Normo Versus Hypofractionated Whole Breast Radiation-Related Acute Toxicities: Evolution Over Time In Systematic Multicentric Real Life Data

ASTRO guidelines from 2011 to 2018 have set moderate hypofractionation as the new standard of care for whole breast radiation therapy. These recommendations are based on selected patients from randomized studies. The purpose of this study is to report large real-life data on the evolution of practices over time and its impact on acute radiation-related toxicities in unselected patients who received moderate hypofractionated versus normofractionated whole breast irradiation. We conducted a multicentric comprehensive systematic electronic data collection cohort study based on treatment characteristics and on a standardized and structured end of treatment data form R&V. Three cancer centers used a common data form for breast cancer patients treated with radiotherapy including 7 items (WHO status, pain, acute toxicities - CTCAE V4-). Between November 2015 and November 2019, 2945 patients, median age, 61.6 years [24-96], were assessed. Most patients (97%) had a WHO status 0-1 with 73% RE+, 62% RP+ and 11% HER2+++. Most were M0 (84%) and 60% were N0. Moderate hypofractionation (HF) (mostly 2.67 Gy/fr) was used in 934 patients (31.7%) and normofractionation (NF) (2 Gy/fr) in 2011 patients (68.3%). Overall acute toxicities were mild with no grade 4 or 5. Most patients had a numerical rating scale for pain 0-2/10 (91%). Dermatitis, breast edema and hyperpigmentation were less frequent with HF than with NF: dermatitis grade 2-3: 10.1% versus 35.3%; Chi-2 = 300; p<0.05; breast edema grade 1-3: 30.4% versus 38.9%; Chi-2 = 20; p<0.05 and hyperpigmentation grade 1-2: 28.8% versus 57.2%; Chi-2 = 223; p<0.05. Hypofractionation use increased after ASTRO recommendations in June 2018: from 20.7% to 40.4%. When we compare the evolution of toxicities before and after recommendations, we found no differences on dermatitis grade 0-3 (Chi2 = 0.5; p = 0.8 for NF and Chi2 = 2.4; p = 0.3 for HF) but statistically significant differences on hyperpigmentation (Chi2 = 11.3; p = <0.05 for NF and Chi2 = 124.8; p = <0.05 for HF) and on breast edema grade 1 (Chi2 = 47.4; p = <0.05 for NF and Chi2 = 7.7; p = 0.02 for HF). We found more hyperpigmentation grade 1-2 and less edema grade 1 with HF after 2018 recommendation (31.8% versus 21.7% and 25.6% versus 34.6% respectively). These results suggest that whole breast HF has acceptable acute toxicities, even lower than NF, in real life unselected breast cancer patients even after an increase of HF indications since ASTRO 2018 guidelines. This evolution of practice, slower than guidelines would expect, was not associated with an evolution of dermatitis but a moderate increase of hyperpigmentation and decrease of breast edema. The monitoring of toxicities in real data appears to be important.