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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

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Abstract
Purpose: The aim of this study was to find clinically relevant MIBG-avid metastatic patterns in patients with newly diagnosed stage 4 neuroblastoma. Methods: Diagnostic I-123-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). Conclusion: 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.
Keywords
MIBG scan, Neuroblastoma, Metastatic patterns, Metastases, Outcome, I-123 METAIODOBENZYLGUANIDINE SCINTIGRAPHY, HIGH-RISK NEUROBLASTOMA, EVENT-FREE SURVIVAL, INRG TASK-FORCE, FOLLOW-UP, IV NEUROBLASTOMA, DIAGNOSIS, CHILDREN, CHEMOTHERAPY, PREDICTION

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MLA
Bleeker, Gitta et al. “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.” EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING 42.2 (2015): 222–230. Print.
APA
Bleeker, G., Van Eck-Smit, B. L., Zwinderman, K. H., Versteeg, R., Van Noesel, M. M., Kam, B. L., Kaspers, G. J., et al. (2015). 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. EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING, 42(2), 222–230.
Chicago author-date
Bleeker, Gitta, Berthe L Van Eck-Smit, Koos H Zwinderman, Rogier Versteeg, Max M Van Noesel, Boen L Kam, Gertjan J Kaspers, et al. 2015. “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.” European Journal of Nuclear Medicine and Molecular Imaging 42 (2): 222–230.
Chicago author-date (all authors)
Bleeker, Gitta, Berthe L Van Eck-Smit, Koos H Zwinderman, Rogier Versteeg, Max M Van Noesel, Boen L Kam, Gertjan J Kaspers, Annelies van Schie, Susan G Kreissman, Gregory Yanik, Barbara Hero, Matthias Schmidt, Genevieve Laureys, Bieke Lambert, Ingrid Øra, Johannes H Schulte, Huib N Caron, and Godelieve A Tytgat. 2015. “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.” European Journal of Nuclear Medicine and Molecular Imaging 42 (2): 222–230.
Vancouver
1.
Bleeker G, Van Eck-Smit BL, Zwinderman KH, Versteeg R, Van Noesel MM, Kam BL, et al. 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. EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING. 2015;42(2):222–30.
IEEE
[1]
G. Bleeker et al., “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,” EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING, vol. 42, no. 2, pp. 222–230, 2015.
@article{5857339,
  abstract     = {Purpose: The aim of this study was to find clinically relevant MIBG-avid metastatic patterns in patients with newly diagnosed stage 4 neuroblastoma. 
Methods: Diagnostic I-123-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). 
Conclusion: 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.},
  author       = {Bleeker, Gitta and Van Eck-Smit, Berthe L and Zwinderman, Koos H and Versteeg, Rogier and Van Noesel, Max M and Kam, Boen L and Kaspers, Gertjan J and van Schie, Annelies and Kreissman, Susan G and Yanik, Gregory and Hero, Barbara and Schmidt, Matthias and Laureys, Genevieve and Lambert, Bieke and Øra, Ingrid and Schulte, Johannes H and Caron, Huib N and Tytgat, Godelieve A},
  issn         = {1619-7070},
  journal      = {EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING},
  keywords     = {MIBG scan,Neuroblastoma,Metastatic patterns,Metastases,Outcome,I-123 METAIODOBENZYLGUANIDINE SCINTIGRAPHY,HIGH-RISK NEUROBLASTOMA,EVENT-FREE SURVIVAL,INRG TASK-FORCE,FOLLOW-UP,IV NEUROBLASTOMA,DIAGNOSIS,CHILDREN,CHEMOTHERAPY,PREDICTION},
  language     = {eng},
  number       = {2},
  pages        = {222--230},
  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},
  url          = {http://dx.doi.org/10.1007/s00259-014-2909-1},
  volume       = {42},
  year         = {2015},
}

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