—68 percent vs. 54 percent for the accelerated therapy group,” he said. “This reflects an imbalance of prognostic factors between the two cohorts, as well as the impact of hormonal therapy on local and regional control.”
He also pointed out that grade, percentage of triple-negative phenotype, HER2 status, and lymphatic vascular invasion were missing from this retrospective analysis, but he allowed that these would be difficult to determine from a retrospective study.
The symposium is co-sponsored by the American Society of Breast Disease, American Society of Breast Surgeons, American Society of Clinical Oncology, American Society for Radiation Oncology, National Consortium of Breast Centers, and the Society of Surgical Oncology.