title: Lack of treatment-related mortality definitions in clinical trials of children, adolescents and young adults with lymphomas, solid tumors and brain tumors: a systematic review.
abstract: BACKGROUND
  There is a lack of standardized definition for treatment-related mortality (TRM), which represents an important endpoint in cancer. Our objective was to describe TRM definitions used in studies of children, adolescents and young adults with lymphomas, solid tumors and brain tumors.
  
  
  METHODS
  We conducted a systematic review of studies enrolling children, adolescents and young adults with lymphomas, solid tumors and brain tumors in which an anti-cancer intervention was randomized, or all study designs in which TRM was a primary or secondary outcome. We searched Ovid MEDLINE, EMBASE and Evidence-Based Medicine Reviews from 1980 to June 2013. Two reviewers evaluated study eligibility and abstracted data.
  
  
  RESULTS
  In total, 67 studies were included and consisted of 62 randomized therapeutic trials and 5 TRM studies. None of the studies (0/67) provided a definition for TRM. Only one randomized trial of rhabdomyosarcoma provided a definition of early death.
  
  
  CONCLUSIONS
  We were unable to identify any TRM definitions used in studies of children, adolescents and young adults with lymphomas, solid tumors and brain tumors. Given that a proportion of this patient population may receive intensive treatment, there is an urgent need for consensus-based definitions of TRM for use across clinical trials.
authors.forename: Thai Hoa
authors.initials: TH
authors.lastname: Tran
authors.forename: Michelle
authors.initials: M
authors.lastname: Lee
authors.forename: Sarah
authors.initials: S
authors.lastname: Alexander
authors.forename: Paul
authors.initials: P
authors.lastname: Gibson
authors.forename: Ute
authors.initials: U
authors.lastname: Bartels
authors.forename: Donna L
authors.initials: DL
authors.lastname: Johnston
authors.forename: Carol
authors.initials: C
authors.lastname: Portwine
authors.forename: Marianna
authors.initials: M
authors.lastname: Silva
authors.forename: Jason D
authors.initials: JD
authors.lastname: Pole
authors.affiliation: Division of Haematology/Oncology, The Hospital for Sick Children, 555 University Ave, Toronto, Ontario M5G 1X8, Canada. lillian.sung@sickkids.ca.
authors.forename: Lillian
authors.initials: L
authors.lastname: Sung
mesh_terms: D000293:Adolescent; D001932:Brain Neoplasms / Q000401:mortality / Q000628:therapy*; D002423:Cause of Death; D002648:Child; D006801:Humans; D008223:Lymphoma / Q000401:mortality / Q000628:therapy*; D009369:Neoplasms / Q000401:mortality / Q000628:therapy*; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome; D055815:Young Adult