title: Predicting radiation-induced valvular heart damage.
abstract: OBJECTIVE
  To develop a predictive multivariate normal tissue complication probability (NTCP) model for radiation-induced heart valvular damage (RVD). The influence of combined heart-lung irradiation on RVD development was included.
  
  
  METHODS
  Multivariate logistic regression modeling with the least absolute shrinkage and selection operator (LASSO) was used to build an NTCP model to predict RVD based on a cohort of 90 Hodgkin lymphoma patients treated with sequential chemo-radiation therapy. In addition to heart irradiation factors, clinical variables, along with left and right lung dose-volume histogram statistics, were included in the analysis. To avoid overfitting, 10-fold cross-validation (CV) was used for LASSO logistic regression modeling, with 50 reshuffled cycles. Model performance was assessed using the area under the receiver operating characteristic (ROC) curve (AUC) and Spearman's correlation coefficient (Rs).
  
  
  RESULTS
  At a median follow-up time of 55 months (range 12-92 months) after the end of radiation treatment, 27 of 90 patients (30%) manifested at least one kind of RVD (mild or moderate), with a higher incidence of left-sided valve defects (64%). Fourteen prognostic factors were frequently selected (more than 100/500 model fits) by LASSO, which included mainly heart and left lung dosimetric variables along with their volume variables. The averaged cross-validated performance was AUC-CV = 0.685 and Rs = 0.293. The overall performance of a final NTCP model for RVD obtained applying LASSO logistic regression to the full dataset was satisfactory (AUC = 0.84, Rs = 0.55, p < 0.001).
  
  
  CONCLUSIONS
  LASSO proved to be an improved and flexible modeling method for variable selection. Applying LASSO, we showed, for the first time, the importance of jointly considering left lung irradiation and left lung volume size in the prediction of subclinical radiation-related heart disease resulting in RVD.
authors: a Institute of Biostructure and Bioimaging, National Council of Research (CNR) , Naples , Italy.|b Department of Advanced Biomedical Sciences , Federico II University School of Medicine , Naples , Italy.
authors: Laura
authors: L
authors: Cella
authors: c Department of Medical Physics , Memorial Sloan Kettering Cancer Center , New York , New York , USA.
authors: Jung Hun
authors: JH
authors: Oh
authors: c Department of Medical Physics , Memorial Sloan Kettering Cancer Center , New York , New York , USA.
authors: Joseph O
authors: JO
authors: Deasy
authors: a Institute of Biostructure and Bioimaging, National Council of Research (CNR) , Naples , Italy.
authors: Giuseppe
authors: G
authors: Palma
authors: a Institute of Biostructure and Bioimaging, National Council of Research (CNR) , Naples , Italy.|b Department of Advanced Biomedical Sciences , Federico II University School of Medicine , Naples , Italy.
authors: Raffaele
authors: R
authors: Liuzzi
authors: a Institute of Biostructure and Bioimaging, National Council of Research (CNR) , Naples , Italy.
authors: Vittoria
authors: V
authors: D'avino
authors: a Institute of Biostructure and Bioimaging, National Council of Research (CNR) , Naples , Italy.|b Department of Advanced Biomedical Sciences , Federico II University School of Medicine , Naples , Italy.
authors: Manuel
authors: M
authors: Conson
authors: d Department of Clinical Medicine and Surgery , Federico II University School of Medicine , Naples , Italy.
authors: Marco
authors: M
authors: Picardi
authors: b Department of Advanced Biomedical Sciences , Federico II University School of Medicine , Naples , Italy.
authors: Marco
authors: M
authors: Salvatore
authors: a Institute of Biostructure and Bioimaging, National Council of Research (CNR) , Naples , Italy.|b Department of Advanced Biomedical Sciences , Federico II University School of Medicine , Naples , Italy.
authors: Roberto
authors: R
authors: Pacelli
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019540:Area Under Curve; D004452:Echocardiography; D005260:Female; D005500:Follow-Up Studies; D006349:Heart Valve Diseases / Q000000981:diagnostic imaging / Q000209:etiology*; D006351:Heart Valves / Q000528:radiation effects*; D006689:Hodgkin Disease / Q000188:drug therapy / Q000532:radiotherapy*; D006801:Humans; D016015:Logistic Models; D008168:Lung / Q000528:radiation effects; D008297:Male; D008875:Middle Aged; D012372:ROC Curve; D011829:Radiation Dosage; D011832:Radiation Injuries / Q000000981:diagnostic imaging / Q000209:etiology*; D011878:Radiotherapy / Q000706:statistics & numerical data; D012044:Regression Analysis; D055815:Young Adult