title: Lack of a dose-effect relationship for pulmonary function changes after stereotactic body radiation therapy for early-stage non-small cell lung cancer.
abstract: OBJECTIVE
  To evaluate the influence of tumor size, prescription dose, and dose to the lungs on posttreatment pulmonary function test (PFT) changes after stereotactic body radiation therapy (SBRT) for early-stage non-small cell lung cancer (NSCLC).
  
  
  METHODS
  The analysis is based on 191 patients treated at 5 international institutions: inclusion criteria were availability of pre- and post-SBRT PFTs and dose-volume histograms of the lung and planning target volume (PTV); patients treated with more than 1 SBRT course were excluded. Correlation between early (1-6 months, median 3 months) and late (7-24 months, median 12 months) PFT changes and tumor size, planning target volume (PTV) dose, and lung doses was assessed using linear regression analysis, receiver operating characteristics analysis, and Lyman's normal tissue complication probability model. The PTV doses were converted to biologically effective doses and lung doses to 2 Gy equivalent doses before correlation analyses.
  
  
  RESULTS
  Up to 6 months after SBRT, forced expiratory volume in 1 second and carbon monoxide diffusion capacity changed by -1.4% (95% confidence interval [CI], -3.4% to 0) and -7.6% (95% CI, -10.2% to -3.4%) compared with pretreatment values, respectively. A modest decrease in PFTs was observed 7-24 months after SBRT, with changes of -8.1% (95% CI, -13.3% to -5.3%) and -12.4% (95% CI, -15.5% to -6.9%), respectively. Using linear regression analysis, receiver operating characteristic analysis, and normal tissue complication probability modeling, all evaluated parameters of tumor size, PTV dose, mean lung dose, and absolute and relative volumes of the lung exposed to minimum doses of 5-70 Gy were not correlated with early and late PFT changes. Subgroup analysis based on pre-SBRT PFTs (greater or equal and less than median) did not identify any dose-effect relationship.
  
  
  CONCLUSIONS
  This study failed to demonstrate a significant dose-effect relationship for changes of pulmonary function after SBRT for early-stage non-small cell lung cancer.
authors.affiliation: Department of Radiation Oncology, University Hospital Wuerzburg, Wuerzburg, Germany. Guckenberger_M@klinik.uni-wuerzburg.de
authors.forename: Matthias
authors.initials: M
authors.lastname: Guckenberger
authors.forename: Rainer J
authors.initials: RJ
authors.lastname: Klement
authors.forename: Larry L
authors.initials: LL
authors.lastname: Kestin
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Hope
authors.forename: Jose
authors.initials: J
authors.lastname: Belderbos
authors.forename: Maria
authors.initials: M
authors.lastname: Werner-Wasik
authors.forename: Di
authors.initials: D
authors.lastname: Yan
authors.forename: Jan-Jakob
authors.initials: JJ
authors.lastname: Sonke
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Bissonnette
authors.forename: Ying
authors.initials: Y
authors.lastname: Xiao
authors.forename: Inga S
authors.initials: IS
authors.lastname: Grills
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D002248:Carbon Monoxide / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005541:Forced Expiratory Volume / Q000502:physiology / Q000528:radiation effects; D006801:Humans; D016014:Linear Models; D008168:Lung / Q000502:physiology / Q000528:radiation effects*; D008175:Lung Neoplasms / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D011653:Pulmonary Diffusing Capacity / Q000502:physiology / Q000528:radiation effects; D011859:Radiography; D016634:Radiosurgery / Q000379:methods*; D011880:Radiotherapy Planning, Computer-Assisted / Q000379:methods; D012189:Retrospective Studies; D047368:Tumor Burden / Q000502:physiology
chemical_list: D002248:Carbon Monoxide