title: Objectively Quantifying Radiation Esophagitis With Novel Computed Tomography-Based Metrics.
abstract: OBJECTIVE
  To study radiation-induced esophageal expansion as an objective measure of radiation esophagitis in patients with non-small cell lung cancer (NSCLC) treated with intensity modulated radiation therapy.
  
  
  METHODS
  Eighty-five patients had weekly intra-treatment CT imaging and esophagitis scoring according to Common Terminlogy Criteria for Adverse Events 4.0, (24 Grade 0, 45 Grade 2, and 16 Grade 3). Nineteen esophageal expansion metrics based on mean, maximum, spatial length, and volume of expansion were calculated as voxel-based relative volume change, using the Jacobian determinant from deformable image registration between the planning and weekly CTs. An anatomic variability correction method was validated and applied to these metrics to reduce uncertainty. An analysis of expansion metrics and radiation esophagitis grade was conducted using normal tissue complication probability from univariate logistic regression and Spearman rank for grade 2 and grade 3 esophagitis endpoints, as well as the timing of expansion and esophagitis grade. Metrics' performance in classifying esophagitis was tested with receiver operating characteristic analysis.
  
  
  RESULTS
  Expansion increased with esophagitis grade. Thirteen of 19 expansion metrics had receiver operating characteristic area under the curve values >0.80 for both grade 2 and grade 3 esophagitis endpoints, with the highest performance from maximum axial expansion (MaxExp1) and esophageal length with axial expansion ≥30% (LenExp30%) with area under the curve values of 0.93 and 0.91 for grade 2, 0.90 and 0.90 for grade 3 esophagitis, respectively.
  
  
  CONCLUSIONS
  Esophageal expansion may be a suitable objective measure of esophagitis, particularly maximum axial esophageal expansion and esophageal length with axial expansion ≥30%, with 2.1 Jacobian value and 98.6 mm as the metric value for 50% probability of grade 3 esophagitis. The uncertainty in esophageal Jacobian calculations can be reduced with anatomic correction methods.
authors.affiliation: Department of Radiation Physics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas; University of Texas Houston Graduate School of Biomedical Science, Houston, Texas. Electronic address: jsniedzielski@mdanderson.org.
authors.forename: Joshua S
authors.initials: JS
authors.lastname: Niedzielski
authors.affiliation: Department of Radiation Physics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas; University of Texas Houston Graduate School of Biomedical Science, Houston, Texas.
authors.forename: Jinzhong
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Biostatistics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas.
authors.forename: Francesco
authors.initials: F
authors.lastname: Stingo
authors.affiliation: Department of Radiation Physics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas; University of Texas Houston Graduate School of Biomedical Science, Houston, Texas.
authors.forename: Mary K
authors.initials: MK
authors.lastname: Martel
authors.affiliation: Department of Radiation Physics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas; University of Texas Houston Graduate School of Biomedical Science, Houston, Texas.
authors.forename: Radhe
authors.initials: R
authors.lastname: Mohan
authors.affiliation: Department of Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Gomez
authors.affiliation: Department of Radiation Physics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas; University of Texas Houston Graduate School of Biomedical Science, Houston, Texas.
authors.forename: Tina M
authors.initials: TM
authors.lastname: Briere
authors.affiliation: Department of Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas.
authors.forename: Zhongxing
authors.initials: Z
authors.lastname: Liao
authors.affiliation: Department of Radiation Physics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas; University of Texas Houston Graduate School of Biomedical Science, Houston, Texas.
authors.forename: Laurence E
authors.initials: LE
authors.lastname: Court
mesh_terms: D019540:Area Under Curve; D002289:Carcinoma, Non-Small-Cell Lung / Q000532:radiotherapy; D004941:Esophagitis / Q000000981:diagnostic imaging* / Q000209:etiology / Q000473:pathology; D004947:Esophagus / Q000000981:diagnostic imaging / Q000473:pathology / Q000528:radiation effects; D006801:Humans; D016015:Logistic Models; D008175:Lung Neoplasms / Q000532:radiotherapy; D009929:Organ Size; D011336:Probability; D012372:ROC Curve; D011832:Radiation Injuries / Q000000981:diagnostic imaging* / Q000473:pathology; D014057:Tomography, X-Ray Computed / Q000379:methods*; D035501:Uncertainty