title: [¹⁸F]fluorodeoxyglucose uptake patterns in lung before radiotherapy identify areas more susceptible to radiation-induced lung toxicity in non-small-cell lung cancer patients.
abstract: OBJECTIVE
  Our hypothesis was that pretreatment inflammation in the lung makes pulmonary tissue more susceptible to radiation damage. The relationship between pretreatment [(18)F]fluorodeoxyglucose ([(18)F]FDG) uptake in the lungs (as a surrogate for inflammation) and the delivered radiation dose and radiation-induced lung toxicity (RILT) was investigated.
  
  
  METHODS
  We retrospectively studied a prospectively obtained cohort of 101 non-small-cell lung cancer patients treated with (chemo)radiation therapy (RT). [(18)F]FDG-positron emission tomography-computed tomography (PET-CT) scans used for treatment planning were studied. Different parameters were used to describe [(18)F]FDG uptake patterns in the lungs, excluding clinical target volumes, and the interaction with radiation dose. An increase in the dyspnea grade of 1 (Common Terminology Criteria for Adverse Events version 3.0) or more points compared to the pre-RT score was used as an endpoint for analysis of RILT. The effect of [(18)F]FDG and CT-based variables, dose, and other patient or treatment characteristics that effected RILT was studied using logistic regression.
  
  
  RESULTS
  Increased lung density and pretreatment [(18)F]FDG uptake were related to RILT after RT with univariable logistic regression. The 95th percentile of the [(18)F]FDG uptake in the lungs remained significant in multivariable logistic regression (p = 0.016; odds ratio [OR] = 4.3), together with age (p = 0.029; OR = 1.06), and a pre-RT dyspnea score of ≥1 (p = 0.005; OR = 0.20). Significant interaction effects were demonstrated among the 80th, 90th, and 95th percentiles and the relative lung volume receiving more than 2 and 5 Gy.
  
  
  CONCLUSIONS
  The risk of RILT increased with the 95th percentile of the [(18)F]FDG uptake in the lungs, excluding clinical tumor volume (OR = 4.3). The effect became more pronounced as the fraction of the 5%, 10%, and 20% highest standardized uptake value voxels that received more than 2 Gy to 5 Gy increased. Therefore, the risk of RILT may be decreased by applying sophisticated radiotherapy techniques to avoid areas in the lung with high [(18)F]FDG uptake.
authors.affiliation: Department of Radiation Oncology (MAASTRO), GROW-School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, The Netherlands. steven.petit@maastro.nl
authors.forename: Steven F
authors.initials: SF
authors.lastname: Petit
authors.forename: Wouter J C
authors.initials: WJ
authors.lastname: van Elmpt
authors.forename: Cary J G
authors.initials: CJ
authors.lastname: Oberije
authors.forename: Erik
authors.initials: E
authors.lastname: Vegt
authors.forename: Anne-Marie C
authors.initials: AM
authors.lastname: Dingemans
authors.forename: Philippe
authors.initials: P
authors.lastname: Lambin
authors.forename: André L A J
authors.initials: AL
authors.lastname: Dekker
authors.forename: Dirk
authors.initials: D
authors.lastname: De Ruysscher
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000532:radiotherapy; D059248:Chemoradiotherapy; D004417:Dyspnea / Q000209:etiology; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D006801:Humans; D016015:Logistic Models; D008168:Lung / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000528:radiation effects; D008175:Lung Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000532:radiotherapy; D008297:Male; D008875:Middle Aged; D064847:Multimodal Imaging / Q000379:methods; D016017:Odds Ratio; D049268:Positron-Emission Tomography; D017564:Radiation Pneumonitis / Q000000981:diagnostic imaging* / Q000378:metabolism; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D012189:Retrospective Studies; D014057:Tomography, X-Ray Computed
chemical_list: D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18