title: A literature-based meta-analysis of clinical risk factors for development of radiation induced pneumonitis.
abstract: BACKGROUND
  The risk of developing side effects after radiotherapy is not only dependent on radiation dose, but may also be affected by patient-related risk factors. Here we perform a literature-based meta-analysis to estimate the effect of various clinical risk factors on the incidence of symptomatic radiation pneumonitis (RP).
  
  
  METHODS
  A systematic review of English language articles in the Pubmed, Embase and Cochrane controlled trials registers. Studies with the mesh term "radiation pneumonitis" or the search term "radiation pneumonitis" were included. Additional studies were identified by manual searching of the references. Studies reporting crude incidence or odds ratios (OR) for radiation pneumonitis vs. age, disease location, smoking status, chemotherapy schedule or comorbidity were included. A systematic overview (meta-analysis) was conducted to synthesize data across multiple studies.
  
  
  RESULTS
  Significant risk factors for RP were: older age (OR = 1.7, p < 0.0001); disease located in mid-lower lung (OR = 1.9, p = 0.002); presence of comorbidity (OR = 2.3, p = 0.007). Ongoing smoking was found to protect against RP (OR = 0.6, p = 0.008). History of smoking tended to protect against RP (OR = 0.7, p = 0.06). Sequential (rather than concomitant) chemotherapy scheduling (OR = 1.6, p = 0.01) increased RP risk, but treatment intensity and patients selection are likely confounders.
  
  
  CONCLUSIONS
  This systematic overview revealed several clinical risk factors for RP that have not been unambiguously identified in the literature. These risk factors should be considered when defining dose-volume constraints for radiation treatment plan optimization.
authors.affiliation: Department of Radiation Oncology, Rigshospitalet, University of Copenhagen, Denmark.
authors.forename: Ivan R
authors.initials: IR
authors.lastname: Vogelius
authors.forename: Søren M
authors.initials: SM
authors.lastname: Bentzen
mesh_terms: D000328:Adult; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000532:radiotherapy*; D015897:Comorbidity; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D015994:Incidence; D008019:Life Style; D008175:Lung Neoplasms / Q000532:radiotherapy*; D008875:Middle Aged; D017564:Radiation Pneumonitis / Q000209:etiology*; D011879:Radiotherapy Dosage; D018570:Risk Assessment; D012307:Risk Factors