Hypofractionation in the era of modulated radiotherapy (RT)

The use of radiation therapy (RT) as a component of breast-conserving therapy (BCT) has been shown to reduce the risk of local-regional recurrence and improve overall survival. As has been the common practice in the United States and Continental Europe, the majority of studies that demonstrated these benefits utilized daily radiation doses ranging from 1.8 to 2.0 Gray (Gy) per day given for approximately 5 weeks. However, due to geographic limitations, patient preferences, and financial considerations, there have been continued attempts to evaluate the efficacy and safety of abbreviated or hypofractionated courses of whole-breast radiation. Two key factors in these attempts have been: 1) advances in radiobiology allowing for a more precise estimation of equivalent dosing, and 2) advances in the delivery of RT (‘modulation’) that have resulted in substantially improved dose homogeneity in the target volume. Hypofractionated schedules have been compared to conventional radiation courses in several randomized controlled trials, as well as many prospective and retrospective experiences. These studies, now with about 10 years of follow-up, have demonstrated equivalent rates of local-regional recurrence, disease-free survival, and overall survival. The rates of toxicity have generally not been increased with hypofractionated regimens; however, certain toxicities may take decades to manifest. The generalizability of these results is unclear, as the majority of patients in the trials were elderly with early-stage hormone-receptor positive disease. Nevertheless, there is now sufficient evidence to recommend hypofractionated whole breast RT for a substantial percentage of patients.