title: Unraveling biophysical interactions of radiation pneumonitis in non-small-cell lung cancer via Bayesian network analysis.
abstract: In non-small-cell lung cancer radiotherapy, radiation pneumonitis≥grade 2 (RP2) depends on patients' dosimetric, clinical, biological and genomic characteristics.
  
  
  
  We developed a Bayesian network (BN) approach to explore its potential for interpreting biophysical signaling pathways influencing RP2 from a heterogeneous dataset including single nucleotide polymorphisms, micro RNAs, cytokines, clinical data, and radiation treatment plans before and during the course of radiotherapy. Model building utilized 79 patients (21 with RP2) with complete data, and model testing used 50 additional patients with incomplete data. A developed large-scale Markov blanket approach selected relevant predictors. Resampling by k-fold cross-validation determined the optimal BN structure. Area under the receiver-operating characteristics curve (AUC) measured performance.
  
  
  
  Pre- and during-treatment BNs identified biophysical signaling pathways from the patients' relevant variables to RP2 risk. Internal cross-validation for the pre-BN yielded an AUC=0.82 which improved to 0.87 by incorporating during treatment changes. In the testing dataset, the pre- and during AUCs were 0.78 and 0.82, respectively.
  
  
  
  Our developed BN approach successfully handled a high number of heterogeneous variables in a small dataset, demonstrating potential for unraveling relevant biophysical features that could enhance prediction of RP2, although the current observations would require further independent validation.
authors.affiliation: Department of Radiation Oncology, The University of Michigan, Ann Arbor, United States.
authors.forename: Yi
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Department of Radiation Oncology, The University of Michigan, Ann Arbor, United States.
authors.forename: Issam
authors.initials: I
authors.lastname: El Naqa
authors.affiliation: Department of Radiation Oncology, The University of Michigan, Ann Arbor, United States.
authors.forename: Daniel L
authors.initials: DL
authors.lastname: McShan
authors.affiliation: Department of Radiation Oncology, The University of Michigan, Ann Arbor, United States.
authors.forename: Dipankar
authors.initials: D
authors.lastname: Ray
authors.affiliation: Department of Radiation Oncology, The University of Michigan, Ann Arbor, United States.
authors.forename: Ines
authors.initials: I
authors.lastname: Lohse
authors.affiliation: Department of Radiation Oncology, The University of Michigan, Ann Arbor, United States.
authors.forename: Martha M
authors.initials: MM
authors.lastname: Matuszak
authors.affiliation: Department of Radiation Oncology, The University of Michigan, Ann Arbor, United States.
authors.forename: Dawn
authors.initials: D
authors.lastname: Owen
authors.affiliation: Department of Radiation Oncology, The University of Michigan, Ann Arbor, United States.
authors.forename: Shruti
authors.initials: S
authors.lastname: Jolly
authors.affiliation: Department of Radiation Oncology, The University of Michigan, Ann Arbor, United States.
authors.forename: Theodore S
authors.initials: TS
authors.lastname: Lawrence
authors.affiliation: Department of Radiation Oncology, Indiana University, Indianapolis, United States.
authors.forename: Feng-Ming Spring
authors.initials: FS
authors.lastname: Kong
authors.affiliation: Department of Radiation Oncology, The University of Michigan, Ann Arbor, United States. Electronic address: rth@med.umich.edu.
authors.forename: Randall K
authors.initials: RK
authors.lastname: Ten Haken
mesh_terms: D019540:Area Under Curve; D001499:Bayes Theorem; D001703:Biophysics; D002289:Carcinoma, Non-Small-Cell Lung / Q000532:radiotherapy*; D006801:Humans; D008175:Lung Neoplasms / Q000532:radiotherapy*; D017564:Radiation Pneumonitis / Q000209:etiology*
keywords: Bayesian network analysis; Biophysical interactions; Lung cancer; Radiation pneumonitis