Breast Brachytherapy Takes a Hit (or Not)

It's the Old Technology, Says Defender

Nick Mulcahy

May 01, 2012

May 1, 2012 — Among older women treated with lumpectomy, breast brachytherapy is associated with more complications than whole-breast irradiation, according to a new retrospective observational study.

Brachytherapy is also associated with a decreased likelihood of long-term breast preservation, but there is no difference in overall survival, according to the study findings, which used Medicare claims data and are published in the May 2 issue of JAMA.

The findings "prompt caution over widespread application of breast brachytherapy" outside of studies, say senior author Benjamin Smith, MD, from the University of Texas M.D. Anderson Cancer Center in Houston, and colleagues.

However, a critic of the study has suggested that these findings are largely irrelevant to current practice.

"It's a study of older technology that has been subsequently improved upon," said Robert Kuske, MD, who is medical director of Arizona Breast Cancer Specialists in Scottsdale. He explained that during the study period, 2003 to 2007, there was only 1 form of breast brachytherapy in use — the single-catheter MammoSite "balloon," which was approved by the US Food and Drug Administration in 2002.

"There has been a mass movement away from this single-channel brachytherapy device," he told Medscape Medical News in an interview.

Dr. Kuske predicted that by the end of 2012, less than 20% of all breast brachytherapy will be performed with this dated method. It has largely been replaced by a number of newer catheters and devices. However, all patients in this study were treated with the older technology, he pointed out.

He added that the study period means that radiation oncologists "were just going up the learning curve" in acquiring their breast brachytherapy skills.

It's an unfair study.

"It's an unfair study because nobody would criticize open-heart surgery today based on complication rates in the first few years after open-heart surgery was introduced," Dr. Kuske explained.

Dr. Smith acknowledged that clinical practice has changed since the final year of the study. "Since 2007, newer brachytherapy catheters have been introduced and are now commonly used," Dr. Smith told Medscape Medical News in an email, adding that "follow-up remains short" with the newer catheters.

He suggested that the impact of this change is not currently knowable.

"There are important similarities and differences between newer catheters and the catheter most commonly used from 2003 to 2007. How these similarities and differences will ultimately impact the effectiveness and side-effect profile of brachytherapy is not entirely known. Further research is needed to evaluate this," he said.

Dr. Kuske has another major objection to the study. It might damage enrollment efforts in an ongoing major clinical trial — the Radiation Therapy Oncology Group (RTOG) 0413 and the National Surgical Adjuvant Breast Project (NSABP) B-39, which compares whole-breast irradiation with partial-breast irradiation.

"Our fear is that the negative publicity resulting from this flawed study will prevent us from completing the all-important randomized phase 3 trial," said Dr. Kuske, who is one of that trial's investigators.

However Dr. Smith and colleagues do not consider this possibility, saying that trial accrual is "likely completing in 2012."

A radiation oncologist not involved with the study said that the findings need to be interpreted carefully.

"This study provides an association, not a causal link, between brachytherapy and these complications," said Jona Hattangadi, MD, from the Harvard Radiation Oncology Program in Boston, Massachusetts, citing a limitation of observational studies, which is acknowledged by the authors.

In an email to Medscape Medical News, Dr. Hattangadi also said: "We won't know for sure whether there are higher complications after this treatment, and why this is, until we have long-term randomized data from the RTOG/NSABP trial."

Findings and Objections

The study authors highlight the advantages of partial-breast irradiation with brachytherapy. Compared with whole-breast irradiation, "brachytherapy irradiates less breast tissue and requires a much shorter course of treatment," write Dr. Smith and colleagues. They are nonetheless concerned that the use of breast brachytherapy "has increased substantially," despite a lack of randomized trial data. Currently, an estimated 10% of all older women with breast cancer are treated with brachytherapy.

While clinicians wait for long-term data, an analysis comparing the 2 methods and outcomes is needed, the authors argue.

In Medicare claims data from 2003 to 2007, the authors found that, among American women 67 years and older with invasive breast cancer who were treated with lumpectomy, 6952 patients were also treated with brachytherapy and 85,783 with whole-breast irradiation.

The 5-year incidence of subsequent mastectomy was higher in women treated with brachytherapy than in those treated with whole-breast irradiation (3.95% vs 2.18%; < .001), and persisted after multivariate adjustment (hazard ratio [HR], 2.19; < .001), the authors report.

Furthermore, at 5 years, an absolute 1.77% (95% confidence interval, 1.30% to 2.24%) excess mastectomy risk in patients treated with brachytherapy, compared with whole-breast irradiation, means that for every 56 women treated with breast brachytherapy, 1 woman undergoes unnecessary mastectomy, the authors note.

Dr. Kuske argued that this 1.7% difference might be statistically significant but is not clinically meaningful.

He suggested that a likely explanation for this increase in mastectomies is a now-corrected problem with the older breast brachytherapy technology, which resulted in the radiation dose sometimes being applied too close to the outer skin of the breast.

"Skin damage and wound-healing complications probably account for the 1.7% difference, not tumor recurrence," he said, referring to one of the oft-stated concerns about only irradiating a portion of a breast with cancer.

The study authors acknowledge that the outcome of subsequent mastectomy could have been a marker for treatment-related complications, but they also say that it could have been related to local tumor recurrence. "Additional studies with detailed pathologic information regarding patterns of failure are needed," they write.

They also found that brachytherapy was associated with more frequent postoperative (within 1 year) infectious complications (16.20% vs 10.33%; < .001; adjusted odds ratio [OR], 1.76) and noninfectious complications (16.25% vs 9.00%; < .001; adjusted OR, 2.03).

Dr. Kuske said that these differences, too, were statistically but not clinically significant.

Overall survival at 5 years was similar between the groups; it was 87.66% in patients treated with brachytherapy and 87.04% in patients treated with whole-breast irradiation (adjusted HR, 0.94; = .26).

This study was supported in part by grants from the National Cancer Institute and by a philanthropic gift from Ann Cazalot and Clarence Cazalot. Dr. Smith reports receiving research support from Varian Medical Systems. Dr. Kuske reports being a paid lecturer for Cianna and Nucletron. Dr. Hattangadi has disclosed no relevant financial relationships.

JAMA. 2012;307:1827-1837. Abstract

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