Birgitte V Offersen1,2, Jan Alsner1, Hanne M Nielsen2, Erik H Jakobsen3, Mette H Nielsen4, Mechthild Krause5, Lars Stenbygaard6, Ingvil Mjaaland7, Andreas Schreiber8, Unn-Miriam Kasti9, Jens Overgaard1. 1. Department of Experimental Clinical Oncology, Aarhus University Hospital, Aarhus, Denmark. 2. Department of Oncology, Aarhus University Hospital, Aarhus, Denmark. 3. Department of Oncology, Lillebaelt Hospital, Vejle, Denmark. 4. Department of Oncology, Odense University Hospital, Odense, Denmark. 5. Department of Radiation Oncology and OncoRay Center, University Hospital and Faculty of Medicine Carl Gustav Carus; Technische Universität Dresden; German Cancer Consortium Dresden; Helmholtz-Zentrum Dresden-Rossendorf; National Center for Tumor Diseases, Dresden; and German Cancer Research Center, Heidelberg, Germany. 6. Department of Oncology, Aalborg University Hospital, Aalborg, Denmark. 7. Department of Oncology, Stavanger University Hospital, Stavanger, Norway. 8. Department of Oncology, Academic Teaching Hospital Dresden-Friedrichstadt, Dresden, Germany. 9. Department of Oncology, Kristiansand Hospital, Kristiansand, Norway.
Abstract
PURPOSE: Given the poor results using hypofractionated radiotherapy for early breast cancer, a dose of 50 Gy in 25 fractions (fr) has been the standard regimen used by the Danish Breast Cancer Group (DBCG) since 1982. Results from more recent trials have stimulated a renewed interest in hypofractionation, and the noninferiority DBCG HYPO trial (ClincalTrials.gov identifier: NCT00909818) was designed to determine whether a dose of 40 Gy in 15 fr does not increase the occurrence of breast induration at 3 years compared with a dose of 50 Gy in 25 fr. PATIENTS AND METHODS: One thousand eight hundred eighty-two patients > 40 years of age who underwent breast-conserving surgery for node-negative breast cancer or ductal carcinoma in situ (DCIS) were randomly assigned to radiotherapy at a dose of either 50 Gy in 25 fr or 40 Gy in 15 fr. The primary end point was 3-year grade 2-3 breast induration assuming noninferiority regarding locoregional recurrence. RESULTS: A total of 1,854 consenting patients (50 Gy, n = 937; 40 Gy, n = 917) were enrolled from 2009-2014 from eight centers. There were 1,608 patients with adenocarcinoma and 246 patients with DCIS. The 3-year rates of induration were 11.8% (95% CI, 9.7% to 14.1%) in the 50-Gy group and 9.0% (95% CI, 7.2% to 11.1%) in the 40-Gy group (risk difference, -2.7%; 95% CI, -5.6% to 0.2%; P = .07). Systemic therapies and radiotherapy boost did not increase the risk of induration. Telangiectasia, dyspigmentation, scar appearance, edema, and pain were detected at low rates, and cosmetic outcome and patient satisfaction with breast appearance were high with either no difference or better outcome in the 40-Gy cohort compared with the 50-Gy cohort. The 9-year risk of locoregional recurrence was 3.3% (95% CI, 2.0% to 5.0%) in the 50-Gy group and 3.0% (95% CI, 1.9% to 4.5%) in the 40-Gy group (risk difference, -0.3%; 95% CI, -2.3% to 1.7%). The 9-year overall survival was 93.4% (95% CI, 91.1% to 95.1%) in the 50-Gy group and 93.4% (95% CI, 91.0% to 95.2%) in the 40-Gy group. The occurrence of radiation-associated cardiac and lung disease was rare and not influenced by the fractionation regimen. CONCLUSION: Moderately hypofractionated breast irradiation of node-negative breast cancer or DCIS did not result in more breast induration compared with standard fractionated therapy. Other normal tissue effects were minimal, with similar or less frequent rates in the 40-Gy group. The 9-year locoregional recurrence risk was low.
RCT Entities:
PURPOSE: Given the poor results using hypofractionated radiotherapy for early breast cancer, a dose of 50 Gy in 25 fractions (fr) has been the standard regimen used by the Danish Breast Cancer Group (DBCG) since 1982. Results from more recent trials have stimulated a renewed interest in hypofractionation, and the noninferiority DBCG HYPO trial (ClincalTrials.gov identifier: NCT00909818) was designed to determine whether a dose of 40 Gy in 15 fr does not increase the occurrence of breast induration at 3 years compared with a dose of 50 Gy in 25 fr. PATIENTS AND METHODS: One thousand eight hundred eighty-two patients > 40 years of age who underwent breast-conserving surgery for node-negative breast cancer or ductal carcinoma in situ (DCIS) were randomly assigned to radiotherapy at a dose of either 50 Gy in 25 fr or 40 Gy in 15 fr. The primary end point was 3-year grade 2-3 breast induration assuming noninferiority regarding locoregional recurrence. RESULTS: A total of 1,854 consenting patients (50 Gy, n = 937; 40 Gy, n = 917) were enrolled from 2009-2014 from eight centers. There were 1,608 patients with adenocarcinoma and 246 patients with DCIS. The 3-year rates of induration were 11.8% (95% CI, 9.7% to 14.1%) in the 50-Gy group and 9.0% (95% CI, 7.2% to 11.1%) in the 40-Gy group (risk difference, -2.7%; 95% CI, -5.6% to 0.2%; P = .07). Systemic therapies and radiotherapy boost did not increase the risk of induration. Telangiectasia, dyspigmentation, scar appearance, edema, and pain were detected at low rates, and cosmetic outcome and patient satisfaction with breast appearance were high with either no difference or better outcome in the 40-Gy cohort compared with the 50-Gy cohort. The 9-year risk of locoregional recurrence was 3.3% (95% CI, 2.0% to 5.0%) in the 50-Gy group and 3.0% (95% CI, 1.9% to 4.5%) in the 40-Gy group (risk difference, -0.3%; 95% CI, -2.3% to 1.7%). The 9-year overall survival was 93.4% (95% CI, 91.1% to 95.1%) in the 50-Gy group and 93.4% (95% CI, 91.0% to 95.2%) in the 40-Gy group. The occurrence of radiation-associated cardiac and lung disease was rare and not influenced by the fractionation regimen. CONCLUSION: Moderately hypofractionated breast irradiation of node-negative breast cancer or DCIS did not result in more breast induration compared with standard fractionated therapy. Other normal tissue effects were minimal, with similar or less frequent rates in the 40-Gy group. The 9-year locoregional recurrence risk was low.
Authors: Icro Meattini; Marta Scorsetti; Fiorenza De Rose; Maria Carmen De Santis; Bruno Meduri; Ciro Franzese; Davide Franceschini; Pierfrancesco Franco; Nadia Pasinetti; Valentina Lancellotta; Patrizia Giacobazzi; Eliana La Rocca; Elisa D'Angelo; Laura Lozza; Lorenzo Livi Journal: J Cancer Res Clin Oncol Date: 2021-01-02 Impact factor: 4.553
Authors: Reshma Jagsi; Kent A Griffith; Frank A Vicini; Eyad Abu-Isa; Derek Bergsma; Amit Bhatt; Joshua T Dilworth; Michael Dominello; Stephen Franklin; David K Heimburger; Isaac Kaufman; Paul G Kocheril; Annette E Kretzler; Peter Paximadis; Jeffrey D Radawski; Eleanor M Walker; Lori Pierce Journal: Int J Radiat Oncol Biol Phys Date: 2021-10-28 Impact factor: 7.038
Authors: M S Thomsen; M Berg; S Zimmermann; C M Lutz; S Makocki; I Jensen; M H B Hjelstuen; S Pensold; M P Hasler; M-B Jensen; B V Offersen Journal: Clin Transl Radiat Oncol Date: 2021-04-06