Will Study Showing Increased Complications Compared to Whole-breast Irradiation Put the Brakes on Brachytherapy?
Many women across the country are receiving brachytherapy before we have any strong randomized data to tell us that it is a good treatment.
—Benjamin D. Smith, MD
In the News focuses on media reports that your patients may have questions about at their next visit. This continuing column will provide summaries of articles in the popular press that may prompt such questions, as well as comments from colleagues in the field.
Older women treated for invasive breast cancer with brachytherapy following lumpectomy were more likely to have complications and subsequent mastectomies compared to women treated with whole-breast irradiation following lumpectomy, according to a retrospective population-based study of more than 92,000 women.
The authors of the study, published in the Journal of the American Medical Association,1 noted that the use of brachytherapy as an alternative to whole-breast irradiation after lumpectomy has increased substantially in recent years, and expressed concern that the number of women “experiencing excess harm associated with brachytherapy may grow proportionally.” But might this study and the coverage it received by consumer and health and medical media put the brakes on brachytherapy for treating breast cancer?
“Our data have caused me to consider the strengths and limitations of brachytherapy in the treatment of breast cancer and to weigh these issues when discussing treatment options with my patients,” Benjamin D. Smith, MD, corresponding author for the JAMA article, said in an interview with The ASCO Post. Dr. Smith is Assistant Professor, Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center in Houston. His coauthors are also from MD Anderson and from the Center for Health and Social Sciences at the University of Chicago.
“Our work helps to highlight some of the potential tradeoffs between brachytherapy and whole-breast irradiation,” Dr. Smith stated, and that information can be discussed with patients in deciding what form of radiation to use following lumpectomy (see sidebar).
Risk of Complications and Subsequent Mastectomies
The study included 92,735 women aged 67 years or older with incident invasive breast cancer identified through the national Medicare data set, which includes all Medicare beneficiaries throughout the United States, the authors noted. Following lumpectomy, 6,952 patients were treated with brachytherapy and 85,783 with whole-breast irradiation.
“This study has almost 7,000 patients treated with brachytherapy, and to my knowledge, this is the largest number of patients treated with brachytherapy in any study in the world’s literature,” Dr. Smith said. “Just the sheer size of this study and its comprehensive nature—including all older Medicare beneficiaries in the U.S. from 2003 to 2007—make our work an important and unique contribution to the literature,” Dr. Smith said.
“Patients were classified as treated with [whole-breast irradiation] vs breast brachytherapy if claims indicating [such] treatment were recorded within 12 months of diagnosis,” the authors stated. Patients were diagnosed between 2003 and 2007, and during that time, the use of brachytherapy among the study population increased from 3.5% to 12.5%.
“Breast brachytherapy was associated with a higher risk of infectious and noninfectious postoperative complications” experienced within 1 year of lumpectomy by 27.6% of patients treated with brachytherapy, compared to 16.9% of patients receiving whole-breast irradiation, the researchers reported. Patients receiving brachytherapy also had a higher 5-year incidence of postradiation complications—25.0% vs 18.8% for patients receiving whole-breast irradiation. These complications included breast pain (experienced by 14.6% of patients receiving brachytherapy vs 11.9% of patients receiving whole-breast irradiation), fat necrosis (8.3% vs 4.1%), and rib fracture (4.5% vs 3.6%). Five-year overall survival was similar—87.7% for patients treated with brachytherapy vs 87.0% for those treated with whole-breast irradiation.
Women treated with brachytherapy had a higher 5-year cumulative incidence of mastectomy (4.0% vs 2.2% in women treated with whole-breast irradiation). “For every 56 women treated with brachytherapy in our cohort, 1 extra mastectomy happened that wouldn’t have happened if all those 56 women had been treated with whole-breast irradiation instead,” Dr. Smith said.
The Medicare data did not indicate why the mastectomies were performed, and the authors noted that cancer recurrence was not confirmed. “It certainly is possible that a mastectomy could be done to manage a severe complication from either brachytherapy or whole-breast radiation,” Dr. Smith noted. “When we excluded patients with any code for any toxicity—and this actually wasn’t in our manuscript, but it was a subsidiary analysis that we conducted—we still found about the same risks of mastectomy in patients with brachytherapy compared to whole-breast irradiation. So I don’t think toxicity was driving this difference, but it is an important limitation of our study, and we can’t really know for sure what the reasons for mastectomy were.”
Suitable vs Unsuitable Candidates
Dr. Smith pointed out that the study included women treated with brachytherapy who would not be considered suitable candidates, according to a consensus statement on partial-breast irradiation published by the American Society for Radiation Oncology (ASTRO) in 2009.2 “I happen to be the first author on that guideline,” noted Dr. Smith, who is Vice Chair of ASTRO’s Clinical Guidelines Committee. The statement “defined patients suitable for brachytherapy as patients age 60 and older with estrogen receptor–positive, stage I breast cancer treated with lumpectomy with negative margins and negative lymph nodes,” Dr. Smith said. “The majority of the patients in our study would have had stage I breast cancer, but some of them could have been patients with higher-stage disease as well.”
Although patients in the study who were treated with brachytherapy were less likely to have axillary lymph node involvement, those who did were at particularly high risk of subsequent mastectomy. The ASTRO consensus statement says “brachytherapy should only be done in the context of a clinical trial if a patient has node-positive breast cancer,” Dr. Smith pointed out. “Having a node-positive breast cancer indicates that there is probably a higher burden of disease in the breast and also that the cancer had to travel to the lymph nodes through the breast tissue itself. So it is likely that it could be a marker for residual breast cancer cells present elsewhere in the breast tissue that would not be encompassed by partial-breast brachytherapy,” he explained.
Awaiting Randomized Trials
“Our results underscore existing controversy over appropriateness of widespread adoption of breast brachytherapy as the sole radiation treatment modality following lumpectomy, because few data are available to quantify benefits and harms of brachytherapy in direct comparison with standard [whole-breast irradiation],” the authors commented. Dr. Smith said “many women across the country are receiving brachytherapy before we have strong randomized data to tell us that it is a good treatment.” High-quality case control studies or matched-pair analyses of patients treated with whole-breast irradiation vs the type of brachytherapy commonly used now are also lacking, he said.
One of the criticisms of the current study cited in the press was that the only form of brachytherapy in use during the study period was a single-catheter device that has largely been replaced by newer catheters and devices.3
“Our study was specifically designed to look at brachytherapy as it was used in the U.S. between 2002 and 2007, but there are other randomized clinical trials that are evaluating different types of partial-breast radiation,” Dr. Smith said. “There’s a large randomized trial in Canada, which is comparing whole-breast to partial-breast irradiation, and in that study the partial-breast irradiation is given with external-beam approaches. A large ongoing study in Italy is looking at intraoperative radiation therapy, which is a type of brachytherapy given at the time of surgery, compared to standard treatments. And other studies are ongoing as well. So several different techniques are being studied in different parts of the world,” he pointed out.
“To address persistent questions,” the authors noted, the ongoing Radiation Oncology Therapy Group (RTOG)/National Surgical Adjuvant Breast and Bowel Project (NSABP) B-39 trial is comparing partial-breast irradiation to whole-breast irradiation. “If patients are randomly assigned to partial-breast irradiation, the physician can choose to treat them with either brachytherapy or external-beam radiation therapy,” Dr. Smith said. “There are some potential technical differences in those two treatments.” Patient accrual began in 2005 and is expected to be completed later this year. ■
Disclosure: Dr. Smith has received research funding from Varian Medical Systems, a maker of equipment for both whole-breast irradiation and brachytherapy.
1. Smith GL, Xu Y, Buchholz TA, et al: Association between treatment with brachytherapy vs whole-breast irradiation and subsequent mastectomy, complications, and survival among older women with invasive breast cancer. JAMA 307:1827-1837, 2012.
2. Smith BD, Arthur DW, Buchholz TA, et al: Accelerated Partial Breast Irradiation Consensus Statement from the American Society for Radiation Oncology (ASTRO). Int J Radiat Oncol Biol Phys 74:987-1001, 2009.
3. Mulcahy N: Breast brachytherapy takes a hit (or not). Medscape Today News. May 1, 2012. Available at www.medscape.com. Accessed May 22, 2012.
“Our study provides critical interim companion data to awaited randomized trials and may help clinicians and patients quantify the risk-benefit ratio of brachytherapy compared with standard therapy,” Benjamin D. Smith, MD, said of a study comparing lumpectomy and either whole-breast irradiation or...
One of the reasons large population-based studies are important is based on the “difference between efficacy—does a treatment work in a highly controlled setting of a phase III randomized clinical trial—and effectiveness—does a treatment work in general practice,” according to Benjamin D. Smith,...