title: Dose escalation for non-small cell lung cancer: analysis and modelling of published literature.
abstract: OBJECTIVE
  To review the published clinical data on non-small cell lung cancer treated with radical radiotherapy to confirm a dose-response relationship as a basis for further dose-escalation trials.
  
  
  METHODS
  Twenty-four published clinical trials were identified, 16 of which - with 29 different standard, hyper- and hypofractionated treatment schedules - were analysed. Prescription doses were converted to biologically-equivalent dose (BED), with a correction for repopulation. Disease-free survival data were corrected for the stage profile of each cohort to allow better comparison of results. We also analysed moderate (grade II and III) lung and oesophageal acute toxicity related to the corrected BED delivered to the tumour.
  
  
  RESULTS
  The clinical data analysed showed good agreement between the observed and modelled disease-free survival at 2 years when compared to the published models of Fenwick (correlation coefficient 0.525, p=0.003) and Martel (correlation coefficient 0.492, p=0.007), indicating a clear tumour dose-response. In the normally fractionated treatments (∼ 2 Gy per fraction), improved disease-free survival was generally observed in the shorter schedules (maximum around 6 weeks). However, the best outcomes were obtained for the hypofractionated schedules. No systematic relationship was seen between prescribed dose and lung or oesophageal acute toxicity, possibly due to dose selection depending on V(20) or MLD in some studies and the diversity of the patients analysed.
  
  
  CONCLUSIONS
  We have demonstrated a dose-response relationship for NSCLC based on clinical data. The clinical data provide a rational basis for selection of dose escalation schedules to be tested in future randomised trials.
authors: The Institute of Cancer Research, Sutton, UK. m.partridge@physics.org
authors: Mike
authors: M
authors: Partridge
authors: Mónica
authors: M
authors: Ramos
authors: Angela
authors: A
authors: Sardaro
authors: Michael
authors: M
authors: Brada
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000532:radiotherapy*; D002986:Clinical Trials as Topic; D018572:Disease-Free Survival; D004307:Dose-Response Relationship, Radiation; D004947:Esophagus / Q000528:radiation effects; D006801:Humans; D008168:Lung / Q000528:radiation effects; D008175:Lung Neoplasms / Q000532:radiotherapy*; D011879:Radiotherapy Dosage