Journal Article

DKFZ-2026-01852

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png 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.

Offersen, B. V. ; Alsner, J. ; Høgsbjerg, K. ; Nielsen, H. M. ; Maae, E. ; Nielsen, M. H. ; Mjaaland, I. ; Maraldo, M. V. ; Kirkove, C. ; Lörincz, T. ; Al-Rawi, S. ; Blix, E. S. ; Schreiber, A. ; Krause, M.DKFZ* ; Kasti, U.-M. ; Matthiessen, L. W. ; Kronborg, C. ; Tramm, T. ; Jensen, M.-B. ; Overgaard, J. ; Committee, D. R. (Collaboration Author)

2026
American Society of Clinical Oncology Alexandria, Va.

Abstract: 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.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.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.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.

Note: #DKTKZFB26# / #NCTZFB26# / 2026 Aug 20;44(24):2278-2289

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Contributing Institute(s):

1. DKTK Koordinierungsstelle Dresden (DD01)
2. Koordinierungsstelle NCT Dresden (DD04)
3. DKTK DD Translationale Radioonkologie (DD02)

Research Program(s):

1. 899 - ohne Topic (POF4-899) (POF4-899)

Appears in the scientific report 2026

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Database coverage:
; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; Essential Science Indicators ; IF >= 40 ; JCR ; Nationallizenz ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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