title: Dose-surface analysis for prediction of severe acute radio-induced skin toxicity in breast cancer patients.
abstract: 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.
  
  
  METHODS
  We evaluated 140 consecutive BC patients undergoing conventional three-dimensional 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 TD50=39 Gy, n=0.38 and m=0.14 [Rs = 0.25, area under the curve (AUC) = 0.77, p = 0.003]. On multivariate analysis, the most predictive model of acute RIST severity was a two-variable model including the skin receiving ≥30 Gy (S30) and psoriasis [Rs = 0.32, AUC = 0.84, p < 0.001].
  
  
  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.
authors.affiliation: a Department of Advanced Biomedical Sciences , Federico II University School of Medicine , Naples , Italy ;
authors.forename: Francesco
authors.initials: F
authors.lastname: Pastore
authors.affiliation: a Department of Advanced Biomedical Sciences , Federico II University School of Medicine , Naples , Italy ;|b Institute of Biostructures and Bioimaging, National Research Council (CNR) , Naples , Italy.
authors.forename: Manuel
authors.initials: M
authors.lastname: Conson
authors.affiliation: b Institute of Biostructures and Bioimaging, National Research Council (CNR) , Naples , Italy.
authors.forename: Vittoria
authors.initials: V
authors.lastname: D'Avino
authors.affiliation: b Institute of Biostructures and Bioimaging, National Research Council (CNR) , Naples , Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Palma
authors.affiliation: a Department of Advanced Biomedical Sciences , Federico II University School of Medicine , Naples , Italy ;|b Institute of Biostructures and Bioimaging, National Research Council (CNR) , Naples , Italy.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Liuzzi
authors.affiliation: a Department of Advanced Biomedical Sciences , Federico II University School of Medicine , Naples , Italy ;|b Institute of Biostructures and Bioimaging, National Research Council (CNR) , Naples , Italy.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Solla
authors.affiliation: a Department of Advanced Biomedical Sciences , Federico II University School of Medicine , Naples , Italy ;
authors.forename: Antonio
authors.initials: A
authors.lastname: Farella
authors.affiliation: a Department of Advanced Biomedical Sciences , Federico II University School of Medicine , Naples , Italy ;
authors.forename: Marco
authors.initials: M
authors.lastname: Salvatore
authors.affiliation: a Department of Advanced Biomedical Sciences , Federico II University School of Medicine , Naples , Italy ;|b Institute of Biostructures and Bioimaging, National Research Council (CNR) , Naples , Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Cella
authors.affiliation: a Department of Advanced Biomedical Sciences , Federico II University School of Medicine , Naples , Italy ;|b Institute of Biostructures and Bioimaging, National Research Council (CNR) , Naples , Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Pacelli
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000532:radiotherapy* / Q000601:surgery; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006801:Humans; D015412:Mastectomy, Segmental; D008875:Middle Aged; D008954:Models, Biological; D015999:Multivariate Analysis; D011446:Prospective Studies; D011832:Radiation Injuries / Q000209:etiology; D011879:Radiotherapy Dosage; D011880:Radiotherapy Planning, Computer-Assisted / Q000379:methods; D020266:Radiotherapy, Conformal / Q000009:adverse effects*; D012867:Skin / Q000528:radiation effects*