title: Modeling radiation pneumonitis risk with clinical, dosimetric, and spatial parameters.
abstract: OBJECTIVE
  To determine the clinical, dosimetric, and spatial parameters that correlate with radiation pneumonitis.
  
  
  METHODS
  Patients treated with high-dose radiation for non-small-cell lung cancer with three-dimensional treatment planning were reviewed for clinical information and radiation pneumonitis (RP) events. Three-dimensional treatment plans for 219 eligible patients were recovered. Treatment plan information, including parameters defining tumor position and dose-volume parameters, was extracted from non-heterogeneity-corrected dose distributions. Correlation to RP events was assessed by Spearman's rank correlation coefficient (R). Mathematical models were generated that correlate with RP.
  
  
  RESULTS
  Of 219 patients, 52 required treatment for RP (median interval, 142 days). Tumor location was the most highly correlated parameter on univariate analysis (R = 0.24). Multiple dose-volume parameters were correlated with RP. Models most frequently selected by bootstrap resampling included tumor position, maximum dose, and D35 (minimum dose to the 35% volume receiving the highest doses) (R = 0.28). The most frequently selected two- or three-parameter models outperformed commonly used metrics, including V20 (fractional volume of normal lung receiving >20 Gy) and mean lung dose (R = 0.18).
  
  
  CONCLUSIONS
  Inferior tumor position was highly correlated with pneumonitis events within our population. Models that account for inferior tumor position and dosimetric information, including both high- and low-dose regions (D(35), International Commission on Radiation Units and Measurements maximum dose), risk-stratify patients more accurately than any single dosimetric or clinical parameter.
authors.affiliation: Department of Radiation Oncology, Washington University School of Medicine, Siteman Cancer Center, St. Louis, Missouri 63110-1032, USA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Hope
authors.forename: Patricia E
authors.initials: PE
authors.lastname: Lindsay
authors.forename: Issam
authors.initials: I
authors.lastname: El Naqa
authors.forename: James R
authors.initials: JR
authors.lastname: Alaly
authors.forename: Milos
authors.initials: M
authors.lastname: Vicic
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Bradley
authors.forename: Joseph O
authors.initials: JO
authors.lastname: Deasy
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology / Q000532:radiotherapy*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D017564:Radiation Pneumonitis / Q000209:etiology*; D011879:Radiotherapy Dosage; D012189:Retrospective Studies; D018709:Statistics, Nonparametric