Skin dose-volume predictors of moderate-severe late side effects after whole breast radiotherapy.

Background: Toxicity after whole breast Radiotherapy is a relevant issue, impacting the quality-of-life of a not negligible number of patients. We aimed to develop a Normal Tissue Complication Probability (NTCP) model predicting late toxicities by combining dosimetric parameters of the breast dermis and clinical factors.

Methods: The skin structure was defined as the outer CT body contour's 5 mm inner isotropic expansion. It was retrospectively segmented on a large mono-institutional cohort of early-stage breast cancer patients enrolled between 2009 and 2017 (n = 1066). Patients were treated with tangential-field RT, delivering 40 Gy in 15 fractions to the whole breast. Toxicity was reported during Follow-Up (FU) using SOMA/LENT scoring. The study endpoint was moderate-severe late side effects consisting of Fibrosis-Atrophy-Telangiectasia-Pain (FATP G ≥ 2) developed within 42 months after RT completion. A machine learning pipeline was designed with a logistic model combining clinical factors and absolute skin DVH (cc) parameters as output.

Results: The FATP G2 + rate was 3.8 %, with 40/1066 patients experiencing side effects. After the preprocessing of variables, a cross-validation was applied to define the best-performing model. We selected a 4-variable model with Post-Surgery Cosmetic alterations (Odds Ratio, OR = 7.3), Aromatase Inhibitors (as a protective factor with OR = 0.45), V20 Gy (50 % of the prescribed dose, OR = 1.02), and V42 Gy (105 %, OR = 1.09). Factors were also converted into an adjusted V20Gy.

Conclusions: The association between late reactions and skin DVH when delivering 40 Gy/15 fr was quantified, suggesting an independent role of V20 and V42. Few clinical factors heavily modulate the risk.