Favorable Safety Profile Of Moderate Hypofractionated Over Normofractionated Radiotherapy In Breast Cancer Patients: A Multicentric Prospective Real-Life Data Farming Analysis

Background: Moderately hypofractionated whole-breast radiotherapy (HFRT) has proven to be as safe and efficient as normofractionated radiotherapy (NFRT) in randomized trials resulting in major changes in clinical practice. Toxicity rates observed in selected clinical trial patients may differ from those observed in unselected patients with possible comorbidities and frailty in real-life. This study aimed to examine the influence of HFRT versus NFRT on acute toxicity and identify risks factors of dermatitis in real-life patients. Materials: and Methods Prospective data from breast cancer patients, treated with locoregional radiotherapy between November 2015 and February 2020 in 3 comprehensive cancer centers, were collected. Through a systematic data-farming strategy, acute toxicity evaluation forms (CTCAEv4.0) were prospectively completed and extracted electronically. The results from each center were then anonymously merged into a single database for analysis. A Chi-2 test was used to compare HFRT and NFRT. Furthermore, risk factors of dermatitis were identified in a sub-study (622 patients) by multivariate logistic regression analysis. Results: In total, 3518 T0-4 N0-3 mostly M0 (85.8%) breast cancer patients with a median age of 60.7 (24–96 years old) were analyzed. Acute grade 2-3 dermatitis, grade 1-3 breast oedema, and grade 1-2 hyperpigmentation were less frequent with HFRT versus NFRT: respectively 8.9% vs 35.1% (Chi-2=373.7; p<0.001), 29.0% vs 37.0% (Chi-2=23.1; p<0.001) and 27.0% vs 55.8% (Chi-2=279.2; p<0.001). Fewer patients experienced pain with HFRT versus NFRT: 33.4% vs 53.7% respectively (Chi-2=137.1; p<0.001). High BMI (OR=2.30 [95% CI, 1.28-4.26], p<0.01), large breast size (OR=1.88 [95% CI, 1.07-3.28], p<0.01) and lumpectomy over mastectomy (OR=0.52 [95% CI, 0.27-0.97], p<0.05) were associated with greater risk factors of grade 2-3 dermatitis in multivariate analysis regardless of NFRT or HFRT. Conclusion: The results of this study suggests that breast HFRT may be a better option even for patients with a high BMI or large breast size. Acute toxicity was low to mild, and lower with HFRT compared to NFRT. Results from real-life data were robust, and support the use of HFRT beyond randomized study populations. Long-term real-life data awaits further investigation.