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Simple Summary  Moderate hypofractionated radiotherapy (HF) has become the standard fractionation scheme for most breast cancer patients. Despite comprehensive data from large, randomized trials, standardized assessment of patient reported outcome (PRO) and physiological changes after HF are largely missing. In this prospective trial focusing on radiodermatitis, HF and conventional normofractionated radiotherapy (CF) were compared using standardized Skindex-16 questionnaire in addition to CTCAE assessment and ultrasound measurement of the skin. The results of the current study complement and confirm existing evidence that HF leads to a lower degree of acute radiodermatitis and better patient reported outcome compared to CF.    Abstract  The current study aims to determine whether hypofractionated radiotherapy (HF) leads to lower rates of acute radiodermatitis compared to conventional normofractionated radiotherapy (CF). A total of 166 patients with invasive breast cancer or DCIS were included in a prospective cohort study. Evaluation of acute radiodermatitis was obtained before radiotherapy, at the end of the treatment (T1), and 6 weeks after the treatment (T2) using CTCAE (v5.0) scores, the Skindex-16 questionnaire, and ultrasound measurement of the skin. CTCAE and Skindex-16 scores in the CF-group were significantly higher compared to the HF group indicating more pronounced side effects at the end of the treatment (CTCAE: CF-RT 1.0 (IQR: 0.0) vs. HF-RT 0.0 (0.25);  p  = 0.03; Skindex-16: CF: 20.8 (IQR: 25.8); HF: 8.3 (27.1);  p  = 0.04). At 6 weeks after the treatment, no significant differences between the two fractionation schemes were observed. Ultrasound based assessment showed that the skin thickness in the treated breast was higher compared to the healthy breast at all time-points. However, no significant difference between HF and CF was seen either at T1 or T2. The current study complements and confirms pre-existing evidence that HF leads to a lower degree of acute radiodermatitis and better patient reported outcome compared to CF at the end of treatment. This should be considered whenever fractionation of adjuvant breast cancer treatment is being discussed.

A Comprehensive Prospective Comparison of Acute Skin Toxicity after Hypofractionated and Normofractionated Radiation Therapy in Breast Cancer