title: Prospective randomized clinical studies involving reirradiation : Lessons learned.
abstract: BACKGROUND
  Reirradiation is a potentially useful option for many patients with recurrent cancer. The purpose of this study was to review all recently published randomized trials in order to identify methodological strengths and weaknesses, comment on the results, clinical implications and open questions, and give advice for the planning of future trials.
  
  
  METHODS
  Systematic review of trials published between 2000 and 2015 (databases searched were PubMed, Scopus and Web of Science).
  
  
  RESULTS
  We reviewed 9 trials, most of which addressed reirradiation of head and neck tumours. The median number of patients was 69. Trial design, primary endpoint and statistical hypotheses varied widely. The results contribute mainly to decision making for reirradiation of nasopharynx cancer and bone metastases. The trials with relatively long median follow-up confirm that serious toxicity remains a concern after high cumulative total doses.
  
  
  CONCLUSIONS
  Multi-institutional collaboration is encouraged to complete sufficiently large trials. Despite a paucity of large randomized studies, reirradiation has been adopted in different clinical scenarios by many institutions. Typically, the patients have been assessed by multidisciplinary tumour boards and advanced technologies are used to create highly conformal dose distributions.
authors.affiliation: Department of Oncology and Palliative Medicine, Nordland Hospital, 8092, Bodø, Norway. carsten.nieder@nlsh.no.|Department of Clinical Medicine, Faculty of Health Sciences, University of Tromsø, 9038, Tromsø, Norway. carsten.nieder@nlsh.no.
authors.forename: Carsten
authors.initials: C
authors.lastname: Nieder
authors.affiliation: Department of Radiation Oncology, University Medical Centre Groningen, 9713, Groningen, The Netherlands.
authors.forename: Johannes A
authors.initials: JA
authors.lastname: Langendijk
authors.affiliation: Department of Radiation Oncology, University Hospital Zürich, 8091, Zürich, Switzerland.
authors.forename: Matthias
authors.initials: M
authors.lastname: Guckenberger
authors.affiliation: Department of Radiation Oncology, University Hospital Freiburg, 79106, Freiburg, Germany.
authors.forename: Anca L
authors.initials: AL
authors.lastname: Grosu
mesh_terms: D006258:Head and Neck Neoplasms / Q000401:mortality* / Q000532:radiotherapy*; D006801:Humans; D009364:Neoplasm Recurrence, Local / Q000401:mortality* / Q000532:radiotherapy*; D015995:Prevalence; D011446:Prospective Studies; D020266:Radiotherapy, Conformal / Q000401:mortality / Q000706:statistics & numerical data; D016032:Randomized Controlled Trials as Topic; D000069475:Re-Irradiation / Q000401:mortality* / Q000706:statistics & numerical data*; D012307:Risk Factors; D015996:Survival Rate; D016896:Treatment Outcome
keywords: Radiation oncology; Radiation retreatment; Radiotherapy; Randomized controlled trial; Research design