KEY POINTS
- DBCG Skagen Trial 1 was a phase III noninferiority trial conducted across 17 centres, comparing conventional 50 Gy in 25 fractions with hypofractionated 40 Gy in 15 fractions for patients with high-risk breast cancer requiring locoregional radiotherapy.
- The primary endpoint was arm lymphedema. Noninferiority required the three-year incidence with 40 Gy to remain within an absolute 5-percentage-point margin, assuming a 10% rate after conventional fractionation.
- Between 2015 and 2021, 2,963 patients consented and 2,908 formed the intention-to-treat cohort: 1,444 received 50 Gy and 1,464 received 40 Gy. Median age was 57 years, with a range of 23–86 years.
- At a median follow-up of 4.1 years, three-year arm-lymphedema incidence was 9.4% with 50 Gy versus 8.0% with 40 Gy. The odds ratio was 0.84 (95% CI 0.62–1.14; p=0.27), comfortably within the prespecified noninferiority margin.
- With median cancer-outcome follow-up of 5.25 years, locoregional recurrence was similar between groups (HR 0.96, 95% CI 0.62–1.51). Distant recurrence was also comparable (HR 1.10, 95% CI 0.89–1.37).
- Breast cancer mortality did not differ significantly (HR 1.25, 95% CI 0.93–1.66), nor did all-cause mortality (HR 1.08, 95% CI 0.85–1.36). No adverse disease-control signal was identified with the shorter course.
CLINICAL TAKEAWAY
Forty Gy in 15 fractions can replace 50 Gy in 25 fractions for locoregional irradiation of high-risk breast cancer without increasing arm lymphedema or compromising reported cancer outcomes. This is strong phase III evidence and should reduce continued reliance on five-week treatment where conventional fractionation remains routine.