title: Predicting pneumonitis risk: a dosimetric alternative to mean lung dose.
abstract: OBJECTIVE
  To determine whether the association between mean lung dose (MLD) and risk of severe (grade ≥3) radiation pneumonitis (RP) depends on the dose distribution pattern to normal lung among patients receiving 3-dimensional conformal radiation therapy for non-small-cell lung cancer.
  
  
  METHODS
  Three cohorts treated with different beam arrangements were identified. One cohort (2-field boost [2FB]) received 2 parallel-opposed (anteroposterior-posteroanterior) fields per fraction initially, followed by a sequential boost delivered using 2 oblique beams. The other 2 cohorts received 3 or 4 straight fields (3FS and 4FS, respectively), ie, all fields were irradiated every day. The incidence of severe RP was plotted against MLD in each cohort, and data were analyzed using the Lyman-Kutcher-Burman (LKB) model.
  
  
  RESULTS
  The incidence of grade ≥3 RP rose more steeply as a function of MLD in the 2FB cohort (N=120) than in the 4FS cohort (N=138), with an intermediate slope for the 3FS group (N=99). The estimated volume parameter from the LKB model was n=0.41 (95% confidence interval, 0.15-1.0) and led to a significant improvement in fit (P=.05) compared to a fit with volume parameter fixed at n=1 (the MLD model). Unlike the MLD model, the LKB model with n=0.41 provided a consistent description of the risk of severe RP in all three cohorts (2FB, 3FS, 4FS) simultaneously.
  
  
  CONCLUSIONS
  When predicting risk of grade ≥3 RP, the mean lung dose does not adequately take into account the effects of high doses. Instead, the effective dose, computed from the LKB model using volume parameter n=0.41, may provide a better dosimetric parameter for predicting RP risk. If confirmed, these findings support the conclusion that for the same MLD, high doses to small lung volumes ("a lot to a little") are worse than low doses to large volumes ("a little to a lot").
authors.affiliation: Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77230-1402, USA. sltucker@mdanderson.org
authors.forename: Susan L
authors.initials: SL
authors.lastname: Tucker
authors.forename: Radhe
authors.initials: R
authors.lastname: Mohan
authors.forename: Raweewan
authors.initials: R
authors.lastname: Liengsawangwong
authors.forename: Mary K
authors.initials: MK
authors.lastname: Martel
authors.forename: Zhongxing
authors.initials: Z
authors.lastname: Liao
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000532:radiotherapy*; D015331:Cohort Studies; D006801:Humans; D015994:Incidence; D008168:Lung / Q000528:radiation effects*; D008175:Lung Neoplasms / Q000532:radiotherapy*; D017564:Radiation Pneumonitis / Q000453:epidemiology / Q000209:etiology* / Q000473:pathology; D011879:Radiotherapy Dosage; D020266:Radiotherapy, Conformal / Q000009:adverse effects* / Q000379:methods; D012189:Retrospective Studies; D018570:Risk Assessment