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

Author(s): Birgitte V. Offersen, MD, PhD^1,2,3; Jan Alsner, PhD¹; Kristine Høgsbjerg, PhD¹; Hanne M. Nielsen, PhD³; Else Maae, PhD⁴; Mette H. Nielsen, PhD⁵; Ingvil Mjaaland, MD⁶; Maja V. Maraldo, PhD⁷; Carine Kirkove, MD⁸; Tamas Lörincz, MD⁹; Sami Al-Rawi, MD¹⁰; Egil S. Blix, PhD^11,12; Andreas Schreiber, MD¹³; Mechthild Krause, PhD^{14,15,16,17,18}; Unn-Miriam Kasti, MD¹⁹; Louise W. Matthiessen, PhD²⁰; Camilla Kronborg, PhD²¹; Trine Tramm, PhD²²; Maj-Britt Jensen, DMSc²³; Jens Overgaard, DMSc¹; on behalf of the DBCG RT Committee;

Source: DOI: 10.1200/JCO-25-02705

Dr. Maen Hussein's Thoughts

Less radiation (40Gy vs 50 Gy) was non inferior in preventing locoregional recurrence and distant mets, also lymphedema rates were not worse. Would love feedback from our rad onc, but it seems less is as good.

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). 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.

Author Affiliations

¹Department of Experimental Clinical Oncology, Aarhus University Hospital, Aarhus, Denmark; ²Aarhus University, Aarhus, Denmark; ³Department of Oncology, Aarhus University Hospital, Aarhus, Denmark; ⁴Department of Oncology, Lillebaelt Hospital, Vejle, Denmark; ⁵Department of Oncology, Odense University Hospital, Odense, Denmark; ⁶Department of Oncology, Stavanger University Hospital, Stavanger, Norway; ⁷Department of Oncology, Rigshospitalet, Copenhagen, Denmark; ⁸Université Catholique de Louvain, Cliniques Universitaires St-Luc, Radiotherapy Department, Bruxelles, Belgium; ⁹Department of Oncology, Aalborg University Hospital, Aalborg, Denmark; ¹⁰Department of Oncology, Zealand University Hospital, Roskilde, Denmark; ¹¹Department of Clinical Medicine, UiT, The Arctic University of Norway, Tromsø, Norway; ¹²Department of Oncology, University Hospital of North Norway, Tromsø, Norway; ¹³Department of Oncology, Academic Teaching Hospital Dresden-Friedrichstadt, Dresden, Germany; ¹⁴Department of Radiation Oncology and OncoRay, University Hospital and Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; ¹⁵German Cancer Consortium (DKTK), Dresden, Germany; ¹⁶Helmholtz-Zentrum Dresden—Rossendorf, Dresden, Germany; ¹⁷National Center for Tumor Diseases (NCT), Dresden, Germany; ¹⁸German Cancer Research Center (DKFZ), Heidelberg, Germany; ¹⁹Department of Oncology, Hospital of Kristiansand, Kristiansand, Norway; ²⁰Department of Oncology, Herlev and Gentofte University Hospital, Herlev, Denmark; ²¹Danish Centre for Particle Therapy, Aarhus, Denmark; ²²Department of Pathology, Aarhus University Hospital, Aarhus, Denmark; ²³Department of Oncology, Danish Breast Cancer Group, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark

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