title: Comparison of radiation-induced normal lung tissue density changes for patients from multiple institutions receiving conventional or hypofractionated treatments.
abstract: OBJECTIVE
  To quantitatively assess changes in computed tomography (CT)-defined normal lung tissue density after conventional and hypofractionated radiation therapy (RT).
  
  
  METHODS
  The pre-RT and post-RT CT scans from 118 and 111 patients receiving conventional and hypofractionated RT, respectively, at 3 institutions were registered to each other and to the 3-dimensional dose distribution to quantify dose-dependent changes in normal lung tissue density. Dose-response curves (DRC) for groups of patients receiving conventional and hypofractionated RT were generated for each institution, and the frequency of density changes >80 Hounsfield Units (HU) was modeled depending on the fractionation type using a Probit model for different follow-up times.
  
  
  RESULTS
  For the pooled data from all institutions, there were significant differences in the DRC between the conventional and hypofractionated groups; the respective doses resulting in 50% complication risk (TD50) were 62 Gy (95% confidence interval [CI] 57-67) versus 36 Gy (CI 33-39) at <6 months, 48 Gy (CI 46-51) versus 31 Gy (CI 28-33) at 6-12 months, and 47 Gy (CI 45-49) versus 35 Gy (32-37) at >12 months. The corresponding m values (slope of the DRC) were 0.52 (CI 0.46-0.59) versus 0.31 (CI 0.28-0.34) at <6 months, 0.46 (CI 0.42-0.51) versus 0.30 (CI 0.26-0.34) at 6-12 months, and 0.45 (CI 0.42-0.50) versus 0.31 (CI 0.27-0.35) at >12 months (P<.05 for all comparisons).
  
  
  CONCLUSIONS
  Compared with conventional fractionation, hypofractionation has a lower TD50 and m value, both suggesting an increased degree of normal tissue density sensitivity with hypofractionation.
authors.affiliation: Department of Radiation Oncology, University of Colorado School of Medicine, Aurora, Colorado. Electronic address: quentin.diot@ucdenver.edu.
authors.forename: Quentin
authors.initials: Q
authors.lastname: Diot
authors.affiliation: Department of Radiation Oncology, University of North Carolina, Chapel Hill, North Carolina.
authors.forename: Lawrence B
authors.initials: LB
authors.lastname: Marks
authors.affiliation: Division of Biostatistics and Bioinformatics, University of Maryland Greenbaum Cancer Center, and Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, Maryland.
authors.forename: Soren M
authors.initials: SM
authors.lastname: Bentzen
authors.affiliation: Department of Radiation Oncology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Suresh
authors.initials: S
authors.lastname: Senan
authors.affiliation: Department of Radiation Oncology, University of Colorado School of Medicine, Aurora, Colorado.
authors.forename: Brian D
authors.initials: BD
authors.lastname: Kavanagh
authors.affiliation: Department of Radiation Oncology, University of North Carolina, Chapel Hill, North Carolina.
authors.forename: Michael V
authors.initials: MV
authors.lastname: Lawrence
authors.affiliation: Department of Radiation Oncology, University of Colorado School of Medicine, Aurora, Colorado.
authors.forename: Moyed
authors.initials: M
authors.lastname: Miften
authors.affiliation: London Regional Cancer Program, London, Ontario, Canada.
authors.forename: David A
authors.initials: DA
authors.lastname: Palma
mesh_terms: D000465:Algorithms; D002289:Carcinoma, Non-Small-Cell Lung / Q000000981:diagnostic imaging / Q000532:radiotherapy*; D003120:Colorado; D019583:Dose Fractionation, Radiation; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D008168:Lung / Q000000981:diagnostic imaging / Q000528:radiation effects*; D008175:Lung Neoplasms / Q000188:drug therapy / Q000532:radiotherapy*; D009426:Netherlands; D009657:North Carolina; D011832:Radiation Injuries / Q000000981:diagnostic imaging; D011880:Radiotherapy Planning, Computer-Assisted / Q000379:methods; D020266:Radiotherapy, Conformal / Q000379:methods; D014057:Tomography, X-Ray Computed