title: Time between the first day of chemotherapy and the last day of chest radiation is the most important predictor of survival in limited-disease small-cell lung cancer.
abstract: OBJECTIVE
  To identify time factors for combined chemotherapy and radiotherapy predictive for long-term survival of patients with limited-disease small-cell lung cancer (LD-SCLC).
  
  
  METHODS
  A systematic overview identified suitable phase III trials. Using meta-analysis methodology to compare results within trials, the influence of the timing of chest radiation and the start of any treatment until the end of radiotherapy (SER) on local tumor control, survival, and esophagitis was analyzed. For comparison between studies, the equivalent radiation dose in 2-Gy fractions, corrected for the overall treatment time of chest radiotherapy, was analyzed.
  
  
  RESULTS
  The SER was the most important predictor of outcome. There was a significantly higher 5-year survival rate in the shorter SER arms (relative risk [RR] = 0.62; 95% CI, 0.49 to 0.80; P = .0003), which was more than 20% when the SER was less than 30 days (upper bound of 95% CI, 90 days). A low SER was associated with a higher incidence of severe esophagitis (RR = 0.55; 95% CI, 0.42 to 073; P < .0001). Each week of extension of the SER beyond that of the study arm with the shortest SER resulted in an overall absolute decrease in the 5-year survival rate of 1.83% +/- 0.18% (95% CI).
  
  
  CONCLUSIONS
  A low time between the first day of chemotherapy and the last day of chest radiotherapy is associated with improved survival in LD-SCLC patients. The novel parameter SER, which takes into account accelerated proliferation of tumor clonogens during both radiotherapy and chemotherapy, may facilitate a more rational design of combined-modality treatment in rapidly proliferating tumors.
authors.affiliation: Department of Radiotherapy, University Hospital Maastricht, University Maastricht, Groel en Ontwikkeling, The Netherlands. dirk.deruysscher@maastro.nl
authors.forename: Dirk
authors.initials: D
authors.lastname: De Ruysscher
authors.forename: Madelon
authors.initials: M
authors.lastname: Pijls-Johannesma
authors.forename: Søren M
authors.initials: SM
authors.lastname: Bentzen
authors.forename: André
authors.initials: A
authors.lastname: Minken
authors.forename: Rinus
authors.initials: R
authors.lastname: Wanders
authors.forename: Ludy
authors.initials: L
authors.lastname: Lutgens
authors.forename: Monique
authors.initials: M
authors.lastname: Hochstenbag
authors.forename: Liesbeth
authors.initials: L
authors.lastname: Boersma
authors.forename: Bradly
authors.initials: B
authors.lastname: Wouters
authors.forename: Guido
authors.initials: G
authors.lastname: Lammering
authors.forename: Johan
authors.initials: J
authors.lastname: Vansteenkiste
authors.forename: Philippe
authors.initials: P
authors.lastname: Lambin
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D018288:Carcinoma, Small Cell / Q000188:drug therapy* / Q000532:radiotherapy*; D017024:Chemotherapy, Adjuvant / Q000379:methods*; D017326:Clinical Trials, Phase III as Topic; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011237:Predictive Value of Tests; D011379:Prognosis; D011879:Radiotherapy Dosage; D018714:Radiotherapy, Adjuvant / Q000379:methods*; D016032:Randomized Controlled Trials as Topic; D016019:Survival Analysis; D013997:Time Factors