title: Use of thoracic radiotherapy for extensive stage small-cell lung cancer: a phase 3 randomised controlled trial.
abstract: BACKGROUND
  Most patients with extensive stage small-cell lung cancer (ES-SCLC) who undergo chemotherapy, and prophylactic cranial irradiation, have persistent intrathoracic disease. We assessed thoracic radiotherapy for treatment of this patient group.
  
  
  METHODS
  We did this phase 3 randomised controlled trial at 42 hospitals: 16 in Netherlands, 22 in the UK, three in Norway, and one in Belgium. We enrolled patients with WHO performance score 0-2 and confirmed ES-SCLC who responded to chemotherapy. They were randomly assigned (1:1) to receive either thoracic radiotherapy (30 Gy in ten fractions) or no thoracic radiotherapy. All underwent prophylactic cranial irradiation. The primary endpoint was overall survival at 1 year in the intention-to-treat population. Secondary endpoints included progression-free survival. This study is registered with the Nederlands Trial Register, number NTR1527.
  
  
  RESULTS
  We randomly assigned 498 patients between Feb 18, 2009, and Dec 21, 2012. Three withdrew informed consent, leaving 247 patients in the thoracic radiotherapy group and 248 in the control group. Mean interval between diagnosis and randomisation was 17 weeks. Median follow-up was 24 months. Overall survival at 1 year was not significantly different between groups: 33% (95% CI 27-39) for the thoracic radiotherapy group versus 28% (95% CI 22-34) for the control group (hazard ratio [HR] 0.84, 95% CI 0.69-1.01; p=0.066). However, in a secondary analysis, 2-year overall survival was 13% (95% CI 9-19) versus 3% (95% CI 2-8; p=0.004). Progression was less likely in the thoracic radiotherapy group than in the control group (HR 0.73, 95% CI 0.61-0.87; p=0.001). At 6 months, progression-free survival was 24% (95% CI 19-30) versus 7% (95% CI 4-11; p=0.001). We recorded no severe toxic effects. The most common grade 3 or higher toxic effects were fatigue (11 vs 9) and dyspnoea (three vs four).
  
  
  CONCLUSIONS
  Thoracic radiotherapy in addition to prophylactic cranial irradiation should be considered for all patients with ES-SCLC who respond to chemotherapy.
  
  
  BACKGROUND
  Dutch Cancer Society (CKTO), Dutch Lung Cancer Research Group, Cancer Research UK, Manchester Academic Health Science Centre Trials Coordination Unit, and the UK National Cancer Research Network.
authors.affiliation: Department of Radiation Oncology, VU University Medical Center, Amsterdam, Netherlands. Electronic address: bj.slotman@vumc.nl.
authors.forename: Ben J
authors.initials: BJ
authors.lastname: Slotman
authors.affiliation: Department of Statistics, The Netherlands Cancer Institute, Amsterdam, Netherlands.
authors.forename: Harm
authors.initials: H
authors.lastname: van Tinteren
authors.affiliation: Department of Radiation Oncology, Erasmus MC, Rotterdam, Netherlands.
authors.forename: John O
authors.initials: JO
authors.lastname: Praag
authors.affiliation: Department of Radiation Oncology, The Netherlands Cancer Institute, Amsterdam, Netherlands.
authors.forename: Joost L
authors.initials: JL
authors.lastname: Knegjens
authors.affiliation: Department of Radiation Oncology, University Medical Center Utrecht, Utrecht, Netherlands.
authors.forename: Sherif Y
authors.initials: SY
authors.lastname: El Sharouni
authors.affiliation: Department of Clinical Oncology, Weston Park Hospital, Sheffield, UK.
authors.forename: Matthew
authors.initials: M
authors.lastname: Hatton
authors.affiliation: IKNL Clinical Research Department, Amsterdam, Netherlands.
authors.forename: Astrid
authors.initials: A
authors.lastname: Keijser
authors.affiliation: Institute of Cancer Sciences, University of Manchester, Manchester, UK.
authors.forename: Corinne
authors.initials: C
authors.lastname: Faivre-Finn
authors.affiliation: Department of Radiation Oncology, VU University Medical Center, Amsterdam, Netherlands.
authors.forename: Suresh
authors.initials: S
authors.lastname: Senan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001530:Belgium; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D009664:Norway; D055752:Small Cell Lung Carcinoma / Q000532:radiotherapy*; D016896:Treatment Outcome; D006113:United Kingdom