title: Clinical, biologic, and prognostic differences on the basis of primary tumor site in neuroblastoma: a report from the international neuroblastoma risk group project.
abstract: OBJECTIVE
  Neuroblastoma (NB) is a heterogeneous tumor arising from sympathetic tissues. The impact of primary tumor site in influencing the heterogeneity of NB remains unclear.
  
  
  METHODS
  Children younger than age 21 years diagnosed with NB or ganglioneuroblastoma between 1990 and 2002 and with known primary site were identified from the International Neuroblastoma Risk Group database. Data were compared between sites with respect to clinical and biologic features, as well as event-free survival (EFS) and overall survival (OS).
  
  
  RESULTS
  Among 8,369 children, 47% had adrenal tumors. All evaluated clinical and biologic variables differed statistically between primary sites. The features that were > 10% discrepant between sites were stage 4 disease, MYCN amplification, elevated ferritin, elevated lactate dehydrogenase, and segmental chromosomal aberrations, all of which were more frequent in adrenal versus nonadrenal tumors (P < .001). Adrenal tumors were more likely than nonadrenal tumors (adjusted odds ratio, 2.09; 95% CI, 1.67 to 2.63; P < .001) and thoracic tumors were less likely than nonthoracic tumors (adjusted odds ratio, 0.20; 95% CI, 0.11 to 0.39; P < .001) to have MYCN amplification after controlling for age, stage, and histologic grade. EFS and OS differed significantly according to the primary site (P < .001 for both comparisons). After controlling for age, MYCN status, and stage, patients with adrenal tumors had higher risk for events (hazard ratio, 1.13 compared with nonadrenal tumors; 95% CI, 1.03 to 1.23; P = .008), and patients with thoracic tumors had lower risk for events (HR, 0.79 compared with nonthoracic; 95% CI, 0.67 to 0.92; P = .003).
  
  
  CONCLUSIONS
  Clinical and biologic features show important differences by NB primary site, with adrenal and thoracic sites associated with inferior and superior survival, respectively. Future studies will need to investigate the biologic origin of these differences.
authors.affiliation: Kieuhoa T. Vo, Katherine K. Matthay, John Neuhaus, and Steven G. DuBois, Benioff Children's Hospital and University of California, San Francisco, San Francisco; Doug Miniati, Kaiser Permanente Medical Center, Roseville, CA; Wendy B. London, Children's Oncology Group Statistics and Data Center and Dana-Farber Children's Hospital Cancer Center, Boston, MA; Barbara Hero, Children's Hospital, University of Cologne, Köln, Germany; Peter F. Ambros, Children's Cancer Research Institute, St Anne Kinderkrebsforschung, Vienna, Austria; Akira Nakagawara, Chiba Cancer Center Research Institute and Chiba University, Chiba, Japan; Kate Wheeler, Oxford Children's Hospital, Oxford; Andrew D.J. Pearson, Institute of Cancer Research and Royal Marsden Hospital, Surrey, United Kingdom; Susan L. Cohn, The University of Chicago, Chicago, IL.
authors.forename: Kieuhoa T
authors.initials: KT
authors.lastname: Vo
authors.affiliation: Kieuhoa T. Vo, Katherine K. Matthay, John Neuhaus, and Steven G. DuBois, Benioff Children's Hospital and University of California, San Francisco, San Francisco; Doug Miniati, Kaiser Permanente Medical Center, Roseville, CA; Wendy B. London, Children's Oncology Group Statistics and Data Center and Dana-Farber Children's Hospital Cancer Center, Boston, MA; Barbara Hero, Children's Hospital, University of Cologne, Köln, Germany; Peter F. Ambros, Children's Cancer Research Institute, St Anne Kinderkrebsforschung, Vienna, Austria; Akira Nakagawara, Chiba Cancer Center Research Institute and Chiba University, Chiba, Japan; Kate Wheeler, Oxford Children's Hospital, Oxford; Andrew D.J. Pearson, Institute of Cancer Research and Royal Marsden Hospital, Surrey, United Kingdom; Susan L. Cohn, The University of Chicago, Chicago, IL.
authors.forename: Katherine K
authors.initials: KK
authors.lastname: Matthay
authors.affiliation: Kieuhoa T. Vo, Katherine K. Matthay, John Neuhaus, and Steven G. DuBois, Benioff Children's Hospital and University of California, San Francisco, San Francisco; Doug Miniati, Kaiser Permanente Medical Center, Roseville, CA; Wendy B. London, Children's Oncology Group Statistics and Data Center and Dana-Farber Children's Hospital Cancer Center, Boston, MA; Barbara Hero, Children's Hospital, University of Cologne, Köln, Germany; Peter F. Ambros, Children's Cancer Research Institute, St Anne Kinderkrebsforschung, Vienna, Austria; Akira Nakagawara, Chiba Cancer Center Research Institute and Chiba University, Chiba, Japan; Kate Wheeler, Oxford Children's Hospital, Oxford; Andrew D.J. Pearson, Institute of Cancer Research and Royal Marsden Hospital, Surrey, United Kingdom; Susan L. Cohn, The University of Chicago, Chicago, IL.
authors.forename: John
authors.initials: J
authors.lastname: Neuhaus
authors.affiliation: Kieuhoa T. Vo, Katherine K. Matthay, John Neuhaus, and Steven G. DuBois, Benioff Children's Hospital and University of California, San Francisco, San Francisco; Doug Miniati, Kaiser Permanente Medical Center, Roseville, CA; Wendy B. London, Children's Oncology Group Statistics and Data Center and Dana-Farber Children's Hospital Cancer Center, Boston, MA; Barbara Hero, Children's Hospital, University of Cologne, Köln, Germany; Peter F. Ambros, Children's Cancer Research Institute, St Anne Kinderkrebsforschung, Vienna, Austria; Akira Nakagawara, Chiba Cancer Center Research Institute and Chiba University, Chiba, Japan; Kate Wheeler, Oxford Children's Hospital, Oxford; Andrew D.J. Pearson, Institute of Cancer Research and Royal Marsden Hospital, Surrey, United Kingdom; Susan L. Cohn, The University of Chicago, Chicago, IL.
authors.forename: Wendy B
authors.initials: WB
authors.lastname: London
authors.affiliation: Kieuhoa T. Vo, Katherine K. Matthay, John Neuhaus, and Steven G. DuBois, Benioff Children's Hospital and University of California, San Francisco, San Francisco; Doug Miniati, Kaiser Permanente Medical Center, Roseville, CA; Wendy B. London, Children's Oncology Group Statistics and Data Center and Dana-Farber Children's Hospital Cancer Center, Boston, MA; Barbara Hero, Children's Hospital, University of Cologne, Köln, Germany; Peter F. Ambros, Children's Cancer Research Institute, St Anne Kinderkrebsforschung, Vienna, Austria; Akira Nakagawara, Chiba Cancer Center Research Institute and Chiba University, Chiba, Japan; Kate Wheeler, Oxford Children's Hospital, Oxford; Andrew D.J. Pearson, Institute of Cancer Research and Royal Marsden Hospital, Surrey, United Kingdom; Susan L. Cohn, The University of Chicago, Chicago, IL.
authors.forename: Barbara
authors.initials: B
authors.lastname: Hero
authors.affiliation: Kieuhoa T. Vo, Katherine K. Matthay, John Neuhaus, and Steven G. DuBois, Benioff Children's Hospital and University of California, San Francisco, San Francisco; Doug Miniati, Kaiser Permanente Medical Center, Roseville, CA; Wendy B. London, Children's Oncology Group Statistics and Data Center and Dana-Farber Children's Hospital Cancer Center, Boston, MA; Barbara Hero, Children's Hospital, University of Cologne, Köln, Germany; Peter F. Ambros, Children's Cancer Research Institute, St Anne Kinderkrebsforschung, Vienna, Austria; Akira Nakagawara, Chiba Cancer Center Research Institute and Chiba University, Chiba, Japan; Kate Wheeler, Oxford Children's Hospital, Oxford; Andrew D.J. Pearson, Institute of Cancer Research and Royal Marsden Hospital, Surrey, United Kingdom; Susan L. Cohn, The University of Chicago, Chicago, IL.
authors.forename: Peter F
authors.initials: PF
authors.lastname: Ambros
authors.affiliation: Kieuhoa T. Vo, Katherine K. Matthay, John Neuhaus, and Steven G. DuBois, Benioff Children's Hospital and University of California, San Francisco, San Francisco; Doug Miniati, Kaiser Permanente Medical Center, Roseville, CA; Wendy B. London, Children's Oncology Group Statistics and Data Center and Dana-Farber Children's Hospital Cancer Center, Boston, MA; Barbara Hero, Children's Hospital, University of Cologne, Köln, Germany; Peter F. Ambros, Children's Cancer Research Institute, St Anne Kinderkrebsforschung, Vienna, Austria; Akira Nakagawara, Chiba Cancer Center Research Institute and Chiba University, Chiba, Japan; Kate Wheeler, Oxford Children's Hospital, Oxford; Andrew D.J. Pearson, Institute of Cancer Research and Royal Marsden Hospital, Surrey, United Kingdom; Susan L. Cohn, The University of Chicago, Chicago, IL.
authors.forename: Akira
authors.initials: A
authors.lastname: Nakagawara
authors.affiliation: Kieuhoa T. Vo, Katherine K. Matthay, John Neuhaus, and Steven G. DuBois, Benioff Children's Hospital and University of California, San Francisco, San Francisco; Doug Miniati, Kaiser Permanente Medical Center, Roseville, CA; Wendy B. London, Children's Oncology Group Statistics and Data Center and Dana-Farber Children's Hospital Cancer Center, Boston, MA; Barbara Hero, Children's Hospital, University of Cologne, Köln, Germany; Peter F. Ambros, Children's Cancer Research Institute, St Anne Kinderkrebsforschung, Vienna, Austria; Akira Nakagawara, Chiba Cancer Center Research Institute and Chiba University, Chiba, Japan; Kate Wheeler, Oxford Children's Hospital, Oxford; Andrew D.J. Pearson, Institute of Cancer Research and Royal Marsden Hospital, Surrey, United Kingdom; Susan L. Cohn, The University of Chicago, Chicago, IL.
authors.forename: Doug
authors.initials: D
authors.lastname: Miniati
authors.affiliation: Kieuhoa T. Vo, Katherine K. Matthay, John Neuhaus, and Steven G. DuBois, Benioff Children's Hospital and University of California, San Francisco, San Francisco; Doug Miniati, Kaiser Permanente Medical Center, Roseville, CA; Wendy B. London, Children's Oncology Group Statistics and Data Center and Dana-Farber Children's Hospital Cancer Center, Boston, MA; Barbara Hero, Children's Hospital, University of Cologne, Köln, Germany; Peter F. Ambros, Children's Cancer Research Institute, St Anne Kinderkrebsforschung, Vienna, Austria; Akira Nakagawara, Chiba Cancer Center Research Institute and Chiba University, Chiba, Japan; Kate Wheeler, Oxford Children's Hospital, Oxford; Andrew D.J. Pearson, Institute of Cancer Research and Royal Marsden Hospital, Surrey, United Kingdom; Susan L. Cohn, The University of Chicago, Chicago, IL.
authors.forename: Kate
authors.initials: K
authors.lastname: Wheeler
authors.affiliation: Kieuhoa T. Vo, Katherine K. Matthay, John Neuhaus, and Steven G. DuBois, Benioff Children's Hospital and University of California, San Francisco, San Francisco; Doug Miniati, Kaiser Permanente Medical Center, Roseville, CA; Wendy B. London, Children's Oncology Group Statistics and Data Center and Dana-Farber Children's Hospital Cancer Center, Boston, MA; Barbara Hero, Children's Hospital, University of Cologne, Köln, Germany; Peter F. Ambros, Children's Cancer Research Institute, St Anne Kinderkrebsforschung, Vienna, Austria; Akira Nakagawara, Chiba Cancer Center Research Institute and Chiba University, Chiba, Japan; Kate Wheeler, Oxford Children's Hospital, Oxford; Andrew D.J. Pearson, Institute of Cancer Research and Royal Marsden Hospital, Surrey, United Kingdom; Susan L. Cohn, The University of Chicago, Chicago, IL.
authors.forename: Andrew D J
authors.initials: AD
authors.lastname: Pearson
authors.affiliation: Kieuhoa T. Vo, Katherine K. Matthay, John Neuhaus, and Steven G. DuBois, Benioff Children's Hospital and University of California, San Francisco, San Francisco; Doug Miniati, Kaiser Permanente Medical Center, Roseville, CA; Wendy B. London, Children's Oncology Group Statistics and Data Center and Dana-Farber Children's Hospital Cancer Center, Boston, MA; Barbara Hero, Children's Hospital, University of Cologne, Köln, Germany; Peter F. Ambros, Children's Cancer Research Institute, St Anne Kinderkrebsforschung, Vienna, Austria; Akira Nakagawara, Chiba Cancer Center Research Institute and Chiba University, Chiba, Japan; Kate Wheeler, Oxford Children's Hospital, Oxford; Andrew D.J. Pearson, Institute of Cancer Research and Royal Marsden Hospital, Surrey, United Kingdom; Susan L. Cohn, The University of Chicago, Chicago, IL.
authors.forename: Susan L
authors.initials: SL
authors.lastname: Cohn
authors.affiliation: Kieuhoa T. Vo, Katherine K. Matthay, John Neuhaus, and Steven G. DuBois, Benioff Children's Hospital and University of California, San Francisco, San Francisco; Doug Miniati, Kaiser Permanente Medical Center, Roseville, CA; Wendy B. London, Children's Oncology Group Statistics and Data Center and Dana-Farber Children's Hospital Cancer Center, Boston, MA; Barbara Hero, Children's Hospital, University of Cologne, Köln, Germany; Peter F. Ambros, Children's Cancer Research Institute, St Anne Kinderkrebsforschung, Vienna, Austria; Akira Nakagawara, Chiba Cancer Center Research Institute and Chiba University, Chiba, Japan; Kate Wheeler, Oxford Children's Hospital, Oxford; Andrew D.J. Pearson, Institute of Cancer Research and Royal Marsden Hospital, Surrey, United Kingdom; Susan L. Cohn, The University of Chicago, Chicago, IL. duboiss@peds.ucsf.edu.
authors.forename: Steven G
authors.initials: SG
authors.lastname: DuBois
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002675:Child, Preschool; D002869:Chromosome Aberrations; D016208:Databases, Factual / Q000706:statistics & numerical data; D005293:Ferritins / Q000378:metabolism; D005784:Gene Amplification; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007223:Infant; D007391:International Cooperation; D053208:Kaplan-Meier Estimate; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D016015:Logistic Models; D000071447:N-Myc Proto-Oncogene Protein; D009367:Neoplasm Staging; D009447:Neuroblastoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D009687:Nuclear Proteins / Q000235:genetics; D015513:Oncogene Proteins / Q000235:genetics; D010386:Pelvic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D011379:Prognosis; D016016:Proportional Hazards Models; D018570:Risk Assessment / Q000379:methods / Q000706:statistics & numerical data; D012307:Risk Factors; D013899:Thoracic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*
chemical_list: C459801:MYCN protein, human; D000071447:N-Myc Proto-Oncogene Protein; D009687:Nuclear Proteins; D015513:Oncogene Proteins; D005293:Ferritins; D007770:L-Lactate Dehydrogenase