Hypo- Versus Standard Fractionated Locoregional Radiotherapy of Patients With High-Risk Breast Cancer in the Randomized Phase III Trial: The Danish Breast Cancer Group Skagen Trial 1
In brief
Short-course 40 Gy radiotherapy causes lymphedema in 8% of patients, comparable to 9.4% with standard 50
In a phase III trial of 2,908 high-risk breast-cancer patients, the 40 Gy/15-fraction schedule produced lymphedema at a rate of 8%, meeting the predefined non-inferiority margin versus 9.4% with the conventional 50 Gy/25-fraction regimen. Recurrence, distant spread, breast-cancer death and overall mortality were also indistinguishable, supporting the shorter regimen as a safe alternative.
- Journal
- Journal of clinical oncology : official journal of the American Society of Clinical Oncology (Q1)
- Published
- 23 July 2026
- Study design
- Randomized controlled trial
- Evidence level
- Level 1, High (CEBM 1b)
- Authors
- Birgitte V Offersen, Jan Alsner, Kristine Høgsbjerg, Hanne M Nielsen, Else Maae, Mette H Nielsen, et al.
- PMID
- 42492022
- DOI
- 10.1200/JCO-25-02705
Why clinicians should know about it
- Picked for Oncology and Radiation Oncology (paper of the day, 24 July 2026): Hypofractionated 40 Gy/15 fx does not increase lymphedema versus 50
Abstract
PURPOSE: Adjuvant radiotherapy for node-positive breast cancer (BC) using 50Gy/25fx has been Danish Breast Cancer Group (DBCG) standard. Hypofractionated radiotherapy based on 40Gy/15fx has been increasingly used; however, it is less frequently for locoregional therapy because of concern over more morbidity. DBCG Skagen trial 1 hypothesized that 40Gy/15fx did not cause more lymphedema than 50Gy/25fx 3 years after radiotherapy without compromising the pattern of failure. METHODS: Skagen trial 1 is a phase III, noninferiority trial randomly assigning high-risk BC patients with an indication for locoregional radiotherapy to standard 50Gy/25fx versus experimental 40Gy/15fx. The primary end point was arm lymphedema; assuming a 3-year incidence with 50Gy/25fx of 10%, noninferiority was predefined to maximum 5% excess incidence with 40Gy/15fx. Accrual continued until 3-year estimates were reported in 1,012 patients. RESULTS: Between 2015 and 2021, 2,963 patients consented from 17 centers; the intention-to-treat cohort comprised 2,908 patients: 1,444 had 50Gy (50%), and 1,464 had 40Gy (50%). The median age was 57 years (range, 23-86). At a median follow-up of 4.1 years (IQR, 3.0-5.0), the 3-year rates of lymphedema were 9.4% (50Gy) versus 8.0% (40Gy), odds ratio 0.84 (95% CI, 0.62 to 1.14), and P = .27, thus within the +5-percentage-point noninferiority margin. The median follow-up for cancer outcomes was 5.25 years (IQR, 4.26 to 6.96). Within 8 years, the hazard ratio for locoregional recurrence was 0.96 (95% CI, 0.62 to 1.51), that for distant recurrence was 1.10 (95% CI, 0.89 to 1.37), that for BC mortality was 1.25 (95% CI, 0.93 to 1.66), and that for all-cause mortality was 1.08 (95% CI, 0.85 to 1.36), thus all with no differences by random assignment. CONCLUSION: 40Gy/15fx for locoregional radiotherapy of BC did not result in more lymphedema compared with 50Gy/25fx. There were no differences in locoregional or distant recurrences, breast cancer mortality, nor all-cause mortality between the random assignment arms.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.