Hypofractionated regional nodal irradiation for breast cancer: examining the data and potential for future studies

Limited data are available examining the role of hypofractionated radiation schedules in the management of women requiring regional nodal irradiation (RNI). The purpose of this review is to examine the available literature for the efficacy (where available) and toxicity of hypofractionated radiation schedules in breast cancer with RNI limited to the axilla and supraclavicular regions. Multiple randomized and prospective studies have documented the safety and efficacy of hypofractionated schedules delivering whole breast irradiation (WBI) alone. Subsets from these randomized trials and smaller prospective/single-institution studies have documented the feasibility of hypofractionated RNI but the limited numbers prevent definitive conclusions and limited efficacy data are available. With regard to possible toxicity affecting organs at risk with RNI, key structures include the breast, skin, heart, lungs, axilla (lymphedema), and brachial plexus. Based on data from several randomized trials, hypofractionated radiation is not associated with significant changes in breast toxicity/cosmesis or cardiac toxicity; the addition of hypofractionated RNI would not be expected to change the rates of breast or cardiac toxicity. While RNI has been shown to increase rates of pulmonary toxicity, hypofractionated RNI has not been associated with more frequent pulmonary complications than standard RNI. Moving forward, future studies will have to evaluate for increased lung toxicity. With regard to lymphedema, data from randomized hypofractionated WBI trials failed to demonstrate an increase in lymphedema and smaller studies utilizing hypofractionated RNI have failed to as well. Data from head and neck cancer as well as hypofractionated breast radiation with RNI have failed to demonstrate an increase in brachial plexopathy with the exception of older trials that used much larger dose per fraction (>4 Gy/fraction) schedules. At this time, published data support the feasibility of hypofractionated RNI and the need for a prospective randomized trial addressing clinical outcomes and toxicity of hypofractionated RNI compared with standard fractionation RNI.