title: Systematic review evaluating the timing of thoracic radiation therapy in combined modality therapy for limited-stage small-cell lung cancer.
abstract: OBJECTIVE
  We employed meta-analytic techniques to evaluate early (E) versus late (L) timing of thoracic radiation therapy (RT) in limited-stage small-cell lung cancer (LS-SCLC). In addition, we assessed the impact of radiation fractionation and chemotherapeutic regimen on timing.
  
  
  METHODS
  Randomized trials published after 1985 addressing timing of RT relative to chemotherapy in LS-SCLC were included. Trials were analyzed by risk ratio (RR), risk difference, and number-needed-to-treat methods.
  
  
  RESULTS
  Overall survival (OS) RRs for all studies were 1.17 at 2 years (95% CI, 1.02 to 1.35; P = .03) and 1.13 at 3 years (95% CI, 0.92 to 1.39; P = .2), indicating a significantly increased 2-year survival for ERT versus LRT patients and suggestive of a similar trend at 3 years. Subset analysis of studies using hyperfractionated RT revealed OS RR for ERT versus LRT of 1.44 (95% CI, 1.17 to 1.77; P = .001) and 1.39 (95% CI, 1.02 to 1.90; P = .04) at 2 and 3 years, respectively, indicating a survival benefit of ERT versus LRT. Studies using once-daily fractionation showed no difference in 2- and 3-year OS RRs for ERT compared with LRT. Studies using platinum-based chemotherapy had OS RRs of 1.30 (95% CI, 1.10 to 1.53; P = .002) and 1.35 (95% CI, 1.07 to 1.70; P = .01) at 2 and 3 years, respectively, favoring ERT. Studies using nonplatinum-based chemotherapy regimens had nonsignificant differences in OS.
  
  
  CONCLUSIONS
  A small but significant improvement in 2-year OS for ERT versus LRT in LS-SCLC was observed, similar to the benefit of adding RT to chemotherapy or prophylactic cranial irradiation. A greater difference was evident for hyperfractionated RT and platinum-based chemotherapy.
authors.affiliation: Multidisciplinary Thoracic Oncology Program, Lineberger Comprehensive Cancer Center, Department of Epidemiology, School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. friedd@med.unc.edu
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Fried
authors.forename: David E
authors.initials: DE
authors.lastname: Morris
authors.forename: Charles
authors.initials: C
authors.lastname: Poole
authors.forename: Julian G
authors.initials: JG
authors.lastname: Rosenman
authors.forename: Jan S
authors.initials: JS
authors.lastname: Halle
authors.forename: Frank C
authors.initials: FC
authors.lastname: Detterbeck
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Hensing
authors.forename: Mark A
authors.initials: MA
authors.lastname: Socinski
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000401:mortality* / Q000473:pathology / Q000532:radiotherapy* / Q000628:therapy; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D016001:Confidence Intervals; D019583:Dose Fractionation, Radiation; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D008175:Lung Neoplasms / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy* / Q000628:therapy; D009367:Neoplasm Staging; D016017:Odds Ratio; D011013:Pneumonectomy / Q000379:methods; D011379:Prognosis; D011879:Radiotherapy Dosage; D018714:Radiotherapy, Adjuvant; D016032:Randomized Controlled Trials as Topic; D018570:Risk Assessment; D016019:Survival Analysis; D016896:Treatment Outcome