title: Reporting of time-to-event end points and tracking of failures in randomized trials of radiotherapy with or without any concomitant anticancer agent for locally advanced head and neck cancer.
abstract: OBJECTIVE
  For multiple reasons, including complexities in anatomy and management, locally advanced squamous cell carcinomas of the head and neck (SCCHNs) represent a challenging disease for the reporting of end points and the tracking of failures.
  
  
  METHODS
  We retrieved all randomized trials published in English that began accrual on or after 1978 and enrolled previously untreated patients with nonmetastatic SCCHN receiving primary radiotherapy with or without any concomitant anticancer agent. The reporting of time-to-event end points and the tracking of failures in these trials were analyzed. Failures were defined as events meeting a prespecified end point definition.
  
  
  RESULTS
  Forty trials involving a total of 125 time-to-event end points were identified. A total of 17 different types of end points were reported. Locoregional control and overall survival accounted for 70% of primary end points. Except for survival, the definitions used for all other end points were heterogeneous. Among 72 end points tracking locoregional failures, 29% did not define the term, whereas 64% specified the absence of complete response as a failure. Overall, the specification of details related to elective neck dissection or salvage surgery to define locoregional failures was deficient. Furthermore, it was rarely stated whether residual disease found during these procedures represents a failure. The methods and timing specifications to assess failures were frequently missing in published reports. The tracking of other types of failure beyond the first failure was reported in only one trial.
  
  
  CONCLUSIONS
  These results support the need to standardize the selection, definition, and reporting of time-to-event end points in clinical trials of locally advanced SCCHN.
authors.affiliation: Princess Margaret Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Christophe
authors.initials: C
authors.lastname: Le Tourneau
authors.forename: Stefan
authors.initials: S
authors.lastname: Michiels
authors.forename: Hui K
authors.initials: HK
authors.lastname: Gan
authors.forename: Lillian L
authors.initials: LL
authors.lastname: Siu
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D017024:Chemotherapy, Adjuvant; D018450:Disease Progression; D018572:Disease-Free Survival; D023381:Endpoint Determination; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D017410:Practice Guidelines as Topic; D016032:Randomized Controlled Trials as Topic / Q000592:standards; D012107:Research Design / Q000592:standards; D016019:Survival Analysis; D013997:Time Factors; D017211:Treatment Failure; D016896:Treatment Outcome