Analysis Provides Reassurance on Radiation's Impact on Lymphedema Risk

Susan McCloskey, MD, MSHS

A new analysis of the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-32 trial presented at the ASTRO 56th Annual Meeting offers substantial evidence that treatment with radiation therapy does not increase the incidence of lymphedema in patients with node-negative breast cancer.

“These results provide much needed reassurance to breast cancer patients regarding the impact of radiation therapy on lymphedema risk,” lead study author Susan McCloskey, MD, MSHS, assistant professor of radiation oncology at The David Geffen School of Medicine at University of California, Los Angeles, said in a statement. “The study findings argue convincingly that radiation therapy to the Level 1 axilla, considered unavoidable ‘collateral damage’ when radiating the whole breast, does not contribute to lymphedema risk beyond surgery.”

In the original NSABP B-32 study, 5611 women with clinically node-negative breast cancer were randomized to sentinel node biopsy (SNB) or SNB + axillary lymph node dissection (ALND). The goal of the study was to determine if SNB was as effective as ALND with fewer side effects. The results showed that the SNB+ALND combination was associated with a significantly greater risk of lymphedema versus SNB alone.

Importantly, for the secondary analysis presented at ASTRO, the trial also provided the opportunity to evaluate the impact of radiation therapy (RT) on lymphedema risk, a significant concern for women undergoing breast cancer treatment. Among the 3916 women in the trial with lymphedema assessments, including 1936 randomly assigned to SNB+ALND and 1980 randomly assigned to SNB, 82.2% (n = 3220) received RT and 17.2% (n = 674) did not. The status was unknown for 0.6% (n = 22) of the patients.

Measures of lymphedema were collected at baseline prior to RT and every 6 months during the 3-year follow-up period. Lymphedema was assessed both by standardized arm measurements by clinicians (objective lymphedema) and via questionnaires completed by patients (subjective lymphedema). Objective lymphedema (clinician measured) was defined as relative arm volume difference (RAVD) >10%, and was determined by a water displacement method. Subjective lymphedema was defined as patient-reported ipsilateral swelling that was “somewhat,” “quite” or “very” bothersome.

Overall, researchers found no greater risk of lymphedema among women receiving RT versus those who did not receive RT. There was no significant difference in standardized arm measurements and no significant difference in patient reports of bothersome arm swelling during 3 years of follow up, suggesting that radiation does not contribute to lymphedema risk beyond surgery over time.

A subgroup analysis at 36 months of follow-up found that among patients in the SNB+ALND group who also received RT, RAVD >10% was detected in 12.4% of women, and 7.4% reported bothersome swelling. In patients who did not receive RT, 16.7% of patients who underwent SNB+ALND had a RAVD >10%, and 8.8% were bothered by swelling.

In the SNB-only group, 7.4% of patients who received RT had RAVD >10%, and 3.2% reported bothersome swelling, versus 4.5% and 4.8%, respectively, among those in this cohort who did not have RT.

“Several recent analyses have suggested that mastectomy rates are on the rise in the United States, and some have suggested that a desire to avoid radiation and its associated toxicities is a contributing factor,” McCloskey said. “This analysis suggests that lymphedema concerns should not be an impediment to women choosing breast conservation and radiation therapy. “

McCloskey SA, Bandos H, JulianT, et al. The Impact of Radiation Therapy on Lymphedema Risk and the Agreement Between Subjective and Objective Lymphedema Measures. Presented at: 2014 ASTRO Annual Meeting; September 14-17, 2014; San Francisco, CA. Presentation Number: 1463.