title: Predictors of high-grade esophagitis after definitive three-dimensional conformal therapy, intensity-modulated radiation therapy, or proton beam therapy for non-small cell lung cancer.
abstract: BACKGROUND
  We analyzed the ability of various patient- and treatment-related factors to predict radiation-induced esophagitis (RE) in patients with non-small cell lung cancer (NSCLC) treated with three-dimensional conformal radiation therapy (3D-CRT), intensity-modulated radiation therapy (IMRT), or proton beam therapy (PBT).
  
  
  METHODS
  Patients were treated for NSCLC with 3D-CRT, IMRT, or PBT at MD Anderson from 2000 to 2008 and had full dose-volume histogram (DVH) data available. The endpoint was severe (grade≥3) RE. The Lyman-Kutcher-Burman (LKB) model was used to analyze RE as a function of the fractional esophageal DVH, with clinical variables included as dose-modifying factors.
  
  
  RESULTS
  Overall, 652 patients were included: 405 patients were treated with 3D-CRT, 139 with IMRT, and 108 with PBT; corresponding rates of grade≥3 RE were 8%, 28%, and 6%, respectively, with a median time to onset of 42 days (range, 11-93 days). A fit of the fractional DVH LKB model demonstrated that the fractional effective dose was significantly different (P=.046) than 1 (fractional mean dose) indicating that high doses to small volumes are more predictive than mean esophageal dose. The model fit was better for 3D-CRT and PBT than for IMRT. Including receipt of concurrent chemotherapy as a dose-modifying factor significantly improved the LKB model (P=.005), and the model was further improved by including a variable representing treatment with >30 fractions. Examining individual types of chemotherapy agents revealed a trend toward receipt of concurrent taxanes and increased risk of RE (P=.105).
  
  
  CONCLUSIONS
  Fractional dose (dose rate) and number of fractions (total dose) distinctly affect the risk of severe RE, estimated using the LKB model, and concurrent chemotherapy improves the model fit. This risk of severe RE is underestimated by this model in patients receiving IMRT.
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77054, USA. dgomez@mdanderson.org
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Gomez
authors.forename: Susan L
authors.initials: SL
authors.lastname: Tucker
authors.forename: Mary K
authors.initials: MK
authors.lastname: Martel
authors.forename: Radhe
authors.initials: R
authors.lastname: Mohan
authors.forename: Peter A
authors.initials: PA
authors.lastname: Balter
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Lopez Guerra
authors.forename: Hongmei
authors.initials: H
authors.lastname: Liu
authors.forename: Ritsuko
authors.initials: R
authors.lastname: Komaki
authors.forename: James D
authors.initials: JD
authors.lastname: Cox
authors.forename: Zhongxing
authors.initials: Z
authors.lastname: Liao
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000532:radiotherapy*; D004941:Esophagitis / Q000209:etiology*; D005260:Female; D006801:Humans; D060828:Induction Chemotherapy / Q000379:methods; D008175:Lung Neoplasms / Q000188:drug therapy / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D061766:Proton Therapy / Q000009:adverse effects*; D011879:Radiotherapy Dosage; D020266:Radiotherapy, Conformal / Q000009:adverse effects* / Q000379:methods; D050397:Radiotherapy, Intensity-Modulated / Q000009:adverse effects* / Q000379:methods