For decades, conventionally fractionated whole breast irradiation (CF-WBI) was used after breast conserving surgery (BCS). Pivotal phase 3 trials on hypofractionated-WBI (HF-WBI) showed its non-inferiority as compared to CF-WBI. However, younger patients (<60 years) are not currently worldwide treated with HF-WBI. The aim of this multi-center comparative study is to confirm the safety of HF-WBI in a real-life series of younger patients.
Between 2010 and 2016, a total of 786 patients aged less than 60 years old with early stage breast cancer were treated with postoperative WBI after BCS in three breast cancer centers: 340 underwent HF-WBI while 446 were treated with CF-WBI. Acute toxicity was evaluated at the end of WBI. Late toxicity was evaluated at 6, 12, 24, and 36 months.
At univariate logistic analysis, hypofractionation showed a significant protective effect in terms of acute edema (p = 0.0001), acute wet desquamation (p = 0.009), chronic edema (p = 0.0001), chronic erythema/pigmentation (p = 0.0001), and breast fibrosis (p = 0.0002). At multivariate logistic analysis, hypofractionation was independent significant factor for acute edema (OR 0.09, 95% CI 0.02 to 0.48; p = 0.005), acute wet desquamation (OR 0.07, 95% CI 0.009 to 0.59; p = 0.014), and chronic edema (OR 0.18, 95% CI 0.04 to 0.75; p = 0.018). Significant association between individual characteristics and toxicity (grade 2 or more) are summarized in Table. 215PToxicity N Protective factor p-value OR (95%CI) Risk factor p-value OR (95%CI) Acute edema 43 Hypofractionation Dmax/Prescribed dose° <107% 0.0001 0.001 0.09 (0.03-0.30) 0.16 (0.06-0.46) Chemotherapy 0.002 2.63 (1.42-4.90) Chronic edema 50 Hypofractionation Dmax/Prescribed dose° <107% 0.0001 0.003 0.20 (0.09-0.44) 0.31 (0.14-0.66) EIC presence Boost dose >10 Gy Breast size >492 cc 0.0001 0.032 0.003 3.0 (1.66-5.46) 9.02 (1.21-67.45) 2.67 (1.41-5.05) Acute erythema/ pigmentation 163 HER2 positive status Trastuzumab 0.002 0.022 0.30 (0.14-0.63) 0.39 (0.18-0.87) Smoking habits Boost dose >10 Gy Breast size >492 cc 0.001 0.038 0.002 2.14 (1.37-3.32) 2.60 (1.06-6.41) 1.78 (1.24-2.54) Chronic erythema/ pigmentation 110 Hypofractionation Dmax/Prescribed dose° <107% 0.0001 0.001 0.40 (0.25-0.63) 0.45 (0.28-0.73) EIC presence Positive FSM Boost dose >10 Gy Breast size >492 cc 0.0001 0.002 0.007 0.034 2.39 (1.54-3.71) 3.47 (1.56-7.71) 15.43 (2.08-114.3) 1.58 (1.04-2.41) Acute wet desquamation 20 Hypofractionation Dmax/Prescribed dose° <107% 0.009 0.047 0.14 (0.03-0.61) 0.29 (0.08-0.99) - - - Breast fibrosis 117 Hypofractionation Tumor grade Ki67 index Dmax/Prescribed dose° <107% 0.0002 0.022 0.023 0.017 0.44 (0.29-0.68) 0.53 (0.31-0.92) 0.60 (0.38-0.93) 0.58 (0.37-0.91) EIC presence Boost dose >10 Gy Breast size >492 cc 0.0001 0.022 0.0001 3.03 (1.99-4.62) 6.76 (2.04-22.45) 2.84 (1.83-4.41)
HF-WBI showed significantly improved toxicity outcomes in terms of both acute skin edema and wet desquamation, and chronic skin edema. HF-WBI after BCS should replace CF-WBI independently of age.
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