title: Response assessment in pediatric rhabdomyosarcoma: can response evaluation criteria in solid tumors replace three-dimensional volume assessments?
abstract: OBJECTIVE
  To investigate (a) interobserver variability for three-dimensional (3D) (based on European Pediatric Soft-Tissue Sarcoma Study Group [EpSSG] guidelines) and one-dimensional (1D) (based on Response Evaluation Criteria in Solid Tumors [RECIST]) response assessments, (b) intermethod variability between EpSSG guidelines and RECIST, and (c) clinically relevant consequences of interobserver and intermethod variability in pediatric patients with rhabdomyosarcoma.
  
  
  METHODS
  The study was approved by the Academic Medical Center Ethics Committee and the Great Ormond Street Hospital Ethics Committee; both committees waived the requirement for informed consent because of the retrospective nature of the study. Data were analyzed from 124 consecutive male and female children and young adults (age range, 1-18 years) with rhabdomyosarcoma at two institutions (1999-2009) with relevant imaging studies. Tumors were measured by two radiologists (1D and 3D measurements) at diagnosis and after induction chemotherapy. Interobserver variability was analyzed by using three different tests, and the intermethod variation was calculated.
  
  
  RESULTS
  Sixty-four eligible patients were included (median age, 4.6 years). Agreement between observers for EpSSG guidelines and RECIST was moderate (κ = 0.565 and 0.592, respectively); interobserver variation led to different potential treatment decisions in nine (14%) and 11 (17%) of the 64 patients, respectively. Comparison of EpSSG guidelines and RECIST resulted in 13 discrepant response classifications (20%), which were equally distributed (under- and overestimation of response) and led to consequences for treatment choice in five patients (8%).
  
  
  CONCLUSIONS
  EpSSG guidelines and RECIST are not interchangeable; neither technique demonstrated superiority in this study. These findings should be taken into account in future study protocol design. Online supplemental material is available for this article.
authors.affiliation: From the Departments of Pediatric Oncology (R.A.S., L.C.M.K., H.N.C., J.H.M.M.) and Pediatric Radiology (R.R.v.R.), Emma Children's Hospital-Academic Medical Center (EKZ-AMC), PO Box 22660, 1100 DD Amsterdam, the Netherlands; Department of Radiology, Great Ormond Street Hospital for Children, London, England (K.M.); and Children and Young People's Department, Royal Marsden Hospital, Sutton, England (J.C.C.).
authors.forename: Reineke A
authors.initials: RA
authors.lastname: Schoot
authors.forename: Kieran
authors.initials: K
authors.lastname: McHugh
authors.forename: Rick R
authors.initials: RR
authors.lastname: van Rijn
authors.forename: Leontien C M
authors.initials: LC
authors.lastname: Kremer
authors.forename: Julia C
authors.initials: JC
authors.lastname: Chisholm
authors.forename: Huib N
authors.initials: HN
authors.lastname: Caron
authors.forename: Johannes H M
authors.initials: JH
authors.lastname: Merks
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D003952:Diagnostic Imaging; D005260:Female; D006801:Humans; D021621:Imaging, Three-Dimensional; D007223:Infant; D008297:Male; D015588:Observer Variation; D012189:Retrospective Studies; D012208:Rhabdomyosarcoma / Q000188:drug therapy*; D016896:Treatment Outcome