Dose-surface analysis for prediction of severe acute radio-induced skin toxicity in breast cancer patients

Background: Severe acute radiation-induced skin toxicity (RIST) after breast irradiation is a side effect impacting the quality of life in breast cancer (BC) patients. The aim of the present study was to develop normal tissue complication probability (NTCP) models of severe acute RIST in BC patients. Patients and methods: We evaluated 140 consecutive BC patients undergoing conventional threedimensional conformal radiotherapy (3D-CRT) after breast conserving surgery in a prospective study assessing acute RIST. The acute RIST was classified according to the RTOG scoring system. Dose-surface histograms (DSHs) of the body structure in the breast region were extracted as representative of skin irradiation. Patient, disease, and treatment-related characteristics were analyzed along with DSHs. NTCP modeling by Lyman-Kutcher-Burman (LKB) and by multivariate logistic regression using bootstrap resampling techniques was performed. Models were evaluated by Spearman's Rs coefficient and ROC area. Results: By the end of radiotherapy, 139 (99%) patients developed any degree of acute RIST. G3 RIST was found in 11 of 140 (8%) patients. Mild-moderate (G1-G2) RIST was still present at 40 days after treatment in six (4%) patients. Using DSHs for LKB modeling of acute RIST severity (RTOG G3 vs. G0- 2), parameter estimates were TD50¼39 Gy, n¼0.38 and m¼0.14 [Rs¼0.25, area under the curve (AUC)¼0.77, p¼0.003]. On multivariate analysis, the most predictive model of acute RIST severity was a two-variable model including the skin receiving30 Gy (S30) and psoriasis [Rs¼0.32, AUC¼0.84, p50.001]. Conclusions: Using body DSH as representative of skin dose, the LKB n parameter was consistent with a surface effect for the skin. A good prediction performance was obtained using a data-driven multivariate model including S30 and a pre-existing skin disease (psoriasis) as a clinical factor.