title: Radical-intent hypofractionated radiotherapy for locally advanced non-small-cell lung cancer: a systematic review of the literature.
abstract: OBJECTIVE
  To identify survival and toxicity characteristics associated with radical-intent hypofractionated radiotherapy for the treatment of stage III non-small-cell lung cancer (NSCLC).
  
  
  METHODS
  Relevant studies were identified from a systematic PubMed search of articles published between January 1990 and January 2014. All studies were peer reviewed and included both retrospective and prospective studies of NSCLC patients being treated with radical hypofractionated radiotherapy. Data on overall survival (OS) and toxicity were extracted from each of the studies where available.
  
  
  RESULTS
  Of 685 studies initially identified by the search, a total of 33 studies were found to be relevant and were included in this systematic review. The number of fractions ranged from 15 to 35, the dose per fraction ranged from 2.3 to 3.5 Gy, and the delivered dose ranged from 45.0 to 85.5 Gy. Fifteen of the studies included concurrent chemotherapy, while 18 did not. OS was found to be associated with tumor biological effective dose, with the Pearson correlation coefficient ranging from 0.34 to 0.48. For both concurrent and nonconcurrent chemoradiotherapy acute pulmonary, late esophageal and late pulmonary incidences of toxicity ranged from 1.2% to 12.2%, but had 95% confidence intervals that included zero. The greatest incidence of toxicity was acute esophageal toxicity at 14.9% (95% confidence interval, 0.7%, 29.1%).
  
  
  CONCLUSIONS
  There is a moderate linear relationship between biological effective dose and OS, and greater acute esophageal toxicity with concurrent chemotherapy. Improving outcomes in stage III NSCLC may involve some form of hypofractionation in the context of systemic concurrent therapy.
authors.affiliation: Department of Radiation Oncology, Western University, London, Ontario; Faculty of Medicine, University of Ottawa, Ottawa, Ontario.
authors.forename: Tyler S
authors.initials: TS
authors.lastname: Kaster
authors.affiliation: Department of Radiation Oncology, Western University, London, Ontario.
authors.forename: Brian
authors.initials: B
authors.lastname: Yaremko
authors.affiliation: Department of Radiation Oncology, Western University, London, Ontario.
authors.forename: David A
authors.initials: DA
authors.lastname: Palma
authors.affiliation: Department of Radiation Oncology, Western University, London, Ontario; Department of Epidemiology and Biostatistics, Western University, London, Ontario. Electronic address: george.rodrigues@lhsc.on.ca.
authors.forename: George B
authors.initials: GB
authors.lastname: Rodrigues
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D009367:Neoplasm Staging; D011446:Prospective Studies; D011832:Radiation Injuries / Q000453:epidemiology*; D011879:Radiotherapy Dosage; D015996:Survival Rate
keywords: Biological effective dose; Clinical outcomes; Hypofractionated radiotherapy; NSCLC; Systematic review