title: Modeling the risk of radiation-induced acute esophagitis for combined Washington University and RTOG trial 93-11 lung cancer patients.
abstract: OBJECTIVE
  To construct a maximally predictive model of the risk of severe acute esophagitis (AE) for patients who receive definitive radiation therapy (RT) for non-small-cell lung cancer.
  
  
  METHODS
  The dataset includes Washington University and RTOG 93-11 clinical trial data (events/patients: 120/374, WUSTL = 101/237, RTOG9311 = 19/137). Statistical model building was performed based on dosimetric and clinical parameters (patient age, sex, weight loss, pretreatment chemotherapy, concurrent chemotherapy, fraction size). A wide range of dose-volume parameters were extracted from dearchived treatment plans, including Dx, Vx, MOHx (mean of hottest x% volume), MOCx (mean of coldest x% volume), and gEUD (generalized equivalent uniform dose) values.
  
  
  RESULTS
  The most significant single parameters for predicting acute esophagitis (RTOG Grade 2 or greater) were MOH85, mean esophagus dose (MED), and V30. A superior-inferior weighted dose-center position was derived but not found to be significant. Fraction size was found to be significant on univariate logistic analysis (Spearman R = 0.421, p < 0.00001) but not multivariate logistic modeling. Cross-validation model building was used to determine that an optimal model size needed only two parameters (MOH85 and concurrent chemotherapy, robustly selected on bootstrap model-rebuilding). Mean esophagus dose (MED) is preferred instead of MOH85, as it gives nearly the same statistical performance and is easier to compute. AE risk is given as a logistic function of (0.0688 MED+1.50 ConChemo-3.13), where MED is in Gy and ConChemo is either 1 (yes) if concurrent chemotherapy was given, or 0 (no). This model correlates to the observed risk of AE with a Spearman coefficient of 0.629 (p < 0.000001).
  
  
  CONCLUSIONS
  Multivariate statistical model building with cross-validation suggests that a two-variable logistic model based on mean dose and the use of concurrent chemotherapy robustly predicts acute esophagitis risk in combined-data WUSTL and RTOG 93-11 trial datasets.
authors.affiliation: Department of Radiation Oncology, Washington University School of Medicine, St Louis, MO, USA.
authors.forename: Ellen X
authors.initials: EX
authors.lastname: Huang
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Bradley
authors.forename: Issam
authors.initials: I
authors.lastname: El Naqa
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Hope
authors.forename: Patricia E
authors.initials: PE
authors.lastname: Lindsay
authors.forename: Walter R
authors.initials: WR
authors.lastname: Bosch
authors.forename: John W
authors.initials: JW
authors.lastname: Matthews
authors.forename: William T
authors.initials: WT
authors.lastname: Sause
authors.forename: Mary V
authors.initials: MV
authors.lastname: Graham
authors.forename: Joseph O
authors.initials: JO
authors.lastname: Deasy
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000532:radiotherapy*; D015331:Cohort Studies; D004941:Esophagitis / Q000209:etiology*; D004947:Esophagus / Q000528:radiation effects*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D011832:Radiation Injuries / Q000150:complications*; D011879:Radiotherapy Dosage; D012306:Risk; D012737:Sex Factors; D047368:Tumor Burden; D015431:Weight Loss