By Rebecca Blinstrub, MSN, FNP-BC, Loyola University Medical Center
After surgery, controlling locoregional breast cancer with radiotherapy is a key step for disease control. Moderate hypofractionation has become an established standard of care in the management of localized breast cancer, reflecting its efficacy in delivering radiotherapy over fewer, larger doses. Recent data suggests that this approach, particularly when applied to regional nodal irradiation (RNI), maintains comparable oncologic and cosmetic outcomes to conventional fractionation schedules, while providing more convenient and shorter treatment times. However, the dearth of long-term efficacy and safety outcomes, and uncertainty about the risk of lymphedema (LA) after hypofractionation has limited its widespread acceptance in clinical practice.
The Phase II HeNRIetta study, presented yesterday by Alfredo I. Urdaneta, MD, was conducted to determine the incidence of moderate-to-severe LA, defined as ≥10% increase in arm circumference compared to the contralateral arm in patients undergoing hypofractionated RNI. A well-established hypofractionation regimen with standardized treatment volumes for node-positive breast cancer was used in women who had undergone definitive surgical resection, including lumpectomy (Lp), mastectomy without reconstruction (M-R), or mastectomy with reconstruction (M+R). The population included both sentinel lymph node (SLN) and axillary lymph node (ALN) dissection cohorts.
The primary objective was to establish the rate of moderate or marked lymphedema at three years post-treatment, measured every six months. Between September 2015 and July 2021, 134 women were enrolled, with 84 undergoing SLN dissection and 50 ALN dissection. The RNI was administered at 42.56 Gy in 16 daily fractions, excluding the dissected axilla from target volumes in ALN patients. The study used a non-inferiority margin of ±7% to compare lymphedema rates with recent historical controls, which were estimated at 6% for SLN and 10% for ALN.
Lymphedema rates at three years were 13.1% in the SLN cohort and 18% in the ALN cohort, which, despite being relatively low, did not meet the non-inferiority criteria set by the protocol. LA was predominantly grade 1, which only minimally impacted instrumental activities of daily living and no grade 3 lymphedema, which would significantly affect self-care activities, was reported. Cosmetic outcomes were favorable, with 85.5% of patients in the lumpectomy group and 75.9% in the mastectomy with reconstruction group achieving excellent or good results at the 36-month follow-up.
Although moderate hypofractionation did not meet the predefined non-inferiority criteria for lymphedema rates, the low incidence and relatively mild severity of lymphedema suggest that moderate hypofractionation remains a viable option for RNI. Given the benefits of moderate hypofractionation in terms of reduced treatment duration and patient convenience, these findings support its broader adoption. Moderate hypofractionation’s overall safety profile, particularly the relatively low rates and mild severity of lymphedema and favorable cosmetic outcomes, may support its use in the treatment of node-positive breast cancer. These results contribute valuable insights into the safety profile of moderate hypofractionation and suggest that concerns about LA should not deter its use in clinical practice.
Abstract 101, Long Term Rates of Lymphedema in Hypofractionated Nodal Regional Irradiation for Women with Breast Cancer: A Phase 2 Clinical Trial – “HeNRIetta” was presented during the SS 01 Breast Cancer 1: Clinical Trials session of ASTRO’s 66th Annual Meeting.
