title: Response Assessment in Paediatric Phase I Trials According to RECIST Guidelines: Survival Outcomes, Patterns of Progression and Relevance of Changes in Tumour Measurements.
abstract: RECIST guidelines constitute the reference for radiological response assessment in most paediatric trials of anticancer agents. However, these criteria have not been validated in children. We evaluated the outcomes and patterns of progression of children/adolescents enrolled in phase I trials in two paediatric drug development units.
  
  
  
  Patients aged ≤21 assessed with RECIST (v1.0 or v1.1) were eligible. Clinico-radiological data were analysed using Mann-Whitney U and log-rank tests to correlate response categories and sum of longest diameters (SLD) with time-to-event variables and overall survival (OS).
  
  
  
  Sixty-one patients (71 enrolments) were evaluated; median age: 12.7 years (range, 3.1-20.9). Overall, 7% achieved complete/partial response (n = 5) and 31% disease stabilisation (n = 22). Median (95% CI) OS (in months) was 29.1 (27.6-30.6) with complete/partial response, 8.9 (2.0-15.8) with stable disease and 2.8 (2.3-3.3) with disease progression (P < 0.001); 32.6% patients with measurable disease presented exclusive progression of existing non-target lesions and/or new lesions. The change in SLD at best response showed a linear correlation with duration of response (r = -0.605; P = 0.004) and time on trial (r = -0.61; P = 0.003), but the change in SLD at progression did not correlate with time to progression (r = -0.219; P = 0.206).
  
  
  
  Response assessment according to RECIST correlated with OS in children/adolescents treated on phase I trials. The reduction in SLD at best response correlated with more prolonged responses. Tumour size did not constitute an optimal method to assess disease progression in one third of patients with measurable disease. Further refinement of current response assessment guidelines will enable the development of paediatric-specific radiological criteria.
authors.affiliation: Children and Young People's Unit, The Royal Marsden NHS Foundation Trust, London, United Kingdom.|Division of Clinical Studies and Cancer Therapeutics, The Institute of Cancer Research, London, United Kingdom.
authors.forename: Fernando
authors.initials: F
authors.lastname: Carceller
authors.affiliation: Paediatric Oncology Department, Clinical Trials Unit, Hospital Niño Jesús, Madrid, Spain.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Bautista
authors.affiliation: Radiology Department, The Royal Marsden NHS Foundation Trust, London, United Kingdom.
authors.forename: Lucy A
authors.initials: LA
authors.lastname: Fowkes
authors.affiliation: Children and Young People's Unit, The Royal Marsden NHS Foundation Trust, London, United Kingdom.|Division of Clinical Studies and Cancer Therapeutics, The Institute of Cancer Research, London, United Kingdom.
authors.forename: Lynley V
authors.initials: LV
authors.lastname: Marshall
authors.affiliation: Paediatric Radiology Department, Hospital Niño Jesús, Madrid, Spain.
authors.forename: Sara I
authors.initials: SI
authors.lastname: Sirvent
authors.affiliation: Children and Young People's Unit, The Royal Marsden NHS Foundation Trust, London, United Kingdom.|Division of Clinical Studies and Cancer Therapeutics, The Institute of Cancer Research, London, United Kingdom.
authors.forename: Julia C
authors.initials: JC
authors.lastname: Chisholm
authors.affiliation: Children and Young People's Unit, The Royal Marsden NHS Foundation Trust, London, United Kingdom.|Division of Clinical Studies and Cancer Therapeutics, The Institute of Cancer Research, London, United Kingdom.
authors.forename: Andrew D J
authors.initials: AD
authors.lastname: Pearson
authors.affiliation: Radiology Department, The Royal Marsden NHS Foundation Trust, London, United Kingdom.
authors.forename: Dow-Mu
authors.initials: DM
authors.lastname: Koh
authors.affiliation: Children and Young People's Unit, The Royal Marsden NHS Foundation Trust, London, United Kingdom.|Division of Clinical Studies and Cancer Therapeutics, The Institute of Cancer Research, London, United Kingdom.|Paediatric Oncology Department, Clinical Trials Unit, Hospital Niño Jesús, Madrid, Spain.|Clinical Research Programme, CNIO (Spanish National Cancer Research Centre), Madrid, Spain.
authors.forename: Lucas
authors.initials: L
authors.lastname: Moreno
mesh_terms: D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D066066:Response Evaluation Criteria in Solid Tumors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents
keywords: RECIST; children; clinical trials; drug development; paediatric; phase I trials