Acute toxicity and quality of life after 5-fraction versus 15-fraction adjuvant radiotherapy following conventional or oncoplastic breast-conserving surgery - a real-world prospective cohort study

Background and purpose: The FAST-Forward trial demonstrated that 26 Gy in 5 fractions for whole breast irradiation (WBI) has similar outcomes as 40 Gy in 15 fractions. Since radiation treatment plans in the Netherlands in general deliver higher target doses, we aimed to compare acute toxicity and quality of life of the adjuvant 26 Gy and the 40 Gy schedules in a real-world setting, including after oncoplastic surgery. Materials and methods: Eligible were women ≥50 years with breast cancer receiving WBI or partial breast irradiation (PBI) between 2018 and 2023 in two Dutch centres, with either 26 Gy/5 fractions in 1 week or 40 Gy/15 fractions in 3 weeks. Acute toxicity was assessed using CTCAE v5.0 during and ≤ 4 weeks following radiotherapy. Patient-reported outcomes were evaluated using EORTC-QLQ-C30/BR23 prior to radiotherapy, at 3 months and 1 year post-radiotherapy. Results: In total, 832 patients received 26 Gy/5 fractions (70.2% WBI, 12.9% oncoplastic surgery) and 845 patients 40 Gy/15 fractions (81.9% WBI, 14.2% oncoplastic surgery). For WBI and PBI, grade ≥ 1 dermatitis and fatigue were less common after 26 Gy than 40 Gy: 61–67 % versus 86–91% and 42–43% versus 56% respectively (p < 0.001–0.005). After oncoplastic surgery, 26 Gy patients less often experienced grade ≥ 1 dermatitis than 40 Gy patients (77% vs 94%, p < 0.001). At 3 months and 1-year post-radiotherapy, 26 Gy and 40 Gy patients reported comparable patient-reported outcomes. Conclusion: We confirmed the safety of the 26 Gy/5 fractions schedule in terms of acute toxicity and quality of life compared to the 40 Gy/15 fractions schedule, also when treated with higher target coverage and following oncoplastic breast-conserving surgery.