title: Combining physical and biologic parameters to predict radiation-induced lung toxicity in patients with non-small-cell lung cancer treated with definitive radiation therapy.
abstract: OBJECTIVE
  To investigate the plasma dynamics of 5 proinflammatory/fibrogenic cytokines, including interleukin-1beta (IL-1β), IL-6, IL-8, tumor necrosis factor alpha (TNF-α), and transforming growth factor beta1 (TGF-β1) to ascertain their value in predicting radiation-induced lung toxicity (RILT), both individually and in combination with physical dosimetric parameters.
  
  
  METHODS
  Treatments of patients receiving definitive conventionally fractionated radiation therapy (RT) on clinical trial for inoperable stages I-III lung cancer were prospectively evaluated. Circulating cytokine levels were measured prior to and at weeks 2 and 4 during RT. The primary endpoint was symptomatic RILT, defined as grade 2 and higher radiation pneumonitis or symptomatic pulmonary fibrosis. Minimum follow-up was 18 months.
  
  
  RESULTS
  Of 58 eligible patients, 10 (17.2%) patients developed RILT. Lower pretreatment IL-8 levels were significantly correlated with development of RILT, while radiation-induced elevations of TGF-ß1 were weakly correlated with RILT. Significant correlations were not found for any of the remaining 3 cytokines or for any clinical or dosimetric parameters. Using receiver operator characteristic curves for predictive risk assessment modeling, we found both individual cytokines and dosimetric parameters were poor independent predictors of RILT. However, combining IL-8, TGF-ß1, and mean lung dose into a single model yielded an improved predictive ability (P<.001) compared to either variable alone.
  
  
  CONCLUSIONS
  Combining inflammatory cytokines with physical dosimetric factors may provide a more accurate model for RILT prediction. Future study with a larger number of cases and events is needed to validate such findings.
authors.affiliation: Department of Radiation Oncology, University of Michigan Medical Center, Ann Arbor, Michigan 48109, USA.
authors.forename: Matthew H
authors.initials: MH
authors.lastname: Stenmark
authors.forename: Xu-Wei
authors.initials: XW
authors.lastname: Cai
authors.forename: Kerby
authors.initials: K
authors.lastname: Shedden
authors.forename: James A
authors.initials: JA
authors.lastname: Hayman
authors.forename: Shuanghu
authors.initials: S
authors.lastname: Yuan
authors.forename: Timothy
authors.initials: T
authors.lastname: Ritter
authors.forename: Randall K
authors.initials: RK
authors.lastname: Ten Haken
authors.forename: Theodore S
authors.initials: TS
authors.lastname: Lawrence
authors.forename: Feng-Ming Spring
authors.initials: FM
authors.lastname: Kong
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy*; D016207:Cytokines / Q000097:blood*; D019583:Dose Fractionation, Radiation; D005260:Female; D006801:Humans; D053583:Interleukin-1beta / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D008168:Lung / Q000528:radiation effects*; D008175:Lung Neoplasms / Q000097:blood / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011832:Radiation Injuries / Q000175:diagnosis*; D020266:Radiotherapy, Conformal / Q000009:adverse effects / Q000379:methods; D053773:Transforming Growth Factor beta1 / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D014408:Biomarkers, Tumor; D016207:Cytokines; D053583:Interleukin-1beta; D015850:Interleukin-6; D016209:Interleukin-8; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha