title: MIBG scans in patients with stage 4 neuroblastoma reveal two metastatic patterns, one is associated with MYCN amplification and in MYCN-amplified tumours correlates with a better prognosis.
abstract: OBJECTIVE
  The aim of this study was to find clinically relevant MIBG-avid metastatic patterns in patients with newly diagnosed stage 4 neuroblastoma.
  
  
  METHODS
  Diagnostic (123)I-MIBG scans from 249 patients (123 from a European and 126 from the COG cohort) were assessed for metastatic spread in 14 body segments and the form of the lesions: "focal" (clear margins distinguishable from adjacent background) or "diffuse" (indistinct margins, dispersed throughout the body segment). The total numbers of diffuse and focal lesions were recorded. Patients were then categorized as having lesions exclusively focal, lesions more focal than diffuse, lesions more diffuse than focal, or lesions exclusively diffuse.
  
  
  RESULTS
  Diffuse lesions affected a median of seven body segments and focal lesions a median of two body segments (P < 0.001, both cohorts). Patients with a focal pattern had a median of 2 affected body segments and those with a diffuse pattern a median of 11 affected body segments (P < 0.001, both cohorts). Thus, two MIBG-avid metastatic patterns emerged: "limited-focal" and "extensive-diffuse". The median numbers of affected body segments in MYCN-amplified (MNA) tumours were 5 (European cohort) and 4 (COG cohort) compared to 9 and 11, respectively, in single-copy MYCN (MYCNsc) tumours (P < 0.001). Patients with exclusively focal metastases were more likely to have a MNA tumour (60% and 70%, respectively) than patients with the other types of metastases (23% and 28%, respectively; P < 0.001). In a multivariate Cox regression analysis, focal metastases were associated with a better event-free and overall survival than the other types of metastases in patients with MNA tumours in the COG cohort (P < 0.01).
  
  
  CONCLUSIONS
  Two metastatic patterns were found: a "limited and focal" pattern found mainly in patients with MNA neuroblastoma that correlated with prognosis, and an "extensive and diffuse" pattern found mainly in patients with MYCNsc neuroblastoma.
authors.affiliation: Department of Paediatric Oncology, Academic Medical Centre/Emma Children's Hospital, PO Box 22700, 1100 DE, Amsterdam, The Netherlands.
authors.forename: Gitta
authors.initials: G
authors.lastname: Bleeker
authors.forename: Berthe L
authors.initials: BL
authors.lastname: van Eck-Smit
authors.forename: Koos H
authors.initials: KH
authors.lastname: Zwinderman
authors.forename: Rogier
authors.initials: R
authors.lastname: Versteeg
authors.forename: Max M
authors.initials: MM
authors.lastname: van Noesel
authors.forename: Boen L
authors.initials: BL
authors.lastname: Kam
authors.forename: Gertjan J
authors.initials: GJ
authors.lastname: Kaspers
authors.forename: Annelies
authors.initials: A
authors.lastname: van Schie
authors.forename: Susan G
authors.initials: SG
authors.lastname: Kreissman
authors.forename: Gregory
authors.initials: G
authors.lastname: Yanik
authors.forename: Barbara
authors.initials: B
authors.lastname: Hero
authors.forename: Matthias
authors.initials: M
authors.lastname: Schmidt
authors.forename: Geneviève
authors.initials: G
authors.lastname: Laureys
authors.forename: Bieke
authors.initials: B
authors.lastname: Lambert
authors.forename: Ingrid
authors.initials: I
authors.lastname: Øra
authors.forename: Johannes H
authors.initials: JH
authors.lastname: Schulte
authors.forename: Huib N
authors.initials: HN
authors.lastname: Caron
authors.forename: Godelieve A
authors.initials: GA
authors.lastname: Tytgat
mesh_terms: D019797:3-Iodobenzylguanidine; D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D064847:Multimodal Imaging; D000071447:N-Myc Proto-Oncogene Protein; D009362:Neoplasm Metastasis / Q000000981:diagnostic imaging / Q000235:genetics / Q000473:pathology; D009447:Neuroblastoma / Q000000981:diagnostic imaging* / Q000235:genetics / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics*; D015513:Oncogene Proteins / Q000235:genetics*; D049268:Positron-Emission Tomography; D011237:Predictive Value of Tests; D011379:Prognosis; D019275:Radiopharmaceuticals; D014057:Tomography, X-Ray Computed
chemical_list: C459801:MYCN protein, human; D000071447:N-Myc Proto-Oncogene Protein; D009687:Nuclear Proteins; D015513:Oncogene Proteins; D019275:Radiopharmaceuticals; D019797:3-Iodobenzylguanidine