title: Meta-analysis of concomitant versus sequential radiochemotherapy in locally advanced non-small-cell lung cancer.
abstract: OBJECTIVE
  The previous individual patient data meta-analyses of chemotherapy in locally advanced non-small-cell lung cancer (NSCLC) showed that adding sequential or concomitant chemotherapy to radiotherapy improved survival. The NSCLC Collaborative Group performed a meta-analysis of randomized trials directly comparing concomitant versus sequential radiochemotherapy.
  
  
  METHODS
  Systematic searches for trials were undertaken, followed by central collection, checking, and reanalysis of updated individual patient data. Results from trials were combined using the stratified log-rank test to calculate pooled hazard ratios (HRs). The primary outcome was overall survival; secondary outcomes were progression-free survival, cumulative incidences of locoregional and distant progression, and acute toxicity.
  
  
  RESULTS
  Of seven eligible trials, data from six trials were received (1,205 patients, 92% of all randomly assigned patients). Median follow-up was 6 years. There was a significant benefit of concomitant radiochemotherapy on overall survival (HR, 0.84; 95% CI, 0.74 to 0.95; P = .004), with an absolute benefit of 5.7% (from 18.1% to 23.8%) at 3 years and 4.5% at 5 years. For progression-free survival, the HR was 0.90 (95% CI, 0.79 to 1.01; P = .07). Concomitant treatment decreased locoregional progression (HR, 0.77; 95% CI, 0.62 to 0.95; P = .01); its effect was not different from that of sequential treatment on distant progression (HR, 1.04; 95% CI, 0.86 to 1.25; P = .69). Concomitant radiochemotherapy increased acute esophageal toxicity (grade 3-4) from 4% to 18% with a relative risk of 4.9 (95% CI, 3.1 to 7.8; P < .001). There was no significant difference regarding acute pulmonary toxicity.
  
  
  CONCLUSIONS
  Concomitant radiochemotherapy, as compared with sequential radiochemotherapy, improved survival of patients with locally advanced NSCLC, primarily because of a better locoregional control, but at the cost of manageable increased acute esophageal toxicity.
authors.affiliation: Unit of Biostatistics and Epidemiology, Institut Gustave-Roussy, 94805 Villejuif Cedex, France. auperin@igr.fr
authors.forename: Anne
authors.initials: A
authors.lastname: Aupérin
authors.forename: Cecile
authors.initials: C
authors.lastname: Le Péchoux
authors.forename: Estelle
authors.initials: E
authors.lastname: Rolland
authors.forename: Walter J
authors.initials: WJ
authors.lastname: Curran
authors.forename: Kiyoyuki
authors.initials: K
authors.lastname: Furuse
authors.forename: Pierre
authors.initials: P
authors.lastname: Fournel
authors.forename: Jose
authors.initials: J
authors.lastname: Belderbos
authors.forename: Gerald
authors.initials: G
authors.lastname: Clamon
authors.forename: Hakki Cuneyt
authors.initials: HC
authors.lastname: Ulutin
authors.forename: Rebecca
authors.initials: R
authors.lastname: Paulus
authors.forename: Takeharu
authors.initials: T
authors.lastname: Yamanaka
authors.forename: Marie-Cecile
authors.initials: MC
authors.lastname: Bozonnat
authors.forename: Apollonia
authors.initials: A
authors.lastname: Uitterhoeve
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Wang
authors.forename: Lesley
authors.initials: L
authors.lastname: Stewart
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Arriagada
authors.forename: Sarah
authors.initials: S
authors.lastname: Burdett
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Pignon
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D017024:Chemotherapy, Adjuvant; D016009:Chi-Square Distribution; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D004947:Esophagus / Q000187:drug effects / Q000528:radiation effects; D019317:Evidence-Based Medicine; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011829:Radiation Dosage; D018714:Radiotherapy, Adjuvant / Q000009:adverse effects; D016032:Randomized Controlled Trials as Topic; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents